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.

Accuracy of lung ultrasound examinations of residual congestion performed by novice residents in patients with acute heart failure.

AIMS: The popularity of B-line-guided congestion assessment by lung ultrasound (LUS) has been increasing. However, the ability of novice residents to detect residual congestion with B-line-guided assessment by LUS after decongestion treatment is poorly understood. In this study, we investigated whether novice residents (no prior echocardiography experience) can acquire the skills for B-line-guided residual congestion assessment and whether the range of variation in assessment is acceptable in actual clinical use. METHODS AND RESULTS: The study included 30 postgraduate first-year novice residents and an expert. The residents underwent training for LUS. At the end of the training session, a set of 15 LUS videos was provided to the residents, and they were asked to estimate the number of B-lines in each video. When the residents' answers greatly differed from the correct answer, we provided feedback to raise awareness of the discrepancies. After the training session, the residents performed residual congestion assessment by LUS after decongestion treatment in patients hospitalized with acute heart failure. The residents identified residual congestion in 57% of the patients. The sensitivity and specificity to identify residual congestion by the residents were 90% and 100%, respectively. The inter-operator agreement between the residents and the expert was substantial (κ = 0.86). The Spearman rank correlation coefficient for the B-lines between the expert and each resident was very high at 0.916 (P < 0.0001). CONCLUSIONS: After a brief lecture, novice residents can achieve proficiency in quantifying B-lines on LUS and can reliably identify residual congestion on LUS.

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.

Volume-outcome relationship in balloon aortic valvuloplasty: results of a consecutive, patient-level data analysis from a Japanese nationwide multicentre registry (J-SHD).

OBJECTIVE: Transcatheter balloon aortic valvuloplasty (BAV) remains an important alternative treatment for severe, symptomatic aortic stenosis. With increasing numbers of BAVs being performed, the need for large-scale volume-outcome relationship assessments has become evident. Here, we aimed to explain such relationships by analysing consecutive, patient-level BAV data recorded in a prospective Japanese nationwide multicentre registry. DESIGN: Prospective study. SETTING: Data of 1920 BAVs performed in 200 Japanese hospitals from January 2015 to December 2019. PARTICIPANTS: The mean patient age was 85 years, and 36.9% of procedures involved male patients. METHODS: The efficacy of BAV was assessed by reducing the mean transaortic valve gradient after the procedure. We also assessed in-hospital complication rates, including in-hospital death, bleeding, urgent surgery, distal embolism, vessel rupture and contrast-induced nephropathy. Based on the distribution of case volume (median 20, IQR 10-46), we divided the patients into high-volume (≥20) and low-volume (<20) groups. In-hospital complication risk was assessed with adjustment by logistic regression modelling. RESULTS: Indications for BAV included palliative/destination (44.2%), bridge to transcatheter aortic valve replacement (34.5%), bridge to surgical aortic valve replacement (7.4%) and salvage (9.7%). Reduction of the mean transaortic valve gradient was similar between the high-volume and low-volume groups (20 mm Hg vs 20 mm Hg, p=0.12). The proportion of in-hospital complications during BAV was 4.2%, and the incidence of complications showed no difference between the high-volume and low-volume groups (4.2% vs 4.1%, p=1.00). Rather than hospital volume, salvage procedure was an independent predictor of in-hospital complications (OR, 4.04; 95% CI, 2.03 to 8.06; p<0.001). CONCLUSION: The current study demonstrated that procedural outcomes of BAV were largely independent of its institutional volume.

Recurrent cardiac arrests caused by Kounis syndrome without typical allergic symptoms.

Kounis syndrome is a rare disease in which coronary spasm or acute coronary syndrome is induced by type I allergy. Concurrence of allergic reaction and chest pain are important clues to establish diagnosis. We report a rare case of Kounis syndrome without obvious signs of allergy.A 52-year-old woman experienced abdominal pain followed by ventricular fibrillation (VF) storm. Ten months earlier, the patient underwent subcutaneous implantable cardioverter-defibrillator implantation based on the previous diagnosis of idiopathic VF. In both episodes, the patient was given dental treatment and administered loxoprofen before VF onset. After we performed loxoprofen provocation test, electrocardiogram revealed ST-segment elevation in leads II, III, and aVF. Moreover, the patient developed VF again. An emergency coronary angiography after recovery showed no significant findings. However, myocardial scintigraphy presented a perfusion-metabolism mismatch in the inferior wall. Furthermore, laboratory test results after provocation revealed increased histamine level. Based on these findings, we diagnosed the patient with Kounis syndrome.Kounis syndrome without typical allergic symptoms is challenging to diagnose. Therefore, suspecting the possibility of allergic reactions and detailed history taking are important, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest. Learning objective: Kounis syndrome is a rare coronary disease with vasospasm or plaque rupture, induced by type I allergy. Since Kounis syndrome without typical allergic symptoms is challenging to diagnose, a high index of suspicion is necessary. Detailed history taking can provide important clues to establish diagnosis, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest.

Association between B-lines on lung ultrasound, invasive haemodynamics, and prognosis in acute heart failure patients.

AIMS: Increased left atrial pressure leads to pulmonary congestion. Although the B-lines in lung ultrasound (LUS) are useful in detecting pulmonary congestion, data regarding the association between B-lines and invasive haemodynamics are inconsistent. This study aimed to explore the correlation of the B-line count by LUS with pulmonary capillary wedge pressure (PCWP) stratified for preserved and reduced ejection fraction (EF) in acute heart failure patients. METHODS AND RESULTS: We performed a prospective observational study on 116 hospitalized patients with acute heart failure (mean age, 75.2 ± 10.3 years), who underwent right heart catheterization before discharge. LUS was performed in eight zones within 4 h of right heart catheterization and compared with PCWP separately in each EF group. Cardiac events were recorded 1 year after discharge. PCWP revealed a clear pivot point at which the B-lines began to increase in the overall cohort and each EF. Specific thresholds of the increase in B-lines were identified at 19 and 25 mmHg for preserved and reduced EF, respectively. Residual congestion at discharge was defined as the presence of ≥6 B-lines. Patients with residual congestion had a higher risk for cardiac events than those without residual congestion (hazard ratio, 12.6; 95% confidence interval, 4.71-33.7; log-rank, P < 0.0001). CONCLUSION: A clear pivot point was associated with increased B-lines count in PCWP at 19 and 25 mmHg for preserved and reduced EF, respectively. Moreover, the increased B-line count above the defined cut-off used to quantify residual congestion was associated with significantly worse outcomes.

Aetiology of chronic heart failure in patients from a super-aged society: the KUNIUMI registry chronic cohort.

AIMS: With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super-aged society. METHODS AND RESULTS: The KUNIUMI registry chronic cohort is a community-based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P < 0.01). The prevalence of atrial fibrillation, and in particular long-standing persistent atrial fibrillation, increased at 70 years of age (P < 0.01). The proportion of patients with heart failure with preserved ejection fraction increased to ~60% when age was over 75 years. Although ischaemic heart disease accounted for 35.0% of chronic heart failure aetiologies, valvular heart disease was the most common cause of chronic heart failure (49.8%). The major types of valvular heart disease were mitral regurgitation and tricuspid regurgitation (27.2% and 21.7%, respectively), both of which increased significantly with age (P < 0.01). The incidence of aortic valve stenosis increased markedly over the age of 85 years (P < 0.01). Atrial functional mitral regurgitation increased with age and was the major cause of mitral regurgitation in patients aged >75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long-standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P < 0.001, respectively). CONCLUSIONS: The KUNIUMI registry chronic cohort showed a change in heart failure aetiology to valvular heart disease in a super-aged society. Effective and comprehensive countermeasures are required to prepare for the rapid rise in heart failure incidence in a super-aged society.

Differences in Prognostic Factors among Patients Hospitalized for Heart Failure According to the Age Category: From the KUNIUMI Registry Acute Cohort.

Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p<0.001). A Cox proportional-hazard regression analysis revealed that the presence of atrial fibrillation [hazard ratio (HR): 23.3, 95% confidence interval (CI): 2.36-231.1, p=0.007] was a notable predictive factor for all-cause death in the ≤65 years old group, whereas the Clinical Frailty Scale score (HR: 1.33, 95% CI: 1.16-1.52, p<0.001) and hypoalbuminemia (HR: 0.49, 95% CI: 0.31-0.78, p=0.003) were predictors in the >85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Association of congestion with worsening renal function in acute decompensated heart failure according to age.

AIMS: Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re-hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re-hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high-aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population-based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. METHODS AND RESULTS: We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re-hospitalization after discharge over a mean follow-up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high-aged patients ≥80 years old, but not for those <80 years old if decongested. Multivariable Cox regression analysis showed that both residual congestion at discharge and WRF were the independent predictors of outcomes for high-aged patients, but residual congestion at discharge, not WRF, was the independent predictor of outcomes for older patients. CONCLUSIONS: Association of residual congestion at discharge with WRF for hospitalized ADHF patients can differ according to age. Our findings showed the importance of WRF and residual congestion at discharge for high-aged ADHF patients and of aggressive diuresis to alleviate congestion for older ADHF patients for better management of such patients in a rapidly ageing society.

Efficacy of Renin-angiotensin-aldosterone-system inhibitors for heart failure with preserved ejection fraction and left ventricular hypertrophy -from the KUNIUMI Registry Acute Cohort.

BACKGROUND: Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. METHODS: We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. RESULTS: In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors' prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR <30 mL/min/1.73 m2, the outcome was similar between patients with and without RAAS inhibitor prescription. Multivariable Cox regression analysis showed that the prescription of RAAS inhibitors was the only independent predictor of outcome in HFpEF patients with LVH and mild-moderate CKD (HR 0.49; 95% CI 0.25-0.94; p = 0.03). CONCLUSIONS: Our findings showed the importance of HFpEF phenogrouping for identifying effective pharmacological treatments.

Importance of Optimized Guideline-Based Therapy for Preventing Rehospitalization of Chronic Heart Failure Patients　- From the KUNIUMI Acute Cohort.

Background: Because the effectiveness of strengthening guideline-based therapy (GBT) to prevent heart failure (HF) rehospitalization of chronic HF patients remains unclear, this study investigated the characteristics of HF patients in the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) acute cohort. Methods and Results: We studied 254 rehospitalized HF patients from the KUNIUMI Registry. Optimized GBT was defined as a Class I or IIa recommendation for chronic HF based on the guidelines of the Japanese Circulation Society. The primary endpoint was all-cause death or first HF rehospitalization after discharge. Outcomes tended to be more favorable for patients who had rather than had not received optimized GBT (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.57-1.19; P=0.27). Similarly, among New York Heart Association (NYHA) Class IV patients, outcomes tended to be more favorable for those who had rather than had not undergone optimized GBT (HR 0.73; 95% CI 0.47-1.12; P=0.15). Importantly, outcomes were significantly more favorable among NYHA Class IV patients aged <79 years who had rather than had not undergone optimized GBT (HR 0.33; 95% CI 0.14-0.82; P=0.02). Multivariate Cox regression analysis showed that optimized GBT was the only independent factor for the prediction of the primary endpoint. Conclusions: Optimized GBT can be expected to play an important role as the next move for chronic HF patients.

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.

Precipitating factors and clinical impact of early rehospitalization for heart failure in patients with heart failure in Awaji Island, Japan.

BACKGROUND: Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF. METHODS AND RESULTS: We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p<0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)]. CONCLUSIONS: We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis.

A successful case of percutaneous transluminal septal myocardial ablation for left ventricular outflow tract obstruction caused by sigmoid septum.

A sigmoid septum is a state of angulation between the basal interventricular septum and the ascending aorta. Although considered to have no clinical importance, it may cause left ventricular outflow tract obstruction (LVOTO) in a hypercontractile state. Percutaneous transluminal septal myocardial ablation (PTSMA) is a catheter-based therapy aimed at improving drug-refractory symptoms in patients with hypertrophic obstructive cardiomyopathy. Few studies have reported the use of PTSMA for patients with LVOTO caused by sigmoid septum. We present a successful case of a 71-year-old female patient who presented with a long history of exertional dyspnea. The presence of a sigmoid septum was revealed on echocardiography. At rest, the left ventricular outflow tract pressure gradient was low and there were no signs of systolic anterior motion (SAM) of the mitral valve; however, during Valsalva maneuver, the gradient increased significantly, and SAM could be seen. We successfully performed PTSMA, resulting in a significant lowering of the pressure gradient and disappearance of SAM. The patient's symptoms dramatically improved by the following day. .

Hypothermic circulatory arrest for aortic dissection with cryoglobulinemia.

Cryoglobulinemia is a cold-reactive autoimmune disease. A 64-year-old man with active cryoglobulinemia presented Stanford type A acute aortic dissection. He had been treated with immunosuppressive drugs and plasma exchange (PE) at our hospital; subsequently, qualitative analysis of cryoglobulin (CG) was negative. He underwent emergency ascending aorta replacement using cardiopulmonary bypass (CPB) under deep hypothermia circulatory arrest with selective cerebral perfusion. The total CPB time, aortic cross-clamp time, and selective cerebral perfusion time were 255, 153, 56 minutes, respectively, and the minimal nasopharyngeal temperature was 17.3°C. Our patient had no significant perioperative complications. Hence, if PE is performed appropriately and CG is negative, patients with cryoglobulinemia who exhibit severe preoperative symptoms can safely undergo surgery with deep hypothermia.

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.

Prognostic Impact of the Clinical Frailty Scale After Balloon Aortic Valvuloplasty.

Background: The clinical frailty scale (CFS) predicts late mortality in patients undergoing transcatheter aortic valve replacement. We evaluated the CFS and other parameters associated with 1-year mortality after balloon aortic valvuloplasty (BAV). Methods and Results: Between January 2013 and May 2018, 148 patients with severe aortic stenosis (AS) who underwent BAV at the present hospital were enrolled. We recorded pre-procedural CFS grade, baseline characteristics, echocardiographic, and hemodynamic parameters. To investigate the potential risk to patients before BAV, we evaluated the Society of Thoracic Surgeons (STS) score. After patients who underwent surgical aortic valve replacement, transcatheter aortic valve replacement or repeat BAV were excluded, we investigated 1-year survival. Of 127 patients, 41 (32.3%) died ≤1 year after BAV, 8 of whom (19.5% of all-cause deaths) had cardiac deaths. Higher grade of CFS and STS score significantly correlated with 1-year mortality. Severe frailty and the high operative risk group (CFS ≥7 and STS score ≥8.7%) had an extremely poor prognosis (1-year mortality, 81.2%). Conclusions: In this BAV cohort, severe frailty was a predictor of 1-year mortality in elderly patients with severe AS.

Skin ulcer due to hemodialysis access-induced distal ischemia treated with arteriovenous fistula banding and endovascular therapy.

A 58-year-old woman with pallor on her left hand due to chronic hemodialysis presented with a recent intractable skin ulcer on her left 3rd finger; the skin perfusion pressure (SPP) was 19 mmHg. Preoperative angiography revealed an occluded proximal left radial artery, no communication between the ulnar and superficial palmar arteries, several collaterals from the left ulnar to the radial artery, and no visualization of the finger arteries. Successful endovascular therapy to the occluded radial artery increased flow to the arteriovenous fistula (AVF), but not to the fingertips. Slightly compressing the AVF augmented the flow and wound blush at the wound sites on the 3rd fingertip, leading to a diagnosis of hemodialysis access-induced distal ischemia (HAIDI). Surgical AVF banding with intra-operative SPP monitoring improved the SPP to 34 mmHg, leading to complete wound healing over 1 month with a preserved AVF. We performed a bilateral temporal artery biopsy and diagnosed giant cell arteritis. As the angiographic wound blush at wound sites is reportedly an important factor for wound healing, angiography with AVF manual compression is essential to diagnose HAIDI and evaluate the blood flow for wound healing. .

Fluid shear stress activates proline-rich tyrosine kinase via reactive oxygen species-dependent pathway.

OBJECTIVE: Fluid shear stress (flow) modulates endothelial cell (EC) function via specific signal transduction events. Previously, we showed that flow-mediated tyrosine phosphorylation of p130 Crk-associated substrate (Cas) required calcium-dependent c-Src activation. Because flow increases reactive oxygen species (ROS) production in ECs and because H(2)O(2) increases tyrosine phosphorylation of proline-rich tyrosine kinase (PYK2), we hypothesized that flow may activate PYK2 via ROS. METHODS AND RESULTS: Exposure of bovine aortic ECs to flow stimulated PYK2 phosphorylation rapidly, with a peak at 2 minutes. The activation of PYK2 and phosphorylation of Cas induced by flow were inhibited by pretreatment with the antioxidant N-acetylcysteine. Flow-induced PYK2 phosphorylation was inhibited by BAPTA-AM, an intracellular calcium chelator. Bovine aortic ECs transfected with kinase-inactive PYK2 showed attenuated flow-stimulated Cas tyrosine phosphorylation. Although flow-induced Cas phosphorylation was inhibited by kinase-inactive Src, PYK2 activation induced by flow was not inhibited by overexpression of kinase-inactive Src. CONCLUSIONS: These results show a redox-sensitive pathway for flow-mediated activation of nonreceptor tyrosine kinase activity that requires ROS and intracellular calcium, but not Src kinase.

Expression of tissue transglutaminase and elafin in human coronary artery: implication for plaque instability.

BACKGROUND: the extracellular matrix (ECM) is an important determinant of plaque instability. Since tissue transglutaminase (tTG) and elafin act as stabilizing factors, they might play a crucial role in the pathogenesis of acute coronary syndrome. We examined their expression in human coronary arteries and the regulation of tTG expression in cultured vascular smooth muscle cells (SMCs). METHODS AND RESULTS: immunohistochemical studies on autopsy samples of human coronary arteries revealed the expression of tTG and elafin in the endothelium, medial SMCs, and the ECM in non-atherosclerotic coronary arteries. Their expression in SMCs, endothelium, and ECM was enhanced in atherosclerotic coronary arteries. In contrast, they were hardly detectable in accumulating macrophages or at the lipid core. Double staining demonstrated that elafin was co-localized with tTG. Moreover, some tTG-expressing cells were positive for TNF-alpha, suggesting that this cytokine might play an important role in the regulation of tTG. Treatment of cultured rat aortic SMCs with TNF-alpha increased their tTG mRNA, protein expression and enzyme activity. CONCLUSIONS: the expression of tTG and elafin increased in atherosclerotic coronary arteries. The investigation with cultured SMCs suggested that TNF-alpha might mediate the upregulation of tTG. Our findings may provide new insights into the mechanism of plaque instability and the pathogenesis of acute coronary syndrome.