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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.

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.

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.

The target of diastolic blood pressure (DBP) remains controversial in patients with coronary artery disease (CAD). We systematically searched PubMed/Medline and the Cochrane Central database for randomized controlled trials (RCTs) assessing the efficacy and safety of reducing DBP in CAD patients from January 1965 to July 2017. Seven placebo-controlled RCTs enrolling 34,814 CAD patients who achieved DBP

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients’ demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients’ demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p

To compare three-dimensional dynamics between implanted Cosgrove-Edwards and Sorin Memo-3D annuloplasty rings during the cardiac cycle. We examined 11 Cosgrove-Edwards rings and 20 Sorin Memo-3D rings after mitral plasty using real-time three-dimensional transesophageal echocardiography. We evaluated ring height, ellipticity, and geometry during one cardiac cycle. Four evenly spaced phases each selected during systole and diastole were assessed using REAL VIEW software. The height of the Cosgrove-Edwards and Sorin Memo-3D rings was similar (2.3 ± 0.8 vs. 1.9 ± 0.9 mm, p = 0.44). The maximum difference in ring height during one cardiac cycle (change in height) was larger for the Cosgrove-Edwards than the Sorin Memo-3D rings (2.3 ± 0.8 vs. 1.5 ± 0.6 mm, p = 0.014). Ellipticity and the maximum difference in ellipticity during one cardiac cycle (change in ellipticity) were larger for Cosgrove-Edwards than Sorin Memo-3D rings (80.0 ± 9.1 vs. 72.0 ± 4.8 %, p = 0.014, respectively, and 12.0 ± 3.1 vs. 6.0 ± 1.8 %, p

Recently, several researchers have demonstrated the association between periodontal disease and coronary artery disease (CAD). Therefore, we herein investigate the association between periodontal diseases and the existence of CAD among the study population who received both coronary angiography and dental examination. A total of 174 consecutive patients with dental examination including radiography and coronary angiography in the same hospitalization were recruited (64.5 +/- 10.3 years, M/F: 94/80). A dentist assessed severity of periodontal status markers (bleeding on probing, probing depthor=6 mm, teeth lost, alveolar bone resorptionhalf of root length by radiography and smoking status). We divided these patients into two groups according to whether they had CAD (CAD group, n = 99) or not (non-CAD group, n = 75) according to the results of coronary angiography. The composite periodontal risk scores calculated from periodontal status markers were higher in the CAD group than in the non-CAD group (P = 0.02). The composite periodontal scores were higher in the CAD group of age60 years old population (P = 0.03) and in the CAD group of patients with normal glucose tolerance (P = 0.04). However, the difference was not significant in the ageor=60 years old population or those with diabetes mellitus or impaired glucose tolerance. In all populations, hypertension, glucose tolerance, statin therapy, and composite of periodontal risk scores were associated with CAD. Multivariate analyses revealed statin therapy, glucose tolerance, and periodontal risk scores were independent and significant risk factors for CAD. Composite periodontal risk scores were independent and significant predictive factors for CAD.

To investigate the distribution of autonomic nerves in the human heart, six autopsied hearts without cardiovascular disease were studied by a histochemical method for acetylcholinesterase (AChE) and by an immunohistochemical method for tyrosine hydroxylase (TH). The density of nerve distribution was microscopically calculated by the point-counting method to evaluate regional distribution of the autonomic nerves. There were more AChE-positive nerves and TH-positive nerves in the atrium than in the ventricle, and more at the base than at the apex in the ventricle. There were more AChE-positive nerves in the subendocardial area than in the subepicardial area of the myocardium. In the atrium, AChE-positive nerves were more numerous than TH-positive nerves. On the other hand, there were more TH-positive nerves than AChE-positive nerves in the ventricle. Predominancy of the distribution density at the anterior to the posterior wall of the ventricle was observed for TH-positive nerves. The different distribution patterns of sympathetic and parasympathetic nerves could modify cardiac performance under both physiologic and pathologic conditions.

We recently reported that oxidative stress is involved in the pathogenesis of coronary spasm. We hypothesized that oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase gene (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) might influence the pathogenesis of coronary spasm. We therefore examined the possible association between the PON1 Q192R or PAF-AH V279F polymorphisms and coronary spasm in 214 patients with coronary spasm and 212 control subjects. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. The incidence of the PON1-192R allele was significantly higher in the coronary spasm group than in the control group (65% vs 53%; P=0.0005). The PAF-AH-279F allele was not associated with coronary spasm (15% vs. 16%; P=0.8781). Multiple logistic regression analysis with forward stepwise selection involving the PON1-192R allele and the environmental risk factors revealed that the most predictive independent risk factor for coronary spasm was the PON1-192R allele (significance=0.0016, OR=2.52), followed by cigarette smoking (significance=0.0007, OR=2.01). We also measured plasma levels of TBARS (thiobarbituric acid-reactive substances) as a marker of oxidative stress. TBARS levels were higher in R/R types than in Q/Q types (2.115+/-0.086 nmol/ml [ n=25] vs 1.676+/-0.102 nmol/ml [ n=11], P0.01). Thus, there is a significant association between the PON1-192R allele and coronary spasm; the PON1-192R allele may play an important role in the genesis of coronary spasm, probably by attenuating the suppression of oxidative stress.

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of αvβ3, but not αvβ5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of αvβ3 and αvβ5 integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express αvβ3 and αvβ5 integrin subunits. The αvβ5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the αvβ3 integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both αvβ3 and αvβ5 integrins. Selective blocking antibodies for αvβ3 and αvβ5 inhibited migration of RASMC and HCSMC by more than 60% (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for αvβ3 and β5 mRNA in uninjuried aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of αvβ3 and β5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased inegrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that αvβ3 and αvβ5 are elevated during neointima formation in the rat and indicates a novel role for αvβ5 participating in mechanisms regulating smooth muscle cell migration.

Acute reocclusion after successful angioplasty is a severe complication. The preventive effects of heparin, the synthetic antithrombin, argtroban, and the defibrinogenating agent batroxobin on reocclusion after balloon angioplasty of thrombotic occlusions were evaluated in canine iliac arteries. After the 2-hour-old thrombus was evaluated by angiography and angioscopy, percutaneous transcatheter angioplasty (PTA) was performed on the thrombotic stenosis. We used one of the three agents, heparin (100 U/kg), the antithrombin argatroban (0.3 mg/kg), or the defibrinogenating agent batroxobin (0.3 U/kg). Then angioscopy and angiography were performed before, just after, and 2 hours after PTA. After PTA, angiography revealed a marked reduction in percent stenosis in all groups (from 88 ± 8% to 24 ± 4% in the heparin group, from 79 ± 7% to 26 + 11% in the argatroban group and from 89 ± 12% to 32 ± 7% in the batroxobin group). At 2 hours after PTA, angiography demonstrated a greater reduction in percent stenosis with argatroban (from 26 ± 11% to 9 ± 3%) and batroxobin (from 32 ± 7% to 10 ± 8%), and maintenance of percent stenosis reduced by PTA with heparin (from 24 ± 5% to 28 ± 9%) when compared with the significant reversal of percent obstruction in the control side. Angioscopic visualization also demonstrated a similar trend. These results show that these antithrombotic drugs have a preventive effect on reocclusion after balloon angioplasty for thrombotic obstruction.

Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.

Coronary artery disease and diabetes are major causes of morbidity and mortality in the Western countries. Unfortunately, by the time these chronic diseases present clinically, irreversible vascular damage has already occurred. Thus, it is critical to identify upstream determinants of disease and target them for preventive measures. The metabolic syndrome is characterized by dyslipidemia, hyperglycemia, hypertension and central obesity. It has been established as a precursor state in which patients are at significantly increased risk of developing cardiovascular disease. Aging is associated with a gradual decline of testosterone levels in men.1 This decrease is accompanied by changes in body composition including increases in adipose mass and decreases in lean body mass, dyslipidemia, insulin resistance and glucose metabolism dysregulation.

Medical agents acting on the renin–angiotensin–aldosterone axis for the treatment of heart failure

The synergistic extraction of such divalent metals as zinc and cadmium with the mixture of 4-benzoyl-3-methyl-1- phenyl-5-pyrazolone(HPMBP or HA) and quaternary ammonium salt (QCl) was investigated as a function of pH, HPMBP and QCl. Highly enhanced extraction was observed in the extraction system. The possible extracted species were ZnA2(AQ)2 and CdA2(AQ) when QCl was capriquat (trioctylmethylammonium chloride). Extraction constants and equilibrium constants in the organic phase were calculated. Similar enhanced extractions were also observed when QCl was a water-soluble quaternary ammonium salt, zephiramine (tetradecyldimethyl- benzylammonium chloride).