Key result
Guideline-directed medical therapy reduces NT-proBNP ~80% in dual-variant dilated cardiomyopathy without short-term LVEF recovery.
Why the study?
Dilated cardiomyopathy is genetically heterogeneous, and in severe non-ischemic cases with familial clustering of heart-failure deaths, genetic testing and pedigree analysis may clarify etiology and guide cascade screening.
Case Report (n=1)
No
This case report describes a rare presentation of severe familial non-ischemic dilated cardiomyopathy harboring coexisting likely pathogenic BAG3 and FLNC variants, highlighting the need for cautious oligogenic interpretation, individualized arrhythmic risk assessment, and family cascade screening.
Answers are grounded in this paper and cite their sources.
May support GDMT initiation in BAG3/FLNC cardiomyopathy; leaves open LVEF recovery and variant-specific prognosis.
Background Dilated cardiomyopathy (DCM) is genetically heterogeneous. In severe non-ischemic DCM with familial clustering of heart-failure deaths, genetic testing and pedigree analysis may clarify etiology and guide cascade screening. Case presentation: A 40-year-old woman presented with progressive dyspnea, chest tightness, and palpitations after an upper respiratory tract infection. Echocardiography showed severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) approximately 20%, left atrial enlargement, functional mitral regurgitation, and a small pericardial effusion. Coronary angiography excluded obstructive coronary disease. Cardiovascular magnetic resonance (CMR) demonstrated global left ventricular hypokinesis and a clinically reported non-ischemic late-gadolinium-enhancement pattern at the papillary-muscle level involving the anterior/lateral wall, consistent with a myocarditis-like presentation on an inherited cardiomyopathy substrate. Guideline-directed therapy reduced NT-proBNP from 4154 to 828 pg/mL, although angiotensin receptor-neprilysin inhibitor therapy was limited by symptomatic hypotension. At 2 months, symptoms and daily activity tolerance improved, but LVEF remained 25%, QTc was 479 ms, and ventricular premature complexes persisted. Whole-exome sequencing identified heterozygous likely pathogenic variants in BAG3 (NM_004281.4:c.180 + 1G > T) and FLNC (NM_001458.5:c.761_779del, p.[Leu254Profs*14]). The daughter carried the BAG3 variant, whereas both children were negative for FLNC. The proband reported heart-failure-related deaths in her father and younger brother during adulthood and in a nephew during childhood. Conclusions The findings support familial, probably autosomal dominant DCM with marked variable expressivity. Coexisting BAG3 and FLNC variants should be interpreted as hypothesis-generating rather than proof of dual-gene causality. Serial imaging, rhythm surveillance, blood-pressure-guided treatment, and follow-up of genotype-positive relatives are essential.
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Wang et al. (2026) conducted a case report in Familial severe non-ischemic dilated cardiomyopathy (n=1). Coexisting likely pathogenic BAG3 (c.180+1G>T) and FLNC (c.761_779del) variants managed with guideline-directed medical therapy was evaluated on Clinical status, NT-proBNP, and left ventricular ejection fraction (LVEF) at 2 months. Guideline-directed therapy in a 40-year-old woman with BAG3 and FLNC variants reduced NT-proBNP from 4,154 to 828 pg/mL, though LVEF remained 25% at 2 months.
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