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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 73 records · Page 4Linked to original sources
PubMed1998

Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients.

AIMS: The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by non-invasive mathematical lumped-parameter modelling of the compliance of the arterial system. METHODS AND RESULTS: Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml x mmHg(-1), P<0.01) and distal (C2, 0.050 +/- 0.011 ml x mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml x mmHg(-1); C2, 0.054 +/- 0.006 ml x mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= - 0.795, P=0.002) and standing (r= - 0.628, P=0.029) positions. CONCLUSIONS: In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.

Aldosterone↗
PubMed1998

Beta-blockers in heart failure.

Beta-blocker therapy for heart failure has gained popularity as a result of recent growing evidence that this group of drugs can reverse or slow the progressive left ventricular dilation that characterizes heart failure. Although the mechanism of this favourable effect on remodelling remains unclear, the present evidence indicates that at least a portion of the long-term benefit of these drugs is mediated through their beta-blocking action. A direct effect on myocyte and interstitial growth may be a key factor in their ability to inhibit the remodelling process. The growing database will eventually raise the possibility that all patients with left ventricular dilation should take one of these drugs. A better understanding of differing mechanisms in individual patients would ideally provide selectivity in the therapeutic approach.

Adrenergic beta-Antagonists↗
PubMed1998

Evaluating pathophysiologic processes rather than clinical end points in improving therapeutic practice.

Cardiovascular clinical trials and clinical practice are currently aimed at reducing morbidity and mortality, but a more efficient and effective guide to therapeutic efficacy would be surrogate markers that track the progression of disease that precipitates clinical end points. Structural alterations of the left ventricle and abnormalities of endothelial function that lead to functional and structural alterations of the vasculature are the best candidates for useful surrogate markers. Methods for quantitating these functional and structural alterations must be validated to provide documentation of their sensitivity and specificity.

Cardiovascular Diseases↗
PubMed1997

Overview of the treatment of heart failure.

Short-term goals of heart failure management are directed toward relieving symptoms such as shortness of breath, decreased exercise tolerance, and lower-extremity edema and improving functional capacity and quality of life. Long-term goals include decreasing mortality and slowing or reversing the underlying cardiac structural abnormalities of heart failure. Improvement in symptomatic endpoints (e.g., exercise tolerance) does not necessarily correlate with endpoints for improved survival (e.g., left ventricular ejection fraction). It is therefore important to evaluate the effects of drugs on these distinct endpoints separately. Symptoms of heart failure are commonly managed with the use of diuretics, vasodilators, and positive inotropes or digoxin. Ideally, therapy should consist of a diuretic plus vasodilator (e.g., angiotensin-converting enzyme [ACE] inhibitor or isosorbide dinitrate plus hydralazine), with or without digoxin. Prevention of further left ventricular dysfunction can be accomplished by inhibiting neurohormonal processes and ventricular remodeling that occur in heart failure using ACE inhibitors, nitrates and hydralazine, or beta blockers. Significant therapeutic advances have been made with respect to symptom relief, hospitalizations, and mortality reduction in patients with congestive heart failure. Despite these advances, patient morbidity and mortality remain high and underscore the necessity for optimal use of existing therapies along with research directed at achieving further improvements in both quality of life and life expectancy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

Adult↗
PubMed1997

Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research.

The SEP identified priorities to support in future basic and clinical research and pointed out directions likely to result in advances against heart failure. The list is not intended to be all-encompassing and does not address, for example, exciting lines of work already under way. Rather, the recommendations are designed to point out gaps in current knowledge not being adequately addressed and highly promising new directions. Although the incidence of heart failure continues to grow, emerging lines of research provide hope that research advances will eventually lead to more effective treatment and ultimately to prevention. This research will be well served by bringing the latest multidisciplinary approaches and the best investigators to focus on the problems of heart failure. It is hoped the efforts of distinguished expert entities such as the task force and SEP will be a useful guide in addressing the needs of the biomedical community and assisting in its success.

Animals↗
PubMed1997

Effect of delayed intervention with ACE-inhibitor therapy on myocyte hypertrophy and growth of the cardiac interstitium in the rat model of myocardial infarction.

The effectiveness of angiotensin-converting enzyme (ACE)-inhibitor therapy in attenuating ventricular remodeling when initiated immediately following myocardial damage is clearly established. Less information, however, is available on the impact of late therapy on the remodeling process, especially its influence on the cellular components of these structural changes. The purpose of this study was to examine the effects of converting enzyme inhibitor therapy commenced 28 days following infarction in the rat on changes in cardiac myocyte dimension and the interstitium. At 28 days following infarction, myocyte cell length (153.9+/-7.3 v 131.1+/-5.9 micron, P=0.0002) and cell volume in the free wall of the left ventricle (38. 5+/-5.0 x 10(3) v31.4+/-3.1 x 10(3), P=0.009) had increased compared with sham-operated rats. Similar changes were noted in the septum and right ventricle. Captopril therapy administered between 28 and 56 days attenuated a further increase in cell length noted in an untreated group in the left ventricle (153.5+/-15.3 v 167.3+/-13.7 micron, P=0.02), right ventricle (153.8+/-20.5 v 173.8+/-2.3 micron, P=0.01) and septum (158.0+/-20.2 v 179.1+/-16.6 micron, P=0.004). There was an increase in hydroxyproline content in the right ventricle and a similar trend in the left ventricle in the untreated myocardial infarction groups. These changes were not altered by captopril therapy. In summary, even late therapy with captopril attenuates progressive myocyte remodeling, which may contribute to the ability of ACE-inhibitor therapy to slow progressive chamber enlargement following infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Vascular abnormalities associated with long-term cigarette smoking identified by arterial waveform analysis.

PURPOSE: Consistent changes in the arterial pulse contour are found with aging and disease states that impair the compliance characteristics of blood vessels that buffer pulsatile phenomena in the arterial tree. We assessed whether vascular adaptation in structure or tone of blood vessels associated with long-term cigarette smoking would influence steady state or pulsatile hemodynamics at a preclinical stage. PATIENTS AND METHODS: We analyzed intraarterial brachial artery waveforms in 35 healthy long-term cigarette smokers and 32 nonsmoking control subjects matched for age and gender. The diastolic pressure decay was segmented into two components: an exponential decay that reflects the compliance characteristics of the large arteries and an oscillatory diastolic waveform generated principally by pulse-wave reflections from small arteries and arterioles. RESULTS: Resting heart rate was higher in smokers than nonsmokers, mean +/- SD (66 +/- 9 versus 60 +/- 10; P < 0.05). Systolic, diastolic, and mean arterial pressures were lower in smokers compared with nonsmokers (P < 0.01 for all). No differences in cardiac output, large artery compliance, or systemic vascular resistance estimates where apparent between groups. A decrease in the amplitude and duration of the diastolic wave, produced by peripheral pulse-wave reflections in the arterial system, was found in smokers compared with nonsmokers (0.04 +/- 0.02 versus 0.7 +/- 0.03; P < 0.001). CONCLUSIONS: Quantitative changes in the arterial waveform were found in long-term smokers compared with nonsmoking control subjects. The altered arterial wave shape marks the presence of abnormal structure or tone in the peripheral vasculature that affects pulsatile arterial function. This measure of vascular injury is detectable at a preclinical stage and may relate to the subsequent risk of morbid events in chronic smokers and aid in clinical risk stratification.

Adult↗
PubMed1997

Safety and efficacy of carvedilol in severe heart failure. The U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. METHODS AND RESULTS: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). CONCLUSION: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Adrenergic beta-Antagonists↗
PubMed1997

Current concepts in the treatment of congestive heart failure.

Heart failure is a complex syndrome; therapy should be aimed at the independent goals of prolonging life and of improving symptoms and quality of life. Some therapies are effective in achieving one goal but not the other. Short-term symptomatic relief may relate to alleviation of haemodynamic abnormalities and of congestion, whereas slowing progression of the disease and reducing mortality involve neurohormonal mechanisms, left ventricular remodelling and arrhythmia generation. Current therapy is moderately effective on these end-points, but newer approaches to management are necessary to produce more profound improvements in morbidity and mortality.

Heart Failure↗