Accuracy of mobile 6-lead electrocardiogram device for assessment of QT interval: a prospective validation study.

INTRODUCTION: Ambulatory assessment of the heart rate-corrected QT interval (QTc) can be of diagnostic value, for example in patients on QTc-prolonging medication. Repeating sequential 12-lead electrocardiograms (ECGs) to monitor the QTc is cumbersome, but mobile ECG (mECG) devices can potentially solve this problem. As the accuracy of single-lead mECG devices is reportedly variable, a multilead mECG device may be more accurate. METHODS: This prospective dual-centre study included outpatients visiting our cardiology clinics for any indication. Participants underwent an mECG recording using a smartphone-enabled 6­lead mECG device immediately before or immediately after a conventional 12-lead ECG recording. Multiple QTc values in both recordings were manually measured in leads I and II using the tangent method and subsequently compared. RESULTS: In total, 234 subjects were included (mean ± standard deviation (SD) age: 57 ± 17 years; 58% males), of whom 133 (57%) had cardiac disease. QTc measurement in any lead was impossible due to artefacts in 16 mECGs (7%) and no 12-lead ECGs. Mean (± SD) QTc in lead II on the mECG and 12-lead ECG was 401 ± 30 and 406 ± 31 ms, respectively. Mean (± SD) absolute difference in QTc values between both modalities was 12 ± 9 ms (r = 0.856; p < 0.001). In 55% of the subjects, the absolute difference between QTc values was < 10 ms. CONCLUSION: A 6-lead mECG allows for QTc assessment with good accuracy and can be used safely in ambulatory QTc monitoring. This may improve patient satisfaction and reduce healthcare costs.

The accuracy of heartbeat detection using photoplethysmography technology in cardiac patients.

INTRODUCTION: Photoplethysmography (PPG) in wearable sensors potentially plays an important role in accessible heart rhythm monitoring. We investigated the accuracy of a state-of-the-art bracelet (Corsano 287) for heartbeat detection in cardiac patients and evaluated the efficacy of a signal qualifier in identifying medically useful signals. METHODS: Patients from an outpatient cardiology clinic underwent a simultaneous resting ECG and PPG recording, which we compared to determine accuracy of the PPG sensor for detecting heartbeats within 100 and 50 ms of the ECG-detected heart beats and correlation and Limits of Agreement for heartrate (HR) and RR-intervals. We defined subgroups for skin type, hair density, age, BMI and gender and applied a previously described signal qualifier. RESULTS: In 180 patients 7914 ECG-, and 7880 (99%) PPG-heartbeats were recorded. The PPG-accuracy within 100 ms was 94.6% (95% CI 94.1-95.1) and 89.2% (95% CI 88.5-89.9) within 50 ms. Correlation was high for HR (R = 0.991 (95% CI 0.988-0.993), n = 180) and RR-intervals (R = 0.891 (95% CI 0.886-0.895), n = 7880). The 95% Limits of Agreement (LoA) were -3.89 to 3.77 (mean bias 0.06) beats per minute for HR and -173 to 171 (mean bias -1) for RR-intervals. Results were comparable across all subgroups. The signal qualifier led to a higher accuracy in a 100 ms range (98.2% (95% CI 97.9-98.5)) (n = 143). CONCLUSION: We showed that the Corsano 287 Bracelet with PPG-technology can determine HR and RR-intervals with high accuracy in cardiovascular at-risk patient population among different subgroups, especially with a signal quality indicator.

Coronary computed tomographic angiography as gatekeeper for new-onset stable angina.

Patients with new-onset stable angina constitute a substantial part of the population seen by cardiologists. Currently, the diagnostic workup of these patients depends on the pre-test probability of having obstructive coronary artery disease. It consists of either functional testing for myocardial ischaemia or anatomical testing by using coronary computed tomographic angiography (CCTA) or invasive coronary angiography. In case the pre-test probability is > 5%, the current guidelines for the management of chronic coronary syndromes do not state a clear preference for one of the noninvasive techniques. However, based on the recently published cost-effectiveness analysis of the PROMISE trial and considering the diagnostic yield in patients with angina and nonobstructive coronary artery disease, we argue a more prominent role for CCTA as a gatekeeper for patients with new-onset stable angina.

Effectiveness of web-based personalised e­Coaching lifestyle interventions.

INTRODUCTION: Interventions to reduce the impact of modifiable risk factors, such as hypercholesterolaemia, smoking, and overweight, have the potential to significantly decrease the cardiovascular disease burden. The majority of the global population is unaware of their own risk of developing cardiovascular disease. Parallel to the lack of awareness, a rise in obesity and diabetes is observed. e­Health tools for lifestyle improvement have shown to be effective in changing unhealthy behaviour. In this study we report on the results of three different trials assessing the effectiveness of MyCLIC, an e­Coaching lifestyle intervention tool. METHODS: From 2008 to 2016 we conducted three trials: 1) HAPPY NL: a prospective cohort study in the Netherlands, 2) HAPPY AZM: a prospective cohort study with employees of Maastricht UMC+ and 3) HAPPY LONDON: a single-centre, randomised controlled trial with asymptomatic individuals who have a high 10-year CVD risk. RESULTS: HAPPY NL and HAPPY AZM showed that e­Coaching reduced cardiovascular risk. Both prospective trials showed a 20-25% relative reduction in 10-year cardiovascular disease risk. A lesser effect was seen in the HAPPY LONDON trial. A low frequency of logins suggests a low degree of content engagement in the e­Coaching group, which could be age related as the mean age of the participants in the HAPPY LONDON study was high. CONCLUSION: e-Coaching using MyCLIC is a low cost and effective method to perform lifestyle interventions and has the potential to reduce the 10-year cardiovascular disease risk.

First real-world experience with mobile health telemonitoring in adult patients with congenital heart disease.

BACKGROUND: Arrhythmias and heart failure are common and invalidating sequelae in adult patients with congenital heart disease (CHD). Mobile health (m-Health) enables daily monitoring and a timely response that might prevent deterioration. We present an observational prospective registry to evaluate feasibility of an m­Health telemonitoring program for managing arrhythmia, heart failure and blood pressure in symptomatic adults with CHD. METHODS: Symptomatic adult patients with CHD are enrolled in an m­Health telemonitoring program, which evaluates single-lead ECG, blood pressure and weight measurements. In case of symptoms extra measurements could be performed. Data are collected by mobile apps, matched with individualised thresholds. Patients are contacted if thresholds were exceeded or if arrhythmias were found, for treatment adjustments or reassurance. Data on emergency care utilisation, hospitalisation and patient-reported outcome measures are used to assess quality of life and self-management. RESULTS: 129 symptomatic CHD patients were invited to participate, 55 participated. Reasons for refusing consent included too time consuming to participate in research (30) and to monitor vital signs (14). At baseline 22 patients were in New York Heart Association class ≥ II heart failure, 43 patients had palpitations or documented arrhythmias, and 8 had hypertension. Mean follow-up was 3.0 months, one patient dropped out, and adherence was 97%. CONCLUSION: The first results indicate that this program is feasible with high adherence.

Cardiac sympathetic activity in chronic heart failure: cardiac 123I-mIBG scintigraphy to improve patient selection for ICD implantation.

Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with 123I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function.

PURPOSE: Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. METHODS: A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [(15)O]H2O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. RESULTS: Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg×ml(-1)×min(-1)×g(-1), p < 0.01) as compared to nonobese patients. Male gender (ß = 40.7, p < 0.001), BMI (ß = 1.61, p < 0.001), smoking (ß = 6.29, p = 0.03) and EAT volume (ß = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. CONCLUSION: EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors.

Takotsubo cardiomyopathy complicated by cardiac tamponade.

We describe a 76-year-old patient with takotsubo cardiomyopathy complicated by cardiac tamponade. Pericardial effusion in takotsubo cardiomyopthy is common but a cardiac tamponade is very rare. The use of anticoagulants may increase the risk of pericardial effusion and should be considered with care.

Cognitive coping and goal adjustment after first-time myocardial infarction: relationships with symptoms of depression.

The authors studied the relationships among cognitive coping strategies, goal adjustment processes (disengagement and reengagement), and depressive symptomatology in a sample of 139 patients who had experienced a first-time acute myocardial infarction between 3 and 12 months before data assessment. They assessed cognitive coping strategies, goal adjustment, and depressive symptoms by the Cognitive Emotion Regulation Questionnaire, the Goal Obstruction Questionnaire, and the Hospital Anxiety and Depression Scale, respectively. Main statistical methods were Pearson correlations and multiple regression analyses. Results show significant associations among the cognitive coping strategies of rumination, catastrophizing, and higher depressive symptoms, as well as among positive refocusing, goal reengagement, and lower depressive symptoms. This suggests that cognitive coping and goal reengagement strategies may be useful targets for intervention.

Post-traumatic growth after a myocardial infarction: a matter of personality, psychological health, or cognitive coping?

The aim of the present study was to focus on the relative contributions of personality, psychological health and cognitive coping to post-traumatic growth in patients with recent myocardial infarction (MI). The sample consisted of 139 patients who had experienced a first-time acute MI between 3 and 12 months before data assessment. Multivariate relationships were tested by means of Structural Equation Modeling. The results showed that besides the contribution of personality and psychological health, a significant amount of variance in growth was explained by the cognitive coping strategies people used to handle their MI. As cognitive coping strategies are generally assumed to be mechanisms that are subject to potential influence and change, this provides us with important targets for intervention.

Cardiac sympathetic neuronal function in left ventricular volume and pressure overload.

OBJECTIVES: In heart failure cardiac sympathetic neuronal function and activity appear to be altered. Although these changes are widely accepted, controversy exists concerning the neurohormonal changes occurring in pressure and volume overloaded hearts. The present study in rabbits was performed to assess the effects of mechanical overload on cardiac sympathetic neuronal function and beta-adrenoceptor density, in relation to left ventricular function. METHODS: In nine rabbits the aortic valve was perforated to induce left ventricular volume overload. Pressure overload was induced by suprarenal banding of the aorta abdominalis (group 1). Five animals were sham operated (group 2). Subanalysis of group 1 was performed for non-failing (n = 5) and failing (n = 4) hearts. Heart failure was defined as any reduction in left ventricular fractional shortening 2 weeks after the second operation compared to baseline. RESULTS: In animals with cardiac overload, left ventricular weight was higher compared with the control animals, 7.99 +/- 1.13 vs. 6.16 +/- 0.86 g (P < 0.02). Left ventricular end diastolic diameter increased from 1.35 +/- 0.16 to 1.57 +/- 0.15 cm (P < 0.005) after surgically induced overload. Left ventricular end systolic diameter and fractional shortening did not change significantly. Myocardial noradrenaline (NA) concentration and beta-adrenoceptor density were significantly lower in group 1 than in group 2, 1005 +/- 393 vs. 1643 +/- 109 ng/g (P < 0.02) and 167 +/- 36 vs. 224 +/- 36 fmol/mg protein (P < 0.03), respectively. Myocardial [123I]-MIBG uptake did not significantly differ between group 1 and 2, 2.1 +/- 0.58 vs. 1.8 +/- 0.44 (%ID/g x kg). A significant positive correlation between myocardial NA concentration and beta-adrenoceptor density was found (r = 0.66, P < 0.02). Myocardial NA concentration was inversely related to left ventricular weight (r =-0.75, P < 0.003). CONCLUSION: The present data indicate that in a condition of cardiac volume and pressure overload, sympathetic activity is enhanced as shown by myocardial noradrenaline depletion and beta-adrenoceptor downregulation. In contrast, no cardiac neuronal dysfunction is observed, even in the stage of early heart failure.

Horner's syndrome in a patient presenting with chest pain.

An altered mental status and peripheral nerve dysfunction are alarming signs in a patient presenting with chest pain. If complicated by acute myocardial infarction, this raises the suspicion of aortic dissection and warrants immediate CT angiography. We report a dramatic case of chest pain in a 79-year-old man with somnolence and Horner's syndrome, subsequently complicated by myocardial infarction. Autopsy demonstrated a type A aortic dissection involving the carotid arteries and the right coronary artery.

Incremental diagnostic value of epicardial adipose tissue for the detection of functionally relevant coronary artery disease.

BACKGROUND AND AIM: To determine the incremental diagnostic value of epicardial adipose tissue (EAT) volume in addition to the coronary artery calcium (CAC) score for detecting hemodynamic significant coronary artery disease (CAD). METHODS AND RESULTS: 122 patients (mean age 61 ± 10 years, 61% male) without a previous cardiac history underwent a non-contrast CT scan for calcium scoring and EAT volume measurements. Subsequently all patients underwent invasive coronary angiography (ICA) in conjunction with fractional flow reserve (FFR) measurements. A stenosis >90% and/or a FFR ≤0.80 were considered significant. Mean EAT volume and CACscore were 128 ± 51 cm(3) and 418 ± 704, respectively. The correlation between EAT volume and the CACscore was poor (r = 0.11, p = 0.24). Male gender (odds ratio [OR] 2.86, p = 0.01), CACscore ([cut-off value 100] OR 3.31, p = 0.003, and EAT volume ([cut-off value 92 cm(3)] OR 4.28, p = 0.01) were associated with flow-limiting disease. The multivariate model revealed that only male gender (OR 2.50, p = 0.045), CAC score (OR 3.60, p = 0.005), and EAT volume (OR 4.95, p = 0.02) were independent predictors of myocardial ischemia. Using the cut-off values of 100 (CAC score) and 92 cm(3) (EAT volume), sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for detecting functionally relevant CAD as indicated by FFR were 71, 57, 77, 50 and 63% and 91, 29, 85, 44 and 52% for the CACscore and EAT volume, respectively. Adding EAT volume to the CAC score and cardiovascular risk factors did not enhance diagnostic performance for the detection of significant CAD (p = 0.57). CONCLUSION: EAT volume measurements have no diagnostic value beyond calcium scoring and cardiovascular risk factors in the detection of hemodynamic significant CAD.

Synthesis and in vitro and in vivo characteristics of an iodinated analogue of the beta-adrenoceptor antagonist carazolol.

A new (radio)iodinated, beta-adrenoceptor ligand, (S)-(-)-4-[3-[(1,1-dimethyl-3-iodo-(2E)-propenyl)-amino]-2- hydroxypropoxy]carbazole (CYBL8E, 1), was prepared. 1 is an iodinated analogue of the high-affinity beta-adrenoceptor antagonist carazolol (2). The asymmetric synthesis was achieved in four steps starting from 4-hydroxycarbazole. The iodine-123-labeled form was obtained by an iododestannylation reaction with [123I]NaI in the presence of H2O2. Using classical in vitro displacement experiments with membrane fractions of cardiac left ventricular muscle, 1 proved to have a high affinity for the receptor (Ki = 0.31 +/- 0.03). Biodistribution studies performed in New Zealand white rabbits demonstrated the specificity of the binding in vivo to the receptor. Uptake of [123I]1 was reduced significantly in both atrial muscle, left ventricular muscle, frontal cortex, cerebellum, and striatum, by the pretreatment of the animals with different beta-adrenoceptor antagonists. In conclusion, 1 is a potent nonselective beta-adrenoceptor antagonist, which binds specifically to the beta-adrenoceptor in vivo, and is therefore a promising radioligand for the imaging of beta-adrenoceptors using single photon emission computerized tomography.

Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.

OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.

Development of radioligands for the imaging of cardiac beta-adrenoceptors using SPECT. Part II: Pharmacological characterization in vitro and in vivo of new 123I-labeled beta-adrenoceptor antagonists.

Cardiac beta-adrenoceptors are assumed to play a key role in chronic heart failure. Although several radioligands labeled with 11C or 18F have been synthesized for imaging purposes with positron emission tomography (PET), so far no optimal ligands are available to image cardiac beta-adrenoceptors using single photon emission tomography (SPECT). In the present study, we characterized four new synthesized analogues of the nonselective beta-adrenoceptor antagonist 4-(3-t-butylamino-2-hydroxypropoxy)-benzimidazol-2-one (CGP12177) and one analogue of the nonselective beta-adrenoceptor antagonist penbutolol. Using classical in vitro displacement studies with left ventricular tissue of New Zealand White rabbits and [125I]iodocyanopindolol as a radioligand, binding affinity to the receptor was determined. From the four analogues, only (2'S,2"E)- [4-(3'-(1",1"-dimethyl-3"-Iodo-2" propenylamino)-2'-hydroxypropoxy)]-benzimidazol-2-one proved to have a high affinity, with Ki = 1.25 +/- 0.09 nM, n = 3. The other analogues showed relatively low affinity, with Ki-values > 1 nM. The analogue of penbutolol ((S)-(-)-[1-(2-Iodophenoxy)]-3'-(tert-butylamino)-2'-propanol) also showed a Ki value of 0.64 +/- 0.26 nM, n = 3. Subsequently, (2'S,2"E)-[4-(3'-(1",1"-dimethyl-3"-Iodo-2" propenylamino)-2'-hydroxypropoxy)]-benzimidazol-2-one and (S)-(-)-[1-(2-Iodophenoxy)]-3'-(tert-butylamino)-2'-propanol were radioactively labeled with 123I to study their biodistribution in New Zealand White rabbits and to determine specific binding. Significant uptake was observed in both lungs and left ventricles. However, both compounds showed high nonspecific binding in vivo because uptake of the radioligand could not be inhibited by preinjection of different (selective- and nonselective-adrenoceptor antagonists and hydrophilic and lipophilic antagonists) antagonists. In conclusion, although two analogues showed reasonable affinity in vitro for the receptor, their binding in vivo proved to be largely nonspecific, suggesting that these two compounds are unsuitable for imaging purposes. However, because marked differences in affinity for the receptor were observed with only little structural changes between compounds, the present results offer future perspectives for the synthesis of a more specific radioligand.