Walter P. Dembitsky

Neurological events during long-term mechanical circulatory support for heart failure ; the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) experience

Background—Progression of heart failure can lead to cardiac transplantation, but when patients are ineligible, long-term mechanical circulatory support may improve survival. The REMATCH trial showed that left ventricular assist devices (LVADs) prolonged survival in patients with end-stage disease, but with a significant number of adverse events. We report on the neurological outcomes in the REMATCH trial. Methods and Results—We examined new neurological events in the 129 patients randomized to either LVAD placement (n= 68) or medical management (n= 61), classified as stroke, transient ischemic attack, toxic-metabolic encephalopathy, and other. There were 46 neurological events: 42 in 30 LVAD patients and 4 in 4 patients in the medical arm (χ2, 30/68 versus 4/61, P < 0.001). Sixteen percent of the LVAD patients had a stroke, with a rate of 0.19 per year (95% CI, 0.10 to 0.33), many occurring in the postoperative period. The stroke rate in the medical arm was 0.052. A Kaplan-Meier survival analysis showed a 44% reduction in the risk of stroke or death in the LVAD group versus the optimal medical group (P = 0.002). The mean interval from implantation to stroke was 221.8 days (± 70.4 days). History of stroke, age, and sepsis were not stroke risk factors in the LVAD group. Conclusions—Fewer than half of the patients in the LVAD group had a neurological event, and there were few neurological deaths. Survival analysis combining stroke or death demonstrated a significant benefit for long-term circulatory support with an LVAD over medical therapy. Future trials will need to address prospectively all neurological outcomes, including neurocognitive function, and the role of long-term neuroprotection.

Thromboendarterectomy for Chronic, Major-Vessel Thromboembolic Pulmonary Hypertension: Immediate and Long-Term Results in 42 Patients

Since 1970, forty-two patients with pulmonary hypertension due to chronic, thromboembolic obstruction of the major pulmonary arteries have had pulmonary thromboendarterectomy at the University of California, San Diego, and the San Diego Veterans Medical Centers. Duration of symptoms before admission averaged 4.4 years, with many alternative diagnoses having been made. At admission, 29 patients had class IV disease by New York Heart Association criteria, and 12, class III. Immediately after surgery, pulmonary vascular resistance declined significantly (p less than 0.001) from 897 +/- 352 dynes/s.cm-5 to 278 +/- 135 dynes/s.cm-5. Seven patients with class IV disease died in the postoperative period. Of the 35 survivors (mean follow-up, 28 months), 16 had class I disease; 18, class II; and 1, class III. Of the 17 patients who have returned for cardiac catheterization at 4 to 12 months after surgery, a further decline (p less than 0.05) in pulmonary vascular resistance has occurred. This experience indicates that the disorder is commoner than we previously suspected and that thromboendarterectomy is feasible, even in patients with severe and protracted hemodynamic compromise.

Prospective, Multicenter Study of Ventricular Assist Device Infections

Background— Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. Methods and Results— One hundred fifty patients scheduled for VAD implantation were enrolled (2006–2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073–0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). Conclusions— This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Human Cardiac Progenitor Cells Engineered With Pim-I Kinase Enhance Myocardial Repair

OBJECTIVES The goal of this study was to demonstrate the enhancement of human cardiac progenitor cell (hCPC) reparative and regenerative potential by genetic modification for the treatment of myocardial infarction. BACKGROUND Regenerative potential of stem cells to repair acute infarction is limited. Improved hCPC survival, proliferation, and differentiation into functional myocardium will increase efficacy and advance translational implementation of cardiac regeneration. METHODS hCPCs isolated from the myocardium of heart failure patients undergoing left ventricular assist device implantation were engineered to express green fluorescent protein (hCPCe) or Pim-1-GFP (hCPCeP). Functional tests of hCPC regenerative potential were performed with immunocompromised mice by using intramyocardial adoptive transfer injection after infarction. Myocardial structure and function were monitored by echocardiographic and hemodynamic assessment for 20 weeks after delivery. hCPCe and hCPCeP expressing luciferase were observed by using bioluminescence imaging to noninvasively track persistence. RESULTS hCPCeP exhibited augmentation of reparative potential relative to hCPCe control cells, as shown by significantly increased proliferation coupled with amelioration of infarction injury and increased hemodynamic performance at 20 weeks post-transplantation. Concurrent with enhanced cardiac structure and function, hCPCeP demonstrated increased cellular engraftment and differentiation with improved vasculature and reduced infarct size. Enhanced persistence of hCPCeP versus hCPCe was revealed by bioluminescence imaging at up to 8 weeks post-delivery. CONCLUSIONS Genetic engineering of hCPCs with Pim-1 enhanced repair of damaged myocardium. Ex vivo gene delivery to modify stem cells has emerged as a viable option addressing current limitations in the field. This study demonstrates that efficacy of hCPCs from the failing myocardium can be safely and significantly enhanced through expression of Pim-1 kinase, setting the stage for use of engineered cells in pre-clinical settings.

Improved patient survival after cardiac arrest using a cardiopulmonary support system

A portable cardiopulmonary bypass system that can be rapidly deployed in a nonsurgical setting using nursing staff was used in 38 patients with cardiovascular collapse refractory to ACLS protocol. Percutaneous or cutdown cannulation sites were: femoral vein-femoral artery (n = 18), right internal jugular vein-femoral artery (n = 2), right atrium-ascending aorta (n = 12), or a combination approach (n = 4). Two patients could not be cannulated. Patient diagnoses were pulmonary emboli (n = 3), failed coronary angioplasty (n = 7), myocardial infarction with cardiogenic shock (n = 5), trauma (n = 7), aortic stenosis (n = 2), postcardiotomy deterioration (n = 10), deterioration after cardiac transplantation (n = 2), cardiomyopathy with shock (n = 1), and ruptured ascending aortic dissection (n = 1). Ninety-five percent of patients (36 of 38) were successfully resuscitated to a stable rhythm. Eight diagnostic procedures (coronary angiography, n = 4; pulmonary angiography, n = 3; and aortography, n = 1) were performed while patients were on cardiopulmonary support. Early deaths resulted from massive hemorrhage (n = 8), inability to cannulate (n = 2), and irreversible myocardial injury (n = 10). Sixty-six percent (24 of 36) of patients successfully cannulated underwent conversion to standard cardiopulmonary bypass with attendant operative procedure or placement of ventricular assist device or total artificial heart. Fifty percent (18 of 36) of patients cannulated were successfully weaned from cardiopulmonary support, and 17% (6/36) are long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter experience : Prevention and management of left ventricular assist device infections

Implantable left ventricular assist devices (LVADs) have demonstrated clinical success in both the bridge-to-transplantation and destination-therapy patient populations; however, infection remains one of the most common causes of mortality during mechanical circulatory support. Thus, serious LVAD infections may negate the benefits of LVAD implantation, resulting in decreased quality of life, increased morbidity and mortality, and increased costs associated with implantation. Prevention of device-related infection is crucial to the cost–effective use of mechanical circulatory support devices. Therefore, adherence to evidence-based infection control and prevention guidelines, meticulous surgical technique and optimal postoperative surgical site care form the foundation for LVAD associated infection prevention.

Clinical strategies and outcomes in advanced heart failure patients older than 70 years of age receiving the HeartMate II left ventricular assist device: a community hospital experience.

OBJECTIVES The primary objective of this study was to determine outcomes in left ventricular assist device (LVAD) patients older than age 70 years. BACKGROUND Food and Drug Administration approval of the HeartMate II (Thoratec Corporation, Pleasanton, California) LVAD for destination therapy has provided an attractive option for older patients with advanced heart failure. METHODS Fifty-five patients received the HeartMate II LVAD between October 5, 2005, and January 1, 2010, as part of either the bridge to transplantation or destination therapy trials at a community hospital. Patients were divided into 2 age groups: ≥ 70 years of age (n = 30) and < 70 years of age (n = 25). Outcome measures including survival, length of hospital stay, adverse events, and quality of life were compared between the 2 groups. RESULTS Pre-operatively, all patients were in New York Heart Association functional class IV refractory to maximal medical therapy. Kaplan-Meier survival for patients ≥ 70 years of age (97% at 1 month, 75% at 1 year, and 70% at 2 years) was not statistically different from patients <7 0 years of age (96% 1 month, 72% at 1 year, and 65% at 2 years, p = 0.806). Average length of hospital stay for the ≥ 70-year age group was 24 ± 15 days, similar to that of the < 70-year age group (23 ± 14 days, p = 0.805). There were no differences in the incidence of adverse events between the 2 groups. Quality of life and functional status improved significantly in both groups. CONCLUSIONS The LVAD patients ≥ 70 years of age have good functional recovery, survival, and quality of life at 2 years. Advanced age should not be used as an independent contraindication when selecting a patient for LVAD therapy at experienced centers.

Epicardial activation and repolarization patterns in patients with right ventricular hypertrophy.

To map globalepicardialrepolarizationpatternsandtestthe “SI” modelofTwave generation, the patterns of epicardial activation and repolarization in patients with chronic pulmonary thromboembolism and right ventricular hypertrophy were studied by computerized mapping techniques and monophasic action potential (MAP) recordings. The ventricular activation patterns were characterizedbydelayed rightventricularactivation and the absenceofnormal early epicardial ventricular breakthrough in some cases. The repolarization patterns were characterized bynonuniform distribution ofTwave morphologies. The Twaves were predominantly positive over the left ventricular epicardium and negative or biphasic over the right ventricularepicardium. Theactivation-recovery (A-R) intervalswere measured from thelocal activation tothemaximal dV/dtoftheupstroke ofthe Twaves (Wyattmethod).Thedifference betweentheA-RintervalsandtheMAPfromonsetofactivationto90%repolarization (MAP90) varies accordingtoTwave morphologyandcould be as highas 96 msec with positiveTwaves, despite significant correlations (r = 0.56–0.90) between MAP90 and A-R intervals for each morphology. BetteroverallcorrelationswerefoundiftheminimaldV/dton thedownslopeofthe positive Twaves was chosen to estimate the time oflocal repolarization (alternative method). Using this method, the mean A-R intervals were the same over the right and left ventricles. Cardiopulmonary bypass significantly prolonged the action potential duration equally at all parts ofthe epicardium. We conclude that in patients with rightventricular hypertrophy, the timeoflocalrepolarization can bestbeestimatedbyour alternativemethod;therightventricle completes activation and repolarization laterthan the leftventricle, and the distribution ofT wave morphologies is nonuniform, with predominantly positive Twaves observed over the left ventricleandnegativeor biphasicTwaves observedover therightventricle. Thesefindings are compatiblewith the SI model ofthe generation ofTwaves.

Emergency resuscitation using portable extracorporeal membrane oxygenation

Manual cardiopulmonary resuscitation is currently the standard treatment for cardiac arrest patients both in and out of the hospital. Accumulated experimental and anecdotal clinical evidence suggests enhanced survival in patients with extreme circulatory decompensation who have been emergently supported with portable cardiopulmonary bypass. Long-term survival is possible even when application is delayed, but early institution of support after cardiac arrest in selected patients offers the best survival advantages. In our hospital this has been achieved by training a team of in-house personnel to emergently prepare, apply, and temporarily manage cardiopulmonary bypass until personnel with greater specialty training arrive. Machinery needed to perform emergency cardiopulmonary bypass is currently available in all hospitals with open heart surgery programs. Simple support is often therapeutic but can also serve as a bridge to definitive diagnostic and other therapeutic procedures. Commercial units are becoming more biocompatible and easier to use, making both wider application and more prolonged support likely in the future.

Cost reduction by combined carotid endarterectomy and coronary artery bypass grafting

A significant cost reduction is likely if patients who require coronary artery bypass grafting with significant carotid stenosis have simultaneous carotid endarterectomy and bypass grafting, provided risk is not increased. To investigate this issue, we retrospectively identified cases from February 1977 to May 1994 with first-time isolated carotid endarterectomy, coronary bypass, or combined procedures. In the isolated carotid endarterectomy population, median age was 69 years and 58% (85/146) were male, as compared with 68 years and 68% (68/100) male in the combined group; median age of the coronary bypass cohort was 65 years and 76% (381/500) male. A significantly higher percentage of patients in the coronary bypass versus combined group were in New York Heart Association functional class IV. In the combined group there was a significantly higher incidence of older age, diabetes, hypertension, hyperlipidemia, renal failure, and congestive heart failure. There was no difference among the three groups with respect to hospital mortality (0%, 3.4%, and 4.0%, respectively) and permanent stroke (0.7%, 1.2%, and 0%, respectively). Hospital costs were