In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .).

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation–contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

Background-Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. Methods and Results-The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4Ϯ11.9 to 125.3Ϯ12.0 mm Hg Pϭ0.02 versus placebo) and diastolic (from 73.2Ϯ6.9 to 75.4Ϯ7.9 mm Hg Pϭ0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. Conclusions-This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651. (Circulation. 2010;122:1789-1796.) Key Words: acetaminophen Ⅲ blood pressure Ⅲ coronary disease Ⅲ endothelium T he Food and Drug Administration has mandated a "black-box warning" for cyclooxygenase-2 (COX-2) selective inhibitors and nonselective nonsteroidal antiinflammatory drugs (NSAIDs) in view of the potential of these agents to increase adverse cardiovascular outcomes. 1 Whereas hundreds of millions of patients worldwide continue to require pain-relieving therapy to maintain an acceptable quality of life, the uncertainty around the cardiovascular safety of NSAIDs and COX-2 inhibitors leaves practitioners and patients with difficult management decisions. Current guidelines recommend acetaminophen as the first-line analgesic of choice for the management of chronic pain despite weaker analgesic potency on the assumption of its greater cardiovascular safety, particularly in patients at high cardiovascular risk or with established cardiovascular disease. 1 Editorial see p 1779 Clinical Perspective on p 1796One of the most commonly used drugs worldwide, a major ingredient in numerous cold and flu medications, and a...

All three definitions of super-response are highly predictive for a favourable outcome after CRT. However, even patients with pronounced reverse left ventricular remodelling experience appropriate ICD discharges during follow-up.