Heart Failure Reviews

Heart failure (HF) is associated with a high morbidity and mortality in the Western World. Our knowledge of the epidemiology, pathophysiology, and therapy has improved dramatically during the last 20 years. Pharmacological treatment, as it stands today, is a combination of preventive and symptomatic strategies. The mainstay life-saving drugs are angiotensin-converting enzyme inhibitors and β-blockers. Additional benefits are obtained when angiotensin-receptor blockers or aldosterone antagonists are added. Digitalis and/or diuretics are useful for symptom reduction. In addition, combination therapy with hydralazine and isosorbide dinitrate is recommended in African Americans.

TakoTsubo cardiomyopathy (TCM) is a unique type of reversible cardiomyopathy that is precipitated by a stressful emotional or physical event. The increasing incidence is due to the greater use of emergency coronary angiography, newer cardiac biomarkers together with more sensitive cardiac imaging techniques. Few case reports have documented how TCM can present with malignant arrhythmias such as torsades de pointes caused by the repolarisation abnormalities or QTc prolongation. Although TCM is usually considered a benign reversible condition, its associated arrhythmic risk is increasingly recognised. TCM often presents as an acute coronary syndrome with unobstructed coronary arteries at angiography. In this patient population, cardiac magnetic resonance (CMR) is a useful tool to establish a differential diagnosis, discriminating TCM from acute myocarditis and myocardial infarction with spontaneous recanalisation. CMR is becoming a promising new diagnostic modality in risk stratifying patients with potential higher arrhythmic risk.

Secondary hyperparathyroidism in heart failure is a consequence of renin–angiotensin–aldosterone activation, chronic hyperaldosteronism, and loop diuretic usage, resulting in calcium excretion. The result is an inflammatory state with adverse effects on myocardial remodeling and systemic complications. Recent literature has suggested that elevated parathyroid hormone predicts adverse outcomes in patients with heart failure independent of serum calcium and phosphate, vitamin D deficiency, and renal insufficiency. Parathyroid hormone has been correlated with elevated brain natriuretic peptide levels, an established biomarker of heart failure severity. There are several limitations to the utilization of parathyroid hormone as a biomarker for heart failure, and further prospective studies need to be conducted to assess the value of multiple parathyroid hormone measurements over time and elucidate the role of parathyroid hormone in diastolic dysfunction. Pending further validation, there is promise for parathyroid hormone as a complementary biomarker in heart failure.

The cardiomyocyte membrane cytoskeleton consists of the costameric proteins that mediate force transduction from the cell to the extracellular matrix, and a sub-membrane network composed of dystrophin and associated proteins. Studies of the precise cellular distribution of dystrophin and of the consequences of genetic mutations leading to abnormal expression of the dystrophin molecule, as occurs in Duchenne and Becker's muscular dystrophies, highlight potential functional roles of this sub-membrane protein complex in cardiomyocytes. Detailed investigation of dystrophin distribution using the complementary cell imaging techniques of immunoconfocal microscopy and freeze-fracture cytochemistry at the electron-microscopical level show that, in contrast to rat cardiomyocytes, the dystrophin network in human cardiomyocytes is locally enriched at costameres. Thus located, the dystrophin network appears to have a mechanical role, involving stabilization of the peripheral plasma membrane during the repetitive distortion associated with cardiac contraction and, in the human myocyte, contributing to lateral force-transduction. Evidence from animal models of muscular dystrophy and from investigation of the interactions of the sub-membrane cytoskeleton with other membrane-associated proteins including ion channels, receptors and enzymes, further suggests a role for dystrophin in organization and regulation of membrane domains. The relative preservation of the membrane cytoskeleton in non-dystrophic dilated cardiomyopathy and in ischemic cardiomyopathy, conditions in which the myocyte contractile apparatus and internal desmin-based cytoskeleton are commonly disrupted, emphasizes the vital role of the membrane cytoskeleton in cell survival. Continued cardiomyocyte survival despite loss of contractile protein organization has implications in the potential for reversibility of left ventricular remodeling that can be achieved in the clinical setting.

Echocardiography plays an important role in patient assessment before cardiac resynchronization therapy (CRT) and can monitor many of its mechanical effects in heart failure patients. Encouraged by the highly variable individual response observed in the major CRT trials, echocardiography-based measurements of mechanical dyssynchrony have been extensively investigated with the aim of improving response prediction and CRT delivery. Despite recent setbacks, these techniques have continued to develop in order to overcome some of their initial flaws and limitations. This review discusses the concepts and rationale of the available echocardiographic techniques, highlighting newer quantification methods and discussing some of the unsolved issues that need to be addressed.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

The aetiology of pericardial effusion has been generally assessed by clinical work-up only, which leaves a large cohort of patients with “idiopathic” effusions virtually undiagnosed. In accordance with the ESC guidelines, this contribution intends to change this attitude. After therapeutic or diagnostic pericardiocentesis of 259 patients with large to moderate pericardial effusions, pericardial fluid, epicardial and pericardial biopsies, and blood samples were analysed by PCR for cardiotropic microbial agents. Cytology, histology, immunohistology of tissue and fluids and laboratory tests were performed. Of the 259 patients, 35 % suffered from an autoreactive aetiology, 28 % suffered from a malignant and 14 % from an infectious cause. Investigating all samples by PCR, we identified viral genomes in 51 (19.7 %) patients, parvovirus B19 (B19 V) being identified in 25 and Epstein–Barr virus (EBV) in 19 cases. In patients with a sole infectious aetiology (n = 36), B19 V was detected in 21 and EBV in 10 cases. When differentiating with regard to the material investigated for the presence of cardiotropic viruses, parvovirus B19 was most often detected in the epicardium and EBV was most frequently detected in the pericardial fluid independent from the final diagnostic categorisation. Bacterial cultures including tests for tuberculosis were all negative. Molecular techniques improve sensitivity, specificity and diagnostic accuracy for the underlying aetiology in pericarditis patients with effusion. The identification of specific viral signatures will help to understand pathogenetic mechanisms in pericarditis and allow to tailor an adequate therapy beyond antiphlogistic treatment.

Coronary atherosclerosis is the most important primary etiologic factor predisposing to the development of heart failure. The mechanisms by which coronary atherosclerosis lead to heart failure likely involve the initial development of regional myocardial dysfunction, later progressing to global ventricular failure and symptomatic congestive disease. A variety of imaging strategies have been investigated for their value in identifying and characterizing markers of atherosclerosis in the effort to detect early cardiac disease. Non-invasive imaging techniques for assessing anatomic or functional manifestations of atherosclerosis include carotid ultrasonography, coronary computed tomography, cardiovascular magnetic resonance imaging, brachial artery reactivity testing, and the ankle-brachial index. Many of these imaging methods are shown to have accuracy, reliability, and the potential to add value to an office-based cardiovascular risk assessment. Further development of such imaging methods could facilitate early intervention in the development of myocardial dysfunction while enhancing our understanding of the natural course of atherosclerotic disease.

Older people often suffer from multiple diseases. Therefore, universal cross-disease outcomes (e.g. functional status, quality of life, overall survival) are more relevant than disease-specific outcomes, and a range of potential outcomes are needed for medical decision-making. To assess how patient-relevant outcomes have penetrated randomized controlled trials (RCTs), reporting of these outcomes was reviewed in heart failure trials that included patients with multimorbidity. We systematically reviewed RCTs (Jan 2011–June 2012) and evaluated reported outcomes. Heart failure was chosen as condition of interest as this is common among older patients with multimorbidity. The main outcome was the proportion of RCTs reporting all-cause mortality, all-cause hospital admission, and outcomes in four domains of health, i.e. functional, signs and symptoms, psychological, and social domains. Of the 106 included RCTs, 50 (47 %) reported all-cause mortality and cardiovascular mortality and 29 (27 %) reported all-cause hospitalization and cardiovascular hospitalization. Of all trials, 68 (64 %) measured outcomes in the functional domain, 80 (75 %) in the domain of signs and symptoms, 65 (61 %) in the psychological domain, and 59 (56 %) in the social domain. Disease-specific instruments were more often used than non-disease-specific instruments. This review shows increasing attention for more patient-relevant outcomes; this is promising and indicates more awareness of the importance of a variety of outcomes desirable for patients. However, patients’ individual goal attainments were universally absent. For continued progress in patient-centred care, efforts are needed to develop these outcomes, study their merits and pitfalls, and intensify their use in research.