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A 19-year-old Japanese man was hospitalized for cardiogenic shock 28 days after receiving a second dose of the coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine. He had had a high fever for three days with vomiting and abdominal pain before arriving at our hospital. The patient visited a local hospital and was diagnosed with heart failure and acute appendicitis. An endomyocardial biopsy specimen showed myocarditis. Thereafter, Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were initiated immediately along with inotropic support and steroid pulse therapy. Given these findings, he was finally diagnosed with multiple inflammatory syndrome and fulminant myocarditis., Internal medicine, 62(3), pp. 411-417; 2023

The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM following endomyocardial biopsy (age, 28-42 years; mean age, 35 years). Biopsied samples were evaluated using microscopy, including immunostaining and electron microscopy. The pathological findings were as follows: myocardial hypertrophy, myocardial fibrosis, and cell infiltration. Two patients were diagnosed with lymphocytic myocarditis, one with eosinophilic myocarditis, one with hypertensive heart disease, and one with a combination of hypertension and myocarditis. Endomyocardial biopsy suggested that the causes of PPCM were varied and related to myocarditis and myocardial overload due to hypertension.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Aims Royal jelly, a creamy substance secreted by honeybees, has been reported to have beneficial effects against dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remain unknown. Hence, we prospectively evaluated whether royal jelly augments vascular endothelial function, which can reflect early atherogenesis, in healthy volunteers. Methods This was a single-center, double-blind, 1:1 randomized placebo-controlled study conducted from October 2018 to December 2019. A total of 100 healthy volunteers were randomly assigned to receive either royal jelly 690 mg or placebo daily for 4 weeks. The primary endpoint was augmentation in vascular endothelial function as assessed using the change in the reactive hyperemia peripheral arterial tonometry index (RH-PAT) index, and the secondary endpoints were the changes in liver function and lipid profiles between baseline and 4 weeks after enrollment. Results The mean age of the participants was 35.0±9.3 years in the placebo group and 36.1±9.1 years in the royal jelly groups; 45% and 50% of the placebo and the royal jelly groups, respectively, were male. The percentage relative change in the RH-PAT index was significantly higher in the royal jelly group than in the placebo group (21.4%±53.1% vs. 0.05%±40.9%, P=0.037). The percentage relative changes in alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than in the placebo group (alanine aminotransferase: -6.06%±22.2% vs. 11.6%±46.5%, P=0.02; γ-glutamyl transpeptidase: -3.45%±17.8% vs. 4.62%±19.4%, P=0.045). Lipid profiles were not significantly different between the two groups. Conclusions Royal jelly might have antiatherogenic property by improving vascular endothelial function. It also augmented liver functions in healthy volunteers.

A 41-year-old Japanese man was admitted to our hospital with acute perimyocarditis 4 weeks after coronavirus disease 2019 (COVID-19) infection. Ten days after admission, the patient showed bilateral facial nerve palsy in the course of improvement of perimyocarditis under treatment with aspirin and colchicine. After prednisolone therapy, perimyocarditis completely improved, and the facial nerve palsy gradually improved. Acute perimyocarditis and facial nerve palsy can occur even 4 weeks after contracting COVID-19., Internal Medicine, 61 (15), pp. 2327-2332; 2022

Aims This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. Methods and results This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16–32. Conclusions According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC.CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

A 17-year-old boy with acute coronary syndrome was admitted to our hospital. He had xanthomas over his elbow and Achilles tendon and a high level of low-density lipoprotein cholesterol; therefore, his initial diagnosis was familial hypercholesterolemia. However, a genetic analysis revealed a compound heterozygous mutation in the ABCG5 gene with a high serum level of sitosterol, leading to the diagnosis of sitosterolemia. After lipid-lowering treatment, percutaneous coronary intervention was performed. Furthermore, a persistently high C-reactive protein level and images of large arteries led to a diagnosis of Takayasu arteritis. To our knowledge, this is the first case of sitosterolemia complicated by Takayasu arteritis.

Background: Despite the beneficial effects of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), they may also cause adverse events (AEs), especially cardiovascular toxicity. The incidence of TKI-induced AEs may vary among ethnic groups, and there is little specific information for Japanese patients. Methods and Results: Sixty-nine consecutive patients who were started on treatment with dasatinib (n=25) or imatinib (n=44) for CML or gastrointestinal stromal tumor (GIST) between December 2008 and December 2019 were retrospectively recruited to the study. We determined the prevalence of AEs through October 2020 and compared the incidence of AEs between the 2 drugs. Baseline characteristics were comparable between the 2 groups. However, compared with the imatinib-treated group, the dasatinib-treated group had a higher incidence of congestive heart failure (CHF; 20.0% vs. 2.3%; P=0.04), pleural effusion (48% vs. 20.5%; P=0.03), pericardial effusion (24% vs. 4.6%; P=0.02), QT prolongation (4 vs. 0 patients; P=0.02), and pulmonary hypertension (3 vs. 0 patients; P=0.04). In the dasatinib-treated group, CHF tended to be associated with tricuspid valve regurgitation pressure gradient, and pleural effusion was observed in all patients. All-cause mortality and other cardiovascular events did not differ significantly between the 2 groups. Conclusions: Cardiotoxic AEs occurred more frequently in Japanese patients with CML and GIST treated with dasatinib than imatinib.

BackgroundMeasurement of coronary microvascular resistance (MR) is essential for diagnosing nonocclusive coronary artery ischemia, but whether coronary branches of different diameters can be similarly assessed using hyperemic microvascular resistance index (hMVRI) calculated from average peak velocity (APV) remains unclear.ObjectivesWe investigated the relationship between coronary arteries of different diameters and hMVRI.MethodThirty patients with suspected angina pectoris and nonobstructive coronary stenosis with fractional flow reserve >0.8 underwent evaluation of all coronary arteries using a Doppler velocity and pressure-equipped guidewire. Vessel diameter (DQCA) was analyzed by quantitative coronary angiography (QCA). Coronary blood flow (CBFQCA) was calculated as πDQCA2/4 (0.5×APV) and hMVRI as distal coronary pressure (Pd) divided by CBFDQCAduring maximal hyperemia.ResultsThe hMVRI was significantly higher for the right coronary artery (RCA) than for the left anterior descending artery (LAD), but no significant differences between arteries were seen for CBFQCAand hMVRIQCA. Although the correlation between CBFQCAand APV was weak in all arteries, CBFQCAdivided into three groups according to DQCAshowed very strong correlations with APV. Slopes of the straight line between APV and CBFQCAfor small-, middle-, and large-diameter groups were 0.48, 0.30, and 0,21, respectively, with slope decreasing as diameter increased. The correlation between APV and CBFQCAwas high for LAD and RCA, but weak for the left circumflex artery.ConclusionsEvaluation of MR in coronary branches requires consideration of vessel diameter.

Background: Cardiovascular events, including pericarditis, myocarditis, and myocardial ischaemia, have been reported as complications following COVID-19 vaccination. Case summary: A 28-year-old Japanese woman diagnosed 10 years earlier with systemic lupus erythematosus and antiphospholipid syndrome was admitted to our hospital because of chest pain and Raynaud’s phenomenon. She had received a second dose of the COVID-19 BNT162b2 mRNA vaccine 28 days earlier. 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) and 201thallium dual myocardial single-photon emission computed tomography demonstrated mildly reduced perfusion of BMIPP in the mid-anterior wall of the left ventricle. Coronary angiography revealed normal coronary arteries; additionally, an endomyocardial biopsy was performed. Histopathological evaluation revealed a normal myocardium without cell infiltration. However, immunostaining for the severe acute respiratory coronavirus (SARS-CoV)/severe acute respiratory coronavirus 2 (SARS-CoV-2) spike protein was positive in the small intramural coronary arteries. The administration of azathioprine (50 mg/day) and amlodipine (5 mg/day) and increases in her prednisolone (10 mg/day) and aspirin doses led to improvements in the symptoms of the patient. Discussion: Our data lead us to speculate that two events in the timeline of the patient, namely, receiving COVID-19 vaccination and the presence of SARS-CoV/SARS-CoV-2 spike protein in small intramural coronary arteries, may be related to the myocardial microangiopathy observed in this patient., European Heart Journal - Case Reports, 7(3), art. no. ytad102; 2023

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are non-selective beta blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker. was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Background The cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness and has been reported to be associated with the severity of coronary artery disease and cardiovascular events. However, whether CAVI can predict the composition of coronary plaques remains unclear. Methods We enrolled 208 patients who underwent percutaneous coronary intervention (PCI) for culprit lesions evaluated with iMAP-intravascular ultrasound (IVUS), a radiofrequency imaging system for characterizing tissues. iMAP-IVUS classified the culprit plaque composition as fibrotic, lipidic, necrotic, or calcified, and the respective absolute volumes [fibrotic volume (FV), lipidic volume (LV), necrotic volume NV, and calcified volume] and their ratios (%) within the total plaque volume were calculated. A plaque with a median %NV of ≥ 33.2% was defined as a larger NV (LNV) plaque. We measured CAVI and divided the patients into two groups according to CAVI ≥8 (high CAVI, n = 164) or Results Culprit plaques had significantly greater absolute NV (p = 0.016), %NV (p = 0.01), and smaller %FV (p = 0.02) in patients with high CAVI than in those with low CAVI. Patients with high CAVI had a higher prevalence of LNV plaques in culprit lesions than those with low CAVI (54% vs. 34%, p = 0.026). CAVI correlated significantly and positively with absolute NV, LV, and negatively with %FV. In logistic regression analysis after adjustment for the classic coronary risk factors and possible variables associated with vulnerable plaques, high CAVI had an independent and significant association with the presence of LNV plaques (OR, 3.37; 95% CI, 1.45–7.79; p = 0.0032). Conclusions A high CAVI is associated with the composition of coronary culprit plaques, particularly increased amount of necrotic tissue, in patients with coronary artery disease undergoing PCI .

A 15 year-old-Japanese girl was admitted to our ward because of syncope. Electrocardiography (ECG) demonstrated sinus bradycardia with heart rate of 52/min. Holter ECG showed no arrhythmia related to syncope. Coronary enhanced computed tomography and cardiac magnetic resonance imaging showed no abnormal findings. Head-up tilt test revealed syncope with sinus arrest. (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy revealed focally decreased uptake on the anterior wall of the left ventricle but generally maintained uptake of MIBG. Finally, she was diagnosed with cardioinhibitory vasovagal syncope (CIVS). Sympathetic nerve abnormalities seemed to be related to CIVS in this patient.

Autonomic disorders are common in patients with systemic lupus erythematosus (SLE), but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including intravenous cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance., Modern Rheumatology Case Reports, 6 (1), pp. 47-51; 2022

A 19-year-old Japanese man was hospitalized for cardiogenic shock 28 days after receiving a second dose of the COVID-19 mRNA-1273 vaccine. He had had a high fever for three days with vomiting and abdominal pain before arriving at our hospital. The patient visited a local hospital and was diagnosed with heart failure and acute appendicitis. An endomyocardial biopsy specimen showed myocarditis. Thereafter, Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were initiated immediately along with inotropic support and steroid pulse therapy. Given these findings, he was finally diagnosed with multiple inflammatory syndrome and fulminant myocarditis.

This study was conducted to investigate the meaning of left ventricular (LV) apical sparing in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).165 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from January 2002 to December 2020 and had sufficient data for two-dimensional speckle tracking echocardiography were enrolled. Of these, 86 patients (52 %) had LV apical sparing (relative apical longitudinal strain index (RapLSI) 1.0). Multivariable logistic regression analysis revealed the following variables were significantly associated with LV apical sparing: interventricular septal thickness in diastole (odds ratio (OR), 1.19; 95 % confidence interval (CI), 1.01-1.41; p 0.05); E/e' ratio (OR, 1.06; 95 % CI, 1.00-1.11; p 0.05); and heart-to-contralateral ratio byApproximately half of ATTRwt-CM patients did not have LV apical sparing at diagnosis. Because RapLSI in ATTRwt-CM significantly changed over time, repeated two-dimensional speckle tracking analysis is important for suspected ATTR-CM patients.

Objective To determine whether autonomic dysfunction in neurosarcoidosis is associated with anti-ganglionic acetylcholine receptor (gAChR) antibodies, which are detected in autoimmune autonomic ganglionopathy. Methods We retrospectively extracted cases of sarcoidosis from 1787 serum samples of 1,381 patients between 2012 and 2018. Anti-gAChR antibodies against the α3 and β4 subunit were measured by luciferase immunoprecipitation to confirm the clinical features of each case. We summarized literature reviews of neurosarcoidosis with severe dysautonomia to identify relevant clinical features and outcomes. Results We extracted three new cases of neurosarcoidosis with severe dysautonomia, among which two were positive for anti-gAChR antibodies: Case 1 was positive for antibodies against the β4 subunit, and Case 2 was positive for antibodies against both the α3 and β4 subunits. We reviewed the cases of 15 patients with neurosarcoidosis and severe dysautonomia, including the three cases presented herein. Orthostatic hypotension and orthostatic intolerance were the most common symptoms. Among the various types of neuropathy, small fiber neuropathy (SFN) was the most prevalent, with seven of nine cases exhibiting definite SFN. Six of eight cases had impaired postganglionic fibers, of which the present three cases revealed abnormality of 123I-MIBG myocardial scintigraphy. Of the 11 cases, 10 were responsive to immunotherapy, except one seropositive case (Case 2). Conclusions The presence of gAChR antibodies may constitute one of the mechanisms by which dysautonomia arises in neurosarcoidosis.

Background: This study investigated factors related to quality of life (QoL) in patients with chronic thromboembolic pulmonary hypertension who completed balloon pulmonary angioplasty (BPA). Methods and Results: Patient QoL and living environment after BPA were evaluated prospectively using the 5-level EQ-5D questionnaire and International Physical Activity Questionnaire Environmental Module (IPAQ-E), respectively. Patients were mailed copies of both surveys. In addition, we reviewed patient charts and collected retrospective clinical data. Relationship between the clinical data and QoL and environmental living factors were investigated. Of the 33 subjects mailed the surveys, sufficient responses were obtained from 22 (71%). Spearman’s rank correlation coefficient showed that psychiatric disorders (r=−0.6865, P

BACKGROUND Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease. METHODS AND RESULTS We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p

A 62-year-old woman with activity-dependent two-to-one atrioventricular block (2:1AVB) and a normal left ventricular ejection fraction was referred to our department for the evaluation of exclusively exercise-induced marked symptoms. The treadmill test helped establish a clear correlation between 2:1AVB and symptoms. The test results demonstrated that exercise-induced marked symptoms were attributed to abrupt transient hypotension combined with relative bradycardia, probably due to increased diastolic mitral and tricuspid regurgitation because of 2:1AVB during moderate-to-heavy exercise. After pacemaker implantation for 2:1AVB, the symptoms and transient hypotension disappeared, and her exercise capacity improved.

Background: Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent upper gastrointestinal bleeding in patients undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of both vonoprazan and prasugrel. This raises concern about the possibility of a CYP3A4-mediated drug-drug interaction between vonoprazan and prasugrel that may lead to attenuation of prasugrel's antiplatelet effect. Methods and Results: We evaluated 88 PCI patients who were taking either vonoprazan (n=45) or proton pump inhibitors (PPIs; n=43) in combination with DAPT (aspirin and prasugrel). Platelet reactivity on prasugrel was assessed using the VerifyNow P2Y12 assay. The primary endpoint was comparison of P2Y12 reaction units (PRU) between patients on vonoprazan and PPIs. PRU >208 and

An autonomic nervous disorder is an important characteristic of cardiac amyloidosis; however, the prevalence of autonomic dysfunction in wild-type transthyretin amyloidosis (ATTRThis is a single-center, retrospective, case-control study. Fifty patients with heart failure (HF) were studied. The etiologies of HF were as follows: ATTRThere was no difference in the CVR-ROur data suggested autonomic dysfunction in patients with ATTR

Background: Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis. Methods and Results: In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P−14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P−14%; odds ratio 28.39, 95% confidence interval 1.89–427.45, P

Objective Associations between aortic stiffness and cardiovascular disease events are mediated in part by pathways that include coronary microvascular dysfunction (CMD) and remodeling. However, the relationship between aortic stiffness and CMD remains unclear. The present study aimed to determine whether aortic stiffness causes CMD as evaluated by the hyperemic microvascular resistance index (hMVRI) in patients with non-obstructive coronary artery disease (CAD). Methods The intracoronary physiological variables in 209 coronary arteries were evaluated in 121 patients with non-obstructive CAD (fractional flow reserve >0.80) or reference vessels. The cardio-ankle vascular index (CAVI) as a measure of aortic stiffness and atherosclerotic risk factors were also measured. Results Univariate analyses showed that hMVRI correlated with age (β=0.24, p=0.007), eicosapentaenoic acid (EPA; β=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (β=-0.22, p=0.014) and CAVI (β=0.30, p=0.001). A multivariate regression analysis identified CAVI (β=0.25, p=0.007) and EPA/AA ratio (β=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI. Conclusion Aortic stiffness may cause CMD in patients with non-obstructive CAD via increased coronary microvascular resistance. Aortic stiffness is associated with CMD which is evaluated as hyperemic microvascular resistance in patients with non-obstructive CAD.

BACKGROUND We previously reported that a high score (2 or 3 points) according to the Kumamoto criteria, a combination of high-sensitivity cardiac troponin T (hs-cTnT) ≥0.308 ng/mL, the length of QRS ≥ 120 ms in electrocardiogram, and left ventricular (LV) posterior wall thickness ≥ 13.6 mm, increases the pretest probability of 99m Tc-labeled pyrophosphate (99m Tc-PYP) scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM). However, some patients with a low score (0 or 1 point) show positive findings on 99m Tc-PYP scintigraphy. Therefore, we evaluated the usefulness of additional examinations, including echocardiographic assessment of myocardial strain, to raise the pretest probability of 99m Tc-PYP scintigraphy for these patients. METHODS AND RESULTS We examined 109 consecutive patients aged ≥70 years with low scores according to the Kumamoto criteria who underwent 99m Tc-PYP scintigraphy. Nineteen patients (17%) had positive 99m Tc-PYP scintigraphy findings. The relative apical longitudinal strain (LS) index (apical LS/ basal LS + mid LS) (RapLSI) was significantly higher in patients with positive than negative 99m Tc-PYP scintigraphy findings (1.04 ± 0.37 vs 0.70 ± 0.28, P

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.

The number of patients aged over 90 years undergoing transthoracic echocardiography (TTE) has increased. Normal echocardiographic measurement values in healthy Japanese aged 20-79 years have been reported by Daimon et al., and in those aged 10-89 years by Okura et al. To date, no researchers have published normal values in healthy Japanese aged over 90 years. To understand the echocardiographic characteristics and establish the normal range, we evaluated patients aged over 90 years who had preserved left ventricular (LV) ejection fraction without cardiovascular disease.Enrolled in the study were consecutive patients aged over 90 years who were examined by TTE at the Ultrasound Imaging Center at Nagasaki University Hospital, Japan, between September 2009 and May 2016. We selected patients with LV ejection fraction 55%, and without cardiac, renal, or aortic disease.Among a total of 956 patients, 73 patients (19 males, 54 females) were admitted. Compared with females, males had significantly higher values of aortic diameter at the sinus of Valsalva and LV diastolic diameter and systolic diameter (P 0.01), significantly lower E wave velocities (P 0.01) and left ventricle mass (P 0.01), and lower values of relative wall thickness (P 0.01). Compared with subjects in their 70s and 80s in the studies by Daimon and Okura, the E and A wave velocities were higher.We established the normal range of TTE parameters in elderly patients who had LV ejection fraction55% without cardiac, renal, or aortic disease. Sex differences were present as well as a tendency towards age-related changes in LV geometry and diastolic function. Most of the patients aged over 90 years had LV hypertrophy and potential diastolic dysfunction.

A 73-year-old Japanese man was admitted with an asymptomatic pulmonary artery aneurysm. However, chest X-ray and contrast-enhanced thoracic computed tomography revealed a protrusion at the second left branch that in fact was a pulmonary artery aneurysm with a diameter of 50 mm. Transesophageal echocardiography showed a bicuspid pulmonary valve, and cardiac catheterization revealed pulmonary stenosis with a pressure gradient of 45 mmHg, but no other heart diseases were noted. An extremely rare pulmonary artery aneurysm associated with an isolated bicuspid pulmonary valve was diagnosed.

Amiodarone-induced thyrotoxicosis (AIT) is a complication of amiodarone therapy that can be difficult to diagnose and manage, especially in patients with dilated cardiomyopathy (DCM). We describe a 47-year-old female patient with DCM who experienced the sudden onset of type II AIT with symptoms mimicking low cardiac output syndrome, namely, general malaise and nausea. Early type II AIT was diagnosed, and effectively treated with prednisolone.

A 65-year-old Japanese woman with an intrapericardial tumor and neck tumor was admitted to our hospital. Intrapericardial tumor had not been resected because of massive bleeding from the hypervascular tumor and its invasion into the pericardium, ascending aorta, and pulmonary artery. The neck tumor had been successfully resected, and paraganglioma was pathologically diagnosed. Abnormal accumulation in the intrapericardial tumor was seen with (123)I-metaiodobenzylguanidine scintigraphy. Moreover, gene mutation of succinate dehydrogenase type D was found. Finally, paraganglioma of the carotid body and intrapericardium was diagnosed.

Background The impact of intra-atrial conduction delay on the recurrence of atrial tachyarrhythmia after radio frequency catheter ablation (RFCA) has not been fully elucidated. Methods We retrospectively analyzed 155 AF patients who were sinus rhythm at the start of RFCA. The conduction time from the onset of the earliest atrial electrogram at the high right atrium (HRA) to the end of the latest electrogram at the coronary sinus (CS) during sinus rhythm was defined as HRA-CS conduction time. Pulmonary vein isolation (PVI) was performed followed by linear roof lesion and complex fractionated atrial electrogram (CFAE) ablation until AF termination. We evaluated atrial tachyarrhythmia recurrence 12 months after RFCA. Results The follow-up data were available for 148 patients. The recurrence of atrial tachyarrhythmia was noted in 28 (18.9%) patients. Atrial tachyarrhythmia recurrence patients had longer HRA-CS conduction times (151.3 ± 22.1 ms vs 160.1 ± 32.6 ms, p = .017). The patients were divided into the long or short HRA-CS conduction time group. The Kaplan–Meier analysis revealed that the long HRA-CS conduction time group held a higher risk of atrial tachyarrhythmia recurrence (log-rank test, p = .019). The multivariable Cox hazard analysis revealed that a long HRA-CS conduction time was a significant risk factor for the recurrence of atrial tachyarrhythmia, despite a long AF duration, persistent AF, and larger left atrial diameter (LAD) were not statistically significant. Conclusions The HRA-CS conduction time was the primary influencing factor that predicted the recurrence of atrial tachyarrhythmia after catheter ablation.

AIMS The prediction of future heart failure (HF) in stable outpatients is often difficult for general practitioners and cardiologists. Recently, the H2 FPEF score (0-9 points) has been proposed for the discrimination of HF with preserved ejection fraction from non-cardiac causes of dyspnoea. The six clinical and echocardiographic variables that constitute the H2 FPEF score include the following: (i) obesity (H); (ii) the use of ≥2 antihypertensive drugs (H); (iii) atrial fibrillation (F); (iv) pulmonary hypertension (P); (v) an age > 60 years (E); and (vi) E/e' > 9 (F). We performed an external validation study that investigated whether the H2 FPEF score could predict future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan. METHODS AND RESULTS In this prospective cohort study, after exclusion of 195 from 551 consecutive, stable Japanese outpatients with at least one cardiovascular risk factor who were enrolled between September 2010 and July 2013, the remaining 356 outpatients (171 men, 185 women, mean age 73.2 years) were eligible for the analysis. We calculated the H2 FPEF score (0-9 points), and followed up the patients for an average of 517 days. In all of the 356 patients, the mean H2 FPEF score was 3.1 ± 1.8, and 15 developed HF-related events during the follow-up period, including cardiovascular death (n = 2) and hospitalization for HF decompensation (n = 13). Multivariate Cox proportional hazards analysis showed that the H2 FPEF score was an independent predictor of future HF-related events (P < 0.001 for all three models). Kaplan-Meier survival curves showed a significantly higher probability of HF-related events in the outpatients with a high H2 FPEF score (P < 0.001). In receiver operating characteristic (ROC) curve analysis, the H2 FPEF score was significantly associated with the occurrence of future HF-related events (P < 0.001). In ROC curve analysis, the sensitivity, specificity, and positive likelihood ratio of a H2 FPEF score of 7 points to predict HF-related events were 47%, 96%, and 11.4%, respectively. CONCLUSIONS The H2 FPEF score could provide useful information for future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan.

A 44-year-old Japanese man was referred to our hospital for the evaluation of paroxysmal hypertension. (123)I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography (SPECT) revealed specific uptake in the left adrenal gland in addition to high levels of serum and urinary catecholamines although computed tomography and magnetic resonance imaging were not able to detect a definite adrenal mass. Left adrenalectomy was performed and he was diagnosed with adrenal medullary hyperplasia (AMH). A diagnosis of unilateral AMH is important because AMH resection can effectively treat hypertension.

Objective: Acute and chronic stress after severe earthquakes can contribute to cardiovascular events, including heart failure (HF). On April 14, 2016, magnitude 7 earthquakes occurred in the Aso region in the western part of Japan. This study aimed to investigate the clinical characteristics of HF in this area after these earthquakes. Methods: We investigated the clinical characteristics and 1-y mortality rate of patients with HF. Nutritional status was evaluated with the Geriatric Nutritional Risk Index (GNRI) and the Prognostic Nutritional Index (PNI). Results: Among a total of 58 cardiovascular events, HF was the most frequently observed (n = 28). The mean age of individuals with HF was 85.5 y. The total incidence of HF was significantly higher compared with the average of the prior 2 y. Disaster influence on mental health was suggested by patient history in 20 patients (71%). The 1-y mortality rate among patients with HF was 50%. Among those who died, 93% had malnutrition status (GNRI Conclusions: Our results demonstrated the poor prognosis of patients with HF following the disaster. The prevalence of malnutrition was high in those patients. Careful follow-up is necessary, especially for older people with frailty.

A 54-year-old Japanese woman was admitted to our ward because of recurrent chest pain at rest for 2 months. She had been treated with nivolumab, an immune checkpoint inhibitor for inoperable advanced hypopharyngeal cancer for 21 months. She had no chest pain after cessation of nivolumab treatment. Cardiac catheterization confirmed the presence of vasospastic angina. Benidipine 8 mg was started, and she had no chest pain even after resuming therapy with nivolumab. Vasospastic angina is an adverse effect of nivolumab.

Vibrio vulnificus is a Gram-negative pathogenic bacterium that causes serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In the ferric-utilization system in V. vulnificus M2799, an isochorismate synthase (ICS) and an outer membrane receptor, VuuA, are required under low-iron conditions, but alternative proteins FatB and VuuB can function as a periplasmic-binding protein and a ferric-chelate reductase, respectively. The vulnibactin-export system is assembled from TolCV1 and several RND proteins, including VV1_1681. In heme acquisition, HupA and HvtA serve as specific outer membrane receptors and HupB is a sole periplasmic-binding protein, unlike FatB in the ferric-vulnibactin utilization system. We propose that ferric-siderophore periplasmic-binding proteins and ferric-chelate reductases are potential targets for drug discovery in infectious diseases.

This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed. During a median follow-up of 615 days, 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.1 ± 7.4 years vs. 78.2 ± 6.2 years, p = 0.009) and had significantly higher interventricular septal thickness in diastole (16.6 ± 3.1 mm vs. 15.3 ± 2.4 mm, p = 0.048), lower RV-GLS (10.9 ± 2.7% vs. 12.8 ± 3.5%, p = 0.010), and lower right ventricular free wall longitudinal strain (RVFWLS) (13.1 ± 3.3% vs. 15.5 ± 3.8%, p = 0.004). In the univariate Cox proportional hazard analysis, age, left atrial volume index (LAVI), RV-GLS, and RVFWLS were significantly associated with cardiovascular death [age, hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.02-1.19, p = 0.010; LAVI, HR, 1.02; 95% CI, 1.00-1.03, p = 0.009; RV-GLS, HR, 0.86; 95% CI, 0.75-0.97, p = 0.017; RVFWLS, HR 0.89; 95% CI, 0.79-1.00; p = 0.041]. Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (HR, 0.86; 95% CI, 0.74-0.99; p = 0.038). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cut-off value of RV-GLS was 11.59% (sensitivity, 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (11.59%) had a significantly higher probability of total cardiovascular death (p = 0.004) and heart failure-related hospitalization (p = 0.013).RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic findings.

Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, has shown remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin:Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL)-induced foam cell formation. Our studies demonstrated that Cur-Bio PLGA NPs (both ratios) maintained the cell viability in THP-1 monocyte-derived macrophages above 80% at all periods. The 1:0.2:10 ratio of Cur-Bio PLGA NPs at a concentration of 250 μg/mL illustrated an enhanced reduction in the relative cholesterol content in the THP-1-derived foam cells compared to the 1:1:10 ratio. Confocal microscopy analysis also revealed a reduction in macrophage-mediated foam cell formation when administered with both the ratios of Cur-Bio PLGA NPs. Relative fold change in the mRNA expression of the genes involved in the inflammatory pathways in the atherosclerotic process downregulated NF-κB, CCL2/MCP-1, CD-36, and STAT-3 activity while upregulating the SCAR-B1 expression when treated with the Cur-Bio PLGA NPs. This study thus highlights the importance of natural-based compounds towards the therapeutic intervention against atherosclerotic activity when administered as preventive medicine.