Jesus Eduardo Rame

Cardiovascular disease remains a major cause of morbidity and mortality, with heart failure representing the common and often irreversible end stage, for which current therapies are largely palliative rather than restorative. Cardiac microcurrent therapy delivers a low-intensity, nondepolarizing direct current across the myocardium and has been proposed to modulate fibrosis, inflammation, and remodeling in heart failure with reduced ejection fraction. In Cardiac Microcurrent I (New York Heart Association III nonischemic heart failure with reduced ejection fraction), left ventricular ejection fraction increased by 12.6% at 6 months, 6-minute walk distance improved by 191 m, and 8 of 10 patients improved to New York Heart Association I within 2 weeks. In the randomized Cardiac Microcurrent II trial, patients showed further improvements, including a 5.1% increase in left ventricular ejection fraction, a reduction in New York Heart Association class (up to 69%), and a 38 m increase in 6-minute walk distance. However, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels did not show a consistent corresponding reduction. In vitro, microcurrent altered the myofibroblast phenotype and reduced the expression of transforming growth factor-β1, collagen, α-smooth muscle actin, and fibronectin. Transcriptomics revealed downregulation of inflammatory and immune pathways, while cardiomyocytes from spontaneously hypertensive rats exhibited enhanced survival and stress resistance. This review combines early clinical observations and preclinical findings to examine potential mechanisms of action and bioelectrical effects of cardiac microcurrent therapy. Given the limited clinical evidence and largely in vitro nature of the data, the current mechanistic findings should be considered preliminary. We highlight key knowledge gaps and propose future studies to define molecular mechanisms, discover biomarkers, analyze key signaling pathways, and evaluate clinical outcomes in adequately powered, sham-controlled trials, which could further validate this therapeutic approach.

Background: Conventional mechanical circulatory support offers limited options for patients with small or restrictive left ventricles. Left atrial inflow (LA–Ao) ventricular assist device (VAD) configuration represents an alternative to conventional apical left ventricular assist device (LVAD). However, outcomes data remain limited. To address this, we evaluated patient characteristics, procedural details, and outcomes of LA–Ao VAD configuration in this population. Methods: A systematic search was conducted to identify case reports and series of patients with small or restrictive left ventricles who underwent LA–Ao LVAD implantation. A total of 21 reports, representing 27 patients, were included. Patient‐level data were extracted for analysis. Results: Thirteen adult and 14 pediatric patients underwent LA–Ao VAD implantation. Median age was 57 [46–62] years in adults and 3.5 [0.8–9] years in children. Hypertrophic cardiomyopathy and restrictive cardiomyopathy were the predominant diagnoses in both adults and children, accounting for 54% (7/13) and 29% (4/14), and 46% (6/13) and 43% (6/14), respectively. Median left ventricular ejection fraction was 44% [39–53] in adults and 45% [36–61] in children, and median left ventricular end‐diastolic diameter was 42 [35–42] mm in adults and 33 [29–34] mm in children. The most used devices were HeartWare HVAD (46%, 6/13) in adults, and Berlin Heart (64%, 9/14) in children. Overall pulmonary capillary wedge pressure decreased from 23 [19–27] to 7 [0–9] mmHg ( p = 0.02), and cardiac index increased from 2.0 [1.3–2.8] to 3.1 [2.7–3.7] L/min/m ² ( p = 0.04). In‐hospital mortality included one fatal case (7.7%) in each group. Overall survival was 85% (11/13) in adults at median follow‐up of 6.7 [4.4–19.9] months and 86% (12/14) in children at 2.3 [1.2–8.1] months. Conclusion: The LA–Ao configuration of VAD is a viable strategy for mechanical circulatory support in patients with small or restrictive left ventricles. It offers effective unloading of the left atrium and improved cardiac index, supporting its role as an alternative to the conventional LVAD approach.

Background: Predicted heart mass (PHM) is a commonly used tool for donor‐to‐recipient size matching. However, incorporating body weight as part of PHM can be considered problematic given its high variability, and low metabolic nature of fat. We sought to assess whether substituting the actual donor and recipient weight with the ideal body weight (IBW) would affect the association of donor‐to‐recipient PHM ratio with 1‐year and overall survival after heart transplantation.Methods: The United Network for Organ Sharing (UNOS) database was queried for adult patients who received a primary heart transplant between January 2000 and September 2021.Results: Both PHM and ideal PHM (IPHM) ratios were associated with one‐year (PHM: p = .003; IPHM: p = .0007) and overall (PHM: p = .02; IPHM: p = .02) survival. In the continuous analysis with restricted cubic splines, both PHM (p = .0003) and IPHM (p = .00001) were associated with relative hazards of death.Conclusion: IPHM is significantly associated with post‐transplant survival and may be a useful compliment to PHM.

Right ventricular (RV) dysfunction is common after left ventricular assist device (LVAD) implantation leading to clinical right heart failure (RHF) associated with worsened survival and quality of life. It is likely that intraoperative events such as anesthesia induction play a role in the development or unmasking of RV dysfunction in addition to known effects from hemodynamic changes that occur after LVAD implantation. The EACH-LVAD Study is a prospective, single-center, single-arm, observational cohort study of adult patients with advanced heart failure undergoing durable LVAD implantation with standard anesthesia induction. Intraoperative RV hemodynamics via central venous pressure, mean pulmonary artery pressure, pulmonary artery pulsatility index, and vasoactive-inotropic score (a simple weighted summation of standardized drug doses) and echocardiographic parameters (RV fractional area change, RV area in diastole, RV basal diameter, septum position, RV function, tricuspid regurgitation) were measured and compared at prespecified timepoints, including postinduction. Postoperative clinical RHF was determined based on published definitions. Forty-two patients receiving a first-time LVAD were included between September 2017 and March 2019. Propofol-based induction was used in 31 patients and etomidate-based induction in eight patients. A significant increase in central venous pressure (CVP; p < 0.001), mean pulmonary artery pressure (mPAP; p < 0.001), and vasoactive inotropic score (VIS; p < 0.001) with associated decrease in pulmonary artery pulsatility index (PAPi; p < 0.001) was observed. Right ventricular function worsened throughout. Right heart failure occurred in 70% of patients. Propofol-based induction was not associated with a higher risk of RHF (relative risk [RR], 1.01 [95% confidence interval {CI}, 0.64–1.61]). The EACH-LVAD study demonstrates an effect of anesthesia induction on worsened RV hemodynamics and echocardiographic changes which may have an effect on the development of RHF.

A bstract: Durable mechanical circulatory support in the form of left ventricular (LV) assist device (LVAD) therapy is increasingly considered in the context of the recovery of native cardiac function. Progressive improvement in LV function may facilitate LVAD explantation and a resultant reduction in device-related risk. However, ascertaining LV recovery remains a challenge. In this study, we investigated the use of trans-aortic valvular flow rate and trans-LVAD flow rate to assess native LV systolic function using a well-established lumped parameter model of the mechanically assisted LV with pre-existing systolic dysfunction. Trans Aortic Valvular Ejection Fraction (TAVEF) was specifically found to characterize the preload-independent contractility of the LV. It demonstrated excellent sensitivity to simulated pharmacodynamic stress tests and volume infusion tests. TAVEF may prove to be useful in the ascertainment of LV recovery in LVAD-supported LVs with pre-existing LV systolic dysfunction.

Continuous-flow left ventricular assist devices (CF-LVAD) have been shown to enhance reverse remodeling and myocardial recovery in certain patients allowing for device removal. We sought to analyze the characteristics and describe outcomes of patients who underwent CF-LVAD explantation at a large academic center. We retrospectively identified all patients who underwent CF-LVAD explants due to recovery from 2006 to 2019. Patient baseline characteristics and data on pre- and postexplant evaluation were collected and analyzed. Of 421 patients who underwent CF-LVAD implantation, 13 underwent explantation (3.1%). Twelve HeartMate II and one HeartWare LVAD were explanted. All patients had nonischemic cardiomyopathy. Median time from heart failure diagnosis to LVAD implant was 12 months (interquartile range [IQR], 2–44) and the median time supported on LVAD was 22 months (IQR, 11–28). Two patients died within 30 days of explant. Three additional patients died during the follow-up period and all were noted to be nonadherent to medical therapy. After a mean follow-up duration of 5 years, overall survival was 52%. Mean pre-explant ejection fraction was 49%, which decreased at most recent follow-up to 32%. Mean pre-explant left ventricular internal diameter in diastole (LVIDD) was 4.37 cm and increased to 5.52 cm at most recent follow-up. Continuous-flow left ventricular assist device explantation is feasible and safe in select patients.

Undisturbed bioelectricity is a prerequisite for normal organ function. This is especially true for organs with high electrical activity such as the heart and the nervous system. Under clinical conditions, however, this can hardly be determined in patients with disturbed organ function and is therefore largely ignored. Here, based on clinical data, we will discuss whether the direct application of an external electric current (in the physiological μA range) together with an electrical field to hearts with impaired pump function can explain the functional improvement of the hearts by edema reduction triggered by electro-osmosis.

Pulmonary hypertension (PH) due to left heart disease is the most common etiology for PH. PH in patients with heart failure with reduced fraction (HFrEF) is associated with reduced functional capacity and increased mortality. PH-HFrEF can be isolated post-capillary or combined pre- and post-capillary PH. Chronic elevation of left-sided filling pressures may lead to reverse remodeling of the pulmonary vasculature with development of precapillary component of PH. Untreated PH in patients with HFrEF results in predominant right heart failure (RHF) with irreversible end-organ dysfunction. Management of PH-HFrEF includes diuretics, vasodilators like angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers or angiotensin-receptor blocker-neprilysin inhibitors, hydralazine and nitrates. There is no role for pulmonary vasodilator use in patients with PH-HFrEF due to increased mortality in clinical trials. In patients with end-stage HFrEF and fixed PH unresponsive to vasodilator challenge, implantation of continuous-flow left ventricular assist device (cfLVAD) results in marked improvement in pulmonary artery pressures within 6 months due to left ventricular (LV) mechanical unloading. The role of pulmonary vasodilators in management of precapillary component of PH after cfLVAD is not well-defined. The purpose of this review is to discuss the pharmacologic management of PH after cfLVAD implantation.