Prevalence Of Coronary Microvascular Dysfunction Research Articles

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P<0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P<0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P=0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P=0.04]. CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

Prevalence of Coronary Microvascular Dysfunction in Patients after Coronary Artery Bypass Grafting

The aim. To analyze the prevalence of coronary microvascular dysfunction (CMD) in patients with coronary artery disease after coronary artery bypass grafting (CABG).&#x0D; Materials and methods. The study was conducted in compliance with the provisions of the Declaration of Helsinki and was approved by the local ethics committee during 2018-2021. Due to recurrent complaints of discomfort/pain behind the sternum or shortness of breath during physical exertion in patients after CABG (average time of occurrence 18 ± 6 months after surgery), as well as positive or doubtful result of the stress testing, 31 patients were re-hospitalized for further examination. To diagnose CMD, echocardiography was performed with intravenous dipyridamole in order to determine the coronary flow reserve. The patency of the grafts was confirmed and newly formed hemodynamically significant coronary artery lesions were excluded during invasive coronary angiography.&#x0D; Results. The mean age was 61.2 ± 2.3 years, the majority of the patients were male (20 [64.5%]). The most common comorbid pathologies in the patients were: hypertension in 29 patients (93.5%), impaired glucose metabolism (diabetes/prediabetes) in 17 (54.8%) subjects, 13 (41.9%) patients had a history of myocardial infarction. Left ventricular ejection fraction according to echocardiography was reduced (less than 55%) in 5 (16.1%) of 31 patients, in others it was preserved. After CABG, there was a trend towards the coronary flow reserve increase, but no significant difference was found (1.89 ± 0.08 vs. 2.11 ± 0.13; p &gt; 0.05). The presence of CMD before and after CABG did not change significantly (13 [41.9%] vs. 12 [38.7%]; p &gt; 0.05).&#x0D; Conclusion. According to the results of the study, CMD is a common pathology in patients with obstructive coronary artery disease and is found in about 40% of patients with repeated myocardial ischemia after CABG. CABG did not affect the frequency of detection of CMD in patients with coronary artery disease before and after the operation.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia

To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53±12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia

Background and aimsMicrovascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). MethodsFour groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. ResultsThe groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. ConclusionsCoronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

The impact of primary percutaneous coronary intervention strategies during ST-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297.

The impact of primary percutaneous coronary intervention strategies during st-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction

Abstract Introduction Up to 20% of ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous coronary intervention (PCI) continue to have persistent angina, which is considered to be a significant side effect of reperfusion therapy and is associated with coronary microvascular dysfunction (CMD). Purpose To determine if there is a correlation between the technique employed in primary PCI in STEMI patients and the prevalence of CMD after reperfusion. Methods This is a prospective single-blinded observational cohort study conducted in a tertiary cardiac care center in the republic of Lithuania. The study enrolled STEMI patients with multivessel coronary artery disease who underwent primary PCI. Three months later, participants underwent staged PCI of their non-culprit vessels and evaluation for CMD. CMD was defined as an index of microcirculatory resistance (IMR) value ≥ 25 U and a coronary flow reserve (CFR) value &amp;lt; 2.5 U. PCI technique, such as direct stenting or conventional stenting (balloon angioplasty followed by stenting), aspiration thrombectomy, and intracoronary glycoprotein IIb/IIIa inhibitor administration, were prospectively documented. We tested for overall differences in patient characteristics and outcomes between groups using Chi-Square (or Kruskal-Wallis) tests and used the Holm-Bonferroni adjustment (or Dunn's tests) for subsequent pairwise tests. We also performed logistic regression. Results 200 patients were enrolled, with 96 (48%) and 104 (52%), respectively, undergoing direct and conventional stenting. The median age was 65.5 [58, 76] years, most patients were men (59.5%) and 46 patients (23%) met criteria for CMD. Baseline characteristics and risk factors were similar between those with and without CMD. Patients who underwent direct stenting were less likely to suffer from CMD compared to those who underwent conventional stenting (10 (10.4%) vs 36 (34.6%); p &amp;lt; 0.001). In the logistic multivariable analysis, direct stenting, aspiration thrombectomy, and administrations of glycoprotein IIb/IIIa had a ROC AUC of 0.765, indicating good predictive ability. In this particular model, direct stenting, aspiration thrombectomy, and the administration of an intracoronary glycoprotein IIb/IIIa inhibitor were associated with decreased odds of the presence of CMD (OR: 0.193, 95% CI: 0.087-0.430, p &amp;lt; 0.001), (OR: 0.243, 95% CI: 0.086-0.688, p = 0.008), and (OR: 0.200, 95% CI: 0.065-0.620, p = 0.005), respectively. Conclusion In STEMI patients undergoing primary PCI, direct stenting is associated with reduced prevalence of CMD compared with conventional stenting. Furthermore, performing aspiration thrombectomy and administering a glycoprotein IIb/IIIa inhibitor was also associated with a lower prevalence of CMD.Forest plot for the outcome of CMDROC for the model of CMD

Gender-related differences in absolute coronary flow and microvascular resistance in patients with angina and non-obstructed coronary arteries (ANOCA)

Abstract Background Women with angina more often have non-obstructive coronary artery disease (ANOCA) compared to males. Coronary microvascular dysfunction (CMD) is responsible for angina in a sizable proportion of ANOCA patients. Intracoronary continuous thermodilution allows direct quantification of absolute coronary flow (Q) and microvascular resistance (Rµ). Purpose To evaluate gender-related differences in the prevalence and pattern of CMD assessed with intracoronary continuous thermodilution in ANOCA patients. Specifically, we assessed resting and hyperemic Q (Qrest and Qhyper), R (Rµ,rest and Rµ,hyper), coronary flow reverse (CFR), and microvascular resistance reserve (MRR) in ANOCA patients stratified by gender. Methods Single-center, prospective study of patients with ANOCA. CMD was invasively assessed by intracoronary continuous thermodilution in the left anterior descending artery (LAD) and defined as CFR&amp;lt;2.5. Results A total of 118 patients (n=49 females and n= 69 males) were enrolled. The mean patient age was 65 years. The mean fractional flow reserve (FFR) was 0.85±0.04, with no difference between the 2 genders. There was no difference in Rµ,rest, Qrest and Qhyper between the two genders. However, Rµ,hyper were higher in females compared to males (p=0.003). Among patients with ANOCA, CMD was more prevalent in females (28% vs 22%, p=0.014). Yet, in both females and males with CMD, a higher Qrest was observed compared to patients without CMD. In male patients, also Qhyper was lower in CMD patients versus those without CMD. Conclusion Among patients with ANOCA and investigated with intracoronary continuous thermodilution, CMD appeared more prevalent in females compared to males. Females had higher microvascular Rµ,hyper compared to males. In both genders, CMD was characterized by higher Qrest, suggestive of functional rather than structural CMD.

Regional differences and coronary microvascular dysfunction in heart failure with preserved ejection fraction.

In heart failure with preserved ejection fraction (HFpEF), regional heterogeneity of clinical phenotypes is increasingly recognized, with coronary microvascular dysfunction (CMD) potentially being a common shared feature. We sought to determine the regional differences in clinical characteristics and prevalence of CMD in HFpEF. We analysed clinical characteristics and CMD in 202 patients with stable HFpEF (left ventricular ejection fraction ≥40%) in Finland, Singapore, Sweden, and United States in the multicentre PROMIS-HFpEF study. Patients with unrevascularized macrovascular coronary artery disease were excluded. CMD was assessed using Doppler echocardiography and defined as coronary flow reserve (adenosine-induced vs. resting flow)<2.5. Patients from Singapore had the lowest body mass index yet highest prevalence of hypertension, dyslipidaemia, and diabetes; patients from Finland and Sweden were oldest, with the most atrial fibrillation, chronic kidney disease, and high smoking rates; and those from United States were youngest and most obese. The prevalence of CMD was 88% in Finland, 80% in Singapore, 77% in Sweden, and 59% in the United States; however, non-significant after adjustment for age, sex, N-terminal pro-brain natriuretic peptide, smoking, left atrial reservoir strain, and atrial fibrillation. Associations between CMD and clinical characteristics did not differ based on region (interaction analysis). Despite regional differences in clinical characteristics, CMD was present in the majority of patients with HFpEF across different regions of the world with the lowest prevalence in the United States. This difference was explained by differences in patient characteristics. CMD could be a common therapeutic target across regions.

The prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF): a systematic review and meta-analysis.

To date, studies on the prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF) have not been summarized and analyzed as a whole. We conducted this systematic review and meta-analysis to assess the prevalence of CMD in patients with HFpEF. The PubMed, Cochrane, and Embase databases were searched from dates of inception until May 1, 2023. The primary outcome was the prevalence of CMD in patients with HFpEF, and values of CMD prevalence were pooled using a random-effects model. In total, 10 studies involving 1267 patients, including 822 with HFpEF and 445 without HFpEF, were included. The pooled prevalence of CMD in patients with HFpEF was 71% (95% CI, 0.63-0.79). In the subgroup analysis, the prevalence of CMD was 79% (95% CI, 0.71-0.87) by invasive measurement and 66% (95% CI, 0.54-0.77) by noninvasive measurement and 67% (95% CI, 0.52-0.82) with CFR < 2.0 and 75.0% (95% CI, 0.71-0.79) with CFR < 2.5. The prevalence of endothelium-independent CMD and endothelium-dependent CMD was 62% (95% CI, 0.53-0.72) and 50% (95% CI, 0.19-0.81), respectively. The prevalence of CMD was 74% (95% CI = 0.69-0.79) and 66% (95% CI = 0.41-0.90) in prospective and retrospective studies, respectively. Compared with the control group, patients with HFpEF had a significantly lower CFR (MD = - 1.28, 95% CI = - 1.82 to - 0.74, P < 0.01) and a higher prevalence of CMD (RR = 2.21, 95% CI = 1.52 to 3.20, P < 0.01). Qualitative analysis demonstrated that CMD might be associated with poor clinical outcomes in patients with HFpEF. In conclusion, this is the first systematic review and meta-analysis of all studies reporting the prevalence of CMD in patients with HFpEF. Our study demonstrates that CMD is common in patients with HFpEF and might be associated with poor clinical outcomes in these patients. Clinicians should attach importance to CMD in the diagnosis and treatment of HFpEF. The number of studies in this field is relatively small. Therefore, more high-quality studies are needed to explore the diagnostic and prognostic value of CMD and the potential role of CMD as a therapeutic target in patients with HFpEF.

Coronary Microvascular Dysfunction in Asymptomatic Patients with Severe Psoriasis

Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.

The coronary microvascular angina cardiovascular magnetic resonance imaging trial: Rationale and design

BackgroundCoronary microvascular dysfunction may cause myocardial ischemia with no obstructive coronary artery disease (INOCA). If functional testing is not performed INOCA may pass undetected. Stress perfusion cardiovascular MRI (CMR) quantifies myocardial blood flow (MBF) but the clinical utility of stress CMR in the management of patients with suspected angina with no obstructive coronary arteries (ANOCA) is uncertain. ObjectivesFirst, to undertake a diagnostic study using stress CMR in patients with ANOCA following invasive coronary angiography and, second, in a nested, double-blind, randomized, controlled trial to assess the effect of disclosure on the final diagnosis and health status in the longer term. DesignAll-comers referred for clinically indicated coronary angiography for the investigation of suspected coronary artery disease will be screened in 3 regional centers in the United Kingdom. Following invasive coronary angiography, patients with ANOCA who provide informed consent will undergo noninvasive endotyping using stress CMR within 3 months of the angiogram. Diagnostic studyStress perfusion CMR imaging to assess the prevalence of coronary microvascular dysfunction and clinically significant incidental findings in patients with ANOCA. The primary outcome is the between-group difference in the reclassification rate of the initial diagnosis based on invasive angiography versus the final diagnosis after CMR imaging. Randomized, controlled trialParticipants will be randomized to inclusion (intervention group) or exclusion (control group) of myocardial blood flow to inform the final diagnosis. The primary outcome of the clinical trial is the mean within-subject change in the Seattle Angina Questionnaire summary score (SAQSS) at 6 months. Secondary outcome assessments include the EUROQOL EQ-5D-5L questionnaire, the Brief Illness Perception Questionnaire (Brief-IPQ), the Treatment Satisfaction Questionnaire (TSQM-9), the Patient Health Questionnaire-4 (PHQ-4), the Duke Activity Status Index (DASI), the International Physical Activity Questionnaire- Short Form (IPAQ-SF), the Montreal Cognitive Assessment (MOCA) and the 8-item Productivity Cost Questionnaire (iPCQ). Health and economic outcomes will be assessed using electronic healthcare records. ValueTo clarify if routine stress perfusion CMR imaging reclassifies the final diagnosis in patients with ANOCA and whether this strategy improves symptoms, health-related quality of life and health economic outcomes. Clinicaltrials.govNCT04805814

Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model.

Increased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously. To compare CMVR between men and women being investigated for chest pain. We used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650-1,205] vs. 680 [520-865] WU, Z = -2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR. CMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women.

Prognostic Significance of Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

The prognostic impact of coronary microvascular dysfunction (CMD) has been scarcely addressed in heart failure with preserved ejection fraction (HFpEF). This study investigated the prevalence and prognostic significance of CMD as measured by a novel pressure wire-free coronary angiography-derived index of microcirculatory resistance (caIMR) on clinical outcomes. Patients diagnosed with HFpEF from 2019 to 2021 were enrolled retrospectively. caIMR was used to quantify microvascular function, and patients were categorised into 2 groups based on their caIMR. The primary end points were composite of all-cause death and heart failure rehospitalisation. Of 137 HFpEF patients, CMD (defined as caIMR ≥ 25) was present in 88 patients (64.2%). Forty-five patients (32.8%) experienced composite events during a mean follow-up of 15 months. Compared with patients with caIMR < 25, those with caIMR ≥ 25 had a notably higher incidence of composite events (16.3% vs 42.0%; P= 0.002). On survival analysis, patients with caIMR ≥ 25 demonstrated a worse prognosis than those with caIMR < 25 for composite events (P= 0.006). Patients with caIMR ≥ 25 in multiple coronary arteries showed a trend to worse outcome than those with caIMR ≥ 25 in a single coronary artery (log-rank P= 0.056). In adjusted analysis, caIMR ≥ 25 was independently predictive of adverse outcomes (adjusted hazard ratio 2.93, 95% confidence interval [CI] 1.28-6.70; P= 0.010). caIMR displayed a significant predictive power for adverse event prediction (area under the receiver operating characteristic curve 0.767, 95% CI 0.677-0.858; P < 0.001). CMD is highly prevalent and is an independent predictor of adverse outcomes in HFpEF patients. Assessment of CMD may identify high-risk patients early for intensified treatment and risk-factor management.

PET-determined prevalence of coronary microvascular dysfunction and different types in a cardio-metabolic risk population.

The aim was to investigate the prevalence of "classical" (predominantly related to alterations in hyperemic MBFs) and "endogen" (predominantly related to alterations in resting MBF) normal coronary microvascular function (nCMF) or coronary microvascular dysfunction (CMD) in a clinical population without flow-limiting obstructive CAD. We prospectively enrolled 239 symptomatic patients with normal pharmacologically-stress and rest myocardial perfusion on 13N-ammonia PET/CT. 13N-ammonia PET/CT concurrently assessed myocardial flow reserve (MFR=MBF stress/MBF rest). Normal nCMF was defined by a MFR of≥2.0, while an abnormal MFR of<2.0 signified CMD. In addition, patients were subgrouped into classical and endogen type of nCMF and CMD, respectively. In the whole study population, CMD was present in 54% (130/239). The classical type was more prevalent than the endogen type of CMD (65% vs 35%, p≤0.008). The classical type of CMD was paralleled by a high prevalence of diabetes mellitus, metabolic syndrome, and obesity, while the endogen type of CMD was accompanied by a higher prevalence of arterial hypertension, obesity, and/or morbid obesity. Further, the classical type of nCMF was more frequently observed that the endogen type (74% vs. 26%, p≤0.007). The endogen type of nCMF was related to lower heart rate and/or arterial blood pressures. In this contemporary clinical study population, slightly more than half of symptomatic patients had CMD with predominance of the classical type. These observations emphasize the need for standardized reporting of CMD to gear individualized and/or intensified medical treatment to improve symptoms and/or clinical outcome in these patients.

Prognostic Impact of Indeterminate Diastolic Function in Patients With Functionally Insignificant Coronary Stenosis

Cardiac diastolic dysfunction is an independent predictor of mortality, regardless of left ventricular (LV) systolic function. However, the current guidelines that define cardiac diastolic dysfunction may underrate the clinical implications of those with indeterminate diastolic function. We sought to evaluate the prognostic implications of indeterminate diastolic function on echocardiography and its association with coronary microvascular dysfunction (CMD). A total of 330 patients without LV systolic dysfunction and significant epicardial coronary stenosis (fractional flow reserve > 0.80) were analyzed from a prospective registry. Cardiac diastolic dysfunction was defined according to 2 algorithms depending on the presence of myocardial disease. First, the presence of myocardial disease and evidence of elevated LV filling pressure indicated diastolic dysfunction. Second, diastolic function in those without myocardial disease was defined using echocardiographic parameters (E/e', e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Patients who did not meet half of the available criteria were classified as having indeterminate diastolic function. Coronary microvascular dysfunction was defined as coronary flow reserve < 2.0 and index of microcirculatory resistance ≥ 25 U. The primary outcome was cardiovascular death or admission for heart failure at 5years. Coronary flow reserve was lower in patients with indeterminate diastolic function compared with those with no diastolic dysfunction (3.5±1.6 vs 3.2±1.6, P=.002). The prevalence of CMD was also higher in patients with indeterminate diastolic function than in those with no diastolic dysfunction (10.6% vs 4.9%, P<.034). Patients with indeterminate diastolic function showed significantly higher risk of cardiovascular death or admission for heart failure than those without indeterminate diastolic function but not greater than those with definite diastolic dysfunction (cumulative incidence: 12.6%, 27.2%, and 32.7%, respectively, log-rank P<.001). Presence of CMD and elevated LV filling pressure (E/e'>14) were independent predictors for cardiovascular death or admission for heart failure in patients with indeterminate diastolic function. Patients with indeterminate diastolic function on echocardiogram showed higher risk of cardiovascular death or admission for heart failure than those with no diastolic dysfunction. Presence of CMD and elevated LV filling pressure were independent predictors for cardiovascular death or admission for heart failure among patients with indeterminate diastolic function.

The role of microvascular dysfunction in the pathogenesis of heart failure with preserved ­efficiency fraction

Background. The results of a growing number of international studies support the assumption that the prevalence of coronary microvascular dysfunction is much higher than previously thought, including in patients with heart failure with preserved ejection fraction.&#x0D; Aim. To study the role of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction in patients with non-obstructive lesions of the coronary arteries.&#x0D; Material and methods. The study included 73 patients with non-obstructive lesions of the coronary arteries. Dynamic single-photon emission computed tomography was used to evaluate the parameters of coronary blood flow reserve. Coronary microvascular dysfunction was defined as the presence of reduced coronary blood flow reserve 2. The distribution of patients was carried out depending on the reserve of coronary blood flow: the first group (n=35) included patients with a reduced reserve 2, the second group with preserved reserve 2 (n=38). Statistical processing of the study results was carried out using nonparametric methods: in the analysis of quantitative indicators, the MannWhitney test was used; in the analysis of qualitative features, the analysis of contingency tables using the Pearson 2 test was performed. To search for relationships between variables, correlation analysis with the calculation of Spearman's correlation coefficients was used.&#x0D; Results. In 82.9% of cases, patients in the first group had heart failure, while in patients in the second group, it was diagnosed only in 44.7% of cases (p=0.014). The values of the coronary blood flow reserve correlated with the size of the left atrium (r=0.527; p=0.001), the E/A (r=0.321, p=0.012) and E/e' ratio (r=0.307; p=0.021). In patients with heart failure, the levels of coronary blood flow reserve correlated with the functional class: in patients with functional class I (n=21), the values of this indicator were 2.87 (2.52; 2.94), with class II (n=8) 1.98 (1.65; 2.16), with functional class III (n=17) 1.51 (1.23; 1.69).&#x0D; Conclusion. The presence of coronary microvascular dysfunction is associated with a higher incidence of heart failure with preserved ejection fraction; values of coronary blood flow reserve correlate with parameters of diastolic dysfunction.

Abstract 12386: The Prevalence of Coronary Microvascular Dysfunction Among Patients With Low Pretest Probability of Coronary Artery Disease

Introduction: Coronary microvascular dysfunction (CMD) is an underdiagnosed cause of chest pain. The 2021 AHA/ACC guidelines do not advocate for testing in patients with chest pain and low pretest probability (PTP &lt;15%) of coronary artery disease (CAD). The prevalence of CMD among patients with low pretest probability is not known. We sought to estimate the prevalence of CMD among patients with chest pain and a low pretest probability of CAD. Methods: We reviewed all the patients referred to positron emission tomography myocardial perfusion imaging (PET-MPI) from May 2011 to January 2022. Patients with chest pain and low PTP of CAD who had normal PET-MPI were included in the analysis. Rest and peak myocardial blood flows (MBF) were measured. Coronary flow reserve (CFR) was calculated as a ratio of peak/rest MBF. CMD was defined as CFR of &lt;2. Results: 1873 patients (age 53.7 ± 9.3 years, 23.6% males) with low PTP and normal PET-MPI were included in the analysis. 372 (20%) patients had MVD. Patients with CMD had lower use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, aspirin, and statin. Diabetes, hypercholesterolemia, and hypertension did not predict CMD. However, female gender (OR: 1.7 95%CI: 1.1- 2.6, p=0.016), age (OR: 1.02 95%CI: 1.00 - 1.04, p=0.023) and BMI (OR: 1.04 95%CI: 1.02 - 1.07, p=0.001) were associated with higher likelihood of MVD. Conclusions: Coronary Microvascular Dysfunction is common among patients with chest pain, low PTP of CAD, and normal myocardial perfusion imaging. Females are more likely to have CMD. Further studies are needed to verify the prognostic value of this population.

Abstract 12216: Prevalence of Coronary Microvascular Dysfunction in Patients With Angina and Known Myocardial Bridge

Introduction: Myocardial bridges are prevalent in patients with and without angina and can present a diagnostic dilemma when evaluating angina. Coronary microvascular dysfunction (CMD) is an important cause of chest pain in patients presenting with angina without obstructive CAD. The prevalence of concomitant CMD and myocardial bridge is not well described. Methods: All patients with known myocardial bridge and chest pain who underwent cardiac catheterization with bridge study at the University of Chicago Medical Center between 2020-2021 were included. All patients underwent pharmacologic testing with dobutamine with measurement of resting flow reserve (RFR). Abnormal RFR was defined as &lt; 0.8. Some patients additionally underwent coronary physiology study with adenosine (Ado) and/or acetylcholine (Ach) with determination of coronary flow reserve (CFR), index of microvascular resistance (IMR), and spasm (for Ach). Abnormal endothelial dependent microvascular function was defined as CFR &lt; 1.5 or IMR &gt; 31 on Ach testing. Abnormal endothelial independent microvascular function was defined as CFR &lt; 2.0 or IMR &gt; 25 on Ado testing. Results: A total of 27 patients (mean age 47 + 9, 60% female) were studied. There were 18 patients with hemodynamically significant bridge of whom 13 underwent surgical unroofing and 9 patients with hemodynamically insignificant bridge of whom 3 underwent surgical unroofing. There was no significant difference in rates of endothelial dependent or independent CMD or angiographic spasm between groups. Further coronary endotype data is displayed in Table 1. Conclusion: Endothelial dependent and independent microvascular dysfunction are prevalent in patients presenting with known myocardial bridge and chest pain and rates are not affected by hemodynamic significance of the bridge. Knowledge of coronary endotype in patients with myocardial bridge may assist in tailoring therapies to improve chest pain.

Sex-differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome – analysis from the multi-center international ILIAS Registry

Abstract Introduction Guideline-directed management of chronic coronary syndrome (CCS) remains focused on obstructive causes of angina, and is based on established therapies derived from studies predominantly including men. This occurs despite documented higher mortality from cardiovascular causes in women compared to men, which is hypothesized to be related to a higher prevalence of coronary microvascular dysfunction (CMD) in women. However, data on the relationship between sex, the different endotypes of CCS, and related sex-specific clinical outcomes are limited. Purpose This study aimed to investigate the relationship between sex and the different endotypes of CCS, as well as sex-specific clinical outcomes of CCS endotypes. Method In patients with stable angina undergoing coronary angiography, the following invasive coronary hemodynamics were characterized: fractional flow reserve (FFR; &amp;lt;0.80 considered abnormal), coronary flow reserve (CFR; &amp;lt;2.0 considered abnormal) and microcirculatory resistance (MR) (hyperemic microvascular resistance; &amp;gt;2.5mmHg/cm/sec or index of microvascular resistance &amp;gt;25 considered abnormal). Patients were stratified into three groups: 1) hemodynamically significant obstructive coronary artery disease (oCAD) (FFR abnormal or a severe coronary stenosis requiring revascularization), 2) no-obstructive coronary artery disease but with CMD (FFR normal, but abnormal CFR and/or MR), or 3) no-obstructive coronary artery disease and no CMD (FFR normal, and normal CFR and MR). We assessed the prevalence of the CCS endotypes across sex, and sex-specific cardiovascular outcomes over a follow-up of 7 years defined as the composite endpoint of death or acute myocardial infarction. Results Amongst a total of 1987 included patients, 1435 (72.2%) were men and 552 (27.8%) were women. oCAD occurred in 904 (45.5%) patients, which was significantly more prevalent in men (48.9% (701/1435) of men vs. 36.8% (203/552) of women, p&amp;lt;0.001). In contrast, CMD was significantly more prevalent in women (19.6% (281/1435) of men vs. 24.1% (133/552) of women, p=0.031). Across the population, either oCAD or CMD occurred in 68.4% of men versus 60.9% of women (p=0.002). There were no sex-specific differences in cardiovascular outcomes across CCS entities (Figure 1). Conclusion In patients evaluated for CCS who underwent clinically indicated coronary angiography and physiological assessment, men were more likely to have oCAD and women were more likely to be classified as CMD. There were no sex-related differences in the prognosis associated with the individual CCS endotypes. Therefore, pathophysiological changes in the coronary circulation potentially underlying angina pectoris are similarly prevalent in men and women, but the high incidence of CMD in women makes women prone to underdiagnosis if no additional physiological measurements are assessed. Funding Acknowledgement Type of funding sources: None.

Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD.