Epicardial Coronary Artery Stenosis Research Articles

Prognostic implications of microvascular resistance reserve in symptomatic patients with intermediate coronary stenosis

Abstract Background Microvascular 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). Objective To evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. Methods The current study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiologic 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. Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. Results Among the total patients, 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), however, it was significantly correlated with index of microcirculatory resistance (R=-0.353, P<0.001), NT-proBNP (R=-0.296, P<0.001), left ventricular filling pressure (E/e’) (R=-0.224, P<0.001), and diastolic dysfunction grade (P<0.001). During median follow-up of 3.3 years (interquartile range from 2.0 to 4.5 years), MRR was significantly associated with MACE risk (HR 1.23 per-1 decrease, 95% CI 1.12-1.36, P<0.001). CMD defined by MRR≤3.0 was associated with an increased MACE risk in both FFR>0.80 (41.0% vs. 26.0%; HRadj 1.59, 95% CI 1.07-2.35, P=0.021) and FFR≤0.80 (34.7% vs. 14.8%; HRadj 2.32, 95% CI 1.12-4.82, P=0.024) groups. Conclusion Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as with increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk of 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 significance of coexistent coronary artery disease in patients undergoing transcatheter aortic valve implantation for aortic stenosis

Abstract Background The optimal management of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) is uncertain. As TAVI expands into lower risk cohorts with longer life expectancies there is increasing need to determine the prognostic significance of coexistent CAD and identify which lesions may benefit from revascularisation. Purpose To evaluate the prognostic significance of coexistent CAD in patients with AS undergoing TAVI stratified according to myocardial territories at risk. Methods Using a retrospective, single-centre, observational registry, patients undergoing TAVI for severe AS between 2015 and 2020 were included. CAD was angiographically determined using computed tomography or invasive coronary angiography. CAD was stratified into 1) low-risk: <70% stenosis in all major epicardial coronary arteries or <50% in the left main (LM); 2) intermediate-risk: ≥70% stenosis in one or two arteries, except the proximal left anterior descending (LAD) and LM; 3) high-risk: ≥70% stenosis in the proximal LAD, ≥70% stenosis in 3 arteries or LM stenosis ≥50%. Patients with previous CABG were categorised as high-risk if: ≥70% stenosis of 3 coronary grafts or graft supplying a proximally stenosed LAD; and intermediate-risk if: ≥70% stenosis of 1 or 2 non-LAD grafts. Baseline characteristics and procedural outcomes were compared between the 3 cohorts, with the impact of CAD on outcomes evaluated after adjustment for demographics and comorbidities. Results 1805 patients were included; median age 84 (79-88), 51% male sex, median logistic Euroscore 13 (8-21). 1281 (71%), 384 (21%) and 140 (8%) patients were characterised as low-, intermediate- and high-risk coronary anatomy respectively. High risk patients were older than the other groups, however, did not have the highest prevalence of comorbidities (Table 1). Other than pacemaker implantation (9% vs 12% vs 6%, p=0.04), there were no differences in procedural complications or in-hospital mortality between groups (Table 1). At a median follow-up of 3.5 (2.3-4.8) years, 920 patients (51%) died, 292 (16%) had hospitalisation for heart failure (HHF) and 565 patients (31%) had a major adverse coronary event (MACE); defined as either myocardial infarction, HHF or cardiovascular death. Coronary anatomical stratification was associated with MACE (Log rank p<0.001) (Figure 1). After multivariate adjustment, high-risk anatomy was associated with all-cause mortality (hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.06-1.68, p=0.013), HHF (HR: 1.49, 95% CI: 1.01-2.21, p=0.046) and MACE (HR: 1.68, 95% CI: 1.27-2.21, p<0.001). Conclusions Whilst the presence of CAD does not impact TAVI procedural safety, untreated high-risk coronary anatomy is associated with future adverse events and may warrant intensive medical therapy and/or revascularisation.

Visual Estimates of Coronary Slow Flow Are Not Associated With Invasive Wire-Based Diagnoses of Coronary Microvascular Dysfunction.

Coronary slow flow (CSF) by invasive coronary angiography is frequently understood to be an indicator of coronary microvascular dysfunction (CMD) in patients with ischemia with nonobstructive coronary arteries. However, the relationship between visual estimates of CSF and quantitative wire-based invasive diagnosis of CMD is uncertain. We prospectively enrolled adults aged ≥18 years with stable ischemic heart disease who were referred for invasive coronary angiography. Individuals with ≥50% epicardial coronary artery stenosis were excluded. Invasive coronary angiography was reviewed for CSF, defined as ≥3 cardiac cycles to opacify distal vessels with contrast. Coronary function testing was performed in the left anterior descending coronary artery using bolus coronary thermodilution techniques to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Invasively determined CMD was defined as abnormal CFR (<2.5), abnormal IMR (≥25), or both. Among 104 participants, the median age was 61.5 years and 79% were female. The median CFR was 3.6 (interquartile range, 2.5-4.7) and the median IMR was 21 (interquartile range, 13.3-28.0). Overall, 24.0% of participants had abnormal CFR, 34.6% had abnormal IMR, and 48.1% had a final diagnosis of invasively determined CMD. CSF was present in 23 participants (22.1%). The proportions of patients with CMD (56.5% versus 45.7%; P=0.36), abnormal CFR (17.4% versus 25.9%; P=0.40), and abnormal IMR (43.5% versus 32.1%; P=0.31) were not different in patients with versus without CSF. Among patients with ischemia with nonobstructive coronary artery, CSF was not associated with abnormal CFR, IMR, or either abnormal CFR or IMR. CSF is not a reliable angiographic surrogate of abnormal CFR or IMR as determined by invasive, wire-based physiology testing. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537586.

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.

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)

Differences in coronary angiographic findings and outcomes between men and postmenopausal women with stable chest pain.

Despite the significant increase in cardiovascular events in women after menopause, studies comparing postmenopausal women and men are scarce. We analyzed data from a nationwide, multicenter, prospective registry and enrolled 2412 patients with stable chest pain who underwent elective coronary angiography. Binary coronary artery disease (b-CAD) was defined as the ≥50% stenosis of epicardial coronary arteries, including the left main coronary artery. Compared with the men, postmenopausal women were older (66.6 ± 8.5 vs. 59.5 ± 11.4 years) and had higher high-density lipoprotein cholesterol levels (49.0 ± 12.8 vs. 43.6 ± 11.6 mg/dl, P < 0.01). The prevalence of diabetes did not differ significantly ( P = 0.40), and smoking was more common in men than in postmenopausal women ( P ≤ 0.01). At enrollment, b-CAD and revascularization were more common in men than in postmenopausal women (50.3% vs. 41.0% and 14.4% vs. 9.7%, respectively; both P < 0.01). However, multivariate analyses revealed that revascularization [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.49-1.08] was not significantly related to sex and a similar result was found in age propensity-matched population (OR: 0.80; 95% CI: 0.52-1.24). During the follow-up period, the secondary composite cardiovascular outcomes were lower in postmenopausal women than in men (OR: 0.55; 95% CI: 0.31-0.98), also consistent with the result using the age propensity-mated population (OR: 0.33; 95% CI: 0.13-0.85). Postmenopausal women experienced coronary revascularization comparable to those in men at enrollment, despite the average age of postmenopausal women was 7 years older than that of men.Postmenopausal women exhibit better clinical outcomes than those of men if optimal treatment is provided.

Serum levels of the endoplasmic-reticulum-stress chaperone GRP78 are associated with inflammation, identify patients with coronary artery disease and predict mortality

Abstract Introduction Endoplasmic-reticulum-stress (ER Stress) and associated chaperones like the ER-Stress moderator GRP78 (glucose-regulated-protein, 78kDa) are involved in the pathogenesis of coronary artery disease (CAD). In addition to their intracellular effects, secretion and extracellular properties of chaperones, including GRP78, were recently described. In a recent study using proteomic data, we found coronary endothelial cells to secrete GRP78 into the extracellular space. Here, we investigated the significance of serum GRP78 in patients undergoing coronary angiography for suspected CAD. Methods Serum concentration of GRP78 was measured by ELISA in an all-comers cohort of 789 patients with clinical indication for coronary angiography. Samples were drawn from the arterial sheath. CAD was defined as &amp;gt;50% stenosis in any major epicardial coronary artery. Patients were stratified according to their clinical presentation (CCS: chronic coronary syndrome or ACS). Clinical endpoint was all-cause mortality after one year. Patients with malignant or active auto-immune diseases were excluded. Results Mean age was 70.8 ± 11.9 years and 65% of patients were male. 24% patients presented with acute coronary syndrome (ACS). CAD was found in 72.4% of patients. Mean GRP78 serum concentration was 2492 ng/ml. Increased levels of GRP78 (&amp;gt; median) were associated with diabetes (29.9% vs. 23.1%, p = 0.03), a higher BMI (28.9 kg/m2 ± 7.1 vs. 27.0 kg/m2 ± 6.0, p &amp;lt; 0.0001) and chronic kidney disease (CKD: 23.3 % vs. 17.1 %, p = 0.03). There was no difference regarding age or sex. We further compared GRP78 levels to other biomarkers including WBC, Hemoglobin, Troponin, Creatinine, and Interleukin-6 (IL-6). There was no association between GRP78 levels and the mentioned biomarkers, except for a positive correlation between GRP78 and levels of Interleukin-6 (Pearson r =0.14, p = 0.004). GRP78 levels were increased in patients with CAD when compared to patients without CAD (2640 ng/ml vs. 2178 ng/ml, p = 0.013). Interestingly, GRP78 levels were lower in patients with ACS than in patients with CCS (2284 ng/ml vs. 2822 ng/ml, p = 0.018). There was no difference between NSTEMI and STEMI patients. Finally, we assessed prognostic relevance of GRP78 in patients with CAD. Increased GRP78 levels were associated with lower occurrence of the clinical endpoint of one-year mortality (5.3% vs. 10.6 % vs. p = 0.016). Increased GRP78 levels were associated with reduced one-year mortality (HR: 0.48 [95% CI: 0.25 - 0.92]). After adjusting for IL-6, age, sex, BMI, diabetes, CKD, and ACS, GRP78 remained an independent predictor of one-year mortality in patients with CAD. Conclusion GRP78 serum levels are generally elevated in patients with CAD but are downregulated during ACS. Reduced levels are associated with increased one-year mortality. These results support previous findings that GRP78 secretion is a protective mechanism in cardiovascular diseases.

Diagonal earlobe crease (Frank's sign) predicts obstructive coronary artery disease with modest accuracy

Abstract Introduction Traditional risk factors for cardiovascular disease (CVD) play an important role in the clinical evaluation of patients with symptoms suggestive of coronary artery disease (CAD). The utility of anthropometric indices, including diagonal earlobe crease (Frank's sign), in predicting the risk of CAD is controversial. Purpose To investigate the association between Frank's sign, traditional CVD risk factors, and obstructive CAD. Methods This prospective study included 1401 patients (mean age 65±10 years, 64% male) who underwent invasive coronary angiography for suspected acute or chronic coronary syndromes. In addition to routine clinical assessment, all patients underwent visual examination of both earlobes for the presence of Frank's sign, defined as a diagonal earlobe fold (Figure A, arrow). All assessments were made by three independent readers, with a majority vote in case of disagreement. Obstructive CAD was defined by invasive coronary angiography as &amp;gt;50% diameter stenosis of the left main coronary artery or &amp;gt;70% diameter stenosis of any other major epicardial coronary artery. Results Unilateral or bilateral Frank’s sign was observed more frequently in patients with obstructive CAD than in those without it (73% vs 68% for unilateral and 55% vs 47% for bilateral Frank’s sign, p&amp;lt;0.05 for both). In the multivariate logistic regression model (Graph), bilateral Frank’s sign was independently associated with CAD [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.17-1.85], along with smoking (OR 1.74, 95% CI 1.38-2.20), diabetes mellitus (OR 1.70, 95% CI 1.32-2.19), male sex (OR 1.99, 95% CI 1.58-2.52), and dyslipidemia (OR 1.52, 95% CI 1.06-2.19). However, diagnostic accuracy of Frank's sign was modest [area under the curve (AUC) 0.54, 95%CI 0.51-0.57] and resembled that of traditional CVD risk factors (Graph). Conclusion Despite being independently associated with obstructive CAD, Frank’s sign is not a reliable clinical marker of CAD due to modest diagnostic accuracy.

The relationship of diagonal earlobe crease (Frank's sign) and obstructive coronary artery disease in patients undergoing coronary angiography.

Traditional risk factors for cardiovascular disease (CVD) play an important role in the clinical evaluation of patients with symptoms suggestive of coronary artery disease (CAD). The utility of the diagonal earlobe crease (DELC) in predicting the presence of CAD is controversial. To investigate the association between DELC, traditional CVD risk factors, and obstructive CAD. This prospective study included 1377 patients (mean age 65 ± 10years, 64% male) who underwent invasive coronary angiography for suspected acute or chronic coronary syndromes. In addition to routine clinical assessment, all patients underwent visual examination of both earlobes for the presence of DELC. All assessments were made by three independent readers, with amajority vote in the case of disagreement. Obstructive CAD was defined by invasive coronary angiography as > 50% stenosis of the left main coronary artery or > 70% stenosis in any other major epicardial coronary artery. Bilateral DELC was observed more frequently in patients with obstructive CAD than in those without it (67% vs. 33%, p = 0.022). In the multivariate logistic regression model, bilateral DELC was independently associated with CAD (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.07-1.74), along with smoking (OR 1.86, 95% CI 1.44-2.38), diabetes mellitus (OR 1.67, 95% CI 1.29-2.15), male sex (OR 2.04, 95% CI 1.61-2.58), and dyslipidemia (OR 1.54, 95% CI 1.12-2.30); however, the diagnostic accuracy of DELC was modest and resembled that of traditional CVD risk factors. Despite being independently associated with obstructive CAD, DELC is not areliable stand-alone clinical marker of CAD due to modest diagnostic accuracy.

Coronary Computed Tomographic Angiography With Fractional Flow Reserve in Patients With Type 2 Myocardial Infarction

BackgroundType 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population. ObjectivesThe goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI. MethodsIn this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFRCT), and plaque volume analyses. ResultsAmong 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFRCT was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFRCT excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%). ConclusionsAmong individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119)

Coronary artery tortuosity and mid-term all-cause mortality of patients with ischemia and non-obstructive coronary arteries.

Background: Coronary artery tortuosity (CAT) is a frequently encountered angiographic feature of patients with ischemia and non-obstructive coronary arteries (INOCA). However, there is limited data regarding the possible correlation between CAT and all-cause mortality in these patients. Aim: To assess the survival prognostic implications of CAT in INOCA patients and the predictors of all-cause mid-term mortality of these patients. Methods: All consecutive INOCA patients, with preserved ejection fraction evaluated for clinical ischemia by coronary angiography in our department between January 2014 and December 2020 were considered for inclusion. Patients with epicardial coronary artery stenosis ≥ 50%, severe pulmonary hypertension, or decompensated extra cardiac disease were excluded. Eleid classification was used for CAT severity characterization. We assessed all-cause mortality in January 2023. Results: Our sample included 328 INOCA patients. 15.54% died during the mean follow-up of 3.75 ± 1.32 years. 79.88% had CAT. CAT patients were older (65.10±9.09 versus 61.24±10.02 years, p=0.002), and more often female (67.18% versus 31.82%, p<0.001). CAT was inversely correlated with all-cause mid-term mortality (OR 0.35, 95%CI 0.16 - 0.77, p=0.01). CAT severity had no impact on survival. In CAT patients the initial multivariable analysis identified NT-proBNP levels (HR 3.96, p=0.01), diabetes mellitus (DM) (HR 4.76, p=0.003), and atrial fibrillation (HR 2.68, p=0.06) as independent predictors of all-cause mortality. In the final analysis, NT-proBNP and DM were the main independent predictors of survival. Conclusions : In our INOCA cohort, CAT patients were older and more likely female. CAT was inversely correlated with mid-term all-cause mortality. NT-proBNP and DM were the main independent predictors of mortality of CAT patients.

Prognostic value of myocardial flow reserve measured with CZT cardiac-dedicated SPECT low-dose dynamic myocardial perfusion imaging in patients with INOCA.

Clinical use of dynamic myocardial perfusion imaging (D-MPI) of cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT is growing, showing a higher application value than conventional SPECT. The prognostic value of ischemia in patients with non-obstructive coronary arteries (INOCA) remains an important challenge for investigation. The primary objective of this study was to investigate the prognostic value of myocardial flow reserve (MFR) measured with low-dose D-MPI of CZT cardiac-dedicated SPECT in the assessment of patients with INOCA. Consecutive screening of patients with INOCA and obstructive coronary artery disease (OCAD) who had coronary angiography (CAG) data was performed within three months before or after D-MPI imaging. The patients who met the inclusion criteria were retrospectively analyzed and follow-up by telephone was performed. The enrolled patients were then divided into the INOCA and OCAD groups. INOCA was defined as signs and/or symptoms of myocardial ischemia but with < 50% epicardial stenosis. OCAD was defined as obstructive stenosis (≥ 50% stenosis) of epicardial coronary arteries or their major branches on the CAG. Medical treatments, Seattle Angina Questionnaire (SAQ) scores, and major adverse cardiac events (MACEs) were studied. The Kaplan-Meier survival curve, Log-rank test, and univariable COX regression analysis were used to evaluate the prognosis of patients and associated predictors, with P < 0.05 being considered statistically significant. A total of 303 patients (159 males and 144 females) were enrolled for the final analysis after excluding 24 patients who were lost to follow-up. The mean age of the included cases was 61.94 ± 8.59 years, of which 203 (67.0%) cases were OCAD and 100 (33.0%) cases were INOCA, respectively. The median follow-up was 16 months (14-21 months). Kaplan-Meier survival curves showed that the incidence of MACE was similar in the INOCA and OCAD groups (log-rankP = 0.2645), while those with reduced MFR showed a higher incidence of MACE than those with normal MFR (log-rankP = 0.0019). The subgroup analysis in the OCAD group revealed that 105 patients with reduced MFR had a higher incidence of MACE than those with normal MFR (log-rankP = 0.0226). The subgroup analysis in the INOCA group showed that 37 patients with reduced MFR had a higher incidence of MACE than those with normal MFR in the INOCA group (log-rankP = 0.0186). Univariable Cox regression analysis showed for every 1 unit increase in MFR, the risk of MACE for INOCA was reduced by 66.1% and that for OCAD by 64.2%. For each 1mL·g-1·min-1 increase in LV-sMBF, the risk of MACE was reduced by 72.4% in INOCA patients and 63.6% in OCAD patients. MFR measured with low-dose D-MPI CZT SPECT provides incremental prognostic value in patients with INOCA. Patients with reduced MFR show an increased risk of MACE, increased symptom burdens, and impaired quality of life. INOCA patients with reduced MFR experienced higher rate of MACE than OCAD patients with normal MFR.

Coronary "Microvascular Dysfunction": Evolving Understanding of Pathophysiology, Clinical Implications, and Potential Therapeutics.

Until recently, it has been generally held that stable angina pectoris (SAP) primarily reflects the presence of epicardial coronary artery stenoses due to atheromatous plaque(s), while acute myocardial infarction (AMI) results from thrombus formation on ruptured plaques. This concept is now challenged, especially by results of the ORBITA and ISCHEMIA trials, which showed that angioplasty/stenting does not substantially relieve SAP symptoms or prevent AMI or death in such patients. These disappointing outcomes serve to redirect attention towards anomalies of small coronary physiology. Recent studies suggest that coronary microvasculature is often both structurally and physiologically abnormal irrespective of the presence or absence of large coronary artery stenoses. Structural remodelling of the coronary microvasculature appears to be induced primarily by inflammation initiated by mast cell, platelet, and neutrophil activation, leading to erosion of the endothelial glycocalyx. This leads to the disruption of laminar flow and the facilitation of endothelial platelet interaction. Glycocalyx shedding has been implicated in the pathophysiology of coronary artery spasm, cardiovascular ageing, AMI, and viral vasculitis. Physiological dysfunction is closely linked to structural remodelling and occurs in most patients with myocardial ischemia, irrespective of the presence or absence of large-vessel stenoses. Dysfunction includes the impairment of platelet and vascular responsiveness to autocidal coronary vasodilators, such as nitric oxide, prostacyclin, and hydrogen sulphide, and predisposes both to coronary vasoconstriction and to a propensity for microthrombus formation. These findings emphasise the need for new directions in medical therapeutics for patients with SAP, as well as a wide range of other cardiovascular disorders.

The imPAct of Trimetazidine on MicrOcirculation after Stenting for stable coronary artery disease (PATMOS study).

Myocardial ischemia is caused by epicardial coronary artery stenosis or atherosclerotic disease affecting microcirculation. Trimetazidine (TMZ), promotes glucose oxidation which optimizes cellular energy processes in ischemic conditions. Small studies demonstrated protective effects of TMZ in terms of reducing myocardial injury after percutaneous coronary intervention (PCI), its effect on microcirculation using contemporary investigative methods has not been studied. The aim of the study was to examine effects of trimetazidine, given before elective PCI, on microcirculation using invasively measured index of microcirculatory resistance (IMR). This was prospective, single blinded, randomized study performed in a single university hospital. It included consecutive patients with an indication for PCI of a single, de novo, native coronary artery lesion. Patients were randomly assigned to receive either TMZ plus standard therapy (TMZ group) or just standard therapy. Coronary physiology indices fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured before and after PCI using coronary pressure wire. We randomized 71 patients with similar clinical characteristics and risk profile, previous medications and coronary angiograms. Patientshad similar values of Pd/Pa, FFR and CFR prior to PCI procedure. After PCI, FFR values were higher in TMZ group, while IMR values were lower in this group respectively (FFR TMZ + 0.89 ± 0.05 vs. TMZ - 0.85 ± 0.06, p = 0.007; CFR TMZ + 2.1 ± 0.8 vs. TMZ- 2.3 ± 1.3, p = 0.469; IMR TMZ + 18 ± 9 vs. TMZ- 24 ± 12, p = 0.028). In two-way repeated measures ANOVA PCI was associated with change in FFR values (TMZ p = 0.050; PCI p < 0.001; p for interaction 0.577) and TMZ with change in IMR values (TMZ p = 0.034, PCI p = 0.129, p for interaction 0.344). Adding trimetazidine on top of medical treatment prior to elective PCI reduces microvascular dysfunction by lowering postprocedural IMR values when compared to standard therapy alone.

Characteristic cardiac capillary pericytes in a Fabry disease patient receiving enzyme replacement therapy

Fabry disease, a lysosomal disorder caused by deficiency in α-galactosidase A, patients report chest pain in the absence of epicardial coronary artery stenosis. Although it is conceivable that coronary microvascular dysfunction due to globotriaosylceramide (GL-3) accumulation within the vasculature causes angina, the precise histology was unknown. A 34-year-old male patient diagnosed with Fabry disease [NM_000169.3:c.1089_1090insTCGC (p.Tyr365Lysfs*11)] and treated for 6 years with enzyme replacement therapy (ERT) was referred to our cardiology department because of palpitations and precordial discomfort. He was diagnosed for paroxysmal atrial fibrillation and subsequently underwent catheter ablation therapy. The procedure resolved his palpitations, but his precordial discomfort remained. Again, coronary angiography showed no organic stenosis. A 24-hour Holter electrocardiogram detected neither arrhythmia nor ischemic changes. Echocardiography showed normal wall motion with diffuse left ventricular hypertrophy. Endomyocardial biopsy revealed severe vacuolated hypertrophied myocytes appearing transparent, like a lace curtain, which is characteristic of Fabry disease (Figure A, A’ and B). Electron microscopic examination revealed abundant lamellar bodies with a myelin-like configuration within cardiomyocytes and interstitial macrophages, indicating GL-3 deposition (Figure C, D and E). We also detected numerous interstitial microcapillaries showing abundant lamellar body deposits within the capillary pericytes but not the endothelial cells (Figure F, F’-1 and F’-2. Pericytes surrounding the endothelial cells can regulate capillary blood flow in microvascular beds. Our pathological findings suggest progressive lamellar body accumulation caused angina by disrupting microvascular circulation. This case highlights progression of microvascular Fabry disease especially in capillary pericytes and also a need for develop therapies targeting capillary circulation.

Investigation of the Relationship Between Triglycerides-Glucose İndex and Coronary Slow Flow: A Retrospective Case-Control Study.

Coronary slow flow (CSF) refers to delayed distal vessel opacification in the absence of epicardial coronary artery stenosis. The etiopathogenic mechanism of CSF is still unclear. This study investigates the relationship between CSF and the triglyceride-glucose (TyG) index. The study sample consisted of 118 CSF patients and 105 patients with normal coronary flow (NCF). The coronary flow rate was measured via the Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) method in all patients. The TyG index was calculated as the logarithm of the [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)]/2 value. A significance level of < 0.05 was adopted as statistically significant. The TyG index, low-density lipoprotein (LDL), body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR) and TFC values, male ratio, and the ratio of smokers were higher, whereas high-density lipoprotein (HDL) levels were significantly lower in the CSF group compared to the NCF group (p<0,05). The correlation analysis revealed that CSF was significantly correlated with TyG index, BMI, NLR, and HDL values. The strongest of these correlations was between CSF and TyG index (r= 0.57, p<0.001). Additionally, the multivariate analysis revealed that TyG index, BMI, NLR ratio, and male gender were independent predictors for CSF (p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that a cut-off value of ≥ 9.28 for the TyG index predicted CSF with a sensitivity of 78% and a specificity of 78.1% [Area under the curve (AUC): 0.868 and 95% Confidence Interval (CI): 0.823-0.914]. The findings of this study revealed a very strong relationship between CSF and TyG index.

Association between coronary flow and aortic stenosis during transcatheter aortic valve implantation.

In patients with aortic stenosis (AS), the coronary flow reserve decreases even in the absence of epicardial coronary artery stenosis. Systolic coronary flow reversal (SFR) reflecting reduced coronary microcirculation, often seen in patients with severe AS, has a potential negative impact on the pathogenesis of cardiac dysfunction. However, there are limited data on the relationship between the severity of AS and SFR, as well as on the benefits of transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the relationship between the severity of AS and efficacy of TAVI in improving SFR. Consecutive patients with AS who had undergone TAVI using transoesophageal echocardiography (TEE) from November 2020 to February 2022 were prospectively enrolled. Coronary flow in the left anterior descending artery as well as the aortic valve peak velocities, and the mean aortic valve pressure gradients (AVPGs), indicating the severity of AS, were measured using intraprocedural TEE before and after TAVI. The following parameters were measured as coronary flow: systolic and diastolic peak velocity (cm/s) and systolic and diastolic velocity-time integral (VTI) (cm). SFR was defined as the presence of a reversal coronary flow component in systole. The enrolled patients were classified into two groups according to the presence or absence of SFR before TAVI. A total of 25 patients were included: 13 had SFR and 12 who had no SFR, before TAVI. Patients with SFR had significantly higher aortic valve peak velocities (451.1±45.9 vs. 372.1±52.1cm/s; P<0.001) and mean AVPGs (49.2±14.5 vs. 30.3±11.6mmHg; P=0.002) than those without. The optimal binary cut-off aortic valve peak velocity values and the mean AVPG associated with the presence of SFR before TAVI were >410.0cm/s (specificity, 75.0%; sensitivity, 92.3%) and >37.4mmHg (specificity, 83.3%; sensitivity, 92.3%), respectively. After TAVI, SFR immediately disappeared in 11 of 13 patients with SFR (84.6%). Overall, the systolic coronary VTI significantly increased after TAVI (2.0±4.7 vs. 6.4±3.2cm, P<0.001), and this increase was greater in patients with SFR than in those without SFR before TAVI (interaction P=0.035). SFR was found to be associated with the severity of AS and with a greater increase in systolic coronary flow immediately after TAVI.

CXCL5 gene polymorphisms and coronary collateralization

BackgroundThe presence of coronary collateralization is heterogenous, even amongst those with similar degrees of epicardial coronary artery stenoses. We hypothesized that genetic variation of CXCL5, a chemokine that mediates angiogenesis, is associated with coronary collateralization. MethodsWe genotyped subjects undergoing coronary angiography for single nucleotide polymorphisms of CXCL5 and determined the presence of spontaneously visible coronary collaterals. ResultsSubjects with collaterals had less angina (46 % vs 59 %, p = 0.006), and prior percutaneous coronary intervention (34 % vs 47 %, p = 0.010), and more hyperlipidemia (90 % vs 82 %, p = 0.018), peripheral arterial disease (25 % vs 17 %, p = 0.041), congestive heart failure (16 % vs 8 %, p = 0.007), and multi-vessel coronary artery disease (41 % vs 24 %, p = 0.0001) compared to those without collaterals. Multi-vessel disease and hyperlipidemia were positive predictors of angiographically visible collaterals while being a carrier of the CXCL5 polymorphism was a negative predictor. ConclusionsCoronary collateralization may, at least in part, be genetically determined.

Perivascular nerve fibres are increased in the epicardium while perivascular adipose tissue is decreased in the myocardium in patients with acute myocardial infarction

Abstract Background Vasospasm is an important etiological factor in the induction of acute myocardial infarction (AMI). PeriVascular Nerve Fibres (PVNF) and PeriVascular Adipose Tissue (PVAT) play an important role in vasoregulation, although detailed information of their role in the heart is missing in AMI patients. In the present study we have analysed PVNF and PVAT in deceased AMI patients. Methods Sections of epicardial coronary arteries were obtained at autopsy from AMI patients (N=16) and controls without heart disease (N=7). Infarct age was between 3 and 6 hours old. Stenosis of epicardial coronary arteries was quantified in a HE stained slide. To analyse the intramyocardial vasculature samples were taken from the left ventricle of the heart (in AMI patients the infarcted area). Nerve fibres were stained using a specific S100 antibody. Putative activation of these nerves was stained using a specific antibody against neuropeptide Y (NPY). S100+ and NPY+ nerve fibres were quantified by light microscopy and were then calculated per square mm of the adventitia surface areas. PVAT was quantified using an Elastica Von Gieson (EvG) staining. Results Stenosis did not correlate with PVNF. AMI patients had a significant increase in PVNF in the epicardium but not in the myocardium. NPY was non-significantly increased in PVNF in the epicardium and myocardium in AMI patients compared with controls. PVAT was significantly decreased in AMI patients compared with controls. Conclusion The increase in PVNF in the epicardium and the decrease of PVAT in the myocardium suggest that they might play a role in AMI induction, independent of the atherosclerotic changed epicardial coronary arteries. Funding Acknowledgement Type of funding sources: None.

"CIRCLE OF VIEUSSENS": A LIFE-SAVING CORONARY ARTERY ANOMALY IN A PATIENT WITH KAWASAKI DISEASE

"CIRCLE OF VIEUSSENS": A LIFE-SAVING CORONARY ARTERY ANOMALY IN A PATIENT WITH KAWASAKI DISEASE