RESUMO
Background: Spontaneous coronary artery dissection (SCAD) is increasingly diagnosed as one of the infrequent causes of acute coronary syndrome. Almost no cause was identified in half of the cases. Here, we report a rare case of spontaneous coronary artery dissection with leucoencephalopathy (SCADLE) associated with a mutation of the thrombospondin Type 1 domain containing 1 (THSD1) gene. Case summary: A 36-year-old lady who presented with ischaemic type chest pain for 4â h duration and found to have anterior ST elevation myocardial infarction. She was thrombolysed with tenecteplase and had good resolution. Her coronary angiogram revealed a spontaneous dissection in the left anterior descending artery (LAD) with TIMI 3 flow. Intra-vascular ultrasound study confirmed the LAD spiral dissection and intramural haematoma. She has had recurrent transient ischaemic attacks 5 years and 7 years ago, and there was a significant family history of young stroke. Her magnetic resonance imaging (MRI) brain showed peri-ventricular white matter hyper-intensities and lacunar infarcts suggestive of leucoencephalopathy. An association with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and SCAD was suspected, and exome gene sequencing followed by genetic analysis was performed. It identified a variant c.67°C > G (p. Arg224Gly) in the THSD1 gene with normal NOTCH gene. Discussion: Thrombospondin Type 1 domain containing 1 gene encodes proteins involving in the extra-cellular matrix (ECM). This THSD1 mutation is inherited as an autosomal dominant fashion and associated with arterial dissections (rare), fibromuscular dysplasia, intra-cranial aneurysm, and subarachnoid haemorrhages. Therefore, SCADLE could be a result of arteriopathy secondary to dysfunction of ECM proteins in cerebral and coronary vasculature resulting in neurological manifestations and MRI features like in CADASIL and SCAD.
RESUMO
BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease. FUNDING: Australian National Health and Medical Research Council.