Trend in Age at the Initial Pacemaker Implantation in Patients With Bradyarrhythmia　- A 50-Year Analysis (1970-2019) in Japan.

BACKGROUND: This study investigated whether the age of patients undergoing pacemaker implantation is increasing.Methods and Results: This study retrospectively reviewed the consecutive cases of 3,582 patients who underwent an initial pacemaker implantation at our hospitals because of symptomatic bradyarrhythmias between 1970 and 2019. The exclusion criteria were: patients with AV block due to cardiac surgery or AV junction ablation, and patients aged <20 years. The patients were divided into 5×10-year groups: those treated in the 1970s (1970-1979), 1980s (1980-1989), 1990s (1990-1999), 2000s (2000-2009), and 2010s (2010-2019). A total of 3,395 patients satisfied the study criteria. The average age at which the patients underwent a first pacemaker implantation increased across the 10-year periods: 63.7±13.2 years in the 1970s, 66.2±12.6 years (1980s), 69.1±12.4 years (1990s), 72.0±11.1 years (2000s), and 75.8±10.0 years (2010s) and advanced significantly in the 1990s, 2000s, and 2010s compared to the 1970s (all P<0.001). The ratio of patients aged ≥80 and ≥90 years increased from 10.6% and 0% in the 1970 s to 38.2% (P<0.001) and 5.2% (P= 0.017) in the 2010s, respectively. CONCLUSIONS: The average age at initial pacemaker implantation increased by 12.1 years over the last 50 years in Japan. In particular, the ratios of ≥80 and ≥90 years as the patients age increased significantly.

The association between impairment of HDL cholesterol efflux capacity and atrial remodeling in atrial fibrillation.

This cross-sectional study enrolled 202 patients with atrial fibrillation (AF) who had undergone catheter ablation and evaluated the association between high-density lipoprotein (HDL) functionality, cholesterol efflux capacity (CEC) of HDL, and the pathophysiology of left atrial structural remodeling. Participants were divided into two groups, based on their left atrial volume index (LAVI) (< 34 mL/m2, n = 60 vs. LAVI ≥ 34 mL/m2, n = 142). We quantified three types of HDL CECs by the presence or absence of cyclic-AMP, as entire, and CEC dependent or not dependent on ATP binding cassette transporter A1 (ABCA1) and termed them Global CEC, ABCA1 CEC, and Non-ABCA1 CEC, respectively. Consequently, Global and Non-ABCA1 CECs were significantly impaired in patients with an enlarged LA (Global CEC: p = 0.039, Non-ABCA1 CEC: p = 0.022). Logistic regression analyses demonstrated that Non-ABCA1 CEC was significantly associated with an enlarged LA after adjusting for the conventional risk factors of AF. Furthermore, the association of higher Non-ABCA1 CEC with an enlarged LA was independent of serum levels of HDL cholesterol and serum myeloperoxidase (Odds ratio of 1 standard deviation higher: 0.64, 95% confidence interval: 0.43-0.95, p = 0.027). The findings of this study indicate the potential contribution of reduced Non-ABCA1 CEC in HDL to the pathophysiology in left atrial structural remodeling of patients with AF.

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.

Primary Cardiac Diffuse Large B-cell Lymphoma Promptly and Safely Diagnosed with Pericardial Effusion Cytology.

Primary cardiac lymphoma is a rare condition with a poor prognosis, and patients are at risk for sudden cardiac death. A prompt diagnosis and early treatment are therefore essential. A 68-year-old woman was admitted for shortness of breath and peripheral edema. Echocardiograms showed massive pericardial effusion and a mass on the free wall of the right atrium and ventricle. Subsequent pericardial effusion cytology revealed diffuse large B-cell lymphoma. We started chemotherapy with rituximab and achieved a good clinical course. This case is made unique by the use of pericardial effusion cytology, which allowed us to diagnose primary cardiac lymphoma promptly and safely.

Infective endocarditis associated with acute myocardial infarction caused by septic emboli.

A 53-year-old Japanese man presented with severe chest pain. He had suffered from persistent fever, muscle pain, arthralgia, and dyspnea on exertion (New York Heart Association class I) for two and half months prior to admission. He had been treated with several antibiotics for two months and prednisolone for almost one month prior to admission. On the day of admission, he had suffered from chest pain at rest, and had come to our hospital. Electrocardiography showed a normal sinus rhythm with significant ST segment elevation in leads V3-6 and abnormal Q waves in leads V4-6. Transthoracic echocardiography demonstrated left ventricular ejection fraction of 52% with severe mitral regurgitation and an 18-mm vegetation on the anterior mitral valve leaflet. Multiple blood cultures identified Streptococcus sanguis. The diagnosis was acute myocardial infarction and mitral regurgitation associated with infective endocarditis (IE). The incidence of acute coronary syndrome caused by IE is quite low in patients with native valves. After a 6-week course of antibiotics, mitral valve replacement and partial cardiomyotomy were performed. Two years after the surgery, follow-up echocardiography showed almost normal left ventricle function and no mitral regurgitation, and the patient has been living an active life without any complications.

A Japanese case of familial cardiac myxoma associated with a mutation of the PRKAR1alpha gene.

Familial cardiac myxoma is inherited as an autosomal dominant syndrome. Here, we report a Japanese case of familial cardiac myxoma identified as a genetic abnormality. The mother experienced multiple recurrence of tumors in the left atrium and left ventricle 40 months after surgical resection of a left atrial myxoma. All recurrent tumors were successfully resected. Her daughter also had a solitary myxoma in the left atrium, but she had no recurrence after the operation. Both patients had lentigines in their face but no endocrine abnormality. Molecular genetic analysis demonstrated involvement of a mutation in the PRKAR1alpha gene.

Vasovagal response induced by a low dose of isoproterenol infusion before tilting-up.

A 56 year-old man was referred to hospital for evaluation of syncopal episodes. During head-up tilt testing, his symptom was reproduced, associated with bradycardia and hypotension, by a low dose of isoproterenol (0.02 microg. kg (-1). min(-1)) infusion in the supine position before tilting-up. Isoproterenol infusion can provoke a vasovagal response without tilting. Careful observation of the patient's hemodynamics is mandatory not only during tilting, but also in the supine position before tilting-up.

Cardiac hemangioma: a report of two cases and review of the literature.

Cardiac hemangioma is extremely rare. We encountered two patients with cardiac hemangioma detected by thoracic echocardiography during a medical checkup. In the first case, transthoracic echocardiography revealed a pedunculated tumor in the left ventricle. Selective left coronary angiography demonstrated that the main feeding artery of the tumor arose from the third diagonal branch of the left anterior descending coronary artery. In the second case, thoracic and transesophageal echocardiography showed an oval tumor arising from the right atrium. Both tumors were successfully resected. Histopathological examination revealed that one of the tumors was a capillary hemangioma and the other was a mixed capillary and cavernous hemangioma. After operation, both patients had an uneventful recovery without any complications.

Effects of orthostatic self-training on head-up tilt testing for the prevention of tilt-induced neurocardiogenic syncope: comparison of pharmacological therapy.

Although a wide variety of medical treatments for neurocardiogenic syncope have been proposed, therapy has largely been emperic based on the mechanisms commonly believed to lead to neurocardiogenic fainting. To determine the utility and efficacy of drug therapy and an orthostatic self-training program in the prevention of tilt-induced neurocardiogenic syncope, we investigated 43 consecutive patients who had shown syncope and were induced by head-up tilt test reproducibly, with either traditional medical treatments or orthostatic self-training at home. The initial 19 of 43 patients were treated with either oral propranolol or disopyramide therapies. The remaining 24 patients were treated with an orthostatic self-training program alone. Effects of these therapies on head-up tilt test were reevaluated in all patients. Propranolol prevented syncope in only six (32%) and disopyramide in five (26%) of the 19 patients. There was no significant difference in the effectiveness between them. Syncope was prevented in nine (47%) patients with either propanolol or disopyramide therapy alone, while in the remaining 10 patients it was not. On the other hand, orthostatic self-training program prevented syncope in 22 (92%) of 24 patients. We concluded that orthostatic self-training program is far more effective than traditional drug therapies. Orthostatic self-training is an effective, safe and well accepted therapy in the prevention of tilt-induced neurocardiogenic syncope.

Superior vena cava syndrome due to fibrosing mediastinitis histologically identical to xanthogranulomatous pyelonephritis.

We present herein a case of superior vena cava (SVC) syndrome caused by localized fibrosing mediastinitis (FM), which had histological features similar to xanthogranulomatous pyelonephritis (XGP). A 63-year-old woman presented with facial swelling 5 months after undergoing right nephrectomy for XGP. Radiologic investigations of the chest confirmed the presence of SVC obstruction due to an intraluminal tumor. The histological features of the tumor were consistent with those of FM and were very similar to those of XGP. Although the pathogenesis of neither FM nor XGP is known, some pathogenic process of FM and XGP may be the same.

What is the optimal increase in resting heart rate with low dose isoproterenol infusion for tilt-induced vasovagal response?

Isoproterenol is widely used as a provocative medium for vasovagal responses during tilt testing. Dose of isoproterenol infusion is generally titrated empirically by increase in resting heart rate before tilt up. To determine the optimal increase in resting heart rate with isoproterenol for tilt-induced vasovagal responses, we studied 97 consecutive patients with unexplained syncope. After the end of a negative baseline tilt (80 degrees for 30 min), the isoproterenol tilt was performed using one of two protocols: two-stage isoproterenol-tilt protocol, with doses of 0.01 and 0.02 microg/kg per min for 10 min each, or one-stage isoproterenol-tilt protocol, with a dose of 1 or 2 microg/min for 10 min. The resting heart rate increase was defined as a percentage increase in the resting heart rate after isoproterenol infusion, compared to the baseline heart rate before the tilt test. In 117 tilt procedures, 28 (93%) of the 30 positive responses occurred with a resting heart rate increase of > or = 21%. With the resting heart rate increase of 60 and 100%, 18 (60%) and 27 (90%) positive responses were observed, respectively. In conclusion, the minimum resting heart rate increase of > or = 21% was required to provoke a vasovagal response during subsequent isoproterenol-tilt (80 degrees for 10 min). Preferably, heart rate should be increased to 60-100% by isoproterenol titration before tilting.