Changes In Coronary Flow Reserve Research Articles

Long-Term Administration of Endothelin Receptor Antagonist Improves Coronary Endothelial Function in Patients With Early Atherosclerosis

Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET(A) receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10(-6) to 10(-4) mol/L) in the left anterior descending coronary artery. N(G)-monomethyl-l-arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus -2.22%, 95% confidence interval -27.37% to 15.28%; P<0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N(G)-monomethyl-l-arginine were similar between the groups at baseline and at 6 months. This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.

Effect of carvedilol on coronary flow reserve in patients with hypertensive left-ventricular hypertrophy

Objective. Patients with hypertensive left-ventricular hypertrophy (LVH) have lower coronary flow reserve (CFR). Whether carvedilol can improve CFR of patients with hypertensive LVH is unknown. We aimed to investigate the effects of carvedilol on CFR in patients with hypertensive LVH. Methods. Sixty-three patients were randomly divided into two groups for treatment with carvedilol or metoprolol. The peak diastolic coronary flow velocity in the left anterior descending coronary artery at rest and at maximal vasodilation with dipyridamole infusion was recorded by transesophageal echocardiography (TEE), then CFR was calculated at baseline and at the end of 6 months of therapy. Left-ventricular mass index (LVMI) was calculated by 2-D echocardiography. Endothelium-dependent and -independent reactivity of the brachial artery was measured. Levels of plasma endothelin-1 (ET1), nitric oxide (NO) and other metabolites were monitored and analyzed before and after 6-month therapy. Results. Both blood pressure and heart rate decreased significantly in the two treatment groups after therapy (p<0.05). With carvedilol treatment, LVMI was lower (p<0.05), endothelium function of the brachial artery was higher (p<0.05), and peak diastolic coronary flow velocity at rest and at maximal vasodilation after dipyridamole infusion was significantly higher (p<0.05) than with metoprolol treatment, which led to a significantly higher CFR (p<0.05). Changes in CFR and LVMI with carvedilol treatment were inversely correlated (R2=0.474, p=0.036). With carvedilol treatment, plasma level of ET-1 was lower, but that of NO was significantly higher than with metoprolol treatment (both p<0.05). Conclusions. The CFR of patients with hypertensive LVH but not coronary artery disease could increase with 6-month carvedilol therapy.

Nebivolol induces parallel improvement of left ventricular filling pressure and coronary flow reserve in uncomplicated arterial hypertension

Our aim was to analyze the effects of 3-month antihypertensive therapy by nebivolol, a beta-blocking agent with nitric oxide-mediated vasodilatory properties, on coronary flow reserve (CFR) and left ventricular filling pressure (LVFP) in uncomplicated arterial hypertension. Twenty newly diagnosed, never treated, uncomplicated hypertensive patients (14 male and six female patients, mean age = 49 years), I-II WHO grade, underwent single-blind nebivolol treatment. At baseline and at 3-month follow-up, patients underwent Doppler echocardiography including pulsed Tissue Doppler of septal mitral annulus: the ratio between transmitral E velocity and myocardial early diastolic velocity (E/Em ratio) was calculated as an index of LVFP degree. Transthoracic Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was also determined. After 3-month nebivolol therapy, rate-pressure product decreased (P < 0.0001). No significant change of left ventricular mass index, relative wall thickness and midwall shortening was detected. Left ventricular end-diastolic diameter and stroke volume were both marginally increased. Nebivolol increased Em (P < 0.0001), reduced E/Em ratio (from 9.0 +/- 1.6 to 8.2 +/- 1.1, P < 0.0001) and enhanced CFR (from 2.07 +/- 0.2 to 2.20 +/- 0.2, P = 0.003), because of increased hyperemic coronary flow velocity (P < 0.001). CFR increase remained significant (P < 0.001) after normalizing resting and dipyridamole coronary velocities for the respective rate-pressure product. The increase of normalized CFR induced by nebivolol was related with E/Em ratio decrease (r = -0.65, P < 0.002). Nebivolol improves LVFP as well as CFR in uncomplicated hypertension. The association between changes of CFR and those of LVFP indicates a possible common denominator between improvement of coronary microvascular function and myocardial stimulation of nitric oxide release induced by the drug.

Concordant improvements in coronary flow reserve and ST‐segment resolution during percutaneous coronary intervention for acute myocardial infarction: A benefit of postconditioning

To assess the effect of ischemic postconditioning on indices of coronary microvascular function during percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI). Myocardial tissue level perfusion remains suboptimal in many patients with STEMI despite restoration of antegrade flow in the epicardial coronary artery. Twenty-four patients with an evolving anterior STEMI were randomized to undergo a previously-validated ischemic postconditioning protocol or usual care during PCI. The extent of resolution of ST segment elevation along with Doppler-tip catheter velocimetry was used as indices of myocardial reperfusion and microvascular function, respectively. Postconditioned patients exhibited a greater, and therefore more rapid, extent of ST segment resolution (postconditioning, 70% +/- 15%; control, 48% +/- 16%; P = 0.0002) by the end of the procedure. Postconditioned patients also exhibited a greater hyperemic coronary vasodilator response at the completion of the procedure (coronary flow velocity reserve, CFVR: postconditioning, 2.2 +/- 0.1; control, 1.5 +/- 0.1; P < 0.0001). The end-procedure CFVR was directly related to the extent of the ST segment resolution (r = 0.85) but inversely related to the absolute magnitude of ST segment elevation at end procedure (r = -0.76). Peak serum creatine kinase was significantly lower in postconditioned patients (postconditioning, 1,524 +/- 435 IU/l; control, 1,862 +/- 561 IU/l; P = 0.03). Ischemic postconditioning, as described, can be expeditiously performed during PCI for STEMI. Concordant changes in coronary flow reserve and ST segment resolution, measures of microcirculatory function, and myocardial perfusion, were greater in postconditioned patients.

Diagnosis of Coronary Restenosis Using Coronary Flow Reserve Measurements Obtained Through Transthoracic Doppler Echocardiography

Background and Objectives: Coronary flow reserve (CFR) decreases in the presence of significant coronary stenosis. Hence, CFR can be used for the detection of restenosis after percutaneous coronary intervention (PCI). However, because CFR can also be affected by other conditions such as endothelial dysfunction, microvascular damage, and left ventricular hypertrophy, the absolute value of CFR is not routinely used for detection of coronary restenosis. We hypothesized that changes in the value of CFR, rather than the absolute CFR value, are better correlated with restenosis in various clinical settings. Subjects and Methods: We studied 99 patients (71 males/28 females, mean age 58±11 years) who underwent successful PCI of the left anterior descending artery. Pre-PCI diagnoses were as follows: 37 unstable angina, 35 stable angina, 27 acute myocardial infarction. CFR using transthoracic Doppler was measured at 48 hours after PCI and at the time of follow-up angiography (6.0±1.5 months later). Coronary flow velocity was measured in the distal left anterior descending artery with a 7 MHz transducer (HDI 5,000, Philips, The Netherlands) at baseline and during intravenous infusion of adenosine (140 μg·kg-·min-). Mean diastolic coronary flow velocities from at least three cardiac cycles were averaged. Results: CFRs in 69 patients without restenosis were 2.55±0.99 at 48 hours after PCI and 2.93±1.00 at follow-up (p 50% in diameter stenosis) decreased significantly from 2.70± 1.01 at 48 hours after PCI to 1.98±0.91 at follow-up (p<0.001). There was a significant difference in CFR change (ratio of CFRfollowup/CFRinitial) between the two groups. CFR change had a better receiver operating characteristics (ROC) curve than absolute CFR for prediction of restenosis [area under the curve (AUC) for absolute CFR= 0.76, AUC for CFR change=0.82]. Conclusion: Restenosis after PCI leads to a significant decrease in CFR, even in the presence of variable baseline CFR values. Serial measurements of CFR can be used to detect restenosis after PCI. (Korean Circ J 2008;38:325-330)

β-Blockers and Coronary Flow Reserve

Coronary flow reserve (CFR) is the maximal increase in coronary blood flow (CBF) above its resting level for a given perfusion pressure when coronary vasculature is maximally dilated. Normally, hyperaemic CBF reaches values at least 2- to 3-fold greater than resting CBF. Reduction of CFR is mainly due to epicardial coronary artery stenosis or to coronary microvascular dysfunction. CFR can be determined by several techniques that measure CBF itself (e.g. positron emission tomography) or CBF velocities (Doppler methods) from which coronary flow velocity reserve is calculated. Hyperaemic coronary vasodilation can be obtained by pharmacological agents (e.g. adenosine and dipyridamole), but also by the cold pressure test. Long-term antihypertensive treatment induces significant improvement of CFR, which is parallel to the regression of left ventricular (LV) hypertrophy. First- and second-generation beta-adrenergic receptor antagonists (beta-blockers) have shown contradictory influences on CFR. This can be explained by the interaction of the effects on CBF at rest, generally reduced by these drugs, and after hyperaemia, when minimal coronary resistance appears to be either increased or reduced. Third-generation beta-blockers (e.g. carvedilol and nebivolol), which have vasodilating capacity, improve hyperaemic CBF. This occurs as a result of a reduction in minimal resistance, which can be attributed to alpha-adrenergic blockade and/or to a nitric oxide-mediated effect. This improvement is clearly beneficial in patients with coronary artery disease and indicates an improved coronary microvascular function. Changes of CFR due to vasodilating beta-blockers improve microvascular angina pectoris or silent ischaemia in patients without epicardial artery stenosis, and are also helpful in predicting the response or the further improvement of LV function to treatment.

Abstract 2083: Improvement in Coronary Flow Reserve is Associated With Late Recovery of Left Ventricular Function After Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy

Background: Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in theses circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in IDC patients. Methods: We studied 20 patients with IDC (mean age 56 ± 15 years, NYHA I–II) who were scheduled to receive carvedilol therapy. All patients were stabilized using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and diuretic treatment. Transthoracic Doppler echocardiography with intravenous infusion of adenosine triphosphate was used to assess CFR in the left anterior descending artery at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 ± 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as Group A (LVEF change ≥10%) and Group B (LVEF change &lt;10%). Results: Although there was no significant difference in CFR between the 2 groups at baseline (Group A vs. Group B, 2.4 ± 1.0 vs. 2.2 ± 0.8; P =NS), CFR was significantly higher in Group A than in Group B at 1 month of therapy (3.7 ± 0.5 vs. 2.5 ± 0.9; P &lt;0.01). The magnitude of CFR change after 1 month of therapy was significantly greater in Group A than in Group B (1.3 ± 0.6 vs. 0.4 ± 0.5; P &lt;0.01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up ( P &lt;0.05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r=0.65, P &lt;0.01). Conclusions: This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.

Changes in Coronary Flow Reserve following Stent Implantation in the Swine Descending Thoracic Aorta

To evaluate coronary flow reserve (CFR) changes following stent implantation in the descending thoracic aorta (DTA) of a porcine model. Six pigs (3 males; 40 to 44 kg) were anesthetized and kept on mechanical ventilation. A 6-F guiding right Judkins catheter was advanced under fluoroscopy to the right coronary artery, and a pressure wire with a temperature sensor was placed within the vessel lumen at a distance of 4 cm from the ostium. CFR was estimated by the thermodilution method before and after maximal coronary vasodilation with 20 mg of intracoronary papaverine. Aortography was also performed to measure aortic diameter. Subsequently, a self-expanding vascular stent was deployed into the DTA just below the left subclavian artery (LSA), and CFR was measured again. All animals were maintained for 3 weeks; at the end of this period, a further CFR was calculated using the same procedure. The mean aortic diameter below the LSA was 12.15+/-0.15 mm. Following stent deployment, the mean aortic diameter measured at the stented segment was 12.58+/-0.11 (p=0.001 versus baseline). The mean CFR value was 4.70+/-2.00 before stent implantation, 2.68+/-0.86 immediately after, and 4.05+/-1.15 at 3 weeks after stenting. Accordingly, CFR values were significantly depressed immediately after stent placement compared with baseline (p=0.027). However, CFR values obtained 3 weeks following stent deployment were similar to the initial values (p=0.59). Stent deployment in the normal swine DTA produces a significant immediate decrease in CFR, which is attenuated 3 weeks later. The clinical impact of CFR changes following DTA endografting remain to be elucidated.

Changes in Coronary Flow Reserve Following Stent Implantation in the Swine Descending Thoracic Aorta

Changes in Coronary Flow Reserve Following Stent Implantation in the Swine Descending Thoracic Aorta

Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after β-blocker therapy in patients with idiopathic dilated cardiomyopathy

Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in these circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in patients with IDC. Eighteen patients with IDC underwent CFR measurements by transthoracic Doppler echocardiography at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 +/- 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as group A (LVEF change > or = 10%) and group B (LVEF change < 10%). Although there was no significant difference in CFR between the 2 groups at baseline, CFR was significantly higher in group A than in group B at 1 month of therapy (3.7 +/- 0.5 vs 2.5 +/- 0.9; P < .01). Coronary flow reserve change after 1 month was significantly greater in group A than in group B (1.3 +/- 0.6 vs 0.4 +/- 0.5; P < .01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up (P < .05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r = 0.65, P < .01). This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.

Improvement of myocardial blood flow by lipid‐lowering therapy with pravastatin is modulated by apolipoprotein E genotype

Objective. Apolipoprotein E (apoE) polymorphism affects the risk of advanced coronary artery disease, but its role in early atherosclerosis remains unknown. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to the apoE genotype. Material and methods. Samples from 44 mildly hypercholesterolaemic men (aged 35±4 years) of an earlier trial were re‐analysed according to apoE genotype. Subjects were randomized to receive either 40 mg/day pravastatin or placebo for 6 months. To assess coronary reactivity, myocardial blood flow was measured by PET at rest and during adenosine infusion. PET studies and lipid analyses were done at baseline and after 6 months of therapy. Results. There were no differences between apoE ϵ3/3 and ϵ4/3 genotypes in basal or adenosine‐stimulated flow or in coronary flow reserve (CFR) at baseline. There was a significant apoE genotype‐by‐treatment group interaction regarding the change in adenosine‐stimulated flow (ANCOVA; p = 0.018) and CFR (p = 0.020) at the end of the study. In the pravastatin group, the adenosine‐stimulated flow increased by 32.5 % in subjects with ϵ3/3 (n = 9), but decreased non‐significantly (−14.4 %) in subjects with ϵ4/3 (n = 9) (p = 0.0009). The corresponding changes in CFR were +17.8 % for ϵ3/3 and (−11.9 % for ϵ4/3 (p = 0.05). There were no significant changes from the baseline values in placebo recipients. After pravastatin treatment, both genotype groups showed a similar decrease in serum total and low‐density lipoprotein cholesterol (p<0.0001 for both). Conclusions. Coronary function improves by 6 months of pravastatin in subjects with the apoE ϵ3/3 genotype, but not in those with the ϵ4/3.

Effect of candesartan on coronary flow reserve in patients with systemic hypertension

Patients with hypertension have structural and functional changes in conductance and resistance vessels. In the absence of coronary stenosis the coronary microvascular function can be analysed by studying the coronary reserve. The aim of this study was to evaluate, non-invasively, the effect of candesartan on coronary microvascular function in hypertensive patients. Twenty-two hypertensive patients (> 40 years) without clinical coronary disease (age 63.86 +/- 10.3 years; women, 59.1%) were studied. In addition to blood pressure (BP), measurement of carotid intima-medial thickness (IMT), left ventricle mass index (LVMI) and the coronary flow reserve (CFR) were evaluated with echography at the beginning, and after 3 months of treatment with 16 mg/day of candesartan. Twelve hypertensive controls (64.50 +/- 10.8 years; women, 58.4%) completed the same study without any change in treatment. A 15% improvement in CFR (3.10 +/- 1.02 to 3.56 +/- 1.06; P = 0.001) was observed simultaneously with the BP reduction. There was no change in CFR in the control group (2.9 +/- 1.1 to 3.01 +/- 0.9; P = 0.23). The IMT was not modified significantly at the end of the follow-up (0.86 +/- 0.1 to 0.83 +/- 0.1 mm; P = 0.103). Candesartan improves the CFR in hypertensive patients. The improvement was not related to BP control or LVMI regression. Patients with a lower CFR show a better response to candesartan. This fact can be demonstrated non-invasively with echography after 3 months of therapy.

1132-160 Restenosis is better associated with change of coronary flow reserve rather than with absolute value of coronary flow reserve

1132-160 Restenosis is better associated with change of coronary flow reserve rather than with absolute value of coronary flow reserve

Changes in Coronary Flow Reserve Assessed by Transthoracic Echocardiography after Lipid-Lowering Therapy in Patients with Hypercholesterolemia

Background：The coronary flow reserve is known to be reduced in patients with hypercholesterolemia, and has also been reported to improve after lipid-lowering therapy. Using transthoracic Doppler echocardiography, the changes in the coronary flow reserve were evaluated after lipid-lowering therapy in hypercholesterolemic patients. Methods：The coronary flow reserve was determined by pulsed-wave Doppler examination at the distal left anterior descending coronary artery before and after five months of lipid-lowering therapy in 14 hypercholesterolemic patients (total cholesterol ≥230 mg/dL) with no other modifiable risk factors of coronary heart disease. Results：In all patients, the total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly decreased after therapy (from 273±27 mg/dL to 199±22 mg/dL, p=0.001, from 182±25 mg/dL to 110±27 mg/dL, p=0.001, respectively). However, there was no significant change in the coronary flow reserve after lipid-lowering therapy (from 2.4±0.5 to 2.5±0.5, p=0.875). The Baseline LDL-cholesterol showed an inverse correlation with the baseline coronary flow reserve (r =-0.649, p=0.012). Conclusions：In the present study, no significant change in the coronary flow reserve was noted after lipid-lowering therapy in hypercholesterolemic patients with no other risk factors of coronary heart disease, although the baseline LDL-cholesterol levels were found to correlate well with the baseline coronary flow reserve. Transthoracic Doppler echocardiography can be used to easily and non-invasively evaluate the changes in the coronary flow velocity, coronary flow reserve and other related parameters. Therefore, a controlled trial using transthoracic Doppler echocardiography relating to the effect of lipid-lowering therapy on patients showing a wider range of baseline risk factors and LDL

Early changes in coronary flow reserve of the culprit vessel after primary PTCA for acute myocardial infarction in patients with no regional contractile improvement at hospital discharge - relationship with viability Phillippe Garot, Olivier Pascal, Marc Simon, Emmanuel Teiger, Pascal Gu�ret, Jean-Luc Dubois-Rand�, Patrick Dupouy. Hopital Henri Mondor, Cr�teil, France

Early changes in coronary flow reserve of the culprit vessel after primary PTCA for acute myocardial infarction in patients with no regional contractile improvement at hospital discharge - relationship with viability Phillippe Garot, Olivier Pascal, Marc Simon, Emmanuel Teiger, Pascal Gu�ret, Jean-Luc Dubois-Rand�, Patrick Dupouy. Hopital Henri Mondor, Cr�teil, France

Effect of CABG on coronary flow reserve in atresia of the left coronary ostium

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.

Relation between Coronary Flow Reserve and Myocardial Perfusion State and Change of Coronary Flow Reserve in Acute Myocardial Infarction

Background and Objectives:The state of the coronary microcirculation is one of the major determinants of the prognosis of patients who have had successful reperfusion for acute myocardial infarction (AMI. We in- vestigated whether the vasodilatory reserve in the infarcted myocardium correlated with the perfusion state at early recovery phase in 12 anterior wall AMI patients. Materials and Method:We measured coronary flow variables with Doppler wire, after successful revascularizaiton by PTCA within 2 weeks following AMI and 13±0.5 months later, in the infarct related artery of AMI pts who received successful thrombolytic th- erapy. Myocardial perfuison state was evaluated by semiquantitative method (opacification score and opa- cification index with myocardial contrast echocardiography (MCE at the same time. Patients were divided into two groups according to initial perfusion status (perfusion defect group (PD (+ , n=7, no-perfusion defect group (PD(-, n=5. Results:10 minutes after completion of the intervention, the coronary flow reserve (CFR was 2.0±0.4 (mean±SD;it increased to 2.7±0.7 (p=0.002 at follow up. The difference of initial CFR was not significant between PD (+ and PD (- group. However, it significantly improved in the PD (- group compared to PD (+ group at follow up (3.19±0.39 vs. 2.39±0.7, p=0.046. Opacification index and initial CFR were significantly correlated (r=0.79, p<0.05. Conclusion:The perfusion state of infarcted myo- cardium was significantly correlated with coronary flow reserve in anterior wall AMI and CFR was significantly improved in patients with relatively preserved myocardial perfusion. (Korean Circulation J 1999;29(12 : 1289-1296

Effect of Long-term Eprosartan Versus Enalapril Antihypertensive Therapy on Left Ventricular Mass and Coronary Flow Reserve in Stage I-II Hypertension

SummaryA double-blind comparator study was performed in 528 hypertensive patients/baseline sitting diastolic blood pressure (SitDBP) 95–114mmHgl. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200–300 mg b.i.d.) or enalapril (5–20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 ± 0.3 and a decrease in CFR in the enalapril group to 1.3 ± 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Change of Coronary Flow Reserve in the Dogs: Influence of Atrial and Ventricular Pacing, Ventricular Preload and Afterload

Background and Objectives:The aim of this study was to analyze the influence of changes in ventricular preload and afterload, atrial and ventricular pacing on the coronary flow reserve (CFR). Method:Five open chest anesthetized dogs were studied in five sequential stages:baseline, saline solution volume loading (293.8± 29.2 ml for 10 min), atrial and ventricular pacing (120, 140, and 160 bpm), and aortic clamp. Coronary blood flow (CBF) was measured with electro-magnetic flowmeter. CFR was defined as the ratio of hyperemic CBF (hCBF) to resting CBF (rCBF). Hyperemia was induced by IV adenosine infusion (1 mg/kg/min). Results: 1) After volume loading wtih saline solution, CFR significantly decreased (p<0.05) because rCBF was increased while hCBF remained unchanged. 2) Atrial pacing produced increase in rCBF but did not change hCBF. Consequently CFR singificantly reduced when heart rate (HR) increased from sinus rhythm to 120, 140, and 160 bpm (p<0.01). 3) Ventricular pacing produced decrease in hCBF but did not change rCBF. Consequently CFR significantly reduced as HR increased from sinus rhythm to 120 (p<0.05) , 140 (p<0.01), and 160 (p<0.01) bpm. 4) After aortic clamp, CFR significantly decreased (p<0.01) because rCBF increased while hCBF remained unchanged. Conclusion:We found that CFR is dependent on the changes in volume loading, HR, and ventricular afterload that may commonly occur in clinical situations. (Korean Circulation J 1999;29(3):251-258)

Is atrial pacing needed for determination of coronary flow reserve by parametric imaging?

Heart rate changes during determination of coronary flow by parametric imaging may influence the flow measurement. Thus, the question is whether atrial pacing is mandatory for determination of coronary flow reserve (CFR) by this technique. CFR was calculated by digital subtraction angiography (parametric imaging) in 10 patients (8 with coronary artery disease and 2 control subjects) during sinus rhythm and during atrial pacing. Flow measurements were determined in the perfusion region of the left anterior descending and circumflex coronary artery, both at rest and after maximal coronary vasodilation with 10 mg intracoronary papaverine. CFR was defined as coronary flow during hyperemia divided by coronary flow at rest. Spontaneous heart rate was 71 ± 15 min −1 at baseline, 73 ± 15 min −1 after papaverine injection and 85 ± 10 min −1 during atrial pacing. Heart rate variations during coronary arteriography were 4 ± 3 min −1 at baseline and 5 ± 4 min −1 after papaverine administration. CFR was 2.61 ± 1.01 during sinus rhythm and 2.67 ± 1.05 during atrial pacing. Mean absolute difference in CFR between sinus rhythm and atrial pacing was 0.31 ± 0.31 (12 ± 10% of CFR during pacing). Spontaneous heart rate variations during coronary arteriography are not associated with significant changes in CFR. Thus, atrial pacing is not mandatory for the determination of CFR by parametric imaging.