Invasive fungal infection after heart transplantation: A 7-year, single-center experience.

BACKGROUND: Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution. METHODS: A prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: By univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32-411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%). CONCLUSIONS: The cumulative incidence was 10.7%. IFIs were associated with pre- and post-HT vancomycin-resistant Enterococcus colonization and/or infection, post-HT renal replacement therapy, anti-thymocyte globulin induction, and antibody-mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re-operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3-12.1) and 1-year mortality (P<.001, OR 9.0, 95% CI 2.3-35.7), but not 3-year mortality. Associations with Hispanic ethnicity must be validated. Optimal strategies for risk reduction and prophylaxis remain undefined.

Percutaneous closure of the aortic valve as a bridge to heart transplantation to treat severe aortic insufficiency after ventricular assist device.

Aortic insufficiency (AI) following rotary left ventricular assist device (LVAD) implantation is an increasingly common problem with inadequately defined treatment options. Percutaneous transcatheter (PTC) closure of the aortic valve (AV) has been described as a potential nonsurgical approach. Alternatively, we present a case of decompensated heart failure due to de novo severe AI following LVAD in which successful PTC closure of the AV resolved the severe AI and allowed for clinical recovery and stability for more than 10 months as a bridge to heart transplantation.

Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.

BACKGROUND: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. METHODS AND RESULTS: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. CONCLUSIONS: A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

Do patients with heart failure benefit from coronary artery bypass grafting?

PURPOSE OF REVIEW: The purpose of this review is to examine the appropriateness of coronary artery bypass grafting (CABG) for the patient with ischemic cardiomyopathy and congestive heart failure. RECENT FINDINGS: CABG is the gold standard therapy for patients with advanced multivessel and left main coronary artery disease. A critical analysis of the Surgical Treatment of Ischemic Heart Failure (STICH) trial confirms the benefit of CABG for patients with ischemic cardiomyopathy. SUMMARY: CABG can be safely applied to patients with heart failure and provides benefit for appropriately selected patients.

Successful implantation of HeartWare HVAD left ventricular assist device with concomitant ascending and sinus of valsalva aneurysms repair.

Coexistence of aortic disease is an uncommon finding in end-stage heart failure patients requiring left ventricular assist device (LVAD) placement. A 38-year-old man with non-ischemic dilated cardiomyopathy was admitted in stage D heart failure. Preoperative computed tomography demonstrated multiple saccular aneurysms of the ascending aorta and sinus of valsalva. We successfully performed complex aortic surgery and the implantation of a continuous-flow LVAD (HeartWare HVAD) (HeartWare International, Framingham, MA). The postoperative course was uneventful. The patient is currently listed for heart transplantation.

Two-Year Follow Up of the LATERAL Clinical Trial: A Focus on Adverse Events.

BACKGROUND: The LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system. METHODS: AEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year. RESULTS: During 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of <30 and 30 to 180 days, and 6 to 12 and 12 to 24 months revealed the highest AE rate at <30 days, with a decrease in total AEs within the first 6 months. After 6 months, most AE rates either stabilized or decreased through 2 years, including a 95% overall freedom from disabling stroke. CONCLUSIONS: Two-year follow-up of the LATERAL trial revealed a favorable morbidity profile in patients supported with the HVAD system, as AE rates were more likely to occur in the first 30 days postimplant, and overall AE rates were significantly reduced after 6 months. Importantly, 2-year freedom from disabling stroke was 95%. These data further support the improving AE profile of patients on long-term HVAD support. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02268942.

Biventricular Support With Intracorporeal, Continuous Flow, Centrifugal Ventricular Assist Devices.

BACKGROUND: The incidence of right ventricular dysfunction requiring right ventricular assist device after left ventricular assist device placement has been reported between 10% to 30%. The mortality rate is higher compared with patients who require left ventricular assist device only; the most effective and safest biventricular assist device remains unknown. We aimed to determine the survival outcomes and frequency of adverse events in patients with two durable, intracorporeal, continuous flow centrifugal pumps for support. METHODS: Between November 2012 and June 2015, 38 patients were identified from INTERMACS received durable, intracorporeal continuous flow centrifugal pumps for biventricular support. Pediatric patients were excluded. Mean age was 47 years, and 74% of patients were male. The common primary diagnoses in this cohort were dilated myopathy, idiopathic (37%) and ischemic (16%). RESULTS: Nineteen participating centers implanted devices in 38 patients; 11 patients died with device in place, 9 patients received a heart transplant, and 18 were alive on support with the right ventricular assist device in place. Survival outcomes were 68% at 6 months and 62% at 12 months. The left ventricular assist device was placed in the left ventricle apex in 91% of cases, and in 9%, the location was not specified. The right ventricular assist device was placed in the right ventricle in 50%, right atrium in 37%, and not specified in 13%. The adverse events included infection 50%, bleeding 44%, respiratory failure 31.6%, and malfunction 26.3%; neurologic dysfunction 26.3%; renal dysfunction 18.4%; and arrhythmia 18.4%. CONCLUSIONS: The use of durable, intracorporeal, continuous flow centrifugal pumps for management of advanced biventricular heart failure is associated with high morbidity and mortality. Further investigation of this device configuration is warranted.

Adverse Event Rates Change Favorably Over Time for Patients Bridged With the HeartWare Left Ventricular Assist Device.

The HeartWare Ventricular Assist System (HVAD) provides significant improvements in survival and quality of life, and here, we seek to evaluate temporal differences in the adverse event (AE) rates. Patients (n = 382) in the ADVANCE bridge-to-transplant and continued access protocol trial were assessed for bleeding, cardiac arrhythmia, infection, ischemic and hemorrhagic stroke, and right heart failure during predetermined time periods (≤30, >30-180, >180-365, >365-730, >730-1,095 days) after HVAD implant. The Kaplan-Meier survival at 30 days, 6 months, 1, 2, and 3 years was 98%, 90%, 84%, 71%, and 63%, respectively. There were significantly fewer total AEs in days >30-180 (events per patient year [EPPY] = 5.34) compared with the first 30 days post HVAD implantation (EPPY = 30.36; p < 0.0001). The total AE rate in days >180-365 (EPPY = 4.09) was also significantly lower than the event rate in days >30-180 (EPPY = 5.34; p < 0.0001). Incidence of cardiac arrhythmias, infections, strokes, and right heart failure were highest immediately post implant and lower rates occurred after 6 months. After 1 year, all AEs exhibited stable rates that were comparable up to 3 years of support (all p > 0.05). This changing risk over time has clinically meaningful implications toward improving patient management.

Gender differences in appraisal of stress and coping 5 years after heart transplantation.

OBJECTIVES: We examined whether gender differences exist regarding stress, symptom distress, coping, adherence, and social support 5 years after heart transplantation. BACKGROUND: Differences exist in health-related quality of life outcomes by gender after heart transplantation; women report poorer outcomes. METHODS: Patients (n = 210, female = 42), were from a prospective, multi-site, study of health-related quality of life long-term after heart transplantation. Patients completed self-report instruments 5 years after heart transplantation (mean = 4.98 ± 0.17 years after transplant). Statistical analyses included two-sample t-tests, Chi-square or Fisher's exact test, and multivariable modeling. RESULTS: Women did not report more overall stress or symptom distress, but reported more difficulty adhering to the transplant regimen, yet more actual adherence than men. Women reported using more negative coping styles, but reported more satisfaction with social support. CONCLUSIONS: Gender differences exist regarding appraisal of stress, coping styles, and coping resources long-term after heart transplantation. These differences may guide tailoring therapy regarding stress, poor coping, and lack of resources.

Chronic descending aortic dissections.

Aortic dissection involving the descending aorta has a predictable and often debilitating course of progressive dilatation that occurs once patients survive the acute phase of the disease. Important factors that impact the rate and degree of dilatation include the persistence of a false lumen channel (and the amount of thrombus), the control of hypertension, and the presence of an underlying connective tissue disorder. The mainstay of management of chronic descending aortic dissections is antihypertensive therapy including beta-blockade until the dissected aorta becomes significantly aneurysmal. Surgical management is recommended at that point. Multiple advances have been made that have improved the results of operative repair of aneurysmal descending aortic dissections including circulation management methodologies, CSF drainage, neurocerebral monitoring, and more recently, endovascular therapies. The presentation, diagnosis and management of chronic descending aortic dissections are discussed.

Nontransplant surgical alternatives for heart failure.

Heart failure is a tremendous burden on society, and on the health care system in particular. Historically, medical treatments have been the only therapies available because patients were felt to be too high risk to undergo conventional cardiac surgical procedures. Cardiac transplantation remains an established therapy for certain patients with end-stage heart failure but it is limited by donor availability and the need for lifelong immunosuppression. Recent advances in myocardial protection, operative techniques, and perioperative care have made it possible for conventional surgery, such as coronary bypass, ventricular reconstruction, and valve repair, to be offered to many patients with advanced heart failure with good short- and long-term results. In 2005, few patients are inoperable.

Health-related quality of life in mechanical circulatory support: Development of a new conceptual model and items for self-administration.

BACKGROUND: Generic and heart failure (HF)-specific health-related quality of life (HRQOL) instruments do not address unique burdens of mechanical circulatory support (MCS). This report describes (1) a conceptual model of adjustment to MCS and HRQOL, (2) the development of a new set of items to assess adjustment and HRQOL, and (3) establishes content validity of the new model and items. METHODS: We interviewed 15 expert clinicians, 16 patients with advanced HF, and 48 MCS patients. A grounded theory approach was used to systemically examine qualitative data. We developed a coding dictionary, with codes organized under concepts. A conceptual model of adjustment to MCS and HRQOL was developed. A set of relevant items was generated from the codes, concepts, and conceptual model. After items were refined, MCS patients participated in cognitive interviews to provide feedback on their relevance and acceptability. RESULTS: Patients described how having HF and MCS affected their daily lives. Three concepts regarding adjustment to MCS and its relationship to HRQOL emerged: (1) effect of disease and treatment (satisfaction with treatment, symptoms, and self-efficacy regarding self-care), (2) resources, and (3) implant strategy. From our codes, concepts, and model, we developed a set of 652 items that were categorized by concept. The item set was reduced from 652 items to 236 (36%), and 120 of these 236 items (51%) underwent cognitive debriefing. Our final set includes 239 items with evidence of content validity. CONCLUSIONS: Our newly developed model on adjustment to MCS and HRQOL and items will undergo further testing in the future.

Change in health-related quality of life from before to after destination therapy mechanical circulatory support is similar for older and younger patients: analyses from INTERMACS.

BACKGROUND: Destination therapy left ventricular assist devices (DT LVADs) are being implanted in older adults on an increasing basis. Older patients have a higher risk for mortality and morbidity post-LVAD, which may impact their health-related quality of life (HRQOL). We aimed to determine the change in HRQOL by age from before implant to 1 year after DT LVAD implant and identify factors associated with the change. METHODS: Data were collected from 1,470 continuous-flow DT LVAD patients at 108 institutions participating in INTERMACS from January 21, 2010 to March 31, 2012. Patients were divided into three cohorts: <60 years of age (n = 457); 60 to 69 years of age (n = 520); and ≥70 years of age (n = 493). HRQOL was measured using the generic EuroQol instrument (EQ-5D-3L). Data were collected pre-implant and 3, 6 and 12 months post-implant. Statistical analyses included descriptive statistics, Kaplan-Meier survival analyses and multivariable regression analyses. RESULTS: HRQOL improved in all patients. Generally, older patients reported better HRQOL than younger patients pre-implant (≥70 years: mean 40; 60 to 69 years: mean 33; and <60 years: mean 31; p < 0.0001) and 1 year post-implant (≥70 years: mean 77; 60 to 69 years: mean 72; <60 years: mean 70; p = 0.01) using the EQ-5D visual analog scale (VAS), with 0 = worst imaginable health state and 100 = best imaginable health state. The magnitude of improvement in EQ-5D scores from pre-implant to 1-year post-LVAD implant was similar in all age groups (≥70 years: mean change 33; 60 to 69 years: mean change 35; <60 years: mean change 35; p = 0.77). Factors associated with improvement in HRQOL from before to 1 year after implant were a lower VAS score pre-implant and fewer rehospitalizations post-implant (R(2) = 61.3%, p < 0.0001). CONCLUSIONS: Older patients reported better HRQOL than younger patients before and after LVAD implantation. The magnitude of improvement was similar for all age groups, with >70% of all patients showing clinically significant increases (>10 points on the VAS). Rehospitalization appears to reduce the magnitude of improvement.

An examination of survival by sex and race in the HeartWare Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) and continued access protocol trials.

BACKGROUND: The Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) trial was a multicenter, prospective trial of the HeartWare Ventricular Assist Device (HVAD). The performance of the HVAD in various demographic sub-groups was evaluated. METHODS: Baseline characteristics, adverse events, and survival were compared for men vs. women and whites vs. non-whites in the combined ADVANCE BTT and continued access protocol trial. Of 332 patients enrolled in these trials, 236 were men and 96 women, with 228 whites and 104 non-whites. RESULTS: At baseline, women had a smaller body surface area (1.8 ± 0.2 vs. 2.1 ± 0.3 m2, p < 0.0001), less hypertension (50.0% vs. 61.9%, p = 0.05), and less ischemic cardiomyopathy (15.6% vs. 45.3%, p < 0.0001). Differences in Kaplan-Meier survival were not significant at 180 days (men, 91.8%; women, 91.7%) and 1 year (men, 85.3%; women, 85.1%) despite adjustment for baseline differences. Men had a lower incidence of early right heart failure and renal and respiratory dysfunction, and a shorter length of stay. In the analysis by race, non-whites were younger than whites and had less ischemic heart failure, more hypertension, and lower creatinine levels at baseline. Non-whites had lower rates of arrhythmia, bleeding requiring rehospitalization, and device malfunctions than whites. Survival was high in non-whites and whites, at 94.1% vs. 90.4% at 180 days and 89.2% vs. 82.8% at 1 year, respectively, despite adjustment for baseline differences. CONCLUSIONS: Although heart failure etiology differed between men and women and between whites and non-whites, sex and race were not factors that affected survival in patients receiving the HVAD as BTT, which was high in all sub-groups.

The HVAD Left Ventricular Assist Device: Risk Factors for Neurological Events and Risk Mitigation Strategies.

OBJECTIVES: The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD). BACKGROUND: Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. METHODS: Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model. RESULTS: A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078). CONCLUSIONS: Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation.

OBJECTIVES: We sought to characterize the temporal return of mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation; to identify its predictors, particularly with respect to annuloplasty type; and to determine whether annuloplasty type influences survival. METHODS: From April 1985 through November 2002, 585 patients underwent annuloplasty alone for repair of functional ischemic mitral regurgitation, generally with concomitant coronary revascularization (95%). A flexible band (Cosgrove) was used in 68%, a rigid ring (Carpentier) in 21%, and bovine pericardial annuloplasty (Peri-Guard) in 11%. Six hundred seventy-eight postoperative echocardiograms were available in 422 patients to assess the time course of postoperative mitral regurgitation and its correlates. Most echocardiograms were performed early after the operation (median, 8 days); 17% were performed at 1 year or beyond. RESULTS: During the first 6 months after repair, the proportion of patients with 0 or 1+ mitral regurgitation decreased from 71% to 41%, whereas the proportion with 3+ or 4+ regurgitation increased from 13% to 28% ( P < .0001); the regurgitation grade was stable thereafter. The temporal pattern of development of 3+ or 4+ regurgitation was similar for Cosgrove bands and Carpentier rings (25%) but substantially worse for Peri-Guard annuloplasties (66%). Small annuloplasty size did not influence postoperative regurgitation grade ( P = .2), although Cosgrove bands were used in most patients receiving 26- and 28-mm annuloplasties. Freedom from reoperation was 97% at 5 years. Annuloplasty type was not associated with survival. CONCLUSIONS: Although initial mitral valve replacement would eliminate the risk of postoperative mitral regurgitation, this strategy has been associated with reduced survival. Therefore the development of additional techniques is necessary to achieve more secure repair of functional ischemic mitral regurgitation.

Systemic radioimmunotherapy using a monoclonal antibody, anti-Tac directed toward the alpha subunit of the IL-2 receptor armed with the alpha-emitting radionuclides (212)Bi or (211)At.

To exploit the fact that IL-2 receptors are expressed by T-cells responding to foreign antigens but not by resting T-cells, humanized anti-Tac (HAT) armed with alpha-emitting radionuclides (212)Bi and (211)At was evaluated in a cynomolgus cardiac allograft model. Control graft survival was 8.2+/- 0.5 days compared with 14.0+/-1.3 days (p<0.01) survival for monkeys treated with (212)Bi labeled HAT and 26.7+/-2.4 days survival (p<0.001 versus controls) with (211)At labeled HAT. Thus, (211)At labeled HAT may have application in organ transplantation and in treatment of IL-2 receptor expressing T-cell leukemia.