Stuart D. Katz, M.D.

Clinical correlates of hemoconcentration during hospitalization for acute decompensated heart failure
Davila, Carlos; Reyentovich, Alex; Katz, Stuart D
2011 Dec;17(12):1018-1022, Journal of cardiac failure
BACKGROUND: Hemoconcentration has been proposed as a putative biomarker of effective decongestion therapy in heart failure patients. The prevalence and clinical correlates of hemoconcentration in hospitalized patients with acute decompensated heart failure (ADHF) have not been previously described. METHODS AND RESULTS: We retrospectively reviewed paired values of hemoglobin at admission and discharge to identify evidence of hemoconcentration in 295 subjects hospitalized with ADHF and determined the association between hemoconcentration and risk of worsening renal function and survival. Subjects with hemoconcentration (n = 75) received higher diuretic doses and demonstrated greater weight loss during hospitalization when compared with subjects without hemoconcentration (median [IQR] loop diuretic dose 180 (120) versus 160 (150) mg, P = .014; mean +/- SD weight loss 4.0 +/- 3.1 versus 2.2 +/- 3.1 kg, P < .001). In univariate analysis, hemoconcentration was associated with increased risk of worsening renal function (odds ratio 2.34, 95% CI 1.27-4.30, P = .006), but decreased risk of all-cause mortality (hazard ratio 0.53, 95% CI 0.29-0.96, P = .035). In multivariate analysis, hemoconcentration remained independently associated with worsening renal function, but not mortality. CONCLUSIONS: Hemoconcentration is significantly associated with increased diuretic dose, greater weight loss, and increased risk of worsening renal function during hospitalization. Hemoconcentration was significantly associated with mortality in univariate analysis, but not in multivariate analysis
— id: 141992, year: 2011, vol: 17, page: 1018, stat: Journal Article,

Differential effects of low-carbohydrate and low-fat diets on inflammation and endothelial function in diabetes
Davis, Nichola J.; Crandall, Jill P.; Gajavelli, Srikanth; Berman, Joan W.; Tomuta, Nora; Wylie-Rosett, Judith; Katz, Stuart D.
2011 NOV-DEC ;25(6):371-376, Journal of diabetes & its complications
Objective: To characterize acute (postprandial) and chronic (after a 6-month period of weight loss) effects of a low-carbohydrate vs. a low-fat diet on subclinical markers of cardiovascular disease (CVD) in adults with type 2 diabetes. Design: At baseline and 6 months, measures of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin were obtained from archived samples (n=51) of participants randomized in a clinical trial comparing a low-carbohydrate and a low-fat diet. In a subset of participants (n=27), postprandial measures of these markers were obtained 3 h after a low-carbohydrate or low-fat liquid meal. Endothelial function was also measured by reactive hyperemic peripheral arterial tonometry during the meal test. Paired t tests and unpaired t tests compared within- and between-group changes. Results: There were no significant differences observed in postprandial measures of inflammation or endothelial function. After 6 months, CRP (mean +/- S.E.) decreased in the low-fat arm from 4.0 +/- 0.77 to 3.0 +/- 0.77 (P=.01). In the low-carbohydrate arm, sICAM decreased from 234 +/- 22 to 199 +/- 23 (P=.001), and soluble E-selectin decreased from 93 +/- 10 to 82 +/- 10 (P=.05.) A significant correlation between change in high-density lipoprotein and change in soluble E-selectin (r=-0.33, P=.04) and with the change in ICAM (r=-0.43, P=.01) was observed. Conclusions: Low-carbohydrate and low-fat diets both have beneficial effects on CVD markers. There may be different mechanisms through which weight loss with these diets potentially reduces CVD risk. (C) 2011 Elsevier Inc. All rights reserved
— id: 149888, year: 2011, vol: 25, page: 371, stat: Journal Article,

Comparison of quantity of left ventricular scarring and remodeling by magnetic resonance imaging in patients with versus without diabetes mellitus and with coronary artery disease
Donnino, Robert; Patel, Sajan; Nguyen, Andrew H; Sedlis, Steven P; Babb, James S; Schwartzbard, Arthur; Katz, Stuart D; Srichai, Monvadi B
2011 Jun 1;107(11):1575-1578, American journal of cardiology
Diabetic patients with coronary artery disease (CAD) are more likely to develop heart failure (HF) than nondiabetic patients, but the mechanism responsible is unclear. Evidence suggests that infarct size and accompanying remodeling may not explain this difference. We used cardiac magnetic resonance (CMR) imaging to compare degree of left ventricular (LV) myocardial scar and remodeling in diabetic and nondiabetic patients with CAD. We evaluated 85 patients (39 diabetic, 46 nondiabetic) who underwent coronary angiography showing obstructive CAD and CMR imaging within 6 months of each other. Myocardial scar was measured by late gadolinium enhancement on CMR imaging and was graded according to spatial and transmural extents on a semiquantitative scale. More diabetic than nondiabetic patients had HF (69% vs 43%, p <0.03); however, groups did not differ in total scar burden (0.94 +/- 0.60 vs 1.17 +/- 0.74, p = NS), spatial extent of scar, or extent of transmural scar. Diabetes remained an independent predictor of HF after adjustment for CAD and other variables. LV ejection fraction (36 +/- 12% vs 37 +/- 14%, p = NS) and end-diastolic volume (215 +/- 56 vs 217 +/- 76 ml, p = NS) were similar for diabetic and nondiabetic patients, respectively. In conclusion, although diabetic patients with CAD had a higher prevalence of HF than nondiabetic patients, there was no difference in myocardial scar, LV volume, or LV ejection fraction. These findings support the theory that mechanisms other than extent of myocardial injury and negative remodeling play a significant role in the development of HF in diabetic patients with CAD
— id: 132572, year: 2011, vol: 107, page: 1575, stat: Journal Article,

Oral contraceptive use, iron stores and vascular endothelial function in healthy women
Friedman, Julie; Cremer, Miriam; Jelani, Qurat Ul-Ain; Huang, Xi; Jian, Jinlong; Shah, Sooraj; Katz, Stuart D
2011 Sep;84(3):285-290, Contraception
BACKGROUND: Increased iron stores are associated with greater cardiovascular risk in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume of menstrual blood loss and increases iron stores, but the link between OCP use, iron stores and cardiovascular risk in premenopausal women has not been characterized. STUDY DESIGN: We conducted a cross-sectional study of 23 healthy OCP users to determine the association between type and duration of OCP exposure, iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in the brachial artery]. RESULTS: Median duration of OCP use was 45 months. FMD in the brachial artery was significantly associated with progestin type used (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not iron stores. In multivariate analysis, progestin type was the only independent predictor of FMD. CONCLUSIONS: Use of OCP containing drospirenone was independently associated with greater FMD in the brachial artery and, thus, a potentially more favorable cardiovascular risk profile, when compared with use of OCP containing estranes/gonanes
— id: 136646, year: 2011, vol: 84, page: 285, stat: Journal Article,

Intakes of dietary iron and heme-iron and risk of postmenopausal breast cancer in the National Institutes of Health-AARP Diet and Health Study
Huang, Xi; Katz, Stuart
2011 Aug;94(2):613-614, American journal of clinical nutrition
— id: 135553, year: 2011, vol: 94, page: 613, stat: Journal Article,

Iron Deficiency in Community-Dwelling US Adults With Self-Reported Heart Failure in the National Health and Nutrition Examination Survey III: Prevalence and Associations With Anemia and Inflammation
Parikh, Ankit; Natarajan, Sundar; Lipsitz, Stuart R; Katz, Stuart D
2011 Sep 1;4(5):599-606, Circulation: Heart Failure
Background- Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized. Methods and Results- Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 mug/L or between 100 and 299 mug/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality. Conclusions- Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort
— id: 137836, year: 2011, vol: 4, page: 599, stat: Journal Article,

Mineralocorticoid-receptor Antagonists in Heart Failure: A Tale of Serendipity and Success
Reyentovich, Alex; Katz, Stuart D
2011 Jun;8(2):87-90, Current heart failure reports
— id: 131959, year: 2011, vol: 8, page: 87, stat: Journal Article,

Treatment with iron of patients with heart failure with and without anemia
Jelani, Qurat-ul-ain; Attanasio, Philipp; Katz, Stuart D; Anker, Stefan D
2010 Jul;6(3):305-312, Heart Failure Clinics
Iron deficiency is a common cause of anemia in otherwise healthy individuals and plays an important role in the development of anemia within the heart failure patient population. Iron-deficient heart failure patients experience worse symptoms and are less exercise tolerant than those without iron deficiency. These symptoms may occur even before clinical anemia is evident. This article reviews studies of the benefits of the use of intravenous iron to treat iron deficiency in anemic and nonanemic heart failure patients and an overview of the physiology and pathophysiology of iron metabolism in chronic heart failure
— id: 111375, year: 2010, vol: 6, page: 305, stat: Journal Article,

Iron in heart failure: friend or foe?
Jelani, Qurat-ul-ain; Katz, Stuart D
2010 Jun;7(2):49-51, Current heart failure reports
— id: 109794, year: 2010, vol: 7, page: 49, stat: Journal Article,

Treatment of anemia in heart failure: potential risks and benefits of intravenous iron therapy in cardiovascular disease
Jelani, Qurat-Ul-Ain; Katz, Stuart D
2010 Sep-Oct;18(5):240-250, Cardiology in review
Iron-deficiency anemia is common in patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a subgroup analysis also suggest that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients
— id: 111597, year: 2010, vol: 18, page: 240, stat: Journal Article,

In search of the optimal measure for assessment of parasympathetic control of heart rate
Katz, Stuart D
2010 Feb;20(1):1-2, Clinical autonomic research
— id: 107275, year: 2010, vol: 20, page: 1, stat: Journal Article,

The plot thickens: hemoconcentration, renal function, and survival in heart failure
Katz, Stuart D
2010 Jul 20;122(3):233-235, Circulation
— id: 111373, year: 2010, vol: 122, page: 233, stat: Journal Article,

Prevalence of Functional Iron Deficiency in Adults With Heart Failure and Associations With Anemia, Inflammation, and Mortality
Parikh, Ankit D.; Natarajan, Sundar; Lipsitz, Stuart R.; Katz, Stuart D.
2010 AUG ;16(8):S77-S77, Journal of cardiac failure
— id: 114013, year: 2010, vol: 16, page: S77, stat: Journal Article,

Effects of recombinant human erythropoietin on platelet activation in acute myocardial infarction: Results of a double-blind, placebo-controlled, randomized trial
Tang, YD; Hasan, F; Giordano, FJ; Pfau, S; Rinder, HM; Katz, SD
2009 DEC ;158(6):941-947, American heart journal
Background Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction (MI). Methods We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute MI treated with aspirin and clopidogrel after successful percutaneous coronary intervention. Results Recombinant human erythropoietin did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMCs when compared with placebo (all Ps < .05). Conclusions In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMCs when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials. (Am Heart J 2009; 158: 941-7.)
— id: 106079, year: 2009, vol: 158, page: 941, stat: Journal Article,

Erectile dysfunction as a harbinger for increased cardiometabolic risk
Billups, K L; Bank, A J; Padma-Nathan, H; Katz, S D; Williams, R A
2008 May-Jun;20(3):236-242, International journal of impotence research
In August 2003, the Minority Health Institute (MHI) convened an Expert Advisory Panel of cardiologists and urologists to design a new practice model algorithm that uses erectile dysfunction (ED) as a clinical tool for early identification of men with systemic vascular disease. The MHI algorithm noted ED as a marker for the presence of cardiovascular disease and suggested that ED may well be a cardiovascular risk equivalent warranting aggressive secondary prevention management strategies, even in the absence of other cardiac or peripheral vascular symptoms. The MHI algorithm stipulates that all men 25 years of age and older should be asked about ED as a routine part of the cardiovascular history during any office visit. The presence of ED should prompt an aggressive assessment for occult vascular disease; many men with erectile difficulty would benefit from early, aggressive management of cardiovascular risk factors with both lifestyle modification and pharmacotherapy to achieve optimal target goals under the existing treatment guidelines. Since publication of the algorithm in 2005, additional research studies have further supported the advisory panel recommendations
— id: 83254, year: 2008, vol: 20, page: 236, stat: Journal Article,

Potential role of statins in the treatment of heart failure
Katz, Stuart D
2008 Aug;10(4):318-323, Current atherosclerosis reports
Based on the findings of retrospective studies, there has been growing interest in the potential therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients with heart failure. The first published prospective randomized study of statins in heart failure patients did not demonstrate improved clinical outcomes (death and nonfatal myocardial infarction or stroke) after treatment with 10 mg daily of rosuvastatin when compared with placebo. However, use of rosuvastatin was associated with a reduced risk of hospitalization when compared with placebo and was well tolerated. Until further information becomes available, routine use of statins is not recommended in the heart failure population
— id: 83267, year: 2008, vol: 10, page: 318, stat: Journal Article,

The prevalence of anemia in chronic heart failure and its impact on the clinical outcomes
Tang, Yi-Da; Katz, Stuart D
2008 Dec;13(4):387-392, Heart Failure Reviews
This review article summarizes the current medical literature reporting on the prevalence and prognostic significance of anemia in patients with heart failure. Almost all currently available data indicate that anemia is common in heart failure populations, with the majority of studies indicating prevalence >20%. Anemia appears to be more highly prevalent in patients with advanced age, with more severe limitations in functional capacity, and with greater severity of co-morbid chronic kidney disease. In most reported studies anemia is an independent predictor of increased mortality risk and increased risk of hospitalization for heart failure. These data provide the rationale for interventional treatment trials to determine if anemia is in the causal pathway for disease progression and increased mortality risk in HF patients
— id: 83256, year: 2008, vol: 13, page: 387, stat: Journal Article,

Effect of acetylcholinesterase inhibition with pyridostigmine on cardiac parasympathetic function in sedentary adults and trained athletes
Dewland, Thomas A; Androne, Ana Silvia; Lee, Forrester A; Lampert, Rachel J; Katz, Stuart D
2007 Jul;293(1):H86-H92, American journal of physiology. Heart & circulatory physiology
Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies, but in some cases these indexes appear to yield discordant information. We utilized pyridostigmine, an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal, to further characterize parasympathetic regulation of rest and postexercise heart rate. We measured time- and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine (30 mg) and matching placebo in randomized, double-blind, crossover trial. In sedentary adults, pyridostigmine decreased resting heart rate [from 66.7 (SD 12.6) to 58.1 beats/min (SD 7.6), P = 0.005 vs. placebo] and increased postexercise heart rate recovery at 1 min [from 40.7 (SD 10.9) to 45.1 beats/min (SD 8.8), P = 0.02 vs. placebo]. In trained athletes, pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo. Time- and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort. The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation. The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway
— id: 83235, year: 2007, vol: 293, page: H86, stat: Journal Article,

Blood volume assessment in the diagnosis and treatment of chronic heart failure
Katz, Stuart D
2007 Jul;334(1):47-52, American journal of the medical sciences
Symptoms of intravascular volume overload and increased cardiac filling pressures in the systemic and pulmonary venous circulations are among the most common complaints in patients with chronic heart failure (CHF). The clinical utility of physical examination for estimation of intravascular volume status in patients with CHF is limited due to poor specificity and sensitivity of most signs of congestion. Direct measurement of blood volume with radioisotope techniques is FDA-approved and has been shown to be closely associated with invasive measurements of cardiac filling pressures in patients with CHF. Unrecognized volume overload is common in CHF patients and is associated with adverse clinical outcomes. Additional work is needed to determine the clinical utility of serial blood volume measurements in the management of patients with CHF
— id: 83244, year: 2007, vol: 334, page: 47, stat: Journal Article,

Iron reduction and cardiovascular outcomes
Sullivan, Jerome L; Katz, Stuart D
2007 May 16;297(19):2075-2075, JAMA
— id: 83242, year: 2007, vol: 297, page: 2075, stat: Journal Article,

Effects of recombinant human erythropoietin on antiplatelet action of aspirin and clopidogrel in healthy subjects: results of a double-blind, placebo-controlled randomized trial
Tang, Yi-Da; Rinder, Henry M; Katz, Stuart D
2007 Sep;154(3):494.e1-494.e7, American heart journal
BACKGROUND: Recombinant human erythropoietin (rHuEpo) reduces myocardial injury in experimental ischemia and has been proposed as a cardioprotective agent for potential use in acute coronary syndromes. Its safety profile in clinical acute ischemic settings is uncertain because rHuEpo has been reported to increase platelet reactivity and the risk of thromboembolism in some disease populations. Whether prothrombotic effects of rHuEpo mitigate the effects of antiplatelet agents used in acute coronary syndrome patients is unknown. METHODS: Recombinant human erythropoietin 100, 200, 400 U/kg, or placebo was given intravenously once daily for 3 consecutive days in a double-blind randomized trial in 96 healthy subjects. A single oral dose of aspirin 325 mg or clopidogrel 300 mg was given immediately after the last dose of study drug. Bleeding time and in vitro high shear stress platelet function assays (PFA)-100 were determined before; 5 hours; and 1, 5, and 7 days after aspirin or clopidogrel. RESULTS: Recombinant human erythropoietin at doses of 100 and 200 U/kg did not alter bleeding time or PFA-100 closure times at any time point when compared with placebo. Recombinant human erythropoietin at a dose of 400 U/kg significantly blunted the post-aspirin increase in bleeding time when compared with placebo (P = .03) but did not alter post-clopidogrel bleeding times nor PFA closure times. The 400-U/kg dose did not change hematocrit but did significantly increase the platelet count at 5 days after study drug administration when compared with placebo (P = .014). CONCLUSION: Short-term rHuEpo at doses up to 200 U/kg did not mitigate the effects of administration of aspirin or clopidogrel on either in vivo or in vitro measures of platelet function in healthy subjects. The 400-U/kg dose attenuated the effects of aspirin on bleeding time and increased the platelet count. Studies of the effects of rHuEpo on platelet function in patients with coronary artery disease are warranted to further characterize dose/safety profile
— id: 83247, year: 2007, vol: 154, page: 494.e1, stat: Journal Article,

Insulin sensitivity, vascular function, and iron stores in voluntary blood donors
Zheng, Haoyi; Patel, Milan; Cable, Ritchard; Young, Lawrence; Katz, Stuart D
2007 Oct;30(10):2685-2689, Diabetes care
OBJECTIVE: Reduced iron stores after blood donation are associated with improved vascular function and decreased cardiovascular risk. We sought to determine whether iron-dependent changes in glucose metabolism may contribute to improved vascular function in blood donors. RESEARCH DESIGN AND METHODS: We conducted a prospective cross-sectional study in 21 high-frequency blood donors (more than eight donations in the last 2 years) and 21 low-frequency blood donors (one to two donations in the last 2 years) aged 50-75 years. Serum markers of iron stores, whole-body insulin sensitivity index (WBISI) during oral glucose tolerance testing, and flow-mediated dilation in the brachial artery were determined in all subjects. RESULTS: Serum ferritin was decreased (median values 23 vs. 36 ng/ml, P < 0.05) and flow-mediated dilation in the brachial artery was increased (median values 5.9 vs. 5.3%, P < 0.05) in high-frequency donors compared with low-frequency donors, respectively, but WBISI (median values 4.8 vs. 4.7) and related measures of glucose tolerance did not differ between groups. Flow-mediated dilation significantly decreased at 1 h after oral glucose loading in both groups, but the decrease in flow-mediated dilation at 1 h did not differ between high- and low-frequency donors. CONCLUSIONS: High-frequency blood donation reduced serum ferritin and increased flow-mediated dilation compared with low-frequency donation but did not improve insulin sensitivity or protect the vascular endothelium from the adverse effects of acute hyperglycemia after oral glucose loading. These findings suggest that the mechanisms linking blood donation to improved vascular function are not likely related to changes in glucose metabolism
— id: 83243, year: 2007, vol: 30, page: 2685, stat: Journal Article,

Comparison of metabolic vasodilation in response to exercise and ischemia and endothelium-dependent flow-mediated dilation in African-American versus non-African-American patients with chronic heart failure
Androne, Ana Silvia; Hryniewicz, Katarzyna; Hudaihed, Alhakam; Dimayuga, Clarito; Yasskiy, Aleksandr; Qureshi, Ghazanfar; Katz, Stuart D
2006 Mar 1;97(5):685-689, American journal of cardiology
Race-related disparities in response to therapy and clinical outcomes have been reported in patients with chronic heart failure (HF). Vascular dysfunction is an important determinant of therapeutic response and clinical outcomes in chronic HF, but race-related differences of vasodilator responses in those with chronic HF have not been previously characterized. We assessed metabolic vasodilation in response to exercise and ischemia and endothelium-dependent flow-mediated dilation in conduit and resistance vessels with strain gauge venous occlusion plethysmography and high-resolution ultrasound imaging in the forearm circulation of 69 African-American and 188 non-African-American patients with chronic HF. African-American patients had a higher prevalence of hypertension than non-African-American patients (59% vs 35%, p = 0.001) and higher mean arterial pressures despite similar HF treatment (93 +/- 2 vs 89 +/- 1 mm Hg, p = 0.045). Forearm vascular resistance in African-American patients was higher than that of non-African-American patients at rest (22.3 +/- 1.8 vs 16.2 +/- 0.8 U, p <0.001), during exercise (4.7 +/- 0.3 vs 3.8 +/- 0.2 U, p = 0.03), and after ischemia (2.0 +/- 0.3 vs 1.5 +/- 0.1 U, p = 0.04). Endothelium-dependent flow-mediated vasodilation was significantly decreased in African-American compared with non-African-American patients in conduit vessels (brachial artery flow-mediated dilation 0.77 +/- 0.43% vs 1.86 +/- 0.24%, p = 0.03) and resistance vessels (post-ischemic forearm hyperemia 110 +/- 11 vs 145 +/- 10 ml/min/100 ml, p = 0.035). Estimates of differences in race-related vasoreactivity did not substantially change and remained at significant or borderline significant levels after adjustment for hypertension. Impaired vasodilation may contribute to differences in therapeutic response and clinical outcomes in African-American patients with chronic HF
— id: 83215, year: 2006, vol: 97, page: 685, stat: Journal Article,

Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options
Tang, Yi-Da; Katz, Stuart D
2006 May 23;113(20):2454-2461, Circulation
— id: 83218, year: 2006, vol: 113, page: 2454, stat: Journal Article,

Iron sucrose augments homocysteine-induced endothelial dysfunction in normal subjects
Zheng, H; Huang, X; Zhang, Q; Katz, S D
2006 Feb;69(4):679-684, Kidney international
Intravenous iron is commonly used in conjunction with erythropoietic agents to treat anemia in patients with chronic kidney disease. Iron has been proposed to promote oxidative stress and endothelial dysfunction in vascular tissues. We studied the acute effects of intravenous iron sucrose on homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. In all, 40 healthy subjects received intravenous iron sucrose 100 mg or placebo over 30 min immediately before ingestion of 100 mg/kg of oral methionine in a double-blind, randomized study. Flow- and nitroglycerin-mediated dilation in the brachial artery, serum markers of iron stores, and homocysteine and nitrotyrosine levels were measured before and after study drug administration. Intravenous iron significantly increased transferrin saturation and non-transferrin-bound iron (NTBI) when compared with placebo. Flow-mediated dilation significantly decreased from baseline 1 h after administration of iron sucrose when compared with placebo (from 6.66+/-0.47 to 1.93+/-0.35% after iron sucrose vs from 6.00+/-0.40 to 5.61+/-0.46% after placebo, P<0.001), but did not differ between groups at 4 h (1.10+/-0.39 vs 1.33+/-0.51%). Nitroglycerin-mediated vasodilation, and homocysteine and 3-nitrotyrosine levels did not differ after administration of iron sucrose and placebo. Intravenous administration of iron sucrose in the setting of transient hyperhomocysteinemia induced by methionine ingestion significantly increased transferrin saturation and plasma levels of NTBI and significantly attenuated flow-mediated dilation in the brachial artery when compared with placebo. This potential mechanistic link between intravenous iron and endothelial dysfunction warrants further study of cardiovascular effects of intravenous iron in anemic chronic kidney disease populations
— id: 132262, year: 2006, vol: 69, page: 679, stat: Journal Article,

Association of extended work shifts, vascular function, and inflammatory markers in internal medicine residents: a randomized crossover trial
Zheng, Haoyi; Patel, Milan; Hryniewicz, Katarzyna; Katz, Stuart D
2006 Sep 6;296(9):1049-1050, JAMA
— id: 83226, year: 2006, vol: 296, page: 1049, stat: Journal Article,

Large-vessel vasculitis in a cardiac allograft
Bader, Feras; Upadya, Shrikanth; Sokol, Seth; Azimi, Nassir; Katz, Stuart D
2005 Jul;21(9):745-745, Canadian journal of cardiology
— id: 83203, year: 2005, vol: 21, page: 745, stat: Journal Article,

Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure
Hryniewicz, Katarzyna; Dimayuga, Clarito; Hudaihed, Alhakam; Androne, Ana Silvia; Zheng, Haoyi; Jankowski, Krzysztof; Katz, Stuart D
2005 Apr;108(4):331-338, Clinical science (London, 1979)
ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner. FMD (flow-mediated dilation) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2 and 4 h after administration of the study drug. Ramipril alone increased FMD at 4 h compared with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4 h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively, all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with CHF, with additive effects evident at 4 h during combination therapy. Therefore further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted
— id: 83192, year: 2005, vol: 108, page: 331, stat: Journal Article,

Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure
Katz, Stuart D; Hryniewicz, Katarzyna; Hriljac, Ingrid; Balidemaj, Kujtim; Dimayuga, Clarito; Hudaihed, Alhakam; Yasskiy, Aleksandr
2005 Jan 25;111(3):310-314, Circulation
BACKGROUND: Endothelial function is known to be impaired in subjects with chronic heart failure (CHF), but the association between endothelial function and subsequent mortality risk in CHF has not been previously reported. METHODS AND RESULTS: Biomarkers of endothelial function in the systemic arterial circulation (flow-mediated dilation [FMD] in the brachial artery) and the pulmonary circulation (exhaled nitric oxide [NO] production during submaximal exercise) were prospectively assessed in 259 subjects with New York Heart Association class II-III CHF. In subjects with FMD measurements (n=149), there were 12 deaths and 5 urgent transplantations over a median follow-up period of 841 days. In subjects with exhaled NO production measurements (n=110), there were 18 deaths and 1 urgent transplantation over a median follow-up period of 396 days. Both decreased FMD and decreased exhaled NO production were associated with increased risk of death or urgent transplantation after adjustment for other known CHF prognostic factors (age, etiology of CHF, functional class, left ventricular ejection fraction) in Cox multivariate proportional-hazards models (adjusted hazard ratio [HR] estimate for a 1% decrease in FMD=1.20; 95% confidence interval [CI], 1.03 to 1.45; P=0.027; adjusted HR estimate for a 1-ppb/min decrease in exhaled NO production=1.31, 95% CI, 1.01 to 1.69, P=0.04). CONCLUSIONS: Endothelial dysfunction in CHF, as assessed by FMD in the brachial artery and exhaled NO production during submaximal exercise, is associated with an increased mortality risk in subjects with both ischemic and nonischemic CHF
— id: 83197, year: 2005, vol: 111, page: 310, stat: Journal Article,

Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure
Katz, Stuart D; Parker, John D; Glasser, Dale B; Bank, Alan J; Sherman, Nancy; Wang, Hao; Sweeney, Michael
2005 Jan 1;95(1):36-42, American journal of cardiology
Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p <0.002). Larger percentages of patients who received sildenafil reported improved erections (74%) and improved intercourse (68%) compared with patients who received placebo (18% and 16%, respectively). Intercourse success rates were 53% among patients who received sildenafil and 20% among those who received placebo. Patients who received sildenafil were highly satisfied with treatment and their sexual life compared with patients who received placebo. Sixty percent of patients who received sildenafil and 48% of patients who received placebo developed adverse events, including transient headache, facial flushing, respiratory tract infection, and asthenia. The incidence of events related to cardiovascular effects was low. Sildenafil is an effective and well-tolerated management of ED in men who have mild to moderate CHF
— id: 83194, year: 2005, vol: 95, page: 36, stat: Journal Article,

Phosphodiesterase 5 inhibition in chronic heart failure and pulmonary hypertension
Patel, Milan D; Katz, Stuart D
2005 Dec 26;96(12B):47M-51M, American journal of cardiology
Erectile dysfunction (ED) is highly prevalent in patients with chronic heart failure (CHF) and is among the most distressing symptoms in this patient population. Although the safety and efficacy of phosphodiesterase 5 (PDE5) inhibitors in the management of ED have been evaluated in many cardiovascular disease populations, scant data are available in patients with CHF. In published studies, the short-term safety and efficacy of sildenafil in patients with stable mild-to-moderate CHF with ED appears to be comparable to that observed in other populations with cardiovascular disease. Evidence is not available on the effects of vardenafil or tadalafil in CHF. In addition to their benefits in the treatment of ED, preliminary studies suggest that PDE5 inhibitors enhance endothelial function in patients with CHF and have beneficial effects on pulmonary hemodynamics and exercise capacity in patients with pulmonary hypertension. Additional studies are needed to determine the therapeutic potential of this class of agents in these disease states
— id: 83211, year: 2005, vol: 96, page: 47M, stat: Journal Article,

Iron stores and vascular function in voluntary blood donors
Zheng, Haoyi; Cable, Ritchard; Spencer, Bryan; Votto, Nancy; Katz, Stuart D
2005 Aug;25(8):1577-1583, Arteriosclerosis, thrombosis, & vascular biology
BACKGROUND: Iron is a pro-oxidant cofactor that may be linked to atherosclerosis progression. Reduction of body iron stores secondary to blood donation has been hypothesized to reduce coronary risk, but retrospective studies have yielded inconsistent findings. We sought to assess the effects of blood donation frequency on body iron stores and physiological and biochemical biomarkers of vascular function associated with atherosclerosis progression. METHODS AND RESULTS: Forty high-frequency voluntary blood donors (> or =8 donations in past 2 years) and 42 low-frequency blood donors (1 to 2 donations in past 2 years) aged 50 to 75 years were randomly selected from American Red Cross of Connecticut blood donor records. Flow-mediated dilation in the brachial artery, serum markers of iron stores, vascular inflammation and oxidative stress, and cardiac risk factors were assessed in all subjects. Serum ferritin was significantly decreased in high-frequency blood donors when compared with low-frequency blood donors (median values 17 versus 52 ng/mL; P<0.001), but hematocrit did not differ between groups. Flow-mediated dilation in the brachial artery was significantly greater in high-frequency donors when compared with low-frequency donors in univariate analysis (5.5+/-2.6% versus 3.8+/-1.6%; P=0.0003) and in multivariate analysis adjusting for cardiac risk factors and other potential confounders. Serum biomarkers of vascular inflammation did not differ between groups but 3-nitrotyrosine, a marker of oxidative stress, was decreased in high-frequency donors when compared with low-frequency donors. CONCLUSIONS: High-frequency blood donors had evidence of decreased body iron stores, decreased oxidative stress, and enhanced vascular function when compared with low-frequency donors. These findings support a potential link between blood donation and reduced cardiovascular risk that warrants further investigation in prospective outcome studies
— id: 83199, year: 2005, vol: 25, page: 1577, stat: Journal Article,

Relation of unrecognized hypervolemia in chronic heart failure to clinical status, hemodynamics, and patient outcomes
Androne, Ana Silvia; Hryniewicz, Katarzyna; Hudaihed, Alhakam; Mancini, Donna; Lamanca, John; Katz, Stuart D
2004 May 15;93(10):1254-1259, American journal of cardiology
Clinically unrecognized intravascular volume overload may contribute to worsening symptoms and disease progression in patients with chronic heart failure (CHF). The present study was undertaken to prospectively compare measured blood volume status (determined by radiolabeled albumin technique) with clinical and hemodynamic characteristics and patient outcomes in 43 nonedematous ambulatory patients with CHF. Blood volume analysis demonstrated that 2 subjects (5%) were hypovolemic (mean deviation from normal values -20 +/- 6%), 13 subjects (30%) were normovolemic (mean deviation from normal values -1 +/- 1%), and 28 subjects (65%) were hypervolemic (mean deviation from normal values +30 +/- 3%). Physical findings of congestion were infrequent and not associated with blood volume status. Increased blood volume was associated with increased pulmonary capillary wedge pressure (p = 0.01) and greatly increased risk of death or urgent cardiac transplantation during a median follow-up of 719 days (1-year event rate 39% vs 0%, p <0.01 by log-rank test). Systolic blood pressure was significantly lower in hypervolemic patients than in those with normovolemia or hypovolemia (107 +/- 2 vs 119 +/- 2 mm Hg, p = 0.008), and hypotension was independently associated with increased risk of hypervolemia in multivariate analysis (odds ratio 2.64 for a 10-mm Hg decrease in systolic blood pressure, 95% confidence interval 1.13 to 6.19, p = 0.025). These findings demonstrate that clinically unrecognized hypervolemia is frequently present in nonedematous patients with CHF and is associated with increased cardiac filling pressures and worse patient outcomes
— id: 83183, year: 2004, vol: 93, page: 1254, stat: Journal Article,

Comparison of suppression of the circulating and vascular renin-angiotensin system by enalapril versus trandolapril in chronic heart failure
Jorde, Ulrich P; Vittorio, Timothy J; Dimayuga, Clarito A; Homma, Shunichi; Rizkala, Adel; Le Jemtel, Thierry H; Katz, Stuart D
2004 Dec 15;94(12):1501-1505, American journal of cardiology
Experimental studies suggest that angiotensin-converting enzyme (ACE) inhibitors with high tissue affinity confer a greater degree of vascular renin-angiotensin system suppression than those with low tissue affinity despite similar suppression of the circulating renin-angiotensin system. To test this hypothesis in a clinical setting, we randomized subjects with chronic heart failure to receive the low tissue affinity ACE inhibitor enalapril or the high tissue affinity ACE inhibitor trandolapril, and assessed the degree of circulating and vascular renin-angiotensin system suppression. Vascular renin-angiotensin system suppression was determined by measuring the pressor response to intravenous injections of angiotensin I. Circulating renin-angiotensin system suppression was determined by measuring plasma angiotensin II. Vascular and circulating renin-angiotensin system suppression, endothelial function (flow-mediated vasodilation), and maximal exercise capacity (peak oxygen uptake) were assessed after a 4-week run-in period on open-label enalapril 40 mg/day and after 8 weeks of randomized double-blind treatment with enalapril 40 mg/day or trandolapril 4 mg/day. Twenty-six men and 4 women (mean age 52 +/- 11 years; mean left ventricular ejection fraction 25 +/- 9%; New York Heart Association class II [n = 16] and III [n = 14]) were studied. After a 2-month randomized treatment period, vascular renin-angiotensin system suppression, circulating renin-angiotensin system suppression, endothelial function, and exercise capacity did not differ between subjects treated with enalapril and those treated with trandolapril. Despite substantial differences in the tissue affinity of enalapril and trandolapril, the degree of vascular renin-angiotensin system suppression achieved with these agents did not differ in subjects with chronic heart failure during long-term therapy
— id: 47320, year: 2004, vol: 94, page: 1501, stat: Journal Article,

Mechanisms and treatment of anemia in chronic heart failure
Katz, Stuart D
2004 Sep-Oct;10(5):243-247, Congestive heart failure
Anemia is highly prevalent in patients with chronic heart failure (HF) and is associated with poor clinical outcomes. Multiple mechanisms contribute to anemia in chronic HF, and subnormal compensatory rise in endogenous erythropoietin levels in response to anemia is one contributory factor. Randomized trials with recombinant human erythropoietin therapy in anemic patients with chronic kidney disease and concomitant heart disease have demonstrated a reduction in left ventricular hypertrophy but variable effects on clinical outcome. Preliminary clinical trials in anemic patients with chronic HF demonstrate that erythropoietin therapy is well tolerated and associated with short-term clinical improvement. The optimum target hemoglobin, erythropoietic agent, and dosing regimen, and the role of iron supplementation in patients with chronic HF, are not known. Additional studies are needed to determine the safety and efficacy of long-term erythropoietic therapy in chronic HF patients
— id: 83186, year: 2004, vol: 10, page: 243, stat: Journal Article,

Treatment of anemia in patients with chronic heart failure
Katz, Stuart D; Mancini, Donna; Androne, Ana Silvia; Hryniewicz, Katarzyna
2004 Feb;10(1 Suppl):S13-S16, Journal of cardiac failure
Anemia occurs frequently in chronic heart failure (CHF) patients and is associated with increased morbidity and mortality risk. Clinical trials with recombinant human erythropoietin in patients with chronic kidney disease and concomitant structural heart disease have demonstrated beneficial effects on ventricular remodeling but variable effects on clinical outcome. Preliminary clinical trials in patients with CHF demonstrate that erythropoietin therapy is well-tolerated and associated with short-term clinical benefits. The optimum target hemoglobin, erythropoietin dosing regimen, and role of iron supplementation in patients with CHF are not known. Darbepoetin alfa is a glycosylated derivative of erythropoietin with a prolonged half-life that may allow less frequent dosing in CHF populations. Additional studies are needed to determine the safety and efficacy of long-term erythropoietic therapy in CHF patients
— id: 83179, year: 2004, vol: 10, page: S13, stat: Journal Article,

Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry
Klapholz, Marc; Maurer, Matthew; Lowe, April M; Messineo, Frank; Meisner, Jay S; Mitchell, Judith; Kalman, Jill; Phillips, Robert A; Steingart, Richard; Brown, Edward J Jr; Berkowitz, Robert; Moskowitz, Robert; Soni, Anita; Mancini, Donna; Bijou, Rachel; Sehhat, Khashayar; Varshneya, Nikita; Kukin, Marrick; Katz, Stuart D; Sleeper, Lynn A; Le Jemtel, Thierry H
2004 Apr 21;43(8):1432-1438, Journal of the American College of Cardiology
OBJECTIVES: We conducted a prospective multicenter registry in a large metropolitan area to define the clinical characteristics, hospital course, treatment, and factors precipitating decompensation in patients hospitalized for heart failure with a normal ejection fraction (HFNEF). BACKGROUND: The clinical profile of patients hospitalized for HFNEF has been characterized by retrospective analyses of hospital records and state data banks, with few prospective single-center studies. METHODS: Patients hospitalized for heart failure (HF) at 24 medical centers in the New York metropolitan area and found to have a left ventricular (LV) ejection fraction of > or 50% within seven days of admission were included in this registry. Patient demographics, signs and symptoms of HF, coexisting and exacerbating cardiovascular and medical conditions, treatment, laboratory tests, procedures, and hospital outcomes data were collected. Analysis by gender and race was prespecified. RESULTS: Of 619 patients, 73% were women, who were on average four years older than men (72.8 +/- 14.1 years vs. 68.6 +/- 13.8 years, p < 0.001). Black non-Hispanic patients comprised 30% of the study population. They were eight years younger than other patients (66.0 +/- 14.2 years vs. 74 +/- 13.5 years p < 0.001). Co-morbid conditions and their prevalence were: hypertension, 78%; increased LV mass, 82%; diabetes, 46%; and obesity, 46%. Before clinical decompensation that precipitated hospitalization, 86% of patients had chronic symptoms compatible with New York Heart Association functional classes II to IV. Factors precipitating clinical decompensation were identified in 53% of patients. In-hospital mortality was 4.2%. CONCLUSIONS: Patients hospitalized for HFNEF are most often chronically incapacitated elderly women with a history of hypertension and increased LV mass. Reasons for clinical decompensation are identified in only one-half of patients
— id: 67415, year: 2004, vol: 43, page: 1432, stat: Journal Article,

Effects of active vs. passive recovery on work performed during serial supramaximal exercise tests
Spierer, D K; Goldsmith, R; Baran, D A; Hryniewicz, K; Katz, S D
2004 Feb;25(2):109-114, International journal of sports medicine
The current investigation was undertaken to determine the effects of active versus passive recovery on work performance during repeated bouts of supramaximal exercise. Six healthy sedentary subjects and 9 moderately trained healthy hockey players performed serial 30-second Wingate anaerobic power tests (WAnT) on a bicycle ergometer interposed with 4 minutes of active recovery at a work rate corresponding to 28 % of VO(2)max or passive recovery at rest. Peak power, mean power, total work achieved, and fatigue index were calculated for the serial WAnT. Capillary blood lactate was determined at 5-minute intervals after the last WAnT during 30 minutes of active or passive recovery. Mean power was significantly greater during active recovery in sedentary subjects when compared with passive recovery (388 +/- 42 vs. 303 +/- 37 W, p < 0.05), but did not differ according to recovery mode in moderately trained hockey players (589 +/- 22 W active vs. 563 +/- 26 W passive, p = 0.14). Total work achieved significantly increased during active when compared with passive recovery in sedentary subjects (34 890 +/- 3768 vs. 27 260 +/- 3364 J, p < 0.02) and moderately trained hockey players (86 763 +/- 9151 vs. 75 357 +/- 8281 J, p < 0.05). Capillary blood lactate levels did not differ during active when compared with passive recovery in sedentary subjects but were significantly lower during active when compared with passive recovery in moderately trained hockey players. These data demonstrate that active recovery at a work rate corresponding to 28 % of VO(2)max increases total work achieved during repeated WAnT when compared with passive recovery in sedentary subjects and moderately trained hockey players
— id: 83178, year: 2004, vol: 25, page: 109, stat: Journal Article,

Comparative costs of home positive inotropic infusion versus in-hospital care in patients awaiting cardiac transplantation
Upadya, Shrikanth P Y; Sedrakyan, Artyom; Saldarriaga, Clara; Nystrom, Karin; Bozzo, Janis; Lee, Forrester A; Katz, Stuart D
2004 Oct;10(5):384-389, Journal of cardiac failure
BACKGROUND: Outpatient positive inotropic support combined with implantation of an automatic implantable cardioverter defibrillator (AICD) may be used as a successful bridge to cardiac transplantation in patients with end-stage heart failure. A detailed comparative cost analysis of this outpatient strategy versus in-hospital care has not been previously reported. METHODS AND RESULTS: Twenty-one United Network for Organ Sharing 1B patients awaiting cardiac transplantation received continuous outpatient inotropic therapy for a total of 3070 patient-days. Daily costs for outpatient and in-hospital treatment were calculated. Nonparametric decision analysis was used to determine the strategy with greatest cost savings (immediate hospital discharge after AICD implantation versus in-hospital care). A threshold analysis was performed to test the robustness of the decision analysis model. The outpatient strategy realized an average savings of $71,300 to $120,500 per patient. Decision analysis showed that no fixed period of in-hospital monitoring was more cost-saving than immediate hospital discharge after AICD implantation. Threshold analysis revealed that AICD costs would need to exceed $82,000 (currently $62,000) or that the difference between the outpatient and the in-hospital costs would need to be < or = $475 per day for any other intermediate strategy to be considered cost-saving. CONCLUSION: Outpatient inotropic therapy combined with AICD implantation in selected patients awaiting cardiac transplantation is an effective cost-minimizing strategy
— id: 83187, year: 2004, vol: 10, page: 384, stat: Journal Article,

Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure
Upadya, Shrikanth; Lee, Forrester A; Saldarriaga, Clara; Verma, Sumit; Sedrakyan, Artyom; Nystrom, Karin; Katz, Stuart D
2004 Apr;23(4):466-472, Journal of heart & lung transplantation
BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation
— id: 83180, year: 2004, vol: 23, page: 466, stat: Journal Article,

Intravenous iron sucrose augments homocysteine-mediated endothelial dysfunction in normal subjects
Zheng, HD; Katz, SD; Huang, X; Zhang, G; Dai, JS
2004 OCT 26 ;110(17):21-21, Circulation
— id: 55932, year: 2004, vol: 110, page: 21, stat: Journal Article,

Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure
Androne, A S; Hryniewicz, K; Goldsmith, R; Arwady, A; Katz, S D
2003 Aug;89(8):854-858, Heart (British Cardiac Society)
OBJECTIVE: To characterise the effects of acetylcholinesterase inhibition with pyridostigmine on parasympathetic tone in patients with chronic heart failure (CHF). DESIGN: Prospective randomised, double blind crossover trial. SETTING: University hospital outpatient heart failure clinic. PATIENTS: 20 ambulatory subjects with stable CHF (mean age 55 years, mean ejection fraction 24%). INTERVENTIONS: Oral administration of a single dose of pyridostigmine 30 mg and matching placebo on separate days. MAIN OUTCOME MEASURES: Heart rate recovery at one minute and three minutes after completion of maximal exercise. RESULTS: Heart rate recovery at one minute after exercise was significantly greater after administration of pyridostigmine than after administration of placebo (mean (SEM) 27.4 (3.2) beats/min v 22.4 (2.4) beats/min, p < 0.01). Heart rate recovery at three minutes after exercise did not differ after administration of pyridostigmine and placebo (mean (SEM) 44.4 (3.9) beats/min v 41.8 (3.6) beats/min, NS). Peak heart rate, peak oxygen uptake, peak respiratory exchange ratio, plasma noradrenaline (norepinephrine) concentrations, and plasma brain natriuretic peptide concentrations did not differ after administration of pyridostigmine and placebo. CONCLUSIONS: Acetylcholinesterase inhibition with pyridostigmine increased heart rate recovery at one minute but not at three minutes after exercise. A specific effect of pyridostigmine on heart rate one minute after exercise suggests that pyridostigmine augments parasympathetic tone in patients with CHF
— id: 83166, year: 2003, vol: 89, page: 854, stat: Journal Article,

Hemodilution is common in patients with advanced heart failure
Androne, Ana-Silvia; Katz, Stuart D; Lund, Lars; LaManca, John; Hudaihed, Alhakam; Hryniewicz, Katarzyna; Mancini, Donna M
2003 Jan 21;107(2):226-229, Circulation
BACKGROUND: Anemia frequently occurs in chronic heart failure (CHF) patients and is associated with a poor prognosis. A low hematocrit may result from an increased plasma volume (hemodilution) or from reduced red blood cell volume (true anemia). The prevalence and clinical outcome of CHF patients with hemodilution is unknown. METHODS AND RESULTS: The prevalence of anemia and its effect on outcome was examined in 196 patients with CHF. The prevalence of hemodilution was assessed in a subset of 37 ambulatory anemic patients with I131-tagged albumin to measure red blood cell and plasma volume. Clinical outcome was monitored. Sixty-one percent of the CHF patients were anemic. The prevalence of anemia increased from 33% in patients with New York Heart Association class II heart failure to 68% in class IV CHF patients. Survival was reduced in anemic patients compared with patients with a normal hematocrit (P<0.05). In the subset of 37 anemic patients, 17 patients (46%) had hemodilution and 20 patients (54%) had a true anemia. Nine patients with hemodilution died or underwent urgent transplant compared with 4 patients in the true anemia group (P<0.04). CONCLUSION: Hemodilution is common in CHF patients. Anemia is associated with a poor prognosis in CHF. Patients with hemodilution tend to do worse than patients with true anemia, which suggests that volume overload may be an important mechanism contributing to the poor outcome in anemic CHF patients
— id: 83155, year: 2003, vol: 107, page: 226, stat: Journal Article,

Comparative effects of carvedilol and metoprolol on regional vascular responses to adrenergic stimuli in normal subjects and patients with chronic heart failure
Hryniewicz, Katarzyna; Androne, Ana Silvia; Hudaihed, Alhakam; Katz, Stuart D
2003 Aug 26;108(8):971-976, Circulation
BACKGROUND: Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol. METHODS AND RESULTS: Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1+/-8.9 U for carvedilol versus 9.0+/-2.7 U for metoprolol and 8.2+/-5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups. CONCLUSIONS: Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by alpha-adrenergic blockade
— id: 83168, year: 2003, vol: 108, page: 971, stat: Journal Article,

Partial reversal of cachexia by beta-adrenergic receptor blocker therapy in patients with chronic heart failure
Hryniewicz, Katarzyna; Androne, Ana Silvia; Hudaihed, Alhakam; Katz, Stuart D
2003 Dec;9(6):464-468, Journal of cardiac failure
BACKGROUND: Cachexia is a common problem in chronic heart failure (CHF) that may be partly mediated by activation of the sympathetic nervous system. The effects of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and noncachectic subjects with CHF has not been previously reported. METHODS AND RESULTS: Body weight and plasma norepinephrine, leptin, and insulin levels were measured in 27 subjects with CHF before and after 6 months of beta-adrenergic receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy, baseline weight, plasma leptin, and plasma insulin levels did not differ between cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were increased in cachectic subjects when compared with noncachectic subjects (930+/-248 pg/mL versus 503+/-109 pg/mL, P=.063). After 6 months of BB therapy, subjects with baseline cachexia demonstrated significantly greater weight gain (+5.2+/-9.6 versus +0.8+/-5.0 kg, P=.027), greater increase in plasma leptin levels (+3.7+/-3.9 versus +1.2+/-4.3 ng/mL, P=.030), and greater decrease in plasma norepinephrine levels (-374+/-261 versus -41+/-122 pg/mL, P=.012) when compared with noncachectic subjects. CONCLUSIONS: Six months of BB therapy with carvedilol or long-acting metoprolol is associated with differential effects on body weight and hormonal levels in cachectic and noncachectic subjects with CHF. Further work is needed to determine the role the sympathetic nervous system in the pathogenesis of cachexia in patients with CHF
— id: 83177, year: 2003, vol: 9, page: 464, stat: Journal Article,

Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure
Katz, S D
2003 Jan-Feb;9(1):9-15, Congestive heart failure
Endothelial dysfunction is associated with impairment of aerobic capacity in patients with heart failure and may play a role in the progression of disease. Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle. Impaired vasodilation in response to nitric oxide derived from vascular endothelium or organic nitrates in vascular smooth muscle may be related in part to increased degradation of the second messenger cyclic guanosine monophosphate by type 5 phosphodiesterase. Sildenafil, a specific type 5 phosphodiesterase inhibitor currently approved for the treatment of erectile dysfunction, has been shown to acutely enhance endothelium-dependent vasodilation in patients with heart failure. Further studies are warranted to characterize the safety and efficacy of type 5 phosphodiesterase inhibition in the treatment of chronic heart failure
— id: 83158, year: 2003, vol: 9, page: 9, stat: Journal Article,

Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure
Mancini, Donna M; Katz, Stuart D; Lang, Chim C; LaManca, John; Hudaihed, Alhakam; Androne, Ana-Silvia
2003 Jan 21;107(2):294-299, Circulation
BACKGROUND: Patients with chronic heart failure (CHF) are frequently anemic. An increase in hemoglobin could enhance exercise performance by increasing oxygen delivery. We investigated the effect of erythropoietin (EPO) on exercise performance in anemic patients with CHF. METHODS AND RESULTS: Twenty-six anemic patients aged 57+/-11 years were randomized to receive EPO (15 000 to 30 000 IU per week) or placebo for 3 months. Parameters measured at baseline and end therapy included blood parameters (hemoglobin, hematocrit, plasma volume), exercise parameters (peak oxygen consumption [VO2], exercise duration, 6-minute walk), muscle aerobic metabolism (half-time of VO2 and near infrared recovery), and forearm vasodilatory function. EPO was well tolerated by all patients. Twelve patients in the EPO group felt improvement versus 1 in the placebo group (P<0.05). There were significant increases in hemoglobin (11.0+/-0.5 to 14.3+/-1.0 g/dL, P<0.05), peak VO2 (11.0+/-1.8 to 12.7+/-2.8 mL. min(-1) x kg(-1), P<0.05) and exercise duration (590+/-107 to 657+/-119 s, P<0.004) in the EPO group but no significant changes in the control group. Resting and hyperemic forearm vascular resistance and indices of the rate of muscle oxidative capacity were unchanged in both groups. CONCLUSION: EPO significantly enhances exercise capacity in patients with CHF. One mechanism of improvement in VO2 is increased oxygen delivery from increased hemoglobin concentration
— id: 83156, year: 2003, vol: 107, page: 294, stat: Journal Article,

Dissociation between exercise hemodynamics and exercise capacity in patients with chronic heart failure and marked increase in ejection fraction after treatment with beta-adrenergic receptor antagonists
Maurer, Mathew; Katz, Stuart D; LaManca, John; Manandhar, Monica; Mancini, Donna
2003 Feb 1;91(3):356-360, American journal of cardiology
— id: 83159, year: 2003, vol: 91, page: 356, stat: Journal Article,

Vasopressor response to angiotensin II infusion in patients with chronic heart failure receiving beta-blockers
Vittorio, Timothy J; Lang, Chim C; Katz, Stuart D; Packer, Milton; Mancini, Donna M; Jorde, Ulrich P
2003 Jan 21;107(2):290-293, Circulation
BACKGROUND: A synergistic interaction between the angiotensin II (Ang II) type 1 receptor and alpha1-adrenergic receptors has been described. We hypothesized that the nonselective beta-antagonist carvedilol, through its alpha1-adrenergic blocking properties, may modulate vascular reactivity to Ang II in patients with chronic heart failure (CHF). Accordingly, we compared the vasopressor response to infused Ang II in patients treated with carvedilol and metoprolol, a selective beta-antagonist. METHODS AND RESULTS: All subjects were treated with carvedilol or metoprolol for at least 3 months. ACE inhibitor therapy was standardized to enalapril 40 mg/d or the maximally tolerated dose. Exogenous Ang II was administered as sequential intravenous bolus injections (2.5 to 30 ng/kg) titrated to a rise in radial artery systolic pressure of > or =20 mm Hg. The dose of Ang II required to elicit a change of 20 mm Hg in radial artery systolic pressure (PD20) defined the vasopressor response to Ang II. Twenty subjects with CHF (mean left ventricular ejection fraction 28+/-9%, New York Heart Association class II [n=13] and III [n=7]) were studied. There was no correlation between plasma Ang II levels and PD20. However, the PD20 was significantly higher in patients treated with carvedilol than in those treated with metoprolol (20 [range 2.5 to 30] versus 5 [range 2.5 to 10] ng/kg, P=0.019). CONCLUSIONS: The vasopressor response to Ang II infusion in patients treated with carvedilol was significantly lower than in patients treated with metoprolol. Whether this is due to the alpha1-adrenergic blocking or other ancillary properties of carvedilol warrants further investigation
— id: 47324, year: 2003, vol: 107, page: 290, stat: Journal Article,

Elevated plasma aldosterone levels despite complete inhibition of the vascular angiotensin-converting enzyme in chronic heart failure
Jorde, Ulrich P; Vittorio, Timothy; Katz, Stuart D; Colombo, Paolo C; Latif, Farhana; Le Jemtel, Thierry H
2002 Aug 27;106(9):1055-1057, Circulation
BACKGROUND: Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensin-converting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF. METHODS AND RESULTS: Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, >15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio < or =0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy. CONCLUSIONS: Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF
— id: 47325, year: 2002, vol: 106, page: 1055, stat: Journal Article,

Peripheral limitations of maximal aerobic capacity in patients with chronic heart failure
Katz, Stuart D; Zheng, Haoyi
2002 Mar-Apr;9(2):215-225, Journal of nuclear cardiology
— id: 83142, year: 2002, vol: 9, page: 215, stat: Journal Article,

Effect of dexrazoxane on homocysteine-induced endothelial dysfunction in normal subjects
Zheng, Haoyi; Dimayuga, Clarito; Hudaihed, Alhakam; Katz, Stuart D
2002 Jul 1;22(7):E15-E18, Arteriosclerosis, thrombosis, & vascular biology
OBJECTIVE: Dexrazoxane is an antioxidant prodrug that on hydrolysis is converted into an intracellular iron chelator. We hypothesized that the antioxidant effects of dexrazoxane would prevent homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. METHODS AND RESULTS: Ten healthy volunteers completed a randomized, double-blind, crossover study. Plasma homocysteine levels and brachial artery endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (sublingual nitroglycerin) responses were measured before and 4 hours after ingestion of L-methionine (100 mg/kg), preceded by intravenous administration of dexrazoxane (500 mg/m2) or placebo over 30 minutes. After placebo, oral methionine increased plasma homocysteine (from 5.1+/-0.4 micromol/L at baseline to 14.2+/-1.3 micromol/L at 4 hours, P<0.001) and decreased FMD (from 3.8+/-0.7% at baseline to 1.2+/-0.5% at 4 hours, P=0.02). Dexrazoxane did not change homocysteine concentrations after methionine administration (14.9+/-1.1 micromol/L at 4 hours, P=0.29 versus placebo) but did completely abrogate the homocysteine-induced reduction in FMD (from 3.5+/-0.5% at baseline to 5.9+/-1.1% at 4 hours, P<0.01 versus placebo). Endothelium-independent responses to sublingual nitroglycerin did not differ after the administration of placebo and dexrazoxane. CONCLUSIONS: Administration of the novel antioxidant agent dexrazoxane prevents homocysteine-induced impairment of vascular endothelial function in the brachial artery of healthy subjects
— id: 83145, year: 2002, vol: 22, page: E15, stat: Journal Article,

Nesiritide (hBNP): a new class of therapeutic peptide for the treatment of decompensated congestive heart failure
Katz SD
2001 Mar;7(2):78-87, Congestive heart failure
Natriuretic peptides are a family of endogenous peptide hormones with vasodilating, natriuretic, diuretic, and lusitropic properties. Administration of pharmacologic doses of exogenous natriuretic peptides may provide therapeutic benefit in patients with chronic heart failure. In controlled clinical trials, short-term administration of nesiritide (human brain natriuretic peptide) to patients with heart failure is associated with improved resting hemodynamics, modest increases in sodium excretion, evidence of suppression of neurohormonal activation, and improvements in symptoms of heart failure. Additional trials to determine the clinical efficacy and safety of nesiritide are warranted. (c)2001 by CHF, Inc
— id: 83141, year: 2001, vol: 7, page: 78, stat: Journal Article,

Acetylcholine-mediated vasodilation in the forearm circulation of patients with heart failure: indirect evidence for the role of endothelium-derived hyperpolarizing factor
Katz, S D; Krum, H
2001 May 1;87(9):1089-1092, American journal of cardiology
Vasomotor responses to intraarterial administration of acetylcholine are mediated by release of nitric oxide, prostaglandins, and an unidentified hyperpolarizing factor from vascular endothelial cells. The contribution of endothelium-derived hyperpolarizing factor (EDHF) to the vasodilatory response to acetylcholine in the skeletal muscle circulation of patients with congestive heart failure (CHF) has not been previously characterized. Accordingly, to specifically assess the role of EDHF, the regional vascular effects of sequential administration of acetylcholine and nitroglycerin in the brachial artery were determined in the forearm circulation with strain-gauge venous occlusion plethysmography in patients with CHF and in normal subjects during combined systemic inhibition of cyclooxygenase activity with indomethacin and regional inhibition of nitric oxide synthase activity with l-N(G)-monomethylarginine (l-NMMA). After administration of indomethacin, infusion of l-NMMA significantly decreased the forearm blood flow response to acetylcholine in normal subjects (5.4 +/- 1.2 to 3.5 +/- 0.6 ml/min/100 ml, p < 0.05) but not in patients with CHF (5.7 +/- 1.3 to 5.7 +/- 1.4 ml/min/100 ml). Infusion of l-NMMA did not change forearm blood flow responses to nitroglycerin in either group. The presence of a noncyclooxygenase, non-nitric-oxide relaxing factor indicates that EDHF, rather than nitric oxide, may be the predominant endothelium-derived substance mediating vasodilation in response to acetylcholine in patients with CHF
— id: 83133, year: 2001, vol: 87, page: 1089, stat: Journal Article,

Sympathetic activation by sildenafil
Katz, S D; Parums, D V
2001 Nov 27;104(22):E119-E120, Circulation
— id: 83138, year: 2001, vol: 104, page: E119, stat: Journal Article,

Effects of beta-blockers on neurohormonal activation in patients with congestive heart failure
Baran, D; Horn, E M; Hryniewicz, K; Katz, S D
2000 Nov;60(5):997-1016, Drugs
The effect of beta-adrenoceptor antagonists (beta-blockers) on neurohormonal activation in patients with congestive heart failure has been the subject of study in numerous small clinical trials. Short term therapy with beta-blockers is associated with a variable acute neurohormonal response which may be determined by the pharmacology of the agent under study and the baseline characteristics of the patient population. Long term therapy with beta-blockers devoid of intrinsic sympathomimetic activity (partial agonist activity) is associated with evidence of decreased plasma markers of activation of the sympathetic nervous system, the renin-angiotensin system, and endothelin-1. Beta1-selective and nonselective beta-blockers appear to be associated with evidence of decreased neurohormonal activation, with differential effects on beta-adrenoceptor density. Agents with partial agonist activity appear to differ from pure antagonists, with some studies reporting evidence of increased neurohormonal activation. The mechanisms by which beta-blockers reduce neurohormonal activation and the clinical relevance of changes in adrenergic function to their use in the treatment of heart failure require further investigation
— id: 83128, year: 2000, vol: 60, page: 997, stat: Journal Article,

Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure
Katz, S D; Balidemaj, K; Homma, S; Wu, H; Wang, J; Maybaum, S
2000 Sep;36(3):845-851, Journal of the American College of Cardiology
OBJECTIVES: To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure. BACKGROUND: Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown. METHODS: Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo. RESULTS: In response to oral administration of a single dose of study drug, the change in flow-mediated vasodilation after release of 1, 3 and 5 min of arterial occlusion was significantly greater in patients receiving sildenafil 25 mg (3.3 +/- 1.9, 3.8 +/- 1.8 and 4.0 +/- 1.8%, respectively, p < 0.05) and patients receiving sildenafil 50 mg (3.7 +/- 1.3, 4.1 +/- 1.1, 3.9 +/- 1.3%, respectively, p < 0.05) than that of patients receiving placebo (0.7 +/- 1.1, 0.2 +/- 1.2, 0.6 +/- 0.8%, respectively). CONCLUSIONS: Acute type 5 phosphodiesterase inhibition with sildenafil 25 and 50 mg increases endothelium-dependent, flow-mediated vasodilation in patients with chronic heart failure when compared with placebo
— id: 83125, year: 2000, vol: 36, page: 845, stat: Journal Article,

Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure
Katz, S D; Maskin, C; Jondeau, G; Cocke, T; Berkowitz, R; LeJemtel, T
2000 Jun;88(6):2138-2142, Journal of applied physiology (Bethesda)
Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 +/- 0.1, 2.9 +/- 0.2, and 5.0 +/- 0.1 ml/100 ml, respectively; P < 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function (r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment
— id: 83123, year: 2000, vol: 88, page: 2138, stat: Journal Article,

Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure
Hamroff, G; Katz, S D; Mancini, D; Blaufarb, I; Bijou, R; Patel, R; Jondeau, G; Olivari, M T; Thomas, S; Le Jemtel, T H
1999 Mar 2;99(8):990-992, Circulation
BACKGROUND: Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. METHODS AND RESULTS: Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. CONCLUSIONS: Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors
— id: 83109, year: 1999, vol: 99, page: 990, stat: Journal Article,

Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure
Katz, S D; Khan, T; Zeballos, G A; Mathew, L; Potharlanka, P; Knecht, M; Whelan, J
1999 Apr 27;99(16):2113-2117, Circulation
BACKGROUND: Impaired endothelium-dependent, nitric oxide (NO)-mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is unknown. METHODS AND RESULTS: To specifically assess the synthetic activity of the L-arginine-NO metabolic pathway, urinary excretion of [15N]nitrates and [15N]urea was determined after a primed continuous intravenous infusion of L-[15N]arginine (40 micromol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise. After infusion of L-[15N]arginine, 24-hour urinary excretion of [15N]nitrates was decreased in patients with congestive heart failure at rest (2.2+/-0.5 versus 8.0+/-2.3 micromol/24 h) and during submaximal exercise (2.4+/-1.2 versus 11. 4+/-4.0 micromol/24 h) compared with control subjects (both P<0.01). After infusion of L-[15N]arginine, 24-hour urinary excretions of [15N]urea at rest in patients with congestive heart failure and control subjects were not different (1.1+/-0.3 versus 1.2+/-0.2 mmol/24 h, P>0.20). CONCLUSIONS: A specific decrease in synthetic activity of the L-arginine-NO metabolic pathway contributes to decreased endothelium-dependent vasodilation in patients with congestive heart failure
— id: 83110, year: 1999, vol: 99, page: 2113, stat: Journal Article,

Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group
Katz, S D; Radin, M; Graves, T; Hauck, C; Block, A; LeJemtel, T H
1999 Jul;34(1):170-176, Journal of the American College of Cardiology
OBJECTIVES: The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2 receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure. BACKGROUND: Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis of vasodilating prostaglandins. METHODS: Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure. RESULTS: Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups. CONCLUSIONS: These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways
— id: 83115, year: 1999, vol: 34, page: 170, stat: Journal Article,

A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: the U.S. ecadotril pilot safety study
O'Connor, C M; Gattis, W A; Gheorghiade, M; Granger, C B; Gilbert, J; McKenney, J M; Messineo, F C; Burnett, J C; Katz, S D; Elkayam, U; Kasper, E K; Goldstein, S; Cody, R J; Massie, B M
1999 Dec;138(6 Pt 1):1140-1148, American heart journal
OBJECTIVE: To determine the short-term safety and tolerability of the addition of ecadotril to conventional therapy in patients with mild to moderate heart failure. METHODS: Fifty ambulatory patients, 18 to 75 years of age, with mild to moderate heart failure, left ventricular ejection fraction </=35%, taking stable doses of angiotensin-converting enzyme inhibitor, diuretics, and optionally digoxin were enrolled in a randomized, double-blind, placebo-controlled dose-escalation study of ecadotril 50 to 400 mg twice daily versus conventional therapy alone. RESULTS: No increases in deaths, serious adverse events, or dropouts from adverse events were observed for the ecadotril group compared with placebo. The serum measures of neurohormonal activation were highly variable. Changes in signs and symptoms of heart failure, New York Heart Association class, and patient self-assessment of symptoms were not observed with ecadotril therapy; however, the study was not designed to detect differences in these parameters. CONCLUSION: In this small pilot study, ecadotril in doses of 50 to 400 mg twice daily was generally well-tolerated and without severe short-term adverse effects in patients with mild to moderate heart failure. Evaluation of the clinical efficacy and long-term safety of ecadotril and other neutral endopeptidase inhibitors in patients with heart failure requires further study
— id: 83117, year: 1999, vol: 138, page: 1140, stat: Journal Article,

Assessment of endothelium-mediated vasodilation of the peripheral circulation by transcutaneous ultrasonography and venous occlusion plethysmography
Wu, H D; Katz, S D; Beniaminovitz, A; Khan, T; DiTullio, M R; Homma, S
1999 ;14(3):143-148, Heart vessels
Transcutaneous ultrasonography is a non-invasive technique with the ability to measure the volumetric blood flow of the peripheral circulation. Peripheral blood flow can be determined by high-resolution imaging of vessel diameter coupled with Doppler assessment of flow velocity. This method, however, has not been validated in vivo. Accordingly, brachial artery flow in response to intraarterial infusion of vasodilators was assessed by ultrasonography in 16 healthy subjects and compared to values obtained simultaneously by venous occlusion plethysmography. Blood flow calculated from ultrasound-derived vessel diameter and flow velocity was found to highly correlate with plethysmographic flow, with r values ranging from 0.83 to 0.99. Using this ultrasound technique combined with plethysmography, the response of conduit and resistance vessels to endothelium-mediated vasodilation was characterized. Doppler velocity rose dramatically with endothelium-dependent acetylcholine (970%), but only modestly with endothelium-independent vasodilators, nitroglycerin (292%) and nitroprusside (340%). Despite eliciting the greatest overall forearm flow response, acetylcholine resulted in a smaller increase in conduit diameter (15.4%) than nitroglycerin (21.8%), and only a comparable change than nitroprusside (14.6%). Taken together, these results suggest that acetylcholine acts predominantly on resistance vessels, whereas nitrovasodilators affect mainly conduit vessels. In summary, transcutaneous ultrasonography can be used reliably to assess flow changes in the peripheral circulation. Combined with plethysmography, this technique is useful for determining the relative contribution of conduit and resistance vessels to peripheral flow, particularly in the assessment of endothelium-mediated vasodilation
— id: 83120, year: 1999, vol: 14, page: 143, stat: Journal Article,

Effect of endothelin-1 on exercise-induced vasodilation in normal subjects and in patients with heart failure
Krum, H; Katz, S D
1998 Feb 1;81(3):355-358, American journal of cardiology
Forearm blood flow (ml/min/100 ml) was determined with strain-gauge venous occlusion plethysmography at rest and in response to handgrip exercise in 7 patients with congestive heart failure and in 9 normal subjects before and after regional administration of endothelin-1 in the brachial artery. Administration of endothelin-1 significantly decreased forearm blood flow at rest and during exercise in normal subjects but did not change it at rest or during exercise in patients with congestive heart failure
— id: 83322, year: 1998, vol: 81, page: 355, stat: Journal Article,

Elbow valgus stress radiography in an uninjured population
Lee, G A; Katz, S D; Lazarus, M D
1998 May-Jun;26(3):425-427, American journal of sports medicine
Valgus instability of the elbow joint is a clinical diagnosis. However, many authors describe valgus stress radiographs as an aid in making this diagnosis. We studied valgus stress radiographs of 20 men (40 elbows) and 20 women (40 elbows), none with a history of elbow trauma or instability. The medial ulnohumeral distance was measured with no stress, valgus stress by gravity, and an applied valgus stress of 25 N (approximately 5 pounds). Measurements were made with the elbow positioned in extension and in 30 degrees of flexion. The increase in medial ulnohumeral gapping with either gravity or 5 pounds of stress was statistically significant at both extension and 30 degrees of flexion compared with the unstressed condition. The difference in ulnohumeral gapping between gravity stress and 5 pounds of valgus stress in extension and in 30 degrees of flexion was also significant. We found no differences with regard to hand dominance or sex. We conclude that uninjured elbows have significant medial ulnohumeral gapping on valgus stress radiography. Although this is an important tool in diagnosing valgus instability of the elbow, it may yield a false-positive assessment of valgus instability. Valgus stress radiographs comparing contralateral elbows may reduce the false-positive rate since there appears to be no significant difference in medial ulnohumeral gapping between the two elbows
— id: 83324, year: 1998, vol: 26, page: 425, stat: Journal Article,

Calcium sensitising agents in heart failure
Mathew, L; Katz, S D
1998 Mar;12(3):191-204, Drugs & aging
Congestive heart failure (CHF) is a common cardiovascular disorder that is characterised, in part, by a decreased cardiac output reserve. Accordingly, there is ongoing interest in the role of positive inotropic agents (e.g. adrenergic agonists and phosphodiesterase type III inhibitors, which mediate their cardiovascular effects via a cyclic adenosine monophosphate-dependent mechanism) in the treatment of CHF. However, enthusiasm for positive inotropic therapy in CHF has been dampened by the results of clinical trials, which have shown that these drugs are associated with an increased risk of mortality. Calcium sensitising agents are a heterogeneous group of positive inotropic agents that mediate their cardiovascular actions (at least in part) by increasing the sensitivity of the contractile elements to calcium. Increased sensitivity to calcium may be related to changes in calcium binding to troponin C, or to direct effects on the actin-myosin complex. In addition, the inhibition of phosphodiesterase type III may contribute to the positive inotropic action of calcium sensitising agents. Five agents with calcium sensitising properties (pimobendan, levosimendan, MCI-154, EMD-53998 and CGP-48506) have been studied as possible therapies for CHF. All of these agents have demonstrated a positive inotropic action in isolated cardiac tissue and in animal models of CHF. In clinical trials, pimobendan, the most extensively studied of these drugs, was well tolerated and was associated with improved exercise tolerance during the first 6 months of therapy; however, it was also associated with a nonsignificant trend towards increased mortality. Because many of the calcium sensitising agents also inhibit phosphodiesterase type III activity, the long term safety of these agents is uncertain. Large-scale survival trials are required to determine the long term safety and efficacy of these agents before their role in the treatment of CHF can be defined
— id: 83323, year: 1998, vol: 12, page: 191, stat: Journal Article,

Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure
Demopoulos, L; Yeh, M; Gentilucci, M; Testa, M; Bijou, R; Katz, S D; Mancini, D; Jones, M; LeJemtel, T H
1997 Apr 1;95(7):1764-1767, Circulation
BACKGROUND: Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown. METHODS AND RESULTS: We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL.kg-1.min-1) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL.min-1.100 mL-1) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 +/- 1.4 to 16.0 +/- 1.6 (P < .001) and 12.4 +/- 1.0 to 15.7 +/- 0.9 (P < .001) mL.kg-1.min-1, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients. CONCLUSIONS: Long-term, nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training
— id: 83313, year: 1997, vol: 95, page: 1764, stat: Journal Article,

Angiotensin II-receptor blockade further reduces afterload safely in patients maximally treated with angiotensin-converting enzyme inhibitors for heart failure
Hamroff, G; Blaufarb, I; Mancini, D; Katz, S D; Bijou, R; Jondeau, G; Olivari, M T; Thomas, S; LeJemtel, T H
1997 Oct;30(4):533-536, Journal of cardiovascular pharmacology
Combined therapy with an angiotensin-II type I receptor (AT1) antagonist and an angiotensin-converting enzyme (ACE) inhibitor results in more complete suppression of the renin-angiotensin system. Accordingly, the blood-pressure response and safety of combining AT1-receptor blockade with losartan for ACE inhibition were evaluated in patients with congestive heart failure who were already treated with maximally recommended or tolerated doses of an ACE inhibitor. Forty-three patients with symptomatic congestive heart failure were evaluated biweekly for 1 month before addition of losartan and weekly during administration of losartan at a daily dose of 25 mg for the first week and 50 mg for the second week. Systolic blood pressure, which remained unchanged before addition of losartan, decreased from 122 +/- 18 mm Hg to 112 +/- 17 and 107 +/- 17 mm Hg (p < 0.001) after 1 week of 25 mg and 1 week of 50 mg losartan, respectively. Diastolic blood pressure also significantly decreased. The decreases in blood pressure were well tolerated by all patients, even by those in whom symptomatic hypotension developed during uptitration of ACE inhibition. Serum potassium and sodium and parameters of renal function remained unchanged. Combining AT1-receptor blockade with losartan to maximally recommended or tolerated ACE inhibition appears safe and leads to further vasodilatation in symptomatic patients with congestive heart failure
— id: 83318, year: 1997, vol: 30, page: 533, stat: Journal Article,

Mechanisms and implications of endothelial dysfunction in congestive heart failure
Katz, S D
1997 May;12(3):259-264, Current opinion in cardiology
The pathogenesis of heart failure is determined by the ventricular and vascular responses to myocellular injury. Experimental and clinical studies suggest that the vascular endothelium may play an important role in modulating progression of ventricular and vascular remodeling in heart failure. Endothelial cell dysfunction has been described in the coronary and skeletal muscle circulations of patients with heart failure and appears to be characterized by decreased endothelial synthesis of nitric oxide and increased production of endothelin-1. The pathogenesis of endothelial dysfunction in heart failure is unknown, but may be related to increased oxidative stress, abnormal regional flow conditions, and cytokine and neurohormonal activation. The specific role of endothelial dysfunction in the pathogenesis of heart failure remains to be determined. If endothelial dysfunction does contribute to progression of disease in early heart failure, specific therapies to enhance endothelial dysfunction may improve long-term morbidity and mortality
— id: 83316, year: 1997, vol: 12, page: 259, stat: Journal Article,

Training improves endothelium-dependent vasodilation in resistance vessels of patients with heart failure
Katz, S D; Yuen, J; Bijou, R; LeJemtel, T H
1997 May;82(5):1488-1492, Journal of applied physiology (Bethesda)
The effects of physical training on endothelium-dependent vasodilation in skeletal muscle resistance vessels were investigated in patients with heart failure. Forearm blood flows (ml.min-1.100 ml-1) in response to brachial arterial administration of acetylcholine (5 x 10(-5) and 5 x 10(-4) M at 1 ml/min) and nitroglycerin (5 x 10(-6) and 5 x 10(-5) M at 1 ml/min) were determined by strain-gauge venous occlusion plethysmography before and after 8 wk of daily handgrip exercise in 12 patients with chronic heart failure. After 8 wk of daily handgrip exercise, the vasodilatory responses to acetylcholine significantly increased from pretraining values, i.e., 16.6 +/- 2.0 vs. 8.6 +/- 1.3 ml.min-1.100 ml-1 (P < 0.05) and 27.5 +/- 1.5 vs. 14.6 +/- 1.7 ml.min-1.100 ml-1 (P < 0.05), respectively, whereas the vasodilatory responses to nitroglycerin did not change. Handgrip exercise training appears to specifically enhance endothelium-dependent vasodilation in the forearm skeletal muscle circulation of patients with heart failure
— id: 83314, year: 1997, vol: 82, page: 1488, stat: Journal Article,

Delayed reversal of impaired metabolic vasodilation in patients with end-stage heart failure during long-term circulatory support with a left ventricular assist device
Khan, T; Levin, H R; Oz, M C; Katz, S D
1997 Apr;16(4):449-453, Journal of heart & lung transplantation
BACKGROUND: Whether increased cardiac output during chronic circulatory support with a left ventricular assist device (LVAD) is associated with improved metabolic vasodilation in the peripheral circulation of patients with congestive heart failure is unknown. METHODS: Forearm blood flow, determined by venous occlusion plethysmography, mean arterial pressure, and cardiac output were measured at rest and after 5 minutes of arterial occlusion (a maximal metabolic vasodilatory stimulus) in 14 patients with severe heart failure before LVAD implantation, and in the early (<4 weeks) and late (8 to 12 weeks) postoperative recovery phases after LVAD implantation. Nine normal subjects served as controls. Vascular conductance was calculated as the ratio of forearm blood flow and mean arterial pressure. RESULTS: Mean arterial pressure and cardiac output increased to normal values in the early and late recovery phases after LVAD implantation. Resting forearm blood flow and vascular conductance were similar to normal subjects in the early and late recovery phases after LVAD implantation. Peak forearm blood flow and vascular conductance were significantly less than control subjects in the early preoperative recovery phase (p < 0.05) but were similar to control subjects in the late postoperative recovery phase after LVAD implantation. CONCLUSIONS: In spite of early normalization of cardiac output, mean arterial pressure, and resting forearm blood flow during chronic circulatory support with the LVAD, peak forearm blood flow, and peak vascular conductance did not increase to values similar to those observed in normal subjects until the late postoperative recovery period. The delayed effect of the LVAD on metabolic vasodilation may be related to flow-dependent changes in the peripheral vasculature of patients with heart failure
— id: 83315, year: 1997, vol: 16, page: 449, stat: Journal Article,

Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide
Katz, S D; Krum, H; Khan, T; Knecht, M
1996 Sep;28(3):585-590, Journal of the American College of Cardiology
OBJECTIVES: This study was undertaken to investigate the role of endothelium-derived nitric oxide in the regulation of forearm blood flow during exercise in normal subjects and patients with congestive heart failure. BACKGROUND: Nitric oxide-mediated vasodilation in response to muscarinic stimulation is impaired in the peripheral circulation of patients with congestive heart failure. Whether nitric oxide-mediated vasodilation during exercise is also impaired in patients with congestive heart failure is unknown. METHODS: Forearm blood flows (ml/min per 100 ml) were determined during rhythmic hand grip exercise at 15%, 30% and 45% of maximal voluntary contraction by venous occlusion plethysmography before and after regional inhibition of nitric oxide synthesis with administration of L-NG-monomethylarginine (L-NMMA) in the brachial artery of 17 patients with congestive heart failure (mean age 49 years, mean left ventricular ejection fraction 0.22) and 10 age-matched normal subjects. RESULTS: Before administration of L-NMMA in the brachial artery, forearm blood flows in patients with congestive heart failure during rhythmic hand grip exercise at 15%, 30% and 45% of maximal voluntary contraction were slightly but not significantly lower than that of normal subjects ([mean +/- SE] 6.8 +/- 1.0, 8.5 +/- 1.0 and 12.9 +/- 1.7 ml/min per 100 ml, respectively, in patients with congestive heart failure vs. 6.6 +/- 1.2, 11.6 +/- 1.9 and 16.2 +/- 1.9 ml/min per 100 ml, respectively, in normal subjects, p = NS). After administration of L-NMMA in the brachial artery, forearm blood flows in normal subjects significantly decreased by 10% to 21% during hand grip exercise but did not change during exercise in patients with congestive heart failure. CONCLUSIONS: Regional inhibition of nitric oxide synthase with administration of L-NMMA in the brachial artery significantly decreased forearm blood flows during rhythmic hand grip exercise in normal subjects but not in patients with congestive heart failure. These findings suggest that nitric oxide-mediated vasodilation during submaximal exercise is impaired in the forearm circulation of patients with congestive heart failure
— id: 83309, year: 1996, vol: 28, page: 585, stat: Journal Article,

Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial
Marcus, L S; Hart, D; Packer, M; Yushak, M; Medina, N; Danziger, R S; Heitjan, D F; Katz, S D
1996 Dec 15;94(12):3184-3189, Circulation
BACKGROUND: The pharmacological effects of infusion of human brain natriuretic peptide (hBNP) in patients with severe congestive heart failure have not been characterized previously. METHODS AND RESULTS: Twenty patients with severe congestive heart failure were randomized in a double-blind, placebo-controlled, crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01, 0.03, and 0.1 microgram/kg per minute) or placebo on 2 consecutive days. At the highest completed dose of the hBNP, mean pulmonary artery pressure decreased from 38.3 +/- 1.6 to 25.9 +/- 1.7 mm Hg; mean pulmonary capillary wedge pressure decreased from 25.1 +/- 1.1 to 13.2 +/- 1.3 mm Hg; mean right atrial pressure decreased from 10.9 +/- 1 to 4.8 +/- 1.0 mm Hg; mean arterial pressure decreased from 85.2 +/- 2.0 to 74.9 +/- 1.7 mm Hg; and cardiac index increased from 2.0 +/- 0.1 to 2.5 +/- 0.1 L/min per square meter (all P < .01 versus placebo). Urine volume and urine sodium excretion increased significantly during hBNP infusion when compared with placebo infusion (90 +/- 38 versus 67 +/- 27 mL/h and 2.6 +/- 2.4 versus 1.4 +/- 1.2 mEq/h, respectively, both P < .05 versus placebo), whereas creatinine clearance and urinary potassium excretion did not change. CONCLUSIONS: Infusion of incremental doses of hBNP is associated with favorable hemodynamic and natriuretic effects in patients with severe congestive heart failure
— id: 83311, year: 1996, vol: 94, page: 3184, stat: Journal Article,

Left ventricular thrombus and the incidence of thromboembolism in patients with congestive heart failure: can clinical factors identify patients at increased risk?
Katz, S D
1995 Apr;2(2):97-102, Journal of cardiovascular risk
Left ventricular thrombus is highly prevalent in patients with congestive heart failure, but the increase of thromboembolic events is low. Reliable clinical indicators of increased thromboembolic risk are not yet available. Clinical decisions to treat patients who have congestive heart failure with oral anticoagulants must be made on an individual basis
— id: 83292, year: 1995, vol: 2, page: 97, stat: Journal Article,

The role of endothelium-derived vasoactive substances in the pathophysiology of exercise intolerance in patients with congestive heart failure
Katz, S D
1995 Jul-Aug;38(1):23-50, Progress in cardiovascular diseases
The vascular endothelium releases vasoactive substances that appear to play an important role in the normal regulation of peripheral vasomotor tone. Nitric oxide, endothelins, prostaglandins, and other endothelium-derived vasodilating and vasoconstricting factors are released by the vascular endothelium in response to a diverse array of hormonal, pharmacologic, chemical, and physical stimuli. Shear stress, produced by pulsatile blood flow at the endothelial cell luminal surface, alters endothelial production of several endothelium-derived vasoactive substances, which may contribute to regional regulation of skeletal muscle blood flow during exercise. Abnormal vascular endothelium function has been shown in both experimental and clinical heart failure. Preliminary data suggest that abnormalities of endothelial function may contribute to increased peripheral vasomotor tone during exercise in patients with congestive heart failure
— id: 83293, year: 1995, vol: 38, page: 23, stat: Journal Article,

Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure
Krum, H; Sackner-Bernstein, J D; Goldsmith, R L; Kukin, M L; Schwartz, B; Penn, J; Medina, N; Yushak, M; Horn, E; Katz, S D
1995 Sep 15;92(6):1499-1506, Circulation
BACKGROUND: Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated. METHODS AND RESULTS: We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block. CONCLUSIONS: Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors
— id: 83296, year: 1995, vol: 92, page: 1499, stat: Journal Article,

Determination of vascular impedance in the peripheral circulation by transcutaneous pulsed Doppler ultrasound
Solomon, S; Katz, S D; Stevenson-Smith, W; Yellin, E L; LeJemtel, T H
1995 Aug;108(2):515-521, Chest
Instantaneous blood flow velocity characteristics and vascular impedance spectra derived noninvasively by pulsed Doppler ultrasound and invasively by electromagnetic flow probe were compared in the canine common femoral artery to validate the pulsed Doppler technique for determination of vascular impedance in the peripheral circulation. Although Doppler ultrasonography is routinely performed to evaluate blood flow velocity patterns in the human peripheral circulation; the validity of this technique to derive peripheral vascular impedance has yet to be investigated. Simultaneous measurements of blood flow velocity were determined by both noninvasive pulsed Doppler ultrasound and surgically implanted electromagnetic flow probe in the common femoral artery of eight dogs and compared in both time and frequency domains. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe and simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were obtained at baseline and after intra-arterial injection of acetylcholine in five additional dogs. During the first 10 to 20% of the cardiac cycle, Doppler ultrasound blood flow velocity was transiently greater than the simultaneously recorded electromagnetic blood flow velocity. During the remainder of the cardiac cycle, the two blood flow velocity waveforms were nearly superimposable. The frequency spectra of the blood flow velocity waveforms derived from Doppler ultrasound and electromagnetic flow probes were similar for harmonies less than 10 Hz. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe with simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were similar at baseline and after regional administration of acetylcholine. Mean vascular resistance (impedance at 0 Hz), characteristic impedance, and the first minima of the impedance modulus derived from Doppler ultrasound and electromagnetic flow probe blood flow velocity measurements were closely correlated at baseline and after dilation with acetylcholine (r > or = 0.89, p < 0.05 for all correlations). Doppler ultrasonography is a convenient and accurate technique for determination of vascular impedance in the peripheral circulation
— id: 83295, year: 1995, vol: 108, page: 515, stat: Journal Article,

Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide-dependent vasodilation in the forearm circulation
Katz, S D; Rao, R; Berman, J W; Schwarz, M; Demopoulos, L; Bijou, R; LeJemtel, T H
1994 Jul;90(1):12-16, Circulation
BACKGROUND: Tumor necrosis factor-alpha (TNF alpha), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNF alpha affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously. METHODS AND RESULTS: Serum concentrations of TNF alpha, interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10(-6) mol/L and 10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum concentrations of TNF alpha were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNF alpha and were closely correlated with TNF alpha serum concentrations (r > or = .81, P < .01 and r > or = .65, P < .05 respectively). In 1 of 17 normal subjects, the serum concentration of TNF alpha was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed. CONCLUSIONS: Increased TNF alpha concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNF alpha and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF
— id: 83298, year: 1994, vol: 90, page: 12, stat: Journal Article,

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure
Schwarz, M; Katz, S D; Demopoulos, L; Hirsch, H; Yuen, J L; Jondeau, G; LeJemtel, T H
1994 Apr;89(4):1609-1614, Circulation
BACKGROUND: Since organic nitroesters and endothelium-derived nitric oxide mediate vasodilation through a final common pathway, that is, by activation of soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could specifically enhance the endothelium-dependent vasodilatory response to acetylcholine (Ach) in patients with congestive heart failure (CHF) and endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium-independent vasodilation were assessed in the forearm circulation of patients with CHF. METHODS AND RESULTS: The forearm blood flow responses to intra-arterial administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients with CHF and 5 age-matched normal subjects before and during intra-arterial infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to 12 hours with measurement of the forearm blood flow responses to Ach at 20 minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow response to intra-arterial administration of two doses of phentolamine (0.05 and 0.5 mg) were determined before and during a 20-minute NTG infusion. Regional administration of NTG 10(-9) mol/L did not change resting forearm blood flow in either normal subjects or patients with CHF. Before administration of NTG 10(-9) mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100 mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20 minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0, 6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not change in normal subjects. The enhanced forearm blood flow responses to administration of Ach observed after 20 minutes of NTG administration in patients with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional administration of NTG did not change the vasodilatory responses to phentolamine. CONCLUSIONS: NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium
— id: 83300, year: 1994, vol: 89, page: 1609, stat: Journal Article,

Regional specificity of peak hyperemic response in patients with congestive heart failure: correlation with peak aerobic capacity
Jondeau, G; Katz, S D; Toussaint, J F; Dubourg, O; Monrad, E S; Bourdarias, J P; LeJemtel, T H
1993 Nov 1;22(5):1399-1402, Journal of the American College of Cardiology
OBJECTIVES. The aim of this study was to compare peak reactive hyperemic blood flows in the forearm and calf of patients with congestive heart failure and in age- and gender-matched normal subjects. In addition, we attempted to correlate peak oxygen consumption with forearm and calf peak reactive hyperemic flows in the patients with heart failure. BACKGROUND. Disparate results have been reported regarding forearm peak reactive hyperemia in patients with congestive heart failure. Because training significantly increases peak reactive hyperemic flow in normal subjects, we hypothesized that in patients with congestive heart failure who curtail walking because of exertional symptoms, calf peak reactive hyperemic flow would be preferentially attenuated and that impairment of calf vasculature may correlate with peak oxygen consumption. METHODS. Forearm and calf blood flows were measured by venous occlusive plethysmography at rest and after 5 min of arterial occlusion in 46 patients with congestive heart failure and 7 age- and gender-matched normal subjects. Peak oxygen consumption was measured during graded exercise on a bicycle ergometer. RESULTS. Calf peak reactive hyperemic flow was lower in patients with congestive heart failure than in normal subjects (22 +/- 1 vs. 32.5 +/- 3.5 ml/min per 100 ml, p < 0.001), whereas forearm peak reactive hyperemic flows were similar in the two groups. Calf peak reactive hyperemic flow was linearly related to peak oxygen consumption (r = 0.58, p < 0.0001), but forearm peak reactive hyperemic flow was not. Forearm and calf peak reactive hyperemic flows were not related at rest or after 5 min of arterial occlusion in the patients with heart failure. CONCLUSIONS. Calf peak reactive hyperemic flow is reduced in patients with congestive heart failure, whereas forearm peak reactive hyperemic flow is identical to that of age- and gender-matched normal subjects. Calf peak reactive hyperemic flow is linearly related to peak oxygen consumption in patients with congestive heart failure, but forearm peak reactive hyperemic flow is not
— id: 83301, year: 1993, vol: 22, page: 1399, stat: Journal Article,

Lactate turnover at rest and during submaximal exercise in patients with heart failure
Katz, S D; Bleiberg, B; Wexler, J; Bhargava, K; Steinberg, J J; LeJemtel, T H
1993 Nov;75(5):1974-1979, Journal of applied physiology (Bethesda)
Systemic and lower limb skeletal muscle lactate metabolism was studied in 10 men with congestive heart failure by use of a primed continuous intravenous infusion of L-(+)-[U-14C]lactate. Arterial and deep femoral venous blood samples were obtained at rest and during 30 min of submaximal exercise. Systemic lactate metabolic turnover rate (Rd) was determined using Steele's isotopic steady-state equation (Rd = isotopic infusion rate/arterial specific activity). Plasma lactate concentrations in the artery and deep femoral vein did not change significantly from resting values during exercise (1.11 +/- 0.13 vs. 1.26 +/- 0.12 and 1.27 +/- 0.12 vs. 1.30 +/- 0.12 mM, respectively), whereas Rd increased from 22.5 +/- 1.8 to 41.6 +/- 4.8 mumol.kg-1.min-1 (P < 0.005). Rd did not significantly correlate with arterial lactate concentration during rest or exercise. Because of simultaneous uptake and release of lactate in skeletal muscle, arterial and deep femoral venous lactate concentrations are not closely related to either systemic or lower limb skeletal muscle lactate metabolism in patients with congestive heart failure
— id: 83302, year: 1993, vol: 75, page: 1974, stat: Journal Article,

Low incidence of stroke in ambulatory patients with heart failure: a prospective study
Katz, S D; Marantz, P R; Biasucci, L; Jondeau, G; Lee, K; Brennan, C; LeJemtel, T H
1993 Jul;126(1):141-146, American heart journal
The current study was undertaken to determine prospectively the risk of cerebral thromboembolism and the prognostic significance of left ventricular thrombus in ambulatory patients with chronic congestive heart failure. A total of 264 ambulatory patients (mean age 62 years, mean left ventricular ejection fraction 27%) were followed prospectively for 24 +/- 9 months to determine the incidence of nonhemorrhagic stroke, transient ischemic attack, and mortality. Two-dimensional echocardiographic studies, performed for clinical indications other than previous systemic thromboembolism in 109 patients, were analyzed to relate the presence of left ventricular thrombus to subsequent outcome. Nine cerebral thromboembolic events occurred in 264 patients during the two-year mean follow-up period, yielding a rate of 1.7 thromboembolic events per 100 patient-years of follow-up. Known risk factors for stroke (hypertension, diabetes mellitus, and/or atrial fibrillation) were present in all nine patients with cerebral thromboembolic events. The 109 patients with echocardiographic studies had more severe heart failure than patients without echocardiographic studies (functional class 2.6 vs 2.1, p < 0.01), greater risk of a thromboembolic event (2.4 vs 1.4 events/100 patient-years of follow-up, p < 0.01), and higher mortality (21.3 vs 5.5 deaths/100 patient-years, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 83303, year: 1993, vol: 126, page: 141, stat: Journal Article,

Impaired acetylcholine-mediated vasodilation in patients with congestive heart failure. Role of endothelium-derived vasodilating and vasoconstricting factors
Katz, S D; Schwarz, M; Yuen, J; LeJemtel, T H
1993 Jul;88(1):55-61, Circulation
BACKGROUND. The vasodilatory response to intra-arterial administration of acetylcholine is reduced in patients with congestive heart failure compared with that of normal subjects. The reduced response to acetylcholine may be related to decreased endothelial release of nitric oxide, interaction with peripheral alpha-adrenergic transmission, or production of cyclooxygenase-dependent vasoconstricting substances. The extent to which each of these mechanisms contributes to the reduced vasodilatory response to acetylcholine in patients with congestive heart failure is not known. METHODS AND RESULTS. Thirty-one patients with congestive heart failure (New York Heart Association functional class II-III) and five age-matched normal subjects were studied. Regional vascular responses in the forearm to infusions of acetylcholine, an endothelium-dependent vasodilator (10(-7) to 10(-5) mol/L) and nitroglycerin, an endothelium-independent vasodilator (10(-6) mol/L) in the brachial artery were determined with venous occlusion plethysmography before and after regional alpha-adrenergic blockade with intra-arterial phentolamine (25 micrograms/min) and systemic cyclooxygenase with oral indomethacin (50 mg). Administration of phentolamine significantly increased resting baseline forearm blood flow in 11 patients with congestive heart failure (2.9 +/- 0.4 to 5.4 +/- 0.8 mL.min-1.100 mL-1) and normal subjects (4.6 +/- 0.3 to 11.3 +/- 2.1 mL.min-1.100 mL-1). Before administration of phentolamine, intra-arterial infusions of acetylcholine 10(-7), 10(-6), and 10(-5) mol/L increased forearm blood flow to 4.0 +/- 1.0, 6.0 +/- 1.7, and 16.1 +/- 4.0 mL.min-1.100 mL-1, respectively, in patients with congestive heart failure and to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.7 +/- 7.9 mL.min-1.100 mL-1, respectively, in normal subjects. After administration of phentolamine, the vasodilatory responses to intra-arterial infusions of acetylcholine and nitroglycerin did not change in either patients or normal subjects. Administration of indomethacin did not alter resting forearm blood flow in 15 patients with congestive heart failure (2.7 +/- 0.4 to 2.7 +/- 0.4 mL.min-1.100 mL-1) or normal subjects (4.6 +/- 0.3 to 5.4 +/- 0.8 mL.min-1.100 mL-1). Administration of indomethacin significantly increased the vasodilatory response to infusion of acetylcholine by an average of 39% in patients with congestive heart failure but did not change the vasodilatory response to acetylcholine in normal subjects. In patients with congestive heart failure, baseline forearm blood flow and the vasodilatory responses to intra-arterial infusions of acetylcholine and nitroglycerin were significantly less than those of normal subjects both before and after administration of phentolamine and indomethacin. CONCLUSIONS. The reduced vasodilatory response to intra-arterial infusion of acetylcholine in patients with congestive heart failure probably results from several coexistent abnormalities in peripheral vascular function, including abnormal production of cyclooxygenase-dependent vasoconstricting factor, impaired endothelial release of nitric oxide, and decreased vascular smooth muscle responsiveness to cyclic GMP-mediated vasodilation
— id: 83306, year: 1993, vol: 88, page: 55, stat: Journal Article,

Peripartum versus idiopathic dilated cardiomyopathy in young women--a comparison of clinical, pathologic and prognostic features
van Hoeven, K H; Kitsis, R N; Katz, S D; Factor, S M
1993 Jun 15;40(1):57-65, International journal of cardiology
Clinicopathologic features of 13 women with peripartum cardiomyopathy were compared to 13 women aged 19 through 38 with idiopathic dilated cardiomyopathy. No presenting clinical or pathologic variable distinguished either group. However, the clinical course differed between the groups. Eleven of 13 patients with idiopathic dilated cardiomyopathy had a poor clinical outcome, defined as persistent heart failure or death. Patients in this group succumbed one year or more after disease onset. Five of 13 patients with peripartum cardiomyopathy had poor outcome, with death occurring 9 months or less after disease onset. The clinical course of peripartum cardiomyopathy appears distinct from that of idiopathic dilated cardiomyopathy in young women
— id: 83304, year: 1993, vol: 40, page: 57, stat: Journal Article,

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement
Hale, P M; McAllister, J P 2nd; Katz, S D; Wright, L C; Lovely, T J; Miller, D W; Wolfson, B J; Salotto, A G; Shroff, D V
1992 Dec;31(6):1085-1096, Neurosurgery
As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair
— id: 83175, year: 1992, vol: 31, page: 1085, stat: Journal Article,

Active skeletal muscle mass and cardiopulmonary reserve. Failure to attain peak aerobic capacity during maximal bicycle exercise in patients with severe congestive heart failure
Jondeau, G; Katz, S D; Zohman, L; Goldberger, M; McCarthy, M; Bourdarias, J P; LeJemtel, T H
1992 Nov;86(5):1351-1356, Circulation
BACKGROUND. In addition to depressed cardiac reserve, peripheral factors may contribute to limit maximal exercise capacity in patients with congestive heart failure (CHF). To investigate the role of reduced active skeletal muscle mass, peak oxygen uptake (VO2, milligrams per kilogram per minute) was determined during maximal symptom-limited exercise involving the lower limbs (LL) alone and the lower limbs and upper limbs (LL+UL) combined in patients with CHF and in normal subjects of similar age and sex. METHODS AND RESULTS. LL bicycle exercise was performed upright with a ramp protocol and continuous expired gas analysis. When respiratory exchange ratio (RER) reached 1.0, UL exercise was initiated at constant load with the use of a cranking device positioned at shoulder level. LL exercise alone and combined LL+UL exercise were performed on separate days in randomized order by 24 patients with CHF and seven normal subjects. In patients with CHF, peak VO2 was greater during combined LL+UL exercise than during LL exercise alone, i.e., 15.8 +/- 0.8 versus 14.2 +/- 0.9 ml.kg-1.min-1 (p < 0.001), whereas in normal subjects, maximal VO2 was similar during the two tests, i.e., 26.7 versus 26.2 ml.kg-1.min-1 (NS). The increase in peak VO2 during combined LL+UL exercise relative to LL exercise alone was almost exclusively observed in patients with peak VO2 < 15 ml.kg-1.min-1 (mean increase, 21.7 +/- 4.1%). Peak VO2 during combined LL and UL exercise did not increase relative to LL exercise alone in patients with peak VO2 > 15 ml.kg-1.min-1 and in normal subjects of similar age and sex, i.e., 0.1 +/- 4.0% and 2.0 +/- 2.3% respectively. CONCLUSIONS. In contrast to normal subjects and patients with moderate CHF, patients with severe CHF do not exhaust their cardiopulmonary reserve during symptom-limited maximal LL exercise on a bicycle
— id: 83172, year: 1992, vol: 86, page: 1351, stat: Journal Article,

Control of arteriolar resistance in heart failure. Partial attenuation of specific phosphodiesterase inhibitor-mediated vasodilation by digitalis glycosides
Jondeau, G; Klapholz, M; Katz, S D; Maher, M; Galvao, M; Levato, P; LeJemtel, T H
1992 Jan;85(1):54-60, Circulation
BACKGROUND. The vasodilatory response to local specific type III phosphodiesterase inhibition with amrinone was evaluated before and immediately after local administration of digoxin in 14 patients with severe congestive heart failure (CHF). METHODS AND RESULTS. A 3F polyethylene catheter was inserted into the common femoral artery for drug administration and pressure monitoring. Mean blood flow velocity (MBFV) was continuously determined in the superficial femoral artery by transcutaneous Doppler ultrasonography. After intra-arterial administration of 10 mg amrinone, group MBFV increased from 7.7 +/- 1.4 to 16.0 +/- 2.1 cm/sec (p less than 0.05, n = 10). Local administration of 20 micrograms digoxin, which was infused over 20 minutes, did not alter group MBFV (i.e., 8.2 +/- 1.6 versus 7.6 +/- 1.5 cm/sec; p = NS, n = 10). The second administration of 10 mg amrinone, which immediately followed completion of local digoxin infusion, increased group MBFV but to a lesser extent than that produced by the first amrinone administration (i.e., 11.9 +/- 1.9 versus 16.0 +/- 2.1 cm/sec; p less than 0.05, n = 10). When placebo was administered instead of digoxin, group MBFV was similar after the first and second administrations of amrinone (i.e., 15.3 +/- 3.3 versus 15.6 +/- 3.8 cm/sec; p = NS, n = 4). CONCLUSIONS. Although local administration of digoxin did not significantly alter baseline vascular tone in patients with CHF, it substantially decreased the direct vasodilatory effect induced by specific type III phosphodiesterase with amrinone
— id: 83231, year: 1992, vol: 85, page: 54, stat: Journal Article,

Anaerobic threshold detection in patients with congestive heart failure
Katz, S D; Berkowitz, R; LeJemtel, T H
1992 Jun 15;69(19):1565-1569, American journal of cardiology
Anaerobic threshold measurements determined either invasively by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respiratory gas exchange analysis (ventilatory threshold) were compared in patients with chronic congestive heart failure. Sixteen patients performed symptom-limited maximal exercise on a bicycle ergometer using a continuous ramp protocol with measurement of arterial lactate concentration at 1 minute intervals, and continuous breath-by-breath analysis of respiratory gas exchange. A specific lactate threshold point was detected in only 7 patients. These 7 patients had significantly greater peak oxygen uptake than did the 9 in whom no specific lactate threshold point was detected (15.9 +/- 1.0 vs 10.5 +/- 0.5 ml/kg/min; p less than 0.05). Ventilatory threshold significantly correlated with lactate threshold in these 7 patients. In the remaining 9 patients, neither lactate nor ventilatory threshold could be reliably determined with methods used in the present study
— id: 83201, year: 1992, vol: 69, page: 1565, stat: Journal Article,

Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure
Katz, S D; Biasucci, L; Sabba, C; Strom, J A; Jondeau, G; Galvao, M; Solomon, S; Nikolic, S D; Forman, R; LeJemtel, T H
1992 Apr;19(5):918-925, Journal of the American College of Cardiology
Impaired endothelial-dependent vasodilation has been demonstrated in two animal models of congestive heart failure and in the coronary circulation of patients with idiopathic dilated cardiomyopathy. To determine whether this impairment contributes to the abnormal peripheral vasomotor tone in patients with congestive heart failure, the local vascular response to intraarterial infusions of graded concentrations (10(-8) M to 10(-5) M) of acetylcholine (an endothelial-dependent vasodilator) and nitroglycerin (a direct-acting vasodilator) was studied in the superficial femoral artery of 19 patients with congestive heart failure (New York Heart Association classes I to IV) and 6 age-matched normal control subjects. The local vascular response was determined from the arterial blood flow velocity pattern obtained by transcutaneous Doppler ultrasonography. Acetylcholine, 10(-5) M, induced a pattern characteristic of vasodilation in all six normal subjects; mean blood flow velocity for the group significantly increased from 11.9 +/- 2.7 to 44.8 +/- 20.9 cm/s (p less than 0.05). In contrast, the same dose of acetylcholine induced a blood flow velocity pattern characteristic of vasodilation in only 4 of the 19 patients with congestive heart failure. Group mean blood flow velocity did not change significantly. Nitroglycerin, 10(-7) M, induced vasodilation in all 6 normal subjects but in only 1 of 19 patients. Nitroglycerin, 10(-5) M, was administered to 10 patients; all 10 demonstrated a pattern characteristic of vasodilation. Thus, acetylcholine-mediated endothelial-dependent vasodilation appears to be impaired in the peripheral vasculature of patients with congestive heart failure. Both endothelial dysfunction and abnormal vascular smooth muscle responsiveness may contribute to abnormal peripheral vasomotor tone
— id: 83188, year: 1992, vol: 19, page: 918, stat: Journal Article,

A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure
Katz, S D; Kubo, S H; Jessup, M; Brozena, S; Troha, J M; Wahl, J; Cohn, J N; Sonnenblick, E H; LeJemtel, T H
1992 Jan;123(1):95-103, American heart journal
Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type III and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 +/- 30 and 124 +/- 33 seconds versus 58 +/- 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 +/- 0.8 and 2.2 +/- 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 +/- 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors
— id: 83233, year: 1992, vol: 123, page: 95, stat: Journal Article,

Peripheral circulatory response in cardiac failure
Le Jemtel, T H; Katz, S D; Sonnenblick, E H
1991 Sep 15;26(9):75-82, Hospital practice (office edition)
Derangements of the peripheral circulation play a major role in the pathophysiology of congestive heart failure. Their appearance coincides with that of the symptoms and signs that characterize the full-blown clinical syndrome. Long-term therapy with ACE inhibitors partially reverses these abnormalities, but the pathologic mechanisms are still poorly understood
— id: 83269, year: 1991, vol: 26, page: 75, stat: Journal Article,