Real-world Cohort Of Patients Research Articles

Patterns of Disease, Risk Factors and Treatment in Chronic Lymphocytic Leukemia (CLL). a retrospective Report of Real World Patient Cohort from United Arab Emirates

Introduction: Chronic Lymphocytic Leukemia (CLL) is an indolent B cell Malignancy. It is the most common type of leukemia in Western Hemisphere (35% of all leukemia (American Cancer Society. Cancer Facts & Figures 2023) but is rare in East Asia. Data about CLL in Middle Eastern countries is scarce. Here we report a retrospective analysis of the patients with CLL seen in a real world setting at the largest cancer center in UAE. Methods: This is a retrospective analysis of patients diagnosed with CLL between January 2018 to September 2022. Data was collected from Electronic Medical Records (EMR) regarding patient demographics, risk profile (genetics) and treatment patterns. Results: Thirty-seven patients with CLL were seen in the study period. They accounted for approximately 3 % of all leukemia patients (Al-Shamsi HO. The State of Cancer Care in the United Arab Emirates in 2022. Clin Pract. 2022 Nov 23;12(6):955-985). The median age was 59 years (range 30 to 88 years.) Sixteen percent of the patients were under the age of 50 years. The majority of the patients were male (5:1). The median WBC at presentation was 30000/μl, Hemoglobin was 112 grams/liter and platelet count was 140000/μl. Approximately one third of the patients (35%, 13 out of 37) have not required any therapy due to early-stage disease and/or comorbidities. Twenty-four patients (65 %) had advanced stage disease and required therapy at the time of diagnosis. FISH results are available for 19/24 patients on therapy. The most common was deletion 13q (8/24) followed by Trisomy 12 (7/24). 17p/TP 53 deletion was seen in3/24 and 1/24 had ATM gene deletion. IGHV mutational analysis is not available for most patients Treatment patterns showed chemoimmunotherapy (CIT) in 10/24 patients (Bendamustine rituximab N=8 and FCR N= 2), BTK inhibitors as single agent 9/24 while 5/24 patients receive Venetoclax R in combination with Anti CD 20 antibody. Conclusion: This is the first report on CLL seen in a large tertiary care center in UAE over a period of 5 years. The number of patients is significantly less (3%) as compared to incidence in western hemisphere (35%) of all leukemia cases. Median age (59 years) is at least a decade earlier than western hemisphere with a preponderance in males. Treatment patterns are being rapidly revised with the availability of BTK inhibitors, Venetoclax R and anti-CD 20 monoclonal antibodies to conform with current guidelines. More epidemiologic investigation is needed to understand the low numbers of patients with CLL reported in this UAE cancer center.

Estimates of Survival and Life Expectancy with Tafasitamab Plus Lenalidomide in the L-Mind Study Compared with Real-World Standard-of-Care for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background The presence of stable plateaus in Kaplan-Meier (KM) survival analyses of clinical trials with ≥5 years of median follow-up raises the issue of the curative potential of immunotherapies for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Mixture cure models (MCM), unlike standard survival analyses, stratify study populations into long-term survivors (LTS) and non-LTS based on statistical modeling approaches. LTS are assumed to not experience a disease-related event (termed “cured” in only a statistical sense) and are assumed to have an all-cause mortality of the age- and gender-matched general populace. Non-LTS experience events based on the outcomes of the underlying study. Based on these analyses, life expectancies for the combined (LTS and non-LTS) study population are estimable (Felizzi F et al. 2021). The final 5-year results of the Phase II L-MIND study (NCT02399085; Duell J et al. 2023) of tafasitamab + lenalidomide (LEN) in patients with R/R DLBCL identified an LTS population, making the study data suitable for MCM analysis. For contextualization, patients from the retrospective, observational RE-MIND2 study (NCT04697160; Nowakowski G et al. 2022; Nowakowski G et al. 2023) who were treated with a wide variety of systemic therapies including polatuzumab vedotin / bendamustine / rituximab (pola-BR) were matched to the L-MIND population. We used various MCM analyses to estimate the proportion of LTS and overall life expectancy in patients from L-MIND compared with matched RE-MIND2 cohorts. Methods Patients from the full analysis set (FAS) from L-MIND (n=80) were 1:1 matched without replacement with a RE-MIND2 comparator cohort, based on 9 covariates originally defined in the RE-MIND2 study, generating 76 matched pairs (M_popn). Two subsets of patients from L-MIND were also defined: those with only one prior line of therapy (pLoT; 1:1 matched to a corresponding RE-MIND2 cohort) generating 39 matched pairs; and those experiencing a response to therapy (non-matched subsets from the 1:1 matched populations). KM curves for the comparisons are displayed, and a semi-parametric MCM was used to estimate the proportion of LTS and combined life expectancy (accounting for LTS and non-LTS) within each population (Cai C et al. 2021; Gressani O et al. 2022). The life expectancy of the general population was estimated using data from the US National Vital Statistics System. Additional MCMs were generated for sensitivity analyses. Results KM curves show improved survival outcomes in the L-MIND M_popn treated with tafasitamab + LEN with up to 5 years of follow-up compared with RE-MIND2 M_popn receiving standard-of-care systemic therapies in an observational setting( Figure 1). The LTS proportion of the L-MIND M_popn was estimated as 40%, and the combined life expectancy was 7.27 years (95% confidence interval [CI]: 5.56-8.93 years). By comparison, the RE-MIND2 M_popn had a LTS proportion and a combined life expectancy of 13% and 2.93 years (CI: 1.68-4.86 years), respectively. The probability of survival among patients with response to therapy in L-MIND or in the observational RE-MIND2 setting is shown in Figure 2. In patients with an objective response in L-MIND M_popn, the LTS proportion was estimated as 59%, with a combined life expectancy of 9.97 years (CI: 7.69-11.79 years). For the subset of patients with response in RE-MIND2 M_popn, the LTS proportion and combined life expectancy were 18% and 3.73 years (CI: 1.99-6.51 years), respectively. Half of the patients in L-MIND received tafasitamab + LEN as second-line therapy; the LTS proportion in this subset was 51%, with a combined life expectancy of 8.24 years (CI: 5.96-10.21 years). Additional subgroup and sensitivity analyses will be presented later. Conclusions The MCM analysis of 5-year data from the L-MIND study suggests that treatment with tafasitamab + LEN tripled the proportion of LTS (40%) when compared with matched real-world patient cohorts receiving systemic therapies (13% LTS). Among patients responding to treatment, the proportion of LTS increased to 59% for those receiving tafasitamab + LEN, compared with 18% for other systemic treatment. The increases in LTS proportion resulted in substantial increases in estimates of life expectancy; these exploratory data warrant further examination in larger patient cohorts.

Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease

ObjectiveOur aim was to investigate the effectiveness and tolerability of antifibrotics in a real-world cohort of patients with rheumatoid arthritis-associated interstitial lung diseases (RA-ILD). MethodsIn this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at Mass General Brigham Integrated Health Care System, a large multi-hospital healthcare system in Boston, MA, USA. We used electronic query to identify all patients with at least 2 RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014–2023). All analyzed patients met 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and had definite RA-ILD according to Bongartz criteria. Data regarding pulmonary function test (PFT) results, adverse events (AEs), tolerability, and clinical data were collected. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (FVCpp) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data. Lung transplant-free survival and drug retention was estimated in a Kaplan-Meier analysis and a Cox regression analysis was performed to identify independent baseline factors associated with lung transplant or mortality. ResultsWe analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53 % male); 40 patients initiated nintedanib and 34 initiated pirfenidone. Median follow-up was 89 weeks (min 4, max 387). There was a significant improvement in the estimated slope of FVCpp after antifibrotic initiation (−0.3 % per year after initiation compared to −6.2 % per year before antifibrotic initiation, p = 0.03). Nintedanib and pirfenidone had similar FVCpp trajectory. Twenty-six patients (35 %) died and 4 (5 %) had undergone lung transplantation during follow-up. Male sex and heavy smoking were each associated with the composite outcome of lung transplant or mortality. AEs were reported in 41 (55 %) patients, with gastrointestinal (GI) AEs being most common (n = 30). The initial antifibrotic was discontinued in 34 (46 %) patients mostly due to GI AEs (n = 19). The median drug retention time was 142 weeks (95 %CI 56, 262) with no difference between nintedanib and pirfenidone (p = 0.68). ConclusionIn this first real-world study of antifibrotic use dedicated to RA-ILD, antifibrotic initiation was associated with a modestly improved trajectory of FVCpp. AEs were frequently reported, particularly GI, and discontinuation was common. However, lung transplant and mortality rates were still high, emphasizing the need for further therapeutic strategies in patients with severe RA-ILD. These real-world data complement previous trial data that investigated efficacy and safety.

Eligibility for screening with low-dose CT in a real-world cohort of patients with lung cancer in Greece: A brief report

IntroductionNELSON and NLST prompted the implementation of lung cancer screening programs in the United States followed by several European countries. This study aimed to assess the sensitivity of different screening criteria among patients with lung cancer in Greece and investigate reasons for ineligibility. MethodsWe performed a retrospective analysis on patients with lung cancer referred to the largest referral center in Athens, Greece, between June 2014 and May 2023. The proportion of patients who would meet the updated USPSTF and NLST criteria was compared to the corresponding proportion of the Greek population over 15 years of age. ResultsOut of 2434 patients with lung cancer, 77.4 % (N = 1883) would meet the updated USPSTF criteria, and 58.9 % (N = 1439) would meet the NLST criteria at diagnosis; the corresponding proportions for the Greek population over 15 years would be 13.8 % and 8.2 %, respectively. Ineligible patients were more likely to be female, former or never-smokers, have adenocarcinoma histology, and have driver mutations (p < 0.001). ConclusionsAlthough the updated USPSTF criteria demonstrated good sensitivity, a substantial proportion of patients with lung cancer would still not be eligible for screening. Future studies to shape a comprehensive screening strategy should focus on the incorporation of additional risk factors for lung cancer, including air pollution and individual genetic susceptibility.

Timing of MOG-IgG Testing Is Key to 2023 MOGAD Diagnostic Criteria.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation. All patients referred to the National neuromyelitis optica spectrum disorder (NMOSD) specialized service at The Walton Center NHS Foundation Trust between 2012 and 2023 with an atypical demyelinating syndrome were evaluated. We systematically applied the 2023 MOGAD diagnostic criteria and previous 2018 International Diagnostic Recommendations for MOG encephalomyelitis to our retrospective cohort. 474 patients were screened and 66 were excluded for lack of clinical information. Preexisting diagnoses within our cohort included the following: MOGAD, n = 127; AQP4-IgG NMOSD, n = 125; seronegative NMOSD, n = 33; multiple sclerosis (MS), n = 10; and other diagnoses, n = 113. Of patients with preexisting MOGAD, 97% (123/127) fulfilled the 2023 MOGAD diagnostic criteria. Three patients with a low-positive MOG-IgG did not meet supportive features though 2/3 had insufficient investigations. Alternative diagnoses could not be excluded in 1 patient with MS-MOGAD overlap. No patients with a non-MOGAD diagnosis were found to fulfill the 2023 diagnostic criteria. The sensitivity and specificity of the 2023 MOGAD diagnostic criteria were 97% and 100% with no false positives, improving on 2018 International Diagnostic Recommendations for MOG encephalomyelitis. Low-positive MOG-IgG results were more often associated with a longer time from disease onset to sampling (p < 0.001). In addition, in patients with a MOG-IgG1 test within 6 months of clinical onset, approximately 25% can become low positive by 6 months. Of patients with preexisting MOGAD, 9% (12/127) had insufficient investigations and examinations to fully evaluate additional supportive features. However, in those who were completely evaluated, supportive features were fulfilled in 97% (111/115). The 2023 MOGAD diagnostic criteria were highly sensitive and specific and closely align with historically established cases of MOGAD. However, because additional supportive features are stipulated for patients with a low-positive MOG-IgG result, missed diagnoses may occur due to delayed testing or insufficient investigations.

Derivation and validation of a noninvasive prediction tool to identify pulmonary hypertension in patients with IPF: Evolution of the model FORD

The administration of inhaled prostanoids to patients with pulmonary hypertension (PH) related to idiopathic pulmonary fibrosis (IPF) and other fibrotic lung diseases improves functional outcomes. Selection of patients with IPF at risk for concomitant PH to undergo right heart catheterization (RHC) remains challenging. We sought to develop a clinical prediction tool based on common noninvasive parameters to identify PH in patients with IPF. A prediction model based on noninvasive parameters was derived from patients enrolled in the ARTEMIS-IPF randomized, placebo-controlled clinical trial. Predictor variables were tested for association with the presence of PH diagnosed based on RHC. The derived multivariable logistic regression model and associated point-score index were then externally validated in a real-world cohort of patients with IPF. Of the 481 patients included in the ARTEMIS-IPF study, 9.8% (N = 47) were diagnosed with PH related to IPF. Four variables were associated with PH and were included in the final model: forced vital capacity/diffusing capacity for carbon monoxide ratio (F), oxygen saturation nadir during 6-minute walk test (6MWT) (O), race (R), and distance ambulated during 6MWT (D). A model containing continuous predictors (FORD calculator) and a simple point-score system (FORD index) performed similarly well in the derivation cohort (area under the curve [AUC]: 0.75 and 0.75, respectively) and validation cohort (AUC: 0.69 and 0.69, respectively). The FORD models are simple, validated tools incorporating noninvasive parameters that can be applied to identify patients at risk of PH related to IPF who may benefit from invasive testing.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy

BackgroundCurrent guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with ‘cardiopulmonary comorbidities’, despite limited available evidence to guide management. Research QuestionDo left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of PAH patients? Study Design and MethodsThe AMBITION trial criteria was used to define the phenotype of PAH patients with risk factors for LHD. Treatment strategy, functional outcome, long term survival and risk discrimination were compared with a reference PAH cohort using the PHSANZ registry. Results487 incident PAH patients diagnosed between 2011-2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors with 384 (78.9%) remaining as reference group. PAH with LHD risk factors were older (66±13 vs. 58±19years, p<0.001), had lower pulmonary vascular resistance (393±266 vs 708±391dynes/sec/cm-5, p=0.031) and worse 6-minute walk distance (286±130 vs. 327±136m, p=0.005) at diagnosis. PAH with LHD risk factors were less likely to receive less initial combination therapy (27% vs. 44%, p=0.02). Changes in 6-minute walk distance at 12-months were similar in both groups, 43±77 in PAH with LHD risk factors and 50±90m in reference group (p=0.5), including when stratified by initial treatment strategy (monotherapy: 40±81 vs. 38±95m p=0.87 and combination therapy: 53±78 vs. 64±106m, p=0.511; PAH with LHD risk factors vs. reference PAH). Functional class improvements were also similar in both groups. REVEAL 2.0 risk score effectively discriminated risk in both populations (C-statistic=0.756 for PAH with LHD risk factors and C-statistic=0.750 for reference PAH). There was no difference in survival between the two groups (log-rank test p=0.29). InterpretationIn a real-word cohort, PAH patients with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected PAH patients with LHD risk factors who were treated with initial combination therapy derived similar functional response compared to reference group. Further studies are needed to phenotype PAH patients with cardiopulmonary comorbidities who may benefit from initial combination therapy.

Impact of eGFR slope upon mortality in a real world heart failure cohort

Abstract Background Heart failure (HF) frequently causes an imbalance in heart and kidney functions, and the prognosis of heart and kidney disease can worsen one another. In addition to the prognostic role of chronic kidney disease (CKD), dynamic changes in renal function have been recognized to portend a poor prognosis in HF patients. Purpose This study aimed to investigate the prevalence of impaired renal function at HF diagnosis and its association with short and long-term outcomes in a real-world cohort of HF patients. In addition, we assessed how dynamic changes in renal function after HF diagnosis might predict HF prognosis. Methods Using a natural language processing algorithm, clinical data of patients with at least one diagnosis of HF (index event) were retrospectively collected. Patients for which the most recent estimated glomerular filtration rate (eGFR) value prior to the index date was ≤ 60 mL/min/1.73m2 and/or had a documented medical history of CKD (including dialysis) were considered as having CKD. A linear mixed effects model was used to show the longitudinal eGFR trajectories during the follow-up period (after index). A Cox proportional hazard model was used to analyse the association between baseline variables and mortality. Finally, joint modelling was used to combine the linear mixed eGFR sub-model with the survival sub-model, to estimate the effect of the current eGFR value and the eGFR slope of the year prior on mortality. Results The study population consisted of 1992 patients with a mean (±SD) age of 74.8 ± 11.7 years and 58% males. In total, 17% had HF with preserved ejection fraction (HFpEF, n = 339) and 70% (n = 1156) presented CKD at the index event. The median follow-up time was 3.16 years and 13% (n = 198) of the patients were deceased after two years. The group of 2-year survivors had significantly lower proportion of CKD at index (55 vs 76%, p &amp;lt; 0.001). The calculated mean yearly decrease of the eGFR value was 4.2 mL/min/1.73m². The multivariate Cox PH model identified age, CVA, diastolic blood pressure, HDL, and log10proBNP as baseline predictors of mortality. Joint modelling showed that a 10 mL/min/1.73m2 lower current eGFR value amongst patients was associated with an increased mortality hazard of 1.30 ± 0.06 (p &amp;lt; 0.001). Additionally, a decrease of 10 mL/min/1.73m2 in eGFR during the year prior indicated an increased mortality hazard of 1.87 ± 0.19 (p &amp;lt; 0.001). Conclusion In a real-world cohort of HF patients, the prevalence of CKD is high and CKD is an independent predictor of mortality. The current eGFR value and the year prior’s eGFR slope adds additional prognostic information and helps to better fine tune the individual mortality hazard. Based on the findings of this analysis, patients with worse prognosis might benefit from a closer and more vigilant follow-up.

Characterizing risk factors for the development of cardiovascular events in CAR-T Patients

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy, which involves ex-vivo engineering of autologous T-cells against cancer cells, has transformed the management of B and plasma cell malignancies, leading to further efforts in identifying new targets and indications. As the use of CAR T therapy expands, understanding its effects on the cardiovascular (CV) system becomes increasingly relevant. The systemic inflammatory response elicited by CAR T therapy can result in cytokine release syndrome (CRS) with manifestations including sinus tachycardia, hypotension, arrhythmias, and in severe cases, left ventricular dysfunction and cardiogenic shock. Risk factors for CAR T related CV events are not well-described. We evaluated risk factors for a primary composite endpoint of adverse CV events in a real-world cohort of patients with B and plasma cell malignancies receiving standard of care (SOC) CAR T therapy. Methods Medical records from all consecutive patients treated with SOC CAR T cell therapy at a U.S. health system from March 2018 to December 2021 were retrospectively reviewed under an IRB approved protocol. Our outcome was a single composite endpoint of clinically significant CV events including arrhythmia, acute coronary syndrome, stroke, CV death, ejection fraction decrease under 52.5%, heart failure exacerbation, and acute pericardial disease. All events resulted in an inpatient cardiology consult, upgrade to an ICU, or outpatient cardiology appointment. A multivariable Fine-Gray model was used to model CV risk and account for the competing risk of non-CV death. Results 123 patients were evaluated with a median follow-up of 16 months. 32 (26.0%) patients experienced the composite endpoint, with 1 CV death and 18 subsequent non-CV deaths, primarily from progressive disease (PD). Of the 91 patients that did not experience an adverse CV event, 35 (28.5%) died of non-CV causes, most commonly PD. In bivariate analysis, history of Coronary Artery Disease, Atrial Fibrillation (AF), Mantle Cell lymphoma, Tyrosine Kinase Inhibitor (TKI) exposure, Eastern Cooperative Oncology Group (ECOG) score ≥ 1, and CRS grade ≥ 2 were associated with the composite outcome (Table 1). A multivariable Fine-Gray regression model developed with stepwise selection showed a history of AF, ECOG score ≥ 1, Hispanic ethnicity, or CRS grade ≥ 2 were simultaneously associated with the composite outcome (Figure 1). Conclusions Risk factors associated with adverse CV events in CAR T include a history of AF, ECOG score ≥1, CRS grade ≥ 2, and Hispanic ethnicity. These findings are limited by sample size and number of events. These predictors, if validated in larger cohorts, have the potential to identify patients at high risk for CV complications who may benefit from multidisciplinary care pre- and post-CAR T infusion. Enhanced collaboration between oncologists and cardiologists to optimize CV function for this high-risk cohort may lead to improved outcomes.

Increasing left ventricular mass and mortality in 303,548 men and women investigated with echocardiography

Abstract Background and Aims Left ventricular hypertrophy (LVH) categories are based on left ventricular mass index (LVMi). This study aimed to generate sex-stratified, statistically-derived thresholds of mortality according to LVMi within a large, real-world patient cohort. Methods and Results Echocardiographic and linked mortality data were extracted from the National Echocardiography Database of Australia. LVH categories were first defined according to American Society of Echocardiography (ASE) criteria in 303,548 adults comprising 155,668 men (aged 61.3±17.3 years) and 147,880 women (61.8±18.3 years). Sex-specific mild to severe thresholds of increasing 5-year mortality based on LVMi increments were generated. Overall, 36,198 men (23.3%) and 38,898 women (26.3%) had LVH. Actual 5-year mortality rose from 16.9%-38.3% and 11.9%-31.2% in men and women with no LVH versus LVH, respectively. The statistical threshold at which LVMi was associated with increased mortality was lower than traditional LVH criteria in both men (Figure A, ≥88g/m2 versus ≥115g/m2) and women (Figure B, ≥82g/m2 versus ≥95g/m2). For men versus lowest-risk LVMi, the fully adjusted risk of 5-year mortality was 14% (95%CI 1.03-1.25) and 68% higher (95%CI 1.49-1.90) when LVMi levels were mildly (88 to &amp;lt;116) to severely (≥140g/m2) increased, respectively. In women, the equivalent LVMi thresholds of 82 to &amp;lt;112 and ≥140g/m2 were associated with a 13% (95%CI 1.03-1.24), and 81% higher (95%CI 1.58-2.08) 5-year mortality risk. Conclusion A high proportion of men and women have LVMi levels associated with elevated mortality risk that are lower than those traditionally used to diagnose or manage LVH. Such individuals may benefit from more proactive recognition and clinical management.

Plasma levels of direct oral anticoagulants in non-valvular atrial fibrillation patients at the time of acute cardioembolic or bleeding events

Abstract Background Direct oral anticoagulants (DOACs) are approved for preventing cardioembolic events in patients with non-valvular atrial fibrillation (NVAF) (1). Unlike Heparin and vitamin K antagonists, DOACs are commonly used without the need for clotting time monitoring, which results in limited data on the correlation between plasma levels and adverse events (2). Objective This study aimed to evaluate, in a real-world cohort of NVAF patients, the relationship between the occurrence of acute cardioembolic or major bleeding events and the plasma levels of DOACs measured at the time of the events. Methods and Results This study included 400 NVAF patients on DOAC therapy from the INSIghT registry who underwent plasma drug level testing at the time of an adverse event (116 cases) or during an elective hospitalization or outpatient visit (284 controls). Out of 116 cases, 74 experienced a cardioembolic event while 42 had a major bleeding. Patients with cardioembolic events presented low (i.e., in the first and second quartiles) DOAC plasma levels (50 vs. 24, p&amp;lt;0.01), while patients with major bleeding events had high (i.e., in the third and fourth quartiles) DOAC plasma levels (25 vs. 14, p&amp;lt;0.01). Conclusions This study highlights the possible association between plasma levels of DOACs and the risk of adverse events, but further research is needed to fully understand the potential benefits DOAC monitoring and individualized dosing.Fig. 1Fig. 2

Depression and heart failure - the incidence of depressive symptoms assessed by the PHQ9 and their association with HF outcomes

Abstract Background Depression is a prevalent, debilitating, and potentially modifiable comorbidity that affects heart failure (HF) patients and is associated with increased mortality and morbidity. Current HF guidelines recommend addressing depression using questionnaires, including the Patient Health Questionnaire-9 (PHQ-9), which is a 9-item questionnaire that can be self-administered in less than 3 minutes. Objectives To evaluate the performance of PHQ-9 in a Portuguese cohort of HF patients and present a practical approach for the screening and management of depression in patients with HF. Methods We conducted a prospective study enrolling consecutive patients observed in the HF clinic from June 2022 to August 2022. Patients answered the PHQ-9 before the beginning of the appointment, during which the physician evaluated the results and managed them according to the suggested protocol. – figure 1. We then evaluated the severity of depression by PHQ-9 at baseline and its association with the levels of serum NT-proBNP, the severity of HF symptoms, and the incidence of a composite of all-cause mortality and HF exacerbation at 90-days follow-up. Results A total of 124 patients were observed in the HF consultation and answered PHQ-9: mean age of 74±12,1years, 68% (n=84) male, 82% (n=102) with NYHA I-II, 48% (n=60) with preserved ejection fraction, 23% (n=29) with a previous diagnosis of depression and on antidepressant therapy. After the evaluation of PHQ-9, 52% (n=65), 27% (n=33), 10% (n=12), 8% (n=10) and 3% (n=4) had minimal, mild, moderate, moderately severe, and severe depression symptoms, respectively. In the no previous depression diagnosis group, 49% (n=46) had at least mild depressive symptoms. The presence of depressive symptoms was associated with higher levels of serum NT-proBNP (r=0.31; p&amp;lt;0.001) and worse HF symptoms assessed by the NYHA classification (p&amp;lt;0,001). Patients who met the composite outcomes (death or HF exacerbation) during follow-up had a significantly higher PHQ-9 score (10±7 vs. 5±5; p&amp;lt;0,001). Conclusions This study confirmed the high prevalence of depressive symptoms in this real-world cohort of HF patients and demonstrated that screening for depressive symptoms can be efficiently integrated in the HF consultation. A higher burden of depressive symptoms was associated with higher serum NT-proBNP, more severe symptoms and higher incidence of death or HF admissions.

Sex differences in cognitive impairment and association with all-cause mortality: a report from a contemporary cohort of patients with atrial fibrillation

Abstract Background Cognitive impairment (Cogn-Imp) in patients with atrial fibrillation (AF) has been associated with adverse outcomes. The impact of sex on the association between AF and Cogn-Imp is complex and there are limited data on specific sex-differences in AF patients with Cogn-Imp and association with outcomes. Purpose To investigate the impact of sex on Cogn-Imp, as well as the association of Cogn-Imp with adverse outcomes at follow-up in a contemporary cohort of patients with AF. Methods We analyzed patients enrolled in prospective observational study of AF patients. Cognitive status was evaluated by the Mini-Mental State Examination (MMSE). Patients were stratified according to MMSE scores obtained at baseline. A MMSE score &amp;lt;24 was considered suggestive of Cogn-Imp. All-cause mortality was the primary outcome. Results A total of 931 AF patients were included (median age 75 [IQR 66-82], CHA2DS2VASc score median 4 [2-5], HASBLED median 1 [1-2]). Almost ninenty percent (830/910, 89.2%) of the patients were treated with oral anticoagulants (OACs). Overall, 159/931 (17.1%) of the patients had a MMSE score &amp;lt;24 at baseline, indicative of Cogn-Imp. Female patients had a significant higher prevalence of Cogn-Imp compared to males (22.2% vs 14.0%, p=0.001). At the multivariable logistic regression analysis (adjusted for age, hypertension, previous stroke, coronary artery disease, diabetes, CKD, PAD, heart failure, AF type and use of OACs) female sex was independently associated with Cogn-Imp (adjusted OR 1.70, 95% CI 1.13-2.57). After a median follow-up of 633 [IQR 199-1503] days, all-cause mortality was 15.6% with a significant higher prevalence in patients with Cogn-Imp vs. No-Cogn-Imp, both for males (33.3% vs 15.8%, p&amp;lt;0.001) and females (29.6% vs 10.5%, p&amp;lt;0.001). Kaplan-Meier analysis showed a lower cumulative survival of patients with Cogn-Imp vs. No-Cogn-Imp (Log Rank p=0.01, Figure). At the adjusted Cox regression analysis, Cogn-Imp was associated with an independent higher risk of all-cause mortality both in males (adjusted HR 1.99, 95% CI 1.17-3.39) and females (adjusted HR 2.03, 95% CI 1.05-3.93). Stratifying the population by age, some differences in terms of association between Cogn-Imp and all-cause mortality were evident (Table). Cognitive impairment was associated with a higher risk of all-cause mortality in female patients aged 75-84 and ≥85 years old, but among males only in patients aged 75-84. Conclusions In a prospective observational real-world cohort of AF patients, female sex was independently associated with a higher occurrence of Cogn-Imp compared to male sex. Cognitive impairment was independently associated with a higher risk of all-cause mortality in both sexes with some differences across age categories suggesting peculiar pathophysiological interactions which warrant further investigations.

Temporal trends in intra-aortic balloon pump use

Abstract Background Intra-aortic balloon pump (IABP) is still the most accessible and available mechanical support solution in acute myocardial infarction patients, especially in cardiogenic shock. Although studies from the last decade failed to prove benefit for routine IABP use in this indication, the benefit of IABP utilization in selected cases is still unknown. Purpose To follow temporal trends in IABP use in a large-scale, real-world cohort of ACS patients. Methods We evaluated IABP utilization and patient’s outcome form the ACS Israel Survey (ACSIS) between 2000-2021. Temporal trends and compared rates of mortality and MACE (comprising death, myocardial infarction, stroke, target vessel revascularization and/or coronary bypass surgery) with IABP at 2 time periods were set: early (2000-2010) and late (2013-2021). Subgroup analysis for cardiogenic shock patients was performed as well. Results Out of 18,662 admitted ACS patients, 692 (3.7%) patients were treated with IABP. The rate of IABP use stood at about 4.5% (511 patients) in the early period and decreased to ∼2.5% (181 patients) in the late period. Patients treated with IABP in the early period had more frequently moderately and severely reduced ejection fraction on admission (64.5% vs 53.2%, p&amp;lt;0.01) and were mostly STEMI patients (71.0% vs 62.4%, p=0.04). On admission and in hospital cardiogenic shock (Killip 4) were presented equally in both periods (14.6% vs. 17.1%, p= 0.66 and 42.8% vs. 41.9%, p=0.90, respectively). 30-day mortality and MACE were comparable between time periods (28% vs 30.7%, p=0.547 and 43.6%vs. 44.1%, p=0.978, respectively) however major bleeding complication was significantly higher in the later period (4.8% vs 11.2%, p=0.04). These observations were consistent also in patients with baseline Killip class 3/4. Conclusions Our real-world data based prospective study demonstrated poor prognosis with IABP during all time periods, suggesting poor outcome in routine as well as selective use.

Accuracy of the GRACE Score for mortality prediction in myocardial infarction with nonobstructive coronary arteries (MINOCA)

Abstract Introduction Myocardial infarction with nonobstructive coronary arteries (MINOCA) patients account for 3.5 to 15% of all myocardial infarctions. The GRACE risk score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome, but the accuracy of the risk score for prognostic stratification in patients with MINOCA remains uncertain. Purpose We aimed to investigate whether the GRACE risk score can predict mortality in a real-world cohort of patients presenting with MINOCA. Methods We retrospectively analyzed patients admitted with MINOCA in a single center. Patients who were diagnosed with myocarditis and Takotsubo syndrome were excluded from the analysis. The GRACE risk score on admission was calculated. Patients were divided into a low-intermediate risk group (≤ 140 points, 71.5%) and a high-risk group (&amp;gt;140 points, 28.5%) according to their GRACE risk scores. Receiver operating characteristic (ROC) analysis was used to quantify the accuracy of the GRACE risk score to estimate both in-hospital and one-year mortality in MINOCA patients. Results Of a total of 3721 myocardial infarction patients, MINOCA was identified in 11.6% (n=430). 313 patients had complete data for the calculation of the GRACE on admission and were included in the analysis. Mean age was 65±12 years, and 49% (n=154) of patients were male. Mean GRACE score was 125±31 points. Patients in the high-risk group were older (74±9 vs. 61±11 years, p&amp;lt;0.001), had a higher incidence of in-hospital mortality (0.4% vs. 5.6%, p=0.008), and had a higher rate of one-year mortality (2.7% vs. 19.5%, p&amp;lt;0.001), compared with the low-intermediate risk group. There were no differences regarding sex and cardiovascular risk factors between the groups. In-hospital mortality was 1.9% and one-year mortality was 7.3%. ROC curve analysis showed that the GRACE risk score has a high value in predicting in-hospital mortality (AUC ROC 0.892; 95% CI 0.798–0.986; p=0.001), and one-year mortality (AUC ROC 0.826; 95% CI 0.739–0.0.914; p&amp;lt;0.001) in MINOCA patients. (Figure 1). The overall c-statistics were similar compared with estimates obtained from patients with myocardial infarction and significant coronary artery disease: in-hospital mortality (AUC ROC 0.0.849; 95% CI, 0.807–0.891; p&amp;lt;0.001); and one-year mortality (AUC ROC 0.776; 95% CI, 0.747–0.806; p&amp;lt;0.001). Conclusions In conclusion, the GRACE risk score provides potentially valuable prognostic information on in-hospital and one-year mortality when applied to MINOCA patients.Figure 1

Temporal association between atrial fibrillation burden in cardiac implantable electronic devices and the risk of heart failure hospitalization

Abstract Background high daily atrial fibrillation (AF) burden measured in cardiac implantable electronic devices (CIEDs) has been shown to be temporally associated with increased stroke risk.1 Purpose We investigated whether AF burden is temporally associated with an increased risk of heart failure (HF) events in a large real-world cohort of patients with CIED devices. Methods We linked a de-identified database of aggregated electronic health records from 2007-2021 to a manufacturer’s device data warehouse with device based continuous diagnostic monitoring data. Patients with dual or triple chamber CIED implants with capability to measure daily AF burden and having HF events with 120 days of AF burden data prior to the HF event were included in this study. HF event was defined as an inpatient admission, emergency department presentation, or observation unit stay in a hospital with primary diagnosis of HF with intravenous diuretics administration. AF burden of ≥5.5 hours (as defined in earlier studies) on any given day was compared during days 1-30 before (case period) and days 91-120 days (control period) before the first HF event in each patient in this case-crossover study.2 Results A total of 7257 earliest HF events with AF burden available in the case and control period were included. The average age of patients was 72 ±12years, with 74% being males, and following co-morbidities diagnosed prior to the HF event: 83% hypertension, 48% diabetes, 74% coronary artery disease, 31% stroke/TIA, 45% CKD, and 27% vascular disease. Comparison of occurrence of AF above threshold (≥5.5 hours on any given day) on days 1-30 versus 91-120 pre-HF event is shown in table to illustrate the effect of temporally proximate AF on risk of HF event. A total of 957 (13%) had discordant arrhythmic state between case and control period, with 763 (11%) having AF ≥5.5 hours on a day in case period versus 194 (2%) in the control period (OR: 3.93; 95% CI: 3.36-6.60). Higher odds of HF event was observed closer the day with AF ≥5.5 hours is to the HF event (table 1). Conclusions In a large real-world population of patients with CIED devices, AF burden of ≥5.5 hours or more on a given day increases risk of worsening HF.Table 1:odds ratio of HF eventFigure 1:Temporal association

Larger change in intra-thoracic impedance before and during heart failure hospitalization is associated with longer length of stay in patients with cardiovascular implanted electronic devices

Abstract Background Intra-thoracic impedance measured in implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRTD) is a measure of intravascular blood volume and have been shown to correlate with intracardiac pressures in previous studies. Purpose We investigated whether amount of change of intrathoracic impedance before admission is associated with length of stay (LOS) during heart failure (HF) hospitalizations in a large real-world cohort of patients with ICD/CRTD devices. Methods We linked a deidentified database of aggregated electronic health record during the period from 2007-2017 to a manufacturer’s device data warehouse with device based continuous diagnostic monitoring data. Patients with ICD/CRTD implants with intra-thoracic impedance measurements were included for this study. HF event was defined as an inpatient, emergency department, or observation unit stay in a hospital with primary diagnosis of HF and intravenous diuretics administration. Relative change of daily intra-thoracic impedance measurement from 60 days prior to admission and date of admission as well as from admission to discharge were compared in HF events with LOS &amp;lt; 5 days and LOS ≥ 5 days using a Wilcoxon rank sum test. Results A total of 17,886 patients with 1.8±1.2 years of follow-up met inclusion criteria. The average age of patients was 66.6 ±12.3 years, with 72% being males, and 51% with ICD devices. The relative change in intra-thoracic impedance from 60 days prior till date of admission and from admission to discharge for HF events with LOS &amp;lt; 5 days and LOS ≥ 5 days are shown in Table. A total of 1456 patients had 1720 HF events of which 874 events had LOS&amp;lt; 5 days and 846 had LOS≥ 5 days. HF events with a longer length of stay (LOS ≥ 5 days) had a higher relative decrease in intra-thoracic impedance prior to admission compared to HF events with a shorter length of stay. HF events with a longer length of stay (LOS≥ 5 days) had a higher relative increase in intra-thoracic impedance during hospital stay. Conclusions In a large real-world population of patients with ICD/CRTD devices, longer length of stay is more likely in patients with a larger relative decrease in intra-thoracic impedance prior to admission, indicating more accumulated fluid. Further, larger relative increase in intra-thoracic impedance during hospital stay was observed in patients with longer length of stay, indicating more fluid removal.

Outcomes of ECLS-SHOCK Eligibility Criteria Applied to a Real-World Cohort.

Cardiogenic shock (CS) exhibits high (~50%) in-hospital mortality. The recently published Extracorporeal life Support in Cardiogenic Shock (ECLS-SHOCK) trial demonstrated the neutral effects of the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on all-cause death, as well as on all secondary outcomes in subjects presenting with myocardial-infarction (MI)-related CS. Here, we compared ECLS-SHOCK eligibility criteria with a real-world cohort of CS patients. ECLS-SHOCK eligibility criteria were applied to a prospective single-center CS registry (the PREPARE CS registry) consisting of 557 patients who were consecutively admitted to the catheterization laboratory (cath lab) of the Medical University of Graz, Austria, due to CS (SCAI C-E). Overall use of mechanical circulatory support (MCS) in this cohort was 19%. Sixty-nine percent of the entire cohort had MI-related CS, 38% of whom would have met ECLS-SHOCK eligibility criteria, thus representing only 27% of the PREPARE CS registry. Exclusion from the ECLS-SHOCK trial was based on patients with initial lactate values below 3 mmol/L (n = 168; 43.6%), aged over 80 years (n = 65; 16.9%), and with a duration of cardiopulmonary resuscitation (CPR) exceeding 45 min (n = 22; 5.7%). The 30-day mortality of patients of the PREPARE CS registry who met the ECLS-SHOCK eligibility criteria was 57.0%, compared to 48.4% of patients in the ECLS-SHOCK trial. The patients' baseline characteristics, however, differed considerably with respect to type of infarction, age, and gender. In a real-world cohort of patients with MI-related CS, only 38% of patients met the eligibility criteria of the ECLS-SHOCK trial. Thus, the impact of the use of VA-ECMO on outcome parameters in MI-related CS, as observed in the ECLS-SHOCK trial, may differ in a more heterogeneous real-world CS population of the PREPARE CS registry.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis

BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141...

The Society of Thoracic Surgeons Intermacs 2023 Annual Report: Focus on Magnetically Levitated Devices

The 14th Annual Report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) describes outcomes of 27,493 patients with a continuous-flow left ventricular assist device (LVAD) from the past decade (2013-2022). In 2022, 2517 primary LVADs were implanted, of which 2512 (99.8%) were fully magnetically levitated (Mag-Lev) devices. This shift to nearly exclusive use of a Mag-Lev device led us to examine its outcomes compared with contemporary (2018-2022) and historical (2013-2017) non-Mag-Lev cohorts. Patients supported by a Mag-Lev device (n= 10,920) had a higher 1- and 5-year survival of 86% (vs 79% and 81%, P < .0001) and 64% (vs 44% and 44%, P < .0001), respectively, than those receiving non-Mag-Lev devices during the contemporary and historical eras. Over 5 years, freedom from gastrointestinal bleeding (72% vs 60%, P < .0001), stroke (87% vs 67%, P < .0001), and device malfunction/pump thrombus (83% vs 54%, P < .0001), but not device-related infection (61% vs 64%, P= .93), was higher with Mag-Lev devices compared with non-Mag-Lev support during the contemporary era. In this large primacy cohort of real-world patients with advanced heart failure, this report underscores markedimprovements in short- and intermediate-term survival and reduction of adverse events with a contemporary Mag-Lev LVAD.