Coronary Microvascular Dysfunction Research Articles

Coronary microvascular dysfunction and atrial reservoir function

BackgroundCoronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr.MethodsConsecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively.ResultsForty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78–0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD.ConclusionPatients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

Impact of Coronary Microvascular Dysfunction in Takotsubo Syndrome: Cause, Consequence or Both?

Impact of Coronary Microvascular Dysfunction in Takotsubo Syndrome: Cause, Consequence or Both?

Coronary Microvascular Disease in Women: Epidemiology, Mechanisms, Evaluation, and Treatment.

Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease.

Renal functional reserve assessment in patients with coronary microvascular dysfuntion and preserved renal function

Abstract Funding Acknowledgements None. Introduction Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. Aim The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73m2 (CKD-EPI) and proteinuria< 400mg/24h]. Methods This is a single-center, prospective study enrolling patients with CMD. We are presenting preliminary resuts. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured invasively. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as ≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - non-CMD group [7 female, 64%, mean age: 52.9±8.8 years) and 14 with INOCA – CMD group (11 female, 79%, mean age : 53.5±10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR<2.5 and IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4±6.3 ml/min/1.73m2, while for control group 36.3±5.8 ml/min/1.73m2 (p<0.005), This difference between groups was found to be statistically significant after controlling for confounding factors. It was found that RFR value for functional CMD endotype was 3.8±2.6 ml/min/1.73m2, while for patients with structural endotype 9.6±7,2 ml/min/1.73m2 (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices (p =0.35, p =0.23 respectively). According to data from 24hr ABPM , there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p=NS for all), as well as no relationship with RFR (p=0.6, p=0.6 respectively) was observed. However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p<0.05). It was not found correlation between RFR and non-dipping phenotype, for both SBP and DBP (p=NS). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to levels of BP or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes could contribute to the individualization of therapeutic interventions.

Microvascular dysfunction associated with reduced nailfold capillary density in patients with ischemia with no obstructive coronary artery disease

Abstract Funding Acknowledgements None. Introduction The impairment of microvascular function present in coronary microcirculation with chronic angina without obstructive coronary arteries. There are insufficient data in the literature regarding possible generalized microangiopathy in this population. Aim The aim of this study is to demonstrate whether patients with Angina with No Obstructive Coronary Artery Disease (ANOCA) compared to individuals without coronary microvascular dysfunction (CMD) are characterized by a different level of nailfold capillaroscopy abnormalities. Methods We examined 18 participants without CMD - non-CMD group [9 female, 50%, mean age: 54.4±8.1 years) and 26 patients with ANOCA - CMD group (22 female, 84,6%, mean age : 53.2±10.7 years). Functional coronary angiography was performed for the assessment of coronary microcirculation in all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. In addition, the assessment of skin microcirculation was performed by capillaroscopy, a non-invasive technique to evaluate small vessels of the microcirculation in the nailfold, using stereomicroscope in all patients. Results In CMD group, mean CFR and IMR were 1.34±0.6 and 44.8±28, respectively. Out of the 26 MVD patients with abnormal CFR, 7 of them (27%) had a normal value of IMR, indicating functional microvascular dysfunction. On the other hand, 18 patients (69%) had an abnormal IMR, indicating structural microvascular dysfunction. Capillary density in patients with MVD was significantly decreased compared to the control group (7.6±2.2 vs 10.9±1.8 vessels/mm, p=0.04). The difference in capillary density between the two groups was statistically significant after adjustment for multiple comparisons (p<0.05). No significant difference was found in body mass index, renal function, medical history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p<0.05). Conclusion Nailfold capillary density was reduced in ANOCA patients compared to control group. These data may provide new insights regarding possible generalized microangiopathy in CMD patients. These results suggest that there is an association between microcirculatory impairment at both heart and peripheral vascular bed level.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Exploring the interplay between coronary microvascular dysfunction and mental health

BackgroundThe intricate relationship between mental health disorders, notably anxiety and depression, and chest pain associated with non-obstructive coronary artery disease has become a focus of investigation. MethodsThis study from the Coronary Microvascular Disease Registry (CMDR) evaluated the association of mental health disorders and coronary microvascular dysfunction (CMD) among patients with angina with no obstructive coronary artery disease (ANOCA)who had undergone comprehensive invasive physiological testing for CMD. Clinical data regarding baseline characteristics, comorbidities, and noninvasive cardiac testing were obtained from chart review. The primary outcome of interest was the potential relationship between mental health diagnoses and the presence of CMD. ResultsOf patients included in the CMDR, 27 % (41/152) had at least one documented mental health disorder diagnosis (International Classification of Diseases, Tenth Revision codes) and CMD. There was no difference in mental health diagnosis prevalence between CMD-positive and CMD-negative patients (21.1 % vs. 28.9 %, p = 0.34). The most common mental health diagnoses were depression (15.8 %) and anxiety (15.8 %). Furthermore, 46.3 % (19/41) of patients with mental health disorders were prescribed psychiatric medications, with the most common being benzodiazepines (26.8 %). ConclusionPatients with chest pain not due to CMD did not have an increased prevalence of mental health disorders compared with patients with ANOCA due to CMD, challenging the notion of a psychosomatic component in the pathogenesis of ANOCA.Clinical Trial Registration: Coronary Microvascular Disease Registry, clinicaltrials.gov, NCT05960474.

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Coronary microvascular dysfunction and inflammation: Insights from the Coronary Microvascular Disease Registry

BackgroundCoronary microvascular dysfunction (CMD) is associated with various inflammatory conditions that worsen endothelial dysfunction. This study aimed to investigate the relationship between CMD and inflammation using common inflammatory markers derived from complete blood count (CBC) analysis. MethodsInformation was gathered from the Coronary Microvascular Disease Registry to examine the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-monocyte ratio (EMR), and monocyte-to-high-density lipoprotein ratio (MHR) in a cohort of patients with angina who showed non-obstructive coronary arteries and underwent invasive physiological assessments for CMD. ResultsOf the 171 patients studied, 126 were CMD-negative and 45 were CMD-positive, constituting two groups of interest. The average age of all patients was 61.7 ± 11.1 years, and 63.7 % were female. No significant differences were observed between the two groups in terms of baseline characteristics, cardiovascular risk factors, or potential anti-inflammatory medications. Furthermore, there were no statistically significant differences in NLR (2.54 ± 3.71 vs. 2.52 ± 2.28, p = 0.97), EMR (0.3 ± 0.21 vs. 0.34 ± 0.29, p = 0.31), or MHR (0.02 ± 0.01 vs. 0.01 ± 0.01, p = 0.54) between CMD-positive and CMD-negative patients. ConclusionOur findings did not show a noteworthy connection between CMD and inflammation, as suggested by various simple CBC-based biomarkers.

Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

C-29 | Utility of invasive bolus thermodilution method in diagnosis of coronary microvascular dysfunction (CMD): Real World data

C-29 | Utility of invasive bolus thermodilution method in diagnosis of coronary microvascular dysfunction (CMD): Real World data

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Usefulness of triglyceride-glucose index and homeostatic model assessment for predicting coronary microvascular dysfunction

Usefulness of triglyceride-glucose index and homeostatic model assessment for predicting coronary microvascular dysfunction

Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry

BackgroundApproximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. MethodsThe DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. ConclusionsDISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

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

Introduction Coronary microvascular disease (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. Methods In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p=0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p&lt;0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p&lt;0.01 and β=-0.17; p=0.04, respectively). Conclusion For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Coronary Microvascular Dysfunction is Present Among Well-Treated Asymptomatic Persons with HIV and Similar to Those with Diabetes

Abstract Background Coronary microvascular dysfunction(CMD) could be a potential underlying mechanism for myocardial disease in HIV. Methods Comparisons of coronary flow reserve corrected for heart rate-blood pressure product(CFRCOR) were made among PWH with no known history of cardiovascular disease(CVD) or diabetes mellitus (DM), persons without HIV(PWOH), and persons with diabetes(PWDM) and no known history of CVD or HIV. Results PWH[n = 39, 74% male, age 55(7)years, body mass index(BMI) 32.3(26.8, 34.9)kg/m2, duration antiretroviral therapy(ART) 13(5)years, CD4+ count 754(598, 961)cells/μl] were similar to PWOH[n = 69, 74% male, age 55(8)years, BMI 32.2(25.6, 36.5)kg/m2] and PWDM[n = 63, 63% male, age 55(8)years, BMI 31.5(28.6, 35.6)kg/m2]. CFRCOR was different among groups: PWOH 2.76(2.37,3.36), PWH 2.47(1.92,2.93), PWDM 2.31(1.98,2.84), overall P = .003. CFRCOR was reduced comparing PWH to PWOH(P = .04) and PWDM to PWOH(P = .007), but did not differ when comparing PWH to PWDM(P = .98). 31% of PWH had CFRCOR &amp;lt; 2.0, a critical cutoff for CMD, compared to 14% of PWOH and 27% with PWDM. 40% of women with HIV had a CFRCOR &amp;lt; 2.0 compared to 6% of women without HIV(P = .02). Conclusion Subclinical CMD is present among chronically infected and well-treated, asymptomatic PWH who are immunologically controlled. This study demonstrates CFR is reduced in PWH compared to PWOH and comparable to PWDM, further highlighting that well-treated HIV infection is a CVD-risk enhancing factor for CMD similar to diabetes.

Correlation of Non-Invasive Transthoracic Doppler Echocardiography with Invasive Doppler Wire-Derived Coronary Flow Reserve and Their Impact on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho -0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.

Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury.

Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Sprague-Dawley rats were subjected to BDL surgery (n = 28) or served as sham-operated (n = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed. BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; p < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, p = 0.041; GLS rest control: -24.05 ± 3.8% vs. BDL: -18.5 ± 5.1%, p = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 p = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration. In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.

Concomitant amyloidosis is the primary cause of endothelial and coronary microvascular dysfunction in carpal tunnel syndrome

Study objectivesPatients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself. DesignProspective observational study. SettingMedeniyet University Goztepe Hospital Participants61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls. InterventionsSubjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT). Main outcome measuresComparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis. ResultsPatients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, p < 0.05 for both) and CFVR (2.4 (2.1–2.8) in CTS and 1.8 (1.6–2.1) in CTS-A groups, p < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60–0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A. ConclusionMost arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis.