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Siling Xu,1 Lu Liu,1 Guoqing Yin,1 Abdul-Quddus Mohammed,1 Xian Lv,1 Cailing Feng,1 Tingting Shi,1 Fuad A Abdu,1 Wenliang Che1,2 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiology, Shanghai Tenth People’s Hospital Chongming Branch, Shanghai, People’s Republic of ChinaCorrespondence: Wenliang Che; Fuad A AbduDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Jingan District, Shanghai, 200072, People’s Republic of ChinaTel +86-21-66307259Fax +86-21-66301051Email chewenliang@tongji.edu.cn; 1691026@tongji.edu.cnPurpose: The association of serum uric acid (SUA) levels with cardiovascular outcomes in patients with coronary artery disease (CAD) has been extensively studied and yielded conflicting results. We aimed to investigate whether the severity of coronary stenosis and ischemia influences the prognostic impact of SUA levels in patients with CAD undergoing D-SPECT.Patients and Methods: This study consecutively included patients who were admitted for CAD in Shanghai Tenth People’s Hospital between June 2014 and August 2018, had complete SUA data and underwent both coronary angiography and D-SPECT within 3 months. Hyperuricemia was defined as an SUA level of > 7 mg/dL in men and > 6 mg/dL in women. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, unplanned coronary revascularization, nonfatal myocardial infarction, ischemic stroke, heart failure, and angina-related hospitalization.Results: A total of 695 patients were included, of whom 432 (62.2%) presented with obstructive CAD and 117 (16.8%) had hyperuricemia. During a median follow-up of 26 months, the incidence rates of MACE in patients with hyperuricemia and normouricemia were 15.2% and 21.1%, respectively. After a multivariable adjustment, hyperuricemia was significantly associated with an increased risk of MACE (HR: 1.39, 95% CI: 1.03– 1.87, p = 0.033) when compared with normouricemia. When repeating the primary analysis in patients with and without obstructive CAD, we showed that hyperuricemia was independently associated with an 80% increased risk of MACE among patients with nonobstructive CAD (HR: 1.80, 95% CI: 1.04– 3.11, p = 0.035), while such a significant association was not found among those with obstructive CAD (HR: 1.18, 95% CI: 0.82– 1.72, p = 0.373). Moreover, we uncovered a U-shaped and linear trajectory of SUA levels with MACE in the obstructive and nonobstructive CAD, respectively. The sex-specific analysis showed that the adverse impact of hyperuricemia was only pronounced in males (HR: 1.73, 95% CI: 1.18– 2.53, p = 0.005) but not in females (HR: 0.98, 95% CI: 0.57– 1.66, p = 0.933).Conclusion: Hyperuricemia is significantly associated with increased risk of MACE in the nonobstructive CAD rather than in the obstructive CAD.Keywords: coronary artery disease, serum uric acid, D-SPECT, nonobstructive, outcomes

We examined differences in clinical profiles, predictors, and outcomes among patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCAs) by sex. Data of 259 (132 males and 127 females) patients with MINOCA were consecutively collected. The primary clinical end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke, heart failure, and angina rehospitalization. Female patients with MINOCA were likely to be older than male patients with higher non-ST elevation myocardial infarction rate. Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were higher in female patients while male patients were more likely to have a smoking history, greater ST elevation myocardial infarction rate, higher diastolic blood pressure, and more alcohol use. During the 2-year follow-up, the incidence of MACE in males and females was similar (18% vs 20.2%, respectively; P = .673). The multivariable predictors of MACE in the female group were age, hypertension, and left ventricular ejection fraction (LVEF), whereas diabetes, smoking, and LVEF were multivariable predictors of MACE in the male group. In conclusion, there were differences in the clinical profiles between sexes. Clinical outcome was similar between male and female patients with MINOCA, whereas predictive risk factors varied.

Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) can be clinically categorized as ST-segment elevation (STE) and non-ST-segment elevation (NSTE), whose clinical prognosis are poorly understood. The aim of this study was to compare the clinical outcome and their predictors of patients with STE and NSTE in MINOCA population. Methods A total of 265 patients with MINOCA (102 with STE, and 163 with NSTE) were consecutively collected. Clinical profile, prognosis, and predictors of all patients were assessed. Results The proportion of patients with NSTE was greater than patients with STE in MINOCA population. Patients with NSTE were older and more likely to be female and had a higher incidence of atrial fibrillation. Both high density lipoprotein (HDL) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were higher in the NSTE group. Patients with STE were more likely to have a history of smoking and a higher diastolic blood pressure. During the 1-year follow up, there were no differences in the outcomes between the STE and NSTE groups, with no significant differences in mortality and a similar rate of major adverse cardiovascular events (MACE) (20.9% vs 19.3%, P = 0.767). The multivariable predictors of MACE in the NSTE groups were age, lower level of total cholesterol, hypertension, and smoking history, whereas reduced left ventricular ejection fraction, and diabetes mellitus were the multivariable predictors of major adverse cardiac events in the STE group. Conclusions There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events.

Myocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients. All consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as

Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity that is characterized by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries on angiography (stenosis

Background: Serum uric acid (SUA) is a well-known predictor of adverse outcomes in patients with various clinical conditions. However, the impact of SUA on patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) remains unclear. Here, we aimed at investigating the potential association between hyperuricemia and the adverse outcomes in MINOCA patients.Methods: Overall, 249 MINOCA patients were enrolled in the present study. Clinical characteristics and laboratory data, were measured in all patients. Based on SUA levels, patients were classified into two groups; the hyperuricemia group [SUA level > 6 mg/dL (360 μmol/L) in women and > 7 mg/dL (420 μmol/L) in men], and the normuricemia group. The primary endpoint of our study was major adverse cardiac events (MACE), defined as cardiovascular death, stroke, heart failure, non-fatal MI, and angina rehospitalization.Results: Seventy-two patients were in hyperuricemia group and 177 in normuricemia group. Fifty-two MACE events were recorded after 30 months of follow-up period. The incidence of MACE was higher in hyperuricemia group compared with normuricemia group (31.9 vs. 16.3%, P = 0.006). Kaplan-Meier survival curves illustrated a significantly increased risk of MACE in hyperuricemia group (log-rank P = 0.006). The multivariable logistic analysis demonstrated that hyperuricemia was independently associated with a high risk of MACE after 30 months of follow-up (OR, 2.234; 95% CI, 1.054–4.737, P = 0.036).Conclusion: Hyperuricemia is associated with adverse outcomes and appears to be an independent predictor of MACE in MINOCA patients. This finding suggests that the SUA levels may serve as a surrogate biomarker related to risk prediction and adverse outcomes of MINOCA patients.

Diastolic dysfunction (DD) with normal systolic function has been elucidated to be associated with heart failure and worse prognosis. The recently introduced single photon emission computed tomography (SPECT) with dedicated cardiac cadmium-zinc-telluride (CZT) cameras (D-SPECT) is a novel method to quantitate left ventricular functional parameters. We aimed to evaluate the prognostic value of DD derived from D-SPECT in coronary artery disease (CAD) patients with normal ejection fraction. All CAD patients who underwent D-SPECT and invasive coronary angiography within 3 months were considered. DD was defined as peak filling rate (PFR) n = 226)—normal PFR; group 2 (n = 67)—ischemia-related DD (abnormal stress PFR and normal rest PFR); and group 3 (n = 106)—rest DD (abnormal rest PFR). The primary clinical endpoint of the present study was a composite of heart failure events (HFE). A total of 399 consecutive CAD patients with normal systolic function undergoing stress D-SPECT were analyzed. The incidence rates of HFE among the three groups were 4.0, 7.5, and 11.3%, respectively. Cox regression analysis showed that the multivariate predictors of HFE were rest PFR, diabetes mellitus, obesity, and old age. DD derived from D-SPECT in CAD patients with normal ejection fraction is predictive of HFE.

Background Cryoballoon ablation has become an effective strategy for the treatment of atrial fibrillation (AF) without coronary artery disease (CAD). AF is usually coupled with CAD. However, the impact of CAD on the outcome of cryoablation in AF patients remains unclear. The objective of our study was to investigate the impact of stable CAD on the efficacy of cryoballoon ablation for AF. Materials and Methods The data of 384 patients who underwent AF cryoablation were consecutively collected. Patients were classified into a CAD group and a non-CAD group. All patients were listed for a scheduled follow-up visit in the outpatient clinics to evaluate the AF recurrence at 1, 3, 6 and 12 months after cryoablation. Results Seventy-four patients (19.3%) suffered from stable CAD, and 31 (8.1%) of them underwent PCI before cryoablation. Cryoablation was performed in 1521 pulmonary veins and 99.1% of pulmonary vein isolation was achieved. Successful follow-up was obtained in 354 patients after a mean of 12 ± 6 months, in which 280 patients (79.1%) had maintained stable sinus rhythm, and 74 patients (20.9%) had AF recurrence. There was no significant difference in AF recurrence between patients with and without CAD (16.4% versus 22.0%). Furthermore, the presence, location and severity of CAD were not associated with AF recurrence after cryoablation while persistent AF, N-terminal pro-brain natriuretic peptide and left atrial diameter served as independent predictors of AF recurrence. Conclusions Cryoballoon ablation is effective for the treatment of AF in stable CAD patients. The presence of CAD has no impact on the AF recurrence after cryoablation.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is characterised by clinical evidence of myocardial infarction with normal or near-normal coronary arteries on angiography (stenosis50%). We investigated clinical features among Chinese MINOCA patients and one-year follow-up on medication management and cardiovascular events.The data of 2029 patients with acute myocardial infarction were consecutively collected. MINOCA patients were identified with coronary angiography (50% stenosis). Clinical features, medication management and cardiovascular events were assessed.One hundred and twenty-eight patients (6.3%) were diagnosed as MINOCA. Compared with the myocardial infarction with obstructive coronary arteries (MI-CAD) patients, the prevalence of traditional risk factors of CAD was lower in MINOCA patients. The levels of TG, LDL-C, cTnT, CK-MB and myoglobin in the MINOCA group were significantly lower, whereas LVEF was higher. MINOCA patients are less likely to receive secondary prevention medication for MI, and use of all recommended drugs decreased at one-year follow-up. MACE in the MINOCA group was lower. After adjusting related risk factors, logistic analysis showed MINOCA was independently associated with lower risk of MACE. Independent predictors for MACE in MINOCA patients were older age (≥60 years), females, atrial fibrillation and reduced LVEF.Compared with MI-CAD, MINOCA was accompanied by fewer traditional risk factors of CAD, less likely to be discharged upon secondary prevention medication of MI and the occurrence of MACE during 1 year follow-up was lower. Older age (≥60 years), females, atrial fibrillation and reduced LVEF were independent risk factors for MACE in MINOCA patients within one year.

BackgroundLow free triiodothyronine (fT3) level is strongly associated with poor prognosis in various patient populations. However, the role of fT3 in the risk of clinical outcomes in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been studied. Our study aimed to evaluate the association between low fT3 levels and the clinical outcomes of MINOCA patients.MethodsA total of 218 MINOCA patients without a history of thyroid disease were enrolled in the study. Demographic, baseline clinical data, thyroid hormones, and other biochemical parameters were assessed in all patients. According to the fT3 levels, the present study was classified into two groups: the low fT3 group (fT3ResultsFifty-nine patients were in the low fT3 group and 159 patients were in the normal fT3 group. Over the two years of follow-up, 36 MACE have occurred. The occurrence of MACE was higher in the low fT3 group compared with normal fT3 group (25.4% vs 13.2%; P=0.031). Kaplan-Meier survival curves showed a significantly increased risk of MACE in patients with low fT3 (log-rank P=0.027). Multivariable logistic regression analysis stated that high fT3 was independently associated with lower risk of MACE after two years of follow up (OR, 0.623; 95% CI, 0.399- 0.972; P=0.037).ConclusionLow fT3 levels were significantly associated with increased risk of MACE in patients with MINOCA. This finding suggests that the fT3 levels may serve as a potential biomarker in risk stratification of MINOCA patients.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been and remained a puzzling heterogeneous entity. The index of microcirculatory resistance (IMR) is a quantitative and specific index for the assessment of microvascular function. However, the role of IMR in MINOCA has not yet been studied. This study aimed to evaluate the prognostic value of coronary microvascular function, as assessed by coronary angiography‑derived index of microvascular resistance (caIMR) in MINOCA patients. Method This study included 109 MINOCA patients. Microvascular function was assessed by caIMR and was analyzed in 280 coronary arteries. The primary endpoint of the study was MACE, defined as cardiovascular death, nonfatal MI, heart failure, stroke and angina rehospitalization. The best cut-off of caIMR was derived from ROC analysis based on MACE prediction. Results The patients were classified into high caIMR (caIMR>43U) and low caIMR (caIMR≤43U) based on a caIMR cut-off value of 43U. High caIMR was observed in 55 (50.5%) patients. A total of 27 MACE occurred during the 2 years of follow-up. MACE rate was significantly higher in patients with high caIMR than in patients with low caIMR (36.4% vs 13.0%, P=0.005). The Kaplan–Meier curves showed a significantly increased risk of MACE in patients with high caIMR (log-rank P=0.001). Cox multivariate analysis showed that caIMR>43 was a highly independent predictor of MACE (HR, 3.08; 95% CI, 1.13 - 8.35; P=0.027). Conclusions caIMR is a strong predictor of clinical outcome among MINOCA patients. The evaluation of IMR can provide an objective risk stratification method for patients with MINOCA.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a special type of myocardial infarction (MI). The GRACE risk score is commonly used to predict major adverse cardiovascular events (MACE) in non-ST-elevation myocardial infarction patients, and the suitability of the GRACE risk score for prognostic stratification in patients with MINOCA remains uncertain. This study aimed to investigate whether the GRACE risk score is capable of predicting MACE in MINOCA patients with NSTE. We calculated the GRACE risk score for 340 consecutive MINOCA patients with NSTE. Patients were divided into a low-intermediate risk group (≤ 140, 48.8%) and a high risk group (>140, 51.2%) according to their GRACE risk scores. The clinical characteristics and outcomes of the patients were assessed. Patients in the high risk group tended to be older and to have more comorbidities. At the 1-year follow-up, the rate of cardiac death in the high risk group was significantly higher than that in the low-intermediate-risk group (p = 0.010). There was no significant difference in non-fatal MI, stroke, heart failure, or cardiovascular-related rehospitalization. The incidence of total MACE was significantly higher in patients with high GRACE risk scores than in patients with low GRACE risk scores (p = 0.006). ROC curve analysis showed that the GRACE risk score has moderate value in predicting MACE in NSTE-MINOCA patients. The area under the ROC curve was 0.710 (95% CI 0.625–0.796, P < 0.001). The GRACE risk score provides potentially valuable prognostic information on clinical outcome when applied to MINOCA patients with NSTE.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has been and remained a puzzling clinical entity. The role of secondary prevention therapy in patients with MINOCA remains unclear. This study aimed to evaluate the associations between secondary prevention medications and outcomes in patients with MINOCA. A total of 259 patients with MINOCA were consecutively enrolled. Basic information and medication of patients were assessed. We defined major adverse cardiovascular events as the primary end point and angina rehospitalization as the secondary end point. Logistic regression models were used to assess the correlation between treatment and outcomes. The proportion of statins, aspirin, clopidogrel, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), and β-blocker used at admission was 88.8%, 86.9%, 84.6%, 51.7%, and 61.4%, respectively. At discharge, patients with MINOCA were less likely to be released on statins, aspirin, clopidogrel, ACEI/ARB, and β-blocker. The use of secondary prevention medications was significantly lower at 2 years of follow-up with the most significant reductions being clopidogrel 29.4%, ACEI/ARB 39.0%, and aspirin 42.3%. About 19.1% of patients with MINOCA suffered adverse events during the follow-up period. Adverse events risk decreased when statins and ACEI/ARB were used, whereas the risk of adverse events was not lower in patients with aspirin, clopidogrel, and β-blocker. In conclusion, patients with MINOCA were less likely to receive secondary prevention medications at the time of discharge and early discontinuation of medications at the time of follow-up. Statins and ACEI/ARB were the only medications substantially associated with lower adverse events; by comparison, aspirin, clopidogrel, and β-blocker seem to have no impact on prognosis.

Background Musclin is involved in the regulation of natriuretic peptide (NP) clearance and may affect the concentration of atrial natriuretic peptide (ANP). It has also been found to play an important role in several diseases, such as diabetes mellitus and hypertension. Both abnormalities in ANP and associated medical history are involved in the pathogenesis of atrial fibrillation (AF). However, plasma concentration of musclin as a biomarker for risk stratification in patients with AF has not been fully investigated. Methods Plasma musclin levels were measured in 290 patients with AF (including 199 paroxysmal AF patients and 91 persistent AF patients) and 120 control subjects. The association between plasma musclin levels and AF onset, as well as its predictive effects on clinical outcomes after cryoballoon ablation were analyzed. Results AF patients were found to have a lower concentration of plasma musclin than healthy controls. Moreover, in the non-diabetic group and normal N-terminal pro-brain natriuretic peptide (NT-proBNP) level group, the association between lower plasma concentration of musclin and AF remained significant. According to receiver operating characteristic (ROC) curve analysis, the optimal cut-off point of musclin for predicting AF onset was 54.94 ng/mL, which had a sensitivity of 81.67% and a specificity of 31.47% [area under the ROC curve (AUC) =60.71%]. In follow-up studies, both diabetes and left atrial size were independent predictors of AF recurrence after ablation, while musclin showed only a modest relationship with the outcome of cryoballoon ablation. Conclusions Our data indicated that decreased musclin was associated with the onset of AF. Moreover, lower plasma levels of musclin were an independent risk factor of AF in non-diabetic patients. Our studies suggest that musclin could be a predictive factor for the onset of AF.