Coronary Microvascular Impairment Research Articles

A Comprehensive Excursus of the Roles of Echocardiography in Heart Transplantation Follow-Up.

Current guidelines for the care of heart transplantation recipients recommend routine endomyocardial biopsy and invasive coronary angiography as the cornerstones in the surveillance for acute rejection (AR) and coronary allograft vasculopathy (CAV). Non-invasive tools, including coronary computed tomography angiography and cardiac magnetic resonance, have been introduced into guidelines without roles of their own as gold standards. These techniques also carry the risk of contrast-related kidney injury. There is a need to explore non-invasive approaches providing valuable information while minimizing risks and allowing their application independently of patient comorbidities. Echocardiographic examination can be performed at bedside, serially repeated, and does not carry the burden of contrast-related kidney injury and procedure-related risk. It provides comprehensive assessment of cardiac morphology and function. Advanced echocardiography techniques, including Doppler tissue imaging and strain imaging, may be sensitive tools for the detection of minor myocardial dysfunction, thus providing insight into early detection of AR and CAV. Stress echocardiography may offer a valuable tool in the detection of CAV, while the assessment of coronary flow reserve can unravel coronary microvascular impairment and add prognostic value to conventional stress echocardiography. The review highlights the role of Doppler echocardiography in heart transplantation follow-up, weighting advantages and limitations of the different techniques.

Quantifying Microvascular Structure in Healthy and Infarcted Rat Hearts Using Optical Coherence Tomography Angiography.

Myocardial infarction (MI) is a life-threatening medical emergency resulting in coronary microvascular dysregulation and heart muscle damage. One of the primary characteristics of MI is capillary loss, which plays a significant role in the progression of this cardiovascular condition. In this study, we utilized optical coherence tomography angiography (OCTA) to image coronary microcirculation in fixed rat hearts, aiming to analyze coronary microvascular impairment post-infarction. Various angiographic metrics are presented to quantify vascular features, including the vessel area density, vessel complexity index, vessel tortuosity index, and flow impairment. Pathological differences identified from OCTA analysis are corroborated with histological analysis. The quantitative assessments reveal a significant decrease in microvascular density in the capillary-sized vessels and an enlargement for the arteriole/venule-sized vessels. Further, microvascular tortuosity and complexity exhibit an increase after myocardial infarction. The results underscore the feasibility of using OCTA to offer qualitative microvascular details and quantitative metrics, providing insights into coronary vascular network remodeling during disease progression and response to therapy.

An Update on Molecular Modes Implicated in Diastolic Impairment in Early Diabetic Cardiomyopathy; Probable Modes of Therapy &Avoidance-A Narrative Review

In case of diabetic patients cardiomyopathy is a significant etiology of heart failure (HF); howeverno clarification exists regarding its pathophysiology. Myocardial hypertrophy as well as diastolic impairment are the logo for Diabetic cardiomyopathy (DbCM), whereas systolic function gets impacted in the latter phase of this disease. Previously we had reviewed Diabetic cardiomyopathy (DbCM with emphasis on epigenetic alterations ,miR changes apart from adipocyte impairment in HF induction, role of SGLT2 hampering agents in beneficial Cardiovascular Outcome Trials (CVOT’s)and renal benefits, role of sirtuins in macrophage Polarization for Diabesity therapy .Here our aim was to posit the pathophysiological mode implicated in myocardial hypertrophy and escalated myocardial stiffness resulting in diastolic impairment .This myocardial stiffness takes place from cellular and extracellular matrix(ECM ) stiffness &cell- matrix crosstalk. Escalated inherent cardiomyocytes stiffness plausibly is the maximum significant cause responsible for myocardial stiffness. It leads to dysfunctional cardiomyocytes cytoskeleton stiffness. Various other modes are implicatedbyT2DM; particularly having significant influence on myocardial stiffening i.e dysfunctional nitric oxide (NO), coronary microvascular impairment, escalated inflammation, as well as Oxidative stress(OS), myocardial Sodium –glucose specific cotransporter 2(SGLT2) modulated actions. Greater insight aids in planning better therapy.Anti diabeticagents, SGLT2 hampering agents have revealed newer ways of benefit ,like sirtuins action , upregulation of nutrient deprivation signaling in addition to downregulation of nutrient surplus signaling, escalated expression &activity of AMP-activated protein kinase(AMPK), Sirtuins (SIRT1), SIRT3 andSIRT6, & Peroxisome Proliferator Activated Receptor γCoactivator -1α(PGC-1α) ,reduction in activation of mammalian target of rapamycin inhibitors (mTOR). Recently Ghosh et al. (2023),advocated targeting sarcoplasmic / cytosolic endoplasmic reticulum Ca2+ -ATPase(SERCA2) ,use of imeglimin which escalates insulin action& along with reverses Pancreatic βcells impairment ,use of anti oxidants, angiotensin receptor neprilysin hampering agents(ARNi),NO stimulating agents. More work is being done regarding combination of empagliflozin with linagliptin &others like semaglutide with .Gradually we will get answers by getting more insight.

Circulating levels of galectin-3 and coronary microvascular perfusion in rheumatoid arthritis patients with suppressed inflammation.

Cardiovascular manifestations are the leading cause of mortality in rheumatoid arthritis (RA). Galectin-3, a lectin protein with major role in cellular, inflammatory, and fibrotic processes, has been introduced as a novel cardiac biomarker. We hypothesized that patients with RA present increased levels of galectin-3, and investigated potential associations with arterial stiffness and coronary microvascular dysfunction. This cross-sectional study enrolled RA patients and non-RA individuals without cardiovascular comorbidities. Galectin-3 and high-sensitivity C-reactive protein (hsCRP) were measured with enzyme-linked immunosorbent assay (ELISA) in serum samples. Subendocardial viability ratio (SEVR), an index of microvascular myocardial perfusion, and pulse wave velocity (PWV), the gold-standard measure of vascular stiffness, were estimated with applanation tonometry. Cardiovascular risk factors and hsCRP were comparable between patients (n = 24) and controls (n = 24). However, galectin-3 was increased [6.9 (6.7) vs 4.6 (4.7)] ng/dl, p = 0.015], and coronary microvascular perfusion was decreased (142.6 ± 22.8 vs 159.7 ± 23.2%, p = 0.028) in RA patients compared to controls, whereas PWV did not significantly differ. Galectin-3 correlated with both PWV and SEVR in univariate analysis. However, after adjustment for cardiovascular risk factors and subclinical inflammation, these associations were rendered non-significant. Galectin-3 appears increased in RA, even among patients with suppressed inflammation in the absence of cardiovascular comorbidities. The observed association of galectin-3 with coronary microvascular perfusion in our study was non-significant after adjustment for cardiovascular risk factors and inflammation. The potential role of galectin-3 as a cardiac biomarker in RA warrants further investigation. Key Points • Galectin-3 has emerged as a novel cardiac biomarker but remains understudied in RA. • Patients with RA present elevated levels of galectin-3 and impaired coronary microvascular perfusion compared to non-RA individuals. • These differences were observed in patients with suppressed inflammation, even in the absence of CVD. • The association of galectin-3 with coronary microvascular impairment in RA warrants further investigation.

Microvascular Dysfunction in COVID-19 Patients with Acute Coronary Syndrome.

Coronavirus disease 2019 (COVID-19) is considered to deteriorate endothelial function through hyperinflammation. We aimed to investigate microvascular dysfunction using the angiographic parameters thrombolysis in myocardial infarction frame count (TFC) and myocardial blush grade (MBG), in COVID-19 patients with acute coronary syndrome (ACS). One hundred and sixty-five patients presented with ACS (62.4% ST elevated myocardial infarction) and underwent percutaneous coronary intervention between March 1 and June 30, 2020, were enrolled in the study. The polymerase chain reaction test was performed in case of suggestive symptoms or typical computerized tomography findings. Twenty-six patients (15.7%) were tested positive for COVID-19. Significantly higher values were observed in TFC in patients with COVID-19 (p<0.001), whereas COVID-19 patients had significantly lower MBGs (Grade 0 and 1) (p<0.001). Peak troponin-I value was also higher in the COVID-19 group (27335 vs. 15959 ng/dL, p=0.006). Mortality risk was higher in COVID-19 patients (38.4% vs. 7.2%, p<0.001). TFC and ejection fraction may predict in-hospital mortality among COVID-19 patients with ACS according to logistic regression results. In correlation analysis, TFC correlated positively with C-reactive protein (r=0.340, p<0.001) and peak troponin-I value (r=0.369, p<0.001). COVID-19 is associated with slow coronary flow and microvascular impairment in ACS.

Improved diagnostic indices for coronary microvascular impairment in ST-elevation myocardial infarction; we've just begun, and now it's time to use them to improve outcomes.

Improved diagnostic indices for coronary microvascular impairment in ST-elevation myocardial infarction; we've just begun, and now it's time to use them to improve outcomes.

Relationship between peripheral arterial reactive hyperemia and the index of myocardial resistance in patients undergoing invasive coronary angiography

BackgroundCoronary microvascular dysfunction is a powerful prognostic factor in patients with coronary artery disease. We investigated the role of reactive digital hyperemia peripheral arterial tonometry (RH-PAT) as a non-invasive tool to identify patients with impaired coronary microvasculature. MethodsPatients undergoing elective coronary angiography were consecutively assessed for peripheral microvascular endothelial function before coronary angiography: both the Reactive Hyperemic Index (RHI) and the Framingham reactive hyperemic index (Endoscore) were measured. During coronary angiography, the Index of microvascular resistance (IMR) was measured in all patients, and an IMR value > 25 identified patients with coronary microvascular impairment. ResultsA total of 47 patients with chronic coronary syndromes candidate to coronary angiography were included. Those with coronary microvascular impairment (n = 18 [38%]) presented with significantly lower RHI (1.68 ± 0.38 vs. 1.94 ± 0.93, p = 0.04) and Endoscore 0.50 ± 0.23 vs. 0.64 ± 0.23, p = 0.04) values as compared with patients with preserved coronary microvasculature. A significant relationship was observed between IMR with both RHI (r = 0.35, p = 0.02) and Endoscore (r = 0.34, p = 0.02). At the multivariable analysis, RHI and Endoscore were the only independent predictors of an IMR > 25. ConclusionsOur study demonstrates that digital reactive hyperemia indexes are lower in patients with high IMR values, suggesting a role for RH-PAT as non-invasive tool for identifying patients with coronary microvascular impairment.

Coronary flow evaluation in heart transplant patients compared to healthy controls documents the inadequacy of the coronary flow velocity reserve metric

Abstract Background Coronary microvasculopathy has impact on prognosis in heart transplantation (HT). Distinct contributions by functional or structural alterations of coronary microcirculation in HT and their prognostic role have not been fully elucidated. Purpose We aimed to identify the mechanisms of coronary microvascular impairment in HT and their possible prognostic implications by applying a comprehensive analysis in a comparative study. Methods Included were 134 patients, surviving at least 5 years, with normal systolic function and no evidence of allograft vasculopathy or symptoms/signs of rejection. To permit comparison, 50 healthy volunteers without cardiovascular diseases, and matched for age and sex, served as controls. All underwent echocardiographic evaluation of microvascular function by the assessment of rest and hyperemic diastolic peak blood velocity (DPVr and DPVh). These paired data enable calculation of coronary flow velocity reserve (CFVR) and its inherent companion that is based on the quadratic mean: CFVRC = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated. A CFVR ≤2.5 was considered abnormal; the median value of DPVh (75 cm/s) and CFVRC (80 cm/s) were selected as cut-offs to classify patients. Results HT patients can be assigned to four groups, based on their CFVR and DPVh (Figure A): group 1 (n=32), discordant with preserved CFVR (3.1±0.4); group 2 (n=60), concordant with preserved CFVR (3.4±0.5); group 3 (n=31), concordant with impaired CFVR (1.8±0.3) and group 4 (n=11), discordant with impaired CFVR (2.0±0.2). Group 3 represents the structural microvascular remodeling with high HMR, while group 4 represents the functional remodeling with low BMR. Intriguingly, group 1 showed lower DPVr (p&amp;lt;0.0001) and lower DPVh (p&amp;lt;0.0001) than controls (Figure B, upper panel) with lower CFVR (p&amp;lt;0.0001), even if normal, and lower CFVRC (p&amp;lt;0.0001) than controls (Figure B, lower panel). Moreover, both BMR and HMR were higher in group 1 than in controls (5.3±1 vs 4.4±1.2, p=0.001 and 1.5±0.3 vs 1.1±0.2, p&amp;lt;0.0001, respectively), suggesting structural microvascular remodeling. Conversely, group 2 was comparable with controls (Figure B). Clinical characteristics of the different groups are shown in the Table. 13/32 (40.6%) patients in group 1 died in a follow up of 28 years and mortality rate was comparable to group 3 (14/31, 45.2%). However, CFVRC was &amp;lt;80 cm/s in all 13 deaths in group 1, yet being characterized by preserved CFVR (Figure C). Conclusions A normal CFVR could hide detection of microvascular damage with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (i.e., less rejections and more often diabetes). Being a dimensionless ratio, CFVR may miss some deaths, yet captured by CFVRC. Thus, the combined use of CFVR and CFVRC provides more complete clinical information on coronary microvasculopathy in HT. Funding Acknowledgement Type of funding source: None

New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography

BackgroundThe contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. MethodsWe studied 15 CS patients (11 female, age 50 ± 9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e′), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. ResultsCMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ± 12 versus 19.6 ± 4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ± 0.6 versus 5.46 ± 1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e′ were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e′ (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). ConclusionsFunctional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.

Coronary microvascular obstruction: the new frontier in cardioprotection.

Cardioprotection aims at infarct size reduction and improvement of clinical outcome from myocardial infarction. The translation of cardioprotection from preclinical and promising proof-of-concept studies to clinical benefit for patients has been largely disappointing. Almost all of these studies which did not translate into clinical benefit had infarct size reduction as the primary endpoint and used protocols selected to achieve infarct size reduction. The present review puts forward the hypothesis that the coronary circulation is a so far neglected target of cardioprotection. Mechanisms of ischemia-reperfusion injury to the coronary circulation are detailed. Clinical methods and measures to assess coronary microvascular impairment in reperfused acute myocardial infarction are presented. A comparison of magnetic resonance imaging data on infarct size vs. coronary microvascular obstruction is made. Finally, the design of studies which are optimized not only for infarct size reduction but also for salvage of the coronary microcirculation is advocated.

Platelet reactivity and coronary microvascular impairment after percutaneous revascularization in stable patients receiving clopidogrel or prasugrel

Background and aimsIncreased platelet reactivity (PR) associated with variable degree of coronary microvascular impairment has been reported in patients on clopidogrel after elective percutaneous coronary intervention (PCI). Prasugrel provides more potent platelet inhibition than clopidogrel, though it is unknown whether it might also prevent PCI-related platelet activation. In stable patients undergoing elective PCI, we compared: (1) the effects of prasugrel vs. clopidogrel on peri-procedural variations of PR and (2) the correlation of platelet inhibition potency with PCI-induced coronary microvascular impairment. MethodsForty thienopyridine-naive patients were randomly assigned to a loading dose of either prasugrel 60 mg (n = 20) or clopidogrel 600 mg (n = 20) at least 12 h before PCI. At the time of PCI, we assessed adenosine diphosphate (ADP)-induced PR with the Multiplate Analyzer, and the pressure-derived index of microvascular resistance (IMR) in the treated coronary, both at baseline and post-procedure. ResultsADP-induced PR was significantly lower in the prasugrel compared with clopidogrel group both at baseline (16.0 ± 8.7 vs. 33.9 ± 18.0 aggregation units [AU], p < 0.001) and post-procedure (16.2 ± 9.0 vs. 39.0 ± 18.6 AU, p < 0.001). A significant peri-procedural increase in PR was observed in the clopidogrel group (p = 0.008), but not in the prasugrel group (p = 0.822). A significant correlation was found between IMR and PR both at baseline (r = 0.458, p = 0.003) and post-PCI (r = 0.487, p = 0.001). ConclusionsA loading dose of prasugrel compared with clopidogrel is able to attenuate PCI-related increase in PR in patients with stable CAD undergoing PCI, which might contribute to the beneficial effect of this drug on peri-procedural coronary microvascular function.

Zumba-induced Takotsubo cardiomyopathy: a case report

BackgroundTakotsubo cardiomyopathy or stress cardiomyopathy is characterized by transient left ventricular apical ballooning in the absence of coronary occlusion. The underlying pathophysiological mechanism is still unclear but possible causes have been proposed mainly catecholamine cardiotoxicity, followed by metabolic disturbance, coronary microvascular impairment, and multivessel epicardial coronary artery vasospasm. Takotsubo cardiomyopathy accounts for 1–2% of patients presenting with acute coronary syndrome with the majority of patients diagnosed with Takotsubo cardiomyopathy being women > 55 years of age. Here, we discuss the case of a 38-year-old woman presenting with typical chest pain, electrocardiography changes and cardiac markers consistent with acute coronary syndrome, who was subsequently diagnosed with Takotsubo cardiomyopathy.Case presentationA 38-year-old healthy American woman with negative past medical history presented to our Emergency Department with chest pain developing while participating in intense outdoor physical activities (Zumba) at a fundraising event. Our patient had typical substernal chest pain induced with exercise and was relieved by sublingual nitroglycerin in the Emergency Department. The pain started after 2 h of intensive Zumba workout. On review of her history, our patient was noted to be taking spironolactone 125 mg once daily for hirsutism for the past year. Our patient denied any family history of cardiac disease or heart failure. She admitted to being a former occasional smoker and to drinking alcohol socially. She denied any illicit drug use. She works as a social worker, and reported that she does not experience much stress in her life and denied any “one big life-changing event” or any major stressful news. While in the Emergency Department, our patient was hemodynamically stable and an electrocardiography was performed and showed sinus rhythm with no ST elevation/depression but noted T-wave inversion in leads I and aVL, and T wave flattening in leads V1 and V2. Her troponin levels were 0.294 and 0.231 consecutively. An echocardiogram was done and showed hypokinetic apical and mid-distal walls and hyperdynamic basal walls of the left ventricle with an ejection fraction of 35–40%, consistent with apical ballooning syndrome. Cardiac catheterization was subsequently done and showed depressed left ventricle systolic function, ejection fraction of 30–35% with anteroapical dyskinesia and no evidence of coronary artery disease.Our patient was diagnosed with Takotsubo cardiomyopathy after fulfilling all four of the Mayo Clinic’s diagnostic criteria and was subsequently treated with a beta blocker, and angiotensin-converting enzyme inhibitor.ConclusionsOur patient did not have one clear trigger for her overt Takotsubo cardiomyopathy other than the Zumba activity. Zumba is considered an activity with excessive sympathetic stimulation leading to catecholamine-induced microvascular spasm or through to direct myocardial toxicity, which is postulated to be behind the pathophysiology of Takotsubo cardiomyopathy. Another interesting finding in our patient was her use of spironolactone, as treatment for hirsutism, which is an aldosterone antagonist. Aldosterone actually potentiates the effects of catecholamine and thus activates the sympathetic system. Spironolactone can thus be considered as cardioprotective against the effects of catecholamine on the heart and that is why it is considered to be beneficial and subsequently improves mortality in chronic heart failure as described in several studies.

Coronary microvascular dysfunction may be related to IGF-1 in acromegalic patients and can be restored by therapy

Background and aimsAcromegaly increases the risk of cardiovascular mortality. Data on the cardiovascular risk in asymptomatic acromegaly are limited. In particular, data on coronary microvascular abnormalities are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic acromegaly. MethodsWe studied 40 acromegalic patients (23 male, age 52 ± 11 years) without clinical evidence of cardiovascular disease, and 40 control subjects matched for age and sex. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperaemic to resting diastolic flow velocity. ResultsCFR was lower in patients than in controls (2.9 ± 0.8 vs. 3.7 ± 0.6, p < 0.0001) and was abnormal (≤2.5) in 13 patients (32.5%) compared with any control subjects (0%) (p < 0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels (r = −0.5, p < 0.004). In patients with CFR≤2.5, IGF-1 was higher (756 [381–898] μg/l versus 246 [186–484] μg/l, p < 0.007) whereas growth hormone (GH) levels were similar (6.3 [2.8–13.7] μg/l versus 5 [2.8–8.9] μg/l, p = 0.8). In multivariable linear regression analysis, IGF-1 was independently associated with CFR (p < 0.0001). In multiple logistic regression analysis, IGF-1 independently increased the probability of CFR≤2.5 (p = 0.009). In four patients with active disease (all with CFR<2.5), treatment with somatostatin analogues normalized CFR. However the other four patients with active disease were not responder. ConclusionsAcromegalic patients have coronary microvascular dysfunction that may be restored by therapy with somatostatin analogues. IGF-1 independently correlates with the coronary microvascular impairment, suggesting the pivotal role of this hormone in explaining the increased cardiovascular risk in acromegaly.

Feasibility, symptoms, adverse effects, and complications associated with noninvasive assessment of coronary flow velocity reserve in women with suspected or known coronary artery disease.

Microvascular coronary impairment, defined as reduced coronary flow reserve, represents the predominant etiologic mechanism of ischemia in women with chest pain and no obstructive coronary artery disease. Transthoracic echocardiography (TTE) is a noninvasive method for assessing coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD). The purpose of this investigation was to define the safety profile, feasibility, adverse events, and rate of complications of the test in women with suspected CAD. We evaluated CFVR in LAD with TTE during adenosine infusion in 1455 women aged 66.4±11.9years. A complete CFVR study was achieved in 1429 pts (feasibility 98.2%), the test being performed also in the early phase of acute coronary syndrome and on obese patients. Minor symptoms or adverse effects occurred in 43.7% of patients not requiring test termination: hyperpnea (16.7%), flushing (9.4%), atypical chest pain (9.9%), headache (6.6%), minor arrhythmias (2.9%), chest pain with EKG changes (1.5%) were the symptoms reported. No major complications were observed. Noninvasive assessment of CFVR in LAD by TTE is a very feasible method with very low incidence of adverse events and complications in women with suspected or known CAD. It is safe and can be used when evaluating female patients with atherosclerotic LAD disease or with coronary microvascular impairment.

Quantitative Assessment of Coronary Microvascular Function: Dynamic Single-Photon Emission Computed Tomography, Positron Emission Tomography, Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

A healthy, functional microcirculation in combination with nonobstructed epicardial coronary arteries is the prerequisite of normal myocardial perfusion. Quantitative assessment in myocardial perfusion and determination of absolute myocardial blood flow can be achieved noninvasively using dynamic imaging with multiple imaging modalities. Extensive evidence supports the clinical value of noninvasively assessing indices of coronary flow for diagnosing coronary microvascular dysfunction; in certain diseases, the degree of coronary microvascular impairment carries important prognostic relevance. Although, currently positron emission tomography is the most commonly used tool for the quantification of myocardial blood flow, other modalities, including single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and myocardial contrast echocardiography, have emerged as techniques with great promise for determination of coronary microvascular dysfunction. The following review will describe basic concepts of coronary and microvascular physiology, review available modalities for dynamic imaging for quantitative assessment of coronary perfusion and myocardial blood flow, and discuss their application in distinct forms of coronary microvascular dysfunction.

A tool for predicting the outcome of reperfusion in ST-elevation myocardial infarction using age, thrombotic burden and index of microcirculatory resistance (ATI score)

Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2. The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.

Bimodal Pattern of Coronary Microvascular Involvement in Diabetes Mellitus.

BackgroundThe contribution of functionally disturbed coronary autoregulation and structurally impaired microvascular vasodilatory function to reduced coronary flow velocity reserve, reflecting impaired coronary microcirculation in diabetes mellitus (DM), has not been clearly elucidated. The objective of this study was to identify the mechanism of coronary microvascular impairment in DM in relation to duration of disease.Methods and ResultsCoronary flow velocities in the anterior descending coronary artery were assessed by transthoracic echocardiography following angiography revealing normal epicardial coronary arteries in 55 diabetic and 47 nondiabetic patients. Average peak flow velocities, coronary flow velocity reserve, and microvascular resistance in baseline and hyperemic conditions (baseline and hyperemic microvascular resistance, respectively) were assessed. Reduced coronary flow velocity reserve in patients with short duration (<10 years) of DM compared with nondiabetic patients was primarily driven by increased baseline average peak flow velocity (26.50±5.6 versus 22.08±4.31, P=0.008) in the presence of decreased baseline microvascular resistance (3.69±0.86 versus 4.34±0.76, P=0.003). In contrast, decreased coronary flow velocity reserve in patients with long‐standing (≥10 years) DM compared with nondiabetic patients was predominantly driven by reduced hyperemic average peak flow velocity (41.57±10.01 versus 53.47±11.8, P<0.001) due to increased hyperemic microvascular resistance (2.13±0.42 versus 1.69±0.39, P<0.001).ConclusionsBoth altered coronary autoregulation and impaired microvascular vasodilatory function contribute to DM‐related coronary microvascular impairment in a time‐dependent manner. DM‐induced early functional microvascular autoregulatory impairment seems to evolve into structural microvascular impairment in the initially overperfused microvascular territory at the later stage of disease.

Usefulness of two-dimensional longitudinal strain pattern to predict left ventricular recovery and in-hospital complications after acute anterior myocardial infarction treated successfully by primary angioplasty.

The aim of this study was to test the usefulness of two-dimensional longitudinal strain pattern in segments with wall motion abnormalities to predict left ventricular recovery and in-hospital cardiac events as well as coronary microvascular impairment (CMI) in patients with recent acute anterior myocardial infarction. Forty-nine consecutive patients with acute myocardial infarction (mean age, 59±13years) treated successfully with primary coronary angioplasty prospectively underwent transthoracic Doppler echocardiography 24hours after angioplasty and during follow-up (6months). A two-dimensional strain analysis, including measurement of the duration of systolic lengthening expressed as a percentage of systolic duration (SL % duration), the lengthening-to-shortening ratio, the postsystolic shortening index in segments with wall motion abnormalities, and global longitudinal strain and left anterior descending coronary artery territory strain, was performed. Cardiac events were defined as a composite of death, reinfarction, and heart failure. CMI was assessed noninvasively by transthoracic Doppler left anterior descending coronary artery investigation <24h after angioplasty and was defined as coronary flow velocity reserve<1.7 and/or a no-reflow pattern (mean coronary flow velocity reserve, 1.8±0.6 in the whole group). At the segmental level, SL % duration, lengthening-to-shortening ratio, and postsystolic shortening index were correlated with recovery (defined as normalization of wall motion abnormalities), whereas in multivariate analysis, only SL % duration independently predicted recovery (threshold level, 40%; area under the curve, 0.76; P<.01). At the patient level, in univariate analysis, SL % duration, global longitudinal strain, left anterior descending coronary artery territory strain, and troponin peak were correlated with recovery (defined as an absolute improvement of left ventricular ejection fraction of >5%). In multivariate analysis, SL % duration was independently related to recovery (area under the curve, 0.78; P<.01). Furthermore, SL % duration was independently linked to cardiac events (n=13) and CMI (n=24) (P<.01 for all). In patients with AMI treated by primary angioplasty, two-dimensional strain predicts left ventricular recovery independently of more traditional parameters and is independently linked to cardiac events and CMI.

Association between serum total antioxidant status and coronary microvascular function in idiopathic dilated cardiomyopathy

Coronary microvascular impairment may cause myocardial ischemia and systolic dysfunction in patients with idiopathic dilated cardiomyopathy (IDC). The study included 41 patients with IDC and 33 healthy control subjects. Serum total antioxidant status (TAS), serum interleukin (IL)-6 levels, and tumor necrosis factor (TNF)-α levels were assayed and coronary flow reserve (CFR) was measured in all subjects via echocardiography. High-sensitivity C-reactive protein (hsCRP) levels were significantly higher in patients with IDC than in the control group (3.42 ± 2.14 vs. 1.91± 1.40, p = 0.001). Serum TAS was statistically lower in patients with IDC than in controls (1.23 ± 0.16 vs. 1.77 ± 0.12, p < 0.001). CFR was statistically and significantly lower in the IDC group (2.10 ± 0.39 vs. 3.09 ± 0.49, p < 0.001). The IDC group was subsequently subdivided into two groups according to CFR values, as CFR ≥ 2 and CFR < 2. HsCRP (4.30 ± 2.42 vs. 2.58 ± 1.42, p = 0.01), TNF-α (16.67 ± 8.08 vs. 10.97 ± 1.63, p = 0.01), and IL-6 (7.54 ± 6.16 vs. 3.14 ± 1.10, p = 0.05) values were significantly higher in the CFR < 2 group compared with the higher CFR group. TAS (1.3 ± 0.16 vs. 1.14 ± 0.10, p < 0.001) was significantly lower in the CFR < 2 group. CFR correlated significantly with hsCRP, TAS, red cell distribution width (RDW), IL-6, and TNF-α. Plasma proinflammatory cytokine levels are increased in patients with IDC. CFR was impaired as a reflection of impaired coronary microvascular dysfunction in association with increasing plasma proinflammatory cytokine levels and hsCRP levels.

Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease

Background and AimsObesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease. Methods and results86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m−2), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p < 0.03 and p < 0.03, respectively). ConclusionsCFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.