Real-world Cohort Of Patients Research Articles

Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities. Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups. Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged <12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients). 42.1% of patients with comorbid vitiligo had severe AA disease (SALT>50) and 27.8% patients without comorbid vitiligo had SALT>50. 28.6% of those with comorbid AD had SALT>50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT>50, all p>0.2. 42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p>.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p>0.5. Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.

Abstract 4124875: Association between Elevated Lipoprotein(a) and Cardiovascular Events and Mortality in a Nationally Representative Sample of US Medicare, Medicaid, and Commercial Enrollees with ASCVD

Background: Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk driver for atherosclerotic cardiovascular disease (ASCVD). Few patients with ASCVD receive Lp(a) screening and real-world data assessing the association between elevated Lp(a) and risk of cardiovascular (CV) events and mortality is limited. Objectives: To examine the association of elevated Lp(a) and risk of CV events and death in an ASCVD population using large US health claims databases. Methods: Patients with ASCVD were pooled from US Medicare, commercial, and Medicaid health plans from 2017 to 2022. Lp(a) levels were linked at the patient level from HealthVerity Lab Data and categorized as: <30 mg/dL (<75 nmol/L), ≥30-<50 mg/dL ( > 75-<125 nmol/L), ≥50-<70 mg/dL ( > 125-<175 nmol/L), ≥70-<90 mg/dL (≥175-<225 nmol/L) and ≥90 mg/dL (≥225 nmol/L). Patients were followed from the 1 st ASCVD diagnosis (index) to insurance plan disenrollment, death, or end of study. Cox regression, adjusted for age, sex, race, insurance, comorbidities, LDL-C, and other risk factors, measured the association between Lp(a) levels and risk of CV events and death. Results: Of 28.8 million ASCVD patients, 180,240 (0.6%) had Lp(a) levels: mean(±SD) age 68.6±1 years, 50.1% male, 5.9% Black, 2.8% Hispanic, 2.1% Asian, 72.8% Medicare, 21.8% commercial, and 5.4% Medicaid. Mean follow-up was 3.7 years; 23.3% and 15.7% had Lp(a) ≥50mg/dL [≥125 nmol/L] and ≥70 mg/dL (≥175 nmol/L), respectively. Black patients had highest median Lp(a) (50 mg/dL/111 nmol/L), followed by Asian (13.5 mg/dL/35.5 nmol/L), White (13 mg/dL/32 nmol/L), and Hispanic (11.5 mg/dL/29 nmol/L) patients. Lp(a) levels of ≥30-<50 mg/dL, ≥50-<70 mg/dL, ≥70-<90 mg/dL, and ≥90 mg/dL were associated with 7%, 10%, 16%, and 26% greater risks of CV events vs. <30 mg/dL (p-values <0.0001; cumulative incidence reported in Figure 1). All-cause mortality risk was also greater for those with Lp(a) ≥90 mg/dL vs. <30 mg/dL: hazard ratio (HR)=1.11, p=0.003. Similar trends persisted for patients with LDL-C ≤70 mg/dL. Conclusion: In this national-scale real-world cohort of patients with ASCVD, Lp(a) testing is infrequent and elevated Lp(a) levels were significantly associated with a greater risk of CV events and mortality.

CTIM-12. A RETROLECTIVE ANALYSIS ON THE SAFETY, EFFICACY AND IMMUNOGENICITY OF 203 GLIOBLASTOMA PATIENTS TREATED WITH PERSONALIZED THERAPEUTIC CANCER VACCINES (PTCV)

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor. Despite of the current SoC, patients have a poor prognosis with a median OS of about 14-17 months.Method, RESULTS We report retrospectively analyzed data from 203 GBM patients (IDH wildtype) who added PTCV derived from patient individual tumor mutations to their treatment regimen in the setting of individual treatment attempts (ITA) in Germany. Data were analyzed re. vaccine induced T cell responses and safety acc. to CTCAE terminology version 5.0. Subsets of patients with and without hypermethylation of the MGMT promoter were further evaluated re. efficacy. Treated patients had a median age of 53 years at diagnosis, started vaccination after a median of 11 months after diagnosis, received a median of 8 immunizations with a median of 20 neoepitope peptides, and had a median follow-up time since first vaccination of 21 months. They usually received SoC (Stupp scheme), often accompanied by additional therapies. In general, the PTCV was well tolerated, and most patients experienced only Grade 1 and 2 AEs. Most frequently injection site reactions were observed (67%). Seven patients developed Grade 3 allergic or anaphylactic reactions after 7 or more vaccinations. For 119 patients T-cell responses against the vaccinated neoepitopes were investigated. Almost all patients developed vaccine induced T-cell responses (97%). 71% of patients showed both CD4+ and CD8+ T-cell responses towards vaccinated peptides. Immune responses usually increased over time peaking within 3-6 months. Median OS of the whole cohort was 26 mo (95% CI 24, 31). Primary GBM patients without recurrence events before the start of vaccination and with or without hypermethylated MGMT promoter status showed a mOS of 41 months (95% CI: 32, NA) or 23 months (95% CI: 20, NA), respectively. CONCLUSION The retrospective data analysis from a real-world cohort of GBM patients suggests that PTCV are safe, immunogenic, and may prolong the survival of patients.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed to investigate this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age, 63 years). The overall response rate was 90% in response-evaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, high-risk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2-3 months prior to start of KRd treatment significantly decreased PFS and OS in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e., delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AE) were observed in 56% of the patients, and non-fatal or fatal AE that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large, real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Skin Rash in metastatic Hormone Sensitive Prostate Cancer Patients Treated with Apalutamide: A Retrospective Multicenter Study in Korea

PurposeSkin rash is a common adverse event in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with apalutamide. This study aims to investigate the incidence rate of skin rash and the predictive value of inflammation markers for skin rash in real-world Korean patients. Materials and MethodsWe conducted a retrospective analysis of patients with prostate cancer (PCa) who received apalutamide across 18 institutions in Korea, with a follow-up period of at least three months. A total of 218 patients were evaluated. ResultsAmong the 214 patients analyzed, 78 (36.4%) developed a skin rash. The severity of the rash was classified as grade 1 (G1) in 27 patients (12.6%), grade 2 (G2) in 29 patients (13.5%), and grade 3 (G3) in 22 patients (10.3%). The median time to onset of any skin rash was 65.5 days (interquartile range, IQR 31.0-88.0). There were no significant differences in inflammation markers before apalutamide administration between patients who developed a rash and those who did not. However, the Monocyte-to-Lymphocyte Ratio (MLR) and Systemic Immune-Inflammation Response Index (SIRI) were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.006, p=0.013, respectively) before apalutamide treatment. After 3 months, Platelet-to-Lymphocyte Ratio (PLR) and SIRI were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.010, p=0.025, respectively) ConclusionIn a real-world cohort of Korean patients, skin rash occurred in 36.4% of cases, with a median time to onset of 65.5 days. Grade 3 skin rash developed in 10.3% of cases. While MLR and SIRI were significantly higher in the G2 plus G3 group, these markers cannot be considered reliable predictors due to a low area under the curve (AUC < 0.7) before apalutamide treatment. However, increased levels of PLR, SII, and SIRI could potentially be useful for monitoring for the risk of severe rash development in these patients.

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage.

Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis. Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBCfirst, TPfirst), in Week 1 (RBCDays1-7, TPDays1-7), Week 2 (RBCDays8-14, TPDays8-14), and Week 3 or thereafter (RBCDay>14, TPDay>14), the highest detected value (RBChighest, TPhighest), as well as the RBC count adjusted for disease duration (RBCadjusted) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival. A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50-70) years and median (IQR) Hunt and Hess score of 4 (3-5) were included. Multivariable analyses revealed that lower values of RBCfirst, RBCadjusted, RBChighest, TPfirst and TPhighest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival. Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real-world cohort of SAH patients requiring external ventricular drainage.

Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort.

Drug-induced long QT syndrome (diLQTS) is an adverse reaction from over 150 FDA-approved medications, posing the risk of triggering torsades de pointes and sudden death. While common genetic variants may modestly impact QT interval individually, their collective effect can significantly amplify risk of diLQTS. Consequently, this study aimed to validate a polygenic risk score (PRS) for diLQTS previously proposed by Strauss et al. A retrospective cohort study was conducted utilizing patients from the Michigan Genomics Initiative prescribed 27 high-risk QT-prolonging drugs and an ECG during the prescription. The primary outcome was marked prolongation of the QTc interval (either >60 ms change from baseline or >500 ms absolute value) during treatment with a high-risk QT-prolonging drug. The primary outcome occurred in 12.0% of n = 6070 self-reported White, 12.4% of 558 African American, and 8.2% of 110 Asian patients. The PRS significantly associated with diLQTS in White patients [adjusted odds ratio = 1.44 (95% CI: 1.09-1.89); P = 0.009]. However the study lacked sufficient statistical power to confirm the PRS as a risk factor in African Americans [adjusted odds ratio = 2.18 (95% CI: 0.98-5.49); P = 0.073] and Asians [adjusted odds ratio = 3.21 (95% CI: 0.69-16.87); P = 0.139] due to smaller sample sizes in these groups. The previously published PRS for diLQTS was validated in a large, real-world cohort, demonstrating its potential as a tool for identifying high-risk patients. Incorporating this PRS into routine clinical practice could enable proactive measures to prevent life-threatening diLQTS.

Comparative Influences of Beta blockers and Verapamil on Cardiac Outcomes in Hypertrophic Cardiomyopathy

Guidelines recommend β blockers (BBs) as first-line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM) and nondihydropyridine calcium channel blockers, particularly, verapamil, as the second-line therapy, despite the absence of comparison trials between those 2 drugs. Because deleterious effects of verapamil have been reported in this setting, the present analysis aimed to evaluate the prognostic impact of BBs and verapamil in a cohort of patients with HCM. From a nationwide cohort of 1,434 patients with a diagnosis of HCM included in the French prospective observational REgistry of hypertrophic cardioMYopathy (REMY), we retrospectively analyzed patients with sarcomeric HCM included in the 3 largest centers and treated either with BBs or verapamil. Patients with a cardiac defibrillator or a pacemaker or who underwent a procedure of atrial fibrillation or septal ablation were excluded. The primary end point was the composite of cardiovascular death, hospitalization for heart failure, and hospitalization for atrial fibrillation. Of 600 patients with HCM, 544 (91%) were treated with BBs and 56 (9%) with verapamil. At inclusion, the 2 groups were comparable concerning the presence/amplitude of obstruction and sudden cardiac death risk factors. At up to 8 years of follow-up (median 3.9 years, interquartile range 2.1 to 5.8), no significant differences were observed in the primary end point (132 [24%] vs 10 [18%] under BBs or verapamil, respectively, hazard ratio 1.84, 95% confidence interval 0.94 to 3.63). In conclusion, in a real-world cohort of low-risk patients with HCM, verapamil therapy was not associated with a higher incidence of adverse events than β-blocker therapy.

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) &amp;lt;30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR &amp;lt;30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT &amp;lt;0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Guideline-directed medical therapy titration for heart failure with ischaemic aetiology and its effect on cardiac remodelling and cardiovascular mortality-from a real world perspective

Abstract Background Contemporary Heart Failure (HF) pharmacological treatment has been reshaped by several landmark trials in recent years, and available evidence strongly encourages treatment up-titration to target doses. Recent literature regarding treatment sequencing demonstrated positive effects of up-titration on major outcomes regardless of HF aetiology. Purpose We investigated a contemporary Heart Failure with Reduced Ejection Fraction (HFrEF) patient cohort and ischaemic aetiology and sought to understand the effects both in terms of echocardiographic remodelling and upon mortality for cardiovascular (CV) causes of contemporary ESC guideline-directed medical therapy (GDMT) on a real-world level. Methods We retrospectively analysed data of consecutive patients with HFrEF and ischaemic genesis followed in our tertiary HF clinic between January 2019 and January 2022. Eligible patients were stratified into two groups: patients treated or not with full doses of ESC GDMT [including angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i)]. Results Overall, 203 patients (mean age 70.1±12.3 years, 165 males) were included into the analysis. Over a mean follow-up of 1223±221.2 days, 115 (56.6) patients achieved the full recommended doses of each drug. Patients with an unsuccessful up-titration had higher end-diastolic volume at transthoracic echocardiography (p for difference at first and second follow-up &amp;lt;0.001; figure 1, panel A), lower left ventricular ejection fraction (40.1±4.3% vs 44.3±7.8 and 38.7±4.9% vs 42.3±5.6% at the first and second follow-up, respectively) and higher CV mortality rates compared to those treated with the maximal doses (figure 1, panel B). Conclusions Up-titration of pharmacotherapy in our real-world cohort of patients with HFrEF and ischaemic aetiology demonstrated a positive effect both on pivotal echocardiographic parameters and on CV mortality. Our data suggest that timely identification and referral of patients with coronary artery disease who fail to achieve complete positive remodelling after an acute event (or during chronic disease course) for HF contemporary treatment implementation should be envisaged.Figure 1

Neurologic recurrence after transcatheter PFO closure in patients with cryptogenic stroke

Abstract Background Patent foramen ovale (PFO) is associated with an increased risk of cryptogenic stroke, and interventional closure is recommended for secondary prevention. However, there is limited real-world data on long-term results. Our objective was to evaluate outcomes following successful transcatheter PFO occlusion. Methods Data from patients undergoing PFO closure for cryptogenic stroke between 2010 and 2015 were analysed to determine short- and long-term outcomes and to identify potential predictors of neurological recurrence. Results 330 patients underwent successful PFO closure. The mean age of patients was 49 (standard deviation (SD) ±12) years, and 55.5% were male. Any in-hospital adverse event was observed in eight patients (2.4%). During a median follow-up of 9.85 (SD ±2.5) years, the combined outcome of transient ischemic attack (TIA), stroke, or death from stroke was observed in 3.6% of patients (0.38 events per 100 person-years). After 5, 10, and 12 years the percentage of patients free of the composite outcome was 97.5%, 96.2%, and 96.2% respectively (Figure 1). New onset atrial fibrillation was detected in 10 patients (3.0%). A thorough analysis of the neurologic recurrences revealed a total number of six cryptogenic strokes (1.8%). Our results revealed that the Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.70, 95% confidence interval [CI]: 0.52 to 0.95; p=0.022) and the number of prior neurologic events (adjHR: 9.78, 95% CI: 2.66 to 35.99; p&amp;lt;0.001) were strong independent predictors of future recurrent neurologic events. Kaplan Meier survival analysis stratified by number of previous neurologic events proved to be statistically significant (p&amp;lt;0.001; Figure 2). Conclusion In this real-world cohort of patients with cryptogenic stroke we observed excellent safety and good efficacy of percutaneous PFO closure, similar to randomized controlled trials or other long-term cohort studies. The rate of recurrent neurological events was low, especially cryptogenic strokes. The RoPE score confirmed good predictive power; in particular, the number of previous neurological events should be taken more into account when determining the indication for closure.

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index &amp;lt;4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index &amp;gt;4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

Incidence of atrial fibrillation detected by an insertable cardiac monitor in a large real-world cohort of heart failure patients with reduced and preserved ejection fraction

Abstract Background Subcutaneous implantable cardiac monitors (ICM) have the capability to detect atrial fibrillation (AF) episodes with high degree of accuracy [1]. Objective We investigated the incidence of AF in patients implanted with an ICM and a clinical history of heart failure (HF) with reduced or preserved left ventricular ejection fraction (LVEF). Methods Patients with history of HF admissions who were implanted with an ICM were identified from the aggregated and de-identified electronic health record (EHR) database during 2007-2021. The device collected data were merged with the EHR data to create a de-identified database of real-world patients. Patients were included if they had ≥180 days of device follow-up. ICMs detect AF based on incoherence of RR intervals and absence of single p-wave between two R-waves [1]. All ICM detected AF episodes stored with at least 30 seconds of ECG at onset were adjudicated using an artificial intelligence (AI) model. The AI model was previously trained and validated using over 60K manually adjudicated episodes and was shown to have an accuracy of over 97% [2]. ICM detected AF episodes with AI model based true probability of AF ≥ 0.9 was analyzed. The Kaplan-Meier incidence curves for AF incidence as a function of episode duration, clinical history of AF, and LVEF are reported. Results A total of 1020 LINQ ICM patients with history of HF admission prior to implant were identified from the deidentified real-world dataset. LVEF was available in 889 (87%) patients, of whom 394 (44%) had EF &amp;lt;50%, and 495 (56%) had EF≥50%. NYHA class was available in 296 (29%) patients, of whom 39 (13%) were class I, 126 (43%) were class II, 112 (38%) were class III, and 19 (6%) were class IV. Patients had an average age of 68±13 years with 52% being males and had clinical history of hypertension in 95%, diabetes in 56%, coronary artery disease in 75%, AF in 57%, stroke/TIA in 51%, and renal dysfunction in 53%. A total of 911 patients with ≥180 days of follow-up (average follow-up of 25.8 months) were included. A total of 8407 episodes from 358 patients were classified by the AI model as true AF. The incidence of AF as a function of episode duration, clinical history of AF and reduced vs preserved LVEF are shown in Figures A, B, and C respectively. Incidence of AF, as detected by an ICM over 42 months of follow-up, was estimated to be 38% to 46% depending on AF episode duration. Estimated 42-month AF incidence was 23% in patients with no clinical history of AF. The 42-month AF incidence was 44% vs 47% in HF patients with reduced versus preserved LVEF. Conclusion Incidence of AF, as detected by an ICM over 3 years of follow-up, was estimated to be in close to half of ICM patients with history of HF events. Close to one fourth of the patients with no prior clinical history of AF had newly detected AF. AF incidence was similar in HF patients with preserved versus reduced LVEF in this real-world cohort.

Premature ventricular contraction burden measured by an insertable cardiac monitor and the incidence of ventricular tachycardia and fibrillation

Abstract Background Insertable cardiac monitors (ICM) have the capability to continuously monitor premature ventricular contraction (PVC) burden over time [1] as well as detect ventricular tachycardia and fibrillation (VT/VF). Objective We investigated the association of PVC burden with incidence of VT/VF in a large real-world cohort of patients implanted with ICMs. Methods Patients implanted with an ICM for various reasons for monitoring and PVC detection turned on were included from the ICM manufacturer's de-identified data warehouse. Patients were included if they had at least 90 days of PVC burden follow-up. Tachycardia episodes that were detected by the ICM were first classified as VT/VF, SVT, or oversensing using an artificial intelligence (AI) model that was pre-trained using over 60,000 manually adjudicated ICM detected tachycardia episodes. If the AI model output probability for VT/VF was greater than 0.2, then those episodes were manually adjudicated for incidence of non-induced spontaneous VT/VF. The PVC burden trends recorded by the device were divided into 4 mutually exclusive patient groups: (1) 0% PVC burden on all days, (2) 1-4% PVC burden on ≥1 day, (3) 5-9% PVC burden on ≥1 day, and (4) &amp;gt;10% PVC on ≥1 day. The incidence rate of spontaneous VT/VF was compared between the PVC burden patient groups using a Generalized Estimating Equations model with negative binomial distribution. Time to first spontaneous VT/VF occurrence after the first day of occurrence of PVC burden for the respective PVC burden groups were estimated using Kaplan-Meier analysis and the groups were compared using the Cox proportional hazards model. Results A total of 5,521 patients were included in the analysis. Patients had an average age of 69±15 years and 49.8% being males. There was a total of 33,393 tachycardia episodes from 2,641 patients that were detected by the ICM. After AI model probability-based adjudications, 691 spontaneous VT/VF episodes were identified from 277 patients. Patients with ≥1 day of PVC burden of 1-4%, 5-9%, and ≥10% were associated with 2.9, 7.3, and 7.8 times increased incidence rate of VT/VF episodes during follow-up period relative to patients with 0% PVC burden on all days of follow-up (Figure A). Kaplan Meier curves for incidence of first spontaneous VT/VF episode for the four groups following occurrence of the first day of qualifying PVC burden for the respective groups are shown in figure B. Patients with a day of PVC burden ≥10% were 3.5 times more likely to develop VT/VF in the future compared to patients with 0% PVC burden on all days. Conclusion Days with high PVC burden, as detected by an ICM with continuous PVC detection capability, were associated with increased risk of VT/VF events in a group of real-world patients implanted with ICMs. PVC burden measured by ICMs may be a risk stratification tool for further investigation to prevent sudden cardiac arrest.

Coronary sinus reducer device for the treatment of refractory angina: a single center experience

Abstract Introduction The coronary sinus Reducer emerged as a complementary therapy in patients with angina refractory to optimal medical therapy and not amenable to revascularization. Aim The aim of this study was to assess the safety and efficacy of the Reducer in a real-world cohort of patients presenting with refractory angina. Methods and population Twenty-six patients with refractory angina, objective evidence of myocardial ischemia attributable to the left coronary artery and deemed unsuitable for revascularization were treated with Reducer at a single center between April 2018 and January 2023. Safety endpoints were procedural success and complications. Efficacy endpoints, assessed at 6-month, were a reduction in Canadian Cardiovascular Society angina (CCS) class and a reduction in pharmacological antianginal therapy. Results Twenty-one (81%) patients had end-stage coronary artery disease without targets for further revascularization (13 had previous CABG ± PCI and 8 had only PCI) and 5 patients had microvascular disease without epicardial stenosis. All procedures were performed via right jugular vein. The mean procedure and fluoroscopy duration were 66±29 and 19±8 minutes. Procedural success was achieved in all patients, with no device related complications. There was one cardiac tamponade, promptly treated with pericardiocentesis. Regarding the efficacy endpoint, 21 patients (81%) had at least 1 grade reduction in CCS class, 13 patients (50%) had at least 2 class reductions, and 7 patients (28 %) became asymptomatic, with a mean reduction of CCS class of 1.4±0.9, from 2.6±0.5 to 1.2±0.9 (p=0.001) at 6-month follow-up. During this time frame, twelve patients (46%) withdrew or reduced the dose of at least one anti-anginal drug. The mean reduction of anti-anginal drugs was 0.54 ±0.86, from 3.5±1.02 to 2.9±1.07 (p=0.04). Conclusion In this real-world, single-center experience, implantation of Reducer was safe and associated with improvement of angina and reduction of anti-anginal drugs intake in patients with refractory angina unsuitable for revascularization.

Assessment of right ventricular function in patients with severe secondary tricuspid regurgitation, following to the TVARC recommendations: association with outcome

Abstract Introduction Severe tricuspid regurgitation (TR) is associated with increased mortality if left untreated. Recently, the Tricuspid Valve Academic Research Consortium (TVARC) has published standardized definitions of disease aetiology and severity, as well as endpoints for future clinical trials. Right ventricular (RV) function assessment represents one of the cornerstones for risk stratification in these patients, but current guidelines do not propose specific cut-off values for the echocardiographic measures. Also, the thresholds proposed by the TVARC have been derived from normative value and not yet validated in large cohorts of TR patients. Purpose To test the prognostic value of the TVARC proposed echocardiographic cut-offs for grading RV-dysfunction (figure1) in a large real-world cohort of patients with severe secondary TR (STR). Methods Consecutive patients from a single centre with first diagnosis of severe secondary STR, and without a cardiac implantable electronic device, were included. Tricuspid annulus plane systolic excursion (TAPSE), RV global and free wall strain (RVGLS and RVFWLS) and fractional area change (FAC) were used to measure RV function. The study endpoint was all-cause mortality, censored for tricuspid valve intervention. Results A total of 1043 patients (mean age 69 ± 13 years, 43% male), were included. Approximately half of the population (45%) was in NYHA class III or IV and 52% was treated with loop diuretics. Overall patients showed mild RV-dilatation (RV end-diastolic area indexed 12.2 [10.1-15.2cm2/m2]) and moderate-to-severe right atrial dilatation (right atrial maximal area indexed: 13.9 [11.0-17.5cm2/m2]). Using the proposed cut-off values, strain analysis identified a higher number of patients with impaired RV function as compared to standard echocardiographic parameters (89% based on RVGLS; 80% based on RVFWS, 61% based on TAPSE and 54% based on RVFAC). During a median follow-up of 51 [IQR 6 - 98] months, 445 (43%) patients died. The Kaplan-Meier survival curves for each echocardiographic parameter of RV-function are shown in Figure 1. TAPSE, which is the most widely used RV-function parameter, was able to clearly identify patients at high and intermediate risk when mildly, moderately and severely impaired. However, patients with normal TAPSE were still at intermediate risk when RVFWLS was (even mildly) reduced (figure 2). We therefore propose a stepwise practical approach including the measure of RVFWLS when measuring normal TAPSE, in order to possibly re-stratify patients into a higher risk group (Figure 2). This novel grading approach remained independently associated with all-cause mortality after correcting for relevant clinical and echocardiographic variables on multivariable analysis. Conclusion Novel TAVRC cut-off values for RV function show prognostic value in patients with severe STR; particularly the combination of TAPSE and RVFWLS could be use in clinical practice for risk stratification.Figure 1Figure 2

Elevated mitral valve pressure gradient following transcatheter edge-to-edge repair is independently associated with inferior outcomes in atrial, but not in ventricular secondary mitral regurgitation

Abstract Background In transcatheter mitral valve edge-to-edge repair (M-TEER), the goal of optimizing post-procedural residual mitral regurgitation inadvertently carries the risk of generating relevant mitral stenosis, resulting in an elevated mean mitral valve pressure gradient (MPG). In patients with primary mitral regurgitation, an elevated post-procedural MPG has been found to independently predict impaired outcomes. However, the effect of elevated post-procedural MPG on outcome after M-TEER in patients with secondary mitral regurgitation (SMR) has yet to be fully elucidated. This study investigated the impact of elevated MPG on outcome in the EuroSMR registry, a large, multi-center real-world cohort of patients with SMR. Methods This retrospective study included patients who underwent M-TEER for SMR between 2009 and 2021 in 12 centers. Patients were stratified into two groups based on SMR etiology: (1) ventricular SMR (vSMR), and (2) atrial SMR (aSMR). The etiology was considered as vSMR in patients with a left ventricular ejection fraction (LV-EF) &amp;lt;50% and aSMR in subjects with preserved left ventricular function (LV-EF ≥50%) and a markedly dilated left atrium (Left Atrial Volume Index [LAVi] ≥40ml/m2). According to the proposed M-VARC threshold, post-procedural MPG was assessed by discharge transthoracic echocardiography and was considered elevated if &amp;gt;5 mmHg. The primary endpoint was all-cause mortality after 5 years, with statistical analysis conducted using Kaplan-Meier and uni- and multivariable Cox Regression analysis. Results Among the 1703 patients in the study (vSMR: n=1420; aSMR: n=283), elevated post-procedural MPG was observed in 9.4% (n=133) of vSMR and 19.1% (n=54) of aSMR patients. Atrial fibrillation was significantly more prevalent in aSMR (78.4% vs. 57.1%, p&amp;lt;0.001). Patients with vSMR had a higher median surgical risk assessed by the EuroScore II (aSMR vs. vSMR: 7.0% [IQR 4.0, 13.1] vs. 4.9% [IQR 2.9, 8.5], p&amp;lt;0.001). Kaplan-Meier analyses for all-cause mortality after 5 years demonstrated significant differences in aSMR patients (low vs. elevated MPG: 48.9% vs. 69.8%, log-rank p&amp;lt;0.01), while there was no difference in vSMR patients (55.7% vs. 60.8%, log-rank p=0.66) (Figure 1). This observed effect remained significant even after accounting for common confounding factors: elevated MPG was an independent predictor for all-cause mortality in aSMR patients (HR=1.86; 95%-CI: 1.14-3.02, p=0.013) but not in vSMR patients (HR=1.00; 95%-CI: 0.74-1.35, p=0.99). Conclusion Our findings suggest that elevated post-procedural MPG is an independent predictor of adverse outcomes in patients with aSMR, but not in those with vSMR. This effect may partially be explained by a reduced left atrial function and higher rates of atrial fibrillation.Figure 1.Study flowchart

Safety of beta-blocker discontinuation after acute coronary syndromes with preserved or mildly reduced left ventricular ejection fraction: a target trial emulation from a real-world cohort.

The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%. In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization. Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68). Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated according to baseline levels and early dynamic changes of ALAT, ASAT, GGT and LDH. Multivariate Cox proportional hazard regression models were generated to identify independent prognosticators for PFS and OS. High baseline levels and non-normalized kinetics of ALAT, ASAT, GGT and LDH were significantly associated with shorter PFS and OS (p < 0.05), which was also reflected by lower response rates. Combining the four parameters at baseline into a 4-Risk-Score resulted in an enhanced prognostic power, as indicated by a higher C-index of 0.693 for OS compared to the individual parameters (≤ 0.663). Patients with all four risk factors present showed the worst PFS and OS. Overall, baseline levels and early kinetics of the four parameters as well as the 4-Risk-Score were identified as independent prognosticators for PFS and OS by multivariate analysis. As standard laboratory parameters, ALAT, ASAT, GGT and LDH are cost-effective and could be easily used either alone or in combination for therapy monitoring of CPI-treated mRCC patients.