Emad Abu Assi

Why and when do patients with heart failure and normal left ventricular ejection fraction die? Analysis of >600 deaths in a community long-term study.

BACKGROUND The aim of the study was to examine the causes of the death of patients with heart failure (HF) and evaluate the differences in this respect between patients with and without depression of left ventricular ejection fraction (LVEF). METHOD All patients hospitalized with HF between 1995 and 2002 in the cardiology service of a tertiary hospital were assessed. LVEF was evaluated by echocardiography during hospitalization and was considered normal when it was > or =50%. After a mean follow-up time of 3.7 +/- 2.8 years, 615 cases had terminated in death. RESULTS The most common cause was refractory HF, both in the whole group (39%) and in both the subgroups defined with respect to LVEF (normal and depressed). There was no statistically significant difference between the normal and depressed subgroups as regard the distribution of deaths, although the depressed group showed a somewhat greater incidence of sudden death (21% as against 16% in the normal group) and a somewhat smaller incidence of death due to refractory HF (37% as against 47%). However, in the depressed LVEF group, the cumulative risk of death due to acute myocardial infarction in the first 1.5 years first increased rapidly and then more slowly, whereas the reverse pattern was held in the normal left ventricular systolic function group, in which it was the cumulative risks of death from noncardiovascular or vascular noncardiac causes that initially increased more rapidly than later. CONCLUSIONS The spectrum of causes of death among patients with HF who have been hospitalized is independent of LVEF in the long term. In the short term, there are differences between patients with normal LVEF and depressed LVEF as regard the dynamics of the risks of death from acute myocardial infarction, noncardiac vascular causes, and noncardiovascular causes. These results may help orient the short-term and long-term management of HF, especially for patients with normal LVEF, for whom there is still no well-established consensus strategy.

High-sensitivity C-reactive protein predicts adverse outcomes after non-ST-segment elevation acute coronary syndrome regardless of GRACE risk score, but not after ST-segment elevation myocardial infarction

INTRODUCTION Atherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). C-reactive protein (CRP) is an acute phase protein that appears in the circulation in response to inflammatory cytokines. The present study investigated the association between high-sensitivity C-reactive protein (hsCRP) on admission and follow-up prognosis after an ACS. METHODS We included 151 consecutive patients admitted to the coronary care unit with a diagnosis of ACS (47% ST-segment elevation myocardial infarction [STEMI]). The primary endpoint was the combination of cardiac death and myocardial reinfarction during the follow-up period (median 19.8 months, interquartile range 16.3-23.7 months). RESULTS The occurrence of follow-up events was significantly related to admission hsCRP level, which was an excellent predictor of cardiac death and reinfarction during follow-up (HR 1.091, 95% CI 1.014-1.174; p=0.019). Stratifying the population based on type of ACS, adjusted by variables associated with cardiac events in univariate analysis (hsCRP, diabetes, depressed ejection fraction and GRACE risk score), hsCRP proved to be an independent predictor of follow-up outcomes only in non-STEMI patients (HR 1.217, 95% CI: 1.093-1.356, p<0.001), not in STEMI patients. The best cutoff level of hsCRP to predict follow-up outcomes was 1.1mg/dl, with sensitivity of 77.8% and specificity of 63.2%. CONCLUSION Although the GRACE risk score is routinely used for stratification of patients with ACS, assessment of hsCRP may provide additional prognostic value in the follow-up of non-STEMI patients.

Relation of Contrast Induced Nephropathy to New Onset Atrial Fibrillation in Acute Coronary Syndrome

Chronic renal failure has been described as a risk factor for the development of atrial fibrillation (AF). The aim of this study was to examine the association between contrast-induced nephropathy (CIN) and new-onset AF in patients with acute coronary syndromes. A total of 1,520 consecutive patients (mean age 67.1 ± 12.7 years) with acute coronary syndromes (34.4% with ST-segment elevation myocardial infarctions) who underwent coronary angiography were studied. CIN was defined as an increase in serum creatinine of 0.5 mg/dl within 72 hours of contrast exposure. The independent effect of AF history (chronic or paroxysmal AF before catheterization) on the development of CIN, as well as the independent effect of CIN on the development of new-onset AF (after catheterization, during the in-hospital phase), were tested by using different logistic regression models. One hundred thirty-nine patients (9.1%) had histories of AF before catheterization (60 with paroxysmal and 79 with chronic AF), and 56 (4.1%) developed new-onset AF after catheterization. Eighty-seven patients (5.7%) had CIN. AF history was a predictor of CIN in univariate analysis (odds ratio 2.19, 95% confidence interval 1.22 to 3.95, p = 0.007) but not in multivariate analysis, after adjusting for confounding variables (odds ratio 1.69, 95% confidence interval 0.89 to 3.22, p = 0.111). In contrast, those with CIN had an increased prevalence of new-onset AF (15.3% vs 3.4%, p <0.001). After adjusting for those variables associated with new-onset AF in the univariate analysis, CIN continued to show a significant association with new-onset AF, with a twofold increased risk (odds ratio 2.45, 95% confidence interval 1.07 to 5.64, p = 0.035). In conclusion, the development of CIN is an independent predictor of new-onset AF in the context of acute coronary syndromes.

Noninvasive Treatment of Acute Myocardial Infarction. Clinical Profile and Predictors of Poor Prognosis

In current clinical practice, only a small percentage of patients with acute coronary syndrome are treated conservatively (receiving neither coronary angiography nor fibrinolysis). Evidence-based clinical practice guidelines recommend that patients suffering an acute myocardial infarction (AMI) undergo invasive intervention, in addition to medical treatment of proven prognostic efficacy; this invasive treatment should take the form of emergent reperfusion therapy for ST segment elevation myocardial infarction (STEMI) and early coronary angiography for non-ST segment elevation myocardial infarction (NSTEMI). Certain clinical situations accompanying acute coronary syndrome exclude patients from this intensive management strategy. The typical clinical profile in such cases is that of a fragile elderly patient with anemia and renal failure or other important comorbidities that justify conservative management. Here we present an analysis of in-hospital and long-term mortality among AMI patients in our population who were assigned to conservative treatment by the on-duty physician. The aim was to identify variables that predict poor prognosis in these patients. We analyzed the records of 4408 patients consecutively admitted to our hospital between 2003 and 2012 with a diagnosis of AMI (1745 with STEMI and 2663 with NSTEMI). Of these patients, 460 received conservative medical treatment (127 [7.3%] with STEMI and 333 [12.5%] with NSTEMI); 84 STEMI patients presented > 24 hours after symptom onset. Among the total group of STEMI patients, 54 (3.1%) received fibrinolytic treatment and all were later examined by angiography. Patients assigned to conservative management tended to be older, and this group included a higher percentage of women and patients with diabetes mellitus, had a worse Killip class, and had lower hemoglobin and higher creatinine readings (Table). All of this, as is well known, implies a poor prognosis for patients receiving conservative medical treatment. Among patients receiving conservative treatment, we analyzed variables associated with a worse prognosis during in-hospital care and long-term follow-up; in-hospital and long-term mortality were analyzed independently in the two types of AMI by multivariate analysis (binary logistic regression for in-hospital mortality and Cox regression for long-term mortality), with adjustments for first-order interactions between covariates. Among NSTEMI patients, univariate analysis indicated an association of high in-hospital mortality with diabetes mellitus (odds ratio [OR] = 1.79; 95% confidence interval [95%CI], 1.02-3.14; P = .042), Killip class II (OR = 6.81; 95%CI, 3.46-13.43; P < .001), hemoglobin (OR = 0.85; 95%CI, 0.73-0.98; P = .027), creatinine (OR = 1.49; 95%CI, 1.17-1.90; P = .001) and troponin (OR = 1.02; 95%CI, 1.01-1.04; P = .001). In-hospital mortality in these patients was also associated with nontreatment with beta-blockers (OR = 0.19; 95%CI, 0.09-0.39; P < .001), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (OR = 0.35; 95%CI, 0.19-0.63; P < .001), or statins (OR = 0.23; 95%CI, 0.16-0.32; P < .001). In the multivariate analysis, only Killip class II persisted as an independent predictor of in-hospital mortality (OR = 4.5; 95%CI, 2.13-9.53; P < .001). Long-term mortality in NSTEMI patients (4.2 2.8 years) was positively associated with the following variables: age (hazard ratio [HR] = 1.06; 95%CI, 1.04-1.08; P < .001), peripheral artery disease (HR = 1.70; 95%CI, 1.18-2.46; P = .005), previous AMI (HR = 1.46; 95%CI, 1.06-2.02; P = .022), Killip class II (HR = 2.43, 95%CI, 1.79-3.28; P < .001), hemoglobin (HR = 0.88; 95%CI, 0.81-0.95; P = .001), creatinine (HR = 1.27; 95%CI, 1.13-1.44; P < .001), and troponin (HR = 1.01; 95%CI, 1.01-1.02; P < .001). Indicators of good prognosis were treatments with beta-blockers (HR = 0.50; 95%CI, 0.37-0.68; P < .001) and statins (HR = 0.55; 95%CI, 0.47-0.66; P < .001). After the multivariate analysis, the following persisted as independent predictors of mortality: age (HR = 1.06; 95%CI, 1.031.09; P < .001), peripheral artery disease (HR = 1.71; 95%CI, 1.06-2.76; P = .028), previous AMI (HR = 1.76; 95%CI, 1.15-2.71; P = .009), Killip class II (HR = 1.59; 95%CI, 1.05-2.41; P = .028), hemoglobin (HR = 0.87; 95%CI, 0.77-0.98; P = .020), creatinine (HR = 1.38; 95%CI, 1.07-1.77; P = .013), and nontreatment with statins (HR = 0.79; 95%CI, 0.62-0.99; P = .042). Among patients with STEMI, univariate analysis showed association of high in-hospital mortality with Killip class II (OR = 8.00; 95%CI, 3.02-21.17; P < .001), creatinine (OR = 1.72; 95%CI, 0.97-3.05; p = .062), and troponin (OR = 1.01; 95%CI, 0.99-1.02; P = .079). Indicators of good prognosis were treatments with betablockers (OR = .21; 95%CI, 0.08-0.56; P = .002), angiotensinconverting enzyme inhibitors or angiotensin II receptor blockers OR = 0.19; 95%CI, 0.08-0.48; P < .001), and statins (OR = 0.15; 95%CI, 0.06-0.36; P < .001). In the multivariable analysis, the only independent predictors of in-hospital mortality were Killip class II (OR = 5.22; 95%CI, 1.44-18.86; P = .012) and treatment with statins (OR = 0.79; 95%CI, 0.06-0.63; P = .006). Long-term mortality of STEMI patients was associated with age (HR = 1.09; 95%CI, 1.04-1.15; P = .001), hemoglobin (HR = 0.86; 95%CI, 0.76-0.97; P = .015), and creatinine (HR = 1.72; 95%CI, 1.182.49; P = .004). After multivariate analysis, only age persisted as an independent mortality predictor (HR = 1.09; 95%CI, 1.04-1.15; p = .001). For in-hospital mortality, we conducted a sensitivity analysis, eliminating patients who died during the first 48 hours (68 with STEMI and 18 with NSTEMI, out of 307 in-hosptial deaths). Killip class II remained as an independent mortality predictor in both the NSTEMI group (OR = 7.41; 95%CI, 4.82-11.39; P < .001) and the STEMI group (OR = 10.58; 95%CI, 6,26-17,89; P < .001), and statins treatment persisted as a predictor of good prognosis in the STEMI group (OR = 0.19; 95%CI, 0.12-0.32; p < .001). Our results clearly show that patients under conservative management have a higher basal risk than those treated invasively, which could justify invasive therapy. Of the variables analyzed, the only independent predictor of in-hospital mortality in the 2 infarction groups is Killip class II, an indicator of major clinical and hemodynamic instability. Notably, age is not a predictor of inhospital mortality in either of the AMI groups, but is a predictor of mortality risk during follow-up. The influence of age on the treatment of acute coronary syndrome was analyzed in the MINAP registry, which showed that the use of invasive treatment was Rev Esp Cardiol. 2015;68(4):343–354

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8–2.5, P<0.001) and bleedings (HR 1.5, 1.1–2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4–0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3–0.8, P=0.02), statins (RR 0.3, 0.2–0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3–0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6–1.5, P=0.9) were neutral. Conclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Primary Prevention of Sudden Death in Patients With Valvular Cardiomyopathy

INTRODUCTION AND OBJECTIVES Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. METHODS This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. RESULTS Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03). CONCLUSIONS All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy.

Another brick in the wall: The impact of ticagrelor use on the incidence of stroke in a large registry

The risk of ischaemic stroke is a common concern among physicians who care for patients with acute coronary syndrome (ACS). These patients typically have multiple cardiovascular risk factors and require treatment with a dedicated medical regimen. The interesting work of Ulvenstam and colleagues seeks to further explore the impact of recent changes in medical treatment following percutaneous coronary interventions (PCIs) on stroke, which is often considered a secondary endpoint in the field of interventional cardiology. In their manuscript, the authors retrospectively evaluated the one-year incidence of ischaemic stroke among 34,933 patients following PCI for acute myocardial infarction (AMI) from 2009 to 2013 in Sweden. They assessed the impact of ticagrelor on ischaemic stroke by dividing the population into two time-blocks based on the introduction of ticagrelor. The first period was from December 2009 to December 2011, during which only clopidogrel was used. During the second period, from December 2011 to December 2013, 40% of patients were treated with clopidogrel and 60% with ticagrelor. Interestingly, there was a 21% relative risk reduction of ischaemic stroke in the second time block with a significant absolute lower incidence of ischaemic stroke (2.2% vs. 1.8%, see Figure 1). Moreover, the authors identified several variables associated with increased stroke risk, including older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and STEMI. The authors concluded that ticagrelor was associated with a significant reduction of ischaemic stroke rate over the time. Dual anti-platelet therapy (DAPT) is considered a standard of care for patients with AMI treated with PCI. The favourable results of the randomized clinical trial PLATO (see Figure 1) led to a progressive replacement of clopidogrel with the newer P2Y12 receptor blocker ticagrelor in the setting of PCI for ACS. However, no difference was observed in ischaemic stroke at 12 months’ follow-up (1.1% in both groups). The difference between the paper of Ulvenstam and the PLATO trial lies in the different populations considered in the two studies, as the authors comprehensively discussed in their paper. In the modern era of evidence-based medicine, results from randomized controlled trials (RCTs) are promptly translated into guidelines that greatly impact our daily practice. Nevertheless, cohorts enrolled in RCTs are usually composed of highly selected patients, substantially different from that seen in real-world practice. Despite the presence of typical cardiovascular risk factors and a higher incidence of STEMI in the PLATO population, patients in the observational study by Ulvenstam et al. were older and more likely to have a history of prior ischaemic stroke, a recognized predictor of further ischaemic cerebral accidents. Moreover, patients with atrial fibrillation with an indication for oral anticoagulation were excluded from PLATO. On the other hand, physicians ordinarily deal with difficulties like the choice of a correct combination of anti-coagulant and anti-platelet drugs along with sub-optimal therapy regimens in patients suffering of both AF and other risk factors for cerebrovascular diseases. These baseline differences may make the real-world population at great risk for ischaemic stroke and help account for the beneficial effect of ticagrelor in regard to the reduction of ischaemic stroke in the real-world population.

Comparative Evaluation of Four Risk Scores for Predicting Mortality in Patients With Implantable Cardioverter-defibrillator for Primary Prevention

INTRODUCTION AND OBJECTIVES Several clinical risk scores have been developed to identify patients at high risk of all-cause mortality despite implantation of an implantable cardioverter-defibrillator. We aimed to examine and compare the predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and SHOCKED) for predicting mortality after defibrillator implantation for primary prevention of sudden cardiac death in a Mediterranean country. METHODS A multicenter retrospective study was performed in 15 Spanish hospitals. Consecutive patients referred for defibrillator implantation between January 2010 and December 2011 were included. RESULTS A total of 916 patients with ischemic and nonischemic heart disease were included (mean age, 62 ± 11 years, 81.4% male). Over 33.4 ± 12.9 months, 113 (12.3%) patients died (cardiovascular origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were 4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise increase in the risk of death throughout the scoring system of each of the scores and all 4 scores identified patients at greater risk of mortality. The scores were significantly associated with all-cause mortality throughout the follow-up period. PACE displayed the lowest c-index value regardless of whether the population had heart disease of ischemic (c-statistic = 0.61) or nonischemic origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic = 0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided similar c-statistic values (P ≥ .09). CONCLUSIONS In this nontrial-based cohort of Mediterranean patients, the 4 evaluated risk scores showed a significant stepwise increase in the risk of death. Among the currently available risk scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than PACE.