Impact of cardiac resynchronization therapy on clinical outcomes in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) can improve survival in left ventricular assist device (LVAD) recipients. However, the impact of cardiac resynchronization therapy (CRT-D) on outcomes in continuous-flow left ventricular assist device (CF-LVAD) patients is not known. We sought to determine if CRT-D improved clinical outcomes in CF-LVAD patients compared with ICDs alone. METHODS AND RESULTS: Sixty-one consecutive CF-LVAD patients with an ICD or CRT-D were evaluated. Impacts of CRT-D on mortality, all-cause hospitalization, and incidence of atrial (AA) and ventricular (VA) arrhythmias after LVAD implantation was compared with patients with ICD alone. Of the 61 LVAD patients, 31 (age 59.8 ± 16 years, 84% male) had CRT-D and 30 (age 57.2 ± 13 years, 74% male) had ICD. Before LVAD implantation, no significant differences were noted between the groups in demographic and clinical characteristics, LVAD indications, and incidence of AA and VA. Over 682 ± 45 days of LVAD support, 8 patients (25.8%) died in the CRT-D arm versus 5 (16.7%) in the ICD arm (P = .35). No differences were noted between the CRT-D and ICD groups in all-cause (96.8 vs 93.3%; P = .63) and HF (19.4 vs 26.7%; P = .78) hospitalizations, left ventricular (LV) end-diastolic diameter (6.4 ± 1.5 vs 6.2 ± 1.1 cm, P = .47), and incidence of AA (35.4% vs 33.3%; P = .80), VA (29% vs 26.6%; P = .86), and ICD shocks (22.6% vs 16.7%; P = .93). Beta-blocker and antiarrhythmic drug use after LVAD implantation was similar in both groups. CONCLUSIONS: In patients with refractory HF who received CF-LVADs, CRT-D, compared with ICD, did not significantly improve mortality, all-cause hospitalization, LV dimensions, and incidence of AA and VA.

Safety and Feasibility of Induction Immunosuppression When Driveline Infection Is an Indication for Cardiac Transplantation.

BACKGROUND: There is a paucity of data on the use of induction immunosuppression in patients with active infections undergoing orthotopic heart transplantation (OHT). We hypothesized that induction immunosuppression in patients with ventricular assist device (VAD) undergoing OHT with localized active driveline infection (DLI) does not lead to worse outcomes. MATERIALS AND METHODS: We retrospectively analyzed our database for bridge-to-transplant VAD patients who underwent OHT and received induction therapy. Patients were stratified into those with and without active DLI at the time of OHT and followed up till death or at least 30 months after OHT. Posttransplant length of stay (LOS), frequency of infections, and mortality were compared between the two groups. RESULTS: Thirty-eight patients (30 males) with mean age of 57.5 ± 13 years with VAD underwent OHT during the study period. Twelve had active DLI. Mean follow-up was 46.4 ± 23.1 months. In the DLI versus non-DLI group, there was no difference in mortality (17 vs. 23%, p = NS), LOS (16.3 ± 5.4 vs. 17.2 ± 13.7, p = NS), postoperative renal function, incidence of hyperacute or late rejection or infection either in the first month (25 vs. 23%, p = NS) or during entire follow-up (92 vs. 88%, p = NS). No patient in the DLI group had infections attributable to the same organism responsible for pretransplant DLI. CONCLUSION: In patients with active DLI, induction immunosuppression after OHT did not increase LOS, infections, or mortality after at least 30 months of follow-up and therefore it appears to be a safe and feasible therapeutic option.

Hematologic markers better predict left ventricular assist device thrombosis than echocardiographic or pump parameters.

BACKGROUND: Left ventricular assist device (LVAD) thrombosis is a life-threatening complication that remains a major clinical problem. Consensus diagnostic criteria do not exist. We investigated whether hematologic, echocardiographic, or pump parameters reliably change during LVAD thrombosis. METHODS: A retrospective analysis of 20 consecutive cases of continuous-flow LVAD thrombosis (Thoratec HeartMate II n = 16, HeartWare HVAD n = 4) was performed. Hematologic markers (lactate dehydrogenase, plasma-free hemoglobin, hemoglobin, creatinine), echocardiographic parameters (left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity), and pump characteristics (speed, power, estimated flow, pulsatility index) were analyzed with one-way repeated measures ANOVA with Tukey post-test or paired Student t-tests. RESULTS: Lactate dehydrogenase and plasma-free hemoglobin were significantly (p < 0.05) elevated at admission for LVAD thrombosis. Hemoglobin and creatinine were not significantly different at admission but changed significantly after admission. Left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity, LVAD speed, power consumption, estimated flow, and pulsatility index were not significantly different at admission for LVAD thrombosis. CONCLUSION: Hematological markers of hemolysis, but not echocardiographic or pump parameters, reliably changed during LVAD thrombosis. Markers of hemolysis are the best early predictors of LVAD thrombosis.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Increased intrathoracic impedance may predict adverse events in LVAD patients.

We describe a 36-year-old male with a HeartWare LVAD and a Medtronic Virtuoso DR pacemaker in whom increased intrathoracic impedance preceded suction events, low LVAD flows, symptoms of a heart failure exacerbation, and hospitalization. Measurement of intrathoracic impedance may identify fluid shifts prior to symptoms and predict adverse events in patients with an LVAD.

The association of pretransplant HeartMate II left ventricular assist device placement and heart transplantation mortality.

Previous United Network for Organ Sharing (UNOS) analysis has shown an increase in posttransplant mortality with pretransplant pulsatile-flow left ventricular assist device (LVAD). Recent studies evaluating continuous-flow LVAD demonstrated improved durability, excellent survival, and improved quality of life. This study investigates the association of preheart transplant continuous-flow LVAD placement and posttransplant mortality using the UNOS database. Heart transplant patients listed after April 2004 (N = 48,090) during the era of HeartMate (HM) II LVAD usage were investigated. Patients with UNOS 1A and 1B status with (n = 1,435) and without HMII (n = 16,379) placement before the heart transplantation were evaluated. Preliminary descriptive statistics suggested an extensive heterogeneity in patient characteristics between HMII LVAD recipients and nonrecipients. Propensity scores (1:2) were used to match HMII LVAD recipients and nonrecipients characteristics and donor characteristics. This resulted in a final sample of 2,265 patients (758 with HMII pretransplant placement and 1,507 without HMII pretransplant placement). The Kaplan-Meier curves were evaluated for the differences in postheart transplant mortality in patients with and without HMII pretransplant placement. A time-dependent Cox regression model was used to study the hazard ratios (HRs) for the association between HMII pretransplant placement and posttransplant survival. The mean age of the study group was 51.9 years old (standard deviation: 12.3). HeartMate II pretransplant placement was associated with no statistically significant difference in the risk of 30 days (HR = 1.23, 95% confidence interval [CI]: 0.79-1.95, p = 0.36) and 1 year posttransplant mortality (HR = 1.31, 95% CI: 0.85-2.01, p = 0.22) compared with non-HMII recipients. The use of HMII LVAD before heart transplantation, however, was associated with a statistically significant 64% lower risk (HR = 0.36, 95% CI: 0.16-0.77, p = 0.01) of mortality among heart transplant patients who survived beyond the first year of transplantation. Continuous-flow LVAD pretransplant placement is associated with improved long-term (>1 year) survival after heart transplantation.

Percutaneous closure of a patent foramen ovale to prevent paradoxical thromboembolism in a patient with a continuous-flow LVAD.

Patent foramen ovale (PFO) may complicate left ventricular assist device (LVAD) therapy. We report a 70-year-old male with a HeartMate II LVAD at increased risk for thromboembolic stroke secondary to a PFO with right-to-left shunting and a large mobile thrombus on his right atrial pacing lead. Via percutaneous intervention, a 25 mm Cribiform Amplatzer atrial septal occluder was successfully deployed across the PFO without complications. This is the first reported case of percutaneous PFO closure to prevent paradoxical thromboembolism in a normoxic patient with an LVAD. In addition, arterial desaturation and the sequelae of chronic hypoxemia were prevented. Strategies to diagnose PFO at the time of LVAD implantation and physiological implications of a right-to-left atrial shunt during mechanical unloading of the failing left ventricle are reviewed.

Catheter ablation of atrial flutter in patients with left ventricular assist device improves symptoms of right heart failure.

Persistent atrial flutter (AFL) in left ventricular assist device (LVAD) recipients can result in loss of AV synchrony, impaired ventricular filling and right heart failure (RHF). The authors report the largest series of HeartMate II (HMII) patients who developed AFL with decompensated RHF, which successfully resolved with AFL ablation. Eight patients with HMII LVAD (mean age, 57±12 years) had medically refractory AFL, with 7 developing de novo AFL after LVAD implant (onset range, 2 days-22 months post-implant). Three patients developed recurrent syncope, 2 had inappropriate implantable cardioverter-defibrillator shocks, and 6 had new or escalating need for inotropes. All had features of decompensated RHF. Seven patients underwent electrophysiology testing where mapping confirmed typical counterclockwise AFL (mean AFL cycle length, 252±49 ms) and radiofrequency ablation of cavotricuspid isthmus restored sinus rhythm in all patients. Complete resolution of symptoms and signs of RHF with improved quality of life were noted in all. No procedural complications were noted. During a mean follow-up of 9±5 months, all patients remained free of atrial flutter. Catheter ablation of AFL in LVAD patients is safe and highly effective, resulting in immediate and significant improvement in symptoms of RHF, and should be considered first-line therapy for AFL in these patients.

Heart transplant vs left ventricular assist device in heart transplant-eligible patients.

BACKGROUND: Patients listed for heart transplant have a prolonged wait time, with continued deterioration, poor quality of life, and 10% mortality. Although recent bridge to transplant (BTT) studies demonstrated 1-year survival similar to heart transplantation, doubt remains about overall effectiveness as a treatment strategy compared with waiting and implanting a left ventricular device (LVAD) only as a last resort. We evaluated 1-year outcome and effectiveness of LVAD vs heart transplantation. METHODS: Patients on the heart transplantation list, either receiving an allograft or LVAD for BTT from January 2009 to December 2009 were evaluated. Of 43 patients treated, 1 received both LVAD and an allograft during same admission was removed from the analysis. All patients but one who received an allograft had prior LVAD. Descriptive and univariate (t test) statistics and Kaplan-Meier survival curve were used for analyses. RESULTS: LVAD for BTT was used in 29 patients (51.4±12.8 years, 6.9% women), and 13 (51.1±11.6 years, 15.38% women) underwent heart transplantation. Initial hospital length of stay was 17.5±14.4 days in BTT group and 14.3±4.6 days in heart transplant group (p=0.44) At 1 year, the total number of days spent in the hospital (operation and related complications), including index hospitalization was 11.6±14.3 days/100 days in BTT and 7.9±9.0 days/100 days in heart transplantation (p=0.38). A total of 41% BTT and 46% heart transplant patients had one readmission within 3 months of the index hospitalization. Infection was the most common cause of readmission in both groups. The 1-year survival was similar for both groups (no hospital death in either group; 3 late deaths in the BTT group). CONCLUSIONS: One-year outcomes for patients eligible for heart transplantation were similar whether they received an allograft or LVAD for BTT. Heart transplant outcome for patients with LVAD were not adversely affected. Improving outcomes for patients treated with LVAD suggest that current decision models for patients eligible for heart transplantation may need to be reevaluated.