Cost-effective analysis of transcatheter aortic valve replacement in patients with severe symptomatic aortic stenosis: A prospective multicenter study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) does not benefit all patients. We performed a prospective multicenter study to investigate the cost-effectiveness of TAVR in a Japanese cohort. METHODS AND RESULTS: We prospectively enrolled 110 symptomatic patients with severe AS who underwent TAVR from five institutions. The quality of life measurement (QOL) was performed for each patient before and at 6 months after TAVR. Patients without an improvement in QOL at 6 months after TAVR were defined as non-responders. Pre-TAVR higher QOL, higher clinical frailty scale predicted the non-responders. Three models, 1) conservative treatment for all patients strategy, 2) TAVR for all patients strategy, and 3) TAVR for a selected patient strategy who is expected to be a responder, were simulated. Lifetime cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. In comparison to conservative therapy for all patients, ICER was estimated to be 5,765,800 yen/QALY for TAVR for all patients and 2,342,175 yen/QALY for TAVR for selected patient strategy patients, which is less than the commonly accepted ICER threshold of 5,000,000 yen/QALY. CONCLUSIONS: TAVR for selected patient strategy model is more cost-effective than TAVR for all patient strategy without reducing QOL in the Japanese healthcare system. TAVR for selected patient strategy has potential benefit for optimizing the TAVR treatment in patients with high frailty and may direct our resources toward beneficial interventions.

Cardiovascular Hospitalizations and Hospitalization Costs in Japan During the COVID-19 Pandemic.

Background: During the COVID-19 pandemic, cardiovascular hospitalizations decreased and in-hospital mortality for ST-elevation myocardial infarction and heart failure increased. However, limited research has been conducted on hospitalization and mortality rates for cardiovascular disease (CVD) other than ischemic heart disease and heart failure. Methods and Results: We analyzed the records of 530 certified hospitals affiliated with the Japanese Circulation Society obtained from the nationwide JROAD-DPC database between April 2014 and March 2021. A quasi-Poisson regression model was used to predict the counterfactual number of hospitalizations for CVD treatment, assuming there was no pandemic. The observed number of inpatients compared with the predicted number in 2020 was 88.1% for acute CVD, 78% for surgeries or procedures, 77.2% for catheter ablation, and 68.5% for left ventricular assist devices. Furthermore, there was no significant change in in-hospital mortality, and the decrease in hospitalizations for catheter ablation and valvular heart disease constituted 47.6% of the total decrease in annual hospitalization costs during the COVID-19 pandemic. Conclusions: Cardiovascular hospitalizations decreased by more than 10% in 2020, and the number of patients scheduled for left ventricular assist device implantation decreased by over 30%. In addition, in response to the COVID-19 pandemic, annual cardiovascular hospitalization costs were reduced, largely attributed to decreased catheter ablation and valvular heart disease.

Validity of Diagnostic Algorithms for Cardiovascular Diseases in Japanese Health Insurance Claims.

BACKGROUND: We aimed to validate a claims-based diagnostic algorithm to identify hospitalized patients with acute major cardiovascular diseases (CVDs) from health insurance claims in Japan.Methods and Results: This retrospective multicenter validation study was conducted at 4 institutes, including Japanese Circulation Society-certified and uncertified hospitals in Japan. Data on patients with CVDs in departmental lists or with International Classification of Diseases, 10th Revision (ICD-10) codes for CVDs hospitalized between April 2018 and March 2019 were extracted. We examined the sensitivity and positive predictive value of a diagnostic algorithm using ICD-10 codes, medical examinations, and treatments for acute coronary syndrome (ACS), acute heart failure (HF), and acute aortic disease (AAD). We identified 409 patients with ACS (mean age 70.6 years; 24.7% female), 615 patients with acute HF (mean age 77.3 years; 46.2% female), and 122 patients with AAD (mean age 73.4 years; 36.1% female). The respective sensitivity and positive predictive value for the algorithm were 0.86 (95% confidence interval [CI] 0.82-0.89) and 0.95 (95% CI 0.92-0.97) for ACS; 0.74 (95% CI 0.70-0.77) and 0.79 (95% CI 0.76-0.83) for acute HF; and 0.86 (95% CI 0.79-0.92) and 0.83 (95% CI 0.76-0.89) for AAD. CONCLUSIONS: The validity of the diagnostic algorithm for Japanese claims data was acceptable. Our results serve as a foundation for future studies on CVDs using nationwide administrative data.

Hospital-associated disability and hospitalization costs for acute heart failure stratified by body mass index- insight from the JROAD/JROAD-DPC database.

BACKGROUND: The impact of body mass index (BMI) on hospital mortality in patients with acute heart failure has been well documented in Asian populations. However, the relationship between BMI, hospital-associated disability (HAD), and hospitalization costs in patients with heart failure is poorly understood. This study aimed to explore the impact of BMI on HAD and hospitalization costs for acute heart failure in Japan. METHODS: From April 2012 to March 2020, the Japanese Registry of All Cardiac and Vascular Disease Diagnosis Procedure Combination (JROAD-DPC) database was used to identify patients with acute heart failure. All patients were categorized into five groups according to the World Health Organization Asian BMI criteria. The hospitalization costs and HAD were evaluated. RESULTS: Among the 238,160 eligible patients, 15.7% were underweight, 42.2% were normal, 16.7% were overweight, 19.3% were obese I, and 6.0% were obese II, according to BMI. The prevalence of HAD was 7.43% in the total cohort, and the risk of HAD increased with a lower BMI. Restricted cubic spline analysis showed a U-shaped relationship between BMI and hospitalization costs for all ages. Furthermore, developing HAD was associated with greater costs compared with non-HAD, regardless of BMI category. CONCLUSIONS: We found that the lower the BMI, the higher the incidence of HAD. A U-shaped association was confirmed between BMI and hospitalization costs, indicating that hospitalization costs increased for both lower and higher BMI regardless of age. BMI could be an important and informative risk stratification tool for functional outcomes and economic burdens.

Relationship Between Heart Failure Hospitalization Costs and Left Ventricular Ejection Fraction in an Advanced Aging Society.

Background: Left ventricular ejection fraction (LVEF) is a basic clinical index that determines the heart failure (HF) treatment strategy. We aimed to evaluate the association between hospitalization costs for HF patient and LVEF in an advanced aging society in a region in Japan. Methods and Results: Consecutive HF patients admitted to Miyazaki Prefectural Nobeoka Hospital between January 2015 and March 2018 were included in the study. The 346 HF patients (mean age 78 years) were divided into 2 groups: HF with reduced ejection fraction (HFrEF; LVEF <40%; n=129) and HF with preserved ejection fraction (HFpEF; LVEF ≥40%; n=217). Median hospitalization costs (in 2017 US dollars) were higher in the HFrEF than HFpEF group, but the difference was not statistically significant ($7,128 vs. $6,580; P=0.189). However, in older adults (age ≥75 years; n=252), median hospitalization costs were significantly higher in the HFrEF than HFpEF group ($7,240 vs. $6,471; P=0.014), and LVEF was an independent factor of hospitalization costs (ß=-0.0301, P=0.006). Median hospitalization costs were significantly lower in the older than younger HFpEF group ($6,471 vs. $7,250; P=0.011), but there was no significant difference in costs between the older and younger HFrEF groups ($7,240 vs. $6,760; P=0.351). Conclusions: The relationship between LVEF and hospitalization costs became more pronounced with age, and LVEF was a negative independent factor for hospitalization costs in the older population.

Association of PM2.5 exposure with hospitalization for cardiovascular disease in elderly individuals in Japan.

Although exposure to particulate matter with aerodynamic diameters ≤ 2.5 µm (PM2.5) influences cardiovascular disease (CVD), its association with CVD-related hospitalizations of super-aged patients in Japan remains uncertain. We investigated the relationship between short-term PM2.5 exposure and CVD-related hospitalizations, lengths of hospital stays, and medical expenses. We analyzed the Japanese national database of patients with CVD (835,405) admitted to acute-care hospitals between 2012 and 2014. Patients with planned hospitalizations and those with missing PM2.5 exposure data were excluded. We classified the included patients into five quintiles based on their PM2.5 exposure: PM-5, -4, -3, -2, and -1 groups, in descending order of concentration. Compared with the PM-1 group, the other groups had higher hospitalization rates. The PM-3, -4, and -5 groups exhibited increased hospitalization durations and medical expenses, compared with the PM-1 group. Interestingly, the hospitalization period was longer for the ≥ 90-year-old group than for the ≤ 64-year-old group, yet the medical expenses were lower for the former group. Short-term PM2.5 exposure is associated with increased CVD-related hospitalizations, hospitalization durations, and medical expenses. The effects of incident CVDs were more marked in elderly than in younger patients. National PM2.5 concentrations should be reduced and the public should be aware of the risks.

Correction to: Three-dimensional assessment of coronary high-intensity plaques with T1-weighted cardiovascular magnetic resonance imaging to predict periprocedural myocardial injury after elective percutaneous coronary intervention.

In the original publication of this article [1] the wording of '3Di-PMR' was different between the text and figures.

Three-dimensional assessment of coronary high-intensity plaques with T1-weighted cardiovascular magnetic resonance imaging to predict periprocedural myocardial injury after elective percutaneous coronary intervention.

BACKGROUND: Periprocedural myocardial injury (pMI) is a common complication of elective percutaneous coronary intervention (PCI) that reduces some of the beneficial effects of coronary revascularization and impacts the risk of cardiovascular events. We developed a 3-dimensional volumetric cardiovascular magnetic resonance (CMR) method to evaluate coronary high intensity plaques and investigated their association with pMI after elective PCI. METHODS: Between October 2012 and October 2016, 141 patients with stable coronary artery disease underwent T1-weighted CMR imaging before PCI. A conventional 2-dimensional CMR plaque-to-myocardial signal intensity ratio (2D-PMR) and the newly developed 3-dimensional integral of PMR (3Di-PMR) were measured. 3Di-PMR was determined as the sum of PMRs above a threshold of > 1.0 for voxels in a target plaque. pMI was defined as high-sensitivity cardiac troponin T > 0.07 ng/mL. RESULTS: pMI following PCI was observed in 46 patients (33%). 3Di-PMR was significantly higher in patients with pMI than those without pMI. The optimal 3Di-PMR cutoff value for predicting pMI was 51 PMR*mm3 and the area under the receiver operating characteristic curve (0.753) was significantly greater than that for 2D-PMR (0.683, P = 0.015). 3Di-PMR was positively correlated with lipid volume (r = 0.449, P < 0.001) based on intravascular ultrasound. Stepwise multivariable analysis showed that 3Di-PMR ≥ 51 PMR*mm3 and the presence of a side branch at the PCI target lesion site were significant predictors of pMI (odds ratio [OR], 11.9; 95% confidence interval [CI], 4.6-30.4, P < 0.001; and OR, 4.14; 95% CI, 1.6-11.1, P = 0.005, respectively). CONCLUSIONS: 3Di-PMR coronary assessment facilitates risk stratification for pMI after elective PCI. TRIAL REGISTRATION: retrospectively registered.

Sex differences in Japanese patients with ruptured aortic aneurysms.

OBJECTIVE: This study aimed to assess the sex differences in clinical presentation and outcomes of Japanese patients with ruptured aortic aneurysm (rAA) using a large nationwide claims-based database in Japan. METHODS: We identified patients hospitalized in certified teaching hospitals in Japan with rAA between April 1, 2012, and March 31, 2015. Patients' characteristics and in-hospital outcomes were compared between men and women. The Barthel index was used for evaluating functional status at discharge by examining the ability to perform basic daily activities. RESULTS: Of 7086 eligible patients, 32.3% (2291/7086) were women. Women were older than men (81.9 years vs 76.1 years; P < .001), had higher prevalence of coma at admission (33.2% vs 25.2%; P < .001), and were less likely to undergo emergency operation including endovascular aneurysm repair (35.7% vs 51.1%; P < .001). The unadjusted mortality rate (62.5% vs 52.0%; P < .001) and Barthel index at discharge (78.7 vs 86.1; P < .001) were significantly worse in women than in men. However, multilevel mixed-effect logistic regression analyses showed that female sex itself was not an independent predictor for in-hospital death (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.04; P = .17). Older age, coma at admission, and vasopressor use were detected as independent predictors for in-hospital death. The same results were confirmed for each rupture site. Stratified analyses showed that older women (threshold, 80 years; OR, 0.81; 95% CI, 0.66-0.98; P = .028) and those who underwent emergency operation (OR, 0.75; 95% CI, 0.61-0.93; P = .009) showed significantly better outcomes than men. CONCLUSIONS: In a univariate analysis, female patients with rAA showed worse mortality than men because of their older age, more severe clinical presentation, and low emergency operation rate. However, after adjustment for covariates, female sex itself was not associated with increased mortality.

Primary Percutaneous Coronary Intervention in Elderly Patients With Acute Myocardial Infarction　- An Analysis From a Japanese Nationwide Claim-Based Database.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) is strongly recommended by guidelines for patients presenting with acute myocardial infarction (AMI), but its applications in elderly patients are less clear.Methods and Results:The JROAD-DPC is a Japanese nationwide registry for patients with cardiovascular diseases combined with an administrative claim-based database. Among 2,369,165 records from 2012 to 2015, data for 115,407 AMI patients were extracted for this study. Elderly patients (≥75 years) comprised 45,645 subjects (39.6%), and received pPCI less frequently (62.2%) than younger patients (79.2%, P<0.001). Clinical variables such as higher age, female sex, higher Killip class, and renal dysfunction, but not functional status on admission, were predictors of non-application of pPCI. Endpoint 30-day mortality increased with aging, and was significantly higher in elderly patients (10.7%) than in younger patients (3.8%, P<0.001). Indeed, pPCI was independently associated with lower 30-day mortality only in subgroups of patients aged ≥60 years. Propensity score-matching analysis confirmed a similar reduction in endpoint 30-day mortality with pPCI in elderly patients. Duration of hospitalization was significantly shorter and functional ability on discharge was significantly better in elderly patients who underwent pPCI. CONCLUSIONS: Elderly patients with AMI underwent pPCI less frequently, but it was consistently associated with better clinical outcome in these patients. Our findings support the proactive application of pPCI for elderly AMI patients when they are eligible for an invasive strategy.

Hospitalization Costs for Patients With Acute Congestive Heart Failure in Japan.

BACKGROUND: With aging of the population, the economic burden associated with heart failure (HF) is expected to increase. However, little is known about the hospitalization costs associated with HF in Japan. Methods and Results: In this cross-sectional study, using data from The Japanese Registry of All Cardiac and Vascular Diseases (JROAD) and JROAD-Diagnosis Procedure Combination databases between 2012 and 2014, we evaluated hospitalization costs for acute cardiovascular diseases (CVDs), including HF. A total of $1,187 million/year (44% of the hospitalization costs for acute CVDs) was spent on patients with HF. We identified 273,865 patients with HF and the median cost per patient was $8,089 ($5,362-12,787) per episode. The top 1% of spenders accounted for 8% ($80 million/year), and the top 5% of spenders accounted for 22% ($229 million/year) of the entire cost associated with HF. The costs associated with HF for patients over 75 years of age accounted for 68% of the total cost. CONCLUSIONS: The costs associated with HF were higher than the hospitalization cost for any other acute CVD in Japan. Understanding how the total hospitalization cost is distributed may allow health providers to utilize limited resources more effectively for patients with HF.

Editor's Choice - Endovascular Repair Versus Surgical Repair for Japanese Patients With Ruptured Thoracic and Abdominal Aortic Aneurysms: A Nationwide Study.

OBJECTIVE: This study compared outcomes after endovascular aneurysm repair (ER) and open surgical repair (OR) of ruptured descending thoracic aortic aneurysms (rDTAA) and ruptured abdominal aortic aneurysms (rAAA) through a nationwide analysis performed in Japan. METHODS: This was a national registry based retrospective comparative study using data from the Japanese Registry of all Cardiac and Vascular Diseases Diagnostic Procedure Combination (JROAD-DPC) database, a nationwide claim based database from more than 600 hospitals. Patients admitted to certificated teaching hospitals with rDTAA and rAAA and treated by either ER or OR between 1 April 2012 and 31 March 2015 were identified. A propensity score matched analysis was performed to compare ER and OR. RESULTS: About 40% of the total cohort (n = 8,302) were managed conservatively for various reasons, including limited options in primary care facilities in certain areas. In total, 983 patients had rDTAA (OR = 511; ER = 472) and 2,320 (OR = 1,754; ER = 566) had rAAA. Altogether, 604 and 1,080 patients were matched with rDTAA and rAAA, respectively. Compared with OR, ER was associated with significantly better in hospital mortality in patients with rDTAA (ER = 22.5%; OR = 29.8% [p < .001]) and similar mortality for those with rAAA (ER = 25.7%; OR = 24.3% [p = .57]). ER involved significantly shorter hospital stays for rDTAA (ER = 25.5; OR = 32 days [p < .001]) and rAAA (ER = 16; OR = 21 days [p < .001]). The median Barthel Index at discharge was ≥75/100 for all groups, and there were no differences between ER and OR. Total medical costs were significantly lower for ER for rDTAA (ER = ¥6.47 million, OR = ¥7.28 million [p < .001]) but were higher for rAAA (ER = ¥4.65 million; OR = ¥3.43 million [p < .001]). CONCLUSION: A Japanese nationwide observational study showed that in hospital outcomes for ER vs. OR were more favourable for rDTAA and comparable for rAAA. ER resulted in an equivalently favourable functional status at discharge and significantly shorter hospital stays.

Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database.

BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.

Calibration between the Estimated Probability of the Risk Assessment Chart of Japan Atherosclerosis Society and Actual Mortality Using External Population: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN).

AIM: In Japan Atherosclerosis Society guidelines for the prevention of atherosclerotic cardiovascular diseases 2012 (JAS2012), NIPPON DATA80 risk assessment chart (ND80RAC) was adopted to estimate the 10-year probability of coronary artery disease (CAD) mortality. However, there was no comparison between the estimated mortality calculated by ND80RAC and actual mortality in external populations. Accordingly, we used the large pooled database of cohorts in Japan, EPOCH-JAPAN, as an external population. METHODS: The participants of EPOCH-JAPAN without a history of cardiovascular disease (15,091 men and 18,589 women aged 40-74 years) were analyzed based on sex. The probability of a 10-year risk of CAD/stroke mortality was estimated by ND80RAC. The participants were divided into both decile of their estimated mortality and three categories according to JAS2012. The calibration between the mean estimated mortality and the actual mortality was performed by the Hosmer and Lemeshow (H-L) test. RESULTS: In both sexes, the estimated CAD mortality was higher than the actual mortality, particularly in higher deciles of estimated mortality, and the estimated stroke mortality was almost concordant with the actual mortality in low/moderate deciles of estimated mortality. As for the categories according to JAS2012, the estimated CAD mortality was higher than the actual mortality in both sexes; actual mortality in Category III was lower than that in Category II in women. However, it increased in the ascending order of category when we excluded the presence of diabetes from Category III. CONCLUSIONS: The estimated CAD mortality by ND80RAC tended to be higher than the actual mortality in the population in which the baseline survey was more recently performed.