Importance of B-Type Natriuretic Peptide in the Detection of Patients With Structural Heart Disease in a Primary Care Setting.

BACKGROUND: Early detection and intervention for preclinical heart failure (HF) are crucial for restraining the potential increase in patients with HF. Thus, we designed and conducted a single-center retrospective cohort study to confirm the efficacy of B-type natriuretic peptide (BNP) for the early detection of preclinical HF in a primary care setting. METHODS AND RESULTS: We investigated 477 patients with no prior diagnosis of HF who were under the care of general practitioners. These patients were categorized into 4 groups based on BNP concentrations: Category 1, 0 pg/mL≤BNP≤35 pg/mL; Category 2, 35 pg/mL200 pg/mL. There was a marked and statistically significant increase in the prevalence of preclinical HF with increasing BNP categories: 19.9%, 57.9%, 87.5%, and 96.0% in Categories 1, 2, 3, and 4, respectively. Compared with Category 1, the odds ratio of preclinical HF in Categories 2, 3, and 4 was determined to be 5.56 (95% confidence interval [CI] 3.57-8.67), 23.70 (95% CI 8.91-63.11), and 171.77 (95% CI 10.31-2,861.93), respectively. CONCLUSIONS: Measuring BNP is a valuable tool for the early detection of preclinical HF in primary care settings. Proactive testing in patients at high risk of HF could play a crucial role in addressing the impending HF pandemic.

Association Between Serum 3-Hydroxyisobutyric Acid and Prognosis in Patients With Chronic Heart Failure　- An Analysis of the KUNIUMI Registry Chronic Cohort.

BACKGROUND: Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.Methods and Results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 µmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. CONCLUSIONS: In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.

Potential relationship between high wall shear stress and plaque rupture causing acute coronary syndrome.

The relationship between high wall shear stress (WSS) and plaque rupture (PR) in longitudinal and circumferential locations remains uncertain. Overall, 100 acute coronary syndrome patients whose culprit lesions had PR, documented by optical coherence tomography (OCT), were enrolled. Lesion-specific three-dimensional coronary artery models were created using OCT data. WSS was computed with computational fluid dynamics analysis. PR was classified into upstream-PR, minimum lumen area-PR, and downstream-PR according to the PR's longitudinal location, and into central-PR and lateral-PR according to the disrupted fibrous cap circumferential location. In the longitudinal 3-mm segmental analysis, multivariate analysis demonstrated that higher WSS in the upstream segment was independently associated with upstream-PR, and thinner fibrous cap was independently associated with downstream-PR. In the PR cross-sections, the PR region had a significantly higher average WSS than non-PR region. In the cross-sectional analysis, the in-lesion peak WSS was frequently observed in the lateral (66.7%) and central regions (70%) in lateral-PR and central-PR, respectively. Multivariate analysis demonstrated that the presence of in-lesion peak WSS at the lateral region, thinner broken fibrous cap, and larger lumen area were independently associated with lateral-PR, while the presence of in-lesion peak WSS at the central region and thicker broken fibrous cap were independently associated with central-PR. In conclusion, OCT-based WSS simulation revealed that high WSS might be related to the longitudinal and circumferential locations of PR.

Real-world clinical outcomes of percutaneous transluminal septal myocardial ablation for patients with drug-refractory hypertrophic obstructive cardiomyopathy: results from a retrospective multicenter registry of non-high-volume centers.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a well-established interventional therapy for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) as an alternative to surgical myectomy. Although guidelines recommend that PTSMA should be performed in institutions with extensive experience, it is not centralized to such high-volume centers in real-world clinical practice. Thus, this study aimed to assess the feasibility of PTSMA in non-high-volume centers. We retrospectively examined patients with HOCM who underwent PTSMA between August 2012 and May 2020 at four institutions that experienced fewer than 20 cases of PTSMA procedures. The primary clinical endpoint was a composite of safety (all-cause death, electrical defibrillation for ventricular tachycardia or fibrillation, cardiac tamponade, permanent pacemaker implantation, and repeated interventions) and efficacy endpoints (repeated interventions [PTSMA or surgical myectomy]). Fifty-eight consecutive patients were enrolled. During the 30-day follow-up, no major clinical adverse events were noted except three patients (5.2%) requiring permanent pacemaker implantation for complete atrioventricular block. The percentage of patients with New York Heart Association functional class 1 or 2 significantly increased from 8.6 to 100% (p < 0.001). In the Cox proportional hazard model, left ventricular outflow tract pressure gradient at rest ≥ 30 mmHg (hazard ratio [HR] 6.56; 95% confidence interval [CI] 1.44-29.90; p = 0.015) and mitral regurgitation grade ≥ 3 (HR 10.75; 95% CI 1.81-63.79; p = 0.009) at the 30-day follow-up were associated with a composite of major clinical adverse events. The current study demonstrated that 58 patients who underwent PTSMA in non-high-volume centers had favorable 30-day clinical outcomes, with a primary composite endpoint rate of 5.2%. A prospective study with a larger sample size and longer follow-up is warranted to verify the safety and efficacy of PTSMA in non-high-volume centers.

Estimating Incidence of Acute Heart Failure Syndromes in Japan　- An Analysis From the KUNIUMI Registry.

BACKGROUND: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. CONCLUSIONS: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

The effect of multiple-inflation balloon aortic valvuloplasty.

Recent improvements of balloon aortic valvuloplasty (BAV) devices and procedures have provided improved outcomes, but it is not clear whether the multiple-inflation BAV technique is effective in patients with symptomatic severe aortic valve stenosis (AS). We conducted an analysis of the impact of multiple-inflation BAV (at least 6 times inflation) on the mean aortic valve area (AVA) and mean aortic valve pressure gradient (AV-PG) in patients with symptomatic severe aortic stenosis as compared with conventional BAV (from single to three times inflation). We identified two studies of multiple-inflation BAV with antegrade approach using Inoue-balloon catheter (425 patients) and four studies of conventional BAV (170 patients) with retrograde approach. Using a random intercept model, we found that multiple-inflation BAV significantly increased mean AVA (mean difference (MD) [95% indicates confidence interval (CI)] = 0.25 [0.16-0.34], P < 0.001) and significantly decreased mean AV-PG (MD [95% CI] = - 20.2 [- 27.8, - 12.70], P < 0.001) as compared with the conventional BAV. Furthermore, despite an extremely high Society of Thoracic Surgeons (STS) score (9.2-14.5), the all-cause mortality rate at one year of multiple-inflation BAV was 16-17%. The results of our analyses indicate that the multiple-inflation BAV technique seem to be effective for patients with symptomatic severe AS as compared with conventional BAV.

Mid-term effect of balloon aortic valvuloplasty on mitral regurgitation in aortic stenosis.

BACKGROUND: Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS. METHODS: Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant. RESULTS: Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05-1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16-3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups. CONCLUSIONS: BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.

A pharmacodynamics comparison of prasugrel and clopidogrel in patients undergoing hemodialysis.

Platelet reactivity in the presence of clopidogrel is deteriorated in patients undergoing hemodialysis (HD). However, the impact of residual platelet reactivity with prasugrel use in Japanese patients on HD remains unclear. This was a prospective, multi-center, single-arm study conducted to compare platelet reactivity of prasugrel 3.75 mg per day vs. clopidogrel 75 mg per day in patients on chronic HD. We assessed P2Y12 reaction units (PRU) using the VerifyNow® P2Y12 test for all enrolled patients at baseline (clopidogrel treatment) and at 14 days (prasugrel treatment) pre- and post-HD. Clinical outcomes data were obtained on day 14. A total of 38 patients on HD were included in this study. The PRU were significantly higher in patients on clopidogrel than in patients on prasugrel in both phases (pre-HD: clopidogrel 226 ± 80 vs. prasugrel 175 ± 82, p < 0.001) (post-HD: clopidogrel 256 ± 67 vs. prasugrel 210 ± 63, p < 0.001). There were no patients with bleeding or adverse events during the two weeks of prasugrel treatment. Prasugrel 3.75 mg per day, adjusted for Japanese patients, inhibited platelet aggregation better than clopidogrel, even after hemodialysis, which might contribute to the reduced incidence of major adverse event in patients undergoing HD.

Lower on-treatment platelet reactivity during everolimus-eluting stent implantation contributes to the resolution of post-procedural intra-stent thrombus: serial OCT observation in the PRASFIT-Elective study.

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.

Neoatherosclerosis and mural thrombus detection after sirolimus-eluting stent implantation.

BACKGROUND: Although both optical coherence tomography (OCT) and angioscopy are robust tools for detecting intrastent thrombi and neoatherosclerosis in vivo, whether OCT findings are comparable with angioscopy findings remains unclear. METHODS AND RESULTS: 22 patients presenting with de novo lesions underwent 26 sirolimus-eluting stent (SES) implantations, with follow-up OCT and angioscopy at 10 months post-implantation for segmental assessment of the proximal, mid-, and distal SES segments (66 segments). The mean signal intensity index (signal intensity of the neointima/signal intensity of fibrous intimal hyperplasia) was quantified for angioscopically detected in-stent yellow and white segments. The detection rate for red thrombi was numerically higher with angioscopy than with OCT (17% vs. 9%; P=0.053). Angioscopically detected in-stent yellow segments were categorized into 3 OCT patterns: "high-attenuation tissue covering struts" (OCT-defined neoatherosclerosis), "high-attenuation tissue underneath struts," and "low-attenuation and low-intensity tissue covering struts"; further, macrophage-like appearance was most frequently observed with OCT-defined neoatherosclerosis (56%, 6.3%, and 0%, respectively, P<0.001). The mean signal intensity index of neoatherosclerosis was significantly lower than that of angioscopically detected in-stent white segments (0.929 vs. 0.997, P=0.004). CONCLUSIONS: Current OCT-based definitions for thrombus detection may underestimate the presence of subclinical red thrombi. Qualitative and quantitative OCT assessments of the neointima may enhance the detection of neoatherosclerosis over SES in vivo.