Gelatin microgel-coated balloon catheter with enhanced delivery of everolimus for long-term vascular patency.

In-stent restenosis (ISR) after percutaneous coronary intervention is a major reason for limited long-term patency due to complex neointimal proliferation caused by vascular injury. Drug-coated balloon (DCB) has been developed to treat various cardiovascular diseases including ISR by providing anti-proliferative drugs into blood vessel tissues. However, a significant proportion of the drug is lost during balloon tracking, resulting in ineffective drug delivery to the target region. In this study, we report an everolimus-coated balloon (ECB) using everolimus-loaded gelatin-hydroxyphenyl propionic acid microgel (GM) with enhanced everolimus delivery to vascular walls for long-term patency. GM with high drug loading (> 97%) was simply prepared by homogenizing enzyme-mediated crosslinked hydrogels. The optimal condition to prepare GM-coated ECB (GM-ECB) was established by changing homogenization time and ethanol solvent concentration (30 ∼ 80%). In vitro sustained everolimus release for 30 d, and cellular efficacy using smooth muscle cells and vascular endothelial cells were evaluated. Additionally, an in vivo drug transfer levels of GM-ECB using rabbit femoral arteries were assessed with reduced drug loss and efficient drug delivery capability. Finally, using ISR-induced porcine models, effective in vivo vascular patency 4 weeks after treatment of ECBs was also confirmed. Thus, this study strongly demonstrates that GM can be used as a potential drug delivery platform for DCB application. STATEMENT OF SIGNIFICANCE: We report an ECB using everolimus-loaded GM prepared by homogenization of enzymatic cross-linked hydrogel. GM showed efficient drug loading (> 97 %) and controllable size. GM-ECB exhibited potential to deliver everolimus in a sustained manner to target area with drug efficacy and viability against SMC and EC. Although GM-ECB had much lower drug content compared to controls, animal study demonstrated enhanced drug transfer and reduced drug loss of GM-ECB due to the protection of encapsulated drugs by GM, and the possible interaction between GM and endothelium. Finally, vascular patency and safety were assessed using ISR-induced porcine models. We suggest an advanced DCB strategy to alleviate rapid drug clearance by bloodstream while improving drug delivery for a long-term vascular patency.

Identifying Atrial Fibrillation With Sinus Rhythm Electrocardiogram in Embolic Stroke of Undetermined Source: A Validation Study With Insertable Cardiac Monitors.

BACKGROUND AND OBJECTIVES: Paroxysmal atrial fibrillation (AF) is a major potential cause of embolic stroke of undetermined source (ESUS). However, identifying AF remains challenging because it occurs sporadically. Deep learning could be used to identify hidden AF based on the sinus rhythm (SR) electrocardiogram (ECG). We combined known AF risk factors and developed a deep learning algorithm (DLA) for predicting AF to optimize diagnostic performance in ESUS patients. METHODS: A DLA was developed to identify AF using SR 12-lead ECG with the database consisting of AF patients and non-AF patients. The accuracy of the DLA was validated in 221 ESUS patients who underwent insertable cardiac monitor (ICM) insertion to identify AF. RESULTS: A total of 44,085 ECGs from 12,666 patient were used for developing the DLA. The internal validation of the DLA revealed 0.862 (95% confidence interval, 0.850-0.873) area under the curve (AUC) in the receiver operating curve analysis. In external validation data from 221 ESUS patients, the diagnostic accuracy of DLA and AUC were 0.811 and 0.827, respectively, and DLA outperformed conventional predictive models, including CHARGE-AF, C2HEST, and HATCH. The combined model, comprising atrial ectopic burden, left atrial diameter and the DLA, showed excellent performance in AF prediction with AUC of 0.906. CONCLUSIONS: The DLA accurately identified paroxysmal AF using 12-lead SR ECG in patients with ESUS and outperformed the conventional models. The DLA model along with the traditional AF risk factors could be a useful tool to identify paroxysmal AF in ESUS patients.

Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium.

BACKGROUND: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. METHODS: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. RESULTS: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and HbA1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HRadj]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HRadj: 1.507; 95% CI: 1.193-1.902; P < 0.001). CONCLUSION: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT04734028.

Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions.

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Diagnostic Value of a Wearable Continuous Electrocardiogram Monitoring Device (AT-Patch) for New-Onset Atrial Fibrillation in High-Risk Patients: Prospective Cohort Study.

BACKGROUND: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation. OBJECTIVE: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHA2DS2-VASc) score had increased detection rates. METHODS: In this nonrandomized multicenter prospective cohort study, we enrolled 320 adults aged ≥19 years who had never experienced atrial fibrillation and whose CHA2DS2-VASc score was ≥2. The AT-Patch was attached to each individual for 11 days, and the data were analyzed for arrhythmic events by 2 independent cardiologists. RESULTS: Atrial fibrillation was detected by the AT-Patch in 3.4% (11/320) of patients, as diagnosed by both cardiologists. Interestingly, when participants with or without atrial fibrillation were compared, a previous history of heart failure was significantly more common in the atrial fibrillation group (n=4/11, 36.4% vs n=16/309, 5.2%, respectively; P=.003). When a CHA2DS2-VASc score ≥4 was combined with previous heart failure, the detection rate was significantly increased to 24.4%. Comparison of the recorded electrocardiogram data revealed that supraventricular and ventricular ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group compared with nonatrial fibrillation group (3.4% vs 0.4%; P=.001 and 5.2% vs 1.2%; P<.001), respectively. CONCLUSIONS: This study detected a moderate number of new-onset atrial fibrillations in high-risk patients using the AT-Patch device. Further studies will aim to investigate the value of early detection of atrial fibrillation, particularly in patients with heart failure as a means of reducing adverse clinical outcomes of atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04857268; https://classic.clinicaltrials.gov/ct2/show/NCT04857268.

Faster smooth muscle cell coverage in ultrathin-strut drug-eluting stent leads to earlier re-endothelialization.

Background: The ultrathin-strut drug-eluting stent (DES) has shown better clinical results than thin- or thick-strut DES. We investigated if re-endothelialization was different among three types of DES: ultrathin-strut abluminal polymer-coated sirolimus-eluting stent (SES), thin-strut circumferential polymer-coated everolimus-eluting stent (EES), and thick-strut polymer-free biolimus-eluting stent (BES) to gain insight into the effect of stent design on promoting vascular healing. Methods: After implanting three types of DES in the coronary arteries of minipigs, we performed optical coherence tomography (OCT) at weeks 2, 4, and 12 (n = 4, each). Afterward, we harvested the coronary arteries and performed immunofluorescence for endothelial cells (ECs), smooth muscle cells (SMCs), and nuclei. We obtained 3D stack images of the vessel wall and reconstructed the en face view of the inner lumen. We compared re-endothelialization and associated factors among the different types of stents at different time points. Results: SES showed significantly faster and denser re-endothelialization than EES and BES at weeks 2 and 12. Especially in week 2, SES elicited the fastest SMC coverage and greater neointimal cross-sectional area (CSA) compared to EES and BES. A strong correlation between re-endothelialization and SMC coverage was observed in week 2. However, the three stents did not show any difference at weeks 4 and 12 in SMC coverage and neointimal CSA. At weeks 2 and 4, SMC layer morphology showed a significant difference between stents. A sparse SMC layer was associated with denser re-endothelialization and was significantly higher in SES. Unlike the sparse SMC layer, the dense SMC layer did not promote re-endothelialization during the study period. Conclusion: Re-endothelialization after stent implantation was related to SMC coverage and SMC layer differentiation, which were faster in SES. Further investigation is needed to characterize the differences among the SMCs and explore methods for increasing the sparse SMC layer in order to improve stent design and enhance safety and efficacy.

Long-term mortality and cardiovascular events of seven angiotensin receptor blockers in hypertensive patients: Analysis of a national real-world database: A retrospective cohort study.

Background and Aims: Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long-term cardiovascular outcomes in Korean patients with hypertension. Methods: Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox-regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan. Results: The median follow-up duration was 5.94 (interquartile range, 5.87-5.97) years. In the crude analysis of all-cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox-regression analysis with adjustment, there was no significant difference in all-cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033-1.127; p = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028-1.106; p = 0.015) were slightly higher. Conclusion: In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long-term mortality and MACEs. Further well-designed prospective studies are required to confirm our findings.

Prediction of functional results of percutaneous coronary interventions with virtual stenting and quantitative flow ratio.

BACKGROUND: The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown. AIM: We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI). METHODS: This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years. RESULTS: We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R = 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R = 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement: -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve [AUC]: 0.856 [0.804-0.909], p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p = 0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p = 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio [HR]: 12.9 [2.32-71.3], p = 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR: 16.98 [2.33-123.29], p = 0.0051). CONCLUSIONS: rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events. CLINICAL TRIAL REGISTRATION: Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560.

Anatomic and Hemodynamic Plaque Characteristics for Subsequent Coronary Events.

Objectives: While coronary computed tomography angiography (CCTA) enables the evaluation of anatomic and hemodynamic plaque characteristics of coronary artery disease (CAD), the clinical roles of these characteristics are not clear. We sought to evaluate the prognostic implications of CCTA-derived anatomic and hemodynamic plaque characteristics in the prediction of subsequent coronary events. Methods: The study cohort consisted of 158 patients who underwent CCTA with suspected CAD within 6-36 months before percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina and age-/sex-matched 62 patients without PCI as the control group. Preexisting high-risk plaque characteristics (HRPCs: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area <4 mm2, or plaque burden ≥70%) and hemodynamic parameters (per-vessel fractional flow reserve [FFRCT], per-lesion ΔFFRCT, and percent ischemic myocardial mass) were analyzed from prior CCTA. The primary outcome was a subsequent coronary event, which was defined as a composite of vessel-specific MI or revascularization for unstable angina. The prognostic impact of clinical risk factors, HRPCs, and hemodynamic parameters were compared between vessels with (160 vessels) and without subsequent coronary events (329 vessels). Results: Vessels with a subsequent coronary event had higher number of HRPCs (2.6 ± 1.4 vs. 2.3 ± 1.4, P = 0.012), lower FFRCT (0.76 ± 0.13 vs. 0.82 ± 0.11, P < 0.001), higher ΔFFRCT (0.14 ± 0.12 vs. 0.09 ± 0.08, P < 0.001), and higher percent ischemic myocardial mass (29.0 ± 18.5 vs. 26.0 ± 18.4, P = 0.022) than those without a subsequent coronary event. Compared with clinical risk factors, HRPCs and hemodynamic parameters showed higher discriminant abilities for subsequent coronary events with ΔFFRCT being the most powerful predictor. HRPCs showed additive discriminant ability to clinical risk factors (c-index 0.620 vs. 0.558, P = 0.027), and hemodynamic parameters further increased discriminant ability (c-index 0.698 vs. 0.620, P = 0.001) and reclassification abilities (NRI 0.460, IDI 0.061, P < 0.001 for all) for subsequent coronary events. Among vessels with negative FFRCT (>0.80), adding HRPCs into clinical risk factors significantly increased discriminant and reclassification abilities for subsequent coronary events (c-index 0.687 vs. 0.576, P = 0.005; NRI 0.412, P = 0.002; IDI 0.064, P = 0.001) but not for vessels with positive FFRCT (≤0.80). Conclusion: In predicting subsequent coronary events, both HRPCs and hemodynamic parameters by CCTA allow better prediction of subsequent coronary events than clinical risk factors. HRPCs provide more incremental predictability than clinical risk factors alone among vessels with negative FFRCT but not among vessels with positive FFRCT. Clinical Trial Registration: PreDiction and Validation of Clinical CoursE of Coronary Artery DiSease With CT-Derived Non-INvasive HemodYnamic Phenotyping and Plaque Characterization (DESTINY Study), NCT04794868.

Surveillance of Arrhythmia in Patients After Myocardial Infarction Using Wearable Electrocardiogram Patch Devices: Prospective Cohort Study.

BACKGROUND: Acute myocardial infarction may be associated with new-onset arrhythmias. Patients with myocardial infarction may manifest serious arrhythmias such as ventricular tachyarrhythmias or atrial fibrillation. Frequent, prolonged electrocardiogram (ECG) monitoring can prevent devastating outcomes caused by these arrhythmias. OBJECTIVE: We aimed to investigate the incidence of arrhythmias in patients following myocardial infarction using a patch-type device-AT-Patch (ATP-C120; ATsens). METHODS: This study is a nonrandomized, single-center, prospective cohort study. We evaluated 71 patients who had had a myocardial infarction and had been admitted to our hospital. The ATP-C120 device was attached to the patient for 11 days and analyzed by 2 cardiologists for new-onset arrhythmic events. RESULTS: One participant was concordantly diagnosed with atrial fibrillation. The cardiologists diagnosed atrial premature beats in 65 (92%) and 60 (85%) of 71 participants, and ventricular premature beats in 38 (54%) and 44 (62%) participants, respectively. Interestingly, 40 (56%) patients showed less than 2 minutes of sustained paroxysmal atrial tachycardia confirmed by both cardiologists. Among participants with atrial tachycardia, the use of ß-blockers was significantly lower compared with patients without tachycardia (70% vs 90%, P=.04). However, different dosages of ß-blockers did not make a significant difference. CONCLUSIONS: Wearable ECG monitoring patch devices are easy to apply and can correlate symptoms and ECG rhythm disturbances in patients following myocardial infarction. Further study is necessary regarding clinical implications and appropriate therapies for arrhythmias detected early after myocardial infarction to prevent adverse outcomes.

Lifestyle Modification in the Management of Metabolic Syndrome: Statement From Korean Society of CardioMetabolic Syndrome (KSCMS).

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients' cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Associations between measurements of central blood pressure and target organ damage in high-risk patients.

BACKGROUND: It is not well-known which components of central blood pressure (CBP) are more influential to target organ damage (TOD). This study aimed to determine the relationship between CBP measurements and various types of TOD in high-risk patients. METHODS: A total of 148 patients who had documented atherosclerotic cardiovascular disease or its multiple risk factors were prospectively enrolled. CBP was measured by using applanation tonometry of the radial artery. The following nine TOD parameters were evaluated: left ventricular mass index, relative wall thickness, septal e' velocity, septal E/e', brachial-ankle pulse wave velocity, ankle-brachial index, estimated glomerular filtration rate, urine protein and obstructive coronary artery disease. RESULTS: The mean age of the study population was 67.1 ± 9.0 years and 108 (73 %) were male. Among four CBP measurements (systolic, diastolic, mean, and pulse pressures), central pulse pressure (CPP) was associated with the largest number of TOD parameters. As CPP increased, the number of TOD increased (P = 0.010), but this association was not observed in other CBP measurements (P > 0.05 for each). CONCLUSIONS: CPP had a stronger correlation with TOD than other CBP measurements. Non-invasive CPP could be a useful indicator for predicting TOD in patients at high coronary risk.

Clinical and Prognostic Impact From Objective Analysis of Post-Angioplasty Fractional Flow Reserve Pullback.

OBJECTIVES: This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings. METHODS: A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient. RESULTS: Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa = 0.633 to 0.819; P < 0.001; intraclass correlation coefficient: 0.776 to 0.901; P < 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P < 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012). CONCLUSIONS: Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Physiological Distribution and Local Severity of Coronary Artery Disease and Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back. BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis. METHODS: The study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years. RESULTS: QFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P < 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P < 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P < 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024). CONCLUSIONS: Both physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560).

Functional Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR. METHODS: The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n = 31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n = 309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up. RESULTS: In the diagnostic cohort, angio-IMR correlated well with IMR (R = 0.778; P < 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR ≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95% CI: 1.670-5.067; P < 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95% CI: 1.157-4.079; P = 0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index = 0.726 vs 0.666 [P < 0.001], net reclassification index = 0.704 [P < 0.001]). CONCLUSIONS: Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

Detection and classification of arrhythmia using an explainable deep learning model.

BACKGROUND: Early detection and intervention is the cornerstone for appropriate treatment of arrhythmia and prevention of complications and mortality. Although diverse deep learning models have been developed to detect arrhythmia, they have been criticized due to their unexplainable nature. In this study, we developed an explainable deep learning model (XDM) to classify arrhythmia, and validated its performance using diverse external validation data. METHODS: In this retrospective study, the Sejong dataset comprising 86,802 electrocardiograms (ECGs) was used to develop and internally variate the XDM. The XDM based on a neural network-backed ensemble tree was developed with six feature modules that are able to explain the reasons for its decisions. The model was externally validated using data from 36,961 ECGs from four non-restricted datasets. RESULTS: During internal and external validation of the XDM, the average area under the receiver operating characteristic curves (AUCs) using a 12­lead ECG for arrhythmia classification were 0.976 and 0.966, respectively. The XDM outperformed a previous simple multi-classification deep learning model that used the same method. During internal and external validation, the AUCs of explainability were 0.925-0.991. CONCLUSION: Our XDM successfully classified arrhythmia using diverse formats of ECGs and could effectively describe the reason for the decisions. Therefore, an explainable deep learning methodology could improve accuracy compared to conventional deep learning methods, and that the transparency of XDM can be enhanced for its application in clinical practice.

Artificial intelligence for detecting electrolyte imbalance using electrocardiography.

INTRODUCTION: The detection and monitoring of electrolyte imbalance is essential for appropriate management of many metabolic diseases; however, there is no tool that detects such imbalances reliably and noninvasively. In this study, we developed a deep learning model (DLM) using electrocardiography (ECG) for detecting electrolyte imbalance and validated its performance in a multicenter study. METHODS AND RESULTS: This retrospective cohort study included two hospitals: 92,140 patients who underwent a laboratory electrolyte examination and an ECG within 30 min were included in this study. A DLM was developed using 83,449 ECGs of 48,356 patients; the internal validation included 12,091 ECGs of 12,091 patients. We conducted an external validation with 31,693 ECGs of 31,693 patients from another hospital, and the result was electrolyte imbalance detection. During internal, the area under the receiving operating characteristic curve (AUC) of a DLM using a 12-lead ECG for detecting hyperkalemia, hypokalemia, hypernatremia, hyponatremia, hypercalcemia, and hypocalcemia were 0.945, 0.866, 0.944, 0.885, 0.905, and 0.901, respectively. The values during external validation of the AUC of hyperkalemia, hypokalemia, hypernatremia, hyponatremia, hypercalcemia, and hypocalcemia were 0.873, 0.857, 0.839, 0.856, 0.831, and 0.813 respectively. The DLM helped to visualize the important ECG region for detecting each electrolyte imbalance, and it showed how the P wave, QRS complex, or T wave differs in importance in detecting each electrolyte imbalance. CONCLUSION: The proposed DLM demonstrated high performance in detecting electrolyte imbalance. These results suggest that a DLM can be used for detecting and monitoring electrolyte imbalance using ECG on a daily basis.

Artificial Intelligence Algorithm for Screening Heart Failure with Reduced Ejection Fraction Using Electrocardiography.

Although heart failure with reduced ejection fraction (HFrEF) is a common clinical syndrome and can be modified by the administration of appropriate medical therapy, there is no adequate tool available to perform reliable, economical, early-stage screening. To meet this need, we developed an interpretable artificial intelligence (AI) algorithm for HFrEF screening using electrocardiography (ECG) and validated its performance. This retrospective cohort study included two hospitals. An AI algorithm based on a convolutional neural network was developed using 39,371 ECG results from 17,127 patients. The internal validation included 3,470 ECGs from 2,908 patients. Furthermore, we conducted external validation using 4,362 ECGs from 4,176 patients from another hospital to verify the applicability of the algorithm across different centers. The end-point was to detect HFrEF, defined as an ejection fraction <40%. We also visualized the regions in 12 lead ECG that affected HFrEF detection in the AI algorithm and compared this to the previously documented literature. During the internal and external validation, the areas under the curves of the AI algorithm using a 12 lead ECG for detecting HFrEF were 0.913 (95% confidence interval, 0.902-0.925) and 0.961 (0.951-0.971), respectively, and the areas under the curves of the AI algorithm using a single-lead ECG were 0.874 (0.859-0.890) and 0.929 (0.911-0.946), respectively. The deep learning-based AI algorithm performed HFrEF detection well using not only a 12 lead but also a single-lead ECG. These results suggest that HFrEF can be screened not only using a 12 lead ECG, as is typical of a conventional ECG machine, but also with a single-lead ECG performed by a wearable device employing the AI algorithm, thereby preventing irreversible disease progression and mortality.