Explore the vast range of titles available.

Parasympathetic control of the heart via the vagus nerve is the primary mechanism that regulates beat-to-beat control of heart rate. Additionally, the vagus nerve exerts significant effects at the AV node, as well as effects on both atrial and ventricular myocardium. Vagal control is abnormal in heart failure, occurring at early stages of left ventricular dysfunction, and this reduced vagal function is associated with worse outcomes in patients following myocardial infarction and with heart failure. While central control mechanisms are abnormal, one of the primary sites of attenuated vagal control is at the level of the parasympathetic ganglion. It remains to be seen whether or not preventing or treating abnormal vagal control of the heart improves prognosis.

Patterns of medical resource use near the end of life may differ across modes of death. The aim of this study was to characterize patterns of inpatient resource use and direct costs for patients with heart failure (HF) who died of sudden cardiac death (SCD), HF, other cardiovascular causes, or noncardiovascular causes during the last year of life. Data were from a randomized trial of exercise training in patients with HF. Mode of death was adjudicated by an end point committee. Generalized estimating equations were used to compare hospitalizations, inpatient days, and inpatient costs incurred during the final year of life in patients who died of different causes, adjusting for clinical and treatment characteristics. Of 2,331 patients enrolled in the trial, 231 died after ≥1 year of follow-up with an adjudicated mode of death, including 72 of SCD, 80 of HF, 34 of other cardiovascular causes, and 45 of noncardiovascular causes. Patients who died of SCD were younger, had less severe HF, and incurred fewer hospitalizations, fewer inpatient days, and lower inpatient costs than patients who died of other causes. After adjustment for patient characteristics, inpatient resource use varied by 2 to 4 times across modes of death, suggesting that cost-effectiveness analyses of interventions that reduce mortality from SCD compared to other causes should incorporate mode-specific end-of-life costs. In conclusion, resource use and associated medical costs in the last year of life differed markedly in patients with HF who experienced SCD and patients who died of other causes.

Whether an angiotensin receptor blocker is of benefit when added to a full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF) is uncertain. The effect of candesartan, compared with placebo, in 2548 patients randomized in the CHARM-Added trial was analyzed according to (i) ACE inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii) combination treatment with ACE inhibitor and β-blocker at baseline. The main outcome was the composite of cardiovascular death or HF hospitalization. The benefit of candesartan was not modified by the dose of ACE inhibitor. In all patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95; interaction P value .26). In patients taking a Food and Drug Administration–designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57-0.98; interaction P value .29). The benefit of candesartan was preserved in patients taking β-blockers in addition to a higher dose of ACE inhibitor and in patients maintaining a high dose of ACE inhibitor throughout follow-up. These clinical findings support the pharmacologic evidence that ACE inhibitors and angiotensin receptor blockers have distinct mechanisms of action and show that their combined use improves outcomes in patients with HF more than an evidence-based dose of ACE inhibitor alone.

A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0.79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different geographical areas.

Opinion statement Despite major advances that have led to effective therapeutic modalities for the treatment of heart failure (HF), this syndrome has continued to be a staggering health problem associated with significant mortality and morbidity. The increasing number of hospital admissions and readmissions related to acute HF continues to pose a fiscal challenge leading to constant interest in development of novel approaches. These point to multiple areas of unmet needs especially in acute HF, thus, necessitating further efforts to develop novel strategies for prevention and treatment of acute HF. One area of continuing focus is targeting the role of autonomic imbalance associated with the development of HF. Autonomic dysregulation, manifested by increased sympathetic drive and reduced parasympathetic activity, has been recognized as a mediator of increased mortality and morbidity in HF and myocardial infarction. Furthermore, vagal withdrawal has been shown to precede acute decompensation, though whether this represents cause or effect is unknown. This review discusses the potential role of autonomic dysregulation as a therapeutic modality for patients with acute decompensated HF.

Heart failure is a progressive clinical syndrome that is characterized by remodeling of the myocardium in response to various stress signals. The past several years has seen remarkable progress in unraveling the molecular and cellular mechanisms of structural and electrical remodeling in HF. Improved understanding of the molecular mechanism of myocardial remodeling has resulted in improved HF therapies and revealed potentially novel therapeutic targets. This review discusses the mechanisms of myocardial remodeling in HF and their clinical manifestations. Current and investigational HF therapies targeting these mechanisms also will be discussed.

Increased aortic stiffness contributes to systolic hypertension and increased cardiovascular risk. The augmentation index (AI), ie, the percentage of central pulse pressure attributed to reflected wave overlap in systole, was proposed as a noninvasive indicator of increased arterial stiffness. We evaluated this hypothesis by investigating relations between AI and other direct measures of aortic stiffness. Tonometric carotid- and femoral-pressure waveforms, Doppler aortic flow, and aortic-root diameter were assessed in 123 individuals with uncomplicated systolic hypertension and 29 controls of comparable age and sex. Carotid–femoral pulse-wave velocity (PWV) was assessed from the carotid–femoral time delay and body-surface measurements. Aortic PWV was assessed from the ratio of the upstroke of carotid pressure and aortic flow velocity and was used to calculate proximal aortic compliance as [aortic area] / [1.06 × (aortic PWV) 2]. Partial correlations (adjusted for age, sex, presence of hypertension, height, weight, and systolic ejection period) showed no association between AI and carotid–femoral PWV ( R = −0.05, P = .54). The AI was significantly though weakly related directly with aortic compliance ( R = 0.21, P = .012) and inversely with aortic PWV ( R = −0.198, P = .017). However, higher stiffness (lower compliance and higher PWV) was associated with lower AI. Increased AI is not a reliable surrogate for increased aortic stiffness. Decreasing AI with decreasing compliance (increasing aortic stiffness) may be attributable to impedance matching and reduced wave reflection at the interface between the aorta and the muscular arteries.

Treatment of diastolic heart failure is divided into acute and chronic management. During acute management, the focus should be treatment of the presenting syndrome, including correction of volume overload, treating hypertension, alleviating ischemia, and controlling tachyarrhythmias. Therefore, acute treatment should include several components: treating volume overload with sodium restriction and diuretics; treating ischemic heart disease with antiplatelet therapy, anticoagulants, and beta blockers; treating hypertension aggressively, using multiple agents if necessary; and treating atrial tachyarrhythmias such as atrial fibrillation with rate-controlling agents, such as beta blockers and possibly nondihydropyridine calcium channel blockers such as diltiazem and verapamil. Antiarrhythmic agents with or without electrical cardioversion may be necessary. Thoroughly evaluate and manage extracardiac precipitants such as anemia and renal failure. Chronic management should also focus on precipitating factors, for which adequate control of hypertension is paramount. Patient education regarding dietary and medication compliance and lifestyle changes is also important. If ischemic heart disease is present, aggressive anti-ischemic therapy is necessary, including revascularization when indicated.

Increased aortic stiffness contributes to systolic hypertension and increased cardiovascular risk. Augmentation index (AI) has been proposed as a noninvasive indicator of increased arterial stiffness. We evaluated this hypothesis by investigating relations between AI and measures of aortic stiffness. Tonometric carotid and femoral pressure waveforms, Doppler aortic flow and aortic root diameter were assessed in 123 individuals with uncomplicated systolic hypertension and 29 controls of comparable age and gender. Carotid-femoral PWV (CFPWV) was assessed from the carotid-femoral time delay and body surface measurements. Aortic PWV (AoPWV) was assessed from the ratio of the upstroke of carotid pressure and aortic flow velocity and was used to calculate proximal aortic compliance (AoC): AoC = (Aortic Area)/(1.06 x AoPWV2). Partial correlations (adjusted for age, sex, presence of hypertension, height and systolic ejection period) showed no association between AI and either PWV (Table). Variable, units Mean ± SD Co-efficient p-value CFPWV, m/s 11.8 ± 3.6 −0.04 0.658 AoPWV, m/s 15.2 ± 5.4 −0.13 0.113 AoC, ln(10−6 cm4/dyne) 1.2 ± 0.6 0.21 0.011 AI was significantly correlated with AoC; however, reduced compliance (increased stiffness) was associated with reduced AI. In conclusion, increased AI is not an indicator of central PWV and may be inversely related to aortic stiffness. Decreasing AI with decreasing compliance (increasing aortic stiffness) may be attributable to impedance matching and reduced wave reflection at the interface between aorta and muscular arteries.

Aldosterone is elevated in heart failure and exerts multiple detrimental effects. In addition to playing key roles in sodium and volume regulation, aldosterone is involved in regulation of autonomic tone, endothelial dysfunction, tissue collagen turnover, myocyte fibrosis, and release of inflammatory modulators. Aldosterone receptor antagonists have proven to be a valuable treatment tool in the management of heart failure due to systolic dysfunction. Blocking the effects of aldosterone can improve many of the functions that are deranged in patients with heart failure, as well as promote excretion of sodium and water and preservation of potassium and hydrogen in the distal renal tubule. These medications can be especially effective at removing fluid from the periphery and soft tissues. Prevention of hypokalemia, which may predispose patients to arrhythmia, is an added benefit. Spironolactone and eplerenone are the two agents in this class that have been studied in patients with heart failure and left ventricular dysfunction. However, aldosterone antagonist therapy may not be appropriate for all patients with heart failure. Therefore, guidelines in managing patients on these medications should be followed to avoid serious electrolyte abnormalities and renal dysfunction. This review examines some of the mechanisms of action and the usefulness of aldosterone blockade in the management of heart failure.