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Objective: Depression and anxiety in patients with an implantable cardioverter-defibrillator (ICD) are associated with adverse outcomes. This study describes the design of the PSYCHE-ICD study and evaluates the correlation between cardiac status and depression and anxiety in ICD patients. Methods: We included 178 patients. Prior to implantation, patients completed validated psychological questionnaires for depression, anxiety and personality traits. Cardiac status was evaluated by means of left ventricular ejection fraction assessment (LVEF), New York Heart Association (NYHA) functional class, 6-minute walk test (6MWT), and 24-h Holter monitoring for heart rate variability (HRV). A cross-sectional analysis was performed. Follow-up with annual study visits, including repeated full cardiac evaluation, will continue 36 months after ICD implantation. Results: Depressive symptoms were present in 62 (35%) and anxiety in 56 (32%) patients. Values of depression and anxiety significantly increased with higher NYHA class (P < 0.001). Depression symptoms were correlated with a reduced 6MWT (411 ± 128 vs. 488 ± 89, P < 0.001), higher heart rate (74 ± 13 vs. 70 ± 13, P = 0.02), higher thyroid stimulation hormone levels (1.8 [1.3–2.8] vs 1.5 [1.0–2.2], P = 0.03) and multiple HRV parameters. Anxiety symptoms were correlated with higher NYHA class and a reduced 6MWT (433 ± 112 vs 477 ± 102, P = 0.02). Conclusion: A substantial part of patients receiving an ICD have symptoms of depression and anxiety at time of ICD implantation. Depression and anxiety were correlated with multiple cardiac parameters, suggesting a possible biological links between psychological distress and cardiac disease in ICD patients.

Background Cor triatriatum sinistra (CTS) is a rare condition where the left atrium (LA) is divided by a thin membrane into an upper and lower chamber. Incidentally, the diagnosis is made in late adulthood, usually because of a favourable variant such as in our patient who presented with partial CTS. Case summary We present the case of a 62-year-old female who presented with COVID-19. She was known for longstanding symptoms of dyspnoea on exertion as well as a minor stroke several years ago. Computed tomography on admission suggested there was a mass in the LA but transthoracic echocardiography and cardiac magnetic resonance imaging revealed the diagnosis of partial CTS in which the superior compartment received pulmonary venous drainage from the right lung and the left-sided pulmonary veins drained into the inferior chamber. Since there were signs of chronic pulmonary oedema she successfully underwent balloon dilatation of the membrane resulting in remission of symptoms and normalization of the pressure in the accessory chamber. Discussion Partial CTS is a rare variant of CTS. Since part of the pulmonary veins drains in the lower chamber of the LA (and thereby unload the right ventricle), it is a favourable variant and patients may present later in life when membrane orifices calcify or it may be discovered as an incidental finding. In some patients requiring intervention, balloon dilatation of the membrane may be considered as an alternative to surgical removal of the membrane by thoracotomy.

Background: Sudden cardiac arrest survivors with a reversible cause are not eligible for implantable cardioverter defibrillator (ICD) implantation. This study aims to evaluate the risk of recurrent ventricular arrhythmia in sudden cardiac arrest survivors with a reversible cause and evaluate if ICD implantation increases survival. Methods: We conducted a systematic review to identify studies evaluating ICD implantation in sudden cardiac arrest survivors with a reversible cause. Outcomes were mortality and appropriate device therapy. Sudden cardiac arrest patients were divided into 4 subgroups: due to acute myocardial infarction; due to coronary artery spasm; due to takotsubo cardiomyopathy; and studies with various reversible causes of cardiac arrest. Results: 27 studies were included, evaluating 11,402 patients. A total of 2570 patients received an ICD. Studies evaluating coronary artery spasm and with various reversible causes showed a relatively high rate of appropriate device therapy (17% and 20%) and described an increased survival in ICD patients. Takotsubo cardiomyopathy was associated with a low mortality and none of the ICD patients received appropriate device therapy. Studies evaluating acute myocardial infarction survivors reported inconsistent results, with high numbers of appropriate device therapy (12–66%), but the mortality-rate of patients with and without an ICD varied. Conclusion: This study shows that the recurrence risk of ventricular arrhythmia varies between different reversible causes of sudden cardiac arrest and should not be evaluated as one entity. Cardiac arrest survivors with a reversible cause can be at risk of recurrent ventricular arrhythmia and selected patients may benefit from ICD implantation.

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. Methods and results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p

BackgroundExtensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA).ObjectivesHypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey-protein formula (eHWF) in CMA children were assessed.MethodsIn this prospective, randomized, international, multi-center study (Trial NL3889), 34 children with confirmed CMA (74% IgE-mediated) underwent a double-blind, placebo-controlled food challenge (DBPCFC) with an eHWF developed with non-porcine enzymes, supplemented with prebiotic short-chain galacto- and long-chain fructo-oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7-day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16-weeks follow-up.ResultsOf the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE-mediated CMA) completed the DBPCFC and 7-day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow-up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient.ConclusionsThe newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability.

Funding Acknowledgements Type of funding sources: None. Background Psychological distress, such as symptoms of anxiety and depression, are frequently present in patients receiving an implantable cardioverter defibrillator (ICD) and they are associated with adverse outcomes. Multiple pathophysiological mechanisms may explain the link between psychological distress and cardiovascular disease, such as autonomic dysfunction, neuro-endocrine alterations and chronic inflammation. Purpose The present study aims to examine the prevalence of psychological distress at time of ICD implantation and evaluates the complex interplay between psychological distress, autonomic function, neuro-endocrine alterations and inflammatory status in ICD patients. Methods We conducted a prospective study that included ICD patients receiving an ICD for primary and secondary prevention of sudden cardiac death. Prior to implantation, patients underwent extensive psychological evaluation, including validated questionnaires for depression, anxiety and personality traits. Cardiac status was evaluated by left ventricular ejection fraction (LVEF) assessment, New York Heart Association (NYHA) functional class evaluation, 6-minute walk test (6MWT), and 24-hour Holter monitoring for heart rate variability (HRV). Thyroid function, catecholamine levels and inflammatory status were also evaluated. Results Of 178 patients included (age 64 ± 12, 79% male, LVEF 35 ± 13%), 35% had symptoms of depression and 32% had symptoms of anxiety. Symptoms of depression and anxiety increased significantly with higher NYHA functional class (P Conclusion A substantial part of ICD patients has symptoms of depression and anxiety at time of ICD implantation. Depression was correlated with a higher NYHA class, reduced exercise capacity, reduced LV-function and alterations in autonomic function, suggesting a biological link between depression and cardiac status. Whether depression and anxiety leads to an increase in ventricular arrhythmias will be determined during further follow-up. Abstract Figure. NYHA class and psychological distress

Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar‐related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter‐defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD‐per‐guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD‐off‐label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5–4.6) of follow‐up, ADT developed in 15% of the ICD‐off‐label group versus 43% of the ICD‐per‐guideline group. Time to ADT was comparable in the ICD‐off‐label and ICD‐per‐guideline groups (hazard ratio (HR), 0.46; P =0.08). No difference in mortality was observed (HR, 0.95; P =0.93). Independent predictors of ADT included age (HR, 1.03; P =0.01), left ventricular end‐diastolic volume HR, (1.05 per 10 mL increase; P P =0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement–cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.

Background Implantable cardioverter defibrillator (ICD) guidelines and risk stratification models of sudden cardiac death (SCD) are applied without differentiation between men and women, based on the assumption that the incidence of ventricular arrhythmias and risk factors of SCD are similar in both sexes. Sex-specific risk factors of SCD may influence studies evaluating the benefit of ICD therapy, for both men and women. Purpose Aim of the study is to assess sex-specific differences in occurrence and predictors of appropriate device therapy (ADT) for ventricular arrhythmias. Methods A multicenter retrospective cohort of 2300 consecutive patients was evaluated, including patients referred for ICD implantation between the years 2009–2018 (age 62±13 years, LVEF 32±12%, 53% ischemic cardiomyopathy [CMP], 28% resynchronization therapy, 65% primary prevention). Exclusion criteria were: (1) patients with hypertrophic CMP, arrhythmogenic right ventricular CMP, systemic infiltrative cardiac disease or channelopathy; (2) lost to follow-up immediately after ICD implantation. Primary endpoint was ADT, defined as anti-tachycardia pacing or shock for ventricular tachyarrhythmia. Secondary endpoints were mortality and inappropriate ICD therapy. Univariable and multivariable Cox regression analyses, stratified by sex, were performed to assess predictors of ADT. Results The cohort primarily consisted of men (75%). After a mean follow-up of 4.8±3.0 years, men experienced more ADT compared to women (25% versus 16%, HR 1.71, p Conclusion This study showed that men were at higher risk of ADT compared to women and that risk factors associated with SCD differ between both sexes. The results strongly suggests that SCD risk stratification models are primarily driven by male patients and sex-specific risk models of SCD are needed to identify those women at high risk of SCD. Figure 1 Funding Acknowledgement Type of funding source: None

Objectives: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). Background: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. Methods: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [ 15O]H 2O and [ 11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. Results: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. Conclusions: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.