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Background Diagnosis of acute myocardial infarction (MI) is challenging in pacemaker patients. Little is known about this patient group. Methods Patients with MI enrolled in the Swiss national AMIS Plus registry between January 2005 and December 2015 were analyzed. All patients with either paced ventricular rhythm or sinus rhythm with intrinsic ventricular conduction (IVC) were included in this study. Outcomes using crude data and propensity score matching were compared between patients with pacemaker rhythm and patients with IVC. The primary endpoint was in-hospital death. Results Data from 300 patients with paced rhythm and 27,595 with IVC were analyzed. Patients with pacemaker rhythm were older (78.2 y vs 65.4 y; p < 0.001), had more comorbidities (Charlson Index (CCI) > 1: 54.0% vs 21.1%; p < 0.001) and a higher rate of heart failure upon presentation (Killip class > 2, 11.0% vs 5.9%; p < 0.001) compared to patients with IVC. Door to balloon time in patients undergoing acute PCI is markedly delayed in contrast to patients with IVC (280 min vs 85 min; p < 0.001). Consequently, crude mortality in patients with pacemakers was high (11.3% vs 4.6%; p < 0.001). However, when analyzed with propensity matching for gender, age, CCI > 1 and Killip > 2, mortality was similar (11.2% vs 10.5%; p = 0.70). Conclusion Pacemaker patients with acute MI represent a high-risk group with doubled crude mortality compared to patients without pacemakers, due to higher age and higher Killip class. Diagnosis is difficult and results in delayed treatment. Treatment algorithms for MI with paced rhythm should possibly be adapted to those used for STEMI or new left bundle branch block. Clinical Trials Registration : NCT01305785. [ABSTRACT FROM AUTHOR]

Background Women with AMI may have worse outcomes than men. However, it is unclear if this is related to differences in treatment, treatment effect or gender specific factors. We sought to determine whether primary percutaneous intervention (PCI) has a differential impact on infarct size, myocardial perfusion and ST segment resolution in men and women with acute myocardial infarction (AMI). Methods A total of 501 AMI patients were prospectively enrolled in the EMERALD study and underwent PCI with or without distal protection. Post hoc gender subset analysis was performed. Results 501 patients (108 women, 393 men) with ST-segment elevation AMI presenting within 6 h underwent primary (or rescue) PCI with stenting and a distal protection device. Women were older, had more hypertension, less prior AMI, smaller BSA, and smaller vessel size, but had similar rates of diabetes (30% versus 20.2%, p = 0.87), LAD infarct, and time-to-reperfusion compared to men. Women more frequently had complete ST-resolution (> 70%) at 30 days (72.8% versus 59.8%, p = 0.02), and smaller infarct size compared to males (12.2 ± 19.6% versus 18.4 ± 18.5%, p = 0.006). At 6 months, TLR (6.9% versus 5.2%) and MACE (11.4% versus 10.3%) were similar for women and men. Conclusions Despite worse comorbidities, women with AMI treated with primary PCI with stenting showed similar early and midterm outcomes compared to men. [ABSTRACT FROM AUTHOR]

Background Low-range troponin elevations without clear coronary manifestations remain a major diagnostic challenge. We sought to determine if troponin velocity could allow for early identification of patients without an obvious cardiac diagnosis and who are at increased risk for cardiac-specific events. Methods & results All patients presenting to South Australian public hospitals between 1 September 2011 and 30 September 2012, with at least two troponin measurements during the first 6 h after ED presentation were included. Diagnoses were classified as ‘coronary’, ‘non-coronary cardiac’, and ‘non-cardiac’ using the International Classification of Diseases 10 codes. The relationship between troponin velocity and cardiac-specific mortality and combined cardiac outcome (death and myocardial infarction) was assessed using Fine and Gray competing risk models in patients with an initial troponin < 52 ng/L. Sensitivity analyses were performed using different initial and maximum troponin cut-off values. In total, 7300 patients were identified. A troponin velocity of 2.5 ng/L/h or greater in the non-cardiac (n = 2793) patient group was significantly associated with an increased risk for 12-month cardiac mortality (sub-hazard ratio [SHR] 2.90, 95% CI 1.33–6.34) and combined cardiac outcome (SHR 2.08, 95% CI 1.01–4.27). This association was consistent for coronary (n = 3835) and non-coronary cardiac (n = 672) patient groups, and remained after sensitivity analyses. Conclusions The significant association observed across all patient groups suggests that troponin velocity could be used for early risk stratification of patients with low-range troponin elevations without clear cardiac symptoms. These results may help guide future clinical trials aimed at assessing the utility of cardiac-targeted interventions in this challenging patient population. [ABSTRACT FROM AUTHOR]

Background In cardiogenic shock (CS) renal dysfunction is an important parameter of inadequate end-organ perfusion and an independent predictor of adverse outcome. Early detection of renal dysfunction is therefore important, and novel biomarkers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM1) and Cystatin C (CysC) have been suggested. However, in high-risk CS patients their role for assessing renal injury has not yet been investigated in comparison to the most widely used serum creatinine. Methods This predefined substudy included 190 patients of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial. Blood samples were collected directly during primary percutaneous coronary intervention, one day and two days after randomization. The primary endpoint for outcome assessment was 1 year mortality. Results Creatinine, NGAL and KIM-1 were significantly higher in non-survivors in comparison to survivors over time in ANOVA (p < 0.001; p = 0.002 and p = 0.04, respectively). In contrast, CysC levels were not associated with the primary endpoint (p = 0.15). Receiver operator characteristics revealed that creatinine at any time point had the best predictive value for 1 year mortality. This was also true when comparing creatinine to different equations for glomerular filtration rate. In multivariable Cox-regression analysis creatinine remained the only significant independent predictor of kidney biomarkers of time to death during the first year. Conclusions Assessment of novel biomarkers such as CysC, NGAL and KIM-1 or calculation of glomerular filtration rate provide no additional prognostic information in patients with CS complicating acute myocardial infarction in comparison to creatinine. [ABSTRACT FROM AUTHOR]

Ischaemia−reperfusion (IR) injury is an important cause of myocardial damage during percutaneous coronary intervention (PCI). There are few therapies in widespread clinical use which impact on IR injury and it remains an important and underutilized target for treatment in acute myocardial infarction. This review will examine the translational scientific evidence for ischaemic conditioning and pharmacological agents including conditioning mimetics such as cyclosporine, anti-inflammatory agents, and those which modify myocardial glucose metabolism. We will address the reasons why many trials have failed to demonstrate clinical benefit and emphasize the need to deliver the right therapy to the right patient, at the right time to achieve successful translation of cardioprotection from bench-to-bedside. We critique trial design and offer advice for future translational trials in the field to ensure that effective treatments can be demonstrated clinically to improve patient outcomes during PCI. [ABSTRACT FROM AUTHOR]

Abstract: Background: The incidence and treatment strategies of acute coronary syndrome (ACS) vary by region. Additionally, the clinical spectrum of ACS is changing and outcomes are improving. Aim: We assessed the incidence, treatment strategies, and outcomes of ACS for a well-defined population within a well-established network of percutaneous coronary intervention (PCI) centers and non-PCI centers. Methods: The CZECH-2 registry included 1221 consecutive patients (mean age: 68±13years; 63.4% males) admitted for suspected ACS to 32 hospitals (including 4 PCI centers) within four Czech counties (total population: 2,370,841 inhabitants) during a 2-month period. Results: The estimated incidence of confirmed ACS was 2149cases/million/year. In 374 (31%) patients, ACS was ruled out during the hospital stay. Coronary angiography (CAG) was performed in 60% of the patients overall and PCI was performed in 59% of the confirmed ACS patients. Killip classifications II–IV on admission were more common in patients with final diagnosis of non ST-elevation myocardial infarction (NSTEMI) than ST-elevation myocardial infarction (STEMI) (37.1% vs. 22.8%; p<0.001). The 30-day mortality rate was 5.7% for the whole study group, 7.3% for STEMI patients, 8.4% for NSTEMI patients, and 1.6% for patients with unstable angina pectoris (UAP), respectively. Conclusions: Almost one-third of the patients admitted for suspected ACS had a different final diagnosis. Among those with confirmed ACS, the use of CAG, PCI, CABG, and effective medications is rational. Outcome in NSTEMI patients was equivalent to those in STEMI patients, mainly due to the high-risk population in this group. [Copyright &y& Elsevier]

Abstract: Background: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). Methods: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. Results: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio=0.95, 95% CI=0.74–1.21, P =0.67). Target lesion revascularization was also comparable between the groups (hazard ratio=0.89, 95% CI=0.65–1.22, P =0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio=0.52, 95% CI=0.28–0.96, P =0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4years (hazard ratio=0.15, 95% CI=0.03–0.70, P =0.02). Conclusions: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4years. Rates of stent thrombosis were significantly lower with BP-DES. [Copyright &y& Elsevier]

Abstract: Objective: Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. Methods: We examined information from the FDA complete response review. Results: FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p=0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p=0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR=1.21, 95% CI: 0.91 to 1.59, p=0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p<0.0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p=0.002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to “softer” endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor. Discussion: The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality. [Copyright &y& Elsevier]

Abstract: The renin–angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted. [Copyright &y& Elsevier]

Abstract: Background: Early abciximab administration in patients requiring transportation to undergo primary percutaneous coronary intervention (PPCI) has been reported to improve clinical outcome. We aimed to verify whether early administration leads to reduced infarct size (IS), assessed by delayed-enhancement magnetic resonance imaging (DE-MRI). Methods: We randomized 110 patients with acute myocardial infarction with symptom-to-diagnosis time <6h to either early (55 patients) or late (55 patients) abciximab administration. DE-MRI was performed at 4days and 6months. The primary end point was IS at 6months. Secondary end points were the rate of ST-segment elevation resolution ≥50% (STR) at 60min after PPCI, the extent of microvascular obstruction at 4days, and the change in IS and transmurality at 6months vs. 4days. Results: DE-MRI was performed in 103 patients after 4days, and in 87 at 6months. The mean IS at 6months was 13.8±9.0% in the early vs. 13.0±9.9% in the Late group (P >0.2). Similarly, microvascular obstruction and the change in IS were not significantly different. The Early group showed a significantly higher STR (94.5% vs. 80.0%, P =0.04) and a larger reduction in infarct transmurality (−9.2±7.0% vs. −5.9±6.4%; P =0.03), while a larger reduction in IS was observed only in patients with ECG-to-Cath Lab time >60min. Conclusions: Early abciximab administration did not lead to a smaller IS at 6-month DE-MRI, and was associated with a significant reduction in IS and transmurality only in patients with longer transportation time, warranting further investigation in this patient subset. [Copyright &y& Elsevier]

Abstract: Background: There is a paucity of data concerning the clinical outcome of patients presenting with acute myocardial infarction (AMI) and near-normal coronary angiograms. The purpose of this study was to evaluate the clinical outcome and the prognosis of the patients with near-normal coronary angiograms who were registered in the Korean Acute Myocardial Infarction Registry (KAMIR). Methods: The subjects were divided into three groups according to findings from coronary angiograms performed between September 2005 and November 2006. Among 8510 consecutive AMI patients, 372 patients (Group I) had near-normal coronary arteries, 6136 patients (Group II) had one- or two-vessel disease, and 2002 patients (Group III) had three-vessel or left main disease. Results: Clinical characteristics, in-hospital mortality, and major cardiac adverse events (MACE) were analyzed. Group I was younger, had the lower prevalence of DM, and showed the higher percentage of previous angina history compared to the other two groups. Group III showed a higher incidence of in-hospital mortality, but there was no significant difference between Group I and Group II (2.6% in Group II and 2.2% in Group I, p =0.952). Furthermore, MACE at 1month, 6months and 12months revealed no significant difference between Groups I and II (12month MACE: 7.8% in Group I and 12.2% in Group II, p =0.359). Conclusions: Patients with near-normal coronary angiograms had similar clinical outcomes and prognosis compared with one- or two-vessel diseased patients presenting with an acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Abstract: Cellular cardiomyoplasty is an investigational technique that may have the potential to reduce myocardial infarct size and improve cardiac function in patients with ischemic heart disease. However, experience with this approach is still limited to a few small trials, some of which were not blinded or had other design problems. The mechanism of benefit, long-term safety, and clinical efficacy of cellular cardiomyoplasty require further study. [Copyright &y& Elsevier]

Abstract: Aim: To examine the impact of primary stent implantation versus balloon angioplasty on long-term outcome (median 8 years) in 117 patients with ST-elevation myocardial infarction (STEMI) from randomized trials. Methods: Enrolled patients were those presenting with STEMI within 12 h of symptom onset. Patients were randomized to either Palmaz–Schatz stent implantation (N =25) or balloon angioplasty (N =23) between January and November 1996; or Palmaz–Schatz (N =26), or Cordis coil stent implantation (N =24) or balloon angioplasty (N =19) between February 1998 and March 1999. Results: Patients (67±11 years) arrived to the hospital within median 2.5 h of symptom onset with Killip 1/2/3/4 grade (72/19/7/2%, respectively). The culprit lesion was located in the left anterior descending (50%), right (39%), or left circumflex coronary artery (11%) with TIMI 0/1/2/3 flow (81/5/12/2%, respectively). Clinical/angiographic features were comparable between the 2 groups. During follow-up, there was a significant reduction in cardiac mortality in the stent group (5%) compared to the angioplasty group (17%, log-rank test p =0.04). In addition, the stent group had a lower target lesion revascularization rate (28% versus 52%, p =0.008), and a significantly lower major adverse cardiac event rate (37% versus 67%, p =0.005), than the angioplasty group. Conclusion: Compared to balloon angioplasty, primary stenting resulted in a sustained beneficial effect on cardiac mortality at 8 years. [Copyright &y& Elsevier]

Abstract: Background: Acute anterior myocardial infarction (MI) caused by proximal occlusion of the left anterior descending coronary artery (LAD), is associated with unfavourable outcome and should be recognized by simple noninvasive methods like the 12-lead electrocardiogram (ECG). Methods: In a prospective post-hoc DANAMI-2 substudy we compared two pre-specified ECG patterns to determine the level of LAD occlusion. The ECG findings were correlated to coronary angiography from the acute phase. The impact on clinical outcome of ECG and angiographic signs of proximal versus distal LAD occlusion was studied. Results: In 146 patients without confounding factors on the ECG, either ST-elevation ≥0.5 mm in lead aVL or any ST-elevation in lead aVR in association with precordial ST-segment elevation in at least two contiguous leads (including V2, V3 or V4) had a sensitivity of 94%, specificity of 49%, positive predictive value of 85% and negative predictive value of 71% to predict a proximal LAD lesion. Surprisingly, ECG or angiographic signs of lesion proximality were not associated with worse outcome at 30 day or 2.7 year follow-up. Conclusions: The site of occlusion in the LAD could be reliably predicted by 12-lead ECG in patients with acute anterior MI. The prognostic significance of the level of occlusion in the LAD in the modern era of acute ST-elevation MI treatment should be reassessed. [Copyright &y& Elsevier]