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Background Diagnostic work-up of patients with hypertrophic cardiomyopathy is crucial for appropriate management. However, the optimal genetic strategy remains debatable. We compared two strategies: targeted testing based on careful examination of clinical red flags versus large multigene panel analysis without gene prioritization. We applied the strategy to the diagnosis of Fabry disease or Hereditary Transthyretin Amyloidosis ( GLA or TTR genes respectively). Results We studied 341 hypertrophic cardiomyopathy index patients. Patients of subgroup 1 (n = 42) had careful clinical analysis and high suspicion of Hereditary Transthyretin Amyloidosis or Fabry disease. They underwent targeted Sanger sequencing. Patients in subgroup 2 (n = 299) did not have clinical selection, and underwent next-generation sequencing analysis of 107 cardiac genes. The yield of genetic testing for pathogenic/likely pathogenic variants in GLA and/or TTR was 28.6% in subgroup 1 (12/42: 5 TTR and 7 GLA ) versus 1.0% in subgroup 2 (3/299: 1 TTR and 2 GLA ), p  < 0.01. Genetic results were obtained after a median of 26.0 days [IQR = 18–59.8] in subgroup 1 versus 193.5 days [IQR = 174–218] in subgroup 2, p  < 0.01. Finally, genetic testing cost was 615.60€ or 769.50€ for TTR or GLA targeted analysis respectively, versus 1503.90€ for multigene panel analysis. Conclusions Both molecular strategies in hypertrophic cardiomyopathy patients are useful for the identification of pathogenic/likely pathogenic variants in TTR/GLA genes. However, targeted genetic testing based on clinical red flags identified causal mutations more efficiently, faster and at a lower cost. Careful clinical analysis is therefore important in guiding molecular strategy and may reduce diagnostic wandering and accelerate delivery of appropriate therapy.

Abstract Aims We aim to describe the incidence of HF hospitalization in France in the post-pandemic era, the prevalence of HF cases and patients' characteristics, management and outcomes while focusing on sex, age and socio-economic differences and to analyse time-trends between 2012 and 2022. Methods and results Based on the French health care database providing medical information for almost the whole French population, patients hospitalized for acute decompensated HF without history of HF in the 5 years were identified by the International Classification of Diseases – 10th revision (ICD-10) codes. In 2022, the estimated prevalence of HF was 1.7% in France and has increased until the COVID-19 pandemic and decreased thereafter. The incidence of acute HF decompensation reached 201.4 per 100 000 inhabitants and has decreased since 2012 (−1% per year). A significant increase of the HF incidence was found in men aged <45 years. Women aged <65 years were less likely to be admitted in a cardiac rehabilitation (CR) unit and had higher probability of one-year mortality compared with men of the same age. One-year mortality was significantly increased in patients from the most deprived area among extreme age group only (under 65 and ≥85 years). One-year rehospitalization rates have decreased significantly, particularly in men aged <75 years. A decrease in ACE/ARBs deliveries was observed in both men and women. Conclusions Despite the decrease in acute HF decompensation incidence and improvements in the management, the prevalence of HF remains stable in France and prognosis remains poor.

Aims The use of large medical or healthcare claims databases is very useful for population‐based studies on the burden of heart failure (HF). Clinical characteristics and management of HF patients differ according to categories of left ventricular ejection fraction (LVEF), but this information is often missing in such databases. We aimed to develop and validate algorithms to identify LVEF in healthcare databases where the information is lacking. Methods and results Algorithms were built by machine learning with a random forest approach. Algorithms were trained and reinforced using the French national claims database [Système National des Données de Santé (SNDS)] and a French HF registry. Variables were age, gender, and comorbidities, which could be identified by medico‐administrative code‐based proxies, Anatomical Therapeutic Chemical codes for drug delivery, International Classification of Diseases (Tenth Revision) coding for hospitalizations, and administrative codes for any other type of reimbursed care. The algorithms were validated by cross‐validation and against a subset of the SNDS that includes LVEF information. The areas under the receiver operating characteristic curve were 0.84 for the algorithm identifying LVEF ≤ 40% and 0.79 for the algorithms identifying LVEF < 50% and ≥50%. For LVEF ≤ 40%, the reinforced algorithm identified 50% of patients in the validation dataset with a positive predictive value of 0.88 and a specificity of 0.96. The most important predictive variables were delivery of HF medication, sex, age, hospitalization, and testing for natriuretic peptides with different orders of positive or negative importance according to the LVEF category. Conclusions The algorithms identify reduced or preserved LVEF in HF patients within a nationwide healthcare claims database with high positive predictive value and low rates of false positives.

Takayasu arteritis (TA) may affect myocardium and cause coronary stenosis. The aim of this study was to assess the prevalence and pattern of myocardial disease in patients with TA, using late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (CMRI). Twenty-seven consecutive patients with TA and 80 age- and gender-matched controls without known cardiovascular disease underwent CMRI. The prevalence of myocardial ischemic disease, as revealed by LGE, was compared between patients with TA and controls, and factors associated with myocardial disease were identified in patients with TA. Myocardial ischemic disease, as characterized by LGE on CMRI, was present in 7 (25.9%) of 27 patients with TA, and imaging with LGE showed a typical pattern of myocardial infarction in 6 patients (22.2%). Although both patients with TA and control subjects shared a similar risk of cardiovascular events, the prevalence of myocardial ischemia was >5× greater in patients with TA (p = 0.002 vs controls). No association was found between myocardial disease in patients with TA and cardiovascular atherosclerotic risk factors. The presence of myocardial scarring tended to be more closely associated with specific features of TA such as renovascular hypertension, older age at the onset of TA symptoms, male gender, aneurysmal dilatation, and Numano type V. In conclusion, finding of a significant and unexpectedly high prevalence of occult myocardial scarring in patients with TA indicates the usefulness of CMRI with LGE for the identification of occult myocardial disease in such patients.

Aims Inherited cardiomyopathies are relatively rare but carry a high risk of cardiac maternal morbidity and mortality during pregnancy and postpartum. However, data for risk stratification are scarce. The new CARPREG II score improves prediction of prognosis in pregnancies associated with heart disease, though its role in inherited cardiomyopathies is unclear. We aim to describe characteristics and cardiac maternal outcomes in patients with inherited cardiomyopathy during pregnancy, and to evaluate the interest of the CARPREG II risk score in this population. Methods and results In this retrospective single‐centre study, 90 consecutive pregnancies in 74 patients were included (mean age 32 ± 5 years), including 28 cases of dilated cardiomyopathy (DCM), 46 of hypertrophic cardiomyopathy, 11 of arrhythmogenic right ventricular cardiomyopathy and 5 of left ventricular noncompaction, excluding peripartum cardiomyopathy. The discriminatory power of several risk scores was assessed by the area under the receiver‐operating characteristic curve (AUC). Median CARPREG II score was 2 [0;3] and was higher in the DCM subgroup. A severe cardiac maternal complication was observed in 18 (20%) pregnancies, mainly driven by arrhythmia and heart failure (each event in 10 pregnancies), with 3 cardiovascular deaths. Forty‐three pregnancies (48%) presented foetal/neonatal complications (18 premature delivery, 3 foetal/neonatal death). CARPREG II was significantly associated with cardiac maternal complications (P < 0.05 for all) and showed a higher AUC (0.782) than CARPREG (0.755), mWHO (0.697) and ZAHARA (0.604). Conclusions Pregnancy in women with inherited cardiomyopathy carries a high risk of maternal cardiovascular complications. CARPREG II is the most efficient predictor of cardiovascular complications in this population.

The aim of this multicenter observational study conducted in France was to determine the prevalence of memory impairment in ambulatory patients aged ≥70 years with chronic heart failure (HF). Two hundred ninety-one cardiologists recruited 912 ambulatory patients with HF (mean age 79.2 ± 5.8 years) from January to November 2009. Memory was evaluated by the delayed-recall Memory Impairment Screen (MIS-D). Memory impairment was defined as MIS-D score ≤6 and severe memory impairment as MIS-D score ≤4. HF was diagnosed 4.4 ± 4.8 years earlier and mean left ventricular ejection fraction was 43.6 ± 12.0%. Memory impairment was found in 416 subjects (45.6%, 95% confidence interval 42.4 to 48.8) and severe memory impairment in 213 subjects (23.4%, 95% confidence interval 20.6 to 26.1), whereas cardiologists only suspected memory impairment in 109 patients (12%; before evaluation by MIS). Determinants of memory disorders included older age, lower education level, depression, history of stroke, renal failure, and less regular physical activity. The severity of memory impairment increased with increasing severity of HF (New York Heart Association classification; p <0.00001). In conclusion, memory impairment in older patients with HF is common. The use of a simple-to-use tool such as the MIS-D may identify patients at risk and enable implementation of management strategies to improve therapeutic compliance.

Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06 × 10⁻⁶, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T). Three more SNPs showed p < 2.21 × 10⁻⁵. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92]), France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻⁴, OR  = 0.63 [95% CI 0.50-0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]). None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using a large SNP panel underscores the influence of common polymorphisms on DCM susceptibility.

The host-microbiota co-metabolite trimethylamine N -oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk. TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.

Recently, two new indexes based on the ratio of transmitral early diastolic velocity (E) to tissue Doppler imaging (TDI), and early diastolic velocity of mitral annulus (E’) and E to propagation velocity (Vp) have been proposed to predict left ventricular (LV) filling pressures. However, little is known about the comparative value of these two indexes. We studied 71 consecutive patients referred for coronary angiography (mean age ± SD, 65 + 11 years; 21 patients with LV ejection fraction [EF] < 50%). Complete Doppler echocardiographic examination including TDI and Vp measurements and direct measurement of LV end-diastolic pressure (LVEDP) were performed simultaneously in the catheterization laboratory. LV filling pressures were considered elevated when LVEDP was ≥ 15 mm Hg. The correlation coefficients between E/E' and E/Vp and LVEDP were 0.68 (p = 0.01) and 0.54 (p = 0.01), respectively, in the overall population. The correlations were better in patients with low LV EF (< 50%) [0.8 (p = 0.01) and 0.77(p = 0.01)] and poor in patients with normal LV EF (0.57 [p = 0.05] and 0.41 [not significant]), respectively. Moreover, Vp measurements had higher interobserver variability compared to E' (14% vs 7%). The cutoff values for both indexes giving the best sensitivity and specificity in identifying LVEDP ≥ 15 mm Hg were 9 for (E/E’) and 2 for (E/Vp) Both E/E' and E/Vp can be used for the evaluation of LV filling pressures. However, the sensitivity of these indexes, especially E/Vp, is hampered by EF. E/E' has a lower variability than Vp and should be preferred for estimation of filling pressures especially in patients with EF > 50%.

RationaleAdaptive servo ventilation (ASV) is contraindicated in patients with systolic heart failure (HF) who have a left ventricular ejection fraction (LVEF) below 45% and predominant central sleep apnoea (CSA). However, the effects of ASV in other HF subgroups have not been clearly defined.ObjectiveThe European, multicentre, prospective, observational cohort trial, FACE, evaluated the effects of ASV therapy on morbidity and mortality in patients with HF with sleep-disordered breathing (SDB); 3-month outcomes in patient subgroups defined using latent class analysis (LCA) are presented.MethodsConsecutive patients with HF with predominant CSA (±obstructive sleep apnoea) indicated for ASV were included from 2009 to 2018; the non-ASV group included patients who refused/were noncompliant with ASV. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention or unplanned hospitalisation for worsening of chronic HF).Measurements and main resultsBaseline assessments were performed in 503 patients, and 482 underwent 3-month follow-up. LCA identified six discrete patient clusters characterised by variations in LVEF, SDB type, age, comorbidities and ASV acceptance. The 3- month rate of primary outcome events was significantly higher in cluster 1 patients (predominantly men, low LVEF, severe HF, CSA; 13.9% vs 1.5%–5% in other clusters, p<0.01).ConclusionFor the first time, our data identified homogeneous patient clusters representing clinically relevant subgroups relating to SDB management in patients with HF with different ASV usage, each with a different prognosis. This may improve patient phenotyping in clinical practice and allow individualisation of therapy.