Concurrent assessment of epicardial coronary artery stenosis and microvascular dysfunction using diagnostic endpoints derived from fundamental fluid dynamics principles.

BACKGROUND: Simultaneously measured pressure and flow distal to coronary stenoses can be combined, in conjunction with anatomical measurements, to assess the status of both the epicardial and microvascular circulations. METHODS AND RESULTS: Assessments of coronary hemodynamics were performed using fundamental fluid dynamics principles. We hypothesized that the pressure-drop coefficient (CDPe; trans-stenotic pressure drop divided by the dynamic pressure in the distal vessel) correlates linearly with epicardial and microcirculatory resistances concurrently. In 14 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire in the setting of both normal and disrupted microcirculation, with the presence of epicardial coronary lesions of lt; 50% area stenosis (AS) and > 50% AS. The CDPe progressively increased from lesions of < 50% AS to > 50% AS and had a higher resolving power (45 +/- 22 to 193 +/- 140 in normal microcirculation; 248 +/- 137 to 351 +/- 140 in disrupted microcirculation) as compared to fractional flow reserve (FFR) and coronary flow reserve (CFR). Strong multiple linear correlation was observed for CDPe with combined FFR and CFR (r = 0.72; p < 0.0001). Further, the ratio of maximum pressure drop coefficient evaluated at the site of stenosis and its theoretical limiting value of minimum cross-sectional area was also able to distinguish different combinations of coronary artery diseases. CONCLUSIONS: The CDPe can be readily obtained during routine pressure and flow measurements during cardiac catheterization. It is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment.

Characterizing momentum change and viscous loss of a hemodynamic endpoint in assessment of coronary lesions.

Myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR(myo) and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient, c, is proposed. The coefficient, c, which accounts for mean pressure drop, Delta p, mean coronary flow, Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished using c. FFR(myo), CFR and c were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemic c decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR(myo) increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreased c. For post-angioplasty lesion, c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreased c compared with a lesion without guidewire. Further, c showed a linear relationship with FFR(myo), CFR and percentage area stenosis for pre-angioplasty, intermediate and post-angioplasty lesion. These baseline values of c were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.

Delineating the guide-wire flow obstruction effect in assessment of fractional flow reserve and coronary flow reserve measurements.

Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR) over pathophysiological conditions in a patient group with coronary artery disease during angioplasty. The vasodilation-distal perfusion pressure (CFR-p(rh)) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is that a guide wire spanning the lesions elevates the pressure gradient and reduces the flow during hyperemic measurements. Maximal CFR-p(rh) was uniquely determined by the intersection of measured CFR and calculated p(rh) of native and residual epicardial lesions in patients without microvascular disease, during angioplasty. Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p(zf)) of approximately 20 mmHg and a corresponding p(rh) of 55 mmHg in the native lesions, which coincided with the level that causes ischemia in human hearts. On this linear curve, values of CFR and FFRmyo (pathophysiological condition) and CFRg and FFRmyog (in the presence of the guide wire) were obtained in native and residual lesions. A strong linear correlation was found between CFR and CFRg [CFR = CFRg x 0.689 + 1.271 (R2= 0.99) for 0.46 mm and CFR = CFRg x 0.757 + 1.004 (R2= 0.99) for 0.35 mm] and between FFRmyo and FFRmyog [FFRmyo = FFRmyog x 0.737 + 0.263 (R2= 0.99) for 0.46 mm and FFRmyo = FFRmyog x 0.790 + 0.210 (R2= 0.99) for 0.35 mm]. This study establishes a strong correlation between CFR and CFRg and between FFRmyo and FFRmyog, which could be used to obtain the true state of occlusion in the coronary artery during angioplasty.