Targeting mitochondrial dysfunction with elamipretide.

Although currently employed therapies for heart failure decrease overall mortality and improve patient quality of life temporarily, the disease is known to progress even for patients who receive all guideline-recommended therapies. This indicates that our concise understanding of heart failure and of disease progression is incomplete, and there is a need for new interventions that may augment, or even supplant, currently available options. A literature review reveals that an exciting, novel area of current research is focused on mitochondria, which are uniquely juxtaposed at the sites of both generation of high-energy molecules and initiation of programmed cell death. Elamipretide is being studied both to maintain cellular biogenetics and prevent reactive oxygen species-induced cell damage by targeting and stabilizing the cardiolipin-cytochrome c supercomplex. Thus far, elamipretide has been shown to increase left ventricular ejection fraction in dog models of heart failure with reduced ejection fraction and to prevent left ventricular remodeling in rats. In early-phase clinical trials, elamipretide administration has not resulted in any severe adverse events, and it has shown promising improvements in cardiac hemodynamics at highest doses. Nonetheless, additional studies are necessary to describe the long-term safety and efficacy of elamipretide.

Meta-analysis comparing outcomes of catheter ablation for ventricular arrhythmia in ischemic versus nonischemic cardiomyopathy.

BACKGROUND: Catheter ablation is an effective treatment for ventricular arrhythmia (VA) in ischemic cardiomyopathy (ICM). However, results in non-ICM (NICM) patients are not satisfactory, and studies comparing differences between NICM and ICM are limited. We conducted a meta-analysis of procedural characteristics and long-term outcomes of catheter ablation for VA, comparing results between ICM and NICM. METHODS: Studies in the PubMed, EMBASE, and Cochrane databases were systematically reviewed. Four studies reporting comparison of catheter ablation of VA between ICM and NICM were examined. The Newcastle-Ottawa Scale was used to appraise study quality. A random-effects model with inverse variance method was used for comparisons. RESULTS: Epicardial approach was significantly more undertaken for the NICM group than in the ICM group (odds ratio [OR]: 0.13; 95% confidence interval [CI]: 0.09-0.18; P < .00001). Mean ablation time (P = .54), fluoroscopy time (P = .55), and procedural time (P = .18) did not differ significantly between the ICM and NICM groups. Procedural failure rates (OR: 0.46; 95% CI: 0.24-0.89; P = .02) and VA recurrence rates (risk ratio [RR]: 0.68; 95% CI: 0.46-1.01; P = .06) were significantly higher in the NICM group than in the ICM group. However, all-cause mortality (RR: 1.37; 95% CI: 0.75-2.49; P = .31) did not differ significantly between groups. CONCLUSIONS: Procedural failure and VA recurrence rates were significantly higher in the NICM group, despite significantly more frequent epicardial access. These highlight the limitations of catheter ablation for VA in NICM, given our current knowledge.

Outcomes of Ultrafiltration in community-based hospitals.

OBJECTIVE: We sought to examine outcomes of ultrafiltration in real world community-based hospital settings. BACKGROUND: Ultrafiltration (UF) is an accepted therapeutic option for advanced decompensated heart failure (ADHF). the feasibility of UF in a community hospital setting, by general cardiologists in a start-up program had not been objectively evaluated. METHODS: We retrospectively analyzed the first-year cohort of ADHF patients treated with UF from 10/1/2019 to 10/1/2020, which totaled 30 patients, utilizing the CHF Solutions Aquadex FlexFlow™ System with active UF rate titration. RESULTS: Baseline patient characteristics were similar to RCTs: mean age 63, 73% male; 27% female; 53% Caucasian; 47% African American; 77% had LVEF ≤ 40. The baseline mean serum creatinine (Cr) was 1.84 ±0.62 mg/dL, mean GFR of 36.95 ±9.60 ml/min. HF re-admission rates were not significantly different than prior studies (17.2% at 30 d, 23.3% at 60 d, but in our cohort, per patient HF re-admission rates were reduced significantly by 60 d (0.30 p = 0.017). CONCLUSION: Our analysis showed success with UF in mainstream setting with reproducible results of significant volume loss without adverse renal effect, mitigation of recurrent Hdmissions, and remarkable subjective clinical benefit.

Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in aldosteronism.

Aldosteronism, or chronic elevation in plasma aldosterone (ALDO) (inappropriate for dietary Na(+) intake), is accompanied by an adverse structural remodeling of the heart and vasculature. Herein, we bring forward a new perspective in which parathyroid hormone (PTH) is identified as a crucial mediator of pathologic cardiac remodeling in aldosteronism. Secondary hyperparathyroidism (SHPT) appears because of the marked urinary and fecal losses of Ca(2+) and Mg(2+) that accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia, providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked to restore extracellular Ca(2+) and Mg(2+) homeostasis, elevations in plasma PTH lead to paradoxical intracellular Ca(2+) overloading of diverse tissues. In the case of cardiomyocytes, the excessive intracellular Ca(2+) accumulation involves both cytosolic free and mitochondrial domains with a consequent induction of oxidative stress by these organelles and lost ATP synthesis. The ensuing opening of their inner membrane permeability transition pore (mPTP) accounts for the osmotic swelling and structural degeneration of mitochondria followed by programed cell necrosis. Tissue repair, invoked to preserve the structural integrity of myocardium accounts for a replacement fibrosis, or scarring, which is found scattered throughout the right and left heart; it represents a morphologic footprint of earlier necrosis. Multiple lines of evidence are reviewed that substantiate the PTH-mediated paradigm and the mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis.