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Introduction: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF. Methods: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time. Results: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387–1.992, p < 0.001). Conclusion: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.

BACKGROUND: The importance of the grade of ischemia (GI) ECG classification in the risk assessment of patients with STEMI has been shown previously. Grade 3 ischemia (G3I) is defined as ST-elevation with distortion of the terminal portion of the QRS complex in two or more adjacent leads, while Grade 2 ischemia (G2I) is defined as ST-elevation without QRS distortion. Our aim was to evaluate the prognostic impact of the GI classification on the outcome in patients with STEMI. METHODS: 7,211 patients from the TOTAL trial were included in our study. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year. RESULTS: The primary outcome occurred in 153 of 1,563 patients (9.8%) in the G3I group vs. 364 of 5,648 patients (6.4%) in the G2I group (adjusted HR 1.27; 95% CI, 1.04 - 1.55; p=0.022). The rate of cardiovascular death (4.8% vs. 2.5%; adjusted HR 1.48; 95% CI 1.09 - 2.00; p=0.013) was also higher in patients with G3I. CONCLUSIONS: G3I in the presenting ECG was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure within one year compared to patients with G2I. Patients with G3I also had a higher cardiovascular death compared to patients with G2I. publishedVersion

Useful tools for risk assessment in patients with STEMI are needed. We evaluated the prognostic impact of the evolving myocardial infarction (EMI) and the preinfarction syndrome (PIS) ECG patterns and determined their correlation with angiographic findings and treatment strategy.This substudy of the randomized Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI (TOTAL) included 7860 patients with STEMI and either the EMI or the PIS ECG pattern. The primary outcome was a composite of death from cardiovascular causes, recurrent MI, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year.The primary outcome occurred in 271 of 2618 patients (10.4%) in the EMI group vs. 322 of 5242 patients (6.1%) in the PIS group [AdjustedHR, 1.54; 95% CI, 1.30 to 1.82; p .001]. The primary outcome occurred in the thrombectomy and PCI alone groups in 131 of 1306 (10.0%) and 140 of 1312 (10.7%) patients with EMI [HR 0.94; 95% CI, 0.74-1.19] and 162 of 2633 (6.2%) and 160 of 2609 (6.1%) patients with PIS [HR 1.00; 95% CI, 0.81-1.25], respectively (pPatients with the EMI ECG pattern proved to have an increased rate of the primary outcome within one year compared to the PIS pattern. Routine manual thrombectomy did not reduce the risk of primary outcome within the different dynamic ECG patterns. The PIS/EMI dynamic ECG classification could help to triage patients in case of simultaneous STEMI patients with immediate need for pPCI.

Background A positive T wave in lead aVR (aVRT+) is an independent prognostic predictor of cardiovascular mortality in the general population as well as in cardiovascular disease. Subjects and methods We evaluated the prognostic impact of aVRT+ in an ECG recorded as close to hospital discharge as possible in acute coronary syndrome patients (n = 527). We divided the patients into three categories based on the findings in the admission ECG: ST elevation, global ischemia and other ST/T changes. Results In the whole study population, and in all the three ECG subgroups, the 10-year all-cause mortality rate was higher in the aVRT+ group than in the aVRT− group. In Cox regression analysis, the age and gender adjusted hazard ratio (HR) for aVRT+ to predict all-cause mortality in the whole study population was 1.43 (95% confidence interval [CI] 1.12–1.83; p = 0.004). To predict cardiovascular mortality, the age and gender adjusted HR for aVRT+ was 1.54 (95% CI 1.14–2.07; p = 0.005) in the whole study population and 2.07 (95% CI 1.07–4.03; p = 0.032) in the category with other ST/T changes. Conclusion In ACS patients with or without ST elevation, but with ischemic ST/T changes in their presenting ECG, a positive or isoelectric T wave in lead aVR in an ECG recorded in the subacute in-hospital stage is associated with all-cause and cardiovascular mortality during long-term follow-up. Clinicians should pay attention to this simple ECG finding at hospital discharge.

Background The importance of grade of ischemia (GI) classification in the risk assessment of patients with ST-elevation myocardial infarction has been shown previously. Grade 3 ischemia (G3I) is defined by the Sclarovsky-Birnbaum grading system as ECG with ST-elevation and distortion of the terminal portion of the QRS complex in two or more adjacent leads, while grade 2 ischemia (G2I) is defined as ECG with ST-elevation without QRS distortion. Methods In a substudy of the international, multicenter, prospective, randomized Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI (TOTAL), we studied the prognostic impact of the grade of ischemia classification on the outcome in patients with STEMI (n=7,211). The primary outcome was a composite of death from cardiovascular causes, recurrent MI, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year. Results The primary outcome occurred in 153 of 1,563 patients (9.8%) in the G3I group vs. 364 of 5,648 patients (6.4%) in the G2I group (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.29 to 1.88; p Conclusions STEMI patients with G3I in the presenting ECG proved to have an increased rate of cardiovascular death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure within one year compared to patients with G2I. Acknowledgement/Funding Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, The unit of Heart Center Co. [Z60064]

Background: Long-term outcome of the three categories of acute coronary syndrome (ACS) in real-life patient cohorts is not well known. The objective of this study was to survey the 10-year outcome of an ACS patient cohort admitted to a university hospital and to explore factors affecting the outcome. Methods: A total of 1188 consecutive patients (median age 73 years) with ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina pectoris (UA) in 2002–2003 were included and followed up for ≥ 10 years. Results: Mortality for STEMI, NSTEMI and UA patients during the follow-up period was 52.5%, 69.9% and 41.0% (p < 0.001), respectively. In multivariable Cox regression analysis, only age and creatinine level at admission were independently associated with patient outcome in all the three ACS categories when analyzed separately. Conclusions: All the three ACS categories proved to have high mortality rates during long-term followup in a real-life patient cohort. NSTEMI patients had worse outcome than STEMI and UA patients during the whole follow-up period. Our study results indicate clear differences in the prognostic significance of various demographic and therapeutic parameters within the three ACS categories.

AIMS Our aim was to compare stenosis severity and plaque content between STEMI culprit lesions with intact fibrous cap (IFC) and those with plaque rupture (PR) in a prospective study. METHODS AND RESULTS We evaluated 93 patients undergoing OCT and thrombectomy as part of a prospective substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial. Culprit lesion morphology was assessable by OCT in 70/93 (75.3%). IFC was found in 31 (44.3%), PR in 34 (48.6%) and calcified nodule in five (7.1%) patients. Following thrombectomy, OCT demonstrated similar lumen area stenosis in IFC (79.3%) and PR (79.6%) (p=0.88). Lumen area stenosis

Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization.The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were ≥75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients ≥75 years of age (3.6% vs 6.6%; P = .03) and in patients75 years of age (1.0% vs 3.2%; P.001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients ≥75 (12.5% vs 2.6%; P.001) and75 (6.7% vs 1.9%; P.001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients ≥75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3).Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access.

Objectives The purpose of this study was to determine the efficacy and safety of radial versus femoral access in women undergoing coronary angiography/intervention. Background The risk of bleeding and vascular access site complications are higher in women than in men. Methods In a pre-specified RIVAL (RadIal Vs femorAL access for coronary intervention) subgroup analysis, we compared outcomes in women (n = 1,861) and men (n = 5,160) randomized to radial versus femoral access. Results Overall, women were at higher risk of major vascular complications compared with men (4.7% vs. 1.7%; p Conclusions Women undergoing coronary angiography and PCI have a higher risk of vascular access site complications compared with men, and radial access is an effective method to reduce these complications.

Background Prior Studies have suggested better outcomes in smokers compared with nonsmokers receiving clopidogrel (“smoker's paradox”). The impact of a more intensive clopidogrel regimen on ischemic and bleeding risks in smokers with acute coronary syndromes requiring percutaneous coronary interventions remains unclear. Methods and Results We analyzed 17 263 acute coronary syndrome patients undergoing percutaneous coronary intervention from the CURRENT ‐ OASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events—Seventh Organization to Assess Strategies in Ischemic Symptoms) trial, which compared double‐dose (600 mg day 1;150 mg days 2–7; then 75 mg daily) versus standard‐dose (300 mg day 1; then 75 mg daily) clopidogrel in acute coronary syndrome patients. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Interactions between treatment allocation and smoking status (current smokers versus nonsmokers) were evaluated. Overall, 6394 patients (37.0%) were current smokers. For the comparison of double‐ versus standard‐dose clopidogrel, there were significant interactions in smokers and nonsmokers for the primary outcome ( P =0.031) and major bleeding ( P =0.002). Double‐ versus standard‐dose clopidogrel reduced the primary outcome among smokers by 34% (hazard ratio [ HR ] 0.66, 95% confidence interval [ CI ], 0.50–0.87, P =0.003), whereas in nonsmokers, there was no apparent benefit ( HR 0.96, 95% CI , 0.80–1.14, P =0.61). For major bleeding, there was no difference between the groups in smokers ( HR 0.77, 95% CI , 0.48–1.24, P =0.28), whereas in nonsmokers, the double‐dose clopidogrel regimen increased bleeding ( HR 1.89, 95% CI , 1.37–2.60, P HR 0.41, 95% CI , 0.24–0.71) and nonsmokers ( HR 0.63, 95% CI , 0.42–0.93; P for interaction=0.19). Conclusions In smokers, a double‐dose clopidogrel regimen reduced major cardiovascular events and stent thrombosis after percutaneous coronary intervention, with no increase in major bleeding. This suggests that clopidogrel dosing in patients with acute coronary syndromes should be personalized, taking into consideration both ischemic and bleeding risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 00335452.

Introduction: Drug-eluting stents (DES) reduce the risk of restenosis after percutaneous coronary intervention. The aim of the study was to evaluate, by intravascular ultrasound (IVUS), the minimum lumen area site in the stented segment and the distribution of intimal hyperplasia in patients presenting with a DES or bare-metal stent (BMS) in-stent restenosis. Methods: The “Nordic Intravascular Ultrasound Study (NIVUS)” study was conducted in Nordic and Baltic countries as a prospective multicenter registry. Two hundred nine patients (DES n = 121 and BMS n = 88) with in-stent restenosis were enrolled. Results: At the minimum lumen area site in the stented segment, the stent area (5.8 ± 2.2 mm 2 vs. 7.6 ± 2.4 mm 2, p < 0.001) and intimal hyperplasia area (2.6 ± 2.0 mm 2 vs. 5.0 ± 2.2 mm 2, p < 0.001) were significantly lower in patients treated with DES compared to BMS. The percentage of stents that did not have a minimum stent area of at least 5.0 mm 2 (under expansion) was higher in DES (58.7% vs. 37.7%, p = 0.008) compared to BMS. Intimal hyperplasia covered 55.4 ± 33.3% of the stent length in the DES compared to 90.7 ± 17.4% in the BMS group, p < 0.001. Focal in-stent restenosis was more often seen in DES treated patients compared to BMS treated patients (DES n = 84 (59.9%) vs. BMS n = 15 (17.0%), p < 0.001). Conclusion: Stent underexpansion was more often seen in DES than BMS in-stent restenosis. DES more often had focal in-stent restenosis with less intimal hyperplasia.

Aims Intracoronary thrombus is disrupted by stent deployment and confounded by the development of intrastent plaque prolapse. This study aims at investigating the feasibility and repeatability of thrombus quantification prior to stent implantation using optical coherence tomography (OCT) in ST-segment elevation myocardial infarction (STEMI) patients. Methods and results Patients were enrolled in an OCT substudy of the TOTAL trial (a randomized trial of routine aspiration ThrOmbecTomy with PCI vs. PCI ALone in patients with STEMI undergoing primary PCI) of aspiration thrombectomy or percutaneous coronary intervention (PCI) alone in primary PCI (PPCI) of STEMI. Using OCT, thrombus burden (TB) and other measures of pre- and post-stent atherothrombus were analysed over the arterial segment defined by the final stent length. Feasibility was 86.2% (25/29 patients) for both pre- and post-stent OCT imaging. Altogether, 8111 OCT cross-sections were analysed. In Bland–Altman analyses of inter-observer variation ( n = 25), the mean pre-stent TB was 8.76% for Observer 1 and 8.97% for Observer 2 (limits of agreement −2.6 to 2.2%). In Bland–Altman analyses of intra-observer variation ( n = 15), the mean pre-stent TB was 8.06% for the first and 7.35% for the second round of analysis by Observer 1 (limits of agreement −1.72 to 3.15%). There was a good correlation between pre-stent TB and pre-stent quadrants with thrombus/mm ( r = 0.97), but only modest correlation between pre-stent TB and post-stent atherothrombotic burden (ATB; r = 0.54). Conclusions Measurement of pre-stent TB by OCT during the PPCI of STEMI is feasible and highly repeatable. Pre-stent TB is only modestly correlated with post-stent ATB, which indicates that pre-stent measurements might be of additional value when assessing the TB in STEMI.

Objectives The authors sought to compare the radiation dose between radial and femoral access. Background Small trials have shown an increase in the radiation dose with radial compared with femoral access, but many were performed during the operators9 learning curve of radial access. Methods Patients were randomized to radial or femoral access, as a part of the RIVAL (RadIal Vs. femorAL) trial (N = 7,021). Fluoroscopy time was prospectively collected in 5740 patients and radiation dose quantified as air kerma in 1,445 patients and dose-area product (DAP) in 2,255 patients. Results Median fluoroscopy time was higher with radial versus femoral access (9.3 vs. 8.0 min, p Conclusions Radiation dose as measured by air kerma was nominally higher with radial versus femoral access, but differences were present only in lower-volume centers and operators. High-volume centers have the lowest radiation dose irrespective of which access site approach that they use. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)

Radial access use has been growing steadily but, despite encourag- ing results, still varies greatly among operators, hospitals, countries and continents. Twenty years from its introduction, it was felt that the time had come to develop a common evidence-based view on the technical, clinical and organisational implications of using the radial approach for coronary angiography and interventions. The European Association of Percutaneous Cardiovascular Interven- tions (EAPCI) has, therefore, appointed a core group of European and non-European experts, including pioneers of radial angioplasty and operators with different practices in vascular access supported by experts nominated by the Working Groups on Acute Cardiac Care and Thrombosis of the European Society of Cardiology (ESC). Their goal was to define the role of the radial approach in modern interventional practice and give advice on technique, training needs, and optimal clinical indications.

Summary Background Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. Methods The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38–0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76–1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43–1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28–0·57; p Interpretation Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. Funding Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

Introduction The performance of exercise electrocardiography (ECG) for the detection of coronary artery disease (CAD) in women has been limited. The recently developed computerized variable, ST-segment depression/heart rate (ST/HR) hysteresis, has been proved to detect CAD in men more accurately than traditional methods. However, the diagnostic performance of ST/HR hysteresis has not been evaluated in women. Materials and methods The study population comprised 161 female patients from the Finnish Cardiovascular Study (FINCAVAS). All patients were referred for a routine bicycle exercise test. The maximum values of ST/HR hysteresis, ST/HR index, ST-segment depression at peak exercise (STpeak), at the end of one (ST1rec) and three (ST3rec) minutes of post-exercise were determined. Significant CAD was present in 48, while 65 women showed no angiographic CAD. Also a group of 48 women with low likelihood of CAD (LLC) was formed. Diagnostic performance of variables was assessed by receiver operating characteristic (ROC) analysis. Furthermore, sensitivity values at 80% specificity and specificities at 80% sensitivity were determined. Results In a comparison between CAD and LLC groups, the ROC areas for ST/HR hysteresis, ST/HR index, STpeak, ST1rec and ST3rec were 0.89, 0.74, 0.65, 0.84 and 0.73, and sensitivities at 80% specificity were 88%, 67%, 52%, 75% and 60%, respectively. Comparing CAD and no-CAD groups, the ROC areas were 0.73, 0.67, 0.56, 0.63 and 0.60, and specificities at 80% sensitivity were 60%, 38%, 27%, 33% and 30%. Conclusions ST/HR hysteresis is a more competent method in CAD detection in women than ST-segment depression or ST/HR index.

Background: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. Study Objectives: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort. Methods: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6–12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms. Results: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients. Conclusion: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.

Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test.The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690AC nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes.Among all subjects, the QTc intervals did not differ between the three genotype groups (por =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately.The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women.

Aspirin has been used for secondary prevention of myocardial infarction (MI) in individuals with coronary disease. Although supported by several large controlled trials, aspirin prevents only a portion of recurrent events.We set out to study the prevalence of long-term aspirin use prior to admission for MI and its significance for medium-term event-free survival; 998 consecutive patients with acute MI admitted to a tertiary center were included in the study.Nearly half (42.4%) of all patients reported long-term use of low-dose aspirin prior to the index event. Prior aspirin use was associated with a 50% increase in the risk of both the combined end point of recurrent unstable angina, recurrent myocardial infarction, stroke, or death (OR 1.49; 95% CI 1.12-2.00, P=0.006) and mortality (OR 1.50; 95% CI 1.03-2.17, P=0.03) during 10-month follow-up. Prior aspirin use was not associated with an increased frequency of added antithrombotic therapy at discharge.We have found that prior aspirin use is common in patients hospitalized for acute MI. Individuals already on aspirin had increased risk of recurrent ischemic events and all-cause mortality during the 10-month follow-up after their index MI.

The diagnostic performance of heart rate variability (HRV) analysis from exercise ECG in the detection of coronary artery disease (CAD) is unknown. Bicycle exercise ECG recordings from The Finnish Cardiovascular Study (FINCAVAS) of angiography-proofed CAD patients (n = 112) and a patient group with a low likelihood of CAD (n = 114) were analyzed. HRV parameters (SDNN, RMSSD, Poincaré SD1 and SD2) were calculated from 1 min segments before exercise, during exercise and after exercise. All the parameters were in addition calculated from heart rate (HR)-corrected RR-interval segments. The ST-segment depressions in each stage were also determined. The diagnostic performance of the parameters was evaluated with the area under the receiver operating characteristic (ROC) curve method. The uncorrected HRV parameters showed the best diagnostic performance in the recovery segments but the correlation with HR was also high (SDNN: 0.758/-0.64, RMSSD: 0.747/-0.60; area under the ROC/correlation coefficient). The HR correction decreased the correlation and the diagnostic performance in recovery segments (SDNN: 0.515/-0.12, RMSSD: 0.609/0.20). The diagnostic performance of ST-level at its best was higher than any of HRV parameters (ST-level: 0.795/0.36). According to the results, the HR correction decreased the diagnostic performance of the recovery phase. The HRV parameters calculated from 1 min segments of exercise test ECG were not as capable as traditional ST-segment analysis. In conclusion, the HRV analysis from exercise or recovery phase seems to be inadequate in the detection of CAD.

Aims As a part of the Finnish Cardiovascular Study, we tested the hypothesis that T-wave alternans (TWA) predicts mortality in a general population of patients referred for a clinical exercise test. Methods and results A total of 1037 consecutive patients (mean age+SD of 58+13 years, 673 men and 364 women) with a clinically indicated exercise test and with technically successful electrocardiographic (ECG) data during a bicycle ergometer test were included in the study. Digital ECGs were recorded and TWA was analysed continuously with the time-domain modified moving average method. The maximum TWA value at heart rate (HR) ,125 b.p.m. was derived and its capacity to stratify risk for all-cause death, cardiovascular death, and sudden cardiac death (SCD) was tested. During a follow-up of 44+7 months (mean+SD), 59 patients died; 34 were due to cardiovascular causes and 20 were due to SCD. In multivariate analysis after adjustment for age, sex, use of b-blockers, functional class, maximal HR during exercise, previous myocardial infarction, and other common coronary risk factors, the relative risk of TWA � 65 mV for SCD was 7.4 (95% CI, 2.8–19.4; P , 0.001), for cardiovascular mortality 6.0 (95% CI, 2.8–12.8; P , 0.001), and for all-cause mortality 3.3 (95% CI, 1.8–6.3; P ¼ 0.001). Conclusion Time-domain TWA analysis powerfully predicts mortality in a general population undergoing a clinical exercise test.

To compare management and outcome of female and male non-ST-elevation acute coronary syndrome (ACS) patients.FINACS Studies are prospective registries of non-ST-elevation ACS patients conducted in 2001, 2003, and 2005 in nine hospitals.The studies enrolled 1,399 patients from which 39% were women. During hospitalisation women were treated less often than men with aspirin (odds ratio [OR]) for women 0.60, 95% confidence interval [CI] 0.41 to 0.88, p=0.03). Women underwent less often in-hospital coronary angiography than men (adjusted OR 0.71, 95% CI 0.55 to 0.93, p=0.01). Also in the subgroup of younger (75 years) high-risk patients, female sex was independent predictor for not performing in-hospital angiography (OR 0.64, 95% CI 0.42 to 0.97, p=0.04). Age-adjusted mortality at 6 months was similar between men and women.Compared to men women received less often aspirin. Women were referred less often to in-hospital coronary angiography. Under-use of in-hospital angiography was evident also in patients with high-risk features when guidelines recommend early invasive treatment.

Background— Patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction are at increased risk for adverse events. It is unclear if image guidance by optical coherence tomography (OCT) can improve outcomes in these patients. We compared OCT-guided versus angiography-guided primary PCI for ST-segment–elevation myocardial infarction among patients in the Thrombectomy Versus PCI Alone (TOTAL) trial. Methods and Results— Among 10 732 patients enrolled in the TOTAL trial, OCT was used for PCI guidance as a part of a prospective substudy in 214 patients. Using 2:1 propensity matching, we identified 428 patients in the trial who had PCI performed with angiography guidance alone. The primary outcome was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. Secondary outcomes included final in-stent angiographic minimum lumen diameter, procedure time, and contrast dose. The final in-stent angiographic minimum lumen diameter was 2.99±0.48 mm in the OCT-guided group versus 2.79±0.47 mm in the angiography-guided group ( P P P P =0.34). Conclusions— OCT-guided primary PCI for ST-segment–elevation myocardial infarction was associated with a larger final in-stent minimum lumen diameter. There was no significant difference in clinical outcomes at 1 year; however, the study was underpowered to detect a treatment effect. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01149044.

Aims Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. Methods and results The TOTAL trial ( N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73–3.22) in the thrombectomy group and 2.88% (95% CI: 2.12–3.90) in the PCI-alone group ( P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm3, P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post–stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. Conclusion Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

Background Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion, which may play an important role in the development of atherosclerosis and coronary artery disease (CAD). The p22phox , a component of the NADPH oxidase, is essential for the activation of this enzyme, and intensive expression of the p22phox has been reported in human atherosclerotic arteries. However, studies on the association of the C242T polymorphism in the p22phox gene with CAD have produced conflicting results, and the relation of this polymorphism with CAD is not well known in a population with acquired risk factors enhancing the NADPH-dependent superoxide production. Methods As part of the Finnish Cardiovascular Study, a case-control study was conducted with 402 high-risk Finnish Caucasian patients undergoing coronary angiography. Genotyping was performed using the 5′ nuclease TaqMan assay. Results The prevalence of the T allele (TT + TC genotypes) was significantly lower among angiographically verified CAD patients (n = 250) than among control subjects (n = 152, P = .013). In contrast to subjects with the CC genotype, the T allele was found protective against CAD (odds ratio=0.531, 95% CI 0.331-0.852, P = .009), and the results remained significant after adjustment for other significant coronary risk factors. Conclusions The T allele in the C242Tpolymorphism of the p22phox gene had a protective effect against the development of CAD despite the exposure of study subjects to risk factors related to excessive NADPH-dependent superoxide production.

We tested whether the Arg389Gly and Ser49Gly polymorphisms of the β1-adrenergic receptor gene ADRB1 and the T393C polymorphism of the G protein α-subunit gene GNAS1 modulate heart rate (HR) and blood pressure responses during an exercise stress test. The study population comprised 890 participants (563 men and 327 women, mean age 58.1 ± 12.6 yr) of the Finnish Cardiovascular Study. Their HR, systolic (SAP), and diastolic arterial pressures (DAP) at rest, during exercise, and 4 min after the test were measured and analyzed by repeated-measurement ANOVA (RANOVA). Genotypes were detected by TaqMan 5′ nuclease assay. In all subjects, and in men and women separately, the T393C of GNAS1 was the only polymorphism with genotype × time interaction in HR over the three study phases ( P = 0.04, RANOVA). None of the polymorphisms presented genotype × time interaction in SAP or DAP responses ( P > 0.10, RANOVA). In all subjects at rest, the Ser49Gly polymorphism of ADRB1 tended ( P = 0.06, ANOVA) to differentiate HR. Arg389Gly polymorphism of ADRB1 affected maximal SAP during exercise ( P = 0.04, ANOVA) and the change in SAP from rest to maximal ( P = 0.03, ANOVA). Arg389 homozygotes, particularly men, were less likely to have ventricular extrasystoles during the exercise (odds ratio = 0.68, 95% confidence interval = 0.51–0.91, P = 0.009, and odds ratio = 0.60, 95% confidence interval = 0.42–0.86, P = 0.006, respectively) than did Gly389 carriers. In conclusion, polymorphisms examined appear to have modulatory effects on hemodynamics in a clinical exercise test setting. However, the effects in absolute numbers were minor and clinically possibly insignificant.

Antithrombotic drugs including glycoprotein (GP) IIb IIIa receptor inhibitors have significantly reduced ischaemic events in coronary disease. Variability in the response to GP receptor inhibitors has been observed both with healthy individuals and in clinical studies. One single nucleotide polymorphism on GP IIIa (PI(A1/A2)) correlates with increased risk for cardiovascular events in many studies. In this study we investigated whether this polymorphism associates with individual differences in the response to GP IIb IIIa receptor inhibitors in healthy individuals. Fresh blood samples were collected randomly from individuals without a history of coronary disease. Blood samples were anticoagulated with either sodium citrate or with PPACK. The ability of different GP IIb IIIa receptor inhibitors (tirofiban, eptifibatide and abciximab) to inhibit platelet aggregation was investigated using a commercial PFA-100 analyser. At baseline, the function of platelets with different PI(A) genotypes did not differ from each other. With sodium citrate anticoagulated samples, tirofiban prolonged the closure time slightly more rapidly when platelets with PI(A 2 A 2) genotype were used than with other genotypes (p0.05) both on epinephrine-collagen and ADP-collagen coated membranes. With eptifibatide or abciximab no differences were observed. If an anticoagulant not affecting Ca(2+) concentration (PPACK) was used, no differences were observed between different GP IIIa genotypes and the ability of any of the GP IIb IIIa receptor inhibitors to prolong the closure time. The effect of tirofiban and eptifibatide was significantly affected by the anticoagulant used (p0.001), whereas abciximab functioned equally regardless of the anticoagulant. Glycoprotein IIIa PI(A2) allele has been found in many studies to associate with risk of thrombosis. In healthy controls the function of GP IIb IIIa receptor inhibitors on platelets with different PI(A) genotypes was modified by anticoagulants used. PI(A) polymorphism does not explain the interindividual variance in the response to GP IIb IIIa receptor inhibitors in healthy individuals. The study, however, demonstrates the importance of the anticoagulant used in in vitro studies and the important role of Ca(2+) concentration with tirofiban and eptifibatide, but not with abciximab.

Treatment of acute myocardial infarction has changed considerably during the last few years with the introduction of primary coronary angioplasty. In the acute phase risk stratification is largely based on simple clinical parameters, laboratory markers of myocardial injury and 12-lead electrocardiography. The electrocardiogram is of crucial importance especially during the first few hours after initiation of chest pain when important therapeutic decisions are made. Biochemical markers of myocardial injury are usually not elevated at that time point. Cases with inferior ST-elevation myocardial infarction from our hospital are presented to show how anatomical interpretation of ECG recorded during chest pain helps to risk stratify patients.

The major challenge in the treatment of ST-elevation myocardial infarction (STEMI) is not only restoration of normal coronary blood flow but also microvascular perfusion. In fact, both electrocardiographic (ST segment resolution) and angiographic measures of myocardial perfusion (myocardial blush grade) have been shown to predict mortality after primary percutaneous coronary intervention (PPCI). Initial enthusiasm for manual thrombectomy arose after the apparent mortality benefit observed in the TAPAS trial (N=1,071). Meta-analyses of small trials suggest that manual thrombectomy improves epicardial and microvascular perfusion with trends towards benefit for survival. On the other hand, meta-analyses of small trials of mechanical thrombectomy show improvement in ST resolution without an effect on survival. Recently, the TASTE trial (N=7,244) showed no reduction in mortality with manual thrombectomy but trends toward reduction in rates of rehospitalisation for recurrent MI and stent thrombosis. The interpretation of TASTE should be cautious given that the trial had a much lower than expected mortality, and modest but important treatment effects cannot be excluded (20-30%). The largest trial, the ongoing TOTAL trial (N=10,700), will help determine the effect of manual thrombectomy for important clinical outcomes. A planned individual patient meta-analysis of the TOTAL and TASTE trials will have approximately 17,000 patients to examine the effect on clinical outcomes.

In this study we compared the diagnostic characteristics of the individual exercise electrocardiographic leads, 3 different lead sets comprising standard leads and the effect of the partition value in the detection of coronary artery disease (CAD). The diagnostic variable used was ST-segment depression at peak exercise, and the study population consisted of 101 patients with CAD and 100 patients with a low likelihood of the disease. The lead system used was the Mason-Likar modification of the standard 12-lead system and exercise tests were performed on a bicycle ergometer. The comparisons were performed by means of receiver-operating characteristic analysis and by determining sensitivities at a fixed 95% specificity. These properties, defined here as diagnostic capacity, were the most efficacious in leads I, −aVR, V 4 , V 5 , and V 6 . Diagnostic capacities in leads aVL, aVF, III, V 1 , and V 2 were quite poor; statistical comparisons indicated significant differences between these leads and lead V 5 (p ≤0.0001 in each case). Use of the maximum value of ST-segment depression at peak exercise derived from all 12 leads produced a considerable decrease in the diagnostic capacity of the exercise electrocardiogram compared with lead V 5 . The exclusion of leads aVL, V 1 , and III improved the diagnostic capacity compared with the 12-lead set, but it was still smaller than that of lead V 5 . With use of a lead set with the 5 best leads increased the diagnostic capacity over other lead sets and over any individual lead. Further improvement was noted when a 50% smaller partition value was applied to leads I and −aVR than for the other leads (p = 0.041). In conclusion, this study suggests that use of leads I, −aVR, V 4 , V 5 , and V 6 is the most influential when differentiating between patients with CAD and patients with a low likelihood of disease using peak exercise ST-segment depression. The effective use of leads I and −aVR requires the partition value applied for these leads to be 50% smaller than that used for the lateral precordial leads.

To evaluate the effect of ST-segment measurement point on diagnostic performance of the ST-segment/heart rate (ST/HR) hysteresis, the ST/HR index, and the end-exercise ST-segment depression in the detection of coronary artery disease, we analysed the exercise electrocardiograms of 347 patients using ST-segment depression measured at 0, 20, 40, 60 and 80 ms after the J-point. Of these patients, 127 had and 13 had no significant coronary artery disease according to angiography, 18 had no myocardial perfusion defect according to technetium-99m sestamibi single-photon emission computed tomography, and 189 were clinically 'normal' having low likelihood of coronary artery disease. Comparison of areas under the receiver operating characteristic curves showed that the discriminative capacity of the above diagnostic variables improved systematically up to the ST-segment measurement point of 60 ms after the J-point. As compared to analysis at the J-point (0 ms), the areas based on the 60-ms point were 89 vs. 84% (p=0.0001) for the ST/HR hysteresis, 83 vs. 76% (p

Objectives The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach. Background RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021),which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non-coronary artery bypass graft major bleeding. Methods In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables. Results In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate-(HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p 0.98). Conclusions Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273) (C) 2014 by the American College of Cardiology Foundation (Less)

OBJECTIVES: To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS). DESIGN: Propensity score-matched cohort study from the database of the Tampere ACS registry. SETTING: A single academic hospital in Finland. PARTICIPANTS: 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias. PRIMARY AND SECONDARY OUTCOME MEASURES: The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up. RESULTS: Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p

In this comparative cross-sectional study, we evaluated whether a novel computerized diagnostic variable, ST-segment depression/heart rate ( ST HR ) hysteresis, which integrates the efficient ST HR analysis during both the exercise and postexercise recovery phases of the exercise electrocardiography (ECG) test, can detect coronary artery disease more accurately than methods using either exercise or recovery phase alone. The study population comprised 347 clinical patients referred for a routine bicycle exercise ECG test at Tampere University Hospital, Finland. Of these, 127 had angiographically proven coronary artery disease, whereas 13 had no coronary artery disease according to angiography, 18 had no perfusion defect according to technetium-99m sestamibi single-photon emission computed tomography, and 189 were clinically normal with respect to cardiac diseases. For each patient, the maximum values of the ST HR hysteresis, ST HR index, end-exercise ST depression, and recovery ST depression were determined from the Mason-Likar modification of the standard 12-lead exercise electrocardiogram (aVL, aVR, and V1 excluded). The diagnostic performance of these continuous diagnostic variables was compared by means of receiver-operating characteristic analysis. The area under the receiver-operating characteristic curve of the ST HR hysteresis was 89%, which was significantly larger than that of the end-exercise ST depression (76%, p ST HR index (83%, p = 0.0023), indicating superior diagnostic performance of the ST HR hysteresis independent of the partition value selection. In conclusion, computerized analysis of the HR-adjusted ST depression pattern during the exercise phase, integrated with the HR-adjusted ST depression pattern during the recovery phase after exercise, can significantly improve the diagnostic performance and clinical utility of the exercise ECG test for the detection of coronary artery disease.

The risk of death varies among patients with ST-elevation myocardial infarction (STEMI) and ECG ST-segment resolution after reperfusion predicts mortality. The time of symptom onset may not be reliable in STEMI and a novel classification based on the analysis of Q and T waves in the ECG at

Background This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial. Methods 124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic–Baltic countries. Results In early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs.16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS (1.1±2.3mm 2 vs. 0.1±0.5mm 2 ; p=0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p=0.02). Stent fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters ≥2.75mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5mm 2 ; p=0.14. Conclusions Very late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation.

Myocardial metabolism in exercise was determined by studying 21 syndromeX patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p=0.006, χ2-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p=0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing ‘slow flow’ or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant. Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p=0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed. Conclusions of this study are not straightforward. SyndromeX was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction. On the other hand, the analysis of washout presumably implies higher fatty acid utilization in patients than in normal controls, which is not a characteristic phenomenon in myocardial ischemia.

To improve the diagnostic power of the exercise electrocardiographic test in detecting myocardial ischemia, the authors have recently developed a diagnostic method called multivariate ST-segment/heart rate (ST/HR) analysis (MUSTA). The goal of this study was to evaluate the validity of MUSTA in different clinical populations and to compare its performance characteristics with ST-segment depression, the ST/HR slope, and the ΔST/HR index in these populations. The computerized exercise electrocardiographic measurements were performed on 1,507 cases, and 382 patients were selected as the study population: 161 with significant coronary artery disease according to coronary angiography and 221 with a low likelihood of coronary artery disease. The diagnostic accuracy of MUSTA in the pooled population was 77.7% (297 out of 382 patients), which was clearly better than the accuracy of 69.6% (266 out of 382 patients) using the conventional ST-segment depression criterion of 0.10 mV in detecting coronary artery disease and exercise-induced myocardial ischemia. According to receiver operating characteristics analysis, MUSTA had significantly better diagnostic power than the other classifiers. These findings suggest that multivariate and compartmental analysis methods like MUSTA can further improve the clinical importance of the exercise electrocardiogram.

In 18 patients the inferior epigastric artery (IEA) was used for myocardial revascularization along with the left internal mammary artery and saphenous vein (4.5 grafts/patient). Preoperative duplex scan assessment of IEA correctly predicted its distal diameter. At operation the mean internal diameter was 1.6 (1.5-2.0) mm distally and 2.1 (2.0-2.5) mm proximally. The mean in situ flow after intraluminal injection of papaverine was 115 (36-210) ml/min in IEA and 136 (56-210) ml/min in internal mammary artery. There was no perioperative death or myocardial infarction. Morbidity associated with IEA harvesting was minor: ultrasonography showed diastasis and slower contraction of the rectus muscle at the harvesting site than contralaterally in one case. The preoperative duplex scan was useful for evaluating IEA size. All the patients were clinically improved. The patency rate at selective IEA angiography 3 months post-operatively was 72% (13/18). This poor early patency of IEA in our small series raises doubts concerning the vessel's suitability for myocardial revascularization.

A repolarization abnormality manifested as T-wave alternans (TWA) in electrocardiogram (ECG) predicts cardiovascular mortality. A common variant in the NOS1AP gene is associated with mortality and QT interval duration, possibly in a gender-specific manner, but data is lacking on potential association with TWA. This study tested association between rs10494366 in NOS1AP and both TWA and 4-year mortality.A total of 1963 Finnish Cardiovascular Study participants (36.6% female, 57.1 ± 13.0 years) were genotyped and their maximal TWA values were measured from continuous ECG recordings during clinical exercise test at rest, exercise and recovery.We observed a significant gender-specific effect of NOS1AP genotype on TWA. In all subjects, there was no statistically significant difference between the three genotypes (TT, TG, GG) in the responses of TWA over the entire exercise test (time-by-genotype interaction p = 0.057). In women, after adjustment for age, coronary heart disease and β-blocker medication status, changes of TWA over different phases of exercise test were significantly associated with NOS1AP genotype (time-by-genotype interaction p = 0.001). In men, NOS1AP rs10494366 was not associated with TWA. During follow-up (mean 47 months), 113 patients died. NOS1AP rs10494366 was not a statistically significant predictor of mortality.The NOSIAP variant rs10494366 influences TWA and TWA response during clinical exercise test in females. Gender-specific effects have also been previously reported for the influence of the variant on QT interval. If replicated, these findings should prompt studies to further elucidate the mechanisms underlying the gender differences in NOS1AP effects on repolarization.

T-wave alternans (TWA) in electrocardiography (ECG) is a marker of cardiac repolarization, the molecular regulation of which is incompletely understood. High TWA and prolonged QT intervals are both associated with ventricular arrhythmias and sudden death. Therefore, we tested the hypothesis of whether the same mutations that influence the QT interval also affect TWA variation. We examined the effect of 3 ion channel gene single nucleotide polymorphisms (SNPs), rs1805127, rs727957 KCNE1, and rs1805124 SCN5A, on TWA during a clinical exercise test. A total of 2008 subjects from the Finnish Cardiovascular Study underwent an exercise test with online ECG recording. TWA was measured by using the time-domain, modified moving average method. Maximum values at rest, during maximal exercise, and during recovery were used as outcome measures in statistical analysis. Moreover, 4-year survival data were collected and ion channel SNPs were determined. TWA was lowest in subjects with the TT genotype of rs1805127 during all phases of the exercise test (RANOVA main effect for genotype, P = 0.018). The result remained significant after adjustment for age, existing coronary heart disease, and β-blocker medication status (RANCOVA, P = 0.035). Of the polymorphisms studied, only rs1805127 had a significant association with mortality ( P = 0.047). The most common G-C haplotype, formed by rs727957 and rs1805127, was associated with TWA (RANOVA, P = 0.007) but not with mortality. The rs1805124 polymorphism was not associated with TWA. The common KCNE1 gene variant rs1805127 is associated with TWA during an exercise test in a Finnish population, which provides additional evidence that KCNE1 genetics may influence cardiac repolarization and cardiovascular mortality.

Aims The aim of the study was to assess two distinct 12-lead electrocardiogram (ECG) patterns and their prognostic value with respect to reperfusion strategy. Methods and results In a DANAMI-2 substudy ( n = 1522), we defined the pre-infarction syndrome (PIS) as ST-elevation accompanied by positive T waves and evolving myocardial infarction (EMI) as pathological Q waves and/or negative T wave. We used a composite of death, clinical re-infarction, or disabling stroke at median 2.7 year follow-up. A higher overall event rate was observed in the EMI group compared with the PIS group [11.4 (9.4–13.9) and 6.9 (6.0–8.0) per 100 person-years, respectively, ratio of the rate (RR) 1.6, P < 0.001]. The EMI pattern was independently predictive of adverse outcome in multivariable analysis (hazard ratio 1.52, confidence interval 1.01–2.30, P = 0.04). The PIS pattern ( n = 952) was associated with lower overall event rate in patients treated with primary percutaneous coronary intervention (PCI) compared with fibrinolytic therapy (FT) [5.5 (4.4–6.9) and 8.5 (7.0–10.4) per 100 person-years, respectively, RR = 0.6, P = 0.004]. No significant difference in the outcome between treatment strategies was observed in the EMI group as a whole. However, in patients with anterior EMI without ECG signs of reperfusion, superiority of primary PCI was driven by a 51% reduction in the relative risk of composite endpoint ( P = 0.008). Conclusion More detailed ECG analysis, involving also Q- and T-wave morphology, is useful for rapid identification of high-risk patients in whom every effort should be made to transfer for primary PCI, or vice versa, for identifying low-risk patients in whom FT might be an alternative option.

Several studies have shown that treatment of coronary heart disease (CHD) does not meet the goals set in recommendations. The aim of this study was to investigate the adequacy of CHD drug treatment and secondary prevention measures, particularly with respect to age and gender biases, in a Finnish university hospital setting. The participant pool consisted of patients in FINCAVAS (Finnish Cardiovascular Study), which is a cohort study recruiting consecutive patients performing a clinical exercise test at Tampere University Hospital, Tampere, Finland. 802 patients (581 men, 221 women) with a prior diagnosis of CHD recruited between October 2001 and December 2004 were included in the analysis. Only roughly 12% of both men and women had an optimal risk factor profile. High blood pressure and hypercholesterolaemia were more common in women than in men, whereas smoking was more frequent among men. Men used ACE inhibitors (32.9% vs 20.4%, respectively), β-adrenoceptor antagonists (80.8% vs 68.3%, respectively) and aspirin (acetylsalicylic acid) [69.7% vs 58.8%, respectively] more frequently than women, but the frequency of use of these medications was also not at the recommended levels in men. Risk factor control is poorer in older than younger age groups. CHD patients, particularly women, who performed an exercise stress test in a university hospital are suboptimally treated.

Based on randomized clinical trials, mortality of acute coronary syndrome (ACS) has been considered to be relatively low. The prognosis of clinical presentations of ACS in real-life patient cohorts has not been well documented.The aim of this study was to evaluate actual clinical outcome across the whole spectrum of ACS in a series of unselected prospectively collected consecutive patients from a defined geographical region, all admitted to one university hospital.A total of 1188 patients with ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina pectoris (UA) were included. Results. In-hospital mortality was 9.6%, 13% and 2.6% (P0.001) and mortality at a median follow-up of 10 months 19%, 27% and 12% (P0.001), for the three ACS categories, respectively. In multivariate Cox regression analysis age, diabetes mellitus type 1, diuretic use at admission, creatinine level, lower systolic blood pressure, STEMI and NSTEMI ACS category were associated with higher mortality during follow-up.In an unselected patient cohort, short-term mortality of MI patients, especially those classified as NSTEMI, still was high despite increasing use of proven treatment modalities.

Background The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile – using genetic, haemodynamic and electrocardiographic (ECG) markers – of individuals at high risk of cardiovascular diseases, events and deaths. Methods and design All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications. Discussion FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers.