Publications by authors named "Yasuhiro Izumiya"

165 Publications

Kihon checklist is useful for predicting outcomes in patients undergoing transcatheter aortic valve implantation.

J Cardiol 2021 Oct 18. Epub 2021 Oct 18.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Frailty is a major risk factor for death and disability following transcatheter aortic valve implantation (TAVI). The Kihon checklist (KCL) is a simple self-reporting yes/no survey consisting of 25 questions and is used as a screening tool to identify frailty in the primary care setting. No clinical studies have focused on frailty calculated by the KCL in the TAVI cohort. We investigated the 3-year prognostic impact of frailty evaluated by the KCL in patients who underwent TAVI.

Methods: This single-center prospective observational study included 280 consecutive patients with symptomatic severe aortic stenosis who underwent TAVI and evaluated pre-procedural physical performance focused on frailty at our institution. We assessed all patients' frailty by the KCL before TAVI, as described previously. We set the primary endpoint as the 3-year all-cause mortality after TAVI.

Results: The median patient age was 84 years (interquartile range, 81-87 years), and 31.1% were men. In the receiver operating characteristics curve, there were no significant differences between the KCL and Cardiovascular Health Study frailty index [area under the curve (AUC) 0.625 versus 0.628; p=0.93), KCL and Rockwood Clinical Frailty Scale (AUC 0.625 versus 0.542; p=0.15), and KCL and Short Physical Performance Battery (AUC 0.625 versus 0.612; p=0.91). The first and second tertiles of the total KCL score were 8 and 12, respectively. The multivariate Cox regression model indicated that the total KCL score [hazard ratio (HR), 1.104; 95% confidence interval (CI), 1.034-1.179; p=0.003], presence of diabetes mellitus (HR, 1.993; CI, 1.055-3.766; p=0.03), and presence of liver disease (HR, 3.007; CI, 1.067-8.477; p=0.04) were independently associated with 3-year all-cause mortality.

Conclusions: The KCL is a simple and useful tool for evaluating frailty status and predicting 3-year all-cause mortality in patients undergoing TAVI.
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http://dx.doi.org/10.1016/j.jjcc.2021.09.014DOI Listing
October 2021

Delayed stenosis regression after drug-coated balloon angioplasty for femoropopliteal artery lesions.

Heart Vessels 2021 Oct 21. Epub 2021 Oct 21.

Department of Cardiovascular Medicine, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.

Paclitaxel has the potential for inducing lumen enlargement by vessel enlargement, healing of dissection, and plaque regression. This study was carried out to determine the possibility of and the relevant factors of delayed stenosis regression after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) artery lesions. A total 105 de novo FP lesions were finalized with DCB angioplasty in our institute between May 2018 and June 2020. Among them, cases in which residual stenosis was detected by duplex ultrasonography (DUS) after the procedure were included in this study. Significant stenosis was defined as peak systolic velocity ratio ≥ 2.4 by DUS. Follow-up DUS was routinely performed 6 months after the procedure, and we defined cases without stenosis as cases of delayed stenosis regression according to the follow-up DUS. DUS showed that 26 (25.5%) of 102 lesions had residual stenosis after DCB angioplasty, and delayed stenosis regression was observed in 12 (57.1%) of 21 lesions 6 months after the procedure. The percentage of lesions containing calcified plaque as detected by intravascular ultrasound analysis was significantly higher in the non-regression group than in the regression group (18.2% vs. 77.8%, p = 0.02). Vessel remodeling and dissection patterns were not associated with delayed stenosis regression. The results of our analyses indicate that delayed stenosis regression may occur after DCB angioplasty for FP lesions in more than half of cases with residual stenosis. Delayed stenosis regression may be difficult in cases of calcified lesions.
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http://dx.doi.org/10.1007/s00380-021-01970-4DOI Listing
October 2021

Achilles tendon thickness is associated with coronary lesion severity in acute coronary syndrome patients without familial hypercholesterolemia.

J Cardiol 2021 Oct 14. Epub 2021 Oct 14.

Department of Cardiovascular Medicine, Ishikiriseiki Hospital, Higashiosaka, Japan; Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba Japan.

Background: Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH.

Methods: From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of <9 mm were enrolled in this study. The severity of coronary lesions was assessed by SYNTAX score derived from coronary angiography at the onset of ACS.

Results: ATT levels were not significantly different among patients with ST-elevation myocardial infarction (STEMI, n=47), non-STEMI (n=12), and unstable angina (n=17). Whereas, both average and maximum ATT were significantly larger in patients with multivessel lesions (n=25) than in those with single-vessel disease (n=51). Furthermore, SYNTAX score was positively correlated with average ATT (r=0.368, p=0.0011) and maximum ATT (r=0.388, p=0.0005). As for the relation to clinical parameters, maximum ATT had positive correlations with body mass index and C-reactive protein. A multiple regression analysis revealed that average and maximum ATT were significantly associated with SYNTAX score, independently of various confounding factors.

Conclusions: Our findings demonstrated that ATT, even though its level was <9 mm, was associated with coronary lesion severity in clinically non-FH patients with early-onset ACS. Apart from diagnosing FH, ATT may be a predictor of the progression of CAD.
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http://dx.doi.org/10.1016/j.jjcc.2021.09.021DOI Listing
October 2021

Somatic Mosaicism in Biology and Disease.

Annu Rev Physiol 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; email:

Contrary to earlier beliefs, every cell in the individual is genetically different due to somatic mutations. Consequently, tissues become a mixture of cells with distinct genomes, a phenomenon termed somatic mosaicism. Recent advances in genome sequencing technology have unveiled possible causes of mutations and how they shape the unique mutational landscape of the tissues. Moreover, the analysis of sequencing data in combination with clinical information has revealed the impacts of somatic mosaicism on disease processes. In this review, we discuss somatic mosaicism in various tissues and its clinical implications for human disease. Expected final online publication date for the , Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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http://dx.doi.org/10.1146/annurev-physiol-061121-040048DOI Listing
October 2021

Improvement of Vascular Endothelial Function Reflects Nonrecurrence After Catheter Ablation for Atrial Fibrillation.

J Am Heart Assoc 2021 Sep 21;10(17):e021551. Epub 2021 Aug 21.

Department of Cardiovascular Medicine Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia-peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia-peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; =0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; =0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log-rank test, <0.001). Conclusions The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia-peripheral arterial tonometry. Long-term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.
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http://dx.doi.org/10.1161/JAHA.121.021551DOI Listing
September 2021

Increased oxidative stress during exercise predicts poor prognosis in patients with acute decompensated heart failure.

ESC Heart Fail 2021 Oct 29;8(5):3885-3893. Epub 2021 Jul 29.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

Aims: Oxidative stress plays an important role in the development and progression of heart failure (HF). Although exercise and oxidative stress are closely related, the effect of acute exercise on reactive oxygen species production and the fluctuation on prognosis are unclear.

Methods And Results: We enrolled 94 patients who were hospitalized for worsening HF (mean age 68.0 ± 14.5 years old, 63.8% male). The changes in diacron-reactive oxygen metabolites (d-ROM) values, a marker of oxidative stress, before and after a cardiopulmonary exercise test were considered as Δd-ROM. The mean follow-up period was 24 ± 13 months, during which 15 patients had all-cause death or left ventricular assist system implantation. Kaplan-Meier analysis demonstrated that all-cause death or left ventricular assist system implantation was significantly higher in the Δd-ROM-positive group than in the Δd-ROM-negative group (log-rank P = 0.047). Elevated Δd-ROM levels were associated with increased mortality risk. Multivariate analysis adjusted for body mass index and peak oxygen uptake revealed that Δd-ROM was an independent prognostic factor of adverse events (Tertile 3 vs. 1; hazard ratio: 4.57; 95% confidence interval: 1.21-29.77; P = 0.022).

Conclusions: Patients with HF who underwent a cardiopulmonary exercise test and had an increased oxidative stress marker level had a poor prognosis. The appropriate exercise intensity could be determined by evaluating the changes in oxidative stress status in response to acute exercise in patients with HF.
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http://dx.doi.org/10.1002/ehf2.13538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497195PMC
October 2021

HE4 Predicts Progressive Fibrosis and Cardiovascular Events in Patients With Dilated Cardiomyopathy.

J Am Heart Assoc 2021 08 29;10(15):e021069. Epub 2021 Jul 29.

Department of Cardiovascular Medicine Faculty of Life Sciences Kumamoto University Kumamoto Japan.

Background Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro. Methods and Results We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (<0.0001). Echocardiography showed that left ventricular end-diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm; <0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4-transfected human embryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis-related genes, and this was accompanied by the activation of extracellular signal-regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal-regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4. Conclusions HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr; Unique identifier: UMIN000043062.
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http://dx.doi.org/10.1161/JAHA.120.021069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475713PMC
August 2021

An Unexpected Complication of Subcutaneous ICD Implantation and its Successful Management.

JACC Case Rep 2020 Jun 17;2(6):889-893. Epub 2020 Jun 17.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious complications. We present a case where an inappropriate lead placement resulted in puncturing the lung parenchyma, and successful management of the lead-related pneumothorax through thoracoscopic lead removal and partial lung resection. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.04.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302020PMC
June 2020

A simple method of sarcopenia detection can predict adverse cardiovascular events in patients with abdominal obesity.

Int J Obes (Lond) 2021 Oct 3;45(10):2214-2220. Epub 2021 Jul 3.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: Although sarcopenic obesity is associated with a higher risk of cardiovascular events compared with obesity without sarcopenia, it is difficult to diagnose sarcopenia in daily clinical settings. Recently, a simple scoring system has been developed to identify sarcopenia patients based on three variables (age, hand grip strength, and calf circumference). However, the utility of this score for cardiovascular risk stratification in patients with abdominal obesity is unknown.

Methods: We calculated the sarcopenia score in 262 patients with abdominal obesity, defined as a waist circumference ≥90 cm in women or ≥85 cm in men. The composite endpoint of this study was cardiovascular mortality, nonfatal myocardial infarction, stroke, unstable angina, and heart failure hospitalization.

Results: Of the 262 patients, 108 had a high sarcopenia score based on previously established criteria (≥105 in men and ≥120 in women). The patients with a high sarcopenia score had a significantly higher plasma level of B-type natriuretic peptide compared with those with a low sarcopenia score (median 56.7, interquartile range [28.2-142.9] vs. 37.9 [13.8-76.1] pg/mL; p < 0.0001). Kaplan-Meier curves revealed a significantly lower event-free survival rate in those with a high compared with a low sarcopenia score (log-rank test p = 0.001), even after adjustment for confounding factors using propensity score matching (log-rank test p = 0.009). Multivariate Cox proportional hazard analysis identified a high sarcopenia score (hazard ratio: 2.46; 95% confidence interval: 1.31-4.64, p = 0.005) as an independent predictor of the primary endpoints. The combination of a high sarcopenia score and low body mass index (<25 kg/m) predicted a significantly higher risk of future adverse events (p = 0.005). Furthermore, patients with a high sarcopenia score and high B-type natriuretic peptide level (≥200 pg/mL) had the poorest prognosis (p < 0.0001).

Conclusions: This simple screening test for sarcopenia can predict future adverse cardiovascular events in patients with abdominal obesity.
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http://dx.doi.org/10.1038/s41366-021-00895-2DOI Listing
October 2021

Acute pulmonary embolism with high-intensity signals on magnetic resonance direct thrombus imaging.

Eur Heart J Cardiovasc Imaging 2021 Oct;22(11):e159

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

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http://dx.doi.org/10.1093/ehjci/jeab123DOI Listing
October 2021

Enhancement patterns detected by multidetector computed tomography are associated with the long-term prognosis of patients with acute myocardial infarction.

Heart Vessels 2021 May 16. Epub 2021 May 16.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

The present study investigated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) without iodine re-injection immediately after primary percutaneous coronary intervention (PCI) for predicting future cardiovascular events after acute myocardial infarction (AMI). We performed a prospective study in which 263 consecutive patients with first AMI successfully treated with primary PCI were enrolled. Sixty-four-slice MDCT without the re-injection of contrast medium was performed immediately after PCI. Myocardial DE was considered to be transmural when involving myocardial thickness ≥ 75% (Group A; n = 104), subendocardial (< 75%, Group B; n = 108), or normal (Group C; n = 51). A semiquantitative scale score was defined for 17 left ventricular segments to investigate the extent of the DE area assessed. We examined the relationship between the presence or absence of transmural DE and long-term cardiovascular event rates. The median follow-up period was 3.5 years. Kaplan-Meier survival curves showed that patient prognosis was poorer in the group with Group A than that in the group with Group B, which was equivalent to that with Group C. A multivariate analysis identified the presence of transmural DE as the strongest predictor for future cardiovascular events (hazard ratio: 3.7; P = 0.023). Transmural myocardial DE immediately following primary PCI without an iodine re-injection for AMI is a major risk factor for future cardiovascular events.
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http://dx.doi.org/10.1007/s00380-021-01868-1DOI Listing
May 2021

Difference in risk factors of silent brain infarction between paroxysmal and persistent atrial fibrillation.

Int J Cardiol Heart Vasc 2021 Apr 18;33:100753. Epub 2021 Mar 18.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi Abenoku, Osaka 545-8585, Japan.

Background: Although silent brain infarction is an independent risk factor for subsequent symptomatic stroke and dementia in patients with nonvalvular atrial fibrillation, little is known regarding differences in risk factors for silent brain infarction between patients with paroxysmal and persistent nonvalvular atrial fibrillation.

Methods: This study population consisted of 190 neurologically asymptomatic patients (mean age, 64 ± 11 years) with nonvalvular atrial fibrillation (119 paroxysmal, 71 persistent) who were scheduled for catheter ablation. All patients underwent brain magnetic resonance imaging to screen for silent brain infarction prior to ablation. Transthoracic and transesophageal echocardiography was performed to screen for left atrial abnormalities (left atrial enlargement, spontaneous echo contrast, or left atrial appendage emptying velocity) and complex plaques in the aortic arch.

Results: Silent brain infarction was detected in 50 patients (26%) [26 patients (22%) in paroxysmal vs. 24 patients (34%) in persistent, p = 0.09]. Multiple logistic regression analysis indicated that age and diabetes mellitus or chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m) were associated with silent brain infarction in patients with paroxysmal nonvalvular atrial fibrillation (p < 0.05), whereas no modifiable risk factors of silent brain infarction were observed in patients with persistent nonvalvular atrial fibrillation.

Conclusions: These findings suggest that intensive intervention for diabetes mellitus and renal impairment from the paroxysmal stage or ablation therapy at the time of paroxysmal stage to prevent progression to persistent nonvalvular atrial fibrillation may prevent silent brain infarction and consequently reduce the risk of future symptomatic stroke.
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http://dx.doi.org/10.1016/j.ijcha.2021.100753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985474PMC
April 2021

Impact of Reactive Oxidative Metabolites Among New Categories of Nonischemic Heart Failure.

J Am Heart Assoc 2021 04 18;10(7):e016765. Epub 2021 Mar 18.

Department of Cardiovascular Medicine Faculty of Life Sciences Graduate School of Medical Science and Center for Metabolic Regulation of Healthy Aging (CMHA) Kumamoto University Kumamoto Japan.

Background We investigated the clinical significance of derivatives of reactive oxygen metabolites (DROMs), a new marker of reactive oxygen species, in patients with nonischemic heart failure (HF) and compared them among new categories of HF. Methods and Results We recruited 201 consecutively hospitalized patients with HF and measured DROM under stable conditions. Then, we divided them according to new categories of HF (HF with reduced ejection fraction [EF], HF with midrangeEF, and HF with preserved EF) without coronary artery disease. In subgroup analysis, we followed EF changes in patients with HF with reduced EF and classified them into HF with recovered EF or nonrecovered EF according to whether EF had improved to >40%. DROMs are significantly and independently associated with HF-related events in patients with NIHF. There were no significant differences in DROM and the probability of HF-related events among HF categories in Kaplan-Meier analysis. However, patients with HF with reduced EF and HF with preserved EF but not HF with midrange EF with HF-related events had higher DROM than those without HF-related events. In subgroup analysis, Kaplan-Meier analysis demonstrated that the probabilities of HF-related events in HF with recovered EF were dramatically decreased. DROM were significantly higher in patients with HF with nonrecovered EF than in HF with recovered EF. In receiver operating characteristic analysis, the cutoff level of DROM for predicting improvements in HF with recovered EF was 347 Carratelli units. Furthermore, the C-statistic value for predicting EF improvement for the DROM levels was 0.703. In multivariable logistic regression analysis, DROM was independently and significantly associated with the prediction of HF with recovered EF. Conclusions DROM measurements can provide important prognostic information for risk stratification in any category of NIHF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000035827.
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http://dx.doi.org/10.1161/JAHA.120.016765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174381PMC
April 2021

Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation.

Circ J 2021 Mar 5. Epub 2021 Mar 5.

Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University.

Background: Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated.Methods and Results:Systemic (Sirt7) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice.

Conclusions: Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases.
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http://dx.doi.org/10.1253/circj.CJ-20-0936DOI Listing
March 2021

Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation.

Nat Metab 2021 02 18;3(2):196-210. Epub 2021 Feb 18.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Ketone bodies are generated in the liver and allow for the maintenance of systemic caloric and energy homeostasis during fasting and caloric restriction. It has previously been demonstrated that neonatal ketogenesis is activated independently of starvation. However, the role of ketogenesis during the perinatal period remains unclear. Here, we show that neonatal ketogenesis plays a protective role in mitochondrial function. We generated a mouse model of insufficient ketogenesis by disrupting the rate-limiting hydroxymethylglutaryl-CoA synthase 2 enzyme gene (Hmgcs2). Hmgcs2 knockout (KO) neonates develop microvesicular steatosis within a few days of birth. Electron microscopic analysis and metabolite profiling indicate a restricted energy production capacity and accumulation of acetyl-CoA in Hmgcs2 KO mice. Furthermore, acetylome analysis of Hmgcs2 KO cells revealed enhanced acetylation of mitochondrial proteins. These findings suggest that neonatal ketogenesis protects the energy-producing capacity of mitochondria by preventing the hyperacetylation of mitochondrial proteins.
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http://dx.doi.org/10.1038/s42255-021-00342-6DOI Listing
February 2021

Severe obstructive sleep apnea is associated with coronary microvascular dysfunction and obstruction in patients with ST-elevation myocardial infarction.

Eur Heart J Acute Cardiovasc Care 2020 Apr 30. Epub 2020 Apr 30.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Japan.

Background: Coronary microvascular dysfunction and obstruction (CMVO) is a strong predictor of a poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Although research has suggested that obstructive sleep apnea (OSA) exacerbates CMVO after primary percutaneous coronary intervention, data supporting a correlation between OSA and CMVO are limited. This study was performed to investigate whether OSA is associated with CMVO, detected as microvascular obstruction on cardiovascular magnetic resonance images, in patients with STEMI.

Methods: Patients (N = 249) with a first STEMI underwent primary percutaneous coronary intervention. CMVO was evaluated on cardiovascular magnetic resonance images based on the presence of microvascular obstruction. OSA was classified into four levels of severity based on the respiratory event index (REI): absent (REI of <5), mild (REI of ≥5 to <15), moderate (REI of ≥15 to <30) and severe (REI of ≥30).

Results: The REI was significantly higher in the presence of microvascular obstruction (n = 139) than in its absence (n = 110) (REI of 12.8 vs. 10.7, respectively; p = 0.023). Microvascular obstruction was observed in 42%, 58%, 57% and 70% of patients in the absent, mild, moderate and severe OSA groups, respectively. Multiple logistic regression analysis showed that severe OSA was associated with increased odds of microvascular obstruction (odds ratio (OR), 5.10; 95% confidence interval (CI),1.61-16.2; p = 0.006). Mild and moderate OSA were also associated with increased odds of microvascular obstruction (mild OSA: OR, 2.88; 95% CI, 1.19-7.00; p = 0.019 and moderate OSA: OR, 3.79; 95% CI, 1.43-10.1; p = 0.008).

Conclusion: Severe OSA was associated with CMVO after primary percutaneous coronary intervention in patients with STEMI.
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http://dx.doi.org/10.1177/2048872620919946DOI Listing
April 2020

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure.

Heart Vessels 2021 Aug 12;36(8):1175-1182. Epub 2021 Feb 12.

Department of Cardiovascular Medicine, Ishikiriseiki Hospital, 18-28, Yayoi-cho, Higashi-Osaka, 579-8026, Japan.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, - 8.02 ± 9.35 to - 1.62 ± 5.09 mL/min/1.73m /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.
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http://dx.doi.org/10.1007/s00380-021-01801-6DOI Listing
August 2021

Organizing Pneumonia as the First Presentation in a Patient with Takayasu Arteritis: A Report of Rare Complication.

Intern Med 2021 Jun 1;60(12):1887-1891. Epub 2021 Feb 1.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Japan.

A 48-year-old woman without any medical history visited an outpatient clinic with a chief complaint of cough persisting for more than 1 year and was diagnosed with organizing pneumonia. Computed tomography showed wall thickening with luminal stenosis of the main branch vessels of the aorta, and a detailed examination including fluorodeoxyglucose-positron emission tomography revealed Takayasu arteritis. There have been some reports of combined organizing pneumonia in similar vasculitis cases, but Takayasu arteritis and organizing pneumonia have not been reported to be associated. This case can be referred to when considering the association of lung lesions with Takayasu arteritis.
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http://dx.doi.org/10.2169/internalmedicine.6316-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263172PMC
June 2021

Dose-Dependent Inhibitory Effect of Rosuvastatin in Japanese Patients with Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases-INVITATION Trial.

J Atheroscler Thromb 2021 Jan 7. Epub 2021 Jan 7.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, and Center for Metabolic Regulation of Healthy Aging (CMHA), Kumamoto University.

Aim: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI.

Methods: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment.

Results: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period.

Conclusions: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.
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http://dx.doi.org/10.5551/jat.59477DOI Listing
January 2021

Prevalence and Risk Factors of Silent Brain Infarction in Patients with Aortic Stenosis.

Cerebrovasc Dis Extra 2020 8;10(3):116-123. Epub 2020 Oct 8.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine Osaka, Osaka, Japan.

Introduction: Silent brain infarction (SBI) is an independent risk factor for subsequent symptomatic stroke in the general population. Although aortic stenosis (AS) is also known to be associated with an increased risk of future symptomatic stroke, little is known regarding the prevalence and risk factors for SBI in patients with AS.

Methods: The study population comprised 83 patients with severe AS with no history of stroke or transient ischemic attack and paralysis or sensory impairment (mean age 75 ± 7 years). All patients underwent brain magnetic resonance imaging to screen for SBI and multidetector-row computed tomography to quantify the aortic valve calcification (AVC) volume. Comprehensive transthoracic and transesophageal echocardiography were performed to evaluate left atrial (LA) abnormalities, such as LA enlargement, spontaneous echo contrast, or abnormal LA appendage emptying velocity (<20 cm/s), and complex plaques in the aortic arch.

Results: SBI was detected in 38 patients (46%). Multiple logistic regression analysis indicated that CHA2DS2-VASc score and estimated glomerular filtration rate (eGFR) were independently associated with SBI (p < 0.05), whereas LA abnormalities and AVC volume were not. When patients were divided into 4 groups according to CHA2DS2-VASc score and eGFR, the group with a higher CHA2DS2-VASc score (≥4) and a lower eGFR (<60 mL/min/1.73 m2) had a greater risk of SBI than the other groups (p < 0.05).

Conclusion: These findings indicate that AS is associated with a high prevalence of SBI, and that the CHA2DS2-VASc score and eGFR are useful for risk stratification.
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http://dx.doi.org/10.1159/000510438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588680PMC
January 2021

Successful treatment for a patient with chronic thromboembolic pulmonary hypertension comorbid with essential thrombocythemia with the JAK2 V617F mutation by balloon pulmonary angioplasty.

Respir Med Case Rep 2020 28;31:101235. Epub 2020 Sep 28.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

A-71-year-old woman was diagnosed as chronic thromboembolic pulmonary hypertension (CTEPH) accompanied by essential thrombocythemia (ET) with JAK2 V617F mutation. Blood test showed remarkable increase of platelet counts (132.9 × 10^4/μL) and elevated plasma BNP level (125.1pg/mL). Right heart catheterization (RHC) revealed remarkably high mean pulmonary arterial pressure (mPAP) of 43 mmHg. We gave her riociguat of 7.5mg, oral anticoagulants, oxygen inhalation for CTEPH, and anagrelide for ET. We performed 4 sessions of balloon pulmonary angioplasty (BPA) in 9 months RHC revealed successful hemodynamic improvement (mPAP = 21 mmHg) after final BPA procedure without riociguat. At six month later after final BPA procedure, RHC showed steadily improvement of mPAP (21 mmHg) without riociguat and oxygen inhalation. She lives well without oxygen inhalation and PH targeted therapy. This is the first report of successful treatment for a patient with CTEPH comorbid with ET with JAK2 V617F mutation by BPA.
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http://dx.doi.org/10.1016/j.rmcr.2020.101235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528185PMC
September 2020

Presence of mitral stenosis is a risk factor of new development of acute decompensated heart failure early after transcatheter aortic valve implantation.

Open Heart 2020 10;7(2)

Cardiovascular Medicine, Osaka City University, Osaka, Japan.

Aims: Acute decompensated heart failure (ADHF) can occur early after transcatheter aortic valve implantation (TAVI), but the risk factors or mechanisms associated with it have not been fully determined. This hypothesis-generating study aimed to investigate the clinical indices associated with the development of ADHF within 72 hours after TAVI and to improve procedural approaches for TAVI.

Method And Results: In this single-centre hypothesis generating prospective observational study, we enrolled 156 consecutive patients with severe aortic stenosis who underwent TAVI between January 2016 and February 2018 at our institution. We set the primary endpoint as the new development of ADHF within 72 hours after TAVI, and clinical indices associated with it were evaluated using a multivariable logistic model. The median age of the patients was 83 (quartile range 80-86) years, 48 (30.8%) were men and the median Society of Thoracic Surgery-Predicted Risk of Mortality was 7.1 (range 5.2-10.4). Mitral stenosis (MS), defined as mean transmitral valve pressure gradient ≥5 mm Hg, was present in 15 (9.6%) patients. After TAVI, the invasive mean transaortic valve pressure gradient (mAVPG) decreased from 48 (36-66) to 7 (5-11) mm Hg, and 12 (7.7%) patients developed ADHF within 72 hours after TAVI. Multivariable logistic regression analysis showed that MS (adjusted OR, 14.227; 95% CI 2.654 to 86.698; p=0.002) and greater decreases in mAVPG (1.038; 1.003 to 1.080; p=0.044) were associated with ADHF.

Conclusions: MS and drastic improvement of mAVPG were associated with new development of ADHF within 72 hours after TAVI.
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http://dx.doi.org/10.1136/openhrt-2020-001348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537436PMC
October 2020

How to Identify Transthyretin Cardiac Amyloidosis at an Early Stage.

Intern Med 2021 Jan 21;60(1):1-7. Epub 2020 Jul 21.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Japan.

Cardiac involvement of systemic amyloidosis is preferentially observed in patients with amyloid light chain amyloidosis or transthyretin amyloidosis (ATTR). Owing to the development of diagnostic modalities and changes in recognition by physicians, transthyretin cardiac amyloidosis (ATTR-CA) is now understood to be a more common cause of heart failure than previously thought. Recent progress in disease-modifying therapeutic interventions, such as transthyretin stabilizers, has resulted in ATTR-CA changing from an incurable disease to a curable disease. These interventions are particularly effective in patients with mild symptoms of heart failure, thus indicating that early detection and a precise diagnosis are important for improving the prognosis. In this review article, we summarize the recent reports of early screening of ATTR-CA and describe some important points regarding the making of a precise diagnosis, especially focusing on histological evaluations.
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http://dx.doi.org/10.2169/internalmedicine.5505-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835474PMC
January 2021

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

J Atheroscler Thromb 2021 Feb 20;28(2):181-193. Epub 2020 May 20.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences and Center for Metabolic Regulation of Healthy Aging (CMHA), Kumamoto University.

Aim: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM.

Methods: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL.

Results: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008).

Conclusions: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.
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http://dx.doi.org/10.5551/jat.54726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957031PMC
February 2021

Severe obstructive sleep apnea is associated with coronary microvascular dysfunction and obstruction in patients with ST-elevation myocardial infarction.

Eur Heart J Acute Cardiovasc Care 2020 Apr 30:2048872620919946. Epub 2020 Apr 30.

Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Japan.

Background: Coronary microvascular dysfunction and obstruction (CMVO) is a strong predictor of a poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Although research has suggested that obstructive sleep apnea (OSA) exacerbates CMVO after primary percutaneous coronary intervention, data supporting a correlation between OSA and CMVO are limited. This study was performed to investigate whether OSA is associated with CMVO, detected as microvascular obstruction on cardiovascular magnetic resonance images, in patients with STEMI.

Methods: Patients ( = 249) with a first STEMI underwent primary percutaneous coronary intervention. CMVO was evaluated on cardiovascular magnetic resonance images based on the presence of microvascular obstruction. OSA was classified into four levels of severity based on the respiratory event index (REI): absent (REI of <5), mild (REI of ≥5 to <15), moderate (REI of ≥15 to <30) and severe (REI of ≥30).

Results: The REI was significantly higher in the presence of microvascular obstruction ( = 139) than in its absence ( = 110) (REI of 12.8 . 10.7, respectively;  = 0.023). Microvascular obstruction was observed in 42%, 58%, 57% and 70% of patients in the absent, mild, moderate and severe OSA groups, respectively. Multiple logistic regression analysis showed that severe OSA was associated with increased odds of microvascular obstruction (odds ratio (OR), 5.10; 95% confidence interval (CI),1.61-16.2;  = 0.006). Mild and moderate OSA were also associated with increased odds of microvascular obstruction (mild OSA: OR, 2.88; 95% CI, 1.19-7.00;  = 0.019 and moderate OSA: OR, 3.79; 95% CI, 1.43-10.1;  = 0.008).

Conclusion: Severe OSA was associated with CMVO after primary percutaneous coronary intervention in patients with STEMI.
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http://dx.doi.org/10.1177/2048872620919946DOI Listing
April 2020

Impact of hydrostatic pressure on fractional flow reserve: in vivo experimental study of anatomical height difference of coronary arteries.

J Cardiol 2020 07 20;76(1):73-79. Epub 2020 Feb 20.

Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Division of Metabolic and Cardiovascular Research, Center for Metabolic Regulation of Healthy Aging, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan.

Background: Although pressure equalization of the sensor-tipped guidewire and systemic pressure is mandatory in measuring fractional flow reserve (FFR), pressure in the distal artery (Pd) with wire advancement can be influenced by hydrostatic pressure related to the height difference between the catheter tip and the distal pressure sensor. We therefore analyzed the impact of hydrostatic pressure on FFR in vivo by modification of the height difference.

Methods: To reveal the anatomical height difference in human coronary arteries, measurement was performed during computed tomography angiography (CTA) of five consecutive patients. Utilizing the healthy coronary arteries of female swine, height difference diversity was reproduced by body rotation and vertical inclination. FFR measurements were performed during maximum hyperemia with adenosine. The height difference was calculated fluoroscopically with a contrast medium-filled balloon for reference.

Results: In human coronary CTA, height averages from the ostium in the left anterior descending artery (34.6 mm) were significantly higher than in the left circumflex (-15.5 mm, p = 0.008) and right coronary arteries (-2.3 mm, p = 0.008). In our swine model, reproduced height variation ranged from -7.2 cm to +6.5 cm. Mean FFR was significantly lower in positive sensor height and higher in negative sensor height compared to the reference height. Linear regression analyses revealed significant correlations between height difference and FFR, observed among all coronary arteries, as well as between the height difference and Pd-aortic pressure mismatch. Subtracting 0.622 mmHg/cm height difference from Pd could correct the expected hydrostatic pressure influence.

Conclusion: Hydrostatic pressure variation resulting from sensor height influenced FFR values might affect interpretation during FFR assessment.
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http://dx.doi.org/10.1016/j.jjcc.2020.01.009DOI Listing
July 2020

Associations between corrected serum calcium and phosphorus levels and outcome in dialysis patients in the Kumamoto Prefecture.

Hemodial Int 2020 04 13;24(2):202-211. Epub 2020 Feb 13.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.

Introduction: Mortality in hemodialysis patients is relatively high; thus, its risk stratification is very important. There are insufficient data describing the current status of the management of serum phosphate and calcium levels.

Methods: We conducted a multicenter, prospective, registry study throughout the Kumamoto Prefecture in Japan. We enrolled 1993 patients at 58 facilities with complete explanatory data, including serum phosphate, corrected calcium, and intact parathyroid hormone levels. We categorized subjects into nine categories according to low, normal, and high levels of phosphate and corrected calcium levels. The endpoint was all-cause mortality.

Results: Of the total number of subjects, 56.1% of the patients were in the normal phosphate and calcium category, and 72% and 77.1% had controlled serum phosphate and calcium levels, respectively. Two hundred twenty-six deaths occurred during the follow-up period. In the nine categories, the highest mortality rates were observed in the highest corrected calcium and lowest phosphate categories. Stepwise backward multivariate regression analyses identified the serum corrected calcium level (OR, 1.38; 95% CI, 1.06-1.79; P = 0.016) and the serum phosphate level (OR, 1.26; 95% CI, 1.08-1.48; P = 0.003) as significant and independent predictors of all-cause mortality.

Conclusions: The corrected serum calcium and phosphate levels are associated with mortality in our dialysis population, with poorest survival in patients with high corrected serum calcium and low serum phosphorus.
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http://dx.doi.org/10.1111/hdi.12824DOI Listing
April 2020

Analysis of the driving mechanism in paroxysmal atrial fibrillation: comparison of the activation sequence between the left atrial body and pulmonary vein.

J Cardiol 2020 06 7;75(6):673-681. Epub 2020 Feb 7.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: It has been shown that most paroxysmal atrial fibrillation (AF) can be terminated by pulmonary vein (PV) isolation alone, suggesting that rapid discharges from PV drive AF. To define the driving mechanism of AF, we compared the activation sequence in the body of left atrium (LA) to that within PV.

Methods: Endocardial noncontact mapping of LA body (LA group; n = 16) and selective endocardial mapping of left superior PV (LSPV) (PV group; n = 13) were performed in 29 paroxysmal AF patients. The frequency of pivoting activation, wave breakup, and wave fusion observed in LA were compared to those in LSPV to define the driving mechanism of AF. Circumferential ablation lesion around left PV was performed after right PV isolation to examine the effect of linear lesion around PV on AF termination both in LA and PV groups.

Results: The frequency of pivoting activation, wave breakup, and wave fusion in PV group were significantly higher than those in LA group (36.5 ± 17.7 vs 5.0 ± 2.2 times/seconds, p < 0.001, 10.1 ± 4.3 vs 5.0 ± 2.2 times/seconds, p = 0.004, 18.1 ± 5.7 vs 11.0 ± 5.2, p = 0.002). Especially in the PV group, the frequency of pivoting activation was significantly higher than that of wave breakup and wave fusion (36.5 ± 17.7 vs 10.1 ± 4.3 times/seconds, p < 0.001, 36.5 ± 17.7 vs 18.1 ± 5.7 times/seconds, p < 0.001). These disorganized activations in LSPV were eliminated by the circumferential ablation lesion around left PV (pivoting activation; 36.5 ± 17.7 vs 9.3 ± 2.3 times/seconds, p < 0.001, wave breakup; 10.1±1.3 times/seconds, p = 0.003, wave fusion; 18.1 ± 5.7 vs 5.7 ± 1.8, p < 0.001), resulted in AF termination in all patients in both LA and PV groups.

Conclusions: Activation sequence within PV was more disorganized than that in LA body. Frequent episodes of pivoting activation rather than wave breakup and fusion observed within PV acted as the driving sources of paroxysmal AF.
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http://dx.doi.org/10.1016/j.jjcc.2020.01.004DOI Listing
June 2020
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