Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: The Kumamoto Cardiac Amyloidosis Survey.

BACKGROUND: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals. METHODS: We conducted a retrospective multicenter observational cohort study. The registry included patients with ATTR-CM diagnosed in two tafamidis-prescription hospital institutes [Japanese Circulation Society (JCS)-certified facilities] and 15 regional cardiovascular facilities in Kumamoto between January 2018 and December 2020. RESULTS: In total, 174 patients were diagnosed with ATTR-CM. The incidence of ATTR-CM was estimated to be approximately 1 per 10,000 person-years in the elderly population (>65 years old) in Kumamoto. Compared with that in the JCS-certified facilities cohort (n=115), age at diagnosis was significantly older (84.5 ± 5.6 vs. 77.5 ± 6.3 years old; p<0.01) in the regional hospitals cohort (n=59). Histological (25% vs. 81%; p<0.01) and genetic diagnosis (7% vs. 82%) were also less frequently performed. Probable (as indicated by positive bone scintigraphy findings with confirmation of monoclonal protein absence) and possible (as indicated by positive bone scintigraphy findings without confirmation of monoclonal protein absence) ATTR-CM accounted for the majority of cases (75% vs. 19%; p<0.01) in the regional hospitals cohort compared to the JCS-certified facilities cohort. There were no cases of hereditary ATTR-CM among the patients who underwent TTR genetic testing (n=98). CONCLUSIONS: We confirmed the incidence of ATTR-CM in Kumamoto and the diagnostic approach used in patients with ATTR-CM. Further prospective studies with a larger sample are needed to validate our results and to further shed light on the epidemiology of ATTR-CM in Japan.

Clinical Features of Patients With Heart Failure After the 2016 Kumamoto Earthquakes.

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 <92 and /or PNI ≤38). 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.

Impact of Killip classification on acute myocardial infarction: data from the SAIKUMA registry.

Therapeutic devices for acute myocardial infarction (AMI) have evolved dramatically in recent years. However, the impact of the Killip classification of AMI outcomes in patients undergoing aggressive percutaneous coronary intervention remains unclear. We performed a 10-year retrospective review of 2062 patients diagnosed with AMI, and divided the data into two 5-year intervals: 2005-2009 (n = 1071), and 2010-2014 (n = 991). No difference was observed in in-hospital mortality rate between the two periods (first period, 11.5% vs second period, 9.7%; P = 0.19). The incidence of stent thrombosis was not significantly different between the two periods, and very few thrombi occurred in patients who received second-generation drug-eluting stents (DES) (0.98%: 5/511). In-hospital mortality due to stent thrombosis was high in the full cohort (15%). During the second period, in-hospital mortality was lower in Killip class 4 patients, although the difference was not significant (59.1 vs 47.5%, P = 0.07). Multivariable logistic regression identified several factors that significantly affected in-hospital mortality, including age [odds ratio (OR) 1.07], left main trunk (OR 2.47), peak CPK value above 5000 IU/L (OR 3.18), and Killip class 4 (OR 15.63). We evaluated trends in in-hospital mortality among patients with AMI over a 10-year period. New DES and the frequent use of mechanical support in patients with hemodynamic compromise tended to improve in-hospital mortality, but the effect was not significant. Notably, Killip class 4 on admission was associated with an estimated 16-fold increased risk of in-hospital death.

Accuracy and usefulness of noninvasive fractional flow reserve from computed tomographic coronary angiography: comparison with myocardial perfusion imaging, echocardiographic coronary flow reserve, and invasive fractional flow reserve.

We present a case of coronary artery disease with intermediate stenosis in the proximal left anterior descending artery, which was evaluated using multiple functional modalities. FFRCT demonstrated a significant perfusion abnormality in the LAD, and the value of FFRCT (0.68) was similar to the value measured by invasive FFR (0.67). However, the other modalities gave discrepant results. In particular, perfusion scintigraphy with thallium showed no evidence of an inducible perfusion abnormality in the LAD territory. The patient was treated by PCI for two tandem lesions in the LAD. FFRCT may have potential as a default noninvasive method for assessment of coronary anatomy and physiology.

Resting angina due to papillary fibroelastoma of the right coronary cusp.

A 63-year-old man with chest pain at rest was referred to our hospital. Transthoracic echocardiography showed a mobile ball-like mass at the top of the right coronary cusp. Subsequently, transesophageal echocardiography also showed a mobile mass at the right coronary cusp. Aortic valve replacement with a mechanical valve was performed under general anesthesia. We diagnosed this condition as papillary fibroelastoma based upon the pathological findings with hematoxylin and eosin staining, and Elastica van Gieson staining. Coronary angiography revealed no organic lesions. The operation was successful, and the patient remains asymptomatic. We speculate that the resting chest pain was induced by transient occlusion of the right coronary orifice by the tumor. We describe this rare case in detail including a review of the literature.

A lotus root-like appearance in both the left anterior descending and right coronary arteries.

A 60-year-old man was referred to our hospital because of dyspnea on exertion. He was diagnosed with heart failure due to an old myocardial infarction. Myocardial stress perfusion scintigraphy revealed inducible myocardial ischemia. Coronary angiography revealed hazy slit lesions in both the left anterior descending (LAD) and right coronary arteries (RCA). We first performed percutaneous coronary intervention (PCI) on the LAD lesion. Subsequently, we performed PCI for the RCA lesion using multiple imaging modalities. We observed a lotus root-like appearance in both the LAD and RCA, and PCI was successful for both vessels. We describe this rare case in detail.

Inadvertent consequences of percutaneous coronary intervention to treat unstable spontaneous coronary artery dissection.

We present two cases of spontaneous coronary artery dissection (SCAD), which were diagnosed and treated with emergent percutaneous coronary intervention (PCI). Patients with ongoing ischemia due to SCAD need emergent coronary revascularization with PCI or coronary artery bypass grafting. We discuss the difficulties of PCI to bail out unstable SCAD regardless of the modern techniques and modalities. Brief reviews of the literature with relevance are included. .

Impact of shear stress and atherosclerosis on entrance-tear formation in patients with acute aortic syndromes.

Weak aortic media layers can lead to intimal tear (IT) in patients with overt aortic dissection (AD), and aortic plaque rupture is thought to progress to penetrating atherosclerotic ulcer (PAU) with intramural hematoma (IMH). However, the influences of shear stress and atherosclerosis on IT and PAU have not been fully examined. Ninety-eight patients with overt AD and 30 patients with IMH and PAU admitted to our hospital from 2002 to 2007 were enrolled. The greater curvatures of the aorta, including the anterior and right portions of the ascending aorta and anterior portion of the aortic arch, were defined as sites of high shear stress. The other portions of the aorta were defined as sites of low shear stress based on anatomic and hydrodynamic theories. Aortic calcified points (ACPs) were manually counted on computed tomography slices of the whole aorta every 10 mm from the top of the arch to the abdominal bifurcation point. IT was more often observed at sites of high shear stress in overt AD than in PAU (73.5 vs 20.0 %, P < 0.0001). Significantly more ACPs were present in PAU than in overt AD (18.6 ± 8 vs 13.3 ± 10, P = 0.007). The present study suggests that high shear stress and less severe atherosclerosis could induce the occurrence of an IT, thereafter progressing to overt AD, and that low shear stress and more severe atherosclerosis could proceed to PAU with IMH. These findings may help to identify the entrance-tear site.

Inadvertent coronary endarterectomy during aspiration thrombectomy with a Thrombuster III GR catheter in a patient with acute coronary syndrome.

We describe a 41-year-old woman who presented with acute ST-segment elevation myocardial infarction. Emergent percutaneous intervention was performed with aspiration thrombectomy followed by coronary artery stenting. White material was extracted from the aspiration catheter. Reperfusion therapy after stenting was successful. After undergoing a cardiac rehabilitation program, she was discharged from hospital on day 10. Pathological examination revealed that the aspirated material consisted of normal vascular components including endothelial and smooth muscle cells. Aspiration thrombectomy is a commonly used procedure with a low complication rate. This case presents the previously unreported complication of coronary artery injury.

Effects of additional treatment of sarpogrelate to aspirin therapy on platelet aggregation and plasma plasminogen activator inhibitor activity in patients with stable effort angina.

INTRODUCTION: Serotonin is secreted from platelets at sites of endothelial injury, where it promotes thrombogenic reactions. Serotonin is reported to be associated with not only coronary artery disease but also cardiac events. MATERIALS AND METHODS: We studied 33 patients with stable effort angina (SEA) (11 patients with multivessel disease (MVD) and 22 patients with single vessel disease (SVD)) and 25 patients with chest pain syndrome (CPS). Sarpogrelate was administered to 22 of 33 patients with SEA in addition to aspirin therapy, and platelet aggregation, plasma serotonin concentration, and plasma plasminogen activator inhibitor (PAI) activity were measured before and 1 week after administration. RESULTS AND CONCLUSIONS: Serotonin level was higher in patients with MVD than in those with SVD (p<0.05) and in those with CPS (p<0.001). The formation of small-sized platelet aggregates was significantly higher in the high serotonin group than in the low serotonin group of SEA patients. The formation of large-sized platelet aggregates was significantly decreased by administration of sarpogrelate (P<0.05). The formation of small- or medium-sized aggregates was not significantly decreased. Plasma PAI activity decreased significantly (P<0.05) although the plasma serotonin concentration did not show significant change by administration of sarpogrelate. Plasma serotonin level is increased in relation to severity of coronary artery disease and plasma serotonin level is associated with increased platelet aggregation. Administration of sarpogrelate in addition to aspirin therapy reduces the increased platelet aggregation and PAI activity, and it may indicate that additional administration of sarpogrelate is useful for patients with SEA.

A case of acute coronary syndrome caused by a giant saddle thrombus at left main coronary artery bifurcation.

An 87-year-old woman who had metastatic lung cancer presented with intermittent chest discomfort. The emergent coronary angiogram showed a giant saddle thrombus at the left main coronary artery bifurcation without flow limitation. We performed thrombolysis with unfractionated heparin and warfarin under careful observation of the thrombus with a 320-row area detector computed tomography (ADCT). Ten days later, the second examination with ADCT revealed complete resolution of the saddle thrombus. During the follow-up, neither chest pain nor enzymatic cardiac damage was reported. In this carefully observed case, a less invasive strategy instead of catheter intervention or strong thrombolysis might have led to a favorable clinical outcome.

An autopsy case of the rupture of a giant aneurysm in a saphenous vein graft: 18 years after CABG.

The saphenous vein is a widely used blood vessel for arterial bypass procedures. Failures of saphenous vein aortocoronary bypass grafts are predominantly the result of subsequent vein graft atherosclerotic disease. Rarely saphenous vein grafts undergo aneurysmal degeneration. This report describes a case of a ruptured aneurysm in a saphenous vein graft that occurred in an 82-year-old female who underwent a coronary artery bypass operation 18 years previously. We could not resuscitate her, but describe the autopsy findings in detail.

B-type natriuretic peptide after hormone therapy in postmenopausal women with chest pain and normal coronary angiogram.

OBJECTIVES: Coronary heart disease is relatively uncommon in premenopausal women but shows a sharp increase after menopause. The decline of endogenous ovarian hormones is commonly assumed to be a major component of this phenomenon. The effects of estrogens on the vasculature have been investigated extensively in previous studies. However, the effects of estrogens on myocardial function have not been evaluated in humans. We sought to examine the effects of hormone therapy (HT) on myocardial function and cardiac natriuretic peptides in postmenopausal women with chest pain and a normal coronary angiogram. DESIGN: Transdermal HT (estradiol: 0.72 mg/2 d) was administered to 15 postmenopausal women with chest pain and a normal coronary angiogram (mean age, 53 y) for 12 weeks, and oral HT (conjugated equine estrogens: 0.625 mg/d) was administered to another 15 postmenopausal women (mean age, 54 y) for 12 weeks. Echocardiography or cardiac catheterization showed no cardiac dysfunction in any woman at baseline. Cardiac function was evaluated by echocardiography, and plasma B-type natriuretic peptide was measured every 4 weeks. RESULTS: B-type natriuretic peptide levels increased after transdermal HT (baseline: 13.1 +/- 3.1, 4 wk: 22.1 +/- 2.9, 8 wk: 33.2 +/- 3.1, 12 wk: 38.4 +/- 3.3 pg/mL; P < 0.01 vs baseline). The levels were also augmented after oral HT (baseline: 14.1 +/- 3.8, 4 wk: 23.2 +/- 3.3, 8 wk: 35.6 +/- 3.9, 12 wk: 39.6 +/- 3.5 pg/mL; P < 0.01 vs baseline). Serial echocardiography showed no changes in ventricular function in either treatment group. At baseline the serum estradiol levels in the transdermal group were comparable with those in the oral group. CONCLUSIONS: The estradiol levels after HT increased in both groups, but there was no significant difference between the two groups. B-type natriuretic peptide levels increased without cardiac dysfunction, and the chest symptoms were relieved in some participants after HT. Thus, estrogen supplementation augments natriuretic peptide levels without harmful effects on ventricular function.

The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome.

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.

Prognostic value of flow-mediated dilation of the brachial artery in patients with cardiovascular disease.

OBJECTIVE: Endothelial dysfunction is thought to represent the initial stage in the development of atherosclerosis. Recently, noninvasive examination of endothelial function has become possible using flow-mediated endothelium-dependent dilation of the brachial artery (FMD) during reactive hyperemia. We examined whether FMD has prognostic value for the prediction of subsequent cardiovascular events. METHODS: Patients were followed prospectively every month until the occurrence of the cardiovascular events. PATIENTS: The study subjects comprised 221 consecutive patients (men 108, mean age 61.4+/-10.6, ischemic heart disease 152, cardiomyopathy 28, arrhythmia 12, valvular disease 5, congenital heart disease 3, and cardioneurosis 21). The mean FMD was 4.77+/-2.85% and this value was used to divide the patients into the 2 groups (Group 1: FMD > or =4.7%; Group 2: FMD <4.7%). RESULTS: There were 110 patients in Group 1 (men 36, mean age 60.5+/-10.9), and 111 patients in Group 2 (men 72, mean age 62.2+/-10.3). Patients were followed until the occurrence of at least 1 of the major clinical cardiovascular events. Seven cardiovascular events occurred in Group 1 (6.4%, 1.14 events per 100 patient-years), while 16 occurred in Group 2 (2.88 events per 100 patient-years). Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiovascular events in Group 2 than in Group 1. CONCLUSION: The present results demonstrated that the magnitude of FMD in the brachial artery was a good predictor of subsequent cardiovascular events.

Relation between platelet microaggregates and ankle brachial index in patients with peripheral arterial disease.

INTRODUCTION: Peripheral arterial disease is one of the systemic atherosclerotic diseases, and patients with the disorder are classified in the high risk group of coronary artery disease. A lower ankle brachial index is a frequent finding in peripheral arterial disease. While platelet microaggregates are a significant predictor of adverse clinical outcome in coronary artery disease, the significance of platelet aggregability in peripheral arterial disease has not been elucidated. MATERIALS AND METHODS: Small platelet aggregates measured using laser-light scattering and ankle brachial index were determined in 42 patients with both coronary artery disease and peripheral arterial disease (peripheral group), 56 patients with only coronary artery disease (coronary group) and 32 patients without both (control group). RESULTS: The level of small platelet aggregates was increased significantly in the peripheral group (4.3 x 10(4) [range 2.2 x 10(4) to 7.4 x 10(4)]) compared with both the coronary (1.1 x 10(4) [range 0.3 x 10(4) to 5.0 x 10(4)]) and control groups (0.5 x 10(4) [range 0.1 x 10(4) to 0.9 x 10(4)]). There was a significant inverse correlation between log small platelet aggregates and ankle brachial index (n=130, r=-0.422, p<0.001). Multivariate logistic regression analysis revealed that a lower ankle brachial index (<0.90) was an independent determinant of increased levels of small platelet aggregates. CONCLUSIONS: Platelet aggregability was increased in patients with peripheral arterial disease with the degree of platelet aggregation being closely associated with ankle brachial index. It is possible that this change in platelet activity may be one mechanism to explain why a lower ankle brachial index is a predictor of poor prognosis in patients with peripheral arterial disease.

Increased plasma levels of thioredoxin in patients with glucose intolerance.

OBJECTIVE: The aim of the present study was to determine the effects of glucose intolerance on oxidative stress in patients with coronary artery disease (CAD). METHODS: The patients were divided into 3 groups, diabetes mellitus (DM), IGT or normal glucose tolerance (NGT) according to the criteria of the American Diabetes Association. PATIENTS: The present study consisted of 178 consecutive patients who underwent diagnostic coronary arteriography and a 75-g glucose tolerance test. RESULTS: The level of plasma thioredoxin, a marker of oxidative stress was measured in every patient during the fasting state. The levels of plasma thioredoxin were significantly higher in the DM and IGT groups than the NGT group. Furthermore, we found that there was a positive association between thioredoxin levels and glycosylated hemoglobin (sigma=0.225, p=0.018). In multivariate logistic regression analysis, glucose intolerance (DM or IGT) was only independently associated with the high levels of thioredoxin. The levels of plasma thioredoxin were significantly higher in the CAD group compared to the non-CAD group. In multivariate logistic regression analysis, high levels of thioredoxin, male, age and hypertension were independently associated with the presence of CAD. CONCLUSION: Glucose intolerance was associated with the high levels of thioredoxin. High levels of thioredoxin were related to the presence of CAD. The measurement of thioredoxin as the marker of oxidative stress may be useful for monitoring the development of the cardiovascular diseases.

Successful coronary stenting of the left anterior descending artery at the branching site of the targeted septal perforator immediately after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy.

We report a case of simultaneous percutaneous treatment of hypertrophic obstructive cardiomyopathy (HOCM) and coronary artery disease. Cardiac catheterization revealed a left ventricular outflow tract pressure gradient (LVOTPG) of 130 mmHg and a significant left anterior descending artery (LAD) stenosis at the site of the 1st major septal branch. The LVOTPG was eliminated by injection of ethanol into the branch. Subsequently, a coronary stent was implanted in the LAD. A coil stent was selected due to possibility of repeat septal ablation in the future. Simultaneous treatment of HOCM and LAD stenosis is considered safe and effective using a coil stent.

Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention.

We investigated whether the assessment of small platelet aggregates before percutaneous coronary intervention (PCI) could predict restenosis after PCI. This was a prospective cohort study that enrolled 189 consecutive patients who had coronary artery disease. In multiple logistic regression analysis, higher levels of preprocedural small platelet aggregates were independently associated with restenosis after PCI. Measurement of small platelet aggregates may serve as a useful clinical variable for stratifying patients who present for PCI.

Platypnea-orthodeoxia syndrome combined with multiple congenital heart anomalies.

A 71-year-old woman was admitted for paralysis on the left side of her body. She developed dyspnea and hypoxemia after admission. Although pulmonary embolism was suspected, hypoxemia and dyspnea occurred repeatedly in spite of anticoagulation therapy. Transesophageal echocardiography revealed a patent foramen ovale (PFO), an atrial septal aneurysm (ASA), and a right-to-left shunt that appeared in an upright position. She was diagnosed with platypnea-orthodeoxia syndrome. Moreover, cardiac catheterization showed congenital anomalies, such as unroofed coronary sinus, partial anomalous pulmonary venous return and persistent left superior vena cava. Simple surgical closure of the ASA and PFO improved all of her symptoms.