Publications by authors named "Ken-Ichi Hirata"

575 Publications

"Pericardial flare" associated with immunoglobulin G4-related disease: A case report - rapid transition from cardiac tamponade to effusive constrictive pericarditis.

J Cardiol Cases 2021 Jul 26;24(1):37-40. Epub 2020 Dec 26.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Immunoglobulin G4-related disease (IgG4-RD) has recently been recognized as a systemic fibroinflammatory disease characterized by IgG4-positive lymphoplasmacytic infiltration. Despite the increased awareness of this disease category, cardiovascular involvement has rarely been reported. An 83-year-old man was admitted because of a moderate amount of pericardial effusion concomitant with bilateral pleural effusion. Despite aggressive heart failure therapy, pericardial effusion increased. He underwent pericardial drainage, and heart failure symptoms significantly improved. After only 1 month, right-sided heart failure with re-accumulation of pericardial fluid recurred, although the results of cardiac catheter examination were not indicative of constrictive pericarditis. Despite the aggressive medication, he developed weight gain and pleural effusion 6 months after pericardial drainage. Based on multimodal hemodynamic and morphological evaluations, he was finally diagnosed with effusive constrictive pericarditis and underwent total pericardiectomy. Based on histopathological findings, the final diagnosis was established as IgG4-RD associated constrictive pericarditis. We report an extremely rare case of IgG4-RD associated pericardial involvement, in which rapid transition from cardiac tamponade to effusive constrictive pericarditis was confirmed. Diagnostic work-up for constrictive pericarditis requires a high index of suspicion. Increased recognition of IgG4-RD associated pericardial involvement could potentially mitigate morbidity and might contribute to improved patient outcomes. < Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by chronic IgG4-positive lymphocyte infiltration that causes fibrosclerotic changes in various tissues and organs. Detailed serial multimodal imaging and physical examination contribute to the recognition of latent constrictive physiology and clinical decision-making. Increased recognition of IgG4-RD associated pericardial involvement could lead to early diagnosis and might contribute to improved patient outcomes.>.
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http://dx.doi.org/10.1016/j.jccase.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258268PMC
July 2021

Intensive Care Unit Admission for Moderate-to-Severe COVID-19 Patients With Known Cardiovascular Diseases or Their Risk Factors - Insights From a Nationwide Japanese Cohort Study.

Circ Rep 2021 Jul 25;3(7):375-380. Epub 2021 Jun 25.

Department of Cardiovascular Medicine, Saga University Saga Japan.

The COVID-19 pandemic has challenged healthcare systems, at times overwhelming intensive care units (ICUs). We aimed to describe the length and rate of ICU admission, and explore the clinical variables influencing ICU use, for COVID-19 patients with known cardiovascular diseases or their risk factors (CVDRF). A post hoc analysis was performed of 693 Japanese COVID-19 patients with CVDRF enrolled in the nationwide CLAVIS-COVID registration system between January and May 2020 (mean [±SD] age 68.3±14.9 years; 35% female); 199 patients (28.7%) required ICU management. The mean (±SD) ICU length of stay (LOS) was 19.3±18.5 days, and the rate of in-hospital death and hospital LOS were significantly higher (P<0.001) and longer (P<0.001), respectively, in the ICU than non-ICU group. Logistic regression analysis revealed that clinical variables reflecting impaired general condition (e.g., high C-reactive protein, low Glasgow Coma Scale score, SpO, albumin level), male sex, and previous use of β-blockers) were associated with ICU admission (all P<0.001). Notably, age was inversely associated with ICU admission, and this was particularly prominent among elderly patients (OR 0.97, 95% confidence interval 0.95-0.99; P=0.0018). One-third of COVID patients with CVDRF required ICU care during the first phase of the pandemic in Japan. Other than anticipated clinical variables, such as hypoxia and altered mental status, age was inversely associated with the use of the ICU, warranting further investigation.
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http://dx.doi.org/10.1253/circrep.CR-21-0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258186PMC
July 2021

Hemodynamic changes during transcatheter atrial septal defect closure predict midterm heart failure deterioration in adults.

Catheter Cardiovasc Interv 2021 Jul 6. Epub 2021 Jul 6.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Objectives: To investigate whether hemodynamic changes during balloon occlusion test (BOT) predict future heart failure (HF) deterioration after transcatheter atrial septal defect closure (tASD-closure).

Background: Midterm HF deterioration can sometimes occur after tASD-closure in adults. Whether hemodynamic changes during tASD-closure can help identify patients at risk is unknown.

Methods: This prospective observational study enrolled 86 consecutive adult patients who underwent tASD-closure. Hemodynamic parameters, including pulmonary capillary wedge pressure (PCWP), were measured at baseline, during BOT, and after tASD-closure. The changes in PCWP during BOT and after tASD-closure were defined as ΔPCWP (Occ-Pre) and ΔPCWP (Post-Pre), respectively. Clinical parameters were evaluated before tASD-closure and during the 3-month follow-up. We assessed the occurrence of HF deterioration (HF requiring hospitalization or additional diuretics) during a 2-year follow-up period and categorized patients into HF (+) and HF (-) groups accordingly. The aforementioned parameters were compared between groups.

Results: Midterm HF deterioration occurred in 12 patients (13.9%). Compared to the HF (-) group, the HF (+) group presented a significantly higher ΔPCWP (Occ-Pre) (9.5 ± 4.4 mmHg vs. 3.0 ± 3.3 mmHg; p < 0.001) and ΔPCWP (Post-Pre) (4.0 ± 2.8 mmHg vs. 0.6 ± 1.8 mmHg; p = 0.004). Receiver operating characteristic curve analysis showed that the ΔPCWP (Occ-Pre) cutoff value of 5.5 mmHg had excellent ability to predict HF deterioration (Area under the curve 0.886 [0.779-0.993], p < 0.001; sensitivity 0.917, specificity 0.824).

Conclusions: Increases in PCWP during BOT predict midterm HF deterioration after tASD-closure. Close surveillance may be needed in patients with a ΔPCWP (Occ-Pre) >5 mmHg.
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http://dx.doi.org/10.1002/ccd.29859DOI Listing
July 2021

Successful catheter ablation approach above the aortic sinus cusp eliminating a ventricular arrhythmia arising from the myocardial crescent beneath the interleaflet triangle: Late gadolinium enhancement magnetic resonance imaging assessment.

Clin Case Rep 2021 Jun 6;9(6):e04169. Epub 2021 May 6.

Section of Arrhythmia Division of Cardiovascular Medicine Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Japan.

A 61-year-old female with 50 000 ventricular premature contractions and a reduced left ventricular ejection fraction of 35% was referred to our center. Although the origin was considered to originate from the junction between the left and right coronary cusp, a single radiofrequency application above the aortic sinus cusp could eliminate it. LGE-MRI was able to reveal the exact location of the single RF lesion.
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http://dx.doi.org/10.1002/ccr3.4169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222747PMC
June 2021

Massive regurgitant jet through the 'entry' and out of the 're-entry' of a dissected left atrial wall: an extremely rare case of mitral regurgitation after prosthetic valve replacement.

Eur Heart J Cardiovasc Imaging 2021 Jun 18. Epub 2021 Jun 18.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

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http://dx.doi.org/10.1093/ehjci/jeab107DOI Listing
June 2021

A rare case of concomitant aortic regurgitation and coronary ostial stenosis due to cardiovascular syphilis.

Eur Heart J Case Rep 2021 Mar 2;5(3):ytab064. Epub 2021 Mar 2.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 6500017, Japan.

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http://dx.doi.org/10.1093/ehjcr/ytab064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186925PMC
March 2021

Metagenomic analysis of gut microbiota reveals its role in trimethylamine metabolism in heart failure.

Int J Cardiol 2021 Sep 5;338:138-142. Epub 2021 Jun 5.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: We had previously reported an increase in trimethylamine N-oxide (TMAO) levels in patients with both compensated and decompensated heart failure (HF) and alteration in gut microbiota composition using 16S rRNA gene amplicon analysis. Although a metagenome-wide analysis showed that choline-TMA lyase levels increased in HF patients, which TMA generation pathway from choline, carnitine, or betaine contributes to the increase in TMAO levels in HF needs to be elucidated.

Methods: We conducted a metagenome-wide shotgun sequencing analysis of gut microbiota and measured the TMAO levels in plasma of 22 HF patients during the compensated phase and 11 age-, sex-, and comorbidity-matched control subjects, whose gut microbiota compositions were reported in a previous 16S rRNA-based analysis.

Results: The abundance of cntA/B was positively correlated with TMAO, especially in HF patients, whereas that of cutC/D or betaine reductase was not correlated either in controls or HF patients. The abundance of cntA/B was mainly derived from the genera Escherichia and Klebsiella either in controls or HF patients.

Conclusion: TMAO levels in plasma depend on the abundance of cntA/B in HF. Although it is difficult to exclude the involvement of confounding factors, microbial dysbiosis connecting the abundance of cntA/B in the gut and the increase of TMAO in plasma can be a therapeutic target for HF.
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http://dx.doi.org/10.1016/j.ijcard.2021.06.003DOI Listing
September 2021

Ventricular tachycardia based on cardiac sarcoidosis with a narrow QRS complex, ablated on the left ventricle free-wall.

Indian Pacing Electrophysiol J 2021 Jun 3. Epub 2021 Jun 3.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

A septuagenarian female with cardiac sarcoidosis suffered from drug refractory ventricular tachycardia (VT) requiring multiple implantable cardioverter-defibrillator shocks. The QRS complex during the VT was very similar to that during sinus rhythm although the QRS width during the VT (142 ms) was relatively wider than that during sinus rhythm (107 ms). The VT exit was located on the ventricular septum close to the His-bundle recording region. However, the critical pathway of this VT was detected on the anterior free wall of the left ventricle (LV), and a radiofrequency application at that site could terminate the VT. No Purkinje potentials were recorded there during the VT or sinus rhythm. According to the electrophysiological study, 3-D mapping, and the response to the ablation, the critical circuit of the VT was surrounded by a protected area of scar associated with cardiac sarcoidosis. As a result, the VT circuit was connected to the basal septal area close to the His-Purkinje system as an outer loop of the VT circuit. This unique trajectory of the VT might have caused a similar QRS morphology to that of sinus rhythm, and the relatively narrow QRS complex despite the critical isthmus was located on the anterior free wall of the LV.
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http://dx.doi.org/10.1016/j.ipej.2021.05.008DOI Listing
June 2021

Successful percutaneous balloon aortic valvuloplasty for worsening paravalvular leakage detected one week after the balloon expandable transcatheter aortic valve replacement.

Cardiovasc Interv Ther 2021 Jun 4. Epub 2021 Jun 4.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.

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http://dx.doi.org/10.1007/s12928-021-00787-2DOI Listing
June 2021

Practical Utility of the Postal Service in Delivering a Self-Fitted, Wearable, Long-Term Electrocardiogram Monitoring Device for Outpatient Care.

Circ Rep 2021 Apr 17;3(5):294-299. Epub 2021 Apr 17.

Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.

Demand is growing for remote electrocardiogram (ECG) monitoring systems in the COVID-19 era in Japan. This study describes initial experiences with a small wireless ECG monitoring device and the utility of delivery via the postal service for outpatient care in Japan. Long-term ECG monitoring following postal delivery of the small ECG device was evaluated in 25 patients. The patients had no difficulties with either the postal delivery or self-fitting and wearing the devices. A median of 57 h monitoring per patient was performed. Arrhythmic events were detected in 8 patients. Most patients were satisfied with both the ECG devices and postal delivery. Postal delivery of ECG devices could be used in clinical practice to achieve less or no in-person contact during the COVID-19 era.
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http://dx.doi.org/10.1253/circrep.CR-21-0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099665PMC
April 2021

Preoperative coupling between right ventricle and pulmonary vasculature is an important determinant of residual symptoms after the closure of atrial septal defect.

Int J Cardiovasc Imaging 2021 May 15. Epub 2021 May 15.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Purposes: The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified.

Methods: In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP).

Results: Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status.

Conclusion: In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure.
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http://dx.doi.org/10.1007/s10554-021-02282-4DOI Listing
May 2021

Relationship among clinical characteristics, morphological culprit plaque features, and long-term prognosis in patients with acute coronary syndrome.

Int J Cardiovasc Imaging 2021 May 12. Epub 2021 May 12.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Culprit lesions of acute coronary syndrome (ACS) could be classified as plaque rupture (PR), erosion, or calcified nodule (CN). We aimed to determine the relationship among clinical characteristics, morphological plaque features, and long-term prognosis in ACS. Patients with ACS, who underwent pre-intervention optical coherence tomography between April 2013 and July 2018 were retrospectively enrolled, and classified into the three groups based on the culprit lesion morphology. In the 436 patients enrolled, incidences of PR, erosion, and CN in ACS culprit lesions were 46.1, 39.9, and 14.0%, respectively. Plaque erosion was more frequent in men aged < 60 years and CN was more frequent in older adults in both sexes (≥ 80 years) (P < 0.001). Patients with CN had a higher incidence of hemodialysis treatment (P < 0.001) and diabetes (P = 0.003). Multivariate analysis revealed that ST elevation myocardial infarction (STEMI) (P = 0.049) and presence of thin-cap fibroatheroma (TCFA) at the culprit lesion were independently associated with PR; in younger patients (< 60 year), preserved left ventricular ejection fraction and lower incidence of TCFA were correlated with plaque erosion; and older age, non-STEMI, or unstable angina pectoris, higher serum brain natriuretic peptide levels, and lower incidence of TCFA were independently associated with CN. Multivariable analysis revealed that CN (odds ratio [OR] 1.990, P = 0.005), male sex (OR 2.012, P = 0.004), and older age (OR 1.036, P < 0.001) were independently associated with future adverse events during a median follow-up of 757 days. Different patient characteristics and morphological features were associated with the type of culprit lesion in patients with ACS.
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http://dx.doi.org/10.1007/s10554-021-02252-wDOI Listing
May 2021

Clinical and Biomarker Profiles and Prognosis of Elderly Patients With Coronavirus Disease 2019 (COVID-19) With Cardiovascular Diseases and/or Risk Factors.

Circ J 2021 05 29;85(6):921-928. Epub 2021 Apr 29.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine.

Background: This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55-64, 65-79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively).

Conclusions: Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.
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http://dx.doi.org/10.1253/circj.CJ-21-0160DOI Listing
May 2021

Association Between Statin Use Prior to Admission and Lower Coronavirus Disease 2019 (COVID-19) Severity in Patients With Cardiovascular Disease or Risk Factors.

Circ J 2021 05 29;85(6):939-943. Epub 2021 Apr 29.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine.

Background: Cardiovascular diseases and/or risk factors (CVDRF) have been reported as risk factors for severe coronavirus disease 2019 (COVID-19).Methods and Results:In total, we selected 693 patients with CVDRF from the CLAVIS-COVID database of 1,518 cases in Japan. The mean age was 68 years (35% females). Statin use was reported by 31% patients at admission. Statin users exhibited lower incidence of extracorporeal membrane oxygenation (ECMO) insertion (1.4% vs. 4.6%, odds ratio [OR]: 0.295, P=0.037) and septic shock (1.4% vs. 6.5%, OR: 0.205, P=0.004) despite having more comorbidities such as diabetes mellitus.

Conclusions: This study suggests the potential benefits of statins use against COVID-19.
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http://dx.doi.org/10.1253/circj.CJ-21-0087DOI Listing
May 2021

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

Int J Cardiovasc Imaging 2021 Aug 3;37(8):2473-2482. Epub 2021 May 3.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.
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http://dx.doi.org/10.1007/s10554-021-02258-4DOI Listing
August 2021

Easy-to-use preload stress echocardiography by using combined dynamic postural stress can identify high-risk patients with heart failure with reduced ejection fraction.

ESC Heart Fail 2021 May 2. Epub 2021 May 2.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Aims: Haemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non-invasive preload stress during dynamic postural alterations achieved by combining both semi-sitting position and passive leg-lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients.

Methods And Results: For this study, 101 patients with HFrEF and 35 age-matched and sex-matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi-sitting position to passive leg-lifting. During a median follow-up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m (P < 0.001) during combined postural stress. By contrast, ΔSVi during combined dynamic postural stress was significantly smaller in patients with cardiovascular events than in those without events (ΔSVi 3.4 ± 4.0 vs. 6.4 ± 3.8 mL/m , P = 0.002), which indicated severely diseased heart operated on a relatively flat portion of the Frank-Starling curve. In a multivariate Cox proportional hazard analysis, ΔSVi (hazard ratio 0.81, P = 0.02) was an independent predictor of future adverse cardiovascular events.

Conclusions: The combined assessment of dynamic postural stress is a non-invasive, simple, quick, and easy-to-use clinical tool for assessing preload reserve and risk stratification in HFrEF patients.
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http://dx.doi.org/10.1002/ehf2.13346DOI Listing
May 2021

Two Gut Microbiota-Derived Toxins Are Closely Associated with Cardiovascular Diseases: A Review.

Toxins (Basel) 2021 04 22;13(5). Epub 2021 Apr 22.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 670-0017, Japan.

Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and renal functions of the host via the production of bioactive metabolites. This review investigated the evidence from several clinical and experimental studies that indicated an association between the gut microbiota-derived toxins and CVDs. We mainly focused on the pro-inflammatory gut microbiota-derived toxins, namely lipopolysaccharides, derived from Gram-negative bacteria, and trimethylamine N-oxide and described the present status of research in association with these toxins, including our previous research findings. Several clinical studies aimed at exploring the effectiveness of reducing the levels of these toxins to inhibit cardiovascular events are currently under investigation or in the planning stages. We believe that some of the methods discussed in this review to eliminate or reduce the levels of such toxins in the body could be clinically applied to prevent CVDs in the near future.
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http://dx.doi.org/10.3390/toxins13050297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143486PMC
April 2021

Effect of heart rate on left ventricular longitudinal myocardial function in type 2 diabetes mellitus.

Cardiovasc Diabetol 2021 04 24;20(1):87. Epub 2021 Apr 24.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Background: Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain.

Methods: We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS < 18%.

Results: GLS in T2DM patients with high HR was significantly lower than that in T2DM patients with low HR (16.3% ± 4.2% vs. 17.8% ± 2.8%; P = 0.03), whereas GLS in normal subjects with high and low HR was similar (20.3 ± 1.7% vs. 20.3 ± 2.0%; P = 0.99). Multivariable logistic regression analysis showed that high HR (odds ratio: 1.04; 95% confidence interval: 1.01-1.07; P = 0.01) was independently associated with GLS < 18% in T2DM patients as well as HbA1c, T2DM duration, LVEF, body mass index, and mitral inflow E and mitral e' annular velocity ratio. One sequential logistic model evaluating the associations between GLS < 18% and clinical variables in T2DM patients showed an improvement with the addition of LVEF and E/e' (P < 0.001) and a further improvement with the addition of high HR (P < 0.001).

Conclusion: Compared with normal subjects, resting HR was associated with LV longitudinal myocardial function in asymptomatic T2DM patients with preserved LVEF. Our findings provide new insights on the management of T2DM patients.
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http://dx.doi.org/10.1186/s12933-021-01278-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070299PMC
April 2021

Accessory pathway analysis using a multimodal deep learning model.

Sci Rep 2021 Apr 13;11(1):8045. Epub 2021 Apr 13.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Hospital, 7-5-2, Kusunoki-Cho, Chuo-Ku, Kobe, Japan.

Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.
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http://dx.doi.org/10.1038/s41598-021-87631-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044112PMC
April 2021

Prediction of the debulking effect of rotational atherectomy using optical frequency domain imaging.

Heart Vessels 2021 Apr 8. Epub 2021 Apr 8.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Whether predicting the rotational atherectomy (RA) effect based on the position of optical frequency domain imaging (OFDI) is accurate remains uncertain. The aim of this study was to evaluate the predictive accuracy of OFDI in identifying RA location and area. Twenty-five patients who underwent RA with OFDI were included. On pre-RA OFDI images, a circle with the dimension of a Rota burr was drawn at the center of the OFDI catheter. The area where the circle overlapped with the vessel wall was defined as the predicted ablation area (P-area), and the actual ablated area (A-area) was measured. The predictive accuracy of OFDI was evaluated as follows: overlapped ablation area (O-area: overlapping P- and A-areas) divided by P-area = %Correct-area, and A-area - O-area divided by A-area = %Error-area. Cross-sections were separated into four categories based on the median values of %Correct- and %Error-area. Among 334 cross-sections, RA effects were confirmed in the predicted location in 87% of them. The median %Correct- and %Error-areas were 43.1% and 64.2%, respectively. Floppy wire, narrow lumen area, OFDI catheter close to the intima, and large arc of calcium were independently associated with good prediction (high %Correct-/low %Error-areas). Non-left anterior descending lesions, OFDI catheter far from the wire, and OFDI catheter and wire far from the intima were associated with irrelevant ablation (low %Correct-/ high %Error-areas). The accuracy of the OFDI-based predictions for RA effects was acceptable with regard to location, but not high with regard to area. Wire types, target vessels, and OFDI catheter and wire positions are important determinants for accurately predicting RA effect using pre-procedural OFDI.
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http://dx.doi.org/10.1007/s00380-021-01811-4DOI Listing
April 2021

Impact of Oral Health Status on Postoperative Complications and Functional Recovery After Cardiovascular Surgery.

CJC Open 2021 Mar 13;3(3):276-284. Epub 2020 Oct 13.

Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Poor oral health status can lead to a deteriorated level of general health and is common among patients undergoing cardiovascular surgery. However, the effect of oral health status on postoperative outcomes in cardiovascular surgery patients remains unclear. Thus, we investigated the effect of preoperative oral health status on postoperative complications and functional recovery after cardiovascular surgery.

Methods: This single-centre retrospective cohort study included 884 inpatients undergoing elective cardiovascular surgery. Oral health status was assessed based on the number of remaining teeth, use of dentures, occlusal support, and periodontal status. We investigated postoperative complications related to surgery and postoperative functional recovery by measuring the reacquisition of walking ability, activities of daily living, and length of postoperative hospital stay.

Results: In this cohort (age 66.9 ± 13.4 years), the mean number of remaining teeth was 18.7 ± 9.4. Patients were grouped based on tertiles of the data distribution of remaining teeth: ≥ 20 teeth (470 patients); 10-19 teeth (137 patients); < 10 teeth (185 patients). The number of missing teeth was associated with age ( < 0.001). The prevalence of postoperative pneumonia and reintubation after surgery was 3.2% and 2.5%, respectively, which was significantly higher in patients with severe tooth loss ( < 0.05 for both). After adjusting for age and other confounding factors, the number of remaining teeth was a statistically significant predictor of functional recovery ( < 0.05).

Conclusions: Preoperative oral health status was related to postoperative respiratory complications and independently associated with functional recovery. Preoperative oral intervention may improve functional recovery after cardiovascular surgery.
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http://dx.doi.org/10.1016/j.cjco.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984977PMC
March 2021

Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice.

J Atheroscler Thromb 2021 Mar 27. Epub 2021 Mar 27.

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences.

Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice.

Methods: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed.

Results: Pemafibrate reduced both triglyceride and non-high-density lipoprotein -cholesterol levels (P<0.01), without affecting body weight. It also decreased circulating levels of AA (P<0.001), thromboxane B (P<0.001), prostaglandin E, leukotriene B (P<0.05), and 5-hydroxyeicosatetraenoic acid (P<0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ-prostaglandin J, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P<0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P<0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function.

Conclusion: Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.
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http://dx.doi.org/10.5551/jat.61101DOI Listing
March 2021

Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

J Am Heart Assoc 2021 Apr 24;10(7):e019687. Epub 2021 Mar 24.

Section of Arrhythmia Division of Cardiovascular Medicine Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Hyogo Japan.

Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.
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http://dx.doi.org/10.1161/JAHA.120.019687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174335PMC
April 2021

An endothelial activin A-bone morphogenetic protein receptor type 2 link is overdriven in pulmonary hypertension.

Nat Commun 2021 03 19;12(1):1720. Epub 2021 Mar 19.

Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, Higashinada, Kobe, Japan.

Pulmonary arterial hypertension is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular endothelial cells, we identify inhibin-β-A as an angiocrine factor produced by pulmonary capillaries. We find that excess production of inhibin-β-A by endothelial cells impairs the endothelial function in an autocrine manner by functioning as activin-A. Mechanistically, activin-A induces bone morphogenetic protein receptor type 2 internalization and targeting to lysosomes for degradation, resulting in the signal deficiency in endothelial cells. Of note, endothelial cells isolated from the lung of patients with idiopathic pulmonary arterial hypertension show higher inhibin-β-A expression and produce more activin-A compared to endothelial cells isolated from the lung of normal control subjects. When endothelial activin-A-bone morphogenetic protein receptor type 2 link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of inhibin-β-A in endothelial cells prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial activin-A-bone morphogenetic protein receptor type 2 link in the progression of pulmonary hypertension, and thus endothelial inhibin-β-A/activin-A might be a potential pharmacotherapeutic target for the treatment of pulmonary arterial hypertension.
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http://dx.doi.org/10.1038/s41467-021-21961-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979873PMC
March 2021

'Strange quadruple rhythm': listen to the writing on the heart wall.

Eur Heart J 2021 Mar 17. Epub 2021 Mar 17.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

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http://dx.doi.org/10.1093/eurheartj/ehab149DOI Listing
March 2021

Prevalence and extent of mitral annular disjunction in structurally normal hearts: comprehensive 3D analysis using cardiac computed tomography.

Eur Heart J Cardiovasc Imaging 2021 May;22(6):614-622

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Aims: Mitral annular disjunction is fibrous separation between the attachment of the posterior mitral leaflet and the basal left ventricular myocardium initially described in dissected hearts. Currently, it is commonly evaluated by echocardiography, and potential relationships with mitral valve prolapse and ventricular arrhythmia have been suggested. However, controversy remains as its prevalence and extent have not been fully elucidated in normal living subjects.

Methods And Results: Systolic datasets of cardiac computed tomography obtained from 98 patients (mean age, 69.1 ± 12.6 years; 81% men) with structurally normal hearts were assessed retrospectively. Circumferential extent of both mitral leaflets and disjunction was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral valvar orifice. Distribution angle within the circumference of the mitral valvar attachment and maximal height of disjunction were quantified. In total, 96.0% of patients demonstrated disjunction. Average distribution angles of the anterior and posterior mitral leaflets were 91.3 ± 9.4° and 269.8 ± 9.7°, respectively. Average distribution angle of the disjunction was 105.1 ± 49.2°, corresponding to 39.0 ± 18.2% of the entire posterior mitral valvar attachment. Median value of the maximal height of disjunction was 3.0 (1.5-7.0) mm. Distribution prevalence map of the disjunction revealed characteristic double peaks, with frequent sites of the disjunction located at the anterior to antero-lateral and inferior to infero-septal regions.

Conclusion: Mitral annular disjunction is a rather common finding in the normal adult heart with bimodal distribution predominantly observed involving the P1 and P3 scallops of the posterior mitral leaflet.
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http://dx.doi.org/10.1093/ehjci/jeab022DOI Listing
May 2021

Cytotoxic T Lymphocyte-Associated Antigen-4 Protects Against Angiotensin II-Induced Kidney Injury in Mice.

Circ Rep 2020 Apr 9;2(6):339-342. Epub 2020 Apr 9.

Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University Kobe Japan.

Chronic inflammation caused by pathogenic immune response is crucial in the pathogenesis of kidney disease. In particular, T-cell-mediated adaptive immune responses evoke pathogenic immunoinflammatory responses and contribute to kidney injury (KI). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a potent negative regulator of T-cell immune responses, protects against immunoinflammatory diseases of the arteries such as atherosclerosis and abdominal aortic aneurysm. However, the role of this molecule in kidney disease remains undetermined. To examine the effects of CTLA-4 overexpression on angiotensin II (AngII)-induced KI, we induced KI in CTLA-4 transgenic/apolipoprotein E-deficient (CTLA-4-Tg/ ) mice or mice fed a high-cholesterol diet by continuously infusing AngII. Overexpression of CTLA-4 ameliorated the development of AngII-induced KI and fibrosis. Moreover, CTLA-4-Tg/ mice had decreased expression of pro-inflammatory molecules in the kidney. CTLA-4 overexpression has a protective effect on AngII-induced KI, and increasing CTLA-4 may be a novel therapeutic strategy to prevent the progression of kidney disease.
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http://dx.doi.org/10.1253/circrep.CR-20-0023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925309PMC
April 2020

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

Circ Rep 2020 Apr 9;2(6):322-329. Epub 2020 Apr 9.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.

The clinical frailty scale (CFS) predicts late mortality in patients undergoing transcatheter aortic valve replacement. We evaluated the CFS and other parameters associated with 1-year mortality after balloon aortic valvuloplasty (BAV). Between January 2013 and May 2018, 148 patients with severe aortic stenosis (AS) who underwent BAV at the present hospital were enrolled. We recorded pre-procedural CFS grade, baseline characteristics, echocardiographic, and hemodynamic parameters. To investigate the potential risk to patients before BAV, we evaluated the Society of Thoracic Surgeons (STS) score. After patients who underwent surgical aortic valve replacement, transcatheter aortic valve replacement or repeat BAV were excluded, we investigated 1-year survival. Of 127 patients, 41 (32.3%) died ≤1 year after BAV, 8 of whom (19.5% of all-cause deaths) had cardiac deaths. Higher grade of CFS and STS score significantly correlated with 1-year mortality. Severe frailty and the high operative risk group (CFS ≥7 and STS score ≥8.7%) had an extremely poor prognosis (1-year mortality, 81.2%). In this BAV cohort, severe frailty was a predictor of 1-year mortality in elderly patients with severe AS.
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http://dx.doi.org/10.1253/circrep.CR-19-0123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925327PMC
April 2020

Optimal Cut-Off of Tricuspid Regurgitation Velocity According to the New Definition of Pulmonary Hypertension - Its Use in Predicting Pulmonary Hypertension.

Circ Rep 2020 Sep 24;2(10):625-629. Epub 2020 Sep 24.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.

The 6th World Symposium on Pulmonary Hypertension proposed that precapillary pulmonary hypertension (PH) be defined as mean pulmonary arterial pressure (mPAP) >20 mmHg instead of mPAP ≥25 mmHg. Peak tricuspid regurgitation velocity (TRV) >3.4 m/s is widely used to predict PH, but it is unclear whether this value remains reliable for the new definition of PH. We found that the optimal cut-off value of peak TRV for 511 PH patients was >2.8 m/s, with a sensitivity of 89.5%, specificity of 73.4%, and area under the curve of 0.89 (P<0.001). Based on the new definition of PH, TRV >2.8 m/s can be considered to indicate a high probability of PH.
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http://dx.doi.org/10.1253/circrep.CR-20-0094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932846PMC
September 2020

Visualization of Inflammation After Cryoballoon Ablation in Atrial Fibrillation Patients - Protocol for Proof-of-Concept Feasibility Trial.

Circ Rep 2020 Feb 13;1(3):149-152. Epub 2020 Feb 13.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.

Atrial fibrosis and inflammation play important roles in perpetuating and initiating atrial fibrillation (AF). Although the fibrotic area can be visualized as a delayed enhancement area on late gadolinium enhancement magnetic resonance imaging (LGE-MRI), atrial inflammation has not yet been visualized on any imaging modality. We describe the protocol for a feasibility study to visualize atrial inflammation on positron emission tomography/MRI (PET/MRI). This is a single-arm, prospective, open-label proof-of concept trial, involving AF patients after cryoballoon ablation (CBA). A total of 30 paroxysmal AF patients will be enrolled and undergo simultaneous PET/MRI for the assessment of regional F-fluorodeoxyglucose (F-FDG) uptake 1 day after the CBA. Furthermore, LGE-MRI will be performed before CBA, and at 1 and 4 weeks after assessing the regional LGE area. The main outcome measures will be (1) the feasibility of imaging inflammation in the left atrium on PET/MRI; and (2) the safety of the intervention. There are few data on the visualization of atrial inflammation using PET/MRI. Establishing the visualization methodology will contribute to elucidating the fundamental histopathologic findings of the progress to fibrosis, and to the planning and execution of a larger definitive trial to test the usefulness of PET/MRI.
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http://dx.doi.org/10.1253/circrep.CR-19-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890275PMC
February 2020