Untangling the Pathophysiologic Link Between Coronary Microvascular Dysfunction and Heart Failure With Preserved Ejection Fraction

Aish Sinha; Haseeb Rahman; Andrew Webb; Ajay M. Shah; Divaka Perera


Eur Heart J. 2021;42(43):4431-4441. 

In This Article

Cardiac–Coronary Coupling

Myocardial perfusion is dependent on CFR and the dynamic interaction between myocardium and microvasculature. As a result of the phasic compression and decompression of intramyocardial vessels, coronary flow is intimately linked to myocardial relaxation and contraction; this process is called cardiac–coronary coupling, which can be readily characterized by coronary wave intensity analysis.[16] Wave intensity analysis defines the nature (accelerating or decelerating flow) and origin (aortic, designated as forward, or microcirculatory, designated as backward) of energy fluxes that govern coronary blood flow (CBF). The backward expansion wave (BEW) is the main driver of flow in the healthy heart and it is secondary to decompression of the microvasculature in early diastole. Therefore, it is directly related to the degree of ventricular relaxation (lusitropy). The other major accelerating wave is the forward compression wave, which corresponds to the rise in aortic pressure after the aortic valve opens in early systole. The major decelerating wave is the backward compression wave (BCW), which arises during isovolumetric contraction. The relative balance of these wave energies is encapsulated in perfusion efficiency, which is the proportion of accelerating energy in relation to total energy flux; perfusion efficiency increases with exercise and pharmacologically induced microvascular dilation in health.[17] In contrast, perfusion efficiency decreases with both exercise and pharmacologically induced microvascular dilation in CMD,[3] primarily driven by attenuation of the accelerating BEW and accentuation of the decelerating BCW during exercise. Attenuation of the BEW during exercise can result from impaired lusitropy and a diastolic dysfunction phenotype that manifests during higher workloads, with resultant subendocardial ischaemia. Alternatively, subendocardial ischaemia during exercise may precipitate ischaemia-induced diastolic dysfunction, with diminished lusitropy subsequently impairing coronary perfusion further and resulting in an ischaemic cascade. As coronary flow is intimately linked with myocardial relaxation (and contraction), it can be challenging to ascertain causality between ischaemia and diastolic dysfunction.

Impaired ventricular relaxation has an adverse impact on coronary flow. In a coronary Doppler study of patients with unobstructed coronary arteries and either normal left ventricular (LV) function or a cardiomyopathic process, early diastolic coronary flow at rest and CFR were attenuated in those with abnormal LV relaxation. Diastolic coronary flow was further reduced with an increase in heart rate in patients with impaired LV relaxation at rest.[18]

These concepts underpin the intimate relationship between coronary flow and ventricular relaxation state (Figure 2). Alteration of this relationship lies at the forefront of the CMD–HFpEF pathophysiology. This will be discussed in more detail later in the review article.

Figure 2.

The left panel represents a normal control: the backward expansion wave becomes augmented on exertion, indicating enhanced lusitropy and myocardial perfusion. The right panel represents a patient with coronary microvascular disease: The backward compression wave indicates deceleration of flow and is augmented during exertion in these patients, whereas the backward expansion wave is attenuated. Note that diastole is defined electrically and all haemodynamic traces are gated to the R wave. The traces of aortic pressure, coronary pressure, and flow velocity are ensemble-averaged waveforms in a single calibrated wave. The wave intensity values (W/m2/s2) are for illustration purposes only and do not represent real data. The transthoracic echocardiogram-derived Doppler traces demonstrate normal left ventricular diastolic function in a control patient and impaired left ventricular diastolic function in a patient with coronary microvascular disease. BCW, backward compression wave; BEW, backward expansion wave; FCW, forward compression wave; FEW, forward expansion wave; LV, left ventricular; TTE, transthoracic echocardiogram.