Search Results (38)

Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in −3.35 standardised mean difference (SMD) (95% CI: −5.13; −1.56), trimetazidine in −1.74 SMD (−2.63; −0.85), traditional Chinese medicine in −1.55 SMD (−2.36; −0.75), beta-blockers in −1.32 SMD (−1.88; −0.77), enhanced external counterpulsation in −1.27 SMD (−2.04; −0.49), stem cell therapy in −1.04 SMD (−1.51; −0.57), lifestyle interventions in −0.86 SMD (−1.15; −0.57), RAAS-inhibitors in −0.83 SMD (−1.31; −0.35) and calcium channel blockers in −0.64 SMD (−0.92; −0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA. Full article

Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant percentage of patients still have compromised microvascular circulation, which is linked to higher cardiovascular mortality and hospitalization for heart failure. The well-known invasive methods, such as the index of microvascular resistance (IMR) and the coronary flow reserve (CFR), have been considered as gold standards. However, they are constrained by their hazards and complexity. Non-invasive techniques, such as echocardiography Doppler for CFR assessment, positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), and some other techniques provide alternatives, but their accessibility, cost and implementation during the peri-AMI period raise obstacles to their wider use. This review highlights both invasive and non-invasive modalities as it examines the diagnostic methods and prognostic significance of CMVD development early after AMI. Enhancing long-term results in this high-risk population requires a thorough understanding of pathophysiology and a commitment to larger diagnostic and prognostic studies for CMVD. Full article

Aortic stenosis (AS) frequently coexists with coronary artery disease (CAD), complicating revascularization decisions. The use of coronary physiology indices, such as the fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and coronary flow reserve (CFR), in AS patients remains debated, particularly after transcatheter aortic valve implantation (TAVI). In this study, we employ computational fluid dynamics (CFD) to evaluate coronary hemodynamics and assess changes in the wall shear stress (WSS) before and after TAVI. Our analysis demonstrates strong agreement between CFD-derived and invasive FFR measurements, confirming CFD’s reliability as a non-invasive tool for coronary physiology assessment. Furthermore, our results show no significant changes in FFR ($p=0.92$), iFR ($p=0.67$), or CFR ($p=0.34$) post-TAVI, suggesting that these indices remain stable following aortic valve intervention. However, a significant reduction in high WSS exposure (59% to 40.8%, $p<0.001$) and the oscillatory shear index (OSI: 0.32 to 0.21, $p<0.001$) was observed, indicating improved hemodynamic stability. These findings suggest that coronary physiology indices remain reliable for revascularization guidance post-TAVI and highlight a potential beneficial effect of aortic stenosis treatment on plaque shear stress dynamics. Our study underscores the clinical utility of CFD modeling in CAD management, paving the way for further research into its prognostic implications. Full article

Cardiovascular disease (CVD) is a leading cause of death, accounting for over 30% of annual global fatalities. Ischemic heart disease, in turn, is a frontrunner of worldwide CVD mortality. With the burden of coronary disease rapidly growing, understanding the nuances of cardiac imaging and risk prognostication becomes paramount. Myocardial perfusion imaging (MPI) is a frequently utilized and well established testing modality due to its significant clinical impact in disease diagnosis and risk assessment. Recently, nuclear cardiology has witnessed major advancements, driven by innovations in novel imaging technologies and improved understanding of cardiovascular pathophysiology. Applications of artificial intelligence (AI) to MPI have enhanced diagnostic accuracy, risk stratification, and therapeutic decision-making in patients with coronary artery disease (CAD). AI techniques such as machine learning (ML) and deep learning (DL) neural networks offer new interpretations of immense data fields, acquired through cardiovascular imaging modalities such as nuclear medicine (NM). Recently, AI algorithms have been employed to enhance image reconstruction, reduce noise, and assist in the interpretation of complex datasets. The rise of AI in nuclear medicine (AI-NM) has proven itself groundbreaking in the efficiency of image acquisition, post-processing time, diagnostic ability, consistency, and even in risk-stratification and outcome prognostication. To that end, this narrative review will explore these latest advances in AI in nuclear medicine and its rapid transformation of the cardiac diagnostics landscape. This paper will examine the evolution of AI-NM, review novel AI techniques and applications in nuclear cardiac imaging, summarize recent AI-NM clinical trials, and explore the technical and clinical challenges in its implementation of artificial intelligence. Full article

Background: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is linked to the progression of cardiovascular conditions, but its role in coronary microcirculation dysfunction (CMD) is not yet clear. Methods: A cross-sectional observational study from July 2023 to May 2024 was conducted in the China–Japan Friendship Hospital, after registration in the ClinicalTrials database (Registry Name: Coronary Microvascular Dysfunction in Angina Patients With Non-obstructive Coronary Artery Disease (ANOCA-CMD); Registry Number: NCT06503640; Registry Date: 23 September 2022). This cross-sectional study involved 76 subjects, including 55 patients with CMD and 21 without CMD, admitted to the China–Japan Friendship Hospital. CMD was defined by a coronary flow reserve (CFR) < 2.5 or index of microvascular resistance (IMR) ≥ 25. sTREM2 levels were measured using an enzyme-linked immunosorbent assay. Linear correlation analysis assessed the relationship between sTREM2 levels and CFR, IMR, microvascular resistance reserve (MRR), and the resistive reserve ratio (RRR). Univariate and multivariate regression analyses further examined the association between sTREM2 and CMD. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of plasma sTREM2 for identifying CMD patients. Results: Elevated sTREM2 levels were found in the CMD group. Correlation analysis showed a significant positive relationship with IMR and an inverse correlation with CFR, MRR, and RRR. After adjusting for confounders, sTREM2 was found to be an independent risk factor for CMD [OR = 1.003, 95% CI 1.001–1.007, p = 0.008]. ROC analysis revealed a sensitivity of 59.46%, specificity of 90.48%, and an AUC of 0.7677 (95% CI: 0.6481–0.8872, p = 0.008) for CMD diagnosis at a threshold of 595.5 pg/mL, indicating good diagnostic performance. Conclusions: Elevated sTREM2 levels in CMD patients indicate its potential as a biomarker. Full article

Background: The choice of software package (SP) for image processing affects the reproducibility of myocardial blood flow (MBF) values in [¹³N]NH₃ PET/CT scans. However, the impact of motion correction (MC) tools—integrated software motion correction (ISMC) or data-driven motion correction (DDMC)—on the inter-software reproducibility of MBF has not been studied. This research aims to evaluate reproducibility among three commonly used SPs and the role of MC. Methods: Thirty-six PET/CT studies from patients without myocardial ischemia or infarction were processed using QPET, Corridor-4DM (4DM), and syngo.MBF (syngo). MBF and coronary flow reserve (CFR) values were obtained without motion correction (NMC) and with ISMC and DDMC. Intraclass correlation coefficients (ICC) and Bland-Altman (BA) plots were used to analyze agreement. Results: Good or excellent reproducibility (ICC ≥ 0.77) was found for rest-MBF values, regardless of the SPs or use of MC. In contrast, stress-MBF and CFR values presented mostly a moderate agreement when NMC was used. The RCA territory consistently had the lowest agreement in stress-MBF and CFR in the comparisons involving QPET. The use of MC, particularly DDMC, enhanced the reproducibility of most of the stress-MBF and CFR values by improving ICCs and reducing bias and limits of agreement (LoA) in BA analysis. Conclusions: MBF quantification agreement between SPs is strong for rest-MBF values but suboptimal for stress-MBF and CFR values. MC tools, especially DDMC, are recommended for improving reproducibility in stress-MBF assessments, although differences in SP reproducibility up to 0.77 mL/g/min in global stress-MBF and up to 0.88 in global CFR remain despite the use of MC. Full article

Background/Objectives: Acute rejection remains a major challenge in pediatric heart transplantation (HT), with limited tools for early diagnosis. In adult HT recipients, microcirculatory dysfunction, as measured by the index of microcirculatory resistance (IMR), has been identified as a potential biomarker of rejection. However, its role in pediatric populations is largely unexplored. This pilot study aimed to evaluate the association between coronary microcirculatory dysfunction and acute rejection in pediatric heart transplant recipients, as well as its relationship with echocardiographic alterations. Methods: This prospective, single-center study included 10 pediatric HT recipients who underwent routine coronary angiography and endomyocardial biopsy. The IMR, coronary flow reserve (CFR), and fractional flow reserve (FFR) were assessed. Acute rejection was classified as either acute cellular rejection (ACR) or antibody-mediated rejection (AMR) based on ISHLT criteria. Echocardiographic parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), right ventricular (RV) dysfunction, and diastolic function. Patients were followed for a median of 9.7 months [IQR: 7.0–11.7]. Results: Patients with a history of acute rejection (40%, n = 4) were exclusively found in the IMR ≥ 15 group (66.7%), while no cases were observed in the IMR < 15 group (0%; p = 0.04). During follow-up, only one patient experienced acute rejection, occurring in the IMR ≥ 15 group, although the difference between groups was not statistically significant (p = 0.39). Both LVEF and GLS were worse in patients with IMR ≥ 15 compared to IMR < 15 (62.5% vs. 76.3% and −17.3% vs. −18.8%, respectively), although these differences did not reach statistical significance. No complications were reported during coronary physiology assessment. Conclusions: Microcirculatory dysfunction, as measured by IMR, was significantly associated with a history of acute cellular rejection in pediatric heart transplant recipients. While its predictive value for acute rejection during follow-up remains unclear due to the small sample size, this pilot study highlights the safety and feasibility of coronary physiology assessment in this population. Larger studies are needed to validate these findings and establish pediatric-specific diagnostic thresholds. Full article

Background/Objectives: Coronary microvascular dysfunction (CMD) is emerging as a critical factor in patients presenting with anginal symptoms without obstructive coronary artery disease (CAD). This study aims to investigate the relationship between invasive measurements of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) using thermodilution techniques, compared to non-invasive assessments of CFR with transthoracic Doppler echocardiography (TDE). Methods: In this observational prospective cross-sectional study, a total of 49 patients, clinically characterized as having angina with no obstructive CAD (ANOCA) or ischemia with no obstructive CAD (INOCA), underwent both TDE and invasive coronary angiography (ICA) followed by thermodilution assessment of CFR and IMR. Results: It was found that there is a statistically significant negative correlation between both non-invasive and invasive CFR measurements and IMR. Specifically, a negative moderate correlation was observed between non-invasive CFR and IMR (r_s = −0.477, p < 0.01), as well as a high negative correlation between invasive CFR and IMR (r = −0.541, p < 0.01). Receiver operating characteristic (ROC) analysis indicated that both non-invasive and invasive CFRs are effective predictors of CMD, defined as IMR > 25. Conclusions: Both noninvasive and invasive CFR measurements are significant independent predictors of CMD. Our results indicate that noninvasive TDE CFR can be a reliable tool for assessing CMD in patients with ANOCA, potentially facilitating earlier diagnosis and management strategies for this patient population. Full article

Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the limitations of current diagnostic approaches. Invasive testing, including coronary reactivity assessment, is considered the gold standard, but it is resource-intensive and not always accessible. Non-invasive methods, such as positron emission tomography (PET) and transthoracic Doppler echocardiography (TTDE), offer alternatives but are limited by varying accuracy and accessibility. Amid these diagnostic challenges, there is increasing interest in circulating biomarkers as adjuncts in CMD evaluation. Biomarkers associated with endothelial dysfunction, inflammation, and oxidative stress, detectable through routine blood tests, may assist in CMD diagnosis, risk stratification, and therapeutic monitoring. These biomarkers can offer insights into CMD pathogenesis and enable early, non-invasive screening to identify patients who may benefit from more invasive investigations. This narrative review examines studies assessing biomarkers in CMD patients with diagnoses confirmed through invasive techniques. Our objective is to focus on circulating biomarkers linked to the invasive evaluation of coronary microcirculation, aiming to advance the understanding of the underlying mechanisms of this prevalent condition and enhance diagnostic accuracy and the clinical management of affected patients. Full article

Background: Coronary microvascular disease is associated with adverse prognosis in a range of cardiovascular diseases, but its prognostic role in patients with aortic stenosis (AS) is unclear. The aim of this systematic review and meta-analysis is to determine the prognostic role of myocardial perfusion and coronary flow reserve, assessed using non-invasive imaging modalities, in patients with AS. Methods: We conducted a systematic review and meta-analysis of all studies assessing myocardial perfusion reserve (MPR) or coronary flow reserve (CFR) in patients with AS and reporting clinical outcomes, from inception to January 2024. The definition of abnormal MPR/CFR and major adverse cardiovascular events (MACE) was that used in each study. Estimates of effect were calculated from hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Four studies comprising 384 participants met the inclusion criteria. Myocardial/coronary blood flow was assessed using Doppler echocardiography (n = 2), PET (n = 1), or cardiac magnetic resonance (n = 1). The median optimal cutoff for MPR/CFR across all studies was 2.01 (range 1.85–2.13), with 109 events. Impaired MPR/CFR was associated with a higher incidence of MACE (HR 3.67, 95% CI: 1.66, 8.09, I² = 63%) in the overall population. Conclusions: Reduced MPR/CFR is associated with increased risk of MACE in patients with AS, although significant heterogeneity exists in published studies. Further studies are required to establish its role in the risk stratification of asymptomatic patients with AS. Full article

Background: Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. Methods: This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. Results: Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e′ (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. Conclusions: Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted. Full article

Coronary artery disease (CAD) is one of the main causes of death in the world. Functional indices such as fractional flow reserve (FFR), coronary flow reserve (CFR) and instantaneous wave-free ratio (iFR) are used to estimate the severity of CAD. Approximately 30–50% of patients have residual myocardial ischaemia even after formally successful percutaneous coronary intervention (PCI). Myocardial perfusion impairment is one of the main factors responsible for recurrence. We propose a novel 1D model of coronary hemodynamics that takes into account myocardial contraction, stenoses and impaired microcirculation. It uses non-invasively acquired data. The model is able to simulate FFR and iFR with a mean relative error of 3% and a standard mean deviation of 0.04. We find that healthy FFR and iFR values in the short and long term do not always correspond to healthy CFR values and recovery of coronary blood flow. We also show that PCI of stenosis also improves hemodynamic indices in adjacent stenosed vessels, with a more pronounced effect in the long term. Full article

Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3–7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho −0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size. Full article

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients’ clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often. Full article

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplantation following heart transplantation (HTX). Surveillance angiography performed yearly is indicated for the early detection of the disease, but it remains of limited sensitivity. Methods: We performed bolus thermodilution-based coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) measurements in HTX patients undergoing yearly surveillance coronary angiography without overt CAV. Results: In total, 27 HTX patients were included who had 52 CFR, IMR, and FFR measurements at a mean of 43 months after HTX. Only five measurements were performed in the first year. CFR decreased significantly by 0.13 every year (p = 0.04) and IMR tended to increase by 0.98 every year (p = 0.051), whereas FFR did not change (p = 0.161) and remained well above 0.80 over time. After one year, CFR decreased significantly (p = 0.022) and IMR increased significantly (p = 0.015), whereas FFR remained unchanged (p = 0.72). Conclusions: The functional status of the epicardial coronary arteries of transplanted hearts did not deteriorate over time. On the contrary, a significant decrease in CFR was noted. In view of the increasing IMR, this is caused by the deterioration of the function of microvasculature. CFR and IMR measurements may provide an early opportunity to diagnose CAV. Full article