Topics in integrated systems physiology

Myocardial perfusion and coronary microcirculation: From pathophysiology to clinical application

This study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.

Although regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.

A total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm.

Patients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: −0.12 ml/g/min; 95% confidence interval: −0.23 to −0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: −0.15 ml/g/min; 95% confidence interval: −0.28 to −0.03 ml/g/min; p = 0.013).

Patients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.

We investigated the effects of intracoronary transplantation of CD34⁺ cells on myocardial perfusion in patients with nonischemic dilated cardiomyopathy (DCM).

We enrolled 21 patients with DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral stem cell mobilization with granulocyte-colony stimulating factor (G-CSF). CD34⁺ cells were collected by means of apheresis. Patients underwent myocardial perfusion imaging, and CD34⁺ cells were injected in the coronary artery supplying viable segments with reduced myocardial perfusion and regional dysfunction. Myocardial perfusion imaging was repeated 6 months later. Clinical response to stem cell therapy was predefined as a change in LVEF >5%. The majority of patients were men (81%) with an overall mean age 53 ± 9 years, LVEF 25 ± 5%, and 6-minute walking distance 354 ± 71 m. Myocardial perfusion defects at rest were observed in 86% of patients and were more common in the left anterior descending territory (50%). At 6 months' follow-up, there was a significant improvement in rest myocardial perfusion scores (6.3 ± 5.8 vs 3.1 ± 4.3; P < .001), LVEF (25 ± 7% vs 29 ± 8%; P = .005), and 6-minute walking distance (354 ± 71 m vs 404 ± 91 m; P < .001). Responders to stem cell therapy had lower summed rest perfusion score at both baseline (3.2 ± 3.0 vs 9.1 ± 6.3; P = .015) and follow-up (1.0 ± 1.5 vs 5.0 ± 5.1; P = .028).

CD34⁺ cell transplantation may lead to improved myocardial perfusion in patients with nonischemic DCM. Patients with less severe myocardial perfusion defects at baseline may have an increased likelihood to respond to intracoronary CD34⁺ cell transplantation.

Myocardial bridge (MB) is defined as a segment of a major epicardial coronary artery the “tunneled artery” that goes intramurally through the myocardium beneath the muscle bridge. Multiple methods have been proposed to assess coronary flow rate among which thrombolysis in acute myocardial infarction frame count was a relatively new semiquantitative method.

Our goal was to determine incidence of MB in the patients undergoing coronary angiography in Mansoura Specialized Hospital, Cardiac Catheterization Laboratory, also to investigate the hypothesis that slow coronary flow rate may be linked to angina or angina like symptoms in patients with MB without stenotic lesions in epicardial coronary arteries using TFC.

Fifteen patients with MB (group I) were retrospectively collected from Mansoura Specialized Hospital, Cardiac Catheterization Laboratory, we review 3000 cases referred to diagnostic coronary angiography to exclude significant coronary artery disease. Fifteen patients with normal coronary angiography served as control (group II). We review the clinical presentations, risk factors, echocardiographic data for both test and control groups. TFC was calculated using a simple continuous index.

The incidence of MB in our study was 0.5%. CTFC in LAD was significantly higher in the patients with MB compared with control. No significant correlation between TFC and echocardiographic parameters.

Myocardial bridging must be considered especially in patients at low risk for coronary atherosclerosis but with angina like chest pain or established myocardial ischemia. We suggest that coronary blood flow is decreased in the patients with MB compared with the patients having normal coronary.