Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy

Abstract Background In patients with advanced non-ischemic cardiomyopathy (NIC), right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA) flow pattern and flow reserve (CFR) are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire) data was obtained in RCA and left anterior descendent coronary artery (LAD) before and after adenosine. Resting RCA phasic pattern (diastolic/systolic) was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV) dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress) more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 ± 3.5 % and 69.4 ± 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS) either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS); RCA vs. LAD was 1.35 vs. 2.85 (p < 0.001). It had no significant correlation among any cardiac mechanical or hemodynamic parameter with RCA-CFR or RCA flow pattern. RCA-CFR had no difference compared with LAD (3.38 vs. 3.34, p = NS), as well as in pulmonary hypertension (3.09 vs. 3.10, p = NS) either in RV dysfunction (3.06 vs. 3.22, p = NS) subgroups. Conclusion In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or hemodynamic parameter with RCA-CFR or RCA phasic flow pattern. RCA flow reserve is still similar to LAD, independently of those right-sided cardiac disturbances.

Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance phase contrast imaging

Comparison of arterial and venous coronary artery bypass flow measurements using 3-T magnetic resonance (MR) phase contrast in correlation with intraoperative Doppler flow measurements.

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans.

Coronary collateral flow in response to endurance exercise training

BACKGROUND: In humans, it is not known whether physical endurance exercise training promotes coronary collateral growth. The following hypotheses were tested: the expected collateral flow reduction after percutaneous coronary intervention of a stenotic lesion is prevented by endurance exercise training; collateral flow supplied to an angiographically normal coronary artery improves in response to exercise training; there is a direct relationship between the change of fitness after training and the coronary collateral flow change. METHODS AND RESULTS: Forty patients (age 61+/-8 years) underwent a 3-month endurance exercise training program with baseline and follow-up assessments of coronary collateral flow. Patients were divided into an exercise training group (n=24) and a sedentary group (n=16) according to the fact whether they adhered or not to the prescribed exercise program, and whether or not they showed increased endurance (VO2max in ml/min per kg) and performance (W/kg) during follow-up versus baseline bicycle spiroergometry. Collateral flow index (no unit) was obtained using pressure sensor guidewires positioned in the coronary artery undergoing percutaneous coronary intervention and in a normal vessel. In the vessel initially undergoing percutaneous coronary intervention, there was an increase in collateral flow index among exercising but not sedentary patients from 0.155+/-0.081 to 0.204+/-0.056 (P=0.03) and from 0.189+/-0.084 to 0.212+/-0.077 (NS), respectively. In the normal vessel, collateral flow index changes were from 0.176+/-0.075 to 0.227+/-0.070 in the exercise group (P=0.0002), and from 0.219+/-0.103 to 0.238+/-0.086 in the sedentary group (NS). A direct correlation existed between the change in collateral flow index from baseline to follow-up and the respective alteration of VO2max (P=0.007) and Watt (P=0.03). CONCLUSION: A 3-month endurance exercise training program augments coronary collateral supply to normal vessels, and even to previously stenotic arteries having undergone percutaneous coronary intervention before initiating the program. There appears to be a dose-response relation between coronary collateral flow augmentation and exercise capacity gained.

Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve

BACKGROUND The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown. METHODS AND RESULTS We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P<0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 (P<0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P<0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses. CONCLUSIONS PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina.

Sympathetic stimulation using the cold pressor test increases coronary collateral flow

BACKGROUND Little is known about the vasomotor function of human coronary collateral vessels. The purpose of this study was to examine collateral flow under a strong sympathetic stimulus (cold pressor test, CPT). METHODS In 30 patients (62 +/- 12 years) with coronary artery disease, two subsequent coronary artery occlusions were performed with random CPT during one of them. Two minutes before and during the 1 minute-occlusion, the patient's hand was immerged in ice water. For the calculation of a perfusion pressure-independent collateral flow index (CFI), the aortic (Pao), the central venous (CVP) and the coronary wedge pressure (Poccl) were measured: CFI = (Poccl - CVP)/(Pao - CVP). RESULTS CPT lead to an increase in Pao from 98 +/- 14 to 105 +/- 15 mm Hg (p = 0.002). Without and with CPT, CFI increased during occlusion from 14% +/- 10% to 16% +/- 10% (p = 0.03) and from 17% +/- 9% to 19% +/- 9% (p = 0.006), respectively, relative to normal flow. During CPT, CFI was significantly higher at the beginning as well as at the end of the occlusion compared to identical instants without CPT. CFI at the end of the control occlusion did not differ significantly from the CFI at the beginning of occlusion with CPT. CONCLUSIONS During balloon occlusion, collateral flow increased due to collateral recruitment independent of external sympathetic stimulation. Sympathetic stimulation using CPT additionally augmented collateral flow. The collateral-flow-increasing effect of CPT is comparable to the recruitment effect of the occlusion itself. This may reflect a coronary collateral vasodilation mediated by the sympathetic nervous system.

Flow disturbances in stent-related coronary evaginations: a computational fluid-dynamic simulation study

Aims: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. Methods and results: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross ectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. Conclusions: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease

Background We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. Methods In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. Results The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infection from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. Conclusions In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Pulsatile flow in coronary bifurcations for different stenting techniques

The objective of this work is to analyze the local hem odynamic changes caused in a coronary bifurcation by three different stenting techniques: simple stenting of the main vessel, simple stenting of the main vessel with kissing balloon in the side branch and culotte. To carry out this study an idealized geometry of a coronary bifurcation is used, and two bifurcation angles, 45º and 90º, are chosen as representative of the wide variety of re al configurations. In order to quantify the influence of the stenting technique on the local blood flow, both numeri- cal simulations and experimental measurements are performed. First, steady simulations are carried out with the commercial code ANSYS-Fluent, and then, experimental measurements with PIV (Particle Image Velocimetry) obtained in the laboratory are used to validate the numerical simulation. The steady computational simulations show a good overall agreement with the experimental data. Second, pulsatile flow is considered to take into account the tran- sient effects. The time averaged wall shear stress, scillatory shear index and pressure drop obtained numerically are used to compare the behavior of the stenting techniques.