Francis D. Pagani

Extended Mechanical Circulatory Support With a Continuous-Flow Rotary Left Ventricular Assist Device

OBJECTIVES This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplantation. BACKGROUND LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism. METHODS In a prospective, multicenter study, 281 patients urgently listed (United Network of Organ Sharing status 1A or 1B) for heart transplantation underwent implantation of a continuous-flow LVAD. Survival and transplantation rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months. RESULTS Of 281 patients, 222 (79%) underwent transplantation, LVAD removal for cardiac recovery, or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval: 65% to 79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-min walk test (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-min walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients. CONCLUSIONS A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life. (Thoratec HeartMate II Left Ventricular Assist System [LVAS] for Bridge to Cardiac Transplantation; NCT00121472).

Intermediate-Term Outcome Of Mitral Reconstruction In Cardiomyopathy

OBJECTIVE Severe mitral regurgitation is a frequent complication of end-stage cardiomyopathy that contributes to heart failure and predicts a poor survival. We studied the intermediate-term outcome of mitral reconstruction in 48 patients who had cardiomyopathy with severe mitral regurgitation and were operated on between June 1993 and June 1997. METHODS Ages ranged from 33 to 79 years (63 +/- 6 years) with left ventricular ejection fractions of 8% to 25% (16% +/- 3%). All patients were receiving maximal drug therapy and were in New York Heart Association class III-IV with severe, refractory 4+ mitral regurgitation. Operatively, all 48 had undersized flexible annuloplasty rings inserted, 7 had coronary bypass grafts for incidental disease, 11 had prior bypass grafts, and 11 also had tricuspid valve repair. RESULTS One operative death occurred as a result of right ventricular failure. Postoperative transesophageal echocardiography revealed mild mitral regurgitation in 7 patients and no mitral regurgitation in 41. There were 10 late deaths, 2 to 47 months after mitral reconstruction. The 1- and 2-year actuarial survivals have been 82% and 71%. At a mean follow-up of 22 months, the number of hospitalizations for heart failure has decreased, and 1 patient has had heart transplantation. Significantly, New York Heart Association class improved from 3.9 +/- 0.3 before the operation to 2.0 +/- 0.6 after the operation. Twenty-four months after the operation, left ventricular volume and sphericity have decreased, whereas ejection fraction and cardiac output have increased. CONCLUSION Whether this favorable modification of left ventricular function and geometry will persist remains unknown. However, mitral repair for cardiomyopathy with mitral regurgitation allows new strategies for these patients.

Seventh INTERMACS annual report: 15,000 patients and counting

The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively.

Sixth INTERMACS annual report: a 10,000-patient database.

The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life.

Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients

The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps, actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies.

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

Preoperative Amiodarone as Prophylaxis against Atrial Fibrillation after Heart Surgery

Background Atrial fibrillation occurs commonly after open-heart surgery and may delay hospital discharge. The purpose of this study was to assess the use of preoperative amiodarone as prophylaxis against atrial fibrillation after cardiac surgery. Methods In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery. Therapy consisted of 600 mg of amiodarone per day for seven days, then 200 mg per day until the day of discharge from the hospital. The mean (±SD) preoperative total dose of amiodarone was 4.8±0.96 g over a period of 13 ± 7 days. Results Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25 percent) and 32 of the 60 patients in the placebo group (53 percent) (P = 0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5 ± 2.6 vs. 7.9 ± 4.3 days, P = 0.04). ...

Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.

OBJECTIVE The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices. METHODS Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified. RESULTS Overall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2-4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3-13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1-4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation. CONCLUSIONS The incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.

The Right Ventricular Failure Risk Score: A Pre-Operative Tool for Assessing the Risk of Right Ventricular Failure in Left Ventricular Assist Device Candidates

OBJECTIVES This study sought to develop a model that estimates the post-operative risk of right ventricular (RV) failure in left ventricular assist device (LVAD) candidates. BACKGROUND Right ventricular failure after LVAD surgery is associated with increased morbidity and mortality, but identifying LVAD candidates at risk for RV failure remains difficult. METHODS A prospectively collected LVAD database was evaluated for pre-operative clinical, laboratory, echocardiographic, and hemodynamic predictors of RV failure. Right ventricular failure was defined as the need for post-operative intravenous inotrope support for >14 days, inhaled nitric oxide for > or =48 h, right-sided circulatory support, or hospital discharge on an inotrope. An RV failure risk score (RVFRS) was created from multivariable logistic regression model coefficients, and a receiver-operating characteristic curve of the score was generated. RESULTS Of 197 LVADs implanted, 68 (35%) were complicated by post-operative RV failure. A vasopressor requirement (4 points), aspartate aminotransferase > or =80 IU/l (2 points), bilirubin > or =2.0 mg/dl (2.5 points), and creatinine > or =2.3 mg/dl (3 points) were independent predictors of RV failure. The odds ratio for RV failure for patients with an RVFRS < or =3.0, 4.0 to 5.0, and > or =5.5 were 0.49 (95% confidence interval [CI] 0.37 to 0.64), 2.8 (95% CI 1.4 to 5.9), and 7.6 (95% CI 3.4 to 17.1), respectively, and 180-day survivals were 90 +/- 3%, 80 +/- 8%, and 66 +/- 9%, respectively (log rank for linear trend p = 0.0045). The area under the receiver-operating characteristic curve for the RVFRS (0.73 +/- 0.04) was superior to that of other commonly used predictors of RV failure (all p < 0.05). CONCLUSIONS The RVFRS, composed of routinely collected, noninvasive pre-operative clinical data, effectively stratifies the risk of RV failure and death after LVAD implantation.

Autologous Skeletal Myoblasts Transplanted to Ischemia-Damaged Myocardium in Humans Histological Analysis of Cell Survival and Differentiation

OBJECTIVES We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.