Daniel Burkhoff MD PhD

Cardiac contractility modulation in patients with advanced heart failure

daniel — Sat, 18 May 2013 20:32:27 +0000

Cardiac contractility modulation (CCM) is a novel device-based therapy for heart failure that involves applying electrical signals during the absolute refractory period of the myocardial action potential. This therapy has been shown to augment the strength of left ventricular contraction independent of myocardial oxygen consumption in animal models as well as human studies of patients with heart failure and reduced ejection fractions. The mechanism underlying CCM is an alteration of myocardial calcium handling in a fashion that extends beyond the traditional pharmacological effects of inotropic agents. Analysis of myocardial tissue from both animal models and human hearts treated by CCM demonstrates a shift of abnormally expressed genes towards normal function, positively affecting pathways involving proteins that regulate calcium cycling and myocardial contraction. CCM effects are proven to be independent of QRS duration; however, clinical studies to date have primarily focused on patients with normal QRS since cardiac resynchronization therapy is a well-established option for patients with heart failure and a prolonged QRS duration. Clinical trials show that CCM improves exercise tolerance, as measured by VO2,peak and quality of life, assessed by the Minnesota Living with Heart Failure Questionnaire. The device is currently available for the treatment of heart failure in Europe. Approval in the USA is pending additional testing currently underway using a protocol approved by the US FDA.

Modeling left atrial volume, shape, and contraction patterns in normal subjects by cardiac magnetic resonance imaging

daniel — Sat, 18 May 2013 20:30:04 +0000

BACKGROUND: Left atrial three-dimensional shape and contraction patterns are not well described. We quantified the LA using three-dimensional cardiac MRI (CMR) in a group of normal subjects. METHODS: Three-dimensional vectors were used to quantitate atrial shape and contraction using a geometric model as a three-dimensional prolate ellipsoid. Atrial area and length at end-systole and end-diastole were made in the horizontal long axis (HLA) and vertical long axis (VLA) planes. Biplane area-length products and the orthogonal LA long axis vector comprised 3 orthogonal vector lengths composed of axis measures for shape and volume calculations at end-diastole and end-systole. Vector fractional shortening in 3 dimensions was calculated for each 3-space orthogonal vector. Echocardiograms were used for comparison. RESULTS: The normal LA is an oblate ellipsoid with significantly longer HLA short axis than the vertical VLA short axis (p<0.001). LA contraction in the long axis dimension is smaller than both HLA and VLA short axis dimensional changes (p<0.001). Linear correlations between LAEDV vs. LASV and LAESV vs. LAEF were highly significant. CONCLUSIONS: This dimensional analysis quantitates normal left atrial shape for the first time, modeled as a prolate 3-D ellipsoid. LA contractile functions and derives mostly from contraction in the HLA and VLA short axis directions. Though LA end-diastolic volume is considered the marker of left atrial health or disease, this notion should be reconsidered in view of LA static and functional modeling in 3 dimensions.

Continuous-flow left ventricular assist devices induce left ventricular reverse remodeling

daniel — Wed, 03 Apr 2013 16:45:30 +0000

No Abstract

Myocardial recovery and the failing heart: myth, magic, or molecular target?

daniel — Tue, 25 Dec 2012 17:43:36 +0000

Medical and device therapies that reduce heart failure morbidity and mortality also lead to decreased left ventricular volume and mass and a more normal elliptical shape of the ventricle. These are due to changes in myocyte size, structure, and organization that have been referred to collectively as reverse remodeling. Moreover, there are subsets of patients whose hearts have undergone reverse remodeling either spontaneously or after medical or device therapies and whose clinical course is associated with freedom from future heart failure events. This phenomenon has been referred to as myocardial recovery. Despite the frequent interchangeable use of the terms “myocardial recovery” and “reverse remodeling” to describe the reversal of various aspects of the heart failure phenotype after medical and device therapy, the literature suggests that there are important differences between these 2 phenomena and that myocardial recovery and reverse remodeling are not synonymous. In this review, we discuss the biology of cardiac remodeling, cardiac reverse remodeling, and myocardial recovery with the intent to provide a conceptual framework for understanding myocardial recovery

Two axial-flow Synergy Micro-Pumps as a biventricular assist device in an ovine animal model

daniel — Tue, 25 Dec 2012 17:41:07 +0000

OBJECTIVE: This study investigated the use of 2 Synergy Micro-Pumps for full biventricular assist device (BiVAD) support. We examined right-sided and left-sided hemodynamic parameters over a range of right-sided and left-sided pump speeds in an acute, fibrillating, non-beating-heart model in sheep. METHODS: Five juvenile sheep (43 +/- 2 kg) were implanted with two Synergy Micro-Pumps (CircuLite Inc, Saddle Brook, NJ), 1 in the right (RV) and 1 in the left ventricle (LV), through a median sternotomy. The RVAD outflow graft was anastomosed end-to-side to the pulmonary artery and the LVAD outflow to the ascending aorta. After surgical implantation of both pumps, ventricular fibrillation was induced and hemodynamic parameters were measured at 9 different levels of RVAD pump speed (from 20,000 to 28,000 rpm at 1,000-rpm increments), while the speed of the LVAD was set constant at 24,000, then at 26,000, and finally, at 28,000 rpm. RESULTS: At a fixed LVAD speed, RVAD and LVAD flow both increased identically as RVAD speed was increased. This was due to redistribution of blood volumes that resulted in resetting of pressure gradients across each pump and each vascular bed in a manner dictated by the pump pressure-flow characteristics. Results were similar with LVAD set at 24,000, 26,000, or 28,000 rpm. At the highest LVAD and RVAD speeds, flow averaged 3.1 +/- 0.7 liters/min, and pressures in the right atrium, pulmonary artery, left atrium, and aorta averaged 2.2 +/- 3.7, 24.4 +/- 6.5, 22.4 +/- 5.5, and 56.6 +/- 8.5 mm Hg, respectively. CONCLUSION: BiVAD support with the 2 Synergy Micro-Pumps is feasible and able to provide full hemodynamic support in sheep. This approach holds promise for providing biventricular partial support in humans and, in particular, for full support in small adults and children