Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients-a SCHEDULE trial substudy.

To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45-61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL-3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL-3Y (r = -0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.

Effect of High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia.

BACKGROUND: There is no consensus on how, when, or at what intensity exercise should be performed after heart transplantation (HTx). We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in the maintenance state after HTx, but studies have not investigated HIT effects in the de novo HTx state. We hypothesized that HIT could be introduced early after HTx and that it could lead to clinically meaningful increases in exercise capacity and health-related quality of life. METHODS: This multicenter, prospective, randomized, controlled trial included 81 patients a mean of 11 weeks (range, 7-16 weeks) after an HTx. Patients were randomized 1:1 to 9 months of either HIT (4×4-minute intervals at 85%-95% of peak effort) or moderate-intensity continuous training (60%-80% of peak effort). The primary outcome was the effect of HIT versus moderate-intensity continuous training on the change in aerobic exercise capacity, assessed as the peak oxygen consumption (Vo2peak). Secondary outcomes included tolerability, safety, adverse events, isokinetic muscular strength, body composition, health-related quality of life, left ventricular function, hemodynamics, endothelial function, and biomarkers. RESULTS: From baseline to follow-up, 96% of patients completed the study. There were no serious exercise-related adverse events. The population comprised 73% men, and the mean±SD age was 49±13 years. At the 1-year follow-up, the HIT group demonstrated greater improvements than the moderate-intensity continuous training group; the groups showed significantly different changes in the Vo2peak (mean difference between groups, 1.8 mL·kg-1·min-1), the anaerobic threshold (0.28 L/min), the peak expiratory flow (11%), and the extensor muscle exercise capacity (464 J). The 1.8-mL·kg-1·min-1 difference was equal to ≈0.5 metabolic equivalents, which is regarded as clinically meaningful and relevant. Health-related quality of life was similar between the groups, as indicated by results from the Short Form-36 (version 2), Hospital Anxiety and Depression Scale, and a visual analog scale. CONCLUSIONS: We demonstrated that HIT was a safe, efficient exercise method in de novo HTx recipients. HIT, compared with moderate-intensity continuous training, resulted in a clinically significantly greater change in exercise capacity based on the Vo2peak values (25% versus 15%), anaerobic threshold, peak expiratory flow, and muscular exercise capacity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier NCT01796379.

Effect of Calcineurin Inhibitor-Free, Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate After Heart Transplantation.

BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or CNI-free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitor Avoidance trial, where de novo HTx patients (n = 115) were randomized to EVR with complete CNI elimination 7 to 11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients, UACR measures were available at 1 year. In 7 patients in the EVR group, a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (P = 0.0004 and P = 0.03, respectively). Median UACR at 1 year was significantly higher in the EVR group (P = 0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r = -0.01, P = 0.9 and r = 0.15, P = 0.26, respectively) and in the EVR group between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r = 0.27, P = 0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function seem dissociated; hence, the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.

Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.

Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.

Early postoperative left ventricular function by echocardiographic strain is a predictor of 1-year mortality in heart transplant recipients.

BACKGROUND: Left ventricular (LV) function can be accurately assessed using two-dimensional speckle-tracking echocardiography. The association between reduced LV global longitudinal strain (LVGLS) magnitude and risk for mortality in heart transplant recipients is unclear. The aim of this study was to test the hypothesis that LVGLS could predict 1-year mortality in heart transplant recipients. METHODS: A total of 176 consecutive adult primary single-organ orthotopic heart transplant recipients were retrospectively evaluated. Of these, 167 had acceptable echocardiographic image quality and were included in the study. N-terminal pro-B-type natriuretic peptide, creatinine, C-reactive protein, and invasive hemodynamic parameters were measured, and echocardiography was performed 1 to 3 weeks after heart transplantation. LVGLS was averaged from regional strain in 16 LV segments. RESULTS: During the first year, 15 patients (9%) died 86 ± 72 days after heart transplantation. LVGLS and LV ejection fraction were decreased in magnitude in nonsurvivors (P < .05). They were older and had higher donor ages. Mean pulmonary capillary wedge pressures were similar in the two groups, while all other hemodynamic parameters were increased in nonsurvivors (P < .05). LVGLS was the only significant (P = .02) noninvasive independent predictor, with a hazard ratio of 1.42 (95% confidence interval, 1.07-1.88; P = .02) per 1% decrease in strain magnitude, while pulmonary vascular resistance was a significant (P < .001) invasive predictor, with a hazard ratio of 3.98 (95% confidence interval, 2.01-7.87) of 1-year mortality in multivariate Cox regression analysis. CONCLUSIONS: Reduced LV function and increased pulmonary vascular resistance are related to poor prognosis in heart transplant recipients. Early assessment of LVGLS might be a noninvasive predictor of 1-year mortality in these patients.