Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation.

BACKGROUND: Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. METHOD: This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. RESULT: A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529-6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). CONCLUSION: Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

The correlation of atherogenic index of plasma with non-obstructive CAD and unfavorable prognosis among patients diagnosed with MINOCA.

BACKGROUND: The atherogenic index of plasma (AIP) is linked to lipid metabolism and has shown considerable prognostic value in cardiovascular disorders. However, its role in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been investigated. We assessed the relationship between AIP, the severity of coronary stenosis, and prognosis in MINOCA. METHODS: We included consecutive patients who were diagnosed with MINOCA. AIP was calculated using the base 10 logarithm of the ratio between the levels of TG and HDL-C. The patients were divided into four groups based on their AIP quartiles: Q1 (AIP<-0.145), Q2 (AIP≥-0.145and≤0.049), Q3 (AIP>0.049and≤0.253), and Q4 (AIP>0.253). All patients underwent follow-up for MACE. RESULTS: The final analysis included 421 patients, with 188 having normal coronaries (0 stenosis) and 233 exhibiting non-obstructive coronary artery disease (CAD) (<50 % stenosis). In the multivariate logistic analysis, highest AIP (Q4) group was significantly associated with increased risk of non-obstructive CAD in MINOCA (OR,1.994;95 % CI:1.075-3.698; P = 0.029). During the follow-up period, MACE occurred in 22.8 % of MINOCA patients. Q4 group exhibited a significantly higher rate of MACE (P = 0.021). Furthermore, when both AIP and coronary stenosis status were considered, the results revealed individuals in the Q4 group with non-obstructive CAD had the highest risk of MACE (log-rank P = 0.027). The adjusted Cox analysis indicated that the Q4 group was associated with a 2.052-fold increase in the HR of MACE. CONCLUSION: AIP exhibits a notable association with the incidence of MACE in MINOCA patients and serves as a substantial marker for non-obstructive CAD in this patient group.

Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Coronary microvascular dysfunction and myocardial infarction with non-obstructive coronary arteries: Where do we stand?

In the past decade, scientific and clinical research has provided a translational perspective on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). MINOCA is characterized by clinical documentation of an acute MI but angiography shows no significant coronary artery obstruction (stenosis <50%). The prevalence of MINOCA is estimated to range from approximately 6 to 10% among MI patients, and those with this condition have a poor prognosis, experiencing high rates of mortality, rehospitalization, and socioeconomic burden. MINOCA represents a major unmet need in cardiovascular medicine, with uncertain clinical management. It is a complex condition that can be caused by various factors, including atherosclerosis, plaque rupture, coronary vasospasm, and microvascular dysfunction. Effective management of MINOCA depends on identifying the underlying mechanism of the infarction, thus a systematic diagnostic approach is recommended. Contemporary data shows that a significant number of patients exhibit structural and functional abnormalities in coronary microcirculation, which is referred to as coronary microvascular dysfunction (CMD). CMD plays a crucial role in patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery stenosis, including MINOCA. Furthermore, conducting a thorough evaluation of coronary function can have significant prognostic and therapeutic implications, since personalized patient management strategies based on this assessment have been shown to improve symptoms and prognosis. Therefore, an accurate and timely diagnosis of CMD is essential for effective patient management, which can be achieved through various invasive and non-invasive methods. This review will discuss the pathophysiological understanding, current diagnostic techniques, and management strategies of patients with MINOCA and CMD.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Prognostic Significance of Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The prognostic impact of coronary microvascular dysfunction (CMD) has been scarcely addressed in heart failure with preserved ejection fraction (HFpEF). This study investigated the prevalence and prognostic significance of CMD as measured by a novel pressure wire-free coronary angiography-derived index of microcirculatory resistance (caIMR) on clinical outcomes. METHODS: Patients diagnosed with HFpEF from 2019 to 2021 were enrolled retrospectively. caIMR was used to quantify microvascular function, and patients were categorised into 2 groups based on their caIMR. The primary end points were composite of all-cause death and heart failure rehospitalisation. RESULTS: Of 137 HFpEF patients, CMD (defined as caIMR ≥ 25) was present in 88 patients (64.2%). Forty-five patients (32.8%) experienced composite events during a mean follow-up of 15 months. Compared with patients with caIMR < 25, those with caIMR ≥ 25 had a notably higher incidence of composite events (16.3% vs 42.0%; P = 0.002). On survival analysis, patients with caIMR ≥ 25 demonstrated a worse prognosis than those with caIMR < 25 for composite events (P = 0.006). Patients with caIMR ≥ 25 in multiple coronary arteries showed a trend to worse outcome than those with caIMR ≥ 25 in a single coronary artery (log-rank P = 0.056). In adjusted analysis, caIMR ≥ 25 was independently predictive of adverse outcomes (adjusted hazard ratio 2.93, 95% confidence interval [CI] 1.28-6.70; P = 0.010). caIMR displayed a significant predictive power for adverse event prediction (area under the receiver operating characteristic curve 0.767, 95% CI 0.677-0.858; P < 0.001). CONCLUSIONS: CMD is highly prevalent and is an independent predictor of adverse outcomes in HFpEF patients. Assessment of CMD may identify high-risk patients early for intensified treatment and risk-factor management.

Association of stress hyperglycemia ratio and poor long-term prognosis in patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. METHODS: A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73-0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan-Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. RESULTS: A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P < 0.001). The Kaplan-Meier curves demonstrate that SHR3 patients had the highest MACE risk compared to SHR1 and SHR2 patients (log-rank P < 0.001). In addition, when both SHR tertiles and diabetes status were considered, those with SHR3 and diabetes had the highest hazard of MACE (log-rank P < 0.001). Multivariate Cox regression analysis showed that the SHR3 is associated with a 2.465-fold increase in the risk of MACE (adjusted HR, 2.465; 95% CI 1.461-4.159, P = 0.001). The ROC curve analysis showed that the optimal SHR cut-off value for predicting clinical MACE among MINOCA was 0.86. CONCLUSION: Our data indicates, for the first time, that SHR is independently associated with poor long-term prognosis in patients suffering from MINOCA. The optimal SHR cut-off value for predicting clinical MACE among MINOCA patients was 0.86. These findings suggest that SHR may play a potential role in the cardiovascular risk stratification of the MINOCA population.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Effect of nonobstructive coronary stenosis on coronary microvascular dysfunction and long-term outcomes in patients with INOCA.

BACKGROUND: Ischemic pain with no-obstructive coronary artery (INOCA) is clinically significant and defined by nonobstructive coronary stenosis <50%. Coronary microvascular dysfunction (CMD) is a relevant cause associated with adverse outcomes. OBJECTIVES: Investigated the effect of no-stenosis (0% stenosis) and non-obstructive (0% < stenosis < 50%) on the prognostic impact of CMD in INOCA. METHOD: A retrospective study assessed the coronary microvascular function in 151 INOCA patients who underwent invasive angiography by the coronary angiography-derived index of microcirculation-resistance (caIMR). CZT-SPECT was performed to evaluate myocardial perfusion imaging (MPI) abnormalities. Chi-square test/Fisher exact test, Student t-test, Kaplan-Meier curve, and Uni-multivariable Cox proportional models were used for analysis. Clinical outcomes were major adverse cardiovascular events (MACE) during a median follow-up of 35 months. RESULT: No-stenosis was present in 71 (47%) INOCA patients, and 80 (53%) were with nonobstructive. CMD (caIMR ≥ 25) was more prevalent in patients with no-stenosis than nonobstructive (76.1% vs. 48.8%, p = .001), along with abnormal MPI (39.4% vs. 22.5%, p = .024). The MACE rates were not different between no-stenosis and nonobstructive stenosis. CMD showed an increased risk of MACE for all INOCA. No-stenosis with CMD had the worst prognosis. Cox regression analysis identified CMD and abnormal MPI as predictors of MACE in all INOCA and patients with no-stenosis. However, no-stenosis and nonobstructive stenosis were not predictors of MACE in INOCA. CONCLUSION: CMD was more frequently present in INOCA with no-stenosis. However, there was no difference in long-term clinical outcomes between no-stenosis and nonobstructive stenosis. CMD could independently predict poor outcomes in INOCA, particularly in patients with no-stenosis.

Prognostic implication of coronary slow flow assessed by cTFC in patients with myocardial infarction with Non-obstructive coronary arteries.

BACKGROUND: Coronary slow flow (CSF) is common and linked to worse cardiovascular events and life-threatening arrhythmias. However, the clinical implication of CSF among myocardial infarction with the non-obstructive coronary artery (MINOCA) has never been studied. We aimed to evaluate the impact of CSF on the MINOCA population. METHODS: Patients diagnosed with MINOCA were consecutively selected. The corrected TIMI frame count (cTFC) was used to evaluate the coronary flow. CSF was defined as cTFC greater than 27 frames per second (FPS) in any of the three coronary arteries. Major adverse cardiovascular events (MACE) are the primary endpoint. Cox regression analysis was used to evaluate the association between CSF and MACE. RESULTS: A total of 158 patients with MINOCA were enrolled, of which 54 (34.2%) patients had CSF. Forty incidents of MACE occurred during the median 28 months of follow-up. The MACE incidence was higher among patients who presented with CSF than the normal coronary flow patients (35.2% vs. 20.2%, p = 0.040). In the Kaplan-Meier analysis, CSF patients had significantly higher rates of MACE (log-rank P = 0.034). Multivariate Cox regression analysis showed that CSF was an independent predictor linked to an increased hazard of MACE (adjusted HR, 2.76; 95% CI, 1.34-5.67; P = 0.006). CONCLUSION: The presence of CSF is associated with a higher risk of adverse events and is an independent predictor of clinical outcomes among patients with MINOCA. This result suggests that CSF might serve as a robust tool to stratify MINOCA patients.

Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). METHODS: CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. RESULTS: Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066-7.146; P = 0.036). CONCLUSION: CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

Prognostic impact of coronary microvascular dysfunction assessed by caIMR in overweight with chronic coronary syndrome patients.

Objective: Coronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS). Methods: CCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE. Results: Two hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI. Conclusions: Impaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.

Combination of White Blood Cell Count to Mean Platelet Volume Ratio and Neutrophil-to-Platelet Ratio Predicts Long-Term Adverse Events in Patients with MINOCA.

Background: White blood cell count to mean platelet volume ratio (WMR) and neutrophil-to-platelet ratio (NPR) have been demonstrated as prognostic inflammatory biomarkers of the acute coronary syndrome. We aimed to evaluate the prognostic value of WMR and NPR among myocardial infarction with nonobstructive coronary arteries (MINOCA) patients. Method: A total of 274 MINOCA patients were enrolled. Baseline clinical data, blood cell panel, and biochemical parameters were evaluated. The patients were classified according to the medians of WMR and NPR. The primary endpoint of the present study was major adverse cardiovascular events (MACE). Multivariable Cox regression analysis was used to assess the effect of independent variables of WMR and NPR on the dependent variable (MACE). Result: The median values of WMR and NPR were 701 and 0.03, respectively. During the median follow-up of 28 months, a total of 58 incidences of MACE occurred. The MACE rate was more frequent in high WMR and high NPR patients. In Kaplan-Meier analysis, the incidence of MACE was higher in WMR>701 and NPR>0.03 (long-rank P = 0.004 and P = 0.002, respectively). The combined high WMR and high NPR showed a significantly higher rate of MACE (long-rank P = 0.001). Cox regression analysis showed that the combined high WMR and high NPR were independent predictors of long-term MACE with the highest hazard ratio (HR, 2.511; 95% CI, 1.271 to 4.960; P = 0.008). Conclusion: High WMR and NPR separately or in combination were correlated with increased risk of MACE among MINOCA patients, suggesting WMR and NPR may assist as a reliable inflammatory marker in risk prediction of MINOCA patients.

Association between Initial Serum Total Bilirubin and Clinical Outcome in Myocardial Infarction with Non-Obstructive Coronary Arteries.

Background: Liver function parameters, particularly serum total bilirubin (TB), are closely associated with cardiovascular diseases. However, the impact of serum TB among patients with myocardial infarction and non-obstructive coronary (MINOCA) remains unknown. Our study investigated the relationship between serum TB at admission and long-term adverse clinical outcomes in MINOCA patients. Methods: A total of 273 consecutive MINOCA patients were categorized into low and high serum TB groups based on the optimal cut-off of 0.9 mg/dl. The primary endpoint was major adverse cardiovascular events (MACE), including cardiac death, non-fatal MI, heart failure, and angina rehospitalization. Receiver-operating characteristic, Cox regression, and Kaplan-Meier analyses were used to evaluate the association of high serum TB with cardiovascular outcomes. Results: High serum TB was found in 68 (24.9%) patients. The incidence of MACE was higher in the high TB group than in the low TB group after a median follow-up of 28 months (30.9 vs. 17.1%, P=0.015). The Kaplan-Meier curve analysis also indicated that patients in the high TB group had a higher risk of developing MACE (log-rank P=0.023). Cox regression analysis showed that high serum TB (>0.9mg/dl) significantly correlated with increased MACE risk (HR=1.90, 95%CI: 1.12-3.22, P=0.018). After adjusting for numerous clinical variables, the high serum TB remained significantly associated with an increased risk of MACE (HR=2.04, 95%CI: 1.05-3.94, P=0.034). Conclusion: High initial serum TB (>0.9mg/dl) is a robust predictor of poor clinical outcomes among MINOCA patients. In clinical settings, assessing serum TB at admission may help identify high-risk patients presenting with MINOCA.

Metabolic syndrome and the risk of adverse cardiovascular events in patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND AND AIMS: Metabolic syndrome (MeS) is recognized as a significant predictor of poor outcomes in coronary artery disease. However, its prognostic implications in myocardial infarction with non-obstructive coronary arteries (MINOCA) have not been examined. We aimed at investigating the role of MeS on the clinical outcomes in MINOCA patients. METHODS AND RESULTS: Patients diagnosed with MINOCA between 2015 and 2019 were included. MeS was defined according to modified NCEP-ATPIII criteria. The primary endpoint was major adverse cardiovascular events (MACE). Cox regression analysis was used to evaluate the correlation between MeS and the hazard of MACE. The integrated discrimination improvement (IDI) and net reclassification index (NRI) were performed to assess MeS incremental predictive value. Of 281 MINOCA patients, 83 (29.5%) patients satisfied the MeS criteria. During a median follow-up duration of 28 months, MINOCA patients with MeS had a notably higher rate of MACE than those without MeS (30.1% vs. 17.6%, respectively P = 0.020). Cox regression analysis revealed that MeS was associated with an increased hazard of MACE (adjusted HR 2.126; 95% CI: 1.193-3.787, P = 0.010). When each component of MeS was analyzed as a categorized variable separately, only high fasting blood glucose and BMI ≥25 kg/m2 were associated with an increased hazard of MACE. Moreover, MeS had an incremental predictive ability for MACE when added to a model with clinical risk factors. CONCLUSION: MeS is relatively common in patients with MINOCA. The presence of MeS significantly increased the hazard of MACE among the MINOCA population.

Does Sex Influence Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries?

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.

Prognostic Significance of Uric Acid in Patients with Obstructive and Nonobstructive Coronary Artery Disease Undergoing D-SPECT.

PURPOSE: 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.

Hyperuricemia Predicts Adverse Outcomes After Myocardial Infarction With Non-obstructive Coronary Arteries.

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.

Prognostic Value of Diastolic Dysfunction Derived From D-SPECT in Coronary Artery Disease Patients With Normal Ejection Fraction.

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) <2.1 end diastolic volume (EDV, ml)/s according to the D-SPECT results. Patients were divided into three groups: group 1 (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.