Patients with single ventricles after bidirectional Glenn (BDG) are placed on ACE inhibitors (ACEIs) to reduce afterload and to decrease systemic to pulmonary collateral flow (SPC). The objective is to determine if ACEI use in BDG patients improves SPC and ventricular function. Single-centre retrospective study of BDG patients who underwent cardiac magnetic resonance (CMR) from 2010 to 2024. Demographics, medication, ventricular function and flow data were collected. Patients included were >1 year old and on ACEI for >3 months prior to CMR. A total of 320 BDG patients were studied, 137 were treated with ACEI with no difference in age, sex, medications (except for ACEI) or body surface area. SPC as a percentage of aortic flow was not different in the ACEI group, whether right (RV) or left ventricle (LV) dominant. Ejection fraction (EF) was lower and end- diastolic volume (EDV) was higher in BDG on ACEI for the entire group and for RV dominant. Although LV EDV was higher with those on ACEI, there was no difference in EF. There was no difference in ventricular dilation or EF on echocardiogram prior to starting drug. SPC positively correlated with EDV. SVC flow was lower for those on ACEI. BDG patients treated with ACEI did not demonstrate decreased SPC. There was a suggestion of no improvement of ventricular performance. Cerebral blood flow is decreased in BDG on ACEI using SVC flow. Findings suggest that routine ACEI use in single ventricle patients post BDG should be considered with caution and age-appropriate and clear indications along with measurable therapeutic targets should be considered.

BackgroundSevere aortic stenosis (AS) causes a pathophysiological cascade, which impairs myocardial blood flow. This effect is exacerbated in the presence of coronary disease (CAD). Treatment with transcatheter aortic valve implantation (TAVI) may promote reversal of these pathophysiological conditions.MethodsWe performed multimodality assessment of cardiac physiology in patients with AS and concurrent CAD requiring percutaneous coronary intervention, prior to and 6 months after undergoing TAVI. Techniques include: coronary angiography and bolus thermodilution-derived indices of microvascular function (coronary flow reserve (CFR); index of microcirculatory resistance (IMR)); stress perfusion cardiac magnetic resonance (CMR) imaging, which was used to measure changes in global myocardial blood flow (MBF) and left ventricular mass (LVM), and computed resting and hyperaemic vessel specific absolute coronary flow (aCBF) and microvascular resistance (MVR) using a computational model of coronary physiology.ResultsData were obtained for seven patients (10 vessels). CFR increased from 1.53 (1.2–1.7) to 2.35 (2.0–2.7) (p=0.037) 6 months post-TAVI. There was a 33% reduction in resting aCBF from 218 mL/min to 146 mL/min (p=0.004). On CMR, resting MBF fell 37% from 3.0±0.98 mL/min/g to 1.9±0.7 mL/min/g (p=0.033) and stress MBF fell 25% from 3.6±0.57 mL/min/g to 2.7±0.7 mL/min/g (p=0.004). Indexed LVM regressed from 79±14 g/m2 to 71±16 g/m2 (p=0.006). MVR remained unchanged.ConclusionsCFR increased following TAVI. The mechanism for this was a significant reduction in resting coronary blood flow measured with CMR and modelled computationally. The unchanged MVR and IMR suggest that resting blood flow reduces due to reduced myocardial demand and myocardial remodelling, rather than changes in resistance.

ObjectiveIdentify predictors for mortality and clinical short-term outcomes in patients with left-sided infective endocarditis (IE).MethodsThis study was a retrospective cohort investigating 376 patients who experienced left-sided IE between 1 January 2013 and 31 December 2022, at the National Cardiovascular Center Harapan Kita Hospital. Bivariate and multivariate statistical analyses were conducted to identify predictors of short-term clinical outcomes.ResultsThe study comprised 376 patients with left-sided IE who received standardised antibiotic therapy, with 56.6% of them undergoing surgical intervention. The observed short-term mortality rate was 18.6%. Furthermore, the morbidity profile during the treatment phase revealed the following incidences: sepsis in 27.1% of cases, intensive care unit stay exceeding 10 days in 18.6% of cases, mechanical ventilation for more than 7 days in 11.4% of cases, stroke in 28.5% of cases and acute renal failure in 57.7% of cases.ConclusionPredictors of short-term mortality outcomes in patients with left-sided IE included New York Heart Association functional class III–IV, aortic valve vegetation involvement, vegetation size ≥10 mm, incomplete antibiotic administration, sepsis and the requirement for renal replacement therapy.

Guidelines strongly recommend reperfusion therapy, including thrombolysis and percutaneous coronary intervention, for ST-elevation myocardial infarction but contraindicate its use in most non-ST-elevation acute coronary syndromes (ACS). This practice largely stems from the landmark fibrinolytic therapy trialists (FTT) meta-analysis, which reported no benefit in patients without ST elevation (STE). However, the FTT included a subgroup from the ISIS-3 trial with substantial methodological issues, potentially obscuring a genuine treatment effect. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing thrombolysis vs placebo or no thrombolysis in ACS. Patients were grouped by ECG findings: STE, ST depression (STD) or absence of STE. All-cause mortality was extracted from each trial's short-term follow-up (typically 21-35 days). We reassessed outcomes with and without inclusion of the ISIS-3 'uncertain diagnosis' subgroup. Nine RCTs (40 226 patients) were analysed. Thrombolysis significantly reduced mortality in patients without STE (excluding isolated STD) (risk ratio (RR): 0.799; 95% CI 0.668 to 0.956; I²=0%). Including the ISIS-3 'uncertain diagnosis' subgroup (representing 42% of the non-STE population) would have eliminated the statistical significance in non-STE patients (RR: 0.928; 95% CI 0.694 to 1.242) and markedly increased heterogeneity (I²=71%). In historical RCTs, thrombolysis was associated with lower short-term mortality in non-STE presentations excluding isolated ST-segment depression, while isolated STD showed no benefit. Legacy conclusions hinge on outdated methods, delayed treatment and heterogeneous ECG definitions (and are sensitive to ISIS-3). This study exposes a material evidence gap in the foundation of current guidelines. Contemporary randomised trials with prespecified ECG criteria, rapid treatment windows and rigorous safety adjudication are needed. CRD42024573681.

Coronary artery disease (CAD) progression and risk of cardiac events differ between women and men during the lifespan. Accordingly, we aimed to explore the impact of sex and age on plaque phenotype in non-obstructive CAD. We included 1189 patients with non-obstructive CAD (48% women) from the Norwegian Registry of Invasive Cardiology and quantitatively assessed each patient's plaque phenotype by coronary CT angiography. Plaque subtypes included calcified (>350 Hounsfield units [HU]), fibrous (131 to 350 HU), fibrofatty (76 to 130 HU) and necrotic core plaques (-30 to 75 HU). The impact of sex on plaque phenotype was assessed after age stratification (≤50, 51-64 and ≥65 years). Total plaque burden adjusted for vessel volume was higher in middle-aged and older women compared with men (all p<0.05). Women had lower proportions of fibrofatty plaques compared with men across all age groups, while middle-aged and older women had higher proportions of calcified and fibrous plaques compared with men. Middle-aged and older men had higher proportions of necrotic core plaques compared with women (all p<0.05). After adjusting for cardiovascular risk factors, female sex remained independently associated with total plaque burden (β=1.0 [0.5 to 1.5], p<0.001), and younger age and male sex with fibrofatty plaque burden (β=-2.8 [-4.4 to -1.2], p<0.001, and β=-3.8 [-4.9 to -2.8], p<0.001, respectively). In non-obstructive CAD, female sex was associated with a higher total plaque burden, whereas male sex and younger age were associated with a higher proportion of vulnerable fibrofatty plaques. Our results highlight important sex differences in plaque phenotypes among patients with non-obstructive CAD during the lifespan, which may impact risk-stratification. NCT04009421.

BackgroundHypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.MethodsIn a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill (irbesartan (37.5 mg) (Australia)/candesartan (2 mg) (USA)), amlodipine (1.25 mg), indapamide (0.625 mg), bisoprolol (2.5 mg) unattended office systolic BP (SBP) at 12 weeks was compared with initial monotherapy (irbesartan (150 mg) (Australia), candesartan (8 mg) (USA)). Heterogeneity was assessed using an interaction term in the mixed cox model. Adherence, ≥80% pill count and treatment inertia were estimated.ResultsIn 653 participants (Australia, 591 (91%); USA, 62 (9%)) a significant drop in mean SBP (6.5 mm Hg (95% CI 4.8 to 8.8; p<0·001)) and diastolic BP (5.6 mm Hg (95% CI 4.5 to 6.9; p<0.001)) in favour of the quadpill was found, with less need for uptitration (p<0.001) and less treatment inertia (non-significant: p=0.303). Adherence was high for both treatment arms (over 80%). Compared with monotherapy, the quadpill effect varied by ethnicity (SBP reduced by White (6.9 mm Hg; 95% CI 4.7 to 9.2), Hispanic (3.3 mm Hg; 95% CI 4.0 to 10.6), Asian (12.3 mm Hg; 95% CI 6.2 to 18.5) and Black/other (1.4 mm Hg; 95% CI −9.0 to 6.3), interaction p=0.032).ConclusionThis prospective individual participant data pooled analysis provides further evidence that the quadpill strategy is superior to initial monotherapy by virtue of improved BP-lowering, less need for uptitration and being associated with less treatment inertia.

BackgroundAortogenic stroke is an important subtype of embolic strokes, yet lacks a diagnostic method for proactive identification. Non-obstructive general angioscopy (NOGA) is a catheter-based technique to observe spontaneously ruptured aortic plaques (SRAPs), a potential embolic source of ischaemic stroke.ObjectivesThis study aimed to identify the embolic source of ischaemic stroke using NOGA.MethodsFrom June 2022 to January 2024, 321 consecutive patients with acute ischaemic stroke were hospitalised. 25 underwent emergent mechanical thrombectomy and NOGA. The aortic arch was screened using NOGA, and atherosclerotic materials from the SRAPs were sampled and pathologically analysed. Transoesophageal echocardiography (TEE) was performed the day after catheterisation to investigate intracardiac thrombus, patent foramen ovale and aortic plaques. The primary outcome was the diagnosis of aortogenic stroke.ResultsNOGA identified seven SRAPs in the aortic arch as potential embolic sources. Of those, one patient with atrial fibrillation and cardiac chamber thrombus was diagnosed as having a cardiogenic stroke. The findings of the six remaining cases included aortic arch plaque (also observed via TEE) (n=2), thrombus in an artificial aortic graft wall (n=1), and cholesterol crystals in sampled materials indicating plaque rupture (n=3). The Brain-Heart team finally diagnosed these 6 cases (24%) as aortogenic stroke. 16 patients were diagnosed with cardiogenic stroke. One was diagnosed with paradoxical embolism. The remaining two cases (8%) with unidentified embolic sources were diagnosed with cryptogenic stroke.ConclusionsUsing a systematic diagnostic protocol for embolic source detection, the Brain-Heart team could proactively diagnose aortogenic stroke and clarify embolic source.

ABSTRACTBackgroundSystemic right ventricle (sRV) patients are at an increased risk of developing heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be a valuable treatment option. This study investigated the changes in ventricular function in sRV failure patients in the first year after starting SGLT2i.MethodsAdult sRV patients from the international, real-world ACHIEVE-SGLT2i registry were included if they had a clinical diagnosis of sRV failure, a transthoracic echocardiogram before starting SGLT2i, and at least one in the first year after starting available for analysis. The primary outcomes were changes in sRV global longitudinal strain (GLS) and fractional area change (FAC). Longitudinal changes were evaluated using linear mixed models.ResultsThirty-nine sRV failure patients (46±9.3 years old, 41% female) were included. Twenty-five (64%) had transposition of the great arteries after an atrial switch procedure and 14 (36%) had congenitally corrected transposition. sRV GLS improved significantly in the first 50 days (−1.4%-point per month, p<0.001) and stabilised afterwards (<0.1%-point per month, p=0.520). Though age had a significant overall negative effect on sRV GLS (0.1%-point per year of age, p=0.049), it did not influence the longitudinal changes after starting SGLT2i. sRV FAC also improved in the first 50 days (3.2%-point per month, p=0.002), after which sRV FAC deteriorated in patients with subpulmonary left ventricular pacing (−0.9%-point per month, p=0.012) while it stabilised in patients without pacing (0.1%-point per month, p=0.573). In the first 50 days, tricuspid annular plane systolic excursion also improved significantly in all patients (1.2 mm per month, p=0.006), and stabilised afterwards (p=0.721).ConclusionsSGLT2i therapy is associated with improvements in systolic ventricular function in sRV failure patients. Despite early improvement in sRV FAC, there was a negative longer term correlation with subpulmonary left ventricular pacing, potentially reflecting adverse effects of subpulmonary ventricular pacing on sRV function.

BackgroundCirculating proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of cholesterol metabolism. Loss-of-function variants in PCSK9 are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and reduced cardiovascular disease (CVD) risk, while gain-of-function variants correlate with elevated LDL-C concentrations and increased CVD risk. This study investigated whether genetically determined LDL-C levels, proxied by four PCSK9 genetic variants, influence common carotid artery atherosclerosis.MethodsThe analysis included 3040 European participants (mean age 64.2±5.4 years; 45.8% men) at high cardiovascular risk from the IMPROVE Study, alongside 49 088 individuals of white British ancestry (mean age 55.2±7.6 years; 47.9% men) from the UK Biobank (UKB). Ultrasonographic measurements of common carotid intima-media thickness (CC-IMTmean, CC-IMTmax, CC-IMTmean-max) were obtained. Four lipid-level affecting genetic variants in the PCSK9 locus were selected for analysis, both individually and in a standardised Lipid-Lowering Allelic Score (LLAS), to assess their effects on LDL-C and PCSK9 levels in the IMPROVE cohort and on ultrasonographic measures in both IMPROVE and UKB.ResultsIn the IMPROVE cohort, PCSK9 variants (rs11206510, rs2479409, rs11591147, rs11583680) exhibited expected effect directions, although not all statistically significant, on LDL-C and PCSK9 levels. The LLAS was negatively correlated with CC-IMTmean, CC-IMTmax and CC-IMTmean-max among women in IMPROVE, and among men and overall in UKB (all p<0.05). Effect sizes were comparable between cohorts.ConclusionsGenetic variants in the PCSK9 locus influence LDL-C levels and CC-IMT, in keeping with proven benefits of PCSK9 inhibitors on atherosclerotic cardiovascular events.

IntroductionTakotsubo cardiomyopathy (TC) is a stress-induced catecholamine acute myocardial dysfunction in the absence of significant coronary disease. The pathophysiology of TC remains poorly understood, and the use of beta-blockers (β-Blockers) appears promising. However, the impact of β-blockers in acute-phase management remains uncertain.AimsWe aimed to conduct a systematic review and meta-analysis evaluating the early use of β-Blocker in TC and its effects on in-hospital mortality.MethodsPubMed, Embase and Cochrane were searched for studies that evaluated the use of BBs in TC patients and its short-term effects. Statistical analysis was performed using RevMan V,5.4.1. The results are expressed using HRs and 95% confidence intervals (CI) were extracted using a random-effects model. Heterogeneity was assessed with I².ResultsWe included five cohort studies, with a total of 5428 patients. The vast majority were women (81%) with a mean age of 70.1±12.6 years. More than half of the patients (52.0%) had previous hypertension. ST-elevation in the first ECG was observed in 37.3% of the patients. Early administration of β-blockers was not associated with a statistically significant reduction in in-hospital mortality (HR 0.78, 95% CI 0.59 to 1.02, p=0.07), and this finding was consistent across different β-blocker types, doses and routes of administration.ConclusionEarly β-Blocker therapy did not significantly influence in-hospital mortality in patients with TC. Future randomised studies are essential to clarify beta-blockers’ role in this setting.PROSPERO registration numberCRD420251055617.