Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum

BackgroundTraditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm² were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable.ResultsIn total, 613 patients were initially recruited, with a mean ± standard deviation AVA of 0.72 ± 0.17 cm². Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n = 1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46–3.26; P < 0.001).ConclusionsArtificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.     

Association between epicardial adipose tissue and left ventricular function in type 2 diabetes mellitus: Assessment using two-dimensional speckle tracking echocardiography

Background and aimsEpicardial adipose tissue (EAT) is the visceral fat between the myocardium and the visceral pericardium. Dysfunctional EAT can cause cardiovascular diseases. The aim of this study was to investigate the association between EAT and left ventricular function in type 2 diabetes mellitus (T2DM) patients by two-dimensional speckle tracking echocardiography (2D-STE).MethodsWe prospectively enrolled 116 T2DM patients who were divided into two groups according to their left ventricular global longitudinal strain (GLS): 53 with GLS <18% and 63 with GLS ≥18%. The thickness of EAT was measured as the echo-free space between the free wall of the right ventricle and the visceral layer of pericardium at end-systole. LV systolic function was evaluated by GLS measured by 2D-STE. LV diastolic function was defined as the ratio of the early diastolic transmitral flow velocity (E) to average mitral annular velocity ($\overline{e}$).ResultsCompared with patients with GLS ≥18% group, the age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobinA1c (HbA1c), E/$\overline{e}$, and thickness of EAT were higher in patients with GLS <18% group (all P < 0.05). Multivariate linear regression analysis revealed that the thickness of EAT was independently associated with left ventricular GLS and E/$\overline{e}$.ConclusionsThickened EAT is associated with impaired left ventricular function in T2DM patients. To investigate the association between EAT and left ventricular function can help us gain a deeper understanding of the pathogenesis of impaired cardiac function in T2DM patients.     

Clinical course of arrhythmogenic right ventricular cardiomyopathy with end-stage heart failure and outcome after heart transplantation

BackgroundFew data exist on the characteristics and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy and advanced heart failure who undergo heart transplantation.AimTo explore the pretransplant course and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy after heart transplantation.MethodsThis observational retrospective monocentric study included all consecutive patients with arrhythmogenic right ventricular cardiomyopathy who underwent heart transplantation during a 13-year period (2006–2019) at Pitié-Salpêtrière University Hospital (Paris).ResultsA total of 23 patients with arrhythmogenic right ventricular cardiomyopathy underwent heart transplantation between 2006 and 2019. The median time from diagnosis to heart transplantation was 9 years, and the median age at transplantation was 50 years. At diagnosis, half of the patients had left ventricular dysfunction, 59% had extensive T-wave inversion and 43% had a history of sustained ventricular tachycardia. Only five patients were involved in intensive sport activity. Indications for heart transplantation were end-stage biventricular dysfunction in 13 patients, end-stage right ventricular heart failure in seven and electrical storm in three. Only three patients had pulmonary hypertension, and half of the patients had atrial arrhythmias. The survival rate 1 year after heart transplantation was 74% (95% confidence interval 53–88%). Eight patients experienced primary graft dysfunction needing extracorporeal membrane oxygenation.ConclusionsPatients with arrhythmogenic right ventricular cardiomyopathy who eventually needed heart transplantation mostly exhibited extended disease with biventricular dysfunction at diagnosis. Intensive sport activity did not seem to be a major determinant. Advanced heart failure usually occurred late in the course of the disease. Primary graft dysfunction after heart transplantation was frequent, and should be anticipated. Additional data are needed to identify the optimal timing for heart transplantation and predictors of end-stage heart failure in patients with arrhythmogenic right ventricular cardiomyopathy.     

Association between difference in blood pressure reduction and risk of cardiovascular events in a type 2 diabetes population: A meta-regression analysis

AimRecent US recommendations indicate a target blood pressure (BP) of 130/80 mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population.MethodsA systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects.ResultsA total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54–0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50–0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP.ConclusionA reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population.     

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

BackgroundInconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods.AimsTo 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.MethodsBetween 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.ResultsOf 1402 patients (67% male; mean age 70 ± 11 years) who completed the follow-up (median 6.5 years, interquartile range 5.6–7.5 years), 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).ConclusionsCluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.     

Asociación entre salud cardiovascular ideal y longitud telomérica en una población de edad avanzada de la cohorte SUN

Introduction and objectivesTelomeres are noncoding regions located at the end of chromosomes and their shortening has been associated with risk factors and cardiovascular disease. The aim of this study was to evaluate the association between ideal cardiovascular health (Life's simple 7) and the odds of having short telomeres in a subsample of participants older than 55 years from the Seguimiento Universidad de Navarra (SUN) study.MethodsWe included 886 participants older than 55 years (645 men and 241 women). Telomere length was measured using a real-time quantitative polymerase chain reaction. Cardiovascular health score was defined by the American Heart Association as a composite score of 7 key risk factors (smoking status, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) with 0 to 2 points for each factor. We categorized this score in tertiles as poor (0-9 points), intermediate (10-11 points) and ideal (12-14 points). The odds of having short telomeres was defined as telomere length below the 20th percentile.ResultsIndividuals with higher ideal cardiovascular health had a lower prevalence of having short telomeres (adjusted OR, 0.60; 95%CI, 0.34-1.05; P trend = .052). This association was statistically significant in men (adjusted OR, 0.37; 95%CI, 0.17-0.83; P trend = .025) but not in women.ConclusionsAn inverse association between cardiovascular health score and short telomeres was found especially for men older than 55 years in the SUN population.The SUN project was registered at ClinicalTrials.gov (Identifier: NCT02669602).     

Consenso de expertos sobre el diagnóstico y el tratamiento de la miocarditis asociada con infección o vacunación contra el SARS-CoV-2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.     

Cardiac screening before returning to elite sport after SARS-CoV-2 infection

BackgroundSARS-CoV-2 infection can induce cardiac damage. Therefore, in the absence of clear data, a cardiac evaluation was recommended for athletes before returning to play after recent SARS-CoV-2 infection.AimTo assess the proportion of anomalies detected by this cardiac screening.MethodsWe reviewed the medical files of elite athletes referred for cardiac evaluation before returning to play after a non-hospitalized SARS-CoV-2 infection (based on a positive polymerase chain reaction or antigen test) from March 2020 to July 2021 in 12 French centres.ResultsA total of 554 elite athletes (professional or national level) were included (median age 22 years, 72.0% male). An electrocardiogram (ECG), echocardiogram and exercise test were performed in 551 (99.5%), 497 (89.7%) and 293 (52.9%) athletes, respectively. We found anomalies with a potential link with SARS-CoV-2 infection in four ECGs (0.7%), three echocardiograms (0.6%) and three exercise tests (1.0%). Cardiac magnetic resonance imaging was performed in 34 athletes (6.1%), mostly due to abnormal first-line examinations, and was abnormal in one (2.9%). The rates of those abnormalities were not higher among athletes with cardiac symptoms or more severe forms of non-hospitalized SARS-CoV-2 infection. Only one athlete had a possible SARS-CoV-2 myocarditis and sport was temporally contraindicated. None had a major cardiac event declared during the follow-up.ConclusionThe proportion of cardiac involvement after non-hospitalized forms of SARS-CoV-2 infection in athletes are very low. Systematic cardiac screening before returning to play seems to be unnecessary.     

Prevalence of liver fibrosis in an unselected general population with high prevalence of obesity and diabetes mellitus. Time for screening?

IntroductionCirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide.AimTo determine the prevalence of advanced liver fibrosis in Mexican general population.MethodsAdult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676.ResultsIn total 695 individuals were included. The mean age was 47.8 ± 16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45 yr. old, 52% were obese and 27% suffered from DM.ConclusionsBased on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.