Current Cardiology Reviews - Volume 11, Issue 1, 2015

Heart failure (HF) is an epidemic associated with significant morbidity and mortality, affecting over 5 million people in the United States and 1-2% of the population worldwide. Observational studies have suggested that a healthy lifestyle can reduce HF risk. Although no clinical trials have targeted the prevention of HF as a primary endpoint, many have evaluated outcomes associated with the development of symptomatic disease (i.e., progression to HF, HF hospitalization or death) as secondary endpoints. Blood pressure treatment represents the most effective strategy in preventing heart failure; each 5 mm Hg decrease in systolic blood pressures reduces the risk of HF development by 24%. Thiazide diuretics appear to be the most efficacious agents in patients with hypertension. Angiotensin converting enzyme inhibitors and angiotensin-II receptor blockers are first line agents for patients with chronic atherosclerosis, diabetes, or chronic kidney disease. Beta blockers appear less effective as single agents and cardioselective agents are preferred. Calcium channel blockers, specifically non-dihydropyridines, should be avoided and alpha blockers should not be used to reduce HF risk.

The pathogenesis of heart failure involves a complex interaction between genetic and environmental factors. Genetic factors may influence the susceptibility to the underlying etiology of heart failure, the rapidity of disease progression, or the response to pharmacologic therapy. The genetic contribution to heart failure is relatively minor in most multifactorial cases, but more direct and profound in the case of familial dilated cardiomyopathy. Early studies of genetic risk for heart failure focused on polymorphisms in genes integral to the adrenergic and renin-angiotensin-aldosterone system. Some of these variants were found to increase the risk of developing heart failure, and others appeared to affect the therapeutic response to neurohormonal antagonists. Regardless, each variant individually confers a relatively modest increase in risk and likely requires complex interaction with other variants and the environment for heart failure to develop. Dilated cardiomyopathy frequently leads to heart failure, and a genetic etiology increasingly has been recognized in cases previously considered to be “idiopathic”. Up to 50% of dilated cardiomyopathy cases without other cause likely are due to a heritable genetic mutation. Such mutations typically are found in genes encoding sarcomeric proteins and are inherited in an autosomal dominant fashion. In recent years, rapid advances in sequencing technology have improved our ability to diagnose familial dilated cardiomyopathy and those diagnostic tests are available widely. Optimal care for the expanding population of patients with heritable heart failure involves counselors and physicians with specialized training in genetics, but numerous online genetics resources are available to practicing clinicians.

Although patients with American College of Cardiology / American Heart Association (ACC/AHA) Stage B heart failure, or asymptomatic left ventricular dysfunction (ALVD) are at high risk for developing symptomatic heart failure, few management strategies have been shown to slow disease state progression or improve long-term morbidity and mortality. Of the pharmacologic therapies utilized in patients with symptomatic disease, only angiotensin converting enzyme (ACE) inhibitors (and to a lesser extent, angiotensin receptor blockers, or ARBs) have been shown to improve clinical outcomes among patients with ALVD. Although evidence to support the use of beta blockers in this setting has been primarily derived from retrospective studies or subgroup analyses, they are generally recommended in most patients with ALVD, especially those with ischemic etiology. Statins are associated with improvements in both major adverse cardiovascular events and heart failure events among patients with a history of acute myocardial infarction. Finally, in eligible patients, placement of an automatic implantable cardioverter defibrillator (ICD) has been associated with reduced mortality rates among those with ALVD due to ischemic cardiomyopathy, and some subgroups may derive benefit from cardiac resynchronization therapy or biventricular pacing.

This review will outline the management of patients with symptomatic systolic heart failure or heart failure with reduced ejection fraction (HFrEF), i.e., those with structural heart disease and previous or current symptoms. Determination of volume status and appropriate diuretic administration is important in heart failure management. Inhibition of the renin-angiotensin-aldosterone and sympathetic nervous systems improves survival and decreases hospitalizations in patients with systolic or reduced ejection fraction HF (HFrEF). Beta blockers and aldosterone antagonists improve ejection fraction. Indications for additional agents including nitrates plus hydralazine, digoxin, statins, omega 3 polyunsaturated fatty acids, anticoagulants, and antiarrhythmics will be discussed. Choice of agents, dose-related effects, strategies to minimize adverse effects, and medications to avoid will be presented.

Implantable cardioverter-defibrillator (ICDs), cardiac resynchronization (CRT) and combination (CRT-D) therapy have become an integral part of the management of patients with heart failure with reduced ejection fraction (HFrEF). ICDs treat ventricular arrhythmia and CRTs improve left ventricular systolic function by resynchronizing ventricular contraction. Device therapies (ICD, CRT-D), have been shown to reduce all-cause mortality, including sudden cardiac death. Hospitalizations are reduced with CRT and CRT-D therapy. Major device related complications include device infection, inappropriate shocks, lead malfunction and complications related to extraction of devices. Improvements in device design and implantation have included progressive miniaturization and increasing battery life of the device, optimization of response to CRT, and minimizing inappropriate device therapy. Additionally, better definition of the population with the greatest benefit is an area of active research.

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidity and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often confronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pulmonary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt consideration of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exercise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF— lower is not always better; and (10) do not forget to consider rare diseases (“zebras”) as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies.

Acute decompensated heart failure (ADHF) continues to increase in prevalence and is associated with substantial mortality and morbidity including frequent hospitalizations. The American Heart Association is predicting that more than eight million Americans will have heart failure by 2030 and that the total direct costs associated with the disease will rise from $21 billion in 2012 to $70 billion in 2030. The increase in the prevalence and cost of HF is primarily the result of shifting demographics and a growing population. Although many large, randomized, controlled clinical trials have been conducted in patients with chronic heart failure, it was not until recently that a growing number of studies began to address the management of ADHF. It is the intent of this review to update the clinician regarding the evaluation and optimal management of ADHF.

Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantation and mechanical circulatory support, as well inotropic agents for the short-term. Despite a growing armamentarium of resources, the clinician must carefully weigh the risks and benefits of each therapy to develop an optimal treatment strategy. While cardiac transplantation remains the only true “cure” for end-stage disease, this resource is limited and the demand continues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior to transplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularly for the non-operative patient, intravenous inotropes can be utilized for symptom control. Regardless of the treatments considered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualized care. While survival is important, most patients covet quality of life above all outcomes. An often overlooked component is the patient’s control over the dying process. It is vital that clinicians make goals-of-care discussions a priority when seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitates these difficult conversations to ensure that all patient needs are ultimately met.

Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmonary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario.

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple therapies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides provide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syndrome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key aspects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively establish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical.

Left ventricular (LV) pressure curve shows early high-magnitude changes in the presence of induced ischemia. A dramatic rise in LV and left atrial end-diastolic pressures occurs within seconds to minutes in the presence of ischemia induced by dynamic or handgrip exercise as well as pacing of 38 to 183% and during short coronary balloon occlusion of 32 to 208% of baseline. Changes in relaxation or volumetric filling rate or ejection fraction were significantly less pronounced. Similar end-diastolic abnormalities occurring mainly in patients with coronary artery disease (CAD) have been shown in noninvasive recordings obtained by pressure transducer placed over the point of maximal LV beat (pressocardiograms). Specifically, the amplitude of the A wave to total excursion of pressocardiogram showed a similar high-magnitude increase after dynamic or handgrip exercise in average by 60 to 142% of baseline; however, changes in pressocardiographic relaxation time indexes were only slightly abnormal. A well-defined “ischemic pattern” of pressocardiographic diastolic changes with handgrip, showed a high prevalence in CAD patients. The assessment of diastolic changes in the presence of handgrip-inducible ischemia using noninvasive pressure transducers might provide after further studies a simple complementary diagnostic tool to assist in identification of patients with atypical or asymptomatic CAD.