齋藤 佑一

BACKGROUND: Coronary flow reserve (CFR) represents entire coronary compensatory capacity, while fractional flow reserve (FFR) is a standard to evaluate functional severity of epicardial coronary artery disease (CAD). ΔFFR, a decrease in a ratio of mean distal coronary pressure to aortic pressure (Pd/Pa) at rest to FFR, is conceptually associated with coronary microvascular function. This study aimed to evaluate the relation of ΔFFR to CFR in patients with stable CAD. METHODS: We performed resting Pd/Pa and FFR measurements in a total of 309 vessels with intermediate coronary artery stenosis in 242 patients. ΔFFR was defined as (resting Pd/Pa - FFR), and pressure bounded-CFR was calculated to estimate low CFR. Vessels were divided as the low CFR and non-low CFR groups. RESULTS: Of 309 vessels, low CFR was observed in 101 (32.7 %). While FFR values were similar (0.78 ± 0.11 vs. 0.78 ± 0.09, p = 0.84), resting Pd/Pa (0.85 ± 0.08 vs. 0.93 ± 0.04, p < 0.001) and ΔFFR (0.07 ± 0.06 vs. 0.15 ± 0.06, p < 0.001) were significantly lower in the low CFR group than in the non-low CFR group. The receiver operating characteristic curve analysis indicated that ΔFFR was predictive for low CFR (area under the curve 0.84, best cut-off value 0.08, p < 0.001). Multivariable analysis identified lower ΔFFR, the left anterior descending coronary artery, and lower hemoglobin and higher brain natriuretic peptide levels as factors associated with low CFR. CONCLUSIONS: In patients with stable CAD, lower ΔFFR was significantly associated with low CFR in intermediate coronary stenosis in patients with stable CAD. ΔFFR may be a simple, practical, and useful surrogate to identify patients with impaired CFR.

Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis of acute myocardial infarction has improved. However, there is still considerable room for improvement. This review article summarizes the latest evidence concerning clinical diagnosis and treatment of acute myocardial infarction.

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

Background <p lang="en">Lower primary percutaneous coronary intervention (PCI) volume is known to be associated with worse outcomes in patients with acute myocardial infarction (MI) at hospital level. The present study aimed to evaluate the relations of primary, elective, and total PCI volume and primary/total PCI volume ratio per hospital to in‐hospital mortality in patients with acute MI undergoing primary PCI. </p> Methods and Results <p lang="en">Using a large nationwide administrative database, we included a total of 83 076 patients from 154 hospitals in Japan undergoing PCI for either acute MI or elective cases. Relations of annual procedural volumes for primary, elective, and total PCI to in‐hospital mortality after acute MI at hospital level were evaluated. The ratio of primary to total PCI volume per hospital was also assessed. The primary end point was the ratio of observed to predicted mortality. Of 83 076 patients, 26 913 (32.4%) underwent primary PCI for acute MI, among whom 1561 (5.8%) died during hospitalization. Overall, observed in‐hospital mortality after acute MI and observed/predicted mortality ratio were higher in hospitals with lower primary, elective, and total PCI volumes. Observed/predicted in‐hospital mortality ratio was higher in hospitals with low primary/total PCI volume ratio, even in those with high total PCI volume. </p> Conclusions <p lang="en">Primary, elective, and total PCI volume at hospitals were inversely associated with in‐hospital mortality in patients with acute MI undergoing primary PCI. Lower ratio of primary to total PCI volume were related to higher in‐hospital mortality, suggesting primary/total PCI volume ratio as an institutional indicator of quality of care for acute MI. </p>

This study sought to investigate the relationship between physiological severity and plaque vulnerability of intermediate coronary artery stenoses as assessed by fractional flow reserve (FFR) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We included vessels where both FFR and NIRS-IVUS were performed. A positive FFR was defined as FFR ≤ 0.80. Lipid core burden index of the entire target vessel (TV-LCBI), maximum LCBI in 4 mm (maxLCBI4mm), and maximum plaque burden (PB) were evaluated using NIRS-IVUS. A vulnerable plaque was defined as a lipid-rich plaque (maxLCBI4mm ≥ 400) with large PB (≥ 70%). A total of 59 vessels of 45 patients were included. Median FFR value was 0.75 [interquartile 0.72, 0.82]. An FFR value of ≤ 0.80 was observed in 42 vessels (71%). TV-LCBI (correlation coefficient [CC] = - 0.331, p = 0.011), lesion length (CC = - 0.350, p = 0.007), and PB (CC = - 0.230, p = 0.080) negatively correlated with FFR value, while maxLCBI4mm did not (CC = - 0.156, p = 0.24). The prevalence of vulnerable plaques (26.2% vs. 29.4%, p > 0.99) and mean TV-LCBI, maxLCBI4mm, and PB values were not significantly different between the vessels with FFR ≤ 0.80 and those with FFR > 0.80. In multivariable logistic models, diabetes mellitus (p = 0.003) and hemoglobin A1c (p = 0.012) were associated with the presence of a vulnerable plaque. In conclusion, the results of the present study suggested that FFR may reflect total lipid burden but not necessarily plaque vulnerability. In patients with coronary artery disease and a high likelihood of rapid atherosclerosis progression, such as diabetes mellitus patients, assessing plaque vulnerability in addition to the functional severity of coronary artery lesions may help stratify better the risk of future events.

OBJECTIVE: Type A acute aortic dissection (AAD), especially that with coronary artery involvement and malperfusion, is a life-threatening disease. In the present study we aimed to investigate the association of surgical treatment and percutaneous coronary intervention (PCI) with in-hospital mortality in patients with type A AAD and coronary artery involvement. METHODS: This retrospective multicenter registry in Japan included 225 patients with type A AAD and coronary artery involvement. Treatment strategies including surgical treatment and/or PCI were left to treating physicians. The primary end point was in-hospital death. RESULTS: Of 225 patients, dissection extended into the right and left coronary arteries and both in 115 (51.1%), 105 (46.7%), and 5 (2.2%), respectively. Overall, 94 (41.8%) patients died during the hospitalization. Coronary angiography was performed in 53 (23.6%) patients, among whom 39 (73.6%) underwent PCI. Surgical repair was performed in 188 (83.6%) patients. In patients who received neither procedure, 33 of 35 (94.3%) died during the hospitalization. PCI was performed as a bridge to surgical repair in 37 of 39 (94.9%) patients, and in-hospital mortality of patients who underwent PCI and surgical procedures was 24.3%. Multivariable analysis identified PCI and surgical procedures as factors associated with lower in-hospital mortality rates. CONCLUSIONS: Coronary artery involvement in type A AAD was associated with high in-hospital mortality of more than 40% in the current era. An early reperfusion strategy with PCI as a bridge to surgical repair might improve clinical outcomes in this fatal condition.

Patients with vasospastic angina (VSA) who are resuscitated from sudden cardiac arrest (SCA) are at a high risk of recurrent lethal arrhythmia and cardiovascular events. However, the benefit of the implantable cardioverter-defibrillator (ICD) therapy in this population has not been fully elucidated. The present study aimed to analyze the prognostic impact of ICD therapy on patients with VSA and SCA. A total of 280 patients who were resuscitated from SCA and received an ICD for secondary prophylaxis were included in the present multicenter registry. The patients were divided into two groups on the basis of the presence of VSA. The primary endpoint was a composite of all-cause death and appropriate ICD therapy (appropriate anti-tachycardia pacing and shock) for recurrent ventricular arrhythmias. Of 280 patients, 51 (18%) had VSA. Among those without VSA, ischemic cardiomyopathy was the main cause of SCA (38%), followed by non-ischemic cardiomyopathies (18%) and Brugada syndrome (7%). Twenty-three (8%) patients were dead and 72 (26%) received appropriate ICD therapy during a median follow-up period of 3.8 years. There was no significant difference in the incidence of the primary endpoint between patients with and without VSA (24% vs. 33%, p = 0.19). In a cohort of patients who received an ICD for secondary prophylaxis, long-term clinical outcomes were not different between those with VSA and those with other cardiac diseases after SCA, suggesting ICD therapy may be considered in patients with VSA and those with other etiologies who were resuscitated from SCA.

<title>Abstract</title>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 updated expert consensus document summarizes the methods of measurements and assessment of IVUS images and the clinical evidence of IVUS use in percutaneous coronary intervention.

Esaxerenone, a mineralocorticoid receptor blocker (MRB), is a new antihypertensive agent. However, esaxerenone-related data with respect to hypertension with heart failure are limited. We investigated the safety and efficacy of esaxerenone in hypertensive patients with heart failure with reduced ejection fraction (HFrEF). Hypertensive patients with HFrEF treated with esaxerenone were retrospectively analyzed at two timepoints (short-term: 35±15 days; mid-term: 167±45 days). Adverse events including hyperkalemia (K⁺ &gt;5.5 mEq/L), worsening renal function (WRF; estimated glomerular filtration rate (eGFR) reduction by ≥20%), and hypotension (systolic blood pressure &lt;90 mmHg) were evaluated. eGFR and K⁺, serum creatinine, and brain natriuretic peptide (BNP) levels at baseline, short-term, and mid-term assessments were compared. Patients administered esaxerenone as their first MRB (first-MRB cohort) and those who converted from another MRB (conversion cohort) were separately analyzed. There were 50 (56±10 years old, 26% female) patients. At the short-term assessment, hyperkalemia or hypotension was not observed at a dose of 2.0±0.9 mg/day. Seven patients (14%) showed WRF. K⁺ was slightly elevated (4.12±0.41 to 4.25±0.39 mmol/L, <italic>p</italic> = 0.07) and eGFR was significantly reduced (66.9±19.6 mL/min/1.73 m² to 62.4±19.7 mL/min/1.73 m², <italic>p</italic> = 0.006). In the conversion cohort, significant changes in K⁺ and eGFR from baseline were not observed at the short-term assessment. BNP levels were consistently improved regardless of the cohorts (first-MRB cohort, 310 [110–370] pg/mL to 137 [47–152] pg/mL, <italic>p</italic> = 0.001; conversion cohort, 181 [30–203] pg/mL to 108 [26–146] pg/mL, <italic>p</italic> = 0.028). At the mid-term assessment, there were no significant changes in K⁺ and eGFR compared with the short-term assessment. In conclusion, esaxerenone was safe for hypertensive patients with HFrEF. Hyperkalemia and hypotension were rarely noted, while eGFR was marginally reduced. Moreover, esaxerenone might be beneficial for HFrEF in terms of BNP level reduction.

BACKGROUND: Vasospastic angina (VSA) is reportedly associated with several clinical characteristics such as smoking and high-density lipoprotein (HDL) cholesterol, in which gender differences are present. For instance, smoking rates among men are higher than those among women, and a normal range of HDL cholesterol differs across genders. However, their impact between men and women on VSA is unclear. METHODS: A total of 797 patients (427 men and 370 women) undergoing intracoronary acetylcholine (ACh) provocation test to diagnose VSA were included. The positive ACh provocation test was defined as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes. Factors contributing to VSA across genders were evaluated by multivariable analyses. RESULTS: Of 797 patients, 414 (51.9%) had positive ACh provocation test. The incidence of positive ACh test was higher in men than in women (56.9% vs. 46.2%, p = 0.003). In the entire study population, current smoking and a lower HDL cholesterol level were determined as factors associated with VSA. In both men and women, an HDL cholesterol level was identified as a factor contributing to positive ACh test. CONCLUSIONS: Among patients suspected for VSA, men as compared with women were more likely to have positive ACh provocation test. While current smoking and an HDL cholesterol level were associated with VSA in the entire study population, a lower HDL cholesterol level was determined as the only factor contributing to positive ACh test across genders, suggesting that HDL cholesterol plays important roles in the mechanism of VSA.

Previous studies indicated that serum uric acid (SUA) level is a marker of endothelial function in subsets of ischemic heart disease (IHD). In the present study, we aimed to evaluate the relation between the SUA level and endothelial function in patients with a broad spectrum of IHD, including obstructive coronary artery disease (CAD) and ischemia with no obstructive CAD (INOCA). Three prospective studies and one retrospective study were pooled, in which the SUA level was measured, and systemic endothelial function was assessed using the reactive hyperemia index (RHI). The primary endpoint of the present study was a correlation of the SUA level with RHI. A total of 181 patients with a broad spectrum of IHD were included, among whom, 46 (25%) had acute coronary syndrome presentation and 15 (8%) had INOCA. Overall, the SUA level was negatively correlated with the RHI (r = −0.22, p = 0.003). Multivariable analysis identified the SUA level and INOCA as significant factors associated with RHI values. In conclusion, in patients with a broad spectrum of IHD, including obstructive epicardial CAD (chronic and acute coronary syndromes) and INOCA, the SUA level was significantly and negatively correlated with systemic endothelial function assessed with the RHI. INOCA, rather than obstructive CAD, was more associated with endothelial dysfunction.

Patients with cancer have an increased risk of cardiovascular events including myocardial infarction (MI) and vice versa, and are at high risks of ischemic and bleeding events after MI. However, short- and long-term clinical outcomes in patients with acute MI based on cancer status are not fully understood. This bi-center registry included 903 patients with acute MI undergoing primary percutaneous coronary intervention in a contemporary setting. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrent MI, and stroke, and major bleedings were evaluated. Of 903 patients, 49 (5.4%) and 65 (7.2%) had active cancer and a history of cancer, and 87 (9.6%) patients died during the hospitalization. In-hospital MACE was not significantly different among the 3 groups (16.3% vs 10.8% vs 10.9%, p = 0.48), whereas the rate of major bleeding events during the index hospitalization was significantly higher in patients with active cancer than their counterpart (20.4% vs 6.2% vs 5.8%, p = 0.002). After discharge, patients with active cancer had an increased risk of MACE and major bleedings compared with those with a history of cancer and no cancer during the mean follow-up period of 853 days. In conclusions, active cancer rather than a history of cancer and no cancer had significant impact on in-hospital bleeding events, and MACE and major bleedings after discharge in patients with acute MI undergoing primary percutaneous coronary intervention.

BACKGROUND: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear. METHODS: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge. RESULTS: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner. CONCLUSION: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention.

Background Previous studies have reported that glucose variability leads to endothelial dysfunction and progression of coronary atherosclerosis. However, few studies have directly evaluated the relation between glucose variability and coronary endothelial function in patients with coronary artery disease (CAD). Methods A total of 38 patients with chronic CAD and a history of coronary drug-eluting stent implantation were enroled. Coronary endothelial function was evaluated by measuring the coronary vasoreactivity using quantitative coronary angiography in the segment distal to implanted stent in response to intracoronary acetylcholine (ACh) infusion (10-7 mol/l). Peripheral endothelial function was also assessed with reactive hyperemia index (RHI). The mean amplitude of glycemic excursion (MAGE) was calculated as a primary metric of glucose variability using a flash glucose monitoring system. Results Of 38 patients, 17 (45%) had diabetes mellitus. The mean levels of glycated hemoglobin, MAGE, and RHI were 6.3 ± 0.8%, 71.4 ± 29.8 mg/dl, and 1.85 ± 0.63. In the distal segment to coronary stent, lumen diameter was constricted by 0.6 ± 7.3% in response to intracoronary ACh infusion compared to that at baseline. While peripheral endothelial function assessed with RHI was not significantly associated with MAGE (r = -0.16, p = 0.35), coronary endothelial function was correlated with MAGE (r = -0.38, p = 0.02). Conclusion Greater glucose variability was significantly associated with coronary rather than peripheral endothelial dysfunction in patients with CAD, suggesting an impact of glucose variability on coronary atherosclerosis. Endothelial function; Coronary artery disease; Acetylcholine; Glucose variability.

Various types of blood pressure (BP) variability have been recognized as risk factors for future cardiovascular events. However, the prognostic impact of in-hospital BP variability in patients with symptomatic peripheral arterial disease (PAD) has not yet been thoroughly investigated. A total of 386 patients with PAD who underwent endovascular therapy in two hospitals were retrospectively included. BP variability was assessed by the coefficient of variation (CV) of systolic BP measured during hospitalization by trained nurses. The primary endpoint was a composite of major adverse cardiovascular events (cardiovascular death, acute coronary syndrome, stroke, and hospitalization for heart failure) and major adverse limb events (major amputation, acute limb ischemia, and surgical limb revascularization). The mean systolic BP and the CV of systolic BP during hospitalization were 130.8 ± 15.7 mmHg and 11.2 ± 4.1%, respectively. During the median follow-up period of 22 months, 80 patients (21%) reached the primary endpoint. Receiver operating characteristic curve analysis showed that the CV of systolic BP significantly predicted major adverse cardiovascular and limb events (area under the curve 0.60, best cutoff value 9.8, P = 0.01). Using the best cutoff value, patients with high BP variability (n = 242) had a higher risk of clinical events than those with low BP variability (n = 144) (26% vs. 12%, P < 0.001). Multivariable analysis indicated that the CV of systolic BP, age, hemodialysis, and atrial fibrillation were associated with the primary endpoint. In conclusion, greater in-hospital systolic BP variability was associated with major adverse cardiovascular and limb events in patients with symptomatic PAD undergoing endovascular therapy.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.

INTRODUCTION: Patients with cancer have an increased risk of cardiovascular disease including ischemic heart disease and vice versa. Anticancer drugs and radiotherapy are known to contribute to endothelial injury and vasospasm. However, the relations between vasospastic angina (VSA) and cancer or its treatment are poorly investigated. METHODS: A total of 786 patients underwent intracoronary acetylcholine (ACh) provocation tests to diagnose VSA. The positive ACh provocation test was defined as angiographic coronary artery spasm accompanied by chest pain and/or ischemic electrocardiographic changes. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. The impact of types of cancer, anticancer drugs, and radiotherapy on VSA was evaluated. RESULTS: Of 786 patients, 38 (4.8%) and 84 (10.7%) had active cancer and a history of cancer, respectively, and 401 (51.0%) were diagnosed as VSA. There was no significant difference in rates of positive ACh test among patients with active cancer, a history of cancer, and no cancer (39.5% vs. 57.1% vs. 50.9%, p = 0.20). Types of cancer and cancer treatment also had no impact on positive ACh provocation test. CONCLUSIONS: In this cross-sectional observational study, we did not find an association of active and a history of cancer with the diagnosis of VSA. Anticancer treatment including chemotherapy and radiotherapy was not significantly associated with positive ACh provocation test.

Uric acid, the end-product of purine metabolism in humans, is not only a cause of gout, but also may play roles in developing cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, coronary artery disease, and cardiovascular death. Several clinical investigations have reported serum uric acid as a predictive marker for cardiovascular outcomes. Although the causal relationship of hyperuricemia to cardiovascular diseases remains controversial, there has been a growing interest in uric acid because of the increased prevalence of hyperuricemia worldwide. This review article summarizes current evidence concerning the relation between hyperuricemia and cardiovascular diseases.

AIM: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. METHODS: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. RESULTS: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. CONCLUSIONS: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.

Objective Glycemic variability is being increasingly recognized as an early indicator of glucose metabolic disorder and may contribute to the development of diabetic vascular complications, such as coronary microvascular dysfunction. The present study sought to investigate the relationship between coronary microvascular function assessed by intracoronary thermodilution method and glycemic variability on a continuous glucose monitoring system (CGMS). Methods We prospectively enrolled 40 patients with or without known diabetes mellitus who had epicardial coronary artery disease referred for coronary angiography and were not treated with diabetic medications. Of these, two had a significant stenosis in the left main coronary artery and were therefore excluded from the analyses. In the end, 38 patients were equipped with a CGMS and underwent intracoronary physiological assessments in the unobstructed left anterior descending artery. The mean amplitude of glycemic excursion (MAGE) and standard deviation were calculated from the obtained CGMS data as indicators of glucose variability. Results Coronary flow reserve (CFR) was negatively correlated with MAGE (r=-0.328, p=0.044) and standard deviation (r=-0.339, p=0.037) on CGMS, while the index of microcirculatory resistance showed no such correlation. Multivariable linear regression analyses showed that MAGE on CGMS was significantly associated with CFR after adjusting for age, sex, fractional flow reserve and hemoglobin A1c. Conclusion Higher MAGE on CGMS was associated with reduced CFR in stable patients with coronary artery disease, suggesting a potential effect of glycemic variability on coronary microvascular flow regulation. A further study with a larger sample size needs to be conducted to confirm our findings.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

The ISCHEMIA was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, non-invasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized COURAGE trial did not support the plausible concept. Although the FAME 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of non-invasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.

Acute kidney injury usually assessed within 48 h after percutaneous coronary intervention (PCI) is associated with poor clinical outcomes, and persistent kidney damage is also strongly related to long-term mortality. However, little is known about longitudinal renal function change from a very early period to long-term follow-up after PCI. A total of 327 patients with stable coronary artery disease underwent elective PCI. Renal function was assessed with serum creatinine levels and estimated glomerular filtration rate (eGFR) at baseline, 1 day after PCI, at 1 year and at the latest follow-up. Kidney injury was defined as an increase in creatinine levels ≥ 0.3 mg/dl or ≥ 50% from baseline at each timepoint. Major adverse cardiovascular events (MACE) was defined as a composite of death, myocardial infarction, and stroke. eGFR was significantly increased 1 day after PCI, while it was progressively decreased at 1-year and long-term follow-up (median 28 months). Overall, eGFR was declined by - 2.3 ml/min/1.73 m2 per year. Only one (0.3%) patient developed kidney injury 1 day after PCI, whereas kidney injury at 1-year and long-term follow-up was observed in 15 (4.6%) and 27 (8.3%). During the follow-up period, 23 (7.0%) patients had MACE. The incidence of subsequent MACE was significantly higher in patients with kidney injury at 1 year than those without. In conclusion, kidney injury within 24 h after elective PCI was rarely observed. eGFR was progressively decreased over time, and mid-term kidney injury at 1 year was associated with future MACE.

BACKGROUND: Vasospastic angina (VSA) reportedly accounts for one form of sudden cardiac arrest (SCA). Intracoronary acetylcholine (ACh) testing is useful for diagnosing VSA although invasive provocation testing after SCA is a clinical challenge. In addition, even if the ACh test is positive, any causal relationship between VSA and SCA is often unclear because patients with VSA may have other underlying cardiac disorders. METHODS: A total of 20 patients without overt structural heart disease who had been fully resuscitated from SCA were included. All patients underwent the ACh provocation test and scrutiny such as cardiac computed tomography or magnetic resonance imaging. Patients were followed up for all-cause death or recurrent SCA including appropriate implantable cardioverter defibrillator therapy. RESULTS: An ACh provocation test was performed 20 ± 17 days after cardiac arrest. Fifteen out of 20 (75.0%) patients had a positive ACh test and 2 (10.0%) had adverse events such as ventricular tachycardia and transient cardiogenic shock during the test. In patients with a positive ACh test, 6 of 15 (40.0%) patients had other overlapping cardiac disorders such as long QT syndrome, Brugada syndrome, cardiac sarcoidosis, myocarditis, or cardiomyopathy. Long-term prognosis was not different regardless of a positive ACh test or the presence of other cardiac disorders overlapping with VSA. CONCLUSIONS: Three-quarters of the patients who had been resuscitated from SCA had a positive ACh test. Further examinations revealed other overlapping cardiac disorders in addition to VSA in 40% of patients with a positive ACh test.

BACKGROUND: High platelet reactivity (HPR) is associated with subsequent thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ABCD-GENE score was developed to identify patients at risk for HPR, incorporating both clinical and genetic factors. However, this score was derived and validated in mostly Caucasian subjects and it has not been validated in an East Asian population. METHOD: Individual patient data from 4 prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay on clopidogrel and genotyping of CYP2C19 was performed after PCI. Study populations included patients with general stable coronary artery disease, hemodialysis, age ≥75 and/or body weight <50 kg, and acute coronary syndrome. VerifyNow P2Y12 reactivity units >208 was defined as HPR. RESULTS: Of 184 patients, 111 (60%) had HPR on clopidogrel. In the receiver operating characteristics curve analyses, the ABCD-GENE score significantly predicted HPR on clopidogrel (AUC 0.78, best cut-off value 9, p < 0.001). Across the 4 studies and their combinations, the diagnostic ability and cut-off values of ABCD-GENE score for HPR on clopidogrel were consistent. CONCLUSIONS: The ABCD-GENE score had significant and moderate diagnostic ability for HPR on clopidogrel in Japanese patients undergoing PCI. The predictivity was consistent across a broad spectrum of patient populations, suggesting the applicability of this novel scoring system in clinical practice worldwide.

AIMS: High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated. METHODS: Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model. RESULTS: In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001). CONCLUSIONS: The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.

Percutaneous coronary intervention has become a standard-of-care procedure in patients with acute and chronic coronary syndromes, in which coronary stent technology is commonly used. In this mini-review article, we summarize the characteristics of contemporary coronary drug-eluting and coated stents.

BACKGROUND: Although current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI). METHODS: Using a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days. RESULTS: The CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67). CONCLUSIONS: The use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.