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Patients with heart failure with reduced ejection fraction (HFrEF) have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Soluble guanylate cyclase (sGC) stimulators have the potential to lower this risk by modifying the nitric oxide-sGC-cyclic guanosine monophosphate cascade - a pathophysiological pathway that has been targeted with limited success in HFrEF previously. Vericiguat, an sGC stimulator, was shown to improve outcomes in patients with HFrEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. However, this trial included patients with recently worsening disease. In this brief review, we discuss the rationale of evaluating sGC stimulators in lower-risk HFrEF patients. First, all key HFrEF medications have been evaluated in both higher- and lower-risk populations, and the treatment effect is not always consistent across the risk spectrum. Second, pre-clinical studies and post-hoc studies of the VICTORIA trial have suggested that sGC stimulators may have cardioprotective effects - these effects may be more apparent when the medication is initiated earlier in the disease process. Third, the effect of vericiguat on cardiovascular mortality remains uncertain and a trial with a longer follow-up in a lower-risk population may allow better assessment of its effect on cardiovascular mortality. Therefore, there is a pertinent need to investigate the effects of vericiguat in optimally treated, low-risk HFrEF patients (i.e. those without recently worsening heart failure)., (© 2022 European Society of Cardiology.)

Acute decompensated heart failure remains the most common cause of hospitalization in older adults, and studies of pharmacological therapies have yielded limited progress in improving outcomes for these patients. This has prompted the development of novel device-based interventions, classified mechanistically based on the way in which they intend to improve central hemodynamics, increase renal perfusion, remove salt and water from the body, and result in clinically meaningful degrees of decongestion. In this review, we provide an overview of the pathophysiology of acute decompensated heart failure, current management strategies, and failed pharmacological therapies. We provide an in depth description of seven investigational device classes designed to target one or more of the pathophysiologic derangements in acute decompensated heart failure, denoted by the acronym DRI 2 P 2 S. Dilators decrease central pressures by increasing venous capacitance through splanchnic nerve modulation. Removers remove excess fluid through peritoneal dialysis, aquaphoresis, or hemodialysis. Inotropes directly modulate the cardiac nerve plexus to enhance ventricular contractility. Interstitial devices enhance volume removal through lymphatic duct decompression. Pushers are novel descending aorta rotary pumps that directly increase renal artery pressure. Pullers reduce central venous pressures or renal venous pressures to increase renal perfusion. Selective intrarenal artery catheters facilitate direct delivery of short acting vasodilator therapy. We also discuss challenges posed in clinical trial design for these novel device-based strategies including optimal patient selection and appropriate end points to establish efficacy.

The ACR and the American College of Cardiology Foundation (ACCF) developed a joint process for determining the appropriate utilization (AU) of cardiovascular imaging modalities in heart failure (HF). This report represents an executive summary of the AU document which was aimed at critically and systematically creating, reviewing, and categorizing clinical situations where physicians order or use imaging tests for patients with suspected, incompletely characterized, or known HF., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the baseline, in-hospital, and post-discharge clinical, laboratory, and neurohormonal profiles of patients hospitalized for worsening heart failure with reduced ejection fraction (EF) who die or are re-admitted for cardiovascular (CV) causes within 90 days of initial hospitalization. Retrospective analysis of 4,133 patients hospitalized for worsening heart failure with EF ≤40% in the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which randomized patients to tolvaptan or placebo, both in addition to standard therapy. Clinical and laboratory parameters were obtained within 48 h of admission, during hospitalization, and post-discharge weeks 1, 4, 8, and every 8 weeks thereafter for a median of 9.9 months. Patients with events within 90 days were compared with those with later/no events. All-cause mortality (ACM) and CV re-hospitalization were independently adjudicated. Within 90 days of admission, 395 patients (9.6%) died and 801 patients (19.4%) were re-hospitalized for CV causes. Significant baseline and longitudinal differences were seen between groups with early versus later (>90 days) or no events at 12 months post-randomization. Post-discharge outcomes were similar in the tolvaptan and placebo groups. Patients with early post-discharge events experienced clinically significant worsening in signs and symptoms, laboratory values, and neurohormonal parameters soon after discharge. Identifying these abnormalities may facilitate efforts to reduce post-discharge mortality and re-hospitalization.

Cardiac sympathetic imaging with meta-iodobenzylguanidine (mIBG) is a noninvasive tool to risk stratify patients with heart failure (HF). In patients with ischemic and nonischemic cardiomyopathy, cardiac mIBG activity is a very powerful predictor of survival. Cardiac sympathetic imaging can help in understanding how sympathetic overactivity exerts its deleterious actions, which may result in better therapy and outcome for patients with HF., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Fluid retention and extracellular volume expansion are frequently encountered complications of congestive heart failure (HF) that can cause morbidity and mortality. Tolvaptan (Otsuka) is an orally administered nonpeptide vasopressin (VP) V2 receptor antagonist that inhibits water reabsorption in the kidney by competitively blocking VP binding, resulting in water diuresis without significantly changing total electrolyte excretion. In the 24-hour period following a 30-mg dose of tolvaptan, urine excretion rate increases and declines as plasma concentrations rise and fall; this uneven effect results in 80% of daily urine output in the first 12 hours. Therefore, the current study was designed to assess the pharmacodynamic effects, pharmacokinetics, and clinical safety of tolvaptan 30 mg QD plus placebo versus 15 mg BID over 7 days in patients with NYHA Class II/III heart failure and persistent fluid overload, SBP > or = 90 mm Hg, and a serum creatinine < or = 3.0 mg/dL. Patients were withdrawn from diuretics for 48 hours before randomization. Statistics were performed with ANCOVA for continuous variables and Mantel-Haenszel mean score test stratified by center for categorical variables. Thirty-nine of 40 patients completed days 1 and 7. There were no significant clinical, pharmacokinetic, or pharmacodynamic differences between the dosing regimens over time. Based on these findings, tolvaptan 30 mg was chosen as the comparator for placebo in a large phase 3 survival trial.

Background: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure., Methods and Results: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6+/-0.7, -5.4+/-0.7, and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0+/-0.4, -3.7+/-0.4, and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11+/-17, 68+/-17, 152+/-19, and 176+/-18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo., Conclusions: In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

Background: Both metoprolol and carvedilol improve cardiac function and prolong survival in patients with heart failure. Carvedilol has broader antiadrenergic effects than metoprolol, but it is not clear whether this characteristic is associated with greater benefits on cardiac function during long-term treatment., Study Design: We performed a meta-analysis of all 19 randomized controlled trials of carvedilol or metoprolol that measured left ventricular ejection fraction before and after an average of 8.3 +/- 0.1 months of treatment in 2184 patients with chronic heart failure. The mean daily doses were 58 +/- 1 mg of carvedilol and the equivalent of 162 +/- 1 mg of extended-release metoprolol. In the 15 placebo-controlled trials, the mean ejection fraction increased more in the trials of carvedilol than in the trials of metoprolol (placebo-corrected increases of +0.065 and +0.038, respectively), P = .0002. In the 4 active-controlled trials that compared metoprolol directly with carvedilol, the mean ejection fraction also increased more in the carvedilol groups than in the metoprolol groups (+0.084 on carvedilol and +0.057 on metoprolol, respectively), P = .009. The difference in favor of carvedilol in the active-controlled trials was nearly identical to the difference observed in the placebo-controlled trials and was apparent in patients with and without coronary artery disease., Conclusion: Long-term treatment with carvedilol produces greater effects on left ventricular ejection fraction than metoprolol when both drugs are prescribed in doses similar to those that have been shown to prolong life.

We reviewed the literature on clinical trials of beta-adrenergic blockade for treatment of heart failure, seeking evidence of reductions in hospital admissions. To analyze the economic implications of six clinical trials, we developed a stochastic cost model to generate estimates of total medical costs resulting from heart failure and related causes. The model includes inpatient, outpatient, and professional cost estimates based on Medicare claims data, and it is driven by traditional endpoint statistics reported in the clinical trial literature. It provides a common framework for comparing cost effectiveness across clinical trials in the absence of detailed cost information collected in the trial. The incremental expected cost per year of life saved is $3,300 for bisoprolol, $2,500 for metoprolol, and $6,700 for carvedilol. The cost per year of life saved for each compound is well below accepted standards for cost effectiveness. These results are sensitive to the cost of drug therapy and the relative mortality rate for the experimental group. For example, if the relative mortality rate of the experimental group were to increase from the reported 40% to 82%, and if the annual cost of the drug were to decrease from $2,000 to $500, then we estimate that carvedilol would break even and the cost per year of life saved would drop to zero. Whether beta-blocker therapy, as assumed, sustains its differential effectiveness in terms of relative mortality risk beyond the study duration has not been demonstrated.

Objectives: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients., Background: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown., Methods: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10)., Results: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy)., Conclusions: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Background: The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%)., Methods: Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug., Results: At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01)., Conclusions: Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.

Background: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction., Methods: Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design., Results: Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 +/- 9 (SE) seconds; exercise time for those taking placebo increased 66 +/- 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3. 4% +/- 0.5% in amlodipine-treated patients and 1.5% +/- 0.5% in placebo-treated patients (P =.007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups., Conclusions: The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.

Ventricular remodeling refers to changes in left ventricular (LV) geometry, mass, and volume in response to myocardial injury or alterations in load. The extent of LV dilatation or remodeling after myocardial infarction (MI) or in patients with heart failure is a strong predictor of both morbidity and mortality. Based on these observations, it is clear that LV remodeling is a maladaptive process. Two classes of drugs appear to inhibit LV remodeling. A large amount of data support the use of angiotensin-converting enzyme (ACE) inhibitors to improve survival and to prevent progressive remodeling. In addition, recent studies suggest that beta-adrenergic blockers have a beneficial effect on both survival and remodeling. These data support a causative role of the renin-angiotensin system and perhaps the sympathetic nervous system in this process. Thus, ACE inhibitors and possibly beta-blockers should be part of the pharmacologic regimen for the treatment of patients with LV dysfunction to prevent progressive LV remodeling.

Since their development, calcium channel blocking agents have stimulated interest in their potential benefit for a variety of cardiovascular disorders, including heart failure. The rationale for the potential benefit of calcium channel blockers in heart failure is multi-factorial, including vasodilation, correction of perturbed diastolic relaxation, anti-ischemic action, and potential for inhibiting myocyte hypertrophy and injury. Despite these potential benefits, the degree of salutary influence has remained controversial, and a number of studies have suggested potential adverse action in patients with heart failure, perhaps linked to either negative inotropic action or to reflex neurohormonal activation. Diversity among different agents, particularly with regard to tissue selectivity and pharmacokinetics may imply substantial differences in the relative benefits and risks in various subgroups of patients with heart failure. One trial with the newer dihydropyridine agent, amlodipine, indicates benefit to survival in patients with moderate to severe heart failure and reduced ejection fraction. The reproducibility of this finding and the mechanism for this benefit deserves further investigation.

We investigated the effects of inhibiting endogenous atrial natriuretic factor (ANF) metabolism on renal hemodynamics, sodium excretion and neurohormones in 12 patients with New York Heart Association functional class II congestive heart failure (CHF) due to left ventricular systolic dysfunction. In a randomized, placebo-controlled, double-blinded fashion, 8 patients received a single oral dose of candoxatril, an inhibitor of renal neutral endopeptidase, and 4 patients received placebo. Candoxatril treatment increased plasma ANF by 70 +/- 71 pg/ml (p < 0.015 vs. placebo) and plasma cGMP by 7.9 +/- 2.7 pmol/ml (p < 0.001 vs. placebo), with maximal effects at 3.5 h. Urinary cGMP more than doubled (p = 0.025 vs. placebo). Candoxatril increased urinary sodium by 2.7 +/- 2.0 mEq/h (p < 0.05 vs. placebo) and significantly elevated filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A significant reduction in aldosterone concentration with a similar trend in plasma renin activity was noted in candoxatril-treated patients. Thus in patients with moderate heart failure, renal neutral endopeptidase inhibition increases urinary sodium excretion. The lack of an effect on renal hemodynamics suggests that this natriuresis results from ANF-mediated inhibition of tubular sodium reabsorption. These findings justify additional investigation into potential clinical benefit of endopeptidase inhibition in patients with CHF.

To assess the long-term changes in cardiac function in asymptomatic patients with severe left ventricular dysfunction, left ventricular (cineangiography) and right ventricular (radionuclide angiography) function were assessed at baseline in 49 patients enrolled in the prevention arm of the Studies of Left Ventricular Dysfunction. After an average follow-up period of 12.4 months, 30 patients (11 randomized to the placebo group and 19 to the enalapril group) could be restudied to assess the progression of ventricular dysfunction. After 1 year of follow-up, the changes in heart rate, left ventricular end-diastolic and systolic pressure and right ventricular volumes were comparable in both groups. However, there were modest but opposite changes in left ventricular end-diastolic volume (+9 ml/m2 with placebo vs. -10 ml/m2 with enalapril, p < 0.05) and end-systolic volume (+5 ml/m2 with placebo vs. -13 ml/m2 with enalapril, p < 0.05). Mean systolic wall stress increased insignificantly in both groups, whereas ejection fraction increased from 29% to 31% in the placebo group and from 28% to 32% with enalapril (p = NS, placebo vs. enalapril). Even in asymptomatic patients with severe left ventricular dysfunction, there was a slow progression of left ventricular dilation. Enalapril administration appeared to slow this progression, but wall stress was not normalized by the treatment at the doses used in the study, indicating that at least one of the stimuli for further remodeling remained present.

Objective: To define the mechanisms underlying left ventricular diastolic dysfunction in patients with congestive heart failure and normal systolic function and to identify the patients at risk for this syndrome., Study Selection: Studies were selected that describe the clinical observations of congestive heart failure with normal systolic function and that provide experimental and clinical insights into the mechanisms responsible for ventricular diastolic dysfunction., Data Synthesis: Recent studies indicate that a large number of patients (up to 40% in some series) presenting with congestive heart failure have preserved left ventricular systolic function. The factors contributing to altered left ventricular diastolic function include fibrosis, hypertrophy, ischemia, and increased afterload. The latter three factors, alone or in combination, predispose to impaired left ventricular relaxation, an active energy-requiring process. Thus, decreased left ventricular diastolic distensibility (increased diastolic pressure at any level of diastolic volume) may arise not only from altered passive elastic properties stemming from fibrosis or increased muscle mass but also from derangements in the dynamics of ventricular relaxation., Results: In patients with essential hypertension, all four of the above mechanisms may be operative. Considering the prevalence of hypertension in the general population, hypertension appears to be an important underlying factor in many patients with heart failure on the basis of diastolic mechanisms. In the patient presenting with dyspnea and elevated filling pressures, but with a nondilated, normally contracting ventricle, treatment with standard heart failure medications (such as digitalis, diuretics, and vasodilators) is often ineffective and may be deleterious. Such patients may respond more favorably to beta-blockers and calcium-channel blockers., Conclusions: Diastolic dysfunction should be considered in the patient presenting with heart failure symptoms but with normal systolic function, particularly in hypertensive patients with left ventricular hypertrophy.

Background: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure., Methods and Results: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo., Conclusions: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

An abstract of the article "Prognostic value and changes in renal function in patients admitted with acute heart failure - results from the EVEREST program," by J. Blair and colleagues is presented.