Peripheral microcirculatory hemodynamic changes in patients with myocardial ischemia.

BACKGROUND: Patients with coronary heart disease demonstrate changes in skin microcirculation and a decrease in cutaneous blood mass. OBJECTIVE: The goal of this study was to assess the feasibility of diagnosing myocardial ischemia based on peripheral microcirculatory variables. METHODS: The skin microcirculatory measurements were monitored using an LPT system comprising a Laser Doppler Flowmeter (LDF), a photoplethysmograph (PPG) and a transcutaneous oxygen tension device (tc-PO2). Concurrently, heart rate and blood pressure were monitored. Measurements were performed before and after exercise stress test. Subjects were divided into ischemic (20) and nonischemic (27) patients based on myocardial perfusion imaging (MPI). RESULTS: The results indicate differences in LPT variables between ischemic and nonischemic patients following exercise, while no differences in the central variable values were observed between the two groups. CONCLUSIONS: Peripheral microcirculatory variables may be useful for non-invasive assessment of myocardial ischemia. The system has clinical potential for sensitive and noninvasive monitoring of vital variables during medical procedures in clinics, as well as in home care for patients who suffer from ischemic cardiac diseases.

Acute coronary syndromes are associated with a reduction of VLA-1+ peripheral blood T cells and their enrichment in coronary artery plaque aspirates.

Memory T cells producing interferon (IFN)γ and expressing very late antigen-1 (VLA-1) integrin collagen receptors are found in carotid atherosclerotic plaques, suggesting their involvement in coronary artery disease (CAD) as well. To determine the role of VLA-1+ T cells in CAD percent of CD3+ T cells binding monoclonal antibodies (mAb) to VLA-1 in peripheral blood (PB), and in coronary plaque material aspirated during coronary arterography and arterial blood, were analyzed in a cohort of 117 patients with CAD and 34 controls without CAD. % VLA-1+ T cells in PB was 0.63 ± 0.09% in controls compared to 0.96 ± 0.95% in patients with CAD (p<0.009). The increase was due to a marked elevation of % VLA-1+ T cells in stable CAD (1.6 ± 0.27%) whereas % VLA-1+ T cells during acute coronary syndromes (ACS) and in patients with ischemia by thalium SPECT scan had significantly lower levels. % VLA-1+ T cells in coronary artery plaque material aspirated during therapeutic angiography in patients with ACS was significantly higher than in arterial blood (1.39 ± 0.96% vs 0.75 ± 0.84%, p<0.035, n=3). Thus, % VLA-1+ T cells increases in the PB during stable CAD but decreases in ACS. The finding of their enrichment in coronary blood containing atherosclerotic plaque aspirates suggests that a shift of VLA-1+ T cells from blood to atherosclerotic plaques may play a role in plaque instability in patients with ACS.

Influence of attenuation correction on transient left ventricular dilation in dual isotope myocardial perfusion imaging in patients with known or suspected coronary artery disease.

The aim of this study was to assess the effect of attenuation correction (AC) on left ventricular (LV) volumes and LV transient ischemic dilatation (TID) during dual-isotope single-photon emission computer tomographic (SPECT) myocardial perfusion imaging (MPI). Ninety-six patients (mean age 58 ± 11 years, 15% women, 38 patients completed exercise and 58 dipyridamole pharmacologic stress tests) assessed for known or suspected coronary artery disease underwent dual-isotope thallium-201 rest and technetium-99m sestamibi stress SPECT MPI with computed tomography-based AC. The TID ratio was calculated separately for non-AC and AC SPECT MPI studies as the ratio of the LV endocardial volume at stress divided by LV endocardial volume at rest. The mean and range of the gated LV ejection fraction during exercise and pharmacologic stress was 54 ± 12% (29% to 80%) and 58 ± 12% (27% to 80%), respectively. In the exercise stress group, the same mean LV endocardial volumes in non-AC and AC stress (76.4 ± 30 and 76.5 ± 28) and rest (66.3 ± 26 and 66.4 ± 24) studies were found (p = 0.90). There was no statistical difference between the mean exercise TID ratio in non-AC and AC studies (1.27 vs 1.31, respectively, p = 0.10). The same mean LV endocardial volumes in non-AC and AC in pharmacologic stress (79.9 ± 42 and 80 ± 41) and rest (71.4 ± 41 and 72.3 ± 37), respectively, were found (p = 0.50). There was no statistical difference between the mean dipyridamole TID ratio in non-AC and AC studies (1.20 vs 1.17, respectively, p = 0.10). In conclusion, LV volumes and TID indexes obtained on SPECT MPI with exercise or pharmacologic stress using dipyridamole are not affected by AC.

Use of electrocardiographic depolarization abnormalities for detection of stress-induced ischemia as defined by myocardial perfusion imaging.

High-frequency mid-QRS (HFQRS) analysis was recently introduced as a tool for identification of stress-induced ischemia. The diagnostic performance of this electrocardiographic technique has not been determined in a large cohort of patients. This study compared the diagnostic performance of HFQRS analysis to conventional ST-segment analysis in detecting exercise-induced ischemia. The study included 996 patients (56 ± 10 years of age, 670 men) referred for exercise myocardial perfusion imaging (MPI), which served as the gold standard of ischemia. High-resolution electrocardiogram was used for computer analysis of HFQRS signals. Number of electrocardiographic leads with ≥50% decrease of HFQRS intensity (L(50%)) was used as an index of ischemia. Perfusion images were evaluated semiquantitatively. Receiver operating characteristic analysis demonstrated an L(50%) ≥3 as the criterion that yielded optimal sensitivity and specificity for diagnosing moderate/severe ischemia. Compared to ST-segment analysis HFQRS analysis was more sensitive (69% vs 39%, p <0.005) and more specific (86% vs 82%, p <0.05). L(50%) correlated with amount of MPI ischemia (R(2) = 0.75, p <0.0001). Multivariate logistic regression analysis demonstrated a significant incremental diagnostic value for the addition of HFQRS data to a model containing pretest and conventional exercise parameters. L(50%) was the best predictor of mild or moderate/severe MPI ischemia. In conclusion, computerized HFQRS analysis improved the diagnostic performance of conventional stress electrocardiogram in detecting exercise-induced ischemia. Thus, this technique might aid in the noninvasive evaluation of coronary artery disease.

Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease.

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, ß blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.

Effect of the metabolic syndrome and hyperuricemia on outcome in patients with coronary artery disease (from the Bezafibrate Infarction Prevention Study).

Hyperuricemia appears to be related to metabolic syndrome (MS), but its impact on cardiovascular risk in patients with MS is unclear. We evaluated the impact of hyperuricemia on cardiovascular risk in patients with MS. Of 2,963 patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention study, 1,410 had MS, as established by the presence of ≥3 of the following 5 criteria: serum fasting glucose >110 mg/dl, triglycerides >150 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic and diastolic blood pressures >130 and 80 mm Hg, respectively, and body mass index >28 kg/m². The remaining 1,553 patients had no MS. Primary end points were defined as occurrence of acute myocardial infarction or sudden cardiac death. Hyperuricemia was defined as serum uric acid levels >7.0 mg/dl in men and >6.0 mg/dl in women, respectively. Higher rate of primary end point was noted in hyperuricemic patients (n = 284) versus normouricemic patients (n = 1,126) with MS (20.1% and 15.3%, respectively, p = 0.05). After adjustment for age, gender, smoking, diabetes, previous myocardial infarction, hypertension, New York Heart Association classes II to IV, estimated glomerular filtration rate, body mass index, total cholesterol, triglycerides, diuretics, antiplatelets, angiotensin-converting enzyme inhibitors, ß blockers, and bezafibrate treatment, hyperuricemic patients with MS demonstrated significantly higher risk for the primary end point compared to normouricemic patients with MS (hazard ratio 1.45, 95% confidence interval 1.00 to 2.17, p = 0.05). In conclusion, hyperuricemia is associated with increased risk of myocardial infarction and sudden cardiac death in patients with MS.

Clinical predictors of stress-induced transient left ventricular dilatation in patients with nonsignificant coronary disease.

Left ventricular transient dilatation (TD) during stress myocardial perfusion imaging has been associated with extensive and severe coronary artery disease (CAD). The authors investigated the clinical predictors of TD in patients with nonsignificant CAD. The authors retrospectively studied 134 consecutive patients with exercise (n=59) or dipyridamole (n=75) stress-induced TD who had undergone coronary angiography within 6 months of the test. Significant CAD was defined as diameter stenosis ≥70% in at least one major coronary artery, and significant left main disease as >50% diameter stenosis. Angiographically-significant CAD was found in 126 patients (94%), and nonsignificant CAD in the remaining 8 patients (6%). No differences in gender, history of smoking, hyperlipidemia, family history of CAD, body mass index, and left ventricular ejection fraction were found between patients with significant and nonsignificant CAD. All 8 nonsignificant CAD patients had a history of either hypertension (7/8) or electrocardiographic criteria for left ventricular hypertrophy (1/8), compared with 58% of the hypertensive patients in the significant CAD group (P=.02). Nonsignificant CAD patients were also characterized by lack of diabetes mellitus (P=.05) or prior myocardial infarction (P=.05). Hypertension seems to be an important clinical predictor of TD in patients with nonsignificant CAD.

Fast track evaluation of patients with acute chest pain: experience in a large-scale chest pain unit in Israel.

BACKGROUND: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness. OBJECTIVES: To assess the routine evaluation of patients presenting to the ED with acute chest pain by means of a cardiologist-based chest pain unit using different noninvasive imaging modalities. METHODS: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography. RESULTS: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 444 patients underwent MDCT, 445 MPS, and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 +/- 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event. CONCLUSIONS: Utilization of the CPU enabled a rapid and thorough evaluation of the patients' primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.

Left ventricular ejection fraction assessment by Tl-201 gated SPECT: a comparison with echocardiography.

BACKGROUND: Few studies including only a limited number of patients have compared left ventricular ejection fraction (LVEF) assessed by 2-dimensional echocardiography (2-DE) and electrocardiography-gated Tl-201 single-photon emission computed tomography (SPECT). HYPOTHESIS: LVEF assessment by Tl-201 gated spect is comparable with LVEF assessed by 2-DE in two different echocardiographic laboratories. MATERIAL AND METHODS: Patients (n = 402) underwent Tl-201 gated SPECT in the same laboratory and 2-DE in 2 different laboratories. Patients were divided into 2 groups according to the study laboratory: group 1, at the tertiary hospital and group 2, at a community laboratory. RESULTS: LVEF evaluations were similar (mean LVEF: 50.73% +/- 11.67% by 2-DE vs 50.11% +/- 11.41% by SPECT in group 1 and 57.27% +/- 7.44% by 2-DE vs 57.41% +/- 8.37% by SPECT in group 2). All LVEF measurements were highly correlated (r = 0.7, P<.001). Baseline characteristics differed between the groups, with a higher prevalence of past myocardial infarction in the in-hospital vs the community echo group (46.7% vs 22.2%, P<.01), resulting in a higher LVEF in the latter, both by 2-DE (mean 50.7% +/- 11.7% vs 57.3% +/- 7.4%, P<.01) and SPECT (50.1% +/- 11.4% vs 57.4% +/- 8.4%, P<.01). CONCLUSIONS: The Tl-201 gated SPECT is a reliable clinical tool for LVEF assessment, with good correlation when compared to 2-DE. It may be routinely used as an alternative for patients with poor acoustic visualization and should be performed systematically in patients undergoing myocardial perfusion imaging with Tl-201.

Serum uric acid for risk stratification of patients with coronary artery disease.

OBJECTIVES: In patients with coronary artery disease (CAD), elevated serum uric acid (SUA) levels may predict worse cardiovascular outcomes. It is known that SUA levels are influenced by renal function. We aimed to assess the predictive value of SUA while taking into account patients' renal function. METHODS: The primary end point (PEP) risk, including fatal or nonfatal myocardial infarction (MI) or sudden death, was assessed by SUA quintiles before and after adjustment for the estimated glomerular filtration rate (eGFR) in 2,796 nondiabetic CAD patients enrolled in the Bezafibrate Infarction Prevention study. RESULTS: The PEP risk increased from the lowest (11.8%) to highest SUA quintile (18.0%), p < 0.005, respectively. After adjustment for age, sex, smoking, prior MI, metabolic syndrome variables, NYHA classes II-IV, heart rate and treatment with bezafibrate, diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers and antiplatelets, the highest SUA quintile exhibited the highest PEP risk [hazard ratio (HR): 1.47 (95% CI: 1.06-2.04)]. Patients in the highest - compared with those in the lowest - quintiles continued to demonstrate an increased PEP risk [HR: 1.46 (95% CI: 1.04-2.06)], even after additional adjustment for the eGFR. CONCLUSION: In nondiabetic patients with CAD, elevated SUA levels are associated with an increased risk of cardiac events, independent of renal function.

Usefulness of combining serum uric acid and C-reactive protein for risk stratification of patients with coronary artery disease (Bezafibrate Infarction Prevention [BIP] study).

Combined assessment of serum uric acid (UA) and C-reactive protein (CRP) compared with single-marker evaluation in patients with coronary artery disease (CAD) was performed. CRP is an independent predictor of cardiac events in patients with or without CAD. Data regarding the prognostic value of UA in patients with CAD are conflicting. The primary end point (fatal or nonfatal myocardial infarction or sudden cardiac death) was related to levels of UA and CRP in 2,966 patients with CAD enrolled in the Bezafibrate Infarction Prevention trial who were followed for a mean period of 6.2 years. Primary end-point rates were directly related to increasing tertiles (from tertile 1 [T1] to tertile 3 [T3]) of UA (12.7%, 12.8%, and 17.6% respectively, p for trend <0.0001) and CRP (11.5%, 14.2%, and 17.3% respectively, p for trend <0.002). By multivariable analysis, T3 UA (>6.25 mg/dl) and T3 CRP (>5.37 mg/dl) were shown to be independently associated with a significant increase in risk for the primary end point (hazard ratio 1.30, 1.01 to 1.68, p = 0.04; hazard ratio 1.31, 1.02 to 1.69, p = 0.03, respectively). Primary end-point rates were similarly high in those patients with a combination of T3 UA and T1 CRP levels (hazard ratio 1.68, 1.05 to 2.66) or a combination of T3 CRP and T1 serum UA levels (hazard ratio 1.64, 1.04 to 2.58) or in patients with T3 of the 2 markers (hazard ratio 1.66, 1.07 to 2.59). In conclusion, combined assessment of UA and CRP levels provides incremental information for risk stratification of patients with CAD with low levels of a single marker.

Usefulness of routine use of multidetector coronary computed tomography in the "fast track" evaluation of patients with acute chest pain.

Recently published American Heart Association/American College of Cardiology guidelines suggest that multidetector computed tomography (MDCT) may be appropriate for investigating acute chest pain (ACP). Only a few small studies have evaluated the use of MDCT in ACP, where it was not part of routine investigation. We sought to evaluate the routine use of MDCT in a large cohort of patients presenting with ACP in a real-world setting. We studied 785 consecutive patients with ACP who underwent evaluation by MDCT or myocardial perfusion scintigraphy after an observation period of > or = 12 hours. Patients with findings suggestive of significant coronary artery disease (CAD) were referred to coronary angiography. Forty-two patients were hospitalized due to evidence of myocardial ischemia and 44 patients were discharged after the observation period. Of the remaining 699 patients, 340 underwent MDCT and 359 myocardial perfusion scintigraphy. In 22 patients (7%) multidetector computed tomogram showed significant CAD and in 32 (9%) patients myocardial perfusion scintigram showed significant ischemia. Significant CAD was confirmed by coronary angiography in 65% and 60%, respectively. Multidetector computed tomogram was nondiagnostic in 31 patients (9%). Extracardiac findings that might be related to ACP and/or necessitated further investigation were demonstrated by multidetector computed tomogram in 71 patients (21%). During 3-month follow-up, 1 patient (0.3%) with negative multidetector computed tomographic and 9 (3%) with negative myocardial perfusion scintigraphic findings developed an acute coronary syndrome or died. Rehospitalization, due to recurrent chest pain, occurred in 9 patients (3.3%) and 21 patients (7.2%), respectively. In conclusion, MDCT could be an appropriate alternative to traditional noninvasive techniques for investigating ACP.

Quantitative analysis of echocardiographic cine-loops using a 2D-strain algorithm in correlation with thallium-201 SPECT imaging.

The aim of this study was to investigate the correlation between the regional left ventricular (LV) contractility, assessed by two-dimensional (2D)-strain echocardiographic images, and regional LV perfusion, determined by thallium-201 single photon emission computed tomography (SPECT) imaging. Forty-five hospitalized patients with suspected myocardial ischemia (32 males, mean age 69 +/- 12 years) have undergone both echocardiography and SPECT imaging on the same day. The echocardiographic data has been obtained in three apical views. The data for each view has been processed by the 2D-strain algorithm, to produce six peak systolic longitudinal strain measurements per view, one per segment. The resulting measurements have been compared with the corresponding regions within the SPECT bull's-eye map (at rest). In order to handle inaccuracies in the positioning of the echocardiographic transducer, the two datasets have undergone registration based on local correlation. The mean correlation coefficients between SPECT perfusion and peak systolic longitudinal strain for the apical long-axis, apical two-chamber, and apical four-chamber views were 0.55 +/- 0.36, 0.47 +/- 0.35, and 0.64 +/- 0.30 respectively (negative correlation coefficients have been considered as zero). The overall mean correlation coefficient was 0.56 +/- 0.34. The scatter graphs of the average values of perfusion and the strain values showed a nonlinear relation between the two parameters. The average correlation coefficient is comparable to the values reported for the correlation between the average LV function, based on visual analysis of echocardiographic imaging, and the average LV perfusion, based on SPECT imaging.

Stress-induced ST-segment elevation in patients without prior Q-wave myocardial infarction.

BACKGROUND: Stress-induced ST-segment elevation is an uncommon finding that usually occurs in patients with prior myocardial infarction (MI). Our purpose was to assess the angiographic and clinical significance of this finding in patients without prior MI. METHODS: Of the 29002 consecutive ambulatory patients who underwent stress myocardial perfusion imaging over a 5-year period, 205 (0.7%) developed stress-induced ST-segment elevation, of whom 39 (19%) had no Q-wave MI in leads showing ST-segment elevation during either exercise (n = 31) or dipyridamole (n = 8) stress myocardial perfusion imaging. All 39 patients were hospitalized and underwent coronary angiography. RESULTS: Significant coronary artery disease was found in all 39 patients: 87% had critical (>or=90%) stenosis, and 59% had multiple vessel disease. During hospitalization, 37 patients (95%) underwent revascularization. CONCLUSIONS: In patients without prior Q-wave MI, stress-induced ST-segment elevation is associated with critical coronary artery disease. Therefore, these patients should be considered for early coronary investigation.

The intensive statin therapy myth.

Statins play an important role in the treatment and prevention of coronary artery disease and atherosclerosis. Currently, however, despite its important qualities, the use of statin therapy in the treatment of CAD patients ranges only between 30 and 60% in Europe, the United States and Israel. A wide gap still exists between the numerous scientific publications demonstrating the beneficial effects of statins and the low rate of implementing the guidelines in practice. A Medline search up to June 2005 on all prospective, double-blind, randomized clinical trials evaluating the impact of intensive statin therapy (any statin dose >40 mg/daily) on clinical outcomes after a 1 year follow-up revealed only eight trials. In all the eight trials, with a follow-up period of 12-60 months, intensive statin therapy was significantly more effective than and at least as safe as placebo or other standard statin regimens. Thus, based on the current evidence-based medicine, intensive statin therapy enables more patients with CAD to achieve the current National Cholesterol Education Program goal for low density lipoprotein, while ensuring a relatively high safety profile.

The assessment of infarct size in postmyocardial infarction patients undergoing thallium-201 tomographic imaging is improved using attenuation correction.

PURPOSE: Attenuation correction (ATC) has been shown to improve the accuracy of thallium-201 single photon emission computed tomography (SPECT) for the detection and evaluation of patients with coronary artery disease. The purpose of this study was to evaluate the value of ATC for the assessment of infarct size in patients after myocardial infarction (MI). MATERIALS AND METHODS: Tl-201 SPECT with ATC was performed on 39 patients with 49 previous MIs. This was followed by radionuclide ventriculography for the assessment of global and regional left ventricular function. Uncorrected and corrected 24-hour redistribution SPECT images were analyzed for regional perfusion using a 5-point segmental scoring scale from 0 (normal) to 4 (absent) thallium uptake. RESULTS: The mean number of segments with scores of >1 and 2 was significantly higher without ATC than with ATC (5.3 +/- 3.6 vs. 3.5 +/- 3.6, P = 0.0001 for scores >1; 3.8 +/- 3.6 vs. 2.5 +/- 3.0, P = 0.0001 for scores of >2, respectively). The mean total number of segments with scores of >1 assessed without ATC was significantly higher compared with that assessed with ATC (16.9 +/- 13.5 vs. 11.2 +/- 12.2, P = 0.0001). Evaluation without ATC demonstrated only a fair correlation between the SPECT parameters (number of segments with scores of >1 and >2, and total score of segments with scores of >1) and left ventricular regional and global function, whereas there was a clear improvement in all the parameters after ATC. With ATC, a decrease in infarct size was demonstrated in 27 of the 49 infarcts (55%). CONCLUSIONS: The improved correlation with left ventricular function indicates that SPECT imaging with ATC provides a more accurate assessment of infarct size in post-MI patients. The use of nonattenuation-corrected SPECT imaging overestimates infarct size in a majority of patients.

External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris.

OBJECTIVES: The goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD). BACKGROUND: In patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described. METHODS: We prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 +/- 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound. RESULTS: External counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 +/- 2.1%, p = 0.01), compared with controls (3.1 +/- 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 +/- 2.8% vs. 10.2 +/- 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 +/- 2.7 nitrate tablets vs. 0.4 +/- 0.5 nitrate tablets, p <0.001 and 4.5 +/- 2.3 nitrate tablets vs. 4.4 +/- 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 +/- 0.5 vs. 1.9 +/- 0.3, p <0.0001 and 3.3 +/- 0.6 vs. 3.5 +/- 0.5, p = 0.89, respectively). CONCLUSIONS: External counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism.

Noninvasive detection of collateral flow to the infarct-related coronary artery in patients after myocardial infarction by Tl-201 tomographic imaging.

BACKGROUND: The determination of viability and perfusion within the infarct zone in post-myocardial infarction patients has both therapeutic and prognostic significance. Reversibility of thallium 201 uptake within the territory of the infarct-related coronary artery (IRA) as shown by single photon emission computed tomography (SPECT) is associated with a jeopardized but viable myocardium. We aimed to test the hypothesis that for post-myocardial infarction patients undergoing Tl-201 stress-redistribution SPECT, a scintigraphic pattern of distal reversibility without proximal reversibility within a defect corresponding to the IRA territory is a marker of collateral flow to the occluded culprit artery. METHODS AND RESULTS: We assessed Tl-201 SPECT imaging results of 78 patients with IRA occlusion as demonstrated by angiography 7 +/- 1 months after myocardial infarction. Angiography demonstrated the presence of collateral flow in 57 patients and its absence in 21 patients. Distal reversibility was present in 42 of the 57 patients with collateral flow (sensitivity, 74%) and was absent in 16 of the 21 patients without collateral flow (specificity, 76%). Collateral flow to the IRA was demonstrated in 42 of 47 patients with distal reversibility (group A) (positive predictive value, 89%) and absent in 16 of 31 patients with a fixed defect without reversibility (group B) (P <.001) (negative predictive value, 52%). CONCLUSIONS: In patients after myocardial infarction, a Tl-201 SPECT redistribution pattern of distal reversibility without proximal reversibility within a defect in the IRA territory is a noninvasive marker of collateral flow to the culprit artery with a high positive predictive value that may provide valuable information on patient management. A larger prospective study in an unselected patient population is needed to further evaluate the clinical value of this marker.

Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution.

BACKGROUND: Systemic delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI). METHODS AND RESULTS: BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4x10(6)) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow. CONCLUSIONS: Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.