Non-dilated left ventricular cardiomyopathy (NDLVC) is the presence of non-ischemic scar or fatty replacement in the left ventricle without left ventricular dilation, with or without global or regional wall motion abnormalities. These myocardial abnormalities cannot be explained solely by abnormal loading conditions or myocardial ischemia.
Pathogenesis
The primary pathogenesis involves genetic predisposition and gene mutations, with significant overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM).
Clinical Manifestations
Most patients with NDLVC are asymptomatic, but some may develop symptoms related to arrhythmias or heart failure. A small number of patients may initially present with severe arrhythmias, such as supraventricular tachycardia (SVT), ventricular fibrillation (VF), and even sudden cardiac death.
Diagnostic Workup
Electrocardiogram (ECG)
Certain ECG features may indicate an underlying genetic cause. For example, conduction abnormalities are commonly seen in NDLVC associated with neuromuscular diseases or sarcoidosis, and low QRS voltage is often observed in NDLVC related to DSP and PLN mutations.
Echocardiography
Echocardiographic findings include reduced global or regional left ventricular systolic function without significant chamber dilation.
Cardiac Magnetic Resonance (CMR)
Non-ischemic myocardial fibrosis and/or fatty replacement detected by CMR with late gadolinium enhancement (LGE) is a key diagnostic criterion. The pattern of fibrosis distribution provides critical clues for identifying the underlying etiology, and the extent of fibrosis has prognostic value.
Endomyocardial Biopsy
The detection of myocardial fibrosis and fatty replacement in biopsy samples is the gold standard for diagnosis.
Genetic Testing
NDLVC is primarily associated with mutations in genes such as DSP, FLNC (truncating variants), DES, LMNA, and PLN, many of which overlap with the genetic basis of DCM and ARVC. Among these, DSP mutations are most strongly associated with NDLVC.
Diagnosis
Diagnostic criteria include:
- Absence of significant left ventricular dilation but the presence of non-ischemic left ventricular scar or fatty replacement, with or without global or regional wall motion abnormalities; alternatively, isolated global left ventricular systolic dysfunction without myocardial scar or fatty replacement
- Exclusion of secondary, primary, and ischemic cardiomyopathies
Differential Diagnosis
NDLVC should be distinguished from other primary and secondary cardiomyopathies associated with reduced systolic function.
Clinical Management
Pharmacological Therapy
Similar to the treatment of DCM, the mainstay of therapy includes beta-blockers, ACE inhibitors (ACEIs), and angiotensin receptor blockers (ARBs).
Sudden Death Prevention
Similar to DCM, the implantation of an implantable cardioverter-defibrillator (ICD) is a key treatment for this phenotype. For primary prevention, ICD implantation should consider both phenotype- and genotype-related sudden death risks. The implantation threshold can be lowered for patients carrying high-risk pathogenic mutations. For example, even if LVEF > 35%, ICD implantation should be considered, especially in the presence of additional risk factors such as ventricular tachycardia and significant LGE on CMR.