C-reactive protein,clinical presentation,and ischemic activity in patients with chest pain and normal coronary angiograms

OBJECTIVES: We sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA). BACKGROUND: Patients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients. METHODS: We studied 137 consecutive CPNCA patients (mean age, 57 +/- 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry. RESULTS: C-reactive protein levels (mg/l) were higher in patients with frequent (2.9 +/- 3.3) and prolonged (3.9 +/- 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 +/- 2.8) and Holter monitoring (3.4 +/- 3.1) compared with patients with occasional (1.3 +/- 1.2; p = 0.002) or shorter chest pain (1.5 +/- 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 +/- 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 +/- 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = -0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2). CONCLUSIONS: The hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.     

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.     

Differences in heart rate turbulence between patients with coronary artery disease and patients with ventricular arrhythmias but structurally normal hearts

The term "heart rate turbulence" (HRT) indicates the physiologic changes in the sinus cycle that follow a ventricular premature complex; impaired HRT denotes abnormalities in cardiac autonomic function. To investigate whether HRT is impaired in patients with stable coronary artery disease (CAD), we studied 29 patients with documented CAD and frequent (>/=30/hour) ventricular premature complexes on Holter monitoring and 31 patients with frequent ventricular arrhythmias but normal hearts (NH-VA). HRT and heart rate variability analyses were analyzed on 24-hour Holter recordings. HRT variables differed significantly between the 2 groups (turbulence onset -0.20 +/- 1.7% vs -0.67 +/- 2.2%, p = 0.00001; turbulence slope 2.83 +/- 1.9 vs 10.83 +/- 7.4 ms/RR, p = 0.0001 in patients with CAD and NH-VA, respectively). The difference was independent of a history of previous myocardial infarction, left ventricular function, and age. Top quartile turbulence onset values (>-0.26%) and bottom quartile turbulence slope values (<2.12 ms/RR) had similar predictive power in discriminating between patients with CAD and NH-VA (positive predictive value 86.7%, negative predictive value 64.4% for both). Among heart rate variables, bottom quartile SD of all RR intervals values (<96.3 ms) only had the same power of HRT variables in discriminating between patients with CAD and NH-VA. Thus, our data show that HRT variables are impaired in patients with CAD patients versus those with NH-VA, indicating abnormalities in the control of short-term cardiac autonomic mechanisms resulting in decreased vagal activity with likely predominant sympathetic activity.     

Left ventricular diastolic pressure-volume relations during exercise (author's transl)

Left ventricular diastolic pressure-volume relations (PVR) were analysed from biplane ventriculograms and simultaneous pressure measurements in 33 patients at rest (R) and during ergometer exercise (E) (8 normals [N], 8 patients with coronary artery disease [CAD], 8 patients with congestive cardiomyopathy [COCM], 5 patients with aortic insufficiency [AI] and 5 patients with pressure overload (4 with aortic stenosis [A-St.] and 1 coarctation of the aorta). In N and AI diastolic PVR was essentially unchanged with E, the time constant of isovolumic relaxation (T) decreased significantly (N: delta T = -24.4 +/- 11.6%, p less than 0.001; AI: delta T = -27.3 +/- 6.8%, p less than 0.005). In CAD diastolic PVR was shifted upwards in all cases with angina pectoris during E (7/8), minimal rate of left ventricular pressure change (dp/dtmin) and T did not change significantly. In COCM diastolic PVR was shifted upwards in 4 cases, while dp/dtmin increased significantly (R = -1107 +/- 327, E = -1508 +/- 626 mm Hg-s-1, p less than 0.05), T on the average was unchanged (R = 53 +/- 10.5, E = 51 +/- 14.2 msec). In A-St. in 3 of 4 cases diastolic PVR was significantly shifted upwards with E, dp/dtmin increased (R = -1633 +/- 93, E = -2093 +/- 170 mm Hg-s-1, p less than 0.001), T in contrast to N and AI was prolonged (R = 33.8 +/- 4, E = 39.9 +/- 1.9 msec). Conclusion: In N and AI diastolic ventricular function is not altered with exercise. In COCM and especially in A-St., however, there are similar alterations like in CAD with angina pectoris. Changes in T indicate that shifts of the PVR with exercise in non-ischemic heart disease are related to a disturbed ventricular relaxation.     

Ischemia at rest is independent of the extent of ventricular dysfunction and arrhythmias in patients with coronary artery disease

To assess the relation between myocardial ischemia, ventricular arrhythmias (VA), and left ventricular (LV) dysfunction, we evaluated 74 patients with coronary artery disease (CAD) using radionuclide angiography (to determine the resting ejection fraction [EF]), resting thallium-201 scintigraphy (to ascertain the extent of resting ischemia), and 24-hour Holter monitoring (to assess VA). Thirty patients had resting ischemia, 26 had resting EF less than 30%, and 27 had repetitive VA. Patients with and without ischemia had similar EFs (36 +/- 14 vs 38 +/- 14, p = NS). Further, patients with and without repetitive forms of VA had a similar number of resting ischemic segments (1.1 +/- 1.7 vs 1.1 +/- 2.2, p = NS). Patients with EFs less than 30 had more VA than patients with EFs greater than or equal to 30 (Holter class 4.3 +/- 2.3 vs 3.0 +/- 1.8, p less than 0.01) but a similar extent of ischemia (1.4 +/- 2.2 vs 1.0 +/- 1.7, p = NS). Thus, while patients with lower EFs have more repetitive forms of VA, ischemia at rest is independent of VA and EF. These data suggest that prognostic stratification of patients with CAD for intervention studies should include a separate consideration of ischemia.     

The effect of vardenafil,a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction,on the cardiovascular response to exercise in patients with coronary artery disease

OBJECTIVES: The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD). BACKGROUND: Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation. METHODS: In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety. RESULTS: Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived. CONCLUSIONS: Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS).     

Usefulness of exercise electrocardiography and thallium scintigraphy in unstable angina pectoris in predicting the extent and severity of coronary artery disease

The safety and efficacy of exercise electrocardiography and thallium scintigraphy early in the course of unstable angina pectoris were assessed 4.6 +/- 1.6 days after admission in 67 patients with unstable angina that stabilized after medical therapy. Coronary arteriography was performed in all patients 5.4 +/- 2.4 days after admission. There was no difference in clinical, exercise or scintigraphic variables between patients with stenoses less than 50% and patients with 1-vessel coronary artery disease (CAD) defined as a diameter stenosis greater than or equal to 50%. Patients with 3-vessel CAD had a significantly shorter exercise duration than patients with less than 50%-diameter narrowing (5.5 +/- 2.2 vs 8.3 +/- 3.3 minutes, respectively), lower exercise heart rate (119 +/- 20 vs 149 +/- 22 beats/min) and systolic blood pressure (156 +/- 29 vs 166 +/- 33 mm Hg), more frequent chest pain (76 vs 20%) and more pronounced ST depression (-1.48 +/- 1.37 vs -0.33 +/- 0.72 mm). In addition, thallium defect size on exercise was greater in the patients with 2-vessel CAD (159 +/- 132 degrees) and 3-vessel CAD (255 +/- 132 degrees) than in patients with no CAD (28 +/- 319 degrees) or 1-vessel CAD (73 +/- 78 degrees), p greater than or equal to 0.05. Multiple regression analysis demonstrated that thallium defect size was the best predictor of extent of CAD, with exercise heart rate and presence of chest pain during exercise also predictive of extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise, lipids, and lipoproteins in older adults: a meta-analysis

The authors used the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in adults 50 years of age and older. Twenty-eight outcomes representing 1427 subjects (806 exercise, 621 control) were available for pooling. Random-effects modeling yielded statistically significant improvements of 1.1%, 5.6%, 2.5%, and 7.1%, respectively, for total cholesterol (mean +/- SEM in mg/dL, -3.3+/-1.7; 95% confidence interval [CI], -6.5 to -0.02; p=0.05), high-density lipoprotein cholesterol (2.5+/-1.0; 95% CI, 0.7-4.4; p=0.01), low-density lipoprotein cholesterol (-3.9+/-1.9; 95% CI, -7.7 to -0.08; p=0.05), ratio of total cholesterol to high-density lipoprotein cholesterol (-0.8+/-0.2; 95% CI, -1.2 to -0.4; p<0.001), but not triglycerides (-7.0+/-3.6; 95% CI, -14.0 to 0.1; p=0.06). After conducting sensitivity analyses, only the improvements in high-density lipoprotein cholesterol and the ratio of total cholesterol to high-density lipoprotein cholesterol remained statistically significant (p<0.05 for both). It was concluded that aerobic exercise increases high-density lipoprotein cholesterol and decreases the ratio of total cholesterol to high-density lipoprotein cholesterol in older adults.     

Significance of plasma nitric oxide/endothelial-1 ratio for prediction of coronary artery disease

Vascular tone is regulated by vasodilators and vasoconstrictors. Endothelin-1 (ET-1) is the predominant vasoconstrictor peptide that constricts vascular smooth muscle, whereas nitric oxide (NO) is the primary vasodilator peptide that relaxes vascular smooth muscle. In this study, the authors examined whether NO/ET-1 ratio is a useful marker for detecting coronary artery disease (CAD), by comparison with evaluation based on vascular endothelial (VE) function. They measured plasma NOX and ET-1 by using ENO-200 and radioimmunoassay, in 38 subjects with normal (NL) coronary arteries (NL group; mean age, 60 +/-12 years) and 25 subjects with CAD (CAD group; mean age, 69 +/- 6 years). VE function (randomized endothelium-dependent [D] and endothelium-independent [I] VE function) was assessed by measuring brachial artery (BA) diameter by using high-resolution ultrasound (7.5 MHz). Soon after these procedures, symptom-limited exercise testing was performed. There were no statistically significant differences in serum lipid concentrations or VED function between the groups. However, the CAD group had a significantly lower NO/ET-1 ratio (1.2 +/- 1.1 vs 2.7 +/- 2.2, p < 0.01) and BA diameter after sublingual nitroglycerin (VEID function: 6 +/- 7% vs 10 +/- 4%, p < 0.05). As expected, the ST segment and treadmill exercise duration were significantly lower in the CAD group. Sensitivity and specificity for detecting CAD by plasma NO/ET-1 ratio (> or =2 .0) were 90% and 85%, respectively; sensitivity and specificity for detecting CAD by ST depression (> or =1 mm) were 80% and 78%, respectively. The present results suggest that plasma NO/ET-1 ratio is a useful biological marker for predicting CAD.     

Factor V G1691A,Prothrombin G20210A,and Methylenetetrahydrofolate Reductase [MTHFR] C677T Gene Polymorphism in Angiographically Documented Coronary Artery Disease

BACKGROUND: Single point mutations in the genes coding for factor V [G1691A; Leiden], prothrombin [PRT; G20210A], and methylenetetrahydrofolate reductase [MTHFR, C677T] were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of coronary artery disease [CAD] remains controversial. The aim of the study was to examine the association of these mutations in CAD. METHODS: A total of 96 patients with angiographically-demonstrated CAD [mean age 55.3 +/- 11.3], and 404 healthy subjects [mean age 50.7 +/- 8.9] were recruited into the study. Fasting plasma homocysteine was determined by HPLC, and genotype analysis was assessed by PCR-RFLP. RESULTS: The carrier frequency of factor V-Leiden (14.6% vs. 15.1%, p = 0.617) and PRT G20210A (3.1% vs. 3.0%; p = 0.936) were similar between patients and controls, respectively. In contrast, the frequency of the MTHFR variant C677T was 71.9% among patients compared with 45.5% in controls (p < 0.001), of which the T/T genotype was significantly higher among patients (31.3%) than controls (4.5%; p < 0.001). Significantly higher homocysteine levels were seen among T/T genotype in both groups compared to non-T/T carriers (p < 0.05), and among patients compared with controls (18.47 +/- 3.73 micromol/L vs. 16.28 +/- 4.16 micromol/L). In addition, the coexistence of MTHFR C677T with FV-Leiden was seen in 10.4% of CAD patients compared 6.9% of controls (p = 0.001). CONCLUSION: While results from this study clearly demonstrate a strong association of hyperhomocysteinemia and homozygosity of the MTHFR C677T, but not FV-Leiden or PRT G20210A, mutations with confirmed CAD, they also suggest a potential role for factor V-Leiden in MTHFR C677T carriers.     

Differential coronary calcification on electron-beam CT between syndrome X and coronary artery disease in patients with chronic stable angina pectoris.

STUDY OBJECTIVES: The differential diagnosis of syndrome X and coronary artery disease (CAD) in patients with evidence of myocardial ischemia may be difficult. The possible difference in coronary calcium detected by electron-beam CT (EBCT) between syndrome X and CAD is rarely evaluated, especially in aged patients with chronic, stable angina. DESIGN AND SETTINGS: Prospective, controlled study at a tertiary referral medical center. PATIENTS AND MEASUREMENTS: Forty patients with syndrome X (85% male) and 53 patients with CAD (89% male) were enrolled. Ten control subjects (90% male) with negative exercise treadmill test results and normal coronary angiographic findings served as control subjects. EBCT determined the coronary calcium scores (CCSs), and standard cardiovascular risk factors of all study subjects were analyzed. RESULTS: The 93 study patients had CCSs that ranged from 0 to 1,857. Coronary calcification was seen in 2 of the 10 control subjects (20%), 21 of the 40 syndrome X patients (52.5%), and 51 of the 53 CAD patients (96.2%) [p < 0.01]. The CCS (median [range]) was significantly lower in syndrome X patients than in CAD patients: 1 (0 to 117) vs 202 (0 to 1,857) [p < 0.001]. Receiver operating characteristic curve analyses also demonstrated that coronary calcification differentiated syndrome X from CAD (area under curve, 0.891; 95% confidence interval, 0.806 to 0.947). Of the CAD patients whose CCSs were < 117 and overlapped with CCSs of syndrome X, multivariate analyses determined CCS > 5 (odds ratio, 13.1; 95% confidence interval, 2.86 to 59.7), hypertension (odds ratio, 6.4; 95% confidence interval, 1.5 to 27.4), and hypercholesterolemia (odds ratio, 6.7; 95% confidence interval, 1.5 to 30.5) to be independent discriminators to differentiate CAD from syndrome X. Patients with CAD had more frequent hypertension than patients with syndrome X. CONCLUSIONS: The coronary calcium detected noninvasively by EBCT was different, though with some overlapping, between patients with syndrome X and CAD. In addition to standard cardiovascular risk factors, CCS determined by EBCT (especially > 117 or = 0) could differentiate between syndrome X and CAD in patients with chronic, stable angina with evidence of myocardial ischemia. Larger trials would be useful to validate CCS on EBCT as a predictor of clinical outcome in these patients.     

Long-term treatment of stable angina pectoris with gallopamil]

BACKGROUND. The effects of long-term treatment with gallopamil 50 mg t.i.d were assessed in 8 patients, 7 males and 1 female, aged 47-69 years, with stable angina pectoris, positive exercise tests, coronary artery disease and no previous myocardial infarction. METHODS. Clinical and ECG parameters as well as exercise testing, 24-hour Holter and echocardiography were assessed before treatment, after 3 months, after 1 and 2 years of treatment, and following final wash-out. RESULTS. Comparing each treatment period to baseline, a significant decrease in resting heart rate (from 66 +/- 9 beats/min at baseline to 56 +/- 7 beats/min after 3 months [p < 0.01], 59 +/- 8 beats/min after 1 year [p < 0.05] and 58 +/- 9 beats/min after 2 years [p < 0.05]), systolic (from 162 +/- 19 mmHg at baseline to 147 +/- 12 mmHg after 3 months [p < 0.05], 146 +/- 20 mmHg after 1 year [p < 0.01] and 146 +/- 27 mmHg after 2 years [p < 0.05]), and diastolic (from 89 +/- 6 mmHg to 82 +/- 7 after 3 months [p < 0.05], 82 +/- 4 after 1 year [p < 0.05] and 83 +/- 4 after 2 years [p < 0.05]) blood pressure was observed. Exercise time significantly improved (from 596 +/- 209 seconds to 802 +/- 66 seconds after 3 months [p < 0.01], 710 +/- 167 seconds after 1 year [p < 0.05] and 723 +/- 125 seconds after 2 year [p < 0.05]), while heart rate and rate-pressure product at peak exercise did not change. The number of ischemic episodes and the total ischemic time per 24 hours significantly decreased (from 35 +/- 15 min to 12 +/- 10 min after 3 months [p < 0.05], 10 +/- 8 min after 1 year [p < 0.05] and 11 +/- 9 min after 2 years [p < 0.05]). Ejection fraction increased (from 66 +/- 10% to 77 +/- 7% after 3 months [p < 0.01], 80 +/- 5% after 1 year [p < 0.01] and 80 +/- 3% after 2 years [p < 0.01]), while contractility, as expressed by the end-systolic stress/end systolic volume ratio remained unchanged. No serious side-effects or biochemical abnormalities developed. CONCLUSIONS. Gallopamil appears to be safe, well tolerated and effective in the long term control of angina pectoris; its effects are fully developed at 3 months and persist unchanged after 2 years. For its hypotensive action and the lack of significant effects on myocardial contractility, gallopamil appears to be potentially useful in patients with associated angina and hypertension and in patients with impaired left ventricular function.     

Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls

Physical and mental stressors result in increased inflammation markers in populations free of coronary artery disease (CAD). However, inflammatory responses to mental and exercise challenges have not been established in patients with CAD. This study investigated the responses of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1, in patients with CAD after successful elective percutaneous coronary intervention (n = 36, 59 +/- 8 years of age, 33% women) and healthy controls without a history of CAD (n = 28, 54 +/- 10 years of age, 36% women). Increases in inflammatory markers were examined in response to mental challenge tasks (anger recall and mental arithmetic) and treadmill exercise. Stress echocardiography was used to rule out stress-induced ischemia as a possible confounding factor. Results showed that CRP increased significantly to mental challenge and exercise (p values <0.01), and CRP responses were higher in patients with CAD than in controls (change in mental arithmetic 0.19 +/- 0.11 vs 0.01 +/- 0.03 mg/L, p = 0.003; change in exercise 0.57 +/- 0.11 vs 0.08 +/- 0.0.03 mg/L, p = 0.001). Increased norepinephrine responses were related to larger CRP and IL-6 increases to mental challenge tasks (p values <0.05). Exercise elicited increased CRP, IL-6, and soluble intercellular adhesion molecule-1 levels (p values <0.01), and these responses were larger than with mental challenge tasks (p values <0.05). In conclusion, mental stress and exercise induce increased levels of inflammatory markers in patients with CAD. These stress-induced increases are larger than in healthy subjects, occur in the absence of myocardial ischemia, and are related to the neurohormonal stress response.     

Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis

Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction.     

Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension

OBJECTIVE: To determine whether lipid microspheres containing prostaglandin E1 (lipo-PGE1) improve pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension (PAH). METHODS: Forty-nine patients with PAH (8 patients with primary pulmonary hypertension, 21 patients with collagen vascular disease, 20 patients with congenital systemic-to-pulmonary shunts) were randomly classified into a conventional therapy group (n = 22) or a group receiving lipo-PGE1 plus conventional drugs (lipo-PGE1 group; n = 27). Echocardiographic pulmonary parameters, New York Heart Association (NYHA) functional class, and Bruce treadmill test results for exercise capacity were recorded before and after treatment. RESULTS: After 2 weeks of treatment with lipo-PGE1 (10 microg bid for 14 days), there were significant improvements in the values (+/- SD) for systolic pulmonary arterial pressure (SPAP) [76.9 +/- 27.9 mm Hg vs 66.5 +/- 22.8 mm Hg, p < 0.001]; total pulmonary resistance (27.2 +/- 13.3 dyne.s.cm(-5) vs 20.2 +/- 10.7 dyne.s.cm(-5), p < 0.001); left ventricular ejection fraction (58.7 +/- 9.6% vs 64.4 +/- 6.8%, p < 0.001); and cardiac output (3.1 +/- 0.8 L/min vs 3.7 +/- 1.1 L/min, p < 0.01). The NYHA functional class decreased from 3.0 +/- 0.6 to 2.5 +/- 0.6 (p < 0.001), and the exercise capacity increased from 2.8 +/- 1.0 to 4.3 +/- 1.3 metabolic equivalents (MET) [p < 0.001]. Compared with the conventional therapy group, the lipo-PGE(1) group achieved significant reduction of SPAP (10.4 +/- 10.3 mm Hg vs 2.2 +/- 5.6 mm Hg, p = 0.002) and a significant elevation of exercise capacity (1.5 +/- 0.9 MET vs 0.6 +/- 1.1 MET, p = 0.018). CONCLUSION: Lipo-PGE1 can decrease pulmonary artery pressure and increase exercise capacity in patients with PAH.     

Residual stress ischaemia is associated with blood markers of myocardial structural remodelling

BACKGROUND: Long-term prognosis of coronary artery disease (CAD) patients is worsened when stress ischemia persists on treatment, but the relationship with adverse cardiac remodelling had never been investigated. AIM: To analyze changes in blood markers of fibrosis in patients with chronic CAD exhibiting exercise ischaemia. METHODS: Circulating markers of collagen: (i) turnover (amino-terminal propeptide of collagen-III [PIIINP]) and (ii) degradation (matrix metalloproteinase 1 [MMP-1]), were obtained in 139 CAD patients referred for exercise 201Tl-SPECT. RESULTS: In the 57 patients who had SPECT-ischaemia, PIIINP was higher (4.3+/-2.9 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.002) and MMP-1 lower (3.8+/-2.1 microg L-1 vs. 4.7+/-2.8 microg L-1, p=0.04) than in the 82 patients without SPECT-ischaemia. PIIINP was independently related to LV volume, SPECT-ischaemia and age, whereas MMP-1 was related to current treatment with ACEI and beta-blockers (p<0.05). In the 104 patients with a normal LV ejection fraction, only PIIINP was related to SPECT-ischaemia (4.1+/-2.2 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.01). CONCLUSION: In patients with chronic CAD, exercise ischaemia is associated with increased collagen-III turnover, independently of concomitant medications and even when LV ejection fraction is normal. Long-term, this increase might relate to adverse cardiac remodelling even when cardiac function is not clearly affected at baseline.     

Functional and prognostic significance of exercise-induced ventricular arrhythmias in patients with suspected coronary artery disease

Our aims were to assess (1) the relation between exercise-induced ventricular arrhythmia (VA) and myocardial wall motion abnormalities during exercise echocardiography in patients with suspected coronary artery disease (CAD), and (2) the effect of this relation on outcome. We studied the clinical and prognostic significance of exercise-induced VA in 1,460 patients (mean age 64 +/- 10 years; 867 men) with intermediate pretest probability of CAD and no history of previous myocardial infarction or revascularization who underwent exercise echocardiography. Exercise-induced VA occurred in 146 patients (10%). Compared with patients without VA, those with VA had a greater prevalence of abnormal exercise echocardiographic findings (48% vs 29%, p = 0.001) and ischemia on exercise echocardiography (39% vs 22%, p = 0.001), greater increase in wall motion score index with exercise (0.14 +/- 0.28 vs 0.06 +/- 0.18, p <0.0001), and a greater percentage of abnormal segments with exercise (21 +/- 30% vs 9 +/- 19%, p <0.0001). During follow-up (median 2.7 years), cardiac death and nonfatal myocardial infarction occurred in 36 patients. In multivariate analysis of combined clinical and exercise stress test variables, independent predictors of cardiac events were exercise-induced VA (chi-square 4.7, p = 0.03) and exercise heart rate (chi-square 18, p = 0.0001). The percentage of abnormal myocardial segments with exercise echocardiography was the most powerful predictor of VA (chi-square 31, p = 0.0001) and cardiac events (chi-square 15, p = 0.0001). In patients with suspected CAD, exercise-induced VA is associated with a greater risk of cardiac death and nonfatal myocardial infarction. This risk is attributed to the relation between VA and the extent and severity of left ventricular functional abnormalities with exercise.     

Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries

STUDY OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINC) is a life-threatening event with many open questions for physicians and patients. There are little data concerning the prognosis for patients with MINC. DESIGN: Retrospective follow-up study. SETTING: Tertiary referral center. PATIENTS: Patients with MINC were investigated and compared to age- and sex-matched control subjects with myocardial infarction due to coronary artery disease (CAD). The patients were examined clinically using stress exercise and hyperventilation tests. Migraine and Raynaud's symptoms were determined by means of a standardized questionnaire. Serum lipoproteins; the seroprevalence of cytomegalovirus, Helicobacter pylori, and Chlamydia pneumoniae infections; and the most frequent causes of thrombophilia were assessed. Measurements and results: From > 4,300 angiographies that were performed between 1989 and 1996, 21 patients with MINC were identified. The mean +/- SD patient age at the time of myocardial infarction was 42 +/- 7.5 years. When compared to control subjects (n = 21), patients with MINC had fewer risk factors for CAD. In contrast, MINC patients had more frequent febrile reactions prior to myocardial infarction (six patients vs zero patients; p < 0.05), and the migraine score was significantly higher (7.1 +/- 6.3 vs 2.2 +/- 4.1; p < 0.01). The seroprevalence of antibodies against cytomegalovirus, C pneumoniae, and H pylori tended to be higher in patients with MINC and CAD as compared to matched healthy control subjects. Three patients with MINC vs none with CAD had coagulopathy. During follow-up (53 +/- 37 months), no major cardiac event occurred in the MINC group; no patients with MINC vs nine with CAD (p = 0.0001) underwent repeated angiography. CONCLUSION: High migraine score and prior febrile infection together with a lower cardiovascular risk profile are compatible with an inflammatory and a vasomotor component in the pathophysiology of the acute coronary event in MINC patients. The prognosis for these patients is excellent.     

Exercise training enhances endothelial function in young men

OBJECTIVES: The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND: Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. METHODS: We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN; an endothelium-independent dilator), using high-resolution external vascular ultrasound. RESULTS: At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/-6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise program. CONCLUSION: Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease.     

Catheter-based percutaneous myocardial laser revascularization in patients with end-stage coronary artery disease

OBJECTIVES: This study evaluates the feasibility and safety of a catheter-based laser system for percutaneous myocardial revascularization and analyses the first clinical acute and long-term results in patients with end-stage coronary artery disease (CAD) and severe angina pectoris. BACKGROUND: In patients with CAD and intractable angina who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment that results in reduced angina pectoris and increased exercise capacity. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality. METHODS: A catheter-based system has been developed that allows creation of laser channels in the myocardium from within the left ventricular cavity. Laser energy generated by a Holmium: YAG (Cardiogenesis Corporation, Sunnyvale, California) laser was transmitted to the myocardium via a flexible optical fiber capped by an optic lens. The optical fiber was maneuvered to the target area under biplane fluoroscopy through a coaxial catheter system permitting movement in three dimensions. RESULTS: Thirty-four patients with severe CAD not amenable to either CABG or PTCA and refractory angina pectoris (Canadian Cardiologic Society [CCS] Angina Scale Class III-IV) were included in the study. Ischemic regions were identified by coronary angiography and confirmed by thallium scintigraphy. The percutaneous myocardial revascularization (PMR) procedure was successfully completed in all patients. In 29 patients, one vascular territory of the left ventricle and in 5 patients, two vascular territories were treated. Eight to fifteen channels were created in each ischemic region. Major periprocedural complications were limited to an episode of arterial bleeding requiring surgical repair. There was one death early after PMR, due to a myocardial infarction (MI) in a nontreated region. Clinical follow-up at 6 months (17 patients) demonstrated significant improvement of angina pectoris (CCS class before PMR: 3.0+/-0.0, six months after PMR: 1.3+/-0.8, p<0.0001) and increased exercise capacity (exercise time on standard bicycle ergometry before PMR: 384+/-141 s, six months after PMR: 514+/-158 s, p<0.05), but thallium scintigraphy failed to show improved perfusion of the laser treated regions. CONCLUSIONS: Percutaneous myocardial revascularization is a new safe and feasible therapeutic option in patients with CAD and severe angina pectoris not amenable to either CABG or PTCA. Initial results show immediate and significant improvement of symptoms and exercise capacity but evidence of improved myocardial perfusion is still lacking.