Benjamin Sun

Advanced Heart Failure Treated with Continuous-Flow Left Ventricular Assist Device

BACKGROUND Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices. METHODS In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity. RESULTS Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups. CONCLUSIONS Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.)

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial.

Background— Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown. Methods and Results— Patients with ejection fraction ⩽35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77–1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35–1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22–0.77; P=0.006). Conclusion— Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary Left Ventricular Assist Devices

Background— Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. Methods and Results— In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. Conclusions— In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

Pump Replacement for Left Ventricular Assist Device Failure Can Be Done Safely and Is Associated With Low Mortality

BACKGROUND Although continuous-flow left ventricular assist devices (LVAD) are durable and reliable, device replacement will be inevitable in some patients. We evaluated the incidence and outcomes of pump replacement procedures with the HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD. METHODS Data were obtained from 1,128 patients implanted from March 2005 to January 2010 with the HeartMate II during the clinical trials for bridge to transplant and destination therapy. The operative mortality associated with the replacement procedure was determined. RESULTS The mean duration of HeartMate II support was 568 ± 535 days (cumulative duration: 1,755 patient-years, longest: 6.5 years). A total of 72 (6.4%) patients underwent 79 LVAD replacements (0.045 events/patient-year) of which 2 were in the initial operation and 77 in separate procedures. Reasons for replacement were percutaneous lead damage (36 events, 3.0%), device thrombosis (25 events, 2.1%), infection (7 events, 0.6%), and miscellaneous other (11 events, 0.9%). The median time to pump replacement was 428 days (range 0 to 1,474). Of the 77 replacement procedures, there were 5 (6.5%) operative deaths within 30 days. The causes of death were device thrombosis, right heart failure, multisystem organ failure, and bleeding. One year after exchange (median 2.1 years after initial implant), 30% had died, 5% were transplanted, and 65% were ongoing and alive. CONCLUSIONS HeartMate II device failure requiring pump replacement is infrequent, but when required can be done safely. These data continue to provide encouraging evidence supporting HeartMate II use for long-term circulatory support.

Worldwide surgical experience with the Paracor HeartNet cardiac restraint device

OBJECTIVE An elastic ventricular restraint device has been developed for patients with heart failure who remain symptomatic despite treatment with standard therapies. The safety and efficacy of this device are under clinical investigation. Six-month data for the first 51 patients treated worldwide are reported. We hypothesize that the Paracor HeartNet device (Paracor Medical, Sunnyvale, Calif), placed through a minithoracotomy in patients with severe dilated cardiomyopathy, improves clinical and functional status. METHODS Fifty-one patients with an ejection fraction of 35% or less, with a New York Heart Association class II or III, and receiving optimal medical therapy for at least 3 months, were selected at 15 sites (3 in Europe, 12 in the United States) to undergo implantation of the HeartNet device through a minithoracotomy. Patients were evaluated at baseline and at 6-month follow-up by echocardiography, the 6-minute walk test, cardiopulmonary exercise testing (partial oxygen pressure in mixed venous blood), New York Heart Association class, and (in the United States) the Minnesota Living with Heart Failure questionnaire. RESULTS The average age was 52 years (30-73 years), with a preponderance of men and nonischemic cause of heart failure. Implantation was accomplished in 50 of 51 patients (98%). Adverse events included 2 in-hospital deaths secondary to pulmonary complications (4%), additional pulmonary complications in 7 patients (14%), arrhythmia in 14 patients (27%), epicardial laceration in 2 patients (4%), and empyema in 1 patient (2%). Six-month data demonstrated significant improvement in the 6-minute walk test (+65.7, P = .002) and Minnesota Living with Heart Failure scores (-15.7, P = .002) and improvement in echocardiographic findings. CONCLUSION The Paracor HeartNet device can be reliably implanted in patients with heart failure and marked reduction of left ventricular function. These data suggest a functional and clinical benefit, with a trend toward reverse remodeling, and support the conduct of a randomized controlled pivotal trial.

Noninvasive assessment of left ventricular assist devices with cardiovascular computed tomography and impact on management

BACKGROUND Left ventricular assist devices (LVADs) provide a bridge to recovery or heart transplantation but require serial assessment. Echocardiographic approaches may be limited by device artifact and acoustic window. Cardiovascular computed tomography (CCT) may provide improved non-invasive imaging of LVADs. We evaluated the diagnostic findings and clinical impact of CCT for non-invasive assessment of patients with LVADs. METHODS CCT examinations performed between 2005 and 2008 in patients with LVADs were identified. Acquisitions were completed on the identical 64-detector-row scanner with intravenous contrast administration. Electrocardiographic gating was used in patients with pulsatile devices, and peripheral pulse gating was used in patients with continuous-flow devices. Comparison was made between CCT results and 30-day outcomes, including echocardiographic and intraoperative findings. RESULTS We reviewed 32 CCT examinations from 28 patients. Indications included evaluation of low cardiac output symptoms, assessment of cannula position, low flow reading on the LVAD, and surgical planning. CCT identified critical findings in 6 patients, including thrombosis and inlet cannula malposition, all confirmed intraoperatively. CCT missed 1 case of intra-LVAD thrombus. Using intraoperative findings as the gold standard, CCTs sensitivity was 85% and specificity was 100%. Echocardiographic LVAD evaluation did not correlate with findings on CCT (kappa = -0.29, 95% confidence interval, -0.73 to 0.13). CONCLUSIONS This preliminary observational cohort study indicates that non-invasive imaging using CCT of LVADs is feasible and accurate. CCT warrants consideration in the initial evaluation of symptomatic patients with LVADs.

Mechanisms of disease: detrimental adrenergic signaling in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is responsible for more than 1 million hospital admissions each year in the US. Clinicians and scientists have developed therapeutic strategies that reduce mortality in patients with chronic heart failure (HF). Despite the widely appreciated magnitude of the ADHF problem, there is still a critical gap in our understanding of the cellular mechanisms involved and effective treatment strategies for hospitalized patients. Irrespective of the etiology, patients with ADHF present with similar symptoms (e.g. edema, altered hemodynamics and congestion) as multiple signaling pathways converge in a common phenotypic presentation. Investigations have shown that patients with ADHF have increased catecholamine levels, which cause chronic stimulation of β-adrenergic receptors. This overstimulation leads to chronic G-protein activation and perturbations in myocyte signaling, as the patients heart attempts to adapt to progressive HF. Over time, these compensatory signaling mechanisms ultimately fail, and maladaptive signaling prevails with progressive worsening of symptoms. This Review summarizes some of the changes that occur during chronic adrenergic stimulation, and examines how downstream contractile dysfunction and myocyte death can alter the prognosis of patients with HF hospitalized for acute events.

Neurocognitive function in destination therapy patients receiving continuous-flow vs pulsatile-flow left ventricular assist device support

BACKGROUND The HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow left ventricular assist device (LVAD) improved survival in destination therapy (DT) patients during a randomized trial compared with pulsatile-flow LVADs. This study documented changes in cognitive performance in DT patients from that trial to determine if there were differences between continuous-flow and pulsatile-flow support. METHODS Data were collected in a sub-study from 96 HeartMate II continuous-flow and 30 HeartMate XVE pulsatile-flow LVAD patients from 12 of the 35 trial sites that followed the same serial neurocognitive (NC) testing protocol at 1, 3, 6, 12, and 24 months after LVAD implantation. Spatial perception, memory, language, executive functions, and processing speed were the domains assessed with 10 standard cognitive measures. Differences over time and between LVAD type were evaluated with linear mixed-effects modeling. RESULTS From 1 to 24 months after LVAD implantation, changes in NC functions were stable or showed improvement in all domains, and there were no differences between the continuous-flow and pulsatile-flow groups. Data at 24 months were only available from patients with the continuous-flow LVAD due to the limited durability of the HeartMate XVE device. There was no decline in any NC domain over the time of LVAD support. Missing data not collected from patients who died could have resulted in a bias toward inflated study results. CONCLUSIONS The NC performance of advanced heart failure patients supported with continuous-flow and pulsatile-flow LVADs shows stabilization or improvement during support for up to 24 months.

Toward a Definitive, Totally Thoracoscopic Procedure for Atrial Fibrillation

PURPOSE Evolution of anti-arrhythmia surgery beyond the Cox maze III has been hampered by the difficulty in implementing a complete lesion set in a truly minimally invasive approach. In this study, we introduce a true port-access procedure that addresses both autonomic and anatomic sources of atrial fibrillation, with real-time verification of all technical endpoints. DESCRIPTION A total of 32 patients with persistent or longstanding persistent atrial fibrillation underwent the totally thoracoscopic anti-arrhythmia procedure incorporating pulmonary vein isolation, mapping of epicardial autonomics, extended linear ablations across critical segments of atrial substrate, and ligation of the left atrial appendage. All aspects of the procedure were confirmed with intraoperative electrophysiologic testing. EVALUATION With 1 week of continuous rhythm surveillance at 3, 6, and 13 months postoperatively in all patients, 21 of 24 patients with 6-month follow-up are in sinus rhythm with no anti-arrhythmia medications. CONCLUSIONS An anti-arrhythmia operation that is highly effective in patients with advanced forms of atrial fibrillation can be safely performed through a totally port-access approach.