John Pierre Greenwood

Aims: Rest late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identifies infarct-pattern scar but does not assess coronary anatomy. We estimated the prevalence of angiographic coronary artery disease (CAD) among adults with heart failure and reduced ejection fraction (HFrEF) or otherwise unexplained left ventricular systolic dysfunction without infarct-pattern LGE. Methods and results: MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched to 27 July 2026. Eligible studies provided separable scar-negative denominators and corresponding angiographic CAD counts from invasive coronary angiography (ICA). Scar-negative was defined as the absence of subendocardial or transmural LGE in a coronary distribution. Random-effects logit meta-analysis used restricted maximum likelihood and Hartung-Knapp confidence intervals. Twenty-two reports representing 20 studies included 2,236 paired LGE-CMR and ICA. 818 patients had infarct-pattern scar, and 1,418 were scar-negative. Eight studies contributed 44 CAD cases among 468 scar-negative patients for ≥50% stenosis, giving a pooled prevalence of 10.8% (95% confidence interval [CI] 7.4–15.4). Five studies contributed 19 CAD cases among 271 scar-negative patients for ≥70% stenosis, giving a pooled prevalence of 7.6% (95% CI 4.4–12.6). Seven studies contributed 33 CAD cases among 679 scar-negative patients for high-risk-pattern CAD, giving a pooled prevalence of 4.9% (95% CI 2.2–10.6) and a 95% prediction interval of 0.8–24.8%. These strata represented different study subsets and were not nested. Conclusion: Among selected adults with HFrEF or otherwise unexplained LVSD who underwent paired LGE-CMR and ICA, absence of infarct-pattern LGE did not exclude angiographic CAD. Further coronary assessment should be considered when resolving that uncertainty would alter diagnosis or management.

To assess the association of transaortic flow-rate (TFR) with symptom-driven aortic valve replacement (AVR) in asymptomatic patients with moderate to severe aortic stenosis (AS). PRIMID was a prospective, multi-centre observational study. Patients with asymptomatic moderate to severe AS underwent transthoracic echocardiography (TTE), cardiopulmonary exercise testing and stress cardiovascular magnetic resonance (CMR) imaging. TFR was calculated as stroke volume divided by left ventricular ejection time. Patients were followed-up for a minimum of one-year initially. The primary outcome was symptom-driven AVR. Long-term follow-up data was obtained through electronic health records. The secondary outcome was long-term major adverse cardiovascular events (MACE) defined as cardiovascular mortality and hospitalisation with heart failure, myocardial infarction, syncope or arrhythmia. We included 171 individuals: mean age 66.21±3.43 years, 76% male, mean aortic valve area 1.12±0.31cm2. At one-year (median: 366 days, IQR: 312-437) there were 47 symptom-driven AVRs. Over long-term follow-up of 6.52 years (IQR: 5.23-7.22), there were 95 symptom-driven AVRs and 47 MACE events. In multivariable models, TFR was associated with symptom-driven AVR at one-year (HR: 0.12, 95%CI: 0.04-0.39, p<0.01), independent of a positive exercise tolerance test and CMR-measured myocardial perfusion reserve. Age (HR: 1.05, 95%CI: 1.01-1.10, p=0.01) and NT-pro-BNP (HR: 1.46, 95%CI: 1.12-1.89, p<0.01) predicted long-term MACE events, while TFR did not (HR: 0.48, 95%CI: 0.13, 1.74, p=0.26). TFR is independently associated with symptom-driven AVR in initially asymptomatic individuals with moderate to severe AS at one-year. TFR may be useful in identifying individuals who will undergo symptom-driven intervention, but prospective randomised data are needed to assess clinical utility.

Background Exercise systolic blood pressure (SBP) indexed to fitness, expressed as SBP divided by peak metabolic equivalents (SBP/MET peak), is associated with cardiovascular events in patients undergoing exercise testing. We aimed to characterise the cardiac phenotype and outcomes of patients with elevated exercise SBP indexed to fitness.Methods We analysed 530 participants with suspected angina from the CE-MARC trial who had complete exercise treadmill testing, invasive coronary angiography (ICA) and cardiovascular magnetic resonance (CMR) imaging. High SBP/MET peak was defined as ≥18 mm Hg/METs. Obstructive coronary artery disease (CAD) was defined by quantitative ICA as ≥70% stenosis in a major epicardial artery. Inducible ischaemia and myocardial scar were assessed by stress perfusion and late gadolinium enhancement CMR, respectively. Major adverse cardiovascular events (MACE) were defined as all-cause death and acute coronary syndrome.Results High SBP/MET peak was present in 310 participants (58.5%) and prevalence increased progressively with the number of diseased vessels, presence of ischaemia and myocardial scar (p<0.01 for all). During a median follow-up of 15.9 years, high SBP/METpeak was associated with MACE after adjustment for age, sex, obstructive CAD, ischaemia and myocardial scar (adjusted HR per 1-unit increase, 1.02 (95% CI 1.00 to 1.03), p=0.012). Higher SBP/METpeak identified a worse prognosis in subgroups with and without obstructive CAD and in those with and without ischaemia or infarction (log-rank, p<0.005 for all).Conclusions Among patients with suspected angina, high SBP/MET peak was associated with myocardial ischaemia and scar and adverse long-term outcomes. However, this association appeared to be driven predominantly by lower exercise capacity rather than peak SBP. SBP/METpeak may therefore represent an exploratory integrated exercise marker requiring external validation.

Percutaneous coronary intervention (PCI) is increasingly used for revascularization of unprotected left main coronary artery disease. Whether intravascular ultrasonographic (IVUS) guidance during PCI results in better clinical outcomes than conventional angiographic guidance alone is uncertain. In an international, multicenter, open-label trial, we randomly assigned patients with unprotected left main coronary artery disease in a 1:1 ratio to undergo either IVUS-guided PCI or angiography-guided PCI. The primary end point was a patient-oriented composite of any stroke, any myocardial infarction, any revascularization, or death from any cause at the longest follow-up. A total of 806 patients underwent randomization; 401 were assigned to undergo IVUS-guided PCI and 405 to undergo angiography-guided PCI. The mean (±SD) age of the patients was 71.4±10.7 years, 78.4% of the patients were men, and 34.7% had diabetes. At a median follow-up of 2.9 years, a primary end-point event had occurred in 135 patients (33.7%) in the IVUS-guided PCI group and in 125 patients (30.9%) in the angiography-guided PCI group (hazard ratio, 1.11; 95% confidence interval, 0.87 to 1.42; P = 0.40). The incidence of death, myocardial infarction, or revascularization appeared to be similar in the two groups. The percentages of patients with procedure-related and overall safety events also appeared to be similar in the two groups. Among patients with unprotected left main coronary artery disease, IVUS-guided PCI showed no additional benefit over angiography-guided PCI with respect to the incidence of stroke, myocardial infarction, any revascularization, or death from any cause at a median follow-up of 2.9 years. (Funded by Philips Image Guided Therapy Devices and Boston Scientific; OPTIMAL ClinicalTrials.gov number, NCT04111770.).

Aims: In individuals with type 2 diabetes mellitus (T2DM), both myocardial ischemia and myocardial infarction (MI) are associated with adverse cardiovascular outcomes. The incremental prognosis of both risks is unknown. We aimed to investigate whether abnormal myocardial perfusion reserve (MPR), as a surrogate marker for ischemia and presence of MI offers incremental prognostic value in predicting major adverse cardiovascular and cerebrovascular events (MACCE) in patients with T2DM. Methods and results: A retrospective multicentre cohort of 572 individuals with T2DM and healthy controls underwent quantitative stress myocardial perfusion cardiovascular magnetic resonance (CMR) to determine MPR and late gadolinium enhancement (LGE) to identify MI. Patients were divided into three groups: MI- and normal MPR, MI+ or abnormal MPR and MI+ and abnormal MPR. Cox proportional hazard models quantified associations between MPR and MI with MACCE (composite of all-cause death, MI, stroke, heart failure hospitalization, and late coronary revascularization>90 days after the CMR scan). Over a median of 28 months (IQR 25–31 months), 81 participants (14%) accrued at least one MACCE, including 25 (4%) deaths. Presence of either abnormal MPR or MI was associated with increased MACCE (MI- and normal MPR: 8% MACCE; MI+ or abnormal MPR: 15% MACCE (adjusted HR compared with normal 1.86 (95% CI 1.06–3.25, P = 0.03)); presence of both MI and abnormal MPR had the highest event rate: 30% MACCE (adjusted HR compared with normal 3.24 (95% CI 1.75–6.01, P < 0.001)). Conclusion: In T2DM, abnormal MPR or MI are associated with MACCE, and the presence of both offers incremental prognostic value.

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are heart muscle diseases with largely opposing structural and functional phenotypes. Yet, both may lead to the same devastating outcomes of advanced heart failure and life-threatening arrhythmias. Using genome-wide association data from 9,365 DCM cases, 5,900 HCM cases, and over 1.2 million controls, we show that DCM and HCM are largely inversely associated across multiple genomic levels. Modeling both disorders as opposing genetic entities, in case-case GWAS approaches, we identify 100 loci (17 novel) underlying the cardiomyopathy spectrum. Several loci map to potential therapeutic targets (e.g., ADM , CACNA2D2 ), and polygenic risk scores derived from these data show strong discrimination between DCM and HCM patients in external datasets (AUC 0.78-0.84; AUPRC ~ 0.85). The pervasive opposing associations suggest that cardiomyocyte-directed therapies may often have opposite effects in DCM versus HCM. Nevertheless, a shared-effect analysis reveals a single locus — near the calcium-buffering gene CASQ2 — and also identifies a concordant genomic component associated with cardiometabolic health and extracardiac risk factors. By leveraging the shared and opposing genetic mechanisms of DCM and HCM, our work defines the genomic architecture of major cardiomyopathy subtypes and suggests new directions for therapeutics and precision medicine in heart failure.

Background: Older male endurance athletes exhibit an increased risk of atrial fibrillation (AF) of which the pathogenesis is unclear. We aimed to determine whether left atrial (LA) remodeling on cardiovascular magnetic resonance, blood pressure during exercise, and bradyarrhythmia on implantable loop recorder monitoring were associated with AF in athletes. Methods: VENTOUX‐AF (Cardiac Magnetic Resonance Assessment of Left Atrial Fibrosis in Veteran Endurance Athletes) was a cross‐sectional study comparing 39 male athletes with AF (27 symptomatic and 12 detected on implantable loop recorder) aged ≥50 years exercising ≥10 hour/week for ≥15 years with 94 exercise‐matched male athletes in sinus rhythm and 33 sedentary male patients with AF. Participants underwent exercise testing and 3‐dimensional late‐gadolinium enhancement cardiovascular magnetic resonance with LA fibrosis quantification. A total of 106 asymptomatic athletes in sinus rhythm at recruitment received implantable loop recorder to detect incident AF and bradyarrhythmia. Results: Exercise systolic (208.5±29.9 versus 192.4±25.9 mm Hg, P =0.008) and exercise diastolic blood pressure (96.4±17.6 versus 88.3±9.7 mm Hg, P =0.02) were greater in athletes with AF than athletes in sinus rhythm. There was no difference in LA remodeling indices including LA fibrosis between these groups. During follow‐up (median 730 days) of 106 athletes in sinus rhythm at baseline with implantable loop recorder, AF cumulative prevalence was 11.3% (12/106) and significantly associated with bradyarrhythmia (hazard ratio 5.89, 95% CI, 1.59–21.8, P =0.008). LA ejection fraction (52.5±11.6 versus 39.1±17.3%, P P =0.02) and exercise systolic blood pressure (208.5±29.9 versus 183.2±30.8 mm Hg, P <0.001) were greater in athletes with AF than sedentary patients with AF. Conclusions: Hypertensive response to exercise was common in athletes with AF but LA remodeling and fibrosis were not. Further studies are required to determine whether these factors play a role in the pathogenesis of AF in athletes.