Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

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.

Impact of vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.

Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.

Prognostic Nutritional Index is Associated with the Degree of Coronary Collateral Circulation in Stable Angina Patients with Chronic Total Occlusion. / O Índice Nutricional Prognóstico está Associado ao Grau de Circulação Colateral Coronariana em Pacientes com Angina Estável e Oclusão Total Crônica.

BACKGROUND: Coronary collateral circulation (CCC) can effectively improve myocardial blood supply to the area of CTO (chronic total coronary occlusion) and can, thus, improve the prognosis of patients with stable coronary syndrome (SCS). The degree of inflammation and some inflammation markers were associated with the development of collaterals. OBJECTIVE: To investigate whether prognostic nutritional index (PNI) has an association with the development of CCC in patients with SCS. METHODS: A total of 400 SCS patients with the presence of CTO in at least one major epicardial coronary artery were included in this study. The patients were divided into two groups according to the Rentrop score. Scores of 0 to 1 were considered poor developed CCC, and scores of 2 to 3 were accepted as good developed CCC. Statistical significance was set as a p-value < 0.05 for all analyses. RESULTS: The mean age of the study cohort was 63±10 years; 273 (68.3%) were males. The poor-developed CCC group had a significantly lower PNI level compared with the good-developed CCC group (38.29±5.58 vs 41.23±3.85, p< 0.001). In the multivariate analysis, the PNI (odds ratio 0.870; 95% confidence interval 0.822-0.922; p< 0.001) was an independent predictor of poorly developed CCC. CONCLUSION: The PNI can be used as one of the independent predictors of CCC formation. It was positively associated with the development of coronary collaterals in SCS patients with CTO.

FUNDAMENTO: A circulação colateral coronária (CCC) pode efetivamente melhorar o suprimento sanguíneo miocárdico para a área de OCT (oclusão coronariana total crônica) e pode, assim, melhorar o prognóstico de pacientes com síndrome coronariana estável (SCE). O grau de inflamação e alguns marcadores de inflamação foram associados ao desenvolvimento de colaterais. OBJETIVO: Investigar se o índice nutricional prognóstico (INP) tem associação com o desenvolvimento de CCC em pacientes com SCE. MÉTODOS: Um total de 400 pacientes com SCE com presença de OTC em pelo menos uma importante artéria coronária epicárdica foi incluído neste estudo. Os pacientes foram divididos em dois grupos de acordo com o escore Rentrop. Escores de 0 a 1 foram considerados CCC pouco desenvolvidas e escores de 2 a 3 foram aceitos como CCC bem desenvolvidas. A significância estatística foi definida como um valor p < 0,05 para todas as análises. RESULTADOS: A média de idade da coorte do estudo foi de 63±10 anos; 273 (68,3%) eram do sexo masculino. O grupo CCC pouco desenvolvido apresentou um nível de INP significativamente mais baixo em comparação com o grupo CCC bem desenvolvido (38,29±5,58 vs 41,23±3,85, p<0,001). Na análise multivariada, o INP (odds ratio 0,870; intervalo de confiança de 95% 0,822-0,922; p<0,001) foi um preditor independente de CCC pouco desenvolvida. CONCLUSÃO: O INP pode ser utilizado como um dos preditores independentes da formação do CCC. Foi positivamente associado ao desenvolvimento de colaterais coronárias em pacientes com SCE com OTC.

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.

The MAPH Score Predicts Coronary Slow Flow. A Retrospective Case-Controlled Study.

AIM: The MAPH score is a new score that combines mean platelet volume (MPV), hematocrit, and total protein, which are markers of whole blood viscosity (WBV). We aimed to investigate the relationship between the MAPH score and the coronary slow flow phenomenon (CSF). MATERIAL AND METHODS: A total of 201 patients were included in the study. 105 had CSF and 96 had normal coronary flow (NCF). Coronary flow was measured by the Thrombolysis in Myocardial Infarction frame count (TFC) method. The patients' MPV, age, hematocrit, and total protein were recorded. High (HSR) and low shear rates (LSR) were calculated, based on total protein and hematocrit values. Cut-off values for CSF were determined using the Youden's index, and the score was determined as 0 or 1 according to the cut-off values. The sum of these scores was the MAPH score. RESULTS: The mean age of the patients included in the study was 51.1±7.9 (n=201, 54.2 % male). Hyperlipidemia, DM, and HT rates of both groups were similar, but the mean age of the CSF group was higher (p=0.773; p=0.549; p=0.848; p <0.001, respectively). Total protein, MPV, hematocrit, HSR and LSR were higher in the CSF group (p< 0.001, for all values). Comparative receiver operating characteristic (ROC) curve analysis showed that the performance of the MAPH score in predicting CSF is better than the performance of these parameters separately. CONCLUSION: A new score, the MAPH score, may be used to identify the presence of CSF.

Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6 h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8 years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (ß - 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

OBJECTIVE: Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15O-water. METHODS: Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500 MBq of 15O-water was infused slowly for 2 min, and the dynamic data were scanned for 6 min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated. RESULTS: In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET. CONCLUSIONS: The ECG-gated dynamic 15O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion.

Haemodynamics of stent-mounted neural interfaces in tapered and deformed blood vessels.

The endovascular neural interface provides an appealing minimally invasive alternative to invasive brain electrodes for recording and stimulation. However, stents placed in blood vessels have long been known to affect blood flow (haemodynamics) and lead to neointimal growth within the blood vessel. Both the stent elements (struts and electrodes) and blood vessel wall geometries can affect the mechanical environment on the blood vessel wall, which could lead to unfavourable vascular remodelling after stent placement. With increasing applications of stents and stent-like neural interfaces in venous blood vessels in the brain, it is necessary to understand how stents affect blood flow and tissue growth in veins. We explored the haemodynamics of a stent-mounted neural interface in a blood vessel model. Results indicated that blood vessel deformation and tapering caused a substantial change to the lumen geometry and the haemodynamics. The neointimal proliferation was evaluated in sheep implanted with an endovascular neural interface. Analysis showed a negative correlation with the mean Wall Shear Stress pattern. The results presented here indicate that the optimal stent oversizing ratio must be considered to minimise the haemodynamic impact of stenting.

Research Progress and Clinical Value of Subendocardial Viability Ratio.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with ischemic heart disease being a major contributor, either through coronary atherosclerotic plaque-related major vascular disease or coronary microvascular dysfunction. Obstruction of coronary blood flow impairs myocardial perfusion, which may lead to acute myocardial infarction in severe cases. The subendocardial viability ratio, also known as the Buckberg index, is a valuable tool for evaluation of myocardial perfusion because it reflects the balance between myocardial oxygen supply and oxygen demand. The subendocardial viability ratio can effectively evaluate the function of the coronary microcirculation and is associated with arterial stiffness. This ratio also has potential value in predicting adverse cardiovascular events and mortality in various populations. Moreover, the subendocardial viability ratio has demonstrated clinical significance in a range of diseases, including hypertension, aortic stenosis, peripheral arterial disease, chronic kidney disease, diabetes, and rheumatoid arthritis. This review summarizes the applications of the subendocardial viability ratio, its particular progress in the relevant research, and its clinical significance in cardiovascular diseases.

Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects.

BACKGROUND: Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease. METHODS: A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity-score matching; primary outcomes were fluoroscopy time and total contrast use. RESULTS: The participants' mean age was 64.1 ± 12.6 years. CMD-assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity-matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37). CONCLUSION: Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

BACKGROUND: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms. OBJECTIVES: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA). METHODS: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes. RESULTS: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors. CONCLUSIONS: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA.