Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study.

AIMS: We have previously reported a significant benefit of vaccination against flu on the incidence of a single and composite end-point of death, myocardial infarction or recurrent ischaemia in patients with myocardial necrosis and planned percutaneous coronary interventions. To determine whether the observed benefits of vaccination against flu were maintained beyond the winter season a 1-year follow-up was conducted. METHODS AND RESULTS: During the winter season, we enrolled prospectively 200 myocardial infarction patients admitted in the first 72 h, and 101 planned angioplasty/stent patients (PCI) without unstable coronary artery disease, prior by-pass surgery, angioplasty or tissue necrosis. Only four patients failed to meet the inclusion criteria. Participants were randomly allocated to receive flu vaccination or remain unvaccinated on top of standard medication (control group). The study was conducted in hospitalized patients with the aim to test the potential beneficial effect of flu vaccination in a secondary prevention scenario. Under intention to treat analysis the incidence of the primary end-point cardiovascular death at 1 year was significantly lower among patients receiving vaccination, 6% as compared with controls, 17% (relative risk with vaccine as compared with controls, 0.34; 95% confidence interval (CI), 0.17 to 0.71; P=0.002). The triple composite end-point occurred in 22% of the patients in the vaccine group vs 37% in controls, hazard ratio 0.59, 95% CI 0.4 to 0.86) P=0.004. The beneficial effect was mainly detected in acute myocardial infarction patients (four events in the active arm vs 21 in the control group, P=0.0002 [95% CI 0.19, 0.07-0.53]), and Cox regression analyses revealed that there was a greater benefit with flu vaccination in patients at high risk according with the TIMI score, and those with non-ST-segment deviation myocardial infarction (95% CI: 0.13 [0.03-0.52]) CONCLUSIONS: Influenza vaccination may reduce the risk of death and ischaemic events in patients suffering from infarction and post-angioplasty during flu season. This effect was significantly evident at 1-year follow-up. Larger confirmatory studies are needed to evaluate the real impact on flu vaccination on outcome after acute coronary syndromes.     

Clinical significance of the calcification of coronary arteries in patients with angiographically normal coronary arteries.

In order to clarify the clinical significance of coronary calcification in patients with angiographically normal coronary arteries, exercise electrocardiography was used and left ventricular function was examined noninvasively and invasively. The patient groups were as follows: (1) patients with coronary artery calcification on only the left anterior descending artery but no narrowing lesion on any other arteries (calcified group), (2) patients with a significant stenosis on only the left anterior descending artery (stenotic group), and (3) the control group. The left ventricular function in the calcified group, as indicated by systolic time intervals and invasive parameters such as ejection fraction and mean systolic ejection rate, showed a depression similar to that in the stenotic group, compared with the control group. The incidence of electrocardiographically ischemic responses to exercise testing was significantly higher in the calcified group (75%, p less than 0.01) and the stenotic group (68%, p less than 0.01) than in the control group (25%). Exercise tolerance time and the maximum double product were markedly smaller in the calcified and the stenotic groups as compared with the control group. These results indicate that the left ventricular function and coronary reserve in the calcified group were reduced and almost identical with those in the stenotic group. The authors conclude that a calcified coronary artery, even if patent, cannot supply an adequate blood flow for the myocardium, resulting in impaired left ventricular function.     

Immediate and long-term results of elective and emergent percutaneous interventions on protected and unprotected severely narrowed left main coronary arteries

Percutaneous revascularization of protected and unprotected left main coronary arteries is associated with acceptable immediate results, but there are significant long-term consequences, including the need for repeat percutaneous intervention (10%), myocardial infarction (7.5%), coronary artery bypass surgery (7%), and death (38%), despite the elective or emergent nature of the procedure.     

Acute coronary syndromes in patients with angiographically normal or near normal (non-obstructive) coronary arteries

Patients with acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) constitute an important, albeit heterogeneous, patient subset of younger patients, more commonly females, who may have lower risk of cardiovascular events compared to patients with obstructive coronary artery disease; however this risk remains substantial, hence needing further investigation to identify the underlying cause and devise a proper therapeutic strategy. A diagnostic algorithm starts during coronary angiography with some essential additional diagnostic steps, such as a left ventricular angiogram that may readily identify the underlying cause, e.g. Takotsubo syndrome, while intravascular imaging and vascular reactivity testing may need to be considered for assessing other diagnostic possibilities (e.g. occult atherosclerotic plaque rupture, spontaneous coronary dissection or microvascular dysfunction). Nevertheless, pursuing further investigation with less risky noninvasive tests, such as echocardiography and cardiac magnetic resonance imaging, may effectively identify the cause of ACSNNOCA (e.g. myocarditis or Takotsubo syndrome), and guide management.     

Effects of metoprolol therapy on cardiac troponin-I levels after elective percutaneous coronary interventions.

AIMS: Beta-blockers (BBs) have been shown to improve survival and reduce the risk of re-infarction in patients following myocardial infarction. There are conflicting data about the effects of BB therapy on cardiac biomarkers after percutaneous coronary interventions (PCIs). The aim of the study was to investigate the effects of BB use on cardiac troponin-I (cTnI) levels in patients who had undergone elective PCI. METHODS AND RESULTS: In this prospective study, 287 patients with coronary artery disease were included. Patients were randomized either to BB or control groups prior to the intervention. Blood samples for cTnI were obtained before and at 6, 24, and 36 h after the procedure. Of the 287 patients included, 143 received metoprolol succinate 100 mg/day, and 144 received no BB and served as the control group. Baseline clinical characteristics of both groups, except for history of coronary artery bypass graft surgery, were similar. We observed no significant difference in the elevation of cTnI levels between the two groups after PCI (BB group, 17 patients, 11.9%; control group, 10 patients, 6.9%; P=0.2). CONCLUSION: Metoprolol succinate therapy seems to have no cardioprotective effect in limiting troponin-I rise after PCI.     

Acetylsalicylic acid (ASA) use among Polish adults with diabetes mellitus

People with diabetes mellitus have higher risk of cardiovascular morbidity and mortality from thrombo-vascular complications than non-diabetics and it is recommended that they should use acetylsalicylic acid (ASA) as anitiplatelet agent regularly. The aim of this study was to examine current physician counseling about ASA therapy and the use of ASA by Polish patients with diabetes. The study involved 464 randomly selected Caucasian diabetic individuals, mainly with type 2 (>98%), who were asked to complete a questionnaire consisting of 16 questions while visiting out-patient medical centres for periodical examination or during hospitalization. We collected data on the prevalence of cardiovascular disease (CVD), frequency of risk factors among diabetic patients and on ASA physician counseling, and on the rate of regular ASA users among the patients. The most self-reported conditions were angina pectoris or prior myocardial infarction (63,6%). Current cigarette smoking was declared by 7,1% of the patients, elevated serum cholesterol levels by 58%, and hypertension by 62,9%. Majority of the patients were overweight, and family history of coronary artery disease (CAD) was reported by 30,2% of the patients. ASA was taken by 67,2% of all the patients and 72,1% of them had taken ASA regularly. The highest percentage (>80%) of regular ASA users was found among diabetic patients with CAD. A minority of the patients who reported stroke (43,9%) or claudication (15,8%) were taking ASA regularly. Number of the patients (32,8%) with CVD risk factor(s) but without diagnosed CVD did not use ASA at all. The majority of the patients (78%) were counseled by their physicians why they should use ASA regularly. In conclusion: the number of regular users of ASA among diabetic patients in Poland with CVD others than CAD or among patients with at least two CAD risk factors is still unsatisfactory. Therefore, while it seems that there is a remarkable growing of ASA therapy world-wide more effort is needed to make this practice a standard of multifactorial, intensive diabetes treatment. Our results also suggest the need for more aggressive education of both doctors and patients.     

Acetylsalicylic acid hypersensitivity in a patient with coronary artery disease and insulin-dependent diabetes mellitus

A case of a patient with unstable coronary artery disease, insulin-dependent diabetes mellitus and acetylsalicylic acid hypersensitivity is presented. Acetylsalicylic acid desensitisation and coronary angioplasty with stent implantation were successfully performed. The patient continues to receive antiplatelet therapy and has stable angina. No late hypersensitivity reactions were seen after a follow-up of 16 months.     

The impact of chronically diseased coronary arteries and stenting on the corrected TIMI frame count in elective coronary angiography and percutaneous coronary intervention procedures.

The impact of chronic coronary obstructions on resting blood flow in stable cardiac patients and the response to percutaneous coronary intervention (PCI) using the TIMI frame count method has not been well documented. We studied the impact of coronary artery stenosis severity on the corrected TIMI frame count (cTFC) in chronically stenosed coronary arteries. We prospectively and quantitatively determined the impact of stenting on the cTFC during elective PCI. METHODS: In substudy 1, analysis was performed to obtain the mean cTFC for arteries with <50% stenosis (Group A), 51-75% stenosis (Group B), 76-85% stenosis (Group C1), 86-95% stenosis (Group C2) and 96-99% stenosis (Group C3). In substudy 2, the cTFC and quantitative coronary angiography were performed pre- and post-PCI. RESULTS: In substudy 1, the cTFC increased exponentially beyond a diameter stenosis of 75% (P < 0.01). However there was no significant difference in the cTFC for coronary arteries with <75% stenosis. In substudy 2, the overall pre- and poststenting cTFC was 17.1 +/- 11.7 and 7.8 +/- 2.7 (P < 0.01) and the TFC index [calculated by dividing the mean cTFC for the relevant artery by the mean cTFC for the corresponding coronary artery in a previously derived control group in our laboratory] was 1.6 +/- 1 and 0.7 +/- 0.2 (P = < 0.01), respectively. CONCLUSION: We have demonstrated that there was a significant increase in the cTFC when the coronary artery stenosis was more than 75% reflecting significant flow abnormalities at this degree of stenosis in chronically diseased coronary arteries. Following stenting there is a significant improvement in the cTFC, which is better than the cTFC for arteries with normal flow, suggesting early hyperaemia.     

Endothelial dysfunction in patients with chest pain and normal coronary arteries.

BACKGROUND. A subgroup of patients with chest pain and angiographically normal epicardial coronary arteries have reduced dilator response to metabolic or pharmacological stimuli, but the mechanisms responsible for this reduced dilator response are unknown. In this study, we have investigated whether microvascular endothelial dysfunction is a cause of the observed reduced vasodilator reserve. METHODS AND RESULTS. The functional response of the microvasculature was studied with rapid atrial pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31 normotensive, with chest pain and normal epicardial coronary arteries (< 10% stenosis) were studied. Endothelial function was tested with incremental infusions of acetylcholine to achieve estimated intracoronary concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent smooth muscle vasomotion was measured using intracoronary sodium nitroprusside. Endothelial dysfunction of epicardial coronary arteries, demonstrated as severe (> 50%) constriction with < 10(-5) M acetylcholine concentration, was evident in five patients (10%). In the remaining 46 patients, coronary blood flow increased with acetylcholine (mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively, but the responses were heterogeneous. There was a correlation between the coronary resistance change with acetylcholine and the change with atrial pacing: r = 0.68, p < 0.001 in these 46 patients. Thus, patients with depressed dilation with atrial pacing had reduced endothelium-dependent dilation with acetylcholine, and vice versa. However, the microvascular dilation caused by sodium nitroprusside was not significantly different between patients with and those without reduced dilation with atrial pacing, indicating that the vasodilator defect was not caused by smooth muscle dysfunction. There were no differences in the vasodilator responses with atrial pacing, acetylcholine, or nitroprusside between normotensive and hypertensive patients. Multivariate regression analysis was performed to determine whether age, sex, serum cholesterol level, hypertension, presence of mild epicardial vessel atherosclerosis, resting left ventricular function, change in left ventricular ejection fraction with exercise, vasodilation with acetylcholine, and vasodilation with sodium nitroprusside were independently related to the vasodilator response to atrial pacing. Only the change in coronary vascular resistance with acetylcholine was independently correlated with the change in resistance with atrial pacing: R2 = 0.46, p < 0.0001. CONCLUSIONS. Patients with chest pain, normal epicardial coronary arteries, and reduced vasodilation in response to atrial pacing appear to have associated endothelial dysfunction of the coronary microvasculature. Thus, microvascular endothelial dysfunction may contribute to the reduced vasodilator reserve with atrial pacing and anginal chest pain in these patients.     

Outcomes following interventions in small coronary arteries with the use of hand-crimped Palmaz-Schatz stents

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions.     

The effect of ergonovine on coronary vasodilatory reserve in patients with angiographically normal coronary arteries.

Ergonovine produces physiologic coronary artery narrowing in many patients without focal coronary spasm. The effect of ergonovine-induced coronary vasoconstriction on coronary vasodilatory reserve is unknown. Therefore we studied 10 patients with atypical chest pain and angiographically normal coronary arteries. The heart rate and blood pressure were recorded continuously and coronary Doppler flow velocity was measured continuously with a 20 MHz Doppler-tipped catheter. Ergonovine caused diffuse narrowing of the vessels in all patients, with a 12% +/- 5% change in diameter of the left anterior descending coronary artery (p less than 0.001). There was a significant change in systolic (17% +/- 12% change; p less than 0.05) and mean arterial pressure (13% +/- 13% change; p less than 0.05), with no significant change in mean coronary flow velocity with ergonovine. Ergonovine also did not attenuate the maximal hyperemic response with papaverine. Thus despite an increase in myocardial demand and a decrease in caliber of conductance coronary vessels, the coronary autoregulatory flow responses were intact after the administration of ergonovine.     

Short- and long-term results of emergency and elective percutaneous interventions on left main coronary artery stenoses.

In this prospective study, we analyzed the short- and long-term outcomes of percutaneous interventions on significant left main coronary artery (LM) stenoses. Between January 1998 and June 2000, 18 patients underwent emergency interventions on unprotected LM stenoses (group 1), while 15 patients had elective interventions on protected LM stenoses (group 2). Despite a procedural success of 88.9% in group 1, event-free in-hospital and mortality rates were 50.0% and 38.9%. After 6.4 +/- 4.4 months of follow-up, late event-free survival and mortality rates were 33.3% and 38.9%. In group 2, procedural success was 100%, with 100% event-free in-hospital survival; late event-free survival and mortality rates were 93.3% and 0% after 6.7 +/- 4.1 months of follow-up. Emergency interventions on LM stenoses remain a procedure with high acute and mid-term mortality. In spite of the high rate of major adverse cardiac events, an acceptable long-term survival can be achieved.     

Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries.

Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.