Pregnancy and cardiac maternal outcomes in women with inherited cardiomyopathy: interest of the CARPREG II risk score.

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.

Characterizing cardiac phenotype in Friedreich's ataxia: The CARFA study.

BACKGROUND: Friedreich's ataxia is an autosomal recessive mitochondrial disease caused by a triplet repeat expansion in the frataxin gene (FXN), exhibiting cerebellar sensory ataxia, diabetes and cardiomyopathy. Cardiac complications are the major cause of early death. AIMS: To characterize the cardiac phenotype associated with Friedreich's ataxia, and to assess the evolution of the associated cardiopathy over 1 year. METHODS: This observational single-centre open label study consisted of two groups: 20 subjects with Friedreich's ataxia and 20 healthy controls studied over two visits over 1 year. All subjects had transthoracic echocardiography, cardiac magnetic resonance imaging, cardiopulmonary exercise testing, quantification of serum cardiac biomarkers and neurological assessment. RESULTS: Patients with Friedreich's ataxia had left ventricular hypertrophy, with significantly smaller left ventricular diastolic diameters and volumes and increased wall thicknesses. Cardiac magnetic resonance imaging demonstrated significant concentric left ventricular remodelling, according to the mass/volume ratio, and focal myocardial fibrosis in 50% of patients with Friedreich's ataxia. Cardiopulmonary exercise testing showed alteration of left ventricular diastolic filling in patients with Friedreich's ataxia, with an elevated VE/VCO2 slope (ventilatory flow/exhaled volume of carbon dioxide). High-sensitivity troponin T plasma concentrations were higher in subjects with Friedreich's ataxia. None of the previous variables changed at 1 year. Neurological assessments remained stable for both groups, except for the nine-hole pegboard test, which was altered over 1 year. CONCLUSIONS: The multivariable characterization of the cardiac phenotype of patients with Friedreich's ataxia was significantly different from controls at baseline. Over 1 year there were no clinically significant changes in patients with Friedreich's ataxia compared with healthy controls, whereas the neurological severity score increased modestly.

Significance of NT-proBNP and High-sensitivity Troponin in Friedreich Ataxia.

BACKGROUND: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease resulting of a triplet repeat expansion guanine-adenine-adenine (GAA) in the frataxin (FXN) gene, exhibiting progressive cerebellar ataxia, diabetes and cardiomyopathy. We aimed to determine the relationship between cardiac biomarkers, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum cardiac high-sensitivity troponin (hsTnT) concentrations, and the extent of genetic abnormality and cardiac parameters. METHODS: Between 2013 and 2015, 85 consecutive genetically confirmed FA adult patients were prospectively evaluated by measuring plasma hsTnT and NT-proBNP concentrations, electrocardiogram, and echocardiography. RESULTS: The 85 FA patients (49% women) with a mean age of 39 ± 12 years, a mean disease onset of 17 ± 11 years had a mean SARA (Scale for the Assessment and Rating of Ataxia) score of 26 ± 10. The median hsTnT concentration was 10 ng/L (3 to 85 ng/L) and 34% had a significant elevated hsTnT ≥ 14 ng/L. Increased septal wall thickness was associated with increased hsTnT plasma levels (p < 0.001). The median NT-proBNP concentration was 31 ng/L (5 to 775 ng/L) and 14% had significant elevated NT-proBNP ≥ 125 ng/L. Markers of increased left ventricular filling pressure (trans mitral E/A and lateral E/E' ratio) were associated with increased NT-proBNP plasma levels (p = 0.01 and p = 0.01). Length of GAA or the SARA score were not associated with hsTnT or NT-proBNP plasma levels. CONCLUSION: hsTnT was increased in 1/3 of the adult FA and associated with increased septal wall thickness. Increased NT-proBNP remained a marker of increased left ventricular filling pressure. This could be used to identify patients that should undergo a closer cardiac surveillance.

Saw-Tooth Cardiomyopathy: Clinical Presentation and Genetic Analysis.

Saw-tooth cardiomyopathy is a very rare disease, and only few cases have been published since its first description 10 years ago. We report the clinical presentation, imaging features and genetic analysis of a saw-tooth cardiomyopathy and argues that it should not be confused with left-ventricular noncompaction. (Level of Difficulty: Intermediate.).

Predictors of Left Ventricular Dysfunction in Friedreich's Ataxia in a 16-Year Observational Study.

BACKGROUND: Friedreich's ataxia (FRDA) is a cerebellar ataxia due to GAA repeat expansions in the FXN gene, and in affected patients, lower left ventricular ejection fraction (LVEF) leads to poorer prognosis. We aimed to identify patients likely to develop worsening LVEF at an early stage. METHODS: We included 115 FRDA patients aged 30 ± 10 years with 620 ± 238 GAA repeats on the shorter allele and disease onset of 15 ± 7 years. RESULTS: At baseline, left ventricular (LV) hypertrophy was present in 53%, with LVEF 65 ± 7%, LV end diastolic diameter (LVEDD) 43 ± 5 mm, septal wall thickness (SWT) 11.8 ± 2.7 mm, and posterior wall thickness 11.1 ± 2.5 mm. After a mean follow-up of 13 ± 6 years, LVEF ≤ 50% was observed in 12 patients. The main determinants of LVEF ≤ 50% were GAA repeat number on the shorter allele (odds ratio [OR] 1.007, 95% confidence interval [CI] 1.003-1.012, p = 0.002), LVEDD (OR 1.217, 95% CI 1.058-1.399, p = 0.006), and SWT (OR 1.352, 95% CI 1.016-1.799, p = 0.04). High-risk patients were predicted 5 years before LVEF ≤ 50% occurred: area under the curve of 0.91, 95% CI 0.85-0.97. Patients with GAA repeats > 800 were categorized as high risk, patients with 500 < GAA < 800 were high risk if LVEDD was ≥ 52.6 mm and SWT was ≥ 13.3 mm, and patients with GAA < 500 were low risk if LVEDD was < 52.6 mm and SWT was < 13.3 mm. CONCLUSIONS: Echocardiographic follow-up combined with size assessment of GAA repeat expansions is a powerful tool to identify patients at high risk of developing LV systolic dysfunction up to 5 years before clinical symptoms. Further studies are mandatory to investigate if these patients would benefit from cardiac interventions.

[Main novelties of the last set of European guidelines for the management of heart failure]. / Que retenir des dernières recommandations européennes sur l'insuffisance cardiaque chronique et aiguë ?

Heart failure is the main chronic disease in cardiology. Its prognosis remains poor despite improvements in its management that allow patients to live increasingly longer with this disease, alternating periods of stability and episodes of decompensation. Treatment guidelines are regularly updated to integrate new results of recent trials that are likely to influence routine care. These guidelines are proposed with different classes of recommendations and difference levels of evidence. It is of paramount importance to summarize the guidelines to make them accessible to the vast majority of cardiologists and easier to read to promote their application. Among the main novelties of the last set of European guidelines for the management of heart failure, we note the proposal for a new classification based on the level of left ventricular ejection fraction (LVEF) with a new class, called heart failure with mid-range ejection fraction (LVEF 40-50 %), new algorithms for diagnosis and treatment, including the diagnosis of heart failure with preserved ejection fraction, a special focus on preventive strategies, the management of comorbidities including iron deficiency, simplification of the indications for cardiac resynchronization therapy, and finally a growing attention to patient pathways and to the management of hospital discharge. According to these guidelines, it is important that the physician choose the appropriate medications; but it is equally fundamental that the patient understands the disease and acquires self-care skills needed to become a real player in its management. This requires patient education, which is underdeveloped in France.

A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia.

IMPORTANCE: Friedreich ataxia (FRDA) is the most common genetic sensory ataxia, and myocardial involvement is a major determinant of survival. OBJECTIVE: To assess FRDA survival and cardiac outcome to adapt future therapeutic trials. DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal follow-up study, all patients with genetically confirmed FRDA seen in the reference center and referred for cardiac evaluation (standard 12-lead electrocardiogram and transthoracic echocardiography) to the cardiology department were enrolled and followed up from April 27, 1990, to July 31, 2013. The setting was the French National Reference Center for Rare Diseases and the Department of Cardiology, Salpêtrière University Hospital, Paris, France. In total, 138 patients with FRDA were followed up. Among 133 patients homozygous for expanded GAA repeats, the mean (SD) age was 31 (10) years (age range, 11-62 years), with a mean (SD) age at disease onset of 16 (8) years (age range, 3-50 years) and a mean (SD) age at first wheelchair use of 26 (9) years (age range, 11-64 years). Cardiac hypertrophy was present in 57.9% (77 of 133), and electrocardiography was normal in 6.8% (9 of 133). MAIN OUTCOMES AND MEASURES: Long-term cardiac outcome and predictors of survival in FRDA. RESULTS: After a mean (SD) follow-up of 10.5 (5.5) years (range, 0.6-23.0 years), the 10-year survival rate was 88.5%. In 80.0% of patients (12 of 15), death was due to cardiac causes. Predictors of survival were a shorter GAA repeat length on the smaller allele of the frataxin gene (hazard ratio [HR], 1.85; 95% CI, 1.28-2.69), left ventricular ejection fraction (HR, 0.42; 95% CI, 0.20-0.89), and left ventricular mass index (HR, 1.19; 95% CI, 1.04-1.36). Two cardiac evolutions were distinguished with a group-based trajectory model, including a low-risk cardiac group (78.6% [81 of 103] with normal ejection fraction at baseline that declined slightly over time but remained within the normal range) and a high-risk cardiac group (21.4% [22 of 103] in which the ejection fraction progressively declined during follow-up). The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time. CONCLUSIONS AND RELEVANCE: Survival in FRDA is determined by cardiac complications, which are dependent on the mutation (ie, the size of the expanded GAA repeat). Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.