Coronary blood flow in heart failure: cause, consequence and bystander

Abstract

Heart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic heart failure is dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, where alterations in coronary blood flow result from and contribute to cardiac contractile dysfunction. Hypertrophic cardiomyopathy is caused by genetic mutations but can also result from increased pressure and volume overload (hypertension, valve disease). Heart failure with preserved ejection fraction is characterized by pronounced coronary microvascular dysfunction, the causal contribution of which is however not clear. The present review characterizes the alterations of coronary blood flow which are causes or consequences of heart failure in its different manifestations. Apart from any potentially accompanying coronary atherosclerosis, all heart failure entities share common features of impaired coronary blood flow, but to a different extent: enhanced extravascular compression, impaired nitric oxide-mediated, endothelium-dependent vasodilation and enhanced vasoconstriction to mediators of neurohumoral activation. Impaired coronary blood flow contributes to the progression of heart failure and is thus a valid target for established and novel treatment regimens.

Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis

“…Together, the induced myocardial adjustments seem to be sufficient to keep LV function at this moment in a compensated state reflecting the latent asymptomatic period of AS also known from human pathophysiology [ 9 ]. Nevertheless, despite a trend to an enhanced myocardial capillarization in AS mice, we observed in vivo and ex vivo a significant restriction in coronary flow reserve well known to be associated with AS in humans [ 23 , 35 , 60 ] and as well a mild increase in circulating troponin levels. Obviously, the current time point represents a period of transition, where a variety of compensation mechanisms still keeps cardiac function in balance but the persisting increased afterload already leads to incipient impairment of coronary flow and cardiomyocyte ultrastructure.…”

Why is endothelial resilience key to maintain cardiac health?

“…However, micro-embolization based on spontaneous erosion on plaque and obstruction of the capillary network as seen in patients with acute coronary syndrome is difficult to model in rodents [55]. Capillary obstructions lead to no-reflow phenomena and may induce distinct EC responses [39,41]. Future analysis of human cardiac tissue from patients suffering myocardial infarction by single-cell technologies may help to validate the findings…”

“…Inhibition of angiotensin II pathways are known for their anti-inflammatory and vasculoprotective effects [21] and may contribute to EC resilience. In addition, the anti-diabetic drug metformin was shown to prevent the formation of oxidative mitochondrial DNA and reduced inflammation-related dysfunction of vessels and the lung in other disease models [41,138].…”

The insulin receptor family in the heart: new light on old insights

“…as occurs in pregnancy or with endurance exercise) is clearly beneficial, necessary and largely reversible on cessation of the stress [ 4 ]. Pathological hypertrophy may develop in diseases such as hypertension which increase cardiac workload, or following myocardial infarction where loss of blood supply to part of the myocardium causes cardiomyocytes to die [ 5 , 6 ]. The resulting deposition of inelastic fibrotic scar tissue increases the workload of surviving cardiomyocytes and these hypertrophy.…”