Coronary Vasomotor Function Research Articles

Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina.

A coronary function test (CFT) isthe recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose. We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL-CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2-20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow-up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm61±21, controls 64±21, overall P=0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group. A significant dose-dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06083155.

Mineralocorticoid receptor antagonism prevents coronary microvascular dysfunction in intermittent hypoxia independent of blood pressure.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), and is associated with increased cardiovascular mortality that may not be reduced by standard therapies. Inappropriate activation of the renin-angiotensin-aldosterone system occurs in IH, and mineralocorticoid receptor (MR) blockade has been shown to improve vascular outcomes in cardiovascular disease. Thus, we hypothesized that MR inhibition prevents coronary and renal vascular dysfunction in mice exposed to chronic IH. Human and mouse coronary vascular cells and male C57BL/6J mice were exposed to IH or room air (RA) for 12 hours/day for 3 days (in vitro) and 6 weeks with or without treatments with spironolactone (SPL) or hydrochlorothiazide (HTZ). In vitro studies demonstrated that IH increased MR gene expression in human and mouse coronary artery endothelial and smooth muscle cells. Exposure to IH in mice increased blood pressure, reduced coronary flow velocity reserve (CFVR), and attenuated endothelium-dependent dilation and enhanced vasoconstrictor responsiveness in coronary, but not renal arteries. Importantly, SPL treatment prevented altered coronary vascular function independent of blood pressure as normalization of BP with HTZ did not improve CFVR or coronary vasomotor function. These data demonstrate that chronic IH, which mimics the hypoxia-reoxygenation cycles of moderate-to-severe OSA, increases coronary vascular MR expression in vitro. It also selectively promotes coronary vascular dysfunction in mice. Importantly, this dysfunction is sensitive to MR antagonism by SPL, independent of blood pressure. These findings suggest that MR blockade could serve as an adjuvant therapy to improve long-term cardiovascular outcomes in patients with OSA.

Spatiotemporal metabolic mapping of ex-situ preserved hearts subjected to dialysis by integration of bio-SPME sampling with non-targeted metabolipidomic profiling.

Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement. Male Yorkshire porcine hearts were subjected to ESHP for 8h with or without dialysis. Alterations in metabolism were studied with an innovative in vivo solid-phase microextraction (SPME) technology coupled with global metabolite profiling at 15min, 1.5, 4, and 8h of perfusion. Bio-SPME sampling was performed by inserting SPME fibres coated with a PAN-based extraction phase containing mixed-mode (C8+benzenesulfonic acid) functionalities into the myocardium to a depth of their entire 8mm coating or immersing them in the perfusate, followed by a 20-min extraction period for the analytes of interest. Dialyzed hearts demonstrated improved bioenergetics as evidenced by accelerated purine metabolism and less pronounced accumulation of intermediates of fatty acid β/ω-oxidation. Metabolic waste accumulation such as pro-inflammatory lipid mediators (e.g., leukotrienes) was mitigated thereby supporting the process of resolution of inflammation through excretion of specialized pro-resolving mediators (resolvins D1/D2, E2, protecin D1). Through implementing the unique analytical pipeline we demonstrated that the addition of dialysis may preserve cardiac metabolism allowing for prolonged ESHP. This strategy has the potential to facilitate high-risk donor organs' reconditioning prior to transplantation.

Asymmetric Dimethylarginine (ADMA) in Cardiovascular Disease, Cardiac Ischemia/reperfusion Injury, and Ischemic Non-obstructive Coronary Artery Disease: Biochemical and Pharmacological Implications

: Several studies have shown that high plasma concentrations of asymmetric dimethylarginine (ADMA), a known endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS), correlate with the severity of coronary artery disease (CAD), with worsening of cardiac ischemia/reperfusion (I/R) injury and coronary atherosclerosis. It is believed that it may be an important risk factor for myocardial infarction. ADMA, when in high concentrations, can determine a significant decrease in the synthesis and bioavailability of NO (Nitric oxide) and therefore alter the mechanisms of regulation of coronary vasodilation and vasomotor function of epicardial coronary arteries. Higher serum ADMA concentration is associated with worsening of post-ischemic remodeling since coronary angiogenesis, vasculogenesis, and collateral coronary growth are seriously impaired. In addition, there are reasons to believe that elevated plasma ADMA levels are related to the development of diseases affecting coronary microcirculation, such as ischemic non-obstructive coronary artery disease (INOCA). With the aim of providing the pharmacologist engaged in the design and discovery of new ADMA-lowering drugs with a complete examination of the subject, in this review, we discuss the most important studies related to the correlations between serum ADMA levels and cardiovascular diseases mentioned above. In addition, we critically discuss the main aspects of enzymology, synthesis, and metabolism of ADMA as a prerequisite for understanding the molecular mechanisms through which high concentrations of ADMA could contribute to promoting cardiovascular diseases. ADMA represents a new target for pharmacological modulation of cardiovascular endothelial function and therefore, there is a possibility of using selective pharmacological ADMA lowering drugs in cardiovascular disease with endothelial dysfunction and high plasma ADMA levels.

New avenues for the assessment of stable ischemic heart disease.

Myocardial ischemia is a complex condition which may result from epicardial and/or microvascular causes involving functional and structural mechanisms. These mechanisms may overlap in a given patient illustrating the difficulties for appropriate management. Assessment of myocardial ischemia can be performed using noninvasive and invasive tools. However, despite living in the era of individualized precision medicine, these tools are not yet used in a broader fashion. Emerging noninvasive techniques such as quantitative perfusion cardiac magnetic resonance imaging (CMR) and stress perfusion computed tomography (CT) or photon-counting CT techniques may contribute to new standards in the assessment of stable angina patients. Invasive evaluation of myocardial ischemia should not only focus on hemodynamically relevant epicardial disease but also involve coronary vasomotor function testing (coronary spasm, coronary flow reserve, and microvascular resistance) where appropriate. Optimal patient management will depend on accurate and comprehensive diagnostic evaluation of myocardial ischemia and development of new treatment options in the future.

Dialysis preserves heart function during ex situ heart perfusion

BackgroundEx situ heart perfusion (ESHP) has been used to optimize donor organs before heart transplantation. However, cardiac function often deteriorates with the development of myocardial edema. The use of dialysis during ESHP could assist in cardiac preservation. MethodsMale Yorkshire pig hearts were subjected to ESHP for 8 hours with or without dialysis. Hearts were supported during nonworking mode (NWM) and working mode (WM) and pressure-volume loops and coronary vasomotor function was evaluated. Finally, tissue biopsies were assessed for mitochondrial function, oxidative stress, and inflammation. ResultsAdding dialysis to ESHP significantly enhanced cardiac function, with improved PRSW at 4 hours (64.09 ± 20.13 vs. 35.08 ± 13.52, p = 0.010) and 8 hours (64.31 ± 9.08 vs. 23.30 ± 19.25, p = 0.0002), Emax at 8 hours (24.67 ± 10.75 vs. 10.62 ± 8.471, p = 0.0477), and EDPVR at 8 hours (644.7 ± 566.68 vs. 86.63 ± 72.05, p = 0.0187). Coronary vasomotor function improved in the dialysis group in endothelium dependent (LogIC50 -7.39 ± 0.25 vs. -2.22 ± 0.76, p < 0.0001) and independent (LogIC50 -6.11 ± 0.19 vs. -4.79 ± 0.11, p < 0.0001) vasorelaxation. Dialyzed hearts also had reduced sensitivity to ET1 (LogEC50 -7.94 ± 0.5 vs. -8.54 ± 0.06, p = 0.0449) and significant changes in endothelin receptor-related protein expression related and oxidative stress. ConclusionsThe combination of dialysis with ESHP improves myocardial and coronary vasomotor preservation and may allow for longer perfusion times.

#FullPhysiology: a systematic step-by-step guide to implement intracoronary physiology in daily practice.

#FullPhysiology is a comprehensive and systematic approach to evaluate patients with suspected coronary disease using PressureWire technology (Abbott Vascular, Santa Clara, CA, USA). This advancement in technology enables the investigation of each component of the coronary circulation, including epicardial, microvascular, and vasomotor function, without significantly increasing procedural time or technical complexity. By identifying the predominant physiopathology responsible for myocardial ischemia, #FullPhysiology enhances precision medicine by providing accurate diagnosis and facilitating tailored interventional or medical treatments. This overview aims to provide insights into modern coronary physiology and describe a systematic approach to assess epicardial flow-limiting disease, longitudinal physiological vessel analysis, microvascular and vasomotor dysfunction, as well as post- percutaneous coronary intervention (PCI) physiological results.

Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT)

BackgroundAngina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. MethodsThe NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered.The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. ConclusionNL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

Vitamin C Deficiency Exacerbates Dysfunction of Atherosclerotic Coronary Arteries in Guinea Pigs Fed a High-Fat Diet.

Vitamin C (vitC) deficiency has been associated with an increased risk of cardiovascular disease; while several putative mechanistic links have been proposed, functional evidence supporting a causal relationship is scarce. In this study, we investigated how vitC deficiency affects coronary artery vasomotor function and the development of coronary atherosclerotic plaques in guinea pigs subjected to chronic dyslipidemia by a high-fat diet regime. Female Hartley guinea pigs were fed either a control (low-fat diet and sufficient vitC) (N = 8) or a high-fat diet with either sufficient (N = 8) or deficient (N = 10) vitC for 32 weeks. Guinea pigs subjected to the high-fat diet developed significant atherosclerotic plaques in their coronary arteries, with no quantitative effect of vitC deficiency. In isolated coronary arteries, vasomotor responses to potassium, carbachol, nitric oxide, or bradykinin were studied in a wire myograph. Carbachol, bradykinin, and nitric oxide mediated relaxation in the coronary arteries of the control group. While vasorelaxation to carbachol and nitric oxide was preserved in the two high-fat diet groups, bradykinin-induced vasorelaxation was abolished. Interestingly, bradykinin induced a significant contraction in coronary arteries from vitC-deficient guinea pigs (p &lt; 0.05). The bradykinin-induced contraction was unaffected by L-NAME but significantly inhibited by both indomethacin and vitC, suggesting that, during vitC deficiency, increased release of arachidonic acid metabolites and vascular oxidative stress are involved in the constrictor effects mediated by bradykinin. In conclusion, the present study shows supporting evidence that poor vitC status negatively affects coronary artery function.

Contemporary and future invasive coronary vasomotor function testing and treatment in patients with ischaemia with no obstructive coronary arteries.

In the current review, we emphasize the importance of diagnostics and therapy in patients with ischaemia with no obstructive coronary arteries (INOCA). The importance of the diagnostic coronary function test (CFT) procedure is described, including future components including angiography-derived physiology and invasive continuous thermodilution. Furthermore, the main components of treatment are discussed. Future directions include the national registration ensuring a high quality of INOCA care, besides a potential source to improve our understanding of pathophysiology in the various phenotypes of coronary vascular dysfunction, the diagnostic CFT procedure, and treatment.

Epicardial atherosclerosis and coronary tortuosity in patients with acetylcholine-induced coronary spasm.

Angina pectoris in the absence of relevant epicardial stenoses is frequently caused by coronary spasm. This mechanism of angina is common yet underdiagnosed in daily clinical practice. The pathophysiology of coronary spasm is complex, multifactorial, and not completely understood. The purpose of this study was to analyze the relationship between macroscopic coronary morphologies and coronary spasm. Epicardial atherosclerosis, coronary vessel tortuosity, coronary aneurysms, and myocardial bridges were analyzed angiographically in 610 patients and a potential association with the result of an intracoronary acetylcholine (ACh) provocation test was investigated. The comparison showed that angiographic morphologic variations in the coronary arteries are related to the occurrence of coronary spasm. We observed a strong association between the presence of epicardial atherosclerosis and epicardial spasm [87 patients of 179 with epicardial spasm had epicardial atherosclerosis (49%) vs. 45 patients of 172 with microvascular spasm (26%) vs. 89 patients of 259 with negative/inconclusive ACh test (36%); P < 0.005]. Moreover, we found a higher frequency of coronary tortuosity in patients with microvascular spasm [99 patients of 172 with microvascular spasm had at least moderate coronary tortuosity (58%) vs. 76 patients of 179 with epicardial spasm (43%) vs. 126 patients of 259 with negative/inconclusive ACh test (49%); P = 0.017]. Multivariable analysis revealed epicardial atherosclerosis (<50% stenosis) on coronary angiography as a predictor for epicardial spasm (OR, 2.096; 95% CI, 1.467-2.995; P < 0.0005). Female sex (OR, 5.469; 95% CI, 3.433-8.713; P < 0.0005), and exertional angina (OR, 2.411; 95% CI, 1.597-3.639; P < 0.0005) were predictors of microvascular spasm in multivariable analysis. In angina patients with no obstructive coronary artery disease, epicardial atherosclerosis is associated with ACh-induced epicardial coronary spasm. Moreover, coronary microvascular spasm is more prevalent in female patients and those with exertional angina. Our results provide insights into the relationship between coronary morphology and coronary vasomotor function.

Coronary tortuosity in patients with acetylcholine-induced coronary microvascular spasm

Abstract Background Angina pectoris in the absence of relevant epicardial stenoses (ANOCA) is frequently caused by coronary microvascular spasm. It has been speculated that the morphology of epicardial coronary arteries is associated with microvascular spasm. One hypothesis is that the vasoconstriction of microvessels leads to intraluminal pressure increase in the vascular segments proximal to the spasm, which may shift the balance of vessel forces toward vessel elongation resulting in coronary tortuosity. Purpose We assessed the relationship between epicardial coronary tortuosity and coronary spasm to elucidate a potential relationship between structural and functional coronary abnormalities. Methods 610 patients (39% male, mean age 61 years) with stable angina yet unobstructed coronary arteries (&amp;lt;50% stenosis) were included in this study. All patients underwent invasive diagnostic coronary angiography followed by intracoronary acetylcholine (ACh) testing according to a standardized protocol. The ACh test was considered “positive” in the presence of (a) angina, ischemic ECG shifts during the test and ≥90% coronary diameter reduction (“epicardial spasm”) or (b) all above without epicardial spasm (“microvascular spasm”). Assessment of coronary tortuosity was performed using left and right coronary images in multiple projections in a blinded fashion. The number and angles of the coronary curves in late diastole determined the severity of coronary tortuosity previously defined by Eleid. Patients were divided into those with at least moderate tortuosity versus those with no or mild tortuosity. Results ACh-testing revealed epicardial spasm in 179 (29%) and microvascular spasm in 172 (28%) patients. The ACh-test was negative/inconclusive in the remaining 259 patients (43%). There were 298 patients (49%) with at least moderate coronary tortuosity. The remaining 312 patients had no or mild coronary tortuosity (51%). Patients with at least moderate tortuosity were more likely to have microvascular spasm (99 patients of 172 with microvascular spasm had at least moderate coronary tortuosity (58%) vs. 76 patients of 179 with epicardial spasm (43%) vs. 126 patients of 259 with negative/inconclusive ACh test (49%), p=0.017). Analysis of coronary tortuosity in patients with positive ACh-test showed that patients with at least moderate coronary tortuosity (n=175) had significantly more microvascular spasm (57%) than epicardial spasm (43%) (p=0.005). We also found that at least moderate coronary tortuosity was significantly more often found in patients with hypertension compared to patients without hypertension (230/438 vs. 71/172, p=0.015). Conclusions In this large cohort of ANOCA patients coronary tortuosity was associated with hypertension and microvascular spasm. Our results provide interesting insights into the relationship of coronary morphology and vasomotor function. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Berthold-Leibinger-Foundation, Ditzingen, Germany

Reference values for intracoronary Doppler flow velocity-derived hyperaemic microvascular resistance index

BackgroundInvasive assessments of microvascular function are rapidly becoming an integral part of physiological assessment in chronic coronary syndromes. ObjectiveWe aimed to establish a reference range for Doppler flow velocity-derived hyperaemic microvascular resistance index (HMR) in a cohort of angina with no significant epicardial coronary obstruction (ANOCA) patients with no structural pathophysiological alterations in the coronary circulation. MethodsThe reference population consisted of ANOCA patients undergoing invasive coronary vasomotor function assessment who had a coronary flow reserve (CFR) >2.5, and had either (1) tested negatively for spasm provocation (n = 12) or (2) tested positively with only angina at rest (n = 29). A reference range for HMR was established using a non-parametric method and correlations with clinical characteristics were determined using a spearman rank correlation analysis. ResultsIn 41 patients median HMR amounted to 1.6 mmHg/cm/s [Q1, Q3: 1.3, 2.2 mmHg/cm/s]. The reference range for HMR that is applicable to 95% of the population was 0.8 mmHg/cm/s (90% CI: 0.8–1.0 mmHg/cm/s) to 2.7 mmHg/cm/s (90% CI: 2.6–2.7 mmHg/cm/s). No significant correlations were found between HMR and clinical characteristics. ConclusionIn this reference population undergoing invasive coronary vasomotor function testing, the 90% confidence interval of the HMR upper limit of normal ranges from 2.6 to 2.7 mmHg/cm/s. A > 2.5 mmHg/cm/s HMR threshold can be used to identify abnormal microvascular resistance in daily clinical practice.

The Conundrum of Coronary Microvascular Dysfunction: A Case Report

Background: Women with signs and symptoms of myocardial ischemia often have no obstructive coronary artery disease by invasive coronary angiography compared to men. Coronary microvascular dysfunction (CMD) is thought to be a key contributory mechanism for myocardial ischemia in women with chest pain and no obstructive CAD. The CMD diagnosis is challenging, and the disease management has so far been empirical because of its multifactorial pathophysiology. Case Illustration: A 60-year-old woman with a history of hypertension and diabetes came to undergo elective diagnostic coronary angiography (DCA) related to complaints of chest pain and tightness that are often felt by patients. ECG examination shows an old myocardial anteroseptal and inferior infarction. Echocardiography examination showed left ventricular dysfunction (LVEF 26%) and right ventricular dysfunction (TAPSE 1.4 cm). From the DCA examination obtained, non-significant stenosis is 30% in mid LAD, whereas RCA, LMCA, and LCx show normal results. The patient is then discharged with optimal medical therapy advice. Discussion: Structural and functional disorders that affect the entire coronary circulation, including microcirculation, are the cause of coronary artery disease symptoms. The subset of disorders that affect the coronary microcirculation itself is called coronary microvascular dysfunction (CMD). Cardinal manifestations of CMD include angina pectoris, dyspnea on exertion, and even heart failure. Patients generally experience a combination of these symptoms. A coronary vasomotor function analysis, both non-invasive and invasive approaches, is needed to diagnose CMD. Conclusion: This case highlights the clinical importance and challenges of diagnosing CMD. In women with signs and symptoms of myocardial ischemia and no obstructive CAD, CMD may be a mechanism leading to symptoms. Therefore, it is important to identify and diagnose in the appropriate clinical setting, as CMD is associated with an increased risk of adverse cardiovascular events.

Principles and pitfalls in coronary vasomotor function testing.

Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking. In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT. For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique). This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.

Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport.

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality, for which effective treatments are lacking. Allicin has been reported to exert therapeutic effects on AMI, but the underlying mechanisms of its action have not been fully elucidated. To investigate this, a rat model of AMI was generated by ligating the left anterior descending branch of the coronary artery. DL-propargylglycine (PAG), a specific hydrogen sulfide (H2S) synthetase inhibitor, was used to examine the effects of allicin on H2S production. Isolated coronary arteries and cardiomyocytes were assessed for vascular reactivity and cellular Ca2+ transport using a multiwire myography system and a cell-contraction-ion detection system, respectively. Allicin administration improved cardiac function and myocardial pathology, reduced myocardial enzyme levels, and increased H2S and H2S synthetase levels. Allicin administration resulted in concentration-dependent effects on coronary artery dilation, which were mediated by receptor-dependent Ca2+ channels, ATP-sensitive K+ channels, and sarcoplasmic reticulum (SR) Ca2+ release induced by the ryanodine receptor. Allicin administration improved Ca2+ homeostasis in cardiomyocytes by increasing cardiomyocyte contraction, Ca2+ transient amplitude, myofilament sensitivity, and SR Ca2+ content. Allicin also enhanced Ca2+ uptake via SR Ca2+-ATPase and Ca2+ removal via the Na+/Ca2+ exchanger, and it reduced SR Ca2+ leakage. Notably, the protective effects of allicin were partially attenuated by blockade of H2S production with PAG. Our findings provide novel evidence that allicin-induced production of H2S mediates coronary artery dilation and regulation of Ca2+ homeostasis in AMI. Our study presents a novel mechanistic insight into the anti-AMI effects of allicin and highlights the therapeutic potential of this compound.

СТЕНОКАРДИЯ БЕЗ ОБСТРУКТИВНОГО ПОРАЖЕНИЯ КОРОНАРНЫХ АРТЕРИЙ (Часть 2). МЕТОДЫ ДИАГНОСТИКИ В КЛИНИЧЕСКОЙ ПРАКТИКЕ

Coronary vasomotor disorders are a common cause of angina pectoris without obstructive lesion of the coronary arteries (CA). Over the past decade, various non-invasive and invasive diagnostic methods have made it possible to comprehensively assess coronary vasomotor function and determine the endotypes of epicardial and microvascular dysfunction, which is important for stratification of cardiovascular risk and individualization of patient treatment. The basis for the diagnosis of the complex interaction of vasodilation and vasoconstriction of various parts of the coronary bed is a comprehensive intracoronary functional testing, which is recommended if the angina symptoms are persisting against the background of angiographically unchanged or moderately stenosed, blood flow non-limiting coronary arteries. The established parameters characterizing adequate vasodilation are coronary blood flow reserve and microvascular resistance. Increased vasoconstriction potential is diagnosed by intracoronary provocation test with acetylcholine, which allows verification of epicardial and/or microvascular vasospasm. The article discusses standardized criteria, non-invasive imaging methods and modern invasive examination algorithms used in the diagnosis of microvascular and vasospastic angina.

Coronary vasomotor dysfunction in cancer survivors treated with thoracic irradiation

BackgroundWe sought to test the hypothesis that thoracic radiation therapy (RT) is associated with impaired myocardial flow reserve (MFR), a measure of coronary vasomotor dysfunction. MethodsWe retrospectively studied thirty-five consecutive patients (71% female, mean ± standard deviation (SD) age: 66 ± 11 years) referred clinically for positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging at a median (interquartile range, IQR) interval of 4.3 (2.1, 9.7) years following RT for a variety of malignancies. Radiation dose-volume histograms were generated for the heart and coronary arteries for each patient. ResultsThe median (IQR) of mean cardiac radiation doses was 12.0 (1.2, 24.2) Gray. There were significant inverse correlations between mean radiation dose and global MFR (MFRGlobal) and MFR in the left anterior descending artery territory (MFRLAD): Pearson’s correlation coefficient = − .37 (P = .03) and − .38 (P = .03), respectively. For every one Gray increase in mean cardiac radiation dose, there was a mean ± standard error decrease of .02 ± .01 in MFRGlobal (P = .04) and MFRLAD (P = .03) after adjustment. ConclusionsIn patients with a history of RT clinically referred for cardiac stress PET, we found an inverse correlation between mean cardiac radiation dose and coronary vasomotor function.

Abstract 12340: Early Restoration of Coronary Vasomotor Function Following Drug-Coated Balloon Only Angioplasty of de novo Lesions

Introduction: We evaluated whether drug-coated balloon (DCB)-treated de novo lesions are prone to vasospasm and how these segments respond to ergonovine and nitrate in comparison with angiographically normal segments and other untreated segments showing prominent vasoreactivity. Hypothesis: DCB angioplasty is an emerging treatment approach for coronary artery disease. Evidences in balloon angioplasty era, however, repeatedly reported the presence of abnormal vasomotor function at balloon-injured segment, leading to fatal spasm. Methods: 68 DCB angioplasty recipients underwent 6-months follow-up coronary angiography. Vasomotor function was assessed using intracoronary injection of incremental dose of ergonovine, followed by nitrate. Percent change of mean lumen diameter was assessed by quantitative coronary angiography at three different sites: DCB-treated segment vs. angiographically normal segment ( control ) vs. normal or mildly diseased segment (diameter stenosis &lt; 30%) showing prominent vasomotor response ( other diseased segment ). Results: All patients were event-free during 6-month follow-up. A total of 87 DCB-treated lesions were analyzed. Significant ergonovine-induced vasospasm developed in 8 patients; however, none of them showed focal spasm involving DCB-treated lesion only. There was no significant difference in mean lumen diameter after ergonovine provocation between DCB-treated lesions vs. angiographically normal segments. However, vasoconstrictor response was greater in other diseased segments than in DCB-treated lesions. After nitrate injection, all segments dilated significantly. Vasoreactivity, defined as combined constrictor and dilator response, was comparable between DCB-treated lesions and controls (p&gt;0.05); while significant difference was found against other diseased segment (p&lt;0.005), implicating the restoration of vasomotor function after DCB angioplasty. Conclusions: Lesion treated by DCB did not harbor increased risk for clinically or angiographically significant vasospasm and showed vasomotor function similar to angiographically normal segments. These findings support feasibility and safety of DCB-only strategy for the treatment of de novo coronary artery disease.

Simultaneous intracoronary testing for endothelial dysfunction and coronary vasospasm in patient with angina and non-obstructive coronary artery disease

Abstract Introduction Currently, two different theories exist on testing for coronary functional disorders in patients with angina and no obstructive coronary artery disease (ANOCA) where either invasive testing for endothelial function or coronary spasm provocation is performed. In this study we aim to assess the concomitant occurrence of both conditions in a cohort of patients with ANOCA undergoing both endothelial function testing and spasm provocation. Methods In this retrospective study, we included 114 patients that have undergone invasive coronary vasomotor function testing for coronary endothelial function and coronary artery spasm provocation. Endothelial dysfunction was defined as a &amp;lt;50% increase in coronary blood flow and/or epicardial coronary diameter reduction compared to baseline in reaction coronary acetylcholine concentrations up to 10–6 mol/L. Coronary artery spasm (CAS), defined as VSA and/or MVA due to microvascular spasm, was defined according to the COVADIS criteria in reaction to coronary acetylcholine concentration up to 10–5 mol/L. Results Among the 114 patients, 90 (78%) could be diagnosed with endothelial dysfunction and 71 (62%) with CAS. In most patients, 60 (54%), endothelial dysfunction and CAS can be diagnosed concurrently, whereas only 30 had endothelial dysfunction without CAS and 11 patients had CAS with a normal endothelial function. Conclusion In this cohort of ANOCA patients undergoing testing for coronary endothelial function and spasm provocation a large overlap of concurrent endothelial dysfunction and spasm provocation was found. These findings suggest a role for simultaneous endothelial function testing and spasm provocation in coronary vasomotor function protocols in order to adequately identify endotypes of ANOCA. Funding Acknowledgement Type of funding sources: None.