Gabriel Greenberg

Hematocrit Level as a Marker of Outcome in ST-Segment Elevation Myocardial Infarction

Anemia is a well-known predictor of a poor outcome in patients with ST-segment elevation myocardial infarction (STEMI). In contrast, data relating erythrocytosis to clinical outcomes in patients with STEMI are limited. Because erythrocytosis predisposes to a prothrombotic state, we hypothesized it would be associated with an increased risk of thrombotic complications in patients with STEMI undergoing primary percutaneous coronary intervention. We studied 1,042 consecutive patients with STEMI who underwent primary percutaneous coronary intervention and were a part of our primary percutaneous coronary intervention registry from 2001 to 2007. Patients with cardiogenic shock and late arrival were excluded. Patients were allocated into 3 groups according to their baseline hematocrit: anemia (<36% for women and <39% for men), normal, erythrocytosis (>46% for women and >47% for men). The clinical outcomes were assessed at 1, 6, and 12 months. The patients with anemia had the greatest clinical risk profile. Patients with erythrocytosis had a lower risk profile than the other 2 groups, except for greater rates of smoking. The mortality rates were greatest among the patients with anemia, followed by the patients with erythrocytosis, who in turn had greater short-term mortality than patients with normal hematocrit. Multivariate analysis, which included patients with erythrocytosis and those with normal hematocrit (excluding the patients with anemia), revealed that erythrocytosis was associated with an odds ratio of 4.3 (95% confidence interval 1.4 to 13, p = 0.01) for 1-month mortality. In conclusion, although not as strong a predictor of mortality as anemia, erythrocytosis might be associated with increased short-term mortality compared to a normal hematocrit. The measurement of hematocrit can be used as a useful prognostic marker in patients with STEMI.

Predictors of Long Term Outcomes in 11,441 Consecutive Patients Following Percutaneous Coronary Interventions

Given the vicissitudes of percutaneous coronary intervention (PCI) technology, epidemiology, and mode of practice, the aim of this study was to define contemporary outcome predictors in a very large consecutive patient cohort. Data from 11,441 consecutive patients who underwent PCI at a tertiary medical center from April 2004 to September 2013 are presented. A comprehensive database was built using various data sources, with outcome end points defined as all-cause mortality and as a composite of death or nonfatal myocardial infarction during follow-up. Candidate variables to influence outcome were chosen a priori and were tested using multivariate time-dependent models to estimate each interaction. Mean follow-up was 5.5 years (range 3 months to 9.5 years). The cohort consisted of 75% men, 42% patients with diabetes, and 61% patients who underwent PCI in acute coronary syndrome settings and 7.8% for ST-elevation myocardial infarction. Drug-eluting stents were used in 43.4% of patients, bare-metal stents in 52%, and balloon angioplasty alone in 4.6%. In multivariate analysis, in addition to already well-recognized predictors of death or myocardial infarction such as advanced age (hazard ratio [HR] 1.031, p <0.001), female gender (HR 1.23, p <0.001), urgent setting (HR 1.23, p <0.001) and diabetes mellitus (HR 1.28, p <0.001), we particularly noted previous anemia (HR 1.55 p <0.001), previous chronic kidney injury (HR 1.93, p <0.001) and previous moderate to severe left ventricular dysfunction (HR 2.29, p <0.001). Drug-eluting stent placement was associated with better outcomes (HR 0.70, p <0.001). In conclusion, this analysis confirms the effect of some known predictors of PCI outcomes. However, the extent of their effect is modest, while other predictors may have a greater influence on outcomes. Risk stratification of PCI patients should take into account kidney injury, anemia, and left ventricular function. Drug-eluting stents provide sustained benefit.

Outcomes of acute heart failure associated with acute coronary syndrome versus other causes

Background: By and large, prior registries and randomized trials have not distinguished between acute heart failure (AHF) associated with acute coronary syndrome (ACS) versus other causes. Aims: To examine whether the treatments and outcomes of ACS-associated AHF are different from non-ACS-associated AHF. Methods: We examined in a prospective, nationwide hospital-based survey the adjusted outcomes of AHF patients with and without ACS as its principal cause. Results: Of the 4102 patients in our national heart failure survey, 2336 (56.9%) had AHF, of whom 923 (39.5%) had ACS-associated AHF. These patients were more likely to receive intravenous inotropes and vasodilators and to undergo coronary angiography and revascularization, but less likely to receive intravenous diuretics. The unadjusted in-hospital, 30-day, one-year, and four-year mortality rates for AHF patients with or without ACS were 6.5% versus 5.0% (P = 0.13), 10.3% versus 7.5% (P = 0.02), 26.6% versus 31.0% (P = 0.02), and 55.3% versus 63.3% (P = 0.0001), respectively. In the multivariate analysis, the adjusted mortality risk for patients with ACS at the respective time points were 1.46 (0.99–2.10), 1.67 (1.22–2.30), 1.02 (0.86–1.20), and 0.93 (0.82–1.04). Conclusions: Patients with ACS-associated AHF seem to have a unique clinical course and perhaps should be distinguished from other AHF patients in future trials and registries.

Outcome of Patients Presenting with ST Elevation Myocardial Infarct and Cardiogenic Shock: A Contemporary Single Center’s Experience

Objectives: Acute ST elevation myocardial infarction (STEMI) presenting with cardiogenic shock (CS) is associated with dismal prognosis. In the last years, significant advances have been made in reperfusion techniques and pharmacological treatment. Therefore, we aimed to assess the outcome of these patients during the past decade and identify major factors that impact their prognosis. Methods: We identified 170 patients who presented with STEMI, CS, and underwent primary percutaneous coronary intervention (PCI) between 2001 and 2011. Patients were allocated into two groups based on period of presentation: 2001–2005 (n = 70) and 2006–2011 (n = 100). Clinical outcomes up to 6 months were evaluated. Results: Patients in the latter period were younger, and had lower rates of renal failure and higher rates of stent use. Despite these differences, mortality did not differ and remained high in both periods (52–59% at 6 months). Time frames from onset of symptoms to arrival to the emergency department and to performance of coronary intervention were similar in both periods. Intra-aortic balloon pump use was similar in both periods. In multivariate analysis, factors associated with 1-month mortality were: diabetes (OR = 3.6, 1.4–9.4, p = 0.007), LVEF <40% (OR = 1.8, 1.3–2.6, p = 0.001), GFR <60 ml/min/m2 (OR = 1.8, 1.3–2.4, p < 0.009) and glycoprotein IIb/IIIa inhibitor use (OR = 0.5, 0.2–1.1, p = 0.08). The combination of diabetes and renal failure was associated with particularly high mortality. Conclusions: Prognosis of patients presenting with STEMI, CS, and treated with primary PCI during the past decade, remains poor. Better risk-stratification may help improve their grave outcome.

Effects of prasugrel pretreatment on angiographic myocardial perfusion parameters in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

ObjectivePrasugrel is a third-generation thienopyridine, with significant pharmacodynamic and clinical advantages over clopidogrel. There are few data on the effects of prasugrel therapy, as compared with clopidogrel, in terms of perfusion during percutaneous coronary intervention (PCI), in patients with ST-elevation myocardial infarction (STEMI). MethodsA total of 128 patients with STEMI, pretreated with prasugrel 60 mg loading dose (mean age=55.9±9.1; 10.9% were women and 18.0% had diabetes), were compared with 128 propensity-matched patients pretreated with clopidogrel 600 mg (mean age=58.7±10.7; 10.2% were women and 19.5% had diabetes) for the primary endpoint of thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade at completion of the PCI. Secondary endpoints included the combined sum of major adverse events: death, reinfarction or target vessel revascularization at 1 year. ResultsMean TIMI flow grade pre-PCI was similar between the two groups (1.31±1.3 in the prasugrel group and 1.30±1.2 in the clopidogrel group, P=0.96). However, after intervention, it was higher in the prasugrel group (2.94±0.24 vs. 2.84±0.37, respectively, P=0.016), as was myocardial blush (2.70±0.76 vs. 2.31±0.52, respectively, P<0.001). The percentage of TIMI 3 after intervention was also higher in the prasugrel group (97.70 vs. 90.60%, P=0.02). The combined rate of major adverse events at 1 year (8.7 vs. 11.6%, P=0.11), as well as total mortality (3.1±5.6 vs. 4.7±9.1%, P=0.52), did not differ between the two groups. ConclusionIn patients with STEMI undergoing primary PCI, pretreatment with prasugrel resulted in better angiographic perfusion results, as compared with pretreatment with clopidogrel.

Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection

αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

Temporal trends in percutaneous coronary interventions thru the drug eluting stent era: Insights from 18,641 procedures performed over 12‐year period

The last decade, regarded as the DES era in PCI, has witnessed significant advances in the management of coronary disease. We aimed to assess temporal trends in the practice and outcome of percutaneous coronary intervention (PCI) during the drug eluting stent (DES) era.

Coronary stenting approaches in the treatment of chronic total occlusion: contemporary registry-based experience.

Aims This ‘real-world’ investigation attempted to determine the long-term prognoses of patients who have undergone successful revascularization of chronic total occlusion (CTO) lesions. Methods All consecutive unselected patients from January 2006 to June 2011, undergoing stenting for CTO (n = 272), were retrospectively identified through an institutional registry. Procedural failure was defined as final diameter stenosis greater than 30% or postdilatation thrombolysis in myocardial infarction flow less than 3. Outcomes were assessed based on stenting type [bare metal stent (BMS), drug-eluting stent (DES), or mixed] in the successful procedural cohort. Multiple logistic regression analyses were used to account for known baseline cardiovascular risk imbalances. The primary endpoint was 2-year target vessel revascularization. Results Overall procedural failure occurred in 55 (20.2%) patients presenting with CTO lesions. Failed revascularization was independently associated with multivessel disease, lesion lengths greater than 15 mm, tortuous segments, and presence of calcifications. Major complications included coronary dissection (10%) and perforation (2%). Of the successful procedures, 141 (64%) underwent pure DES, 46 (21%) pure BMS, and 34 (15%) mixed stenting. At 2-year follow-up, fewer patients in the DES group required repeat revascularization compared to the mixed stenting group (6 vs. 26%; P = 0.002). Mixed stenting was an independent predictor of long-term target vessel revascularization (adjusted odds ratio 2.1, 95% confidence interval 1.1–4.1, P = 0.02) compared to DES. Conclusions Failed revascularization of CTO lesions occurs in a fifth of patients and appears to be associated with complex vessel anatomy. Our data suggest that DES use in this setting are associated with improved 2-year clinical endpoints compared with pure BMS or mixed stenting approaches.

Prediction of mortality in hospital survivors of STEMI: External validation of a novel acute myocardial infarction prognostic score

INTRODUCTION & OBJECTIVE Recently we developed and internally-validated the Soroka Acute Myocardial Infarction (SAMI) Score for prediction of all-cause long-term mortality (c-statistic 0.83-0.94) among hospital-survivors of AMI. We aimed to perform an external-validation of the SAMI score for long-term risk-stratification of STEMI patients undergoing PCI. METHODS & SETTINGS A prospective registry of 1273 STEMI patients treated using primary PCI and discharged alive from Rabin Medical Center in Israel between 2004 and 2014 (age 60.8 ± 12.5 years, 83% males) was utilized for the validation. Chi-square test and logistic regression were used for calibration, and c-statistic (ROC procedure) for discrimination assessment of the SAMI score. RESULTS All-cause mortality following one- and 5-years post-discharge was 3.8% and 8.1%, respectively. SAMI score values ranged between (-5) and (+15) points (median 2-points). In a univariate analysis the SAMI score variables were significantly associated with 1- and 5-years mortality. Higher SAMI score was associated with increased risk for dying: a one-point increase was associated with OR of 1.33 (95%CI: 1.24-1.42, p < 0.001) and 1.37 (95%CI: 1.29-1.44, p < 0.001) for 1- and 5-years mortality respectively. No statistically significant difference was found in the currently observed mortality rates by groups of SAMI score and the expected mortality rates as per the SAMI score index. The c-statistics were 0.82 and 0.83 for 1- and 5-year mortality, respectively. CONCLUSIONS The SAMI score is a simple, robust and now also externally-validated prognostic tool for prediction of long-term all-cause mortality in hospital survivors of STEMI.