Seventeen-Year Mortality following the Acute Coronary Syndrome: Gender-Specific Baseline Variables and Impact on Outcome.

BACKGROUND: Gender differences in outcome and its predictors in patients with acute coronary syndrome (ACS) continue to be debated. OBJECTIVES: To assess long-term mortality and explore its association with the baseline variables in women and men. METHODS: We followed 2,176 consecutive patients (665 women and 1,511 men) with ACS admitted to a single hospital and still alive after 30 days for a median of 16 years 8 months. RESULTS: At the end of the follow-up, 415 (62.4%) women and 849 (56.2%) men had died (unadjusted hazard ratio [HR] for women/men 1.18 (95% confidence interval [CI], 1.05-1.33, p =0.005). After adjustment for age, the HR was reversed to 0.88 (95% CI, 0.78-1.00, p =0.04). Additional adjustment for potential confounders yielded a HR of 0.86 (95% CI, 0.76-0.98, p = 0.02). Using multivariable Cox regression, previous heart failure, previous or new-onset atrial fibrillation, and psychotropic drugs at discharge were significantly associated with increased long-term mortality in men only. Known hypertension, elevated creatinine, and inhospital Killip class >1/cardiogenic shock were significantly associated with mortality only in women. For late mortality, hypertension and inhospital Killip class >1/cardiogenic shock interacted significantly with gender. CONCLUSION: For patients with ACS surviving the first 30 days, late mortality was lower in women than in men after adjusting for age. The effects of several baseline characteristics on late outcome differed between women and men. Gender-specific strategies for long-term follow-up of ACS patients should be considered.

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

BACKGROUND: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat. METHODS: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined. RESULTS: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study. CONCLUSIONS: Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility. CLINICAL TRIALS REGISTRATION: EudraCT 2011-004804-38.

Transient repolarization alterations dominate the initial phase of an acute anterior infarction--a vectorcardiography study.

OBJECTIVE: To study effects of ischemia-reperfusion on ventricular electrophysiology in humans by three-dimensional electrocardiography. METHODS: Fifty-seven patients with first-time acute anterior ST elevation myocardial infarction were monitored from admission and >24h after symptom onset with continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global ventricular depolarization and repolarization (VR) measures were compared at maximum vs. minimum ST vector magnitude (STVM) (median 208; 111-303 vs. 362; 165-1359min after symptom onset). RESULTS: At maximum vs. minimum STVM the Tarea (overall VR dispersion) almost tripled (118 vs. 41µVs; p<0.0001), the T-loop bulginess was 90% greater (Tavplan 0.91 vs 0.48µV; p<0.0001), and Tpeak-end/QT was 39% larger (0.32 vs 0.23; p<0.0001). QRSarea (overall dispersion of depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer at minimum STVM. CONCLUSIONS: Ischemia-reperfusion was accompanied by profound and transient alterations of VR dispersion, while changes in depolarization were modest and delayed.

Multimarker risk assessment including osteoprotegerin and CXCL16 in acute coronary syndromes.

OBJECTIVE: CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes. METHODS AND RESULTS: We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84-5.82; P<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62-2.92; P<0.0001), and 2.22 for heart failure (95% CI, 1.67-2.96; P<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months. CONCLUSIONS: Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.

Interleukin-18 as a predictor of future events in patients with acute coronary syndromes.

OBJECTIVE: The aim of this study was to assess the short- and long-term prognostic significance of interleukin-18 (IL-18) levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: In patients hospitalized with ACS (median age, 66 years; 30% females), we evaluated associations of serum IL-18 levels from day 1 (n=1261) with the short- (<3 months) and long-term (median, 7.6 years) risk of death, development of congestive heart failure (CHF), and myocardial infarction (MI). IL-18 was not significantly associated with short-term mortality. In the long term, IL-18 levels were significantly related to all-cause mortality, even after adjustment for clinical confounders (hazard ratio [HR], 1.19; 95% confidence interval, 1.07 to 1.33; P=0.002). Long-term, cardiovascular mortality was univariately related to IL-18, and the adjusted relation between noncardiovascular mortality and IL-18 was highly significant (HR, 1.36; 95% confidence interval, 1.11 to 1.67; P=0.003). IL-18 independently predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long term. Measurements from day 1 of ACS and 3 months after ACS had a similar power to predict late outcome. CONCLUSIONS: The addition of the measurement of IL-18 to clinical variables improved the prediction of risk of all-cause and noncardiovascular mortality. The association between IL-18 and noncardiovascular mortality is intriguing and warrants further study.

Plasma renin activity has a complex prognostic role in patients with acute coronary syndromes.

BACKGROUND: Plasma renin activity (PRA) has been related to all-cause mortality and cardiovascular events in patients with cardiovascular disease. However, data from patients with acute coronary syndromes (ACS) are sparse. METHODS: Determination of PRA was made in 550 patients with ACS, including a subgroup of 287 patients not on treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or diuretics, and without heart failure. We evaluated the relations between PRA and all-cause mortality after three years and long-term, and to cardiovascular events after median 8.7 years. Adjustments were made for variables that influenced the hazard ratio (HR) > 5% for the relation between PRA and outcome. RESULTS: Baseline PRA was associated with all-cause mortality during three-years (unadjusted HR 1.74 per 1 SD increase in logarithmically transformed PRA; 95% confidence interval (CI) 1.39-2.16, p < 0.0001) and long-term (HR 1.12, CI 1.00-1.25, p = 0.046). After adjustments, only the three-year association remained significant. In unadjusted analyses, PRA was associated with cardiovascular death, but not with nonfatal cardiovascular events. In the subgroup there was an inverse relation between PRA and long-term all-cause mortality. CONCLUSION: Higher PRA was a significant independent predictor of all-cause mortality after three years, but not at long-term follow-up and not significantly associated with cardiovascular incidence. The renin-angiotensin-system pathophysiology is of great interest, not least due to its association with the COVID-19 pandemic. Our findings indicate a need for further research on the prognostic/predictive aspects of the renin-angiotensin-system in ACS.

Soluble CXCL16 predicts long-term mortality in acute coronary syndromes.

BACKGROUND: CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor for oxidized low-density lipoprotein that is expressed in atherosclerotic lesions. Proteolytic cleavage of membrane-bound CXCL16 releases soluble CXCL16, which may promote migration of effector T cells and augment a proatherogenic inflammatory response. We hypothesized that soluble CXCL16 concentrations are associated with long-term outcome in patients with acute coronary syndromes. METHODS AND RESULTS: We assessed the association between circulating CXCL16 levels obtained within 24 hours after admission and time to death in 1351 patients (median age 67 years, 30% female) with a diagnosis of unstable angina, non-ST-segment-elevation myocardial infarction, or ST-segment-elevation myocardial infarction. During a median follow-up time of 81 months, 377 patients died. Increased levels of CXCL16 were prognostically unfavorable; the fourth versus first quartile was associated with higher risk of death (hazard ratio 2.1; 95% CI 1.6 to 2.8; P<0.0001), triple risk of developing heart failure (hazard ratio 3.0; 95% CI 1.8 to 5.1; P<0.0001), and a doubling of the risk of rehospitalization for myocardial infarction (hazard ratio 2.1; 95% CI 1.3 to 3.3; P=0.002). After adjustment for conventional risk markers, logarithmically transformed CXCL16 level remained a strong independent indicator of long-term mortality (hazard ratio 1.21; 95% CI 1.09 to 1.36 per 1 SD increase in CXCL16; P=0.0006) and congestive heart failure development (hazard ratio 1.25; 95% CI 1.05 to 1.48; P=0.01). In a subsample of 714 patients, after further adjustment for troponin T, high-sensitive C-reactive protein, pro-B-type natriuretic peptide, and left ventricular ejection fraction, CXCL16 still provided significant additional prognostic information on mortality (hazard ratio 1.21; 95% CI 1.02 to 1.42 per 1 SD increase in CXCL16; P=0.02). CONCLUSIONS: In patients with an acute coronary syndrome, CXCL16 levels obtained within 24 hours of admission are associated with long-term mortality after adjustment for other risk factors.

Prognostic value of circulating chromogranin A levels in acute coronary syndromes.

AIMS: To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs). METHODS AND RESULTS: We measured circulating CgA levels on day 1 in 1268 patients (median age 67 years, 70% male) with ACS admitted to a single coronary care unit of a Scandinavian teaching hospital. The merit of CgA as a biomarker was evaluated after adjusting for conventional cardiovascular risk factors. During a median follow-up of 92 months, 389 patients (31%) died. The baseline CgA concentration was strongly associated with increased long-term mortality [hazard ratio per 1 standard deviation increase in logarithmically transformed CgA level: 1.57 (1.44-1.70), P < 0.001], heart failure hospitalizations [1.54 (1.35-1.76), P < 0.001], and recurrent myocardial infarction (MI) [1.27 (1.10-1.47), P < 0.001], but not stroke. After adjustment for conventional cardiovascular risk markers, the association remained significant for mortality [hazard ratio 1.28 (1.15-1.42), P < 0.001] and heart failure hospitalization [hazard ratio 1.24 (1.04-1.47), P = 0.02], but not recurrent MI. CONCLUSION: CgA is an independent predictor of long-term mortality and heart failure hospitalizations across the spectrum of ACSs and provides incremental prognostic information to conventional cardiovascular risk markers.

Homeostatic Chemokines and Prognosis in Patients With Acute Coronary Syndromes.

BACKGROUND: The chemokines CCL19 and CCL21 are up-regulated in atherosclerotic disease and heart failure, and increased circulating levels are found in unstable versus stable coronary artery disease. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of CCL19 and CCL21 in acute coronary syndrome (ACS). METHODS: CCL19 and CCL21 levels were analyzed in serum obtained from ACS patients (n = 1,146) on the first morning after hospital admission. Adjustments were made for GRACE (Global Registry of Acute Coronary Events) score, left ventricular ejection fraction, pro-B-type natriuretic peptide, troponin I, and C-reactive protein levels. RESULTS: The major findings were: 1) those having fourth quartile levels of CCL21 on admission of ACS had a significantly higher long-term (median 98 months) risk of major adverse cardiovascular events (MACE) and myocardial infarction in fully adjusted multivariable models; 2) high CCL21 levels at admission were also independently associated with MACE and cardiovascular mortality during short-time (3 months) follow-up; and 3) high CCL19 levels at admission were associated with the development of heart failure. CONCLUSIONS: CCL21 levels are independently associated with outcome after ACS and should be further investigated as a promising biomarker in these patients.

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden.

BACKGROUND: Our understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging. METHODS: As part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18-50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations. RESULTS: In faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge. INTERPRETATION: In contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection.

Symptoms of chest pain and dyspnea and factors associated with chest pain and dyspnea 10 years after coronary artery bypass grafting.

BACKGROUND: The purpose of the study is to describe (a) changes in physical activity and symptoms of chest pain and dyspnea during 10 years after coronary artery bypass grafting (CABG) and (b) risk indicators for chest pain and dyspnea 10 years after CABG. METHODS: This is a prospective observational study in Western Sweden. The study includes all patients who underwent CABG without simultaneous valve surgery and with no previous CABG between June 1, 1988, and June 1, 1991. All patients were prospectively followed up for 10 years. Evaluation of symptoms took place via postal inquiries before, 5, and 10 years after the operation. RESULTS: In all, 2,000 patients participated in a survey evaluating chest pain and dyspnea during 10 years after CABG. The overall 10-year mortality was 32%. The proportion of patients with no chest pain increased from 3% before surgery to 56% 5 years after the operation and 54% after 10 years. There was only one predictor for chest pain after 10 years and that was the duration of angina pectoris before surgery. The proportion of patients with no dyspnea increased from 12% before surgery to 40% after 5 years but decreased to 31% after 10 years. The most significant predictors for dyspnea after 10 years were female sex, obesity, diabetes mellitus, high age, duration of angina pectoris, functional class before CABG, and number of days in intensive care unit after CABG. CONCLUSION: During 10 years after CABG, one third died. After 10 years, 54% of the survivors were free from chest pain and 31% were free from dyspnea. Predictors for chest pain and dyspnea could be defined and reflected age, history, sex, obesity, preoperative complications, and symptom severity.

Serum neutrophil gelatinase-associated lipocalin (NGAL) concentration is independently associated with mortality in patients with acute coronary syndrome.

BACKGROUND: Circulating neutrophil gelatinase-associated lipocalin (NGAL) concentration increases in cardiovascular disease, but the long-term prognostic value of NGAL concentration has not been evaluated in acute coronary syndrome (ACS). We examined the association between NGAL concentration and prognosis in patients with ACS after non-ST-elevation myocardial infarction (NSTEMI) or STEMI. METHODS AND RESULTS: NGAL concentration was measured in blood from 1121 consecutive ACS patients (30% women, mean age 65 years) on the first morning after admission. After adjustment for 14 variables, NGAL concentration predicted long-term (median 167 months) mortality (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.61, P = 0.003) for quartile (q) 4 of NGAL concentration. NGAL concentrations also predicted long-term mortality (HR = 1.63, 95% CI 1.31-2.03, P < 0.001, N = 741) when adjusting for Global Registry of Acute Coronary Events (GRACE) score, left ventricular ejection fraction (LVEF), and pro-B-type natriuretic peptide (proBNP) and C-reactive protein (CRP) concentrations. With these adjustments, NGAL concentration predicted long-term mortality in NSTEMI patients (HR = 2.02, 95% CI 1.50-2.72, P < 0.001) but not in STEMI patients (HR = 1.32, 95% CI 0.95-1.83, P = 0.100). In all patients, the combination of NGAL concentration and GRACE score yielded an HR of 5.56 (95% CI 4.37-7.06, P < 0.001) for q4/q4 for both variables. CONCLUSION: NGAL concentration in ACS is associated with long-term prognosis after adjustment for clinical confounders. Measuring circulating NGAL concentration may help to identify patients-particularly those with NSTEMI-needing closer follow-up after ACS.

Impact of diagnosis and sex on long-term prognosis in acute coronary syndromes.

BACKGROUND: There is limited information on long-term outcome in patients surviving the acute phase of an acute coronary syndrome (ACS). As yet, the effects of the type of syndrome and sex on mortality and morbidity in the long run have not been well described. METHODS: We studied 1618 patients <80 years old with ACS and alive 30 days after hospitalization in a coronary care unit. The patients were followed for 5 years. They were divided into 4 groups according to the type of ACS (ST-segment elevation myocardial infarction [STEMI], non-STEMI, unstable angina pectoris high risk, and unstable angina pectoris low risk). RESULTS: There was no significant sex difference in unadjusted 5-year mortality (P = .20). After adjustment for age, the hazard ratio with the corresponding 95% CI for a higher late 5-year mortality in women in relation to men was 0.89 (0.70-1.13, P = .34). Women were hospitalized for heart failure significantly more frequently during follow-up, a significance that disappeared after adjustment for age. Non-STEMI was associated with a significantly higher long-term mortality than STEMI, before but not after adjustment for covariates (hazard ratio [95% CI] 1.02 [0.75-1.37], P = .92). Of these, age, ST depression on admission, and early revascularization with percutaneous coronary intervention appeared to be of particular importance. Non-STEMI had a significantly higher rate of acute/subacute revascularization during follow-up, even after adjustment for age. CONCLUSIONS: Before, but not after, adjustment for covariates, a diagnosis of non-STEMI was associated with a poorer prognosis than other types of ACS. Small sex differences in long-term outcome in survivors of ACS were found.

Low risk is associated with poorer quality of life than high risk following acute coronary syndrome.

BACKGROUND: Morbidity after acute coronary syndromes includes both physical and mental disorders affecting quality of life. The aim of this investigation was to study quality of life at a 3-month follow-up in patients with acute coronary syndrome, with the main objective of exploring whether unstable angina pectoris and myocardial infarction (MI) patients differ in this respect. METHODS: This investigation was part of a prospective risk stratification study of consecutive patients with acute coronary syndrome of whom 814 below the age of 75 years (278 diagnosed with unstable angina pectoris and 536 with myocardial infarction) accepted an invitation to a follow-up visit 3 months after discharge. At follow-up, the patients completed the Cardiac Health Profile, a disease-specific quality of life questionnaire, designed to evaluate perceived cognitive, emotional, social and physical function. RESULTS: Quality of life was mainly influenced by patient characteristics and previous history. The Cardiac Health Profile scores in unstable angina pectoris patients were significantly higher (i.e. poorer quality of life) than myocardial infarction patients at the 3-month visit (34, 22, 50; median, 25th, 75th percentile and 30, 19, 44; median, 25th, 75th percentile, respectively, P=0.006). The adjusted odds ratio for a poorer quality of life in unstable angina pectoris patients in relation to myocardial infarction patients was 1.39 (95% confidence interval 1.03, 1.87; P=0.03). The highest Cardiac Health Profile scores were seen in the unstable angina pectoris patients without electrocardiogram signs of ongoing ischemia and/or elevated markers of myocardial necrosis. CONCLUSION: Patients with unstable angina pectoris, especially of the low-risk type, and therefore treated accordingly, are more likely to experience poorer quality of life following an acute hospitalization than patients with other types of acute coronary syndrome. Once myocardial infarction or high-risk unstable angina pectoris has been ruled out, these patients still require a careful and systematic follow-up.

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up.

OBJECTIVES: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity. METHODS: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A2 group IIA (sPLA2-IIA), and intercellular adhesion molecule-1 (ICAM-1) were measured on days 1 and 4 and after 3 and 30 months. RESULTS: The highest levels of CRP and sPLA2-IIA were seen on day 4 but for IL-6 on day 1. These three markers, but not ICAM-1, were significantly related to disease severity, CKMB, and ejection fraction. Patients in Killip class II-IV had higher levels than those in Killip class I. The individual acute-phase responses correlated with marker levels at 3 and 30 months. ICAM-1 correlated with the development of congestive heart failure. CONCLUSIONS: In ACS there seems to be an individual predisposition to inflammatory response. Plasma IL-6 is the first marker to rise, while sPLA2-IIA and CRP peak later. All three markers, especially CRP, may discriminate between MI and non-MI. ICAM-1 seems to reflect other aspects of the inflammatory processes than the other markers. The results emphasize the complexity of the inflammatory response in ACS and stress the need for further studies involving multiple markers.

Value of the QRS-T area angle in improving the prediction of sudden cardiac death after acute coronary syndromes.

BACKGROUND: Prediction of sudden cardiac death (SCD) after acute coronary syndromes (ACS) remains a challenge. Although electrophysiology measures obtained by 3-D vectorcardiography (VCG) shortly after ACS may be useful predictors of SCD, they have not been adopted into clinical practice. The main objective of our study was to assess whether the VCG-derived QRS-T area angle (between area vectors) and the QRS-T angle (between maximum vectors) have additional value beyond standard risk factors in predicting SCD after ACS. METHODS AND RESULTS: We studied 643 consecutive ACS patients for whom data on VCG and echocardiography during the index hospitalization were available. Seventy-seven patients (12%) died, 37 (6%) from SCD and 21 (3%) from other cardiac causes during the 30-month follow-up. After adjusting for 9 standard risk factors (age, sex, diabetes, previous stroke, left ventricular ejection fraction; and estimated glomerular filtration rate, heart rate, systolic blood pressure<100mmHg, and Killip class>1 on admission), QRS-T area angle and QRS-T angle were shown to have independent predictive value for both SCD and all cardiac deaths. Reclassification analysis showed that both measures had additional predictive value beyond the 9 standard risk factors. For SCD, net reclassification improvements for QRS-T area angle and QRS-T angle were 46% and 45% and relative integrated discriminative improvements were 16% and 13% (vs the average~11% of the 9 standard risk factors). CONCLUSIONS: The VCG-derived QRS-T area angle and QRS-T angle improved prediction of SCD after ACS beyond standard risk factors. Further evaluation of their clinical utility and cost-effectiveness is therefore warranted.

N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes.

BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. METHODS AND RESULTS: Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; P<0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). CONCLUSIONS: N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.

Usefulness of atrial size inequality as an indicator of abnormal left ventricular filling.

Although pulsed Doppler echocardiography estimates current left ventricular (LV) filling, left atrial (LA) size reflects LV filling and pressure over time. However, the wide normal LA size range may blunt this diagnostic tool. Our objective was to compare the intraindividual atrial area difference (LA--right atrial [RA] area) and absolute LA area in their detection of a LA enlargement with respect to the degree of current LV filling impairment. We examined patients with acute coronary syndromes in sinus rhythm and without valvular disease (n = 154), and age- and gender-matched healthy controls (n=50) with echocardiography, applying pulsed Doppler international recommendations to group the patients according to the LV filling pattern: 0, normal; 1, delayed relaxation; 2, an isolated abnormal mitral pulmonary venous A-wave duration difference; 3, pseudonormal; and 4, restrictive. The LA and RA areas were measured in the 4-chamber view. Control values defined the normal range of: absolute LA area, LA area adjusted for body height, and LA-RA area. These areas indicated a LA enlargement in: (1) controls, 2%, 2%, and 4%, respectively; (2) patients with LV filling graded as normal/mildly impaired (groups 0 and 1), 15%, 17%, and 46%, respectively; moderately impaired (group 2), 26%, 29%, and 52%, respectively; and severely impaired (group 3 and 4), 42%, 38%, and 54%, respectively. Unequally sized atria appear to detect LA enlargement sensitively, especially when Doppler evidence of LV filling pathology is sparse. Clinically, with no obvious current cause for LA enlargement, a diagnosed "atrial size inequality" may still indicate a history of such causes.

Treatment and short-term outcome in women and men with acute coronary syndromes.

OBJECTIVE: To study differences in treatment and early morbidity and mortality in relation to gender, type of acute coronary syndrome (ACS) and age in patients under 80 years of age. METHODS: We studied 1744 consecutive patients with ACS with assumed decreasing order of severity [ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina of high- and low-risk types] admitted to the coronary care unit at Sahlgrenska University Hospital. RESULTS: The use of thrombolysis and percutaneous coronary interventions (PCI) did not differ significantly between gender groups and women did not suffer from more severe complications than men. Treatment with beta-blockers, ACE inhibitors and aspirin was used on a similar scale among women and men. In-hospital complications and use of intravenous drugs were strongly associated with severity of disease in a similar way among women and men. The mortality rates at 30 days were 12.4% and 7.4% in MI with and without ST-segment elevation, but only 1.3% and 1.0% in unstable angina of high- and low-risk types. The use of primary PCI decreased with age, as did coronary angiography and PCI in the subacute phase, irrespective of gender. CONCLUSION: Among patients <80 years with ACS admitted to a coronary care unit, the suspicion that women are treated less aggressively than men could not be verified. Nor did women suffer from more complications or have a significantly higher 30-day mortality than men. Elderly patients were significantly less likely to undergo invasive procedures than those of a younger age, irrespective of gender.

Determinants for an impaired quality of life 10 years after coronary artery bypass surgery.

OBJECTIVE: To identify determinants of an inferior quality of life (QoL) 10 years after coronary artery bypass grafting (CABG). SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: All patients from Western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery and no previous CABG. MAIN OUTCOME MEASURES: Questionnaires for evaluating QoL 10 years after the operation. Three different instruments were used: The Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the Physical Activity Score (PAS). RESULTS: 2000 patients underwent CABG, of whom 633 died during 10 years of follow-up. Information on QoL at 10 years was available in 976 patients (71% of survivors). A history of diabetes and chronic obstructive pulmonary disease were the two independent predictors for an inferior QoL with all three instruments. Furthermore, there were three predictors of an inferior QoL with two of the instruments: high age, female sex and a history of hypertension. A number of factors predicted an inferior QoL with one of the instruments. These were the duration of angina pectoris and functional class prior to CABG, renal dysfunction, a history of cerebrovascular disease, obesity, height, duration of respirator treatment and requirement of inotropic drugs postoperatively. In addition, when introducing preoperative QoL into the model a low QoL before surgery was a strong independent predictor also of an inferior QoL 10 years after CABG. CONCLUSION: Variables independently predictive of an impaired QoL 10 years after CABG, irrespective of the instrument used, were an impaired QoL prior to surgery, chronic obstructive pulmonary disease and a history of diabetes. However, other factors reflecting gender, the previous history as well as postoperative complications were also associated with the QoL 10 years later in at least one of these instruments.