Significant Coronary Artery Stenosis Research Articles

#941 Pentraxin-3 as a marker of coronary artery disease in hemodialysis patients

Abstract Background and Aims Pentraxin-3 (PTX3), a novel inflammatory biomarker, has been recognized as a predictor of cardiovascular events in the general population, including coronary artery disease (CAD). Although PTX3 is elevated in dialysis patients, its potential diagnostic value for the estimation of CAD severity is still insufficiently studied. The aim of this study was to evaluate the association between PTX3 and CAD in hemodialysis patients. Method This cross-sectional study included 60 angina-free chronic hemodialysis patients (60% men, mean age 60 ± 11 years, mean dialysis vintage 26 ± 14 months). Coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) were performed to evaluate CAD burden and stenosis severity, which was defined as significant if obstructing more than 50% of the vessel lumen. PTX3 was quantified using an enzyme-linked immunosorbent assay kit. Results Significant coronary artery stenosis was detected in 24 (40%) patients, of which the majority (17; 70.83%) had one-vessel disease. PTX3 was 194.82 ± 68.58 ng/mL in patients with significant CAD, whereas 83.55 ± 11.89 ng/mL in those without significant coronary artery stenosis (p = 0.028). PTX3 levels tend to increase in patients with CACS higher than 200 Agatston units, however statistically significant difference was not reached (p = 0.504). PTX3 levels correlated with age (p < 0.05) and c-reactive protein (p = 0.007), while negatively correlated with body mass index (p < 0.05). Conclusion PTX3 is significantly increased in hemodialysis patients with coronary artery disease. Further studies should elucidate if including PTX3 as a marker for detecting CAD prior to invasive imaging could improve cardiovascular risk stratification even in angina-free hemodialysis patients.

#2919 Renal functional reserve assessment in patients with coronary microvascular dysfunction and preserved renal function—experience of a center

Abstract Background and Aims Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73 m2 (CKD-EPI) and proteinuria< 400 mg/24 h]. Method This is a single-center, prospective study enrolling patients with INOCA. We are presenting preliminary results. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients and we estimated coronary flow reserve (CFR) and index of microvascular resistance (IMR). In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2 gr/kg). Normal RFR was defined as ≥30 ml/min/1.73 m2. Also, patients with INOCA were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 22 participants have been enrolled so far in study: 10 without CMD—control group [7 female, mean age: 54.4 ± 8.1 years) and 12 with INOCA—CMD group (9 female, 75%, mean age: 53.5 ± 10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR<2.5 and an IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4 ± 6.3 ml/min/1.73 m2, while for non-CMD group 36.3 ± 5.8 ml/min/1.73 m2 (p < 0.005), relationship that remained statistically significant after controlling for confounding factors. Regarding the two endotypes of MVD, it was found that RFR for the patients with the functional endotype is 3.5 ± 2.4 ml/min/1.73 m2, while for those with the structural endotype 9.3 ± 6.9 ml/min/1.73 m2 (p-value = 0.061). Furthermore, no statistically significant relationship emerged between RFR and IMR, CFR indices (p = 0.347, p = 0.263). According to data from 24 hr ABPM, there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p = 0.594, p = 0.243), as well as no relationship with RFR (p = 0.553, p = 0.594). However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p < 0.05). It was not found correlation between RFR and non-dipping phenotype, both for SBP and DBP (p = 0.561, p = 0.238). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to blood pressure or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes—such as INOCA and pathological RFR—could contribute to the individualization of therapeutic interventions.

High Risk Non-ST Elevation Myocardial Infarction - A Case Report

Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide. Electrocardiogram (ECG) remains an important tool in the diagnosis of acute myocardial infarction (MI) and further risk stratification. ST segment elevation myocardial infarction (STEMI) is a medical emergency requiring early diagnosis and prompt reperfusion of occluded coronary artery to prevent morbidity and mortality. Recent studies have shown that a subset of patients with acute MI in the absence of ST segment elevation (non-ST elevation myocardial infarction [NSTEMI]) have an acute occlusion of the culprit artery on coronary angiography. The Aslanger’s pattern is a specific ECG finding in acute inferior myocardial infarction with multivessel disease. It allows identification of inferior wall myocardial infarction that does not show ST elevation in contiguous leads but needs rapid evaluation by coronary angiogram and revascularization. We presented a case of acute coronary syndrome whose ECG showed Aslanger’s pattern and was confirmed to have significant stenosis of the left main coronary artery and right coronary artery (RCA) by coronary angiogram. STEMI criteria of ST elevation involving two contiguous leads may not be sufficient in diagnosing critical coronary artery occlusions in clinical practice. Keywords: Acute Myocardial Infarction; Aslanger’s Pattern; ST-Elevation; NSTEMI

Role of myocardial strain imaging in diagnosing inducible myocardial ischemia with treadmill contrast-enhanced stress echocardiography

IntroductionThe aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain undergoing treadmill contrast-enhanced stress echocardiography (SE).MethodsWe retrospectively enrolled all patients who underwent invasive coronary angiography after treadmill contrast-enhanced SE. Rest and peak-stress myocardial GLS, segmental LS, and LS of 4-chamber (CH), 2-CH, and 3-CH views were reported. Luminal stenosis of more than 70% or fractional flow reserve (FFR) of < 0.8 was considered significant.ResultsIn total 33 patients were included in the final analysis, among whom sixteen patients (48.4%) had significant coronary artery stenosis. Averaged GLS, 3-CH, and 4-CH LS were significantly lower in patients with critical coronary artery stenosis compared to those without significant stenosis (-17.1 ± 7.1 vs. -24.2 ± 7.2, p = 0.041), (-18.2 ± 8.9 vs. -24.6 ± 8.2, p = 0.045) and (-14.8 ± 6.2 vs. -22.8 ± 7.8, p = 0.009), respectively. Receiver operating characteristic (ROC) analysis of ischemic and non-ischemic segments demonstrated that a cut-off value of -20% of stress LS had 71% sensitivity and 60% specificity for ruling out inducible myocardial ischemia (Area under the curve was AUC = 0.72, P < 0.0001).ConclusionMyocardial LS measured with treadmill contrast-enhanced stress echocardiography demonstrates potential value in identifying patients with inducible myocardial ischemia.

Four-dimensional computed tomography is useful for detection of apical sparing of cardiac amyloidosis.

A 73-year-old male was admitted because of recurrent syncope. He was diagnosed with transient bradycardia caused by a 2:1 atrioventricular block, and he underwent cardiac computed tomography (CT) using 320 detector-row CT to screen for coronary artery disease. Significant coronary artery stenosis was not detected, but diffuse late iodinate enhancement was found on the epi-myocardium and endo-myocardium of the interventricular septum, and endo-myocardium of the anterior and lateral left ventricular (LV) myocardium (LVM) on CT. The ejection fraction and global longitudinal strain (LS) of LVM were 53.97% and - 9.87% on CT. Apical sparing was present, meaning the LS of LV apical segments were preserved compared with basal segments on CT. Pathological findings of LVM demonstrated loss of myocardial cells and extra-cellular amyloid deposition on the direct fast scarlet staining. He was finally diagnosed with transthyretin amyloidosis.

Renal functional reserve assessment in patients with coronary microvascular dysfuntion and preserved renal function

Abstract Funding Acknowledgements None. Introduction Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. Aim The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73m2 (CKD-EPI) and proteinuria&amp;lt; 400mg/24h]. Methods This is a single-center, prospective study enrolling patients with CMD. We are presenting preliminary resuts. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured invasively. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as ≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - non-CMD group [7 female, 64%, mean age: 52.9±8.8 years) and 14 with INOCA – CMD group (11 female, 79%, mean age : 53.5±10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR&amp;lt;2.5 and IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4±6.3 ml/min/1.73m2, while for control group 36.3±5.8 ml/min/1.73m2 (p&amp;lt;0.005), This difference between groups was found to be statistically significant after controlling for confounding factors. It was found that RFR value for functional CMD endotype was 3.8±2.6 ml/min/1.73m2, while for patients with structural endotype 9.6±7,2 ml/min/1.73m2 (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices (p =0.35, p =0.23 respectively). According to data from 24hr ABPM , there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p=NS for all), as well as no relationship with RFR (p=0.6, p=0.6 respectively) was observed. However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p&amp;lt;0.05). It was not found correlation between RFR and non-dipping phenotype, for both SBP and DBP (p=NS). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to levels of BP or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes could contribute to the individualization of therapeutic interventions.

[15O]H2O myocardial perfusion PET: Added value of relative stress perfusion deficit in the prediction of significant coronary artery stenosis in a mixed population

BackgroundIt remains unknown whether estimation of the relative stress perfusion deficit offers added value in the prediction of significant coronary artery stenosis in myocardial perfusion imaging with [15O]H2O PET in a population with high prevalence of established cardiac disease. MethodsDuring eight months, we consecutively included all patients undergoing [15O]H2O PET and subsequent invasive coronary angiography (ICA). Significant stenosis was defined from ICA as fractional flow reserve ≤0.8 or coronary artery narrowing of ≥70%. We calculated absolute and relative total perfusion deficits (aTPD and rTPD, respectively) as semiquantitative measures of the extent and severity of reduced stress perfusion. A multivariate logistic regression analysis was performed to test the adjusted associations (odds ratio (OR) with 95% CI) with significant coronary artery stenosis. ResultsOf 800 patients undergoing [15O]H2O PET, 144 underwent ICA, where 142 patients had an aTPD ≥3% and 79 (55%) of these had at least one significant stenosis. In an adjusted analysis rTPD (OR10% increase = 2.12 (1.44-3.12), P<0.001), previous coronary artery bypass grafting (CABG) (OR = 0.11 (0.03-0.36), P<0.001) and reduced left ventricular ejection fraction (LVEF) (OR = 0.25 (0.08-0.84), P=0.02) were independently associated with significant stenosis, whereas the association with aTPD (OR10% increase = 1.14 (0.98-1.32), P=0.08) was modest. ConclusionsIn the presence of an absolute perfusion deficit (aTPD ≥3%), rTPD may improve the prediction of significant stenosis in a heterogeneous population of patients examined with [15O]H2O PET. Furthermore, previous CABG and reduced LVEF are associated with non-stenotic perfusion deficiencies suggesting caution when interpreting myocardial perfusion imaging in such patients.

Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis &lt;50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p&lt;0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p&lt;0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p &lt;0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

Association of postsystolic shortening on stress echocardiography and significant coronary artery stenosis:A single-centre retrospective cohort study.

Postsystolic shortening (PSS) is one of the proposed quantitative measures to predict myocardial ischaemia in the stress echocardiographic (SE) evaluation. It is previously known that hypo-/akinesia (HA) correlates well with coronary stenosis. However, some patients undergoing SE only present with PSS, and their risk of significant coronary stenosis is less clear. This study aimed to evaluate the association between PSS and significant coronary stenosis compared with HA. This was a retrospective cohort study at the hospital of S:t Görans, Stockholm, Sweden. All patients who underwent SE to investigate inducible ischaemia between 1 January2018 and 15 October 2021were eligible for inclusion. Exclusion criteria were normal SE and inconclusive test. Pathological SE were divided into two groups, patients with HAand those with PSS. Outcome was significant coronary artery stenosis visualized by invasive coronary angiography. The final study population consisted of 108 patients (73 PSS, 35 HA). The presence of HA was associated with a higher risk of significant stenosis compared to those with PSS (63% vs. 23%, p < 0.001). This relationship was observed among males (p < 0.001), but not among females (p = 0.133). Nonsignificant stenosis trended to be more common among patients with PSS (21% vs. 6%, p = 0.053) CONCLUSIONS: The finding of PSS without HA was associated with a lower risk of significant coronary stenosis than HA. However, patients with PSS still often had nonsignificant coronary stenosis and PSS in the evaluation for nonobstructive coronary artery disease (CAD) should be further investigated.

Early and Long-Term Results of Simultaneous and Staged Revascularization of Coronary and Carotid Arteries.

Carotid artery disease is prevalent among patients with coronary heart disease. The concomitant severe lesions in the carotid and coronary arteries may necessitate either simultaneous or staged revascularization involving coronary bypass and carotid endarterectomy. However, there is presently a lack of consensus on the optimal choice of surgical treatment tactics for patients with significant stenoses in both carotid and coronary arteries. The aim of the current study was to compare the 30-day and long-term outcomes of coronary and carotid artery revascularization surgery based on the simultaneous or staged surgical tactics. This single-center retrospective study involved 192 patients with concurrent coronary artery disease and carotid artery stenosis ≥ 70%, of whom 106 patients underwent simultaneous intervention (CABG + CEA) and 86 patients underwent staged CABG/CEA. The mean time between stages ranged from 1 to 4 months (mean 1.88 ± 0.9 months). The endpoints included death from any cause, non-fatal stroke, non-fatal myocardial infarction (MI), and major adverse cardiovascular events (MACEs) (death + non-fatal MI + non-fatal stroke) within 30 days after the last intervention and in the long-term follow-up period (median follow-up-6 years). The 30-day all-cause mortality, incidence of postoperative non-fatal MI, non-fatal stroke, and MACEs did not exhibit differences between the groups after single-stage and staged interventions. However, the overall risk of postoperative complications (adjusted for the risk of any complication per patient) (OR 2.214, 95% CI 1.048-4.674, p = 0.035), as well as the duration of ventilatory support (p = 0.004), was elevated in the group after simultaneous interventions compared with the staged intervention group. This difference did not result in an increased incidence of death and MACEs in the group after simultaneous interventions. In the long-term follow-up period, there were no significant differences observed when comparing simultaneous or staged surgical tactics in terms of overall survival (54.9% and 62.6% in Groups 1 and 2, respectively, P log-rank = 0.068), non-fatal stroke-free survival (45.6% and 33.6% in Groups 1 and 2, respectively, P log-rank = 0.364), non-fatal MI-survival (57.6% and 73.5% in Groups 1 and 2, respectively, P log-rank = 0.169), and MACE-free survival (7.1% and 30.2% in Groups 1 and 2, respectively, P log-rank = 0.060). The risk factors associated with an unfavorable outcome included age, smoking, BMI, LV EF, and atherosclerosis of the lower extremity arteries. This study revealed no significant difference in the impact of simultaneous CABG + CEA or staged CABG/CEA on the incidence of death, stroke, MI, and MACEs over a 30-day and long-term follow-up period. Although the immediate results indicated an increased risk of a complicated course (attributable to overall complications) and more prolonged ventilation after simultaneous CABG + CEA compared with staged CABG/CEA, this did not lead to an increase in fatal complications. Therefore, the implementation of either tactic is considered eligible and appropriate following a thorough operative risk assessment.

Ten questions about myocardial infarction with non-obstructed coronary arteries

The term "MINOCA" refers to myocardial infarction with non-obstructed coronary arteries and has been used to define acute myocardial infarction with no angiographic evidence of significant epicardial coronary artery stenosis. Patients with MINOCA represent a rather heterogeneous group of acute coronary syndrome, and this may account for the wide variation in the incidence of MINOCA in different studies. Several pathogenic mechanisms have been suggested to underlie MINOCA, but the condition continues to represent a diagnostic and therapeutic challenge for the cardiologist. Therefore, an adequate diagnostic assessment, carefully characterizing the pathogenic mechanisms, and a selection of more targeted treatments are needed to improve clinical outcomes. In this focused review, we will try to provide answers to the most common questions on the causes, diagnosis, treatment, and outcomes of MINOCA.

Improvement of quality of life indicators in patients with metabolic syndrome after correction of hemodynamically significant coronary stenoses and dyslipidemia

It is known that metabolic syndrome is currently the leading cause of the development of cardiovascular pathology, which occupies a leading position in the structure of mortality not only in the Russian population, but also in the world. The prevalence of MS is growing, which is associated with stressful professions, eating disorders. The presence of MS is associated with arterial hypertension and atherosclerosis of the arteries of any localization. In this regard, the purpose of our study was to study the quality of life in patients with MS, depending on the severity of coronary atherosclerosis. Materials and methods: The study included 239 patients (142 men, 97 women) with MS with atherosclerosis of the coronary and carotid arteries. The number of subjects in group 1 (n=141), of which 101 were men and 40 were women. The second group consisted of 84 male and 14 female patients (n=98). The control group consisted of 70 people (27 men, 43 women) with grade 1-3 hypertension. The age of the subjects was 31-56 years. All patients underwent: collection of complaints and anamnesis, assessment of body mass index (BMI); determination of the lipid spectrum, blood glucose, glycated hemoglobin. Microalbuminuria and glomerular filtration rate were determined. Instrumental studies were carried out: ultrasound examination of brachiocephalic vessels with determination of the thickness of the intima-media complex and the percentage of carotid artery stenosis; coronary angiography on the General Electric Innova 3100 angiographic complex. Based on the results of coronary angiography, the patients were divided into two subgroups: group 1 - with coronary artery stenosis of less than 50% (n=141), group 2 - with stenosis of 50% or more (n=98), group 3 (control) without stenotic lesions of the coronary arteries. A non-specific questionnaire “SF-36 Health Status Survey” was used to assess the quality of life. Results: assessing physical functioning and mental health, there was a significant decrease in these indicators in patients of group 2, in whom, according to coronary angiography, hemodynamically significant coronary artery stenoses were diagnosed, a strong correlation (r=0.730; p=0.005) was revealed between deterioration in quality of life and hemodynamically significant stenosis of the carotid and coronary arteries. Restriction of physical activity and reduction of daily activities were more significant in group 2 compared to groups 1 and 3. The feeling of uncertainty with restless expectation and fears, as well as a feeling of depression prevailed in men. However, patients after percutaneous coronary intervention, as well as with lipidogram correction, assessed the quality of life with some restriction of physical activity, but with significant social functioning. Conclusions: hemodynamically significant atherosclerosis of the carotid and coronary arteries is a predictor of deterioration in the quality of life, especially in men. The use of the international questionnaire “SF-36 Health Status Survey” is appropriate for assessing the health and vital activity in patients with MS and hypertension, with signs of atherosclerosis. The interaction of a cardiologist, an endocrinologist and a psychotherapist are justified for the most optimal management of patients with comorbid pathology.

Impact of Pressure Guidewire on Model-Based FFR Prediction.

Fractional Flow Reserve (FFR) is used to characterize the functional significance of coronary artery stenoses. FFR is assessed under hyperemic conditions by invasive measurements of trans-stenotic pressure thanks to the insertion of a pressure guidewire across the coronary stenosis during catheterization. In order to overcome the potential risk related to the invasive procedure and to reduce the associated high costs, three-dimensional blood flow simulations that incorporate clinical imaging and patient-specific characteristics have been proposed. Most CCTA-derived FFR models neglect the potential influence of the guidewire on computed flow and pressure. Here we aim to quantify the impact of taking into account the presence of the guidewire in model-based FFR prediction. We adopt a CCTA-derived FFR model and perform simulations with and without the guidewire for 18 patients with suspected stable CAD. Presented results show that the presence of the guidewire leads to a tendency to predict a lower FFR value. The FFR reduction is prominent in cases of severe stenoses, while the influence of the guidewire is less pronounced in cases of moderate stenoses. From a clinical decision-making point of view, including of the pressure guidewire is potentially relevant only for intermediate stenosis cases.

Prognostic Implications of Microvascular Resistance Reserve in Symptomatic Patients With Intermediate Coronary Stenosis

BackgroundMicrovascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). ObjectivesThe aim of this study was to evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. MethodsThe present study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiological assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR) ≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR ≤3.0. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. ResultsAmong the study group, 172 patients (31.4%) had FFR ≤0.80, and 200 patients (36.6%) had CMD defined by MRR ≤3.0. MRR showed no significant correlation with FFR (R = −0.031; P = 0.469), but it was significantly correlated with the index of microcirculatory resistance (R = −0.353; P < 0.001), N-terminal pro–B-type natriuretic peptide (R = −0.296; P < 0.001), left ventricular filling pressure (E/e′ ratio) (R = −0.224; P < 0.001), and diastolic dysfunction grade (P < 0.001). During a median follow-up period of 3.3 years (Q1-Q3: 2.0-4.5 years), MRR was significantly associated with MACE risk (HR: 1.23 per 1-U decrease; 95% CI: 1.12-1.36; P < 0.001). CMD defined by MRR ≤3.0 was associated with an increased MACE risk for both FFR >0.80 (41.0% vs 26.0%; adjusted HR: 1.59; 95% CI: 1.07-2.35; P = 0.021) and FFR ≤0.80 (34.7% vs 14.8%; adjusted HR: 2.32; 95% CI: 1.12-4.82; P = 0.024). ConclusionsDecreased MRR was associated with the presence of cardiac diastolic dysfunction as well as increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk for a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis. (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function [DIAST-CMD]; NCT05058833)

Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. The study protocol was completed in 110 participants (mean age, 62years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Predictors of Revascularization in Patients with Unstable Angina.

The factors that determine the necessity of coronary artery revascularization in patients with unstable angina (UA) have been supported by limited data. Therefore, this study aimed to identify the predictors of revascularization in patients with UA. The study included the recorded data of 3668 patients with UA who underwent cardiac catheterization (age 66 ± 9.2, men 70%); 2615 of them (71%) underwent revascularization (percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), or hybrid revascularization. The remaining 1053 patients (29%) had no significant coronary stenosis and were regarded as controls. Multivariable logistic regression analysis was performed to separate the predictors of revascularization. It was found that severe angina (OR 2.7, 95%CI 1.9-3.7), male gender (OR 1.4, 95%CI 1.1-1.7), and hyperlipidemia were the predictors of revascularization. It was also noted that intraventricular conduction disorders including left and right bundle branch blocks and a history of previous revascularization and myocardial infarction were associated with lower odds of revascularization. Overall, however, the predictive value of the studied factors proved to be poor and may still point to the multifactorial nature of significant coronary artery stenosis and the need for revascularization in patients with UA.

Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias.

A group of 32 unrelated individuals, aged 63 ± 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.

Coronary Artery Disease Is Related to Methylation Disorders Caused by the c.1286A&gt;C MTHFR Polymorphism and to Low Serum 5-MTHF and Folic Acid Concentrations—Preliminary Results

Background: Single nucleotide polymorphisms in gene encoding is the key enzyme in the folates pathway, methyltetrahydrofolate reductase (MTHFR), which causes methylation disorders associated with coronary artery disease (CAD). We evaluated associations between methylation disorders caused by MTHFR gene polymorphisms and the blood folate concentrations (folic acid, 5-MTHF) in CAD patients. Methods: Study group: 34 patients with CAD confirmed by invasive coronary angiography (ICA). Controls: 14 patients without CAD symptoms or significant coronary artery stenosis, based on ICA or multislice computed tomography (MSCT) with coronary artery calcification (CAC) scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined using Liquid Chromatography-Mass Spectrometry (LC-MS). Results: The c.[1286A&gt;C];[1286A&gt;C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to the (CAD−) cohort and to the selected general European “CEU_GENO_PANEL” population sample. The concentration of 5-MTHF and folic acid in subgroups of CAD+ patients with methylation disorders categorized by genotypes and CAD presence (CAD+) was always lower in CAD+ subgroups compared to non-CAD individuals (CAD−). Conclusions: Further studies on a larger scale are needed to implicate the homozygous c.1286A&gt;C MTHFR variant as CAD genetic marker and the 5-MTHF as CAD biomarker. Identification of high CAD risk using genetic and phenotypic tests can contribute to personalized therapy using an active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymorphisms.

Updates on Prognostication of Takotsubo Cardiomyopathy: A Literature Review

Abstract Takotsubo cardiomyopathy (TTC), commonly known as “broken heart syndrome” or “stress cardiomyopathy,” is characterized by transient left ventricular (LV) systolic dysfunction, usually in the absence of significant obstructive coronary artery stenosis. The pathophysiology of TTC remains elusive; however, the three most common plausible mechanisms include catecholamine surge causing myocardial stunning, multivessel coronary spasm, and microvascular dysfunction. Although initially thought to be a benign, reversible, and transient disorder, newer research data demonstrate that TTC may sometimes have severe short-term complications and some long-term residual effects. Several risk factors have been associated with the outcomes of TTC. In this review, we aim to provide a comprehensive review of the prognostication of TTC in the context of different clinical variables presented in multiple research studies. Various clinical factors, including the types of TTC triggers, the patient’s sex, the presence of cardiogenic shock, atrial arrhythmias, LV tract obstruction, and the presence of certain other clinical comorbidities may significantly impact patient outcomes in TTC patients. A thorough understanding of these factors helps clinicians to better prognosticate the outcome of their patients. Furthermore, early institution of aggressive treatment interventions in the presence of these risk factors may improve the subsequent clinical course.