Microvascular dysfunction in patients with heart failure with preserved ejection fraction: A meta-analysis.

BACKGROUND: Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification. MATERIALS AND METHODS: On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as "Heart failure with preserved ejection fraction," "HFpEF," "microvascular dysfunction," and "MVD." The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF. RESULTS: Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%-76.2%), with a substantial degree of heterogeneity (I2 = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them. CONCLUSIONS: This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.

PET-MRI of Coronary Artery Disease.

Simultaneous positron emission tomography and magnetic resonance imaging (PET-MRI) combines the anatomical detail and tissue characterization of MRI with the functional information from PET. Within the coronary arteries, this hybrid technique can be used to identify biological activity combined with anatomically high-risk plaque features to better understand the processes underlying coronary atherosclerosis. Furthermore, the downstream effects of coronary artery disease on the myocardium can be characterized by providing information on myocardial perfusion, viability, and function. This review will describe the current capabilities of PET-MRI in coronary artery disease and discuss the limitations and future directions of this emerging technique. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Stable patients with suspected myocardial ischemia: comparison of machine-learning computed tomography-based fractional flow reserve and stress perfusion cardiovascular magnetic resonance imaging to detect myocardial ischemia.

BACKGROUND: Machine-Learning Computed Tomography-Based Fractional Flow Reserve (CT-FFRML) is a novel tool for the assessment of hemodynamic relevance of coronary artery stenoses. We examined the diagnostic performance of CT-FFRML compared to stress perfusion cardiovascular magnetic resonance (CMR) and tested if there is an additional value of CT-FFRML over coronary computed tomography angiography (cCTA). METHODS: Our retrospective analysis included 269 vessels in 141 patients (mean age 67 ± 9 years, 78% males) who underwent clinically indicated cCTA and subsequent stress perfusion CMR within a period of 2 months. CT-FFRML values were calculated from standard cCTA. RESULTS: CT-FFRML revealed no hemodynamic significance in 79% of the patients having ≥ 50% stenosis in cCTA. Chi2 values for the statistical relationship between CT-FFRML and stress perfusion CMR was significant (p < 0.0001). CT-FFRML and cCTA (≥ 70% stenosis) provided a per patient sensitivity of 88% (95%CI 64-99%) and 59% (95%CI 33-82%); specificity of 90% (95%CI 84-95%) and 85% (95%CI 78-91%); positive predictive value of 56% (95%CI 42-69%) and 36% (95%CI 24-50%); negative predictive value of 98% (95%CI 94-100%) and 94% (95%CI 90-96%); accuracy of 90% (95%CI 84-94%) and 82% (95%CI 75-88%) when compared to stress perfusion CMR. The accuracy of cCTA (≥ 50% stenosis) was 19% (95%CI 13-27%). The AUCs were 0.89 for CT-FFRML and 0.74 for cCTA (≥ 70% stenosis) and therefore significantly different (p < 0.05). CONCLUSION: CT-FFRML compared to stress perfusion CMR as the reference standard shows high diagnostic power in the identification of patients with hemodynamically significant coronary artery stenosis. This could support the role of cCTA as gatekeeper for further downstream testing and may reduce the number of patients undergoing unnecessary invasive workup.

Diagnostic performance of deep learning and computational fluid dynamics-based instantaneous wave-free ratio derived from computed tomography angiography.

BACKGROUND AND OBJECTIVES: Both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are widely used to evaluate ischemia-causing coronary lesions. A new method of CT-iFR, namely AccuiFRct, for calculating iFR based on deep learning and computational fluid dynamics (CFD) using coronary computed tomography angiography (CCTA) has been proposed. In this study, the diagnostic performance of AccuiFRct was thoroughly assessed using iFR as the reference standard. METHODS: Data of a total of 36 consecutive patients with 36 vessels from a single-center who underwent CCTA, invasive FFR, and iFR were retrospectively analyzed. The CT-derived iFR values were computed using a novel deep learning and CFD-based model. RESULTS: Mean values of FFR and iFR were 0.80 ± 0.10 and 0.91 ± 0.06, respectively. AccuiFRct was well correlated with FFR and iFR (correlation coefficients, 0.67 and 0.68, respectively). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of AccuiFRct ≤ 0.89 for predicting FFR ≤ 0.80 were 78%, 73%, 81%, 73%, and 81%, respectively. Those of AccuiFRct ≤ 0.89 for predicting iFR ≤ 0.89 were 81%, 73%, 86%, 79%, and 82%, respectively. AccuiFRct showed a similar discriminant function when FFR or iFR were used as reference standards. CONCLUSION: AccuiFRct could be a promising noninvasive tool for detection of ischemia-causing coronary stenosis, as well as facilitating in making reliable clinical decisions.

Impact of invasive aortic pulse pressure on coronary microvascular endothelial-independent dysfunction and on mortality in non-obstructive coronary artery disease.

BACKGROUND: Pulse pressure (PP), a raw index of arterial stiffness, is inversely related to coronary microvascular function, even among patients with non-obstructive coronary artery disease (CAD), as per non-invasive studies. We aimed to determine whether invasive aortic PP is associated with coronary microvascular endothelial dysfunction (CMED) and/or coronary microvascular endothelial independent dysfunction (CMEID) in patients with non-obstructed CAD. METHODS: We retrospectively analysed a cohort of 1894 patients (mean age, 51.2 years; 1261 (66.6%) women) who presented with chest pain and non-obstructive CAD (angiographic stenosis <50%); coronary vasoreactivity was assessed in the mid-left anterior descending artery. The patients were classified based on whether aortic PP was high (≥50 mm Hg). CMEID was defined as abnormal coronary flow reserve (<2.5) or hyperaemic myocardial resistance (>2.0 mm Hg/cm/s), CMED was defined as abnormal acetylcholine-induced per cent change of coronary blood flow (≤50%). RESULTS: Patients with high aortic PP had a higher rate of CMEID than those with low aortic PP (40.9 vs 25.2%, p<0.001). Conversely, aortic PP was not associated with CMED. On multivariate analysis, high aortic PP was associated with CMEID occurrence (OR 1.42, 95% CI 1.13 to 1.78; p=0.003). On follow-up (median, 150 months), all-cause death was more frequent among patients with vs without high aortic PP (20.1% vs 7.3%, log-rank p<0.001) and HR was 2.08 (95% CI 1.34 to 3.32, p=0.002) on multivariate cox regression analysis. Furthermore, among patients with low aortic PP, CMEID was an independent risk factor for all-cause mortality (HR 2.04, 95% CI 1.01 to 4.16, p=0.048). CONCLUSION: In patients with non-obstructive CAD, invasive aortic PP was significantly associated with CMEID, but not with CMED. High aortic PP was an independent predictor of all-cause mortality, but CMEID was an independent risk factor in patients with low aortic PP.

Preprocedural transthoracic Doppler echocardiography to identify stenosis associated with increased coronary flow after revascularisation.

The benefit of percutaneous coronary intervention (PCI) has been reported to be associated with functional stenosis severity defined by fractional flow reserve (FFR). This study aimed to investigate the predictive ability of preprocedural transthoracic Doppler echocardiography (TDE) for increased coronary flow. A total of 50 left anterior descending arteries (LAD) that underwent TDE examinations were analysed. Hyperaemic LAD diastolic peak velocity (hDPV) was used as a surrogate of volumetric coronary flow. The increase in coronary flow was evaluated by the metric of % hDPV-increase defined by 100× (post-PCI hDPV-pre-PCI hDPV)/pre-PCI hDPV. The two groups divided by the median value of % hDPV-increase were compared, and the determinants of a significant coronary flow increase defined as more than the median % hDPV-increase were explored. After PCI, FFR values improved in all cases. hDPV significantly increased from 53.0 to 76.0 mm/s (P < 0.01) and the median % hDPV-increase was 45%, while hDPV decreased in 10 patients. On multivariable analysis, pre-PCI FFR and hDPV were independent predictors of a significant coronary flow increase. Preprocedural TDE-derived hDPV provided significant improvement of identification of lesions that benefit from revascularisation with respect to significant coronary flow increase.

Severe coronary artery spasm during left atrial appendage closure plus catheter ablation for atrial fibrillation: case presentation.

BACKGROUND: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation (RFCA) as a hybrid procedure is commonly performed to treat atrial fibrillation (AF). Although this treatment carries a low risk of coronary artery spasm (CAS), and has never been observed in LAAC procedure, caution still needed to be taken. We presented a case of CAS that occurred in an AF patient during the hybrid procedure. CASE PRESENTATION: The patient was a 65-year-old man with paroxysmal AF who developed CAS during RFCA and LAAC. In this case, LAAC was performed ahead of RFCA. After atrial septal puncture, the occluder was advanced into left atrium through delivery sheath, and successfully deployed in the LAA. After verifying the assessment of "PASS" criteria, we decided to release the device. However, before releasing the occluder in LAAC, the patient's blood pressure (BP) fell to 70/45 mmHg with heart rate (HR) drop and ST-segment elevation in II, III, and aVF and reciprocal ST-segment depression in I and aVL. Isotonic sodium chloride load was administered. After 3 min, the BP and HR raised, and ST-segment returned to normal. The occluder was successfully released after the stable condition of the patient. Then, RFCA was sequentially performed. When isolating the right pulmonary veins, the patient's BP and HR fell again with ST-segment elevation in inferior leads. Spontaneous ventricular tachycardia and fibrillation developed rapidly and defibrillation was performed immediately with success. Coronary angiography revealed the obstruction of the right coronary artery which disappeared completely after intracoronary nitroglycerin injection (1 mg). Under systemic diltiazem infusion, the RFCA procedure was accomplished. After the procedure, the patient recovered without any neurologic deficit, and CAS has never recurred with isosorbide mononitrate treatment during follow-up. CONCLUSIONS: CAS is a rare complication associated with AF hybrid procedure. Attention should be paid to this rare but potentially life-threatening complication.

Effect of Calcification Based on Computer-Aided System on CT-Fractional Flow Reserve in Diagnosis of Coronary Artery Lesion.

This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group (FFR ≤ 0.8) and nonischemic group (FFR > 0.8). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group (P < 0.05). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference (P > 0.05). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group (P < 0.05). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups (P > 0.05). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.

A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers.

Patients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).

Normalized Subendocardial Myocardial Attenuation on Coronary Computed Tomography Angiography Predicts Postoperative Adverse Cardiovascular Events: Coronary CTA VISION Substudy.

BACKGROUND: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery. METHODS: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUBnormalized, and TRANSnormalized, respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction. RESULTS: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUBnormalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUBnormalized, patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANSnormalized, as a continuous variable, was also found to be a predictor of MACE (P=0.027). CONCLUSIONS: Our study demonstrates that SUBnormalized and TRANSnormalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Luteolin alleviates ischemia/reperfusion injury-induced no-reflow by regulating Wnt/ß-catenin signaling in rats.

The no-reflow phenomenon induced by ischemia-reperfusion (I/R) injury seriously limits the therapeutic value of coronary recanalization and leads to a poor prognosis. Previous studies have shown that luteolin (LUT) is a vasoprotective factor. However, whether LUT can be used to prevent the no-reflow phenomenon remains unknown. Positron emission tomography perfusion imaging, performed to detect the effects of LUT on the no-reflow phenomenon in vivo, revealed that LUT treatment was able to reduce the no-reflow area in rat I/R models. In vitro, LUT was shown to reduce the hypoxia-reoxygenation injury-induced endothelial permeability and apoptosis. The levels of malondialdehyde, reactive oxygen species and NADPH were also measured and the results indicated that LUT could inhibit the oxidative stress. Western blot analysis revealed that LUT protected endothelial cells from I/R injury by regulating the Wnt/ß-catenin pathway. Overall, we concluded that the use of LUT to minimize I/R induced microvascular damage is a feasible strategy to prevent the no-reflow phenomenon.

TLR4-Myd88 pathway upregulated caveolin-1 expression contributes to coronary artery spasm.

AIM: To study the role of toll-like receptors 4-myeloid differentiation factor 88 (TLR4-Myd88) dependent caveolin-1 (Cav-1) expression modulation in coronary artery spasm (CAS) and explore the underlying pathogenic mechanisms. METHODS AND RESULTS: Lipopolysaccharide (LPS) and acetylcholine (Ach) were used to develop the in vitro and in vivo models mimicking the physiological CAS microenvironment. LPS-induced upregulation of Cav-1 expression in mouse coronary and aorta endothelial cells was shown by western blot and immunofluorescence (IF) staining (p < 0.01). Caveolin-1-knockout (Cav-1-/-) mice had reduced aortic inflammation after LPS challenge, and fewer ST segment changes were observed through electrocardiogram (ECG) monitoring compared to wild type mice after LPS and ACh administration. In vitro, pretreating human umbilical vein endothelial cells (HUVECs) with siCav-1 to knock down Cav-1 expression reduced the endothelial inflammation following LPS challenge. SiCav-1 also partially reversed the attenuated Ca2+ concentration after LPS and ACh administration compared to the control group, which was evaluated by fluorescent molecular probing for Ca2+ alternation monitoring (p < 0.05). TLR4 and Myd88 downregulation by siRNA partially blocked the increased Cav-1 mRNA and protein expressions following LPS treatment, as well as partially reversed the decreased NO production evaluated by nitrate reductase method and the impaired Ca2+ concentration of endothelial cells induced by LPS and ACh. CONCLUSION: These findings suggested that Cav-1, which was upregulated by TLR4-Myd88, served as an important modulator of CAS microenvironment establishment in vivo and in vitro, making it a potential pharmacologic target for the treatment of vasospasm via reduced endothelial cell inflammation.

Predicting haemodynamic significance of coronary stenosis with radiomics-based pericoronary adipose tissue characteristics.

AIM: To investigate the diagnostic performance of the radiomics features of pericoronary adipose tissue (PCAT) in determining haemodynamically significant coronary artery stenosis as evaluated by fractional flow reserve (FFR). MATERIALS AND METHODS: A total of 92 patients with clinically suspected coronary artery disease who underwent coronary computed tomography (CT) angiography (CCTA), invasive coronary angiography (ICA), and FFR examination within 1 month were included retrospectively, and 121 lesions were randomly assigned to the training and testing set. Based on manual segmentation of PCAT, 1,116 radiomics features were computed. After radiomics robustness assessment and feature selection, radiomics models were established using the different machine-learning algorithms. The area under the receiver operating characteristic (ROC) curve (AUC) and net reclassification index (NRI) were analysed to compare the discrimination and reclassification abilities of radiomics models. RESULTS: Two radiomics features were selected after exclusions, and both were significantly higher in coronary arteries with FFR ≤0.8 than those with FFR >0.8. ROC analysis showed that the combination of CCTA and decision tree radiomics model achieved significantly higher diagnostic performance (AUC: 0.812) than CCTA alone (AUC: 0.599, p=0.015). Furthermore, the NRI of the combined model was 0.820 and 0.775 in the training and testing sets, respectively, suggesting the radiomics features of PCAT had were effective in classifying the haemodynamic significance of coronary stenosis. CONCLUSIONS: Adding PCAT radiomics features to CCTA enabled identification of haemodynamically significant coronary artery stenosis.

White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial.

BACKGROUND: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). METHODS: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). RESULTS: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. CONCLUSION: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

Relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious coronary artery anomalies.

BACKGROUND: Congenital coronary artery anomalies (CCAAs) have the potential for life-threatening complications, including malignant ventricular arrhythmias and sudden cardiac death (SCD). In this study, we aimed to evaluate the relationship between impaired repolarization parameters and poor cardiovascular clinical outcomes in patients with potentially serious CCAAs. METHODS: This retrospective study included 85 potentially serious CCAA patients (mean age: 54.7 ± 13.6 years; male:44) who were diagnosed with conventional and coronary computed tomography angiography (CCTA). All patients underwent transthoracic echocardiography and 12-lead surface electrocardiography. Cardiac events were defined as sustained ventricular tachycardia or fibrillation, syncope, cardiac arrest and SCD. RESULTS: The presence of interarterial course (IAC) was confirmed by CCTA in 37 (43.5%) patients. During a median follow-up time of 24 (18-50) months, a total of 11 (12.9%) patients experienced cardiac events. The presence of IAC was significantly more frequent and Tp-e interval, Tp-e/QTc ratio and frontal QRS/T angle (fQRSTa) were significantly greater in patients with poor clinical outcomes. Moreover, the presence of IAC, high Tp-e/QTc ratio and high fQRSTa were found to be independent predictors of poor clinical outcomes and decreased long-term cardiac event-free survival in these patients. A net reclassification index was +1.0 for the Tp-e/QTc ratio and +1.3 for fQRSTa which were confirmable for additional predictability of these repolarization abnormalities. CONCLUSION: Impaired repolarization parameters, including wider fQRSTa, prolonged Tp-e interval, and increased Tp-e/QTc ratio, and IAC may be associated with poor cardiovascular clinical outcomes in potentially serious CCAA patients.