Publications by authors named "Yasuchika Takeishi"

436 Publications

A sudden rise in pacing threshold of left ventricular lead associated with myocardial ischemia.

J Arrhythm 2021 Jun 3;37(3):693-695. Epub 2021 Apr 3.

Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.

We report for the first time a sudden rise in the pacing threshold of the left ventricular lead due to myocardial ischemia after cardiac resynchronization therapy with defibrillator implantation, and its recovery to the baseline after the revascularization.
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http://dx.doi.org/10.1002/joa3.12536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207431PMC
June 2021

Significance of Contact Force on Esophageal Thermal Injury During Relative High-Power Short-Duration Ablation of Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2021 Jun 11;14(6):e009897. Epub 2021 Jun 11.

Department of Cardiovascular Medicine (T.K., K.A., N.H., M.N., S.Y., T.Y., T.M., A.Y., Y.T.), Fukushima Medical University, Fukushima, Japan.

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http://dx.doi.org/10.1161/CIRCEP.121.009897DOI Listing
June 2021

Serum TRACP5b, a Marker of Bone Resorption, Is Associated With Adverse Cardiac Prognosis in Hospitalized Patients With Heart Failure.

CJC Open 2021 Apr 13;3(4):470-478. Epub 2020 Dec 13.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Background: Tartrate-resistant acid phosphatase type 5b (TRACP5b) is derived from osteoclasts, and has been used as a marker of osteoporosis (bone resorption). Although heart failure (HF) is associated with catabolic bone remodelling, serum TRACP5b levels have not been rigourously examined in patients with HF.

Methods: We conducted a prospective observational study of 688 decompensated HF patients who had been discharged and whose TRACP5b had been measured. These patients were divided into tertiles on the basis of serum TRACP5b levels: first (TRACP5b < 316 mU/dL, n = 229), second (TRACP5b 316-489 mU/dL, n = 229), and third (TRACP5b ≥ 490 mU/dL, n = 230). We compared the patient baseline characteristics, exercise capacity, and their postdischarge prognosis, including cardiac mortality and cardiac events such as cardiac death and worsening HF.

Results: Age was significantly higher, and prevalence of female sex and anemia was significantly higher in the third tertile than in the first and second tertiles ( < 0.05, respectively). Circulating TRACP5b levels were correlated with peak breath-by-breath oxygen consumption, but not with left ventricular ejection fraction. In the Kaplan-Meier analysis (mean follow-up, 426 days), cardiac mortality and cardiac event rates progressively increased from the first to the third tertiles ( < 0.05, respectively). In the multivariable Cox proportional hazard analysis, the third tertile was an independent predictor of cardiac mortality and cardiac events (cardiac mortality hazard ratio, 2.493;  = 0.040; cardiac events hazard ratio, 1.687;  = 0.030).

Conclusions: High serum levels of TRACP5b, a marker of bone resorption, are associated with high cardiac mortality and cardiac events, accompanied by impaired exercise capacity.
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http://dx.doi.org/10.1016/j.cjco.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129440PMC
April 2021

Autonomic cardiogastric neural interaction after pulmonary vein isolation in patients with atrial fibrillation.

J Interv Card Electrophysiol 2021 May 6. Epub 2021 May 6.

Department of Cardiovascular Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Purpose: Clinical significance of reduced vagal activity following pulmonary vein isolation (PVI) for atrial fibrillation (AF) remains unclear. Periesophageal vagal nerve injury following PVI may be a powerful contributing factor of decreased vagal tone.

Methods: Drug-refractory 51 AF patients (31 males, 64 ± 11 years), who underwent successful PVI, were enrolled. We performed esophagogastroduodenoscopy 2 days after PVI and assessed delayed gastric emptying (DGE). Additionally, the coefficient of variance of R-R interval (CVRR) as a surrogate for vagal tone was measured before PVI, as well as at 1 day and 3 months after PVI. The patients were divided into two groups, patients with DGE and patients without DGE, and changes in CVRR were compared.

Results: After PVI, 12 out of 51 patients (23.5%) had DGE. The baseline CVRR did not differ between the patients with (n = 12) and those without (n = 39) DGE (median 3.13%, interquartile range 1.69-5.13 vs. median 3.76%, interquartile range 2.96-5.90, P = 0.297). However, CVRR at 1 day after PVI was significantly lower in the patients with DGE than in those without (median 1.49%, interquartile range 0.90-2.19 vs. median 2.59%, interquartile range 1.58-3.86, P = 0.035), and then CVRR at 3 months became similar between the two groups, suggesting that the two groups had different changes in vagal tone after PVI. The recurrence of AF was similar at 3-6 months after PVI between the two groups.

Conclusions: A significantly decreased CVRR immediately after PVI is a sign of DGE incidence, implying collateral damage to the esophagus.
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http://dx.doi.org/10.1007/s10840-021-01004-zDOI Listing
May 2021

Cardio-Ankle Vascular Index Reflects Impaired Exercise Capacity and Predicts Adverse Prognosis in Patients With Heart Failure.

Front Cardiovasc Med 2021 29;8:631807. Epub 2021 Mar 29.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

We aimed to assess the associations of CAVI with exercise capacity in heart failure (HF) patients. In addition, we further examined their prognosis. We collected the clinical data of 223 patients who had been hospitalized for decompensated HF and had undergone both CAVI and cardiopulmonary exercise testing. For the prediction of an impaired peak oxygen uptake (VO) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. In the multivariate logistic regression analysis for predicting impaired peak VO, high CAVI was found to be an independent factor (odds ratio 2.343, = 0.045). We divided these patients based on CAVI: the low-CAVI group (CAVI < 8.9, = 145) and the high-CAVI group (CAVI ≥ 8.9, = 78). Patient characteristics and post-discharge cardiac events were compared between the two groups. The high-CAVI group was older (69.0 vs. 58.0 years old, < 0.001) and had lower body mass index (23.0 vs. 24.1 kg/m, = 0.013). During the post-discharge follow-up period of median 1,623 days, 58 cardiac events occurred. The Kaplan-Meier analysis demonstrated that the cardiac event rate was higher in the high-CAVI group than in the low-CAVI group (log-rank = 0.004). The multivariate Cox proportional hazard analysis revealed that high CAVI was an independent predictor of cardiac events (hazard ratio 1.845, = 0.035). High CAVI is independently associated with impaired exercise capacity and a high cardiac event rate in HF patients.
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http://dx.doi.org/10.3389/fcvm.2021.631807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044779PMC
March 2021

Visit-to-Visit Blood Pressure Variability Predicts Atrial Fibrillation Recurrence After Pulmonary Vein Isolation in Patients With Hypertension and Atrial Fibrillation.

Circ Rep 2021 Mar 18;3(4):187-193. Epub 2021 Mar 18.

Department of Cardiovascular Medicine, Fukushima Medical University Fukushima Japan.

The impact of preprocedural visit-to-visit blood pressure variability (BPV) on pulmonary vein isolation (PVI) outcome in patients with hypertension (HTN) and atrial fibrillation (AF) remains unclear. This study enrolled 138 AF patients with HTN who underwent successful PVI. Patients were classified into 2 groups, those with AF recurrence (AF-Rec; n=42) and those without AF recurrence (No-AF-Rec; n=96). Blood pressure (BP) was measured at least 3 times during sinus rhythm, and systolic and diastolic BPV (Sys-BPV and Dia-BPV, respectively) were defined as the standard deviation of BP. Clinical characteristics were compared between the 2 groups, and the relationship between BPV and AF recurrence was investigated. Sys-BPV and Dia-BPV were significantly higher in the AF-Rec than No-AF-Rec group (Sys-BPV: 10.6±3.7 vs. 6.9±3.5; Dia-BPV: 7.3±3.1 vs. 4.8±3.0; P<0.05 for both). Receiver operating characteristic analysis revealed Sys-BPV 9.1 and Dia-BPV 5.7 as cut-off values for AF recurrence. Kaplan-Meyer analysis demonstrated higher AF recurrence in patients with Sys-BPV >9.1 and Dia-BPV >5.7 (P<0.05 for both). Cox multivariate regression analysis revealed that Sys-BPV >9.1 and Dia-BPV >5.7 were independent predictors of AF recurrence (hazard ratios 3.736 and 2.958, respectively; P<0.05 for both). Sys-BPV and Dia-BPV were associated with AF recurrence in AF patients with HTN.
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http://dx.doi.org/10.1253/circrep.CR-21-0014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024017PMC
March 2021

Myeloproliferative neoplasm-driving Calr frameshift promotes the development of pulmonary hypertension in mice.

J Hematol Oncol 2021 Mar 30;14(1):52. Epub 2021 Mar 30.

Department of Blood Transfusion and Transplantation Immunology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Frameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calr mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calr mice) showed a slight splenic enlargement. Phosphorylated STAT3 (pSTAT3) was upregulated in BM cells of both knock-in mice. In BM transplantation (BMT) recipients from Calr mice, although PB cell counts were not different from those in BMT recipients from Calr mice, Calr BM-derived macrophages exhibited elevations of pSTAT3 and Endothelin-1 levels. Strikingly, BMT recipients from Calr mice developed more severe pulmonary hypertension (PH)-which often arises as a comorbidity in patients with MPNs-than BMT recipients from Calr mice, with pulmonary arterial remodeling accompanied by an accumulation of donor-derived macrophages in response to chronic hypoxia. In conclusion, our murine model with the frameshifted murine Calr presented an ET phenotype analogous to human MPNs in molecular mechanisms and cardiovascular complications such as PH.
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http://dx.doi.org/10.1186/s13045-021-01064-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011226PMC
March 2021

Endothelin-1 Upregulates Activin Receptor-Like Kinase-1 Expression via G/RhoA/Sp-1/Rho Kinase Pathways in Human Pulmonary Arterial Endothelial Cells.

Front Cardiovasc Med 2021 23;8:648981. Epub 2021 Feb 23.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vasoconstriction and organic stenosis. It has been demonstrated that endothelin-1 (ET-1) induces pulmonary vasoconstriction through the activation of RhoA. In addition, a gene mutation of activin receptor-like kinase (ACVRL)-1 is recognized in PAH patients. However, little is known about the association between ET-1 and ACVRL-1. In the present study, we aimed to investigate the effect of ET-1 on ACVRL-1 expression and delineate the involvement of the G/RhoA/Rho kinase pathway. ET-1 was added to culture medium of human pulmonary arterial endothelial cells (PAECs). Pre-treatment with pertussis toxin (PTX) or exoenzyme C3 transferase (C3T) was performed for inhibition of G or RhoA, respectively. Rho kinase was inhibited by Y27632. Mithramycin A was used for inhibition of Sp-1, which is a transcriptional factor of ACVRL-1. The active form of RhoA (GTP-RhoA) was assessed by pull-down assay. ACVRL-1 expression was increased by ET-1 in the PAECs. Pull-down assay revealed that ET-1 induced GTP-loading of RhoA, which was suppressed by pre-treatment with PTX or C3T. Further, PTX, C3T, and Y27632 suppressed the ET-1-induced ACVRL-1 expression. ET-1 increased the activity of the ACVRL-1 promoter and stabilized the ACVRL-1 mRNA. Sp-1 peaked 15 min after adding ET-1 to the PAECs. PTX and C3T prevented the increase of Sp-1 induced by ET-1. Inhibition of Sp-1 by mithramycin A suppressed ET-1-induced ACVRL-1 upregulation. The present study demonstrated that ET-1 increases ACVRL-1 expression in human PAECs the G/RhoA/Rho kinase pathway with the involvement of Sp-1.
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http://dx.doi.org/10.3389/fcvm.2021.648981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940194PMC
February 2021

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data.

Clin Res Cardiol 2021 Mar 11. Epub 2021 Mar 11.

Department of Cardiology, Maastricht University Medical Centre, PO Box 5800, 6202AZ, Maastricht, The Netherlands.

Background: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.

Methods: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m, 18.5-25.0 kg/m; 25.0-30.0 kg/m; 30.0 kg/m). Primary endpoints included all-cause mortality and HF hospitalization-free survival.

Results: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.

Conclusions: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).
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http://dx.doi.org/10.1007/s00392-021-01822-1DOI Listing
March 2021

Comparison of the Apnea-Hypopnea Index Determined by a Peripheral Arterial Tonometry-Based Device With That Determined by Polysomnography - Results From a Multicenter Study.

Circ Rep 2020 Oct 16;2(11):674-681. Epub 2020 Oct 16.

Department of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University Saitama Japan.

Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P<0.001) with acceptable agreement. The strong correlation between pAHI and AHI-PSG was observed in patients with CVD (n=55; P=0.849; P<0.001) and without CVD (n=65; r=0.927; P<0.001). The presence or absence of CVD did not affect the relationship between pAHI and AHI-PSG (P=0.225). A PAT-based device provides a reliable AHI in a Japanese patient population, even in patients with CVD. These findings may help reduce the number of patients with undiagnosed SDB and CVD.
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http://dx.doi.org/10.1253/circrep.CR-20-0097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937496PMC
October 2020

Prevalence, Predictors, and Mid-Term Outcomes of Non-Home Discharge After Transcatheter Aortic Valve Implantation.

Circ Rep 2020 Oct 1;2(10):617-624. Epub 2020 Oct 1.

Department of Cardiology, Sakakibara Heart Institute Tokyo Japan.

Transcatheter aortic valve implantation (TAVI) has been widely used as a valued alternative to surgical aortic valve replacement. In cardiovascular surgeries, discharge disposition has been widely investigated. We examined the prevalence and predictors of non-home discharge after TAVI, and the prognosis based on discharge destination. We retrospectively analyzed 732 consecutive patients undergoing TAVI, and divided them into 2 groups: the home group (discharged directly home; n=678 [92.6%]) and the non-home group (n=54 [7.4%]). From baseline and procedural characteristics, peripheral artery disease (PAD; odds ratio [OR] 2.73; 95% confidence interval [CI] 1.25-5.97; P=0.012), previous stroke (OR 2.57; 95% CI 1.03-6.45; P=0.045), albumin level (OR 0.16 per 1-g/dL increase; 95% CI 0.07-0.39; P<0.001), and procedural stroke (OR 31.6; 95% CI 10.9-91.7; P<0.001) were independently associated with non-home discharge. In Kaplan-Meier analysis, the non-home group had worse survival than the home group (log-rank, P=0.001). In multivariate analysis, male sex, atrial fibrillation or atrial flutter, and low albumin concentrations were associated with all-cause mortality, but non-home discharge was not (P=0.18). Non-home discharge was recorded for 7.4% of patients undergoing TAVI, and was associated with PAD, nutritional status, and previous and procedural stroke. Non-home discharge reflects worse baseline characteristics, and may be a marker of mid-term outcome after TAVI.
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http://dx.doi.org/10.1253/circrep.CR-20-0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933692PMC
October 2020

Association between atrial fibrillation and white blood cell count after the Great East Japan Earthquake: An observational study from the Fukushima Health Management Survey.

Medicine (Baltimore) 2021 Feb;100(6):e24177

Radiation Medical Science Center for the Fukushima Health Management Survey.

Abstract: We had earlier reported about the increase in the prevalence of atrial fibrillation (AF) among residents in the evacuation zone of Fukushima Prefecture after the Great East Japan Earthquake. In the present investigation, we explored the association between the prevalence of AF and white blood cell (WBC) count after the earthquake through an observational cross-sectional study.A total of 14,800 participants (6427 men and 8373 women) were included in the Fukushima Health Management Survey. For the present study, 12-lead electrocardiogram tracings and the WBC count and its subtypes were obtained and analyzed. The odds ratios (ORs) of AF after the earthquake and the 95% confidence intervals (CIs) for one standard deviation of differential WBC count were calculated after adjustments for age and other potential confounding factors using the logistic regression model.Our results revealed a prevalence of AF of 1.8% (269 participants) after the earthquake. Monocyte count and neutrophil/lymphocyte ratio exhibited a significant association with the prevalence of AF in the multivariable-adjusted model. The adjusted ORs of monocyte count and neutrophil/lymphocyte ratio for AF were 1.21 (95% CI, 1.05-1.40, P = .01) and 1.22 (95% CI, 1.01-1.44, P < .05), respectively.The prevalence of AF was associated with increased monocyte count and neutrophil/lymphocyte ratio among residents in the evacuation zone in Fukushima Prefecture, suggesting that inflammation and psychological stress could be important factors mediating the development of AF after the earthquake.
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http://dx.doi.org/10.1097/MD.0000000000024177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886431PMC
February 2021

Crucial role of hematopoietic JAK2V617F in the development of aortic aneurysms.

Haematologica 2021 Feb 11. Epub 2021 Feb 11.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima.

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.
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http://dx.doi.org/10.3324/haematol.2020.264085DOI Listing
February 2021

Electrophysiological properties and involvement of anatomical factors for the prediction of intramural origin in patients with ventricular tachyarrhythmia arising from the left ventricular outflow tract.

J Interv Card Electrophysiol 2021 Feb 9. Epub 2021 Feb 9.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Purpose: To elucidate the electrophysiological predictors of the intramural origins of left ventricular outflow tract-ventricular tachyarrhythmias (LVOT-VAs), and to clarify the involvement of anatomical factors.

Methods: Twenty-nine successfully ablated LVOT-VAs patients with origins in the aortomitral continuity (AMC) (n = 8), aortic sinus of valsalva (ASV) (n = 9), great cardiac vein (GCV) (n = 5), and intramural myocardium (n = 7) were enrolled. Intramural origins were defined as when effective ablation from AMC and epicardium (ASV and/or GCV) was needed. The local activation time difference (LATD) was calculated as follows: (earliest AMC activation) - (earliest epicardial activation), and was presented as an absolute value. Electrophysiological parameters and anatomical factors predisposing the intramural origins were investigated.

Results: LATD of intramural origins was significantly shorter than that of AMC and GCV (4.5 ± 2.6 vs. 12.1 ± 7.4 vs. 17.4 ± 4.7, P < 0.05), respectively. In multivariate logistic regression analysis, LATD was associated with intramural origins (odds ratio: 0.711, confidence interval: 0.514-0.985, P = 0.040). ROC analysis revealed LATD of 7 ms as cut-off value. In computed tomography analysis, some patients who had thick fat tissue below the GCV, and an unusual GCV running pattern might be misdiagnosed as intramural origins.

Conclusion: LATD ≤ 7 ms was associated with intramural origins, but with some anatomical limitations.
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http://dx.doi.org/10.1007/s10840-021-00959-3DOI Listing
February 2021

Symptomatic Long QT syndrome Coexisting with Asymptomatic Acetylcholine-induced Vasospasm.

Intern Med 2021 Feb 1. Epub 2021 Feb 1.

Department of Cardiovascular Medicine, Fukushima Medical University, Japan.

We herein report a rare case of long QT syndrome (LQTS) coexisting with acetylcholine (Ach)-induced vasospasm. A 31-year-old woman experienced cardiopulmonary arrest during running. LQTS was diagnosed by an electrocardiogram, and the coexistence of Ach-induced vasospam was determined by an Ach provocation test on coronary angiography. Although an implantable cardioverter defibrillator was placed, a beta-blocker was not prescribed for two reasons: first, the patient showed Ach-induced vasospasm alone with no symptoms and no ST change by Ach injection, and second, the use of beta-blockers alone in such patients carries a risk of vasospasm-induced ventricular fibrillation.
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http://dx.doi.org/10.2169/internalmedicine.6475-20DOI Listing
February 2021

Anti-mitochondrial Antibodies in Patients with Dilated Cardiomyopathy.

Intern Med 2021 15;60(2):201-208. Epub 2021 Jan 15.

Department of Cardiovascular Medicine, Fukushima Medical University, Japan.

Objective It has been reported that anti-mitochondrial antibodies (AMAs) recognize mitochondrial antigens and are associated with some diseases involving multiple organs, such as primary biliary cholangitis, Sjögren syndrome, Hashimoto's thyroiditis, systemic sclerosis, interstitial pneumoniae, dilated cardiomyopathy, and tubulointerstitial nephritis. In the current study, we examined the prevalence of AMAs in patients with dilated cardiomyopathy (DCM) and their clinical characteristics. Methods We enrolled 270 patients with DCM. We measured serum AMAs and analyzed the associated factors. Out of the 270 patients, positive AMAs were detected in 3 patients (1.1%; mean age, 68 years old; 2 men). These three patients had a significantly higher prevalence of primary biliary cholangitis and myopathy and levels of alanine alkaline phosphatase than those who were negative for said antibodies. There were no significant differences in the levels of B-type natriuretic peptide, aspartate transaminase, and left ventricular ejection fraction between these groups of patients. During the follow-up period, two of the three patients died due to respiratory failure. The other patient survived but experienced type II respiratory failure. Conclusion The prevalence of AMAs in 270 DCM patients was only 1.1%, and these patients suffered from respiratory failure.
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http://dx.doi.org/10.2169/internalmedicine.5422-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872813PMC
April 2021

Effects of daily alcohol intake on glomerular filtration rate over three years.

Fukushima J Med Sci 2021 Apr 6;67(1):1-7. Epub 2021 Jan 6.

Department of Cardiovascular Medicine, Fukushima Medical University.

Background: The association between daily alcohol intake and changes in renal function in the Japanese general population is not well established.

Methods: We analyzed data from 150 residents who underwent specific health checkups held in Mishima Town in 2016 and 2019. We divided participants on the basis of alcohol consumption: residents with daily alcohol intake of < 20 g/day (the none-to-low group, n = 104, 69.3%); those with daily alcohol intake of ≥ 20 but < 40 g/day (the intermediate group, n = 30, 20.0%); and those with daily alcohol intake of ≥ 40 g/day (the high group, n = 16, 10.7%). We compared baseline characteristics. The primary endpoint was a decrease in estimated glomerular filtration rate (eGFR), defined as the decrease in eGFR greater than the median decrease over three years.

Results: The three-year changes in eGFR were +0.3 (-4.8, +3.0), -2.3 (-5.1, +1.2), and -4.9 (-8.2, -2.9) mL/min/1.73 m in the none-to-low, intermediate, and high groups, respectively (P = 0.007). In the multivariate logistic regression analysis, a high amount of alcohol intake was independently associated with a decrease in eGFR, with adjusted odds ratio of 11.418 (95% confidence interval 1.554-83.879, P = 0.017).

Conclusion: A high average daily alcohol intake is associated with a decrease in eGFR.
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http://dx.doi.org/10.5387/fms.2020-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075561PMC
April 2021

Soluble fibrin monomer complex is associated with cardio- and cerebrovascular events in patients with heart failure.

Int J Cardiol Heart Vasc 2021 Feb 24;32:100697. Epub 2020 Dec 24.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Background: A biomarker of fibrin formation, the soluble fibrin monomer complex (SFMC), is abnormally elevated in a variety of clinical situations of hypercoagulability. The aim of the present study was to examine the prognostic impact of SFMC, with regard to increased risk of major cardio- and cerebrovascular events (MACCE) and all-cause mortality, on patients with heart failure (HF).

Methods And Results: We conducted a prospective observational study where we analyzed data of 723 hospitalized patients with decompensated HF who were discharged alive and whose SFMC had been measured in a stable condition prior to discharge. The patients were divided into tertiles based on SFMC levels: the first (SFMC < 1.7 μg/ml, n = 250), second (≤1.8 SFMC < 2.9 μg/ml, n = 233), and third (3.0 μg/ml ≤ SFMC, n = 240) tertiles. The prevalence of chronic kidney disease and anemia was significantly higher in the third tertile than in the first and second tertiles. In contrast, age, sex, CHADS-Vasc score, left ventricular ejection fraction, and prevalence of hypertension, diabetes and atrial fibrillation did not differ among the tertiles. In the Kaplan-Meier analysis, accumulated event rates of both MACCE and all-cause mortality progressively increased from the first to third tertiles (log-rank P < 0.05, respectively). In the multivariate Cox proportional hazard analysis, the third tertile was found to be an independent predictor of MACCE (HR 2.014, P = 0.046) and all-cause mortality (HR 1.792, P = 0.036).

Conclusion: SFMC is an independent predictor of adverse prognosis in patients with HF.
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http://dx.doi.org/10.1016/j.ijcha.2020.100697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772787PMC
February 2021

Association between platelet distribution width and prognosis in patients with heart failure.

PLoS One 2020 29;15(12):e0244608. Epub 2020 Dec 29.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Background: The prognostic impact of platelet distribution width (PDW), which is a specific marker of platelet activation, has been unclear in patients with heart failure (HF).

Methods And Results: We conducted a prospective observational study enrolling 1,746 hospitalized patients with HF. Patients were divided into tertiles based on levels of PDW: 1st (PDW < 15.9 fL, n = 586), 2nd (PDW 15.9-16.8 fL, n = 617), and 3rd (PDW ≥ 16.9, n = 543) tertiles. We compared baseline patients' characteristics and post-discharge prognosis: all-cause death; cardiac death; and cardiac events. The 3rd tertile showed the highest age and levels of B-type natriuretic peptide compared to other tertiles (1st, 2nd, and 3rd tertiles; age, 69.0, 68.0, and 70.0 years old, P = 0.038; B-type natriuretic peptide, 235.2, 171.9, and 241.0 pg/mL, P < 0.001). Left ventricular ejection fraction was equivalent among the tertiles. In the Kaplan-Meier analysis, rates of all endpoints were the highest in the 3rd tertile (log-rank P < 0.001, respectively). The Cox proportional hazard analysis revealed that the 3rd tertile was associated with adverse prognosis (all-cause death, hazard ratio [HR] 1.716, P < 0.001; cardiac death, HR 1.919, P < 0.001; cardiac event, HR 1.401, P = 0.002).

Conclusions: High PDW is a novel predictor of adverse prognosis in patients with HF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244608PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771660PMC
March 2021

Glasgow-Blatchford Score Predicts Post-Discharge Gastrointestinal Bleeding in Hospitalized Patients with Heart Failure.

J Clin Med 2020 Dec 17;9(12). Epub 2020 Dec 17.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima 960-1247, Japan.

Background: The Glasgow-Blatchford Score (GBS) is one of the most widely used scoring systems for predicting clinical outcomes for gastrointestinal bleeding (GIB). However, the clinical significance of the GBS in predicting GIB in patients with heart failure (HF) remains unclear.

Methods And Results: We conducted a prospective observational study in which we collected the clinical data of a total of 2236 patients (1130 men, median 70 years old) who were admitted to Fukushima Medical University Hospital for acute decompensated HF. During the post-discharge follow-up period of a median of 1235 days, seventy-eight (3.5%) patients experienced GIB. The GBS was calculated based on blood urea nitrogen, hemoglobin, systolic blood pressure, heart rate, and history of hepatic disease. The survival classification and regression tree analysis revealed that the accurate cut-off point of the GBS in predicting post-discharge GIB was six points. The patients were divided into two groups: the high GBS group (GBS > 6, = 702, 31.4%) and the low GBS group (GBS ≤ 6, = 1534, 68.6%). The Kaplan-Meier analysis showed that GIB rates were higher in the high GBS group than in the low GBS group. Multivariate Cox proportional hazards analysis adjusted for age, malignant tumor, and albumin indicated that a high GBS was an independent predictor of GIB (hazards ratio 2.258, 95% confidence interval 1.326-3.845, = 0.003).

Conclusions: A high GBS is an independent predictor and useful risk stratification score of post-discharge GIB in patients with HF.
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http://dx.doi.org/10.3390/jcm9124083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766138PMC
December 2020

The relationship between red cell distribution width and cardiac autonomic function in heart failure.

J Arrhythm 2020 Dec 8;36(6):1076-1082. Epub 2020 Oct 8.

Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.

Background: Both increases in red cell distribution width (RDW) levels and autonomic dysfunction are considered to be correlated with worsening heart failure. However, the relation of RDW levels to autonomic function remains uncertain. We aimed to investigate the association of RDW levels in heart failure with autonomic function, evaluated by heart rate variability (HRV) and heart rate turbulence (HRT), and prognosis.

Methods: We studied 222 hospitalized patients with stable heart failure before discharge, and Holter recordings (HRV and HRT) were performed. Additionally, RDW levels were measured, and high RDW was defined as over 14.5%. We then divided the patients into two groups based on RDW levels: high RDW group (>14.5%, n = 92) and low RDW group (≤14.5%, n = 130). The relation of RDW to autonomic function and prognosis was assessed.

Results: In the high RDW group, severely impaired HRV and HRT were found compared to the low RDW group. In the linear regression analysis after the adjustment of multiple confounders, RDW levels were correlated with a low-frequency (LF) to high-frequency (HF) ratio and very low-frequency (VLF) power (LF to HF ratio, β = -0.146,  = .027, and VLF power, β = -0.137,  = .041, respectively). During the observation period (median 1400 days), cardiac events (re-hospitalization of heart failure, cardiac death or sudden death) were found in 73 (32.8%) patients. The Kaplan-Meier analysis demonstrated that the high RDW group had a higher rate of cardiac events compared to the low RDW group (45.6% vs 23.8%, log-rank  < .001).

Conclusion: High RDW levels were correlated with autonomic dysfunction, resulting in poor clinical outcomes.
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http://dx.doi.org/10.1002/joa3.12442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733562PMC
December 2020

Intrarenal Doppler ultrasonography reflects hemodynamics and predicts prognosis in patients with heart failure.

Sci Rep 2020 12 17;10(1):22257. Epub 2020 Dec 17.

Department of Cardiovascular Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

We aimed to clarify clinical implications of intrarenal hemodynamics assessed by intrarenal Doppler ultrasonography (IRD) and their prognostic impacts in heart failure (HF). We performed a prospective observational study, and examined IRD and measured interlobar renal artery velocity time integral (VTI) and intrarenal venous flow (IRVF) patterns (monophasic or non-monophasic pattern) to assess intrarenal hypoperfusion and congestion in HF patients (n = 341). Seven patients were excluded in VTI analysis due to unclear imaging. The patients were divided into groups based on (A) VTI: high VTI (VTI ≥ 14.0 cm, n = 231) or low VTI (VTI < 14.0 cm, n = 103); and (B) IRVF patterns: monophasic (n = 36) or non-monophasic (n = 305). We compared post-discharge cardiac event rate between the groups, and right-heart catheterization was performed in 166 patients. Cardiac index was lower in low VTI than in high VTI (P = 0.04), and right atrial pressure was higher in monophasic than in non-monophasic (P = 0.03). In the Kaplan-Meier analysis, cardiac event rate was higher in low VTI and monophasic groups (P < 0.01, respectively). In the Cox proportional hazard analysis, the combination of low VTI and a monophasic IRVF pattern was a predictor of cardiac events (P < 0.01). IRD imaging might be associated with cardiac output and right atrial pressure, and prognosis.
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http://dx.doi.org/10.1038/s41598-020-79351-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746684PMC
December 2020

Red Blood Cell Distribution Width Is a Predictive Factor of Anthracycline-Induced Cardiotoxicity.

Front Cardiovasc Med 2020 30;7:594685. Epub 2020 Oct 30.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Red blood cell distribution width (RDW) is associated with prognosis in widespread cardiovascular fields, but little is known about relationship with the onset of cancer therapeutics-related cardiac dysfunction (CTRCD). The purpose of this study was to assess whether RDW could predict the onset of CTRCD by anthracycline. Consequential 202 cancer patients planed for anthracycline treatment were enrolled and followed up for 12 months. The patients were divided into 2 groups based on the median value of baseline RDW before chemotherapy [low RDW group, = 98, 13.0 [12.6-13.2]; high RDW group, = 104, 14.9 [13.9-17.0]]. Cardiac function was assessed serially by echocardiography at baseline (before chemotherapy), as well as at 3, 6, and 12 months after chemotherapy with anthracycline. Baseline left ventricular end systolic volume index and ejection fraction (EF) were similar between two groups. After chemotherapy, EF decreased at 3- and 6-month in the high RDW group [baseline, 64.5% [61.9-68.9%]; 3-month, 62.6% [60.4-66.9%]; 6-month, 63.9% [60.0-67.9%]; 12-month, 64.7% [60.8-67.0%], = 0.04], but no change was observed in low RDW group. The occurrence of CTRCD was higher in high RDW group than in low RDW group (11.5 vs. 2.0%, = 0.008). When we set the cut-off value of RDW at 13.8, sensitivity and specificity to predict CTRCD were 84.6 and 62.0%, respectively. Multivariable logistic regression analysis revealed that baseline RDW value was an independent predictor of the development of CTRCD [odds ratio 1.390, 95% CI [1.09-1.78], = 0.008]. The value of net reclassification index (NRI) and integrated discrimination improvement (IDI) for detecting CTRCD reached statistical significance when baseline RDW value was added to the regression model including known risk factors such as cumulative anthracycline dose, EF, albumin, and the presence of hypertension; 0.9252 (95%CI 0.4103-1.4402, < 0.001) for NRI and 0.1125 (95%CI 0.0078-0.2171, = 0.035) for IDI. Baseline RDW is a novel parameter to predict anthracycline-induced CTRCD.
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http://dx.doi.org/10.3389/fcvm.2020.594685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673199PMC
October 2020

Shear Wave Dispersion Predicts Liver Fibrosis and Adverse Outcomes in Patients with Heart Failure.

J Clin Med 2020 Dec 6;9(12). Epub 2020 Dec 6.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.

Background: It has been recently reported that liver stiffness assessed by transient elastography reflects right atrial pressure (RAP) and is associated with worse outcomes in patients with heart failure (HF). However, the relationship between shear wave dispersion (SWD, a novel indicator of liver viscosity) determined by abdominal ultrasonography and RAP, and the prognostic impact of SWD on HF patients have not been fully examined. We aimed to clarify the associations of SWD with parameters of liver function test (LFT) and right heart catheterization (RHC), as well as with cardiac events such as cardiac death and worsening HF, in patients with HF.

Methods: We performed abdominal ultrasonography, LFT and RHC in HF patients ( = 195), and followed up for cardiac events. We examined associations between SWD and parameters of LFT and RHC.

Results: There were significant correlations between SWD and circulating levels of direct bilirubin (R = 0.222, = 0.002), alkaline phosphatase (R = 0.219, = 0.002), cholinesterase (R = -0.184, = 0.011), and 7S domain of collagen type IV (R = 0.177, = 0.014), but not with RAP (R = 0.054, = 0.567) or cardiac index (R = -0.015, = 0.872). In the Kaplan-Meier analysis, cardiac event rate was significantly higher in the high SWD group (SWD ≥ 10.0 (m/s)/kHz, = 103) than in the low SWD group (SWD < 10.0 (m/s)/kHz, = 92; log-rank, = 0.010). In the Cox proportional hazard analysis, high SWD was associated with high cardiac event rates (hazard ratio, 2.841; 95% confidence interval, 1.234-6.541, = 0.014). In addition, there were no interactions between SWD and all subgroups, according to the subgroup analysis.

Conclusions: SWD assessed by abdominal ultrasonography reflects liver fibrosis rather than liver congestion, and is associated with adverse prognosis in HF patients.
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http://dx.doi.org/10.3390/jcm9123953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762121PMC
December 2020

Clinical impact of long PR-interval and presence of late gadolinium enhancement on hospitalized patients with non-ischemic heart failure.

Ann Noninvasive Electrocardiol 2021 03 1;26(2):e12818. Epub 2020 Dec 1.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Background: The combination of electrical and structural remodeling may have a strong effect on the prognosis of non-ischemic heart failure (HF). We aimed to clarify whether prolonged PR-interval and the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) influence the outcomes of patients with non-ischemic HF.

Methods: We studied 262 consecutive hospitalized patients with non-ischemic HF. In a clinically stable condition, a 12-lead electrocardiogram and CMR were performed, and the clinical characteristics and outcomes were investigated.

Results: During the follow-up of 967.7 ± 851.8 days, there were 68 (25.9%) cardiac events (HF or sudden death, re-hospitalization due to HF, or ventricular tachyarrhythmias). In a multivariable analysis, a median rate-adjusted PR (PRa)-interval of ≥173.5 ms and the presence of LGE were associated with cardiac events with a hazard ratio of 1.690 and 2.045 (p = .044 and p = .006, respectively). Study subjects were then divided into four groups based on long (≥173.5 ms) or short (<173.5 ms) PRa-interval and LGE status: short PRa/non-LGE (n = 80), long PRa/non-LGE (n = 72), short PRa/LGE (n = 51), and long PRa/LGE (n = 59). Cardiac events were 16.2% in short PRa/non-LGE, 25.0% in long PRa/non-LGE, 27.4% in short PRa/LGE, and 38.9% in long PRa/LGE (p = .026), respectively. The multivariable Cox proportional hazard analysis showed that long PRa/LGE was an independent predictor for cardiac events compared to short PRa/non-LGE (hazard ratio, 3.378, p = .001).

Conclusions: The combination of a long PRa-interval and the presence of LGE provide a better predictive value of cardiac events in non-ischemic HF.
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http://dx.doi.org/10.1111/anec.12818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935097PMC
March 2021

Greetings from the new Editor-in-Chief.

J Cardiol 2021 01 20;77(1). Epub 2020 Nov 20.

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jjcc.2020.11.001DOI Listing
January 2021

Associations of the Prognostic Nutritional Index with the Cardiac Function and Survival after Cardiac Resynchronization Therapy.

Intern Med 2021 Apr 28;60(7):985-991. Epub 2020 Oct 28.

Department of Cardiovascular Medicine, Fukushima Medical University, Japan.

Objective The relationship between changes in the nutritional status after cardiac resynchronization therapy (CRT) and the prognosis has not been fully elucidated. We aimed to evaluate the changes in the nutritional status as assessed by the prognostic nutritional index (PNI) and their associations with the improvement in the cardiac function and subsequent clinical outcomes. Methods The study population consisted of 119 patients with a CRT-device. They were divided into 2 groups, based on whether their PNI had increased at 6 months after CRT-device implantation (positive ΔPNI group, n=73) or not (negative ΔPNI group, n=46). The left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured before and six months after CRT-device implantation. We compared the changes in the cardiac function and prevalence of adverse events (re-hospitalization due to worsening heart failure or all cause death) between the two groups. Results In the positive ΔPNI group, the LVEDV (186±93 mL vs. 149±71 mL, p<0.05) and LVESV (134±75 mL vs. 98±62 mL, p<0.05) were significantly decreased 6 months after CRT-device implantation. In addition, the LVEF (31±11% vs. 37±12%, p<0.05) was significantly increased after CRT-device implantation. In the negative ΔPNI group, no significant changes were observed in any echocardiographic parameters. During a median follow-up period of 914 days, there were 67 (56.3%) adverse events. In the Kaplan-Meier analysis, the positive ΔPNI group was associated with a lower risk of adverse events than the negative ΔPNI group (50.6% vs. 65.2%, log-rank p=0.042). Conclusion Our results suggest that improvement in the cardiac function after CRT-device implantation is associated with increases in the PNI, resulting in favorable outcomes.
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http://dx.doi.org/10.2169/internalmedicine.5961-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079914PMC
April 2021

Cardio-Ankle Vascular Index Predicts Post-Discharge Stroke in Patients with Heart Failure.

J Atheroscler Thromb 2020 Sep 25. Epub 2020 Sep 25.

Department of Cardiovascular Medicine, Fukushima Medical University.

Aim: We aimed to evaluate the significance of the cardio-ankle vascular index (CAVI) to predict stroke in patients with heart failure (HF).

Methods: This was a prospective observational study, which recruited clinical data from a total of 557 patients who had been hospitalized for HF and undergone CAVI. According to the receiver operating characteristic curve analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.64. We divided the patients into two groups: the high-CAVI group (HF patients with CAVI ≥ 9.64, n=111, 19.9%) and the low-CAVI group (HF patients with CAVI <9.64, n=446, 80.1%). We compared the patients' characteristics and post-discharge prognosis. The primary endpoint was stroke.

Results: The high-CAVI group was older (73.0 vs. 65.5 years old, P<0.001). Male sex (73.9% vs. 61.4%, P=0.015), coronary artery disease (47.7% vs. 36.1%, P=0.024), and diabetes mellitus (54.1% vs. 37.4%, P=0.001) were more prevalent in the high-CAVI group. In contrast, there was no difference in left ventricular ejection fraction, and prevalence of hypertension and dyslipidemia. The Kaplan-Meier analysis demonstrated that post-discharge stroke rate was higher in the high-CAVI group than in the low-CAVI group (log-rank P=0.005). In multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of stroke, with an adjusted hazard ratio of 3.599, compared to low CAVI.

Conclusion: CAVI independently predicts stroke in patients with HF.The trial registration number: UMIN000029132.
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http://dx.doi.org/10.5551/jat.58727DOI Listing
September 2020