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The Food and Drug Administration (FDA) last approved a new oral drug (hydralazine–isosorbide dinitrate) for patients with heart failure and a reduced ejection fraction in 2005 — and this drug was recommended only for self-identified black patients who continued to have symptoms despite evidence-based treatment. 1 The angiotensin-receptor blocker eplerenone was approved for the treatment of heart failure in 2003. (In 2012, the European Medicines Agency approved ivabradine, which has not received FDA approval.) Now, a novel drug, LCZ696, a dual inhibitor of angiotensin II receptor and neprilysin, may prove to be the first disruptive agent to the heart-failure treatment algorithm, . . .

Acute heart failure (AHF) is a syndrome defined as the new onset (de novo heart failure (HF)) or worsening (acutely decompensated heart failure (ADHF)) of symptoms and signs of HF, mostly related to systemic congestion. In the presence of an underlying structural or functional cardiac dysfunction (whether chronic in ADHF or undiagnosed in de novo HF), one or more precipitating factors can induce AHF, although sometimes de novo HF can result directly from the onset of a new cardiac dysfunction, most frequently an acute coronary syndrome. Despite leading to similar clinical presentations, the underlying cardiac disease and precipitating factors may vary greatly and, therefore, the pathophysiology of AHF is highly heterogeneous. Left ventricular diastolic or systolic dysfunction results in increased preload and afterload, which in turn lead to pulmonary congestion. Fluid retention and redistribution result in systemic congestion, eventually causing organ dysfunction due to hypoperfusion. Current treatment of AHF is mostly symptomatic, centred on decongestive drugs, at best tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. As a consequence, AHF is still associated with high mortality and hospital readmission rates. There is an unmet need for increased individualization of in-hospital management, including treatments targeting the causative factors, and continuation of treatment after hospital discharge to improve long-term outcomes. Acute heart failure (AHF) is a syndrome characterized by signs and symptoms of heart failure (typically systemic congestion) that occurs in the presence of an underlying cardiac dysfunction (previously diagnosed, undiagnosed or new-onset) and precipitating factors. AHF is associated with high mortality and hospital readmission rates.

Leading cardiologists discuss PARADIGM-HF, a trial of angiotensinneprilysin inhibition versus enalapril in advanced heart failure. Leading cardiologists discuss PARADIGM-HF, a trial of angiotensin–neprilysin inhibition versus enalapril in advanced heart failure. View the video of this roundtable discussion and contribute your comments.

Sudden cardiac death (SCD) is a common cause of death in the general population, occurring in 300,000 to 350,000 people in the United States alone. Currently, there are no data supporting implantable cardioverter-defibrillator therapy in patients who underwent orthotopic heart transplant (OHT) with low left ventricular ejection fraction (LVEF). In this retrospective study, we included all patients who underwent primary OHT at our institution from 2007 to 2013. We compared the cause of death in patients who underwent OHT and evaluated the correlation of the cause of death and the patients' LVEF. Our objectives were to determine whether patients who underwent OHT with LVEF <35% are at increased risk for SCD compared with those who underwent OHT with normal LVEF. To summarize our results, a total of 345 patients were included in our study (mean age 50 ± 14 years, 68% men). The mean follow-up was 1,260 ± 698 days. Forty patients (11.5%) died >6 months after OHT. Surviving patients had higher LVEF compared with deceased patients (64 ± 7% and 50 ± 24%, respectively, p ≤0.001). In all, 10 (25%) of the deceased patients died suddenly, 9 (23%) from sepsis, and 8 (20%) from malignancy. Of the 11 deceased patients with LVEF ≤35%, 2 patients (18%) died suddenly compared with 9 SCDs among the 29 deceased patients (31%) with LVEF >35% (p = 0.54). In conclusion, patients who underwent OHT who died were more likely to have LVEF <35%, and a quarter of the deceased patients who underwent OHT died suddenly. A reduced LVEF was not associated with an increased risk of SCD.

Cardiac-resynchronization therapy (CRT) received Food and Drug Administration approval for use in selected patients with left ventricular systolic dysfunction in 2001. Since that time, CRT has been embraced as a recommended approach to achieve meaningful clinical improvement in patients who have heart failure with a reduced left ventricular ejection fraction (LVEF) and who continue to have symptoms despite optimal medical therapy. 1 A number of pivotal randomized trials and scores of additional safety and effectiveness trials have consistently shown that CRT improves the LVEF, quality of life, and functional status in symptomatic patients with an LVEF of less than 35% and . . .

Granulomatous diseases are a rare cause of hypercalcemia. The pathogenesis is presumed to be from endogenous production of 1,25-dihydroxyvitamin D by activated macrophages in granulomatous lesions, which harbor the 1 α-hydroxylase enzyme. Herein the first case of hypercalcemia associated with giant cell myocarditis, an unusual type of granulomatous process, is reported. In this case, a patient with giant cell myocarditis had development of progressive heart failure and cardiorenal syndrome that required biventricular support. One year later, hypercalcemia associated with a relatively high 1,25-vitamin D level and a concomitantly suppressed parathyroid hormone level developed in the presence of stage 4 chronic kidney disease. Her other workup of hypercalcemia was unrevealing for vitamin D intoxication and multiple myeloma. Computed tomography of her chest showed no signs of hilar lymphadenopathy. Her calcium levels returned to normal with low-dose steroid therapy and have remained normal following a successful heart transplant. This case illustrates an unusual cause of hypercalcemia thought to be due to extrarenal calcitriol production associated with giant cell myocarditis.

In the United States and Europe, approximately 90% of heart failure hospitalizations are due to symptoms and signs of sodium and fluid excess. Congestion is associated with heart failure progression. Venous congestion, rather than a reduced cardiac output, may be the primary hemodynamic factor driving worsening renal function in patients with acutely decompensated heart failure. According to data from large national registries, approximately 40% of hospitalized heart failure patients are discharged with unresolved congestion, which may contribute to unacceptably high re-hospitalization rates. Diuretics reduce the symptoms and signs of fluid overload, but their effectiveness can be reduced by excess salt intake, underlying chronic kidney disease, renal adaptation to their action, and neurohormonal activation. In addition, the production of hypotonic urine limits the ability of loop diuretics to reduce total body sodium. Ultrafiltration is the mechanical removal of fluid from the vasculature. Hydrostatic pressure is applied to blood across a semipermeable membrane to separate isotonic plasma water from blood. Because solutes in blood freely cross the semipermeable membrane, fluid can be removed without causing significant changes in the serum concentration of electrolytes and other solutes. Relatively small, mostly single-center clinical studies of ultrafiltration have shown that removal of isotonic fluid may relieve symptoms of congestion and restore diuretic responsiveness in patients with diuretic resistance. These studies have also shown a favorable effect on neurohormonal activation. When compared with intravenous diuretics, ultrafiltration similarly changed dyspnea scores but reduced re-hospitalizations (28 of 87 patients (32%) versus 16 of 89 patients (18%), P  < 0.037) in a randomized controlled trial of patients with decompensated heart failure. Future larger controlled clinical trials should evaluate further the effect of ultrafiltration on patients’ outcomes, including survival.

The chairs of the ESC Task Force, the chairs of the ACC/AHA/HFSA Writing Committee, and an independent opinion leader in the field offer their expert insight into the new guidelines for the management of heart failure, highlighting what is new, what the main differences are between the two sets of guidelines, and what steps should be taken to improve the guidelines in future updates. Heart failure (HF) is a global epidemic affecting millions of individuals worldwide. Although important progress has been made in the management of HF, this condition remains a common cause of morbidity and death. Since the publication of the previous sets of guidelines for the management of HF, new diagnostic and therapeutic options for HF have emerged. Now, both the ESC and the ACC/AHA/HFSA have simultaneously published an update of their guidelines incorporating, among others, recommendations for the use of new pharmacological therapies for the treatment of HF. For this Viewpoint article, we have asked the chairs of the ESC Task Force, the chairs of the ACC/AHA/HFSA Writing Committee, and an independent opinion leader in the field to offer their expert insight into the new guidelines, highlighting what is new, what the main differences are between the two sets of guidelines, and what steps should be taken to improve the guidelines in future updates.

Urgent heart transplant candidates classified as United Network for Organ Sharing status 1B who require continuous infusions of inotropic agents for hemodynamic stability often have hemodynamic, electrical, or multisystem decompensation. This multicenter trial will study both traditional safety and efficacy parameters and the physiologic mechanisms of benefit of the addition to conventional therapy of nesiritide, a recombinant analog of brain-type natriuretic peptide, in this population. TMAC is a prospective, randomized, parallel, multicenter, double-blind, placebo-controlled study in patients awaiting heart transplantation who meet United Network for Organ Sharing status 1B criteria (N = 120) and receive continuous dobutamine or milrinone through a double-lumen central catheter for at least 3 consecutive days before randomization. Patients will receive standard care and continuous intravenous inotrope therapy plus a 28-day continuous infusion of nesiritide or placebo. There will be up to 6 months of follow-up. Primary efficacy end point will be days alive after treatment without renal, hemodynamic, or electrical worsening at completion. Secondary analyses will evaluate effects on hemodynamics, echocardiographic parameters, endogenous brain-type natriuretic peptide levels, modification of diet in renal disease–calculated glomerular filtration rate, and all-cause and cardiovascular mortality. Two mechanistic substudies will evaluate the effect on iohexol-determined glomerular filtration rate and assess changes in lung mechanics. This investigation will provide key data for clinical profiles of heart transplant candidates bound to inotropic support. It will investigate the efficacy and safety (especially renal) of nesiritide and provide mechanistic insight into benefits of its use for the relief of breathlessness.

Background Acute heart failure (AHF) with reduced left-ventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown. Methods and results A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17–31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7–18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [−6.3 mmHg (95 % CI −7.4 to −5.2 mmHg) and −5.8 mmHg (95 % CI −7.6 to −4.0 mmHg), respectively] and RAP [−2.9 mmHg (95 % CI −3.8 to −2.1 mmHg) and −2.8 mmHg (95 % CI −3.8 to −1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs ( r 2  = 0.90, p  < 0.001). Vasodilators and inotropes had no short-term effect of renal function. Conclusion The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.