Aetiology and clinical manifestations of patients with non‐dilated left ventricular cardiomyopathy

Non-dilated left ventricular (LV) cardiomyopathy (NDLVC) is a new entity introduced in the recently published 2023 European Society of Cardiology (ESC) guidelines for the management of cardiomyopathies.1 It is an umbrella term encompassing the presence of (i) non-ischaemic LV fibrosis or fatty replacement in the absence of LV dilatation, with or without global or regional motion abnormalities, or (ii) isolated global LV hypokinesia (i.e. LV ejection fraction LVEF 50%) in 21 cases (61.7%); LV fibrosis with LV systolic dysfunction (LVEF <50%) in 2 cases (5.9%); isolated LV systolic dysfunction without fibrosis in 11 cases (32.4%). Patients with LV fibrosis were more likely to have a genetic aetiology, while those with isolated LV systolic dysfunction without fibrosis had largely unidentified aetiology (idiopathic NDLVC). Among the 34 patients who underwent CMR, a definitive diagnosis of ALVC according to the 2024 updated Padua criteria was reached in 14 cases (41.2%). This diagnosis was mainly based on the presence of a ring-like pattern of fibrosis on CMR and a P/LP variant in an ALVC-associated gene. These 14 cases were distributed as follows: 11 patients with genetic NDLVC, 2 patients with idiopathic NDLVC, and 1 patient with inflammatory NDLVC. Thus, the diagnosis of ALVC was common among patients with genetic NDLVC (11/15 cases 73.3% who underwent CMR) and uncommon in those with inflammatory or neuromuscular NDLVC (1/5 cases 20.0% and 0/2 cases 0.0%, respectively). This study describes for the first time the aetiological spectrum of consecutive patients with NDLVC. The findings reveal that the aetiology is heterogeneous, with more than one-third having an underlying genetic aetiology, nearly one-fifth having an inflammatory or neuromuscular condition, and in the remaining cases, a comprehensive diagnostic work-up fails to identify an underlying aetiology. A genetic cause was more frequent in patients with LV fibrosis at CMR compared with patients with isolated LV systolic dysfunction without fibrosis. Myocarditis-like onset is a common clinical presentation, with nearly one-third of cases uncovering a P/LP variant in DSP, confirming the emerging notion that myocarditis can uncover a genetic cardiomyopathy.6 Finally, while most patients with genetic NDLVC fulfilled diagnostic criteria for ALVC, the diagnosis of ALVC was rarely observed in patients with an inflammatory or neuromuscular aetiology. These observations support the concept of the 2023 ESC guidelines that the NDLVC phenotype represents a starting disease phenotype. It should be considered as a working diagnosis that promptly triggers a multiparametric approach leading to an aetiological diagnosis and, ultimately, individualized management. Indeed, risk stratification for adverse cardiovascular events and treatment can vary significantly among patients presenting with the same NDLVC phenotype but different underlying aetiologies.1 This study has several limitations, including a small sample size and its retrospective nature. Larger multicentre cohort studies are needed to confirm these findings. Furthermore, future research on the role of clinical, molecular, and imaging features in predicting the underlying aetiology will be crucial for guiding the diagnostic work-up and is essential for early diagnosis and management. Additionally, assessing the pattern of disease progression in patients with NDLVC could provide valuable information for a tailored management of affected patients. We are grateful to Dr. Santo Dellegrottaglie and Dr. Alessandra Scatteia for their valuable contribution as cardiac magnetic resonance experts in the field. We are also grateful to our nurses Michela Piscopo and Daniela Lafera for their precious contribution in managing patients with cardiomyopathies. Conflict of interest: none declared.