T2-weighted imaging is commonly used to measure myocardial salvage in reperfused myocardial infarction but is hindered by poor reproducibility and indistinct boundaries. Early gadolinium enhancement (EGE) emerges as an alternative for measuring the area at risk. This study aims to evaluate the determinants of the myocardial salvage index (MSI) derived from EGE and its prognostic implications.

We analyzed acute cardiac magnetic resonance scans of 453 reperfused patients with ST-segment-elevation myocardial infarction (mean age, 60±12 years; 389 men) from April 2017 to July 2023 at a single center retrospectively. EGE was collected at 3 minutes after contrast agent injection, where hyperintense areas (signal intensities > mean+2SD of remote myocardium) were considered as the area at risk, plus the hypointense core within. MSI was calculated as the ratio of salvageable myocardium to the area at risk. Major adverse cardiovascular events included cardiovascular death, hospitalization for heart failure, reinfarction, and unplanned revascularization for the target vessel.

During a median follow-up of 3.2 years (interquartile range, 1.6-4.7 years), at least one major adverse cardiac event occurred in 91 participants (20.1%). The median MSI was 35.0% (interquartile range, 22.9-59.5%), with smaller MSI observed in patients with larger infarcts (P<0.001). Linear regression identified prepercutaneous coronary intervention Thrombolysis in Myocardial Infarction flow (β=3.35, P<0.001) and microvascular obstruction (β=-11.92, P<0.001) as independent determinants of MSI. Multivariable Cox regression showed that every 10% increase in MSI was associated with a 32% reduction in major adverse cardiac event risk (hazard ratio, 0.68 [95% CI, 0.53-0.86]; P=0.001). A graded response was observed between MSI and cardiovascular death and reinfarction. MSI greater than the median was associated with nontarget vessel-related reinfarctions but not target vessel-related ones (nontarget, P=0.027; target vessel, P=0.36). Good reproducibility was reported with EGE-measured area at risk (intraobserver, intraclass correlation coefficient [ICC]=0.95; interobserver, ICC=0.89).

EGE-derived MSI was associated with prepercutaneous coronary intervention Thrombolysis in Myocardial Infarction flow and microvascular injuries. It was an independent predictor of major adverse cardiac events. Our results highlight the prognostic potential of EGE imaging in acute myocardial infarction.

Coronary microvascular dysfunction has been associated with adverse cardiovascular events following acute myocardial infarction. This study evaluates the role of the angiography-derived index of microcirculatory resistance (angio-IMR) in predicting myocardial damage in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI).

In this post hoc analysis of the CLEVER-ACS (Controlled-Level Everolimus in Acute Coronary Syndromes) trial, the associations between post-PCI angio-IMR of infarct-related coronary arteries (IRAs) and infarct size, microvascular obstruction, and left ventricular ejection fraction at 30 days as assessed by cardiac magnetic resonance were investigated. High post-PCI angio-IMR was defined as ≥40 mm Hg*s . In non-IRAs, angio-IMR was measured before IRA-PCI. A total of 52 IRAs and 94 non-IRAs of 52 patients were analyzed. Post-PCI angio-IMR was 41.5 (interquartile range [IQR], 28.5-55.7) mm Hg*s  in IRAs and pre-PCI angio-IMR was 43.7 (IQR, 31.7-54.0) mm Hg*s in non-IRAs (P=0.70). Patients with high post-PCI angio-IMR (52%) exhibited a larger myocardial infarct size (36.0 [IQR, 23.0-52.5] g versus 14.5 [IQR, 6.50-26.5] g, P<0.001) and a lower left ventricular ejection fraction (46.5% [IQR, 39.5%-49.5%] versus 55.0% [IQR, 48.0%-61.4%], P=0.002) at 30 days as compared with those with low post-PCI angio-IMR values. Post-PCI angio-IMR positively correlated with myocardial infarct size (r=0.45, P=0.001) and extent of microvascular obstruction (r=0.40, P=0.004) at 30 days. Post-PCI angio-IMR predicted myocardial infarct size (area under the curve, 0.78 [IQR, 0.65-0.92]; P=0.001) and extent of microvascular obstruction (area under the curve, 0.74 [IQR, 0.60-0.89]; P=0.009) at 30 days.

In patients with ST-segment-elevation myocardial infarction, post-PCI angio-IMR was identified as independent predictor of myocardial infarct size and extent of microvascular obstruction.

URL: https://clinicaltrials.gov; Unique Identifier: NCT01529554.

The growing prevalence in the diagnosis of INOCA (Ischemia with Non-Obstructive Coronary Arteries), ANOCA (Angina with Non-Obstructive Coronary Arteries), and MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) highlights the need to reassess their clinical relevance. Historically regarded as benign syndromes, emerging evidence suggests that these conditions may cause serious cardiovascular events and considerable long-term disability. Additionally, emerging studies suggest that non-obstructive coronary artery disease (CAD) may have a higher prevalence compared to traditional obstructive forms of CAD. This leads to the need to better clarify the underlying pathogenic mechanisms as well as the risk factors associated with these syndromes. This is precisely the aim of this review, which focuses on the complex and heterogeneous mechanisms underlying these syndromes as well as the associated risk factors. This review also sums up the diagnostic steps necessary to achieve an accurate diagnosis, along with the interventional and pharmacological approaches to be implemented in light of the latest evidence.

The assessment of coronary function and microcirculation in patients with ST-segment elevation myocardial infarction (STEMI) may be useful to guide long-term prognosis, but the research is limited. This study aimed to investigate the value of angio-based fraction flow reserve (AccuFFR) and an index of microcirculatory resistance (AccuIMR) after percutaneous coronary intervention (PCI) for evaluating the long-term prognosis of STEMI patients.

Data of patients with STEMI who underwent PCI at Peking University Third Hospital between January 2017 and March 2022 were retrospectively analyzed. AccuFFR and AccuIMR were analyzed immediately after primary PCI. According to AccuFFR and AccuIMR, patients were classified into 4 groups: normal coronary function, macrovascular disorder, microvascular disorder, and mixed disorder.

A total of 1297 patients were enrolled. The median follow-up time was 35 (24, 58) months. The risks of major adverse cardiovascular events (MACE), all-cause death, cardiovascular death, and readmission for heart failure in the mixed disorder group were significantly higher than those in the other 3 groups (all P < 0.001). Both AccuFFR (hazard ratio [HR], 0.948 per 0.01 increase; 95% confidence ratio [CI], 0.914-0.983; P = 0.004) and AccuIMR (HR, 1.018; 95% CI, 1.009-1.027; P < 0.001) were independent predictors of MACE. A nomogram model was established to predict MACE after PCI in patients with STEMI at 1, 3, and 5 years. The receiver-operating characteristic (ROC) curve, C-index, and calibration curve showed that the model had high discrimination.

Coronary function and microcirculation assessment immediately after primary PCI are important in evaluating the prognosis of patients with STEMI.

NCT06435728.

Several methods for measuring IMR derived from angiography have been developed. AngioIMR is a novel method for the assessment of angiography-derived IMR with no requirement for a wire and hyperemia. The prognostic value of AngioIMR is unknown in STEMI patients. We aimed to provide the prognostic value of AngioIMR in patients with ST-elevation myocardial infarction (STEMI).

This study included patients with STEMI who underwent invasive coronary angiography and primary percutaneous coronary intervention (PPCI). AngioIMR was calculated using computational flow and pressure simulation immediately after PPCI. The presence of significant coronary microvascular dysfunction was defined as AngioIMR > 40. The primary outcome was a composite of all cause death or hospitalization for heart failure (MACE).

A total of 178 patients were included (65.0 ± 12.8 years on average, 74 % male gender). An AngioIMR > 40 was found in 72 patients. During a median follow-up of 2.9 (2.3-6.9) years, a primary endpoint was observed in 56 patients. By Kaplan-Meier analysis, the risk of MACE was significantly higher in patients with AngioIMR > 40 (log-rank P < 0.01). An Angio IMR > 40 was significantly associated with the occurrence of the primary endpoint in univariate (70 % vs 27 %; hazard ratio 4.519; 95 % CI: 2.550-8.009; p < 0.0001) and multivariate analysis (Hazard ratio 4.282; 95 % CI: 2.325-7.886; p < 0.0001). AngioIMR model showed incremental prognostic value compared to a model with clinical and imaging risk predictors (C-index 0.84 vs 0.79; p = 0.04).

Elevated AngioIMR showed a independent prognostic significance in STEMI patients. In addition to well-known risk factors, assessment of coronary microvascular dysfunction can be a feasible approach for early prevention and a therapeutic target in STEMI patients.

Angiography-derived microcirculatory resistance (AMR) is proposed as a novel, pressure- temperature-wire-free and less-invasive method to evaluate coronary microvascular dysfunction (CMD). This study aims to examine the prognostic role of CMD assessed by AMR in predicting adverse events in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD).

This retrospective cohort study included ACS with CKD patients in the China-Japan Friendship Hospital from January 2016 to November 2022. The patients were divided into CMD and non-CMD groups based on AMR values of less than or greater than 250 mmHg*s/m.

A total of 345 eligible patients were included in this study. During a median follow-up of 23.0 months, higher prevalence rate of MACEs (28.3% vs. 15.1%, P = 0.003) and death (20.2% vs. 4.1%, P = 0.001) were observed in the CMD group. In multivariate Cox regression analysis, patients in the group of CMD had a 1.843 times higher hazard ratio (HR) for developing MACEs (HR: 1.843, 95% CI: 1.071-3.174, P = 0.027) and 5.325 times higher HR for developing death (HR: 5.325, 95% CI: 1.979-14.327, P < 0.001) for every 10 mmHg*s/m increment in AMR. The incorporation of AMR improved the predictive accuracy of the GRACE score for MACEs and death.

This study indicates that the AMR is significantly related to poor prognosis among patients with ACS and CKD. Furthermore, AMR could improve the predictive power of the GRACE risk score. These results indicated that AMR may serve as a valuable clinical tool for classification, risk stratification or therapy individualization in these patients.

Coronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary heart disease (CHD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CHD has not been systemically quantified.

We searched electronic databases for studies on patients with CHD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios.

We included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P<.01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P<.01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value=.95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P<.01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P<.01) (interaction P value<.01).

CMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CHD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CHD populations.

In patients diagnosed with ST-segment elevation myocardial infarction (STEMI), despite exhibiting normal patency in the culprit arteries following percutaneous coronary intervention (PCI), coronary microvessels do not recover adequately, leading to microvascular dysfunction (MVD). Limited data are available regarding microcirculation assessed through invasive measures during the midterm period. This study aimed to investigate the assessment of MVD in STEMI patients using the index of microvascular resistance (IMR) during the midterm period.We prospectively evaluated 41 patients with STEMI who underwent PCI. IMR was measured by placing a coronary pressure wire with intravenous adenosine at 1 week as the acute phase and at 6 months after primary PCI as the midterm period. An improvement in IMR was observed from baseline to follow-up, with values changing from 30.00 (15.00-45.50) to 19.00 (10.50-30.50) (P = 0.020). The degree of MVD significantly decreased during follow-up (from 61.0% to 34.1%, McNemar's test: P = 0.016). Compared to patients with normal microcirculation, those with MVD (IMR > 25) at midterm follow-up exhibited significantly elevated levels of brain natriuretic peptide (180.25 [68.25-370.65] pg/mL versus 75.90 [18.70-169.70] pg/mL, P = 0.043) and prolonged symptom-onset-to-balloon time (727.00 [213.50-1170.00] minutes versus 186.00 [125.00-316.00] minutes, P = 0.002).These findings indicate that the extent of MVD 6 months post-PCI has significantly diminished compared to discharge levels and is associated with symptom-onset-to-balloon time. Therefore, MVD in patients with STEMI can potentially improve in the midterm under specific circumstances.

In this review article, we provide an overview of the definition and application of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), coronary flow reserve (CFR), and index of microvascular resistance (IMR) in the diagnosis, prognosis, and management of coronary microvascular dysfunction. We discuss their respective limitations as it relates to microvascular dysfunction. In each section, we review the most recent evidence supporting their use in microvascular and epicardial coronary artery disease. We also highlight specific clinical conditions with emerging indications for the use of these indices, including in the setting of microvascular dysfunction due to acute myocardial infarction, heart failure with preserved ejection fraction, and post-cardiac transplant.

Intravascular ultrasound (IVUS)-guided optimization of suboptimal fractional flow reserve (FFR) following percutaneous coronary intervention (PCI) results in a significant increase in both post-PCI FFR and minimal lumen and stent areas (MLA and MSA, respectively). However, the impact of clinical presentation with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) versus chronic coronary syndrome (CCS) on the efficacy of PCI optimization remains unknown.

This was a prespecified subgroup analysis of the FFR REACT trial comparing IVUS-guided PCI optimization versus no further treatment in 291 patients with a post-PCI FFR < 0.90. Post-PCI physiology and pre optimization IVUS findings were compared between patients presenting with NSTE-ACS versus CCS, as well as optimization strategy, final FFR and IVUS findings.

Out of 291 patients, 130 (44.7%) presented with NSTE-ACS. Median post-PCI FFR was similar in patients with NSTE-ACS and CCS (0.85 for both, p = 0.55). Pre optimization IVUS findings did not differ significantly between both groups and subsequent optimization strategy was comparable (p = 0.71). In both NSTE-ACS and CCS, optimization resulted in a significant increase (p < 0.01 for all) of similar magnitude in median FFR (0.02 vs. 0.03, p = 0.80), MLA (0.37 vs. 0.50 mm2, p = 0.46) and MSA (0.29 vs. 0.32 mm2, p = 0.61), respectively. The clinical impact of IVUS-guided optimization on 2-year target vessel failure showed no signs of heterogeneity based on clinical presentation (interaction p = 0.36).

In patients undergoing FFR-directed IVUS-guided optimization, post-PCI FFR, pre optimization IVUS findings and optimization strategy did not differ significantly between patients presenting with either NSTE-ACS or CCS, with comparable improvements in FFR, MLA and MSA.

This study aims to elucidate the association between serum levels of circular RNAs circ_0001879 and circ_0004104 and the occurrence of coronary microcirculation disorders along with post-PCI prognosis in individuals with stable coronary heart disease.

A cohort of 92 patients diagnosed with stable coronary heart disease and subjected to PCI between June 2020 and June 2022 at our institution was assembled. Patients were categorized into an exposed group (n = 60) and a non-exposed group (n = 32), predicated on the coronary angiography-derived microcirculation resistance index (caIMR).

Comparative analysis revealed significantly elevated levels of circ_0001879 and circ_0004104 in the serum of the exposed group compared to the non-exposed group, with statistical significance (P < 0.05). Post-PCI, both caFFR and caIMR values demonstrated a marked increase in comparison to pre-surgical measurements within both groups, with the exposed group exhibiting lower indices post-surgery relative to the non-exposed group, indicative of superior microcirculatory outcomes (P < 0.05). Furthermore, serum levels of circ_0001879 and circ_0004104 were inversely correlated with favorable prognosis, with lower levels observed in patients with positive outcomes (P < 0.05). The predictive accuracy for poor prognosis, as indicated by the area under the curve (AUC), was enhanced when circ_0001879 and circ_0004104 were considered in tandem (AUC = 0.934), surpassing the predictive power of individual assessments (Z combination vs circ_0001879 = 2.439, Z combination vs circ_0004104 = 2.317, P < 0.05).

Elevated serum levels of circ_0001879 and circ_0004104 are observed in stable coronary heart disease patients and are significantly associated with the presence of coronary microcirculation disorders and post-PCI prognosis, underscoring their potential as prognostic biomarkers.

Coronary slow flow (CSF) is a common phenomenon of coronary microcirculation dysfunction, and is closely related to elevated blood glucose and fibrinogen (FIB) levels. However, whether immediate blood glucose and FIB levels affect coronary blood flow during primary percutaneous coronary intervention (PCI) remains unclear.

To explore the correlation between admission blood glucose (ABG), fibrinogen (FIB) and slow blood flow during primary PCI for acute ST segment elevation myocardial infarction (STEMI).

A total of 497 patients who underwent coronary angiography in the cardiology department of the 904th Hospital of the Joint Logistics Support Force from December 2018 to December 2022 due to STEMI were selected consecutively, and then were divided into two groups based on whether slow blood flow occurred during primary PCI: slow blood flow group (n = 117) and control group (n = 380). Detecting the ABG, FIB and other indicators of patients in each group, and using logistic regression analysis and receiver operating characteristic (ROC) curve to analyze independent risk factors for slow blood flow during primary PCI, and further evaluating the prognosis of patients.

The levels of ABG and FIB in patients with slow blood flow were significantly higher than those in the control group (P < 0.05). The results of multivariate logistic regression analysis suggested that FIB and ABG were independent risk factors for slow blood flow during primary PCI (both P < 0.05). ROC curve analysis showed that ABG, FIB, and their combination all had predictive value for slow blood flow during primary PCI (all P < 0.05), and the area under the curve (AUC) of the combined indicator was higher than that of any single indicator, with statistical significance (P < 0.05). KM curve analysis suggested that the prognosis of patients in slow blood flow group were poor.

Both elevated ABG and FIB could predict slow blood flow during primary PCI, and the diagnostic value of the combined indicator was superior to that of any single indicator, which could be used for the evaluation of slow blood flow during primary PCI, so as to evaluate the prognosis of patients with STEMI.

In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography.

The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations.

We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%.

Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography.

Traditionally, coronary angiography was restricted to visual estimation of contrast-filled lumen in coronary obstructive diseases. Over the previous decades, considerable development has been made in quantitatively analyzing coronary angiography, significantly improving its accuracy and reproducibility.  Notably, the integration of artificial intelligence (AI) and machine learning into quantitative coronary angiography (QCA) holds promise for further enhancing diagnostic accuracy and predictive capabilities. In addition, non-invasive fractional flow reserve (FFR) indices, including computed tomography-FFR, have emerged as valuable tools, offering precise physiological assessment of coronary artery disease without the need for invasive procedures. These innovations allow for a more comprehensive evaluation of disease severity and aid in guiding revascularization decisions. This review traces the development of QCA technologies over the years, highlighting key milestones and current advancements. It also explores prospects that could revolutionize the field, such as AI integration and improved imaging techniques. By addressing both historical context and future directions, the article underscores the ongoing evolution of QCA and its critical role in the accurate assessment and management of coronary artery diseases. Through continuous innovation, QCA is poised to remain at the forefront of cardiovascular diagnostics, offering clinicians invaluable tools for improving patient care.

We retrospectively investigated the relationship between cardiopulmonary exercise testing (CPET) parameters and coronary microvascular dysfunction (CMD) using a novel angiography-based index of microcirculatory resistance (AccuIMR) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) with complete revascularization. In 418 patients, the culprit vessel AccuIMR was calculated after successful primary PCI. CPET was conducted 44.04 ± 19.28 days after primary PCI. Overall, 157 patients (37.6%) showed elevated AccuIMR (> 40 U) in the culprit vessels. The LVEF was significantly lower in the CMD group than in the Non-CMD group. The CMD group showed worse results in VO2peak, peak O2-pulse, and VE/VCO2 slope than the Non-CMD group. Spearman correlation analysis suggested that VO2peak (r = -0.354), peak O2-pulse (r = -0.385) and VE/VCO2 slope (r = 0.294) had significant linear correlations with AccuIMR (P < 0.001). Multivariable logistic regression analysis showed that AccuIMR was the independent predictor of reduced VO2peak and elevated VE/VCO2 slope. The proportions of positive and equivocal ECG results and early O2-pulse flattening in the CMD group were significantly higher than those in the Non-CMD group, and AccuIMR was the only independent predictor of these ischemia-relating indicators, suggesting that patients with CMD had significant noninvasively detectable myocardial ischemia.

Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients.

This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation.

TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46-0.64; p = 0.426), and 0.80 (95 % CI 0.73-0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors.

TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.

Functional coronary angiography (FCA) is a novel modality for assessing the physiology of coronary lesions, going beyond anatomical visualization by traditional coronary angiography. FCA incorporates indices like fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR), which utilize pressure measurements across coronary stenoses to evaluate hemodynamic impacts and to guide revascularization strategies. In this review, we present traditional and evolving modalities and uses of FCA. We will also evaluate the existing evidence and discuss the applicability of FCA in various clinical scenarios. Finally, we provide insight into emerging evidence, current challenges, and future directions in FCA.

Lately, a large number of stable ischemic patients, with no obstructed coronary arteries are being diagnosed. Despite this condition, which is being described as angina with no obstructive coronary arteries (ANOCA), was thought to be benign, recent evidence report that it is associated with increased risk for adverse cardiovascular outcomes. ANOCA is more frequent in women and, pathophysiologically, it is predominantly related with microvascular dysfunction, while other factors, such as endothelial dysfunction, inflammation and autonomic nervous system seem to also play a major role to its development, while other studies implicate ANOCA and microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction. For establishing an ANOCA diagnosis, measurement including coronary flow reserve (CFR), microvascular resistance (IMR) and hyperemic microvascular resistance (HMR) are mostly used in clinical practice. In addition, new modalities, such as optical coherence tomography (OCT) are being tested and show promising results for future diagnostic use. Regarding management, pharmacotherapy consists of a wide selection of drugs, according to the respected pathophysiology of the disease (vasospastic angina or microvascular dysfunction), while research for new treatment options including interventional techniques, is currently ongoing. This review, therefore, aims to provide a comprehensive analysis of all aspects related to ANOCA, from pathophysiology to clinical managements, as well as clinical implications and suggestions for future research efforts, which will help advance our understanding of the syndrome and establish more, evidence-based, therapies.

Microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) has important prognostic implications. While invasive index of microvascular resistance (IMR) have been shown to predict the occurrence and extent of MVO, the role of the angiography-based microvascular resistance (Angio-IMR) for this purpose remains unknown. The present study aims to perform a head-to-head comparison of wire-based and angiography-derived microcirculatory resistance (IMR and Angio-IMR, respectively) for the detection of MVO.

Patients with a first STEMI and multivessel disease underwent CMR for detection of MVO, and angio-IMR and IMR measurements during PPCI and at 30 day follow up, both in STEMI culprit and non-culprit vessels.

58 patients were included (mean age 60.7 ± 9.9 years, 82% male). At the time of PPCI, angio-IMR and IMR exhibited significant correlation (r = 0.70, P < 0.001), and agreement (coefficient of agreement 0.58). Both indices showed good predictive value of MVO [Angio IMR: AUC 0.79 (95% CI: 0.667-0.928); IMR: AUC 0.70 (95% CI: 0.539-0.853); p = 0.15]. Angio-IMR 40 U and IMR 34 U were identified as best cut-offs for prediction of MVO. In non-culprit vessels, angio-IMR and IMR also correlated well (rho = 0.59, p < 0.001), with overall lower mean values compared to culprit vessels (Angio-IMR: 36 vs. 23; IMR: 39 vs. 22, p < 0.001 for both comparisons).

Angio-IMR constitutes a valid alternative to wire-based IMR in predicting MVO in STEMI. Angio-IMR and IMR show a good correlation in the acute and subacute STEMI phases, both in culprit and non-culprit vessels.

The index of microcirculatory resistance is a reliable measure for evaluating coronary microvasculature, but its prognostic value in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear.

This study aimed to evaluate the prognostic impact of postpercutaneous coronary intervention (PCI) angiography-derived index of microcirculatory resistance (angio-IMR) in patients with NSTEMI.

The culprit vessel's angio-IMR was measured after PCI in 2,212 NSTEMI patients at 3 sites. The primary endpoint was 2-year major adverse cardiac events (MACEs), defined as a composite of cardiac death, readmission for heart failure, myocardial reinfarction, and target vessel revascularization.

The mean post-PCI angio-IMR was 20.63 ± 4.17 in NSTEMI patients. A total of 206 patients were categorized as the high post-PCI angio-IMR group according to maximally selected log-rank statistics. Patients with angio-IMR >25 showed a higher rate of MACEs than those with angio-IMR ≤25 (32.52% vs 9.37%; P < 0.001). Post-PCI angio-IMR >25 was an independent predictor of MACEs (HR: 4.230; 95% CI: 3.151-5.679; P < 0.001) and showed incremental prognostic value compared with conventional risk factors (AUC: 0.774 vs 0.716; P < 0.001; net reclassification index: 0.317; P < 0.001; integrated discrimination improvement: 0.075; P < 0.001).

In patients undergoing PCI for NSTEMI, an increased post-PCI angio-IMR is associated with a higher risk of MACEs. The addition of post-PCI angio-IMR into conventional risk factors significantly improves the ability to reclassify patients and estimate the risk of MACEs. (Angiograph-Derived Index of Microcirculatory Resistance in Patients With Acute Myocardial Infarction; NCT05696379).

Cardiogenic shock (CS) complicating myocardial infarction is associated with poor outcomes. Data among Asian populations are scarce. We aimed to investigate the long-term outcomes, prognostic factors, and predictors of CS among Asian ST elevation myocardial infarction (STEMI) patients.

This was a retrospective cohort study of consecutive patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI within our regional STEMI network between 2015 and 2019. The long-term outcomes of those with and without CS were compared. Clinical predictors of outcomes and development of CS were investigated.

A total of 1791 patients who underwent PPCI were included. Patients completed at least 2 years' follow-up with a median follow-up period of 2.6 years (IQR 1.0, 3,9). Overall, 208/1791 (11.6 %) STEMI patients developed CS. These patients were older (61.1 ± 12.5 vs 57.8 ± 12.2, P < 0.001) and mostly men (87.0 %). All-cause mortality (59.9 % vs 4.7 % P < 0.001), cardiac mortality (43.8 % vs 2.2 %, P < 0.001) and major adverse cardiovascular events (MACE) was significantly higher in the CS group (59.1 % vs 14.0 %, P < 0.001). Independent predictors of survival were higher index LVEF (adjusted hazards ratio [aHR] 0.967, 95 %CI 0.951-0.984, p < 0.001) and higher arterial pH at onset of shock (aHR 0.750, 0.626-0.897, p = 0.002). Increased serum lactate concentration independently predicts poor prognosis (aHR 1.084, 95 % CI 1.046-1.124, p < 0.001).

In Asian STEMI patients who underwent PPCI, CS was associated with poor outcomes. Higher LVEF on index admission was associated with better outcomes; while lactic acidosis independently predicted mortality.

Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

The Angiographic Microvascular Resistance (AMR), derived from a solitary angiographic view, has emerged as a viable substitute for the Index of Microcirculatory Resistance (IMR). However, the prognostic significance in ST-Segment Elevation Myocardial Infarction (STEMI) patients is yet to be established. This research endeavors to explore the prognostic capabilities of AMR in patients diagnosed with STEMI.

In this single-center, retrospective study, 232 patients diagnosed with STEMI who received primary Percutaneous Coronary Intervention (PCI) were recruited from January 1, 2018, to June 30, 2022. Utilizing the maximally selected log-rank statistics analysis, participants were divided into two cohorts according to an AMR threshold of 2.55 mmHg*s/cm. The endpoint evaluated was a composite of all-cause mortality or hospital readmission due to heart failure.

At a median follow-up of 1.74 (1.07, 3.65) years, the composite endpoint event was observed in 28 patients within the higher AMR group and 8 patients within the lower AMR group. The higher AMR group showed a significantly higher risk for composite outcome compared to those within the low-AMR group (HRadj: 3.33; 95% CI 1.30‒8.52; p = 0.03). AMR ≥ 2.55 mmHg*s/cm was an independent predictor of the composite endpoint (HR = 2.33; 95% CI 1.04‒5.21; p = 0.04). Furthermore, a nomogram containing age, sex, left ventricle ejection fraction, post-PCI Quantitative Flow Ratio (QFR), and AMR was developed and indicated a poorer prognosis in the high-risk group for STEMI patients at 3 years. (HR=4.60; 95% CI 1.91‒11.07; p < 0.01).

AMR measured after PCI can predict the risk of all-cause death or readmission for heart failure in patients with STEMI. AMR-involved nomograms improved predictive performance over variables alone.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI.

We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD.

A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs. 24.36±2.73 kg/m2, P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs. 54.5%, P=0.011; 61.9% vs. 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence.

The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.

Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease.

This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization.

During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate.

An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.

This article provides a summary of the clinical spectrum of no obstructive coronary arteries. We describe the pathologies, invasive and noninvasive assessment, and management strategies.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Despite prompt epicardial recanalization in patients presenting with ST-segment elevation myocardial infarction (STEMI), coronary microvascular obstruction and dysfunction (CMVO) is still fairly common and is associated with poor prognosis. Various pharmacological and mechanical strategies to treat CMVO have been proposed, but the positive results reported in preclinical and small proof-of-concept studies have not translated into benefits in large clinical trials conducted in the modern treatment setting of patients with STEMI. Therefore, the optimal management of these patients remains a topic of debate. In this Review, we appraise the pathophysiological mechanisms of CMVO, explore the evidence and provide future perspectives on strategies to be implemented to reduce the incidence of CMVO and improve prognosis in patients with STEMI.

Optimal myocardial reperfusion during primary percutaneous coronary intervention (pPCI) is increasingly recognized to be beyond restoring epicardial coronary flow. Both invasive and non-invasive tools have highlighted the limitation of using this metric, and more efforts are focused towards achieving optimal reperfusion at the level of the microcirculation. Recent data highlighted the close relationship between thrombus burden and impaired microcirculation in patients presenting with ST-segment elevation myocardial infarction (STEMI). Moreover, distal embolization was an independent predictor of mortality in patients with STEMI. Likewise, the development of no-reflow phenomenon has been directly linked with worse clinical outcomes. Adjunctive thrombus aspiration during pPCI is intuitively intended to remove atherothrombotic material to mitigate the risk of distal embolization and the no-reflow phenomenon (NRP). However, prior trials on the use of thrombectomy during pPCI did not support its routine use, with comparable clinical endpoints to patients who underwent PCI alone. This article aims to review the existing literature highlighting the limitation on the use of thrombectomy and provide future insights into trials investigating the role of thrombectomy in contemporary pPCI.

Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques.

This study aimed to examine the influence of vessel volume on bolus thermodilution measurements.

We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment.

Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001).

In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.