Early optical coherence tomography evaluation of donor-transmitted atherosclerosis and cardiac allograft vasculopathy: insights from a prospective, single-center study.

BACKGROUND: The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality. METHODS: HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up. RESULTS: A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3 ± 0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p = 0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p = 0.008) while maximal intimal thickness ≥0.5 mm was not. CONCLUSIONS: Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.

The Interaction of Amiodarone and Continuous-flow Left Ventricular Assist Device Use in Risk of Severe Primary Graft Dysfunction Following Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) increases morbidity and mortality after heart transplant. Here we investigated (1) the association of continuous-flow left ventricular assist device (CF-LVAD), amiodarone, and severe PGD and (2) the safety of amiodarone discontinuation in CF-LVAD patients. METHODS: Retrospective, single-center study of heart transplant recipients was conducted to investigate the association of risk factors and severe PGD. Patients were grouped into 4 groups based on the presence (denoted +) or absence (denoted -) of amiodarone and CF-LVAD. Prospective amiodarone discontinuation was undertaken to investigate its safety in a cohort of CF-LVAD patients. Study endpoints were severe PGD and recurrence of arrhythmia. RESULTS: Severe PGD was strongly associated with CF-LVAD and amiodarone use, and its prevalence is highest if both risk factors were present (CF-LVAD-/amiodarone - 1.5%, CF-LVAD -/amiodarone+ 4.5%, CF-LVAD+/amiodarone - 7.1%, CF-LVAD+/amiodarone+ 21.8%; P < 0.01). The product of every 1-y additional CF-LVAD support by every 100 mg amiodarone was associated with severe PGD (adjusted odds ratio, 1.43; 95% confidence interval, 1.15-1.78; P < 0.01). Amiodarone was prospectively discontinued in 28 CF-LVAD patients. Of them, 6 patients had recurrence of arrhythmia requiring treatment or heart failure admission. There were no deaths. Nine patients in whom amiodarone had been discontinued had heart transplants with no severe PGD. CONCLUSIONS: Amiodarone and CF-LVAD were independently associated with severe PGD. The combination of both risk factors was associated with a higher prevalence of severe PGD. Amiodarone discontinuation was associated with recurrence of arrhythmia in 6 CF-LVAD patients. There was no mortality associated with amiodarone discontinuation.

Gastrointestinal angiodysplasia in heart failure and during CF LVAD support.

Angiodysplasias (AGD) are common sites of bleeding in the gastrointestinal (GI) tract after Continuous Flow Left Ventricular Assist Device (CF-LVAD) implantation. We sought to investigate whether AGDs are formed as a result of LVAD physiology or preexist as a consequence of heart failure. Thirty-six subjects with HF reduced EF (HFrEF) underwent video capsule endoscopy (VCE) to assess for the presence of AGD. Fifty-three subjects without HF who underwent VCE for a nonbleeding indication formed a control group. The prevalence of AGD was significantly higher in the HFrEF compared to the non-HF controls (50% vs 13%, p = 0.0002). This association persisted after controlling for age and comorbidities. Within the HFrEF cohort, higher Ang2, NT-proBNP and BUN were associated with the presence of AGD. AGD in the GI tract are associated with HFrEF. This is the first description of a new pathology associated with HFrEF and adds to our understanding of CF LVAD associated GI bleeding.

Relation of Peripheral Venous Pressure to Central Venous Pressure in Patients With Heart Failure, Heart Transplant, and Left Ventricular Assist Device.

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations.

Feasibility of high-intensity interval training in patients with left ventricular assist devices: a pilot study.

AIMS: Patients with left ventricular assist device (LVAD) suffer from persistent exercise limitation despite improvement of their heart failure syndrome. Exercise training (ET) programmes to improve aerobic capacity have shown modest efficacy. High-intensity interval training (HIIT), as an alternative to moderate continuous training, has not been systematically tested in this population. We examine the feasibility of a short, personalized HIIT programme in patients with LVAD and describe its effects on aerobic capacity and left ventricular remodelling. METHODS AND RESULTS: Patients on durable LVAD support were prospectively enrolled in a 15-session, 5 week HIIT programme. Turndown echocardiogram, Kansas City Cardiomyopathy Questionnaire, and cardiopulmonary exercise test were performed before and after HIIT. Training workloads for each subject were based on pretraining peak cardiopulmonary exercise test work rate (W). Percentage of prescribed training workload completed and adverse events were recorded for each subject. Fifteen subjects were enrolled [10 men, age = 51 (29-71) years, HeartMate II = 12, HeartMate 3 = 3, and time on LVAD = 18 (3-64) months]. Twelve completed post-training testing. HIIT was well tolerated, and 90% (inter-quartile range: 78, 99%) of the prescribed workload (W) was completed with no major adverse events. Improvements were seen in aV̇O2 at ventilatory threshold [7.1 (6.5, 9.1) to 8.5 (7.7, 9.3) mL/kg/min, P = 0.04], work rate at ventilatory threshold [44 (14, 54) to 55 (21, 66) W, P = 0.05], and left ventricular end-diastolic volume [168 (144, 216) to 159 (124, 212) mL, n = 7, P = 0.02]. HIIT had no effect on maximal oxygen consumption (V̇O2peak ) or Kansas City Cardiomyopathy Questionnaire score. CONCLUSIONS: Cardiopulmonary exercise test-guided HIIT is feasible and can improve submaximal aerobic capacity in stable patients with chronic LVAD support. Further studies are needed on its effects on the myocardium and its potential role in cardiac rehabilitation programmes.

Predicted heart mass-based size matching among recipients with moderate pulmonary hypertension: Outcomes and sex effect.

BACKGROUND: There is a lack of evidence to guide appropriate donor sizing in recipients with moderate pulmonary hypertension (pHTN) awaiting heart transplantation (HTx). It is common practice to oversize donor hearts for such recipients to prevent post-operative right ventricular failure. Therefore, our objective was to determine if oversizing in pre-transplant moderate pHTN provides a survival advantage. METHODS: The United Network for Organ Sharing database was analyzed to include HTx recipients from 1994 to 2016. Recipients were considered as having moderate pHTN if the pulmonary vascular resistance (PVR) was 2.5 to 5 Wood units (WU) or transpulmonary gradient (TPG) was 10 to 18 mm Hg. Heart size mismatch was determined using the predicted heart mass equations. A size mismatch of ≥15% in either direction was considered undersized or oversized, respectively. Ninety-day and 1-year survival were analyzed based on size matching via univariate and Cox regression analysis. Propensity matching was performed to specifically evaluate the effect of donor sex among male transplant recipients. RESULTS: Among 29,441 HTx recipients, 10,666 had moderate pHTN by PVR criteria and 12,624 HTx patients had moderate pHTN according to TPG criteria. Among patients with a PVR of 2.5 to 5 WU, oversizing was not associated with lower mortality compared with matched hearts at 90 days (7.6% vs 7.4%; p = 0.75) and 1 year (12.1% vs 11.3%; p = 0.26). Conversely, undersizing the donor was associated with a higher 90-day (10.6% vs 7.6% vs 7.4%; p < 0.01) and 1-year (15.3% vs 12.1% vs 11.3%; p < 0.01) mortality than recipients receiving oversized or matched hearts, respectively. On Cox regression analysis, there was no benefit with oversizing at 90 days (hazard ratio [HR] 0.88; p = 0.23) and 1 year (HR 0.99; p = 0.90), whereas undersizing was associated with higher 90-day (HR 1.32; p = 0.02) and 1-year mortality (HR 1.23; p = 0.03) compared to size-matched controls. Among patients with moderate pHTN based on TPG of 10 to 18 mm Hg, neither undersizing nor oversizing was predictive of mortality at 90 days and 1 year according to Cox regression analysis. Propensity matching revealed that female-to-male transplantation had similar 1-year mortality to male-to-male transplantation, and there was no advantage to oversizing female donors for male recipients. CONCLUSIONS: In this registry-based analysis, there was no benefit to oversizing donors for cardiac transplant recipients with moderate pHTN. Elimination of this restriction could increase the donor pool and reduce wait times for such recipients.