Hyperemic Coronary Blood Flow Research Articles

Modeling cardiac microcirculation for the simulation of coronary flow and 3D myocardial perfusion.

Accurate modeling of blood dynamics in the coronary microcirculation is a crucial step toward the clinical application of in silico methods for the diagnosis of coronary artery disease. In this work, we present a new mathematical model of microcirculatory hemodynamics accounting for microvasculature compliance and cardiac contraction; we also present its application to a full simulation of hyperemic coronary blood flow and 3D myocardial perfusion in real clinical cases. Microvasculature hemodynamics is modeled with a compliant multi-compartment Darcy formulation, with the new compliance terms depending on the local intramyocardial pressure generated by cardiac contraction. Nonlinear analytical relationships for vessels distensibility are included based on experimental data, and all the parameters of the model are reformulated based on histologically relevant quantities, allowing a deeper model personalization. Phasic flow patterns of high arterial inflow in diastole and venous outflow in systole are obtained, with flow waveforms morphology and pressure distribution along the microcirculation reproduced in accordance with experimental and in vivo measures. Phasic diameter change for arterioles and capillaries is also obtained with relevant differences depending on the depth location. Coronary blood dynamics exhibits a disturbed flow at the systolic onset, while the obtained 3D perfusion maps reproduce the systolic impediment effect and show relevant regional and transmural heterogeneities in myocardial blood flow (MBF). The proposed model successfully reproduces microvasculature hemodynamics over the whole heartbeat and along the entire intramural vessels. Quantification of phasic flow patterns, diameter changes, regional and transmural heterogeneities in MBF represent key steps ahead in the direction of the predictive simulation of cardiac perfusion.

Personalized Pressure Conditions and Calibration for a Predictive Computational Model of Coronary and Myocardial Blood Flow

Predictive modeling of hyperemic coronary and myocardial blood flow (MBF) greatly supports diagnosis and prognostic stratification of patients suffering from coronary artery disease (CAD). In this work, we propose a novel strategy, using only readily available clinical data, to build personalized inlet conditions for coronary and MBF models and to achieve an effective calibration for their predictive application to real clinical cases. Experimental data are used to build personalized pressure waveforms at the aortic root, representative of the hyperemic state and adapted to surrogate the systolic contraction, to be used in computational fluid-dynamics analyses. Model calibration to simulate hyperemic flow is performed in a “blinded” way, not requiring any additional exam. Coronary and myocardial flow simulations are performed in eight patients with different clinical conditions to predict FFR and MBF. Realistic pressure waveforms are recovered for all the patients. Consistent pressure distribution, blood velocities in the large arteries, and distribution of MBF in the healthy myocardium are obtained. FFR results show great accuracy with a per-vessel sensitivity and specificity of 100% according to clinical threshold values. Mean MBF shows good agreement with values from stress-CTP, with lower values in patients with diagnosed perfusion defects. The proposed methodology allows us to quantitatively predict FFR and MBF, by the exclusive use of standard measures easily obtainable in a clinical context. This represents a fundamental step to avoid catheter-based exams and stress tests in CAD diagnosis.

Personalized coronary blood flow model based on CT perfusion to non-invasively calculate fractional flow reserve

Coronary outlet resistance, influenced by quantification and distribution of total hyperemic coronary blood flow, is critical for accurately estimating the computation of fractional flow reserve from computed tomography angiography (FFRCT). However, accurate estimation of FFRCT is still a challenging task due to the impractical of non-invasively measuring coronary outlet resistance in the clinic. While traditional methods have been used to estimate outlet resistance through population-averaged physiological assumption models, individual differences between patients limit the reliability of the models. In this work, we propose a personalized coronary flow model based on dynamic stress computed tomographic perfusion (CTP), called CTPV, to achieve a noninvasive estimation of the outlet resistance and FFRCT. The CTPV model employs myocardial blood flow (MBF) obtained from CTP to quantify the total hyperemic coronary blood flow directly. Then, myocardial perfusion territories corresponding to coronary artery branches are proposed to distribute the outlet coronary blood flow. For this purpose, we use the Voronoi algorithm to segment the myocardial perfusion territory. Finally, the outlet resistance and FFRCT are estimated based on the outlet coronary blood flow. Experiment studies on a clinical dataset consisting of 138 vessels from 86 subjects show the superiority of our CTPV model against the CTPD and LVMD models, including the method of quantifying total hyperemic coronary blood flow based on left ventricular myocardial mass (LVM) and distributing the outlet coronary blood flow based on outlet diameter. The CTPV model estimates a higher AUC for FFRCT (AUC = 0.96) than the CTPD model (AUC = 0.93) and the LVMD model (AUC = 0.92). The accuracies of CTPV, CTPD, and LVMD models are 90.6%, 87.7%, and 84.1%, respectively. Additionally, we use different outlet truncation locations to evaluate the repeatability of the CTPV and CTPD models for estimating FFRCT on a random dataset of 10 vessels. The result shows that the repeatability of the CTPV model is better than the CTPD model. These compelling results evince that the proposed CTPV model can accurately estimate the coronary outlet resistance and improve the diagnostic performance and repeatability of FFRCT.

13N-Ammonia myocardial blood flow quantitation in patient with aneurismal coronary artery disease

Aneurysmal coronary artery disease includes coronary artery aneurysms and ectasia; this condition has been associated with poor long-term outcomes. Few studies have explored myocardial blood flow 13N-ammonia PET/CT MPI added value. We present a 45-year-old man who came to the emergency department with chest pain. After a physical examination and laboratory studies, he was diagnosed with very high-risk unstable angina and referred to the catheterization laboratory. Coronary angiography showed the culprit lesion in the LCx and was treated by angioplasty and stent. LAD was found with coronary artery ectasia (TIMI 2 flow grade) and the RCA with aneurysmal disease in the proximal and middle segments (TIMI 3 flow grade). Medical treatment was decided for these findings and the patient was discharged. Two weeks later, we performed a 13N-ammonia PET/CT MPI founding apical, inferior, and inferoseptal severe ischemia, and reduced hyperemic coronary blood flow and coronary flow reserve in the RCA territory. Flow was normal in the LAD territory. Although coronary angiography remains the gold standard for evaluating these coronary abnormalities, it does not show the physiological compromise. Therefore 13N-ammonia PET/CT MPI should be performed as a complementary noninvasive imaging approach.

Concurrently Low Coronary Flow Reserve and Low Index of Microvascular Resistance Are Associated With Elevated Resting Coronary Flow in Patients With Chest Pain and Nonobstructive Coronary Arteries.

Coronary microvascular function can be distinctly quantified using the coronary flow reserve (CFR) and index of microvascular resistance (IMR). Patients with low CFR can present with low or high IMR, although the prevalence and clinical characteristics of these patient groups remain unclear. One hundred ninety-nine patients underwent coronary microvascular assessments using coronary thermodilution techniques. A pressure-temperature sensor-tipped guidewire measured proximal and distal coronary pressure, whereas the inverse of the mean transit time to room temperature saline was used to measure coronary blood flow. The CFR and IMR were quantified during adenosine and acetylcholine hyperemia. Low adenosine and acetylcholine CFR was observed in 70 and 49 patients, respectively, whereas low CFR/low IMR to adenosine and acetylcholine was observed in 39(56%) and 19(39%) patients, respectively. Despite similar adenosine CFR, patients with low CFR/low IMR had increased resting (2.8±1.2 versus 1.3±0.4s-1) and hyperemic coronary blood flow (4.8±1.5 versus 2.1±0.5s-1) compared with patients with low CFR/high IMR (both P<0.01). The same pattern was observed in response to acetylcholine. Patients with low CFR/low IMR to adenosine were younger (56±12 versus 63±10 years), women (84% versus 66%), had fewer coronary risk factors (1.1±1.0 versus 1.6±1.1), lower hemoglobin A1c (5.8±0.7 versus 6.1±0.9 mmol/L), and thinner septal thickness (8.5±2.5 versus 9.9±1.6 mm) compared with patients with low CFR/high IMR to adenosine (all P<0.05). Low CFR/low IMR to adenosine and acetylcholine are associated with elevated resting coronary blood flow and preserved hyperemic coronary blood flow. These patients present with distinct phenotypic characteristics. Simultaneous CFR and IMR measures appear necessary to differentiate these endotypes.

Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups.Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction.Results: The median FFR value was 0.83 [0.79–0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05).Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Intracoronary Saline-Induced Hyperemia During Coronary Thermodilution Measurements of Absolute Coronary Blood Flow: An Animal Mechanistic Study.

BackgroundAbsolute hyperemic coronary blood flow and microvascular resistances can be measured by continuous thermodilution with a dedicated infusion catheter. We aimed to determine the mechanisms of this hyperemic response in animal.Methods and ResultsTwenty open chest pigs were instrumented with flow probes on coronary arteries. The following possible mechanisms of saline‐induced hyperemia were explored compared with maximal hyperemia achieve with adenosine by testing: (1) various infusion rates; (2) various infusion content and temperature; (3) NO production inhibition with L‐arginine methyl ester and endothelial denudation; (4) effects of vibrations generated by rotational atherectomy and of infusion through one end‐hole versus side‐holes. Saline infusion rates of 5, 10 and 15 mL/min did not reach maximal hyperemia as compared with adenosine. Percentage of coronary blood flow expressed in percent of the coronary blood flow after adenosine were 48±17% at baseline, 57±18% at 5 mL/min, 65±17% at 10 mL/min, 82±26% at 15 mL/min and 107±18% at 20 mL/min. Maximal hyperemia was observed during infusion of both saline at body temperature and glucose 5%, after endothelial denudation, l‐arginine methyl ester administration, and after stent implantation. The activation of a Rota burr in the first millimeters of the epicardial artery also induced maximal hyperemia. Maximal hyperemia was achieved by infusion through lateral side‐holes but not through an end‐hole catheter.ConclusionsInfusion of saline at 20 mL/min through a catheter with side holes in the first millimeters of the epicardial artery induces maximal hyperemia. The data indicate that this vasodilation is related neither to the composition/temperature of the indicator nor is it endothelial mediated. It is suggested that it could be elicited by epicardial wall vibrations.

Linking Coronary Microvascular and Cardiac Diastolic Dysfunction in Diabetes: Are Women More Vulnerable?

Accumulating evidence has demonstrated a clear association of coronary microvascular dysfunction with poor cardiac outcomes (1–4). For example, in patients with normal myocardial perfusion imaging, coronary microvascular dysfunction is a powerful predictor of major adverse cardiac events and improves risk discrimination in clinical risk models (1). Furthermore, these studies suggest that coronary microvascular dysfunction may underlie the increased cardiac risk associated with some comorbid conditions. Particularly, in patients with diabetes, the presence of coronary microvascular dysfunction effectively accounted for all of the increased cardiac mortality compared with patients with diabetes with no coronary microvascular dysfunction (5). Whether sex differences exist with regard to coronary dysfunction and outcomes in patients with diabetes has not been addressed; however, it is critically needed given the impact of diabetes to abrogate the cardiovascular protection afforded by female sex hormones (6). Coronary microvascular dysfunction is defined clinically as a coronary flow reserve (CFR) (ratio of resting to maximal hyperemic coronary blood flow) <2 in the absence of obstructive coronary artery disease (CAD) (4). Previous work has revealed important sex-specific relationships between coronary dysfunction and ultimate outcomes in broad patient populations referred for angiography (1,3). Namely, prospective examination revealed that symptomatic intermediate-to-high–risk women, but not men, with impaired CFR experience increased cardiovascular events (3). This has been attributed largely to the underlying cause of impaired CFR in women …

P903Effect of elective percutaneous coronary intervention on hyperemic absolute coronary blood flow volume and microvascular resistance

P903Effect of elective percutaneous coronary intervention on hyperemic absolute coronary blood flow volume and microvascular resistance

Coronary Physiology During Exercise and Vasodilation in the Healthy Heart and in Severe Aortic Stenosis

BackgroundSevere aortic stenosis (AS) can manifest as exertional angina even in the presence of unobstructed coronary arteries. ObjectivesThe authors describe coronary physiological changes during exercise and hyperemia in the healthy heart and in patients with severe AS. MethodsSimultaneous intracoronary pressure and flow velocity recordings were made in unobstructed coronary arteries of 22 patients with severe AS (mean effective orifice area 0.7 cm2) and 38 controls, at rest, during supine bicycle exercise, and during hyperemia. Stress echocardiography was performed to estimate myocardial work. Wave intensity analysis was used to quantify waves that accelerate and decelerate coronary blood flow (CBF). ResultsDespite a greater myocardial workload in AS patients compared with controls at rest (12,721 vs. 9,707 mm Hg/min−1; p = 0.003) and during exercise (27,467 vs. 20,841 mm Hg/min−1; p = 0.02), CBF was similar in both groups. Hyperemic CBF was less in AS compared with controls (2,170 vs. 2,716 cm/min−1; p = 0.05). Diastolic time fraction was greater in AS compared with controls, but minimum microvascular resistance was similar. With exercise and hyperemia, efficiency of perfusion improved in the healthy heart, demonstrated by an increase in the relative contribution of accelerating waves. By contrast, in AS, perfusion efficiency decreased due to augmentation of early systolic deceleration and an attenuated rise in systolic acceleration waves. ConclusionsInvasive coronary physiological evaluation can be safely performed during exercise and hyperemia in patients with severe aortic stenosis. Ischemia in AS is not related to microvascular disease; rather, it is driven by abnormal cardiac-coronary coupling.

Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure.

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.

Clinical importance of hyperemic coronary blood flow (thrombolysis in myocardial infarction-intravenous flow) after primary percutaneous coronary intervention.

We aimed to investigate clinical, demographic and angiographic factors associated with hyperemic coronary blood flow (HCBF) and the relation of HCBF with mortality at 30 days. Our study included 809 consecutive patients with acute ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention (PCI). We divided corrected thrombolysis in myocardial infarction (TIMI) frame count (TFC) values into three tertiles: less than 14, 14-28 and more than 28. Corrected TFC less than 14 was defined as HCBF or TIMI intravenous flow. The primary end-point of the present study was all-cause mortality within 30 days. Among the HCBF group (n = 58), the patients with poor myocardial perfusion demonstrated the highest mortality rate within the 30-day follow-up period (33%). Low TIMI myocardial perfusion grade, history of no smoking, left ventricular ejection fraction (LVEF), and high Killip status and low LVEF were found to be independently associated with 1-month all-cause mortality. The present study showed that HCBF after primary PCI has a high 30-day mortality when associated with impaired reperfusion.

Comparison of low and high dose intracoronary adenosine and acetylcholine in women undergoing coronary reactivity testing: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Women with signs and symptoms of myocardial ischemia who are referred for invasive coronary angiography often have no evidence of obstructive coronary artery disease (CAD) [1]. Forty-five to sixty percent of these patients have abnormal coronary vasomotion due to endothelial or non-endothelial dependent macro- or microvascular coronary dysfunction [1–3]. Abnormal coronary vasomotion is linked with adverse cardiovascular outcomes, suggesting that additional coronary reactivity testing (CRT), beyond standard angiography, is needed in clinical practice to appropriately risk stratify these patients [2–6]. CRT with intra-coronary adenosine and acetylcholine (ACh) is used to identify vascular dysfunction, yet ascending dosing of these agents is time-consuming. We aimed to determine if 1) coronary flow reserve (CFR) was different after low or high dose adenosine, and 2) change in coronary artery cross sectional area (CSA) and coronary blood flow (CBF) was different after low or high dose ACh. Eighty -six women with no obstructive CAD, who were enrolled in the WISE Coronary Vascular Dysfunction Study (WISE-CVD, www.clinicaltrials.gov Identifier {type:clinical-trial,attrs:{text:NCT00832702,term_id:NCT00832702}}NCT00832702), underwent CRT using a Doppler guide wire (Volcano ®FloWire 300cm) in a proximal left coronary. CFR was recorded in response to low dose (18μg) and high dose (36μg) intra-coronary adenosine. Change in CSA and CBF were determined after intra-coronary low dose ACh (10−6 mol/L infusion for total of 0.364μg) and high dose ACh (10−4 mol/L infusion for total of 36.4μg). The protocol was approved by the local institutional review board, and written informed consent was obtained from each participant. On average, the women included in this analysis were 54 (±12.2) years old; 36.7% had hypertension; 13.9% had dyslipidemia; 45.6% had a history of tobacco use; 70.9% were Caucasian; and 10% had diabetes. The average CFR after low dose adenosine was 2.6 ± 0.6, and the average CFR after high dose adenosine was 2.5 ± 0.6. The CFR obtained after low dose adenosine was not significantly different from the CFR obtained after high dose adenosine in the same subject (mean of paired difference 0.06 ± 0.3, p-value = 0.11). The changes in CBF and CSA after low and high dose ACh are shown in the Table. On average CBF increased 15% ± 32% with low dose ACh, but increased 92% ± 102% with high dose ACh. In the same subject the increase in CBF was 77% higher after high dose ACh compared with after low dose ACh (p-value < 0.0001). The CSA of the proximal left anterior descending artery (LAD) and the LAD 5 mm distal to the flow wire remained essentially the same after low dose ACh, but decreased slightly after high dose ACh. On average, in the same subject the change in CSA of the proximal LAD was 4% smaller after high dose ACh compared with after low dose ACh (p-value = 0.05). Table Comparison of cross-sectional area and coronary blood flow change with use of low vs. high dose acetylcholine. Our data indicate that escalating dosing of adenosine to detect non-endothelial dependent microvascular coronary dysfunction may not be needed. These findings are consistent with previous work that suggests that intracoronary doses of adenosine as low as 16 μg achieve maximal hyperemia [7]. For the purpose of our testing, we have used relatively lower doses of adenosine (18 μg and 36 μg) that test its non-endothelial dependent effects on the coronary circulation. At higher doses of adenosine, it becomes an epicardial coronary vasodilator, and would test hyperemic CBF due to both endothelial and non-endothelial dependent effects [8]. Our ACh dosing was selected based on the pioneering work by Ludmer et al. that demonstrated that patients with atherosclerosis and suspected endothelial dysfunction have paradoxical vasoconstriction in response to intra-coronary infusions of ACh at doses of 10−6 mol/L or less [9]. Other studies have demonstrated a very high incidence of abnormal coronary spasm in response to intracoronary ACh in patients with suspected endothelial dysfunction when using even higher doses of intracoronary ACh (100–200 μg) [1,10]. The results of our analysis also suggest that higher dose ACh (36.4μg [10−4 mol/L]) has greater diagnostic utility than lower dose ACh (0.364μg [10−6 mol/L]), as higher dose ACh resulted in a significantly greater increase in CBF compared with low dose ACh, and on average only high dose ACh demonstrated an inappropriate decrease in CSA in this group of women with suspected endothelial dysfunction. Among women with evidence of ischemia but no obstructive CAD, low and high dose adenosine produced similar augmentation in coronary flow velocity, but low and high dose ACh produced different results. For clinically indicated CRT, low dose adenosine but high dose ACh appear to be indicated.

Influence of Type of Aortic Valve Prosthesis on Coronary Blood Flow Velocity

Severe aortic valve stenosis is associated with high resting and reduced hyperemic coronary blood flow. Coronary blood flow increases after aortic valve replacement (AVR); however, the increase depends on the type of prosthesis used. The present study investigates the influence of type of aortic valve prosthesis on coronary blood flow velocity. The blood flow velocity in the left anterior descending coronary artery (LAD) and the right coronary artery (RCA) was measured intraoperatively before and after AVR with a stentless bioprosthesis (Sorin Freedom Solo; n = 11) or a bileaflet mechanical prosthesis (St. Jude Medical Regent; n = 11). Measurements were made with an X-Plore epicardial Doppler probe (Medistim, Oslo, Norway) following induction of hyperemia with an adenosine infusion. Preoperative and postoperative echocardiography evaluations were used to assess valvular and ventricular function. Velocity time integrals (VTI) were measured from the Doppler signals and used to calculate the proportion of systolic VTI (SF), diastolic VTI (DF), and normalized systolic coronary blood flow velocities (NSF) and normalized diastolic coronary blood flow velocities (NDF). The systolic proportion of the LAD VTI increased after AVR with the St. Jude Medical Regent prosthesis, which produced higher LAD SF and NSF values than the Sorin Freedom Solo prosthesis (SF, 0.41 ± 0.09 versus 0.29 ± 0.13 [P = .04]; NSF, 0.88 ± 0.24 versus 0.55 ± 0.17 [P = .01]). No significant changes in the LAD velocity profile were noted after valve replacement with the Sorin Freedom Solo, despite a significant reduction in transvalvular gradient and an increase in the effective orifice area. AVR had no effect on the RCA flow velocity profile. The coronary flow velocity profile in the LAD was significantly influenced by the type of aortic valve prosthesis used. The differences in the LAD velocity profile probably reflect differences in valve design and the systolic transvalvular flow pattern.

Coronary microvascular dysfunction after elective percutaneous coronary intervention: Correlation with exercise stress test results

ObjectivesWe assessed whether exercise stress test (EST) results are related to the presence of coronary microvascular dysfunction (CMVD) in patients undergoing elective percutaneous coronary intervention (PCI). BackgroundPrevious studies showed that EST is poorly reliable in predicting restenosis after PCI; some studies also showed CMVD in the territory of the treated vessel. MethodsWe studied 29 patients (age 64±6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the left anterior descending (LAD) coronary artery, undergoing successful PCI with stent implantation. EST and assessment of coronary microvascular function were performed 24h, 3months and 6months after PCI. Coronary blood flow (CBF) response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography. ResultsPatients with ST-segment depression ≥1mm at EST performed 24h after PCI (n=11, 38%) showed a lower CBF response to adenosine compared to those with negative EST (1.65±0.4 vs. 2.11±0.4, respectively, p=0.003), whereas the difference in CBF response to CPT was not significant (1.44±0.4 vs. 1.64±0.3, respectively; p=0.11). At 3-month and 6-month follow-up a positive EST was found in 12 (41%) and 13 (44%) patients, respectively; patients with positive EST also had lower CBF response to adenosine compared to those with negative EST (3months: 1.69±0.3 vs. 2.20±0.3, respectively; 6months: 1.66±0.2 vs. 2.32±0.3, respectively; p<0.001 for both). ConclusionsPositive EST after elective successful PCI consistently reflects impairment of hyperemic CBF due to CMVD, which persists over a follow-up period of 6months.

Effects of the prototype serotonin 5-HT 1B/1D receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP 8–37 on myocardial reactive hyperemic response in conscious dogs

The triptans, serotonin 5-HT 1B/1D receptor agonists exemplified by sumatriptan, are a mainstay migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans constrict human coronary artery in vitro, and there are case reports of myocardial infarction in patients using sumatriptan. However, preclinical studies with sumatriptan in normal dogs have failed to demonstrate effects on resting coronary flow. Calcitonin gene-related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP receptor antagonist peptide CGRP 8–37, is a new antimigraine mechanism which also has been reported to have no effect on coronary flow in normal, non-stressed animals. The goal of the present studies was to compare the effects of sumatriptan (10 μg/kg/min i.v.) and CGRP 8–37 (30 μg/kg/min i.v.) on systemic and coronary hemodynamics in conscious dogs under resting conditions and during myocardial reactive hyperemia following a brief 15 s of coronary artery occlusion. Neither CGRP 8–37 nor sumatriptan affected resting coronary flow. However, whereas CGRP 8–37 had no effect on myocardial reactive hyperemic response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow (baseline vs treatment: 75.4 ± 12.7 vs 60.0 ± 10.3 ml/min, P < 0.05), reactive hyperemic flow (16.7 ± 5.2 vs 11.6 ± 3.3 ml, P < 0.05) and the repayment of coronary blood flow debt following coronary artery occlusion (484 ± 76 vs 369 ± 57%, P < 0.05), indicating an impairment in coronary blood flow reserve. The positive control nitric oxide synthase inhibitor L-NNA (30 mg/kg/30 min i.v.) likewise significantly attenuated myocardial reactive hyperemic response. These findings provide evidence for a differentiation between CGRP receptor antagonism and triptan effects on coronary vascular function.

Coronary blood flow during reperfusion as an index of the extend of microvascular damage: Experimental study

The “no-reflow” phenomenon is characterized by distinct areas of microvascular damage and compromised regional myocardial blood flow, after a period of ischemia, despite restoration of epicardial vessel patency. The aim of our study was to examine the relation between baseline and hyperemic coronary blood flow (CBF) at reperfusion to the extent of the no-reflow phenomenon (NRP) in a porcine experimental model of ischemia–reperfusion.

Oral Administration of 17β-Estradiol Over 3 Months Without Progestin Co-Administration Does Not Improve Coronary Flow Reserve in Post-Menopausal Women: A Randomized Placebo-Controlled Cross-Over CMR Study

Several large epidemiological outcome studies did not demonstrate a benefit of combined estrogen-progestin replacement treatment (HRT) on cardiovascular events in elderly postmenopausal women. Whether progestin antagonism is responsible for these negative results or the natural estrogen 17ss-estradial (E2) itself is not effective in the coronary circulation is unknown. To assess the effect of 3 months of E2 treatment on the coronary circulation, i.e., on coronary flow reserve (CFR), in postmenopausal women without established coronary artery disease (CAD). In a double-blind placebo-controlled cross-over design postmenopausal women (60 +/- 5 years, n = 14) were randomized to either start with placebo or E2 (Estrofem, Novo Nordisk, Copenhagen, Denmark) 2 mg/d given orally over 3 months and to switch thereafter for another 3 months of therapy. At baseline, a stress echocardiography was performed to exclude CAD. CFR was determined by coronary sinus CMR flow measurements (with motion-adapted gating and interactive acquisition window control; spatial/temporal resolution of 0.8 x 0.9 mm2/25-30 ms) which were performed at rest and during vasodilation (dipyridamole 0.56 mg/kg over 4 minutes IV) at baseline, and after 3 and 6 months of therapy, respectively. Hemodynamics such as heart rate and systolic and diastolic blood pressure were not different for the control and E2 group. For CFR and for resting and hyperemic coronary sinus blood flow, no differences between the placebo and E2 group were found (2-way ANOVA for repeated measurements). Reproducibility of phase-contrast CMR measurements of CFR was -1.1 +/- 4.9%. In elderly postmenopausal women without significant CAD, oral administration of E2 over 3 months without a progestin co-administration does not improve CFR. This finding yields partly explanation for some large epidemiological trials which could not demonstrate a clinical cardiovascular benefit of HRT in elderly women.

Relationship between coronary flow velocity reserve and aortic stiffness

We examined the hypothesis that a stiff aorta is associated with reduced coronary blood flow (CBF) and CBF response to percutaneous coronary intervention (PCI). Aortic mechanical properties are thought to affect CBF, with increased stiffness associated with decreased coronary perfusion. Animal studies are conflicting, and human evidence is lacking. Even less is known about the effects of aortic stiffness on the CBF response to successful PCI. In 18 subjects undergoing elective PCI, a Doppler velocity guidewire was positioned proximal to a severe coronary stenosis to measure resting and adenosine-induced hyperemic CBF before and after PCI. Stenosis severity was assessed with Doppler velocity and pressure guidewires. Aortic mechanical indexes measured included central pulse-wave velocity (cPWV) and central pulse pressure (cPP). PCI was successful in all subjects (diameter stenosis: 88 ± 9% to 2 ± 7%; coronary flow velocity reserve: 1.8 ± 0.6 to 3.0 ± 0.8; fractional flow reserve: 0.57 ± 0.19 to 0.92 ± 0.06; all P &lt; 0.001). With the adjustment for age and gender, resting and hyperemic CBF were inversely related to cPWV irrespective of the presence of stenosis (resting: before PCI, r2 = 0.452, P &lt; 0.01; after PCI, r2 = 0.261, P = 0.043; hyperemic: before PCI r2 = 0.503, P = 0.005; after PCI r2 = 0.500, P = 0.002), whereas they were related to cPP in absence of stenosis (resting: r2 = 0.368, P = 0.022; hyperemic: r2 = 0.370, P = 0.016). Hyperemic CBF response ( P = 0.005) and hyperemic CBF improvement from PCI ( P = 0.025) were less marked in a stiff aorta than a compliant aorta. A stiff aorta is associated with a reduction in CBF, a lower hyperemic CBF response, and may reduce the improvement in hyperemic CBF after successful PCI.

Aortic stiffness affects the coronary blood flow response to percutaneous coronary intervention

We examined the hypothesis that a stiff aorta is associated with reduced coronary blood flow (CBF) and CBF response to percutaneous coronary intervention (PCI). Aortic mechanical properties are thought to affect CBF, with increased stiffness associated with decreased coronary perfusion. Animal studies are conflicting, and human evidence is lacking. Even less is known about the effects of aortic stiffness on the CBF response to successful PCI. In 18 subjects undergoing elective PCI, a Doppler velocity guidewire was positioned proximal to a severe coronary stenosis to measure resting and adenosine-induced hyperemic CBF before and after PCI. Stenosis severity was assessed with Doppler velocity and pressure guidewires. Aortic mechanical indexes measured included central pulse-wave velocity (cPWV) and central pulse pressure (cPP). PCI was successful in all subjects (diameter stenosis: 88 +/- 9% to 2 +/- 7%; coronary flow velocity reserve: 1.8 +/- 0.6 to 3.0 +/- 0.8; fractional flow reserve: 0.57 +/- 0.19 to 0.92 +/- 0.06; all P < 0.001). With the adjustment for age and gender, resting and hyperemic CBF were inversely related to cPWV irrespective of the presence of stenosis (resting: before PCI, r2 = 0.452, P < 0.01; after PCI, r2 = 0.261, P = 0.043; hyperemic: before PCI r2 = 0.503, P = 0.005; after PCI r2 = 0.500, P = 0.002), whereas they were related to cPP in absence of stenosis (resting: r2 = 0.368, P = 0.022; hyperemic: r2 = 0.370, P = 0.016). Hyperemic CBF response (P = 0.005) and hyperemic CBF improvement from PCI (P = 0.025) were less marked in a stiff aorta than a compliant aorta. A stiff aorta is associated with a reduction in CBF, a lower hyperemic CBF response, and may reduce the improvement in hyperemic CBF after successful PCI.