OBJECTIVES:To evaluate the impact of a tailored organizational intervention on the support for family caregivers. METHODS:A convergent mixed-methods study was conducted in 17 organizations (6 hospices, 5 home care organizations, 3 nursing homes, 2 hospitals, 1 transmural organization) between November 2021 and August 2023. The intervention comprised a structured practice improvement trajectory during which each organization conducted a structured workshop to define organization-specific goals to improve their support for family caregivers and to develop an action plan to achieve those goals. The action plan was implemented over 1 year with intermittent evaluations. Pre- and post-intervention surveys were distributed among healthcare professionals (paired) and bereaved family caregivers (non-paired) to assess provided and received support. Data were analyzed with mixed models and regression analyses. Post-intervention focus groups with project team members and final evaluation reports were analyzed with qualitative content analysis. RESULTS:Survey respondents were 97 healthcare professionals (83% nursing staff), 123 family caregivers pre-intervention, and 99 family caregivers post-intervention. Only healthcare professionals of home care organizations reported a significant increase in attending to family caregivers' wellbeing and needs (scale 0-20; β = 3.65; 95%CI: 1.33-5.97). Family caregivers' reports of healthcare professionals attending to their wellbeing and needs did not change (scale 0-2; β = 0.17; 95%CI: -0.04-0.38). Across settings, healthcare professionals evaluated the care they provided more positively post-intervention (scale 0-8; β = 0.65, 95%CI: 0.38-0.97). In home care, family caregivers also evaluated care more positively (scale 0-8; β = 2.12; 95%CI: 0.89-3.34). Four focus groups and 17 evaluation reports indicated improvements at 3 levels: the support for family caregivers (increased awareness of healthcare professionals, changes in work processes, more structured support), the healthcare team (more skills, confidence, available tools), and the organization (fostering sustainability). SIGNIFICANCE OF RESULTS:A tailored organizational intervention can strengthen the support of family caregivers in healthcare organizations.

Background Systemic right ventricle (sRV) patients are at an increased risk of developing heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be a valuable treatment option. This study investigated the changes in ventricular function in sRV failure patients in the first year after starting SGLT2i.Methods Adult sRV patients from the international, real-world ACHIEVE-SGLT2i registry were included if they had a clinical diagnosis of sRV failure, a transthoracic echocardiogram before starting SGLT2i, and at least one in the first year after starting available for analysis. The primary outcomes were changes in sRV global longitudinal strain (GLS) and fractional area change (FAC). Longitudinal changes were evaluated using linear mixed models.Results Thirty-nine sRV failure patients (46±9.3 years old, 41% female) were included. Twenty-five (64%) had transposition of the great arteries after an atrial switch procedure and 14 (36%) had congenitally corrected transposition. sRV GLS improved significantly in the first 50 days (−1.4%-point per month, p<0.001) and stabilised afterwards (<0.1%-point per month, p=0.520). Though age had a significant overall negative effect on sRV GLS (0.1%-point per year of age, p=0.049), it did not influence the longitudinal changes after starting SGLT2i. sRV FAC also improved in the first 50 days (3.2%-point per month, p=0.002), after which sRV FAC deteriorated in patients with subpulmonary left ventricular pacing (−0.9%-point per month, p=0.012) while it stabilised in patients without pacing (0.1%-point per month, p=0.573). In the first 50 days, tricuspid annular plane systolic excursion also improved significantly in all patients (1.2 mm per month, p=0.006), and stabilised afterwards (p=0.721).Conclusions SGLT2i therapy is associated with improvements in systolic ventricular function in sRV failure patients. Despite early improvement in sRV FAC, there was a negative longer term correlation with subpulmonary left ventricular pacing, potentially reflecting adverse effects of subpulmonary ventricular pacing on sRV function.

Coronary graft failure (CGF) may occur early after coronary bypass graft surgery (CABG). The study aimed to identify clinical and perioperative risk factors and to evaluate the long-term clinical impact of symptomatic early CGF. Patients who underwent clinically indicated coronary angiography (CAG) prior to post-CABG discharge between 2012 and 2022 were included. Symptomatic early CGF was defined as a dysfunctional coronary graft, evaluated on clinically indicated CAG, caused by stenosis of the proximal or distal anastomosis or bypass conduit, bypass occlusion, thrombosis, reduced flow (TIMI < 1) and kinking/tenting. Patients were divided into symptomatic early CGF and non-early CGF groups. Kaplan-Meier and multivariate analysis estimated cumulative survival free of major adverse cardiovascular events (MACE: death, myocardial infarction and revascularisation) up to 5 years’ follow-up and identified predictors of symptomatic early CGF. A total of 92 patients (79

Background: Patients with nonischemic cardiomyopathies (NICMs) are at a risk for end-stage heart failure and death from ventricular arrhythmias. Implanted defibrillators (ICDs) protect against sudden arrhythmic death, but several studies suggest that ventricular arrhythmias are associated with worse outcomes despite ICDs. Objectives: This study evaluated the relationship of ventricular tachycardia (VT) with total mortality and nonsudden cardiovascular death (NSCVD) in NICM patients with ICDs enrolled in 2 multicentre trials. Methods: Patient-level data were analyzed from 2 prospective trials: DANISH (Danish Trial to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic Heart Failure on Mortality) (ICD for primary prevention of sudden death) and dilated cardiomyopathy-VT (VT ablation). Primary endpoints were all-cause mortality or heart transplantation, and the secondary endpoint was NSCVD. Analyses included the entire group with multivariable analysis, a propensity-matched subgroup with and without VT at entry, VT patients with recent-onset VT in dilated cardiomyopathy-VT, and DANISH patients experiencing VT after primary prevention ICD. Results: Among 828 patients (median age 64 years, 23.3% females, median left-ventricular ejection fraction of 36%), 148 deaths occurred during a median follow-up of 3.9 years, with 78 (53%) due to NSCVD. Despite younger age and better left-ventricular ejection fraction, VT was independently associated with a >4-fold increase in mortality or transplantation (adjusted HR: 4.27 [95% CI: 2.60-7.03]) and a 7-fold increase in NSCVD (adjusted HR: 7.28 [95% CI: 3.80-13.97]). The findings were consistent across all subgroups. Conclusions: Patients with NICM experiencing VT are at an increased risk for mortality and NSCVD, suggesting that VT can be a marker for a more severe cardiomyopathy with important clinical implications.

Routine defibrillation threshold (DFT) testing at the time of implantable cardioverter-defibrillator (ICD) implantation is no longer recommended because testing did not improve shock efficacy or reduce arrhythmic death. However, patients with severe chronic kidney disease (CKD) were not included in these trials and might benefit from DFT testing. International guidelines shed no light on the subject of the effect of kidney function on DFT testing in patients with CKD. In this retrospective study, we aimed to identify the success and safety of DFT in patients with CKD stages 1–5 (ages 55–80 years) undergoing primary transvenous ICD implantation. A total of 451 patients were stratified into three groups based on kidney function: group 1 with CKD stage 1–2 (n = 294), group 2 with CKD stage 3–4 (n = 90), and group 3 with CKD stage 5 (n = 67). Ventricular fibrillation was induced 827 times. The median number of threshold testing per patient was two (interquartile range 1–2; range 1–7). No evidence of between CKD-group differences in ICD defibrillation success rates could be found when using all patient attempts, regardless of correction for energy levels (p = 0.262). DFT-related complications occurred in 16 patients (3.5

INTRODUCTION:Chest pain accounts for ∼10% of emergency department visits, though most cases are not acute coronary syndrome (ACS), underscoring the need for effective prehospital triage. The HARTc 2.0 study evaluates the modified History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) score incorporating point-of-care (POC) high-sensitivity cardiac troponin-I (hs-cTnI) capillary fingerprick testing with sex-specific cut-offs to improve ACS risk stratification. The randomized controlled trial compares a prehospital triage strategy using this modified HEART score and a 0/2-hour POC hs-cTnI algorithm to standard care using HEAR score and in-hospital 0/1-hour hs-cTnT testing. Cost-effectiveness and diagnostic timing are also assessed. METHODS AND ANALYSIS:The HARTc 2.0 study consists of 4 prospective phases to improve prehospital risk stratification for patients with suspected ACS. Phase 0 investigates technical operability of the Siemens Atellica VTLi POC hs-cTnI device. Phase 1 verifies preanalytical and analytical performance. Phase 2 evaluates clinical comparability between modified HEART score (with POC hs-cTnI) and standard HEART score. Phase 3 is a multicenter randomized controlled trial assessing the impact of prehospital risk stratification-into low, intermediate, or high-risk for ACS-on clinical decision-making, time-to-diagnosis, and cost-effectiveness. CONCLUSION:This trial evaluates modified HEART score with POC hs-cTnI testing, incorporating sex-specific cut-offs, to improve prehospital ACS risk stratification. Phases 0 and 1 confirm the reliability of capillary whole blood POC hs-cTnI. Furthermore, the trial is a randomized trial which evaluates prehospital risk stratification for ACS using a 0/2-hour POC hs-cTnI algorithm on clinical decision-making, time-to-diagnosis, as well as its cost-effectiveness. Improved prehospital risk stratification for ACS aims to enhance triage accuracy, time-to-diagnosis and time-to-treatment, thereby reducing unnecessary hospital admissions and improve resource allocation in prehospital and emergency care. TRIAL REGISTRATION:NL80873.000.22, NL9475 (registered in the Dutch Trial Register, the Netherlands).

Background:Family caregivers of people with dementia in nursing homes may need support from healthcare providers, especially when death is approaching. Objective:To increase our understanding of family caregivers' experiences in their relative's last week of life before and during the pandemic, their needs for emotional, practical, and spiritual support, and the extent to which those needs are accommodated by healthcare providers. Design:Survey among bereaved family caregivers of people with dementia recruited from six nursing homes in the Netherlands in 2018-2019 and 2020-2022. Results:The questionnaire was completed by 165 family caregivers (response rate: 55%). Most respondents (79%) rated the overall care they received as "excellent," "very good," or "good." More respondents reported a need for emotional (74%) and practical (64%) support than for spiritual support (37%). Emotional and practical support were more commonly "always" or "most of the time" provided (63% and 51%, respectively) than spiritual support (22%). Differences existed in the presence of practical, emotional, and spiritual support needs (p < 0.001) and the frequency in which those support types were provided when there was a need (p < 0.001). The overall care that was received was more likely to be rated as "excellent" or "very good" when a higher frequency of emotional (p < 0.001), spiritual (p < 0.002), or practical (p < 0.001) support was reported. Before and during the pandemic, family caregivers' responses were mostly similar. Conclusion:Family caregivers had support needs that were not always met, which was especially the case for spiritual support needs. Healthcare providers should be trained to accommodate support needs and refer to appropriate support services when necessary.

BACKGROUND:Cancer and cancer treatment may accelerate the development of cardiovascular disease. With the improved prognosis of cancer survivors, cardiovascular events are increasing in this patient group. However, it is unknown whether the prevalence of coronary atherosclerosis is increased in patients with a history of cancer. This study aims to evaluate the prevalence and severity of coronary atherosclerosis in different age groups of cancer survivors compared to matched controls. METHODS:Consecutive cancer survivors aged > 30 years who underwent evaluation for stable coronary artery disease with coronary computed tomography angiography (CCTA) were included in this retrospective study. Propensity score matching was performed and cancer survivors were matched 1:2 to a control population without oncological history. The presence of coronary atherosclerosis was assessed in both groups. RESULTS:The study population consisted of 312 cancer survivors and 624 matched controls. Median age at CCTA scan was 59.2 [50.3-67.5] years and 66.0% was female. Coronary atherosclerosis was observed in 257 (82.4%) cancer survivors compared to 459 (73.6%) control patients with an Odds Ratio (OR) of 1.68 [95% CI: 1.19-2.36], P = .003. Mainly younger cancer survivors aged between 30 and 59 years had an increased prevalence of coronary atherosclerosis with an OR of 2.21 [95% CI: 1.40-3.49] compared to control patients (P = .001). In addition, thoracic radiotherapy showed a significant association with increased prevalence of atherosclerosis in the younger population with an OR of 3.29 ([95% CI: 1.70-6.38], P < .001). CONCLUSIONS:Patients with a history cancer have an increased prevalence of coronary atherosclerosis on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30 to 59 years.

The prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) patients is a debatable topic. Several studies have indicated that BAV patients have a lower prevalence of CAD compared with patients with a tricuspid aortic valve (TAV), but the effects of age and gender have not always been considered. This systematic review provides an overview of articles which report on CAD in BAV and TAV patients. Searches were executed in April 2021 and January 2022 according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines in three online databases: Medline, Embase, and Scopus. Screening and data extraction was done by two investigators separately. Primary and secondary outcomes were compared between BAV and TAV patients; a fixed effects model was used for correcting on confounders. Literature search yielded 1,529 articles with 44 being eligible for inclusion. BAV patients were younger (56.4 ± 8.3 years) than TAV patients (64 ± 10.3 years, p < 0.001). All CAD risk factors and CAD were more prevalent in TAV patients. No significant difference remained after correcting for age and gender as confounders. BAV patients have a lower prevalence of CAD and CAD risk factors compared with TAV patients. However, when the age differences between both groups are considered in the analyses, a similar prevalence of both CAD and CAD risk factors is found.

BACKGROUND:Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking. OBJECTIVES:This study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population. METHODS:All patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected. RESULTS:In total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9-13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001). CONCLUSIONS:SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.

Objectives To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis.Design Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio.Setting Primary care, recruitment from February 2020 to August 2022.Participants 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)).Interventions Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution).Main outcome measures Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability.Results Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability.Conclusions Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis.Trial registration number WHO ICTRP NL8193.

AIMS:To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA). METHODS AND RESULTS:Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P-values = 0.005, 0.016, and 0.004, respectively). CONCLUSION:The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis.

We previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature. Consecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018–2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined. A total of 201 patients were included (85.57

INTRODUCTION:Pulmonary infarction is a common sequela of pulmonary embolism (PE) but lacks a diagnostic reference standard. CTPA in the setting of acute PE does not reliably differentiate infarction from other consolidations, such as reversible alveolar hemorrhage or atelectasis. We aimed to assess the diagnostic accuracy for recognizing pulmonary infarction on CT in the acute phase of PE, with follow-up CT as reference. MATERIALS AND METHODS:Initial and follow-up CT scans of 33 patients with acute PE were retrospectively assessed. Two radiologists independently evaluated the presence and size of suspected pulmonary infarction on the initial CT. Confirmation of infarction was established by detection of residual densities on follow-up CT. Sensitivity, specificity and interobserver variability were calculated. RESULTS:In total, 60 presumed infarctions were found in 32 patients, of which 34 infarctions in 21 patients could be confirmed at follow-up. On patient-level, observers' sensitivity/specificity were 91 %/9 %, and 73 %/46 %, respectively, with interobserver agreement by Kappa's coefficient of 0.17. Confirmed infarctions were usually larger than false positive lesions (median approximate volume of 6.6 mL [IQR 0.84-21.3] vs. 1.3 mL [IQR 0.57-6.5], p = 0.040), but still small. An occluding thrombus in a supplying vessel was predictive for confirmed infarction (OR 11, 95%CI 2.1-55), but was not discriminative. CONCLUSIONS:Pulmonary infarction is a common finding in acute PE, and generally small. Radiological identification of infarction was challenging, with considerable interobserver variability. Complete obstruction of the supplying (sub)segmental pulmonary artery was found as the strongest predictor for pulmonary infarction but was not demonstrated to be discriminative.

Abstract Background Right ventricular (RV) adverse remodelling is a complex process, consisting of progressive RV dilatation and RV systolic dysfunction. Both parameters individually are important prognostic markers in patients receiving cardiac resynchronization therapy (CRT). The prognostic value of assessing both parameters into one model has not been evaluated. Purpose The current study evaluated RV size and RV systolic function prior to CRT implantation and their association with outcome. Methods Patients who underwent CRT implantation and had echocardiographic data on RV size (assessed by indexed RV end-diastolic area [RVEDAi], using sex-specific cut-off values to define RV dilatation: RVEDAi >12.6 cm2/m2 for men and RVEDAi >11.5 cm2/m2 for women) and RV systolic function (measured by tricuspid annular plane systolic excursion [TAPSE], with TAPSE <17 mm considered RV dysfunction) before implantation, were included in the present analysis. The primary end-point was all-cause mortality. The incremental prognostic value of RV size and RV systolic function was assessed by likelihood-ratio testing evaluating the change in global chi-square values. Results A total of 773 patients (mean age 66±10 years, 75% males) were included in the current analysis, of which 509 patients (66%) had RV dilatation and/or dysfunction, with respectively 253 patients (33%) and 408 patients (53%) showing RV dilatation or RV systolic dysfunction. The cumulative survival rates for the overall population were 97%, 91% and 72% at 1-, 2- and 5-years, respectively. Five-year survival was significantly better in patients with normal RV size compared to patients with RV dilatation (log-rank p<0.001). Similarly, patients with normal RV systolic function had significantly better five-year survival, compared to patients with reduced RV systolic function (log-rank p<0.001). Multivariable Cox regression analysis for all-cause mortality showed that RV size and RV systolic function, assessed as continuous as well as categorical variables, were independently associated with all-cause mortality both individually and in combination (Figure 1). Larger RV size was associated with worse all-cause mortality, whereas better RV systolic function was associated with better all-cause mortality at 5-years follow-up. In addition, the evaluation of RV size plus RV function provided incremental prognostic value over the evaluation of RV size or RV function alone (likelihood-ratio test p<0.005 for all models; Figure 2). Conclusions Patients receiving CRT often present with RV dilatation and/or dysfunction, which are associated with significantly worse survival, compared to patients with normal RV size and function. Prognostic assessment in CRT recipients should include both RV size and function, since the combination of both parameters provides incremental prognostic value to assess all-cause mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Society of Cardiology (ESC)

Background:Osteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF). Objectives:This study sought to evaluate the association between age at sarcoma diagnosis and incident HF. Methods:A retrospective cohort study was performed at the largest sarcoma center in the Netherlands among patients with an osteosarcoma or Ewing sarcoma. All patients were diagnosed and treated over a 36-year period (1982-2018) and followed until August 2021. Incident HF was adjudicated through the universal definition of heart failure. Determinants including age at diagnosis, doxorubicin dose, and cardiovascular risk factors were entered as fixed or time-dependent covariates into a cause-specific Cox model to assess their impact on incident HF. Results:The study population consisted of 528 patients with a median age at diagnosis of 19 years (Q1-Q3: 15-30 years). Over a median follow-up time of 13.2 years (Q1-Q3: 12.5-14.9 years), 18 patients developed HF with an estimated cumulative incidence of 5.9% (95% CI: 2.8%-9.1%). In a multivariable model, age at diagnosis (HR: 1.23; 95% CI: 1.06-1.43) per 5-year increase, doxorubicin dose per 10-mg/m2 increase (HR: 1.13; 95% CI: 1.03-1.24), and female sex (HR: 3.17; 95% CI: 1.11-9.10) were associated with HF. Conclusions:In a large cohort of sarcoma patients, we found that patients diagnosed at an older age are more prone to develop HF.

Tisagenlecleucel (formerly, CTL019), an anti-CD19 chimeric antigen receptor T-cell therapy, is studied intensively in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. 1,2Laetsch et al 3 published important results on the 3-year update of tisagenlecleucel within the ELIANA trial.This has been published as clinical trial updates that provide an opportunity to spread and share the new results as soon as possible from these studies.This phase 2 trial was focused on pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.This correspondence focuses on the survival analysis that was published by Laetsch et al, 3 in which the authors found that in 79 patients who received tisagenlecleucel from 2015 to 2019, the responses were durable and with a manageable safety profile.In the previously reported primary analysis conducted in 75 patients, with a median follow-up of 13.1 months, the overall remission rate was 81%, with 59% of responders remaining relapse-free at 12 months. 1Although the clinical relevance of the study by Laetsch is clear, some methodological issues can be raised concerning the use of statistical methodology and the choices made in the analysis with potential impact on final conclusions.Some concerns can be raised about some applications of survival analysis methodology in certain parts of the article, specifically the Kaplan-Meier (K-M) analyses. 4he analysis of relapse-free survival is questionable.