Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Imaging is pivotal in the evaluation of native valve regurgitation and echocardiography is the primary imaging modality for this purpose. The imaging assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy and function, and the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation largely relies on the results of imaging. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing native valve regurgitation. The present document aims to present clinical guidance for the multi-modality imaging assessment of native valvular regurgitation.

Background—: Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. Methods and Results—: Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A _1C , but neither body mass index nor the insulin resistance index (homeostasis model assessment–insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A _1C . Conclusion—: Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in “metabolically healthy” obese patients at early stage in insulin resistance.

In the western world, calcific aortic stenosis (AS), the most common valvular heart disease, represents a major public health burden.¹ Currently, there is no pharmacological treatment that prevents or slows the progression of AS.² Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are the only therapies to significantly improve both survival and symptoms^3,4 and are recommended in symptomatic patients with severe AS.^5,6 Quiz Ref ID The management of patients with asymptomatic severe AS, particularly the choice between early intervention vs watchful waiting, continues to be a matter of debate.^7,8 Current guidelines advocate delaying AVR until symptoms or left ventricular (LV) systolic dysfunction develop.^5,6 However, observational studies in 2010⁹ and 2015¹⁰ have suggested that early elective AVR might improve outcomes in patients with severe asymptomatic AS. This approach has been reinforced by continued advances in surgical techniques and aortic valve prostheses, the advent of TAVR, and the low perioperative mortality and morbidity rates achieved in valve centers of reference.^11,12 However, preemptive surgery before onset of symptoms or LV systolic dysfunction is considered in only a selected group of patients after careful risk stratification. This is at least in part because the evidence for intervention in asymptomatic severe AS is derived from small, heterogeneous, retrospective, single-center studies, which have generally included the need for AVR (not always motivated by the development of symptoms or LV dysfunction) in the composite study end point.^13-20 Moreover, decision making for AVR remains particularly difficult in older patients in whom it is sometimes unclear if the benefits of intervention outweigh the risk.^5,6

The glycocalyx constitutes the first line of the blood tissue interface and is thus involved in many physiological processes, deregulation of which may lead to microvascular dysfunction. Because administration of LPS is accompanied by severe microvascular dysfunction, the purpose of the study was to investigate microvascular glycocalyx function during endotoxemia. Bolus infusion of LPS (10 mg kg⁻¹) to male Sprague-Dawley rats elicited the development of hyporeactivity to vasoactive agents and microvascular derangements, including decreased capillary density and significant increases in intermittent and stopped flow capillaries in the small intestine muscularis layer compared with controls. LPS elicited plasma hyluronan release and reduction in endothelial surface thickness, indicative of glycocalyx degradation. Because endothelial glycocalyx is extremely sensitive to free radicals, oxidative stress was evaluated by oxidation of dihydrorhodamine in microvascular beds and levels of heart malondialdehyde and plasma carbonyl proteins, which were all increased in LPS-treated rats. Activated protein C (240 μg kg⁻¹ h⁻¹) enhanced systemic arterial pressure response to norepinephrine in LPS-treated rats. Activated protein C (240 μg kg⁻¹ h⁻¹) prevented capillary perfusion deficit in the septic microvasculature that were associated with reduced oxidative stress and preservation of glycocalyx. Our findings support the conclusion that LPS induces major microcirculation dysfunction accompanied by microvascular oxidative stress and glycocalyx degradation that may be limited by activated protein C treatment.