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Abstract Background Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. Methods From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. Results Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort. Conclusions In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

AimHearing loss, affecting a significant portion of the global population, is prevented with peroxisome proliferator-activated receptor γ agonism. Understanding potential protective treatments is crucial for public health. We examine the effect of telmisartan, an antihypertensive drug and partial peroxisome proliferator-activated receptor γ agonist, on hearing loss in patients with hypertension.Method and resultsThis retrospective cohort analysis used data from the OMOP Common Data Model database, encompassing information from three tertiary institutions in South Korea. The study included a substantial sample size of 860,103 people diagnosed with hypertension. The study included individuals who had been medically diagnosed with hypertension and had been prescribed antihypertensive drugs, including telmisartan. The study design was established to evaluate the comparative effects of telmisartan and other hypertension medications on hearing loss. We used propensity score matching (PSM) to create a balanced cohort, reducing potential biases between the telmisartan and non-telmisartan groups. From the initial 860,103 patients with hypertension, a propensity score matched cohort was derived from 20,010 patients, with 2,193 in the telmisartan group. After PSM, lower incidence of total hearing loss was observed in the telmisartan group compared to the non-telmisartan group during the 3-year follow-up (0.5% vs. 1.5%, log-rank p = 0.005). In subgroup analysis, this study showed consistent results that lower incidence of total hearing loss was higher in the telmisartan group than in the non-telmisartan group.ConclusionTelmisartan was associated with reducing certain types of hearing loss in patients with hypertension. Further research is needed to confirm these findings and understand the mechanisms.

Abstract BackgroundAccurate medical advice is paramount in ensuring optimal patient care, and misinformation can lead to misguided decisions with potentially detrimental health outcomes. The emergence of large language models (LLMs) such as OpenAI’s GPT-4 has spurred interest in their potential health care applications, particularly in automated medical consultation. Yet, rigorous investigations comparing their performance to human experts remain sparse. ObjectiveThis study aims to compare the medical accuracy of GPT-4 with human experts in providing medical advice using real-world user-generated queries, with a specific focus on cardiology. It also sought to analyze the performance of GPT-4 and human experts in specific question categories, including drug or medication information and preliminary diagnoses. MethodsWe collected 251 pairs of cardiology-specific questions from general users and answers from human experts via an internet portal. GPT-4 was tasked with generating responses to the same questions. Three independent cardiologists (SL, JHK, and JJC) evaluated the answers provided by both human experts and GPT-4. Using a computer interface, each evaluator compared the pairs and determined which answer was superior, and they quantitatively measured the clarity and complexity of the questions as well as the accuracy and appropriateness of the responses, applying a 3-tiered grading scale (low, medium, and high). Furthermore, a linguistic analysis was conducted to compare the length and vocabulary diversity of the responses using word count and type-token ratio. ResultsGPT-4 and human experts displayed comparable efficacy in medical accuracy (“GPT-4 is better” at 132/251, 52.6% vs “Human expert is better” at 119/251, 47.4%). In accuracy level categorization, humans had more high-accuracy responses than GPT-4 (50/237, 21.1% vs 30/238, 12.6%) but also a greater proportion of low-accuracy responses (11/237, 4.6% vs 1/238, 0.4%; PPP ConclusionsGPT-4 has shown promising potential in automated medical consultation, with comparable medical accuracy to human experts. However, challenges remain particularly in the realm of nuanced clinical judgment. Future improvements in LLMs may require the integration of specific clinical reasoning pathways and regulatory oversight for safe use. Further research is needed to understand the full potential of LLMs across various medical specialties and conditions.

Abstract Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p

Background Carriers of CYP2C19 loss‐of‐function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. Methods and Results The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel‐based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3‐year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all‐cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3‐year clinical outcomes. Conclusions In older patients, the presence of any CYP2C19 loss‐of‐function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. Registration URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

Background No large‐scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real‐world registry. Methods and Results A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%; P=0.102) and the complication rate (6.9% versus 6.6%; P>0.999) were similar between the TAPT and DAPT groups. At 2‐year follow‐up, the incidence of major adverse limb events (16.6% versus 19.4%; P=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%; P=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158–0.794]; P=0.012). Conclusions In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.

Abstract Aims Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long‐term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long‐term clinical outcomes and their associated factors in patients with late‐stage DMD. Methods and results A total of 116 patients with late‐stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all‐cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow‐up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log‐rank P = 0.005). In the multivariable Cox regression analysis, brain‐natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019–1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651–52.148, P = 0.011) were significant predictors of all‐cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log‐rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005–1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704–10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. Conclusions Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late‐stage DMD, irrespective of LVEF.

BackgroundOlder patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy.MethodsWe selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years.ResultsIn patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group.ConclusionsOlder patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease.

ObjectivesThis study aimed to evaluate and compare the diagnostic accuracy of machine learning (ML)- fractional flow reserve (FFR) based on optical coherence tomography (OCT) with wire-based FFR irrespective of the coronary territory.BackgroundML techniques for assessing hemodynamics features including FFR in coronary artery disease have been developed based on various imaging modalities. However, there is no study using OCT-based ML models for all coronary artery territories.MethodsOCT and FFR data were obtained for 356 individual coronary lesions in 130 patients. The training and testing groups were divided in a ratio of 4:1. The ML-FFR was derived for the testing group and compared with the wire-based FFR in terms of the diagnosis of ischemia (FFR ≤ 0.80).ResultsThe mean age of the subjects was 62.6 years. The numbers of the left anterior descending, left circumflex, and right coronary arteries were 130 (36.5%), 110 (30.9%), and 116 (32.6%), respectively. Using seven major features, the ML-FFR showed strong correlation (r = 0.8782, P < 0.001) with the wire-based FFR. The ML-FFR predicted wire-based FFR ≤ 0.80 in the test set with sensitivity of 98.3%, specificity of 61.5%, and overall accuracy of 91.7% (area under the curve: 0.948). External validation showed good correlation (r = 0.7884, P < 0.001) and accuracy of 83.2% (area under the curve: 0.912).ConclusionOCT-based ML-FFR showed good diagnostic performance in predicting FFR irrespective of the coronary territory. Because the study was a small-size study, the results should be warranted the performance in further large-scale research.

BackgroundDiabetes mellitus (DM) is a critical risk factor for the pathogenesis and progression of coronary artery disease, with a higher prevalence of complex coronary artery disease, including bifurcation lesions. This study aimed to elucidate the optimal stenting strategy for coronary bifurcation lesions in patients with DM.MethodsA total of 905 patients with DM and bifurcation lesions treated with second-generation drug-eluting stents (DES) from a multicenter retrospective patient cohort were analyzed. The primary outcome was the 5-year incidence of target lesion failure (TLF), which was defined as a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization.ResultsAmong all patients with DM with significant bifurcation lesions, 729 (80.6%) and 176 (19.4%) were treated with one- and two-stent strategies, respectively. TLF incidence differed according to the stenting strategy during the mean follow-up of 42 ± 20 months. Among the stent strategies, T- and V-stents were associated with a higher TLF incidence than one-stent strategy (24.0 vs. 7.3%, p < 0.001), whereas no difference was observed in TLF between the one-stent strategy and crush or culotte technique (7.3 vs. 5.9%, p = 0.645). The T- or V-stent technique was an independent predictor of TLF in multivariate analysis (hazard ratio, 3.592; 95% confidence interval, 2.117–6.095; p < 0.001). Chronic kidney disease, reduced left ventricular ejection fraction, and left main bifurcation were independent predictors of TLF in patients with DM.ConclusionT- or V-stenting in patients with DM resulted in increased cardiovascular events after second-generation DES implantation.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03068494?term=03068494&draw=2&rank=1, identifier: NCT03068494.

Abstract Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding. Trial registration: NCT02707445 ( https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1 ).

Abstract Machine learning approaches using intravascular optical coherence tomography (OCT) to predict fractional flow reserve (FFR) have not been investigated. Both OCT and FFR data were obtained for left anterior descending artery lesions in 125 patients. Training and testing groups were partitioned in the ratio of 5:1. The OCT-based machine learning-FFR was derived for the testing group and compared with wire-based FFR in terms of ischemia diagnosis (FFR ≤ 0.8). The OCT-based machine learning-FFR showed good correlation (r = 0.853, P

Abstract Background The influence of intensive glucose control in diabetic patients on the macrovascular outcomes is controversial. Thus, this study aimed to elucidate the effect of preprocedural hemoglobin A1c (HbA1c) on clinical outcomes after endovascular therapy for lower extremity artery disease (LEAD) in diabetic patients. Methods Diabetic patients were enrolled from the retrospective cohorts of a Korean multicenter endovascular therapy registry and were divided according to the HbA1c level during index admission into the optimal (

Abstract Background and objectives Atrial fibrillation is a known risk factor for cryptogenic stroke and therefore requires early detection and prompt management. We investigated predictors of stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia but not atrial fibrillation. Subjects and methods We investigated 390 patients (219 men, mean age 67 ± 12 years) diagnosed with stroke and non-sustained atrial tachycardia on 24-h Holter monitoring and recorded the total number of atrial premature contractions identified by the Holter monitor. Multiple atrial premature contractions were defined as atrial premature contractions > 34 beats/day. We analyzed the rates of 5-year freedom from stroke recurrence or atrial fibrillation and investigated independent predictors of stroke recurrence and undiagnosed atrial fibrillation. Results The mean follow-up period was 35 ± 21 months, and the overall stroke recurrence rate was 9.0%. Kaplan–Meier survival analysis revealed that the rate of freedom from stroke recurrence was significantly lower in patients with multiple atrial premature contractions. Also, the patients with multiple atrial premature contractions had higher cumulative incidence rate of new-onset AF (p = 0.019). Multivariate analysis showed that multiple atrial premature contractions (hazard ratio 2.49, 95% confidence interval 1.05–5.88, p = 0.038), cigarette smoking status (hazard ratio 2.66, 95% confidence interval 1.15–6.17, p = 0.022), and the left atrial volume index (hazard ratio 1.05, 95% confidence interval 1.01–1.09, p = 0.020) were significantly associated with stroke recurrence in patients with cryptogenic stroke. However, these factors were not statistically significant predictors of future onset of atrial fibrillation. Conclusions Multiple atrial premature contractions were significantly correlated with an increased left atrial volume index, which could predict future onset of atrial fibrillation and stroke recurrence. This study showed that multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke without atrial fibrillation.