Intracoronary Doppler Research Articles

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium

Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ((111)In-oxine). Radiolabeled proangiogenic progenitor cells (7.6+/-3.0 MBq, mean+/-SD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by (18)F-fluorodeoxyglucose-positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9+/-4.7% (range, 1% to 19%; n=17) of total radioactivity was detected in the heart, which declined to 2+/-1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (<or=14 days; 6.3+/-2.9%; n=8) and progressively decreased in patients treated in an intermediate phase (>14 days to 1 year; 4.5+/-3.2%; n=4) or a chronic stage (infarct age >1 year; 2.5+/-1.6%; n=5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant (P<0.05) predictors of proangiogenic progenitor cell homing. In patients after myocardial infarction undergoing intracoronary infusion of (111)In-oxine-labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve.

L‐Arginine preferentially dilates stenotic segments of coronary arteries thereby increasing coronary flow

Oxidized LDL cholesterol and cytokines increase arginase and decrease nitric oxide (NO) synthase expression in human endothelial cells, leading to a decrease in NO production. In arteriosclerotic plaques, characterized by increased oxidized LDL and cytokine levels, a sustained local NO reduction might enhance sensitivity of the downstream guanylyl cyclase system towards an acute NO increase. We tested whether application of the NO synthase substrate l-arginine (l-arg, 150 micromol min(-1)) or the NO donor isosorbide dinitrate (ISDN; 0.3 mg) preferentially dilates stenotic coronary artery segments (CS) subsequently increasing poststenotic coronary blood flow (CBF) in patients with coronary artery disease (CAD). Changes in coronary diameter and circumferential surface area were assessed by quantitative coronary angiography (QCA) in a nonstenotic upstream segment, the CS, downstream the CS and in a reference vessel (n = 24). CBF was estimated in a subset of 13 patients by QCA and intracoronary Doppler. CS ranged from 62% to 89% (77 +/- 5%). l-arg increased minimal luminal diameter of the stenotic segment from 0.98 +/- 0.06 to 1.14 +/- 0.07 mm (P < 0.05) without affecting other coronary segments. Poststenotic CBF increased by 24 +/- 3%. ISDN dilated all segments again with a predominance of CS (25 +/- 4%) and increased poststenotic CBF by 38 +/- 9%. In a multifactorial anova, a medication with an angiotensin-converting enzyme inhibitor (decreasing inflammation and radical formation) and a ratio of LDL/HDL <3.5 were predictive for an l-arg-induced dilation. The increase in poststenotic CBF without affecting nondiseased arteries highlights the therapeutic potential of l-arg in patients with CAD.

Myocardial Bridging in Absence of Coronary Artery Disease: Proposal of a New Classification Based on Clinical-Angiographic Data and Long-Term Follow-Up

Background: There is no widely accepted classification to guide therapy in patients with symptomatic myocardial bridging (MB). Methods: A retrospective analysis of 157 patients with chest pain, angiographic MB of the left anterior descending artery without obstructive coronary artery disease (CAD) was performed. Patients were evaluated for clinical symptoms, objective signs of ischemia by stress test, intracoronary Doppler flow measurement and coronary flow reserve. 100 patients without CAD or MB served as controls. Results: There was no difference in clinical symptoms and objective signs of ischemia between controls and patients with MB. The length of MB was 22.6 ± 7.8 mm, maximal systolic luminal diameter reduction 71 ± 16%, and maximal mid-diastolic luminal reduction 34.7 ± 13% as demonstrated by quantitative coronary angiography (QCA). Intracoronary Doppler showed significantly increased average peak flow velocity (APV), average systolic peak velocity (ASPV), average diastolic peak flow velocity (ADPV), and maximal peak velocity (MPV) in MB versus proximal and distal segments at rest and after maximal vasodilatation (p < 0.001 for all parameters). Coronary flow reserve was significantly higher proximally (2.9 ± 0.9) compared with segments distal to the MB (2.0 ± 0.6, p < 0.01). We propose a new MB classification for symptomatic patients with MB:Type A:incidental finding on angiography, no objective signs of ischemia; Type B: objective signs of ischemia, and Type C: with or without objective signs of ischemia and altered intracoronary hemodynamics (by QCA/CFR/intracoronary Doppler). 5-Year follow-up data based on this classification showed that types B and C responded well to β-blockers or calcium channel antagonists. Patients with type C refractory to medical therapy were treated with stenting of the MB. Conclusion: Patients with MB without CAD did not have a higher prevalence of chest pain or abnormal non-invasive stress tests compared to patients without CAD or MB. Intracoronary hemodynamic measurement is a novel approach that may be valuable in defining the functional significance of MB. We propose a classification of symptomatic patients with MB without CAD using non-invasive and invasive parameters to guide therapeutic choices.

Relation Between the Assessment of Microvascular Injury by Cardiovascular Magnetic Resonance and Coronary Doppler Flow Velocity Measurements in Patients With Acute Anterior Wall Myocardial Infarction

We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. Twenty-seven patients with first anterior ST-segment elevation MI successfully treated with primary PCI were included. Coronary blood flow velocity was measured during recatheterization 4 to 8 days after primary PCI. These measurements were related to MO determined by late gadolinium-enhanced (LGE) CMR performed the day before recatheterization. Early systolic retrograde flow was observed in 0 of 8 patients without MO on LGE CMR and in 10 (53%) of 19 patients with MO (p = 0.01). The extent of MO correlated with the diastolic-systolic velocity ratio (r = 0.44; p = 0.02), diastolic deceleration time (r = -0.61; p = 0.001), diastolic deceleration rate (r = 0.75; p < 0.0001), and coronary flow velocity reserve of the infarct-related artery (r = -0.44; p = 0.02). Furthermore, multivariate regression analyses, including extent of MO, infarct size, and transmural necrosis on LGE CMR, revealed that extent of MO was the only independent factor related to early systolic retrograde flow and diastolic deceleration rate. Assessment of microvascular injury by LGE CMR corresponds well to evaluation by intracoronary Doppler flow measurements. By means of CMR, quantification of myocardial function, infarct size, and microvascular injury can accurately be performed with a single noninvasive technique in patients with acute MI.

Windkesselness of coronary arteries hampers assessment of human coronary wave speed by single-point technique

A novel single-point technique to calculate local arterial wave speed (SPc) has recently been presented and applied in healthy human coronary arteries at baseline flow. We investigated its applicability for conditions commonly encountered in the catheterization laboratory. Intracoronary pressure (P(d)) and Doppler velocity (U) were recorded in 29 patients at rest and during adenosine-induced hyperemia in a distal segment of a normal reference vessel and downstream of a single stenosis before and after revascularization. Conduit vessel tone was minimized with nitroglycerin. Microvascular resistance (MR) and SPc were calculated from P(d) and U. In the reference vessel, SPc decreased from 21.5 m/s (SD 8.0) to 10.5 m/s (SD 4.1) after microvascular dilation (P < 0.0001). SPc was substantially higher in the presence of a proximal stenosis and decreased from 34.4 m/s (SD 18.2) at rest to 27.5 m/s (SD 13.4) during hyperemia (P < 0.0001), with a concomitant reduction in P(d) by 20 mmHg and MR by 55.4%. The stent placement further reduced hyperemic MR by 26% and increased P(d) by 26 mmHg but paradoxically decreased SPc to 13.1 m/s (SD 7.7) (P < 0.0001). Changes in SPc correlated strongly with changes in MR (P < 0.001) but were inversely related to changes in P(d) (P < 0.01). In conclusion, the single-point method yielded erroneous predictions of changes in coronary wave speed induced by a proximal stenosis and distal vasodilation and is therefore not appropriate for estimating local wave speed in coronary vessels. Our findings are well described by a lumped reservoir model reflecting the "windkesselness" of the coronary arteries.

Comparison of Accuracy in the Prediction of Left Ventricular Wall Motion Changes Between Invasively Assessed Microvascular Integrity Indexes and Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Patients With ST-Elevation Myocardial Infarction

We compared the accuracy in predicting regional wall motion score index (RWMSI) changes between microvascular integrity indexes measured during primary percutaneous coronary intervention (PCI) and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in ST-elevation myocardial infarction (STEMI). Fifty patients with STEMI were enrolled. Microvascular integrity indexes were measured using an intracoronary Doppler wire and a pressure wire after primary PCI. We performed FDG-PET 7 days after PCI. RWMSI on follow-up echocardiogram (5.8 +/- 1.7 months) revealed good correlations with coronary flow reserve (r = -0.442, p = 0.002), diastolic deceleration time (r = -0.511, p <0.001), microvascular resistance index (r = 0.443, p = 0.002), coronary wedge pressure (r = 0.474, p <0.001), and FDG uptake rate (r = -0.571, p <0.001). There were no significant differences in areas under the curve for predicting RWMSI changes between microvascular integrity indexes and FDG-PET (coronary flow reserve 0.696, diastolic deceleration time 0.731, microvascular resistance index 0.748, coronary wedge pressure 0.694, Thrombolysis In Myocardial Infarction myocardial perfusion grade 0.702, and FDG-PET 0.755). In conclusion, microvascular integrity indexes assessed during primary PCI are useful and comparable to FDG-PET in predicting left ventricular functional changes in STEMI.

Hibernating Myocardium

See related article, pages 103–112 Winter hibernation carries the promise of rejuvenation in the spring. In a similar fashion, myocardial “hibernation” describes a clinical phenomenon in which patients with ischemic left ventricular dysfunction demonstrate improved cardiac function following bypass surgery.1 The signature of myocardial hibernation is decreased blood flow with preserved glucose uptake, as demonstrated by positron emission tomography imaging, and identifies individuals with ischemic cardiomyopathy who may benefit from revascularization.2 In experimental models of hibernating myocardium, oxygen consumption is reduced in the absence of active ischemia.3,4 This implies that hibernation is a coordinated response to balance myocardial energy utilization with energy production capacity.5 However, within hibernating myocardium, several morphological and functional changes have been observed that can identify regions in which complete revascularization may not result in normalization of contraction.6–10 In fact, those myocardial regions with the greatest metabolic abnormalities in the hibernating tissue demonstrate the longest delay in recovery.11 In the current issue, Page et al12 demonstrate that the process of hibernation is associated with altered expression of mitochondrial proteins. Using 2D differential-in-gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry in a swine model of hibernation, they have found that key mitochondrial proteins associated with the electron transport chain are reduced. The functional importance of the decreased protein expression is documented by reduced activity measurements of the pyruvate dehydrogenase complex, cytochrome c oxidase, and citrate synthase. The parallel reductions in mitochondrial proteins and contractile function 5 months after placement of the coronary artery constrictor suggest that the “downregulation” of electron transport proteins is related to the reduced oxygen consumption. In fact, the reductions in ATPase correlate with the reduction in subendocardial blood flows in the hibernating myocardium. In addition, “upregulation” of several cytosolic proteins has been observed, including …

Correlation Between the Serum Bilirubin Level and the Coronary Microvascular Integrity in Diabetic Patients

Background and Objectives: Bilirubin has a protective role in suppressing atherosclerosis and coronary artery disease by its potent physiological antioxidant properties. There has been no comparative study on the relation between the bilirubin level and the coronary microvascular function in diabetic patients. This study investigated whether the bilirubin level correlates with the coronary microvascular integrity in diabetes by assessing the coronary flow velocities after successful percutaneous coronary intervention (PCI). Subjects and Methods: Fifty patients (31 males and 19 females, mean age 60±11) with angina and who received elective PCI were studied. Using an intracoronary Doppler wire, the coronary flow velocity reserve (CFR), the hyperemic microvascular resistance index and the phasic coronary flow velocity patterns were measured after PCI. Results: The mean value of the fasting blood glucose was 211±88 mg/dL, the man value of glycated hemoglobin A1c (HbA1c) was 8.1±1.6% and the mean serum total bilirubin level was 0.59±0.21 mg/dL. CFR was significantly correlated with the serum bilirubin level (r=0.485, p<0.001), HbA1c (r=-0.432, p=0.003) and the fasting blood glucose (r=-0.361, p=0.011). On multivariate analysis, HbA1c, bilirubin and left ventricular hypertrophy showed independent relationships with coronary microvascular dysfunction (p=0.003, p=0.004, p=0.033, respectively). Conclusion: These results suggest that glycemic control and elevated serum bilirubin may protect diabetic patients from coronary microvascular dysfunction. (Korean Circ J 2008;38:425-431)

Abstract 699: Intracoronary Infusion Of Bone Marrow-derived Progenitor Cells In Patients With Non-ischemic Dilated Cardiomyopathy Is Associated With An Increase Of Coronary Blood Flow In The Target Vessel

We recently could demonstrate that intracoronary administration of bonemarrow-derived progenitor cells (BMC) is associated with improved target area contractility and enhanced cardiac function in patients (pts) with nonischemic dilated cardiomyopathy (DCM). The influence of coronary microvascular dysfunction on development and progression of DCM in the absence of epicardial artery atherosclerosis has been demonstrated in experimental studies. Therefore, to get insights into potential mechanisms of BMC therapy in pts with DCM, we performed a substudy of the TOPCARE-DCM trial, assessing coronary blood flow (CBF) by intracoronary Doppler measurements. Methods 13 pts (age 31 to 64 yrs; ejection fraction 28 ± 14 %) were included. A mean number of 353 ± 119 * 10 6 BMC were infused into the left anterior descending (LAD) artery using the stop-flow technique. Doppler-derived CBF velocities in the target (LAD) as well as in a reference vessel (left circumflex artery, ref) were obtained at baseline prior to BMC administration and at 3 months’ angiographic follow up (FU). Results Heart rate, blood pressure and coronary artery lumen diameter did not differ between initial and FU measurements. Basal coronary vascular resistance (VR) decreased after 3 months in the target and in the ref vessel (target 6.32 ± 2.43 vs 5.43 ± 2.28, p &lt; 0.01; ref 6.72 ± 2.15 vs 5.41 ± 1.94 mmHg*s/cm, p = 0.03). In contrast, adenosine-induced minimal VR decreased only in the target vessel but not in the ref vessel (target 1.53 ± 0.60 vs 1.31 ± 0.65, p &lt; 0.01; ref 1.60 ± 0.45 vs 1.49 ± 0.45 mmHg*s/cm, p = ns). Due to the selective decrease in adenosine-induced minimal VR of the target vessel, the coronary flow reserve normalized for the ref vessel increased from 1.0 ± 0.2 to 1.2 ± 0.3 (p &lt; 0.05). Likewise, the CBF increased in the target vessel (from 48 ± 18 to 62 ± 25 ml/min, p = 0.02), but remained unchanged in the ref vessel (from 40 ± 21 to 48 ± 18 ml/min, p = ns). Conclusions In pts with nonischemic DCM, intracoronary BMC infusion is associated with a significant improvement in microvascular function of the target area. Whether improved microvascular function as a potential mechanism underlying the beneficial effects of BMC is causally linked to an improved cardiac contractile function has to be analysed in larger studies.

Abstract 3339: Effects of Atorvastatin 10 mg versus 40 mg in Eight Months Follow-up Coronary Flow Reserve and Clinical Events in Patients with Acute Myocardial Infarction

Background: Circulating bone marrow-derived stem cells are capable of homing to sites of myocardial infarction and endothelial disruption, thereby restoring myocardial function and microvascular integrity after acute myocardial infarction. We compared the effects of atorvastatin 10 mg versus 40 mg in follow-up clinical events and in restoring coronary flow reserve (CFR) during the 8 months follow-up in patients with acute myocardial infarction. Methods: CFR, which is reflective of the integrity of coronary microvasculature, was measured by using intracoronary Doppler wire in 102 consecutive patients with acute myocardial infarction 5 days after the successful primary coronary intervention with sirolimus-eluting stents. Stented patients were randomly assigned to either atorvastatin 10 mg (ATOR10, n=52) or atorvastatin 40 mg (ATOR40, n=50). All patients received aspirin and clopidogrel. Clinical events such as death, myocardial infarction, and target lesion revascularization (TLR) were compared during the 8-month follow-up. Results: CFR increased significantly in both groups during the 8 months follow-up (1.9 ± 0.6 at baseline vs. 2.6 ± 0.7 at follow-up in the ATOR10, p&lt;0.05; 1.9 ± 0.7 at baseline vs. 2.9 ± 0.8 at follow-up in the ATOR40, p&lt;0.05). The changes from baseline in CFR was greater in the ATOR40 Group compared with the ATOR10 Group (1.0 ± 0.8 vs. 0.7 ± 0.6, p&lt;0.05, respectively). The numbers of CD34+ and CXCR4+ cells were significantly greater in the ATOR40 Group compared with the ATOR10 Group (13 ± 10 vs. 6 ± 6, p&lt;0.05, respectively for CD34 cells and 15 ± 14 vs. 10 ± 9, p&lt;0.05, respectively for CXCR4+ cells per 1uL). Clinical events such as death (0 patient in the ATOR10 vs. 2 patients in the ATOR40, p=0.247), myocardial infarction (2 patients in the ATOR10 vs. 1 patient in the ATOR40, p=0.557), and TLR (2 patients in the ATOR10 vs. 2 patients in the ATOR40, p=0.692) demonstrated no significant differences during the follow-up. Conclusion: The increases from baseline in CFR, CD34+ cells and CXCR4+ cells were significantly greater in the ATOR40 Group compared with the ATOR10 Group. However, the improvement in left ventricular systolic function and the rate of clinical events revealed no significant differences between the 2 groups.

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

BackgroundIn 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.MethodsTwenty 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.ResultsLV 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. ConclusionIn 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.

Acute decrease of coronary flow after indomethacin delivery in newborn lambs

To document the effects of indomethacin (IND) on coronary flow. We studied nine premature lambs during the first day of life. The gestational age varied between 132 and 134 days (term 145 days) and weight 3.1-4.7 kg. Coronary flow velocities were recorded with an intracoronary Doppler guide wire in the proximal left anterior descending coronary artery (LAD). Average peak flow velocity was measured before, during and after an intravenous IND injection of 0.2 mg per kilogram of body weight. IND increased systemic blood pressure (p < 0.05) and rate pressure product (RPP; p < 0.05) indicating that IND increased cardiac workload. IND decreased coronary average peak flow velocity in all lambs (p < 0.05). The maximal fall in coronary velocity appeared after 3 min (range 1-7 min) and was regained 10 min (range 4-53 min) after the drug delivery. The maximal reduction of coronary average peak flow velocity was 52% (median 26). The recovery time was directly related to the maximal reduction of the coronary average peak flow velocity (R = 0.91, R(2) 0.84, p < 0.002). Coronary flow velocity decreased markedly in premature born lambs given a bolus dose of IND.

Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction

The Doppler Substudy of the randomized, double-blind, placebo-controlled Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial aimed to investigate the effects of intracoronary infusion of bone marrow-derived progenitor cells (BMCs) on coronary blood flow regulation in patients with reperfused acute myocardial infarction. In a total of 58 patients (BMC group, n=30; placebo group, n=28), coronary flow reserve (CFR) in the infarct artery and a reference vessel was assessed by intracoronary Doppler at the time of study therapy (4.2+/-0.1 days after acute myocardial infarction) and at the 4-month follow-up. Initial CFR was reduced in the infarct artery compared with the reference vessel in both groups (BMC: 2.0+/-0.1 versus 2.9+/-0.2, P<0.05; placebo: 1.9+/-0.1 versus 2.8+/-0.2; P<0.05). At the 4-month follow-up, CFR in the infarct artery had slightly improved in the placebo group (+0.88+/-0.18; P<0.001 versus initial) but was markedly increased by 90% (+1.80+/-0.25; P=0.005 versus placebo) in BMC-treated patients, resulting in a normalization of CFR (3.8+/-0.2; P<0.001 versus initial and placebo at 4 months). In the infarct vessel, adenosine-induced minimal vascular resistance index declined slightly in the placebo group (from 1.77+/-0.12 to 1.52+/-0.15 mm Hg x s/cm; P<0.05) but considerably decreased by -29+/-6% in the BMC group (from 1.86+/-0.19 to 1.20+/-0.12 mm Hg x s/cm; P<0.05 versus initial and placebo at 4 months). Intracoronary BMC therapy after acute myocardial infarction restores microvascular function of the infarct-related artery, which is associated with a significant improvement in maximal vascular conductance capacity. These data provide clinical proof of concept that progenitor cell transplantation promotes vascular repair.

Examination of the Microcirculation Damage in Smokers Versus Nonsmokers With Vasospastic Angina Pectoris

Endothelial dysfunction is considered one of the mechanisms underlying vasospastic angina pectoris (VSA). It is also known that smokers have abnormalities in endothelial dysfunction. Although smoking is a major risk factor for coronary artery disease, microvascular abnormalities have not been well shown. We investigated clinical characteristics and coronary reactivity with adenosine triphosphate in smokers with VSA. Twenty-two consecutive patients whose coronary spasm was documented in the left anterior descending (LAD) coronary artery with acetylcholine were enrolled. Coronary blood flow responses were also evaluated by intracoronary Doppler flow velocity recordings in the LAD coronary artery. Average peak velocities (APVs) were measured at baseline and intracoronary administration of adenosine triphosphate (50 microg) in 11 smokers (age 60+/-9 years; 8 men) and 11 nonsmokers (age 61+/-10 years, 5 men). Coronary flow reserve (CFR) was calculated by the ratio of baseline to hyperemic APV. Multivessel spasm was demonstrated in 6 smokers and only 2 nonsmokers (p<0.05). APV at rest in smokers (13.4+/-3.0 cm/s) was similar to that in nonsmokers (13.5+/-2.9 cm/s). However, CFR in smokers (2.6+/-0.7) was significantly lower than in nonsmokers (3.4+/-0.8; p<0.05). In conclusion, multivessel spasm was demonstrated in smokers in clinical settings, and microcirculation damage is prominent in smokers with VSA.

On the paradox of exercise: coronary atherosclerosis in an apparently healthy marathon runner

An asymptomatic and apparently healthy 64-year-old marathon runner underwent comprehensive cardiovascular risk assessment as part of a prospective study on calcified coronary plaque burden in master marathon runners. His profile suggested a low 10-year cardiovascular risk. Conventional risk-factor assessment, coronary artery calcium quantification, bicycle stress test, echocardiography, coronary angiography, intravascular ultrasonography, including virtual histology, and intracoronary Doppler ultrasonography. Severe coronary atherosclerosis of the left anterior descending, mid left circumflex, and left main arteries. Stenting of the left anterior descending artery, CABG surgery, and intensive risk-factor modification. The patient was also advised against participating in future marathon competitions.

Distal left circumflex coronary artery flow reserve recorded by transthoracic Doppler echocardiography: a comparison with Doppler-wire

BackgroundCoronary flow reserve (CFR) recording by means of transthoracic echocardiography (TTDE) in all the main distal coronary arteries is a challenge for advanced echocardiography. Validation studies of TTDE versus Doppler-wire (DW) recordings are available for Left Anterior Descending artery (LAD) and the Posterior Descending coronary artery (PD), but lacking for the more technically challenging Left Circumflex coronary artery (LCx).AimTo evaluate the reliability of TTDE in assessing CFR in LCx when compared to the intracoronary Doppler flow-wire gold standard.Methodswe evaluated 5 patients (age = 60 ± 9 years, 5 males) on LCx by TTDE and invasive CFR assessment. TTDE recording was performed using a low-frequency probe, with a four-chamber as a guiding 2D view. The 2 tests were performed on different days and in random order within 48 hours in a blind fashion. Vasodilator stimulus was adenosine, intravenously (140 γ/kg/min × 3–6 min) for TTDE and intracoronary (40 γ bolus) for DW recordings.ResultsCFR values on LCx ranged from 1.9 to 2.8 for DW, and from 2.0 to 3.0 for TTDE, with an overall correlation of R = 0,85 (p = 0,06); normal (CFR > 2.5) or abnormal (CFR < 2.5) value was concordantly identified by the 2 techniques in 4 out 5 cases (80%).ConclusionCFR of LCx artery can be obtained noninvasively with TTDE.

Gender Differences in the Treatment for Acute Myocardial Infarction

Accumulating evidence over the last several decades regarding the treatment and outcomes for coronary artery disease reveals disparities that have a clear relationship to gender. It had previously been thought that these differences were related to gender bias in physicians’ approach to treatment; thus, the term Yentl syndrome was coined in 1991.1 As the volume of literature expanded and clinical studies included more women, it became clear that outcomes after treatment for coronary artery disease, particularly acute myocardial infarction, were different for women compared with men. Women have a well-documented higher mortality after acute myocardial infarction.2 Much of this disparity has been attributed to differences in age and attendant comorbidities. Female patients with coronary artery disease typically are older, have a higher prevalence of risk factors, and have a lower functional status than their male counterparts.3,4 Additionally, women appear to be at higher risk than men when diabetes, hypertriglyceridemia, and metabolic syndrome are present. The underuse of revascularization procedures in women has been suggested as an explanation, but it has not been uniformly demonstrated to explain increases in mortality. Some studies have suggested a link to less aggressive hospital care of female patients, including the underuse of revascularization, as an explanation for their increased mortality.5 Other studies have indicated age and comorbidity as the primary factors leading to mortality differences.6 Still other studies suggest no evidence of undertreatment.7,8 Article p 833 Gender differences in the clinical outcome of patients with acute myocardial infarction may be explained in part by the female status. Several conditions found only in women hint at differences in the pathophysiology of ischemic vascular disease between the sexes. Such female-specific conditions include early menopause, gestational diabetes, peripartum vascular dissection, preeclampsia and eclampsia, polycystic ovarian syndrome, low-birth-weight children, and hypothalamic hypoestrogenemia. Several …

Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease

Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease (IHD) by interfering with physiological regulation of coronary tone. To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting, we measured the effect of an acute oxidative stress (breathing 100% oxygen) on coronary capacitance artery diameter (quantitative angiography) and blood flow velocity through the coronary microcirculation (intracoronary Doppler ultrasonography) before and after treatment with the antioxidant vitamin C (3-g intravenous infusion) in 12 IHD patients undergoing a clinical coronary interventional procedure. Relative to room air breathing, 100% oxygen breathing promptly reduced coronary blood flow velocity by 20% and increased coronary resistance by 23%, without significantly changing the diameter of capacitance arteries. Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level, and it prevented the reinduction of coronary constriction with rechallenge with 100% oxygen. This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD, and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation. This observation may have relevance for clinical practice.

Issue Highlights

HomeCirculationVol. 115, No. 5Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published6 Feb 2007https://doi.org/10.1161/circ.115.5.547Circulation. 2007;115:547ASSOCIATIONS OF GESTATIONAL AGE AND INTRAUTERINE GROWTH WITH SYSTOLIC BLOOD PRESSURE IN A FAMILY-BASED STUDY OF 386 485 MEN IN 331 089 FAMILIES, by Lawlor et al.Many previous studies have provided support for the fetal origins of disease. Investigators have hypothesized that fetal undernutrition contributes to poor growth and programs individuals for hypertension in later life. Skeptics have raised concerns, however, that studies supporting the developmental origins hypothesis may reflect residual confounding by socioeconomic factors. Lawlor and colleagues took advantage of Swedish birth and military service registries of 386 485 singleton-born men from 331 089 families to study the associations of birth weight and gestational age with subsequent systolic blood pressure at age 17 to 19 years. The investigators report that birth weight was inversely associated with systolic blood pressure; per 1-SD difference in birth weight, there was a −0.21 mm Hg difference in siblings, whereas nonsiblings had −0.12 mm Hg lower systolic blood pressure. They also observed that increasing gestational age was inversely associated with young adult systolic blood pressure. By taking advantage of a large unique sibling data set, the Lawlor et al study suggests that the link between gestational age, lower birth weight, and adult blood pressure does not merely reflect confounding by socioeconomic status. See p 562.EFFECTS OF NORMAL BLOOD PRESSURE, PREHYPERTENSION, AND HYPERTENSION ON CORONARY MICROVASCULAR FUNCTION, by Erdogan et al.Coronary flow reserve (CFR) has been shown to be impaired in patients with hypertension. Left ventricular hypertrophy contributes, but other mechanisms likely contribute as well. Prehypertension is also associated with an increased cardiovascular morbidity and mortality. Whether prehypertension is associated with impaired CFR is less well studied. The study by Erdogan et al in this issue of Circulation evaluated CFR using transthoracic Doppler echocardiography before and after intravenous dipyridamole infusion. CFR was significantly lower in hypertensive patients than in prehypertensive and normal patients, but prehypertension was also lower than in normal patients. Both hypertension and prehypertension were significant predictors of a lower CFR in a multivariable model. Other factors included systolic and diastolic blood pressure, high-sensitivity C-reactive protein levels, left atrial diameter mitral E deceleration time, and mitral A velocity. These findings are consistent with the concept that mildly elevated blood pressure is associated with abnormal coronary flow response, although the degree of impairment is less than in hypertension. See p 593.DETECTION OF CORONARY MICROEMBOLIZATION BY DOPPLER ULTRASOUND IN PATIENTS WITH STABLE ANGINA PECTORIS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTIONS, by Bahrmann et al.During percutaneous coronary intervention, mechanical disruption of the atherosclerotic plaque by balloon inflation may result in embolization of particles to the microvasculature, resulting in increased postprocedural troponin and high-sensitivity C-reactive protein levels. Mechanistic studies have found that once coronary microvascular occlusion occurs, this leads to ventricular contractile dysfunction. Interestingly, this phenomenon was attributed to an inflammatory reaction and not a decrease in blood flow. Previous studies have shown that an intracoronary Doppler guide wire is able to detect, and quantify, in real time, microemboli that are released by percutaneous coronary intervention. In this issue of Circulation, Bahrmann et al extend these findings to demonstrate the relationship between percutaneous coronary intervention–induced coronary microembolization and postprocedural increases in myocardial necrosis and inflammation. See p 600.Visit http://circ.ahajournals.org:Clinician UpdateApical Ballooning Syndrome: An Important Differential Diagnosis of Acute Myocardial Infarction. See p e56.Images in Cardiovascular MedicineLeft Ventricular Aneurysm Associated With Mucopolysaccharidosis Type VI Syndrome (Maroteaux–Lamy Syndrome). See p e60.Tricyclic Cardiotoxicity Treated With Sodium Bicarbonate. See p e63.An Unusual Cause of Hand Cellulitis. See p e65. Download figureDownload PowerPointCorrespondenceSee p e67. Previous Back to top Next FiguresReferencesRelatedDetails February 6, 2007Vol 115, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.115.5.547 Originally publishedFebruary 6, 2007 PDF download Advertisement

Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

Intracoronary Doppler guidewires can be used for real-time detection and quantification of microembolism during percutaneous coronary interventions (PCIs). We investigated whether the frequency of Doppler-detected microembolism is related to the incidence of myonecrosis during elective PCI. The study population included 52 consecutive patients (aged 64+/-10 years; 36 men, 16 women) with coronary artery disease who underwent elective PCI of a single-vessel stenosis. Using intracoronary Doppler ultrasound, we compared the frequency of microembolism during PCI in 22 patients with periprocedural non-ST-segment elevation myocardial infarctions (pNSTEMI) and 30 patients without pNSTEMI. The 2 groups were comparable with regard to their clinical and procedural characteristics. In the group with pNSTEMI, the total number of coronary microemboli after PCI (27+/-10 versus 16+/-8, P<0.001) was higher than in the group without pNSTEMI. Although high-sensitivity C-reactive protein plasma levels were similar before PCI (2.9+/-2.2 versus 3.4+/-1.7 mg/L, P=NS), they were higher in the group with pNSTEMI after PCI (12.6+/-10.4 versus 6.1+/-5.1 mg/L, P<0.05). Microembolic count independently correlated to postprocedural cardiac troponin I elevation (r=0.565, P<0.001), coronary flow velocity reserve (r=-0.506, P<0.001), and baseline average peak velocity (r=0.499, P<0.001). Patients with pNSTEMI had a significantly higher frequency of coronary microembolization during PCI, and their systemic inflammatory response and microvascular impairment after PCI were more pronounced. Intracoronary Doppler ultrasound provides evidence that pNSTEMI in patients undergoing elective PCI is caused by microembolization during the procedure.