Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction.

BACKGROUND: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant (TBX20tv) and DCM/LVNC. METHODS: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. RESULTS: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P<0.0001) and 99.76 (95% CI, 34.60-287.62; P<0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. CONCLUSIONS: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv-associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.

NHS England-funded CT fractional flow reserve in the era of the ISCHEMIA trial.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2016 guidelines (CG95) recommend patients with new stable chest pain be investigated with computed tomography coronary angiography (CTCA). An updated guideline (MTG32) recommended using CT fractional flow reserve (CTFFR) as a gatekeeper to invasive coronary angiography (ICA) for patients with coronary stenosis on CTCA. Subsequently, NHS England negotiated a UK-wide contract with HeartFlow, the provider of CTFFR. We describe our experience with CTFFR and consider the impact of the recent ISCHEMIA trial on these guidelines. METHODS: We prospectively collected ICA and revascularisation data on all patients undergoing CTFFR from January 2019 to March 2020. RESULTS: One-hundred and twenty-five of 140 patients completed CTFFR analysis. Eighty-one patients had CTCA stenosis >50%. Thirty-six had positive CTFFR; 29 underwent ICA with 22 (75.9%) revascularised. Forty-five had negative CTFFR; 14 underwent ICA and four (28.6%) were revascularised. The average cost of investigation per patient (PP) was £971.95. Had these patients undergone ICA directly with no functional test after CTCA, the average cost would be £932.51 PP. CONCLUSION: Our revascularisation rates suggest that CTFFR can potentially be a gatekeeper to ICA but does not necessarily yield cost savings.