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Aims: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms. Methods and results: In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E/eʹratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E/eʹratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40. Conclusion: Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.

Background:Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.Methods:We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.Results:Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P < 0.001, n = 40) and 59.5% in the SoC arm (P < 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).Conclusion:Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

Purpose: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. Methods: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use. Results: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77–0.98) and non-statin users (aHR 0.80, 95% CI 0.74–0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant. Conclusion: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.

On May 26, 2021, the European Medical Device Regulation (EU-MDR) entered into effect resulting in a major shift in the requirements for assessment of medical devices in Europe. The EU-MDR Cardiovascular Collaboratory (EU-MCVC) was founded to contribute to the development of faster, more efficient, and more effective pathways for innovation of cardiac medical devices. A registry is an organized system that collects uniform data and evaluates specified outcomes in a population defined by a disease, condition, or exposure. Most registries have been created to improve the quality of care and provide feedback to physicians, hospitals, and health providers. Clinical registries represent an ideal construct for scientific, clinical, and policy-making collaboration. We describe diverse experiences from 5 European countries and address the traditional quality components in clinical trials. Continued collaboration is expected among academics, clinical trialists, patient representatives, regulatory experts, research organizations, registry platforms, regulatory bodies, and industry partners. Data quality is a primary concern and registry leaders need to optimize data quality to become regulatory compliant. A collaborative approach among medical device stakeholders may improve quality of care, reduce costs, and provide faster access to innovative technologies, with the common objective of improving cardiovascular care and outcomes.

01 januari 2023, Item does not contain fulltext, BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging during supine exercise at (sub)maximal oxygen consumption (VO(2) ) offers unique diagnostic insights. However, maximal VO(2) is not achievable in the supine position and standardizing submaximal exercise intensities remains challenging. Using heart rate or workload could be a viable option to translate VO(2) -based submaximal exercise intensities. AIM: To translate submaximal exercise intensities upright cycling exercise (UCE) to supine push-pull exercise (SPPE), by comparing heart rate or workload determined during UCE, with heart rate and workload during SPPE at similar exercise intensities. METHODS AND RESULTS: Sixteen healthy young adults (20.4 ± 2.2 years; 8 female) underwent cardiopulmonary UCE and SPPE testing [mean ± standard deviation maximal VO(2) : 3.2 ± 0.6 vs. 5 ± 0.3 L min(-1) , p < 0.001 and median (interquartile range) of the maximum workload: 310 (244, 361) vs. 98 (98, 100), p < 0.001, respectively]. Heart rate at 40% and 60% of maximal VO(2) , as determined by UCE, showed low bias (-3 and 0 bpm, respectively) and wide limits of agreement (±26 and ±28 bpm, respectively), in Bland-Altman analysis. VO(2) /Workload relation was exponential and less efficient during SPPE compared to UCE. Generalized estimated equation analysis predicted model-based mean workload during SPPE, with acceptable 95% confidence interval. CONCLUSION: Heart rate during UCE at submaximal exercise intensities can reasonably well be used to for SPPE in healthy subjects. Using workload, an ergometer specific, model-based mean can be used to determine exercise intensities during SPPE. Individual variations in response to posture and movement change are high. During clinical interpretation of exercise CMR, individual exercise intensity has to be considered.

01 januari 2023, Item does not contain fulltext, In patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise capacity is challenged by changes in body composition during growth. Our aim was to create an overview of disease-specific exercise capacity in children with CHD. We performed a multicentre retrospective study of exercise capacity of CHD patients, aged 6-18 years, tested between January 2001 and October 2018. Sex-specific distribution graphs were made using the LMS method and height to relate to body size. We included all CHD with N > 50, including severe defects (e.g., univentricular heart, tetralogy of Fallot) and "simple" lesions as ventricular septum defect and atrial septum defect. We included 1383 tests of 1208 individual patients for analysis. The peak oxygen uptake (VO(2)peak, 37.3 ml/min/kg (25th-75th percentile 31.3-43.8)) varied between specific defects; patients with univentricular hearts had lower VO(2peak) compared with other CHD. All groups had lower VO(2peak) compared to healthy Dutch children. Males had higher VO(2peak), W(peak) and O(2)pulse(peak) than females. Sex- and disease-specific distribution graphs for VO(2peak), W(peak) and O2pulse(peak) showed increase in variation with increase in height. Conclusion: Disease-specific distribution graphs for exercise capacity in children with CHD from a large multicentre cohort demonstrated varying degrees of reduced VO(2peak) and W(peak). The distribution graphs can be used in the structured follow-up of patients with CHD to predict outcome and identify patients at risk. What is Known: • Children with congenital heart disease (COnHD) are at risk to develop heart failure, arrhytmia's and other complications. Exercise capacity may be an important predictor for outcome in children with ConHD. In children, the interpretation of exercise capacity poses an additional challenge related to physical changes during growth.

Item does not contain fulltext, BACKGROUND: Biomarkers might help to improve diagnosis, surveillance and risk stratification of thoracic aortic disease (TAD). We explored the association between a broad spectrum of cardiovascular biomarkers with clinical characteristics and thoracic aortic diameter in TAD patients. METHODS: Venous blood-samples were obtained in 158 clinically stable TAD patients visiting our outpatient clinic (2017-2020). TAD was defined as a thoracic aortic diameter ≥ 40 mm, or genetic confirmation (hereditary TAD). The cardiovascular panel III of the Olink multiplex platform was used for batch analysis of 92 proteins. A comparison was made between biomarker levels in patients with and without previous aortic dissection and/or surgery, and with and without hereditary TAD. Linear regression analyses were applied to identify (relative, normalized) biomarker concentrations associated with the absolute thoracic aortic diameter (AD(max)), and thoracic aortic diameter indexed for body surface area (ID(max)). RESULTS: Median age of study patients was 61.0 (IQR 50.3-68.8) years, 37.3% females. Mean AD(max) and ID(max) were 43.3 ± 5.4 mm and 21.3 ± 3.3 mm/m(2). After multivariable adjustment, Matrix Metalloproteinase-3 (MMP-3) and Insulin-like growth factor binding protein 2 (IGFBP-2) showed a significant positive association with AD(max) and ID(max), respectively. Patients with previous aortic surgery/dissection had higher N-terminal-pro hormone BNP (NTproBNP) (median 3.67 [IQR 3.01-3.99] vs 2.84 [2.32-3.26], p ≤0.001). Patients with hereditary TAD had higher Trem-like transcript protein 2 (TLT-2) (median 4.64 [IQR 4.45-4.84]) than those with non-heriditary TAD (4.40 [4.17-4.64]; p = 0.00042). CONCLUSIONS: Among a broad range of biomarkers, MMP-3 and IGFBP-2 were associated with disease severity in TAD patients. The pathophysiological pathways uncovered by these biomarkers, and their potential clinical use warrants further research.

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01 juni 2023, Contains fulltext : 294354.pdf (Publisher’s version ) (Open Access), OBJECTIVE: As thoracic aortic disease (TAD) is generally asymptomatic, biomarkers are needed to provide insight into early progression. We aimed to examine the association between circulating blood biomarkers and the maximal thoracic aortic diameter (TADmax). METHODS: In this cross-sectional study, consecutive adult patients with a thoracic aortic diameter ≥40 mm and/or genetically proven hereditary TAD (HTAD) visiting our specialised outpatient clinic between 2017 and 2020 were prospectively included. Venous blood sampling and CT angiography and/or transthoracic echocardiography of the aorta were performed. Linear regression analyses were performed and estimates were presented as mean difference in TADmax in mm per doubling of standardised biomarker level. RESULTS: In total, 158 patients were included (median age 61 (50.3-68.8) years, 37.3% female). HTAD diagnosis was confirmed in 36 of 158 (22.7%) patients. TADmax was 43.9±5.2 mm in men vs 41.9±5.1 in women (p=0.030). In unadjusted analysis, significant associations with TADmax were found for interleukin-6 (1.15 (95% CI 0.33 to 1.96), p=0.006), growth differentiation factor-15 (1.01 (95% CI 0.18 to 1.84), p=0.018), microfibrillar-associated protein 4 (MFAP4) (-0.88 (95% CI -1.71 to 0.05), p=0.039) and triiodothyronine (T3) (-2.00 (95%CI -3.01 to 0.99), p<0.001). The association of MFAP4 with TADmax was stronger in women (p for interaction=0.020) and for homocysteine, an inverse association with TADmax was observed when compared with men (p for interaction=0.008). When adjusted for age, sex, hyperlipidaemia and HTAD, total cholesterol (1.10 (95% CI 0.27 to 1.93), p=0.010) and T3 (-1.20 (95% CI -2.14 to 0.25), p=0.014) were significantly associated with TADmax. CONCLUSIONS: Circulating biomarkers indicative of inflammation, lipid metabolism and thyroid function might be associated with TAD severity. Possible distinct biomarker patterns for men and women warrant further investigation.

Item does not contain fulltext, AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Objective: To assess the cost-effectiveness of a cardiac rehabilitation (CR) program specifically designed for cardiac patients with obesity vs standard CR. Design: Cost-effectiveness analysis based on observations in a randomized controlled trial. Setting: Three regional CR centers in the Netherlands. Participants: Cardiac patients (N=201) with obesity (BMI≥30 kg/m2) referred to CR. Interventions: Participants were randomized to a CR program specifically designed for patients with obesity (OPTICARE XL; N=102) or standard CR. OPTICARE XL included aerobic and strength exercise and behavioral coaching on diet and physical activity during 12 weeks, followed by a 9-month after-care program with “booster” educational sessions. Standard CR consisted of a 6- to 12-week aerobic exercise program, supplemented with cardiovascular lifestyle education. Main Outcome Measures: An economic evaluation, with an 18-month time horizon, in terms of quality-adjusted life years (QALYs) and costs from the societal perspective was performed. Costs were reported in 2020 Euros, discounted at a 4% annual rate, and health effects were discounted at a 1.5% annual rate. Results: OPTICARE XL CR and standard CR resulted in comparable health gain per patient (0.958 vs 0.965 QALYs, respectively; P=.96). Overall, OPTICARE XL CR saved costs (-€4542) compared with the standard CR group. The direct costs for OPTICARE XL CR were higher than for standard CR (€10,712 vs €9951), whereas indirect costs were lower (€51,789 vs €57,092), but these differences were not significant. Conclusions: This economic evaluation showed no differences between OPTICARE XL CR and standard CR in health effects and costs in cardiac patients with obesity.

Background: We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. Methods: In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. Results: Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10–0.41) and (0.13 (0.10–0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. Conclusion: LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr. Graphical abstract: [Figure not available: see fulltext.].

Background and aims: Despite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. Methods: We performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. Results: We studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). Conclusions: In routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered.

Objective: To assess the cost-effectiveness of a cardiac rehabilitation (CR) program specifically designed for cardiac patients with obesity vs standard CR. Design: Cost-effectiveness analysis based on observations in a randomized controlled trial. Setting: Three regional CR centers in the Netherlands. Participants: Cardiac patients (N=201) with obesity (BMI≥30 kg/m2) referred to CR. Interventions: Participants were randomized to a CR program specifically designed for patients with obesity (OPTICARE XL; N=102) or standard CR. OPTICARE XL included aerobic and strength exercise and behavioral coaching on diet and physical activity during 12 weeks, followed by a 9-month after-care program with “booster” educational sessions. Standard CR consisted of a 6- to 12-week aerobic exercise program, supplemented with cardiovascular lifestyle education. Main Outcome Measures: An economic evaluation, with an 18-month time horizon, in terms of quality-adjusted life years (QALYs) and costs from the societal perspective was performed. Costs were reported in 2020 Euros, discounted at a 4% annual rate, and health effects were discounted at a 1.5% annual rate. Results: OPTICARE XL CR and standard CR resulted in comparable health gain per patient (0.958 vs 0.965 QALYs, respectively; P=.96). Overall, OPTICARE XL CR saved costs (-€4542) compared with the standard CR group. The direct costs for OPTICARE XL CR were higher than for standard CR (€10,712 vs €9951), whereas indirect costs were lower (€51,789 vs €57,092), but these differences were not significant. Conclusions: This economic evaluation showed no differences between OPTICARE XL CR and standard CR in health effects and costs in cardiac patients with obesity.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined.METHODS: This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling.DISCUSSION: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adheren

Objective: Patients with classic infantile Pompe disease are born with a hypertrophic cardiomyopathy, which resolves after treatment with Enzyme replacement therapy (ERT). We aimed to assess potential deterioration of cardiac function over time using myocardial deformation analysis. Methods: Twenty-seven patients treated with ERT were included. Cardiac function was assessed at regular time intervals (before and after start with ERT) using conventional echocardiography and myocardial deformation analysis. Separate linear mixed effect models were used to asses temporal changes within the first year and the long-term follow-up period. Echocardiograms of 103 healthy children served as controls. Results: A total of 192 echocardiograms were analyzed. Median follow-up was 9.9 years (IQR: 7.5–16.3). Mean LVMI before start of ERT was increased 292.3 g/m2 (95% CI: 202.8–381.8, mean Z-score + 7.6) and normalized after 1 year of ERT 87.3 g/m2 (CI: 67.5–107.1, mean Z-score + 0.8, p < 0.001). Mean shortening fraction was within normal limits before start of ERT, up to 22 years of follow-up. Cardiac function measured by RV/LV longitudinal, and circumferential strain was diminished before start of ERT, but normalized (<−16%) within 1 year after start of ERT, and all remained within normal limits during follow-up. Only LV circumferential strain gradually worsened in Pompe patients (+0.24%/year) during follow-up compared to controls. LV longitudinal strain was diminished in Pompe patients, but did not change significantly over time compared to controls. Conclusion: Cardiac function, measured using myocardial deformation analysis, normalizes after start of ERT, and seems to remain stable over a median follow-up period of 9.9 years.

Background Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis. Methods Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. Results Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62–0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47–1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3‑years follow-up was 3.7% yielding a number needed to treat of 27. Conclusion ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker.