Relationship between beta-blocker and angiotensin-converting enzyme inhibitor dose and clinical outcome following acute myocardial infarction.

BACKGROUND: Benefit of ß-blockers (BB) and angiotensin-converting-enzyme inhibitors (ACEI) on mortality following acute myocardial infarction (MI) is well demonstrated. This study assessed the impact of BB and ACEI doses administered following ST-elevation MI on mortality and outcome up to 1 year. METHODS AND RESULTS: The French prospective observational cohort "RIMA" included 1,461 MI patients. Dosing of BB and ACEI given at 24 h and at time of discharge was assessed as follows: no treatment; <50% of target dose; or ≥50% of target dose. For in-hospital mortality, after MI, the use of BB in the first 24 h, but not ACEI, was associated with significantly lower event rate on multivariate analysis (OR, 5.78; 95% CI: 2.62-12.76, P<0.001). In contrast at 1 year, use of higher doses of ACEI, but not BB, was associated with significantly lower CV mortality, readmission for heart failure and the composite of CV mortality and readmission for heart failure (HR, 2.65; 95% CI: 1.32-5.31, P=0.006 for absence of ACEI at discharge). CONCLUSIONS: Prescription of BB in the first 24 h was independently associated with a lower in-hospital mortality following MI. There appeared to be a significant dose effect on outcome with regard to <50% vs. ≥50% of target dose, which requires confirmation in further large-scale clinical studies.

Prognostic impact of body mass index on in-hospital bleeding complications after ST-segment elevation myocardial infarction.

BACKGROUND: ST-elevation myocardial infarction (STEMI) remains a major cause of mortality despite early revascularization and optimal medical therapy. Tailoring individual management by considering patients' specificities may help in improving post-STEMI survival. AIM: To evaluate whether in-hospital bleeding complications may be involved in post STEMI prognosis among overweight patients. METHODS: We prospectively included 2070 patients with a STEMI between January 2005 and December 2012 in the French observational cohort, "Registre d'Infarctus Maine-Anjou". Bleeding Academic Research Consortium (BARC) in-hospital bleeding complications were recorded. RESULTS: Of 705 patients (35.3%) were presented as being of normal weight, defined as a body mass index (BMI) < 25 kg/m², 877 (43.9%) had a BMI between 25 and 30 kg/m² and 416 (20.8%) had a BMI ≥ 30 kg/m². One-year cardiovascular mortality was lower for BMI ≥ 25 kg/m² (5.3% and 7.1%) patients than for normal weight patients (10.8%) (P = 0.001). We found an interaction between the effect of BARC 3 on mortality and BMI groups. While a BARC 3 was related to a higher 1-year mortality in general (HR: 2.58, 95%CI: 1.44-4.64, P ≤ 0.001), prognosis was even worse in normal weight patients (HR: 2.97, 95%CI: 1.61-5.5, P < 0.001) than for patients with a BMI ≥ 25 kg/m² (HR: 1.94, 95%CI: 1.02-3.69, P = 0.041). CONCLUSION: Normal weight patients presented higher rates of in-hospital bleeding complications and lower survival after a STEMI. Excess mortality might be due to greater vulnerability to bleeding amongst normal weight patients.

De novo atrial fibrillation as an independent prognostic marker after ST-segment elevation myocardial infarction: Results from the RIMA registry.

BACKGROUND: Atrial fibrillation (AF) is common in ST-segment elevation myocardial infarction (STEMI), but its influence on prognosis remains controversial. AIM: We examined the 1-year prognostic value of AF in STEMI, distinguishing patients with prior AF from patients with de novo AF. METHODS: Between January 2004 and December 2015, 3173 STEMI patients were enrolled in the RIMA registry (Registre des Infarctus en Maine Anjou). They were divided into 3 groups: (1) AF-free patients; (2) patients with known prior AF; and (3) patients with de novo AF during hospitalization (including admission). We defined 3 primary outcomes at 1-year post-discharge: cardiovascular mortality, readmission for heart failure (HF), and stroke. Temporal onset of de novo AF was also studied. RESULTS: A total 158 patients (5%) had prior AF, and 278 (8.8%) presented de novo AF. Prior AF patients were significantly older [81 (73;86) years] with more comorbidities, but de novo AF patients presented with a greater creatine kinase peak and lower left ventricular ejection fraction [LVEF=44 (35;50)% for de novo AF vs 50 (40;55)% for prior AF, p<0.001]. At 1-year follow-up, cardiovascular mortality was higher in cases of AF (13.5% for prior AF vs 9.2% for de novo AF, compared with 2.4% for AF-free patients, p<0.001). After adjustments, only de novo AF was correlated with cardiovascular mortality (hazard ratio 2.49; 95% CI 1.32-4.67; p=0.004), but both types of AF were correlated with readmission for HF. There was no significant difference in respect of stroke between prior AF, de novo AF, and AF-free (2.2%, 0.5%, and 0.8%, respectively, p=0.327). Finally, outcomes did not differ between AF occurring <24h after admission (n=127) and de novo AF occurring within ≥24h (n=151). CONCLUSION: De novo AF was independently associated with 1-year cardiovascular mortality. It should not be considered as an intercurrent event of STEMI, but rather as a strong prognostic marker.

Relation of Quantity of Subepicardial Adipose Tissue to Infarct Size in Patients With ST-Elevation Myocardial Infarction.

According to the so-called obesity paradox, obesity might present a protective role in patients with myocardial infarction. We aimed to assess the influence of the epicardial adipose tissue (EAT) volume on cardiac healing and remodeling in patients with acute ST-elevation myocardial infarction. We prospectively included 193 consecutive patients presenting a first STEMI without known coronary artery disease. Cardiac magnetic resonance imaging was performed at baseline and after a 3-month follow-up. EAT volume was computed, and the population was divided into quartiles: the highest quartile of EAT defining the high EAT group (h-EAT). h-EAT was associated with increased body mass index, higher rate of history of hypertension, and smaller infarct size at initial CMR assessment (18.3 ± 11.9% vs 23 ± 13.7% of total left ventricular [LV] mass, p = 0.041). Moreover, microvascular obstruction was less frequent in the h-EAT group (36.2% vs 59.3%, p = 0.006). There were no differences in LV ejection fraction (LVEF), LV volumes, systolic wall stress, coronary artery burden, and clinical events during the index hospitalization between the EAT groups at baseline and at follow-up. Linear regression analysis showed h-EAT to be associated with smaller infarct size at baseline (ß coefficient = -3.25 [95% CI -5.89 to -0.61], p = 0.016). h-EAT also modified positively the effect of infarct size on LV remodeling, as assessed by the change in LVEF (p = 0.046). In conclusion, h-EAT was paradoxically related to smaller infarct size and acted as an effect modifier in the relation between the extent of infarct size and LVEF changes. Patients with higher extent of EAT presented better cardiac healing.

End-systolic wall stress predicts post-discharge heart failure after acute myocardial infarction.

BACKGROUND: Compensatory mechanisms activated after myocardial infarction include an increase in systolic wall stress (SWS) and activation of the neurohormonal system. Nevertheless, left ventricular ejection fraction (LVEF) and infarct size are the established primary predictors of outcome after ST-segment elevation myocardial infarction. AIMS: To assess the relative impact of various cardiac magnetic resonance (CMR) imaging variables, such as infarct size, LVEF and SWS, on pre- and post-discharge heart failure (HF). METHODS: CMR was performed in a prospective study involving 169 patients with first ST-segment elevation myocardial infarction. Common CMR findings, such as SWS, were computed. RESULTS: Mean SWS was 16.3±5.1×10(3)N·m(-2), and was systematically higher in patients exhibiting either pre- or post-discharge HF (18.9±5.7 and 21.3±7.6×10(3) N·m(-2), respectively). SWS was moderately related to initial infarct size (r=0.405; P <0.001). In total, 28 patients presented with HF during the hospitalization phase and 14 during follow-up, with a median time of event of 93 days (25th-75th percentiles, 29-139.25 days). The univariate predictors of HF were age, LVEF, infarct size, SWS, microvascular obstruction, anterior infarction and heart rate at admission. Multivariable analysis revealed infarct size and age to be the predictors of predischarge HF, while SWS and heart rate at admission predicted post-discharge HF. The greatest SWS quartile provided a negative predictive value of 95.9%. CONCLUSION: Regardless of LVEF and infarct size, SWS was shown to be an independent predictor of post-discharge HF after ST-segment elevation myocardial infarction.

Predictive Factors of Pericardial Effusion After a First Acute Myocardial Infarction and Successful Reperfusion.

The aim of the study was to identify the determinants of pericardial effusion (PE) after a first myocardial infarction (MI). Cardiac magnetic resonance enables early analysis of multiple post-MI parameters; 193 patients with a first ST-elevation MI admitted to the Angers University Hospital (France) were enrolled prospectively. Cardiac magnetic resonance was performed at baseline (median of 5 days [4 to 7]) and repeated at a 3-month follow-up to investigate left ventricular (LV) volumes, LV ejection fraction, infarct size, microvascular obstruction (MVO), systolic wall stress (SWS), and PE presence and extent. A 1-year follow-up was also performed. Overall, 113 patients (58.5%) showed a PE with a median size of 31.6 ± 24.0 ml in the event that a PE was present. Patients with PE typically presented larger initial infarct sizes and LV volumes, and higher SWS, with more depressed LV ejection fraction and more frequent MVO and pleural effusions. Patients with PE exhibited higher rates of heart failure during hospitalization. At follow-up, there was no relevant PE, with no pericardiocentesis required. The multivariate analysis revealed SWS (odds ratio [OR] 1.092 [95% CI 1.007 to 1.184], p = 0.042), infarct size (OR 1.048 [95% CI 1.014 to 1.083], p = 0.003), and MVO extent (OR 1.274 [95% CI 1.028 to 1.579], p = 0.018) to be independent predictors for PE presence and volume. One patient died of LV free wall rupture during initial hospitalization, with only "small" PE found. In conclusion, infarct size, MVO, and SWS were independently related to PE presence and volume. Post-MI PE was found in 58.5% of cases, being regressive at follow-up. Among these patients with early reperfusion and optimal medical therapy, PE volume did not seem to be related to future clinical events.

Remote ischaemic preconditioning in intermittent claudication.

BACKGROUND: Remote ischaemic preconditioning (RIPC) protects tissues against ischaemia-reperfusion (I/R) injury, a common occurrence in several clinical settings. AIMS: To evaluate whether RIPC has a beneficial impact on walking disability in arterial intermittent claudication. METHODS: A total of 20 patients with proven intermittent claudication underwent two treadmill walking tests with a 7-day interval in between; they were randomized according to the order in which they received either RIPC or a control procedure before the first treadmill test, with a crossover at the second test. Patients received three cycles of alternating 5-minute inflation and 5-minute deflation of blood-pressure cuffs on both arms, with inflation to a pressure of 200 mmHg in the RIPC procedure or 10mmHg in the control procedure. Walking distances and limb oxygenation data, assessed with transcutaneous oximetry and near infrared spectroscopy measurements, were obtained during both RIPC and control procedures in all patients. RESULTS: Similar exercise intensities were achieved after the control and RIPC procedures. Walking distances did not significantly differ after the control and RIPC procedures (204 [141-259]m vs 215 [162-442]m, respectively; P=0.22). Similarly, no difference was observed in terms of transcutaneous oxygen pressure change and near infrared spectroscopy measurements during exercise between the two procedures. CONCLUSION: RIPC did not improve walking distance or limb ischaemia variables in patients with peripheral artery disease and intermittent claudication.

ECG characteristics according to the presence of late gadolinium enhancement on cardiac MRI in hypertrophic cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) on cardiac MRI (CMR) has been described as an independent predictive factor of cardiovascular events among patients with hypertrophic cardiomyopathy (HCM). LGE and Q waves are considered as myocardial scar markers but their relation in the context of HCM is poorly established and has to be more supported. The objective of the study was to compare ECG findings in the presence or absence of LGE. METHODS: 42 patients with HCM confirmed by CMR were included in the study. ECG abnormalities including abnormal Q waves and five ECG scores of left ventricular hypertrophy were assessed and compared according to LGE presence and its extension. Some CMR features, such as septal to posterior wall thickness ratio, were also studied according to the presence of LGE and the presence of abnormal Q waves. RESULTS: Abnormal Q waves were more prevalent in the LGE (+) group (60% vs 12%; p=0.002), but there was no correlation between location of Q waves on ECG and territory of LGE on CMR. Among patients with LGE, quantitative analysis of LGE was not different in the presence or absence of Q waves. In contrast to the LGE mass, septal to posterior wall thickness was higher in patients with abnormal Q waves (2.3±0.7 vs 1.6±0.5; p=0.012). CONCLUSIONS: Although abnormal Q waves were more prevalent in the presence of LGE, no correlation was found with the LGE location and extent. These data suggest that abnormal electrical activation of the hypertrophied ventricular septum represented by a high septal to posterior wall thickness ratio seems to be an important mechanism of abnormal Q waves in HCM.

CMR assessment after a transapical-transcatheter aortic valve implantation.

AIMS: To describe the time course of myocardial scarring after transapical-transcatheter aortic valve implantation (TA-TAVI) with the Edwards SAPIEN XT™ and the Edwards SAPIEN™ prosthesis in a 3-month follow-up study using cardiac magnetic resonance imaging (CMR). METHODS: In 20 TA-TAVI patients, CMR was performed at discharge and 3 months (3M). Cine-MRI was used for left ventricular (LV) functional assessment, and late gadolinium enhancement (LGE) imaging was employed for detecting the presence of myocardial scarring. Special attention was given to any artifacts caused by the prosthesis, which were consequently defined using a three-grade artifact scale. RESULTS: We systematically reported the presence of small LGE hyperintensity relating to the apical segment, with no variation found between discharge and 3M (2.8±1.6g vs. 2.35±1.1g). LV ejection fraction, end-diastolic, and end-systolic volumes did not significantly vary. A small area of apical akinesia was observed, with no improvement at follow-up. Whereas the Edwards SAPIEN XT™ prosthesis and the Edwards SAPIEN™ prosthesis are both constituted by metallic stenting structure, the Edwards SAPIEN™ was responsible for a larger signal void, thus potentially limiting the diagnostic performance of CMR. CONCLUSIONS: CMR may be performed safely in the context of TA-TAVI. The presence of a very small apical infarction correlating with focal akinesia was observed. As expected, the Edwards SAPIEN XT™ prosthesis was shown to be particularly suitable for CMR assessment.

Endoplasmic reticulum stress pathway involvement in local and remote myocardial ischemic conditioning.

Remote ischemic perconditioning (RIPer) and local ischemic postconditioning (IPost) are promising methods to decrease ischemia-reperfusion injury. We tested whether these two methods were effective in reducing infarct size through activation of endoplasmic reticulum (ER) stress response, a potential survival pathway. Rats exposed to myocardial ischemia-reperfusion were allocated to one of six groups: control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated during coronary artery occlusion; control + 4-PBA, injection of ER stress inhibitor 4-phenylbutyrate (4-PBA) 1 h before coronary occlusion; IPost + 4-PBA; and RIPer + 4-PBA. Infarct size was significantly reduced in IPost and RIPer groups (33.32% ± 3.65% and 21.86% ± 3.98%, respectively) compared with the control group (54.86% ± 6.01%, P < 0.05). Western blot analysis of GRP78 (glucose-regulated protein) level and cleaved activating transcription factor 6, two ER stress markers, demonstrated an enhancement of ER stress response in IPost group but not in RIPer group at 15-min reperfusion. Furthermore, 4-PBA abolished cardioprotection induced by IPost (infarct size 53.75 ± 3.49 vs. 33.32 ± 3.65%, P < 0.05) but not by RIPer (28.80 ± 10.45% vs. 21.86 ± 3.98%, not statistically significant). GRP78 and cleaved activating transcription factor 6 levels were no longer increased in IPost group after 4-PBA. These findings point to a role for ER stress response in cardioprotection against reperfusion injury in IPost but not RIPer, suggesting differences in cardioprotective mechanisms between local and remote conditioning.