Search

Objectives: This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart., Background: Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among microvasculature, fibrosis, and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown, and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial., Methods: Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n = 15) and from normal donors (n = 8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size, and glycogen content. Ultrastructural assessment was done with electron microscopy., Results: Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p = 0.001) and a 36% decrease in microvascular lumen area (p = 0.028). We also identified, in agreement with these findings, ultrastructural and immunohistochemical evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural, or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration., Conclusions: The LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features might guide future studies of unloading-induced reverse remodeling of the failing human heart., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation appears to be associated with increased mortality. However, the determination of which patients are at greater risk of developing postoperative RVF remains controversial and relatively unknown. We sought to determine the preoperative risk factors for the development of RVF after LVAD implantation. The data were obtained for 175 consecutive patients who had received an LVAD. RVF was defined by the need for inhaled nitric oxide for >/=48 hours or intravenous inotropes for >14 days and/or right ventricular assist device implantation. An RVF risk score was developed from the beta coefficients of the independent variables from a multivariate logistic regression model predicting RVF. Destination therapy (DT) was identified as the indication for LVAD implantation in 42% of our patients. RVF after LVAD occurred in 44% of patients (n = 77). The mortality rates for patients with RVF were significantly greater at 30, 180, and 365 days after implantation compared to patients with no RVF. By multivariate logistic regression analysis, 3 preoperative factors were significantly associated with RVF after LVAD implantation: (1) a preoperative need for intra-aortic balloon counterpulsation, (2) increased pulmonary vascular resistance, and (3) DT. The developed RVF risk score effectively stratified the risk of RV failure and death after LVAD implantation. In conclusion, given the progressively growing need for DT, the developed RVF risk score, derived from a population with a large percentage of DT patients, might lead to improved patient selection and help stratify patients who could potentially benefit from early right ventricular assist device implantation., (Copyright 2010 Elsevier Inc. All rights reserved.)

Left ventricular assist device (LVAD) implantation before heart transplantation has been associated with formation of antibodies directed against human leukocyte antigens (HLA), often referred to as sensitization. This study investigated whether prior sensitization or LVAD type affected the degree of post-implantation sensitization. The records of consecutive HeartMate (HM) I and HM II LVAD patients were reviewed. Panel reactive antibody (PRA) was assessed before LVAD implantation and biweekly thereafter. Sensitization was defined as PRA > 10%, and high-degree sensitization was defined as PRA > 90%. An HM LVAD was implanted in 64 patients, and 11 received a HM II LVAD as a bridge to transplant. Ten HM I patients (16%) were sensitized before LVAD implantation (HM I-S), and 54 (84%) were not (HM I-Non-S). Nine HM I-S patients (90%) became highly sensitized (PRA > 90%) compared with 9 HM I-Non-S patients (16.7%; p < 0.001). The PRA remained elevated (> 90%) in 8 of the 9 (88.9%) highly sensitized HM I-S patients vs 5 of the 9 (55.6%) HM I-Non-S highly sensitized patients. The PRA levels in the rest of the HM I-S highly sensitized patients declined from 93% +/- 4% to 55% +/- 15% (p = 0.01). Among the 11 HM II patients, 1 (9%) was sensitized before LVAD implantation (PRA, 40%) and the PRA moderately increased to 80%. No other HM II patient became sensitized after implantation. Thus, 1 of 11 (9%) HM II patients became sensitized compared with 29 of 64 (45%) HM I patients (p = 0.04). Pre-sensitized patients are at higher risk for becoming and remaining highly HLA-allosensitized after LVAD implantation. The HeartMate II LVAD appears to cause less sensitization than HeartMate I.

An increasing number of patients are living with ventricular assist devices (VADs). Many of these patients will require noncardiac surgery for conditions not directly related to their VADs. The aim of this study was to assess the risks and outcomes of noncardiac surgery in these patients. Perioperative and follow-up data from patients with VADs who underwent noncardiac surgery from 1993 to 2006 were analyzed. In that period, 184 VADs were implanted in 155 patients. Thirty-seven patients (24%) subsequently underwent 59 noncardiac surgeries. The mean duration of VAD support before surgery was 229 days. Bleeding was the most common postsurgical complication (10%), necessitating reexploration in 20% of abdominal surgeries. Thirty-day mortality was 12%. No deaths were caused by direct complications of surgery. Successful transplantation occurred in 72% of bridge to transplantation patients who required noncardiac surgery, compared with 71% of these patients who did not require noncardiac surgery (relative risk 1.0, p = 0.9). The average duration of VAD support after noncardiac surgery for destination therapy patients was 324 days, most of which time was spent at home. In conclusion, outcomes after noncardiac surgery in patients with VADs are favorable, and most patients continue to benefit from the intended purpose of mechanical circulatory support after recovering from noncardiac surgery.

Objective: Destination therapy experience using long-term left ventricular assist devices was analyzed relative to the benchmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial to evaluate the potential for improving outcomes with this groundbreaking therapy for advanced heart failure., Methods: The largest single-center experience with destination therapy in the United States (Utah Artificial Heart Program, LDS Hospital, Salt Lake City, UT) was retrospectively analyzed. All destination therapy recipients (n = 23) presented with chronic, advanced heart failure, meeting indications for destination therapy adopted from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. All received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif), with 87% receiving an improved XVE model. Advanced practice guidelines were implemented using a multidisciplinary approach. Survivals (Kaplan-Meier, log-rank analyses) and adverse events (Poisson regression) were compared with those of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (n = 68)., Results: Survival in the destination therapy group was significantly increased (P = .007), with an overall reduction in mortality of 66%. The 2-year survival was 77% for destination therapy compared with 29% for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (P < .0001). The 1-year survival was 77% for destination therapy compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 52% (P = .036). Adverse events decreased by 38% (3.90 per patient-year in the destination therapy group compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 6.32). Factors related to severity of illness met Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure-like criteria for both groups., Conclusions: This analysis provides evidence that long-term destination therapy can be improved well beyond the pioneering experience of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible.

Management of heart failure (HF) remains complex with low 5-year survival. The Seattle Heart Failure Model (SHFM) is a recently described risk score derived predominantly from clinical trial populations that may enable the prediction of survival in patients with HF. This study sought to validate the SHFM in an independent, nonclinical trial-based HF population. Patients (n = 4,077) from the hospital-based Intermountain Heart Collaborative Study registry with a diagnosis of HF were evaluated using prospectively collected data (mean +/- SD follow-up 4.4 +/- 3.1 years). The SHFM was used to calculate a risk score for each patient. Receiver-operating characteristic area under the curve provided SHFM predictive ability for a composite end point of survival free from death, transplantation, or left ventricular assist device implantation. Addition of creatinine, serum urea nitrogen, diabetes status, and B-type natriuretic peptide (BNP) to the SHFM was also evaluated. Patient age averaged 67 +/- 13 years and 61% were men. Area under the curves were 0.70 (95% confidence interval 0.66 to 0.70), 0.67 (95% confidence interval 0.66 to 0.69), 0.67 (95% confidence interval 0.065 to 0.68), and 0.66 (95% confidence interval 0.63 to 0.67) for 1-, 2-, 3-, and 5-year survivals, respectively. Area under the curves were slightly attenuated in patients >75 years of age (n = 1,339), implantable cardioverter-defibrillator recipients (n = 693), and patients with an ejection fraction >40% (n = 1,634). BNP added significantly to the model (area under the curve +0.06). BNP was found to add additional predictive ability at 1 year (area under the curve change +0.05) and nominally at 5 years (area under the curve change +0.02). In conclusion, the SHFM predicts survival in patients with HF in a hospital-based population, with areas under the curve similar to those from data on which models were initially fit.

Background: Heart failure (HF) patients may require cardiac assist device implantation prior to transplantation (Tx) because of either acute cardiogenic shock (ACS), with no prior history of HF, or for progression of pump failure in the setting of chronic HF., Aims: To investigate whether patients implanted with a cardiac assist device for ACS, have similar post-Tx outcomes as those who underwent cardiac assist device implantation because of progressive chronic HF., Methods and Results: We compared post-Tx outcomes of consecutive patients bridged due to ACS (Acute Group) with the outcomes of patients bridged due to deterioration of chronic HF (Chronic Group). Seventy-three patients had a cardiac assist device implanted and underwent subsequent cardiac Tx. Thirty-five patients (48%) had a cardiac assist device implanted due to ACS, most often caused by massive acute myocardial infarction, and 38 patients (52%) because of progressive chronic HF. Despite greater compromise at the time of implantation, the Acute Group recovered satisfactorily and underwent Tx with similar post-Tx survival rates as the Chronic Group patients [1-year survival: 88.6% vs 86.8%, p=0.80, actuarial survival (mean follow-up 4.2 years): 80.0% vs 81.6%, p=0.86)]. Furthermore, no significant differences were observed between the 2 groups in various post-Tx events., Conclusion: Patients with ACS who underwent emergency cardiac assist device implantation as bridge to Tx had similar post-Tx outcomes as their more chronically ill counterparts who underwent device implantation on a non-urgent basis.

Objective: Allosensitization of left ventricular assist device recipients has been associated with perioperative transfusion of cellular blood products. The relative sensitizing contribution of leukofiltered cellular blood products, however, remains unclear. We investigated the pattern of sensitization in left ventricular assist device recipients in relation to cellular blood product transfusions received., Methods: Seventy-one consecutive nonsensitized recipients of the HeartMate left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) as a bridge to transplantation were reviewed. Panel-reactive HLA antibody levels at consecutive times after device implantation were correlated with perioperative cellular blood product transfusions., Results: Fifty-four patients received leukofiltered cellular blood products (transfused), whereas 17 patients received only fresh-frozen plasma (nontransfused). Among nontransfused patients, 58.8% (10/17) became sensitized during mechanical support, versus 35.2% of transfused patients (19/54, P = .15). There was a trend toward more sensitization during the 12 weeks after device placement in nontransfused patients. Kaplan-Meier analysis revealed significantly more sensitization in nontransfused patients than in transfused patients, despite equal rates of transplantation (P = .05). A dose-response analysis revealed significant trends toward less sensitization and lower peak panel-reactive antibody level with more cellular blood product transfusions (P = .04). Multivariate Cox regression revealed only increasing transfusions to be associated with a reduced risk of sensitization (hazard ratio 0.18, P = .01)., Conclusions: Sensitization becomes more prevalent with increasing length of support. Avoidance of perioperative leukocyte-filtered cellular blood product transfusions does not decrease the incidence or degree of HLA sensitization. Conversely, cellular blood product transfusions may be associated with lessened alloimmunization and may mitigate the sensitization seen in recipients of the HeartMate left ventricular assist device as a bridge to transplantation.

Background: The use of left ventricular assist devices is associated with human leukocyte antigen (HLA) allosensitization. We investigated whether prophylactic treatment with low-dose intravenous immunoglobulin (IVIG), analogous to the use of IgG anti-D (anti-Rh) in preventing Rh immunization, can abrogate HLA allosensitization after left ventricular assist device implantation., Methods: We retrospectively reviewed the data from 84 consecutive heart failure patients who underwent implantation of a left ventricular assist device as a bridge to transplantation. After implantation, panel reactive antibody (PRA) was measured biweekly to assess sensitization (defined by PRA > 10%). Patients who were sensitized before left ventricular assist device implantation were excluded from further analysis (n = 12). Patients who either did not require perioperatively transfusions of cellular blood products or received other immunomodifying regimens were also excluded from further analysis (n = 21). The rest of the patients were divided into two groups based on whether they received IVIG, 10 g daily for 3 days (IVIG group, n = 26; non-IVIG group, n = 25). The decision as to whether patients received IVIG was not randomized but was based on surgeon preference., Results: The sensitization rates (expressed as ratio of sensitized patients to total patients at risk) in the two groups were similar at consecutive time points (2, 4, 6, 8, 12, 20 weeks) after left ventricular assist device implantation. Also, mean PRA at the same time points did not differ between the two groups. Overall, 34.6% (9 of 26) of the IVIG group became sensitized during mechanical support, compared with 32% (8 of 25) of the non-IVIG group (p = 1.0). A PRA of 90% or greater (high-degree sensitization) occurred in 15.3% (4 of 26) of the IVIG group and 12.0% (3 of 25) of the non-IVIG group (p = 0.5)., Conclusions: The use of low-dose prophylactic IVIG after left ventricular assist device implantation affects neither the incidence nor the severity of HLA allosensitization.

Background: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS., Methods: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups., Results: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001)., Conclusion: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.

Background: Left ventricular assist devices (LVADs) have improved survival in patients with end-stage heart failure. Compared with previous trials, the Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial enrolled patients with more advanced heart failure and high prevalence of intravenous inotropic therapy. This study analyzes, on a post hoc basis, outcomes in patients undergoing inotropic infusions at randomization., Methods and Results: Of 129 patients randomized, 91 were receiving intravenous inotropic therapy at randomization to LVAD or optimal medical management (OMM). Mean systolic pressure was 100 versus 107 mm Hg in those not receiving inotropes, serum sodium was 134 versus 137 mEq/L, and left ventricular ejection fraction was 17% for both groups. LVADs improved survival throughout follow-up for patients undergoing baseline inotropic infusions (P=0.0014); for the LVAD group versus the OMM group, respectively, 6-month survival was 60% versus 39%, 1-year survival rates were 49% versus 24%, and 2-year survival rates were 28% versus 11%. For 38 patients not undergoing inotropic infusions, 6-month survival was 61% for those with LVADs and 67% for those with OMM, whereas 1-year rates were 57% and 40%, respectively (P=0.55). Quality-of-life scores for survivors improved. Median days out of hospital for patients on inotropic therapy at randomization were 255 with LVAD and 105 with OMM., Conclusions: Despite severe compromise, patients undergoing inotropic infusions at randomization derived major LVAD survival benefit with improved quality of life. Patients not undergoing inotropic infusions had higher survival rates both with and without LVAD, but differences did not reach significance. Future studies should prespecify analyses of inotropic and other therapies to determine how disease severity and parallel medical treatment influence the benefits offered by mechanical circulatory support.

Objectives: A protocol was designed to diagnose the common malfunctions of a left ventricular assist device (LVAD)., Background: Mechanical circulatory support, primarily with an LVAD, is increasingly used for treatment of advanced heart failure (HF). Left ventricular assist device dysfunction is a recognized complication; but heretofore, a systematic method to accurately diagnose LVAD dysfunction has not been thoroughly described., Methods: We developed a catheter-based protocol designed to characterize a normally functioning LVAD and diagnose multiple types of dysfunction. A total of 15 studies of 10 patients supported with an LVAD were reviewed. All patients had been evaluated due to concerns regarding LVAD dysfunction., Results: Of 15 examinations performed, 11 documented severe LVAD inflow valve regurgitation. One of these cases proved to have coexistent severe mitral valve regurgitation. One case was diagnosed with distortion of the LVAD outflow graft. One case of suspected embolization from the pumping chamber excluded the outflow graft as the source of emboli. One study had aortic insufficiency., Conclusions: As LVAD use for treatment of end-stage HF becomes widespread and durations of support are extended, dysfunction will be increasingly prevalent. This catheter-based protocol provided a practical method to diagnose multiple causes of LVAD dysfunction.