齋藤 佑一

BACKGROUND: Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear. METHOD: A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. RESULTS: Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm. CONCLUSIONS: Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.

Introduction: Several measures of blood pressure (BP) variability have been associated with kidney disease and cardiovascular events. Although BP is routinely measured during hospitalization in daily practice, the prognostic impact of in-hospital BP and its variability are uncertain. Methods: A total of 226 participants who underwent elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) were included. BP was measured by trained nurses during the 4-day hospitalization for PCI. BP variability was assessed by standard deviation (SD) and coefficient variation of systolic BP. Estimated glomerular filtration rate (eGFR) was calculated at baseline and follow-up (≥6 months). The cardiovascular end point was defined as a composite of cardiovascular death, acute coronary syndrome, stroke, heart failure hospitalization, and any coronary revascularization. Results: In-hospital BP was measured 9.5 ± 0.8 times. During a median follow-up period of 1.7 years, mean eGFR change was −1.7 mL/min/1.73 m2 per year, and 35 (15.5%) participants met the cardiovascular end point. Mean systolic BP and SD were negatively correlated with eGFR change. In the receiver operating characteristic curve analysis, SD of systolic BP predicted the cardiovascular end point (AUC 0.63, best cutoff value 14.2 mm Hg, p = 0.003). Kaplan-Meier analysis demonstrated a significantly higher incidence of the cardiovascular end point in patients with SD of systolic BP ≥14.2 mm Hg compared to their counterpart (p = 0.003). A multivariable analysis showed SD of systolic BP as an independent predictor for the cardiovascular end point. When assessed with coefficient variation, BP variability was similarly related to eGFR change and clinical outcomes. Conclusion: Greater in-hospital BP variability was associated with renal function decline and cardiovascular events in patients with stable CAD.

BACKGROUND: Previous studies showed the relation of mental distress such as anxiety and depression to coronary vasoconstriction and myocardial ischemia. However, the mental health status of patients suspected to have vasospastic angina is unclear. METHODS: A total of 99 patients underwent intracoronary acetylcholine (ACh) provocation tests for the diagnosis of vasospastic angina and mental health assessment using the 12-item General Health Questionnaire (GHQ-12) and State-Trait Anxiety Inventory Form Y (STAI Y-2). Patients with binary GHQ-12 ≥ 4 were defined as having poor mental health. RESULTS: Median GHQ-12 and STAI Y-2 were 3 [1, 6] and 44 [36, 50]. Forty-one (41%) patients had binary GHQ-12 ≥ 4, and 48 (48%) had positive ACh provocation tests. The number of provoked vasospasms and rate of electrocardiographic change and chest pain during ACh tests were not significantly different between patients with and without GHQ-12 ≥ 4. The incidence of positive ACh provocation test was similar between the two groups (49% vs. 48%, p = 1.00). The multivariable analysis indicated that younger age, no history of percutaneous coronary intervention and no diabetes mellitus were factors associated with higher GHQ-12 and/or STAI Y-2 scores. CONCLUSIONS: More than 40% of patients who underwent ACh provocation tests had poor mental condition. No impact of mental distress on positive ACh tests was found in this study.

BACKGROUND: Ticagrelor and prasugrel are novel and potent P2Y12 inhibitors. Ticagrelor 90mg or 60mg twice daily is known to reduce ischemic events but be associated with an increased risk of bleeding in patients with prior myocardial infarction in Western countries. Although ticagrelor 90mg twice daily was tested in a randomized clinical trial in East Asia, the clinical significance of ticagrelor 60mg twice daily is unclear. This study aimed to evaluate platelet inhibition of low-dose ticagrelor compared to prasugrel in Japanese patients. METHODS: A total of 33 patients with prior myocardial infarction (>3 months) who received aspirin and prasugrel 3.75mg once daily were enrolled. Prasugrel was switched to ticagrelor 60mg twice daily. Platelet inhibition was assessed by VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline and 14 days after switching to ticagrelor. P2Y12 reaction unit (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR) and PRU≥262 as high on-treatment platelet reactivity. RESULTS: Ticagrelor treatment resulted in significantly lower PRU [10 (7-39) vs. 143 (102-201), p<0.001] and a higher rate of LPR (94% vs. 24%, p<0.001), compared to prasugrel treatment. Neither patients treated with ticagrelor nor prasugrel had high on-treatment platelet reactivity. During 2-week follow-up on ticagrelor therapy, no major bleeding occurred in both groups, while four minor bleeding events were observed. CONCLUSION: In Japanese patients with prior myocardial infarction, significantly lower PRU and a higher rate of LPR were observed on ticagrelor 60mg twice daily compared to prasugrel 3.75mg once daily.

Previous studies reported that elevated serum uric acid level was associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and is believed to play important roles in coronary atherosclerosis. However, the relation between XOR and coronary lipid plaque is unclear. Patients with stable coronary artery disease who underwent elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively included. They were divided into 3 groups according to plasma XOR activities based on a previous report: low, normal, and high. Quantitative coronary angiography and gray-scale IVUS were analyzed. The primary end point was coronary lipid plaques in a nontarget vessel assessed by NIRS-IVUS with lipid core burden index (LCBI) and maximum LCBI in 4 mm (maxLCBI4mm). Out of 68 patients, 26, 31, and 11 patients were classified as low, normal, and high XOR activity groups. Quantitative coronary angiography demonstrated that the high XOR activity group had longer lesion length, smaller minimum lumen diameter, and higher percentage of diameter stenosis in a nontarget vessel among the 3 groups. Gray-scale IVUS analysis also showed smaller lumen area in the high XOR activity group than the others. LCBI (102.1 ± 56.5 vs 65.6 ± 48.5 vs 55.6 ± 37.8, p = 0.04) and maxLCBI4mm (474.4 ± 171.6 vs 347.4 ± 181.6, 294.0 ± 155.9, p = 0.04) in a nontarget vessel were significantly higher in the high XOR group than in the normal and low groups. In conclusion, elevated XOR activity was associated with coronary lipid-rich plaque in a nontarget vessel in patients with stable coronary artery disease.

Percutaneous coronary intervention (PCI) has become a standard-of-care procedure in the setting of angina or acute coronary syndrome. Antithrombotic therapy is the cornerstone of pharmacological treatment aimed at preventing ischemic events following PCI. Dual antiplatelet therapy as the combination of aspirin and P2Y12 inhibitor has been proven to decrease stent-related thrombotic risks. However, the optimal duration of dual antiplatelet therapy, an appropriate P2Y12 inhibitor, and the choice of aspirin versus P2Y12 inhibitor as single antiplatelet therapy remain controversial. Furthermore, the combined use of oral anticoagulation in addition to antiplatelet therapy is a complex issue in clinical practice, such as in patients with atrial fibrillation. The key challenge concerning the optimal antithrombotic regimen is ensuring a balance between protection against thrombotic events and against excessive increases in bleeding risk. In this review article, we summarize the current evidence concerning antithrombotic therapy in patients with coronary artery disease undergoing PCI.

In patients with atrial fibrillation (AF), concomitant coronary artery disease is often present, and vice versa. Although both AF and coronary artery disease need antithrombotic therapy to reduce ischemic events, optimal antithrombotic regimens for patients with AF undergoing percutaneous coronary intervention (PCI) remain unclear. Triple therapy, a combination of oral anticoagulant plus dual antiplatelet therapy with aspirin and P2Y12 inhibitor, has been used for patients with AF undergoing PCI as an initial antithrombotic strategy in the recent decade. However, triple therapy is well-known to induce severe bleeding events. Recently, several clinical trials have been published and guideline recommendations have been updated. This review article summarizes current evidence concerning antithrombotic therapy in patients with AF undergoing PCI.

© 2019, Japanese Association of Cardiovascular Intervention and Therapeutics. Intravascular ultrasound (IVUS) provides precise anatomic information in coronary arteries including quantitative measurements and morphological assessment. To standardize the IVUS analysis in the current era, this expert consensus document summarizes the methods of measurements and assessment of IVUS images.

Percutaneous coronary intervention (PCI) has become a standard-of-care procedure in patients with acute and chronic coronary syndrome. Adjunctive antithrombotic therapy following PCI is the cornerstone of pharmacological treatment to prevent ischemic events. Dual antiplatelet therapy, a combination of aspirin and a P2Y12 inhibitor, has been proven as an initial antithrombotic regimen to reduce thrombotic events in patients undergoing PCI. However, the optimal antithrombotic strategy such as appropriate duration of dual antiplatelet therapy and the safe and effective combination of oral anticoagulation with antiplatelet therapy remains under debate. Since Japanese patients have different risk profiles for both thrombotic and bleeding events compared with Western population, optimal antithrombotic regimen may be different. Recently, the evidence in this field has been rapidly evolving and the antithrombotic strategy varies widely in clinical practice. In this clinical expert consensus document, we provide an in-depth review concerning antithrombotic strategies after PCI from Japanese perspective.

Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.

Approximately 50% of patients with acute myocardial infarction including ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction have multivessel (MV) coronary artery disease. Recently, the evidence for beneficial outcomes associated with MV percutaneous coronary intervention (PCI) compared with culprit-only PCI has increased. However, optimal timing of non-culprit revascularization, appropriate lesion assessment in non-culprit vessels, and the best treatment strategy for patients with cardiogenic shock remain unclear. This review summarizes current evidence and focuses on the PCI strategies in patients with acute myocardial infarction and MV disease.

We experienced a young woman with congestive heart failure (CHF) caused by renovascular hypertension (RVH) and subsequent hypertensive heart disease. She underwent tumor resection and intraoperative radiation therapy because of neuroblastoma at age 2. She was diagnosed with RVH and hypertensive heart disease due to radiation-induced renal artery stenosis at age 12. Thereafter, she was hospitalized with CHF caused by uncontrolled RVH at age 19, and renal autotransplantation with extraction of left kidney was performed after the recovery of CHF. Her blood pressure has been well controlled without CHF readmission during four years of follow-up after the operation.

OBJECTIVES: Coronary endothelial and circulatory dysfunction plays important roles in the pathogenesis of vasospastic angina (VSA). However, a complete understanding of the entire coronary circulation including microvasculature in patients with VSA is lacking. PATIENTS AND METHODS: A total of 32 patients without obstructive coronary artery disease in the left descending coronary artery, who underwent an intracoronary acetylcholine (ACh) provocation test for diagnosis of VSA, were enrolled prospectively. A positive diagnosis of the ACh test was defined as total/subtotal coronary artery narrowing accompanied by chest pain and/or ischemic ECG changes. Angina frequency and severity at baseline, and 1 and 3 months were recorded. Coronary circulation was evaluated invasively using a thermodilution method by obtaining the mean transit time (Tmn) at rest and hyperemia, coronary flow reserve, and index of microcirculatory resistance. Systemic endothelial function was assessed by the reactive hyperemia index. RESULTS: There were 14 (44%) and 18 (56%) patients with and without a positive ACh provocation test. The baseline characteristics did not differ significantly between the two groups. Patients with VSA had a significantly lower reactive hyperemia index compared with those without VSA (1.70±0.33 vs. 2.12±0.53, P=0.02). Coronary flow reserve, index of microcirculatory resistance, and hyperemic Tmn were not different between the two groups, whereas resting Tmn was significantly longer in patients with VSA (1.20±0.44 vs. 0.71±0.37, P=0.002). Although the frequency and severity of angina improved from baseline to 1 and 3 months in patients with both positive and negative ACh tests, there was no difference between the two groups. CONCLUSION: Patients with VSA had decreased resting coronary flow and impaired endothelial function.

AIM: Serum uric acid (SUA) level is known to have a prognostic value in patients with acute coronary syndrome (ACS). Endothelial function plays an important role in the development of cardiovascular disease. Although relation between SUA level and endothelial function has been previously studied in various populations, it is partially understood in patients with ACS. METHODS: A total of 55 patients with ACS with measurements of SUA level and reactive hyperemia index (RHI) to evaluate endothelial function were included. They were classified into three groups according to the tertiles of SUA level. The tertiles of SUA level were as follows: low tertile, ≤ 5.2 mg/dl; intermediate tertile, 5.3 to 6.5 mg/dl; and high tertile, ≥ 6.6 mg/dl. RESULTS: Mean SUA level and RHI were 5.8±1.5 mg/dl and 1.88±0.58. There was a significant negative correlation between SUA level and RHI (r=-0.41, p=0.002). RHI was stepwisely observed in favor of the higher tertile groups (2.14±0.74 vs. 1.84±0.45 vs. 1.67±0.38, p=0.04). Multivariate analysis showed elevated SUA level as an independent predictor of reduced RHI. CONCLUSION: Elevated SUA level was significantly associated with endothelial dysfunction in patients with ACS, possibly leading to subsequent poor outcomes following ACS.

BACKGROUND: The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across the coronary artery stenosis (i.e., ΔIBS) has been reported to negatively correlate with fractional flow reserve. Fractional flow reserve after coronary stenting is known as a predictor of target vessel revascularization (TVR). However, the relation between ΔIBS and TVR is unclear. METHODS: Seven hundred and three vessels which underwent percutaneous coronary intervention with stents were screened. Vessels without IVUS-guidance and follow-up information were excluded. Intraluminal IBS values were measured using IB-IVUS in cross-sections at the ostium of the target vessel and at the distal reference of implanted stent. ΔIBS was calculated as (distal IBS) - (ostium IBS). RESULTS: A total of 393 vessels were included. Mean ΔIBS at postprocedure was 6.22 ± 5.65. During the follow-up period (11.2 ± 3.1 months), 24 cases (6.1%) had TVR. ΔIBS was significantly greater in the vessels with TVR than in those without (11.10 ± 5.93 vs. 5.90 ± 5.49, P <0.001). In receiver operating characteristic curve analysis, ΔIBS significantly predicted TVR (AUC 0.74, best cut-off value 8.24, P < 0.001). Multiple logistic regression analysis showed use of drug eluting stent and ΔIBS ≥ 8.24 as independent predictors of TVR. CONCLUSIONS: ΔIBS at postprocedure was significantly associated with TVR. IVUS may be able to predict TVR by physiological assessment with measurement of ΔIBS.

We recently reported that preoperative endothelial dysfunction [i.e., reactive hyperemia index (RHI) ≤ 1.64] predicted short-term postoperative adverse events in patients undergoing cardiovascular surgery. However, the relationship between preoperative RHI and long-term cardiovascular risk in these patients is unclear. A total of 195 patients with at least 1-year follow-up who underwent cardiovascular surgery were included. Preoperative endothelial function was assessed by RHI. The primary outcome was a composite of cardiac death, stroke, myocardial infarction, rehospitalization due to heart failure, and any coronary revascularization. Nineteen patients (9.7%) met the primary outcome, including cardiac death (n = 7), stroke (n = 5), heart failure (n = 9), and coronary revascularization (n = 2) during a median follow-up of 20 months. There was no significant difference in the baseline characteristics between patients with RHI ≤ 1.64 (n = 86) and those with RHI > 1.64 (n = 109). The primary outcome occurred in 13 patients with RHI ≤ 1.64 (15.1%) and in 6 patients with RHI > 1.64 (5.5%). Kaplan-Meier analysis demonstrated a significantly higher incidence of the primary outcome in patients with RHI ≤ 1.64 compared to their counterpart (hazard ratio 2.94; 95% confidence interval 1.12-7.75; p = 0.02). Multivariate analysis showed diabetes and RHI ≤ 1.64 as independent predictors for the primary outcome. In conclusion, preoperative endothelial dysfunction assessed by RHI was associated with long-term cardiovascular events in patients undergoing cardiovascular surgery.

BACKGROUND: Vasospastic angina (VSA), which often causes acute coronary syndrome (ACS), can be diagnosed by intracoronary acetylcholine (ACh) provocation test. However, the safety and usefulness of ACh provocation test in ACS patients on emergency coronary angiography (CAG) compared to non-emergency settings are unclear. METHODS: A total of 529 patients undergoing ACh provocation test during emergency or non-emergency CAG were included. Patients with resuscitated cardiac arrest were excluded. The primary endpoint was adverse events defined as a composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, cardiac tamponade, and stroke within 24 h after ACh provocation test. RESULTS: There were no significant differences of the clinical characteristics between the groups of emergency (n = 84) and non-emergency (n = 445) ACh provocation test. The rate of positive ACh provocation test was similar between the 2 groups (50% vs. 49%, p = 0.81). Similarly, the incidence of adverse events in patients with emergency and non-emergency ACh provocation test did not significantly differ (1.2% vs. 1.3%, p = 1.00). CONCLUSION: ACh provocation test can be safely performed in ACS patients with no obstructive culprit lesions on emergency CAG, and may be useful to diagnose VSA in those patients.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. Although outpatient coronary angiography has been widely performed in current clinical settings, the feasibility and safety of ACh provocation test in outpatient services are unclear. A total of 323 patients, who electively underwent ACh provocation test in hospitalization and outpatient services, were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, and cardiac tamponade, were evaluated. There were 201 patients (62%) in the hospitalization group and 122 patients (38%) in the outpatient group. The incidence of positive ACh provocation test was similar between the 2 groups (47 vs. 54%, p = 0.21). Coronary angiography in the outpatient group was performed through the radial artery, mostly (98%) with a 4 F sheath. Venous access site was not significantly different between the 2 groups, and the sheath size was 5 F in all cases. There were 2 cases (1.0%) of cardiac complications in the hospitalization group, whereas 1 case (0.8%), which led to unexpected hospitalization, occurred in the outpatient group. In conclusion, intracoronary ACh provocation test for the diagnosis of vasospastic angina in outpatient services was feasible and safe in selected patients.

BACKGROUND: The aim of this study was to investigate microvascular function in patients with valvular heart disease (VHD), which causes chronic left ventricular volume and/or pressure overload, therefore change in coronary microvascular hemodynamics. PATIENTS AND METHODS: We prospectively enrolled 30 patients with VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and eight mitral regurgitation) and 30 controls. Intracoronary physiological assessments were performed in the unobstructed left anterior descending artery using a pressure-temperature sensor guidewire at rest and hyperemia. RESULTS: The index of microcirculatory resistance (IMR) was similar between the two groups (16.2±6.5 vs. 16.2±8.5, P=0.997), whereas coronary flow reserve (CFR) was lower in the VHD group compared with the controls (3.2±1.4 vs. 4.3±1.7, P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean transit time were similar between VHD and controls, whereas resting mean transit time was significantly shorter (0.70±0.29 vs. 0.89±0.39, P=0.035) and baseline resting microvascular resistance was significantly lower in the VHD group compared with the controls (58.1±25.4 vs. 78.1±36.7, P=0.011). Patients with aortic stenosis showed numerically higher IMR values than aortic regurgitation, mitral regurgitation, and controls, although this was not statistically significant (20.4±6.9, P=0.14). CFR was significantly correlated with log high-sensitivity cardiac troponin T levels in patients with VHD (r=-0.523, P=0.004). CONCLUSION: CFR was reduced in patients with VHD compared with controls, despite similar microvascular function as assessed by IMR. This appeared to be mainly because of an increased resting coronary flow accompanied by a decreased resting coronary microvascular resistance rather than microvascular disease.

BACKGROUND: Cardiovascular surgery is one of the highest risk procedures in the field of surgery. Preoperative assessment of endothelial function has been reported as useful for predicting postoperative adverse events (AEs). The aim of this study was to investigate the relationship between endothelial function assessed by reactive hyperemia index (RHI) and AEs after cardiovascular surgery.Methods and Results:A prospective observational study of 197 patients who underwent cardiovascular surgery was conducted. RHI was measured before the surgery. The primary endpoint was a composite of postoperative death, reoperation, stroke, newly required dialysis, deep sternum infection, and prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without a prior history of AF. In the receiver-operating characteristic curve analysis, RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93). Patients with RHI ≤1.64 had more AEs than those with RHI >1.64 (16.3% vs. 4.5%, P=0.005). Multiple logistic regression analysis showed the number of surgical procedures and RHI ≤1.64 as significant predictors of AEs. CONCLUSIONS: Preoperative endothelial dysfunction assessed by RHI was associated with postoperative AEs in patients with cardiovascular surgery.

BACKGROUND: Prevalence of myocardial bridging of the left anterior descending coronary artery (LAD) in patients with takotsubo syndrome (TTS) has been demonstrated. However, the impact of myocardial bridging on in-hospital outcome has not been fully evaluated. METHODS: A total of 144 consecutive patients with TTS were enrolled. Coronary angiography and left ventriculography were performed in all patients and absence of obstructive coronary disease explaining the left ventricular contraction abnormality was confirmed. Myocardial bridging was diagnosed when a dynamic compression in systole, so-called "milking effect", was observed in the LAD. We evaluated differences in the clinical characteristics and in-hospital outcome between patients with and without myocardial bridging. Furthermore, multiple logistic regression analysis was performed to predict in-hospital death. RESULTS: Myocardial bridging was observed in 33 patients (23%). In-hospital death was more frequent in patients with myocardial bridging (21% vs. 6%, p=0.02), which was due mainly to a higher non-cardiac death in those patients (15% vs. 5%, p=0.049). Multiple logistic regression analysis demonstrated myocardial bridging (odds ratio=12.0, 95% CI=2.52-78.5, p<0.01) as one of the independent predictors of in-hospital death. CONCLUSION: Myocardial bridging is an independent predictor of in-hospital death in patients with TTS.

BACKGROUND: Myocardial bridge (MB) has been reported to induce cardiac complications including coronary vasospasm. Although MB has some anatomical and morphological variations, the association of these variations with vasospasm is unclear. The aim of this study was to investigate the relation between morphological severity of MB and vasospasm induced by acetylcholine (ACh) provocation test. METHODS: A total of 392 patients without coronary stent in the left anterior descending artery (LAD) undergoing intracoronary ACh provocation test were included. Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. MB was identified on coronary angiography as a milking effect. Total bridged length and maximum percent systolic compression of MB in the LAD were analyzed quantitatively. RESULTS: MBs in the LAD were identified in 140 patients (36%), mostly in the mid segment. Patients with MB in the LAD had greater number of provoked vasospasm in the LAD and positive ACh provocation test compared to those without. The bridged length positively correlated with percent systolic compression of MB (r=0.37, p<0.001). In the receiver operating characteristic curve analysis, both bridged length and percent systolic compression of MB significantly predicted the provoked LAD spasm (AUC 0.74, p<0.001, and AUC 0.68, p<0.001). Multivariate regression analysis demonstrated these factors as independent predictors for provoked LAD spasm. CONCLUSION: MB, especially morphologically severe MB, may induce greater coronary vasospasm.

The difference in the intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across a coronary artery stenosis (i.e., ΔIBS) has previously shown a negative correlation with fractional flow reserve, reflecting an impaired coronary blood flow. Periprocedural myocardial injury (PMI) after coronary stenting has also been associated with coronary circulatory dysfunction. The aim of this study was to investigate the relation between ΔIBS after coronary stenting and PMI. A total of 180 patients who underwent elective coronary stenting under IVUS guidance for a single lesion were included. Intraluminal IBS was measured using IB-IVUS in cross sections at the ostium of the target vessel and at the distal reference of the stent. ΔIBS was calculated as (distal IBS value) - (ostium IBS value). PMI was defined as an elevation of troponin I >5 times the 99th percentile upper reference limit (>0.45 ng/ml) within 24 hours after the procedure. The mean ΔIBS after coronary stenting was 6.52 ± 5.71. There was a significantly greater use of the rotational atherectomy, the number of stents, the total stent length, and ΔIBS in patients with PMI than those without. In the receiver operating characteristic curve analysis, ΔIBS significantly predicted PMI (area under the curve 0.64, best cut-off value 7.88, p = 0.001). Multiple logistic regression analysis determined that the total stent length, the use of rotational atherectomy, and ΔIBS were independent predictors of PMI. In conclusion, greater ΔIBS assessed by IB-IVUS was significantly associated with PMI after coronary stenting in patients with a stable coronary artery disease.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48 h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p = 0.01) and body mass index (OR 0.88 CI 0.78-0.99, p = 0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.

According to the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50 μg for the right coronary artery (RCA), and 20, 50 and 100 μg for the left coronary artery (LCA). However, provocation by low doses of ACh in patients with low vasoreactivity may be less needed, and the requirement of 50 μg of ACh for the LCA in these patients has not been evaluated. In the present study, patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing (i.e., angiographic coronary artery spasm) accompanied by chest pain and/or ischemic electrocardiographic changes. Coronary artery constriction was visually evaluated and defined as coronary artery diameter reduction <25 or 25-90% in patients without angiographic coronary artery spasm by 20 µg of ACh in the LCA. There were 33 out of 249 patients (13%) with LCA spasm by 20 µg of ACh. In subjects without LCA spasm by 20 µg of ACh, patients with coronary constriction <25% (n = 101) by 20 µg of ACh in the LCA rarely showed coronary artery spasm induced by 50 μg of ACh in the LCA, in comparison to those with coronary constriction 25-90% (n = 115) (2.6 vs. 32.7%, p < 0.001). None of the patients with coronary constriction <25% by 20 µg of ACh in the LCA had cardiac complications associated with administration of ACh. In conclusion, omission of 50 µg of ACh in the LCA may be possible when there is little coronary artery constriction by 20 µg of ACh in the LCA during provocation test, leading to less contrast and shortens overall procedure time.

OBJECTIVES: The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter intravascular ultrasound (IVUS) across the coronary stenosis was reportedly correlated with fractional flow reserve (FFR) in the left descending coronary artery. The aim of this study was to investigate the novel physiological assessment using IVUS in all coronary arteries. PATIENTS AND METHODS: Fifty-four patients with 57 coronary lesions underwent both FFR and IVUS. Intraluminal IBS was analyzed using integrated backscatter IVUS in cross-sections at the ostium and the distal site of the target vessel. ΔIBS was calculated as: (distal IBS)-(ostium IBS). RESULTS: Both ΔIBS (r=-0.50, P<0.01) and minimum lumen area (MLA) (r=0.55, P<0.01) showed significant correlations with FFR. There were significant correlations between FFR and ΔIBS in the right and left descending coronary arteries (r=-0.60, P=0.02, and r=-0.58, P<0.01), but not in the left circumflex (r=0.30, P=0.44). In receiver operating characteristic curve analyses, ΔIBS predicted FFR less than or equal to 0.80 (area under the curve=0.82, P<0.01, best cutoff value=6.78), as with MLA (area under the curve=0.83, P<0.01, best cutoff value=2.38). FFR progressively decreased in association with ΔIBS greater than or equal to 6.78 and MLA less than or equal to 2.38, and was the lowest when these were combined. CONCLUSION: ΔIBS was correlated with FFR in right and left descending coronary arteries. IVUS may assess coronary artery stenosis anatomically and physiologically.

BACKGROUND: Baseline coronary artery diameter and coronary artery dilation response to nitrate are associated with coronary vasoreactivity. OBJECTIVES: The present study investigated the predictive value of coronary artery tone for a positive intracoronary acetylcholine (ACh) provocation test. METHODS: A total of 197 patients who underwent an ACh provocation test in the right coronary artery were included. A positive ACh provocation test was defined as transient total or subtotal occlusion of a coronary artery with signs/symptoms of myocardial ischemia. The segment, from the ostium to the bifurcation, of the right coronary artery was analyzed quantitatively. Coronary artery dilation response to isosorbide dinitrate (ISDN) was defined as the mean lumen diameter after an intracoronary injection of ISDN divided by the diameter before administration of ACh (i.e. baseline coronary artery diameter). RESULTS: After the administration of ACh, 49 patients (24.9%) had a positive ACh provocation test. Smaller baseline right coronary artery diameter (2.35±0.45 vs. 2.73±0.48 mm, P<0.001) and greater right coronary artery dilation response to ISDN (1.34±0.12 vs. 1.15±0.11, P<0.001) were observed in patients with a positive ACh provocation test. The receiver operating characteristic curve for baseline coronary artery diameter poorly predicted the occurrence of a positive ACh provocation test (area under the curve 0.71). The predictive values of dilation response of the right coronary artery to ISDN for the occurrence of a positive ACh provocation test (area under the curve 0.87) was significantly better compared with that of baseline right coronary artery diameter (P<0.001). CONCLUSION: Coronary artery dilation response to nitrate is a more accurate predictor of a positive intracoronary ACh provocation test compared with baseline coronary artery diameter.

A 59-year-old woman with a history of bronchial asthma presented with a prolonged fever and eosinophilia. There was transient proteinuria and troponin level was elevated. Antineutrophil cytoplasmic antibody was negative and she did not fulfil criteria for eosinophilic granulomatosis with polyangitis (EGPA). Echocardiography showed a large apical mass in the left ventricle, but there was no systolic dysfunction, local asynergy or ventricular remodelling. On MRI, apical mass was compatible with a thrombus and endocardial region was diffusely damaged. Loeffler endocarditis-like cardiac manifestation led to meticulous examination, which found no aetiology for eosinophilia. Finally, renal biopsy revealed eosinophil infiltration and glomerular angionecrosis, confirming as EGPA. This case highlights the isolated large cardiac thrombus as a rare presenting sign for EGPA and underscores current complicated strategy to diagnose EGPA. Of note, this clinical challenge was mostly caused by inchoate comprehension of hypereosinophilia-related disorders.

BACKGROUND: Based on the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50 μg for the right coronary artery (RCA), and 20, 50 and 100 μg for the left coronary artery (LCA). However, the requirement for each dose of ACh has not been fully evaluated. METHODS AND RESULTS: A total of 249 patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic ECG changes. Positive ACh provocation test was observed in 116 patients (47%). Patients without vasospasm in the LCA had a lower incidence of vasospasm in the RCA induced by 20 μg of ACh compared with those with vasospasm in LCA (0.8% vs. 27.5%, P<0.001). Similarly, vasospasm in the LCA induced by 20 μg of ACh was observed less frequently in patients without than with vasospasm in the RCA (6.1% vs. 26.7%, P<0.001). In all patients without vasospasm in the other coronary artery, intracoronary administration of 50 μg of ACh was performed without any complications. CONCLUSIONS: Skipping the provocation test with 20 μg of ACh in patients without coronary artery spasm in the other coronary artery may be possible. (Circ J 2016; 80: 1820-1823).

Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the pathogenesis of the relation between SUA level and coronary plaque characteristics has not been fully evaluated. The aim of this study was to investigate the relation between SUA level and plaque composition of nonculprit lesions in patients with ACS. A total of 81 patients with ACS who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were included. They were classified into 3 groups according to tertiles of SUA level. Using integrated backscatter (IB)-IVUS system, tissue components were classified into 4 categories: calcium deposits, dense fibrosis, fibrosis, and lipid. Tertiles of SUA level were as follows: low tertile <5.0 mg/dl; intermediate tertile 5.0 to 6.4 mg/dl; and high tertile >6.4 mg/dl. There was a trend toward greater vessel volume in the high tertile group than in the low and intermediate tertile groups (19.4 ± 3.7 vs 17.4 ± 4.4 vs 16.7 ± 4.1 mm(3)/mm, p = 0.05). There was no significant difference in lumen volume between the 3 groups. Plaque volume was significantly greater in the high than in the low tertile group (8.6 ± 2.4 vs 6.7 ± 2.2 mm(3)/mm, p = 0.01). IB-IVUS analysis demonstrated greater lipid (59.1 ± 9.1% vs 49.7 ± 10.9% vs 51.1 ± 9.3%, p = 0.001) and less fibrous components (36.8 ± 7.8% vs 44.3 ± 7.8% vs 43.2 ± 6.7%, p <0.001) in the high than in the low and intermediate tertile groups. Multivariate analysis showed high SUA as an independent predictor of increasing lipid volume. In conclusion, elevated SUA level is associated with greater lipid content of coronary plaque in patients with ACS than in patients with normal levels.