Left ventricular assist device unloading effects on myocardial structure and function: Current status of the field and call for action

Purpose of review: Myocardial remodeling driven by excess pressure and volume load is believed to be responsible for the vicious cycle of progressive myocardial dysfunction in chronic heart failure. Left ventricular assist devices (LVADs), by providing significant volume and pressure unloading, allow a reversal of stress-related compensatory responses of the overloaded myocardium. Herein, we summarize and integrate insights from studies which investigated how LVAD unloading influences the structure and function of the failing human heart. Recent findings: Recent investigations have described the impact of LVAD unloading on key structural features of cardiac remodeling - cardiomyocyte hypertrophy, fibrosis, microvasculature changes, adrenergic pathways and sympathetic innervation. The effects of LVAD unloading on myocardial function, electrophysiologic properties and arrhythmias have also been generating significant interest. We also review information describing the extent and sustainability of the LVAD-induced myocardial recovery, the important advances in understanding of the pathophysiology of heart failure derived from such studies, and the implications of these findings for the development of new therapeutic strategies. Special emphasis is given to the great variety of fundamental questions at the basic, translational and clinical levels that remain unanswered and to specific investigational strategies aimed at advancing the field. Summary: Structural and functional reverse remodeling associated with LVADs continues to inspire innovative research. The ultimate goal of these investigations is to achieve sustained recovery of the failing human heart. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Ventricular assist devices: Pharmacological aspects of a mechanical therapy

Heart failure (HF) is a global epidemic that continues to cause significant morbidity and mortality despite advances in medical therapy. Ventricular assist device technology has emerged as a therapeutic option to bridge patients with end-stage HF to heart transplantation or as an alternative to transplantation in selected patients. In some patients, mechanical unloading induced by ventricular assist devices leads to improvement of myocardial function and a possibility of device removal. The implementation of this advanced technology requires multiple pharmacological interventions, both in the perioperative and long-term periods, in order to minimize potential complications and improve patient outcomes. We herein review the latest available evidence supporting the use of specific pharmacological interventions and current practices in the care of these patients: anticoagulation, bleeding management, pump thrombosis, infections, arrhythmias, right ventricular failure, hypertension, desensitization protocols, among others. Areas of uncertainty and ground for future research are also highlighted. © 2012 Elsevier Inc. All rights reserved

Risk Factors Predictive of Right Ventricular Failure After Left Ventricular Assist Device Implantation

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation appears to be associated with increased mortality. However, the determination of which patients are at greater risk of developing postoperative RVF remains controversial and relatively unknown. We sought to determine the preoperative risk factors for the development of RVF after LVAD implantation. The data were obtained for 175 consecutive patients who had received an LVAD. RVF was defined by the need for inhaled nitric oxide for ≥48 hours or intravenous inotropes for >14 days and/or right ventricular assist device implantation. An RVF risk score was developed from the β coefficients of the independent variables from a multivariate logistic regression model predicting RVF. Destination therapy (DT) was identified as the indication for LVAD implantation in 42% of our patients. RVF after LVAD occurred in 44% of patients (n = 77). The mortality rates for patients with RVF were significantly greater at 30, 180, and 365 days after implantation compared to patients with no RVF. By multivariate logistic regression analysis, 3 preoperative factors were significantly associated with RVF after LVAD implantation: (1) a preoperative need for intra-aortic balloon counterpulsation, (2) increased pulmonary vascular resistance, and (3) DT. The developed RVF risk score effectively stratified the risk of RV failure and death after LVAD implantation. In conclusion, given the progressively growing need for DT, the developed RVF risk score, derived from a population with a large percentage of DT patients, might lead to improved patient selection and help stratify patients who could potentially benefit from early right ventricular assist device implantation. © 2010 Elsevier Inc. All rights reserved

Impact of mechanical unloading on microvasculature and associated central remodeling features of the failing human heart

Objectives: This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart. Background: Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among microvasculature, fibrosis, and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown, and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial. Methods: Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n = 15) and from normal donors (n = 8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size, and glycogen content. Ultrastructural assessment was done with electron microscopy. Results: Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p = 0.001) and a 36% decrease in microvascular lumen area (p = 0.028). We also identified, in agreement with these findings, ultrastructural and immunohistochemical evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural, or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration. Conclusions: The LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features might guide future studies of unloading-induced reverse remodeling of the failing human heart. © 2010 American College of Cardiology Foundation