Objectives To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced ...decompensated heart failure (ADHF). Background Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. Methods A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine ≥0.3 mg/dl during hospitalization. Results In the study cohort (age 57 ± 14 years, cardiac index 1.9 ± 0.6 l/min/m2 , left ventricular ejection fraction 20 ± 8%, serum creatinine 1.7 ± 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 ± 7 mm Hg vs. 12 ± 6 mm Hg, p < 0.001) and after intensive medical therapy (11 ± 8 mm Hg vs. 8 ± 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Conclusions Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.
Inotropes Francis, Gary S., MD; Bartos, Jason A., MD, PhD; Adatya, Sirtaz, MD
Journal of the American College of Cardiology,
05/2014, Letnik:
63, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Inotropes have been fundamental to resuscitation of acute cardiogenic shock for decades. Heart failure and cardiogenic shock, in severe cases, are syndromes characterized in many patients by a ...reduction in myocardial contractile force. While inotropes successfully increase cardiac output, their use has been plagued by excessive mortality due to increased tachycardia and myocardial oxygen consumption leading to arrhythmia and myocardial ischemia. There is a pressing need for new inotropic agents that avoid these harmful effects. This review describes the mechanism of action and the clinical utility of some of the older inotropic agents, which are still commonly used, and provides an update for physicians on the development of newer inotropic drugs. The field is rapidly changing, and it is likely that new agents will be designed that improve systolic performance without necessarily increasing the myocardial oxygen consumption.
Abstract
Aims
Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute ...myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial.
Methods and results
We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients.
Conclusion
Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs.
Trial registration
Clinicaltrials.gov identifier: NCT01458405.
Abstract Patients undergoing maintenance hemodialysis develop both structural and functional cardiovascular abnormalities. Despite improvement of dialysis technology, cardiovascular mortality of this ...population remains high. The pathophysiological mechanisms of these changes are complex and not well understood. It has been postulated that several non-traditional, uremic-related risk factors, especially the long-term uremic state, which may affect the cardiovascular system. There are many cardiovascular changes that occur in chronic kidney disease including left ventricular hypertrophy, myocardial fibrosis, microvascular disease, accelerated atherosclerosis and arteriosclerosis. These structural and functional changes in patients receiving chronic dialysis make them more susceptible to myocardial ischemia. Hemodialysis itself may adversely affect the cardiovascular system due to non-physiologic fluid removal, leading to hemodynamic instability and initiation of systemic inflammation. In the past decade there has been growing awareness that pathophysiological mechanisms cause cardiovascular dysfunction in patients on chronic dialysis, and there are now pharmacological and non-pharmacological therapies that may improve the poor quality of life and high mortality rate that these patients experience.
The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their ...effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.
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