BACKGROUND: Immune checkpoint inhibitors (ICIs) can enhance antitumor immunity but they also cause severe myocarditis. The impact of sex on presentation, biomarkers, and outcomes remains unclear. This study investigates...BACKGROUND: Immune checkpoint inhibitors (ICIs) can enhance antitumor immunity but they also cause severe myocarditis. The impact of sex on presentation, biomarkers, and outcomes remains unclear. This study investigates sex-specific risk factors and predictors in clinically suspected ICI-induced myocarditis. METHOD: Patients diagnosed with clinically suspected ICI-induced myocarditis at a single institute (2018-2024) were retrospectively reviewed. Baseline characteristics, laboratory markers, echocardiographic parameters, and outcomes, were compared between female and male. The primary endpoint was all-cause mortality. The composite endpoint included all-cause mortality, myocardial infarction, malignant arrhythmias, clinically suspected myocarditis recurrence, cardiogenic shock, severe infection, tumor progression, and assisted ventilation. Sex-stratified analyses were performed to identify predictors of adverse outcomes using Cox regression, with additional sensitivity analyses including propensity score matching (PSM) and bootstrap validation. RESULTS: The cohort comprised 135 males (74%) and 44 females (26%), with a median follow-up of 36.1 months (interquartile range: 12.4-61.3 months). Female had better overall survival (p = 0.0071), though 30-day mortality and cardiac mortality were similar between sexes. Male also had a higher hazard of adverse outcomes than female with composite endpoint (p = 0.006). In multivariable models, male sex remained independently associated with higher all-cause and composite mortality (HR = 2.56, p = 0.001). Myoglobin and pro-BNP were significant predictors among males, whereas no consistent biomarker predictors were identified in females. The findings remained robust after PSM and bootstrap resampling. CONCLUSION: Significant sex-specific differences exist in clinically suspected ICI-induced myocarditis. Female sex is associated with better survival, underscoring the need for sex-based risk stratification.
BACKGROUND: Many patterns from the entire strain and TDI curves remain uninvestigated. OBJECTIVES: We investigated whether applying signal analysis with supervised machine learning (ML) to strain and TDI curves would imp...BACKGROUND: Many patterns from the entire strain and TDI curves remain uninvestigated. OBJECTIVES: We investigated whether applying signal analysis with supervised machine learning (ML) to strain and TDI curves would improve the prediction of heart failure (HF) or cardiovascular death (CV death) compared with conventional echocardiographic parameters, and whether it would reveal previously unrecognized prognostic signal-derived parameters. METHODS: In total, 744 novel signal-analytical parameters extracted from 18 strain curves and 6 TDI curves were evaluated using ML and compared with a baseline ML model trained on 17 conventional echocardiographic parameters. The primary endpoint was a combined endpoint of incident HF or CV death within five years. RESULTS: The analysis included 2589 subjects from the Copenhagen City Heart Study (CCHS) for training the ML model and 916 subjects from the LOOP Study for external testing. In total, 126 subjects (4.9%) met the primary endpoint in CCHS, whereas 59 subjects (6.4%) met the primary endpoint in the LOOP Study. The models incorporating signal analysis, both stand-alone and combined with conventional parameters, significantly increased discrimination compared to the baseline model based on conventional parameters in the external test cohort (Baseline model: AUC 0.721, CI 0.639:0.802 vs. signal analytical model: AUC 0.790, CI 0.730:0.850, p = 0.031 and combined model: AUC 0.788, CI 0.727:0.849, p = 0.021). CONCLUSION: A ML model based on signal analysis of strain and TDI curves from echocardiographic examinations modestly improved 5-year discrimination for incident HF or CV death compared to a model based on conventional echocardiographic parameters.
INTRODUCTION: Drug coated balloon (DCB) angioplasty aims to reduce restenosis rates. However, studies suggest that only 10-20% of the drug is delivered to the vessel wall. Given this significant barrier to success, intra...INTRODUCTION: Drug coated balloon (DCB) angioplasty aims to reduce restenosis rates. However, studies suggest that only 10-20% of the drug is delivered to the vessel wall. Given this significant barrier to success, intra-operative methods for evaluating drug deposition could improve outcomes. This study has two key aims: 1) to determine if optical coherence tomography (OCT) can detect paclitaxel crystals; 2) to establish if OCT can be used to quantify geographical drug deposition. METHODS: A benchtop vessel imaging phantom was used to validate OCT detection of crystal deposition. OCT was performed before and after DCB angioplasty and post-intervention images were evaluated for signals consistent with paclitaxel crystals. Mean geographical drug deposition was measured by the percentage of luminal circumference demonstrating signal. This method was subsequently applied to 5 patent tibial artery specimens from patients who underwent lower extremity amputation due to peripheral artery disease and compared with 5 tibial artery specimens treated with plain old balloon angioplasty (POBA). RESULTS: Paclitaxel crystal deposition was consistently identified on OCT in the benchtop phantom model. The mean geographical percentage deposition was 6.5%. In the patent arterial specimens, paclitaxel was also visualized, and mean geographical deposition was 11.3%. In contrast, no paclitaxel crystals were identified on OCT in the arteries treated with POBA. CONCLUSION: This study has shown that paclitaxel crystal can be identified and geographical deposition quantified using OCT. This could pave the way to optimizing DCB angioplasty and unlock our understanding of the mechanistic relationship of DCB angioplasty and plaque morphology.
BACKGROUND: Physical activity levels of cardiac rehabilitation attendees with coronary heart disease (CHD) are low. This study examined whether frequency of physical activity measurement (Measure It!; self-report and ste...BACKGROUND: Physical activity levels of cardiac rehabilitation attendees with coronary heart disease (CHD) are low. This study examined whether frequency of physical activity measurement (Measure It!; self-report and step-tracker daily steps; <5 min) influenced ActiGraph accelerometer-measured physical activity in insufficiently active cardiac rehabilitation attendees with CHD. METHODS: This two-arm multicentre randomised trial with concealed allocation and blinded assessments included cardiac rehabilitation attendees (n = 190) randomised to either 2 or 5-physical activity measurements (2-PAM or 5-PAM) over 24-weeks. The primary outcome was daily minutes of moderate-to-vigorous physical activity (MVPA; accelerometry). Secondary outcomes included daily steps (accelerometry), body-mass-index, waist circumference and quality-of-life (AQoL-6D). RESULTS: Adjusted point estimates of effect for change in MVPA (Cohen's f = 0.05) and daily steps (Cohen's f = 0.14) were higher at 24-weeks for the 5-PAM group than 2-PAM group but did not reach a-priori statistical significance at this small-medium effect size. For daily steps (difference-in-difference 447 steps/day, 95% CI: -44-to-938, p = 0.075) the observed effect may be considered a clinically meaningful margin. Quality-of-life significantly improved within groups over time (p < 0.001). Most participants received the Measure It! intervention as intended (2-PAM 2-measures: 76% (n = 71/94); 5-PAM ≥4-measures: 92% (n = 87/95)). CONCLUSION: The Measure It! very brief physical activity measurement intervention delivered 6-weekly by cardiac rehabilitation clinicians over 24-weeks (5-PAM) may be an efficient and effective approach to increase daily steps and MVPA in insufficiently activity cardiac rehabilitation attendees with CHD. However, larger trials are required as this trial was designed to detect a larger effect, and findings should be interpreted with caution.
Kai T, Ajiro D, Yoshida T
… +16 more, Sekiguchi M, Kobayashi Y, Tanaka T, Saito A, Shoji T, Oda R, Miyahara D, Harashima Y, Shiokawa N, Okuno T, Sato Y, Kuwata S, Ogawa Y, Sakamoto M, Izumo M, Akashi YJ
BACKGROUND: The geometric orifice area (GOA) measured by four-dimensional computed tomography (4D-CT) offers a flow-independent anatomical assessment of aortic stenosis (AS). However, its quantitative relationships with...BACKGROUND: The geometric orifice area (GOA) measured by four-dimensional computed tomography (4D-CT) offers a flow-independent anatomical assessment of aortic stenosis (AS). However, its quantitative relationships with effective orifice areas (EOA) from echocardiography and catheterization, as well as the hemodynamic factors underlying their relationship and their relevance to markers of left-ventricular load, remain insufficiently defined. METHODS: GOA was obtained at individualized peak systole by CT planimetry, and EOA and EOA were calculated using the continuity and Gorlin equations. Associations, agreement, and bias between GOA and each EOA were evaluated using correlation analysis, Passing-Bablok regression, and Bland-Altman plots. Multivariable regression identified hemodynamic determinants of EOA-to-GOA ratios. Hierarchical regression assessed the incremental explanatory value of valve area indices for preprocedural NT-proBNP. RESULTS: GOA demonstrated excellent reproducibility (intraclass correlation coefficient 0.95). GOA correlated strongly with EOA (r = 0.67) and EOA (r = 0.65), whereas the correlation between EOA and EOA was moderate (r = 0.55). Passing-Bablok analysis revealed proportional bias for both modalities. Stroke volume index significantly increased both EOA-to-GOA and EOA-to-GOA ratios. Only GOA provided a statistically significant but modest incremental explanatory value for preprocedural NT-proBNP (ΔR = 0.03; p = 0.02), whereas neither EOA nor EOA significantly improved model performance. CONCLUSIONS: CT-derived GOA is a highly reproducible, flow-independent anatomical metric that correlates strongly with physiological valve areas while offering additional clinical insight. Variability in EOA-to-GOA scaling underscores the complementary roles of anatomical and functional assessments in characterizing AS severity.
BACKGROUND: Patients with heart failure and preserved ejection fraction (HFpEF) present with elevated left atrial pressures. The elevation in pulmonary venous pressures and lung interstitial fluid accumulation is exacerb...BACKGROUND: Patients with heart failure and preserved ejection fraction (HFpEF) present with elevated left atrial pressures. The elevation in pulmonary venous pressures and lung interstitial fluid accumulation is exacerbated by exercise. An analysis on the lung extravascular fluid (lung B-lines) combined with lung diffusing capacity for carbon monoxide (DLCO) with its subcomponents, alveolar-capillary membrane conductance (Dm) and capillary volume (Vcap) has not been performed. PURPOSE: To assess the association between resting pulmonary diffusing capacity and exercise-induced pulmonary congestion in HFpEF patients. METHODS: DLCO, Dm and Vcap were measured in 40 stable HFpEF subjects (age = 73 ± 8; BMI = 27,1 ± 4,3 kg/m2) and in healthy controls at rest with parallel assessment of B-lines during combined Stress Echocardiography and Cardiopulmonary Exercise Test (ESE-CPET). B-lines evaluation of both hemithorax was performed at rest and at peak of exercise. RESULTS: Compared to controls, HFpEF group exhibited lower DLCO and Dm at rest and a higher number of B-lines at peak of exercise with a significant correlation observed for HFpEF but not for controls (resting DLCO vs peak B-lines in HFpEF: R = - 0,66, P < 0,001; resting Dm vs peak B-lines in HFpEF: R = - 0,72, P <0,001). We found also a significant negative correlation between Dm at rest with VE/VCO2 slope (R = - 0,51, P < 0,001), and Dm at rest with E/e' at peak of stress test in HFpEF group (R = - 0,59, P < 0,001), reflecting a ventilatory/perfusion mismatch along with an elevation of left ventricular filling pressures exacerbated by exercise. CONCLUSIONS: In HFpEF altered pulmonary gas exchange capacity at rest, and an excessive lung extravascular water at rest and during effort are combinatory factors affecting exercise performance. The true cause-effect relationship between these variables needs to be tested by mechanicistic experimental studies.
AIMS: Atrial reservoir strain reflects atrial compliance and global cardiac filling pressure. Although left atrial reservoir strain (LASr) has been associated with adverse outcomes in heart failure (HF), the prognostic s...AIMS: Atrial reservoir strain reflects atrial compliance and global cardiac filling pressure. Although left atrial reservoir strain (LASr) has been associated with adverse outcomes in heart failure (HF), the prognostic significance of combined left and right atrial reservoir strain remains unclear. METHODS: We retrospectively analyzed 1147 patients with chronic HF and left ventricular ejection fraction (LVEF) < 50% who underwent comprehensive transthoracic echocardiography between January 2018 and May 2023. LASr and right atrial reservoir strain (RASr) were assessed using two-dimensional speckle-tracking echocardiography. Patients were stratified into four groups according to high or low LASr and RASr based on median values. The primary endpoint was a composite of cardiac death or HF hospitalization. Event-free survival rate was evaluated using Kaplan-Meier analysis and associations with outcomes were assessed using Cox proportional hazards models. RESULTS: During a median follow-up of 34 months, 221 composite events occurred. Event-free survival differed significantly among the four groups (log-rank test, P < 0.01). Patients with concomitantly low LASr and low RASr had the highest risk of cardiac death or HF hospitalization. After adjustment for age, sex, LVEF, left atrial volume index and tricuspid regurgitation velocity, combined low LASr and low RASr remained independently associated with adverse outcomes (hazard ratio 2.43, 95% confidence interval 1.64-3.61; P < 0.01). CONCLUSIONS: Combined assessment of LASr and RASr identified a distinct high-risk phenotype in patients with chronic HF and reduced LVEF. Bi-atrial reservoir strain provides clinically relevant prognostic information beyond conventional echocardiographic measures and may improve risk stratification.
BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) may be associated with exertional ischemia, ventricular arrhythmias, and adverse outcomes. The relationship between high-risk anatomic features and functio...BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) may be associated with exertional ischemia, ventricular arrhythmias, and adverse outcomes. The relationship between high-risk anatomic features and functional consequences remains incompletely defined. Coronary computed tomography angiography (CCTA) and exercise-stress myocardial perfusion scintigraphy (SPECT) present as complementary modalities for integrated assessment of anatomy, ischemia, and arrhythmias. METHODS: We retrospectively studied consecutive adults with AAOCA undergoing CCTA and exercise-stress ^99mTc-SPECT between 2010 and 2025 at two centers. Inducible ischemia was defined as a summed difference score (SDS) ≥4. A composite endpoint (death, myocardial infarction, angina requiring evaluation, ventricular arrhythmias, or coronary revascularization) was assessed during follow-up. Discriminative performance of ECG, CCTA, SPECT, and combined imaging models was evaluated using ROC analysis. RESULTS: Thirty-five patients (mean age 51 ± 15 years; 89% men) were included. At least one high-risk CCTA feature was present in 60% of cases, and inducible ischemia occurred in 51%. An interarterial course was significantly associated with SPECT positivity (67% vs. 12%, p = 0.007). Ventricular arrhythmias during exercise were more frequent in SPECT-positive patients (50% vs. 13%, p = 0.03). During a median follow-up of 59 months, the combined CCTA+SPECT model showed the highest discrimination (AUC 0.76). CONCLUSIONS: Integrating CCTA with exercise-SPECT links high-risk anatomy to functional and arrhythmic manifestations and may improve risk stratification in adults with AAOCA.
BACKGROUND: Understanding how baseline conditions influence alerts and adverse events in patients with heart failure (HF) and cardiac implantable electronic devices (CIEDs) under remote monitoring (RM) is crucial for pat...BACKGROUND: Understanding how baseline conditions influence alerts and adverse events in patients with heart failure (HF) and cardiac implantable electronic devices (CIEDs) under remote monitoring (RM) is crucial for patient management. However, the impact of HF alerts on clinical outcomes remains poorly defined. OBJECTIVE: To assess the impact of HF alerts on adverse outcomes and to identify clinical trajectories based on individual baseline risk factors. METHODS: We conducted a single-center, retrospective study including HF patients implanted with a CIED and provided with RM. We modeled patients trajectories using a semi-Markov, four-state framework with six possible transitions, encompassing a HF score alert state, HF Hospitalization (HFH) state and all-cause death. Cox proportional hazards models assessed the effects of baseline covariates on transition rates and evaluated the impact of HF alert occurrence on outcomes, treated as time-dependent covariates. RESULTS: A total of 511 patients (median age 69.9 years [IQR 61.4-77.1]) were included. During a median follow-up of 1.8 years [IQR 0.7-3.9], 60 patients (11.7%) transitioned to an HF score alert state, of whom 6 (10%) and 12 (20%) respectively experienced an HFH and died without a prior HFH. From the baseline group, 29 patients (5.7%) transitioned directly to death and 53 patients (10.4%) had an HFH. Of the 59 total patients who experienced an HFH, 19 (32%) died during follow-up. The transition to a HF score alert state was significantly associated with all-cause death (HR 6.99, 95% CI 1.89-25.94; p = 0.004) while not statistically significant associated with HFH (HR 0.58, 95% CI 0.13-2.69; p = 0.65). CONCLUSIONS: Using a multistate model, we characterized clinical trajectories in HF patients and observed the effects of different covariates on transition rates.
BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are increasingly used in hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, yet emerging data suggest potential cardiotoxicity, including atria...BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are increasingly used in hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, yet emerging data suggest potential cardiotoxicity, including atrial arrhythmias (AA). Understanding incidence and outcomes of AA is essential as indications for CDK4/6 inhibitors expand. OBJECTIVES: To evaluate the incidence of new-onset AA and associated outcomes in patients with HR+/HER2- breast cancer treated with CDK4/6 inhibitors. METHODS: We conducted a retrospective cohort study of patients who received CDK4/6 inhibitors for HR+/HER2- breast cancer at Mayo Clinic from 2015 to 2024. The primary outcome was incidence of AA (atrial fibrillation, atrial flutter, or atrial tachycardia). Secondary outcomes included cerebrovascular events and all-cause mortality. Fine-Gray subdistribution hazard models and Cox regression models were used to assess risk factors for AA and all-cause mortality, respectively. RESULTS: Among 2773 patients, 59% received palbociclib, 28% abemaciclib, and 14% ribociclib. New-onset AA occurred in 42, cumulative incidence at 5 years of 2.1% (95% CI 1.5-2.8%). No significant differences in 5-year AA incidence were observed between agents: 1.5% (95% CI 0.7-2.8%), 2.3 (95% CI 1.6-3.2%), 1.0 (95% CI 0.3-2.6%) (p = 0.49). Multivariable analysis identified age at treatment as the only independent predictor of AA (HR 1.07, 95% CI 1.04-1.09, p < 0.001). New-onset AA was associated with increased mortality (HR 1.56, 95% CI 1.10-2.20, p = 0.012). CONCLUSIONS: Patients who receive CDK4/6 inhibitors for breast cancer experience a low but measurable risk of new-onset atrial arrhythmias. There was no significant difference in new-onset AA risk between agents. Prospective studies are needed to define mechanisms and guide monitoring strategies.
BACKGROUND: Percutaneous coronary intervention registries are pivotal for monitoring cardiovascular care. While several registries exist across the Asia-Pacific region, methodological diversity limits regional comparison...BACKGROUND: Percutaneous coronary intervention registries are pivotal for monitoring cardiovascular care. While several registries exist across the Asia-Pacific region, methodological diversity limits regional comparison. This systematic review aimed to summarize methodological characteristics, patient profiles, and in-hospital mortality rates in Asia-Pacific percutaneous coronary intervention registries. METHODS: A systematic literature search was conducted across MEDLINE, Embase, Scopus, Web of Science, and ProQuest Central, up to June 2025. Data on registry design, dataset characteristics, patient demographics, cardiovascular risk factors, procedural details, and in-hospital outcomes were extracted and synthesized qualitatively, with in-hospital mortality rates pooled using a random-effects model. RESULTS: A total of 27 studies encompassing 16 unique registries from nine countries were included. Despite targeting similar populations of patients with coronary artery disease undergoing intervention, marked heterogeneity existed in dataset structure, variable definitions, and data management approaches. Across all registries, men predominated, and hypertension and dyslipidemia were the most prevalent cardiovascular risk factors. The proportion of patients presenting with ST-elevation myocardial infarction ranged from 6.8% to 58.7%. In-hospital mortality rates ranged from 0.26% to 2.80%, with most registries reporting rates around 0.9-1.6%. CONCLUSIONS: The Asia-Pacific region would benefit from unified dataset standards to enhance data harmonization and comparability. While in-hospital mortality rates varied, they generally fell within international benchmarks, suggesting effective acute management. Further longitudinal data are needed to evaluate long-term outcomes and the broader impact of registry-based monitoring on enhancing quality in cardiovascular care.
Juhasz V, Quinaglia T, Drobni ZD
… +13 more, Gilman HK, Heemelaar JC, Neuberg DS, Han Y, Ky B, Kwong RY, Januzzi JL, Asnani A, Redd RA, Mousavi N, Jerosch-Herold M, Scherrer-Crosbie M, Neilan TG
BACKGROUND: Anthracyclines can be associated with impaired left ventricular (LV) deformation, measured by global longitudinal strain (GLS) and global circumferential strain (GCS). Whether atorvastatin protects against an...BACKGROUND: Anthracyclines can be associated with impaired left ventricular (LV) deformation, measured by global longitudinal strain (GLS) and global circumferential strain (GCS). Whether atorvastatin protects against anthracycline-induced reductions in GLS and GCS is unknown. We investigated whether atorvastatin attenuates these declines during anthracycline-based chemotherapy. METHODS: In the STOP-CA trial, participants with lymphoma treated with anthracyclines were randomized to placebo (n = 150) or atorvastatin (n = 150) for 12 months. Cardiac MRI-derived GLS and GCS measurements were performed at baseline and 12 months using feature tracking (FT). The primary endpoint was a ≥ 15% relative decrease in LV GLS. The secondary endpoint was a ≥ 1SD decrease in LV GCS. RESULTS: Of 300 participants, 188 (mean age 51 ± 16 years, 48% female, 93 with atorvastatin) had paired LV GLS, and 177 had paired LV GCS data with similar values in both groups at baseline. A ≥ 15% relative decrease in LV GLS was observed among 19% in the atorvastatin and 28% in the placebo group (P = 0.23). The proportion of participants with a ≥ 1SD decrease (3.2% unit) in LV GCS at 12 months was lower in the atorvastatin group (25% vs. 42%, Odds Ratio: 0.46, 95% Confidence Interval 0.24-0.87, P = 0.024). At 12 months, LV GCS values were lower in the placebo group (20.2 ± 3.3% vs. 19.3 ± 2.7%, P = 0.012). CONCLUSION: Atorvastatin decreased the odds of a significant decline in LV GCS, a predictor of adverse cardiac outcomes in patients undergoing anthracycline-based chemotherapy. Atorvastatin did not significantly attenuate the odds of a decline in LV GLS. (Clinical trial registration: NCT02943590; https://clinicaltrials.gov/study/NCT02943590).
BACKGROUND: Despite successful percutaneous coronary intervention (PCI), patients with non-ST-segment elevation myocardial infarction (NSTEMI) remain at risk of major adverse cardiovascular events (MACE). The combined pr...BACKGROUND: Despite successful percutaneous coronary intervention (PCI), patients with non-ST-segment elevation myocardial infarction (NSTEMI) remain at risk of major adverse cardiovascular events (MACE). The combined prognostic value of pericoronary fat attenuation index (FAI), a marker of coronary inflammation from coronary computed tomography angiography (CCTA), and angiography-derived microcirculatory resistance (AMR), a marker of microvascular dysfunction, is underexplored. METHODS: This retrospective cohort included 508 NSTEMI patients who underwent successful PCI after pre-procedural CCTA. FAI and AMR were measured. The primary endpoint was MACE during follow-up. Sensitivity analyses using 1-year and 2-year time-restricted endpoints were performed to validate the robustness of the findings. Cox regression and machine learning models were used. Mediation analysis assessed the pathway from FAI to outcomes via AMR. RESULTS: Over a median follow-up of 620 days, MACE occurred in 146 patients (28.7%). High FAI (hazard ratio [HR] 1.03, P < 0.001) and high AMR (HR 1.75, P < 0.001) were independent predictors. The combined "High AMR/High FAI" phenotype had the highest risk. The FAI-AMR model improved prediction over a baseline clinical model (C-index increase Δ = 0.055, net reclassification improvement [NRI] = 0.809, integrated discrimination improvement [IDI] = 0.139, all P < 0.05). Exploratory mediation analysis suggested that approximately 29.4% of the statistical association between FAI and MACE was accounted for by AMR (P < 0.001). CONCLUSION: FAI and AMR are independent and complementary predictors of post-PCI MACE in NSTEMI. Their combined assessment identifies a high-risk phenotype and adds prognostic value. Microcirculatory dysfunction partially mediates the link between inflammation and outcomes, suggesting potential therapeutic targets.