Larson, Kathryn

ABSTRACTBackgroundIdiopathic inflammatory myopathies, beyond inclusion body myositis (IBM), have demonstrated an increased risk of adverse cardiovascular outcomes, particularly myocardial infarction (MI). This study evaluated the risk of cardiovascular disease in IBM.MethodsWe conducted a non‐concurrent cohort study utilizing the expanded Rochester Epidemiologic Project, including 50 patients with IBM, matched 1:6 to age‐, sex‐, and calendar year‐matched referents without IBM. Baseline cardiovascular risk factors were recorded. Differences in baseline covariates were adjusted by the inverse probability of treatment weighting method. Participants were followed from the index date forward to determine relative risks (RR) and hazard ratios (HR) for the development of cardiovascular outcomes including MI, ischemic stroke, cardiomyopathy, congestive heart failure (CHF), and peripheral vascular disease (PVD).Results50 patients with IBM and 294 matched population referents were included. Baseline cardiovascular risk factors were similar between groups. Aspirin use was more common (28% vs. 18%, p = 0.03) and statin use less common (26% vs. 38%, p = 0.04) in IBM versus referents. Patients with IBM had an increased hazard of MI compared to referents [HR: 5.79, 95% CI (2.51, 13.36)]. The risk of MI remained consistently elevated across all models, after accounting for potential confounders. For PVD, 16/50 IBM patients versus 16/287 referents were excluded due to pre‐existing PVD at index (p < 0.001). Among remaining participants, RR for PVD was 2.38 (0.82, 6.9). IBM was not associated with an increased risk of ischemic stroke, cardiomyopathy, or CHF.ConclusionsIBM is associated with increased risk of MI compared to population referents. Heightened cardiovascular monitoring and prevention strategies are needed in IBM.

Abstract Aims We aimed to clarify the extent to which cardiac and peripheral impairments to oxygen delivery and utilization contribute to exercise intolerance and risk for adverse events, and how this relates to diversity and multiplicity in pathophysiologic traits. Methods and results Individuals with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnoea (controls) underwent invasive cardiopulmonary exercise testing and clinical follow-up. Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously-proposed, non-exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n = 643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8 L/min, p = 0.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8 ml/dl, p &lt; 0.001) compared to dyspnoeic controls (n = 219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08–2.79 for 0–1 vs. ≥2 phenogroup traits present). Conclusions Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non-cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome.