Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects.

BACKGROUND: Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease. METHODS: A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity-score matching; primary outcomes were fluoroscopy time and total contrast use. RESULTS: The participants' mean age was 64.1 ± 12.6 years. CMD-assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity-matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37). CONCLUSION: Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.

"The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy".

BACKGROUND: Ischemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. METHODS AND RESULTS: The INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. CONCLUSIONS: The INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial.

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

Characterizing Mechanisms of Ischemia in Patients With Myocardial Bridges.

BACKGROUND: Myocardial bridges (MBs) are prevalent and can be associated with acute and chronic ischemic syndromes. We sought to determine the substrates for ischemia in patients with angina with nonobstructive coronary arteries and a MB in the left anterior descending artery. METHODS: Patients with angina with nonobstructive coronary arteries underwent the acquisition of intracoronary pressure and flow during rest, supine bicycle exercise, and adenosine infusion. Coronary wave intensity analysis was performed, with perfusion efficiency defined as accelerating wave energy/total wave energy (%). Epicardial endothelial dysfunction was defined as a reduction in epicardial vessel diameter ≥20% in response to intracoronary acetylcholine infusion. Patients with angina with nonobstructive coronary arteries and a MB were compared with 2 angina with nonobstructive coronary arteries groups with no MB: 1 with coronary microvascular disease (CMD: coronary flow reserve, <2.5) and 1 with normal coronary flow reserve (reference: coronary flow reserve, ≥2.5). RESULTS: Ninety-two patients were enrolled in the study (30 MB, 33 CMD, and 29 reference). Fractional flow reserve in these 3 groups was 0.86±0.05, 0.92±0.04, and 0.94±0.05; coronary flow reserve was 2.5±0.5, 2.0±0.3, and 3.2±0.6. Perfusion efficiency increased numerically during exercise in the reference group (65±9%-69±13%; P=0.063) but decreased in the CMD (68±10%-50±10%; P<0.001) and MB (66±9%-55±9%; P<0.001) groups. The reduction in perfusion efficiency had distinct causes: in CMD, this was driven by microcirculation-derived energy in early diastole, whereas in MB, this was driven by diminished accelerating wave energy, due to the upstream bridge, in early systole. Epicardial endothelial dysfunction was more common in the MB group (54% versus 29% reference and 38% CMD). Overall, 93% of patients with a MB had an identifiable ischemic substrate. CONCLUSIONS: MBs led to impaired coronary perfusion efficiency during exercise, which was due to diminished accelerating wave energy in early systole compared with the reference group. Additionally, there was a high prevalence of endothelial and microvascular dysfunction. These ischemic mechanisms may represent distinct treatment targets.

Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial.

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.

Study on the Therapeutic Value of Shexiang Tongxin Dropping Pills in Patients with Stable Angina Pectoris of Coronary Heart Disease Complicated with Cognitive Impairment

Background: There is a pressing need to identify pharmaceuticals that are both safe and efficacious, with lower toxicity, for the treatment of stable angina pectoris in individuals suffering from coronary heart disease. The aim of this paper is to explore the therapeutic value of Shexiang Tongxin Dropping Pills in patients with stable angina pectoris of coronary heart disease complicated with cognitive impairment. Methods: 200 patients with stable angina pectoris combined with cognitive dysfunction and coronary heart disease admitted to our hospital from January 2022 to June 2023 were retrospectively selected as the study objects. According to the treatment method, the subjects were divided into a control group and a study group, with 100 cases in each group. The control group received conventional oral Western medicine, and the study group underwent treatment with Shexiang Tongxin Dropping Pills in addition to traditional Western medicine. The course of treatment was eight weeks. The enhancement in angina pectoris, cognitive function level, self-care ability, and clinical efficacy of both groups were assessed by comparing the conditions before and after the treatment. Results: After treatment, the frequency and duration of angina pectoris attacks in both groups were significantly lower than before, and the study group was lower than the control group (p < 0.05). The Montreal Cognitive Assessment (MoCA) score of both groups was higher than before, and the score of the study group was significantly higher than that of the control group (p < 0.05). Neuropsychiatric Inventory (NPI) scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). Traditional Chinese Medicine (TCM) syndrome scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). ... (AU)

Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-induced morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly that with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD and also to investigate and guide the treatment of additional complications that can affect further prognosis. This comprehensive review provides insight into the main pathophysiological mechanisms of CMD in hypertensive patients, offering an integrated diagnostic approach as well as an overview of currently available therapeutical modalities.

[Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina].

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Effects of remote ischemic preconditioning on coronary blood flow and microcirculation.

This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.

Coronary Venous Pressure and Microvascular Hemodynamics in Patients With Microvascular Angina: A Randomized Clinical Trial.

Importance: The role of the coronary venous circulation in regulating myocardial perfusion and its potential in treating microvascular angina is unexplored. Objective: To evaluate whether an increase in coronary venous pressure modifies microvascular resistance in patients with microvascular angina. Design, Setting, and Participants: This was a blinded, sham-controlled, crossover, randomized clinical trial that enrolled participants between November 2021 and January 2023. Participants for this physiology end point study were recruited from the Cardiology Center of the University of Medicine in Mainz, Germany. Patients with moderate/severe angina pectoris (Canadian Cardiovascular Society class 2-4) due to microvascular dysfunction (as defined by the thermodilution-based index of microvascular resistance >25 mm Hg × s). Exclusion criteria were epicardial coronary disease, second- and third-degree atrioventricular block, severe valvular heart disease, cardiomyopathy, and pulmonary or kidney disease. Intervention: Inflation of an undersized balloon placed in the cardiac coronary sinus (CS), hereafter referred to as balloon and the deflated balloon in the right atrium, referred to as sham. Measurements were performed at rest and during maximal coronary hyperemia. Both patients and final assessors were blinded to the randomization sequence. Main Outcomes and Measures: Hemodynamic parameters, including aortic (Pa) and distal (Pd) coronary pressure, coronary sinus pressure (Pcs), right atrial pressure (Pra), and the mean transit time (inverse of blood flow [Tmn]), were measured. Results: A total of 20 patients (median [IQR] age, 69 [64-75] years; 11 female [55.0%]) were included in the study. Two patients (10%) had diabetes, 6 (30%) had hypercholesterolemia, 15 (75%) had hypertension, and 3 (15%) were active smokers. The inflation of the CS balloon caused a significant increase in CS pressure at rest and during hyperemia (300% and 317% increase, respectively, compared with sham, both P < .001), a decrease in hyperemic distal coronary pressure (median [IQR], sham: 92 [80-100] mm Hg; balloon: 79 [75-93] mm Hg; P = .01) and mean transit time (sham: 0.39 [0.23-0.62] s; balloon: 0.26 [0.17-0.46] s; P = .008). As a result, CS occlusion led to a decrease in both resting coronary resistance (median [IQR], sham: 59 [37-87] mm Hg × s; balloon: 42 [31-67] mm Hg × s; P = .005) and the primary end point hyperemic coronary resistance (mean [IQR], sham: 31 [23-53] mm Hg × s; balloon: 14 [8-26] mm Hg × s; P < .001). Conclusion and Relevance: Increased coronary venous pressure led to a reduction of microvascular resistances in patients with microvascular angina, a mechanism with potential implications for the therapy of this complex disease. Trial Registration: ClinicalTrials.gov Identifier: NCT05034224.

Understanding Patient Characteristics and Coronary Microvasculature: Early Insights from the Coronary Microvascular Disease Registry.

Coronary angiography has limitations in accurately assessing the coronary microcirculation. A new comprehensive invasive hemodynamic assessment method utilizing coronary flow reserve (CFR) and the index of microvascular resistance (IMR) offers improved diagnostic capabilities. This study aimed to present early real-world experience with invasive hemodynamic assessment of the coronary microvasculature in symptomatic patients with nonobstructive coronary artery disease (CAD) from the Coronary Microvascular Disease Registry, which is a prospective, multi-center registry that standardized the evaluation of patients with angina and nonobstructive CAD who underwent invasive hemodynamic assessment of the coronary microvasculature using the Coroventis CoroFlow Cardiovascular System. All patients underwent comprehensive invasive hemodynamic assessment. Analysis was performed on the first 154 patients enrolled in the Coronary Microvascular Disease Registry; their mean age was 62.4 years and 65.6% were female. A notable proportion of patients (31.8%) presented with a Canadian Cardiovascular Society Angina Score of 3 or 4. Coronary microvascular dysfunction was diagnosed in 39 of 154 patients (25.3%), with mean fractional flow reserve of 0.89 ± 0.43, mean resting full cycle ratio of 0.93 ± 0.08, mean CFR of 1.8 ± 0.9, and mean IMR of 36.26 ± 19.23. No in-hospital adverse events were reported in the patients. This study demonstrates the potential of invasive hemodynamic assessment using CFR and IMR to accurately evaluate the coronary microvasculature in patients with nonobstructive CAD. These findings have important implications for improving the diagnosis and management of coronary microvascular dysfunction, leading to more targeted and effective therapies for patients with microvascular angina.

Microvascular arterial disease of the brain and the heart: a shared pathogenesis.

Microvascular arterial disease in the heart manifest as coronary microvascular dysfunction. This condition causes microvascular angina and is associated increased morbidity and mortality. Microvascular arterial disease in the brain is referred to as cerebrovascular small vessel disease. This is responsible for 45% of dementias and 25% of ischaemic strokes. The heart and brain share similar vascular anatomy and common pathogenic risk factors are associated with the development of both coronary microvascular dysfunction and cerebrovascular small vessel disease. Microvascular disease in the heart and brain also appear to share common multisystem pathophysiological mechanisms. Further studies on diagnostic approaches, epidemiology and development of disease-modifying therapy seem warranted.

Exploring the active ingredients and mechanism of Shenzhi Tongxin capsule against microvascular angina based on network pharmacology and molecular docking.

BACKGROUND: Microvascular angina (MVA) substantially threatens human health, and the Shenzhi Tongxin (SZTX) capsule demonstrates a remarkable cardioprotective effect, making it a potential treatment option for MVA. However, the precise mechanism of action for this medication remains unclear. This study utilized network pharmacology and molecular docking technology to investigate the active components and potential mechanisms underlying the efficacy of the SZTX capsule in alleviating MVA. METHODS: The main ingredients of the SZTX capsule, along with their targets proteins and potential disease targets associated with MVA, were extracted from public available databases. This study utilized the STRING database and Cytoscape 3.7.2 software to establish a protein-protein interaction network and determine key signaling pathway targets. Subsequently, the DAVID database was utilized to conduct Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses on the intersection targets. To further investigate the molecular interactions, Autodock and PyMOL software were employed to perform molecular docking and visualize the resulting outcomes. RESULTS: A total of 130 and 142 bioactive ingredients and intersection targets were identified respectively. Six core targets were obtained through protein-protein interaction network analysis. Gene Ontology enrichment analysis showed that 610 biological processes, 75 cellular components, and 92 molecular functions were involved. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that SZTX capsule molecular mechanism in the treatment of MVA may be related to several pathways, including mitogen-activated protein kinases, PI3K-Akt, HIF-1, and others. The results of molecular docking showed that the 7 key active ingredients of SZTX capsule had good binding ability to 6 core proteins. CONCLUSION: SZTX capsule potentially exerts its effects by targeting multiple signaling pathways, including the mitogen-activated protein kinases signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. This multi-target approach enables SZTX capsule to inhibit inflammation, alleviate oxidative stress, regulate angiogenesis, and enhance endothelial function.

Coronary Microvascular Disease Assessed by 82-Rubidium Positron Emission Tomography Myocardial Perfusion Imaging Is Associated With Small Vessel Disease of the Kidney and Brain.

Background Coronary microvascular disease (CMD) may be part of a systemic small vessel disease that also manifests as neurological impairment and kidney disease. However, clinical evidence supporting a potential link is scarce. We assessed whether CMD is associated with an increased risk of small vessel disease in the kidney and brain. Methods and Results A retrospective multicenter (n=3) study of patients clinically referred to 82-rubidium positron emission tomography myocardial perfusion imaging was conducted between January 2018 and August 2020. Exclusion criterion was reversible perfusion defects >5%. CMD was defined as myocardial flow reserve (MFR) ≤2. The primary outcome, microvascular event, was defined by hospital contact for chronic kidney disease, stroke, or dementia. Among 5122 patients, 51.7% were men, median age 69.0 [interquartile range, 60.0-75.0] years, 11.0% had left ventricular ejection fraction ≤40%, and 32.4% had MFR ≤2. MFR was associated with baseline estimated glomerular filtration rate after multivariable adjustment (ß=0.04 [95% CI, 0.03-0.05]; P<0.001). During a median follow-up of 3.05 years, 383 (7.5%) patients suffered an event (253 cerebral and 130 renal), more frequently in patients with MFR ≤2 versus MFR >2 (11.6% versus 5.5%, P<0.001). MFR ≤2 was associated to outcome with a hazard ratio (HR) of 2.30 (95% CI, 1.88-2.81, P<0.001) and an adjusted HR of 1.62 (95% CI, 1.32-2.00, P<0.001). Results were consistent across subgroups defined by presence of irreversible perfusion defects, estimated glomerular filtration rate, diabetes, left ventricular ejection fraction, and previous revascularization. Conclusions This is the first large-scale cohort study to link CMD to microvascular events in the kidney and brain. Data support the hypothesis that CMD is part of a systemic vascular disorder.

Coronary Microvascular Disease in Contemporary Clinical Practice.

Coronary microvascular disease (CMD) causes myocardial ischemia in a variety of clinical scenarios. Clinical practice guidelines support routine testing for CMD in patients with ischemia with nonobstructive coronary artery disease. Invasive testing to identify CMD requires Doppler or thermodilution measures of flow to determine the coronary flow reserve and measures of microvascular resistance. Acetylcholine coronary reactivity testing identifies concomitant endothelial dysfunction, microvascular spasm, or epicardial coronary spasm. Comprehensive testing may improve symptoms, quality of life, and patient satisfaction by establishing a diagnosis and guiding-targeted medical therapy and lifestyle measures. Beyond ischemia with nonobstructive coronary artery disease, testing for CMD may play a role in patients with acute myocardial infarction, angina following coronary revascularization, heart failure with preserved ejection fraction, Takotsubo syndrome, and after heart transplantation. Additional education and provider awareness of CMD and its role in cardiovascular disease is needed to improve patient-centered outcomes of ischemic heart disease.

Evaluating the pure effect of weight on cardiac function in patients with cardiac syndrome X.

BACKGROUND: Obese patients have more coronary artery disease (CAD) risk factors that may affect myocardial function. We aimed to assess the ability of echocardiography-derived conventional parameters, left atrial strain, and global longitudinal strain to detect early diastolic and systolic dysfunction in obese individuals with almost no CAD risk factors. METHOD: We studied 100 participants with structurally normal hearts, ejection fractions above 50%, almost normal coronary arteries in coronary angiogram (syndrome X), and no cardiovascular risk factor except dyslipidemia. Participants were classified as normal-weight (BMI < 25.0 kg/m2 , n = 28) and high-weight (BMI ≥ 25.0 kg/m2 , n = 72). Conventional echocardiographic parameters and two-dimensional speckle tracking (2DSTE) were used to measure peak LA strain and global longitudinal strain to evaluate diastolic and systolic function, respectively. RESULT: There was no significant difference in the standard and conventional echocardiographic parameters between the two groups. 2DSTE echocardiographic parameters of the longitudinal deformation of the LV myocardium were not significantly different within the two groups. However, there were significant differences between the subjects with normal-weight and high-weight in terms of LA strain (34.51 ± 8.98% vs. 39.06 ± 8.62%, p = .021). The normal-weight group had lower LA strain, in compression with the high-weight group. All echocardiographic parameters were in the normal range. CONCLUSION: In the present study we demonstrated that global longitudinal subendocardial deformations, for the evaluation of systolic function, and conventional echocardiographic parameters, for the evaluation of diastolic function, were not significantly different between normal- and high-weight groups. Although LA strain was higher among overweight patients, it was not above the normal range of diastolic dysfunction.

Haemodynamic and metabolic adaptations in coronary microvascular disease.

OBJECTIVE: We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD). METHODS: Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12). RESULTS: The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03). CONCLUSIONS: Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).