The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein-mediated drug interaction?

We present 3 patients diagnosed with rhabdomyolysis 1-6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein-, organic anion transporting polypeptide (OATP) 1B1-, 1B3- and 2B1-mediated transport of rosuvastatin in vitro with half-maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 µM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1-fold, whereas the OATP-mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin-induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans.

The prognostic significance of Q waves and T wave inversions in the ECG of patients with STEMI: A substudy of the TOTAL trial.

BACKGROUND: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies. METHODS: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories. RESULTS: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern. CONCLUSIONS: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome.

The prognostic significance of the electrical QRS axis on long-term mortality in acute coronary syndrome patients - The TACOS study.

INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.

The Effect of Atrial Fibrillation on the Long-Term Mortality of Patients with Acute Coronary Syndrome: The TACOS Study.

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.

The prognostic significance of grade of ischemia in the ECG in patients with ST-elevation myocardial infarction: A substudy of the randomized trial of primary PCI with or without routine manual thrombectomy (TOTAL trial).

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.

The prognostic significance of a positive or isoelectric T wave in lead aVR in patients with acute coronary syndrome and ischemic ECG changes in the presenting ECG - Long-term follow-up data of the TACOS study.

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.

Long-term outcome of pre-specified ECG patterns in acute coronary syndrome.

BACKGROUND: Long-term outcome of real-life acute coronary syndrome (ACS) patients with selected ECG patterns is not well known. PURPOSE: To survey the 10-year outcome of pre-specified ECG patterns in ACS patients admitted to a university hospital. METHODS: A total of 1184 consecutive acute coronary syndrome patients in 2002-2003 were included and followed up for 10 years. The patients were classified into nine pre-specified ECG categories: 1) ST elevation; 2) pathological Q waves without ST elevation; 3) left bundle branch block (LBBB); 4) right bundle branch block (RBBB) 5) left ventricular hypertrophy (LVH) without ST elevation except in leads aVR and/or V1; 6) global ischemia ECG (ST depression ≥0.5 mm in 6 leads, maximally in leads V4-5 with inverted T waves and ST elevation ≥0.5 mm in lead aVR); 7) other ST depression and/or T wave inversion; 8) other findings and 9) normal ECG. RESULTS: Any abnormality in the ECG, especially Q waves, LBBB, LVH and global ischemia, had negative effect on outcome. In age- and gender adjusted Cox regression analysis, pathological Q waves (HR 2.28, 95%CI 1.20-4.32, p = .012), LBBB (HR 3.25, 95%CI 1.65-6.40, p = .001), LVH (HR 2.53, 95%CI 1.29-4.97, p = .007), global ischemia (HR 2.22, 95%CI 1.14-4.31, p = .019) and the combined group of other findings (HR 3.01, 95%CI 1.56-6.09, p = .001) were independently associated with worse outcome. CONCLUSIONS: During long-term follow-up of ACS patients, LBBB, ECG-LVH, global ischemia, and Q waves were associated with worse outcome than a normal ECG, RBBB, ST elevation or ST depression with or without associated T-wave inversion. LBBB was associated with the highest mortality rates.

Comparison of the prognostic role of Q waves and inverted T waves in the presenting ECG of STEMI patients.

BACKGROUND: Both Q waves and T-wave inversion (TWI) in the presenting ECG are associated with a progressed stage of myocardial infarction, possibly with less potential for myocardial salvage with reperfusion therapy. Combining the diagnostic information from the Q- and T-wave analyses could improve the prognostic work-up in ST-elevation myocardial infarction (STEMI) patients. METHODS: We sought to determine the prognostic impact of Q waves and TWI in the admission ECG on patient outcome in STEMI. We formed four groups according to the presence of Q waves and/or TWI (Q+TWI+; Q-TWI+; Q+TWI-; Q-TWI-). We studied 627 all-comers with STEMI derived from two patient cohorts. RESULTS: The patients with Q+TWI+ had the highest and those with Q-TWI- the lowest 30-day and one-year mortality. One-year mortality was similar between Q-TWI+ and Q+TWI-. The survival analysis showed higher early mortality in Q+TWI- but the higher late mortality in Q-TWI+ compensated for the difference at 1 year. The highest peak troponin level was found in the patients with Q+TWI-. CONCLUSION: Q waves and TWI predict adverse outcome, especially if both ECG features are present. Q waves and TWI predict similar one-year mortality. Extending the ECG analysis in STEMI patients to include both Q waves and TWI improves risk stratification.

Acute coronary syndrome of very unusual etiology.

Aortitis is one of many possible manifestations of tertiary syphilis. Aortic disease is the most common of all cardiovascular syphilitic lesions. Aortic diseases caused by tertiary syphilis include aortitis, aortic root dilation, aneurysm formation, aortic regurgitation and coronary ostial stenosis. A less common manifestation of syphilitic aortitis is coronary artery ostial narrowing related to aortic wall thickening. We report a case of a 40-year-old male patient admitted with a clinical picture of acute coronary syndrome (unstable angina). He had no risk factors for coronary artery disease. The physical examination revealed nothing remarkable. The admission electrocardiogram (ECG) showed ST segment depression in the anterolateral and inferior leads (Figure 1). The coronary angiogram showed critical ostial stenosis of the right (RCA) and left main coronary artery (Figure 2a, b). Cardiac-computed tomography showed aortic wall thickening with involvement of bilateral coronary ostia (Figure 2b, c). The patient was referred for coronary bypass surgery after treatment with two doses of penicillin G. The laboratory test was strongly positive for syphilitic infection. Postoperative treatment with benzathine penicillin, in doses recommended for tertiary syphilis, was implemented.

Outcome of all-comers with STEMI based on the grade of ischemia in the presenting ECG.

BACKGROUND: Grade 3 ischemia (G3I) in the 12­lead electrocardiogram (ECG) predicts poor outcome in patients with ST-elevation myocardial infarction (STEMI). The outcome of G3I in "real-life" patient cohorts is unclear. METHODS: The aim of the study was to establish the prognostic significance of grade 2 ischemia (G2I), G3I and the STEMI patients excluded from ischemia grading (No grade of ischemia, NG) in a real-life patient population. We assessed in-hospital, 30-day and 1-year mortality as well as other endpoints. RESULTS: The NG patients had more comorbidities and longer treatment delays than the two other groups. Short-term and 1-year mortality were highest in patients with NG and lowest in patients with G2I. Maximum troponin level was highest in G3I, followed by NG and G2I. In logistic regression multivariable analysis, NG was independently associated with 1-year mortality. CONCLUSIONS: NG predicted poor outcome in STEMI patients. G2I predicted relatively favorable outcome.

Poor long-term outcome in acute coronary syndrome in a real-life setting: Ten-year outcome of the TACOS study.

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.

The Association of Atrial Fibrillation Before Percutaneous Coronary Intervention With 1-Year Outcome in ST-Elevation Myocardial Infarction Patients.

BACKGROUND: We aimed to determine the association of atrial fibrillation (AF) with 1-year outcome in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: Patients (n = 8830) enrolled in the Trial of Routine Aspiration Thrombectomy with PCI vs PCI Alone in Patients With STEMI (TOTAL) were followed for 1 year. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening class IV heart failure. The presence or absence of AF was determined from a single pre-PCI electrocardiogram. RESULTS: Patients with AF (n = 437; 4.9%) were older, and more often had a history of stroke, hypertension, or myocardial infarction. The rate of the primary outcome was higher in the AF group than in the sinus rhythm (SR) group (17.4% vs 7.4%, P < 0.001), as was the rate of cardiovascular death (9.8% vs 3.3%, P < 0.001). In multivariable analysis, AF was independently predictive of the primary outcome (adjusted hazard ratio [aHR] 1.68; 95% confidence interval [CI], 1.30-2.16, P < 0.001), cardiovascular death (aHR 1.69; 95% CI, 1.19-2.40, P = 0.003), all-cause mortality (aHR 1.63; 95% CI, 1.18-2.24, P = 0.003), and severe heart failure (aHR 1.96; 95% CI, 1.25-3.07, P = 0.003). Among patients who were in SR, the primary outcome occurred in 307 of 4252 (7.2%) in the thrombectomy group and 310 of 4141 (7.5%) in the PCI alone group, and among those with AF, these rates were respectively 42 of 218 (19.3%) and 34 of 219 (15.5%) (P interaction = 0.26). CONCLUSIONS: In STEMI patients, AF on the pre-PCI electrocardiogram is associated with a higher risk of the primary composite cardiovascular outcome, all-cause and cardiovascular death, and severe heart failure during 1-year follow-up than it is in patients with SR.

CONTEXTE: Notre objectif était de déterminer le lien entre la fibrillation auriculaire (FA) et le résultat à un an de patients ayant subi un infarctus du myocarde avec élévation du segment ST (STEMI) puis une intervention coronarienne percutanée (ICP) primaire. MÉTHODOLOGIE: Les patients (n = 8 830) admis à l'étude TOTAL ( T rial o f Routine Aspiration T hrombectomy with PCI vs PCI Al one in Patients With STEMI) ont été suivis pendant une année. Le principal critère d'évaluation était composé des décès d'origine cardiovasculaire, de l'infarctus du myocarde récurrent, du choc cardiogénique ou de l'apparition/aggravation d'une insuffisance cardiaque de classe IV. La présence ou l'absence de FA était établie à partir d'un seul électrocardiogramme effectué avant l'ICP. RÉSULTATS: Les patients atteints de FA (n = 437; 4,9 %) étaient âgés, et la plupart avaient des antécédents d'AVC, d'hypertension ou d'infarctus du myocarde. La fréquence des manifestations liées au principal critère d'évaluation était plus élevée dans le groupe FA que dans le groupe en rythme sinusal (17,4 % vs 7,4 %, p < 0,001); il en était de même pour le taux de décès d'origine cardiovasculaire (9,8 % vs 3,3 %, p < 0,001). Dans une analyse multivariée, la FA était indépendamment prédictive des manifestations liées au principal critère d'évaluation (rapport des risques instantanés ajusté [RRIa] : 1,68; intervalle de confiance [IC] à 95 % : 1,30-2,16, p < 0,001), décès d'origine cardiovasculaire (RRIa : 1,69; IC à 95 % : 1,19-2,40, p = 0,003), mortalité toutes causes confondues (RRIa : 1,63; IC à 95 % : 1,18-2,24, p = 0,003) et insuffisance cardiaque grave (RRIa : 1,96; IC à 95 % : 1,25-3,07, p = 0,003). Parmi les patients en rythme sinusal, les manifestations du principal critère d'évaluation sont survenues chez 307 patients sur les 4 252 (7,2 %) du groupe ayant subi une thrombectomie, et chez 310 patients sur les 4 141 (7,5 %) du groupe ayant subi une ICP sans thrombectomie; parmi ceux atteints de FA, ces taux étaient respectivement de 42 sur 218 (19,3 %) et de 34 sur 219 (15,5 %) (p interaction = 0,26). CONCLUSIONS: Chez les patients ayant subi un STEMI, la détection d'une FA à l'électrocardiogramme réalisé avant l'ICP est associée à un risque accru de manifestation cardiovasculaire liée au principal critère d'évaluation composé, de décès toutes causes confondues et d'origine cardiovasculaire, et d'insuffisance cardiaque grave, pendant la première année de suivi comparativement aux patients en rythme sinusal.

The high-risk ECG pattern of ST-elevation myocardial infarction: A substudy of the randomized trial of primary PCI with or without routine manual thrombectomy (TOTAL trial).

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (pinteraction = 0.679). CONCLUSIONS: Patients 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.