Helèn Boden

Relationship between discharge heart rate and mortality in patients after acute myocardial infarction treated with primary percutaneous coronary intervention

AIMS In patients with coronary artery disease, the prognostic value of heart rate has been mainly evaluated in patients with left ventricular dysfunction. Patients with ST-segment elevation acute myocardial infarction (STEMI) are currently treated with primary percutaneous coronary intervention (PCI) and in this contemporary population of patients, the relationship between heart rate and mortality during a follow-up >1 year has not been investigated. METHODS AND RESULTS The population comprised 1453 STEMI patients treated with primary PCI. Resting heart rate was measured before discharge and all patients were followed prospectively. MAIN OUTCOME MEASURE the endpoints were defined as all-cause mortality and cardiovascular mortality. The median follow-up duration was 40 months. During this period, 83(6%) patients died of which 52(4%) died from cardiovascular disease. After adjusting for parameters reflecting a greater infarct size and the presence of heart failure, heart rate at discharge remained a strong predictor of mortality. Patients with a heart rate of ≥70 b.p.m. had a two times increased risk of cardiovascular mortality at 1- and 4-year follow-up compared with patients with a heart rate <70 b.p.m.. In addition, every increase of 5 b.p.m. in heart rate at discharge was associated with a 29 and 24% increased risk of cardiovascular mortality at 1- and 4-year follow-up, respectively. CONCLUSION In STEMI patients treated with primary PCI and optimal medical therapy, heart rate at discharge was an important predictor of mortality up to 4 years follow-up even after adjustment for parameters reflecting a greater infarct size and the presence of heart failure.

Influence of Gender on Ischemic Times and Outcomes After ST-Elevation Myocardial Infarction

Previous studies investigating the influence of gender on ST-segment elevation myocardial infarction have reported conflicting results. The aim of this study was to assess the influence of gender on ischemic times and outcomes after ST-segment elevation myocardial infarction in patients treated with primary percutaneous coronary intervention in modern practice. The present multicenter registry included consecutive patients with ST-segment elevation myocardial infarctions treated with primary percutaneous coronary intervention at 3 hospitals. Adjusted mortality rates were calculated using Cox proportional-hazards analyses. In total, 3,483 patients were included, of whom 868 were women (25%). Women were older, had a higher risk factor burden, and more frequently had histories of malignancy. Men more often had cardiac histories and peripheral vascular disease. Ischemic times were longer in women (median 192 minutes [interquartile range 141 to 286] vs 175 minutes [interquartile range 128 to 279] in men, p = 0.002). However, multivariate linear regression showed that this was due to age and co-morbidity. All-cause mortality was higher at 7 days (6.0% in women vs 3.0% in men, p <0.001) and at 1 year (9.9% in women vs 6.6% in men, p = 0.001). After adjustment, female gender predicted 7 day all-cause mortality (hazard ratio 1.61, 95% confidence interval 1.06 to 2.46) and cardiac mortality (hazard ratio 1.58, 95% confidence interval 1.03 to 2.42) but not 1-year mortality. Moreover, gender was an independent effect modifier for cardiogenic shock, leading to substantially worse outcomes in women. In conclusion, ischemic times remain longer in women because of age and co-morbidity. Female gender independently predicted early all-cause and cardiac mortality after primary percutaneous coronary intervention, and a strong interaction between gender and cardiogenic shock was observed.

Association between left ventricular global longitudinal strain and adverse left ventricular dilatation after ST-segment-elevation myocardial infarction.

Background—Myocardial infarct size is a major determinant of left ventricular (LV) remodeling after ST-segment–elevation myocardial infarction. We evaluated whether LV global longitudinal strain (GLS), proposed as a novel marker of infarct size, is associated with 3- and 6-month LV dilatation after ST-segment–elevation myocardial infarction. Methods and Results—In the first ST-segment–elevation myocardial infarction patients treated with primary percutaneous coronary intervention, baseline LVGLS was measured with 2-dimensional speckle-tracking echocardiography. Patients were dichotomized according to median value. The independent relationship between GLS groups and LV end-diastolic volume at 3 and 6 months (adjusted for clinical and echocardiographic variables) was assessed. The final study population comprised 1041 patients (60±12 years; 76% men). Median LVGLS was −15.0%. Patients with baseline LVGLS >−15.0% exhibited greater LV dilatation at 3 and 6 months compared with patients with GLS ⩽−15.0% (LV end-diastolic volume 123±44 versus 106±36 mL and 121±43 versus 102±34 mL, respectively; global group–time interaction P<0.001). This association retained the same statistical significance after adjustment for various relevant demographic, clinical, and echocardiographic characteristics. Further, net reclassification improvement index demonstrated significant incremental value of LVGLS for prediction of LV end-diastolic volume increase (0.14 [95% confidence interval, 0.00034–0.29]; P=0.04). Conclusions—LVGLS before discharge after ST-segment–elevation myocardial infarction is independently associated with LV dilatation at follow-up.

Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction

BACKGROUND Antiplatelet drug resistance is a well-known problem, causing recurrent cardiovascular events. Multiple genetic polymorphisms have been related to antiplatelet resistance by several large trials, however data from common clinical practice is limited. We examined the influence of previously described polymorphisms, related to aspirin and clopidogrel resistance, on treatment outcome in a real life unselected population of patients presenting with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. METHODS AND RESULTS This cohort study consisted of 1327 patients with STEMI. Patients were treated according to a standardized guideline-based protocol. Nine polymorphisms, COX1 (-842A>G), P2Y1 (893C>T), GPIa (807C>T), GPIIIa (PlA1/A2), CYP2C19 (*2, *3 and *17), ABCB1 (3435T>C) and PON1 (576A>G), were genotyped. During 1 year of follow up the primary endpoint, a composite of cardiac death or recurrent myocardial infarction, was reached in 86 patients. The COX1 and CYP2C19*2 polymorphisms were associated with the primary endpoint, HR 2.55 (95% CI 1.48-4.40), P=0.001 and HR 2.03 (1.34-3.09) P=0.001, respectively. The combined analysis demonstrated a 2.5-fold increased risk for individuals with ≥ 2 risk alleles, P=6.9 × 10(-9). The association of COX1 was driven by mortality related events whereas that of CYP2C19*2 was mainly attributed to myocardial infarction and stent thrombosis. CONCLUSION In this unselected, real life population of STEMI patient on dual-antiplatelet therapy, the polymorphisms COX1 -842A>G and CYP2C19*2 were determinants of thrombotic complications during follow-up. We show that in a clinical setting, testing for these polymorphisms could be of value in the identification of STEMI patients at risk for recurrent cardiovascular events.

Cardiovascular mortality and heart failure risk score for patients after ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention (data from the Leiden MISSION! infarct registry)

The risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as the primary end point. Primary percutaneous coronary intervention in patients with STEMI has improved the outcome significantly and might have changed the relative contribution of different risk factors. Our patient population included 1,484 consecutive patients admitted with STEMI who had undergone primary percutaneous coronary intervention. The clinical, angiographic, and echocardiographic data obtained during hospitalization were used to derive a risk score for the prediction of short-term (30-day) and long-term (1- and 4-year) cardiovascular mortality and hospitalization for heart failure. During a median follow-up of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age ≥70 years, Killip class ≥2, diabetes, left anterior descending coronary artery as the culprit vessel, 3-vessel disease, peak cardiac troponin T level ≥3.5 μg/L, left ventricular ejection fraction ≤40%, and heart rate at discharge ≥70 beats/min as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed using the areas under the receiver operating characteristic curves was good (0.84, 0.83, and 0.81 at 30 days and 1 and 4 years, respectively), and the patients could be allocated to low-, intermediate-, or high-risk categories with an event rate of 1%, 6%, and 24%, respectively. In conclusion, the current risk model demonstrates for the first time that 8 parameters readily available during the hospitalization of patients with STEMI treated with primary percutaneous coronary intervention can accurately stratify patients at long-term follow-up (≤4 years after the index infarction) into low-, intermediate-, and high-risk categories.

Prevalence of dyssynchrony and relation with long-term outcome in patients after acute myocardial infarction.

The impact of left ventricular (LV) dyssynchrony on the long-term outcomes of patients with acute myocardial infarction (AMI) remains unknown. The purpose of the present study was to evaluate the prevalence of LV dyssynchrony after AMI and the potential relation with adverse events. A total of 976 consecutive patients admitted with AMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was performed <48 hours after admission. LV dyssynchrony was assessed with speckle-tracking imaging and calculated as the time difference between the earliest and latest activated segments. Patients were followed up for the occurrence of all-cause mortality (the primary end point) or the composite secondary end point (heart failure hospitalization and all-cause mortality). Within 48 hours of admission for the index infarction, mean LV dyssynchrony was 61 ± 79 ms, and 14% of the patients demonstrated a ≥130-ms time difference, defined as significant LV dyssynchrony. During a mean follow-up period of 40 ± 17 months, 82 patients (8%) reached the primary end point. In addition, 36 patients (4%) were hospitalized for heart failure. The presence of LV dyssynchrony was associated with an increased risk for all-cause mortality and hospitalization for heart failure during long-term follow-up (adjusted hazard ratio 1.06, 95% confidence interval 1.05 to 1.08, p <0.001, per 10-ms increase). Moreover, LV dyssynchrony provided incremental value over known clinical and echocardiographic risk factors for the prediction of adverse outcomes. In conclusion, LV dyssynchrony is a strong predictor of long-term mortality and hospitalization for heart failure in a population of patients admitted with ST-segment elevation AMI treated with primary percutaneous coronary intervention.

Influence of coronary vessel dominance on short-and long-term outcome in patients after ST-segment elevation myocardial infarction

AIMS Prognostic importance of coronary vessel dominance in patients with ST-elevation myocardial infarction (STEMI) remains uncertain. The aim of this study was to assess influence of coronary vessel dominance on the short- and long-term outcome after STEMI. METHODS AND RESULTS Coronary angiographic images of consecutive patients presenting with first STEMI were retrospectively reviewed to assess coronary vessel dominance. Patients were followed after STEMI during a median period of 48 (IQR38-61) months for the occurrence of all-cause mortality and the composite of reinfarction and cardiac death. The population comprised 1131 patients of which 971 (86%) patients had a right dominant, 102 (9%) a left dominant, and 58 (5%) a balanced system. After 5 years of follow-up, the cumulative incidence of all-cause mortality was significantly higher in patients with a left dominant system, compared with a right dominant and balanced system (log-rank P = 0.013). Moreover, a left dominant system was an independent predictor for 30-day mortality (OR 2.51, 95% CI 1.11-5.67, P = 0.027) and the composite of reinfarction and cardiac death within 30-days after STEMI (OR 2.25, 95% CI 1.09-4.61, P = 0.028). In patients surviving first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome. CONCLUSIONS A left dominant coronary artery system is associated with a significantly increased risk of 30-day mortality and early reinfarction after STEMI. After surviving the first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome.

Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment.

Abstract.  Boden H, van der Hoeven BL, Karalis I, Schalij MJ, Jukema JW (Leiden University Medical Center, Leiden, The Netherlands). Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment (Review). J Intern Med 2012; 271: 521–536.

In-hospital major bleeding and its clinical relevance in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

Advances in antithrombotic therapy for ST elevation myocardial infarction (STEMI) enhance the risk of bleeding. Therefore, the incidence, determinants, and prognostic implications of in-hospital major bleeding after primary percutaneous coronary intervention for STEMI were investigated. In 963 consecutive patients, the incidence of bleeding was evaluated according to commonly used classifications including Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines, Thrombolysis In Myocardial Infarction, Global Use of Strategies To Open coronary arteries, and Bleeding Academic Research Consortium. Multivariate regression analyses investigated determinants of bleeding and the relation between bleeding and 1-year all-cause mortality. Large variability in incidence existed depending on classification (1.3% to 21%). Female gender, heart rate, creatinine, multivessel disease, cardiogenic shock, and procedural failure were independently associated with bleeding. One-year mortality reached 10.2% in bleeders versus 2.0% in nonbleeders (p <0.001). Bleeding was independently associated with an increased risk of 1-year mortality (hazard ratio [HR] 2.41, p <0.017). Assessment of individual classifications confirmed the increased risk of mortality for Bleeding Academic Research Consortium (HR 2.27, p = 0.048), but not for Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines, Thrombolysis In Myocardial Infarction, and Global Use of Strategies To Open coronary arteries bleeding. Thrombotic events occurred more frequently in bleeders (5.8% vs 1.5%, p <0.001); however, bleeding remained independently related to mortality with a negligible reduction in HR (2.25, p = 0.028) after adjustment. In conclusion, in-hospital major bleeding was frequently observed after STEMI, but a widespread variation in incidence existed depending on the applied definition. Patient and procedural characteristics were related to bleeding, allowing identification of high-risk patients. In-hospital major bleeding was independently associated with 1-year all-cause mortality; however, not all bleeding classifications proved equally relevant to prognosis. The relation between bleeding and mortality was shown not to be driven by the higher rate of thrombotic events among bleeders.

Association between angiographic culprit lesion and out-of-hospital cardiac arrest in ST-elevation myocardial infarction patients

BACKGROUND Factors related to the occurrence of out-of-hospital cardiac arrest (OHCA) in ST-elevation myocardial infarction (STEMI) are still poorly understood. The current study sought to compare STEMI patients presenting with and without OHCA to identify angiographic factors related to OHCA. METHODS This multicenter registry consisted of consecutive STEMI patients, including OHCA patients with return-of-spontaneous circulation. Patients were treated with primary percutaneous coronary intervention (PCI) and therapeutic hypothermia when indicated. Outcome consisted of in-hospital neurological recovery, scored using the Cerebral Performance Categories (CPC) scale, and 1-year survival. Logistic regression was used to identify factors associated with OHCA and survival was displayed with Kaplan-Meier curves and compared using log rank tests. RESULTS In total, 224 patients presented with OHCA and 3259 without OHCA. Average age was 63.3 years and 75% of patients were male. OHCA occurred prior to ambulance arrival in 68% of patients and 48% required intubation. Culprit lesion was associated with OHCA: risk was highest for proximal left coronary lesions and lowest for right coronary lesions. Also, culprit lesion determined the risk of cardiogenic shock and sub-optimal reperfusion after PCI, which were strongly related to survival after OHCA. Neurological recovery was acceptable (CPC≤2) in 77.1% of OHCA patients and did not differ between culprit lesions. CONCLUSIONS In the present STEMI population, coronary culprit lesion was associated with the occurrence of OHCA. Moreover, culprit lesion influenced the risk of cardiogenic shock and success of reperfusion, both of which were related to prognosis of OHCA patients.