The prevention of congestive heart failure: left ventricular dilation and its management

Left ventricular dilation and remodelling occur in 35-40% of anterior transmural myocardial infarcts and these events are important antecedents to the development of late congestive heart failure. This process commences within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and the uninfarcted regions of myocardium are equally involved in the process. Thinning of the left ventricular wall occurs mainly as a result of cell slippage. In addition, compensatory hypertrophy occurs in the uninfarcted segment of the myocardium. While this hypertrophy may initially be physiological, it ultimately appears to become a pathological process and thereby contributes to pump dysfunction. At the present time there are encouraging data to suggest that nitroglycerin, administered in the setting of the acute infarction, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process. Whether a patent infarct related artery further limits dilation is uncertain and is currently under investigation.     

Coronary reserve of the hypertensive heart: relationship to left ventricular hypertrophy

We investigated the relationship between electrocardiographic left ventricular hypertrophy with ST-changes, and coronary circulation and myocardial metabolism in 25 patients with essential hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg). No patients had abnormal coronary arteriograms. They were categorized in two groups: non-hypertrophy group; cases with no hypertrophy on echocardiograms (interventricular septum and posterior wall thickness less than or equal to 11 mm), and hypertrophy group; cases with hypertrophy (wall thickness greater than or equal to 12 mm). Supine bicycle ergometry (50 watts, 50 rpm, 15 min) was performed during coronary sinus catheterization and electrocardiography. For cardiac hemodynamics, the coronary circulation and myocardial metabolism were observed at rest and during exercise. There was no significant difference in unit coronary blood flow (coronary blood flow per 100 gm) before exercise between the two groups. Unit coronary blood flow was significantly greater in the non-hypertrophy group after exercise. However, total coronary blood flow (coronary blood flow per 100 gm x left ventricular mass) showed no significant difference between the two groups. Coronary vascular resistance per 100 gm was higher in the hypertrophy group during exercise, though there was no significant difference at rest. Myocardial oxygen extraction O2 (A-C) was not different between the two groups at rest and during exercise, but unit myocardial oxygen consumption (MVO2) during exercise was higher in the non-hypertrophy group than in the hypertrophy group. The lactate extraction ratio tended to decrease in the hypertrophy group during exercise, and tended to increase in the non-hypertrophy group. Myocardial potassium flux tended to increase in the hypertrophy group during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contemporary medical management of left ventricular dysfunction and congestive heart failure.

OBJECTIVE: The primary purpose of this review was to address the following question: based on the best available evidence, what should be the current medical management of congestive heart failure (CHF)? DATA SOURCES: The major sources for this review were from searches of the English language literature, including computer and bibliography reviews, of all randomized, controlled clinical trials and overview analyses of positive inotropic agents, preload/afterload reduction agents and beta-blocker medications in CHF. STUDY SELECTION: The number of studies reviewed was approximately 40. The major criterion for selection was that the studies be of CHF patients in randomized controlled clinical trials, particularly with a mortality/survival endpoint. Additional clinical trials of nonmortality endpoints in CHF patients and mortality trials in non-CHF patients were also selected to support possible pathophysiological insights for future CHF trials. DATA EXTRACTION: The data, particularly for the accompanying tables, were initially extracted by a single reviewer using common qualitative guidelines as far as was possible within the different temporal, etiological and geographic frameworks of the original component studies. Conclusions are drawn from this data synthesis and from published overviews. DATA SYNTHESIS: Angiotensin converting enzyme (ACE) inhibition therapy is effective in reducing mortality and morbidity in severe left ventricular dysfunction and CHF. Other systemic vasodilators may also be beneficial. The effects of digitalis on survival and morbidity in CHF are presently uncertain, but should be resolved in the near future. Other inotropic agents, at least in the long term, are clinically detrimental. Diuretics decrease morbidity, but their effect on mortality in CHF remains unknown. Beta-blocker and magnesium therapy offer promise in CHF, but await definitive clinical trials evaluation. CONCLUSIONS: The current medical therapy of CHF should definitely include ACE inhibitors, probably diuretics and possibly other vasodilators. Further viable trials of promising new, and older heretofore under-evaluated, CHF therapies are needed. Additionally, innovative strategies are needed to deal with this disease which has an increasing prevalence. Two strategies, primary prevention of CHF and a 'Heart Function Clinic', are discussed.     

Heart failure in hypertensive patients with left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is supposed to be a useful marker of cardiovascular complications during the course of hypertension. Authors compared the presence of heart failure, left ventricular diastolic dysfunction and chronic atrial fibrillation in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Hospital records of 192 hypertensives treated in our medical department during years 1996-1999 were analysed. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. Presence of LVH was found in 128 patients (mean age 65.9 years), absence of LVH in 64 patients (mean age 64.8 years). Both groups of hypertensives were matched by demographic parameters, by the presence of hyperlipidemia, by smoking habits. Hypertensive patients with left ventricular hypertrophy were more often treated by ACE inhibitors. There were statistically significant more patients with heart failure, left ventricular diastolic dysfunction and chronic atrial fibrillation in LVH-positive patients than in LVH-negative once. There was also statistically significant lower ejection fraction (50.3 +/- 11.4% vs 56.5 +/- 7.4%) in LVH-positive patients than in LVH-negative once. Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease with a high contribution to the development of chronic heart failure.     

Transition from asymptomatic left ventricular dysfunction to congestive heart failure

One of the main goals of modern management and care of heart failure is to prevent the disease to progress toward congestion and death. The achievement of such an objective may, in fact, guarantee a sufficient quality of life and reduce the exposure of patients to the most common life-threatening complications associated with the congestive stage of the disease. Early identification of left ventricular dysfunction as well as a better knowledge of the mechanisms that favor the progression to more advanced stages of heart failure are fundamental requirements for the proper treatment of asymptomatic heart failure and for preventing the transition to symptomatic and more severe heart failure. The authors reviewed the literature on this topic, with emphasis on a series of studies they performed, to characterize the pathophysiologic profile of mild heart failure and the mechanisms that are possibly involved in the progression to congestive heart failure.     

52例高血压左心室肥厚患者的心率变异性临床分析

目的　探讨高血压左心室肥厚患者的心率变异性。方法　分析 36例正常对照组和 5 2例高血压左心室肥厚患者的心率变异性。结果　高血压左心室肥厚患者的 2 4h正常 RR间期标准差 ( SDNN)和心率变异指数 ( HRVI)明显低于正常组 ( P<0 .0 1) ,其中离心性组明显。结论　高血压左心室肥厚患者心率变异性较正常人减低     

Intact systolic left ventricular function in clinical congestive heart failure

Clinical congestive heart failure (CHF) is traditionally associated wtih significant left ventricular (LV) systolic dysfunction. Over a 1-year period, 58 patients with CHF and intact systolic function (LV ejection fraction [EF] 62 ± 11%) were identified. An objective clinical-radiographic CHF score was used to document the clinical impression. Based on radionuclide evaluation of peak filling rate, 38 % of these patients were found to have a significant abnormality in diastolic function as measured by peak filling rate (< 2.50 end-diastolic volume/s). An additional 24% of the patients had probable diastolic dysfunction with borderline abnormal peak filling rate measurements (2.5 to 3.0 end-diastolic volume/s). The disease states most frequently associated with CHF and intact systolic function were coronary artery disease and systemic hypertension. During a 3-month sampling period 42% of patients with clinical diagnosis of CHF referred to the nuclear cardiology laboratory were found to have intact systolic function; thus, intact systolic function is not uncommon in patients with clinical CHF. Abnormal diastolic function is the most frequently encountered mechanism for the occurrence of CHF. Definition of systolic and diastolic function appears relevant for development of optimal therapeutic strategies for the treatment of patients with CHF.     

Candesartan cilexetil improves left ventricular function, left ventricular hypertrophy, and endothelial function in patients with hypertensive heart disease.

Patients with hypertension often develop left ventricular (LV) hypertrophy and deterioration of the cardiac and endothelial functions. Recent clinical trials have shown the added benefits of angiotensin II receptor blockers in hypertensive patients. Twenty-nine patients with hypertensive heart disease (HHD) underwent echocardiography, radionuclide ventriculography and the measurement of endothelial function before and after administration of candesartan (8 mg/day). The subjects were divided into poorly controlled blood pressure (BP) (group P, n=6) and well controlled BP (group C, n=23). Endothelial function was evaluated from flow-dependent dilation, which was calculated as the percent change of the radial artery diameter during reactive hyperemia after upper arm occlusion, measured with a high-resolution ultrasound system. In group C, LV diastolic function and endothelial function were significantly (p<0.05) improved at 3 months after administration, LV systolic function and hypertrophy were significantly (p<0.05) improved after 6 months and these effects were maintained at 12 months. Even in group P, LV function, LV hypertrophy, endothelial function and brain natriuretic peptide were significantly (p<0.05) improved at 6 months after administration. In patients with HHD, candesartan improves LV systolic and diastolic function, LV hypertrophy and endothelial function within 6 months of administration, regardless of the control of BP.     

Diabetes mellitus, left ventricular dysfunction and congestive heart failure]

Diabetes is a well known risk factor for the development of congestive heart failure. Epidemiological evidence in the community underscores the prevalence of left ventricular systolic dysfunction in diabetic patients as 2-fold with respect to non-diabetic ones, with half of them completely asymptomatic. Diastolic dysfunction in diabetic hearts, in comparison with non-diabetic, is even more frequent. The high prevalence has been explained by the frequent coexistence of an underlying diabetic cardiomyopathy, hypertension and ischemic heart disease. In these patients, the diabetic metabolic derangement, together with the early activation of sympathetic nervous system, induce a decrease of myocardial function. The activation of renin-angiotensin system results in an unfavorable cardiac remodeling. The progression from myocardial damage to overt dysfunction and heart failure is often asymptomatic for a long time and frequently undiagnosed and untreated. Currently, the widespread availability of echocardiography and possibly the use of cardiac natriuretic peptides, may allow for an earlier recognition of most of such patients. In heart failure, diabetic patients have a worse prognosis than non-diabetics. The available pharmacological treatments, such as ACE-inhibitors, beta-blockers and possibly angiotensin receptor blockers, togheter with a tight glycemic control, may be effective to reverse the remodeling process and prevent cardiovascular events. In order to identify most of the diabetic patients at risk of development of left ventricular dysfunction and to prevent its progression to overt heart failure, it seems important to elaborate a screening strategy in order to diagnose and treat most of diabetic patients with myocardial damage.     

Excessive activation of matrix metalloproteinases coincides with left ventricular remodeling during transition from hypertrophy to heart failure in hypertensive rats

OBJECTIVES: We sought to elucidate how the local activation of matrix metalloproteinases (MMPs) is balanced by that of the endogenous tissue inhibitors of MMP (TIMPs) during left ventricular (LV) remodeling. BACKGROUND: Although it is known that the extracellular matrix (ECM) must be altered during LV remodeling, its local regulation has not been fully elucidated. METHODS: In Dahl salt-sensitive rats with hypertension, in which a stage of concentric, compensated left ventricular hypertrophy (LVH) at 11 weeks is followed by a distinct stage of congestive heart failure (CHF) with LV enlargement and dysfunction at 17 weeks, we determined protein and messenger ribonucleic acid (mRNA) levels of LV myocardial TIMP-2 and -4 and MMP-2, as well as their concomitant activities. RESULTS: No changes were found at the LVH stage. However, during the transition to CHF, TIMP-2 and -4 activities, protein and mRNA levels were all sharply increased. At the same time, the MMP-2 mRNA and protein levels and activities, as determined by gelatin zymography, as well as by an antibody capture assay, showed a substantial increase during the transition to CHF. The net MMP activities were closely related to increases in LV diameter (r = 0.763) and to systolic wall stress (r = 0.858) in vivo. CONCLUSIONS: Both TIMPs and MMP-2 remained inactive during hypertrophy, per se; they were activated during the transition to CHF. At this time, the activation of MMP-2 surpassed that of TIMPs, possibly resulting in ECM breakdown and progression of LV enlargement.     

Hypertensive heart disease: relationship of silent ischemia to coronary artery disease and left ventricular hypertrophy

ECG evidence of silent ischemia occurs commonly in patients with systemic hypertension, but its relationship to left ventricular hypertrophy (LVH), large-vessel coronary artery disease (CAD), and neurohumoral factors remains unclear. Accordingly we validated the results of the echocardiographic method used to measure left ventricular (LV) mass in the Soviet Union by comparison with necropsy measurements in 30 patients, and we examined the relationships in 46 men with essential hypertension among ST segment depression during ambulatory monitoring, exercise stress and transesophageal pacing (n = 38), and LV mass, catheterization evidence of CAD (n = 25), and neurohumoral factors (plasma catecholamines and platelet aggregability). Echocardiographic measurements of LV mass by both the Soviet and Penn methods were closely correlated with necropsy values (r = 0.78 and 90, respectively; both p less than 0.001). During ambulatory monitoring from 1 to 17 episodes of greater than or equal to 1 mm ST depression occurred in 26 of 46 (65%) patients with hypertension; ischemia was also provoked by exercise or pacing stress in most but not all of these patients (65% and 80%, respectively). Neither ST depression nor the occurrence of additional episodes of symptomatic angina was related to the presence of coronary obstruction at catheterization; patients with and without ST depression did not differ in age, blood pressure, or LV mass.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium antagonists and left ventricular function: effects of nitrendipine in congestive heart failure

Calcium antagonists can affect the arterial vasculature, the venous capacitance vessels and the myocardium. The net effect of these agents on left ventricular (LV) performance depends on the interaction of effects on these 3 vascular components, and the state of LV function at the time that the drugs are administered. A calcium antagonist with profound arterial vasodilator effect might favorably influence LV performance even if it had negative inotropic properties. To demonstrate the direct effect of nitrendipine, a 1,4 dihydropyridine, on LV performance, the acute hemodynamic response to oral nitrendipine was studied in 8 patients with congestive heart failure. Administration of 10 to 20 mg of nitrendipine reduced preload, caused a decrease in both pulmonary wedge pressure and systemic vascular resistance, produced a modest decrease in blood pressure and an increase in stroke volume. In addition, plasma norepinephrine levels were significantly decreased. Plasma renin activity also tended to decrease. These data confirm that the drug can favorably alter performance of the failing left ventricle and further suggest that the vasodilator effect is not accompanied by reflex neurohumoral stimulation.     

Impaired left ventricular functional reserve in hypertensive patients with left ventricular hypertrophy

To determine whether patients with hypertension and especially those with left ventricular hypertrophy have subtle changes in cardiac function, we measured the increase in left ventricular ejection fraction and in systolic blood pressure to end-systolic volume index ratio with exercise in 40 hypertensive patients and 16 age-matched normotensive volunteers. Twenty-two hypertensive patients without hypertrophy had normal end-systolic wall stress at rest and exercise responses. In contrast, the 18 patients with echocardiographic criteria for left ventricular hypertrophy demonstrated a significant increase in end-systolic wall stress at rest compared with normal subjects (69 +/- 16 vs. 55 +/- 15 10(3) x dyne/cm2, p less than 0.05) despite having normal resting left ventricular size and ejection fraction. In patients with left ventricular hypertrophy, the increase in ejection fraction with exercise was less than in the normotensive control subjects (7 +/- 7 vs. 12 +/- 8 units, p less than 0.05), and delta systolic blood pressure to end-systolic volume with exercise was reduced (3.3 +/- 3.8 vs. 8.3 +/- 7.7 mm Hg/ml/m2, p less than 0.05). The hypertensive patients with hypertrophy displayed a shift downward and to the right in the relation between systolic blood pressure to end-systolic volume ratio and end-systolic wall stress compared with control subjects and hypertensive patients without left ventricular hypertrophy. Thus, hypertensive patients with left ventricular hypertrophy by echocardiography and normal resting ejection fraction exhibit abnormal ventricular functional responses to exercise. This finding may have implications in identifying patients at higher risk for developing heart failure.