Microvascular Resistance Reserve Research Articles

Effects of age on microvascular function in patients with normal coronary arteries.

It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rμ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rμ (Rμ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rμ (Rμ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

Prognostic Value of Microvascular Resistance Reserve Measured Immediately After PCI in Stable Coronary Artery Disease.

Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease. This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization. During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate. An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.

Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n=1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95%CI: 2.31-7.50; P< 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

The Influence Of Epicardial Resistance On Microvascular Resistance Reserve.

The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. We tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. In a cohort of 16 patients that had undergone proximal left anterior descending artery stenting, we created four grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) in order to assess their response to changing epicardial resistance. Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ±0.05; mild: 0.72 ±0.04; moderate: 0.61 ±0.05; severe: 0.48 ±0.09, p<0.001). This translated into a linear decrease in mean hyperaemic coronary flow (no stenosis: 170.5 ±66.8 ml/min; mild: 149.8 ±58.8 ml/min; moderate: 124.4 ±53.0 ml/min; severe: 94.0 ±45.2 ml/min, p<0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ±0.9; mild: 2.2 ±0.8; moderate: 1.8 ±0.7; severe: 1.4 ±0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (p<0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ±1.0; mild: 3.0 ±1.0; moderate: 2.9 ±1.0; severe: 2.8 ±1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (p<0.001). MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study

Background and aimsMicrovascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). MethodsIn this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. ResultsAmong 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). ConclusionsOur study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

Impact of sex on the assessment of the microvascular resistance reserve

BackgroundThe microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AimThe aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. MethodsFrom the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. ResultsA total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47–0.96, p = 0.027) and men (HR 0.84, 0.74–0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. ConclusionThe MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

Microvascular Resistance Reserve assessed by bolus and continuous thermodilution

Abstract Aim The main limitation of Coronary flow reserve (CFR) as an index to assess coronary microvascular function, is that it is influenced by epicardial resistance. Microvascular Resistance Reserve (MRR) has been recently introduced as a metric that is truly specific for the coronary microcirculation. MRR can, in principle, be derived from any tool that measure flow and pressure. The aim of the present study was to compare CFR and MRR as derived by bolus (CFRbolus and MRRbolus, respectively) and continuous thermodilution (CFRcont and MRRcont, respectively). Methods and Results A total of 175 patients were studied. Bolus and continuous thermodilution measurements were performed in the LAD in all patients. The MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressures. Coefficient of variation was calculated to assess the precision of both methods. Mean CFRbolus was higher than the corresponding value of CFRcont (3.47±1.42 and 2.67±0.81, respectively, p&amp;lt;0.001, mean bias 0.80). Also mean MRRbolus was higher than the corresponding value of MRRcont (4.40±1.99 vs 3.22±1.02, respectively p&amp;lt;0.001, mean bias 1.2) The correlation between CFR and MRR values obtained by both approaches was weak (R= 0.28 (0.14 to 0.41) for CFR; R=0.26 (0.16 to 0.39) for MRR; p&amp;lt;0.001 for both). Continuous thermodilution had a smaller dispersion of data for both CFR (CoV= 30.2% vs 46.6% respectively, p&amp;lt;0.001) and MRR (CoV= 31.7 % vs 45.2% vs, respectively, p&amp;lt;0.001). Conclusion Bolus thermodilution significantly overestimates continuous thermodilution-derived CFR and MRR and shows a larger scatter of the data. Therefore, bolus thermodilution seems a less appropriate method to assess microvascular function than is continuous thermodilution.

Validation of pressure - derived microvascular resistance reserve (MRR) by Doppler wire measurement - the impact of correction for the error of hydrostatic pressure

Abstract Background The pressure-bounded coronary flow reserve (CFRpb) defines the possible CFR interval (between CFRpbmin and CFRpbmax) using intracoronary pressure data. However, its correlation to the Doppler wire measurement was reported to be poor, partly due to the non-inclusion of the hydrostatic pressure error in the calculations. Microvascular resistance reserve (MRR), a specific index of coronary microcirculation, can be calculated from CFR and intracoronary pressure data (Pa: aortic pressure, Pd: distal pressure) by the following equation: MRR= CFR; × (Pa, rest)/(pd, hyper). Purpose We aimed to design a prediction model of MRR using intracoronary pressure data and to validate the results against the gold-standard Doppler wire measurement. Methods In our study, hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. After hydrostatic pressure error correction, the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined by the aforementioned equation. In the training population, 23 actual MRRp-3D were defined within the pressure-bounded interval by hemodynamic calculations using the measured intracoronary pressure data and the angiography-based 3D anatomical features. These results were analyzed by regression analyses to find relations between the MRRpb and the actual MRRp-3D. Results Using the established linear relation (MRRpredicted=1.04+0.51×MRRpbmax), our prediction was tested in the population of 21 patients undergoing the gold standard Doppler wire measurements, and a significant correlation was found (r=0.54, p=0.01). If the area stenosis was included in the prediction model, the correlation had even improved (r=0.63, p=0.004). In parallel, the Bland-Altman analysis showed reduced mean differences between the predicted MRR and the MRR values determined during the Doppler wire measurement from 0.04 (±1.96SD: 0.88, –0.8) to –0.01 (±1.96SD: 0.77, –0.79). The latter prediction utilized the quadratic relation between the area stenosis in % (AS) and the ratio of the (MRRmax−MRRp-3D)/(MRRmax−MRRmin) (ratio=0.0047+0.0067×AS+0.000039×AS2). Conclusions The MRR can be predicted reliably by our simple model to assess microvascular function. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement (especially with the inclusion of area stenosis) provides a simultaneous physiological assessment of the macro- and microvasculature.Flow chart of the calculations

In vivo validation of intra-coronary absolute flow measurements and comparison of reliability between different microvascular indices and the microvascular resistance reserve

Abstract Background Coronary microvascular dysfunction plays a major role in patients with cardiac ischemia without flow limiting epicardial coronary stenosis, takotsubo cardiomyopathy, aortic valve stenosis and heart failure with preserved ejection fraction. In clinical practice, the index of microvascular resistance (IMR) and coronary flow reserve (CFR), and more recently the absolute coronary blood flow (ABF), absolute coronary resistance (ACR) and the microvascular resistance reserve (MRR) are used as parameters to measure resistance and flow using continuous coronary thermodilution. Purpose Firstly, to validate ABF measured with continuous coronary thermodilution in vivo against epicardial doppler-measured flow. Secondly, to assess reliability and reproducibility in-vivo of different microvascular indices. Methods For the purpose of this study coronary measurements were conducted in two large animal models and in patients, all with the appropriate ethical committee approval. For the first part of the study, fourteen sheep underwent repeated paired measurements of ABF and ACR (with use of continuous thermodilution) with different saline infusion speeds, as well as IMR, CFR and MRR in multiple coronary vessels. Seven additional sheep underwent these measurements while having simultaneous measurements with epicardial coronary flow probes (gold standard) in an open-chest model. The epicardial flow probes were placed on the proximal left anterior descending and circumflex artery. Maximal hyperemia was induced with adenosine (CFR and IMR) or infusion of saline at a rate of 30ml/min (ABF, ACR and MRR). For the second part of the study, in 41 patients receiving routine microvascular assessment, IMR and CFR measurements were duplicated by a single operator, after re-calibration, to assess the reproducibility of the measurement. The combined animal and human data resulted in the analysis of 408 coronary measurements made in 88 coronary vessels during 65 heart catheterizations. Results In sheep, ABF measured with continuous thermodilution (with saline infusion speeds from 5ml/min to 30ml/min) was accurate when compared with epicardial flow measurements. (Table 1, Fig 1A) Notably, the continuous thermodilution measurement had the tendency to slightly overestimate ABF. (Table 1, Fig 1B) The two methods were equivalent within 15% (Two one-sided test: mean difference: -8.73%; 95% CI: -14.40 to -3.06%, p= 0.016). When comparing test-retest reproducibility between the indices, CFR performed the worst while ACR and MRR performed the best. MRR had a significantly better reproducibility than the IMR. (Table 1, Fig 1C). Conclusion ABF can accurately be determined by continuous coronary thermodilution. MRR and ACR have a significantly superior reliability and reproducibility compared to IMR and CFR. Unlike ACR, MRR is not vessel or territory-size dependent and is therefore the index of choice for future research and clinical assessment of the microcirculation.

Endotypes of coronary microvascular dysfunction in patients with and without Diabetes Mellitus

Abstract Background Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of ventricular dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR). Recently, two different endotypes of CMD, structural and functional were identified, based on CFR and minimal resistance (Rm-hyp) values. Purpose To compare the patterns of CMD among patients with and without diabetes mellitus by continuous intracoronary thermodilution. Methods Consecutive patients with angina and non-obstructive coronary artery disease undergoing absolute flow measurement with continuous intracoronary thermodilution between 2020 and 2022 were included. Considering a CFR threshold of 2.5, patients were divided into 4 groups, CMD with and without diabetes (DM-CMD and NDM-CMD respectively), and two control groups with and without diabetes (DM-Control and NDM-Control group, respectively). Rm-hyp threshold of 390 (median value) was used to divide structural and functional endotypes (Rm-hyp above or below the threshold respectively). Results 204 patients were included (NDM-CMD=62 vs NDM-Control=77 and dm-CMD=38 vs dm-Control=27). The prevalence of CMD among diabetic patients was 58%. Both CFR and MRR were significantly reduced in both CMD groups compared to the control groups. DM-CMD and NDM-CMD patients had both lower Rm-hyp and higher Rm-rest as compared to the control groups. Among patients with CMD, DM-CMD had higher Rm-hyp compared to NDM-CM patients (480±163 vs 420±124 WU, respectively, p=0.04) and had a higher prevalence of structural endotype (78% vs 58%), p=0.03) which was higher among patients with insulin-dependent diabetes than in those without. Conclusions In patients with DM structural microvascular dysfunction is the most prevalent endotype. Functional endotype is more frequent among those with non-insuline dependent DM. Therefore, CMD in diabetic patients appears to be a continuum, evolving from a functional pattern to a structural one as the disease progresses.

Gender-related differences in absolute coronary flow and microvascular resistance in patients with angina and non-obstructed coronary arteries (ANOCA)

Abstract Background Women with angina more often have non-obstructive coronary artery disease (ANOCA) compared to males. Coronary microvascular dysfunction (CMD) is responsible for angina in a sizable proportion of ANOCA patients. Intracoronary continuous thermodilution allows direct quantification of absolute coronary flow (Q) and microvascular resistance (Rµ). Purpose To evaluate gender-related differences in the prevalence and pattern of CMD assessed with intracoronary continuous thermodilution in ANOCA patients. Specifically, we assessed resting and hyperemic Q (Qrest and Qhyper), R (Rµ,rest and Rµ,hyper), coronary flow reverse (CFR), and microvascular resistance reserve (MRR) in ANOCA patients stratified by gender. Methods Single-center, prospective study of patients with ANOCA. CMD was invasively assessed by intracoronary continuous thermodilution in the left anterior descending artery (LAD) and defined as CFR&amp;lt;2.5. Results A total of 118 patients (n=49 females and n= 69 males) were enrolled. The mean patient age was 65 years. The mean fractional flow reserve (FFR) was 0.85±0.04, with no difference between the 2 genders. There was no difference in Rµ,rest, Qrest and Qhyper between the two genders. However, Rµ,hyper were higher in females compared to males (p=0.003). Among patients with ANOCA, CMD was more prevalent in females (28% vs 22%, p=0.014). Yet, in both females and males with CMD, a higher Qrest was observed compared to patients without CMD. In male patients, also Qhyper was lower in CMD patients versus those without CMD. Conclusion Among patients with ANOCA and investigated with intracoronary continuous thermodilution, CMD appeared more prevalent in females compared to males. Females had higher microvascular Rµ,hyper compared to males. In both genders, CMD was characterized by higher Qrest, suggestive of functional rather than structural CMD.

Continuous vs Bolus Thermodilution to Assess Microvascular Resistance Reserve.

Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) can, in principle, be derived by any method assessing coronary flow. The aim of this study was to compare CFR and MRR as derived by continuous (CFRcont and MRRcont) and bolus thermodilution (CFRbolus and MRRbolus). A total of 175 patients with chest pain and nonobstructive coronary artery disease were studied. Bolus and continuous thermodilution measurements were performed in the left anterior descending coronary artery. MRR was calculated as the ratio of CFR to fractional flow reserve and corrected for changes in systemic pressure. In 102 patients, bolus and continuous thermodilution measurements were performed in duplicate to assess test-retest reliability. Mean CFRbolus was higher than CFRcont (3.47 ± 1.42 and 2.67 ± 0.81 [P< 0.001], mean difference 0.80, upper limit of agreement 3.92, lower limit of agreement-2.32). Mean MRRbolus was also higher than MRRcont (4.40 ± 1.99 and 3.22 ± 1.02 [P< 0.001], mean difference 1.2, upper limit of agreement 5.08, lower limit of agreement-2.71). The correlation between CFR and MRR values obtained using both methods was significant but weak (CFR, r=0.28 [95%CI: 0.14-0.41]; MRR, r=0.26 [95%CI: 0.16-0.39]; P< 0.001 for both). The precision of both CFR and MRR was higher when assessed using continuous thermodilution compared with bolus thermodilution (repeatability coefficients of 0.89 and 2.79 for CFRcont and CFRbolus, respectively, and 1.01 and 3.05 for MRRcont and MRRbolus, respectively). Compared with bolus thermodilution, continuous thermodilution yields lower values of CFR and MRR accompanied by an almost 3-fold reduction of the variability in the measured results.

The microvascular resistance reserve: one size fits all, but mostly one.

The microvascular resistance reserve: one size fits all, but mostly one.

Microvascular resistance reserve, does one size fit all?

Microvascular resistance reserve, does one size fit all?

TCT-23 Comparison of Reliability Between Current Indices for Microvascular Assessment and the New Microvascular Resistance Reserve Using Continuous Coronary Thermodilution

TCT-23 Comparison of Reliability Between Current Indices for Microvascular Assessment and the New Microvascular Resistance Reserve Using Continuous Coronary Thermodilution

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

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. 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). 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.

Factors Associated with Impaired Resistive Reserve Ratio and Microvascular Resistance Reserve

Coronary microvascular dysfunction (CMD) is described as an important subset of ischemia with no obstructive coronary artery disease. Resistive reserve ratio (RRR) and microvascular resistance reserve (MRR) have been proposed as novel physiological indices evaluating coronary microvascular dilation function. The aim of this study was to explore factors associated with impaired RRR and MRR. Coronary physiological indices were invasively evaluated in the left anterior descending coronary artery using the thermodilution method in patients suspected of CMD. CMD was defined as a coronary flow reserve <2.0 and/or index of microcirculatory resistance ≥25. Of 117 patients, 26 (24.1%) had CMD. RRR (3.1 ± 1.9 vs. 6.2 ± 3.2, p < 0.001) and MRR (3.4 ± 1.9 vs. 6.9 ± 3.5, p < 0.001) were lower in the CMD group. In the receiver operating characteristic curve analysis, RRR (area under the curve 0.84, p < 0.001) and MRR (area under the curve 0.85, p < 0.001) were both predictive of the presence of CMD. In the multivariable analysis, previous myocardial infarction, lower hemoglobin, higher brain natriuretic peptide levels, and intracoronary nicorandil were identified as factors associated with lower RRR and MRR. In conclusion, the presence of previous myocardial infarction, anemia, and heart failure was associated with impaired coronary microvascular dilation function. RRR and MRR may be useful to identify patients with CMD.

Microvascular resistance reserve in the presence of functionally significant epicardial stenosis and changes after revascularization.

In the presence of functionally significant epicardial lesions, microvascular resistance reserve (MRR) calculation needs incorporation of collateral flow. Coronary fractional flow reserve (FFRcor ) requiring coronary wedge pressure (Pw ), which is an essential part of the true MRR calculation, is reportedly estimated by myocardial FFR (FFRmyo ) not requiring Pw measurement. We sought to find an equation to calculate MRR without the need for Pw . Furthermore, we assessed changes in MRR after percutaneous coronary intervention (PCI). An equation to estimate FFRcor was developed from a cohort of 230 patients who underwent physiological measurements and PCI. Corrected MRR was calculated using this equation and compared with true MRR in 115 patients of the different set of the validation cohort. True MRR was calculated using FFRcor . FFRcor and FFRmyo showed a strong linear relationship (r2 =0.86) and an equation was FFRcor =1.36 × FFRmyo - 0.34. This equation provided no significant difference between corrected MRR and true MRR in the validation cohort. Pre-PCI lower coronary flow reserve and higher index of microcirculatory resistance were independent predictors of pre-PCI decreased true MRR. True MRR significantly decreased after PCI. In conclusion, MRR can be accurately corrected using an equation for FFRcor estimation without Pw .