Sudden cardiac death after heart transplantation: a population-based study.

AIMS: The epidemiology of sudden cardiac death (SCD) after heart transplantation (HTx) remains imprecisely described. We aimed to assess the incidence and determinants of SCD in a large cohort of HTx recipients, compared with the general population. METHODS AND RESULTS: Consecutive HTx recipients (n = 1246, 2 centres) transplanted between 2004 and 2016 were included. We prospectively assessed clinical, biological, pathologic, and functional parameters. SCD was centrally adjudicated. We compared the SCD incidence beyond the first year post-transplant in this cohort with that observed in the general population of the same geographic area (registry carried out by the same group of investigators; n = 19 706 SCD). We performed a competing risk multivariate Cox model to identify variables associated with SCD. The annual incidence of SCD was 12.5 per 1,000 person-years [95% confidence interval (CI), 9.7-15.9] in the HTx recipients cohort compared with 0.54 per 1,000 person-years (95% CI, 0.53-0.55) in the general population (P < 0.001). The risk of SCD was markedly elevated among the youngest HTx recipients with standardized mortality ratios for SCD up to 837 for recipients ≤30 years. Beyond the first year, SCD was the leading cause of death. Five variables were independently associated with SCD: older donor age (P = 0.003), younger recipient age (P = 0.001) and ethnicity (P = 0.034), pre-existing donor-specific antibodies (P = 0.009), and last left ventricular ejection fraction (P = 0.048). CONCLUSION: HTx recipients, particularly the youngest, were at very high risk of SCD compared with the general population. The consideration of specific risk factors may help identify high-risk subgroups.

Time trends in infectious and chronic disease consultations in Dakar, Senegal: Impact of COVID-19 sanitary measures.

Background: The impact of COVID-19 sanitary measures on the time trends in infectious and chronic disease consultations in Sub-Saharan Africa remains unknown. Methods: We conducted a cohort study on all emergency medical consultations from January 2016 to July 2020, from SOS Medecins in Dakar, Senegal. The consultation records provided basic demographic information such as age, ethnicity (Senegalese or Caucasian), and sex as well as the principal diagnosis using an ICD-10 classification ("infectious", "chronic", and "other"). We first investigated how the pattern in emergency consultation differed from March to July 2020 compared to previous years. Then, we examined any potential racial/ethnic disparities in COVID-19 consultation. Results: We obtained data on emergency medical consultations from 53 583 patients of all ethnic origins. The mean age of patients was 37.0 (standard deviation (SD) = 25.2) and 30.3 (SD = 21.7) in 2016-2019 and 45.5 (SD = 24.7) and 39.5 (SD = 23.3) in 2020 for Senegalese and Caucasian patients, respectively. The type of consultations between January and July were similar from 2016 to 2019; however, in 2020, there was a drop in the number of infectious disease consultations, particularly from April to May 2020, when sanitary measures for COVID-19 were applied (average of 366.5 and 358.2 in 2016-1019 and 133.0 and 125.0 in 2020). The prevalence of chronic conditions remained steady during the same period (average of 381.0 and 394.7 in 2016-2019 and 373.0 and 367.0 in 2020). In a multivariate analysis adjusted for age and sex, infectious disease consultations were significantly more likely to occur in 2016-2019 compared to 2020 (2016 odds ratio (OR) = 2.39, 2017 OR = 2.74, 2018 OR = 2.39, 2019 OR = 2.01). Furthermore, the trend in the number of infectious and chronic consultations was similar among Senegalese and Caucasian groups, indicating no disparities among those seeking treatment. Conclusions: During the implementation of COVID-19 sanitary measures, infectious disease rates dropped as chronic disease rates remained stagnant in Dakar. We observed no racial/ethnic disparities among the infectious and chronic consultations.

Clustering of patients with inconclusive non-invasive stress testing referred for vasodilator stress cardiovascular magnetic resonance.

BACKGROUND: Inconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods. AIMS: To identify patient subgroups by phenotypic unsupervised clustering, integrating clinical and cardiovascular magnetic resonance data to unveil pathophysiological differences between subgroups of patients with inconclusive stress tests. METHODS: Between 2008 and 2020, consecutive patients with a first inconclusive non-invasive stress test referred for stress cardiovascular magnetic resonance were followed for the occurrence of major adverse cardiovascular events (defined as cardiovascular death or myocardial infarction). A cluster analysis was performed on clinical and cardiovascular magnetic resonance variables. RESULTS: Of 1402 patients (67% male; mean age 70±11years) who completed the follow-up (median 6.5years, interquartile range 5.6-7.5years), 197 experienced major adverse cardiovascular events (14.1%). Three distinct phenogroups were identified based upon unsupervised hierarchical clustering of principal components: phenogroup 1=history of percutaneous coronary intervention with viable myocardial infarction and preserved left ventricular ejection fraction; phenogroup 2=atrial fibrillation with preserved left ventricular ejection fraction; and phenogroup 3=coronary artery bypass graft with non-viable myocardial scar and reduced left ventricular ejection fraction. Using survival analysis, the occurrence of major adverse cardiovascular events (P=0.007), cardiovascular mortality (P=0.002) and all-cause mortality (P<0.001) differed among the three phenogroups. Phenogroup 3 presented the worse prognosis. In each phenogroup, ischaemia was associated with major adverse cardiovascular events (phenogroup 1: hazard ratio 2.79, 95% confidence interval 1.61-4.84; phenogroup 2: hazard ratio 2.59, 95% confidence interval 1.69-3.97; phenogroup 3: hazard ratio 3.16, 95% confidence interval 1.82-5.49; all P<0.001). CONCLUSIONS: Cluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.

Barriers to up-titrated antihypertensive strategies in 12 sub-Saharan African countries: the Multination Evaluation of hypertension in Sub-Saharan Africa Study.

BACKGROUND: Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. The high burden of elevated blood pressure (BP) in black people has been emphasized. Guidelines recommend two or more antihypertensive medications to achieve a BP control. We aimed to identify factors associated with prescription of up-titrated antihypertensive strategies in Africa. METHODS: We conducted a cross-sectional study on outpatient consultations for hypertension across 12 SSA countries. Collected data included socioeconomic status, antihypertensive drugs classes, BP measures, cardiovascular risk factors and complication of hypertension. We used ordinal logistic regression to assess factors associated with prescription of up-titrated strategies. RESULTS: The study involved 2123 treated patients with hypertension. Patients received monotherapy in 36.3 vs. 25.9%, two-drug in 42.2 vs. 45% and three and more drugs strategies in 21.5 vs. 29.1% in low (LIC) and middle (MIC) income countries, respectively. Patients with sedentary lifestyle [OR 1.4 (1.11-1.77)], complication of hypertension [OR 2.4 (1.89-3.03)], former hypertension [OR 3.12 (2.3-4.26)], good adherence [OR 1.98 (1.47-2.66)], from MIC [OR 1.38 (1.10-1.74)] and living in urban areas [OR 1.52 (1.16-1.99)] were more likely to be treated with up-titrated strategies. Stratified analysis shows that in LIC, up-titrated strategies were less frequent in rural than in urban patients (P for trend <0.01) whereas such difference was not observed in MIC. CONCLUSION: In this African setting, in addition to expected factors, up-titrated drug strategies were associated with country-level income, patient location and finally, the interplay between both in LIC. These results highlight the importance of developing policies that seek to make multiple drug classes accessible particularly in rural and LIC.

Sociodemographic determinants of change in cardiovascular health in middle adulthood in a bi-racial cohort.

BACKGROUND AND AIMS: Cardiovascular health (CVH), as many other aspects of health, is socially patterned. However, little is known about the socioeconomic determinants of following a more or less favourable pattern of CVH change at midlife. METHODS: We used data on 11,049 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, population-based, bi-racial cohort that included participants aged 44-66 years in 1987-1989, who attended a second visit 6 years later. At both visits, CVH was assessed with the American Heart Association's Life's Simple 7 (LS7) score ranging 0-14, based on 7 metrics: cholesterol, blood glucose, blood pressure, smoking, body mass index, physical activity, and diet. An LS7 score ≥8 was considered ideal, <8 was considered poor. Multivariable logistic regression models were used. In a first sample (N = 4416) of participants who started with a poor CVH, we modelled odds of improvement (Poor-Ideal vs. Poor-Poor). In a second sample (N = 6633) with baseline ideal CVH, we modelled odds of deterioration (Ideal-Poor vs. Ideal-Ideal). The determinants considered were baseline age, sex, race, educational level, income and working status. RESULTS: The majority (8,347, 75.5%) of participants remained in the same CVH category at both waves: 28.7% poor-poor, and 46.8% ideal-ideal. The remaining 24.5% were evenly split between improving (11.2%) and deteriorating (13.2%). Compared to poor-poor CVH, older participants displayed higher odds of improving to ideal CVH (OR>58yvs < 50y = 1.41; 95% CI:1.17, 1.69), whereas Black race (vs White, OR = 0.68; 0.57, 0.80), low education (vs high, OR = 0.65; 0.53, 0.79) and low income (vs high, OR = 0.71; 0.57, 0.87)) were associated with lower odds of improvement. Compared to ideal-ideal CVH, Black participants (OR = 1.59; 1.33, 1.89), with low education (OR = 1.98; 1.64, 2.39), low income (OR = 1.57; 1.30, 1.88), and non-working (vs currently working, OR = 1.27; 1.06, 1.51) had greater odds of deterioration to poor CVH. CONCLUSIONS: We identified vulnerable groups at higher risk of worsening their CVH over time: Black people, with low income, low education, and who are unemployed. Efforts to reduce income and educational gaps and address structural racism, which shapes the distribution of health-promoting and health-harming resources, are paramount to reduce inequities in CVH.

Phenotypic Clustering of Patients With Newly Diagnosed Coronary Artery Disease Using Cardiovascular Magnetic Resonance and Coronary Computed Tomography Angiography.

Background: Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial. Objective: Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD. Materials and Methods: Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed. Results: Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 ± 12 years) completed follow-up [median 6.8 (IQR 5.9-9.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all p < 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70-5.62; PG2, HR = 3.62, 95% CI, 2.31-5.7; PG3, HR = 3.55, 95% CI, 2.3-5.49; all p < 0.001]. The study presented some key limitations that may impact generalizability. Conclusions: Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.

Impact of Pulmonary Valve Replacement on Ventricular Arrhythmias in Patients With Tetralogy of Fallot and Implantable Cardioverter-Defibrillator.

OBJECTIVES: This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring by implantable cardioverter-defibrillators (ICDs). BACKGROUND: Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias. METHODS: Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval [CI]: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 [95% CI: 0.10 to 0.89]; p = 0.031). CONCLUSIONS: In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Impact of effective regurgitant orifice area on outcome of secondary mitral regurgitation transcatheter repair.

OBJECTIVES: To assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients' selection. METHODS: Using the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO. RESULTS: Among 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm2 in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm2; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm2, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm2, respectively (P = 0.05). CONCLUSION: All-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm2, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm2 who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.

Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.