Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Short-term dual antiplatelet therapy in diabetic patients admitted for acute coronary syndrome treated with a new-generation drug-eluting stent.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent. METHODS: In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up. RESULTS: A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups. CONCLUSIONS: This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients.

Changes and prognostic value of cardiopulmonary exercise testing parameters in elderly patients undergoing cardiac rehabilitation: The EU-CaRE observational study.

OBJECTIVE: We aimed 1) to test the applicability of the previously suggested prognostic value of CPET to elderly cardiac rehabilitation patients and 2) to explore the underlying mechanism of the greater improvement in exercise capacity (peak oxygen consumption, VO2) after CR in surgical compared to non-surgical cardiac patients. METHODS: Elderly patients (≥65 years) commencing CR after coronary artery bypass grafting, surgical valve replacement (surgery-group), percutaneous coronary intervention, percutaneous valve replacement or without revascularisation (non-surgery group) were included in the prospective multi-center EU-CaRE study. CPETs were performed at start of CR, end of CR and 1-year-follow-up. Logistic models and receiver operating characteristics were used to determine prognostic values of CPET parameters for major adverse cardiac events (MACE). Linear models were performed for change in peak VO2 (start to follow-up) and parameters accounting for the difference between surgery and non-surgery patients were sought. RESULTS: 1421 out of 1633 EU-CaRE patients performed a valid CPET at start of CR (age 73±5.4, 81% male). No CPET parameter further improved the receiver operation characteristics significantly beyond the model with only clinical parameters. The higher improvement in peak VO2 (25% vs. 7%) in the surgical group disappeared when adjusted for changes in peak tidal volume and haemoglobin. CONCLUSION: CPET did not improve the prediction of MACE in elderly CR patients. The higher improvement of exercise capacity in surgery patients was mainly driven by restoration of haemoglobin levels and improvement in respiratory function after sternotomy. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5166.

Predictors for one-year outcomes of cardiorespiratory fitness and cardiovascular risk factor control after cardiac rehabilitation in elderly patients: The EU-CaRE study.

INTRODUCTION: Studies on effectiveness of cardiac rehabilitation (CR) in elderly cardiovascular disease patients are rare, and it is unknown, which patients benefit most. We aimed to identify predictors for 1-year outcomes of cardiorespiratory fitness and CV risk factor (CVRF) control in patients after completing CR programs offered across seven European countries. METHODS: Cardiovascular disease patients with minimal age 65 years who participated in comprehensive CR were included in this observational study. Peak oxygen uptake (VO2), body mass index (BMI), resting systolic blood pressure (BPsys), and low-density lipoprotein-cholesterol (LDL-C) were assessed before CR (T0), at termination of CR (T1), and 12 months after start of CR (T2). Predictors for changes were identified by multivariate regression models. RESULTS: Data was available from 1241 out of 1633 EU-CaRE patients. The strongest predictor for improvement in peak VO2 was open chest surgery, with a nearly four-fold increase in surgery compared to non-surgery patients. In patients after surgery, age, female sex, physical inactivity and time from index event to T0 were negative predictors for improvement in peak VO2. In patients without surgery, previous acute coronary syndrome and higher exercise capacity at T0 were the only negative predictors. Neither number of attended training sessions nor duration of CR were significantly associated with change in peak VO2. Non-surgery patients were more likely to achieve risk factor targets (BPsys, LDL-C, BMI) than surgery patients. CONCLUSIONS: In a previously understudied population of elderly CR patients, time between index event and start of CR in surgery and disease severity in non-surgery patients were the most important predictors for long-term improvement of peak VO2. Non-surgery patients had better CVRF control.

Impact of age on the comparison between short-term vs 12-month dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-Year follow-up results of the REDUCE trial.

BACKGROUND AND AIMS: The impact of advanced age on the optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary revascularization (PCI) is still greatly debated. Therefore, the aim of the present sub-analysis of the REDUCE trial was to assess the impact of age on the comparison between a short 3 months vs standard 12 months DAPT in ACS patients treated with the COMBO Dual Stent Therapy. METHODS: The REDUCE trial is a prospective, multicenter, investigator-initiated study that randomized ACS patients undergoing PCI with the COMBO drug eluting stent to either 3 or 12 months of DAPT. The study population was divided according to age (

Offering, participation and adherence to cardiac rehabilitation programmes in the elderly: a European comparison based on the EU-CaRE multicentre observational study.

AIMS: Cardiac rehabilitation (CR) is strongly recommended but participation of elderly patients has not been well characterized. This study aims to analyse current rates and determinants of CR referral, participation, adherence, and compliance in a contemporary European cohort of elderly patients. METHODS AND RESULTS: The EU-CaRE observational study included data from consecutive patients aged ≥ 65 with acute coronary syndrome, revascularization, stable coronary artery disease, or heart valve replacement, recruited in eight European centres. Rates and factors determining offering, participation, and adherence to CR programmes and compliance with training sessions were studied across centres, under consideration of extensive-outpatient vs. intensive-inpatient programmes. Three thousand, four hundred, and seventy-one patients were included in the offering and participation analysis. Cardiac rehabilitation was offered to 80.8% of eligible patients, formal contraindications being the main reason for not offering CR. Mean participation was 68.0%, with perceived lack of usefulness and transport issues being principal barriers. Mean adherence to CR programmes of participants in the EU-CaRE study (n = 1663) was 90.3%, with hospitalization/physical impairment as principal causes of dropout. Mean compliance with training sessions was 86.1%. Older age was related to lower offering and participation, and comorbidity was associated with lower offering, participation, adherence, and compliance. Intensive-inpatient programmes displayed higher adherence (97.1% vs. 85.9%, P < 0.001) and compliance (full compliance: 66.0% vs. 38.8%, P < 0.001) than extensive-outpatient programmes. CONCLUSION: In this European cohort of elderly patients, older age and comorbidity tackled patients' referral and uptake of CR programmes. Intensive-inpatient CR programmes showed higher completion than extensive-outpatient CR programmes, suggesting this formula could suit some elderly patients.

Optimal Medical Therapy Prescription in Patients with Acute Coronary Syndrome in the Netherlands: A Multicenter Pilot Registry.

BACKGROUND: Unlike neighboring countries, the Netherlands does not have a national acute coronary syndrome (ACS) registry to evaluate quality of care. OBJECTIVE: We conducted a pilot registry in two hospitals to assess the prescription of guideline-recommended therapies in Dutch patients with ACS. METHODS: We included all consecutive patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (n = 1309) admitted to two Dutch percutaneous coronary intervention centers between March 2015 and February 2016. We collected follow-up medication use and reasons for discontinuation at discharge and 1, 6, and 12 months post-discharge. We assessed the use of optimal medical therapy (OMT), defined as the combined prescription of aspirin, P2Y12 inhibitors, statins, ß-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. RESULTS: OMT prescription was 43.2% at discharge, 60.1% at 1 month, and 28.7% at 12 months. At 1 month, OMT prescription was significantly lower in patients with NSTEMI (51.8 vs. 65.7% for STEMI; p < 0.001). OMT prescription was lower in women (6 months: 55.4 vs. 62.0%, p = 0.036) and in elderly patients. CONCLUSION: In this pilot study that aimed to extend a national Dutch ACS registry to patients with STEMI and NSTEMI, OMT prescription was comparable to that in other local registries, was lower in women and patients with NSTEMI, and decreased with increasing age.

Beta-blocker effect on ST-segment: a prespecified analysis of the EARLY-BAMI randomised trial.

OBJECTIVE: The effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation. METHODS: The EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI). RESULTS: An ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1-3 mm; 4-6 mm;>6 mm residual ST-deviation). CONCLUSIONS: In patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.

Training intensity and improvements in exercise capacity in elderly patients undergoing European cardiac rehabilitation - the EU-CaRE multicenter cohort study.

OBJECTIVES: Guidelines for exercise intensity prescription in Cardiac Rehabilitation (CR) are inconsistent and have recently been discussed controversially. We aimed (1) to compare training intensities between European CR centres and (2) to assess associations between training intensity and improvement in peak oxygen consumption ([Formula: see text]O2) in elderly CR patients. METHODS: Peak [Formula: see text]O2, heart rate and work rate (WR) at the first and second ventilatory thresholds were measured at start of CR. Training heart rate was measured during three sessions spread over the CR. Multivariate models were used to compare training characteristics between centres and to assess the effect of training intensity on change in peak [Formula: see text]O2. RESULTS: Training intensity was measured in 1011 out of 1633 EU-CaRE patients in 7 of 8 centers and the first and secondary ventilatory threshold were identified in 1166 and 817 patients, respectively. The first and second ventilatory threshold were found at 44% (SD 16%) and 78% (SD 9%) of peak WR and 78% (SD 9%) and 89% (SD 5%) of peak heart rate, respectively. Training intensity and session duration varied significantly between centres but change in peak [Formula: see text]O2 over CR did not. Training above the first individual threshold (ß 0.62, 95% confidence interval [0.25-1.02]) and increase in training volume per hour (ß 0.06, 95%CI [0.01-0.12]) were associated with a higher change in peak [Formula: see text]O2. CONCLUSION: While training intensity and volume varied greatly amongst current European CR programs, changes in peak [Formula: see text]O2 were similar and the effect of training characteristics on these changes were small.

MINOCA: The caveat of absence of coronary obstruction in myocardial infarction.

AIMS: Whether patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) have better outcomes than patients with obstructive coronary artery disease remains contradictory. The current study focussed on the clinical profile and prognosis of MINOCA patients. METHODS AND RESULTS: We performed a retrospective analysis of patients with acute coronary syndrome (ACS) admitted to the Isala hospital in Zwolle, the Netherlands, between 2006 and 2014. A total of 7693 patients were categorized into three groups: MINOCA, single-vessel obstructive ACS (SV-ACS), and multi-vessel obstructive ACS (MV-ACS). MINOCA patients (5.2% of the total population) were more likely to be female (51.5% vs. 30.3% and 26.0% in SV-ACS and MV-ACS, respectively, p < 0.001 for both). The prevalence of risk factors in the MINOCA group was in between the SV-ACS and MV-ACS groups. Logistic regression revealed a lower odds of dying in SV-ACS (odds ratio (OR) = 0.70 (p = 0.04)) and a similar odds in MV-ACS (OR = 0.88, p = 0.45) compared to MINOCA. CONCLUSIONS: Patients with MINOCA show an 'intermediate' risk profile with mortality rates in between those of both ACS groups. Hence, MINOCA should be recognised as a potential risk factor for mortality, requiring adequate treatment and follow-up.

Clinical outcomes after cardiac rehabilitation in elderly patients with and without diabetes mellitus: The EU-CaRE multicenter cohort study.

BACKGROUND: The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. METHODS: 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. RESULTS: 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. CONCLUSIONS: While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166.

Cardiac rehabilitation of elderly patients in eight rehabilitation units in western Europe: Outcome data from the EU-CaRE multi-centre observational study.

AIMS: The European Cardiac Rehabilitation in the Elderly (EU-CaRE) HORIZON 2020 project compares the sustainable effects of cardiac rehabilitation (CR) in elderly patients. METHODS AND RESULTS: A total of 1633 patients with coronary artery disease (CAD) or heart valve replacement (HVR), with or without revascularization, aged 65 or above, who participated in CR were included. Peak oxygen uptake (VO2peak), smoking, body mass index, diet, physical activity, serum lipids, psychological distress and medication were assessed before and after CR (T0 and T1) and after 12 months (T2). Patients undergoing coronary artery bypass surgery or surgical HVR had lower VO2peak at T0 and a greater increase to T1 and T2 (2.8 and 4.4 ml/kg/min, respectively) than CAD patients undergoing percutaneous or no revascularization (1.6 and 1.4 ml/kg/min, respectively). After multivariable adjustment, earlier CR uptake was associated with greater improvements in VO2peak. The proportion of CAD patients with three or more uncontrolled risk factors declined from 58.4% at T0 to 40.1% at T2 (p < 0.0001). Psychological distress scores all improved and adherence to medication was overall good at all sites. There were significant differences in risk factor burden across sites, but no CR program was superior to others. CONCLUSIONS: The outcomes of VO2peak in CR programs across Europe seemed mainly determined by timing of uptake and were maintained or even further improved at 1-year follow-up. Despite significant improvements, 40.1% of CAD patients still had three or more risk factors not at target after 1 year. Differences across sites could not be ascribed to characteristics of the CR programs offered.

Predictors of pre-rehabilitation exercise capacity in elderly European cardiac patients - The EU-CaRE study.

AIMS: Functional capacity is an important endpoint for therapies oriented to older adults with cardiovascular diseases. The literature on predictors of exercise capacity is sparse in the elderly population. In a longitudinal European study on effectiveness of cardiac rehabilitation of seven European countries in elderly (>65 years) coronary artery disease or valvular heart disease patients, predictors for baseline exercise capacity were determined, and reference ranges for elderly cardiac patients provided. METHODS: Mixed models were performed in 1282 patients (mean age 72.9 ± 5.4 years, 79% male) for peak oxygen consumption relative to weight (peak VO2; ml/kg per min) with centre as random factor and patient anthropometric, demographic, social, psychological and nutritional parameters, as well as disease aetiology, procedure, comorbidities and cardiovascular risk factors as fixed factors. RESULTS: The most important predictors for low peak VO2 were coronary artery bypass grafting or valve surgery, low resting forced expiratory volume, reduced left ventricular ejection fraction, nephropathy and peripheral arterial disease. Each cumulative comorbidity or cardiovascular risk factors reduced exercise capacity by 1.7 ml/kg per min and 1.1 ml/kg per min, respectively. Males had a higher peak VO2 per body mass but not per lean mass. Haemoglobin was significantly linked to peak VO2 in both surgery and non-surgery patients. CONCLUSIONS: Surgical procedures, cumulative comorbidities and cardiovascular risk factors were the factors with the strongest relation to reduced exercise capacity in the elderly. Expression of peak VO2 per lean mass rather than body mass allows a more appropriate comparison between sexes. Haemoglobin is strongly related to peak VO2 and should be considered in studies assessing exercise capacity, especially in studies on patients after cardiac surgery.

Cardiac rehabilitation in the elderly patient in eight rehabilitation units in Western Europe: Baseline data from the EU-CaRE multicentre observational study.

BACKGROUND: Due to the progressive deconditioning, comorbidities and higher complication rates, elderly patients are in particular need of cardiac rehabilitation. We compared elderly patients (65+ years old) participating in cardiac rehabilitation, focusing on baseline characteristics, risk factor control and functional assessment. METHODS: The EU-CaRE study is a prospective study comparing cardiac rehabilitation in eight centres across Western Europe. Consecutive patients with acute coronary syndrome, stable coronary artery disease and heart valve replacement undergoing cardiac rehabilitation were included. RESULTS: Of 1633 patients (median age 72 years) participating, 54% had acute coronary syndrome, 33% had stable coronary artery disease and 13% followed valve replacement. Fifty-five per cent had undergone percutaneous coronary intervention and 29% coronary artery bypass grafting. Characteristics varied across centres: 23% (17-27%) were women, 4% (0-12%) were of non-European origin and 16% (4-32%) were living alone. Median time from index event to start of cardiac rehabilitation varied from 11 to 49 days (p < 0.001). Mean VO2peak was relatively low (16 mL/kg per min) and varied significantly between the participating centres, largely unaffected by multivariable adjustment. Overall patients received guideline recommended treatment: 93% (87-97%) were on a statin and 70% (55-85%) an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. However, risk factor control was inadequate: 58% had three or more risk factors not controlled. CONCLUSION: EU-CaRE provides a snapshot of the elderly population with heart disease participating in cardiac rehabilitation across countries in Western Europe. Risk factors and exercise capacity indicate the continued need for cardiac rehabilitation in these patients. Of concern, the lag-time to start of cardiac rehabilitation needs improvement in many centres.

Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry.

AIMS: Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes. METHODS AND RESULTS: Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14-0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor. CONCLUSION: In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.

Impact of a Graded Exercise Program on V˙O2peak and Survival in Heart Failure Patients.

INTRODUCTION: Although exercise therapy has the potential to improve health outcomes of patients with chronic heart failure (CHF), less than 50% of patients adhere to prescribed physical activity guidelines 1 yr after cardiac rehabilitation. We aimed to assess the effects of an extended cardiac rehabilitation program with 12 months of graded exercise therapy (GET) and resistance exercise training (RT) on exercise capacity and long-term survival in patients with CHF. METHODS: This prospective cohort study included 60 CHF patients between 2009 and 2010. The GET-RT program consisted of exercise sessions at 6 d·wk. Total training time of aerobic exercises increased incrementally every other week without changing exercise intensity. Resistance exercise training consisted of 8 exercises with a durable resistance band. Guidance consisted of a step-down approach from in-hospital to home-based training. Cardiopulmonary exercise tests were performed at baseline, 3, 6, and 12 months. Subsequently, patients were propensity score matched on a 1:2 ratio with controls (n = 117) from a CHF registry of patients from the same clinic receiving usual out-patient care and the incidence of all-cause mortality was compared between both groups. RESULTS: Baseline V˙O2 peak was 15.0 mL·min·kg and significantly elevated at 3 months (+1.1 mL·min·kg (95% CI, 0.4-1.8), 6 months (+2.9 mL·min·kg (95% CI, 1.1-2.9) and 12 months (+2.6 mL·min·kg (95% CI, 1.4-3.8). During 8 yr of follow-up 23 (38.3%) patients of the GET-RT program died versus 63 (53.8%) patients of the control group (P = 0.063). CONCLUSIONS: The 12-month GET-RT program was associated with an improved fitness during 1-yr follow-up, whereas a tendency toward better survival rates was observed during long-term follow-up.

Comparison of Outcomes and Intervention Among Patients With Non-ST-Segment Elevation Acute Myocardial Infarction of Those With a Left Circumflex Versus Those With a Non-Left Circumflex-Related Coronary Artery (From the ELISA-3 Trial).

Previous studies found that patients with an acute coronary syndrome (ACS) due to occlusion of the left circumflex (LC) coronary artery often present without ST-elevation, leading to a delay in diagnosis and revascularization, a larger infarct size, and a worse prognosis. In this subgroup analysis of the ELISA-3 study (early or late intervention in high-risk non-ST-segment elevation acute coronary syndromes [NSTE-ACS]) incidence, characteristics and prognosis of LC-related NSTE-ACS was investigated, and the outcome of early versus late invasive strategy was compared. In 383 of 542 patients the culprit vessel could be identified, with the LC artery in 112 (29%) of them. Patients with LC-related ACS had more often single vessel disease and underwent percutaneous coronary intervention more and CABG less frequently. The primary end point of the combined incidences of death, myocardial infarction, and recurrent ischemia at 30-day follow-up occurred in 9.0% of LC versus 16.5% of non-LC-related ACS (p = 0.057). Enzymatic infarct size and incidence of bleeding were comparable. Of patients with LC-related ACS, 62 were assigned to an early and 50 to a late invasive treatment with a median time from admission to angiography of 5.5 and 65.7 hours, respectively. The primary end point occurred in 9.7% and 8.0%, respectively (p = 1.00) with comparable enzymatic infarct size and bleeding. In conclusion, no significant differences in outcome were found between patients with an LC- and a non-LC-related NSTE-ACS. In LC-related NSTE-ACS, angiography within 12 hours of admission is feasible but not superior to angiography after more than 48 hours.

Trends in optimal medical therapy prescription and mortality after admission for acute coronary syndrome: a 9-year experience in a real-world setting.

Aims: Optimal medical therapy (OMT) is recommended in acute coronary syndrome (ACS) patients. Few studies present temporal trends of OMT prescription and its impact on outcomes in a real-world setting. We aimed to evaluate OMT prescription in a real-world ACS population and its relation to mortality during almost a decade. Methods and results: Consecutive ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (NSTEMI) patients (n = 9202) admitted to a single Dutch tertiary hospital between 2006 and 2014 were included and followed for drug prescription and mortality up to 1 year. Optimal medical therapy was defined as prescription of aspirin, P2Y12inhibitors, statin, beta-blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Optimal medical therapy prescription was 43.7% at discharge, 46.6% at 30-days, and 25.5% at 1-year. Optimal medical therapy prescription at discharge was lower among NSTEMI patients (34.5% vs. 49.2%, P < 0.001). Optimal medical therapy prescription at discharge, 30-days and 1-year and mortality outcomes did not change during the study period. After adjustment for baseline and admission characteristics, OMT at discharge was associated with a reduction in mortality in patients who survived hospitalization for the index event [adjusted hazard ratio: 0.66, 95% confidence interval (0.46-0.93)]. Conclusions: In this single-centre observational registry with >9000 patients reflecting almost a decade of ACS care, <50% of patients were on OMT at discharge. Prescription of OMT and mortality outcomes remained stable during the study period. After adjustment, OMT prescription at discharge was associated with reduced mortality in ACS survivors. Further contemporary randomized studies are warranted to determine the role of beta-blockers and ACEi/ARBs in ACS patients with preserved left ventricular ejection fraction.

Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction.

OBJECTIVE: We undertook a subgroup analysis of the On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2), a placebo-controlled, double-blind, randomised trial, in order to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and long-term (5 years) mortality and to investigate the effect of prehospital tirofiban administration on mortality in relation to NT-proBNP levels. METHODS: A total of 984 patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) were randomised to either in ambulance tirofiban or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hours thereafter (post PCI). RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post PCI. Patients with baseline NT-proBNP values above the median (137 pg/mL) had higher 30-day (5.1% vs 0.2%, p<0.001), 1-year (7.0% vs 0.7%, p<0.001) and 5-year (20.3% vs 4.9%, p<0.001) mortality as compared with patients with values below the median. Using multivariate Cox analysis, NT-proBNP above the median was an independent predictor for 5-year mortality (HR 2.73, 95% CI 1.47 to 5.06; p=0.002). Patients with values above the median who received early tirofiban treatment had significant lower mortality compared with patients treated with placebo at 30 days (2.7% vs 7.5%, p=0.021) and 1 year (4.5% vs 9.4%, p=0.043). At 5 years, a lower but non-significant mortality rate was maintained in the treatment group (18% vs 22.4%, p=0.265). CONCLUSIONS: In patients with STEMI, baseline NT-proBNP level independently predicts long-term mortality. In patients with baseline NT-proBNP levels above the median, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality, suggesting that high-risk patients may derive particular benefit. This finding should be confirmed in other studies. TRIAL REGISTRATION NUMBER: ISRCTN06195297.

Field triage in the ambulance versus referral via non-percutaneous coronary intervention centre in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A systematic review.

AIMS: The purpose of this study was to determine whether direct ambulance transport of ST-elevation myocardial infarction (STEMI) patients to a percutaneous coronary intervention (PCI) hospital (field triage) leads to a lower 30-day mortality compared to transport via a referral non-PCI hospital (referral via a spoke centre) in STEMI patients. METHODS AND RESULTS: We performed a systematic review of interventions. An experienced librarian searched in PubMed, EMBASE.com and The Cochrane Library (via Wiley) from January 1980-February 2013. Studies that examined field triage and/or referral via a spoke centre in STEMI patients treated with primary or facilitated PCI were included. Two authors independently conducted the study selection and data extraction. Multivariable frequency weighted logistic regression analysis was performed to assess the effect of the type of transfer on the outcome measures. We identified 14 randomised clinical trials (RCTs), including 20 transfer groups and 4474 participants. Thirty-day mortality was lower in patients who underwent field triage (3.0%; 95% confidence interval (CI) 2.2-4.2) compared to patients who were referred via a spoke centre (4.7%; 95% CI 4.0-5.5). In multivariable frequency weighted logistic regression analysis, field triage was independently associated with a lower incidence of 30-day mortality (odds ratio (OR): 0.58; 95% CI 0.37-0.89). CONCLUSION: Field triage compared to referral via a spoke centre leads to a lower 30-day mortality in STEMI patients. Therefore, direct ambulance transport to a PCI hospital should become the transfer type for STEMI patients.