A case of vasovagal syncope associated with carotid sinus hypersensitivity: Effectiveness of tilt training and subsequent squatting.

A 43-year-old man fainted on a train and was transported to our hospital by an ambulance. No structural heart diseases or neurological abnormalities were observed. Electrocardiogram on admission demonstrated a junctional escape rhythm with bradycardia at 39 bpm. Sick sinus syndrome was excluded from electrophysiological studies. He had lifelong episodes of recurrent syncope that occurred due to emotional stress in daily life and pain associated with medical procedures. Since both the head-up tilt and carotid sinus massage tests showed a positive response, he was diagnosed with vasovagal syncope (VVS) and carotid sinus hypersensitivity. He was encouraged to continue the modified tilt training at home, which included leaning on the wall and squatting if leaning was intolerant. Thereafter, syncope was not observed in his daily life. This case highlights the importance of an accurate diagnosis, full education, and home training for recurrent syncope. This case also suggests that the carotid sinus may be involved in the neural network that causes VVS. Learning objective: Reflex syncope includes both vasovagal syncope (VVS) and carotid sinus syndrome (CSS); however, VVS is discriminated from CSS according to current guidelines. We encountered a case of VVS associated with carotid sinus hypersensitivity. Recurrent syncope disappeared with modified tilt training characterized by conventional tilting and subsequent squatting when tilting was intolerant. This case indicates that the carotid sinus may be involved in the neural network responsible for VVS.

Impact of adaptive cardiac resynchronization therapy in patients with systolic heart failure: Beyond QRS duration and morphology.

BACKGROUND: Mechanical and electrical restoration by cardiac resynchronization therapy (CRT) with adaptive pacing algorithm (aCRT) in heart failure patients with a moderately wide (120-149 ms) QRS has not been fully evaluated. The purpose of this study was to investigate the therapeutic effect of aCRT compared with conventional biventricular CRT (BiV-CRT) regardless of QRS morphology. METHODS: Seventeen consecutive patients with a QRS ≥120 ms, regardless of morphology, underwent CRT device implantation with an aCRT pacing algorithm. Propensity score matched analysis was performed to evaluate the impact of aCRT on the improvement in mechanical and electrical parameters after CRT device implantation using historical controls (HC) from the clinical registry of BiV-CRT (START trial). RESULTS: Left ventricular (LV) volume significantly decreased after CRT in all patients in both the aCRT and HC groups. The difference in relative reduction of LV end-systolic volume (LVESV) was not significantly different between the 2 arms. QRS shortening after CRT was significantly greater in the aCRT group than in the BiV-CRT group, and the difference was prominent in patients with a moderately wide QRS (120-149 ms). In patients with a moderately wide QRS, the relative reduction in LVESV [39 (29-47)% vs. 2 (-6-20)%, p = 0.04] and proportion of LV volume responders (90% vs. 38%, p = 0.04) were significantly greater in the aCRT group than in the HC group. The proportion of volume responders was not significantly different in patients with a wide QRS (≥150 ms). CONCLUSIONS: The aCRT algorithm improved electrical and mechanical parameters in patients with a moderately wide QRS, regardless of QRS morphology.

Case Report: QT Prolongation and Abortive Sudden Death Observed in an 85-Year-Old Female Patient With Advanced Lung Cancer Treated With Tyrosine Kinase Inhibitor Osimertinib.

Cardiac arrest occurred in an 85-year-old female administered osimertinib for advanced lung cancer expressing epidermal growth factor receptor (EGFR) mutations. Electrocardiogram (ECG) recorded at recurrence of spontaneous circulation showed sinus rhythm associated with mild QT prolongation (QTc = 455 ms) to which silent myocardial ischemia and coadministration of itraconazole and herbal drug causing hypokalemia (2.1 mEq/L) may have contributed. Discontinuation of osimertinib, itraconazole and herbal drug, potassium supplementation and percutaneous coronary intervention alleviated QT prolongation (QTc = 432 ms). Osimertinib is the third-generation tyrosine kinase inhibitor lengthening QT interval, and careful monitoring of ECG, serum potassium and drugs coadministered during chemotherapy including osimertinib are highly required.

Cardiac function response to stenting in atherosclerotic renal artery disease with and without heart failure: results from the Carmel study.

AIMS: Consensus-derived guidelines recommend renal stenting for patients with atherosclerotic renal artery disease (ARAD) and heart failure (HF). The aim of this prospective multi-centre observational study was to verify our hypothesis that changes in E/e', an echocardiographic correlate of left ventricular (LV) filling pressure, following renal stenting may differ between ARAD patients with and without HF. METHODS AND RESULTS: This study enrolled de novo ARAD patients undergoing renal stenting at 14 institutions. The primary endpoint was the difference in E/e' change between ARAD patients with and without HF. Clinical and echocardiographic data were prospectively collected at baseline, the day following renal stenting, and 1 month and 6 months afterwards. ARAD patients with HF were defined as patients with New York Heart Association (NYHA) Class 2 and more, or a history of HF hospitalization. A total of 76 patients were included, and 39% were ARAD patients with HF. ARAD patients with HF had significantly lower estimated glomerular filtration rate (P = 0.028) and higher NYHA functional class (P < 0.001) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (P = 0.001) than ARAD patients without HF. Also, ARAD patients with HF had significantly lower LV ejection fraction (P = 0.003) and e'-velocity (P = 0.003) and higher E/e' ratio (P = 0.001), left atrial volume index (LAVI) (P = 0.046), LV end-diastolic volume (LVEDV) (P = 0.001), LV end-systolic volume (LVESV) (P = 0.001), and LV mass index (P = 0.009) than ARAD patients without HF. All procedures were successful. In contrast to blood pressure and renal function, there was a significant interaction in E/e' (Pinteraction  < 0.001) between time and HF, and ARAD patients with HF showed a significant (P < 0.001) decrease in E/e' albeit those without HF. By the same token, there was a significant interaction in NYHA class (Pinteraction  < 0.001), MLHFQ score (Pinteraction  = 0.018), E-velocity (Pinteraction  = 0.002), LAVI (Pinteraction  = 0.001), LVEDV (Pinteraction  = 0.003), and LVESV (Pinteraction  = 0.001) between time and HF with a significant improvement in all these variables in ARAD patients with HF (NYHA class, P = 0.001; MLHFQ score, P = 0.002; E-velocity, P = 0.005; LAVI, P = 0.001; LVEDV, P = 0.017; and LVESV, P = 0.011). CONCLUSIONS: Change in LV filling pressure after renal stenting differed between ARAD patients with and without HF, with a significant improvement in LV filling pressure in patients with HF-ARAD. These unique findings might support clinical cardiac benefits of renal stenting in ARAD patients with HF.

Sick Sinus Syndrome Observed in a Patient with Cholinesterase Deficiency.

A 58-year-old woman complained of general fatigue and was diagnosed with sick sinus syndrome (SSS) by ambulatory electrocardiogram, which demonstrated sinus arrest at midnight and paroxysmal atrial fibrillation (AF) at nighttime. Since her plasma cholinesterase (ChE) activity had been persistently zero, she was diagnosed with ChE deficiency. She refused permanent pacemaker implantation, and treatment with positive chronotropic drugs is ongoing. A novel association of ChE deficiency with SSS is theoretically possible rather than coincident, considering that ChE plays a key role in cholinergic influences on the sinus node leading to sinus bradyarrhythmia and on the atria, causing vagally mediated AF.

Complex regional pain syndrome induced by pacemaker implantation for sick sinus syndrome.

A 53-year-old woman reported burning pain, muscle weakness, and dysesthesia of the left arm 2 months after permanent pacemaker insertion in the ipsilateral side for the treatment of sick sinus syndrome. Complex regional pain syndrome (CRPS) induced by pacemaker implantation was diagnosed. In 2017, her pulse generator became exhausted and was exchanged carefully to avoid exacerbation of CRPS, under the application of local anesthesia and premedication. Six months later, the patient's grip strength in her left hand remained lower relative to that in her right hand. Although rare, the presence of CRPS following device implantation should be remembered.

Metastatic esophageal cancer presenting as shock by injury of vagus nerve mimicking baroreceptor reflex: A case report.

RATIONALE: Neurogenic shock is generally typified by spinal injury due to bone metastases in cancer patients, but continuous disturbance of the vagus nerve controlling the aortic arch baroreceptor can cause shock by a reflex response through the medulla oblongata. PATIENT CONCERNS: A 43-year-old woman with dysphagia presented to our hospital. Computed tomography showed a primary tumor adjacent to and surrounding half the circumference of the descending aorta, and multiple cervical lymph node metastases, including a 55 × 35-mm lymph node overlapping the root of the left vagus nerve. Squamous esophageal cancer (T4bN3M1, stage IV) was diagnosed. Whereas shock status initially appeared soon after left cervical pain, suggesting pain-induced neutrally-mediated syncope, sustained bradycardia and hypotension occurred even after alleviation of pain by opioids. DIAGNOSIS: Disturbance of the left vagus nerve associated with the aortic arch baroreceptor by a large left cervical lymph node metastasis was considered as the cause of shock, pathologically mimicking the baroreceptor reflex. INTERVENTIONS: Systemic steroid administration was performed, and radiotherapy for both the primary site and lymph node metastasis was started 2 days after initiating steroid treatment. OUTCOMES: Four days after initiating steroid administration, hypotension and bradycardia were improved and stable. LESSONS: Disturbance of the vagus nerve controlling the aortic arch baroreceptor should be kept in mind as a potential cause of neurogenic shock in cancer patients, through a pathological reflex mimicking the baroreceptor reflex.

Manifestation of J wave induced by acetylcholine applied for a coronary spasm provocation test in a patient with aborted sudden cardiac death.

A 51-year-old man with a resuscitation episode was referred to our hospital. Coronary angiography revealed a focal spasm overlapped with organic stenosis where a bare metal stent was implanted. Acetylcholine (ACh) provocation test did not induce chest pain. It revealed no discernible ST-T changes but unmasked a J wave at the end of the QRS complex, which was associated with short-coupled repetitive premature ventricular beats. A J wave reportedly appears immediately before the onset of ventricular fibrillation caused by vasospastic angina. However, a J wave observed newly after a coronary spasm provocation test using ACh without ST-T changes is informative when considering the mechanisms of the J wave.

Cardiac metastasis of squamous cell carcinoma of the thyroid gland with severe disseminated intravascular coagulation: A case report.

Distant metastasis of primary squamous cell carcinoma (SCC) of the thyroid gland is rare and, to the best of our knowledge, cardiac metastasis has not been reported to date. A 57-year-old man underwent surgery and adjuvant chemoradiotherapy for stage IVA SCC of the thyroid gland. After 3 months, the patient was admitted to the Kyushu University Hospital (Fukuoka, Japan) with subcutaneous hematomas of the left thigh and lower leg, and he was diagnosed with cardiac and mediastinal lymph node metastases of SCC of the thyroid gland with severe disseminated intravascular coagulation (DIC). Echocardiography revealed a mass, 52 mm in greatest diameter, protruding from the interventricular septum towards the right ventricle. Weekly administration of paclitaxel and concurrent irradiation of the cardiac and lymph node metastases were performed. Eighteen days after the initiation of chemoradiotherapy, the DIC and hematomas had significantly improved, and the cardiac metastasis was stable. However, 2 months after admission, the patient developed dyspnea and multiple nodular shadows appeared to be spreading in the subpleura of the lungs bilaterally, which were initially suspected to be pulmonary tumor embolisms. Prednisolone and subsequent administration of lenvatinib were not effective and the patient succumbed to respiratory failure. Severe DIC caused by extremely rare cardiac metastasis of SCC of the thyroid gland was effectively controlled by chemoradiotherapy. However, intensive local control appears to be required for this condition.

Anticoagulation Stability Depends on CHADS2 Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation.

AIM: Although warfarin remains important despite the widespread use of nonvitamin K antagonist oral anticoagulants (NOACs), to date, the reality of warfarin use in the "NOACs era" is unclear. This multicenter observational study aimed to clarify the key factors contributing to warfarin treatment stability. METHODS: The practical use of warfarin, stability of warfarin therapy, and factors contributing to this stability were investigated in community-based hospitals through a real-world study. Clinical data were retrospectively extracted from the medical records of warfarin-treated Japanese patients (age, 71.3±5.5 years) with atrial fibrillation (AF), prosthetic heart valve, or other concerns requiring anticoagulation. Treatment stability was considered as time in therapeutic range of international normalized ratio of prothrombin time (TTR: %). The factors contributing to TTR were investigated, including CHADS2 score components. RESULTS: Mean CHADS2 score was highest (1.38±0.88, p＜0.001), and most CHADS2 score components in addition to hepatorenal dysfunction were factors contributing to the low TTR in patients with AF (n=176). The similarity was found in overall patients who were prescribed warfarin (n= 518). TTR decreased according to the CHADS2 score component accumulation. Gender, dose and prescription interval of warfarin, and co-administration of antiplatelet agents did not correlate with the low TTR. CONCLUSIONS: This retrospective study demonstrated that the CHADS2 score component accumulation and hepatorenal dysfunction are factors significantly contributing to the low TTR, which is indicative of poor warfarin treatment stability, in patients such as those with AF.

Retrospective analysis of cardiovascular diseases related to chemotherapies for advanced solid tumor patients.

Appropriate management of cardiovascular diseases (CVDs) related to chemotherapy for solid tumors is important for safe oncologic treatment. However, prediction of the onset and progression of CVDs has not generally been established in Japan. We carried out a retrospective analysis of advanced or recurrent solid tumor patients who received chemotherapies in a single institution. Patient characteristics, chemotherapy regimens, adverse events, CVDs before chemotherapy, and diagnosis of CVDs in association with chemotherapy were assessed. During the period from April 2006 to March 2012, 394 patients were examined. Cardiac diseases (CDs), hypertension (HT), or arterial thrombosis or venous thromboembolism were prevalent in 37 (9.4%), 22 (5.6%), five (1.3%), and 14 (3.5%) cases, respectively. HT (14.5%) and venous thrombosis (5.8%) were frequent in patients who received bevacizumab-containing chemotherapy. Four cases with left ventricular dysfunction experienced a decrease of ejection fraction and early filling/atrial filling (E/A) and E/A tended to decrease before ejection fraction. Ninety (62.1%) of 145 cases showed an increase in the D-dimer (DD) level before chemotherapy, and a further increase in DD level was found when venous thrombosis occurred. Relative risks of the disease progression of HT, CD, and thromboembolism because of chemotherapy were 1.3, 1.9, and 3.6, respectively. A decrease in E/A and an increase in DD were suggested to be valuable for early diagnosis of the respective onsets of left ventricular dysfunction and venous thrombosis related to chemotherapy. We conclude that patients with previous CD tend to have disease progression of CD during chemotherapy.

Quantification of coronary flow using dynamic angiography with 320-detector row CT and motion coherence image processing: Detection of ischemia for intermediate coronary stenosis.

OBJECTIVES: Anatomical coronary stenosis is not always indicative of functional stenosis, particularly for intermediate coronary lesions. The purpose of this study is to propose a new method for quantifying coronary flow using dynamic CT angiography for the whole heart (heart-DCT) and investigate its ability for detecting ischemia from intermediate coronary stenosis. METHODS: Participants comprised 36 patients with coronary artery disease who underwent heart-DCT using 320-detector CT with tube voltage of 80kV and myocardial perfusion scintigraphy (MPS). Heart-DCT was continuously performed at mid-diastole throughout 15-25 cardiac cycles with prospective ECG-gating after bolus injection of contrast media (12-24ml). Dynamic datasets were computed into 90-100 data sets by motion coherence image processing (MCIP). Next, time-density curves (TDCs) for coronary arteries with a diameter >3mm were automatically calculated for all phases using MCIP. On the basis of the maximum slope method, coronary flow index (CFI) was defined as the ratio of the maximum upslope of coronary artery attenuation to the upslope of ascending aorta attenuation on the TDC, and was used to quantify coronary flow. CFIs for the proximal and distal sites of coronary arteries with mild-to-moderate stenosis were calculated. Coronary territories were categorized as non-ischemic or ischemic by MPS. Receiver-operating-characteristic (ROC) analysis was performed to determine the optimal cutoff for CFI to detect ischemia. RESULTS: Distal CFI was significantly lower for ischemia (0.26±0.08) than for non-ischemia (0.50±0.17, p<0.0001). No significant difference in proximal CFI was seen between ischemia (0.55±0.23) and non-ischemia (0.62±0.24). ROC analysis revealed 0.39 as the optimal cutoff for distal CFI to detect ischemia, with C-statistics of 0.91, 100% sensitivity, and 75% specificity. CONCLUSIONS: This novel imaging technique allows coronary flow quantification using heart-DCT. Distal CFI can detect myocardial ischemia derived from intermediate coronary stenosis.

Intraluminal superior vena cava metastasis from adenosquamous carcinoma of the duodenum: A case report.

In 2013, a 76-year-old male with a cardiac pacemaker was diagnosed with adenosquamous carcinoma of the duodenum. Subsequently, a pancreatoduodenectomy and lymph node dissection were performed, and 12 cycles of adjuvant chemotherapy (modified FOLFOX6 regimen), which consisted of fluorouracil, leucovorin and oxaliplatin, were administered via a central venous catheter. At 5 months after the completion of adjuvant chemotherapy, the patient experienced the sudden onset of severe pain at the back right of the ear, edema of the right side of the face and right jugular vein dilatation. Computed tomography (CT) revealed filling defects in the superior vena cava (SVC) and right brachiocephalic vein, indicating catheter-induced venous thrombosis. Although the catheter was removed and anti-coagulation therapy, aspiration of the thrombosis and ballooning dilatation were performed immediately, the patient's symptoms were not ameliorated. Notably, histological examination following thrombus aspiration revealed metastatic cancer cells, and fluorodeoxyglucose-positron emission tomography/CT identified metabolically active nodules in the SVC at locations consistent with the initial duodenal tumors detected by CT and in the first thoracic vertebrae. The tumor thrombus rapidly increased in size and resulted in worsening dyspnea. Subsequently, radiotherapy was performed, followed by chemotherapy, which relieved the systemic symptoms and suppressed the tumor growth. Adenosquamous carcinoma of the duodenum is extremely rare, and to the best of our knowledge, intraluminal SVC metastasis as a result of adenosquamous carcinoma of the duodenum has not been reported previously. The placement of a cardiac pacemaker, central venous catheter and tumor cells possessing high metastatic potential are hypothesized to have contributed to this rare case of metastasis.

Mortality benefit of participation in BOOCS program: a follow-up study for 15 years in a Japanese working population.

OBJECTIVE: This study aims to demonstrate the protective effect on mortality among participants of a health education program, Brain-Oriented Obesity Control System (BOOCS). METHODS: A quasi-experimentally designed, 15-year (1993 to 2007) follow-up study was conducted with a total of 13,835 male and 7791 female Japanese workers. They were divided into three groups: participants in the program (1565 males and 742 females), nonparticipant comparative obese controls (1230 males and 605 females), and nonparticipant reference subjects (11,012 males and 6426 females). Hazard ratios were calculated with survival curves drawn to evaluate the mortality effects by the program participation. RESULTS: The male participants showed significantly lower mortality risk for all causes of death at hazard ratio = 0.54 (95% confidence interval: 0.31 to 0.94) with significantly different survival curves (P = 0.014 by log-rank test) than obese controls. CONCLUSIONS: The results support a protective effect on mortality by participating in BOOCS program.

Impaired deformability of circulating erythrocytes obtained from nondiabetic hypertensive patients: investigation by a nickel mesh filtration technique.

INTRODUCTION: Hypertension is associated with microcirculatory disturbance, and erythrocyte deformability is a major determinant of the microcirculation. However, impairment of erythrocyte deformability in hypertensive patients in relation to antihypertensive treatment is unclear. The present study aimed to investigate this impairment in hypertensive patients under treatment using a highly sensitive and quantitative nickel mesh filtration technique. METHODS: Deformability was evaluated by filterability, defined as the flow rate of a hematocrit-adjusted erythrocyte suspension relative to that of saline under a specific filtration pressure in a pressure-flow curve obtained by continuous filtration. Baseline characteristics of hypertensive patients (n = 101) and age-matched normotensive subjects (n = 14) were obtained from medical records, and diabetic patients were excluded. RESULTS: Erythrocyte deformability in the hypertensive group was significantly (p = 0.010) lower (87.8 ± 2.2 %) than that of the normotensive group (89.4 ± 1.7 %) and inversely proportional (r = -0.303, p = 0.002) to the mean blood pressure (BP) measured on blood sampling for the filtration study. Stepwise multiple regression analysis demonstrated that this impairment was mostly attributable to the mean BP (p = 0.001), whereas current smoking and episodes of stroke or coronary artery disease were not contributors. DISCUSSION: These findings indicate that erythrocyte deformability is impaired in the hypertensive patients, which depends on the current BP control rather than target organ damage.

Successful chemoradiotherapy for undifferentiated malignant neoplasm arising from the left pulmonary artery.

Undifferentiated malignant neoplasms, which occur primarily in the pulmonary artery, are extremely rare and associated with poor outcomes as there is no effective therapy. A 67-year-old woman visited our hospital with complaints of dry cough and dyspnea on exertion. A contrast-enhanced chest computed tomography revealed an intravascular tumor obstructing the left pulmonary artery and a pedunculated lesion extending to the main and right pulmonary artery. Multiple metastases in the lung, bones and bilateral adrenal glands were identified by fluorodeoxyglucose-positron emission tomography. A small sample was obtained by catheter aspiration biopsy of the intravascular tumor, and examination revealed undifferentiated small atypical cells. The tumor was diagnosed as an undifferentiated neoplasm arising from the pulmonary artery based on immunohistochemical findings, including the absence of expressions of organ-specific markers. Systemic chemotherapy (paclitaxel and carboplatin) and concurrent radiation were performed as treatment for the primary tumor. Marked shrinkage of the intravascular tumor was achieved, and no serious adverse events were observed during therapy. Chemotherapy was continued for 5 months, but the patient died because of tumor progression 9 months after the initial diagnosis. Chemoradiotherapy has efficacy against undifferentiated neoplasm of the pulmonary artery.

Infective endocarditis caused by Listeria monocytogenes forming a pseudotumor.

A 73-year-old woman with breast cancer and metastasis under chemotherapy suffered from fever, pleural effusion and pericardial effusion. Despite the administration of treatment with cefozopran and prednisolone, the patient's fever relapsed. An electrocardiogram identified a new complete atrioventricular block and an echocardiogram revealed vegetation with an unusual pseudotumoral mass in the right atrium. Blood cultures grew Listeria monocytogenes. The patient was eventually diagnosed with right-sided infective endocarditis, which improved following the six-week administration of ampicillin and gentamicin. Homemade yoghurt was suspected to be the cause of infection in this case. Listeria endocarditis is rare; however, physicians should pay more attention to preventing this fatal disease in immunocompromised patients.