212 Assessment of Left Ventricular Contractile Reserve in Patients with Severe Symptomatic Aortic Stenosis and Preserved Ejection Fraction

Abstract

133 patients have been tested, including newly diagnosed cardiac cases, patients negative for other cardiac gene testing, and patients who have phenotype/genotype incompatibility where contribution of more than one gene is suspected. 41/ 133 (30%) patients have at least one potentially pathogenic variant. 22 patients have multiple plausible variants. We present data from the cardiac cohort tested to date and cases illustrating the utility and complexity of gene panel testing for cardiac disease including; 1) A paediatric patient with Left Ventricular Non-Compaction (LVNC), dilated aortic root and sinus brachycardia heterozygous (on the PC 71 gene panel) for a novel TMEM43 variant c.994A>G, p. (Thr332Ala) of unknown clinical significance. Further testing using a bespoke 138 gene cardiac panel from the Focused Exome detected a novel splice variant in the HCN4 gene associated with LVNC and primary sinus brachycardia (Milano et al, 2014). This patient's mother who has aortic dilation and regurgitation was heterozygous for the TMEM43 variant and the half-brother who also has dilated aortic root and LVNC did not carry either variant. 2) A large Dilated Cardiomyopathy (DCM) family with variable severity between family members, one affected cousin was heterozygous for a variant of uncertain significance in MYBPC3 c.3384G>C, p. (Glu1128Asp) and another affected cousin heterozygous for a truncating TTN variant, c.89244del, p.(Phe29748Leufs*7). Further family studies are ongoing. Detailed phenotypic assessment (using a clinical proforma) has been shown to increase diagnostic yield in patients with complex cardiac disease.

Early hemodynamic changes after transcatheter aortic valve implantation in patients with severe aortic stenosis measured by invasive pressure volume loop analysis

“…This finding is surprising, as over the long-term diastolic function is expected to recover and, therefore, EDP to decline. The fundament for these favorable hemodynamic changes are a larger valve orifice and remodeling of the LV after TAVI [22,23]. Our results suggest, that in the early phase after valve implantation, diastolic function is impaired.…”

“…Moreover, preload recruitable stroke work is considered to be insensitive to preload and afterload [19,20]. Cabaco et al suggest that patients with aortic stenosis and preserved EF with LV hypertrophy have diminished contractile reserve, especially during increased heart rate, a condition that is given during rapid ventricular pacing [22]. However, robust data or more conclusive explanations for this phenomenon do not exist so far.…”