Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

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.

Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

AIMS: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. METHODS AND RESULTS: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). CONCLUSION: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Coronary microcirculation in nonculprit vessel territory in reperfused acute myocardial infarction.

BACKGROUND: There is an ongoing debate on the extension of reperfusion-related microvascular damage (MVD) throughout the remote noninfarcted myocardial regions in patients with ST-elevation myocardial infarction (STEMI) that undergo primary percutaneous intervention (pPCI). The aim of this study was to elucidate the impact of reperfusion on remote microcirculatory territory by analyzing hemodynamic alterations in the nonculprit-vessel in relation to reperfusion. METHODS: A total of 20 patients with STEMI undergoing pPCI were included. Peri-reperfusion temporal changes in hemodynamic parameters were obtained in angiographically normal nonculprit vessels before and 1-h after reopening of the culprit vessel. Intracoronary pressure and flow velocity data were compared using pairwise analyses (before and 1-h after reperfusion). RESULTS: In the non-culprit vessel, compared to the pre-reperfusion state, mean resting average peak velocity (33.4 ± 9.4 to 25.0 ± 4.9 cm/s, P < 0.001) and mean hyperemic average peak velocity (53.5 ± 14.4 to 42.1 ± 10.66 cm/s, P = 0.001) significantly decreased; whereas baseline (3.2 ± 1.0 to 4.0 ± 1.0 mmHg.cm-1.s, P < 0.001) and hyperemic microvascular resistance (HMR) (1.9 ± 0.6 to 2.4 ± 0.7 mmHg.cm-1.s, P < 0.001) and mean zero flow pressure (Pzf) values (32.5 ± 6.9 to 37.6 ± 8.3 mmHg, P = 0.003) significantly increased 1-h after reperfusion. In particular, the magnitude of changes in HMR and Pzf values following reperfusion were more prominent in patients with larger infarct size and with higher extent of MVD in the culprit vessel territory. CONCLUSION: Reperfusion-related microvascular injury extends to involve remote myocardial territory in relation to the magnitude of the adjacent infarction and infarct-zone MVD. (GUARD Clinical TrialsNCT02732080).

A systematic review and meta-analysis of the effect of high-intensity statin on coronary microvascular dysfunction.

OBJECTIVE: The purpose of this meta-analysis is to evaluate the role of high-intensity statin pretreatment on coronary microvascular dysfunction in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). METHODS: PubMed, Cochrane, and Embase were searched. This meta-analysis selection included randomized controlled trials (RCTs), involving high-intensity statin pretreatment as active treatment, and measurement of thrombolysis in myocardial infarction (TIMI), myocardial blush grade (MBG) or index of microvascular resistance (IMR) in coronary heart disease (CHD) patients undergoing PCI. I2 test was used to evaluate heterogeneity. Pooled effects of continuous variables were reported as Standard mean difference (SMD) and 95% confidence intervals (CI). Pooled effects of discontinuous variables were reported as risk ratios (RR) and 95% confidence intervals (CI). Random-effect or fix-effect meta-analyses were performed. The Benefit was further examined based on clinical characteristics including diagnosis and statin type by using subgroup analyses. Publication bias was examined by quantitative Egger's test and funnel plot. We performed sensitivity analyses to examine the robustness of pooled effects. RESULTS: Twenty RCTs were enrolled. The data on TIMI < 3 was reported in 18 studies. Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI after PCI (RR = 0.62, 95%CI: 0.50 to 0.78, P < 0.0001). The data on MBG < 2 was reported in 3 studies. The rate of MBG < 2 was not different between groups (RR = 1.29, 95% CI: 0.87 to 1.93, P = 0.21). The data on IMR was reported in 2 studies. High-dose statin pretreatment significantly improved IMR after PCI comparing with non-high-dose statin (SMD = -0.94, 95% CI: -1.47 to -0.42, P = 0.0004). There were no significant between-subgroup differences in subgroups based on statin type and diagnosis. Publication bias was not indicated by using quantitative Egger's test (P = 0.97) and funnel plot. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI and IMR after PCI. In the future, RCTs with high quality and large samples are needed to test these endpoints.

Validation of pressure-bounded coronary flow reserve using invasive coronary physiologic assessment.

Coronary flow reserve (CFR) represents entire coronary compensatory capacity. While CFR assessment is recommended to identify patients at an increased risk of cardiovascular events and coronary microvascular dysfunction, invasive CFR measurement is often technically challenging. Although not well validated yet, pressure-bounded CFR (pbCFR) has been proposed as a simple surrogate to estimate impaired CFR. In this study, we evaluated coronary physiological characteristics of low pbCFR using detailed invasive assessment. Invasive physiological assessment including resting ratio of distal coronary pressure to aortic pressure (Pd/Pa), fractional flow reserve (FFR), resting and hyperemic mean transit time, index of microcirculatory resistance (IMR), CFR, resistive reserve ratio, and microvascular resistance reserve (MRR) was performed in 107 patients in the left anterior descending coronary artery. pbCFR was calculated only with resting Pd/Pa and FFR. Patients were divided into low pbCFR and non-low pbCFR groups. Of 107 patients, 50 (46.7%) had low pbCFR. FFR (0.90 ± 0.05 vs. 0.83 ± 0.05, p < 0.001), hyperemic mean transit time (0.27 ± 0.17 vs. 0.21 ± 0.12, p = 0.04), and IMR (20.4 ± 13.2 vs. 15.0 ± 9.1, p = 0.01) were significantly higher in the low pbCFR group than their counterpart. While directly measured CFR did not differ significantly (4.4 ± 2.3 vs. 5.1 ± 2.8, p = 0.18), MRR was lower in the low pbCFR group (5.4 ± 3.0 vs. 6.8 ± 3.8, p = 0.047). The rates of CFR < 2.0 and IMR ≥ 25 were not significantly different between the 2 groups. In conclusion, although CFR did not differ significantly, IMR and MRR were impaired in patients with low pbCFR, suggesting pbCFR as a potential surrogate of coronary microvascular function in clinical practice.

Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). METHODS: CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. RESULTS: Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066-7.146; P = 0.036). CONCLUSION: CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

Coronary Microcirculatory Function Indicated by Coronary Angiography-Derived Index of Microvascular Resistance in Patients Undergoing Rotational Atherectomy.

Background: There are scarce published data reporting the effect of rotational atherectomy (RA) on coronary microcirculation function. Objectives: We aimed to evaluate coronary microcirculation function indicated by the coronary angiography-derived index of microvascular resistance (caIMR) in patients undergoing RA. Methods: RA procedures between January 2013 and December 2021 were retrospectively analyzed. We investigated coronary microcirculation function indicated by caIMR as well as peri-procedural adverse events among the study population. All caIMR measurements were performed using a FlashAngio system. The primary outcome was a composite of post-RA thrombolysis in myocardial infarction (TIMI) flow grade < 3 in the target vessel, myocardial injury, procedure-related myocardial infarction, and cardiac death during hospitalization. Results: A total of 155 RA procedures were analyzed. The post-RA caIMRs were significantly higher than pre-RA caIMRs in the target vessels (16.0 ± 7.0 vs. 14.5 ± 7.5, p = 0.029). Patients with post-RA caIMR ≥ 25 accounted for nearly 12% of those with pre-RA caIMR < 25. Patients with post-RA thrombolysis in myocardial infarction (TIMI) flow grade < 3 had a significantly higher pre-RA caIMR (23.5 ± 10.2 vs. 13.7 ± 6.6, p = 0.005), and the proportion of patients with pre-RA caIMR ≥ 25 in the group with TIMI flow grade < 3 was greater (61.5% vs. 38.5%, p < 0.001) than that in the group with TIMI flow grade of 3. Maximum RA time of each pass (odds ratio: 1.127, 95% confidence interval: 1.025-1.239, p = 0.014) and pre-RA caIMR ≥ 25 (odds ratio: 3.254, 95% confidence interval: 1.054-10.048, p = 0.040) were identified to be the independent predictors of the primary outcome for patients who underwent RA. Conclusions: There were significant changes in the coronary microcirculation function of the target vessels after receiving RA as indicated by increased post-RA caIMR compared to pre-RA caIMR. Patients with baseline coronary microcirculatory dysfunction were more likely to have post-RA TIMI flow grade < 3, whereas those with pre-RA caIMR ≥ 25 experienced worse outcomes.

Accurate assessment of coronary blood flow by continuous thermodilution technique: Validation in a swine model.

OBJECTIVE: To assess the accuracy of coronary thermodilution measurements made with the RayFlow® infusion catheter. BACKGROUND: Measurements of absolute coronary blood flow (ABF) and absolute microvascular resistance (Rµ ) by continuous coronary thermodilution can be obtained in humans but their accuracy using a novel dedicated infusion catheter has not yet been validated. We compared ABF values obtained at different infusion rates to coronary blood flow (CBF) values obtained using flow probes, in swine. METHODS: Twelve domestic swine were instrumented with coronary flow probes placed around the left anterior descending and circumflex coronary arteries. ABF was assessed with the RayFlow® infusion catheter during continuous saline infusion at fixed rates of 5 (n = 14), 10 (n = 15), 15 (n = 19), and 20 (n = 12) ml/min. RESULTS: In the 60 measurements, ABF measured using thermodilution averaged 41 ± 17 ml/min (range from 17 to 90) and CBF values obtained with the coronary flow probes averaged 37 ± 18 ml/min (range from 8 to 87). The corresponding Rµ values were 1532 ± 791 (range from 323 to 5103) and 1903 ± 1162 (range from 287 to 6000) Woods units using thermodilution and coronary flow probe assessments, respectively. ABF and Rµ values measured using thermodilution were significantly correlated with the corresponding measurements obtained using coronary flow probes (R = 0.84 [0.73-0.95] and R = 0.80 [0.69-0.88], respectively). CONCLUSIONS: ABF and Rµ assessed by continuous saline infusion through a RayFlow® catheter closely correlate with measurements obtained with the gold standard coronary flow probes in a swine model.

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements.

AIM: Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. METHODS AND RESULTS: For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20 automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump).  A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rµ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rµ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59).  Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″ vs. 4'36″ ± 0'33″, p = 0.013). CONCLUSION: Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements.

GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated.

BACKGROUND: Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect. METHODS: We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). RESULTS: There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60. CONCLUSION: The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation. TRIAL REGISTRATION: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.

New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography.

BACKGROUND: The contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. METHODS: We studied 15 CS patients (11 female, age 50 ±â€¯9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e'), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. RESULTS: CMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ±â€¯12 versus 19.6 ±â€¯4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ±â€¯0.6 versus 5.46 ±â€¯1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e' were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e' (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). CONCLUSIONS: Functional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.

Optical coherence tomography-defined plaque vulnerability in relation to functional stenosis severity stratified by fractional flow reserve and quantitative flow ratio.

OBJECTIVES: We sought to investigate that the quantitative flow ratio (QFR) might be associated with optical coherence tomography (OCT)-defined plaque vulnerability. BACKGROUND: Both functional stenosis severity and plaque instability are related to adverse clinical outcomes in patients with coronary artery disease. Recent studies have shown an association between physiological stenosis severity and the presence of thin-cap fibroatheroma (TCFA). Measurement of QFR is a novel method for rapid computational estimation of fractional flow reserve (FFR). METHODS: We investigated 327 de novo intermediate-to-severe coronary lesions in 295 stable patients who underwent OCT, FFR, and QFR computation. The lesions were divided into tertiles based on either the FFR or QFR. The OCT findings were compared among these tertiles of FFR and QFR. Each tertile was defined as follows: FFR-T1 (FFR < 0.72), FFR-T2 (0.72 ≤ FFR ≤ 0.79), and FFR-T3 (FFR > 0.79) and QFR-T1 (QFR < 0.73), QFR-T2 (0.73 ≤ QFR ≤ 0.78), and QFR-T3 (QFR > 0.78). RESULTS: The prevalence of OCT-defined TCFA showed graded differences in proportion to the QFR tertiles (25.0% vs. 12.8% vs. 6.6%, p = .003). An overall significant difference in the prevalence of TCFA was found among FFR tertiles (p = .048), although pairwise comparison did not show statistical significance. Compared with FFR-based classifications, the model that integrated the FFR and QFR categorization improved the incremental reclassification efficacy (relative integrated discrimination improvement, 0.069; p = .002; continuous net reclassification improvement, 0.356; p = .022) for predicting the presence of TCFA. CONCLUSIONS: OCT-defined plaque instability was associated with the QFR in angiographically intermediate-to-severe lesions. Compared with the FFR alone, the QFR can provide incremental efficacy in predicting the presence of TCFA.

Index of microvascular resistance and outcomes following intra-coronary thrombolysis with percutaneous intervention in STEMI: a meta-analysis of randomized control trials.

Microvascular obstruction following percutaneous coronary intervention (PCI) is highly prevalent and independently associated with adverse clinical outcomes. Microvascular obstruction is determined by index of the microvascular resistance. We performed a systematic review with meta-analysis of all published randomized clinical trials (RCTs) studying the effect of intra-coronary thrombolysis with PCI as compared to standard treatment among patients with ST-segment elevated myocardial infarction. We included 6 RCTs summing up to 947 patients in the final analysis. Intra-coronary thrombolysis resulted in significantly lower index of microvascular resistance [standardized mean difference: - 13.74, 95% confidence interval (CI): - 16.74 to - 10.73, P value < 0.001, I2 = 0%]. There was no difference noted in the occurrence of major adverse cardiac events with intra-coronary thrombolysis as compared to standard treatment [Odds ratio: 0.71, 95% CI: 0.46-1.08, P value = 0.11,  I2 = 0%]. The absence of heterogeneity deferred us from using dose-response analysis to account for altering dose used across studies. The results of the present meta-analysis highlights the role of intra-coronary thrombolysis in reducing microvascular obstruction. No effect of intra-coronary thrombolysis was noted on the occurrence of major adverse cardiac events.

Continuous thermodilution to assess absolute flow and microvascular resistance: validation in humans using [15O]H2O positron emission tomography.

AIMS: Continuous thermodilution is a novel technique to quantify absolute coronary flow and microvascular resistance (MVR). Notably, intracoronary infusion of saline elicits maximal hyperaemia, obviating the need for adenosine. The primary aim of this study was to validate continuous thermodilution in humans by comparing invasive measurements to [15O]H2O positron emission tomography (PET). As a secondary goal, absolute flow and MVR were compared between invasive measurements obtained with and without adenosine. METHODS AND RESULTS: Twenty-five patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive assessment. Absolute coronary flow and MVR were measured in the left anterior descending and left circumflex artery using a dedicated infusion catheter and a temperature/pressure sensor-tipped guidewire. Invasive measurements were performed with and without adenosine. In order to compare invasive flow measurements with PET perfusion, subtending myocardial mass of the investigated vessels was derived from CCTA using the Voronoi algorithm. Invasive and non-invasive measurements of adenosine-induced hyperaemic flow and MVR showed strong correlation (r = 0.91; P < 0.001 for flow and r = 0.85; P < 0.001 for MVR) and good agreement [intraclass correlation coefficient (ICC) = 0.90; P < 0.001 for flow and ICC = 0.79; P < 0.001 for MVR]. Absolute flow and MVR also correlated well between measurements with and without adenosine (r = 0.97; P < 0.001 for flow and r = 0.98; P < 0.001 for MVR) and showed good agreement (ICC = 0.96; P < 0.001 for flow and ICC = 0.98; P < 0.001 for MVR). CONCLUSIONS: Continuous thermodilution is an accurate method to measure absolute coronary flow and MVR, which is evidenced by strong agreement with [15O]H2O PET derived flow and resistance. Absolute flow and MVR correlate highly between invasive measurements obtained with and without adenosine, which confirms that intracoronary infusion of room temperature saline elicits steady-state maximal hyperaemia.

Invasive coronary physiology: a Dutch tradition.

Invasive coronary physiology has been applied since the early days of percutaneous transluminal coronary angioplasty, and has become a rapidly emerging field of research. Many physiology indices have been developed, tested in clinical studies, and are now applied in daily clinical practice. Recent clinical practice guidelines further support the use of advanced invasive physiology methods to optimise the diagnosis and treatment of patients with acute and chronic coronary syndromes. This article provides a succinct review of the history of invasive coronary physiology, the basic concepts of currently available physiological parameters, and will particularly highlight the Dutch contribution to this field of invasive coronary physiology.

Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study.

INTRODUCTION: Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution-derived test "the index of microvascular resistance" (IMR) with the aim of determining the (i) IMR level in women with chest pain and non-obstructive CAD and if (ii) IMR is modified by high-dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation. MATERIALS AND METHODS: The study was a randomized, double-blind, single-center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF-36 and EQ-5D questionnaires, and biochemical values were assessed at baseline and 6 months later. RESULTS AND CONCLUSIONS: In the placebo group IMR was 14.6 (SD 5.7) at baseline and 14.4 (SD 6.5) at follow-up. In the rosuvastatin group IMR was 16.5 (SD 7.5) at baseline and 14.2 (SD 5.8) at follow-up. IMR did not differ significantly between the two study groups at follow-up controlled for preintervention values. C-reactive protein (CRP) was comparable between the groups at baseline, while at follow-up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; p = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT01582165, EUDRACT 2011-002630-39.3tcAZ).

Microvascular Dysfunction Related to Progressive Left Ventricular Remodeling due to Chronic Occlusion of the Left Anterior Descending Artery in an Adult Porcine Heart.

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.