A Case of Refractory Variant Angina.

Coronary vasospasm is defined as the abnormal contraction of an epicardial coronary artery. Variant angina is a severe form of coronary vasospasm, reflecting transmural ischemia with ST-T elevation on an electrocardiogram. A pharmacologic spasm provocation test during coronary angiography is the gold standard evaluation for patients who have not been diagnosed with coronary vasospasm by a non-invasive test. The sensitivity and specificity of pharmacologic spasm provocation testing have been reported to be very high in patients with variant angina. Here, we report the case of a 61-year-old woman who had refractory variant angina. Although a pharmacologic spasm provocation test did not lead to a definitive diagnosis, she had recurrent acute coronary syndrome due to coronary vasospasm. Physicians should be aware of the limitations of the spasm provocation test, even in patients with refractory variant angina.

A Case of Father-Son Juvenile Acute Myocardial Infarction.

Coronary artery ectasia (CAE) is a cause of juvenile myocardial infarction. The causes of CAE include arteriosclerosis, vasculitis such as Kawasaki disease, and genetic contribution. There are few reports about familial aggregation of CAE-related juvenile myocardial infarction. We report an unusual case of father-son juvenile myocardial infarction owing to CAE. (Level of Difficulty: Beginner.).

Coronary Vasospasm in a Patient With Argininosuccinic Aciduria.

A 39-year-old male was referred for treatment of hypertension. He had been treated for argininosuccinic aciduria since 8 months of age. Therapeutic drugs, including l-arginine, sodium phenylbutyrate, and antiepileptic drugs, had been prescribed. A detailed medical history revealed that he complained of chest discomfort under psychologic stress. A 12-lead electrocardiogram showed abnormal q waves in lead III and aVF. Transthoracic echocardiography showed hypokinesia of the left ventricular posterior wall. The patient was diagnosed with myocardial infarction because of coronary vasospastic angina by intracoronary acetylcholine provocation test. Argininosuccinic aciduria is a genetic disorder of the urea cycle caused by a deficiency of argininosuccinate lyase. Reduction of the enzymatic activity leads to a decrease in nitric oxide production, even if arginine is supplemented. Our case report supports the significance of endothelial function in the pathogenesis of coronary vasospasm.

Coefficient of R-R interval variations under deep breathing load in patients with wild-type transthyretin amyloid cardiomyopathy: A case-control study.

Background and Aims: An autonomic nervous disorder is an important characteristic of cardiac amyloidosis; however, the prevalence of autonomic dysfunction in wild-type transthyretin amyloidosis (ATTRwt) has not been established. Analysis of the R-R interval coefficient of variation (CVR-R) is a noninvasive method to measure parasympathetic activity. We aimed to assess autonomic dysfunction of ATTRwt and determine the utility of CVR-R for the detection of ATTRwt in other cardiac diseases. Methods: This is a single-center, retrospective, case-control study. Fifty patients with heart failure (HF) were studied. The etiologies of HF were as follows: ATTRwt, n = 10; previous myocardial infarction (MI), n = 20; and left ventricular hypertrophy (LVH) due to other disease processes (e.g., aortic stenosis), n = 20. We measured the CVR-R at rest (CVR-Rrest), CVR-R with deep breaths (CVR-Rbreath), and the change rate (CVR-Rdiff rate). The relative change formula is as follows: CVR-Rdiff rate = (CVR-Rbreath - CVR-Rrest)/CVR-Rrest × 100 (%). Results: There was no difference in the CVR-Rrest levels among the three groups. The CVR-Rdiff rate levels in the ATTRwt group were significantly lower (ATTRwt: -8.77 [-43.8 to 10.9]; LVH: 67.4 [38.7 to 89.4]; MI: 83.7 [60.4 to 142.9]). Based on the receiver operative characteristic curve analysis to identify ATTRwt in HF, the best cut-off value for the CVR-Rdiff rate was 19.7 (area under the curve: 0.848). Conclusion: Our data suggested autonomic dysfunction in patients with ATTRwt. Measurement of the CVR-R in HF patients may be a convenient support tool for the detection of ATTRwt.

[Minimally Invasive Cardiac Surgery for a Left Atrial Myxoma with Atrial Septal Defect:Report of a Case].

A 48-year-old woman presented with abnormal electrocardiogram was diagnosed as having a left atrial tumor by echocardiography. She was asymptomatic and had no history of cardiac abnormality. Transthoracic echocardiography revealed a relatively hyperechoic and heterogenous tumor with the diameter of 5~6 cm originated from the left atrial septum but could not detect atrial septal defect. Transesophageal echocardiography showed atrial septal defect of fossa ovalis but failed to uncover shunt flow behind the tumor. We diagnosed as left atrial myxoma complicated with atrial septal defect, and an operation was performed through small right intercostal thoracotomy. The tumor was excised and the atrial septal defect was completely repaired after pulmonary vein isolation. The post-operative course was uneventful. Cardiac myxoma coexisting atrial septal defect is rare, and preoperative transesophageal echocardiography is considered essential for the diagnosis of coexistent lesions especially in the patients minimally invasive cardiac surgery is planned.was uneventful. Cardiac myxoma coexisting atrial septal defect is rare, and preoperative transesophageal echocardiography is considered essential for the diagnosis of coexistent lesions especially in the patients minimally invasive cardiac surgery is planned.

Dose-Dependent Inhibitory Effect of Rosuvastatin in Japanese Patients with Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases-INVITATION Trial.

AIM: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. METHODS: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. RESULTS: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. CONCLUSIONS: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

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.

[Impending Paradoxical Embolization in a Patient with a Thrombus Straddling the Patent Foramen Ovale].

The patent foramen ovale (PFO) is known as a risk of paradoxical embolism in patients with deep venous thromboses. However, PFO is usually found after systemic embolic symptoms become apparent. A 60-year-old male had complained of dyspnea for two weeks. Ultrasound echocardiography showed a thrombus straddling PFO, and venous echography showed blood clots in the right popliteal and soleus veins. Contrast computed tomography revealed multiple pulmonary embolisms and a thrombus in the right atrium expanding to the left atrium through the atrial septum. The straddling thrombus in the atrium and pulmonary thrombi were extirpated under circulatory arrest with deep hypothermia. An inferior vena cava filter was inserted intravenously four days after surgery. The patient was discharged on the 19th postoperative day without any signs of thromboembolism. Prompt surgery is considered important to prevent thromboembolism in the case of impending paradoxical embolism.

[Long Term Patency of Saphenous Vein Graft Using the Automated Proximal Anastomosis System Compared with the Hand-sewn Anastomosis System].

Backgrounds：The purpose of this study was to compare the long term patency of PAS-Port system with other hand-sewn anastomosis system. METHODS: From 2009 to 2018, a total of 79 anastomoses were done in coronary bypass surgery with PAS-Port system, and a total of 252 anastomoses with Enclose Ⅱ. Among them, 76 anastomoses with PAS-Port system (group P) and 246 anastomoses of enclose Ⅱ (group E) were evaluated using angiography or multislice computer tomography. We compared age, gender, emergency rate, hospital death and cerebral infarction between the 2 groups and evaluated the patency of the grafts from post-operative day 5 to year 10 to obtain their long term graft patency. RESULTS: Group P was significantly older, more male, and higher emergency rate. One patient in group P died of septic multiorgan failure and 1 died in group E of intestinal tract necrosis. Early patency rates of the graft were 97.4% in Group P and 93.9% in Group E. Long term patency rates were also comparable, but PAS-Port system showed tendency toward a higher rate of patency( log rank p=0.057). CONCLUSIONS: The long term patency rate of PAS-Port automated proximal anastomosis is comparable with that of hand-sewn anastomosis.

[The Third Operation for Prosthetic Valve Detachment Caused by Aortitis Syndrome without Aortic Ectasia;Report of a Case].

We report a surgical case of a 58-year-old woman with aortitis syndrome is presented. The patient had undergone aortic valve replacement (AVR) with a mechanical prosthesis. Five months later, re-AVR was performed because of prosthetic valve detachment and severe regurgitation. Five years after the re-operation, valve detachment with severe perivalvular leakage was noted again. The 3rd AVR was performed with a biological prosthesis. This time, the prosthetic valve was fixed by 2-0 Ticron sutures buttressed with a felt strip from outside of the aorta at the site of detachment. Administration of prednisolone has been continued for 16 years since the 1st operation. No valve detachment has been noted for 8 years since the 3rd operation.

Dose-dependent INhibitory effect of rosuVastatin In Japanese patienTs with Acute myocardial infarcTION on serum concentration of matrix metalloproteinases - INVITATION trial.

BACKGROUND: Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid-rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a critical role in inflammatory processes underlying plaque rupture. Some reports suggested statins inhibit the increased MMP levels after AMI. However, there are a few comparison studies between the different dosages of the same statin and circulating levels of MMPs. PURPOSE: This study will preliminarily investigate the potential effects of appropriate or low dose of rosuvastatin on circulating MMPs levels in AMI patients. Moreover, we will also obtain plasma from patients while undergoing diagnostic angiography to determine differences in various cardiac sites and peripheral vessels. METHODS: This study is a multicenter, open-label, randomized, parallel-group study to be conducted to compare the appropriate or low dose of rosuvastatin in the effect on serum levels of inflammatory markers in AMI patients. The eligible patients undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive either appropriate or low-dose rosuvastatin daily using a web-based randomization software within 24h after PCI. The low-dose group will be treated with rosuvastatin 2.5mg once daily with a follow-up. The appropriate-dose group will begin treatment with rosuvastatin 5mg once daily, and the dose of rosuvastatin will be titrated to 10mg within 4 weeks. During administration of the study treatment, subjects will undergo laboratory testing including MMPs and be monitored for the occurrence of adverse events up to 24 weeks. The primary endpoint will be the change rate of MMPs at 24 weeks after administration. CONCLUSIONS: INVITATION will compare the appropriate or low dose of rosuvastatin in the effects on serum levels of inflammatory markers including MMPs in AMI patients. This study will provide significant information on rosuvastatin as an anti-inflammatory agent for AMI.

Clinical Impact of Telemedicine Network System at Rural Hospitals Without On-Site Cardiac Surgery Backup.

BACKGROUND: In Japan, catheterization laboratories are available in each medical service area. However, cardiovascular centers capable of surgical procedures are concentrated in urban areas. Critically ill patients with complex coronary lesions must be transferred to receive advanced medical care. Interhospital conferencing is necessary for an optimal patient transfer. We investigated the benefit and utility of a Digital Imaging and Communications in Medicine (DICOM) telemedicine network at a rural hospital without on-site cardiac surgery backup in Japan. MATERIALS AND METHODS AND RESULTS: The Kumamoto telemedicine network consists of 2 high-volume centers and 12 rural low-volume hospitals without on-site cardiac surgery. Between January 2010 and December 2014, 293 teleconferences were conducted. At the Aso Medical Center, a low-volume hospital, teleconferences were carried out in 48 cases (30 coronary artery disease, 6 peripheral artery disease, 3 aortic aneurysm, 3 deep vein thrombosis, 2 inflammatory aortitis, 1 annuloaortic ectasia, 1 cardiac tamponade, 1 myocarditis, and 1 heart failure). After the conferences were initiated, 10 cases (20.8%) were transferred to the high-volume center. We investigated the prevalence of patient transfer before and after network system deployment. Telemedicine-based collaborative care significantly decreased the frequency of patient transfers from the Aso area. CONCLUSIONS: The Kumamoto telemedicine network enabled open communication between distant hospitals. This collaboration has the potential to improve cardiac care in rural areas.

Heart attacks triggered by huge mud slides in mountain regions and severe flooding in inhabited areas.

BACKGROUND: On July 12, 2012, heavy rains struck southwest Japan, particularly in the Mount Aso area. Huge mud slides in the mountains destroyed houses, and heavy rains caused severe flooding in the inhabited areas. We investigated the incidence of cardiovascular events after the disaster. METHODS: We investigated patients who were admitted to the emergency department (ED) from July 12 to August 31 in 2012. We reviewed all patients with cardiovascular events, including acute myocardial infarction (AMI), angina attack, worsening of congestive heart failure (CHF), cardiopulmonary arrest (CPA), arrhythmias, tako-tsubo cardiomyopathy (TC), and symptomatic venous thromboembolism (VTE). RESULTS: The total number of cardiovascular events was 28 (14 supraventricular arrhythmias, 3 angina attacks, 1 AMI, 1 VTE, 4 CHF, 1 TC and 4 CPA). There was a significant increase in cardiovascular events during the follow-up period in 2012 in comparison with the average number of these events over the same time period during the prior 2 years (16.8 vs. 5.1/month, p<0.01). There was a sharp increase in cardiovascular events in the first week after the disaster. A second peak was observed 7 weeks after the disaster. Two patients with angina attack were previously diagnosed as having vasospastic angina. The incidence rate of AMI did not increase. CONCLUSION: An increase in cardiovascular events was observed after severe rainfalls and mud slides. Prevention of disaster-induced cardiovascular events should be a priority regardless of the magnitude of the disaster.

[Surgical treatment of unroofed coronary sinus coexisting with paroxysmal atrial fibrillation; diagnosis by multidetector computed tomography; report of a case].

We experienced a rare case of an unroofed coronary sinus without a persistent left superior vena cava. A 55-year-old man, who was diagnosed with cerebral infarction, presented with suspected atrial septal defect (ASD) coexisting with paroxysmal atrial fibrillation. Before the operation, we diagnosed this case as coronary sinus ASD by contrast-enhanced coronary computed tomography (CT). There was a 20 mm segment of abnormal communication between the base of the left atrium and the roof of the coronary sinus. We repaired the defect by simple direct closure from the left atrium side, so that the coronary veins drained into the right atrium. The postoperative course was uneventful. Imaging played a crucial role in the diagnosis. Coronary CT angiography is well suited to help identify asymptomatic congenital heart disease.

Myocardial bridging is associated with coronary atherosclerosis in the segment proximal to the site of bridging.

BACKGROUND: Myocardial bridging is a common finding on multi-detector computed tomography (MDCT). The segment proximal to a myocardial bridge is frequently atherosclerotic, although the tunneled segment is spared. This study aimed to investigate whether myocardial bridging identified by MDCT is an independent risk factor for coronary atherosclerosis. METHODS AND RESULTS: Patients (n=188) with suspected coronary disease underwent MDCT using a 40-detector or 64-detector instrument. We reviewed the baseline characteristics (age, body mass index, smoking history, presence of hypertension, dyslipidemia, and diabetes mellitus) and the results of MDCT angiography. Two radiologists evaluated the coronary artery for myocardial bridging and coronary atherosclerosis and made a diagnosis by consensus. Significant independent risk factors for coronary atherosclerosis were investigated by multivariate logistic regression analysis. We identified 50 bridges in the middle segment of the left anterior descending artery (LAD). There were no patients with significant stenosis in the tunneled segment. Multivariate analysis showed that age, diabetes mellitus, and myocardial bridging in the mid-LAD were significantly associated with coronary atherosclerosis in the proximal LAD (p<0.05). Age, diabetes mellitus, and the absence of myocardial bridging in the mid-LAD were significantly associated with coronary atherosclerosis in the mid-LAD (p<0.05). CONCLUSION: The segment proximal to a segment with myocardial bridging is frequently involved in atherosclerosis, although the tunneled segment is spared. Myocardial bridging in the mid-LAD is an independent risk factor for coronary atherosclerosis in the proximal LAD.

Peripheral endothelial function and cardiovascular events in high-risk patients.

BACKGROUND: Endothelial dysfunction is a key component of vascular vulnerability. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, can noninvasively evaluate endothelial function. This study was designed to determine the additional prognostic value of endothelial function to the Synergy Between PCI With Taxus and Cardiac Surgery Score (SYNTAXsc) and the Framingham Risk Score (FRS) in predicting cardiovascular events in high-risk patients. METHODS AND RESULTS: We undertook a two-center prospective study in 528 stable patients at high-risk for cardiovascular events from the years 2006-2011. The RHI was measured before coronary angiography and coronary complexity was assessed by SYNTAXsc. After optimal therapies including coronary revascularization, there was follow-up with patients until August 2012. Cardiovascular events consist of cardiovascular death, myocardial infarction, unstable angina, ischemic stroke, coronary revascularization, heart failure-induced hospitalization, aortic disease, and peripheral arterial disease. During 1468 person-years of follow-up, 105 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis identified B-type natriuretic peptide (BNP), SYNTAXsc, and RHI as independent cardiovascular event predictors (hazard ratio [95% confidence interval]: natural logarithm of BNP per 0.1: 1.019 [1.002 to 1.037]; P=0.023, SYNTAXsc per tertile: 2.426 [1.825 to 3.225]; P<0.0001, RHI per 0.1: 0.761 [0.673 to 0.859]; P<0.0001). When RHI was added to the FRS, BNP, and SYNTAXsc, net reclassification index was significantly improved (27.5%; P<0.0001), with a significant increase in the C-statistic (from 0.728 [0.679 to 0.778] to 0.766 [0.726 to 0.806]; P=0.031). CONCLUSIONS: Advanced endothelial dysfunction significantly correlated with near future cardiovascular events in high-risk patients. This physiological vascular measurement improved risk discrimination when added to the FRS, BNP, and SYNTAXsc. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov (http://www.clinicaltrials.gov). Unique identifier: NCT00737945.

Basal and ischemia-induced transcardiac troponin release into the coronary circulation in patients with suspected coronary artery disease.

BACKGROUND: Cardiac troponin is a specific biomarker for cardiomyocyte necrosis in acute coronary syndromes. Troponin release from the coronary circulation remains to be determined because of the lower sensitivity of the conventional assay. We sought to determine basal and angina-induced troponin release using a highly sensitive troponin assay. METHODS AND RESULTS: The cardiac troponin T levels in serum sampled from the peripheral vein (PV), the aortic root (AO), and the coronary sinus (CS) were measured in 105 consecutive stable patients with coronary risk factor(s) and suspected coronary artery disease (CAD) and in 33 patients without CAD who underwent an acetylcholine provocation test. At baseline, there was a significant increase in the troponin levels from AO [9.0 (6.4, 13.1) pg/mL for median (25(th), 75(th) percentiles)] to CS [10.3 (7.3, 15.5) pg/mL, p<0.001] in 96 (91.4%) patients and the difference was 1.1 (0.4, 2.1) pg/mL, which reflected basal transcardiac troponin release (TTR). TTR was positively correlated with PV levels (r = 0.22, p = 0.03). Male sex, left ventricular hypertrophy determined by echocardiography, T-wave inversion, and CAD correlated with elevated TTR defined as above: median, 1.1 pg/mL. A significant increase in TTR was noted in 17 patients with coronary spasms [0.6 (0.2, 1.2) pg/mL, p<0.01] but not in 16 patients without spasms [0.0 (-0.5, 0.9) pg/mL, p = 0.73] after the acetylcholine provocation. CONCLUSION: Basal TTR in the coronary circulation was observed in most of the patients with suspected CAD and risk factor(s). This sensitive assay detected myocardial ischemia-induced increases in TTR caused by coronary spasms.

Coronary plaque component in patients with vasospastic angina: a virtual histology intravascular ultrasound study.

BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart disease. However, tissue components of coronary plaque in patients with vasospastic angina (VSA) have been unknown. This study used virtual histology (VH)-intravascular ultrasound (IVUS) to elucidate the tissue component of spastic coronary arteries and its gender differences in patients with VSA. METHODS: According to acetylcholine provocation tests, the study subjects (42 patients [19 men, 23 women, 61 ± 13 years]) were divided into 2 groups: the VSA group of 26 patients and the non-VSA group of 16 patients. After nitrate injection, IVUS volumetric analysis was done, and the parameters were compared between the groups. RESULTS: Although clinical demographics were almost identical between the groups, VSA group had lower plasma adiponectin level (5.9 ± 3.3 µg/ml vs. 11.2 ± 7.6 µg/ml, p=0.007) and tended to have higher high-sensitivity C-reactive protein (0.15 ± 0.24 mg/dl vs. 0.06 ± 0.04 mg/dl, p=0.1) than non-VSA group. VSA group had diffusely thickened intima (% plaque volume, 34 ± 11% vs. 27 ± 7%, p=0.01) compared with non-VSA group. However, plaque components of patients with VSA were similar with that of non-VSA patients (dense calcium, 4 ± 6% vs. 3 ± 4%; necrotic core, 10 ± 9% vs. 8 ± 6%; fibrofatty, 19 ± 16% vs. 22 ± 11%; and fibrous, 67 ± 16% vs. 67 ± 9%). Although male patients with VSA had atherogenic lipid and metabolic profiles than female VSA patients, there were no significant gender differences in the volumetric IVUS parameters and plaque components. CONCLUSIONS: Compared with non-VSA patients, VSA patients had diffusely thickened fibrous-dominant coronary plaque without gender difference, and that might suggest the role of vasospasm in the development of atherosclerosis.