Abstract: The major aim of this review was to ascertain whether effective evidence-based treatments for acute coronary syndromes (ACS) are underutilized in women in various geographic areas compared with men. The focus of our review was the relative use of effective treatments in patients with coronary angiographic evidence of obstructive coronary disease, defined as a lumen stenosis >50% of the adjacent non-diseased arterial diameter. We searched MEDLINE, and the Cochrane Database between January 1998 and May 2008. Only a few of the published clinical registries on ACS provide data on treatments dichotomized by confirmed coronary angiographic disease. Consequently, we also accessed individual patient-level data from 3 established ACS registries: the Finnish TACOS (Tampere Acute COronary Syndrome), the British EMMACE 2 (Evaluation of Methods and Management of Acute Coronary Events) and the Argentine PACS-ITALSIA (Prognosis in Acute Coronary Syndromes and the ITALian hospital Sindrome Isquemico Agudo). Despite presenting with higher risk characteristics and having higher in-hospital and 6 months risk of death, women with ACS and obstructive coronary artery disease were apparently treated less aggressively with secondary preventive drugs than were men, being less likely to receive aspirin, beta-blockers and statins at discharge. Overall, coronary revascularization appears to be performed in a similar proportion of women and men - once angiography has been performed and the coronary anatomy is known. However, substantial geographic variation exists in the relative rate of coronary angiography in men and women. In United Kingdom coronary revascularization tends to be done less frequently in women. Our study, therefore, demonstrates a gender bias in the delivery of secondary drug treatments for ACS, even for patients with documented significant coronary disease.
Abstract: BACKGROUND: We describe the clinical characteristics, treatments and in-hospital case-fatality rates in an unselected population of patients admitted for acute myocardial infarction. METHODS: From January 2000 to June 2007, we tracked consecutive patients who were admitted to 7 tertiary referral and 21 county hospitals in Romania for medical treatment of ST-segment elevation acute myocardial infarction. These patients were enrolled in the Romanian Registry for ST-segment Elevation Myocardial Infarction. For this prospective study, we collected data on demographic characteristics, cardiovascular risk factors, various aspects of treatment for myocardial infarction, and in-hospital death. RESULTS: The 9186 patients in the study group had a mean age of 63.8 years. The median time from onset of symptoms to thrombolysis was 230 (interquartile range 120-510) minutes. Of the 9186 patients, 4986 (54.3%) had hypertension, 1974 (21.5%) had diabetes mellitus, 3545 (38.6%) had lipid disorders and 4653 (50.7%) were smokers. The in-hospital mortality rate was 12.7% (1170 deaths). The study group consisted of 2893 women and 6293 men. The women were older than the men and had higher rates of hypertension and diabetes mellitus but were less likely to be smokers. A smaller proportion of women than men presented within 2 hours after onset of symptoms (23.1% v. 34.4%, p < 0.001). Smaller proportions of women received thrombolytics (40.8% v. 53.5%, p < 0.001), anticoagulants (93.4% v. 95.2%; p = 0.001), antiplatelet agents (88.3% v. 91.2%, p < 0.001) and primary percutaneous coronary interventions (1.5% v. 2.2%, p = 0.030). The risk of in-hospital death was greater for women, even after adjustment for confounders (odds ratio 1.33, 95% confidence interval 1.13-1.56; p < 0.001). INTERPRETATION: The rates of reperfusion therapy for patients with acute myocardial infarction were low, and in-hospital case-fatality rates were high in this study. Excess in-hospital mortality was more pronounced among women.
Abstract: BACKGROUND: Vagal fibres are distributed both in the perivascular connective tissue and in the adventitia around the circumference of arteries, and contribute to coronary artery dilation. The aim of the manuscript is to examine whether morphologic changes of the vessel wall due to the atherosclerotic process might be associated with autonomic nervous system dysfunction. METHODS AND RESULTS: We studied 42 patients with single vessel disease referred for percutaneous coronary revascularization. Patients underwent intravascular ultrasound at the site of the ischemia-related artery before intervention. The autonomic nervous system activity was assessed by the analysis of heart rate variability (HRV) in the frequency domain. The high frequencies (HF) are predominantly under the influence of the parasympathetic system, while the low/high frequency (LF/HF) ratio represents an index of sympatho-vagal balance. Plaque plus media cross-sectional area was inversely related to HF components (r=-0.34, p<0.05), and directly related to LF/HF ratio (r=0.38, p<0.05). Patients with expansive remodeling showed lower HF values (0.07+/-0.06 nu versus 0.14+/-0.09 nu, p<0.01) and higher LH/HF ratio (2.1+/-1.1 versus 1.4+/-1.1; p<0.05). LF changes were independent of any morphologic features. On multivariate analyses the remodeling index was the only independent determinant of HF and LF/HF ratio. CONCLUSIONS: Outward stretch of the vessel wall behind the plaque, as a consequence of increasing plaque size and expansive arterial remodeling is associated to autonomic dysfunction namely due to impairment of the vagal tone. It is unknown if remodeling is a cause of vagal impairment or if vagal impairment may contribute to arterial remodeling.
Abstract: Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion.
Abstract: Optical coherence tomography (OCT) is a recently developed technology capable of micron-scale imaging. Its high resolution (10-20 microm) makes intravascular OCT imaging the most interesting method for assessing atherosclerotic plaque microstructure in patients suffering from coronary artery disease. OCT allowed measurement of the thickness of the plaque fibrous cap, as well as identification of intima, media, and external elastic membrane in patients with normal coronary arteries. However, significant limitations still exist, including poor penetration in non-transparent tissue. The aim of this review is to give an update on OCT on the basis of the existing literature, with an overview of the strong and weak features of this technique.
Abstract: Mechanisms underlying coronary spasm are still poorly understood. The aim of the study was to assess the hypothesis that fluctuations in the development of coronary spasm might reflect inputs from the adjacent esophageal system. We enrolled patients admitted to the coronary care unit for episodes of nocturnal angina. Seven patients with variant angina and five with coronary artery disease (CAD) had concurrent ECG and esophageal manometric monitoring. ECG monitoring documented 28 episodes of ST elevation in variant angina patients and 16 episodes of ST depression in CAD patients. Manometric analysis showed that esophageal spasms resulted remarkably more frequently in variant angina patients (143 total spasms; individual range 9-31) than in CAD patients (20 total spasms; individual range 0-9; P < 0.01). Time series analysis was used to assess fluctuations in the occurrence of abnormal esophageal waves and its relationship with spontaneous episodes of ST shift. Episodes of esophageal spasm in CAD were sporadic (<1 in 30 min) and not related to ECG-recorded ischemia. In the variant angina group, esophageal spasms were time related to ischemia (>1 into 5 min before ECG-recorded ischemia) (P < 0.05). A bidirectional analysis of causal effects showed that the influence processes between esophageal and coronary spasms were mutual and reciprocal (transfer function model, P < 0.05) in variant angina. We concluded that in variant angina patients, episodes of esophageal spasms and myocardial ischemia influenced each other. Mechanisms that cause esophageal spasm can feed back to produce coronary spasm. Coronary spasm may feed forward to produce additional episodes of esophageal spasm.
Abstract: Rheumatic heart disease, the sequel of acute rheumatic fever, is a very common cause of cardiovascular mortality and morbidity all over the world, and is the predominant indication for cardiac surgery in the industrialized countries. Diagnosis of rheumatic chronic carditis may sometimes be difficult because valvular regurgitation may not always be detected by routine clinical auscultation. A recent report from the World Health Organization Expert Committee recognizes the usefulness of echocardiography Doppler in providing supporting evidence for diagnosis of rheumatic carditis in the presence of equivocally pathological murmur, and recommends that patients with subclinical carditis should be managed as rheumatic heart disease until proven otherwise, because the disease still represents a major health problem. The aim of this review is to give an update on the disease by underlining changes made by the World Health Organization on disease diagnosis and patient management.
Abstract: This study was performed to assess the strengths and weaknesses of optical coherence tomography (OCT) intravascular imaging in identifying plaque morphology. Seventy-nine postmortem human coronary arterial sections classified as fibrous-cap atheromas, calcific plaques, fibrous plaques, and complicated lesions were studied. OCT was able to identify 45% of fibrous-cap atheromas (kappa=0.27, p<0.01), 68% of fibrocalcific plaques (kappa=0.40, p<0.001), 83% of fibrous plaques (kappa=0.37, p<0.001), and 100% of complicated lesions (all thrombi; kappa=1, p<0.001). Misinterpretation was caused mainly by the low OCT signal penetration, which could not detect lipid pools or calcium behind thick fibrous caps, and by an inability to distinguish calcium deposits from lipid pools or the opposite. Lesions with thick (>150 microm) caps were histologically identified as 25 thick fibrous-cap atheromas, 8 fibrocalcific plaques, and 5 fibrous plaques; all these lesions were relatively "stable." In contrast, lesions with fibrous caps<150 microm were either vulnerable or stable lesions (11 thin-fibrous-cap atheromas and 11 fibrocalcific plaques). In conclusion, although OCT images may give an indication of the overall composition of large homogenous signal-poor regions, such as lipids or calcified areas, they could be unreliable in differentiating areas with heterogenous compositions. OCT may easily recognize relatively stable lesions.
Abstract: BACKGROUND: The prognostic implication of chest pain associated with normal or near-normal findings on angiography is still unknown. We explored outcomes and methods of risk stratification in patients with nonobstructive coronary artery disease in the setting of non-ST-segment elevation acute coronary syndromes. METHODS: Data were pooled from 3 Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 11B, TIMI 16, and TIMI 22). Angiographic data were available on 7656 patients with non-ST-segment elevation acute coronary syndromes. The primary end point of this analysis was the composite of the rates of death, myocardial infarction, unstable angina requiring rehospitalization, revascularization, and stroke at 1-year follow-up. Outcomes were evaluated by mean of the TIMI risk score for developing at least 1 component of the primary end point. RESULTS: Angiographic findings showed that 710 (9.1%) of 7656 patients had nonobstructive coronary artery disease; 48.7% of these had normal coronary arteries (0% stenosis), and 51.3% had mild coronary artery disease (>0% to <50% stenosis). A primary end-point event occurred in 101 patients (12.1%). It is noteworthy that a 2% event rate of deaths and myocardial infarctions had occurred in these patients at the 1-year follow-up. Event rates of death and myocardial infarction increased significantly as the TIMI risk score increased from 0.6% for a score of 1 to 4.0% for a score greater than 4. CONCLUSIONS: Patients with non-ST-segment elevation acute coronary syndromes with nonobstructive coronary artery disease detected by angiography have a substantial risk of subsequent coronary events within 1 year. The risk is not univariately high, and the TIMI risk score helps to reveal patients at high risk.
Abstract: BACKGROUND: Morbidity of patients with Syndrome X (SX; chest pain and normal coronary angiograms) is high and is associated with continuing episodes of chest pain and hospitalization. Impairment of microvascular endothelial function caused by increased oxidative stress has been suggested to be a mechanism of the disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the vascular wall. This study sought to establish whether combination treatment with ACE inhibitors and statins reduces oxidative stress and improves quality of life of patients with cardiac SX. METHODS AND RESULTS: Forty-five patients with SX were randomly assigned to receive either a combination of ramipril (10 mg/d) and atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of extracellular SOD and its relation to flow-dependent endothelium-mediated dilation (FMD) and quality of life (exercise capacity and score with Seattle Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients with SX who received atorvastatin and ramipril had significantly reduced (P=0.001) SOD levels (188.1+/-29.6 U/mL). No significant changes were seen on placebo (262.9+/-48.8 U/mL). Reduction of SOD after therapy was negatively correlated with FMD (r=0.38; P=0.01) and positively with total cholesterol (r=-0.56; P<0.001). At follow-up, patients taking atorvastatin and ramipril improved their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by 64.1%). CONCLUSIONS: Six months of therapy with atorvastatin and ramipril improves endothelial function and quality of life of patients with SX. Reduced SOD activity may reflect low superoxide anion production. Benefits of these drugs may be related to reduction of oxidative stress.
Abstract: BACKGROUND: The prognosis for women with chest pain and angiographically normal coronary arteries is believed to be totally benign. Previous studies, however, did not account for the delay of a decade or so in the development of coronary artery disease that women may experience. METHODS AND RESULTS: This study assessed long-term follow-up of 42 women with de novo angina, evidence of reversible myocardial perfusion defects on SPECT, and normal coronary angiograms. At recruitment, all women underwent endothelial function testing (intracoronary acetylcholine) during catheterization. Patients were followed up for >10 years. Angiography was repeated at the end of the follow-up in 37 patients. At recruitment, 22 patients developed diffuse vasoconstriction during acetylcholine in the absence of identifiable focal coronary spasm (acetylcholine-positive group). The remaining 20 patients showed vasodilation (acetylcholine-negative group). At the end of follow-up, in the acetylcholine-positive group, 1 patient developed cardiac death, 13 still complained of chest pain, and 8 had remission of symptoms. In the acetylcholine-negative group, all patients showed complete resolution of chest pain beginning 6 to 36 months after baseline assessment. Angiography showed development of coronary artery disease in the 13 symptomatic patients in the acetylcholine-positive group. CONCLUSIONS: In women with angiographically normal-appearing coronary arteries, persistence of chest pain over the years often relates to development of coronary artery disease. Endothelial dysfunction in a setting of normal coronary arteries is a sign of future development of atherosclerosis.
Abstract: We studied the effect of pravastatin on coronary perfusion after percutaneous transluminal coronary angioplasty. An exercise test performed within 2 weeks after percutaneous transluminal coronary angioplasty induced reversible perfusion defects in 66% of patients taking pravastatin and 64% of those taking placebo. At follow-up, the exercise test still induced reversible perfusion defects in 3% of patients taking pravastatin and 29% of those taking placebo.
Abstract: AIMS: Cardio-cardiac reflexes may be evoked by both myocardial ischaemia and coronary occlusion itself. The aim of the study was to assess the intrapatient behaviour of autonomic nervous system balance during spontaneous and balloon-induced coronary ischaemia. METHODS AND RESULTS: We studied a group of patients admitted to the coronary care unit for acute coronary syndrome without ST-segment elevation who experienced spontaneous episodes of myocardial ischaemia during bed rest and ECG monitoring. The inclusion criterion was 80-90% lumen stenosis, amenable to angioplasty. Balloon coronary occlusion was performed at 4-6 atmospheres for 120 s. Autonomic nervous system activity was assessed by heart rate variability (HRV) analysis in frequency domain. We analysed 14 episodes of spontaneous ischaemia and 14 episodes of balloon coronary occlusion. During spontaneous ischaemia, HRV showed an increase in the low/high frequencies ratio (11.8 +/- 5.7), as compared to 5 min before and 5 min after (4.4 +/- 2.7 and 3.9 +/- 1.8, respectively) (p = 0.001). The opposite occurred during balloon coronary occlusion (0.8 +/- 0.4 vs. 3.9 +/- 2.0 and 5.1 +/- 2.1, respectively; p = 0.001). CONCLUSIONS: Balloon inflation and occlusion evokes baroreceptor vagal predominance in response to a stretch stimulus of the coronary artery. Conversely, spontaneous occlusion during unstable angina is accompanied by naturally occurring sympathetic activation. Sympathetic activation may have a role in the natural history of the disease.
Abstract: AIM: Previous animal studies suggested that vagal tone contributes to tonic dilatation of coronary arteries. We hypothesized that low parasympathetic activity might be among the causes of coronary instability in the setting of acute coronary syndrome without ST-segment elevation. METHODS AND RESULTS: We studied 172 consecutive patients. Vagal and sympathetic activities were assessed by time domain measures of heart rate variability. PNN50 <3% was used as a marker of low parasympathetic activity. At 6-month follow-up 32 patients developed coronary events. Coronary events were lower during hospitalization (n=9) than during follow-up (n=23). Extremely low values of parasympathetic activity (pNN50 <3%) were strongly related to subsequent events (P<0.001). PNN50 <3% was found in 56% of patients having adverse events versus 5% of patients who had good outcome. Among patients who had pNN50 <3%, 18 patients (72%) had subsequent coronary events vs seven patients (28%) who had a good outcome. CONCLUSIONS: These data show that in acute coronary syndrome without ST-segment elevation, a significant number of patients developing subsequent coronary events have a loss of vagal tone. Simple electrocardiographic variables, as pNN50 <3%, may be of great clinical value in identifying patients at high risk of subsequent coronary events even after apparent clinical stabilization.
