A pathogenic TTN variant and active myocardial inflammation co-occurred in a patient with dilated cardiomyopathy, demonstrating complex gene-environment interactions in primary myocardial disease.
This case highlights the diagnostic challenges and complexity of gene-environment interactions in patients presenting with genetic dilated cardiomyopathy and concurrent myocardial inflammation.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Primary cardiomyopathies present significant diagnostic challenges to clinical practice due to their diverse aetiologies and overlapping clinical features, often complicating the identification of a definitive cause. We here report the case of a patient with a Titin (TTN) -related dilated cardiomyopathy (DCM) and ongoing inflammation. Case Report A 75-year-old woman presented with a one-month history of worsening fatigue, palpitations, and chest discomfort. At admission, she presented with sinus tachycardia, without congestive signs. NT-proBNP (13423pg/mL) and high-sensitivity troponin T (21ng/mL) were both increased. The thoracic CT showed bilateral pleural effusion and mediastinal lymphadenopathy. The transthoracic echocardiography showed severe biventricular dysfunction, severe functional mitral regurgitation, and an estimated pulmonary artery systolic pressure of 60 mmHg. She was started on IV diuretics and slow up-titration of guideline directed medical therapy (GDMT). Coronary angiography showed no significant lesions. Cardiac MRI showed severe left ventricular (LV) dilation and reduced LV ejection fraction (LVEF 28%). T2 mapping and extracellular volume fraction were increased. Late gadolinium enhancement (LGE) displayed a mixed pattern with septal mid-wall and infero-lateral subendocardial patterns. Thus, these findings raised suspicion for inflammatory cardiomyopathy. After discharge, the patient was referred for further workup. At 3 months, she was asymptomatic, tolerating maximal doses of GDMT. Laboratory assessment showed increased inflammatory markers, i. e. plasma neopterin (14. 1nmol/L; N10) and soluble interleukin 2 receptor (sIL-2R) (2767pg/mL, N: 458-1997), despite normal angiotensin converting enzyme. A high-resolution chest CT showed complete lymphadenopathies involution. However, whole-body 18FDG PET/CT scan, performed with adequate diet preparation, showed increased radiotracer uptake in the LV (SUV 7. 8). Genetic testing identified a pathogenic heterozygous TTN variant (c. 76109₇6110del p. ). At 3 months follow-up, the patient is currently asymptomatic (NYHA I), with partially improved LVEF (∼40%). Further aetiological workup for a possible inflammatory trigger, using a dedicated algorithmic – including LV endomyocardial biopsy to exclude granulomas or chronic viral and/or lymphocytic myocarditis –, is being contemporized (figure). Conclusion Genetic DCM and ongoing myocardial inflammation was detected in this case. Whether these findings are due to a TTN flare or an extrinsic trigger (e. g. , post-infectious chronic myocarditis, which may explain the mediastinal lymphadenopathy that resolved in the second chest CT), is being actively investigated. This case illustrates the complexity of gene-environment interactions and diagnostic challenges in primary myocardial disease.
Correia et al. (Sun,) reported a other. A pathogenic TTN variant and active myocardial inflammation co-occurred in a patient with dilated cardiomyopathy, demonstrating complex gene-environment interactions in primary myocardial disease.