Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy

AbstractOBJECTIVESWe performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC).BACKGROUNDPatients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur.METHODSWe studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (kmono) were assessed at rest and during submaximal dobutamine infusion (20 μg/kg body weight per min).RESULTSGlobal MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 ± 0.21 vs. 2.7 ± 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = −0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 ± 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 ± 0.13 vs. 1.90 ± 0.18, p < 0.05). During dobutamine infusion kmonowas higher in the mismatch regions than in the normal regions (0.104 ± 0.017 vs. 0.087 ± 0.016 min−1, p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest kmono(r = −0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism.CONCLUSIONSPatients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC

Development and external validation of predictive models for prevalent and recurrent atrial fibrillation: a protocol for the analysis of the CATCH ME combined dataset

Background: Atrial fibrillation (AF) is caused by different mechanisms but current treatment strategies do not target these mechanisms. Stratified therapy based on mechanistic drivers and biomarkers of AF have the potential to improve AF prevention and management outcomes. We will integrate mechanistic insights with known pathophysiological drivers of AF in models predicting recurrent AF and prevalent AF to test hypotheses related to AF mechanisms and response to rhythm control therapy. Methods: We will harmonise and combine baseline and outcome data from 12 studies collected by six centres from the United Kingdom, Germany, France, Spain, and the Netherlands which assess prevalent AF or recurrent AF. A Delphi process and statistical selection will be used to identify candidate clinical predictors. Prediction models will be developed in patients with AF for AF recurrence and AF-related outcomes, and in patients with or without AF at baseline for prevalent AF. Models will be used to test mechanistic hypotheses and investigate the predictive value of plasma biomarkers. Discussion: This retrospective, harmonised, individual patient data analysis will use information from 12 datasets collected in five European countries. It is envisioned that the outcome of this analysis would provide a greater understanding of the factors associated with recurrent and prevalent AF, potentially allowing development of stratified approaches to prevention and therapy management