Search

Background: The quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in 3 groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up., Methods: Of 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n = 68 HT MCS, n = 93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models., Results: For the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average ± SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS = 22.58 ± 1.1, HT MCS = 19.53 ± 1.33, Long-term MCS = 19.49 ± 1.3, p = 0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF., Conclusions: Determination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Gastrointestinal bleeding (GIB) affects up to 40% of continuous-flow left ventricular assist device (CF-LVAD) recipients. A higher risk of GIB is seen in CF-LVAD recipients with lower device pulsatility without a known mechanism. One hypothesis is that the novel hemodynamics in CF-LVAD recipients affect angiogenesis signaling. We aimed to (1) measure serum levels of angiopoietin (Ang)-1, Ang-2, and VEGF-A in CF-LVAD recipients with and without GIB and in healthy controls and (2) evaluate correlations of those levels with hemodynamics., Methods: We recruited 12 patients with CF-LVADs (six who developed GIB after device implantation) along with 12 age-matched controls without heart failure or GIB and measured Ang-1, Ang-2, and VEGF-A levels in serum samples from each patient., Results: CF-LVAD recipients had significantly higher Ang-2 and lower Ang-1 levels compared to controls with no difference in VEGF-A levels. CF-LVAD recipients with GIB had lower Ang-1 levels than those without GIB. There were trends for pulse pressure to be positively correlated with Ang-1 levels and negatively correlated with Ang-2 levels in CF-LVAD recipients with no correlation observed in healthy controls., Conclusion: CF-LVAD recipients demonstrated a shift toward a pro-angiogenic phenotype in the angiopoietin axis that is significantly associated with GIB and may be linked to low pulse pressure., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose, (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Context: Research priority guidelines highlight the need for examining the "dose" components of palliative care (PC) interventions, such as intervention adherence and completion rates, that contribute to optimal outcomes., Objectives: Examine the "dose" effect of PC intervention completion vs. noncompletion on quality of life (QoL) and healthcare use in patients with advanced heart failure (HF) over 32 weeks., Methods: Secondary analysis of the ENABLE CHF-PC intervention trial for patients with New York Heart Association (NYHA) Class III/IV HF. "Completers" defined as completing a single, in-person outpatient palliative care consultation (OPCC) plus 6 weekly, PC nurse coach-led telehealth sessions. "Non-completers" were defined as either not attending the OPCC or completing <6 telehealth sessions. Outcome variables were QoL and healthcare resource use (hospital days; emergency department visits). Mixed models were used to model dose effects for "completers" vs "noncompleters" over 32 weeks., Results: Of 208 intervention group participants, 81 (38.9%) were classified as "completers" with a mean age of 64.6 years; 72.8% were urban-dwelling; 92.5% had NYHA Class III HF. 'Completers' vs. "non-completers"" groups were well-balanced at baseline; however "noncompleters" did report higher anxiety (6.0 vs 7.0, P < 0.05, d = 0.28). Moderate, clinically significant, improved QoL differences were found at 16 weeks in "completers" vs. "non-completers" (between-group difference: -9.71 (3.18), d = 0.47, P = 0.002) but not healthcare use., Conclusion: Higher intervention completion rates of an early PC intervention was associated with QoL improvements in patients with advanced HF. Future work should focus on identifying the most efficacious "dose" of intervention components and increasing adherence to them., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Midterm change in health-related quality of life (HRQOL) by left ventricular assist device (LVAD) implant strategy is unknown. The purpose of this study was to examine HRQOL by pre-operative implant strategy from before to 2 years after surgery., Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support were stratified into 3 groups based on pre-implant device strategy: destination therapy (DT) (n = 2,901), bridge to transplant (BTT) (n = 2,209), and bridge to candidacy (BTC) (n = 3,076). HRQOL data were collected before and 2 years after surgery using the generic EQ-5D-3L survey and heart failure-specific Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Statistical analyses included chi-square tests, analysis of variance, paired t-tests, and general linear random effects models., Results: Between April 1, 2008 and June 30, 2013, 4,422 patients and 1,660 patients (majority males and ≥50 years) who received primary continuous flow LVADs completed baseline EQ-5D-3L and KCCQ-12 questionnaires, respectively, whereas 1,615 and 1,408 patients completed EQ-5D-3L and KCCQ-12 questionnaires at 2 years, respectively. Although paired t-tests and general linear random effects models showed that both heart failure-specific and generic HRQOL improved for all groups across time (p-values <0.05), some differences in HRQOL were found by implant strategy at baseline and 2 years, with a pattern favoring better functioning for patients with BTT. The BTT group reported significantly higher overall HRQOL pre-implant using the KCCQ-12 (BTT = 37.09, BTC = 33.57, and DT = 33.56) and at 2 years using the EQ-5D-3L (BTT = 75.18, BTC = 72.27, and DT = 70.87) (p-values <0.05), although these differences were not clinically important differences. Differences in HRQOL domains were also found., Conclusions: Using generic and heart failure-specific instruments, overall HRQOL generally improved from before to 2 years after mechanical circulatory support implant regardless of implant strategy, although important domain-specific differences by group were identified., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated., Methods: The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2-related factor 2 (Nrf-2)-regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility., Results: Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2-activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2-regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN., Conclusions: HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF., Methods: Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation, LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry., Results: Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts., Conclusions: Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: There is a dearth of literature regarding management and outcomes of patients with a left ventricular assist device (LVAD) for advanced heart failure who develop intracranial hemorrhage (ICH). We conducted a case series from 2 centers highlighting patient outcomes and prognostic factors to help clinicians better understand and care for these high-risk patients., Methods: A case series from 2 large-volume institutions (defined as large by the Nationwide Inpatient Sample hospital size, i.e., >500 beds both with Departments of Neurosurgery and Advanced Heart Failure-Cardiology) was conducted to clarify the prognosis of patients with an LVAD and ICH. We included patients who were being treated with an LVAD who developed ICH. Patient-specific demographics and data regarding heart failure and intracranial hemorrhage characteristics were collected and analyzed to determine which factors contributed to overall survival., Results: We analyzed 59 unique ICHs in patients being treated with an LVAD for heart failure. Initial Glasgow Coma Scale score, presence of midline shift, and ICH size were factors found to be predictive of mortality. One institution had a sicker patient population including patients with ICH with lower Glasgow Coma Scale score, presence of midline shift, and greater hemorrhage size, which led to overall higher mortality compared with the second institution., Conclusions: Patients being treated with an LVAD who develop ICH have poor outcomes. Predictive factors for same-admission mortality are lower initial Glasgow Coma Scale score, presence of midline shift, and greater ICH volume., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate predictors of stroke during left ventricular assist device (LVAD) support from data available prior to implantation, and quantify stroke-related morbidity and mortality., Background: Stroke is a major complication after LVAD. Pre-implant factors that influence stroke are not well understood., Methods: We evaluated all patients in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were implanted with continuous flow LVADs from May 1, 2012, to March 31, 2015. Pre-operative risk factors for stroke and stroke incidence, morbidity, and mortality were analyzed., Results: During the study period, 7,112 patients underwent continuous flow LVAD placement. Median follow-up was 9.79 months (range 0.02 to 34.96 months). Of all patients, 752 (10.57%) had at least 1 stroke, with an incidence rate of 0.123 strokes per patient-year. A total of 447 (51.38%) strokes were ischemic and 423 (48.62%) were hemorrhagic. Patients with hemorrhagic stroke had worse survival than those with ischemic strokes (30-day survival: 45.3% vs. 80.7%; p < 0.001). Of patients with a first stroke, 13% had a second stroke. Pre-implant predictors of stroke were female sex (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.25 to 1.82; p < 0.001), pre-implant systolic blood pressure (HR: 1.01; 95% CI: 1.00 to 1.01; p = 0.002), heparin-induced thrombocytopenia (HR: 3.68; 95% CI: 1.60 to 8.47; p = 0.002), intra-aortic balloon pump (HR: 1.21; 95% CI: 1.01 to 1.46; p = 0.043), and primary cardiac diagnosis (ischemic/other/unknown) (p = 0.040)., Conclusions: Despite improvements in LVAD technology, stroke-related morbidity and mortality is substantial. Further investigation is necessary to decrease the risk of this devastating complication., (Copyright © 2017 American College of Cardiology Foundation. All rights reserved.)

Objectives: This study assessed patient and physician perceptions of heart failure (HF) disease severity and treatment options., Background: The prognosis for ambulatory patients with advanced HF on medical therapy is uncertain, yet has important implications for decision making regarding transplantation and left ventricular assist device (LVAD) placement., Methods: Ambulatory patients with advanced HF (New York Heart Association functional class III to IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4 to 7) on optimized medical therapy were enrolled across 11 centers. At baseline, treating cardiologists rated patients for perceived risk for transplant, LVAD, or death in the upcoming year. Patients were also surveyed about their own perceptions of life expectancy and willingness to undergo various interventions., Results: At enrollment, physicians regarded 111 of 161 patients (69%) of the total cohort to be at high risk for transplant, LVAD, or death, whereas only 23 patients (14%) felt they were at high risk. After a mean follow-up of 13 months, 61 patients (38%) experienced an endpoint of 33 deaths (21%), 13 transplants (8%), and 15 LVAD implants (9%). There was poor discrimination between risk prediction among both patients and physicians. Among physician-identified high-risk patients, 77% described willingness to consider LVAD, but 63% indicated that they would decline 1 or more other simpler forms of life-sustaining therapy such as ventilation, dialysis, or a feeding tube., Conclusions: Among patients with advanced HF, physicians identified most to be at high risk for transplantation, LVAD, or death, whereas few patients recognized themselves to be at high risk. Patients expressed inconsistent attitudes toward lifesaving treatments, possibly indicating poor understanding of these therapies. Educational interventions regarding disease severity and treatment options should be introduced prior to the need for advanced therapies such as intravenous inotropic therapy, transplantation, or LVAD., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients., Methods: Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation., Results: The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01)., Conclusions: Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The Cardiac Transplant Research Database (CTRD) collected data from 26 U.S. institutions from January 1, 1990 to December 31, 2008 providing the opportunity for construction of a comprehensive multivariable model of risk for death after transplantation. We analyzed risk factors for death over 19 years of experience to determine how risk profiles have changed over time and how they interact with age., Methods: A multivariable parametric hazard model for death was created for 7,015 patients entered into the CTRD. Variables collected over 19 years of experience were examined as potential risk factors and tested for interaction with date of transplantation to determine if their relative risk (RR) changed over time., Results: The hazard for death post-transplant occurred in 2 phases: an early phase of acute risk lasting <1 year, and a late phase of relatively low, gradually increasing risk (<0.1 event/year). In the early phase, predictive models showed that ventricular assist device (VAD) at the time of transplant did not increase the RR of death for recipient transplant at 30 years of age, but the RR of death was increased by 60% (p = 0.04) at 60 years of age. Of the late-phase variables found to be risk factors, the RR of age, date of transplant and pulmonary vascular resistance changed with respect to transplant year. The overall risk of death dropped importantly over the study period, but the RR of all other variables remained unchanged. RR was 2.6 (p < 0.0001) for 25-year-old African-American (AA) versus non-AA recipients and 1.6 for 60-year-old AA recipients (p = 0.02)., Conclusion: Over 19 years, the baseline risk of death has decreased, but the specific risk factors and the magnitudes of their RR have remained unchanged. Therefore, despite advances in clinical management and improvement in overall survival, the risk profile for death after cardiac transplantation is similar to that in 1990., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study sought to assess feasibility, safety, and potential efficacy of a novel implantable extra-aortic counterpulsation system (C-Pulse) in functional class III and ambulatory functional class IV heart failure (HF) patients., Background: 30% to 40% of HF patients suffer from poor functional status and quality of life (QoL) but are not in need of end-stage treatments. We undertook a multicenter single-arm study to assess the C-Pulse System in such patients., Methods: New York Heart Association (NYHA) functional class III or ambulatory functional class IV HF patients were eligible. Safety was assessed continuously through 12 months. Efficacy measurements included changes from baseline to 6 and 12 months in NYHA functional class, Minnesota Living with Heart Failure (MLWHF) and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, 6-min walk distance (6MWD), and exercise peak oxygen consumption (pVO2; 6 months only)., Results: Twelve men and 8 women (56.7 ± 7 years, 34 to 71 years of age) with ischemic (n = 7) or nonischemic (n = 13) cardiomyopathy were implanted. There was no 30-day mortality and no neurological events or myocardial infarctions through 12 months. At 6 months, there were 3 deaths (1 device-related). One-year survival was 85%. At 6 months, C-Pulse produced improvements in NYHA functional class (3.1 ± 0.3 to 1.9 ± 0.7, p = 0.0005), MLWHF (63.6 ± 19.9 to 40.2 ± 23.2, p = 0.0005), and KCCQ scores (43.6 ± 21.1 to 65.6 ± 21.5, p = 0.0002), but not 6MWD (275.5 ± 64.0 to 296.4 ± 104.9, p = NS) or pVO2 (14.5 ± 3.6 to 13.1 ± 4.4, p = NS). Improvements continued at 12 months, with 6MWD change becoming statistically significant (336.5 ± 91.8, p = 0.0425)., Conclusions: Use of C-Pulse in this population is feasible, appears safe, and improves functional status and QoL. A prospective, multicenter, randomized controlled trial is underway. (C-Pulse IDE Feasability Study-A Heart Assist System; NCT00815880)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac transplantation remains the best treatment option for patients with end-stage, NYHA class IV heart failure who have failed conventional therapy. However, transplant rates have remained static largely due to limited organ donor supplies. Therefore, appropriate allocation of this precious resource is critical to maximize benefit, both at a patient level and at a societal level. Neurologic diseases, such as cerebrovascular disease and peripheral neuropathy, are prevalent in this patient population, as the major risk factors for heart disease place patients at risk for neurologic disease as well. Examples include hypertension, smoking, hypercholesterolemia, obesity, and diabetes. Pretransplant neurologic evaluation is very important to identify conditions that may limit survival after cardiac transplantation. In general, systemic diseases exacerbated by immunosuppression, conditions limiting ability to rehabilitate, and dementias are considered contraindications. Post-transplant neurologic complications are divided into central versus peripheral, and early versus late. The most common early complication is ischemic stroke. Other serious complications include hemorrhagic stroke, encephalopathy, and critical illness neuropathy. Over the long term, post-transplant immunosuppressive regimens are considered "a double edged sword." Although immunosuppressive medications are critical to preventing rejection and allograft dysfunction, they do have significant risk of morbidity and mortality associated with them, including neurologic side-effects. These include: (1) drug toxicities, such as lowering of seizure thresholds; (2) encephalopathy, such as posterior reversible encephalopathy syndrome (PRES); (3) infections; (4) malignancies, such as post-transplant lymphoproliferative disorder (PTLD). Many of the same considerations discussed in adult heart transplant recipients apply to pediatric heart transplant recipients as well. In children, seizures are the most common neurologic complication, although other neurologic complication rates are comparable., (© 2014 Elsevier B.V. All rights reserved.)

Background: Although continuous-flow left ventricular assist device (LVAD) support has become standard therapy, the complexities of device and patient management remain a challenge. In particular, percutaneous site infections (PSI) are a serious complication during the post-implant course. We sought to study the incidence, risk factors, and clinical effect of PSI., Methods: Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry. All adult patients who received a primary intracorporeal continuous flow LVAD between June 2006 and September 2010 were included. Descriptive statistics, Kaplan-Meier depictions, and multivariable analysis in the parametric hazard domain were used for statistical analysis., Results: A total of 239 PSIs were documented in 197 of 2,006 recipients (9.8%) of a continuous-flow LVAD. Mean follow-up was 8.1 months. Mean time to development of a PSI was 6.6 months. At 1 year after implant, nearly 19% of continuous-flow LVAD recipients developed a PSI. Multivariate analysis showed younger age (hazard ratio, 1.20; p < 0.0001) was the only factor predicting a PSI. Continuous-flow LVAD recipients who did not develop a PSI had improved survival (p = 0.004). Twenty-three patients died after development of a PSI. Sepsis was the most common cause of death (26.1%)., Conclusions: PSIs occur in approximately 19% of continuous-flow LVAD recipients by 12 months after implant. Young age is the only predictor of PSI. Importantly, development of a PSI adversely affects survival. Efforts to enhance driveline integration and to develop future totally implantable systems are warranted., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We report the implantation of a HeartWare left ventricular assist device in a child. A 9-year-old girl presented in cardiogenic shock complicated by an embolic stroke. Catheter-based thrombolysis partially reversed the neurologic deficit, but worsening cardiac failure prompted consideration of mechanical circulatory support (MCS). Limited available pericardial space, anticoagulation requirements, and thromboembolic potential favored the use of the HeartWare left ventricular assist device (HeartWare International, Inc, Framingham, MA). After device implantation and intensive physical rehabilitation, the patient underwent successful cardiac transplantation after 60 days of support., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study was conducted to determine the effect of a disease-management model termed an "intensive surveillance protocol" (ISP) on survival in ventricular assist device (VAD) patients. This intervention consisted of a formalized, protocol-driven, multi-disciplinary team approach to VAD patient follow-up initiated August 1, 2006. The goal was to attain an internal program benchmark of 70% survival at 2 years. Historically, 2-year survival after VAD implant has been sub-optimal, and no patient management algorithms have been formally tested to determine their effect on 2-year survival., Methods: The study comprised 76 patients, of whom 26 had a VAD as destination therapy (DT) and 50 as a bridge to transplant (BTT), from July 1, 2003, to June 30, 2008. Survival before and after initiation of ISP was compared. A parametric hazard multivariable analysis, with a time-varying covariable for implementation of ISP, was used to evaluate of other factors affecting survival., Results: Survival at 16 months was 100% for DT patients who received a VAD after August 1, 2006 vs 64% for the earlier era (p = 0.06). For BTT, 16- month survival was 71% vs 43% (p = 0.03). Predicted 2-year survival before and after implementation of the ISP improved from 30% to 87% for DT (p = 0.02) and from 20% to 61% for BTT patients (p = 0.01). Predictors of midterm survival by multivariable analysis included ISP (p = 0.004), younger age (p = 0.03), non-emergent implant (p < 0.0001), and isolated left ventricular VAD (p < 0.0001). After adjustment for covariables, the ISP was associated with a 70% reduction in the hazard for death for the entire cohort (p = 0.004). The effect of ISP was also significant in the patients who received the HeartMate XVE (Thoratec, Pleasanton, CA), which spanned both eras of the study., Conclusions: Survival improved for DT and BTT VAD patients after implementation of the ISP, with a dramatic decrease in hazard for death. Although the transition from pulsatile to axial flow technology occurred during the study period and likely contributed to improved outcomes, the institution of the ISP provided an important and significant contribution to improved survival through a proactive approach to patient management, allowing earlier identification of potential adverse events. For optimal outcomes, VAD patients require intensive follow-up surveillance protocols that have previously become standard in the care of heart transplant patients., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The use of large, pulsatile left ventricular assist devices (LVADs) has been limited in women because of their small body size., Methods: We compared the survival outcomes, quality of life, and adverse events in 465 patients (104 women, 361 men) with advanced systolic heart failure in their first 18 months of support with the HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow LVAD for bridge to transplantation., Results: During the first 18 months, there were no differences in survival between women and men while on LVAD support (73% ± 3% vs 73% ± 5%, p = 0.855) but fewer women (40%) underwent heart transplantation than did men (55%; p = 0.001). More women continued on support after 18 months (p = 0.007). Median duration of support was 238 days for women and 184 days for men (p = 0.003). Mortality was 20% for women and 19% for men (p = 0.89). Adverse events were similar, with the exception of hemorrhagic stroke, which occurred more frequently in women (0.10 vs 0.04 events/patient-year, p = 0.02), and device-related infections, which occurred less frequently in women (0.23 vs 0.44, p = 0.006). Functional capacity and quality of life at 6 months improved significantly in women and men., Conclusions: Continuous-flow left ventricular assistance as a bridge to transplantation is associated with similar survival rates in women and men. Differences observed in higher stroke rates and fewer infections among women require further study., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to estimate the relationship of age, race and gender to rejection and infection across time with respect to age at time of transplant, year of transplantation and immunosuppressive era., Methods: The study group consisted of 10,131 patients from 29 institutions in the Cardiac Transplant Research Database (n = 7,368, from 1990 to 2008) and 32 institutions in the Pediatric Heart Transplant Study (n = 2,763, from 1993 to 2008). The probabilities of rejection death and infection death were estimated with a parametric time-related model and adjusted for gender, ethnicity, date of transplant and age., Results: Actuarial survival by age at transplant showed that, when compared with the majority of patients transplanted between the ages of 30 to 60 years, death due to rejection at 5 years was highest among those transplanted at 10 to 30 years of age (p < 0.0001) and lowest in those transplanted at >60 years of age. Death due to infection at 5 years was highest among patients >60 years of age. Risk factors for death from rejection included age (p < 0.0001), female gender (p = 0.0001), black race (p < 0.0001) and transplant date (p < 0.0001); for infection death, risk factors were age (p < 0.0001), date of transplant (p < 0.0001), age (p = 0.002) and black race (p = 0.01). Modeling with respect to age at time of transplant showed an inverse relationship between infection and rejection death. Among patients transplanted at >60 years of age, there was a steep increase in infection-related deaths and a decrease in rejection deaths. Risk for rejection was elevated among young adults 10 to 30 years of age at time of transplant, particularly for black females., Conclusion: Death from rejection affects adolescents and young adults preferentially, especially black recipients, whereas death from infection preferentially affects patients >60 years of age. Relative risk of infection vs rejection death with respect to recipient age should be considered in therapeutic plans for recurrent rejection, particularly in adolescents and the elderly., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Donor and recipient risk factors for rejection and infection have been well characterized. The contribution of demographic factors, especially age at the time of transplantation to morbidity and mortality due to rejection and infection, is much less well understood., Methods: Using parametric hazard analysis and multivariate risk-factor equations for infection and rejection events, we quantitatively determined the relationship of fundamental demographic variables (age, race and gender) to infection and rejection. These analyses were conducted with respect to date of transplant and age at the time of transplantation. The patient group consisted of all primary heart transplants performed at the University of Alabama at Birmingham during the years 1990 to 2007 (n = 526)., Results: Risk factors for rejection within 12 months post-transplantation were date of transplant (p < 0.0001) and age at the time of transplantation (young adults 10 to 30 years of age, p < 0.0001). Risk factors for infection were date of transplant (p < 0.0001) and age at the time of transplantation (young children and older adults, p < 0.0001). There were three immunosuppressive eras in 1990 to 2007. Notably, although the proportion of patients experiencing rejection and infection events decreased during each successive immunosuppressive era, the relative relationship of infection to rejection, as well as age at the time of transplantation, remained similar into the most recent era. The maximal frequency of rejection events and rejection death occurred among patients transplanted at ages 10 to 30 years. Conversely, the frequency of infection events was minimal within the same group. In the oldest and youngest patients receiving transplants, infection was the predominant cause of death and rates of rejection events decreased., Conclusions: These data show that evolving immunosuppressive strategies have successfully reduced rejection and infection frequencies, and those patients transplanted at 30 to 60 years of age have the lowest frequency of rejection/infection events. However, individuals transplanted at younger or older ages, especially non-white recipients in the 10- to 30-year age group, experience significantly more infection or rejection. Therefore, programs should increase the level of surveillance in these patients and consider modification of immunosuppressive regimens in order to lower the frequency of infection and rejection events., (Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

In this report we describe our experience with ibutilide, a relatively new Class III anti-arrhythmic agent, in 8 heart transplant patients with supraventricular tachycardia in various settings (3 patients with rejection, 2 after endomyocardial biopsy). Ibutilide treatment was successful in all patients, with the arrhythmia recurring early in 1 patient. There were no complications.

Background: Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH., Methods: Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean (+/-SD) duration of 984+/-468 days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals., Results: Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p<0.001). Significant and sustained improvement in 6MW distance (p=0.022) and Borg dyspnea score (p=0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p<0.001), 6MW distance (p=0.001), and Borg dyspnea scale (p=0.020) compared to baseline., Conclusions: Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, well-tolerated, and associated with further clinical improvements.

Background: Infection rates for ventricular assist devices (VADs) are improving but the presence of infections remains problematic. Intraperitoneal pump placement may decrease the rate of infection., Methods: This study is a single-institution, retrospective comparison of infections for an extraperitoneal vs an intraperitoneal position with a polytetrafluoroethylene (PTFE) sheet separating the VAD from visceral organs. Implants were performed by a single surgical team from January 1, 2002 to May 31, 2006 (n = 65) for bridge-to-transplant or destination therapy. Patients with paracorporeal pumps (17 patients) or implant times of <30 days (n = 7; 4 died, 3 ongoing, 0 with pocket infections) were excluded. Thirty-five pulsatile left VADs were analyzed, whereas 6 rotary VADs were excluded from analysis. Twenty-three pulsatile VADs were placed in an extraperitoneal pocket (pocket patients) in 18 patients (5 patients had more than one left VAD implant), whereas 12 patients had intraperitoneal (IP patients) VAD placement., Results: Infection with the implanted VAD occurred in 8 of 23 pocket implants (mean support 310 +/- 249 days) and 0 of 12 IP implants (mean support 220 +/- 131 days; pocket vs IP infections: p = 0.003). Staphylococcus and Enterococcus accounted for most of the infections. Four infections in the pocket group recurred during VAD support. Two infected pocket patients had dehiscence of the mid-line wound., Conclusions: Infections of implanted VADs are associated with serious morbidity (e.g., prolonged antibiotic therapy, recurrent device infections and wound dehiscence). Placing VADs in an intraperitoneal position with a PTFE barrier to protect the viscera may reduce the prevalence of these infections.

Background: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation., Methods: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function., Results: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006)., Conclusions: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

Management of mild to moderate aortic insufficiency in patients with a left ventricular assist device remains controversial. We report 3 patients with aortic insufficiency and pulsatile left ventricular assist devices treated with a central aortic valve coapting suture. Two of the repairs have been durable for more than 1 year and aspirin appears to be sufficient anticoagulation.

Background: The relationship between post-heart transplant cachexia and obesity with subsequent morbidity and mortality has not yet been reported. Therefore, the purposes of this study were to: (1) describe change in body mass index (BMI) from before transplant through 5 years after transplant; (2) identify risk factors for increased BMI at 1 year post-transplant; and (3) determine whether post-transplant BMI is associated with post-transplant morbidity and mortality., Methods: Patients (n = 3,540) were from a non-random sample having received a heart transplant between January 1, 1996 and December 31, 2001 at 33 institutions of the Cardiac Transplant Research Database (CTRD). Patients were divided into groups using cut-offs for categories of BMI. Data were assessed according to frequencies, measures of central tendency, Pearson correlations, chi-square tests, multiple regression and stratified actuarial analyses with log-rank tests for comparisons. The level of statistical significance was set at p = 0.05., Results: The number of obese patients increased significantly from immediately before heart transplant to 5 years later (17% vs 38%) (p < 0.0001). Risk factors for increased BMI at 1 year after heart transplant (explaining 56% of variance) included increased BMI at transplant, younger age, black race, non-ischemic etiology of heart disease, Status I at time of transplant and non-use of mycophenolate mofetil. Patients who were underweight or obese at 1 year post-transplant were at greater risk for rejection over time than patients who were of normal weight or overweight (p = 0.009)., Conclusions: Both demographic and clinical factors are related to increased BMI at 1 year after heart transplantation. Post-transplant cachexia and obesity are risk factors for poor clinical outcomes after heart transplantation.

Background: Ventricular assist devices (VADs) are commonly used to bridge patients to heart transplantation. Recipients of VADs may develop anti-human histocompatibility leukocyte antigen antibodies, as reflected by elevated panel-reactive antibodies (PRA). The purpose of this study was to evaluate the relationship between bridging with VAD before heart transplantation and development of cellular rejection, humoral rejection, and allograft vasculopathy after transplantation., Methods: Data on all patients who underwent cardiac transplantation between July 1994 and February 2001 at Rush Presbyterian St Luke's Medical Center were retrospectively reviewed. Data collected included sex, age, etiology of cardiomyopathy, percentage panel reactive antibodies (by cytotoxic method), type and duration of mechanical circulatory support, transfusion history, rejection history (both cellular and humoral) after cardiac transplantation, and development of allograft vasculopathy. Cellular rejection was treated when International Society of Heart and Lung and Transplantation Grade 2 or greater in the first 12 months after transplant and Grade 3 or greater after 12 months and treated with intensification of immunosuppression. Humoral rejection was defined clinically as allograft dysfunction by echocardiography without evidence of cellular rejection on endomyocardial biopsy or allograft vasculopathy. Allograft vasculopathy was defined by presence of any degree of luminal narrowing or pruning of distal vessels by coronary arteriography. Statistical analyses were performed by chi-square test, Fisher's exact test, and Wilcoxon rank sum test, as appropriate., Results: Ninety-eight patients underwent cardiac transplantation during the study period (87 men, mean age 49 years, 46 ischemic etiology). Of these, 48 were bridged with HeartMate VAD (20 patients received vented electric device, 28 received pneumatic device). Nineteen percent of VAD patients had a peak pretransplant PRA > or =10% vs 2% of patients without VAD (p = 0.014). PRA > or =10%, use of VAD, or duration of VAD support did not predict development of humoral rejection. Use of VAD did not predict development of cellular rejection or allograft vasculopathy. VAD use was not associated with sudden death after heart transplantation. In the entire group of 98 patients, neither humoral nor cellular rejection predicted development of allograft vasculopathy. Longer ischemic time correlated with increased cellular rejection and humoral rejection after transplantation (p = 0.01)., Conclusions: Some patients bridged to cardiac transplantation with VADs have increased PRA before heart transplantation, but this does not appear to translate into increased risk of either humoral or cellular rejection after transplantation or development of allograft vasculopathy as detected by coronary angiography.

An acquired form of sideroblastic anemia has been described in association with several drugs, especially anti-microbial agents. A case of sideroblastic anemia is presented in a patient with a left ventricular assist device drive-line infection who was receiving linezolid, an antibiotic used for serious infections with gram-positive organisms. This patient's anemia resolved after discontinuation of the drug; he subsequently underwent an uncomplicated orthotopic heart transplant with no recurrence of anemia. As linezolid has been shown to have hematologic side effects, blood count monitoring is recommended in patients receiving this drug for long-term therapy.

Management of anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac transplantation, represents a difficult clinical problem and no clear management strategy exists. The cases of 2 patients with HIT who underwent cardiac transplantation using differing anticoagulation strategies are presented with a discussion of potential advantages and pitfalls of each approach used.

Background: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone., Methods: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR > or = 3 Wood units, PVRI (pulmonary vascular resistance index) > or = 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure--mean capillary wedge pressure) > or = 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR > or = 4, PVRI > or = 6 and TPG > or = 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants., Results: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM)(all p = 0.002) and pulmonary capillary wedge pressure (PCWP)(p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02)., Conclusion: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.