RESUMO
BACKGROUND: Many genetic non-ischemic dilated cardiomyopathies (NICM) cause ventricular tachycardias (VT) originating from scar substrate identified as areas of low electrogram voltage. Substrate locations vary and the causes of scar are not well defined. OBJECTIVE: This study evaluated VT substrate locations in genetic NICM patients undergoing VT ablation to evaluate spatial relationships between specific variants and substrate locations. METHODS: In this retrospective case series analysis, 32 patients (age 55 +/- 16 years, 94% male, left ventricular ejection fraction 34 +/- 13%) with genetic NICM referred for VT ablation between October 2018 and November 2022 at a single medical center were evaluated. Scar locations were defined as areas of low unipolar/ bipolar voltage. RESULTS: Of the thirty-two patients evaluated, mutations in TTN (n=11 of 32), LMNA (n=6 of 32), PKP2 (n=5 of 32), MYBPC3 (n=3 of 32), DSP (n=2 of 32), TTR (n=1 of 32), FLNC (n=1 of 32), AGL (n=1 of 32), DES (n=1 of 32), DSG2 (n=1 of 32), were observed. Substrates associated with mutations in TTN were only observed in basal subregions, predominantly anterior (100%), and septal (50%) regions. LMNA mutations were associated with fibrosis in mid inferolateral (60%) and apical inferolateral (60%) regions. Substrate location for individuals with PKP2 mutations were solely observed in the right ventricle, predominantly basal inferolateral regions. CONCLUSION: Understanding spatial relationships between genetic variants causing NICM and VT substrate locations can help lead to generalizable regions in patients with genetically related NICM presenting in VT which can be investigated during ablation procedures.
RESUMO
OBJECTIVE: Inhibition of adenosine kinase (ADK), via augmenting endogenous adenosine levels exerts cardiovascular protection. We tested the hypothesis that ADK inhibition improves microvascular dilator and left ventricle (LV) contractile function under metabolic or hemodynamic stress. METHODS AND RESULTS: In Obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid rats, treatment with the selective ADK inhibitor, ABT-702 (1.5 mg/kg, intraperitoneal injections for 8-week) restored acetylcholine-, sodium nitroprusside-, and adenosine-induced dilations in isolated coronary arterioles, an effect that was accompanied by normalized end-diastolic pressure (in mm Hg, Lean: 3.4 ± 0.6, Obese: 17.6 ± 4.2, Obese + ABT: 6.6 ± 1.4) and LV relaxation constant, Tau (in ms, Lean: 6.9 ± 1.5, Obese: 13.9 ± 1.7, Obese + ABT: 6.0 ± 1.1). Mice with vascular endothelium selective ADK deletion (ADKVEC KO) exhibited an enhanced dilation to acetylcholine in isolated gracilis muscle (lgEC50 WT: -8.2 ± 0.1, ADKVEC KO: -8.8 ± 0.1, P < .05) and mesenteric arterioles (lgEC50 WT: -7.4 ± 0.2, ADKVEC KO: -8.1 ± 1.2, P < .05) when compared to wild-type (WT) mice, whereas relaxation of the femoral artery and aorta (lgEC50 WT: -7.03 ± 0.6, ADKVEC KO: -7.05 ± 0.8) was similar in the two groups. Wild-type mice progressively developed LV systolic and diastolic dysfunction when they underwent transverse aortic constriction surgery, whereas ADKVEC -KO mice displayed a lesser degree in decline of LV function. CONCLUSIONS: Our results indicate that ADK inhibition selectively enhances microvascular vasodilator function, whereby it improves LV perfusion and LV contractile function under metabolic and hemodynamic stress.
