Daly, Richard C.

Despite the growing acceptance of left ventricular assist device (LVAD) therapy to improve survival and quality of life in heart failure (HF) patients, uncertainties persist regarding the definition of a successful implant. We sought to define an innovative approach to assess success and subsequently compare preoperative variables affecting outcomes. From January 2007 to 2015, 278 patients underwent LVAD implantation. Median age at implant was 62 years and 81% patients were males. Indication for support was bridge-to-transplantation in 36% patients and the etiology of HF was ischemic in 49% patients. Based on clinically relevant and accepted standards, we defined successful LVAD implant as someone who was alive or transplanted at 2 years, had two or less readmissions in the first year, had no major adverse events in the first year, and had a New York Heart Association class of ≤ II at 6 months. Follow-up was obtained for a median of 1.7 years for a total of 605 patient-years-of-support. Based on our criteria, 81/278 (29%) patients were defined as having a successful implant. Univariate predictors of LVAD failure included destination therapy indication (hazard ratio [HR] = 2.11 [1.24, 3.58]), ischemic cardiomyopathy (HR = 1.73 [1.02, 2.94]), and a higher left ventricular ejection fraction (HR = 1.54 [1.07, 2.22]). After multivariable analysis, only destination therapy indication (HR = 2.2 [1.28, 3.78]) was found to be independently predictive of success failure. Despite an overall trend toward improved outcomes on device therapy, our criteria classified only one-third of patients as successful. Continued improvements in adverse event profiles, appropriate patient selection, and optimal time of implantation, together hold the key to improve outcomes after LVAD therapy.

Abstract Aims Early studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new-generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long-term CAV progression and clinical outcomes in a large contemporary HT cohort. Methods and results We analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow-up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow-up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV-associated events (hazard ratio 0.48, 95% confidence interval: 0.27–0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all-cause mortality and CAV-associated events (hazard ratio 0.58, 95% confidence interval: 0.38–0.91; P = 0.019). Conclusions Early initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV-related events and mortality.

Abstract Aims Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α), and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Methods and results Atrial tissues were obtained from 16 patients with T2D and 25 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-β1 subunits were significantly downregulated, but the ratio of BK-α/BK-β1 was unchanged in the coronary arterioles of T2D patients. Conclusions Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were abnormal in the coronary microvasculature of diabetic patients, due to decreased protein expression and altered intrinsic properties of BK channels.

Background. Lungs are allocated in the United States using the lung allocation score (LAS). We investigated the effect of LAS trends on lung transplant-related costs, healthcare utilization, and mortality. Methods. Utilization data from Mayo Clinic (Florida and Minnesota) from 2005 to 2015 were obtained from the electronic health records (N = 465). Costs were categorized as 1-year posttransplant or transplant episode and standardized using 2015 Medicare reimbursement and cost-to-charge ratios. Regression analysis was used to assess the relationship of LAS to length of stay (LOS), mortality, and cost of transplant. Results. The mean LAS at transplant increased from 45.7 to 58.3 during the study period, whereas the 1-year survival improved from 88.1% to 92.5% (P < 0.0001). The proportion of patients transplanted with LAS of 60 or greater increased from 16.9% to 33.3%. Posttransplant, overall, and intensive care unit LOS increased with increasing LAS. Patients with higher LAS had substantially higher transplant episode costs. An increase of LAS at transplant by 10 points increased inflation-adjusted costs by 12.0% (95% confidence interval, 9.3%–14.5%). Conclusions. The mean LAS at transplant has significantly increased over time associated with increases in LOS, resource utilization and cost. Lung allocation score has not jeopardized overall survival, but a high LAS (>60) at transplant is associated with increased mortality.

Background The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt. Methods We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained. Results Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg−1·min−1) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late. Conclusions This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Background Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post–left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. Methods and Results We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18–2.53; P =0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35–3.18; P =0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P <0.0001) and a significant reduction in requirements of DM medications. Conclusions DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.

Atrial fibrillation (AF) and tricuspid regurgitation (TR) are common in patients undergoing left ventricular assist device (LVAD) implantation. TR progression is associated with the presence of AF, and questions remain as to who benefits from tricuspid valve procedures (TVPs). We examined the impact of preoperative AF on TR progression after LVAD implantation. From February 2007 to May 2014, 250 patients underwent LVAD implantation at our institution. Patients with concomitant TVP were excluded from this analysis (113 patients). The indication for LVAD was destination therapy in 80 patients (58%) and the etiology of heart failure was ischemic in 73 (53%). Follow-up was available in all early survivors for a total of 393 patient-years of support. Of the 137 non-TVP patients, 52 (38%) had AF preoperatively. Observed overall survival at 1, 3, and 5 years was 82%, 67%, and 55%, respectively. Median grade of TR increased from 2 preoperatively to 3 (p = 0.04) in the AF group and 2.2 (p = 0.75) in the non-AF group at 5 years of follow-up. We also observed a significant difference in the degree of TR between groups at 3 months (p = 0.03) and 12 months (p = 0.01) postimplantation, and a trend toward significance at 18 (p = 0.06) and 24 (p = 0.07) months. The presence of AF is associated with early progression of TR after LVAD implantation. Addition of concomitant TVP in patients with preoperative AF may be considered in patients with less than severe TR. The impact of these findings on right ventricular failure/remodeling remains to be evaluated.

Wait times have increased for patients approved for heart transplants. We reviewed United Network for Organ Sharing (UNOS) data for 14,242 patients listed for isolated heart transplant (2009–2013) to develop a risk score model for timing left ventricular assist device (LVAD) implantation in bridge-to-transplant patients. We used a multivariable Cox proportional hazards regression model with subsequent bootstrap resampling for internal validation to develop a scoring system that combined risk factors, weighted by the corresponding regression coefficients, to define an individual’s risk score. Four risk factors were identified (body mass index, blood type, region, and urgency status) to be significantly and independently associated with wait time (p < 0.001), showing adequate model discrimination (C = 0.704) and calibration. Higher risk scores correlated with shorter wait times. Our model corresponded closely with observed transplant rates, predicting longer wait times for lower status, larger size, certain blood groups, and some UNOS regions. This tool has the potential to more accurately describe the wait-time duration for an individual patient, which may influence care decisions. The wait-time discrepancies (blood types/regions) reinforce the need to reevaluate the geographic-allocation policy. The proposed review of the UNOS heart allocation policy may make this model especially relevant.