Background The point mutation at position 3243 in the mitochondrial MT-TL1 gene (m.3243A > G) is a rare cause of hypertrophic cardiomyopathy (HCM). Information about HCM progression over time and occurrence of different cardiomyopathies in m.3243A > G carriers of the same family is still lacking. Case summary A 48-year old male patient was admitted to a tertiary care hospital with chest pain and dyspnea. Bilateral hearing loss required hearing aids at the age of 40. A short PQ interval, narrow QRS complex and inverted T-waves in lateral leads were present on electrocardiogram. HbA1c of 7.3 mmol/L indicated prediabetes. Echocardiography excluded valvular heart disease and detected non-obstructive hypertrophic cardiomyopathy with slightly reduced left ventricular ejection fraction (LVEF 48%). Coronary artery disease was ruled out by coronary angiography. Myocardial fibrosis determined by repeated cardiac MRI progressed over time. Endomyocardial biopsy excluded storage disease, Fabry disease, infiltrative and inflammatory cardiac disease. Genetic testing revealed m.3243A > G mutation in the MT-TL1 gene associated with mitochondrial disease. Clinical evaluation and genetic testing of the patients’ family revealed five genotype-positive relatives with heterogeneous clinical phenotypes including deafness, diabetes mellitus, kidney disease and both hypertrophic and dilated cardiomyopathy. Discussion In patients with unexplained symmetric HCM with heterogenic clinical phenotypes at the organ levels mitochondrial disease should be taken into consideration, particularly in the context of matrilinear transmission. m.3243A > G mutation is associated with a mitochondrial disease in the index patient and five family members and leads to the diagnosis of maternal inherited diabetes and deafness (MIDD) with intra-familial variability of different cardiomyopathy forms.

Aims To determine the conditions under which early hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve implantation (TAVI) becomes hemodynamically relevant. Methods and results The study included 100 patients (age: 81.5 ± 5.5 years; female 63%), thereof 50 patients with HALT. After anonymization and randomization, blinded readers measured maximum thrombus thickness per prosthesis (MT_pr) and movement restriction (MR_pr) on ECG-gated whole heart cycle CTA. These measurements were compared with echocardiographic mean pressure gradient (mPG), its increase from baseline (ΔmPG) and doppler velocity index (DVI). Hemodynamic valve deterioration (HVD) was defined as mPG > 20mmHg. Age, body mass index, valve type, valve size, left ventricular ejection fraction and atrial fibrillation were considered as influencing factors. Multiple regression analysis revealed that only valve size (p = 0.001) and MT_pr (p = 0.02) had a significant influence on mPG. In an interaction model valve size moderated the effect of MT_pr on mPG significantly (p = 0.004). Subgroup analysis stratified by valve sizes showed a strong correlation between MT_pr and echocardiographic parameters for 23 mm valves (mPG: r = 0.57, ΔmPG: r = 0.68, DVI: r = 0.55, each with p < 0.001), but neither for 26 mm nor 29 mm valves (r < 0.2, p > 0.2 for all correlations). Six of seven prostheses with HVD had a 23 mm valve diameter, while one had 29 mm (p = 0.02). Conclusion Early HALT rarely causes significant mPG increase. Our study shows that valve size is a key factor influencing the hemodynamic impact of HALT. In small valve sizes, mPG is more likely to increase. Our study is the first to offer in vivo evidence supporting previous in vitro findings on this topic.

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