Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude alternative causes of left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. A significant proportion of DCM cases have an underlying genetic or inflammatory basis. Measurement of LV size and ejection fraction remain central to diagnosis, risk stratification, and treatment, but other aspects of cardiac remodeling inform prognosis and carry therapeutic implications. Assessment of myocardial fibrosis predicts both risk of sudden cardiac death and likelihood of LV functional recovery, and has significant potential to guide patient selection for cardioverter-defibrillator implantation. Detailed mitral valve assessment is likely to assume increasing importance with the emergence of percutaneous interventions for functional mitral regurgitation. Detection of pre-clinical DCM could substantially reduce morbidity and mortality by allowing early instigation of cardioprotective therapy.

Although having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.

ObjectivesCardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality.BackgroundProgressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis.MethodsIn a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up.ResultsiECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m2 vs. 16.1 ± 3.2 ml/m2 in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m2; 51% of patients), extracellular expansion (iECV ≥22.5 ml/m2; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups. Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009).ConclusionsCMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis. This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement. (The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936)

Background-Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Methods and Results-Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr 1 )apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all PϽ0.0001). Vasodilatation to acetylcholine (Pϭ0.01) but not apelin (Pϭ0.3) or sodium nitroprusside (Pϭ0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all PϽ0.05). Systemic infusions of (Pyr 1 )apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all PϽ0.01) but increased heart rate only in control subjects (PϽ0.01). Conclusions-Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure. (Circulation.

Background— To assess cardiovascular actions of APJ agonism during prolonged (Pyr 1 )apelin-13 infusion and renin–angiotensin system activation. Methods and Results— Forty-eight volunteers and 12 patients with chronic stable heart failure attended a series of randomized placebo–controlled studies. Forearm blood flow, cardiac index, left ventricular dimensions, and mean arterial pressure were measured using bilateral venous occlusion plethysmography, bioimpedance cardiography, transthoracic echocardiography, and sphygmomanometry, respectively, during brief local (0.3–3.0 nmol/min) and systemic (30–300 nmol/min) or prolonged systemic (30 nmol/min) (Pyr 1 )apelin-13 infusions in the presence or absence of renin–angiotensin system activation with sodium depletion or angiotensin II coinfusion. During sodium depletion and angiotensin II coinfusion, (Pyr 1 )apelin-13–induced vasodilatation was preserved ( P <0.02 for both). Systemic intravenous (Pyr 1 )apelin-13 infusion increased cardiac index, whereas reducing mean arterial pressure and peripheral vascular resistance index ( P <0.001 for all) irrespective of sodium depletion or angiotensin II (0.5 ng/kg per minute) coinfusion ( P >0.05 for all). Prolonged 6-hour (Pyr 1 )apelin-13 infusion caused a sustained increase in cardiac index with increased left ventricular ejection fraction in patients with chronic heart failure (ANOVA; P <0.001 for all). Conclusions— APJ agonism has sustained cardiovascular effects that are preserved in the presence of renin–angiotensin system activation or heart failure. APJ agonism may hold major promise to complement current optimal medical therapy in patients with chronic heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00901719, NCT00901888, NCT01049646, NCT01179061.

Apelin, the endogenous ligand for the G-protein-coupled APJ receptor, is emerging as a key hormone in cardiovascular homoeostasis. It is expressed in a diverse range of tissues with particular preponderance for the cardiovascular system, being found in both the heart and vasculature. Apelin is the most potent in vitro inotrope yet identified and causes endothelium- and nitric oxide-dependent vasodilatation. It also appears to have a role in lipid and glucose metabolism as well as fluid homoeostasis. One of the key emerging features of the apelin--APJ system is its interaction with the renin-angiotensin system with the respective receptors sharing marked sequence homology, forming heterodimers, and mediating opposing physiological actions. To date, both preclinical and limited clinical studies suggest that the apelin--APJ system may have an important role in the pathogenesis of heart failure. Although the apelin--APJ system is downregulated, the inotropic actions of apelin persist and are enhanced in failing hearts without inducing ventricular hypertrophy. In combination with its interaction with the renin-angiotensin system, APJ agonism may provide a new therapeutic target in the treatment of acute and chronic heart failure. In this review, we highlight key aspects of the apelin--APJ system in health and disease, and consider its translational and therapeutic potential. The diverse actions of the apelin--APJ system have implications for understanding the pathophysiology of, and development of treatments for, several major cardiovascular diseases.

Autonomic cardiovascular function is impaired in IBS, manifest as attenuated cardio-vagal tone, and relative sympathetic excess during stimulated conditions.

Physical examination of the cardiovascular system is central to contemporary teaching and practice in clinical medicine. Evidence about its value focuses on its diagnostic accuracy and varies widely in methodological quality and statistical power. This makes collation, analysis, and understanding of results difficult and limits their application to daily clinical practice. Specific factors affecting interpretation and clinical application include poor standardisation of observers' technique and training, the study of single signs rather than multiple signs or signs in combination with symptoms, and the tendency to compare physical examination directly with technological aids to diagnosis rather than explore diagnostic strategies that combine both. Other potential aspects of the value of physical examination, such as cost effectiveness or patients' perceptions, are poorly studied. This review summarises the evidence for the clinical value of physical examination of the cardiovascular system. The best was judged to relate to the detection and evaluation of valvular heart disease, the diagnosis and treatment of heart failure, the jugular venous pulse in the assessment of central venous pressure, and the detection of atrial fibrillation, peripheral arterial disease, impaired perfusion, and aortic and carotid disease. Although technological aids to diagnosis are likely to become even more widely available at the point of care, the evidence suggests that further research into the value of physical examination of the cardiovascular system is needed, particularly in low resource settings and as a potential means of limiting inappropriate overuse of technological aids to diagnosis.