Current Cardiology Reviews (v.11, #1)

Preface by Jian'an Wang (1-1).

Stage A: Can Heart Failure Be Prevented? by Ilya M. Danelich, Brent N. Reed, Carla A. Sueta (4-9).
Heart failure (HF) is an epidemic associated with significant morbidity and mortality, affecting over 5 millionpeople in the United States and 1-2% of the population worldwide. Observational studies have suggested that a healthylifestyle can reduce HF risk. Although no clinical trials have targeted the prevention of HF as a primary endpoint, manyhave evaluated outcomes associated with the development of symptomatic disease (i.e., progression to HF, HF hospitalizationor death) as secondary endpoints. Blood pressure treatment represents the most effective strategy in preventingheart failure; each 5 mm Hg decrease in systolic blood pressures reduces the risk of HF development by 24%. Thiazidediuretics appear to be the most efficacious agents in patients with hypertension. Angiotensin converting enzyme inhibitorsand angiotensin-II receptor blockers are first line agents for patients with chronic atherosclerosis, diabetes, or chronic kidneydisease. Beta blockers appear less effective as single agents and cardioselective agents are preferred. Calcium channelblockers, specifically non-dihydropyridines, should be avoided and alpha blockers should not be used to reduce HF risk.

Genetics and Heart Failure: A Concise Guide for the Clinician by Cecile Skrzynia, Jonathan S. Berg, Monte S. Willis, Brian C. Jensen (10-17).
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 multifactorialcases, but more direct and profound in the case of familial dilated cardiomyopathy. Early studies of genetic riskfor 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 therapeuticresponse to neurohormonal antagonists. Regardless, each variant individually confers a relatively modest increasein 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 casespreviously considered to be “idiopathic”. Up to 50% of dilated cardiomyopathy cases without other cause likely are due toa heritable genetic mutation. Such mutations typically are found in genes encoding sarcomeric proteins and are inheritedin an autosomal dominant fashion. In recent years, rapid advances in sequencing technology have improved our ability todiagnose familial dilated cardiomyopathy and those diagnostic tests are available widely. Optimal care for the expandingpopulation 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 Bheart 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 andmortality. 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 clinicaloutcomes among patients with ALVD. Although evidence to support the use of beta blockers in this setting has beenprimarily derived from retrospective studies or subgroup analyses, they are generally recommended in most patients withALVD, especially those with ischemic etiology. Statins are associated with improvements in both major adverse cardiovascularevents and heart failure events among patients with a history of acute myocardial infarction. Finally, in eligiblepatients, placement of an automatic implantable cardioverter defibrillator (ICD) has been associated with reduced mortalityrates among those with ALVD due to ischemic cardiomyopathy, and some subgroups may derive benefit from cardiacresynchronization therapy or biventricular pacing.

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

Device Therapies: New Indications and Future Directions by Prabhat Kumar, Jennifer D. Schwartz (33-41).
Implantable cardioverter-defibrillator (ICDs), cardiac resynchronization (CRT) and combination (CRT-D) therapyhave 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 designand implantation have included progressive miniaturization and increasing battery life of the device, optimization of responseto CRT, and minimizing inappropriate device therapy. Additionally, better definition of the population with thegreatest benefit is an area of active research.

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with highrates of morbidity and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, cliniciansare often confronted with these patients and yet have little guidance on how to effectively diagnose and managethem. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolicdysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and considerinvasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosisof HFpEF; (4) elevated pulmonary artery systolic pressure on echocardiography in the presence of a normal ejectionfraction should prompt consideration of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patientswith unexplained dyspnea or exercise tolerance; (6) all patients with HFpEF should be systematically evaluated for thepresence 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 evaluatingand treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients withHFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies.

Acute Decompensated Heart Failure Update by John R. Teerlink, Khalid Alburikan, Marco Metra, Jo E. Rodgers (53-62).
Acute decompensated heart failure (ADHF) continues to increase in prevalence and is associated with substantialmortality and morbidity including frequent hospitalizations. The American Heart Association is predicting that morethan eight million Americans will have heart failure by 2030 and that the total direct costs associated with the disease willrise from $21 billion in 2012 to $70 billion in 2030. The increase in the prevalence and cost of HF is primarily the resultof shifting demographics and a growing population. Although many large, randomized, controlled clinical trials have beenconducted in patients with chronic heart failure, it was not until recently that a growing number of studies began to addressthe management of ADHF. It is the intent of this review to update the clinician regarding the evaluation and optimalmanagement of ADHF.

Advanced Therapies For End-Stage Heart Failure by Jason N. Katz, Sarah B. Waters, Ian B. Hollis, Patricia P. Chang (63-72).
Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantationand 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 demandcontinues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior totransplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularlyfor the non-operative patient, intravenous inotropes can be utilized for symptom control. Regardless of the treatmentsconsidered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualizedcare. While survival is important, most patients covet quality of life above all outcomes. An often overlookedcomponent is the patient's control over the dying process. It is vital that clinicians make goals-of-care discussions a prioritywhen seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitatesthese difficult conversations to ensure that all patient needs are ultimately met.

Pulmonary Hypertension: Types and Treatments by Lisa J. Rose-Jones, Vallerie V. Mclaughlin (73-79).
Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leadsto restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failureonce 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 andexercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-basedtreatment options with pulmonary vasodilators are available for those with PAH and should be employed early. It is essentialthat patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially bedangerous if employed in the wrong clinical scenario.

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence by Amanda E. Pruett, Amanda K. Lee, J. Herbert Patterson, Todd A. Schwartz, Jana M. Glotzer, Kirkwood F. Adams, Jr. (80-89).
Optimizing management of patients with heart failure remains quite challenging despite many significant advancesin drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supportsmultiple 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 implementdue to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeuticchoices. Natriuretic peptides provide additional information of significant clinical value in the diagnosis and estimation ofrisk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides inheart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatmentand achieve better outcomes in this syndrome. Initial, innovative, proof-of-concept studies have provided encouragingresults 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 growingpublic health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due tothis syndrome is critical.

Left ventricular (LV) pressure curve shows early high-magnitude changes in the presence of induced ischemia. Adramatic rise in LV and left atrial end-diastolic pressures occurs within seconds to minutes in the presence of ischemiainduced by dynamic or handgrip exercise as well as pacing of 38 to 183% and during short coronary balloon occlusion of 32to 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 innoninvasive 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-magnitudeincrease after dynamic or handgrip exercise in average by 60 to 142% of baseline; however, changes inpressocardiographic relaxation time indexes were only slightly abnormal. A well-defined “ischemic pattern” ofpressocardiographic 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 pressuretransducers might provide after further studies a simple complementary diagnostic tool to assist in identification ofpatients with atypical or asymptomatic CAD.