Obstructive Epicardial Coronary Artery Disease Research Articles

Traditional Cardiovascular Risk Factors and Coronary Microvascular Disease in Women and Men- A Single Center Study.

Introduction Coronary microvascular disease (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 non-obstructive 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 non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 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 (CFR) (β=-0.29; p<0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (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.

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.

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.

Diagnostic value of computed tomography myocardial perfusion imaging to detect coexisting microvascular dysfunction in patients with obstructive epicardial coronary artery disease.

Computed tomography myocardial perfusion (CT-MP) has reported usefulness in assessing hemodynamically significant epicardial coronary artery lesions. However, the diagnostic ability of the absolute coronary flow using CT-MP to detect coronary microvascular dysfunction (CMD) remains elusive. This prospective cohort study aimed to assess the diagnostic value of CT-MP in evaluating coexisting CMD in patients with functionally significant epicardial coronary stenosis and to analyze the predictive factors of lesions with CMD. Sixty-eight patients with chronic coronary syndrome (CCS) and de novo single functionally significant stenosis [fractional flow reserve (FFR) ≤0.80] were studied. CMD was defined as an index of microcirculatory resistance ≥25. We compare clinical background and CT-MP findings between patients with and without CMD (CMD, n=29; non-CMD, n=39). CT-MP, and quantitative and qualitative plaque assessments were included in computed tomography angiography assessment. Logistic regression analysis was performed to predict CMD. FFR, invasive wire-derived coronary flow reserve (CFRwire) and index of microcirculatory resistance were 0.68 [interquartile range (IQR), 0.59-0.74], 1.71 (IQR, 1.24-2.88), and 22.6 (IQR, 15.1-34.5), respectively. The rest and hyperemic-myocardial blood flow (MBF) and CT-MP-derived CFR (CFRCT-MP) were 0.83 (0.64-1.03) mL/min/g, 2.14 (1.30-2.92) mL/min/g, and 2.19 (1.44-3.37), respectively. In the territories with CMD, hyperemic-MBF was significantly lower than in those without [1.68 (IQR, 0.84-2.44) vs. 2.31 (IQR, 1.67-3.34) mL/min/g, P=0.015] and the prevalence of CFRCT-MP <2.0 was higher in the lesions with CMD than in those without (62.1% vs. 28.2%, P=0.011), while FFR values were similar. Fibrofatty and necrotic core component volume was greater in the vessels with CMD than in those without [31.8 (IQR, 19.0-48.9) vs. 25.1 (IQR, 17.2-32.1) mm3, P=0.045]. Multivariable logistic regression analysis showed that hyperemic-MBF and fibrofatty and necrotic core component volume were independent predictors of CMD territories [odds ratio (OR) =0.583; 95% confidence interval (CI): 0.355-0.958; P=0.033 and OR =1.040; 95% CI: 1.010-1.070; P=0.011]. Quantitative assessment of absolute coronary flow using pre-percutaneous coronary intervention (PCI) CT-MP, and comprehensive plaque analysis using computed tomography angiography may help detect coexisting subtended microvascular dysfunction in territories with functionally significant epicardial coronary lesions. Further studies are required to elucidate the clinical significance of coexisting CMD in patients with CCS undergoing PCI.

Intra-coronary physiology in contemporary percutaneous coronary intervention and anginal therapy with a focus on microvascular disease

Coronary physiological measurements have transformed the treatment of coronary artery disease (CAD), with increasing evidence supporting the use of pressure wire guided revascularisation. Advances in microvascular assessment have enabled clinicians to discern angina aetiology even in patients without obstructive epicardial coronary artery disease, paving the way for more effective tailored therapy. In this article, the authors will examine pressure wire indices, their role in influencing clinical outcomes and future directions.

Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease.

Distinguishing obstructive epicardial coronary artery disease (CAD) from microvascular dysfunction and diffuse atherosclerosis would be of immense benefit clinically. However, quantitative measures of absolute myocardial blood flow (MBF) integrate the effects of focal epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. In this study, MFR and relative perfusion quantification were combined to create integrated MFR (iMFR) which was evaluated using data from a large clinical registry and an international multi-center trial and validated against invasive coronary angiography (ICA). This study included 1,044 clinical patients referred for 82Rb rest/stress positron emission tomography myocardial perfusion imaging and ICA, along with 231 patients from the Flurpiridaz 301 trial (clinicaltrials.gov NCT01347710). MFR and relative perfusion quantification were combined to create an iMFR map. The incremental value of iMFR was evaluated for diagnosis of obstructive stenosis, adjusted for patient demographics and pre-test probability of CAD. Models for high-risk anatomy (left main or three-vessel disease) were also constructed. iMFR parameters of focally impaired perfusion resulted in best fitting diagnostic models. Receiver-operating characteristic analysis showed a slight improvement compared to standard quantitative perfusion approaches (AUC 0.824 vs. 0.809). Focally impaired perfusion was also associated with high-risk CAD anatomy (OR 1.40 for extent, and OR 2.40 for decreasing mean MFR). Diffusely impaired perfusion was associated with lower likelihood of obstructive CAD, and, in the absence of transient ischemic dilation (TID), with lower likelihood of high-risk CAD anatomy. Focally impaired perfusion extent derived from iMFR assessment is a powerful incremental predictor of obstructive CAD while diffusely impaired perfusion extent can help rule out obstructive and high-risk CAD in the absence of TID.

Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know.

Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.

P78 PSYCHIATRIC PATHOLOGIES PREVALENCE OF IN TAKOTSUBO SYNDROME

Abstract Background Tako Tsubo syndrome (TTS) is characterized by transient alterations of ventricular kinetics (ATC) in the absence of obstructive epicardial coronary artery disease. Materials 39 cases of TTS that came to our observation from 2005 to 2019 are described, the diagnosis was made on the basis of evidence of ATC, ECG alterations, increase necrosis markers in the absence of obstructive coronary disease, excluding myocarditis. Results 39 patients (PZ) (35 females and 4 males) diagnosed with TTS had an average age of 61 ± 13.21 years and symptoms at onset were mainly angina in 28 PZs (72%), dyspnea was present in 8 (20%) and syncope in 3 (8%). ECG changes were characterized by ST depression and/or negative T waves in 30 patients (77%), in 9 (23%) the ST segment was elevated. ATV involved apical segments (SAP) in 27 PZ (69%), 4 (10%) the basal segments (SBA), 2 (5%) the middle segments (SME) and 6 (15%) had focal points abnormalities (FOC). The average Ejection Fraction (FE) on admission was 36.85%, in PZ with ATV of SAP 33.96%, when involved SBA 41%, SME 43.5% and FOC 44.83%. Haemodynamic conditions were stable in 33 pts (84%), 3 pts (8%) presented cardiogenic shock, 3 (8%) pulmonary edema. Arrhythmias were present in 1/3 of the cases. Atrial fibrillation in 38%, extrasystolic arrhythmia in 30%, one patient with sustained ventricular tachycardia, and three patients with total BAV (23%) of which one in shock. In 10% of cases (4 PZ) there was a subvalvular aortic gradient at discharge disappeared. In 8% (3 PZ) was a recurrent TTS. 92% of the PZ reported a psychophysical stress in the 24 hours preceding the event, and a psychiatric pathology was present in 90%. However, only in 60% of cases the psychiatric diagnosis was known on admission, in the remaining 40% the diagnosis was made subsequently, and among the PZ being treated only in ¼ of the cases was it judged adequate. Conclusions In our series, SAP involvement was associated with lower EF values and greater hemodynamic compromise. Involvement of SME, SBA or FOC was associated with higher EF values and less hemodynamic compromise. A psychiatric pathology was present in over 90% of the PZ even if in 40% of the cases it was not ascertained at the time of admission, and in 75% of the PZ in which the diagnosis was known, the treatment was not adequate.

Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients

BackgroundTransthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described.Methods and resultsThe prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis.ConclusionsWhile oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.

Analysis of Coronary Angiography and Revascularization Rates Made Over 5 Years in Public Institutions in Türkiye.

Coronary angiography is currently the gold standard anatomic imaging method used to diagnose obstructive epicardial coronary artery disease. In patients with critical coronary stenosis, surgical or percutaneous revascularization is provided. Normal coronary artery ratio in coronary angiography is an indirect indicator of patient selection quality. The aim of our study is to evaluate the efficiency of coronary angiography by examining the revascularization rates according to years in patients who underwent coronary angiography. Revascularization rates will be determined by analyzing retrospectively the number of patients who underwent coronary angiography in our country between 2016 and 2021 and were revascularized interventionally or surgically. The number of patients who underwent percutaneous, surgical, and total revascularization were proportioned to the number of coronary angiography, and their percentages were determined. From 2016 to 2019, there was a continuous increase in the number of coronary angiography. In 2020, the lowest coronary angiography numbers (n = 222.159) of the last 6 years were seen with the effect of the COVID-19 pandemic. In 2021, it was observed that the number of coronary angiography increased again with the relaxation of pandemic measures and the approaching of hospital admissions to old levels. It is seen that revascularization is performed in up to one-third of the patients who underwent coronary angiography. Similar to the rest of the world, revascularization rates as a result of coronary angiography procedures performed in our country are low. With this result, it should not be concluded that coronary angiography is not used effectively; on the contrary, the efficiency of coronary angiography can be increased by more effective use of noninvasive tests.

Abstract 11882: Exploring Abnormalities in Coronary Vascular Resistance Reserve as a Distinct Feature of The Hfpef Syndrome in Women

Introduction: Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but mechanisms underlying this female predominance are incompletely understood. Impaired systemic vasodilatory reserve and coronary microvascular dysfunction have been separately described as key abnormalities of HFpEF. However, the coronary vascular resistance reserve (CVRR), defined as the drop in coronary vascular resistance (CVR) from rest to peak stress, and its sex-specific nuances have not been explored in HFpEF. We sought to: (1) determine whether stress CVR differs between HFpEF and controls, and (2) assess sex differences in CVRR in HFpEF. Methods: We performed a cross-sectional study of 32 HFpEF participants and 26 controls, all without obstructive epicardial coronary artery disease. HFpEF was defined according to ESC Guidelines. Dipyridamole stress 82 Rb positron emission tomography was performed, and rest and stress CVR was calculated by dividing mean arterial pressure by coronary flow at rest and stress. Multivariable linear regression assessed (1) the association of HFpEF with stress CVR; and (2) the association of female sex with CVRR in patients with and without HFpEF. Results: Mean age was 74±7 years, 67% were women and mean LVEF was 62±5%: no difference between HFpEF and controls (P&gt;0.05 for each). Results of the multivariable models are summarized in the Image. HFpEF was independently associated with higher global left ventricular CVR at peak vasodilatory stress. In addition, women had lower global left ventricular CVRR as compared to men, and this was unique to women with HFpEF. Results were the same for coronary-specific CVR and CVRR (analyses not shown). Conclusions: To our knowledge, this is the first study to non-invasively explore CVR and CVRR in HFpEF. Our findings suggest increased stress CVR in HFpEF, with a distinct abnormality in CVRR in women with HFpEF. Abnormal CVRR in women may contribute to the female predominance of HFpEF.

Abstract 13820: Four Revelations on the Table of Truth: A Confounding Case of ST Elevation

Background: We present a case of a patient with new onset ST elevation on EKG, found to have multiple pathologies on emergent cardiac catheterization. Case: A 81 yo woman with no prior cardiac problems; with syncope 3 days ago, came to the emergency department with worsening left-sided chest pain, that started a few hours earlier. Vitals were within normal limits. She was noted to have left facial ecchymosis, from the fall. She had an otherwise normal physical exam. Her EKG on presentation showed ST elevation in anterior leads with deep T wave inversions. She was planned for emergent cardiac catheterization following noncontrast head CT that showed no intracranial bleed. In the lab, she had no evidence of obstructive epicardial coronary artery disease. However, we noted abnormally slow filling of coronaries (suggestive of microvascular dysfunction) and evidence of a myocardial bridge in the mid-segment of the left anterior descending artery. Since neither of these would explain her acute presentation, a left ventriculogram was performed that showed apical ballooning suggestive of Takotsubo cardiomyopathy and filling defect consistent with thrombus. MRI brain showed acute ischemic stroke involving the right occipital lobe which was likely the physical stressor in her case. Discussion: Takotsubo cardiomyopathy is frequently associated with ST elevations and T wave inversions on EKG. It is hypothesized that microvascular dysfunction may be more common in Takotsubo cardiomyopathy and may explain its increased incidence among post-menopausal women and the correlation with emotional and physical stressors. Myocardial bridge of the left anterior descending artery has been associated with stress cardiomyopathy in up to 76% of cases. Conclusion: This is a rare case of stress cardiomyopathy that presented with both evidence of microvascular dysfunction and prominent myocardial bridge, with all three conditions being diagnosed in the cardiac catheterization lab.

A study protocol for an observational cohort investigating cardiac transthyretin amyloidosis flow reserve before and after Tafamidis treatment: The AMYTRE study.

IntroductionAnginal symptoms and signs of ischemia have been reported in some patients with cardiac transthyretin amyloidosis (ATTR) without obstructive epicardial coronary artery disease (CAD). Few studies found that coronary microvascular dysfunction was highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD. The purpose of this study is to confirm the coronary microvascular dysfunction, and to go further with evaluation of the effect of Tafamidis on microvascular dysfunction after 24 months of treatment.Methods and analysisThis study is a multicentric, prospective, observational cohort study. Adult patients with confirmed ATTR cardiomyopathy seen in the nuclear medicine departments of three large referral centers and treated with Tafamidis will be included. At baseline, patients will have a clinical and echocardiography evaluation. They will undergo a dynamic rest/stress cardiac scintigraphy with flow and reserve measurements before and 24 months after Tafamidis introduction. The primary outcome of this study will be the variation of stress and rest myocardial blood flow and flow reserve between baseline and 24 months after treatment. The effect of Tafamidis will be assessed by an intention to treat analysis.Ethics and disseminationThe study has received the following approvals: Orleans Hospital Research Committee (CHRO-2021-05) and Sud-Mediterranée IV Regional Ethics Committee (21 06 02). Results will be made available to physicians, the funders, and other researchers.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT05103943], identifier [NCT05103943].

Impact of intravenous administration of anisodamine on coronary microvascular dysfunction in patients with obstructive epicardial coronary artery disease after percutaneous coronary intervention

Purpose: To analyze intravenous administration of anisodamine’s impact on coronary microvasculardysfunction (CMD) in obstructive epicardial coronary artery disease (CAD) patients who had undergone percutaneous coronary intervention (PCI).Methods: Enrollment of 210 patients in Shanghai Chest Hospital, Shanghai Jiaotong University with CMD was done in a randomized-controlled study. They were divided randomly into groups, viz, anisodamine (A) group and nitrate (N) group. A 14-day course of treatment was carried out in each group. 99mTc-MIBI myocardial perfusion imaging (MPI), treadmill exercise test (TET) and two dimensional echocardiography (TDE) were performed, and the symptoms of angina pectoris were recorded before and after treatment according to the classification, frequency, and duration of angina, as defined by Canadian Cardiovascular Society (CCS).Results: After treatment, summed stress score (SSS) and summed rest score (SRS) of MPI in group A significantly decreased after treatment (p &lt; 0.001, respectively) and were remarkably lower than those in group N (p &lt; 0.001, respectively). The CCS class in group A improved after treatment (p &lt; 0.001) and was also better than in group N (p &lt; 0.001). The frequency and duration of angina attack in group A significantly reduced after treatment (p &lt; 0.001, respectively) and were notably lower than in group N (p &lt; 0.001, respectively). Left ventricular ejection fraction in group A after treatment was higher than that before treatment (p = 0.046) and than that in group N (p = 0.048). Furthermore, the side effects of anisodamine were slight and tolerable.Conclusion: Intravenous administration of anisodamine is a potentially suitable optional treatment for CMD in patients with obstructive epicardial CAD who have undergone PCI.

Nuclear Cardiology in Women and Underrepresented Minority Populations.

To outline sex-specific features of coronary artery disease (CAD) that should be considered in the assessment of women, including those from ethnic minority populations with suspected stable ischemic heart disease (IHD). Second, to determine the latest nuclear imaging tools available to assess microvascular CAD. Latest studies indicate that women are more likely to have ischemia with no obstructive coronary arteries (INOCA) and paradoxically have worse outcomes. Therefore, the evaluation of women with suspected IHD should include assessing microvascular and epicardial coronary circulation. The prevalence of CAD is increasing in younger women due to the increased cardiovascular disease (CVD) risk burden. CAD is often underrecognized in these patients. There is increasing recognition that INOCA is not benign and should be accurately diagnosed and managed. Nuclear imaging assesses the full spectrum of CAD from microvascular CAD to multivessel obstructive epicardial CAD. Further research on myocardial blood flow (MBF) assessment with PET MPI is needed.

The Impact of Ischemia Assessed by Magnetic Resonance on Functional, Arrhythmic, and Imaging Features of Hypertrophic Cardiomyopathy

Aims: The aim of the study is to investigate the association between the degree of ischemia due to coronary microvascular dysfunction (CMD) and the left ventricular (LV) tissue characteristics, systolic performance, and clinical manifestations in hypertrophic cardiomyopathy (HCM).Methods and Results: This prospective study enrolled 75 patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential, and radial strains analysis. Electrocardiogram, 24-h Holter recording, and cardiopulmonary exercise testing (CPET) were performed to assess arrhythmias and functional capacity. In total, 47 (63%) patients were men with the mean age of 54.6 (14.8) years, 51 (68%) patients had non-obstructive HCM, maximum wall thickness (MWT) was 20.2 (4.6) mm, LV ejection fraction (LVEF) was 71.6 (8.3%), and ischemic burden was 22.5 (16.9%) of LV. Greater MWT was associated with the severity of ischemia (β-estimate:1.353, 95% CI:0.182; 2.523, p = 0.024). Ischemic burden was strongly associated with higher values of native T1 (β-estimate:9.018, 95% CI:4.721; 13.315, p < 0.001). The association between ischemia and LGE was significant in following subgroup analyses: MWT 15–20 mm (β-estimate:1.941, 95% CI:0.738; 3.143, p = 0.002), non-obstructive HCM (β-estimate:1.471, 95% CI:0.258; 2.683, p = 0.019), women (β-estimate:1.957, 95% CI:0.423; 3.492, p = 0.015) and age <40 years (β-estimate:4.874, 95% CI:1.155; 8.594, p = 0.016). Ischemia in ≥21% of LV was associated with LGE >15% (AUC 0.766, sensitivity 0.724, specificity 0.659). Ischemia was also associated with atrial fibrillation or flutter (AF/AFL) (OR-estimate:1.481, 95% CI:1.020; 2.152, p = 0.039), but no association was seen for non-sustained ventricular tachycardia. Ischemia was associated with shorter time to anaerobic threshold (β-estimate: −0.442, 95% CI: −0.860; −0.023, p = 0.039).Conclusion: In HCM, ischemia associates with morphological markers of severity of disease, fibrosis, arrhythmia, and functional capacity.

Acute coronary syndrome with non-obstructive coronary arteries (ACS-NOCA) in patients with hypertrophic cardiomyopathy

ObjectivesOur study aimed to determine the prevalence and prognosis of acute coronary syndrome with non-obstructive coronary artery (ACS-NOCA) in patients with hypertrophic cardiomyopathy (HCM).Methods and resultsWe enrolled a total of 200 consecutive patients with HCM over a 139-month period from 2002 to 2013. The study found that 28 patients (14% of overall patients, 51% of patients with ACS) had ACS-NOCA, and 18 patients (9% of overall patients, 86% of patients with acute MI) had MINOCA as initial clinical presentations. The highest prevalence of non-obstructive coronary artery disease (NOCA) in patients with HCM was found in acute ST-elevation myocardial infarction (STEMI) (100%), followed by non-STEMI (82%), and unstable angina (29%). Patients with ACS-NOCA had more frequent ventricular tachycardia and lower resting left ventricular (LV) outflow tract gradients than those with no ACS-NOCA (p < 0.05 for all). The ACS-NOCA group had a lower probability of HCM-related death compared with the no ACS-NOCA group and the significant coronary artery disease (CAD) group (p-log-rank = 0.0018).ConclusionsMINOCA or ACS-NOCA is not an uncommon initial presentation (prevalence rate 9–14%) in patients with HCM. NOCA was highly prevalent (51–86%) in patients with HCM presenting with ACS and had a favorable prognosis. Our findings highlight as a reminder that in an era of rapid reperfusion therapy, ACS in patients with HCM is not only a result of obstructive epicardial CAD, but also stems from the complex cellular mechanisms of myocardial necrosis.

Coronary microvascular dysfunction in hypertrophic cardiomyopathy – impact from tissue characteristics to clinical manifestations

Abstract Background Coronary microvascular dysfunction (CMD) is an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). Purpose This study investigated the role of CMD in tissue characteristics, left ventricular (LV) systolic performance and clinical manifestations in HCM. Methods This prospective study enrolled patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential and radial strains analysis. Electrocardiogram and 24 hours Holter recording were performed to assess arrhythmias. Results 75P were enrolled, 47 (63%) males, mean age 54.6 (14.8) years; 51 patients (68%) had non obstructive HCM, mean maximum wall thickness (MWT) was 20.2 (4.6)mm, LV ejection fraction 71.6 (8.3)%, ischemic burden 22.5 (16.9)% of LV. Greater MWT was associated the severity of ischemia (β-estimate: 1.809, 95% CI: 1.073; 2.545; p&amp;lt;0.001). Ischemic burden was strongly associated with higher values of native T1 (β-estimate: 9.018, 95% CI: 4.721, 13.315; p&amp;lt;0.001). An association between ischemia and the extent of LGE was found (β-estimate: 2.02, 95% CI: 0.93, 3.10; p&amp;lt;0.001). Ischemia in ≥21% of LV was associated with LGE &amp;gt;15% (AUC 0.766, sensitivity 0.724, specificity 0.659). In multivariable analysis, in the overall population, MWT and LGE were independently associated with ischemia, however the evidence of association between ischemia and extent of LGE became weaker (β-estimate: 1.070, 95% CI: −0.106; 2.245; p=0.074). In subgroup analysis, the association between ischemia and LGE remained significant in individuals with MWT 15–20mm, non-obstructive HCM, female and age &amp;lt;40 years. The severity of ischemia was not associated with markers of LV systolic function, namely LVEF, longitudinal, radial and circumferential strain A strong evidence of association was found between ischemia and atrial fibrillation/flutter (AF/AFL) (OR: 1.481, 95% CI: 1.020,2.152; p=0.039), but no association was verified with non-sustained ventricular tachycardia. Conclusion In HCM, CMD is related to the severity of LV hypertrophy. Ischemia secondary to CMD promotes fibrosis and is associated with an increase in the odds of AF/ALF. Funding Acknowledgement Type of funding sources: None.

Impact of Serum Uric Acid Level on Systemic Endothelial Dysfunction in Patients with a Broad Spectrum of Ischemic Heart Disease.

Previous studies indicated that serum uric acid (SUA) level is a marker of endothelial function in subsets of ischemic heart disease (IHD). In the present study, we aimed to evaluate the relation between the SUA level and endothelial function in patients with a broad spectrum of IHD, including obstructive coronary artery disease (CAD) and ischemia with no obstructive CAD (INOCA). Three prospective studies and one retrospective study were pooled, in which the SUA level was measured, and systemic endothelial function was assessed using the reactive hyperemia index (RHI). The primary endpoint of the present study was a correlation of the SUA level with RHI. A total of 181 patients with a broad spectrum of IHD were included, among whom, 46 (25%) had acute coronary syndrome presentation and 15 (8%) had INOCA. Overall, the SUA level was negatively correlated with the RHI (r = −0.22, p = 0.003). Multivariable analysis identified the SUA level and INOCA as significant factors associated with RHI values. In conclusion, in patients with a broad spectrum of IHD, including obstructive epicardial CAD (chronic and acute coronary syndromes) and INOCA, the SUA level was significantly and negatively correlated with systemic endothelial function assessed with the RHI. INOCA, rather than obstructive CAD, was more associated with endothelial dysfunction.

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.