Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. METHODS: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive ß, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of ß at peak stress to ß at rest, averaged across LV myocardial regions of interest. RESULTS: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). CONCLUSIONS: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Arterial Input Function (AIF) Correction Using AIF Plus Tissue Inputs with a Bi-LSTM Network.

Background: The arterial input function (AIF) is vital for myocardial blood flow quantification in cardiac MRI to indicate the input time-concentration curve of a contrast agent. Inaccurate AIFs can significantly affect perfusion quantification. Purpose: When only saturated and biased AIFs are measured, this work investigates multiple ways of leveraging tissue curve information, including using AIF + tissue curves as inputs and optimizing the loss function for deep neural network training. Methods: Simulated data were generated using a 12-parameter AIF mathematical model for the AIF. Tissue curves were created from true AIFs combined with compartment-model parameters from a random distribution. Using Bloch simulations, a dictionary was constructed for a saturation-recovery 3D radial stack-of-stars sequence, accounting for deviations such as flip angle, T2* effects, and residual longitudinal magnetization after the saturation. A preliminary simulation study established the optimal tissue curve number using a bidirectional long short-term memory (Bi-LSTM) network with just AIF loss. Further optimization of the loss function involves comparing just AIF loss, AIF with compartment-model-based parameter loss, and AIF with compartment-model tissue loss. The optimized network was examined with both simulation and hybrid data, which included in vivo 3D stack-of-star datasets for testing. The AIF peak value accuracy and ktrans results were assessed. Results: Increasing the number of tissue curves can be beneficial when added tissue curves can provide extra information. Using just the AIF loss outperforms the other two proposed losses, including adding either a compartment-model-based tissue loss or a compartment-model parameter loss to the AIF loss. With the simulated data, the Bi-LSTM network reduced the AIF peak error from -23.6 ± 24.4% of the AIF using the dictionary method to 0.2 ± 7.2% (AIF input only) and 0.3 ± 2.5% (AIF + ten tissue curve inputs) of the network AIF. The corresponding ktrans error was reduced from -13.5 ± 8.8% to -0.6 ± 6.6% and 0.3 ± 2.1%. With the hybrid data (simulated data for training; in vivo data for testing), the AIF peak error was 15.0 ± 5.3% and the corresponding ktrans error was 20.7 ± 11.6% for the AIF using the dictionary method. The hybrid data revealed that using the AIF + tissue inputs reduced errors, with peak error (1.3 ± 11.1%) and ktrans error (-2.4 ± 6.7%). Conclusions: Integrating tissue curves with AIF curves into network inputs improves the precision of AI-driven AIF corrections. This result was seen both with simulated data and with applying the network trained only on simulated data to a limited in vivo test dataset.

Analysis of correlative factors of female coronary slow-flow phenomenon: A retrospective study.

The coronary slow-flow phenomenon (CSFP) is a manifestation of coronary artery disease wherein coronary angiography reveals no apparent stenosis; however, there is a delay in blood flow perfusion. Given its increased occurrence in male patients, with the majority of subjects in previous studies being male, this study aimed to explore whether distinct risk factors are present in female patients with CSFP. This single-center retrospective study focused on female patients diagnosed with CSFP by using coronary angiography. Eligible patients meeting the predefined inclusion and exclusion criteria were divided into the study group (presenting with CSFP) and control group (displaying normal epicardial coronary arteries). Comparative analyses of clinical and diagnostic data were performed. Ninety-two patients with CSFP and an equal number of controls were enrolled in this study. Patients with CSFP exhibited a higher prevalence of smokers (P = .017) and a heightened incidence of diabetes mellitus (DM) (P = .007). Significantly elevated levels of total cholesterol (TC) (P = .034) and free fatty acids (FFA) (P = .016) were observed in the CSFP group compared to those in the control group. Additionally, patients with CSFP displayed lower levels of apolipoprotein E (ApoE) (P = .092), free thyroxine (FT4) (P = .001), and total thyroxine (TT4) (P = .025). Logistic regression analysis indicated that smoking (P = .019), FFA (P < .001), ApoE (P = .015), and FT4 (P < .001) were independent risk factors for CSFP, accounting for confounding factors. Additionally, the area under the ROC curve (AUC) of the combined effect of smoking, ApoE, FT4, and FFA on CSFP was 0.793 (95% CI: 0.729-0.857, P < .01). In addition to the established risk factors for smoking, diabetes, and hyperlipidemia, female patients with CSFP exhibited significant differences in apoE, FFA, FT4, and TT4 levels compared to the control group. Smoking, FFA, and FT4 levels emerged as independent risk factors for CSFP.

Coronary microvascular dysfunction and atrial reservoir function.

BACKGROUND: Coronary 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. METHODS: Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively. RESULTS: Forty-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. CONCLUSION: Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

Epicardial fat volume is associated with primary coronary slow-flow phenomenon in patients with severe aortic stenosis undergoing transcatheter valve implantation.

BACKGROUND: Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF. METHODS: Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms. RESULTS: Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107-180] vs. 113 ml [IQR 89-147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002-1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004-1.026]; p = 0.009). CONCLUSION: Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.

Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO. METHODS: Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM). RESULTS: A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM. CONCLUSION: Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.

The triglyceride-glucose index as a predictive marker for coronary slow flow phenomenon.

OBJECTIVE: The triglyceride-glucose index (TyG) has been proposed as a marker of insulin resistance (IR) and has shown associations with cardiovascular diseases. This study aimed to investigate the relationship between the TyG and the coronary slow flow phenomenon (CSFP) and explore the index's potential as a predictor of this condition. PATIENTS AND METHODS: A total of 187 patients who underwent coronary angiography were included; of these, 91 patients were diagnosed with CSFP, and 96 patients with normal coronary flow served as a control group. The TyG was calculated using fasting triglyceride and glucose levels. RESULTS: The results showed that the TyG was significantly higher in the CSFP group compared with the control group (p < 0.001). Additionally, the TyG exhibited a moderate positive correlation with the thrombolysis-in-myocardial-infarction frame count in coronary arteries (p < 0.001). A multivariate logistic regression analysis revealed that the TyG, along with gender, ejection fraction, and uric acid, remained significant predictors of CSFP (p < 0.05). CONCLUSIONS: This study's findings suggest that the TyG may serve as a useful marker for identifying individuals at risk of CSFP and provide insights into the potential role of IR in its pathophysiology.

Computed tomography myocardial perfusion imaging to detect myocardial ischemia in patients with anxiety and obstructive coronary heart disease post-exposure to mental stressors.

This study aims to measure myocardial blood flow (MBF) using dynamic CT- myocardial perfusion imaging (CT-MPI) combined with mental stressors in patients with obstructive coronary artery disease (OCAD) and in patients with anxiety and no obstructive coronary artery disease (ANOCAD). A total of 30 patients with OCAD with 30 patients with ANOCAD were included in this analysis. Using the 17-segment model, the rest and stress phase MBF of major coronary arteries in participants were recorded respectively. Compared with ANOCAD patients, OCAD patients were more likely to have localized reduction of MBF (p < 0.05). For patients with ANOCAD, both global MBF and MBF of the main coronary arteries in the stress phase were lower than those in the rest phase (all p < 0.05), but there was no significant difference in MBF among the main coronary arteries in the rest or stress phase (p = 0.25, p = 0.15). For patients with OCAD, the MBF of the target area was lower than that of the non-target area in both the rest and stress phase, and the MBF of the target area in the stress phase was lower than that in the rest phase (all p < 0.05). However, there was no significant difference in MBF between the rest or stress phase in the non-target area (p = 0.73). Under mental stress, the decrease in MBF in ANOCAD patients was diffuse, while the decrease in MBF in OCAD patients was localized. Dynamic CT-MPI combined with mental stressors can be used to detect MBF changes in anxiety patients.

MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

[Correlation between insulin resistance and coronary collateral circulation in patients with chronic total coronary occlusion].

OBJECTIVE: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism. METHODS: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis. RESULTS: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways. CONCLUSION: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

Retrograde chronic total occlusion percutaneous coronary intervention via ipsilateral collaterals.

BACKGROUND: There is limited data on retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) via ipsilateral epicardial collaterals (IEC). AIMS: To compare the clinical and angiographic characteristics, and outcomes of retrograde CTO PCI via IEC versus other collaterals in a large multicenter registry. METHODS: Observational cohort study from the Prospective Global registry for the study of Chronic Total Occlusion Intervention (PROGRESS-CTO). RESULTS: Of 4466 retrograde cases performed between 2012 and 2023, crossing through IEC was attempted in 191 (4.3%) cases with 50% wiring success. The most common target vessel in the IEC group was the left circumflex (50%), in comparison to other retrograde cases, where the right coronary artery was most common (70%). The Japanese CTO score was similar between the two groups (3.13 ± 1.23 vs. 3.06 ± 1.06, p = 0.456); however, the IEC group had a higher Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score (1.95 ± 1.02 vs. 1.27 ± 0.92, p < 0.0001). The most used IEC guidewire was the SUOH 03 (39%), and the most frequently used microcatheter was the Caravel (43%). Dual injection was less common in IEC cases (66% vs. 89%, p < 0.0001). Technical (76% vs. 79%, p = 0.317) and procedural success rates (74% vs. 79%, p = 0.281) were not different between the two groups. However, IEC cases had a higher procedural complications rate (25.8% vs. 16.4%, p = 0.0008), including perforations (17.3% vs. 9.0%, p = 0.0001), pericardiocentesis (3.1% vs. 1.2%, p = 0.018), and dissection/thrombus of the donor vessel (3.7% vs. 1.2%, p = 0.002). CONCLUSION: The use of IEC for retrograde CTO PCI was associated with similar technical and procedural success rates when compared with other retrograde cases, but higher incidence of periprocedural complications.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Interoceptive signals from the heart and coronary circulation in health and disease.

This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and coronary artery. A small proportion of cardiac receptors attached to thick myelinated vagal afferents are tonically active during the cardiac cycle. Dependent upon location, these mechanoreceptors detect fluctuations in atrial volume and coronary arterial perfusion. Atrial volume and coronary arterial signals contribute to beat-to-beat feedback control and physiological homeostasis. Most cardiac receptors are attached to thinly myelinated or nonmyelinated C fibres, many of which are unresponsive to the cardiac cycle. Of these, there are many chemically sensitive cardiac receptors which are activated during myocardial stress by locally released endogenous substances. In contrast, some tonically inactive receptors become activated by irregular ventricular wall mechanics or by distortion of the ischaemic myocardium. Furthermore, some are excited both by chemical mediators of ischaemia and wall abnormalities. Reflex responses arising from cardiac receptors attached to thinly myelinated or nonmyelinated are complex. Impulses that project centrally through vagal afferents elicit sympathoinhibition and hypotension, whereas impulses travelling in cardiac sympathetic afferents and spinal pathways elicit sympathoexcitation and hypertension. Two opposing cardiac reflexes may provide a mechanism for fine-tuning a composite haemodynamic response during myocardial stress. Sympathetic afferents provide the primary pathway for transmission of cardiac nociception to the central nervous system. However, activation of sympathetic afferents may increase susceptibility to life-threatening arrhythmias. Notably, the cardiac sympathetic afferent reflex predominates in pathophysiological states including hypertension and heart failure.