Ranel Loutati

Background: Interventricular septal (IVS) thickness is routinely measured by echocardiography, yet its prognostic significance in heart failure (HF), and whether it differs by sex, remains uncertain. Methods: This retrospective study included patients with HF from the SHEBAHEART registry (2009-2025). IVS thickness was classified as normal (1.3 cm), using identical thresholds by sex. Associations with all-cause mortality were evaluated using Kaplan-Meier analysis and multivariable Cox models adjusted for age, body mass index, systolic blood pressure, comorbidities, and left ventricular ejection fraction, with formal testing for sex-by-IVS interaction. Results: Among 20,836 patients (median age, 74 years; 39% women), 41% had mild and 18% had severe IVS thickening. During a median follow-up of 4 years, 11,930 patients (57%) died; 4-year Kaplan-Meier cumulative mortality increased across IVS categories (35%, 39%, and 42%; P < 0.001). In primary complete-case analysis (n = 13,902), the sex-by-IVS interaction was significant (P = 0.030). Adjusted hazard ratios (95% confidence intervals) for mild and severe thickening were 1.16 (1.07-1.26) and 1.19 (1.08-1.32) in women, compared with 1.02 (0.96-1.09) and 1.07 (0.99-1.16) in men. The sex-by-IVS interaction remained significant in multiple-imputation and time-varying Cox analyses, but not with sex-specific IVS reference partitions. Conclusions: With common absolute IVS thresholds, increased septal thickness was more strongly associated with all-cause mortality in women than in men with HF. These findings support evaluation of IVS thickness as a potential component of sex-specific risk stratification in HF.

Aims: Paroxysmal atrial fibrillation (AF) is underdiagnosed due to its intermittent and asymptomatic nature. We evaluated whether a deep neural network (DNN) applied to transthoracic echocardiograms (TTEs) acquired in sinus rhythm can discriminate between patients with and without documented AF and identify individuals at increased risk for subsequent AF documentation and adverse outcomes. Methods and results: We retrospectively analysed 85 686 TTE studies (2009–21). A DNN was applied to apical four-chamber and parasternal long-axis videos without Doppler. AF ground truth was based on International Classification of Diseases (ICD) codes, electrocardiogram, Holter, or prior echocardiographic documentation of AF. The dataset was split into training (60%), validation (20%), and an independent test set (20%). In the test cohort, we assessed discrimination performance. Among patients without prior AF, we evaluated associations between model classification and subsequent AF documentation and a composite outcome of all-cause mortality, heart failure hospitalization, or stroke. The test set included 17 121 patients (median age 66 years [interquartile range, IQR 54–75]; 57.6% male), of whom 3449 (20.1%) had prior AF. The model achieved an area under the receiver operating characteristic curve of 0.85, with sensitivity 0.80 and specificity 0.72. At the selected threshold, 6581 patients (38.4%) were classified as model-positive, including 3832 (58.2%) without prior AF. Among patients without prior AF, model-positive classification was associated with subsequent AF documentation [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.33–2.04] and with the composite outcome (adjusted HR 1.24; 95% CI 1.13–1.35). Conclusion: Deep learning applied to sinus-rhythm TTE demonstrates discrimination for AF and identifies an imaging-derived signal associated with subsequent AF documentation and adverse outcomes.

Objective: This study aimed to evaluate the risk of clinically meaningful muscle‐ and liver‐related outcomes associated with concomitant colchicine–statin therapy in a real‐world setting, and to determine whether concomitant therapy increases the incidence of toxicity compared with either agent alone. Methods: This was a retrospective cohort study using the national Clalit Health Services database (≈5.4 million insured individuals). Adults with gout or familial Mediterranean fever between 2010 and 2024 were categorized into four exposure groups: no treatment, colchicine only, statin only, or concomitant therapy. Propensity‐score matching was used to balance baseline characteristics. The primary outcome was creatine kinase (CK) elevation >3× the upper limit of normal (ULN), and secondary outcomes included alanine transaminase elevation >5× the ULN, myopathy, liver disease, and hospitalizations related to these conditions. Results: Eligible participants before and after propensity‐score matching were 104,066 and 31,839, respectively (no treatment n = 7,146; colchicine only n = 7,146; statin only n = 9,030; concomitant therapy n = 8,517). Compared with no treatment, CK elevations >3× ULN were observed with statin therapy (hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.39–1.93]) and concomitant colchicine–statin therapy (HR 1.74 [95% CI 1.44–2.09]) but not with colchicine therapy alone (HR 1.08 [95% CI 0.89–1.31]). Clinically diagnosed myopathy was infrequent and showed a graded increase across exposure groups, with the highest risk observed in the concomitant treatment group (HR 1.50 [95% CI 1.31–1.72]). Conclusion: Although colchicine–statin concomitant therapy was associated with higher rates of laboratory and clinical adverse events, the additional risk beyond statin monotherapy was small, supporting their use when clinically indicated.

Aims: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have transformed heart failure (HF) management, yet their effect in patients with concomitant tricuspid regurgitation (TR) remains unclear. We evaluated the association of SGLT2i use with clinical outcomes in HF patients with and without TR. Methods and results: We analysed a cohort of patients with HF (2014–2024) who underwent echocardiography within 90 days of diagnosis. Patients were stratified by significant TR and SGLT2i use. The primary outcome was a composite of all-cause mortality and HF hospitalization. TR progression was a secondary outcome. Inverse probability treatment weighting and time-dependent Cox models were used to adjust for baseline and treatment differences. Among 28 940 HF patients [median age 75 (IQR 66–83), 43% women], 4043 (14%) had significant TR, and 2320 (8%) received SGLT2i. Over a median follow-up of 3.5 years (IQR 1–7) and 79 313 echocardiograms, 11 646 (40%) patients experienced the primary outcome. Significant TR was independently associated with worse outcomes [adjusted HR (aHR) 1.21, 95% CI 1.14–1.28, P < 0.001] while SGLT2i use was associated with lower event rates (aHR 0.79, 95% CI 0.69–0.92; P = 0.002), with consistent associations across TR strata (aHR 0.65 with vs. 0.83 without significant TR; P for interaction = 0.180). SGLT2i was also associated with 28% reduced risk for TR progression (95% CI 0.58–0.90; P < 0.001). Results were consistent across HF subtypes and sensitivity analyses. Conclusion: Significant TR portends worse prognosis in HF. SGLT2i therapy is associated with improved outcomes and attenuated TR progression in this high-risk population, with findings limited by the observational design and potential residual confounding.

Aims: Elevated uric acid (UA) levels correlate with worse heart failure (HF) outcomes, but past studies used single UA measurements. The effect of intra-individual UA fluctuations, beyond mean levels, is unclear. This study assesses the relationship between serum UA variability and adverse clinical outcomes in HF patients. Methods: We analyzed 18,115 HF patients from the SHEBAHEART registry (2009–2025) with at least three UA measurements within three years of diagnosis. UA variability was quantified as the mean deviation (MD) from each patient’s average UA level and divided into quartiles: Q1 (≤−0.69 mg/dL), Q2–Q3 (>−0.69 and p < 0.001). These associations remained after propensity score matching and across HF subgroups. Conclusions: UA variability is a robust, independent predictor of mortality and HF hospitalization. Serial UA monitoring may enhance risk stratification in HF management.

Background: Intensive Cardiovascular Care Units (ICCUs) are critical in managing high-acuity cardiovascular conditions, yet contemporary data on evolving admission patterns and their association with outcomes are limited. Methods: We conducted a retrospective cohort study of all patients admitted to a tertiary-care ICCU between July 2019 and December 2024. Patients were stratified by admission period: early (2019–2021) and late (2022–2024). Baseline characteristics, index diagnosis, interventions, complications, and mortality outcomes were compared. The primary endpoints were in-hospital and one-year mortality. Results: The study included 6266 patients (median age 69 years, 32% female). Of them, 3125 and 3141 patients were admitted in the early and late periods, respectively. Patients in the later period exhibited a higher burden of co-morbidities, including increased rates of atrial fibrillation, cognitive impairment, and dialysis (p < 0.05 for all). The pattern of index diagnoses shifted, showing an increase in heart failure (5.6% vs. 3.7%, p = 0.001) and malignant arrhythmia admissions (13.9% vs. 9.3%, p < 0.001), alongside a decline in cases of NSTEMI and pulmonary embolism. The use of urgent percutaneous coronary intervention, transcatheter valvular interventions, and microaxial pumps increased, whereas intra-aortic balloon pump usage declined. In-hospital mortality remained consistent between the periods at 2.7%. However, adjusted one-year mortality was significantly reduced in the later period (adjusted HR 0.84, 95% CI 0.71–0.98, p = 0.037). Conclusions: Over five years, ICCU admissions showed increasing complexity and evolving procedural trends. Despite higher acuity, adjusted one-year survival improved, highlighting care advances and the value of continuous data-driven ICCU optimization.

Aims: To examine the association between a personal history of cancer and the likelihood of a cardiovascular diagnosis among patients presenting with chest pain. Methods and results: We analyzed data from consecutive adult patients hospitalized with a primary diagnosis of chest pain between 2007 and 2022, excluding those with active cancer or ST-elevation myocardial infarction. Patients were categorized into two groups: cancer survivors and other patients. The primary outcome was a cardiovascular probable diagnosis, defined as a composite of non-ST-segment elevation myocardial infarction, pulmonary embolism, new-onset atrial fibrillation, or mortality within 30 days. The final cohort included 37 819 patients with a median age of 65 years (Q1–Q3: 55–75), of whom 24 644 (65%) were men. Among these, 1838 (5%) had a history of cancer. A multivariable logistic regression model demonstrated that cancer survivors were 70% more likely to reach the study primary endpoint compared with other patients (P < 0.001). A propensity score matching model consistently demonstrated that cancer survivors were 40% more likely to meet the study endpoint (95% CI 1.2–1.7, P < 0.001). Over a median follow-up of 4.3 years (Q1–Q3: 2.1–7.3), 7035 (19%) patients died. Kaplan-Meier survival analysis indicated a cumulative probability of death of 29% ± 22% for cancer survivors vs. 12% ± 9% for other patients (P < 0.001, Log rank). Conclusion: Among patients admitted to the hospital with chest pain, a personal history of cancer is independently associated with a significantly higher likelihood of receiving a final cardiovascular diagnosis.

Background/Objectives: Existing data regarding the kinetics of cardiac troponin I (cTnI) are limited. The aim of the current study was to evaluate the kinetics of highly sensitive (hs) cTnI following acute myocardial infarction (MI) in a large-scale, real-world cohort. Methods: A prospective observational cohort study included all consecutive patients admitted to the intensive cardiovascular care unit (ICCU) with ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) who underwent percutaneous coronary intervention (PCI) between January 2020 and April 2024. Hs-cTnI concentrations were measured at the time of presentation and daily thereafter. Results: A total of 1174 STEMI patients [191 females (16.3%)] with a mean age of 63 years and 767 NSTEMI patients [137 females (17.9%)] with a mean age of 66.7 years were enrolled. The average hs-cTnI peak levels were 77,937.99 ng/L and 24,804.73 ng/L for STEMI and NSTEMI patients, respectively. A single peak of hs-cTnI was observed in 83% and 78% of STEMI and NSTEMI patients, respectively, while two peaks were observed in 11% and 19% and three or more peaks were observed in 6% and 3% of STEMI and NSTEMI patients, respectively. A higher number of peaks was associated with a lower ejection fraction and more in-hospital complications. Additionally, a higher number of peaks correlated with a higher in-hospital mortality rate among NSTEMI patients. Conclusions: Most STEMI and NSTEMI patients displayed a monophasic kinetic pattern of hs-cTnI peak levels. However, a greater number of hs-cTnI peaks was linked to a higher incidence of clinical complications, lower ejection fraction, and increased mortality.

Background: High-sensitivity cardiac troponin (hs-cTn) is useful for detecting acute myocardial infarction, but chronic hemodialysis patients often have elevated baseline levels that exceed the upper reference limit (URL). This study aimed to determine whether hs-cTnI levels in asymptomatic hemodialysis patients exceed the URL established for the general population, evaluate the impact of high-flux hemodialysis on hs-cTnI concentrations, and examine associations between hs-cTnI levels and subsequent hospitalization or mortality. Methods: A prospective, single-center cohort study was conducted at a tertiary care center from August 2023 to July 2024. Blood samples for hs-cTnI were collected from asymptomatic hemodialysis patients aged ≥ 40 years, measured before and after dialysis within one month. Patients were followed for up to 12 months. Results: Fifty-six patients were enrolled. The mean hs-cTnI levels were 28.4 ng/L pre-dialysis and 27.9 ng/L post-dialysis, with ranges of <6–223 ng/L and <6–187 ng/L, respectively. The mean hs-cTnI delta between pre- and post-dialysis was −0.5 ng/L, with 52% showing a negative delta, 30% no change, and 18% a positive delta. No association was found between baseline hs-cTnI levels and mortality or hospitalization during follow-up. Conclusions: Most asymptomatic hemodialysis patients had hs-cTnI levels in the “gray zone”, thus neither confirming nor excluding acute myocardial infarction. Dialysis did not significantly affect hs-cTnI levels, and elevated baseline hs-cTnI was not linked to increased mortality or hospitalization over 12 months.