Norifumi Kubo

Clinical Characteristics and Long-Term Prognosis of Vasospastic Angina Patients Who Survived Out-of-Hospital Cardiac Arrest: Multicenter Registry Study of the Japanese Coronary Spasm Association

Background—Coronary artery spasm plays an important role in the pathogenesis of ischemic heart disease; however, its role in sudden cardiac death remains to be fully elucidated. We examined the clinical characteristics and outcomes of patients with vasospastic angina (VSA) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. Methods and Results—Between September 2007 and December 2008, 1429 patients with VSA (male/female, 1090/339; median, 66 years) were identified. They were characterized by a high prevalence of smoking and included 35 patients who survived out-of-hospital cardiac arrest (OHCA). The OHCA survivors, as compared with the remaining 1394 non-OHCA patients, were characterized by younger age (median, 58 versus 66 years; P<0.001) and higher incidence of left anterior descending coronary artery spasm (72% versus 53%, P<0.05). In the OHCA survivors, 14 patients underwent implantable cardioverter-defibrillator (ICD) implantation while intensively treated with calcium channel blockers. Survival rate free from major adverse cardiac events was significantly lower in the OHCA survivors compared with the non-OHCA patients (72% versus 92% at 5 years, P<0.001), including appropriate ICD shocks for ventricular fibrillation in 2 patients. Multivariable analysis revealed that OHCA events were significantly correlated with major adverse cardiac events (hazard ratio, 3.25; 95% confidence interval, 1.39 to 7.61; P<0.01). Conclusions—These results from the largest vasospastic angina cohort indicate that vasospasm patients who survived OHCA are high-risk population. Further studies are needed to determine whether implantable cardioverter-defibrillator therapy improves patient prognosis.

Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association.

AIMS Provocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association. METHODS AND RESULTS A total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not. CONCLUSION The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients.

Prognostic Stratification of Patients With Vasospastic Angina A Comprehensive Clinical Risk Score Developed by the Japanese Coronary Spasm Association

OBJECTIVES The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. BACKGROUND Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. METHODS The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. RESULTS Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. CONCLUSIONS We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.

Peak C-Reactive Protein Level Predicts Long-Term Outcomes in Type B Acute Aortic Dissection

Acute aortic dissection (AAD) is associated with an inflammatory reaction, as evidenced by elevated inflammatory markers, including C-reactive protein (CRP). The association between the peak CRP level and long-term outcomes in type B AAD has not been systematically investigated. The purpose of this study was to investigate whether the peak CRP level during admission predicts long-term outcomes in type B AAD. We conducted a clinical follow-up study of type B AAD. We divided the study population into 4 groups according to the tertiles of peak CRP levels (T1: 0.60 to 9.37 mg/dL; T2: 9.61 to 14.87 mg/dL; T3: 14.90 to 32.60 mg/dL; and unavailable peak CRP group). Multivariate Cox regression analysis was applied to investigate whether the tertiles of peak CRP predict adverse events even after adjusting for other variables. A total of 232 type B AAD patients were included in this analysis. The median follow-up period was 50 months. CRP reached its peak on day 4.5±1.7. Mean peak CRP values in T1, T2, and T3 were 6.4±2.4, 12.0±1.5, and 19.5±4.0 mg/dL, respectively. There were 65 events (39 deaths and 26 aortic events) during the follow-up. T3 and T2 (versus T1) were strong predictors of adverse events (T3: hazard ratio: 6.02 [95% CI: 2.44 to 14.87], P=0.0001; T2: hazard ratio: 3.25 [95% CI: 1.37 to 7.71], P=0.01) after controlling for all of the confounding factors. In conclusion, peak CRP is a strong predictor for adverse long-term events in patients with type B AAD.

Clinical ResearchCoronary Artery DiseasePrognostic Stratification of Patients With Vasospastic Angina: A Comprehensive Clinical Risk Score Developed by the Japanese Coronary Spasm Association

OBJECTIVES The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. BACKGROUND Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. METHODS The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. RESULTS Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. CONCLUSIONS We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.

Further ST Elevation at Reperfusion by Direct Percutaneous Transluminal Coronary Angioplasty Predicts Poor Recovery of Left Ventricular Systolic Function in Anterior Wall AMI

Some patients with acute myocardial infarction (AMI) develop further ST elevation at reperfusion by percutaneous transluminal coronary angioplasty (PTCA). This study reports the ST deviation at reperfusion by direct PTCA in relation to the clinical factors and the recovery of left ventricular (LV) systolic function. Fifty-two patients with anterior wall AMI were treated with direct PTCA. They were classified into the following 3 groups according to the change in ST elevation at reperfusion: increase of > or = 20% (ST reelevation); reduction of > or = 20% (ST resolution); and the other (ST no change). Angina pectoris preceding AMI occurred less often in the ST reelevation group (ST reelevation group, 38%; ST no change group, 81%; ST resolution group, 70%; p < 0.05). Recovery of LV ejection fraction during the first month after direct PTCA was significantly poor in the ST reelevation group in contrast to the ST resolution group (ST reelevation group, -6.3 +/- 13%; ST no change group, 18 +/- 20%; ST resolution group, 45 +/- 29%; p < 0.0001). The change in ST elevation at reperfusion was an index predicting the recovery of LV systolic function in the reperfusion by direct PTCA.

Impact of acute hyperglycemia during primary stent implantation in patients with ST-elevation myocardial infarction

BACKGROUND Acute hyperglycemia is associated with increased mortality rates in patients with acute coronary syndrome. OBJECTIVE This study aimed to evaluate the relationship between the glucose level and clinical variables during primary intervention in patients with ST-elevation acute myocardial infarction (STEMI). METHODS AND RESULTS Of consecutive 94 patients with STEMI treated by primary stent implantation, acute hyperglycemia (plasma glucose level on admission>198 mg/dl) was recognized in 29 patients. There were no significant differences in baseline characteristics, except for the presence of diabetes and HbA(1c) level, between patients with and without acute hyperglycemia. In patients with acute hyperglycemia, corrected TIMI frame counts were significantly higher compared with those in patients without acute hyperglycemia (46.3+/-30.3 vs. 34.0+/-17.9, p=0.02). And corrected TIMI frame count was independently associated with plasma glucose level (p=0.006). Maximum level of creatine kinase (CK) and CK-MB were significantly higher in patients with acute hyperglycemia (CK, 4840.0+/-4690.3 vs. 2410.7+/-2302.9 IU, p=0.001; CK-MB, 315.3+/-257.7 vs. 195.9+/-191.1, p=0.01). CONCLUSION The presence of acute hyperglycemia was associated with the impairment of epicardial coronary flow after primary stent implantation. This mechanism might be responsible for the increased infarct size.

Elevation of plasma placental growth factor in the patients with ischemic cardiomyopathy

BACKGROUND Placental growth factor (PlGF), which is a member of the vascular endothelial growth factor family, stimulates angiogenesis and collateral growth in ischemic tissues. In addition, PlGF has been known to be a useful biomarker of vascular inflammation. This study was undertaken to examine whether plasma PlGF levels were increased in patients with congestive heart failure (CHF). METHODS Ninety-eight patients with systolic heart failure (ejection fraction <40%) and twenty control subjects were enrolled. The patients were divided into four subgroups according to the criteria of NYHA functional class. Plasma PlGF, tumor necrosis factor (TNF)-alpha, brain natriuretic peptide (BNP), norepinephrine, high-sensitive C-reactive protein (hs-CRP) were determined. RESULTS In analysis of all the subjects, there was no significant difference in plasma PlGF levels among the subgroups of NYHA classes and the controls. In the ischemic cardiomyopathy (ICM) patients, however, plasma PlGF levels were significantly increased according to the severity of NYHA class; control: 8.9+/-0.5; NYHA I: 9.4+/-1.1, NYHA II: 9.7+/-1.9, NYHA III: 14.6+/-1.2, NYHA IV: 17.9+/-1.9 pg/ml (p=0.0006). Plasma PlGF levels correlated positively with BNP (r=0.53, p=0.0003) and hs-CRP (r=0.23, p=0.02) in the ICM patients, whereas there was not any correlation between plasma PlGF levels and other variable values in the non-ICM patients. CONCLUSIONS In the ICM patients, plasma PlGF levels are increased according to the severity of heart failure. These results may indicate that augmented release of PlGF is involved in the pathogenesis of cardiomyopathy derived from chronic myocardial ischemia.

Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction.

BACKGROUND The effects of physical training on ventricular remodeling after extensive anterior acute myocardial infarction (AMI) have not yet been defined. This randomized controlled study examines whether exercise aggravates left ventricular (LV) remodeling in patients with extensive anterior AMI. METHODS Forty-eight consecutive patients with a first extensive anterior AMI and an LV ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3 days of onset were randomly allocated to a training group (n = 24) or a control group (n = 24). Exercise intensity was determined by the heart rate of each patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was performed, followed by a supervised exercise program at VT for 12 weeks. The LVG was reassessed after the exercise program. We then calculated the global LV volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and systolic expansion volume index (SEVI), a new parameter for measuring the infarction site expansion at the end-systolic phase. RESULTS Both EDVI and ESVI significantly decreased in the control group from 1 to 4 months after onset (91.2 +/- 26.1 to 83.3 +/- 24.0 mL/m2, P <.05; 52.4 +/- 22.5 to 45.7 +/- 18.8 mL/m2, P <.01, respectively), but not in the exercise group. The SEVI also significantly decreased in the control group from 1 to 4 months (33.1 +/- 16.9 to 25.7 +/- 13.9 mL/m2, P <.05), but not in the training group (34.2 +/- 12.9 to 36.5 +/- 15.5 mL/m2, P = not significant). CONCLUSION Exercise while healing in patients with extensive anterior AMI, even at the VT level, induces LV enlargement and thus might aggravate LV remodeling. Therefore, in these patients, clinicians should consider withholding exercise training for at least 8 weeks, versus the 3-week period used in this trial.

Plaque Characteristics of the Coronary Segment Proximal to the Culprit Lesion in Stable and Unstable Patients

Identifying vulnerable plaque is important for preventing an acute coronary event. The present study examined the relationship between the clinical presentation of coronary artery disease and the plaque characteristics of nonculprit segment assessed by virtual histology intravascular ultrasound (VH‐IVUS).