No abstract

In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.

The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) provides new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5,267 individuals across the spectrum of cardiac physiology, and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms, and demonstrate that these data, coupled with TTNtv position, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause for DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses we provide evidence for a length-dependent, dominant negative mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.

In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

Background-We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. Methods and Results-We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, ␤-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the ␤ 2 -agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2Ϯ12.6 years (16 male patients), patients were on 2.0Ϯ0.9 inotropes, 7 (35%) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39Ϯ0.43 L ⅐ min Ϫ1 ⅐ m Ϫ2 , pulmonary capillary wedge pressure was 31.5Ϯ5.7 mm Hg, and heart failure history was 3.4Ϯ3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2%) were explanted after 286Ϯ97 days. Eight had symptomatic heart failure for Յ6 months and 4 for Ͼ6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70Ϯ7%, left ventricular end-diastolic diameter was 48.6Ϯ5.7 mm, left ventricular end-systolic diameter was 32.3Ϯ5.7 mm, mV O 2 was 21.6Ϯ4 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 , pulmonary capillary wedge pressure was 5.9Ϯ4.6 mm Hg, and cardiac index was 3.6Ϯ0.6 L ⅐ min Ϫ1 ⅐ m Ϫ2 . Estimated survival without heart failure recurrence was 83.3% at 1 and 3 years. After a 430.7Ϯ337.1-day follow-up, surviving explants had an ejection fraction of 58.1Ϯ13.8%, left ventricular end-diastolic diameter of 59.0Ϯ9.3 mm, left ventricular end-systolic diameter of 42.0Ϯ10.7 mm, and mV O 2 of 22.6Ϯ5.3 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 . Conclusions-Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy. (Circulation. 2011;123:381-390.)

Valve-sparing operations are possible in a large proportion of patients with aneurysms of the ascending aorta and the medium and long-term results are encouraging.

No abstract

The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System [ENDURANCE SUPPLEMENTAL TRIAL] [DT2]; NCT01966458).