P4HA1 Promotes Cell Migration and Colonization in Hypopharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: This study aimed to identify key molecules associated with the survival of patients with hypopharyngeal squamous cell carcinoma (HpSCC) by combining in silico and in vitro analyses. MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened using the Gene Expression Omnibus database. For DEGs, we performed functional enrichment and protein-protein interaction network analyses to identify potential biological functions and hub genes. Functional analysis of HpSCC cell lines verified the critical roles of the hub genes. RESULTS: DEGs were associated with the extracellular matrix. Among the hub genes, high expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1) was significantly associated with shorter survival. In addition, P4HA1 knockdown inhibited cell migration and colonization. Suppression of cell proliferation was demonstrated using P4HA1-selective inhibitors. CONCLUSION: P4HA1 may be a useful therapeutic target for the treatment of HpSCC.

Effect of HER2-targeted therapy on PDX and PDX-derived organoids generated from HER2-positive salivary duct carcinoma.

BACKGROUND: We previously established a patient-derived xenograft (PDX) model, patient-derived organoids (PDOs), and PDX-derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2-positive SDC. METHODS: The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. RESULTS: The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. CONCLUSION: For the first time, we demonstrated the efficacy of anti-HER2 therapy in HER2-positive SDC using preclinical models of SDC PDX and PDXO.

Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting.

PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. METHODS: Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. RESULTS: Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. CONCLUSION: We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies.

AV timing in pacemaker patients with first-degree AV block: which is preferable, intrinsic AV conduction or pacing?

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E' ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E' ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/E' ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/E' ratio under intrinsic AV conduction or RV pacing.

Association between the health insurance status and clinical outcomes among patients with acute heart failure in Japan.

The relationship between the socioeconomic status, including the health insurance status, and prognosis of heart failure (HF) has been recognized as an important concept for stratifying the risk in HF patients and is gaining increasing attention worldwide even in countries with a universal healthcare system. However, the impact of the Japanese health insurance status on outcomes among patients admitted for acute HF has not been fully clarified. We enrolled 771 patients admitted for acute HF between January 2018 and December 2019 and collected data on the in-hospital mortality, length of the hospital stay, and cardiac events, defined as cardiovascular death and readmission for HF within 1 year after discharge. Patients were divided into two groups according to their insurance status, i.e., public assistance (n = 87) vs. other insurance (n = 684). The public assistance group was significantly younger and had a higher rate of diabetes, smoking, ischemic and hypertensive heart disease, and low estimated glomerular filtration rate (all P < 0.05). Pharmacological/invasive heart failure therapy, in-hospital mortality, and the 90-day cardiac event rate after discharge did not differ between the groups. However, the public assistance group had a significantly higher 1-year cardiac event rate than the other insurance groups (P = 0.025). After adjusting for covariates, public assistance was independently associated with the 1-year cardiac event rate (HR: 2.15, 95% CI: 1.42-3.26, P < 0.001). Acute HF patients covered by public assistance received the same quality of medical care, including invasive therapy. As a result, no health disparities were found in terms of the in-hospital mortality and 90-day cardiac event rate, unlike overseas surveys. Nevertheless, HF patients with public assistance had a higher risk for the long-term prognosis than those with other insurance. Comprehensive HF management is required post-discharge.

Prognostic Value of Liver Stiffness Measured by Two-Dimensional Elastography in Acute Decompensated Heart Failure with Preserved Ejection Fraction.

Liver stiffness (LS) assessed by ultrasound elastography reflects right-sided filling pressure and offers additional prognostic information in patients with acute decompensated heart failure (ADHF). However, the prognostic value of LS in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the prognostic value of LS measured by two-dimensional shear wave elastography (2D-SWE) in patients with HFpEF.We prospectively enrolled 80 patients hospitalized for decompensated HFpEF between September 2019 and June 2020. Patients were categorized into three groups based on the tertile values of LS at discharge.The third tertile LS group had an older age; more advanced New York Heart Association functional class; higher total bilirubin, γ-glutamyl transferase (GGT), N-terminal pro-B type natriuretic peptide (NT pro-BNP), and Fibrosis-4 index; a larger right ventricle diastolic diameter, higher tricuspid regurgitation pressure gradient, and a larger maximal inferior vena cava diameter. During a median [interquartile range] follow-up period of 212 (82-275) days, 25 (31.2%) patients suffered composite end points (all-cause mortality and rehospitalization for worsening HF). The third tertile LS group had a significantly higher rate of composite end points (log-rank P = 0.002). A higher LS and the third tertile LS were significantly associated with the composite end points, even after adjusting for a conventional validated HF risk score and other previously reported prognostic risk factors.Increased LS measured by 2D-SWE reflects the severity of liver impairment by liver congestion and fibrosis, underlying right HF, and provides additional information for the prediction of poor outcomes in HFpEF.

FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation.

BACKGROUND/AIM: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan- Meier plotter using data from an HNSCC patient database. RESULTS: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1. CONCLUSION: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.

Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method.

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.

Clinical significance of spleen stiffness in patients with acute decompensated heart failure.

AIMS: Congestive splenomegaly is a classic sign of organ congestion in acute decompensated heart failure (ADHF). Shear wave elastography (SWE) allows the measurement of spleen stiffness (SS). We hypothesized that SS could quantify the severity of splenic congestion and predict adverse events in ADHF. METHODS AND RESULTS: This study included two cohorts: a haemodynamic cohort (62 HF patients) and an outcome cohort (115 ADHF patients). SS was measured by two-dimensional SWE on the same day of right heart catheterization in the haemodynamic cohort. Right atrial pressure (RAP) independently correlated with SS (ß = 0.32, P = 0.002). SS was measured in the outcome cohort before discharge. The 115 patients were divided into three groups on the basis of the tertile value of SS. The third tertile SS group had a higher prevalence of severe tricuspid regurgitation, higher N-terminal B-type natriuretic peptide (NT pro-BNP), and larger right ventricular diastolic diameter, than had the first tertile group and the second tertile group. During a median follow-up period of 105 (77-135) days, adverse events occurred in 25 patients (one death and 24 rehospitalizations for HF). The third tertile SS group had a significantly higher rate of adverse events (P < 0.001). A higher SS was independently associated with adverse events after adjusting for conventional validated risk score, liver function test, liver stiffness, and estimated RAP. CONCLUSIONS: The degree of SS at discharge can be used as a marker of residual splenic congestion, which is predictive of adverse events in patients with ADHF.

Association of renal resistance index and arterial stiffness on clinical outcomes in patients with mild-to-moderate renal dysfunction and presence or absence of heart failure with preserved ejection fraction.

The renal arterial resistance index (RI) and the brachial-ankle pulse wave velocity (baPWV) are known as indicators of renal vascular resistance/systemic vascular damage and systemic arterial stiffness. The clinical significance of those parameters on clinical outcomes is poorly known in patients with and without heart failure with preserved ejection fraction (HFpEF). Baseline clinical data and the RI assessed by renal Doppler data, baPWV were obtained in patients with (HFpEF group, n = 60) and without HFpEF (non-HFpEF group, n = 51) who had a reduced estimated glomerular filtration rate (eGFR) of > 30 and < 60 mL/min/1.73 m2). We investigated the association between the RI and baPWV and major clinical outcomes including hospitalization for heart failure, cardiovascular death, myocardial infarction or unstable angina or other cardiovascular events and death from another cause. The RI and baPWV were greater in the HFpEF group than in the non-HF group (0.75 ± 0.07 vs. 0.69 ± 0.08, p < 0.001; 2002 ± 430 vs. 1762 ± 300 cm/s, p = 0.001). The RI correlated significantly with baPWV in the HFpEF (r = 0.382, p = 0.003) and non-HFpEF groups (r = 0.414, p = 0.002). During the median follow-up period of 54 months, major clinical outcomes occurred in 41 (36.9%) patients. The RI value, statin use and the presence of HFpEF were major factors for predicting clinical outcomes by multivariate analysis. Among the patients who had mild-to-moderate renal dysfunction, an increased RI and baPWV were observed in HFpEF patients as compared to non-HFpEF patients, but the baPWV similarly correlated with the RI value regardless of HFpFE patients or not. The strong association between the high RI value and presence of HFpEF and major clinical outcomes, suggests that not only the presence of HFpEF but also the high RI value may help to identify the high-risk patients leading to poor clinical outcomes.

Clinical Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Infective Endocarditis.

Risk stratification of patients with infective endocarditis (IE) is difficult. The Controlling Nutritional Status (CONUT) score is an index of immune function and nutritional status. We investigated the prognostic value of the CONUT score in IE and whether its prognostic value differed between IE patients with and without indications for surgery.Clinical records were retrospectively evaluated for 92 patients with IE treated at Nihon University Itabashi Hospital and Nihon University Hospital between January 2014 and May 2019. The CONUT score was determined upon admission, and patients were divided into two groups at the median score (≤ 7 [n = 50] and ≥ 8 [n = 42]). The primary outcome was all-cause mortality at 90 days after admission.The high CONUT group had significantly higher C-reactive protein and N-terminal pro-brain natriuretic peptide levels, as well as a significantly lower hemoglobin and estimated glomerular filtration rate (all P < 0.05), and considerably more valve perforation (26% versus 8%, P < 0.05). Kaplan-Meier analysis revealed that mortality was significantly higher in the high CONUT group (P < 0.001). Even after adjusting for the propensity score based on IE risk factors, a higher CONUT score was still associated with mortality. A receiver-operating characteristic analysis revealed that a CONUT score ≥ 8 had a sensitivity of 86% and specificity of 76% for predicting all-cause mortality. A CONUT score ≥ 8 was most strongly associated with mortality in patients with surgical indications (P < 0.001).In patients with IE, a higher CONUT score was significantly associated with inflammation, heart failure, renal dysfunction, anemia, valve dysfunction, and short-term mortality, especially in patients with surgical indications.

Desmin-related myopathy characterized by non-compaction cardiomyopathy, cardiac conduction defect, and coronary artery dissection.

Desmin-related myopathy (DRM) is a rare heritable cardiac and skeletal muscle disease caused by mutations in the desmin gene (DES). DRM is generally characterized by skeletal muscle weakness, conduction disturbance, and dilated cardiomyopathy. However, the clinical cardiac phenotypes of DRM are not yet fully understood. Herein, we report the first case of DRM with the de novo missense DES mutation, R454W, that is characterized by left ventricular non-compaction cardiomyopathy, progressive cardiac conduction defect, spontaneous coronary artery dissection, and no skeletal muscle weakness. Our case findings suggest that clinicians should genetically test patients who have cardiomyopathy, progressive cardiac conduction defect, and coronary artery dissection, even if the patient has neither family history of DRM nor skeletal muscle symptoms.

Narrower QRS may be enough to respond to cardiac resynchronization therapy in lightweight patients.

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

Effect of epicardial fat and metabolic syndrome on reverse atrial remodeling after ablation for atrial fibrillation.

BACKGROUND: Metabolic syndrome/epicardial adipose tissue (EAT) plays an important role in atrial fibrillation (AF). Although reverse atrial remodeling (RAR) often occurs after AF ablation, the effects of EAT on RAR remain unknown. METHODS: Study subjects were 104 patients in whom transthoracic echocardiography (TTE) was performed before AF ablation and 3, 6, and 12 months afterward. EAT was assessed in terms of its thickness adjacent to the right ventricular anterior wall in the TTE parasternal view. RAR was defined as >10% reduction in the left atrial volume (LAV) index by the 3-month follow-up examination. RESULTS: Postablation RAR occurred in 57/104 (55%) patients. RAR absence was associated with a relatively thick EAT (4.92 ± 1.65 vs. 3.92 ± 1.17 mm, P = 0.0005), small LAV index (24.6 ± 7.5 vs. 28.8 ± 10.6 mL/m2, P = 0.0233), and metabolic syndrome (62% vs. 28%, P = 0.0006). Metabolic syndrome and EAT were shown to be independent predictors of RAR absence. Thick EAT was significantly associated with AF recurrence after ablation (5.05 ± 2.19 mm vs. 4.17 ± 1.16 mm for no AF recurrence group, P = 0.0116), but metabolic syndrome was not (48% vs. 42%, P = 0.6189). Despite no change in body weight, EAT thickness decreased significantly by 12 months in patients without AF recurrence (4.17 ± 1.16 vs. 3.65 ± 1.16 mm, P < 0.0001). CONCLUSIONS: EAT and metabolic syndrome appear to be strongly associated with RAR absence, but only the thick EAT was significantly associated with the postablation AF recurrence. Our findings, especially the thinning of EAT, suggest that thick EAT lead to AF vulnerability but that EAT reduction favorably affects ablation outcome.

Prognostic Relevance of Liver Stiffness Assessed by Transient Elastography in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Acute decompensated heart failure (ADHF) is often accompanied by liver congestion through increased right atrial pressure (RAP). Liver stiffness (LS) assessed non-invasively using transient elastography is related to increased RAP and liver congestion in patients with general HF. We investigated the relationship of LS with clinical and echocardiographic variables and outcomes in patients with ADHF.Methods and Results:The subjects were 105 patients with ADHF admitted to hospital between October 2016 and June 2017. Patients were divided into 2 groups based on median LS at admission (low LS <8.8 kPa [n=52] vs. high LS ≥8.8 kPa [n=53]). Death from cardiovascular disease and readmission for HF were primary endpoints. Total bilirubin and γ-glutamyl transpeptidase levels, MELD-XI score, diameters of the inferior vena cava and right ventricle, and severity of tricuspid regurgitation were greater in the high LS group (all P<0.05). During a median (interquartile range) follow-up period of 153 (83-231) days, cardiac events occurred in 29 patients (54%) in the high LS group and in 13 (25%) in the low LS group (P=0.001). After adjusting for variables that influence organ congestion, a high LS ≥8.8 kPa was still significantly associated with cardiac events (all P<0.05). CONCLUSIONS: Increased LS measured by transient elastography reflects RAP elevation, hepatic congestion, and hepatic dysfunction. LS upon admission may be a useful prognostic marker in patients with ADHF.

Calcified Amorphous Tumor-Induced Acute Cerebral Infarction.

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.

Small, smooth, nonmobile cardiac myxoma detected by transesophageal echocardiography following recurrent cerebral infarction: a case report.

BACKGROUND: Cardiac myxoma is known to cause repeated events of cerebral embolism. Soft and irregularly shaped myxomas with high mobility are associated with a higher occurrence of cerebral embolism. In contrast, nonmobile cardiac myxomas with a round regular shape are rarely considered to be a cause of cerebral embolism. In this case, we present a patient with recurrent cerebral embolism associated with a small and nonmobile cardiac myxoma of round regular shape. CASE PRESENTATION: A 76-year-old Japanese man presented to our hospital with weakness in his right upper extremity. He had a history of right frontal lobe infarction in the previous month. T2-weighted magnetic resonance imaging revealed an area of hyperintensity in the left precentral gyrus, indicating acute cerebral infarction. Transthoracic echocardiography revealed normal left ventricular function and no abnormalities. However, transesophageal echocardiography showed a small and nonmobile left atrial tumor with round regular shape attached to the ostium secundum of the atrial septum. Based on these findings, we diagnosed recurrent cerebral infarction due to embolization caused by left atrial myxoma, and cardiac tumor extraction was performed on hospitalization day 36. The excised tumor measured 0.6 × 0.6 × 0.5 cm and was diagnosed as cardiac myxoma by histologic examination. CONCLUSIONS: Even small and nonmobile cardiac myxomas with a round regular shape may cause recurrent cerebral infarction. The diagnosis of this type of atrial myxoma is elusive and transesophageal echocardiography was an effective method of detection. In a clinical situation, this type of cardiac myxoma may be overlooked as a cause of cerebral infarction.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae.

BACKGROUND Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). CASE REPORT A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient's heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient's condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. CONCLUSIONS This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block.

Giant Thrombus Formation Immediately After Mitral Valvuloplasty.

Patients with atrial fibrillation (AF) are at risk of cardioembolism.(1,2)) Atrial thrombus formation associated with AF typically occurs in the left atrial appendage (LAA);(3)) therefore, transesophageal echocardiography (TEE) is important for detection of such a thrombus and measurement of LAA flow velocity.(4,5)) LAA closure is routinely performed during mitral valve surgery in patients with AF to prevent cardiogenic stroke.(6)) We report the case of a 65-year-old woman with severe mitral regurgitation (MR) and AF in whom a giant thrombus formed almost immediately after mitral and tricuspid valvuloplasty and concurrent LAA resection. No atrial thrombus or spontaneous echo contrast (SEC) was detected by TEE before the surgery. However, a giant intramural thrombus was detected in the left atrium 7 days after surgery. It was thought that the atrial dysfunction as well as the change in morphology of the left atrium resulting from the severe MR complicated by AF and congestive heart failure produced a thrombotic substrate. This case suggests that careful surveillance for thrombus formation and careful maintenance of anticoagulation therapy are needed throughout the perioperative period even if no SEC or thrombus is detected before surgery.

Endovascular aortic repair increases vascular stiffness and alters cardiac structure and function.

BACKGROUND: Endovascular aortic repair (EVAR) is performed in patients with thoracic or abdominal aortic aneurysm because it is less invasive than conventional open repair. However, the effects of EVAR on vascular and cardiac function remain to be clarified. METHODS AND RESULTS: We studied the effects of EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for abdominal and/or thoracic aneurysm with preserved ejection fraction. Echocardiography and brachial-ankle pulse wave velocity (baPWV) data were collected before, 1 week, and 1 year after EVAR. Although no changes in blood pressure were found, baPWV, left ventricular mass index (LVMI), and left atrial volume index were significantly elevated at both post-op time periods after EVAR compared with baseline data. The changes in LVMI correlated with those in baPWV (R=0.32, P<0.05). Among the 22 patients who were successfully followed up, 13 showed deterioration in exercise tolerance 1 year after EVAR. Diastolic wall strain, an index for LV distensibility, was lower at baseline in patients with worsening exercise tolerance than in those with unchanged tolerance. CONCLUSIONS: EVAR increased vascular stiffness and induced LV hypertrophy and diastolic dysfunction without a corresponding elevation of blood pressure in the acute and chronic phases. In addition, low LV distensibility at baseline was associated with the impairment of exercise tolerance. EVAR-induced stiffness of arteries leads to limited clinical symptoms.