Multimodality Risk Assessment of Patients with Ischemic Heart Disease Using Deep Learning Models Applied to Electrocardiograms and Chest X-rays.

Comprehensive management approaches for patients with ischemic heart disease (IHD) are important aids for prognostication and treatment planning. While single-modality deep neural networks (DNNs) have shown promising performance for detecting cardiac abnormalities, the potential benefits of using DNNs for multimodality risk assessment in patients with IHD have not been reported. The purpose of this study was to investigate the effectiveness of multimodality risk assessment in patients with IHD using a DNN that utilizes 12-lead electrocardiograms (ECGs) and chest X-rays (CXRs), with the prediction of major adverse cardiovascular events (MACEs) being of particular concern.DNN models were applied to detection of left ventricular systolic dysfunction (LVSD) on ECGs and identification of cardiomegaly findings on CXRs. A total of 2107 patients who underwent elective percutaneous coronary intervention were categorized into 4 groups according to the models' outputs: Dual-modality high-risk (n = 105), ECG high-risk (n = 181), CXR high-risk (n = 392), and No-risk (n = 1,429).A total of 342 MACEs were observed. The incidence of a MACE was the highest in the Dual-modality high-risk group (P < 0.001). Multivariate Cox hazards analysis for predicting MACE revealed that the Dual-modality high-risk group had a significantly higher risk of MACE than the No-risk group (hazard ratio (HR): 2.370, P < 0.001), the ECG high-risk group (HR: 1.906, P = 0.010), and the CXR high-risk group (HR: 1.624, P = 0.018), after controlling for confounding factors.The results suggest the usefulness of multimodality risk assessment using DNN models applied to 12-lead ECG and CXR data from patients with IHD.

Cost-Effectiveness of Dapagliflozin for Chronic Kidney Disease in Japan.

BACKGROUND: The cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease (CKD) has not been evaluated in Japan, so we analyzed the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor, for CKD stages 3a and 3b.Methods and Results: We used the Markov model for CKD to assess the costs and benefits associated with and without dapagliflozin from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as per quality-adjusted life-years (QALYs). An ICER <5 million Japanese yen (JPY)/QALY was judged to be cost-effective. The effect of dapagliflozin on renal and cardiovascular events was based on published clinical trials. In patients with CKD stage 3a, the ICER of dapagliflozin over standard treatment was 4.03 million JPY/QALY gained. With a cost-effectiveness threshold of 5 million JPY/QALY gained, the cost-effectiveness probability of dapagliflozin over standard treatment was 52.6%. In patients with CKD stage 3b, the ICER of dapagliflozin over standard treatment was 0.12 million JPY/QALY gained. The cost-effectiveness probability of dapagliflozin over standard treatment was 75.2%. CONCLUSIONS: The results seemed to show acceptable cost-effectiveness when dapagliflozin was used for CKD stage 3b. On the other hand, cost-effectiveness of dapagliflozin for CKD stage 3a was ambiguous, and further validation is needed.

Cost-Effectiveness of Management for Hospitalized Patients.

The cost and/or cost-effectiveness for inpatient management according to the gender of attending physicians remain to be elucidated.Hospitalization costs were extracted from the Diagnosis Procedure Combination (DPC) -based payment system. Using a dataset of 7,457 hospitalized patients with cardiovascular diseases in our hospital from 2012 to 2018, we compared the actual cost of inpatient management by female cardiologists with that by male cardiologists. Next, we estimated the cost-effectiveness of inpatient management according to the gender of the attending cardiologist. The cost of initial hospitalization per patient was similar between the patients treated by a female or male middle-grade cardiologist ($17,527 ± 14,158, versus $17,358 ± 15,183, P = 0.69). As an analysis on cost-effectiveness, the incremental cost of hospitalization managed by male middle-grade cardiologists was $67 per patient as compared with female middle-grade cardiologists. Concordantly, evaluation of the incremental cost-effectiveness ratio per quality-adjusted life year gained showed that the inpatient management by female cardiologists was dominant over that by male cardiologists.Inpatient management by female cardiologists was more cost-effective as compared with that by male cardiologists. Physician gender might have a considerable effect on medical economics.

A Real-World Comparison of 1-Year Survival and Expenditures for Transcatheter Aortic Valve Replacements: SAPIEN 3 Versus CoreValve Versus Evolut R.

OBJECTIVES: New versions of balloon-expandable and self-expandable valves for transcatheter aortic valve replacement (TAVR) have been developed, but few studies have examined the outcomes associated with these devices using national-level data. This study aimed to elucidate the clinical and economic outcomes of TAVR for aortic stenosis in Japan through an analysis of real-world data. METHODS: This retrospective cohort study was performed using data from patients with aortic stenosis who had undergone transfemoral TAVR with Edwards SAPIEN 3, Medtronic CoreValve, or Medtronic Evolut R valves throughout Japan from April 2016 to March 2018. Pacemaker implantation, mortality, and health expenditure were examined for each valve type during hospitalization and at 1 month, 3 months, 6 months, and 1 year. Generalized linear regression models and Cox proportional hazards models were used to examine the associations between the valve types and outcomes. RESULTS: We analyzed 7244 TAVR cases (SAPIEN 3: 5276, CoreValve: 418, and Evolut R: 1550) across 145 hospitals. The adjusted 1-year expenditures for SAPIEN 3, CoreValve, and Evolut R were $79 402, $76 125, and $75 527, respectively; SAPIEN 3 was significantly more expensive than the other valves (P < .05). The pacemaker implantation hazard ratios (95% confidence intervals) for CoreValve and Evolut R were significantly higher (P < .001) than SAPIEN 3 at 2.61 (2.07-3.27) and 1.80 (1.53-2.12), respectively. The mortality hazard ratios (95% confidence intervals) for CoreValve and Evolut R were not significant at 1.11 (0.84-1.46) and 1.22 (0.97-1.54), respectively. CONCLUSIONS: SAPIEN 3 users had generally lower pacemaker implantation and mortality but higher expenditures than CoreValve and Evolut R users.

Cost-Effectiveness of Obstructive Sleep Apnea Screening and Treatment Before Catheter Ablation for Symptomatic Atrial Fibrillation.

Background: Although management of obstructive sleep apnea (OSA) has been recommended to improve outcomes of catheter ablation (CA) in patients with symptomatic atrial fibrillation (AF), the most cost-effective way of preprocedural OSA screening is undetermined. This study assessed the cost-effectiveness of OSA management before CA for symptomatic AF. Methods and Results: A Markov model was developed to assess the cost-effectiveness of 3 OSA detection strategies before CA: no screening; Type 3 portable monitor (PM)-guided screening; and polysomnography (PSG)-guided screening. The target population consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with 50% prevalence of OSA. We used a 5-year horizon, with sensitivity analyses for significant variables and scenario analyses for lower and higher OSA prevalence (30% and 70%, respectively). In the base-case, both types of OSA screening were dominant (less costly and more effective) relative to no screening. Although PSG-guided management was more effective than PM-guided management, it was more costly and therefore did not show clear benefit. These findings were replicated in cohorts with lower and higher OSA risks. Conclusions: OSA screening before CA is cost-effective in patients with symptomatic AF, with PM screening being the most cost-effective. Physicians should consider OSA management using this simple tool in the decision making for treatment of symptomatic AF.

Cost-Effectiveness of Percutaneous Coronary Intervention Compared With Medical Therapy for Ischemic Heart Disease in Japan.

BACKGROUND: The cost-effectiveness of percutaneous coronary intervention (PCI) for ischemic heart disease is undetermined in Japan. The aim of this study was to analyze the cost-effectiveness of PCI compared with medical therapy for ST-elevation myocardial infarction (STEMI) and angina pectoris (AP) in Japan.Methods and Results:We used Markov models for STEMI and AP to assess the costs and benefits associated with PCI or medical therapy from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), and ICER <¥5 m per QALY gained was judged to be cost-effective. The impact of PCI on cardiovascular events was based on previous publications. In STEMI patients, the ICER of PCI over medical treatment was ¥0.97 m per QALY gained. The cost-effectiveness probability of PCI was 99.9%. In AP patients, the ICER of fractional flow reserve (FFR)-guided PCI over medical treatment was ¥4.63 m per QALY gained. The cost-effectiveness probability of PCI was 50.4%. The ICER of FFR-guided PCI for asymptomatic patients was ¥23 m per QALY gained. CONCLUSIONS: In STEMI patients, PCI was cost-effective compared with medical therapy. In AP patients, FFR-guided PCI for symptomatic patients could be cost-effective compared with medical therapy. FFR-guided PCI for asymptomatic patients with myocardial ischemia was not cost-effective.

Cost-Effectiveness of PCSK9 Inhibitor Plus Statin in Patients With Triple-Vessel Coronary Artery Disease in Japan.

BACKGROUND: The addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces the rate of cardiovascular events. This study examined the cost-effectiveness of PCSK9 inhibitor+statin compared with standard therapy (statin monotherapy) in the treatment of triple-vessel coronary artery disease (CAD) in Japan. Methods and Results: A Markov model was applied to assess the costs and benefits associated with PCSK9 inhibitor+statin over a projected 30-year period from the perspective of a public healthcare payer in Japan. The incremental cost-effectiveness ratio (ICER), expressed as the quality-adjusted life-years (QALYs), was estimated. The effects on survival and numbers of events were based on the FOURIER trial and the CREDO Kyoto registry. The ICER of PCSK9 inhibitor+statin over standard therapy was 13.5 million (95% confidence interval 7.6-23.5 million) Japanese Yen (JPY) per QALY gained for triple-vessel CAD. The probability of the cost-effectiveness of PCSK9 inhibitor+statin vs. standard therapy was 0.0008% at a cost-effectiveness threshold of 5 million JPY. In patients with poorly controlled familial hypercholesterolemia (FH) with triple-vessel CAD, the ICER was 3.4 million JPY per QALY gained. CONCLUSIONS: PCSK9 inhibitor plus statin did not show good cost-effectiveness for triple-vessel CAD; however, it showed good cost-effectiveness for patients with triple-vessel CAD and poorly controlled FH in Japan.

Cost-Effectiveness of Statin Plus Eicosapentaenoic Acid Combination Therapy for Cardiovascular Disease Prevention in Japanese Patients With Hypercholesterolemia　- An Analysis Based on the Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS).

BACKGROUND: The addition of eicosapentaenoic acid (EPA) to statin therapy has been shown to reduce cardiovascular events. This study examined the cost-effectiveness of EPA plus statin (EPA+statin) combination therapy compared with statin monotherapy for primary and secondary prevention of cardiovascular disease (CVD) in Japan.Methods and Results:A Markov model was applied to assess the costs and benefits associated with EPA+statin combination therapy over a projected 30-year period from the perspective of a public healthcare funder in Japan. The incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), was estimated for primary prevention and secondary prevention of CVD in patients with hypercholesterolemia. Impact on survival and number of events were based on the Japan EPA Lipid Intervention Study. Sensitivity analyses examined the influence of various input parameters on costs and outcomes of treatment. ICER was ¥29.6 million per QALY gained in primary prevention and ¥5.5 million per QALY gained in secondary prevention. The probabilities that EPA+statin combination therapy would be cost-effective compared with statin monotherapy were 39% in primary prevention and 49% in secondary prevention at a cost-effectiveness threshold of ¥5 million per QALY gained. Sensitivity analyses showed that EPA was cost-effective in secondary prevention. CONCLUSIONS: EPA+statin combination therapy showed acceptable cost-effectiveness for secondary prevention, but not primary prevention, of CVD in patients with hypercholesterolemia in Japan.

Cost effectiveness of transcatheter aortic valve implantation in patients with aortic stenosis in Japan.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a less invasive treatment for elderly patients with aortic stenosis. However, the cost of TAVI is a major issue. This study analyzed the cost effectiveness of TAVI in Japan. METHODS: We developed an economic model to evaluate the quality-adjusted life years (QALYs) and costs of TAVI, surgical aortic valve replacement (SAVR), and medical therapy over a 10-year time horizon from the perspective of Japanese public healthcare payers. The first model compared transapical or transfemoral TAVI with Sapien valve implantation and medical therapy in inoperable patients. The second model compared transfemoral TAVI with Sapien XT valve implantation and SAVR in operable patients with intermediate surgical risk. We assumed a cost-effectiveness threshold of 5,000,000yen per QALY, and assessed the cost-effectiveness probability with 100,000 simulations. We performed a broad sensitivity analysis to assess the effect of uncertainty on our results. RESULTS: Among inoperable patients, the incremental cost-effectiveness ratio for TAVI compared with medical therapy was 3,918,808yen per QALY. In operable patients, the incremental cost-effectiveness ratio for TAVI compared with SAVR was 7,523,821yen per QALY. The cost-effectiveness probability of TAVI was 60% for inoperable patients and 46% for operable patients. Among inoperable patients, the cost-effective threshold of TAVI was <7,759,085yen. Among operable patients, the cost-effective threshold of TAVI was <5,427,439yen. CONCLUSIONS: This study suggests that TAVI has good cost effectiveness for inoperable patients, but not for operable patients.

Cost-Effectiveness Analysis of Cardiovascular Disease Treatment in Japan.

The quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) are important concepts in cost-effectiveness analysis, which is becoming increasingly important in Japan. QALY is used to estimate quality of life (QOL) and life years, and can be used to compare the efficacies of cancer and cardiovascular treatments. ICER is defined as the difference in cost between treatments divided by the difference in their effects, with a smaller ICER indicating better cost-effectiveness. Here, we present a review of cost-effectiveness analyses in Japan as well other countries. A number of treatments were shown to be cost-effective, e.g., statin for secondary prevention of cardiovascular disease, aspirin for primary prevention of cardiovascular disease, DOAC for high-risk atrial fibrillation, beta blockers, ACE inhibitors, and ARB for heart failure, sildenafil and bosentan for pulmonary hypertension, CABG for multi-vessel coronary disease, ICD for ventricular tachycardia, and CRT for heart failure with low ejection fraction, while others were not cost-effective, e.g., epoprostenol for pulmonary hypertension and LVAD for end-stage heart failure. Further investigations are required regarding some treatments, e.g., PCSK-9 inhibitors for familial hypercholesterolemia, PCI for multi-vessel coronary disease, catheter ablation for atrial fibrillation, and TAVI for severe aortic stenosis. Ethical aspects should be taken into consideration when utilizing the results of cost-effectiveness analysis in medical policy.