Rosenbaum, Andrew N

AbstractOver the last half‐century, left ventricular assist device (LVAD) technology has progressed from conceptual therapy for failed cardiopulmonary bypass weaning to an accepted destination therapy for advanced heart failure. The history of LVAD engineering is defined by an initial development phase, which demonstrated the feasibility of such an approach, to the more recent three major generations of commercial devices. In this review, we explore the engineering challenges of LVADs, how they were addressed over time, and the clinical outcomes that resulted from each major technological development. The first generation of commercial LVADs were pulsatile devices, which lacked the appropriate durability due to their number of moving components and hemocompatibility. The second generation of LVADs was defined by replacement of complex, pulsatile pumps with primarily axial, continuous‐flow systems with an impeller in the blood passageway. These devices experienced significant commercial success, but the presence of excessive trauma to the blood and in‐situ bearing resulted in an unacceptable burden of adverse events. Third generation centrifugal‐flow pumps use magnetically suspended rotors within the pump chamber. Superior outcomes with this newest generation of devices have been observed, particularly with respect to hemocompatibility‐related adverse events including pump thrombosis, with fully magnetically levitated devices. The future of LVAD engineering includes wireless charging foregoing percutaneous drivelines and more advanced pump control mechanisms, including synchronization of the pump flow with the native cardiac cycle, and varying pump output based on degree of physical exertion using sensor or advanced device‐level data triggers.

AbstractIntroductionCardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS.ObjectiveTo determine if CRT improved cardiac remodeling in patients with CS.MethodsWe retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed.ResultsOur cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT‐D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT‐P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end‐diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow‐up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died.ConclusionsOur findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Data on pre-implant hemodynamic optimization before continuous flow left ventricular assist device placement (CF-LVAD) with respect to patient-centered outcomes remain limited. Consecutive patients undergoing CF-LVAD implant between 2007 and 2017 were identified. Hemodynamic variables, trends, and laboratory studies were evaluated pre-LVAD implant in a logistic regression model to identify predictors of the primary composite endpoint: the need for right ventricular assist device therapy, the requirement for hemodialysis at 90 days, and 30-day mortality. Multivariate modeling identified three variables significantly associated with the primary endpoint: right ventricular stroke work index (RVSWI), right atrial pressure (RAP), and blood urea nitrogen (BUN); all immediately pre-LVAD, p < 0.01. Optimal dichotomization points were 500 mmHg*ml*m−2, 12 mmHg, and 40 mg/dL. The three-component model identified an AUC of 0.77 (p < 0.0001) for the composite endpoint. Optimization of 2/3 parameters, 1/3, and 0/3 was associated with odds ratios of 3.5 (95% CI, 1.1−11.7), 7.2 (95% CI, 2.1−24.2), and 20.6 (95% CI, 5.3−80.6), respectively, relative to those patients who were fully optimized (3/3 parameters). The number of optimized parameters was also associated with 1-year overall survival (p = 0.02). Low RVSWI, high RAP, and high BUN were independently associated with adverse outcomes after the CF-LVAD implant, demonstrating a stepwise association with severe postimplant adverse events.

A 77 year old man previously implanted with a HeartMate II left ventricular assist device (LVAD) as destination therapy and an implantable cardioverter defibrillator presented with a left upper lobe squamous cell lung cancer. Oncology determined that proton beam therapy was indicated for treatment, and a multidisciplinary team of radiation physicists, radiation oncologists, and LVAD providers developed a protocol to proceed safely. He was successfully treated with combined proton beam radiation therapy and reduced dose chemotherapy. This case demonstrates feasibility and considerations of proton beam therapy for malignancy relevant to patients with implantable cardiac devices including LVADs.

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

In patients with advanced heart failure (HF), temporary mechanical circulator support (TMCS) is used to improve hemodynamics, via left ventricular unloading, and end-organ function as a bridge to definitive therapy. While listed for cardiac transplantation, use of TMCS may be prolonged, preventing adequate mobility. Here, we describe the technique for placement of a percutaneous axillary intra-aortic balloon pump (IABP) using single-site arterial access to facilitate ambulation and subsequent safe removal without surgery or a closure device. Retrospective review of the experience with this approach at a single institution between September 2017 and February 2020 documented feasibility and safety. Baseline demographics, hemodynamic data, and clinical outcomes were collected. Thirty-eight patients had a total of 56 IABPs placed. There were no significant access site or cerebrovascular complications. One fifth of IABPs (21.4%) had balloon failure or migration, requiring placement of a new device, though no patients had significant complications from balloon failure. The majority (81.6%) of patients in the cohort on axillary IABP support were ambulatory and ultimately received the intended therapy (63.2% transplant, 13.2% durable left ventricular assist device, 5.3% other cardiac surgery). Percutaneous, axillary IABP is feasible and associated with an acceptable complication rate as a bridge to definitive therapy.

AbstractA combined right and left‐sided heart catheterization (RHC/LHC) protocol was recently reported to optimize patients supported by left ventricular assist device (LVAD). Using this platform, we sought to evaluate the prognostic significance of several hemodynamic indices, including left ventricular end‐diastolic pressure (LVEDP) and transaortic gradient (peak aortic pressure ‐ peak left ventricular pressure in systole, TAG). We evaluated all patients undergoing RHC/LHC at our institution from 2015 through 2018, and comprehensive clinical data were obtained. Primary end points were (1) a composite outcome that included hospitalization or death and (2) 1‐year overall survival after catheterization. Forty‐two patients were included in the analysis. Optimization resulted in normalization of hemodynamic parameters; all variables were significantly improved from baseline (P ≤ .05). On univariate modeling, final LVEDP was associated with the primary end point (hazard ratio [HR], 1.2 per 1‐mm Hg increase; 95% CI, 1.1‐1.3; P = .002). After adjusting for LVAD speed, TAG, and cardiac index in a multivariate model, the association between LVEDP and the composite end point remained significant (HR, 1.2 per 1‐mm Hg increase; 95% CI, 1.1‐1.4; P = .001). In the setting of LVAD support, inadequate LV unloading was a significant marker of poor outcomes with time, suggesting that LVEDP is a central prognostic marker in this population.

Following implantation of continuous-flow left ventricular assist devices, mechanical off-loading results in improved resting hemodynamics; however, peak exercise capacity generally does not increase substantially. This study evaluated patients supported by continuous-flow left ventricular assist devices who were invasively monitored during exercise to define parameters that underpin exercise capacity and outcomes. A review of all patients supported by continuous-flow left ventricular assist devices who underwent supine bicycle ergometry exercise testing with measurement of pulmonary gas exchange during right heart catheterization for evaluation of dyspnea at one institution between 2007 and 2018 was performed (n = 22). The primary outcome of this investigation was death or heart failure hospitalization. Although resting filling pressures were relatively preserved, resting cardiac index (Fick) was low (2.1 ± 0.5 mL/kg/min). An impaired cardiac output reserve was present in 75% of patients. On univariate modeling, patients with supine exercise–induced hypoxemia (O 2 saturation <90%) experienced significantly diminished hospitalization-free survival (unadjusted hazard ratio = 11.0, confidence interval = 2.4–57.2, p = 0.003), which persisted despite adjustment for right heart catheterization peak VO 2 and peak cardiac output (adjusted hazard ratio = 25, confidence interval = 3.6–322, p = 0.001). Our findings suggest that supine exercise testing provides additional prognostic utility in the continuous-flow left ventricular assist device population.