Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Acute onset of constrictive pericarditis due to acute myelomonocytic leukemia: A case and literature review.

We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

Machine learning-based gait analysis to predict clinical frailty scale in elderly patients with heart failure.

Aims: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods and results: We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from 7 centres between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the light gradient boosting machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen's weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs [CWK 0.866, 95% confidence interval (CI) 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively]. During a median follow-up period of 391 (inter-quartile range 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (hazard ratio 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates. Conclusion: Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.

Influence of epicardial adipose tissue inflammation and adipocyte size on postoperative atrial fibrillation in patients after cardiovascular surgery.

Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT-conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor-alpha (TNF-α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.

Two-Year Clinical Outcome of MitraClip Transcatheter Edge-to-Edge Repair From the J-MITRA Registry Data.

BACKGROUND: The introduction of transcatheter edge-to-edge repair for moderate-to-severe or severe mitral regurgitation (MR) utilizing the MitraClip system became reimbursed and clinically accessible in Japan in April 2018. This study presents the 2-year clinical outcomes of all consecutively treated patients who underwent MitraClip implantation in Japan and were prospectively enrolled in the Japanese Circulation Society-oriented J-MITRA registry.Methods and Results: Analysis encompassed 2,739 consecutive patients enrolled in the J-MITRA registry with informed consent (mean age: 78.3±9.6 years, 1,550 males, STS risk score 11.7±8.9), comprising 1,999 cases of functional MR, 644 of degenerative MR and 96 in a mixed group (DMR and FMR). The acute procedure success rate was 88.9%. After MitraClip implantation, >80% exhibited an MR grade ≤2+ and the trend was sustained over the 2 years. Within this observation period, the mortality rate was 19.3% and the rate of heart failure readmissions was 20.6%. The primary composite endpoint, inclusive of cardiovascular death and heart failure readmission, was significantly higher in patients with functional MR than in with degenerative MR (32.0% vs. 17.5%, P<0.001). CONCLUSIONS: The 2-year clinical outcomes after MitraClip implantation were deduced from comprehensive data within an all-Japan registry.

Prolonged delirium during hospitalization is associated with worse long-term and short-term outcomes in patients with acute heart failure.

BACKGROUND: The association between prolonged delirium during hospitalization and long-term prognosis in patients with acute heart failure (AHF) admitted to the cardiac intensive care unit (CICU) has not been fully elucidated. METHODS: We conducted a prospective registry study of patients with AHF admitted to the CICU at 2 hospitals from 2013 to 2021. We divided study patients into 3 groups according to the presence or absence of delirium and prolonged delirium as follows: no delirium, resolved delirium, or prolonged delirium. Main outcomes were in-hospital mortality and 3-year mortality after discharge. RESULTS: A total of 1555 patients with AHF (median age, 80 years) were included in the analysis. Of these, 406 patients (26.1%) developed delirium. We divided patients with delirium into 2 groups: the resolved delirium group (n = 201) or the prolonged delirium group (n = 205). Multivariate Cox proportional hazards models for long-term prognosis demonstrated that the prolonged delirium group had a higher incidence of all-cause death (hazard ratio [HR], 1.52; 95% CI, 1.08 to 2.14) and non-cardiovascular death (HR, 1.84; 95% CI, 1.21 to 2.78) than the resolved delirium group. Regarding in-hospital outcomes, multivariate logistic regression modeling showed that prolonged delirium is associated with all-cause death (odds ratio [OR], 9.55; 95% confidential interval [CI], 2.99 to 30.53) and cardiovascular death (OR, 13.02; 95% CI, 2.86 to 59.27) compared with resolved delirium. CONCLUSIONS: Prolonged delirium is associated with worse long-term and short-term outcomes than resolved delirium in patients with AHF.

Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study.

AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.

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.

Exercise Capacity and Clinical Outcomes in Chronic Heart Failure Patients with Mild Tricuspid Regurgitation.

AIM: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). METHODS AND RESULTS: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR (n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR (n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8-5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50-6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35-6.55). CONCLUSIONS: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.

Association of coronary plaque morphology with inflammatory biomarkers and target lesion revascularization in patients with chronic coronary syndrome: an optical coherence tomography study.

BACKGROUND: The characteristics of high-risk coronary atherosclerosis evaluated using optical coherence tomography (OCT) can have a prognostic role. Inflammatory biomarkers may be related to the severity of coronary artery disease. This study investigated the association of high-risk morphological features of coronary plaques on OCT with circulating levels of inflammatory biomarkers and target lesion revascularization (TLR). MATERIALS AND METHODS: We prospectively analyzed the data of 30 consecutive patients with chronic coronary syndrome who underwent percutaneous coronary intervention (PCI) using OCT. The levels of interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, pentraxin 3, vascular endothelial growth factor, and monocyte chemoattractant protein-1 (MCP-1) were measured in plasma samples. Coronary plaque characteristics were scored quantitatively in the form of coronary plaque risk score (CPRS). The estimated high-risk plaque characteristics for TLR were plaque rupture, plaque erosion, calcified nodule, lipid-rich plaque, thin-cap fibroatheroma, cholesterol crystals, macrophage infiltration, microchannels, calcification angle >90°, and microcalcifications. Each high-risk feature carries 1 point. Patients were defined as having a low CPRS (CPRS ≤3) or a high CPRS (CPRS ≥4). RESULTS: The primary outcome was TLR. TLR occurred in 6 (20%) patients within 15 months of PCI. High CPRS on OCT was directly correlated with TLR (P=0.029). In logistic regression analysis, CPRS was associated with TLR (odds ratio, 10.0; 95% confidence interval, 1.34-74.5). Serum MCP-1 level was significantly correlated with the CPRS (P=0.020). CONCLUSIONS: In patients with chronic coronary syndrome, CPRS may be a surrogate predictor of TLR. Serum MCP-1 may aid in the detection of high-risk coronary atherosclerosis.

Differences in blood flow dynamics between balloon- and self-expandable valves in patients with aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR). METHODS: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR. RESULTS: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups. CONCLUSIONS: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients.

Impact of Cardiac Power Output on Exercise Capacity and Clinical Outcome in Patients With Chronic Heart Failure.

Less data are available regarding the impact of cardiac power output on exercise capacity or clinical outcome in patients with chronic heart failure (CHF). The study enrolled 280 consecutive patients with CHF referred for cardiopulmonary exercise testing and right-sided heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization or death. Cardiac power output was calculated as (mean arterial pressure × CO) ÷ 451. Patients with low cardiac power output (<0.53 W, n = 99) were older and had a higher brain natriuretic peptide level than patients with high cardiac power output (≥0.53W, n = 181). Cardiac power output was correlated with peak oxygen consumption (peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) in cardiopulmonary exercise testing, whereas each of cardiac output or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (interquartile range 1.0 to 6.0) years. Patients with low cardiac power output had about a 2-fold higher risk of events than those with a high cardiac power output (hazard ratio 1.97, 95% confidence interval 1.12 to 3.48). In the multivariable Cox regression, a 0.1-W decrease in cardiac power output was associated with 19% increased adverse events (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). In conclusion, cardiac power output was associated with reduced exercise capacity and poor clinical outcome, suggesting that cardiac power output is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting cardiac power output to improve the exercise capacity or clinical outcome in patients with CHF.