ObjectiveThe biological age progression of the heart varies from person to person. We developed a deep learning model (DLM) to predict the biological age via ECG to explore its contribution to future cardiovascular diseases (CVDs).MethodsThere were 71,741 cases ranging from 20 to 80 years old recruited from the health examination center. The development set used 32,707 cases to train the DLM for estimating the ECG-age, and 8,295 cases were used as the tuning set. The validation set included 30,469 ECGs to follow the outcomes, including all-cause mortality, cardiovascular-cause mortality, heart failure (HF), diabetes mellitus (DM), chronic kidney disease (CKD), acute myocardial infarction (AMI), stroke (STK), coronary artery disease (CAD), atrial fibrillation (AF), and hypertension (HTN). Two independent external validation sets (SaMi-Trop and CODE15) were also used to validate our DLM.ResultsThe mean absolute errors of chronologic age and ECG-age was 6.899 years (r = 0.822). The higher difference between ECG-age and chronological age was related to more comorbidities and abnormal ECG rhythm. The cases with the difference of more than 7 years had higher risk on the all-cause mortality [hazard ratio (HR): 1.61, 95% CI: 1.23–2.12], CV-cause mortality (HR: 3.49, 95% CI: 1.74–7.01), HF (HR: 2.79, 95% CI: 2.25–3.45), DM (HR: 1.70, 95% CI: 1.53–1.89), CKD (HR: 1.67, 95% CI: 1.41–1.97), AMI (HR: 1.76, 95% CI: 1.20–2.57), STK (HR: 1.65, 95% CI: 1.42–1.92), CAD (HR: 1.24, 95% CI: 1.12–1.37), AF (HR: 2.38, 95% CI: 1.86–3.04), and HTN (HR: 1.67, 95% CI: 1.51–1.85). The external validation sets also validated that an ECG-age >7 years compare to chronologic age had 3.16-fold risk (95% CI: 1.72–5.78) and 1.59-fold risk (95% CI: 1.45–1.74) on all-cause mortality in SaMi-Trop and CODE15 cohorts. The ECG-age significantly contributed additional information on heart failure, stroke, coronary artery disease, and atrial fibrillation predictions after considering all the known risk factors.ConclusionsThe ECG-age estimated via DLM provides additional information for CVD incidence. Older ECG-age is correlated with not only on mortality but also on other CVDs compared with chronological age.

Background: It is unknown whether direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic-valve replacement (TAVR). Also, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) in patients who had undergone successful TAVR and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on four-dimensional computed tomography (CT) at 6-month. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging (MRI) and the serial changes of neurological and neurocognitive function between 6-month and immediate post-TAVR. Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group than in the DAPT group (9.8% vs. 18.4%; absolute difference, −8.5%; 95% confidence interval [CI], −17.8% to 0.8%; P=0.076). The percentage of patients with new cerebral lesions on brain MRI (edoxaban vs. DAPT; 25.0% vs. 20.2%; difference, 4.8%; 95% CI, −6.4% to 16.0%) and median total new lesion number and volume were not different between two groups. Also, the percentages of patients with worsening of neurological and neurocognitive function were not different among the groups. The incidence of any or major bleeding events were not different between two groups. We found no significant association of the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. Conclusions: In patients without an indication for long-term anticoagulation after successful TAVR, the incidence of leaflet thrombosis was numerically lower with edoxaban than with DAPT, but this was not statistically significant. The effect on new cerebral thromboembolism and neurological or neurocognitive function were also not different between two groups. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research.

Background: glycated hemoglobin (HbA1c) provides information on diabetes mellitus (DM) management. Electrocardiography (ECG) is a noninvasive test of cardiac activity that has been determined to be related to DM and its complications. This study developed a deep learning model (DLM) to estimate HbA1c via ECG. Methods: there were 104,823 ECGs with corresponding HbA1c or fasting glucose which were utilized to train a DLM for calculating ECG-HbA1c. Next, 1539 cases from outpatient departments and health examination centers provided 2190 ECGs for initial validation, and another 3293 cases with their first ECGs were employed to analyze its contributions to DM management. The primary analysis was used to distinguish patients with and without mild to severe DM, and the secondary analysis was to explore the predictive value of ECG-HbA1c for future complications, which included all-cause mortality, new-onset chronic kidney disease (CKD), and new-onset heart failure (HF). Results: we used a gender/age-matching strategy to train a DLM to achieve the best AUCs of 0.8255 with a sensitivity of 71.9% and specificity of 77.7% in a follow-up cohort with correlation of 0.496 and mean absolute errors of 1.230. The stratified analysis shows that DM presented in patients with fewer comorbidities was significantly more likely to be detected by ECG-HbA1c. Patients with higher ECG-HbA1c under the same Lab-HbA1c exhibited worse physical conditions. Of interest, ECG-HbA1c may contribute to the mortality (gender/age adjusted hazard ratio (HR): 1.53, 95% conference interval (CI): 1.08–2.17), new-onset CKD (HR: 1.56, 95% CI: 1.30–1.87), and new-onset HF (HR: 1.51, 95% CI: 1.13–2.01) independently of Lab-HbA1c. An additional impact of ECG-HbA1c on the risk of all-cause mortality (C-index: 0.831 to 0.835, p < 0.05), new-onset CKD (C-index: 0.735 to 0.745, p < 0.01), and new-onset HF (C-index: 0.793 to 0.796, p < 0.05) were observed in full adjustment models. Conclusion: the ECG-HbA1c could be considered as a novel biomarker for screening DM and predicting the progression of DM and its complications.

Background: Accumulated experience and advances in device technology have led to the increasing off-label use of transcatheter aortic valve replacement (TAVR) for pure native aortic valve regurgitation (PNAR). This study aimed to evaluate the procedural and long-term outcomes of using newer-generation transcatheter heart valves (THVs) versus early-generation self-expanding CoreValve (Medtronic, Minneapolis, USA) to treat PNAR. Methods: TAVRs were performed with the use of early-(N=15) and newer-generation (N=10) THVs in a total of 25 consecutive PNAR patients at an intermediate-to-high risk for surgical aortic valve replacement [mean Society of Thoracic Surgeons (STS) score of 6.8±4.5]. Procedural and clinical outcomes were reported according to the Valve Academic Research Consortium 2 criteria. The primary end-point of the study was all-cause mortality, myocardial infarction (MI), disabling stroke, and readmission due to heart failure. Results:The device success rate of the newer-generation THVs was significantly higher than that of the early-generation CoreValve (100% vs. 33%, P<0.01), which was mainly driven by less frequent need for implanting a second THV (0% vs. 53%, P<0.01). Although the procedural success rates were 100% for both early-and newer-generation valves, the mean procedure fluoroscopic times which the newer-generation device group required, were significantly shorter (P<0.01) and the amount of contrast medium used in this group, markedly smaller (P<0.01), compared to those of the early-generation CoreValve group. During a median follow-up of 14 months, event-free survival was better in patients undergoing TAVR with the newer-generation THVs, although the differences were not statistically significant (log-rank test, P=0.137).According to multivariate analysis, a higher baseline STS score and longer intensive care unit stays are independent predictors of adverse outcomes.Conclusions: Evidently, the treatment of PNAR with TAVR using the newer-generation THVs yielded better procedural outcomes and is a valuable therapeutic option in selective patients.

Purpose: In this study, transapical transcatheter mitral valve-in-valve implantation (TAMVI) was compared with surgical redo mitral valve replacement (SRMVR) in terms of clinical outcomes.Methods: We retrospectively identified patients with degenerated mitral bioprosthesis or failed annuloplasty rings who underwent redo SRMVR or TAMVI at our medical center. Clinical outcomes were based on echocardiography results.Results: We retrospectively identified patients with symptomatic mitral bioprosthetic valve dysfunction (n = 58) and failed annuloplasty rings (n = 14) who underwent redo SRMVR (n = 36) or TAMVI (n = 36). The Society of Thoracic Surgeons Predicted Risk of Mortality scores were higher in the TAMVI group (median: 9.52) than in the SRMVR group (median: 5.59) (p-value = 0.02). TAMVI patients were more severe in New York Heart Association (p-value = 0.04). The total procedure time (skin to skin) and length of stay after procedures were significantly shorter in the TAMVI group, and no significant difference in mortality was noted after adjustment for confounding factors (p-value = 0.11). The overall mean mitral valve pressure gradient was lower in the TAMVI group than in the SRMVR group at 24 months (p &lt; 0.01). Both groups presented a decrease in the severity of mitral and tricuspid regurgitation at 3–24 months.Conclusions: In conclusion, the statistical analysis is still not robust enough to make a claim that TAMVI is an appropriate alternative. The outcome of the patient appears only to be related to the patient's pre-operative STS score. Additional multi-center, longitudinal studies are warranted to adequately assess the effect of TAMVI.

Rationale:Pulmonary embolism is a potentially devastating medical condition. Although deep-vein thrombosis is the most common etiology, a nonthrombotic pulmonary embolism is not uncommon.Patient concerns:A 45-year-old woman was admitted to our hospital for progressive effort dyspnea for 3 weeks.Diagnosis:Echocardiography revealed a mobile mass extending from the right atrium to the bilateral proximal pulmonary artery. As the mass was no response to thrombotic therapy, intravenous leiomyomatosis was suspected. Computed tomography (CT) revealed a hypo-attenuated tumor extending from the ovarian vein to the pulmonary artery.Interventions:A 1-stage operation for the surgical removal of the tumor, right salpingo-oophorectomy and subtotal hysterectomy were performed. Surgical specimen was identified as uterine leiomyomatosis without malignant transformation.Outcomes:The patient was followed- up for 2 years and subsequent CT did not reveal any notable lesions.Lessons:Nonthrombotic pulmonary embolism is a potentially life-threatening complication. This case indicated intravenous leiomyomatosis should be considered in the differential diagnosis for certain cases. Complete surgical excision was the only curative treatment.

BackgroundAlbumin, an important component of fluid balance, is associated with kidney, liver, nutritional, and cardiovascular diseases (CVD) and is measured by blood tests. Since fluid balance is associated with electrocardiography (ECG) changes, we established a deep learning model (DLM) to estimate albumin via ECG.ObjectiveThis study aimed to develop a DLM to estimate albumin via ECG and explored its contribution to future complications.Materials and MethodsA DLM was trained for estimating ECG-based albumin (ECG-Alb) using 155,078 ECGs corresponding to albumin from 79,111 patients, and another independent 13,335 patients from an academic medical center and 11,370 patients from a community hospital were used for internal and external validation. The primary analysis focused on distinguishing patients with mild to severe hypoalbuminemia, and the secondary analysis aimed to provide additional prognostic value from ECG-Alb for future complications, which included mortality, new-onset hypoalbuminemia, chronic kidney disease (CKD), new onset hepatitis, CVD mortality, new-onset acute myocardial infarction (AMI), new-onset stroke (STK), new-onset coronary artery disease (CAD), new-onset heart failure (HF), and new-onset atrial fibrillation (Afib).ResultsThe AUC to identify hypoalbuminemia was 0.8771 with a sensitivity of 56.0% and a specificity of 90.7% in the internal validation set, and the Pearson correlation coefficient was 0.69 in the continuous analysis. The most important ECG features contributing to ECG-Alb were ordered in terms of heart rate, corrected QT interval, T wave axis, sinus rhythm, P wave axis, etc. The group with severely low ECG-Alb had a higher risk of all-cause mortality [hazard ratio (HR): 2.45, 95% CI: 1.81–3.33] and the other hepatorenal and cardiovascular events in the internal validation set. The external validation set yielded similar results.ConclusionHypoalbuminemia and its complications can be predicted using ECG-Alb as a novel biomarker, which may be a non-invasive tool to warn asymptomatic patients.

ObjectiveCurrent guidelines recommend that transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) with aortic stenosis (AS) should only be performed in selected patients. However, we consider it even more crucial to identify what the really important factors are while determining long-term outcomes in patients with BAV undergoing TAVR, which is precisely the aim of this study.MethodsWe retrospectively evaluated consecutive patients who underwent TAVR with balloon-expandable Sapien XT or Sapien 3 valves (Edwards Lifesciences, Irvine, CA) for the treatment of severe bicuspid AS. The primary end points were major adverse cardiac and cerebral events (MACCE), that is, mortality, non-fatal myocardial infarction (MI), disabling stroke, valve failure needing reintervention, or clinically relevant valve thrombosis during follow-up.ResultsA total of 56 patients who underwent TAVR with Sapien XT (n = 20) or Sapien 3 (n = 36) were included. The device and procedural success rates were similar between the two TAVR valves; however, the newer-generation Sapien 3 yielded a trend toward better long-term clinical outcomes than the early-generation Sapien XT did (MACCE rates 35 vs. 11%, p = 0.071). In the multivariate Cox proportional hazards analyses, the presence of calcified raphe &gt; 4 mm was the only independent predictor of long-term MACCE (hazard ratio: 6.76; 95% confidence interval: 1.21–37.67, p = 0.029).ConclusionTAVR performed by a skilled heart team, while using newer-generation balloon-expandable Sapien 3 valve, may yield better long-term clinical outcomes compared to TAVR using early-generation Sapien XT valve. Moreover, the presence of calcified raphe &gt;4 mm is an independent determinant of adverse clinical outcomes.