Epicardial Coronary Artery Disease Research Articles

Invasive assessment of coronary microvascular dysfunction with MACEs: a meta-analysis

Abstract Aims Although obstructive coronary artery disease (CAD) is considered a prerequisite for myocardial ischemia, it is established that abnormalities of coronary microcirculation may restrict myocardial perfusion in the absense of CAD. Coronary microvascular dysfunction (CMD) is likely associated with elevated risk for MACEs. We performed a meta-analysis of randomized controlled trials to determine the prognostic value of CMD, assessed by invasive techniques, in predicting cardiovascular endpoints in patients without epicardial CAD. Methods and results We identified all studies between 1 January 2000 and 1 December 2023, where coronary flow was invasively measured and clinical outcomes were reported. We included RCTs and all prospective and retrospective studies with a control group, which measured coronary flow reserve (CFR) and/or index of microcirculatory resistance (IMR), as assessed invasively. The endpoints were all-cause mortality and MACEs, including cardiovascular death, myocardial infarction, hospitalization for heart failure (HF) and coronary revascularization. Twenty-five articles enrolling a total of 9.800 subjects (mean age: 55.5±10.6 years) were included with a mean follow-up period of 37 months were eventually deemed eligible for our final analysis. Of these, 3.421 (34,9%) patients had CFR<2.5 and/or IMR>25, indicating CMD, while 6.379 (65,1%) subjects were found without CMD. The analysis of the pooled results demonstrated that the presence of CMD depicted by abnormal CFR and/or IMR was associated with a substantially higher risk for all-cause mortality during a median follow-up period of 3.2 years. The odds ratio for all-cause mortality in patients with CMD compared with those without CMD was 2.31 (95% CI: 1.62 - 2.54, p<0.01). A similar effect of abnormal CFR and IMR was also observed for cardiovascular morality (HR 2.47, 95% CI: 1.81 - 3.38, p<0.01). In addition, the composite of revascularization was also assessed in the total of the selected studies. In particular, the pooled analysis demonstrated a positive association of CMD with a higher future risk for revascularization (HR 1.87, 95% CI: 1.33 – 2.62, p<0.01). The composite of hospitalization for heart failure was also assessed. In addition, the pooled analysis demonstrated a positive association between CMD and hospitalization for HF (HR 2.50, 95% CI: 1.63 - 3.85, p<0.01).A similar effect of abnormal CMD was also observed for myocardial infraction (HR 1.73, 95% CI: 1.33 - 2.24). Elevated IMR (>40) seems to be to be prognostically more relevant than abnormal CFR in the setting of acute myocardial infarction. Conclusions CMD is associated with a nearly 3-fold increase in mortality and a 2-fold increase in major adverse cardiac events. Impaired coronary flow is strongly associated with increased risk of all-cause mortality and MACEs. Future studies and randomized controlled trials are needed to identify strategies to diagnose and treat CMD.

Invasive quantitative assessment of coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy

Abstract Background Patients (P) with hypertrophic cardiomyopathy (HCM) commonly suffer from coronary microvascular dysfunction (CMD) - the affection of function/structure of the coronary microvasculature. Invasive assessment of CMD through thermodilution methods allows for the calculation of coronary flow reserve (CFR) and index of microvascular resistance (IMR). These methods, while extensively studied in the context of non-obstructive coronary artery disease and myocardial infarction, have not been thoroughly validated in HCM P. Objectives To invasively assess the presence of CMD in P with HCM and to determine clinical predictors of invasively assessed CMD. Methods In a prospective single-centre study, we opportunistically recruited consecutive adult P with an established diagnosis of HCM with or without LVOTO that had an indication to pursue elective coronarography – such as pre-procedural evaluation for alcoholic septal ablation (ASA) or exclusion of epicardial coronary artery disease. P characteristics and coronary hemodynamic invasive assessment data were extracted. CFR was calculated as the ratio between resting and hyperemia mean transit times (TmnRest;TmnHyper). IMR was calculated as the ratio between distal coronary pressure (Pd) and the inverse of TmnHyper (IMR=Pd/TmnHyper-1). A cutoff of ≤22.0 in IMR, an ≥d 2 in CFR was used. We excluded P with end-stage HCM (LV EF <50% and/or or left ventricular wall thinning), or with epicardial coronary artery disease. Continuous variables were reported as mean ± SD or median and IQR depending on data distribution pattern and categorical data as frequencies and percentages. A linear regression model was used to test predictors of IMR and CFR involvement. Results 25 HCM P with a mean age of 63±10 years were included, 14 (56%) were female. In 20 (80%) of the P the cause for coronary angiography was ASA. All P referred for ASA had LVOTO and were on beta-blocker therapy (Table 1.). Median CFR was 2.5 [1.5-3] and median IMR was 19 [14-22], both within normal range. A total of 13 (44%) P had a reduced CFR and 5 (20%) of P had an increased IMR. 14 P (56%) had an altered CFR or IMR value, with the presence of a functional CMD phenotype in 10 P (40%) (Table 2). Angina was associated with a higher IMR (5.3, 95% CI - 0.05-10, p=0.053) and for each +1 increase in CCS a larger increase in the likelihood of a higher IMR was observed (CCS 1, +7 (95%CI 0.68 – 14); CCS 2, +9 (95%CI 4 – 14); CCS 3, 10 (95%CI 2 – 18)). A similar but non significant trend was observed for higher CCS correlating with lower CFR (Table 3). Conclusion In a prospective cohort of HCM P submited to invasive angiographic evaluation 56% had at least one invasive measure compatible with CMD. Angina, and a higher degree of anginal symptoms correlated positively with the presence of higher IMR and therefore with a higher level of CMD. In the future, we intend to correlate these findings with multimodality imaging/clinical outcomes.Patient characteristics and LR results

Correlation of coronary and carotid atheroma volume in patients with severe and familial hypercholesterolemia (VOCCA-3D HF)

Abstract Background Stratifying the risk of CV event of familial hypercholesterolemia (FH) patients is not always simple, as they usually are excluded from CV disease risk estimation scores. It has become increasingly clear over the last several years that the heterogeneity in risk among patients with FH is far greater than previously appreciated. To that end, not all patients with FH will require the use of PCSK9 inhibitors. Aim We described the type of coronary artery disease (CAD) in patients with severe and familial hypercholesterolemia and without known atherosclerotic cardiovascular disease and searched for the best determinants of CAD. We searched for correlation between epicardial adipose tissue and CAD. Methods We evaluated the atherosclerosis burden with a combination of calcium score (CAC), computed tomography angiography, and the quantification of coronary atheroma volume and the analysis of the composition of the plaques, alongside with the use of ultrasonography of supra-aortic trunks with 3D quantification of atheroma volume. We also evaluated epicardial adipose tissue volume with CT. Results We analyzed 89 individuals with LDL-c > 190 mg/dL, with a mean age of 56,7 years. LDL-c burden was high (maximal LDL-c level across life of 2.77 g/L in mean, duration of hypercholesterolemia of 21.5 years in mean). Forty percent of the individuals had a CAC score of zero, and only one patient had non-calcified atheroma despite a CAC score of zero. Among patients with CAD, 50% had a CAC > 100 AU, 9% had a stenosis > 50%. Coronary atheroma volume amounted to a median of 50.9 mm3 in patients with CAD, representing 4% of the analyzed coronary lumen volume, and was mainly made of calcified and non-calcified fibrous plaques. At-risk plaques were not frequent (9% of low-attenuation plaques, 15.2% of positive remodeling and 2% of napkin-ring sign) in patients with CAD. Fifty percent of the individuals had no carotid plaque. Among various clinical and biological risk factors (LDL-year-score, age, blood pressure, smoking, familial history, diabetes), the carotid atheroma volume was the only variable to be independently correlated with both CAC (t=3.1, p=0.006) and coronary atheroma volume (t=4.9, p<0.001). Epicardial adipose tissue was not associated with CAD. Conclusion A significant part of the patients with severe and familial hypercholesterolemia has no CAD, however half of the patients with CAD have an important atherosclerosis burden, which can be well predicted by the carotid atheroma volume. Such a screening could help identify the individuals who would benefit the most from intensive cholesterol-lowering drugs.CAC categoriesType of coronary plaques

The association between mammographic breast density, epicardial adipose tissue volume and coronary artery disease

Abstract Background Dysfunctional adipose tissue is strongly linked to cardiometabolic disease. Epicardial adipose tissue (EAT) which is measurable on cardiac computed tomography (CT) is well correlated with cardiovascular disease (CVD), however it is not reported clinically. Breast mammography mandates reporting of breast density (BD), which is also a marker of breast adipose tissue quantity with less dense breasts indicating greater adipose tissue volume. Given the widespread use of screening mammography, this presents an opportunity to employ BD as a possible surrogate for CVD risk. Purpose To evaluate the correlation between BD, EAT and coronary artery disease (CAD). Methods Single-centre, retrospective, cross-sectional study, including women who had both clinically indicated coronary computed tomography angiogram (CCTA) and mammography. Epicardial adipose tissue volume (EATv) was quantified using semi-automated software (QFAT 2.0). BD was visually assessed by standard 4-level Breast Imaging-Reporting and Data System (BI-RADS) grade with grade A-B representing low density, and C-D representing high density. CAD was categorised as presence/absence of any coronary artery plaque, and CAD severity was quantified using the Coronary Artery Disease Reporting and Data Systems (CAD-RADS) score, with CAD-RADS 1-2 representing mild disease, CAD-RADS 3 moderate disease and CAD-RADS 4 severe disease. CAD analyses were adjusted for modifiable (hypertension, dyslipidaemia, diabetes, body mass index) and non-modifiable (age, past smoking, family history, breast cancer) risk factors. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Results Among 153 patients (mean age 62±10), 103 (67.3%) had low BD (high breast adiposity). Compared with high BD, low BD patients were older, had greater rates of hypertension, had significantly higher mean EAT (106.6 ± 43.0 vs 81.0 ± 31.6ml, p<0.001) (Figure 1), and body mass index (30.5 ± 6.3 vs 26.4 ± 5.4kg/m², p<0.001). Adjusted for age and hypertension, EATv remained independently predictive of low BD (OR:1.02 [1.01-1.03], p=0.006). Low BD made up a higher proportion of mild (76.5%), moderate (73.9%) and severe (80.0%) disease. Low BD was strongly associated with presence of CAD (prevalence 75% vs 48%, OR 3.21 [1.58-6.53], p=0.001) independent of EATv (p=0.25), and independent of modifiable (OR: 2.69 [1.24-5.92], p=0.012) and non-modifiable (OR: 2.42 [1.04-5.85], p=0.047) risk factors (Figure 2). Conclusions Low breast density is associated with higher EATv and independently associated with CAD presence beyond EATv and other risk factors. Consequently, mammographic breast density may act as an early risk identification tool for CAD in women.

Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease

Abstract Background Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown. Purpose To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD. Methods In a prospective registry-based cohort study of 306 patients without obstructive CAD (<50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] <2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]<50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD). Results Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p<0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1). Conclusions Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome

Abstract Background Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored. Purpose Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications. Methods This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period. Results All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130). Conclusions Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.

Primary inflammatory disease in heart failure with preserved ejection fraction

Abstract Background Inflammation plays a fundamental role in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of underlying systemic inflammatory diseases represented by rheumatoid arthritis. Purpose This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and primary inflammatory diseases. Methods Consecutive patients undergoing hemodynamic exercise testing with concurrent expiratory gas analysis to evaluate dyspnea of unknown cause were identified. HFpEF was defined as left ventricular ejection fraction ≥50% and pulmonary capillary wedge pressure ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF were divided into groups with and without primary inflammatory diseases. Patients without inflammatory disease were divided into tertiles according to the value of C-reactive protein (CRP). Results Of 982 consecutively evaluated patients with HFpEF diagnosed (577 female, mean age 68 years), 79 (8%) had primary inflammatory disease. In multivariable logistic regression, female sex (OR 1.88; 95% CI 1.01-3.52), higher resting heart rate (OR 1.18; 95% CI 1.08-1.30), lower hemoglobin level (OR 0.84; 95% CI 0.70-0.99), absence of history of atrial fibrillation (OR 0.45; 95% CI 0.24-0.86) and absence of epicardial coronary artery disease (OR 0.45; 95% CI 0.22-0.93) were independently associated with inflammatory disease. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with inflammatory disease, reflected by lower arterial-venous oxygen content difference (Ca-vO2) at rest (4.2±0.7 mL/dL vs 4.6±1.0 mL/dL, P<.001) and during exercise (9.3±2.2 mL/dL vs 10.4±2.2 mL/dL, P<.001) (Figure 1A), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCO2 slope) was also more impaired (38.0±7.9 vs 36.2±7.3, P=.035). The HFpEF patients without inflammatory disease falling in the highest tertile of CRP) displayed lower Ca-vO2 during exercise, more closely resembling peripheral deficits observed in those with inflammatory disease (Figure 1B). During a median follow-up of 3.0 years, the composite outcome of all-cause deaths and HF hospitalization occurred in 127 patients (14%). Patients with HFpEF and inflammatory disease showed a higher incidence of composite outcome than those without (log-rank P=.030; Figure 2). Patients with inflammatory disease had higher risk of composite outcome compared to those without in adjusted analyses (HR 1.93; 95% CI 1.15-3.23), which was primarily attributable to higher risk of HF hospitalization (HR 2.85; 95% CI 1.08-7.52). Conclusion Patients with HFpEF and primary inflammatory disease have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared to those without.

IMPACT OF DYSLIPIDEMIA ON CORONARY HEART DISEASE IN WOMEN (REVIEW)

Introduction:The increase in the level of lipids in the blood is one of the risk factors for cardiovascular diseases (due to atherosclerosis and thrombosis) increasing premature morbidity, disability, financial cost and mortality, not only in the EU and the USA, but also in countries developing worldwide. It has been proven that lipid disorders promote the development of atherosclerosis and its clinical consequences such as CVD including (coronary heart disease, acute myocardial infarction, peripheral artery disease, heart failure and sudden death). Combinations of lipoprotein levels and lipid fractions play a major risk role in terms of coronary heart diseases. Purpose: Evidence of dyslipidemia as a risk factor for CVD, especially in obese women who suffer from metabolic syndrome or diabetes and have lipid profiles that negatively affect the risk of coronary heart disease. Methodology: International literature review in PubMed, CINAHL, Am J Cardiology, Int J Public Health; in accordance with the purpose and objectives of the study. Result: Coronary heart diseases are the leading cause of death among women and men although they are less common and appear later in women than in men. Each year 345,000 women suffer from an initial or recurrent myocardial infarction, and 261,000 women die from MI. Compared to men, women, and especially women in the postmenopausal period, remain at high risk for coronary disease. In women, calcification occurs 10 to 15 years later. Multiple angiographic studies of coronary arteries have shown a lower rate of epicardial coronary artery disease in women than in age-matched men. Elevated levels of Lp (a) appear to be more associated with the occurrence of coronary heart disease than with the severity of coronary artery disease in both sexes. Outcome data in women using lipid-lowering medications other than statins are extremely limited. Conclusion: The importance of a healthy lifestyle should begin in childhood and continue throughout life. Although the benefits of lipid-lowering therapy in women with cardiovascular disease are clear, more data are needed in those without cardiovascular disease. Clinical trials for lipid-lowering women with cardiovascular disease to date have used a strategy focused on lowering LDL-cholesterol, which may not be optimal for women who have low HDL-cholesterol or triglyceride levels. which are very important factors affecting coronary heart disease. It remains to be determined whether outcomes among women will improve if treatment strategies are directed toward more aggressive and comprehensive modification of lipoprotein profiles.

Myocardial Ischemia: Differentiating between Epicardial Coronary Artery Atherosclerosis, Microvascular Dysfunction and Vasospasm in the Catheterization Laboratory.

Ischemic heart disease is currently the most common cause of mortality and morbidity worldwide. Although myocardial ischemia is classically determined by epicardial coronary atherosclerosis, up to 40% of patients referred for coronary angiography have no obstructive coronary artery disease (CAD). Ischemia with non-obstructive coronary artery disease (INOCA) has typically been underestimated in the past because, until recently, its prognostic significance was not completely clear. This review aims to highlight differences and patterns in myocardial ischemia caused by epicardial obstructive CAD, coronary microvascular dysfunction (CMD) or vasomotor abnormalities and to elucidate the state of the art in correctly diagnosing these different patterns.

The emerging role of cardiovascular magnetic resonance in the evaluation of cardiac involvement in systemic sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune rheumatic disease, characterized by vascular, inflammatory and fibrotic alterations. Cardiac involvement is the « fatal tip of the iceberg» in SSc, as it leads to high morbidity/mortality. Cardiovascular imaging modalities play an important role in the early diagnosis and treatment assessment of cardiac involvement. Echocardiography is the corner stone for evaluation of cardiac involvement, providing information about function, wall motion, pulmonary pressure, pericardium and valvular disease. It is a low-cost modality, widely available, without radiation and with great experience among cardiologists. However, it is a window and operator dependent modality and cannot provide tissue characterization information, absolutely necessary for diagnosis and treatment of cardiac involvement in SSc. Cardiovascular magnetic resonance (CMR) can perform myocardial function and tissue characterization in the same examination without radiation, has excellent reproducibility and is window and operator independent. The great advantage of CMR is the capability to assess peri- myo-vascular inflammation, myocardial ischemia and presence of replacement and diffuse myocardial fibrosis in parallel with ventricular function assessment. The modified Lake Louise criteria including T2, native T1 mapping and extracellular volume fraction (ECV) has been recently used to diagnose inflammatory cardiomyopathy. According to expert recommendations, myocardial inflammation should be considered if at least 2 indices, one T2 and one T1 parameter are positive, whereas native T1 mapping and ECV assess diffuse fibrosis or oedema, even in the absence of late gadolinium enhancement (LGE). Moreover, transmural/subendocardial LGE following the distribution of coronary arteries and diffuse subendocardial fibrosis not related with epicardial coronary arteries are indicative of epicardial and micro-vascular coronary artery disease, respectively. To conclude, CMR can overcome the limitations of echocardiography by identifying acute/active or chronic myocardial inflammation/fibrosis, ischemia and myocardial infarction using classic and parametric indices in parallel with biventricular function assessment

Emerging Predictors by Non-HDL-C/HDL-C Ratio and Novel Biomarkers for Coronary Slow Flow Phenomenon.

The coronary slow-flow (CSF) phenomenon is a condition characterized by delayed coronary opacification during diagnostic angiography without the presence of epicardial coronary artery disease. This mini-review explores various emerging predictors and biomarkers associated with CSF, aiming to address the potential diagnostic tools. A comprehensive analysis of recent studies has investigated different biomarkers, including growth differentiation factor 15, galectin 3, microRNA (miRNA)-22, miRNA-155, interleukin 34, soluble vascular cell adhesion molecule-1, long non-coding RNA, plasma choline, adropin, and lipid markers non-high-density lipoprotein cholesterol (HDL-C)/HDL-C ratio to enhance understanding and predict CSF. Additionally, we have summarizes the major findings and significant limitations observed in various studies on CSF biomarkers. The implications of these findings suggest significant advancements in personalized treatment strategies and improved prognostic outcomes for patients exhibiting CSF.

Effects of age on microvascular function in patients with normal coronary arteries.

It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rμ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rμ (Rμ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rμ (Rμ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

CORRELATION BETWEEN RETINAL MICROCIRCULATION, ECHOCARDIOGRAPHIC PARAMETERS AND MYOCARDIAL CORONARY FLOW RESERVE

Objective: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated the possible relationship between retinal microcirculation, positron emission tomography myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi) Design and method: Nineteen hypertensive patients (mean age 65 ± 11, 10 F) without flow-limiting epicardial coronary artery disease underwent patients wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera, echocardiography, including MEEi computation, and cardiac 13NH3 positron emission tomography (13NH3 PET) with assessment of myocardial coronary flow reserve (CFR). A positive 13NH3 PET was defined as a ratio of stress (regadenoson) myocardial blood flow (MBF)/mass and resting MBF/mass lower than 2. Results: No significant differences of demographic parameters were observed between patients with positive (n=6) vs negative (n=13) 13NH3 PET. In all patients WLR was significantly related to BMI (0,50, p=0.02), age (r=0.49, p=0.03)and LVMi (r=0.48, p=0.03) at univariate analysis. A negative correlation was also observed between WLR and total CFR (-0.64, p=0.003) and MMEi (-0.35, p=0.13). The relationship between WLR and CFR remained significant after adjustment for age and BMI (r=-0.49, p=0.047). Conclusions: In hypertensive patients without flow-limiting epicardial coronary artery disease, retinal WLR could reflect the presence of structural alterations in coronary microcirculation, possibly contributing to an impairment of CFR and to early LV dysfunction, as detected by low values of MEEi.

C-30 | Coronary Functional Angiography results in patients with and without history of Epicardial Coronary Artery Disease

C-30 | Coronary Functional Angiography results in patients with and without history of Epicardial Coronary Artery Disease

Traditional Cardiovascular Risk Factors and Coronary Microvascular Dysfunction in Women and Men: A Single-Center Study

Introduction: Coronary microvascular dysfunction (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex-associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. Methods: In this single-center, prospective registry, we enrolled patients with nonobstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results: Overall, 245 patients with nonobstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range: 59, 75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p = 0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (β = −0.29; p < 0.01 and β = −0.15; p = 0.05, respectively) and lower resistive reserve ratio (β = −0.28; p < 0.01 and β = −0.17; p = 0.04, respectively). Conclusion: For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Diagnostic Ability of Manual Calcification Length Assessment on Non-Electrocardiographically Gated Computed Tomography for Estimating the Presence of Coronary Artery Disease.

Background: Coronary artery calcification score (CACS) on electrocardiography (ECG)-gated computed tomography (CT) is used for risk stratification of atherosclerotic cardiovascular disease, which requires dedicated analytic software. In this study, we evaluated the diagnostic ability of manual calcification length assessment on non-ECG-gated CT for epicardial coronary artery disease (CAD). Methods: A total of 100 patients undergoing both non-ECG-gated plain CT scans with a slice interval of 1.25 mm and invasive coronary angiography were retrospectively included. We manually measured the length of the longest calcified lesions of coronary arteries on each branch. The relationship between the number of coronary arteries with the length of coronary calcium > 5, 10, or 15 mm and the presence of epicardial CAD on invasive angiography was evaluated. Standard CACS was also evaluated using established software. Results: Of 100 patients, 49 (49.0%) had significant epicardial CAD on angiography. The median standard CACS was 346 [7, 1965]. In both manual calcium assessment and standard CACS, the increase in calcium burden was progressively associated with the presence of epicardial CAD on angiography. The receiver operating characteristic curve analysis showed similar diagnostic abilities of the two diagnostic methods. The best cut-off values for CAD were 2, 1, and 1 for the number of vessels with calcium > 5, 10, and 15 mm, respectively. Overall, the diagnostic ability of manual calcium assessment was similar to that of standard CACS > 400. Conclusions: Manual assessment of coronary calcium length on non-ECG-gated plain CT provided similar diagnostic ability for the presence of significant epicardial CAD on invasive angiography, as compared to standard CACS.

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation

BackgroundCoronary 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. MethodThis 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. ResultA 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). ConclusionElevated 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.

Heterogeneity of coronary vascular function and myocardial oxygenation in women with angina and non-obstructive coronary artery disease.

Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischaemic symptoms may be related to alterations in microvascular structure and function. We examined the use of breathing-enhanced oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) using vasoactive breathing manoeuvres to assess myocardial oxygenation in women with ANOCA. We recruited women (aged 40-65 years) from two sites in Canada who presented to healthcare with persistent retrosternal chest pain and found to have ANOCA, or without a history of cardiovascular disease. All participants were scanned using a clinical 3T MRI scanner, and OS-CMR images were acquired over a breath hold following paced hyperventilation to measure global and regional measurements of heterogeneity. Fifty-four women with ANOCA (age: 55 ± 6.2 years) and 48 healthy controls (age: 51.2 ± 4.8 years) were recruited. There was no significant difference in volume, function, mass, or global myocardial oxygenation between the two groups [mean %Δ in signal intensity (SI): 4.9 (±7.3) vs. 4.5 (±10.1), P = 0.82]. Women with ANOCA had higher regional variations in myocardial oxygenation in circumferential [median %Δ in SI: 5.1 (2.0-7.6) vs. 2.2 (1.4-3.5), P = 0.0004] and longitudinal directions [median %Δ in SI: 11.4 (5.4-16.7) vs. 6.0 (3.0-7.0), P = 0.001], which remained present in a multivariate model. Heterogeneous myocardial oxygenation may explain ischaemic symptoms without any associated epicardial obstructive coronary artery disease. Regional variations in myocardial oxygenation on OS-CMR could serve as an important diagnostic marker for microvascular dysfunction in women with ANOCA.

Spectrum of Ischemic Heart Disease Throughout a Woman's Life Cycle.

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in both genders; however, young women fare the worst, likely reflecting the more complex spectrum of IHD in women when compared to men. Substantial sex-based differences exist in the underlying risk factors, risk enhancers, presentation, diagnosis, and pathophysiology of IHD that are mainly attributed to the influence of female sex hormones. This article reviews the spectrum of IHD including obstructive epicardial coronary artery disease (CAD), myocardial infarction with no obstructive coronary artery disease, ischemia with no obstructive coronary artery disease, spontaneous coronary artery dissection, coronary microvascular dysfunction, vasospastic angina, and coronary thrombosis/embolism that occur in women throughout various stages of their life cycle. We aim to update clinicians on the diagnosis and management of these various types of IHD and highlight where further randomized controlled studies are needed to determine optimal treatment and inform guideline-directed medical therapy.