Aortic valve stenosis is associated with systemic endothelial dysfunction. This observation may provide a mechanistic insight into the emerging association between AVS and cardiovascular events.

Noninvasive PASE is a simple, rapid, safe, and diagnostically efficient option for patients with permanent PM and suspected or known CAD.

Cardiovascular and metabolic vulnerability have an early developmental origin. We evaluated the potential influence of innate life factors, including the metabolism of the mother and the sex of the offspring, on cardiometabolic risk, including organ-specific insulin resistance, subclinical cardiac dysfunction, and DNA oxidative damage throughout the lifespan. Methods: Two female minipigs were studied during late pregnancy, and their offspring were restudied at the ages of 1 mo (n 5 11), 6 mo (n 5 9), and 9 mo (n 5 10, 6 offspring and 4 age-matched animals). We measured insulin-mediated glucose disposal in skeletal muscle, adipose tissue, liver, and myocardium using 18 F-FDG PET; cardiac function using 2-dimensional strain echocardiography; and DNA damage using the comet assay. Results: Glucose metabolism showed the 2 sows to have differences similar to those in their respective 1-mo-old offspring. Over time, compared with female animals, male animals developed myocardial insulin resistance (male animals vs. female animals: 34 6 5 vs. 58 6 8 mmol/min/kg at 6 mo, P 5 0.03; 29 6 8 vs. 60 6 7 mmol/min/kg at 9 mo, P 5 0.02). Cardiac function progressively deteriorated in male animals from 1 mo (radial strain, 260% 6 7%; strain rate, 25.4 6 0.9 s 21 ) to 6 mo (radial strain, 241% 6 5%; strain rate, 22.5 6 0.2 s 21 , P , 0.05 vs. 1 mo) and 9 mo (radial strain, 232% 6 5%; strain rate, 21.6 6 0.2 s 21 , P , 0.01 vs. 1 mo) and was significantly different from that in female animals (radial strain, 248% 6 4%; strain rate, 23.1 6 0.2 s 21 , P , 0.05 and P , 0.01, respectively). Oxidative damage was reduced in female animals and increased in male animals across age categories (P , 0.05). Conclusion: The metabolism of minipig offspring is influenced by maternal insulin sensitivity during early life stages. Sex-related effects prevail thereafter in healthy minipigs, documenting a precocious onset of cardiometabolic vulnerability in male offspring.

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Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT-VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT-VTI * LVOT cross sectional area), at least in the acute setting. Objective To assess the prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41-49%) LVEF and moderate-to-severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed-up for the endpoint of cardiovascular death. Results 203 patients were enrolled in the study (74±11 years, 66% men, 47% ischemic etiology, HFrEF 86%, LVEF 31±9%, mean LVOT-VTI 21±6 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta-blockers (95%), ACE-inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (82%). Seventy-seven patients (38%) had permanent atrial fibrillation and 46 (23%) a cardiac resynchronization therapy device. Over a median follow-up of 18 (7-33) months, 30 patients died, 24 of whom for a cardiovascular cause, and 10 underwent mitral valve repair/replacement. When stratified according to the optimal prognostic cut-off of LVOT-VTI, patients with a LVOT-VTI <16 cm (n=36) showed the greater risk of cardiovascular death (Log Rank 18.2, p<0.001, Figure). Similarly, patients with a LVEF <33% (n=122) showed a higher risk of cardiovascular death (Log Rank 5.5, p=0.019). Nevertheless, at Cox regression analysis, a unit decrease in LVOT-VTI (hazard ratio, HR 0.87 [95%CI 0.79-0.95], p=0.002) but not in LVEF (p=0.729) was associated with a higher risk of cardiovascular death (Figure). Conclusion Left ventricular forward volume, noninvasively estimated through LVOT-VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.