Endomyocardiofibrosis in the Americas Collaborative Study: The EMF-SIAC Registry.

Endomyocardiofibrosis (EMF) is a restrictive cardiomyopathy characterized by subendocardial fibrosis due to eosinophilic myocardial infiltration. EMF may commonly present with heart failure (HF) or atrial fibrillation (AF). Immunosuppression can be effective in early stages, but not in the chronic phase. Our objective was to describe the characteristics of EMF patients in the Americas. This registry is a retrospective multicenter cross-sectional study including patients ≥18 years-old with EMF diagnosed by imaging methods, according to the Mocumbi criteria. Clinical, biochemical, and imaging variables were analyzed. On the 54 patients included, 28 (52%) were male with an age of 47 years. The etiology was idiopathic in 47 (87%) patients, familial in 4 (7%), and secondary to chemotherapy in 2 (3.5%). We detected a history of HF in 41 patients (76%), AF in 19 (35%), and ischemic stroke in 8 (15%). The diagnosis was made by echocardiography in all patients, and 38% had Cardiac Resonance or Computed Tomography. Thirty-five patients (65%) presented a left ventricular ejection fraction ≥50%, 11 (21%) severe mitral regurgitation, and 18 (33%) severe tricuspid regurgitation. In 17 patients (32%) the diagnosis was confirmed by endomyocardial biopsy. Among medical therapy, 72% received beta-blockers, 63% vasodilators, 65% mineralocorticoid antagonists, 7.4% SGLT2 inhibitors, and 11% corticosteroids. Subendocardial resection was performed in 9 (16%) patients and mitral valve replacement in 11 (20%) patients. In conclusion, EMF patients had a high prevalence of HF, AF, and embolic events. The diagnosis was frequently made in an advanced stage when HF management and surgery were the only effective treatments.

Association between continuous-flow left ventricular assist device infections requiring long-term antibiotic use and post-heart transplant morbidity and mortality.

BACKGROUND AND AIM OF STUDY: There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD. METHODS: This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively. RESULTS: We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups. CONCLUSION: LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant.

Exercise rehabilitation in cardiac resynchronization: systematic review and a meta-analysis.

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I2 was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO2 was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I2 = 53%, high quality). AT-VO2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I2 = 0.0%, moderate quality).Peak VO2 and AT-VO2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

Comparison of Heart Transplantation Outcomes: Adult Congenital Heart Disease vs Matched Cardiac Patients in a Quaternary Reference Centre.

BACKGROUND: The number of transplantations performed for adult congenital heart disease (ACHD) patients is increasing. We sought to compare survival and post-transplantation complications, including graft failure, rejection, dialysis, and use of a right ventricular assist device, between ACHD and a cohort of dilated (DCM) and ischemic (ICM) cardiomyopathy patients matched by age and year of transplantation. METHODS: We retrospectively reviewed our single-institution heart transplantation database and selected all patients who had surgery from 1988 to 2017. In our primary analysis, we looked at survival and post-transplantation complications across cardiomyopathy groups. Our secondary analysis was matched to mitigate era effects as well as differences in age at transplant. RESULTS: We analyzed a cohort consisting of 303 heart transplant patients with cardiomyopathy due to either 1) ACHD (n = 38), 2) ICM (n = 110), or 3) DCM (n = 155). Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. There was no statistically significant survival difference across groups. The 1-year survival was 68.5% for ACHD, 85.4% for ICM, and 85.5% for DCM. In multivariable analysis, ICM and DCM patients showed a 66% lower risk of death relative to the ACHD group. The matched analysis showed no significant difference in survival across groups. CONCLUSIONS: ACHD patients represent a growing high-risk patient cohort referred for transplantation. To improve survival outcomes we need to address modifiable risk factors.

The effect of pre-heart transplant body mass index on posttransplant outcomes: An analysis of the ISHLT Registry Data.

We evaluated the effect of pre-heart transplant body mass index (BMI) on posttransplant outcomes using the International Society for Heart and Lung Transplantation Registry. Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. We assessed 38 498 recipients from 2000 to 2014 stratified by pretransplant BMI. Ten-year survival was 56% in underweight, 59% in normal weight, 57% in overweight, 52% in obese class I, 54% in class II, and 47% in class III patients (P < 0.001). Mortality was increased in underweight (HR 1.29, 95% CI 1.24-1.35), obese class I (HR 1.19, 95% CI 1.13-1.26), class II (HR 1.20, 95% CI 1.08-1.32), and class III patients (HR 1.45, 95% CI 1.15-1.83). Obesity was independently associated with increased death from myocardial infarction, chronic rejection, infection, and renal dysfunction. An underweight BMI lead to increased death from infection, acute and chronic rejection, malignancy, and bleeding. Obese patients had a higher incidence of renal dysfunction, diabetes, stroke, acute rejection, cardiac allograft vasculopathy, and malignancy, and underweight recipients had increased acute rejection. We have shown that pretransplant obese and underweight patients have increased post-heart transplant mortality and morbidity. This has implications for candidate selection and posttransplant management.

Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta-analysis.

PURPOSE: Sudden cardiac death (SCD) is an important post-transplant problem being responsible for ~10% of deaths. We conducted a systematic review and meta-analysis to evaluate incidence and predictors of post-heart transplant SCD and the use of implantable cardiac defibrillator (ICD). METHODS: Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post-transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years using random effects models. We qualitatively summarized predictors. RESULTS: This study includes 55 studies encompassing 47 901 recipients. The pooled incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by two moderate-quality studies were older donor age, younger recipient age, non-Caucasian race, reduced left ventricular ejection fraction, rejection, infection, and cancer. Authors rarely reported on ICD use. CONCLUSION: This meta-analysis found that post-transplant SCD risk in heart transplant recipients is higher than that in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk.

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO2 ) or B-type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%) deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When adjusted for BNP or peak VO2 , frailty was not associated with a significant risk of all-cause death. However, when peak VO2 is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO2 (HR 1.72, P = .006).

Changes in circulating progenitor cells are associated with outcome in heart failure patients: a longitudinal study.

BACKGROUND: Circulating progenitor cells (CPCs) are involved in the process of endothelial repair and are a prognostic factor in cardiovascular diseases. We evaluated the association between serial measurements of CPCs and functional capacity and outcomes in heart failure (HF). METHODS: We included 156 consecutive consenting ambulatory HF patients (left ventricular ejection fraction < 40%). We evaluated CPCs and functional capacity (peak VO2) every 6 months for up to 2 years. CPCs were measured as early-outgrowth colony-forming units (EO-CFUs) and circulating CD34+, VEGFR2+ and/or CD133+ cells. We recorded mortality, HF hospital admissions, transplant, and ventricular assist device. RESULTS: The mean age was 55 ± 15 years. A decrease in CD34+VEGFR2+ cells was independently associated with increased functional capacity; a 10-cell decrease in CD34+VEGFR2+ cells was associated with an increase of 0.2 mL/kg/min in peak VO2 (P < 0.05). We found an interaction effect (P = 0.02) between EO-CFUs and diabetes: in patients without diabetes, a 10-EO-CFU increase was independently associated with increased peak VO2 of 0.28 mL/kg/min (P = 0.01), and in patients with diabetes, a decrease in EO-CFUs was associated with an increased peak VO2 (P < 0.05). Higher EO-CFUs were associated with reduced mortality (hazard ratio, 0.25; 95% confidence interval, 0.09-0.69). CONCLUSIONS: We noted differential relations between CPCs and outcomes in patients with vs without diabetes. Higher EO-CFUs and lower CD34+VEGFR2+ cells were associated with improved functional capacity and reduced mortality in nondiabetic patients. In patients with diabetes, lower EO-CFUs were associated with improved functional capacity. The basis for these differences requires further examination.

Clinical differences between continuous flow ventricular assist devices: a comparison between HeartMate II and HeartWare HVAD.

BACKGROUND: The HeartWare ventricular assist device (HVAD) is a new generation centrifugal flow VAD recently introduced in Canada. The objective of this study was to compare the HVAD device to the HeartMate II (HMII) axial flow device. Very few studies have compared clinical outcomes between newer generation VADs. METHODS: All perioperative and follow-up data on LVAD recipients were collected prospectively in our institutional database. Between January 2006 and April 2012, 46 consecutive patients underwent implantation of either an HVAD (n=13) or a HMII (n=33) device. Pre-implant demographics, perioperative and postoperative clinical outcomes were reviewed between groups. RESULTS: Overall, the baseline characteristics, demographics, co-morbidities and laboratory values were comparable between the two groups. The majority of the patients were Interagency Registry for Mechanical Assisted Circulatory Support 3-4 (92% in both groups) and most of the patients were bridge to transplant (75% in HMII vs. 79% in HVAD). Survival and the incidence of perioperative bleeding, renal dysfunction, liver dysfunction, and infection were similar between the groups. However, HVAD devices had a significantly higher incidence of gastrointestinal (GI) bleeding (31% vs. 0% in HMII patients, p<0.01) and stroke (44% vs. 10% in HMII patients, at one year p=0.04). Hemorrhagic strokes were more frequent in patients with HVAD (three of the five episodes vs. one of the three episodes in HMII patients, p=0.06). CONCLUSION: While device complications were comparable, patients with HVAD experienced a significantly higher incidence of stroke and GI bleeding and therefore refinement in patients' management may decrease incidence of these complications.

Using heart failure instruments to determine when to refer heart failure patients to palliative care.

AIM: The purpose of this study was to determine whether the Edmonton Symptom Assessment Scale (ESAS) or the Palliative Performance Scale (PPS) are associated with traditionally used scores for heart failure patients -- specifically, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), an overall health visual analog scale (VAS), and the Seattle Heart Failure Model (SHFM). Furthermore, we sought to determine whether the PPS or the ESAS provided additional information on quality of life, symptom severity, or prognosis above that provided by the traditional scores for patients with heart failure. METHODS: We administered the ESAS, MLHFQ, VAS, PPS, and SHFM in a shuffled manner to 78 New York Heart Association Functional Classification (NYHA-FC) Ill-IV ambulatory heart failure patients. Pearson's r correlation was used to determine whether the scores from the ESAS and PPS correlated with the scores from the MLHFQ, VAS, and SHFM. RESULTS: The sample was predominately male (62.8 percent), mean age 60.1 +/- 13 years, with a diagnosis of idiopathic cardiomyopathy (45 percent). Moderate correlations were found between the ESAS and MLHFQ (r = 0.483, p < 0.01), the ESAS and VAS (r = -0.345, p < 0.01), the PPS and MLHFQ (r = -0.54, p < 0.01), and the PPS and VAS (r = 0.53, p < 0.01). There was no significant correlation between the PPS and SHFM. CONCLUSION: The results of this study suggest that administration of the ESAS and PPS provides additional information on symptom severity and functional decline for patients with heart failure. Standardized administration of these scales may aid in the assessment and evaluation of heart failure patients.

Circulating proangiogenic progenitor cells independently predict functional capacity in heart failure patients.

BACKGROUND: Endothelial dysfunction is an important underlying mechanism in the pathophysiology of heart failure (HF). Circulating proangiogenic progenitor cells (CPCs) are endothelial and hematopoietic progenitor cells involved in the process of vasculogenesis repairing damaged and dysfunctional endothelium. Our aim was to evaluate whether an independent association exists between CPCs and functional capacity in HF patients. METHODS: This cross-sectional study included 121 ambulatory HF patients with reduced left ventricular ejection fraction seen at a single institution. We analyzed the association between CPCs, measured as circulating CD34+VEGFR2+ cells and early outgrowth colony forming units (EO-CFUs), and patients' functional capacity measured as peak oxygen consumption (VO2). RESULTS: The mean age was 55 ± 11 years; 96 patients (79%) were male. Forty-three patients (36%) had ischemic cardiomyopathy. Patients were taking optimal HF therapy (96% taking ß-blockers, 91% taking renin-angiotensin inhibitors, and 60% had an implanted internal cardiac defibrillator). In univariate analyses, CD34+VEGFR2+ cells were inversely associated with peak VO2 (P = 0.02) while EO-CFUs showed a positive association with peak VO2 (P < 0.01). These associations persisted after adjusting for sex, New York Heart Association class, body mass index, diabetes, cardiac resynchronization therapy, ischemic cardiomyopathy and b-type natriuretic peptide levels. CONCLUSIONS: Cultured EO-CFUs may represent a measure of functional capacity and vasculogenesis potential while CD34+VEGFR2+ cells represent the mobilized cells in response to endothelial damage. Our study suggests that lower EO-CFUs (worse cell function) and higher CD34+VEGFR2+ cells are associated with poorer functional capacity.