Calcific aortic valve disease (CAVD) is one of the most prevalent heart valve diseases and is characterized by progressive stiffening and calcification of the aortic valve. For decades, CAVD has been treated with surgical intervention. In recent years, some progress has been made in understanding the pathogenesis of CAVD and the exploration of novel therapeutic strategies, leading to the identification of potential therapeutic targets and innovative treatment approaches. This review systematically outlines the pathophysiological advances in CAVD over the past 5 years, proposing a 3-stage model for disease progression: inflammatory, fibrotic, and calcification stages. In addition, recent clinical trials investigating pharmacological therapies, such as those targeting lipid metabolism, vitamin K pathways, and calcium-phosphorus balance, are summarized and discussed. These developments hold promise for improving patient outcomes and revolutionizing the management of CAVD.

Background: Hospital-associated disability (HAD), characterized by a worsening of activities of daily living and physical function following hospitalization, is a common complication in older adults during the course of acute care hospitalization. HAD is a significant concern affecting older adults undergoing transcatheter aortic valve implantation (TAVI).

Methods and Results: This retrospective study investigated 243 consecutive patients who underwent elective transfemoral TAVI between January 2016 and April 2022. HAD was defined as a decrease of at least 1 point in the Short Physical Performance Battery (SPPB) assessed before discharge compared with before TAVI. Logistic regression identified the first ambulation day after TAVI as an independent predictor of HAD incidence (odds ratio 1.500; 95% confidence interval [CI] 1.115–2.008; P=0.007). Patients with HAD had significantly lower body mass index, hemoglobin, and albumin, and higher serum creatinine. All-cause mortality was significantly higher in patients with than without HAD (log-rank P<0.001). Kaplan-Meier analysis confirmed poorer survival in patients with HAD, regardless of the degree of decline in SPPB. Multivariate Cox analysis regression identified HAD as a predictor of all-cause death (hazard ratio 4.249; 95% CI 1.798–10.04; P<0.001).

Conclusions: The timing of the first ambulation was associated with the incidence of HAD. Promoting early mobilization may reduce the risk of HAD after TAVI.

Background: The SAPIEN 3 Ultra RESILIA (S3UR) is the latest balloon-expandable valve used in transcatheter aortic valve implantation (TAVI). However, hemolysis is a potential concern with the S3UR. This Japanese single-center retrospective study evaluated the prevalence and associated factors of subclinical hemolysis in the S3UR compared with the SAPIEN 3 (S3).

Methods and Results: We analyzed data for 339 patients who underwent TAVI for severe aortic stenosis and completed a 1-month follow-up (S3UR, n=69; S3, n=270). Subclinical hemolysis was defined as an increase lactate dehydrogenase >2.5-fold from baseline. The prevalence of subclinical hemolysis at 1 month was significantly higher in the S3UR than S3 group (14.5% vs. 2.7%; P<0.001). Notably, subclinical hemolysis was more frequently observed in the S3UR group when mild paravalvular leak (PVL) remained at 1 month. Univariate analysis revealed that mild or greater PVL at 1 month, decreasing annular oversizing, and increasing the difference between the mean diameter of the sinus of Valsalva (SOV) and transcatheter heart valve (THV) size were associated with subclinical hemolysis in the S3UR group.

Conclusions: Remaining mild or greater PVL and using an undersized THV relative to the annulus and SOV were associated with subclinical hemolysis in the S3UR. These findings highlight the importance of selecting a THV size that appropriately matches the aortic valve complex and ensuring adequate THV expansion to prevent subclinical hemolysis.

Background: To consider transcatheter aortic valve-in-surgical aortic valve (TAV-in-SAV) as a secondary intervention, the risk of coronary obstruction during future TAV-in-SAV should be assessed prior to initial SAV replacement (SAVR), especially in Japanese patients with a small body size and aortic root anatomy. In this study we simulated the risk of coronary obstruction and identified associated anatomical factors.

Methods and Results: We retrospectively analyzed pre- and post-SAVR computed tomography scans of 115 patients and simulated the risk of coronary obstruction. High risk was defined as postoperative coronary arteries located below the risk plane (RP) and a valve-to-coronary distance <4 mm or a valve-to-aorta distance <2 mm; 28.7% of patients were classified as high risk. Preoperative right and left coronary artery heights of ≥22 and ≥18 mm, respectively, were important parameters for classifying patients with postoperative coronary arteries located above or below the RP. An expected valve-to-sinotubular junction (STJ) distance (defined as the difference between the preoperative STJ diameter and the expected internal valve diameter) ≥7 mm was another important parameter to stratify patients into low- and high-risk categories.

Conclusions: TAV-in-SAV was anatomically unfeasible in 28.7% of patients, and the coronary obstruction risk was associated with aortic root anatomy and implanted valve size. These results may provide a basis for considering TAV-in-SAV as a secondary option in Japanese patients with a small body size and aortic root anatomy.

Background: Right ventricular (RV) dysfunction negatively affects mitral valve transcatheter edge-to-edge repair (M-TEER) outcomes in patients with ventricular secondary mitral regurgitation (vSMR). However, RV dysfunction occurs in the late phase of heart failure, when it may not respond to interventions. The pulsatile component of RV afterload, pulmonary artery (PA) compliance, is a sensitive parameter that decreases before RV dysfunction occurs. We explored the utility of PA compliance in predicting cardiac events after M-TEER.

Methods and Results: We analyzed 107 patients with vSMR who underwent M-TEER and in whom right heart catheter parameters were measured in a conscious state. Twenty-four patients had a cardiac event. There were no differences in patient characteristics or echocardiographic parameters between groups with and without cardiac events. PA compliance was significantly reduced in the event group, but other RV function parameters did not differ between the 2 groups. Receiver operating characteristic curve analysis revealed an optimal prognostic cut-off value for PA compliance of 2.7 mL/mmHg. In multivariate Cox regression, reduced PA compliance (<2.7 mL/mmHg) was strongly associated with cardiac events. Kaplan-Meier analysis revealed PA compliance had significant prognostic power for the composite outcome of cardiac events (log-rank P<0.01).

Conclusions: Reduced PA compliance (hemodynamically derived in the conscious state) was a strong prognostic indicator in patients with vSMR who underwent M-TEER.

Background: This study evaluated the utility of myocardial strain analysis on computed tomography (CT) using state-of-the-art image analysis software to predict the prognosis of patients who underwent transcatheter aortic valve replacement (TAVR).

Methods and Results: We included 126 patients with severe aortic valve stenosis (AS) who underwent preoperative CT. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death (including unknown death based on medical records), hospitalization due to heart failure, and fatal arrhythmia. Twenty-four (19%) patients experienced MACE. Global longitudinal strain (GLS), circumferential strain (GCS), radial strain (GRS) of the left ventricular (LV) myocardium (LVM), LV ejection fraction on CT, and the percentage of patients administered aspirin or statins was significantly lower among patients with than without MACE (all P<0.05). The percentage of patients with AF, a history of congestive heart failure, and tolvaptan or oral anticoagulants administration was significantly higher among patients with than without MACE (all P<0.05). In multivariate survival analysis using a Cox proportional hazard model, LV-GLS ≥−9.92% on CT (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.89–10.48; P=0.0007) and aspirin (HR 0.27; 95% CI 0.10–0.70; P=0.0074) or statin (HR 0.33; 95% CI 0.13–0.84; P=0.02) administration were significant predictors of prognosis after TAVR.

Conclusions: Our findings indicate that LV-GLS on CT is a sensitive predictor of prognosis after TAVR.

Background: The aim of this study was to retrain our existing deep learning-based fully automated aortic valve leaflets/root measurement algorithm, using computed tomography (CT) data for root dilatation (RD), and assess its clinical feasibility.

Methods and Results: 67 ECG-gated cardiac CT scans were retrospectively collected from 40 patients with RD to retrain the algorithm. An additional 100 patients’ CT data with aortic stenosis (AS, n=50) and aortic regurgitation (AR) with/without RD (n=50) were collected to evaluate the algorithm. 45 AR patients had RD. The algorithm provided patient-specific 3-dimensional aortic valve/root visualization. The measurements of 100 cases automatically obtained by the algorithm were compared with an expert’s manual measurements. Overall, there was a moderate-to-high correlation, with differences of 6.1–13.4 mm²for the virtual basal ring area, 1.1–2.6 mm for sinus diameter, 0.1–0.6 mm for coronary artery height, 0.2–0.5 mm for geometric height, and 0.9 mm for effective height, except for the sinotubular junction of the AR cases (10.3 mm) with an indefinite borderline over the dilated sinuses, compared with 2.1 mm in AS cases. The measurement time (122 s) per case by the algorithm was significantly shorter than those of the experts (618–1,126 s).

Conclusions: This fully automated algorithm can assist in evaluating aortic valve/root anatomy for planning surgical and transcatheter treatments while saving time and minimizing workload.

Background: Pulmonary valvular regurgitation in postoperative patients with repaired tetralogy of Fallot (rTOF) significantly impairs exercise capacity and causes right heart failure. Quantitative evaluation of the pulmonary valvular regurgitation fraction (PRF) by cardiac magnetic resonance (CMR) is commonly used to determine the indication for surgical or catheter interventions, but less commonly using echocardiography.

Methods and Results: We retrospectively investigated the feasibility and validation of vector flow mapping (VFM) for the quantification of PRF (VFM-PRF) in 34 pediatric patients with rTOF, comparing it to CMR-derived PRF (CMR-PRF) and other qualitative or semiquantitative echocardiographic indices. Each predictive value for CMR-PRF ≥40% was assessed using receiver operating characteristic curves. VFM-PRF and CMR-PRF showed good agreement, with a correlation coefficient of 0.90 and the highest predictive value for CMR-PRF ≥40%, resulting in an area under the curve of 0.93. Other conventional echocardiographic parameters demonstrated poor predictive accuracy.

Conclusions: This is the first report to demonstrate the accurate quantification of PRF by echocardiography using VFM in pediatric patients with rTOF, showing good agreement with CMR results. Particularly in children, VFM may be clinically useful in determining the indication for reintervention for pulmonary valve replacement, offering a possible alternative to CMR, which often requires deep sedation and general anesthesia.

Background: Transcatheter closure of paravalvular leak (PVL) has become an established treatment for patients at prohibitive surgical risk. However, few studies have examined the feasibility of transcatheter closure using Amplatzer occluders in Japanese patients with mitral PVL.

Methods and Results: Twelve patients (mean [±SD] age 78±7 years) with heart failure, hemolytic anemia, or both after surgical mitral prosthetic valve replacement (mechanical valve, 75%) underwent transcatheter PVL closure with Amplatzer Vascular Plug II (AVP-II)/Amplatzer Duct Occluder II (ADO-II) between 2014 and 2021 at Toho University Ohashi Medical Center. We examined procedural, in-hospital, 30-day, and 1-year outcomes. All procedures were performed under general anesthesia using an antegrade transseptal approach, and the procedures were successful in all cases. The mean (±SD) number of Amplatzer occluders deployment per patient was 2.9±1.1, and in 2 patients the combined use of ADO-II was required. The mitral PVL grade decreased notably from 3+ to 1+, with residual PVL being mild or absent in 9 patients. There were no all-cause mortalities, major adverse events, or device-related complications at the 30-day follow-up. At 1 year, all-cause mortality was 16.7% and 3 (25%) patients required reintervention because of the recurrence of clinical symptoms.

Conclusions: Our findings suggest that transcatheter PVL closure with AVP-II/ADO-II can be feasible and safe in Japanese patients with mitral PVL, leading to satisfactory early clinical outcomes.

Background: There is a paucity of data on safety of calcium channel blockers (CCB) in patients with severe aortic stenosis (AS) and hypertension.

Methods and Results: Among 2,460 patients with severe AS and hypertension receiving antihypertensive therapy in the CURRENT AS registry-2, we compared the clinical outcomes between patients taking antihypertensive therapy with CCB (CCB group) and without CCB (no CCB group). In the entire study population, CCB was prescribed in 1,763 patients (71.7%), which was the most commonly prescribed antihypertensive agents. The prescription rates of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and thiazides were 61.9%, 25.6%, and 7.3% in the CCB group, and 75.8%, 54.4%, and 6.0% in the no CCB group. In the propensity score matched cohort, the cumulative 3-year incidence of all-cause death or hospitalization for heart failure was not different between the CCB and no CCB groups (38.3% vs. 38.7%, log-rank P=0.65; HR, 0.94; 95%CI, 0.77–1.15; P=0.56). The cumulative 3-year incidence of syncope was low regardless of CCB prescription (1.1% vs. 1.0%, P=0.74).

Conclusions: Among patients with severe AS and hypertension, CCB was the most commonly prescribed antihypertensive agents, and antihypertensive therapy with CCB was associated with comparable clinical outcomes to antihypertensive therapy without CCB. Syncope was rarely seen in patients with severe AS and hypertension receiving antihypertensive therapy regardless of CCB prescription.

Background: Both underweight and overweight are recognized as important factors influencing outcomes in patients undergoing cardiovascular surgery. This study investigated the effects of body mass index (BMI) on hospital-associated disability (HAD) and hospitalization costs in patients undergoing elective cardiovascular surgery (coronary artery bypass grafting, valve surgery, aortic surgery) by analyzing data from the Japanese Registry of All Cardiac and Vascular Diseases – Diagnosis Procedure Combination (JROAD-DPC) database.

Methods and Results: All patients in the JROAD-DPC database were categorized into 5 groups according to the World Health Organization BMI criteria for Asians. HAD was defined as a decrease of ≥5 points in the Barthel Index from admission to discharge. The primary outcome was the prevalence of HAD, and the secondary outcome was hospitalization costs. Among the 228,891 patients included in the study, the median BMI was 23.2 kg/m². The prevalence of HAD was 8.7%, with a U-shaped relationship between BMI and HAD, indicating that both extremely low and high BMIs were associated with a higher incidence of HAD. Hospitalization costs also showed a U-shape relationship with BMI, with higher costs for patients with HAD.

Conclusions: Low BMI in any age group was associated with HAD, and older people with a BMI considered too high also had HAD. BMI could be an important risk stratification tool for functional outcomes and economic burden in patients undergoing elective cardiovascular surgery.

Background: The Revised Cardiac Risk Index (RCRI) has been incorporated into preoperative assessment guidelines and is used for simple preoperative screening; however, validation studies within large populations are limited. Moreover, although sex differences in perioperative risk are recognized, their effect on the performance of the RCRI remains unclear. Therefore, in this study we evaluated whether sex differences exist in the risks within the strata classified by the RCRI.

Methods and Results: The Japan Medical Data Center database based on claim and health examination data in Japan between January 2005 and April 2021 was used. A total of 161,359 noncardiac surgeries performed during hospitalization were analyzed. The main outcome was the 30-day risk of major adverse cardiovascular events. Although there was no significant sex difference among those with an RCRI ≥1, males had a significant hazard rate (1.32 [95% confidence interval, 1.03–1.68]) of postoperative events in the low-risk group with an RCRI of 0. However, this significant difference was not detected in the population excluding those who underwent breast and gynecological surgeries.

Conclusions: The RCRI achieved reasonable risk stratification in validation using Japanese real-world data regardless of sex. Although further detailed analysis is necessary to determine the sex differences, the validity of using the RCRI for screening purposes is supported at this stage.

Background: Although tricuspid regurgitation (TR) is no longer considered a negligible disease, its detailed status in real-world heart failure (HF) patients remains unknown.

Methods and Results: From the KUNIUMI registry, we evaluated data for 1,646 consecutive HF patients. The primary endpoint was all-cause mortality over a median follow-up period of 3.0 years (interquartile range 1.4–3.0 years). Of the 1,646 HF patients, 369 (22.4%) had moderate or greater TR; the mean (±SD) age of these patients was 82.0±8.5 years. Atrial functional TR was the most common etiology of TR in HF patients with moderate or greater TR (70.7%), and was more common in HF patients with severe than moderate TR (75.5% vs. 65.3%; P=0.032). The mortality rate was high in HF patients with severe and moderate TR (27.1% and 17.0%, respectively). During follow-up, 33.1% of HF patients with moderate TR progressed to severe TR, and showed unfavorable all-cause mortality compared with those with unchanged TR. Atrial functional TR was a more common etiology in HF patients with moderate TR and worsened TR than in those with unchanged TR (84.6% vs. 59.5%; P=0.004). Right atrial enlargement was independently correlated with worsened TR.

Conclusions: Moderate or greater TR was prevalent in 22.4% of the real-world super-aged HF population. Even HF patients with moderate TR had poor outcomes, with right atrial remodeling a key factor for worsened TR.

Background: The prognostic significance of the 6-minute walk distance (6MWD) in patients with severe aortic stenosis (AS) has not been thoroughly investigated.

Methods and Results: This study evaluated 998 patients with severe AS who underwent a 6-min walk test as part of a large multicenter prospective cohort. Patients were categorized as either fast walkers (6MWD ≥300 m; n=515) or slow walkers (6MWD <300 m; n=483). During a median follow-up of 2.3 years, 861 (86.3%) patients underwent surgical or transcatheter aortic valve replacement (AVR; 87.0% of fast walkers vs. 85.5% of slow walkers). The cumulative 3-year incidence of death was significantly lower among fast walkers than slow walkers (10.9% vs. 31.7%; P<0.001). After adjusting for confounders, slow walkers had a significantly higher risk of all-cause mortality than fast walkers (hazard ratio 2.36; 95% confidence interval 1.55–3.58; P<0.001). Stratified analysis by initial treatment strategy revealed that the cumulative 3-year incidence of all-cause death was consistently lower among fast walkers than slow walkers (initial AVR strategy: 10.1% vs. 28.1% [P<0.001]; conservative strategy: 13.4% vs. 46.7% [P<0.001]). Among asymptomatic patients managed conservatively, fast walkers demonstrated a remarkably low cumulative 3-year incidence of all-cause death (8.1%).

Conclusions: The 6MWD is a reliable prognostic marker for patients with severe AS, regardless of initial treatment strategy.