Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

Purpose: Metabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients. Patients and methods: We prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake (V’O₂) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (IC_dyn)) with percentage of maximal HR and CMI. Results: Aerobic capacity (median interquartile ranges) peak V’O₂, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL·kg^-1·min^-1 and CMI worsened according to GOLD severity. The optimal knot of IC_dyn was equal to −0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6). Conclusion: COPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.

Rationale: Pulmonary hypertension is a serious cardiopulmonary complication of sickle cell disease, but the prognostic impact of hemodynamic parameters remains poorly defined. Objectives: This study aimed to assess the clinical and long-term prognostic relevance of hemodynamic parameters in sickle cell disease. Methods: Data were analyzed from the French ETENDARD cohort. All 398 participants underwent echocardiography; those with tricuspid regurgitation velocity ≥2.5 m/s proceeded to right heart catheterization. Over a minimum 10-year follow-up, we examined the clinical and prognostic significance of hemodynamic variables. Measurements and Main Results: Pulmonary hypertension defined by a mean pulmonary arterial pressure (mPAP) >20 mm Hg was identified in 44 patients (11%). Among them, 26 (6.5%) had a pulmonary arterial wedge pressure ≤15 mm Hg, and 18 (4.5%) had a pulmonary arterial wedge pressure >15 mm Hg. Mortality during follow-up was 11.1%. A significant association was found between pulmonary vascular resistance (PVR) levels and mortality risk, with a threshold identified at 1.5 Wood units (WU) through receiver operating characteristic curve analyses. In patients with mPAP >20 mm Hg and PVR ≥1.5 WU, the adjusted hazard ratio for mortality was 4.27 (95% confidence interval, 1.88–9.74; P < 0.001). A hemolytic phenotype and the presence of systemic complications, including hypertension, left ventricular diastolic dysfunction, renal impairment, and leg ulcers, were associated with elevated PVR and increased mortality risk. Conclusions: A PVR threshold of 1.5 WU emerges as a key predictor of mortality in patients with an mPAP above 20 mm Hg, particularly when assessed in conjunction with markers of hemolysis and systemic complications.

Cardiovascular complications are the leading cause of mortality in sickle cell anemia (SCA) patients. While extensive data have identified diastolic dysfunction (DD) to increase morbidity and mortality, the unique hemodynamic conditions inherent to SCA challenge the current recommendations to assess diastolic function. Thus, there is an urgent need to refine the echocardiographic definition of DD to improve risk stratification and therapeutic strategies in SCA patients. We analyzed data from the French multicentric Etendard cohort and compared them with an age‐ and sex‐matched control group from the Copenhagen City Heart Study (CCHS). We focused on left ventricular diastolic parameters, specifically lateral e′ velocity (e′ lat), E/e′ ratio, and indexed left atrial volume (LAVi), assessing their association with clinical outcomes over a 12‐year follow‐up. Etendard SCA patients ( n = 379) had an early impaired diastolic function compared to the CCHS controls ( n = 672). This was particularly obvious in young SCA patients ( n = 252, age ≤ 38 years) in whom e′ lat was associated with prognosis ( p = 0.01), with an optimal cut‐off value below 11 cm/s. Indeed, young SCA patients with DD had a fourfold increased 12‐year mortality rate as compared with SCA patients without DD (16 vs. 4%, p < 0.001). Additionally, e′ lat correlated with 6‐min walk test, NT pro‐BNP levels, diastolic blood pressure, and lactate dehydrogenase levels. In young SCA patients, our data contribute to refine the diagnosis of diastolic dysfunction evaluation. We highlight the prognostic value below 11 cm/s of lateral e′ velocity and its association with key contributors of cardiac impairment such as hemolysis and systemic vasculopathy. Trial Registration: ClinicalTrials.gov identifier: NCT00434902