Discharge Information About Adverse Drug Reactions Indicates Lower Self-Reported Adverse Drug Reactions and Fewer Concerns in Patients After Percutaneous Coronary Intervention.

AIM: There are discrepancies between the information patients desire about adverse drug reactions (ADRs) and the information they receive from healthcare providers; this is an impediment to shared decision-making. This study aimed to establish whether patients received information about ADRs resulting from prescribed pharmacotherapy, before hospital discharge, after percutaneous coronary intervention (PCI) and to determine whether receiving information about ADRs was associated with incidence of self-reported ADRs or concerns related to prescribed pharmacotherapy. METHODS: CONCARDPCI, a prospective multicentre cohort study including 3,417 consecutive patients after PCI, was conducted at seven high-volume referral PCI centres in two Nordic countries. Clinical data were collected from patients' medical records and national quality registries. Patient-reported outcome measures were registered 2 months (T1), 6 months (T2), and 12 months (T3) after discharge. Covariate-adjusted logistic regression yielded adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: At discharge, 38% of participants had been informed about potential ADRs. For these patients, the incidence of self-reported ADRs was significantly lower at T1 (aOR 0.61, 95% CI 0.50-0.74; p<0.001), T2 (aOR 0.60, 95% CI 0.49-0.74; p<0.001), and T3 (aOR 0.57, 95% CI 0.46-0.71; p<0.001). Those who were not informed reported higher levels of concern about prescribed pharmacotherapy at all measuring points (p<0.001 for all comparisons). Those living alone (aOR 0.73, 95% CI 0.57-0.92; p=0.008), who were female (aOR 0.57, 95% CI 0.44-0.72; p<0.001), and with three or more versus no comorbidities (aOR 0.61, 95% CI 0.44-0.84; p=0.002) were less likely to receive information. CONCLUSION: A substantial proportion of patients were not informed about potential ADRs from prescribed pharmacotherapy after PCI. Patients informed about ADRs had lower incidences of self-reported ADRs and fewer concerns about prescribed pharmacotherapy.

Phenotyping Self-Reported Health Profiles in Octogenarians and Nonagenarians After Percutaneous Coronary Intervention: A Latent Profile Analysis.

BACKGROUND: Little is known about self-reported health in octogenarians (≥80 years) and nonagenarians (≥90 years) following percutaneous coronary intervention (PCI), including characteristics of different health outcomes. This study aimed to phenotype latent health profiles of self-reported health in older adults 2 months post-PCI. METHODS: A prospective, multicentre, real-world study (CONCARDPCI) of 270 octogenarians and nonagenarians was performed with five validated and standardised measures of self-reported health at 2 months post-PCI. Latent profile analysis was used to identify health profiles, and multinomial logistic regression analyses were used to investigate the associations between patient characteristics and health profiles. RESULTS: Three latent health profiles were identified: The Poor health profile included 29%, the Moderate health profile included 39%, and the Good health profile included 32% of the participants. Older adults who were frail (OR 2.50, 95% CI 1.17-5.33), had a low exercise level (OR 0.49, 95% CI 0.39-0.95), and low alcohol intake (OR 0.61, 95% CI 0.39-0.95) were more likely to belong to the Poor health profile relative to the Good health profile. Furthermore, older age (OR 1.19, 95% CI 1.03-1.37) and lower exercise level (OR 0.64, 95% CI 0.43-0.97) were associated with belonging to the Moderate health profile relative to the Good health profile. CONCLUSION: Two months after PCI, most participants displayed having Moderate to Good health profiles. Those with a Poor health profile were more likely to be frail and less active. These findings highlight that follow-up care has to be patient-centred and tailored to improve the health status of older adults.

Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study.

BACKGROUND: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). METHODS: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. FINDINGS: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6). INTERPRETATION: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. FUNDING: Abbott Vascular, Infraredx, and The Medicines Company.

Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial.

INTRODUCTION: Short term hypothermia has been suggested to have cardio protective properties in acute myocardial infarction (AMI) by reducing infarct size as assessed by troponins. There are limited data on the kinetics of these biomarkers in comatose out-of-hospital cardiac arrest (OHCA) patients, with and without AMI, undergoing targeted temperature management (TTM) in the ICU. PURPOSE: The aim of this post hoc analyses was to evaluate and compare the kinetics of two high-sensitivity cardiac troponins in OHCA survivors, with and without acute myocardial infarction (AMI), during TTM of different durations [24 h (standard) vs. 48 h (prolonged)]. METHODS: In a sub-cohort (n = 114) of the international, multicentre, randomized controlled study "TTH48" we measured high-sensitive troponin T (hs-cTnT), high-sensitive troponin I (hs-cTnI) and CK-MB at the following time points: Arrival, 24 h, 48 h and 72 h from reaching the target temperature range of 33 ± 1 °C. All patients diagnosed with an AMI at the immediate coronary angiogram (CAG)-18 in the 24-h group and 25 in the 48-h group-underwent PCI with stent implantation. There were no stent thromboses. RESULTS: Both the hs-cTnT and hs-cTnI changes over time were highly influenced by the cause of OHCA (AMI vs. non-AMI). In contrast to non-AMI patients, both troponins remained elevated at 72 h in AMI patients. There was no difference between the two time-differentiated TTM groups in the kinetics for the two troponins. CONCLUSION: In comatose OHCA survivors with an aetiology of AMI levels of both hs-cTnI and hs-cTnT remained elevated for 72 h, which is in contrast to the well-described kinetic profile of troponins in normotherm AMI patients. There was no difference in kinetic profile between the two high sensitive assays. Different duration of TTM did not influence the kinetics of the troponins. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01689077, 20/09/2012.

QRS fragmentation is associated with increased risk of ventricular arrhythmias in high-risk patients; Data from the SMASH 1 Study.

INTRODUCTION: QRS fragmentation (fQRS), defined as the presence of additional spikes within the QRS complex, has been associated with myocardial conduction abnormalities and arrhythmogenicity. OBJECTIVE: We aimed to assess whether fQRS is associated with incident ventricular arrhythmias (VA) in high-risk patients treated with implantable cardioverter-defibrillator (ICD) for primary and secondary prevention. METHODS: In a prospective observational multicenter study, we included 495 patients treated with ICD. fQRS was analyzed according to previously validated criteria, by two physicians blinded for outcome data. Incident VA were obtained from ICD recordings. RESULTS: ECG recordings interpretable for fQRS were available in 459 patients (93%), aged 66 ± 12 years with left ventricular ejection fraction 40% ± 13%. fQRS was present in 52 patients (11%) with comparable baseline characteristics to patients without fQRS, except higher age, higher prevalence of coronary artery disease (CAD), lower prevalence of cardiomyopathy, and more frequently a secondary prevention ICD indication. Among patients with native QRS, those with fQRS had similar QRS duration and axis to those without fQRS. During 3.1 ± 0.7 years follow-up, 126 patients (28%) had ≥1 VA . fQRS was associated with increased risk of VA (HR 3.41 [95% CI 2.27-5.13], p < .001), which persisted after adjusting for age, gender, sex, BMI, CAD, heart failure, renal function, ICD indication, QRS duration, QRS axis, Q waves, and bundle branch block. fQRS was more strongly associated with VA in patients with a primary (HR 6.05 [95% CI 3.16-11.60]) versus secondary (HR 2.39 [95% CI 1.41-4.04]) ICD indication (p-for-interaction = .047). CONCLUSIONS: fQRS is associated with threefold increased risk of VA in high-risk patients, independent of established risk factors.

Worst lead ST deviation and resolution of ST elevation at one hour for prediction of myocardial salvage, infarct size, and microvascular obstruction in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: ECG changes after revascularization predicts improved outcome for patients with ST-elevation myocardial infarction (STEMI). Worst lead residual (WLR) ST deviation and resolution of worst lead ST elevation (rST elevation) are simple measures that can be obtained early after PCI. The objective of the current study was to investigate whether simple ECG measures, obtained one hour following PCI, could predict cardiac magnetic resonance (CMR)-derived myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) in patients with STEMI included in the MITOCARE trial. METHODS: The MITOCARE trial included 165 patients with a first-time STEMI presenting within six hours of symptom onset. The current analysis included patients that had an ECG recorded at baseline and one hour after PCI and underwent CMR imaging after 3-5 days. Independent core laboratories determined WLR ST deviation, rST elevation, and the CMR variables (MSI, IS, and MVO). RESULTS: 83 patients with a mean age of 61 years were included. 83.1% were males and 41% had anterior infarctions. In logistic regression models, WLR ST deviation was a statistically significant predictor of IS (OR 2.2, 95% CI 1.3-3.8) and MVO (OR 2.8, 95% CI 1.5-5.2), but not of MSI (OR 0.8, 95% CI 0.5-1.2). rST elevation showed a trend toward a significant association with IS (OR 0.3, 95% CI 0.1-1.0), but not with the other CMR variables. CONCLUSION: WLR ST deviation one hour after PCI was a predictor of IS and MVO. WLR ST deviation, a measure easily obtained from ECGs following PCI, may provide important prognostic information in patients with STEMI.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end point study.

BACKGROUND: Current guidelines on the use of ß-blockers in post-acute myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF) are based on studies before the implementation of modern reperfusion and secondary prevention therapies. It remains unknown whether ß-blockers will reduce mortality and recurrent MI in contemporary revascularized post-MI patients without reduced LVEF. DESIGN: BETAMI is a prospective, randomized, open, blinded end point multicenter study in 10,000 MI patients designed to test the superiority of oral ß-blocker therapy compared to no ß-blocker therapy. Patients with LVEF ≥40% following treatment with percutaneous coronary intervention or thrombolysis and/or no clinical signs of heart failure are eligible to participate. The primary end point is a composite of all-cause mortality or recurrent MI obtained from national registries over a mean follow-up period of 3 years. Safety end points include rates of nonfatal MI, all-cause mortality, ventricular arrhythmias, and hospitalizations for heart failure obtained from hospital medical records 30 days after randomization, and from national registries after 6 and 18 months. Key secondary end points include recurrent MI, heart failure, cardiovascular and all-cause mortality, and clinical outcomes linked to ß-blocker therapy including drug adherence, adverse effects, cardiovascular risk factors, psychosocial factors, and health economy. Statistical analyses will be conducted according to the intention-to-treat principle. A prespecified per-protocol analysis (patients truly on ß-blockers or not) will also be conducted. CONCLUSIONS: The results from the BETAMI trial may have the potential of changing current clinical practice for treatment with ß-blockers following MI in patients without reduced LVEF. EudraCT number 2018-000590-75.

Effects of interval training on inflammatory biomarkers in patients with ischemic heart failure.

Objectives. Exercise training has been proposed to have anti-inflammatory effects. We examined whether aerobic interval training (AIT) can attenuate the inflammatory response in ischemic heart failure (HF) as measured by serum biomarkers representing a broad spectrum of activated inflammatory pathways. Design. We conducted a controlled prospective trial recruiting 30 patients (19 in the AIT group and 11 in the control group) with ischemic HF and an implantable cardioverter defibrillator (ICD). This study is a sub study of the previously reported "Aerobic interval training in patients with heart failure and an ICD" (Eur J Prev Cardiol. 22 March 2015; 22:296-303). Patients in the AIT group exercised for 12-weeks completing a total of 36 AIT sessions. We analyzed serum levels of C-reactive protein, pentraxin-3, osteoprotegerin, brain natriuretic peptide, neopterin, and soluble tumor necrois factor type 1 and 2, all known to predict an adverse outcome in HF, at baseline and following the 12-week AIT intervention. Results. The AIT group significantly increased peak oxygen uptake and improved endothelial function compared to the sedentary control group. No statistically significant changes in serum levels of the biomarkers were detected from baseline following the AIT intervention and, there were no significant differences in changes of these mediators between the AIT and the control group. Conclusions. A 12-week AIT intervention, although improving exercise capacity and endothelial function, did not attenuate serum inflammatory biomarkers in stable ischemic HF patients with an ICD on optimal medical therapy.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). METHODS: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. RESULTS: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. CONCLUSIONS: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Impact of an exercise training program on cardiac neuronal function in heart failure patients on optimal medical therapy : A randomized Iodine-123 metaiodobenzylguanidine scintigraphy study.

BACKGROUND: The syndrome of heart failure (HF) is characterized by left ventricular dysfunction and a compensatory chronic over activation of the sympathetic nervous system. We wanted to investigate if the beneficial effects of exercise training (ET) in HF patients on optimal medical therapy (OMT) are associated with alterations in cardiac sympathetic activity. METHODS: Cardiac sympathetic activity was evaluated at baseline and after 12 weeks using metaiodobenzylguanidine scintigraphy in 23 patients with stable HF participating in the SmartEx trial. Patients with HF in New York Heart Association class II or III and left ventricular ejection fraction <35 % were randomized to three different ET groups. RESULTS: We found no statistically significant changes in cardiac sympathetic activity after 12 weeks of ET. Heart to mediastinum (H/M) ratio at 15 minutes (0.00174 ± 0.0841, P = 0.922), H/M ratio at 4 hours (-0.00565 ± 0.1163, P = 0.818) and washout ratio (WR) (-1.2666 ± 16.5412, P = 0.717). A further group-wise analysis of the three ET groups did not show any difference between the groups. CONCLUSION: A 12-week ET program did not alter the abnormal cardiac sympathetic activity in stable HF patients on modern OMT.

The significance of ST-elevation in aVL in anterolateral myocardial infarction: An assessment by cardiac magnetic resonance imaging.

BACKGROUND: Anterolateral myocardial infarction (MI) is traditionally defined on the electrocardiogram by ST-elevation (STE) in I, aVL, and the precordial leads. Traditional literature holds STE in lead aVL to be associated with occlusion proximal to the first diagonal branch of the left anterior descending coronary artery. However, concomitant ischemia of the inferior myocardium may theoretically lead to attenuation of STE in aVL. We compared segmental distribution of myocardial area at risk (MaR) in patients with and without STE in aVL. METHODS: We identified patients in the MITOCARE study presenting with a first acute MI and new STE in two contiguous anterior leads from V1 to V6 , with or without aVL STE. Patients underwent cardiac magnetic resonance imaging 3-5 days after acute infarction for quantitative assessment of MaR. RESULTS: A total of 32 patients met inclusion criteria; 13 patients with and 19 without STE in lead aVL. MaR > 20% at the basal anterior segment was seen in 54% of patients with aVL STE, and 11% of those without (p = 0.011). MaR > 20% at the apical inferior segment was seen in 62% and 95% of patients with and without aVL STE, respectively (p = 0.029). The total MaR was not different between groups (44% ± 10% and 39% ± 8.3% respectively, p = 0.15). CONCLUSION: Patients with anterior STEMI and concomitant STE in aVL have less MaR in the apical inferior segment and more MaR in the basal anterior segment.

Correlation of anteroseptal ST elevation with myocardial infarction territories through cardiovascular magnetic resonance imaging.

BACKGROUND: Anteroseptal ST elevation myocardial infarction (STEMI) is traditionally defined on the electrocardiogram (ECG) by ST elevation (STE) in leads V1-V3, with or without involvement of lead V4. It is commonly taught that such infarcts affect the basal anteroseptal myocardial segment. While there are suggestions in the literature that Q waves limited to V1-V4 represent predominantly apical infarction, none have evaluated anteroseptal ST elevation territories. We compared the distribution of the myocardium at risk (MaR) in STEMI patients presenting with STE limited to V1-V4 and those with more extensive STE (V1-V6). METHODS: We identified patients in the MITOCARE study presenting with a first acute STEMI and new STE in at least two contiguous anterior leads from V1 to V6. Patients underwent cardiac magnetic resonance (CMR) imaging three to five days after acute infarction. RESULTS: Thirty-two patients met inclusion criteria. In patients with STE in V1-V4 (n = 20), myocardium at risk (MaR) > 50% was seen in 0%, 85%, 75%, 100%, and 90% in the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. The group with STE in V1-V6 (n = 12), MaR > 50% was seen in 8%, 83%, 83%, 92%, and 83% of the same segments. CONCLUSIONS: Patients with acute STEMI and STE in leads V1-V4, exhibit MaR in predominantly apical territories and rarely in the basal anteroseptum. We found no evidence to support existence of isolated basal anteroseptal or septal STEMI. "Anteroapical" infarction is a more precise description than "anteroseptal" infarction for acute STEMI patients exhibiting STE in V1-V4.

Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices of the acuteness of ischemia (based on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We assessed whether severe ischemia with or without acute ischemia is predictive of infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection fraction (LVEF) in anterior versus inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary percutaneous coronary intervention (pPCI). LVEF was measured by echocardiography 30days after pPCI. RESULTS: ECG analysis of 85 patients with available CMR resulted in 20 (23%) cases with severe and non-acute ischemia, 43 (51%) with non-severe and non-acute ischemia, 17 (20%) with non-severe and acute ischemia, and 5 (6%) patients with severe and acute ischemia. In patients with anterior STEMI (n=35), ECG measures of severity and acuteness of ischemia identified significant and stepwise differences in myocardial damage and function. Patients with severe and non-acute ischemia had the largest IS, smallest MSI and lowest LVEF. In contrast, no difference was observed in patients with inferior STEMI (n=50). CONCLUSIONS: The applicability of ECG indices of severity and acuteness of myocardial ischemia to estimate myocardial damage and salvage potential in STEMI patients treated with pPCI, is confined to anterior myocardial infarction.

Appropriateness of anteroseptal myocardial infarction nomenclature evaluated by late gadolinium enhancement cardiovascular magnetic resonance imaging.

BACKGROUND: In traditional literature, it appears that "anteroseptal" MIs with Q waves in V1-V3 involve basal anteroseptal segments although studies have questioned this belief. METHODS: We studied patients with first acute anterior Q-wave (>30ms) MI. All underwent late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI). RESULTS: Those with Q waves in V1-V2 (n=7) evidenced LGE >50% in 0%, 43%, 43%, 57%, and 29% of the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. Patients with Q waves in V1-V3 (n=14), evidenced involvement was 14%, 43%, 43%, 50%, and 7% of the same respective segments. In those with extensive anterior Q waves (n=7), involvement was 0%, 71%, 57%, 86%, and 86%. CONCLUSIONS: Q-wave MI in V1-V2/V3 primarily involves mid- and apical anterior and anteroseptal segments rather than basal segments. Data do not support existence of isolated basal anteroseptal or septal infarction. "Anteroapical infarction" is a more appropriate term than "anteroseptal infarction."

Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Administration of the Mitochondrial Permeability Transition Pore Inhibitor, TRO40303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins.

OBJECTIVES: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TRO40303, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The effects of TRO40303 on pro-inflammatory cytokines and acute-phase proteins were assessed. METHODS: STEMI patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TRO40303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-1ß, IL-6, IL-10, TNF, and high-sensitive C-reactive protein at various time points (0, 12, and 72 h) after PCI. Further, potential differences between groups in the change of biomarker levels between 0 and 72 h, 0 and 12 h, and 12 and 72 h were tested. RESULTS: There were no statistically significant differences between the two groups, neither in levels of pro-inflammatory cytokines nor in levels of acute-phase proteins, and there were no statistically significant differences in the change of biomarker levels between the groups considering the time intervals from 0 to 72 h, from 0 to 12 h, and from 12 to 72 h. CONCLUSION: The administration of the mPTP, TRO40303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI.

Confronting one's vulnerability - patients with chest pain participating in a high-intensity exercise programme.

AIMS AND OBJECTIVES: To explain the transitional process that individuals with unexplained chest pain undergo while participating in an exercise training programme over time. BACKGROUND: Angina-like chest pain in patients with no obstructive coronary artery disease is a growing problem. Functional limitations, restricted daily activities and reduced quality of life are reported. In addition, physical activity is avoided in this population. DESIGN: The study follows a qualitative classic grounded theory (Glaser ). METHODS: Three times a week for 12 weeks, twelve patients with no obstructive coronary artery disease participated in a high-intensity aerobic exercise training programme supervised by physiotherapists and nurses. The data collection was based on diaries and interviews about the experience and analysed according to the principles of classic grounded theory. RESULTS: The core category was identified as 'confronting one's vulnerability' and included three subcategories: 'balancing existential uncertainty', 'transforming bodily perceptions' and 'becoming a more capable person'. CONCLUSION: The transition was described as a process of becoming more capable. Health professionals should be aware of the significance of high-intensity exercise training for people with unexplained chest pain and of the underlying dimension of vulnerability. RELEVANCE TO CLINICAL PRACTICE: Understanding the transition process that people with unexplained chest pain undergo while participating in a high-intensity exercise training programme promotes a person-centred approach. Taking this substantive theory into consideration will improve the prerequisites for establishing person-centred care.

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM. Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016. Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C. Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group. Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted. Trial Registration: clinicaltrials.gov Identifier: NCT01689077.

Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results.

AIM: The MITOCARE study evaluated the efficacy and safety of TRO40303 for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). METHODS: Patients presenting with STEMI within 6 h of the onset of pain randomly received TRO40303 (n = 83) or placebo (n = 80) via i.v. bolus injection prior to balloon inflation during primary percutaneous coronary intervention in a double-blind manner. The primary endpoint was infarct size expressed as area under the curve (AUC) for creatine kinase (CK) and for troponin I (TnI) over 3 days. Secondary endpoints included measures of infarct size using cardiac magnetic resonance (CMR) and safety outcomes. RESULTS: The median pain-to-balloon time was 180 min for both groups, and the median (mean) door-to-balloon time was 60 (38) min for all sites. Infarct size, as measured by CK and TnI AUCs at 3 days, was not significantly different between treatment groups. There were no significant differences in the CMR-assessed myocardial salvage index (1-infarct size/myocardium at risk) (mean 52 vs. 58% with placebo, P = 0.1000), mean CMR-assessed infarct size (21.9 g vs. 20.0 g, or 17 vs. 15% of LV-mass) or left ventricular ejection fraction (LVEF) (46 vs. 48%), or in the mean 30-day echocardiographic LVEF (51.5 vs. 52.2%) between TRO40303 and placebo. A greater number of adjudicated safety events occurred in the TRO40303 group for unexplained reasons. CONCLUSION: This study in STEMI patients treated with contemporary mechanical revascularization principles did not show any effect of TRO40303 in limiting reperfusion injury of the ischaemic myocardium.