Pilot study on VF-waveform based algorithms for early detection of acute myocardial infarction during out-of-hospital cardiac arrest.

INTRODUCTION: On-scene detection of acute coronary occlusion (ACO) during ongoing ventricular fibrillation (VF) may facilitate patient-tailored triage and treatment during cardiac arrest. Experimental studies have demonstrated the diagnostic potential of the amplitude spectrum area (AMSA) of the VF-waveform to detect myocardial infarction (MI). In follow-up, we performed this clinical pilot study on VF-waveform based discriminative models to diagnose acute MI due to ACO in real-world VF-patients. METHODS: In our registry of VF-patients transported to a tertiary hospital (Nijmegen, The Netherlands), we studied patients with high-quality VF-registrations. We calculated VF-characteristics prior to the first shock, and first-to-second shock changes (Δ-characteristics). Primary aim was to assess the discriminative ability of the AMSA to detect patients with ACO. Secondarily, we investigated the discriminative value of adding ΔAMSA-measures using machine learning algorithms. Model performances were assessed using C-statistics. RESULTS: In total, there were 67 VF-patients with and 34 without an ACO, and baseline characteristics did not differ significantly. Based on the AMSA prior to the first defibrillation attempt, discrimination between ACO and non-ACO was possible, with a C-statistic of 0.66 (0.56-0.75). The discriminative model using AMSA + ΔAMSA yielded a C-statistic of 0.80 (0.69-0.88). CONCLUSION: These clinical pilot data confirm previous experimental findings that early detection of MI using VF-waveform analysis seems feasible, and add insights on the diagnostic impact of accounting for first-to-second shock changes in VF-characteristics. Confirmative studies in larger cohorts and with a variety of VF-algorithms are warranted to further investigate the potential of this innovative approach.

Electrocardiographic recording direction impacts ventricular fibrillation waveform measurements: A potential pitfall for VF-waveform guided defibrillation protocols.

AIM: In cardiac arrest, ventricular fibrillation (VF) waveform analysis has identified the amplitude spectrum area (AMSA) as a key predictor of defibrillation success and favorable neurologic survival. New resuscitation protocols are under investigation, where prompt defibrillation is restricted to cases with a high AMSA. Appreciating the variability of in-field pad placement, we aimed to assess the impact of recording direction on AMSA-values, and the inherent defibrillation advice. METHODS: Prospective VF-waveform study on 12-lead surface electrocardiograms (ECGs) obtained during defibrillation testing in ICD-recipients (2010-2017). AMSA-values (mVHz) of simultaneous VF-recordings were calculated and compared between all limb leads, with lead II as reference (proxy for in-field pad position). AMSA-differences between leads I and II were quantified using Bland-Altman analysis. Moreover, we investigated differences between these adjacent leads regarding classification into high (≥15.5), intermediate (6.5-15.5) or low (≤6.5) AMSA-values. RESULTS: In this cohort (n = 243), AMSA-values in lead II (10.2 ± 4.8) differed significantly from the other limb leads (I: 8.0 ± 3.4; III: 12.9 ± 5.6, both p < 0.001). The AMSA-value in lead I was, on average, 2.24 ± 4.3 lower than in lead II. Of the subjects with high AMSA-values in lead II, only 15% were classified as high if based on assessments of lead I. For intermediate and low AMSA-values, concordances were 66% and 72% respectively. CONCLUSIONS: ECG-recording direction markedly affects the result of VF-waveform analysis, with 20-30% lower AMSA-values in lead I than in lead II. Our data suggest that electrode positioning may significantly impact shock guidance by 'smart defibrillators', especially affecting the advice for prompt defibrillation.

The sustained effects of extending cardiac rehabilitation with a six-month telemonitoring and telecoaching programme on fitness, quality of life, cardiovascular risk factors and care utilisation in CAD patients: The TeleCaRe study.

INTRODUCTION: The aim of this study was to assess the acute and sustained effects of a six-month heart-rate-based telerehabilitation programme, following the completion of cardiac rehabilitation (CR), on peak oxygen uptake (peakVO2), quality of life (QoL), cardiovascular risk factors and care utilisation in patients with coronary artery disease (CAD). METHODS: A total of 122 patients with CAD were randomised, after the completion of CR, to an intervention group with six months of telemonitoring and telecoaching (TELE) or a control group with a traditional six-month follow-up programme with monthly calls (CON). The primary outcome was peakVO2 at 12 months, to assess the sustained effects of TELE. The secondary outcomes included QoL, cardiovascular risk factors (lipid spectrum), major adverse cardiovascular events (MACE) and habitual physical activity. RESULTS: PeakVO2 increased significantly from baseline to 12 months in TELE (+2.5 mL·kg-1min-1 (95% CI 1.5-3.2)) and CON (+1.9 mL·kg-1min-1 (95% CI 1.0-2.5)), and did not differ between groups (P = 0.28). Similarly, QoL (P = 0.31), total cholesterol (P = 0.45), MACE (P = 0.86) did not differ between groups and in time. DISCUSSION: Extending CR with a heart-rate-based telerehabilitation programme did not yield additional sustainable health benefits compared with regular care with monthly telephone calls. These observations highlight that both telerehabilitation and regular care with monthly telephone calls may prevent the typically observed reductions in peakVO2 following the completion of a CR programme.Trial registration: Dutch Trial Register NL4140 (registered 6 December 2014).

Influence of Pregnancy on Aortic Diameter in Women With the Turner Syndrome.

Women with Turner syndrome (TS) have high prevalence of cardiovascular anomalies. Literature suggests pregnancy is associated with a higher dissection risk, presumably preceded by aortic dilatation. Whether the aortic diameter truly changes during pregnancy in TS is not well investigated. This study aims to evaluate ascending aortic diameter change during pregnancy and reports on cardiac events during and directly after pregnancy. This tertiary hospital retrospective study investigated all TS women pregnancies (2009 to 2018). Outcome parameters included aortic diameter growth and aortic complications, specifically dissection. Thirty-five pregnancies in 30 TS women, 57% assisted by oocyte donation. Mean age at delivery 32 ± 5 years. In 27 pregnancies of 22 women imaging was available. From over 350 childless TS women a comparison group of 27 was individually matched. The median ascending aortic diameter growth between pre- and postpregnancy imaging was 1.0 mm (IQR -1.0; 2.0), no significant change (p = 0.077). Whether the patient had a bicuspid aortic valve (p = 0.571), monosomy X or mosaic karyotype (p = 0.071) or spontaneous pregnancy or resulting from oocyte donation (p = 0.686) had no significant influence on diameter change. Aortic growth between pregnancy and matched childless group (0.23 vs 0.32 mm/year, p = 0.788) was not significant over 3.3 ± 2 versus 4.4 ± 1 years. During pregnancy or the first 6 months after delivery no aortic complications were observed. In conclusion, this study suggests pregnancy in TS women does not induce faster ascending aortic diameter increase. Also not in presence of a bicuspid aortic valve, monosomy X karyotype, and oocyte donation. No aortic complications occurred. Based on current study pregnancy in TS women seems safe.

Exercise and myocardial injury in hypertrophic cardiomyopathy.

OBJECTIVE: Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants. METHODS: Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (< or >13 ng/L), a rise was defined as a >50% or >20% increase, respectively. RESULTS: Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p<0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p<0.001). CONCLUSIONS: Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand.

Differences in Aortopathy in Patients with a Bicuspid Aortic Valve with or without Aortic Coarctation.

OBJECTIVE: The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is assumed to be associated with a higher risk of ascending aortic dilatation and type A dissection, and current European Society of Cardiology (ESC) guidelines advise therefore to operate at a lower threshold in the presence of CoA. The aim of our study is to evaluate whether the coexistence of CoA in BAV patients is indeed associated with a higher risk of ascending aortic events (AAE). METHODS: In a retrospective study, all adult BAV patients visiting the outpatient clinic of our tertiary care center between February 2003 and February 2019 were included. The primary end point was an ascending aortic event (AAE) defined as ascending aortic dissection/rupture or preventive surgery. The secondary end points were aortic dilatation and aortic growth. RESULTS: In total, 499 BAV patients (43.7% female, age 40.3 ± 15.7 years) were included, of which 121 (24%) had a history of CoA (cBAV). An aortic event occurred in 38 (7.6%) patients at a mean age of 49.0 ± 13.6 years. In the isolated BAV group (iBAV), significantly more AAE occurred, but this was mainly driven by aortic valve dysfunction as indication for aortic surgery. There was no significant difference in the occurrence of dissection or severely dilated ascending aorta (>50mm) between the iBAV and cBAV patients (p = 0.56). The aortic diameter was significantly smaller in the cBAV group (30.3 ± 6.9 mm versus 35.7 ± 7.6 mm; p < 0.001). The median aortic diameter increase was 0.23 (interquartile range (IQR): 0.0-0.67) mm/year and was not significantly different between both groups (p = 0.74). CONCLUSION: Coexistence of CoA in BAV patients was not associated with a higher risk of aortic dissection, preventive aortic surgery, aortic dilatation, or more rapid aorta growth. This study suggests that CoA is not a risk factor in BAV patients, and the advice to operate at lower diameter should be reevaluated.

Diagnostic performance of the basic and advanced life support termination of resuscitation rules: A systematic review and diagnostic meta-analysis.

AIM: To minimize termination of resuscitation (TOR) in potential survivors, the desired positive predictive value (PPV) for mortality and specificity of universal TOR-rules are ≥99%. In lack of a quantitative summary of the collective evidence, we performed a diagnostic meta-analysis to provide an overall estimate of the performance of the basic and advanced life support (BLS and ALS) termination rules. DATA SOURCES: We searched PubMed/EMBASE/Web-of-Science/CINAHL and Cochrane (until September 2019) for studies on either or both TOR-rules in non-traumatic, adult cardiac arrest. PRISMA-DTA-guidelines were followed. RESULTS: There were 19 studies: 16 reported on the BLS-rule (205.073 patients, TOR-advice in 57%), 11 on the ALS-rule (161.850 patients, TOR-advice in 24%). Pooled specificities were 0.95 (0.89-0.98) and 0.98 (0.95-1.00) respectively, with a PPV of 0.99 (0.99-1.00) and 1.00 (0.99-1.00). Specificities were significantly lower in non-Western than Western regions: 0.84 (0.73-0.92) vs. 0.99 (0.97-0.99), p < 0.001 for the BLS rule. For the ALS-rule, specificities were 0.94 (0.87-0.97) vs. 1.00 (0.99-1.00), p < 0.001. For non-Western regions, 16 (BLS) or 6 (ALS) out of 100 potential survivors met the TOR-criteria. Meta-regression demonstrated decreasing performance in settings with lower rates of in-field shocks. CONCLUSIONS: Despite an overall high PPV, this meta-analysis highlights a clinically important variation in diagnostic performance of the BLS and ALS TOR-rules. Lower specificity and PPV were seen in non-Western regions, and populations with lower rates of in-field defibrillation. Improved insight in the varying diagnostic performance is highly needed, and local validation of the rules is warranted to prevent in-field termination of potential survivors.

Meta-Analysis Comparing Cardiac Arrest Outcomes Before and After Resuscitation Guideline Updates.

Updates of resuscitation guidelines have limited high-level supporting evidence. Moreover, the overall effect of such bundled practice changes depends not only on the impact of the individual interventions but also on their interplay and swift functioning of the entire chain of survival. Therefore, real-world data monitoring is essential. We performed a meta-analysis of comparative studies on outcomes before and after successive guideline updates. On January 16, 2019, we searched for comparative studies (PubMed, Web-of-Science, Embase, and the Cochrane Libraries) reporting outcomes before and after resuscitation guidelines 2005, 2010, and 2015. We followed PRISMA, Cochrane, and Moose-recommendations. Studies on outcomes during the 2005 versus 2000 guideline period (n = 23; 40,859 patients) reported significantly higher ROSC (odds ratio [OR] 1.21 [1.04 to 1.42], p = 0.014), survival to admission (OR 1.34 [1.09 to 1.65], p = 0.005), survival to discharge (OR 1.46 [1.25 to 1.70], p <0.001), and favorable neurologic outcome (OR 1.35 [1.01 to 1.81], p = 0.040). Studies on outcomes during the 2010 versus 2005 guideline period (n = 11; 1,048,112 patients) indicated no difference in ROSC (OR 1.25 [95% confidence interval 0.95 to 1.63], p = 0.11), whereas survival to discharge improved significantly (OR 1.30 [1.17 to 1.45], p <0.001). Only 2 studies reported on neurologic outcomes, both showing improved outcome after the 2010 guideline update. No data on the 2015 guidelines were available. This meta-analysis on real-world data of >1 million patients demonstrates improved outcomes after the 2005 and 2010 resuscitation guideline updates, and a lack of data on the 2015 guideline. In conclusion, although limited in terms of causality, this study suggests that the sum of all efforts to improve outcomes, including updated CPR guidelines, contributed to increased survival after cardiac arrest.

Association between Lifelong Physical Activity and Disease Characteristics in HCM.

PURPOSE: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. METHODS: We enrolled n = 22 genotype positive/phenotype negative (G+/P-) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G-/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. RESULTS: We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P- subjects (16 [10-29] vs 14 [6-26] metabolic equivalent of task-hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). CONCLUSIONS: Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

Feasibility and Outcomes of Transcatheter Aortic Valve Implantation Using the Left Axillary Artery as Primary Access Site.

BACKGROUND: The femoral artery is generally used as primary access for transcatheter aortic valve implantation. However, peripheral artery disease often precludes femoral access. The purpose of this study was to describe clinical outcome of transcatheter aortic valve implantation using the left axillary artery (LAA) as primary access site. METHODS: From December 2008 until June 2016, data on all consecutive patients treated with a Medtronic device through the LAA at our hospital were registered, and outcome was prospectively collected according to the updated Valve Academic Research Consortium-2 criteria. Mortality check was performed nationally. RESULTS: In total, 362 patients were included (median age 80 years [range, 76 to 84]; logistic European System for Cardiac Operative Risk Evaluation 17% ± 12%). Successful axillary access was achieved in 99%. Medtronic CoreValve (86%) and Evolut R (14% [Medtronic, Minneapolis, MN]) were implanted. Major vascular complications occurred in 5% of patients, 1% was LAA related. Life-threatening bleeding and major bleeding were observed in 2% and 10%, respectively. Additional complications were new left bundle branch blood (30%), new permanent pacemaker (11%), and stroke (1%). There were 6 procedural deaths (2%) and 19 deaths (5%) within 30 days. One-year mortality rate was 19%. CONCLUSIONS: This is the first study reporting outcome after transcatheter aortic valve implantation using the LAA as default access. We conclude that it is highly feasible and safe with low rates of major vascular complications, bleeding, and stroke.

Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy.

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGEext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

Correction to: Imaging the myocardial ischemic cascade.

In the original publication of the article, the seventh author name "Matthias Gutberlet" has been misspelt.

Imaging the myocardial ischemic cascade.

Non-invasive imaging plays a growing role in the diagnosis and management of ischemic heart disease from its earliest manifestations of endothelial dysfunction to myocardial infarction along the myocardial ischemic cascade. Experts representing the North American Society for Cardiovascular Imaging and the European Society of Cardiac Radiology have worked together to organize the role of non-invasive imaging along the framework of the ischemic cascade. The current status of non-invasive imaging for ischemic heart disease is reviewed along with the role of imaging for guiding surgical planning. The issue of cost effectiveness is also considered. Preclinical disease is primarily assessed through the coronary artery calcium score and used for risk assessment. Once the patient becomes symptomatic, other imaging tests including echocardiography, CCTA, SPECT, PET and CMR may be useful. CCTA appears to be a cost-effective gatekeeper. Post infarction CMR and PET are the preferred modalities. Imaging is increasingly used for surgical planning of patients who may require coronary artery bypass.

Ventricular fibrillation waveform characteristics of the surface ECG: Impact of the left ventricular diameter and mass.

BACKGROUND: Despite a promising association between VF waveform characteristics and prognosis after resuscitation, studies with VF-guided treatment have so far not improved outcomes. While driven by the idea that the VF waveform reflects arrest duration, increasing evidence suggests that pre-existent disease-related changes of the myocardium affect ECG-characteristics of VF as well. In this context, we studied the impact of the left ventricular (LV) diameter and mass. METHODS: Cohort of 193 ICD-patients with defibrillation testing at the Radboudumc (2010-2014). Surface ECG-recordings (leads I,II,aVF,V1,V3,V6) were analysed to study amplitude and frequency characteristics of the induced VF. Both for LV diameter and mass, patients were categorised in two groups, using echocardiographic data (ASE-guidelines). RESULTS: In all ECG-leads, dominant and median frequencies were significantly lower in patients with (n=40) than in patients without (n=151) an increased LV diameter. The mean amplitude and amplitude spectrum area (AMSA) did not differ. In contrast, we observed no differences in frequency characteristics in relation to the LV mass, whereas mean amplitude (I,aVF,V3) and AMSA (I,V3) were significantly higher in patients with (n=57) than in patients without (n=120) an increased LV mass. CONCLUSIONS: Frequency characteristics of VF were consistently lower in case of an increased LV diameter. Whereas LV mass does not affect the frequency of the VF waveform, amplitudes seem higher with increasing mass. These findings add to the current knowledge of factors that modulate VF characteristics of the surface ECG and provide insight into factors which may be accounted for in future studies on VF-guided resuscitative interventions.

Shock Index More Sensitive Than Cardiogenic Shock in ST-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

BACKGROUND: Cardiogenic shock (CS) is a strong predictor of mortality in patients with ST-elevation myocardial infarction (STEMI), but there is evidence that shock index (SI), taking into account both blood pressure and heart rate, is a more sensitive and powerful predictor. We investigated the independent impact of SI and CS on 30-day and 1-year mortality in patients with STEMI, treated by primary percutaneous coronary intervention (PCI).Methods and Results:In 7,412 consecutive patients with STEMI treated with primary PCI, the predictive value of either SI or CS on 1-year mortality was assessed. Best cut-off value of SI, determined using receiver operating characteristic (ROC) curve, was 0.7, with an ROC AUC of 0.66 (95% CI: 0.65-0.67), compared with an ROC AUC of 0.60 (95% CI: 0.59-0.61) for CS (P<0.001). At admission, 387 patients (5.2%) had CS and 1,567 patients (21.1%) had SI ≥0.7. The adjusted hazard ratio of mortality in patients with SI ≥0.7 and in CS patients was, respectively, 3.3 (95% CI: 2.4-4.6) and 3.1 (95% CI: 2.1-4.6) after 30 days, and 2.3 (95% CI: 1.8-2.9) and 3.1 (95% CI: 2.2-4.2) after 1 year. CONCLUSIONS: SI identifies more patients with increased risk of mortality, and seems to be a more sensitive prognostic predictor than CS in patients with STEMI treated by primary PCI.

Endurance exercise-induced changes in BNP concentrations in cardiovascular patients versus healthy controls.

BACKGROUND: Healthy athletes demonstrated increased B-type natriuretic peptide (BNP) concentrations following exercise, but it is unknown whether these responses are exaggerated in individuals with cardiovascular risk factors (CVRF) or disease (CVD). We compared exercise-induced increases in BNP between healthy controls (CON) and individuals with CVRF or CVD. Furthermore, we aimed to identify predictors for BNP responses. METHODS: Serum BNP concentrations were measured in 191 participants (60±12yrs) of the Nijmegen Marches before (baseline) and immediately after 4 consecutive days of walking exercise (30-50km/day). CVRF (n=54) was defined as hypertension, hypercholesterolemia, obesity or smoking and CVD (n=55) was defined as a history of myocardial infarction, heart failure, atrial fibrillation or angina pectoris. RESULTS: Individuals walked 487±79min/day at 65±10% of their maximum heart rate. Baseline BNP concentrations were higher for CVD (median: 28.1pg/ml; interquartile range: 13-50, p<0.001) compared to CVRF (3.9pg/ml; 0-14) and CON (5.5pg/ml; 0-14). Post-exercise BNP concentrations were elevated in CVD (35.7pg/ml, 17-67, p=0.01), but not in CVRF participants (p=0.11) or CON (p=0.07). No cumulative effect in BNP concentrations was observed across the consecutive walking days (p>0.05). Predictors for post-exercise BNP (R2=0.77) were baseline BNP, beta-blocker use and age. CONCLUSION: Prolonged moderate-intensity walking exercise increases BNP concentrations in CVD participants, but not in CVRF and CON. BNP increases were small, and did not accumulate across consecutive days of exercise. These findings suggest that prolonged walking exercise for multiple consecutive days is feasible with minimal effect on myocardial stretch, even for participants with CVD.

Rationale and design of a randomised clinical trial for an extended cardiac rehabilitation programme using telemonitoring: the TeleCaRe study.

BACKGROUND: Despite the known positive effects of cardiac rehabilitation and an active lifestyle, evidence is emerging that it is difficult to attain and sustain the minimum recommendations of leisure time physical activity. The long-term benefits are often disappointing due to lack of adherence to the changes in life style. Qualitative research on patients' perspectives suggests that motivation for lifestyle change tends to diminish around 3 months after the index-event. The time most cardiac rehabilitation programmes end. The aim of the present study is to determine if prolongation of a traditional cardiac rehabilitation programme with additional heart rate based telemonitoring guidance for a period of 6 months results in better long term effects on physical and mental outcomes, care consumption and quality of life than traditional follow-up. METHODS: In this single centre randomised controlled trial 120 patients with an absolute indication for cardiac rehabilitation will be randomised in a 1:1 ratio to an intervention group with 6 months of heart rate based telemonitoring guidance or a control group with traditional follow-up after cardiac rehabilitation. The primary endpoint will be VO2peak after 12 months. Secondary endpoints are VO2peak after 6 months, quality of life, physical-, emotional- and social functioning, cardiac structure, traditional risk profile, compliance to the use of the heart rate belt and smartphone, MACE and care-consumption. DISCUSSION: The TeleCaRe study will provide insight into the added value of the prolongation of traditional cardiac rehabilitation with 6 months of heart rate based telemonitoring guidance. TRIAL REGISTRATION: Dutch Trial Register: NTR4644 (registered 06/12/14).

Randomized evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: rationale and design of the REDUCE trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with drug eluting stents (DES) is still under debate. Recent meta-analyses on ≤6months versus 12months DAPT suggest that bleeding rates can be reduced, without a higher rate of thrombotic complications. In particular, the COMBO dual therapy stent, being associated with early re-endothelialization, may allow for a reduction of the duration of DAPT without increasing the thrombotic risk, while reducing the risk of bleeding complications. AIM: The aim of the REDUCE trial is to demonstrate the non-inferiority of a combined efficacy and safety endpoint of a short-term 3months DAPT strategy as compared to standard 12-month DAPT strategy in ACS patients treated with the COMBO stent. DESIGN: A prospective, multicenter, randomized study designed to enroll 1500 patients with ACS treated with the COMBO stent. Patients will be randomized before discharge in a 1:1 fashion to either 3 or 12months of DAPT. A clinical follow-up is scheduled at 3, 6, 12, and 24months. The primary endpoint is the time to event as defined by the occurrence of one of the following: all cause mortality, myocardial infarction, stent thrombosis, stroke, target vessel revascularization or bleeding (Bleeding Academic Research Council type II, III and V) within 12months. The study has recruited patients since July 2014, and the results are expected in 2017. SUMMARY: A reduction of the DAPT duration in ACS patients after PCI without affecting the thrombotic risk is an attractive option with regard to the associated bleeding risk. The REDUCE trial will be the first to investigate the efficacy and safety of a 3-month DAPT strategy compared to a 12-month DAPT strategy in an ACS only population treated with the COMBO stent.