Abstract
Mechanical dyssynchrony affects left ventricular (LV) mechanics and coronary perfusion. Due to the confounding effects of their bi-directional interactions, the mechanisms behind these changes are difficult to isolate from experimental and clinical studies alone. Here, we develop and calibrate a closed-loop computational model that couples the systemic circulation, LV mechanics, and coronary perfusion. The model is applied to simulate the impact of mechanical dyssynchrony on coronary flow in the left anterior descending artery (LAD) and left circumflex artery (LCX) territories caused by regional alterations in perfusion pressure and intramyocardial pressure (IMP). We also investigate the effects of regional coronary flow alterations on regional LV contractility in mechanical dyssynchrony based on prescribed contractility-flow relationships without considering autoregulation. The model predicts that LCX and LAD flows are reduced by 7.2%, and increased by 17.1%, respectively, in mechanical dyssynchrony with a systolic dyssynchrony index of 10% when the LAD's IMP is synchronous with the arterial pressure. The LAD flow is reduced by 11.6% only when its IMP is delayed with respect to the arterial pressure by 0.07 s. When contractility is sensitive to coronary flow, mechanical dyssynchrony can affect global LV mechanics, IMPs and contractility that in turn, further affect the coronary flow in a feedback loop that results in a substantial reduction of dPLV/dt, indicative of ischemia. Taken together, these findings imply that regional IMPs play a significant role in affecting regional coronary flows in mechanical dyssynchrony and the changes in regional coronary flow may produce ischemia when contractility is sensitive to the changes in coronary flow.
Highlights
Heart failure (HF) is a complex syndrome associated with significant morbidity, mortality and socioeconomic burden
The key findings of this study are: (1) an increase in time delay t (SDI) in the IMPLCX waveform with respect to IMPLAD, left ventricle (LV), and arterial pressure waveforms produces a decrease in left circumflex artery (LCX) flow and an increase in left anterior descending artery (LAD) flow; (2) a time delay t in both IMPLAD and IMPLCX waveform with respect to the LV and arterial pressure waveforms causes both LAD and LCX coronary flow to decrease; (3) prescribing a direct relationship between regional contractility and its corresponding coronary flow (Figure 3) can affect global LV mechanics, hemodynamics and function, which in turn further affects the coronary flow in a feedback loop in mechanical dyssynchrony, especially when contractility is highly sensitive to flow
We show that regional coronary flows in the LCX and LAD are altered by asynchronous LV contraction due to changes in the arterial pressure, LV pressure, IMPLAD and IMPLCX waveforms as discussed below
Summary
Heart failure (HF) is a complex syndrome associated with significant morbidity, mortality and socioeconomic burden. One study in LBBB patients with normal coronary arteries had an abnormal increase in lactate production during a highrate of pacing, suggesting that perfusion changes associated with mechanical dyssynchrony may induce ischemia (Breithardt and Breithardt, 2012). It is, unclear if this ischemia, plausibly induced by changes in perfusion during mechanical dyssynchrony can reduce myocardial contractility, which in turn, causes further changes to the coronary flow that may exacerbate ischemia. Due to the confounding effects of the two-way interactions between LV mechanics and coronary flow during mechanical dyssynchrony, it is difficult to isolate the mechanisms behind these changes from experimental and clinical measurements alone
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
