Vy Dang

Introduction. Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of all HF cases, affecting ~2.5 million patients in 2019. Individuals with HFpEF present typical signs and symptoms of HF such as shortness of breath, edema, fatigue, left ventricle (LV) hypertrophy, and diastolic dysfunction.² LV hypertrophy and remodeling can occur as a beneficial, adaptive process to protect the heart against pressure overload but also can progress pathologically to LV dysfunction and HF through maladaptation.³ In a recent clinical study, coronary microvascular dysfunction (CMD) was detected in 72% of patients with HFpEF who were at higher risk for severe cardiac injury and mortality. CMD is a disorder affecting the coronary microvasculature, which leads to coronary blood flow dysregulation and may explain HFpEF in the absence of epicardial coronary artery obstruction.^4,5 However, the underlying mechanism linking CMD and HFpEF remains unclear. Methods. A recent study in the swine with diabetes, hypercholesterolemia, and chronic kidney diseases suggested the link between CMD and HFpEF begins with systemic low-grade inflammation from various comorbidities leading to endothelial cell dysfunction.⁶ Endothelial cells are key players in the synthesis/release of nitric oxide (NO), a crucial molecule that has vasodilative, anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. To study the endothelial NO abnormality in the pathogenesis of CMD, researchers tracked myocardial changes in response to endothelial NO synthase inhibition in rodents.⁷ Another group of researchers examined the relationship between microvascular dysfunction and development of structural/functional changes in the myocardium using a hypertrophic cardiomyopathy rodent model.⁸ Results. Loss of endothelial NO function lead to early CMD,⁷ which subsequently caused deficits in myocardial perfusion and oxygen delivery.⁸ Protective fibrosis and LV remodeling occurred in response to myocardial ischemia and developed into pathological LV hypertrophy, diastolic dysfunction, and heart failure. The researchers suggested that these pathologies may occur through a complex interplay of precipitating events instead of a linear timeline. Conclusion. Despite the adverse role of CMD in recurrent ischemia, fibrosis, and LV dysfunction in the absence of obstructive atherosclerosis, current pharmacological and interventional approaches for CMD treatment are limited in clinical practice, in addition to the heavy reliance on invasive detection of reduced coronary flow reserve for diagnosis. Further development of noninvasive diagnostic methods is necessary such as recently suggested miRNAs as biomarkers⁹ or dynamic cardiac T₁ MRI mapping⁷ to assess coronary microvascular status. Development of strategies and tools to correct endothelial dysfunction is also essential for CMD prevention and treatment.

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