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.

A Review of the Role of Imaging Modalities in the Evaluation of Viral Myocarditis with a Special Focus on COVID-19-Related Myocarditis.

Viral myocarditis is inflammation of the myocardium secondary to viral infection. The clinical presentation of viral myocarditis is very heterogeneous and can range from nonspecific symptoms of malaise and fatigue in subclinical disease to a more florid presentation, such as acute cardiogenic shock and sudden cardiac death in severe cases. The accurate and prompt diagnosis of viral myocarditis is very challenging. Endomyocardial biopsy is considered to be the gold standard test to confirm viral myocarditis; however, it is an invasive procedure, and the sensitivity is low when myocardial involvement is focal. Cardiac imaging hence plays an essential role in the noninvasive evaluation of viral myocarditis. The current coronavirus disease 2019 (COVID-19) pandemic has generated considerable interest in the use of imaging in the early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related myocarditis. This article reviews the role of various cardiac imaging modalities used in the diagnosis and assessment of viral myocarditis, including COVID-19-related myocarditis.

Hypothyroidism Is Associated With Longer Hospital Stay Following Implantation Of Left Ventricular Assist Device.

BACKGROUND: There has been a steady and consistent rise in the use of left ventricular assist devices in the management of patients with advanced heart failure. Hypothyroidism also remains one of the most common endocrine conditions with a significant impact on the development and overall outcomes of heart failure. The authors analyzed the National Inpatient Sample to evaluate the effect of hypothyroidism on the in-hospital outcomes of patients with end-stage heart failure following the placement of left ventricular assist device. METHODS: The national inpatient sample was queried to identify all adult patients who had LVAD placement from 2004 to 2014. They were subsequently divided into those with hypothyroidism and those without hypothyroidism. The primary outcome was in-hospital mortality. Other outcomes were acute kidney injury, length, and cost of hospitalization. Logistic regression models were created to determine the outcomes of interest. RESULTS: Of 2643 patients in the study, 5.4% had hypothyroidism, and 94.6% did not. The hypothyroid patients were significantly older compared to the non-hypothyroid patients (mean age 58.6 years vs 49.95 years, P-value <.0001). Both groups had similar gender composition. In-hospital mortality was similar across both groups. However, there was a higher incidence of acute kidney injury (AKI) in the hypothyroid group (adjusted odds ratio [aOR 1.83, P-value <.001]). Hypothyroid patients had longer hospital stays (adjusted mean difference [aMD] 5.19, P-value .0001). Hospital charges were also higher in the hypothyroid group. CONCLUSION: This study found that LVAD is associated with longer hospital stay in hypothyroid patients with heart failure.

Outcomes of uninterrupted vs interrupted Periprocedural direct oral Anticoagulants in atrial Fibrillation ablation: A meta-analysis.

BACKGROUND: Studies indicate that uninterrupted anticoagulation (UA) is superior to interrupted anticoagulation (IA) in the periprocedural period during catheter ablation of atrial fibrillation. Still IA is followed in many centers considering the bleeding risk. This meta-analysis compares interrupted and uninterrupted direct oral anticoagulation during catheter ablation of atrial fibrillation. METHODS: A systematic search into PubMed, EMBASE, and the Cochrane databases was performed and five studies were selected that directly compared IA vs UA before ablation and reported procedural outcomes, embolic, and bleeding events. The primary outcome of the study was major adverse cerebro-cardiovascular events. RESULTS: The meta-analysis included 840 patients with UA and 938 patients with IA. Median follow-up was 30 days. Activated clotting time (ACT) before first heparin bolus was significantly longer with UA (P = .006), whereas mean ACT was similar between the two groups (P = .19). Total heparin dose needed was significantly higher with IA (mean, ‒1.61; 95% CI, ‒2.67 to ‒0.55; P = .003). Mean procedure time did not vary between groups (P = .81). Overall complication rates were low, with similar major adverse cerebro-cardiovascular event (P = .40) and total bleeding (P = .55) rates between groups. Silent cerebral events (SCEs) were significantly more frequent with IA (log odds ratio, ‒0.90; 95% CI, ‒1.59 to ‒0.22; P < .01; I 2, 33%). Rates of major bleeding, minor bleeding, pericardial effusion, cardiac tamponade, and puncture complications were similar between groups. CONCLUSIONS: UA during atrial fibrillation ablation has similar bleeding event rates, procedural times, and mean ACTs as IA, with fewer SCEs.

Predictors, burden and impact of cardiac arrhythmias among patients hospitalized with end-stage liver disease.

BACKGROUND: Cirrhotic cardiomyopathy, hyperammonemia, and hepatorenal syndrome predispose to cardiac arrhythmias in End-stage liver disease (ESLD). OBJECTIVES: Among ESLD hospitalizations, we evaluate the distribution and predictors of arrhythmias and their impact on hospitalization outcomes. METHODS: We selected ESLD records from the Nationwide Inpatient Sample (2007-2014), identified concomitant arrhythmias (tachyarrhythmias and bradyarrhythmias), and their demographic and comorbid characteristics, and estimated the effect of arrhythmia on outcomes (SAS 9.4). RESULTS: Of 57,119 ESLD hospitalizations, 6,615 had arrhythmias with higher odds with increasing age, males, jaundice, hepatorenal syndrome, alcohol use, and cardiopulmonary disorders. The most common arrhythmias were atrial fibrillation, cardiac arrest/asystole, and ventricular tachycardia. After propensity-matching (arrhythmia: no-arrhythmia, 6,609:6,609), arrhythmias were associated with 200% higher mortality, 1.7-days longer stay, $32,880 higher cost, and higher rates of shock, respiratory and kidney failures. CONCLUSIONS: Due to worse outcomes with arrhythmias, there is a need for better screening and follow-up of ESLD patients for dysrhythmias.

Inferior Outcomes of Patients With Acute Myocardial Infarction and Comorbid Protein-Energy Malnutrition.

BACKGROUND: Protein-energy malnutrition (PEM) diminishes amino acid and energy availability, impairing the body's healing capability after injury, such as in myocardial damage following acute myocardial infarction (AMI). AIMS: We sought to investigate the influence of PEM on clinical outcomes of AMI. METHODS: We identified records with a primary discharge diagnosis of AMI from the Nationwide Inpatient Sample (2012-2014), stratified by concomitant PEM. We matched PEM to no-PEM (1:1) using a greedy algorithm-based propensity methodology and estimated the impact of PEM on health outcomes (SAS 9.4). RESULTS: Of the 332,644 hospitalizations for AMI, 11,675 had concomitant PEM accounting for roughly $US 1.5 billion and over 119,792 hospital days. PEM was associated with older age (74.43- vs. 66.90-years; P < 0.0001), female sex (49.19% vs. 38.44%; P < 0.0001), black race (12.78% vs. 10.46%; P < 0.0001), and higher comorbidity burden (Deyo > 3: 32.77% vs. 16.69%; P < 0.0001). After propensity matching, PEM was associated with higher mortality (Adjusted odds ratio [AOR]: 1.59 [1.46-1.73]), cardiogenic shock (AOR: 2.26 [2.08-2.44]), discharge to secondary facilities (AOR: 2.21 [2.10-2.33]), charges ($135,500 [$131,956-139,139] vs. $81,084 [$79,241-82,970]), cardiac artery bypass surgery (AOR:1.81 [1.66-1.97]), intra-aortic balloon pump placement (AOR: 1.83 [1.65-2.04]) and longer length of stay (10.15- vs. 5.52-days). CONCLUSIONS: PEM is a predisposing factor for devastating clinical outcomes among AMI hospitalizations. Higher prevention, identification and management of PEM among high-risk individuals (older age, female sex, and black race) residing in the community are needed.

Meta-Analysis Comparing WatchmanTM and Amplatzer Devices for Stroke Prevention in Atrial Fibrillation.

Background: For patients with atrial fibrillation who are at high risk for bleeding or who cannot tolerate oral anticoagulation, left atrial appendage (LAA) closure represents an alternative therapy for reducing risk for thromboembolic events. Objectives: To compare the efficacy and safety of the Amplatzer and WatchmanTM LAA closure devices. Methods: A meta-analysis was performed of studies comparing the safety and efficacy outcomes of the two devices. The Newcastle-Ottawa Scale was used to appraise study quality. Results: Six studies encompassing 614 patients were included in the meta-analysis. Overall event rates were low for both devices. No significant differences between the devices were found in safety outcomes (i.e., pericardial effusion, cardiac tamponade, device embolization, air embolism, and vascular complications) or in the rates of all-cause mortality, cardiac death, stroke/transient ischemic attack, or device-related thrombosis. The total bleeding rate was significantly lower in the WatchmanTM group (Log OR = -0.90; 95% CI = -1.76 to -0.04; p = 0.04), yet no significant differences was found when the bleeding rate was categorized into major and minor bleeding. Total peridevice leakage rate and insignificant peridevice leakage rate were significantly higher in the WatchmanTM group (Log OR = 1.32; 95% CI = 0.76 to 1.87; p < 0.01 and Log OR = 1.11; 95% CI = 0.50 to 1.72; p < 0.01, respectively). However, significant peridevice leakages were similar in both the devices. Conclusions: The LAA closure devices had low complication rates and low event rates. Efficacy and safety were similar between the systems, except for a higher percentage of insignificant peridevice leakages in the WatchmanTM group. A randomized controlled trial comparing both devices is underway, which may provide more insight on the safety and efficacy outcomes comparison of the devices.

Protein-Energy Malnutrition and Outcomes of Hospitalizations for Heart Failure in the USA.

Chronically elevated cytokines from un-abating low-grade inflammation in heart failure (HF) results in Protein-Energy Malnutrition (PEM). However, the impact of PEM on clinical outcomes of admissions for HF exacerbations has not been evaluated in a national data. From the 2012 to 2014 Nationwide Inpatient Sample (NIS) patient's discharge records for primary HF admissions, we identified patients with concomitant PEM, and their demographic and comorbid factors. We propensity-matched PEM cohorts (32,771) to no-PEM controls (1:1) using a greedy algorithm-based methodology and estimated the effect of different clinical outcomes (SAS 9.4). There were 32,771 (∼163,885) cases of PEM among the 541,679 (∼2,708,395) primary admissions for HF between 2012 and 2014 in the US. PEM cases were older (PEM:76 vs no-PEM:72 years), Whites (70.75% vs 67.30%), and had higher comorbid burden, with Deyo-comorbidity index >3 (31.61% vs 26.30%). However, PEM cases had lower rates of obesity, hyperlipidemia and diabetes. After propensity-matching, PEM was associated with higher mortality (AOR:2.48 [2.31 to 2.66]), cardiogenic shock (3.11[2.79 to 3.46]), cardiac arrest (2.30[1.96 to 2.70]), acute kidney failure (1.49[1.44 to 1.54]), acute respiratory failure (1.57[1.51 to 1.64]), mechanical ventilation (2.72[2.50 to 2.97]). PEM also resulted in higher non-routine discharges (2.24[2.17 to 2.31]), hospital cost ($80,534[78,496 to 82,625] vs $43,226[42,376 to 44,093]) and longer duration of admission (8.6[8.5 to 8.7] vs 5.3[5.2 to 5.3] days). In conclusion, PEM is a prevailing comorbidity among hospitalized HF subjects, and results in devastating health outcomes. Early identification and prevention of PEM in HF subjects during clinic visits and prompt treatment of PEM both in the clinic and during hospitalization are essential to decrease the excess burden of PEM.