A case of arrhythmogenic right ventricular cardiomyopathy with biventricular involvement.

We reported a case of a young adult male aged 18 years admitted in our institution for syncope during a basketball match. No previous symptoms were reported. Electrocardiogram (ECG) showed T-wave inversion in the anterior leads and an incomplete right bundle branch block. Surprisingly, a complete echocardiographic evaluation demonstrated the presence of severe right ventricular enlargement with significant wall motion abnormalities, apical aneurysm and reduced systolic function. Cardiac Magnetic Resonance was pathognomonic for a fibro-fatty replacement of both ventricles. We decided for a subcutaneous defibrillator implantation and, after inducing a ventricular fibrillation to test the device status, epsilon wave appeared on the ECG. This clinical scenario depicted an advanced arrhythmogenic right ventricular cardiomyopathy at its first clinical manifestation.

Between risk charts and imaging: how should we stratify cardiovascular risk in clinical practice?

Cardiovascular (CV) risk prediction has a central role in primary CV prevention. Several risk charts have been developed in the attempt to identify subjects at risk who might benefit from more aggressive interventions. However, risk charts show main limitations and they remain underutilized in general practice. The addition of novel risk markers has substantially failed to improve risk charts discrimination power. Imaging has recently gained relevance in CV risk stratification for its ability to detect subclinical atherosclerosis. Although extending non-invasive imaging to all asymptomatic middle-aged people is currently not recommended, its progressive spread may provide information on preclinical atherosclerosis and detection of de facto initial disease might overcome some limitations of conventional risk stratification charts.

Prognostic implications of renal dysfunction in patients hospitalized with heart failure: data from the last decade of clinical investigations.

Numerous studies over the last decade have demonstrated that renal dysfunction and worsening renal function (WRF) are common in patients hospitalized for heart failure (HHF) and appear to be associated with poor in-hospital and post-discharge outcomes. Unfortunately, its etiology has not been completely understood, and its prediction during hospitalization remains challenging. The evaluation of renal impairment during hospitalization should take into consideration the underlying renal substrate (e.g., predisposing clinical comorbidities such as diabetes and hypertension), initiating mechanisms (e.g., in-hospital therapies such as diuretics), and amplifying factors (neurohormonal and hemodynamic profile changes). Various patterns of WRF may have different prognostic implications and may require different therapeutic approaches. WRF may be initially classified by duration (transient vs. persistent) and by etiology (elevated venous pressures vs. arterial underfilling). Other critical contributing factors during hospitalization include progressive left ventricular dysfunction, neurohormonal activation, and medications. Transient WRF as a result of aggressive therapy targeting congestion may not be associated with poor outcomes. Persistent WRF seen in patients with severe hemodynamic derangements may be associated with poor post-discharge prognosis. Future investigations must clarify the pathophysiological correlates of various patterns of WRF. To date, there is an unmet clinical need to achieve adequate control over congestion while preserving renal function in HHF patients. Thus, the aim of this review is to provide an in-depth and critical interpretation of the available data on the prognostic importance of RD and WRF during hospitalization in an effort to improve HF management.

High-density lipoprotein levels and risk of cardiovascular events: a review.

High-density lipoprotein cholesterol (HDL-C) is a strong and independent predictor of major cardiovascular events in a wide range of patients. The relationship between HDL-C cholesterol and cardiovascular risk appears to be linear, continuous, negative and independent of other risk factors such as blood pressure, smoking and BMI. In addition, the inverse relationship between HDL-C and cardiovascular events does not depend on low-density lipoprotein cholesterol (LDL-C) levels, so a substantial residual cardiovascular risk is maintained also in individuals with LDL-C levels below the target recommended by scientific guidelines. Furthermore, a strong relationship among HDL-C levels, progression of atherosclerosis and risk of cardiovascular diseases has been also demonstrated. Treatments that increase HDL-C levels have been shown to be effective in reducing incidence of cardiovascular diseases both in primary and secondary prevention settings. However, proof that increasing HDL-C levels by pharmacological treatment is able to confer a reduction in major cardiovascular outcomes independent of changes in LDL-C or triglycerides levels is not completely defined. Among currently available compounds, statins do not seems to have a sufficient effect on HDL-C profile. Studies on fibrates have shown inconclusive results. Although niacin has been demonstrated to reduce the incidence of major cardiovascular events paralleling the regression of atherosclerosis, significant side-effects still limit its use. The potential benefit of cholesterol ester transfer protein inhibition is still under investigation. The combination therapy of fibrates with statins is also controversial. Thus, despite the potentially favorable effect of raising HDL-C levels, the available guidelines still do not consider HDL-C levels as a specific target for therapy. Further studies are needed to assess the role of new compounds to raise HDL-C levels or modify HDL composition and functionality.

Congestion as a therapeutic target in acute heart failure syndromes.

This review begins by discussing the importance of clinical congestion as the dominant presenting manifestation of acute heart failure syndromes (AHFS). The pathophysiology of the cardiorenal syndrome is reviewed, including its relationship to the use of current therapy, that is, loop diuretics. The review then summarizes results from recent clinical trials evaluating therapy for AHFS, with a focus on those studies investigating ultrafiltration and vasopressin antagonists, and also, but more briefly, vasodilators and inotropic agents. Possible reasons for the success and failure of various therapeutic strategies directed at the congested state are discussed. The review concludes with recommendations for possible new strategies and specific investigations designed to benefit from the lessons learned from both the recent successful trials and the more numerous failures.

Diuretic therapy in heart failure: current controversies and new approaches for fluid removal.

Hospitalization for heart failure is a major health problem with high in-hospital and postdischarge mortality and morbidity. Non-potassium-sparing diuretics (NPSDs) still remain the cornerstone of therapy for fluid management in heart failure despite the lack of large randomized trials evaluating their safety and optimal dosing regimens in both the acute and chronic setting. Recent retrospective data suggest increased mortality and re-hospitalization rates in a wide spectrum of heart failure patients receiving NPSDs, particularly at high doses. Electrolyte abnormalities, hypotension, activation of neurohormones, and worsening renal function may all be responsible for the observed poor outcomes. Although NPSD will continue to be important agents to promptly resolve signs and symptoms of heart failure, alternative therapies such as vasopressine antagonists and adenosine blocking agents or techniques like veno-venous ultrafiltration have been developed in an effort to reduce NPSD exposure and minimize their side effects. Until other new agents become available, it is probably prudent to combine NPSD with aldosterone blocking agents that are known to improve outcomes.

Aldosterone receptor blockade in patients with left ventricular systolic dysfunction following acute myocardial infarction.

Left ventricular systolic dysfunction (LVSD) is a common complication of acute myocardial infarction (AMI) that occurs in approximately 30% of post-AMI patients, and results in a threefold increase in in-hospital and 6-month mortality, regardless of type of AMI. Post-AMI care has evolved to include early reperfusion, antiplatelet therapy, hydroxymethylglutaryl coenzyme A reductase inhibitors (stains), beta blockers, angiotentsin-converting enzyme inhibitors, and angiotensin receptor blockers. Despite these therapies, however, there is still an excess of sudden cardiac death (SCD), especially in patients with severe LVSD and in the first 30 days post-AMI. Aldosterone has been shown to be elevated in patients with post-AMI LVSD and to have deleterious effects on the myocardium, including endothelial dysfunction, collagen deposition, inflammation, apoptosis, and autonomic instability, leading to left ventricular remodeling and SCD. Aldosterone blockade with eplerenone has been shown to reduce mortality even in the presence of optimal post-AMI therapy in patients with post-AMI LVSD. Despite this, eplerenone is underutilized in real-world clinical practice. Care must be taken to follow renal function and potassium balance in patients treated with eplerenone.

Review of current and investigational pharmacologic agents for acute heart failure syndromes.

Acute heart failure syndromes (AHFS) are a major public health problem and present a therapeutic challenge to clinicians. Commonly used agents in the treatment of AHFS include diuretics, vasodilators (eg, nitroglycerin, nitroprusside, nesiritide), and inotropes (eg, dobutamine, dopamine, milrinone). Patients admitted to hospital with AHFS and low cardiac output state (AHFS/LO) represent a subgroup with very high inhospital and postdischarge mortality rates. Most of these patients require intravenous inotropic therapy. However, the use of current intravenous inotropes has been associated with risk for hypotension, atrial and ventricular arrhythmias, and possibly increased postdischarge mortality, particularly in those with coronary artery disease. Consequently, there is an unmet need for new agents to safely improve cardiac performance (contractility and/or active relaxation) in this patient population. This article reviews a selection of current and investigational agents for the treatment of AHFS, with a main focus on the high-risk patient population with AHFS/LO.

Hyponatremia in acute heart failure syndromes: a potential therapeutic target.

Mild hyponatremia is common in patients hospitalized for worsening heart failure, and it is a major predictor of post-discharge mortality and morbidity irrespective of left ventricular ejection fraction. Recent data also suggest that standard therapy for heart failure does not improve or normalize serum sodium concentration during hospitalization. There are conclusive data that vasopressin antagonists improve or normalize serum sodium in this patient population. However, it is not known if this improvement or normalization in serum sodium is associated with an improvement in post-discharge outcomes. Future trials with vasopressin antagonists in patients hospitalized with worsening heart failure and hyponatremia are in order.

Congestion is an important diagnostic and therapeutic target in heart failure.

Most hospitalizations for acute heart failure syndrome (AHFS) are related to clinical congestion as a result of high left ventricular diastolic pressure (LVDP) rather than to low cardiac output. Patients frequently develop "hemodynamic congestion" (high LVDP) several days to weeks before the onset of symptoms and signs of clinical congestion. By the time symptoms and signs are evident, patients generally require hospitalization. High LVDP increases left ventricular (LV) wall stress and possibly contributes to neurohormonal activation and LV remodeling, thereby contributing to progression of heart failure (HF). Congestion is a major predictor of both morbidity and mortality in HF. Some methods may aid in the evaluation of silent hemodynamic congestion, but these assessment tools are generally underused. Identification of hemodynamic congestion, before the clinical manifestations appear, may potentially prevent hospitalization and slow the progression of HF by allowing life-saving interventions to be implemented sooner.