Thermodilution-derived Coronary Flow Reserve Research Articles

Comparing Pressure-Bounded Versus Thermodilution-Derived Coronary Flow Reserve in Unobstructed Coronary Arteries

Comparing Pressure-Bounded Versus Thermodilution-Derived Coronary Flow Reserve in Unobstructed Coronary Arteries

C-11 | Correlation Between Thermodilution-Derived Coronary Flow Reserve and Rubidium-82 PET Myocardial Flow Reserve in Patients Undergoing Invasive Coronary Function Testing

C-11 | Correlation Between Thermodilution-Derived Coronary Flow Reserve and Rubidium-82 PET Myocardial Flow Reserve in Patients Undergoing Invasive Coronary Function Testing

Noninvasive transthoracic doppler flow velocity and invasive thermodilution to assess coronary flow reserve.

Coronary flow reserve (CFR) provides prognostication and coronary physiological information, including epicardial coronary stenosis and microvascular function. The relationship between stress transthoracic Doppler echocardiography (TDE)-derived coronary flow velocity reserve (CFRS-TDE) and thermodilution-derived coronary flow reserve (CFRthermo) before and after elective percutaneous coronary intervention (PCI) remains unclear. This single-center prospective registry study evaluated patients who underwent fractional flow reserve (FFR)-guided elective PCI for left anterior descending artery (LAD) lesions with wire-based invasive physiological measurements and pre- and post-PCI stress TDE examinations. A total of 174 LAD lesions from 174 patients were included in the final analysis. A modest correlation was detected between the pre-PCI CFRS-TDE and the pre-PCI CFRthermo (r=0.383, P<0.001). The frequently used CFRS-TDE threshold of 2.0 corresponded to a pre-PCI CFRthermo of 2.18. Pre-PCI CFRS-TDE underestimated pre-PCI CFRthermo [1.89 (1.44-2.31) vs. 2.05 (1.38-2.93), P<0.001]. Both CFRS-TDE and CFRthermo increased significantly post-PCI [pre-PCI CFRS-TDE 1.89 vs. post-PCI CFRS-TDE 2.33, P<0.001; pre-PCI CFRthermo 2.05 (1.38-2.93) vs. post-PCI CFRthermo 2.59 (1.63-3.55), P<0.001]. In contrast, there was no significant relationship between changes in CFRS-TDE and changes in CFRthermo after PCI (r=0.008, P=0.915) or between post-PCI CFRS-TDE and post-PCI CFRthermo (r=0.054, P=0.482). Pre-PCI CFRS-TDE and CFRthermo are modestly correlated, but post-PCI CFRS-TDE and CFRthermo have no correlation. CFRS-TDE and CFRthermo are not interchangeable, particularly post-PCI, suggesting that the two metrics represent different coronary physiologies after PCI.

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.

Long-term changes in coronary physiology after aortic valve replacement.

The detrimental effects of long-standing severe aortic stenosis (AS) often include left ventricular hypertrophy (LVH) and exhaustion of coronary flow reserve (CFR), the reversibility of which is unclear after valve replacement. Our aims were to 1) investigate whether CFR in the left anterior descending artery (LAD) would improve following valve replacement, and if the change was related to changes in hyperaemic coronary flow (QLAD) and minimal microvascular resistance (Rμ,LAD); and 2) investigate the relationship between changes in CFR and changes in left ventricular mass (LVM) and stroke work (LVSW). We measured intracoronary bolus thermodilution-derived CFR, and continuous thermodilution-derived QLAD and Rμ,LAD before and 6 months after aortic valve replacement. Cardiac magnetic resonance imaging was used to quantify left ventricular anatomy and function for the calculation of LVM and LVSW. Results: Thirty-four patients were included (17 patients had transcatheter aortic valve implantation; 14 had surgical valve replacement with a bioprosthesis and 3 with a mechanical prosthesis) who underwent invasive assessment in the LAD. CFR increased from 2.5 (interquartile range [IQR] 1.5-3.3) at baseline to 3.1 (IQR 2.2-5.1) at follow-up (p=0.005), despite no significant change in QLAD (230±106 mL/min to 250±101 mL/min; p=0.26) or Rμ,LAD (347 [IQR 247-463] to 287 [IQR 230-456]; p=0.20). When indexed for LVM, QLAD was 39% (IQR 8-98%) higher at follow-up compared with baseline (p<0.001). The improvement in CFR was correlated with ΔLVSW, r= -0.39; p=0.047. Conclusions: CFR in the LAD increased significantly at follow-up although global hyperaemic flow and minimal microvascular resistance remained unchanged. Thus, a decrease in resting flow was the cause of CFR improvement. CFR improvement was associated with reduction in LVSW.

851 REPEATABILITY OF BOLUS AND CONTINUOUS THERMODILUTION FOR ASSESSING CORONARY MICROVASCULAR FUNCTION

Abstract Introduction The bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged over years as the standard of reference to invasively define coronary microvascular dysfunction (CMD). However, the technique still presents some limitations, mainly related to the fact that manual injection of saline bolus accounts for some variance in the measurements. Continuous intracoronary thermodilution has been recently introduced as a tool to directly quantify absolute coronary flow and microvascular resistance both at rest and during hyperemia and has shown to be safe and operator independent. Microvascular resistance reserve (MRR), derived from continuous thermodilution, has been validated as novel index specific for microcirculation and independent from myocardial mass. Purpose To compare head-to-head the intra-observer repeatability of bolus and continuous thermodilution for assessing microvascular function. Methods Patients undergoing coronary angiography in the absence of obstructive coronary artery disease were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were performed in duplicates in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo first bolus thermodilution or first continuous thermodilution assessment. Results A total of 102 patients were enrolled. Average FFR was 0.86±0.06. Coronary Flow Reserve (CFR) calculated with continuous thermodilution (CFRthermo) was significantly lower than bolus thermodilution-derived CFR (CFRbolus) (2.63±0.65 and 3.29±1.17, respectively, p&amp;lt;0.001). CFRthermo showed a lower variability and a higher agreement than CFRbolus (variability 12.74 ± 10.41% vs 31.26±24.85%, respectively, p&amp;lt;0.001; ICC= 0.78 (0.70-0.85) and 0.48 (0.32-0.62), respectively, p&amp;lt;0.001, Figure 1). Both MRR and IMR showed a good agreement (ICC 0.81 (0.74-0.87) and 0.80 (0.71-0.86)) but the variability of the MRR was significantly lower (12.44 ± 10.06% vs 24.24±19.27, respectively, p&amp;lt;0.001, figure 1). Reproducibility data of all indices derived from duplicated measurements of bolus and continuous thermodilution are reported in Figure 2. Conclusion Continuous intracoronary thermodilution has a higher repeatability than bolus thermodilution in the assessment of CMD.

Repeatability of bolus and continuous thermodilution for assessing coronary microvasculatory function

Abstract Introduction The bolus thermodilution-derived index of microcirculatory resistance (IMR) has emerged over years as the standard of reference to invasively define coronary microvascular dysfunction (CMD). However, the technique still presents some limitations, mainly related to the fact that manual injection of saline bolus accounts for some variance in the measurements. Continuous intracoronary thermodilution has been recently introduced as a tool to directly quantify absolute coronary flow and microvascular resistance both at rest and during hyperemia and has shown to be safe and operator independent. Microvascular resistance reserve (MRR), derived from continuous thermodilution, has been validated as novel index specific for microcirculation and independent from myocardial mass. Purpose To compare head-to-head the intra-observer repeatability of bolus and continuous thermodilution for assessing microvascular function. Methods Patients undergoing coronary angiography in the absence of obstructive coronary artery disease were prospectively enrolled. Bolus and continuous intracoronary thermodilution measurements were performed in duplicates in the left anterior descending artery (LAD). Patients were randomly assigned in a 1:1 ratio to undergo first bolus thermodilution or first continuous thermodilution assessment. Results A total of 102 patients were enrolled. Average FFR was 0.86±0.06. Coronary Flow Reserve (CFR) calculated with continuous thermodilution (CFRthermo) was significantly lower than bolus thermodilution-derived CFR (CFRbolus) (2.63±0.65 and 3.29±1.17, respectively, p&amp;lt;0.001). CFRthermo showed a lower variability and a higher agreement than CFRbolus (variability 12.74±10.41% vs 31.26±24.85%, respectively, p&amp;lt;0.001; ICC= 0.78 (0.70–0.85) and 0.48 (0.32–0.62), respectively, p&amp;lt;0.001, Figure 1). Both MRR and IMR showed a good agreement (ICC 0.81 (0.74–0.87) and 0.80 (0.71–0.86)) but the variability of the MRR was significantly lower (12.44±10.06% vs 24.24±19.27, respectively, p&amp;lt;0.001, Figure 1). Reproducibility data of all indices derived from duplicated measurements of bolus and continuous thermodilution are reported in Table 2. Conclusion Continuous intracoronary thermodilution has a higher repeatability than bolus thermodilution in the assessment of CMD. Funding Acknowledgement Type of funding sources: None.

Comparison of Doppler Flow Velocity and Thermodilution Derived Indexes of Coronary Physiology.

ObjectivesThe aim of this study was to compare Doppler flow velocity and thermodilution-derived indexes and to determine the optimal thermodilution-based diagnostic thresholds for coronary flow reserve (CFR).BackgroundThe majority of clinical data and diagnostic thresholds for flow-based indexes are derived from Doppler measurements, and correspondence with thermodilution-derived indices remain unclear.MethodsAn international multicenter registry was conducted among patients who had coronary flow measurements using both Doppler and thermodilution techniques in the same vessel and during the same procedure.ResultsPhysiological data from 250 vessels (in 149 patients) were included in the study. A modest correlation was found between thermodilution-derived CFR (CFRthermo) and Doppler-derived CFR (CFRDoppler) (r2 = 0.36; P < 0.0001). CFRthermo overestimated CFRDoppler (mean 2.59 ± 1.46 vs 2.05 ± 0.89; P < 0.0001; mean bias 0.59 ± 1.24 by Bland-Altman analysis), the relationship being described by the equation CFRthermo = 1.04 × CFRDoppler + 0.50. The commonly used dichotomous CFRthermo threshold of 2.0 had poor sensitivity at predicting a CFRDoppler value <2.5. The optimal CFRthermo threshold was 2.5 (sensitivity 75.54%, specificity 81.25%). There was only a weak correlation between hyperemic microvascular resistance and index of microvascular resistance (r2 = 0.19; P < 0.0001), due largely to variation in the measurement of flow by each modality. Forty-four percent of patients were discordantly classified as having abnormal microvascular resistance by hyperemic microvascular resistance (≥2.5 mm Hg · cm−1 · s) and index of microvascular resistance (≥25).ConclusionsCFR calculated by thermodilution overestimates Doppler-derived CFR, while both parameters show modest correlation. The commonly used CFRthermo threshold of 2.0 has poor sensitivity for identifying vessels with diminished CFR, but using the same binary diagnostic threshold as for Doppler (<2.5) yields reasonable diagnostic accuracy. There was only a weak correlation between microvascular resistance indexes assessed by the 2 modalities.

Thermodilution-derived volumetric resting coronary blood flow measurement in humans.

Quantification of microvascular function requires the measurement of flow and resistance at rest and during hyperaemia. Continuous intracoronary thermodilution accurately measures coronary flow during hyperaemia. The aim of this study was to investigate whether continuous coronary thermodilution using lower infusion rates also enables volumetric coronary blood flow measurements (in mL/min) at rest. In 59 patients (88 arteries), the ratio of distal to proximal coronary pressure (Pd/Pa), as well as absolute blood flow (in mL/min) by continuous thermodilution, was recorded using a pressure/temperature guidewire. Saline was infused at rates of 10 and 20 mL/min. In 27 arteries, Doppler average peak velocity (APV) was measured simultaneously. Pd/Pa, APV, thermodilution-derived coronary flow reserve (CFRthermo) and coronary flow velocity reserve (CFVR) were assessed. In 10 arteries, simultaneous recordings were obtained at saline infusion rates of 6, 8, 10 and 20 mL/min. Compared to baseline, saline infusion at 10 mL/min did not change Pd/Pa (0.95±0.05 versus 0.94±0.05, p=0.49) or APV (22±8 versus 23±8 cm/s, p=0.60); conversely, an infusion rate of 20 mL/min induced a decrease in Pd/Pa and an increase in APV. Stable thermodilution tracings were obtained during saline infusion at 8 and 10 mL/min, but not at 6 mL/min. Mean values of CFRthermo and CFVR were similar (2.78±0.91 versus 2.76±1.06, p=0.935) and their individual values correlated closely (r=0.89, 95% CI: 0.78-0.95, p<0.001). In addition to hyperaemic flow, continuous thermodilution can quantify absolute resting coronary blood flow; therefore, it can be used to calculate coronary flow reserve and microvascular resistance reserve.

Pressure-bounded coronary flow reserve to assess the extent of microvascular dysfunction in patients with ST-elevation acute myocardial infarction.

Assessment of microvascular function in patients with ST-elevation acute myocardial infarction (STEMI) may be useful to determine treatment strategy. The possible role of pressure-bounded coronary flow reserve (pb-CFR) in this setting has not been determined. In this study we aimed to compare pb-CFR with thermodilution-derived physiology including the index of microcirculatory resistance (IMR) and CFRthermo in a consecutive series of patients enrolled in the OxAMI study. Moreover, we aimed to assess the presence of microvascular obstruction (MVO) and myocardial injury on cardiovascular magnetic resonance (CMR) imaging performed at 48 hours and six months in STEMI patients stratified according to pb-CFR. Thermodilution-pressure-wire assessment of the infarct-related artery was performed in 148 STEMI patients before stenting and/or at completion of primary percutaneous coronary intervention (PPCI). The extent of the myocardial injury was assessed with CMR imaging at 48 hours and six months after STEMI. Post-PPCI pb-CFR was impaired (<2) and normal (>2) in 69.9% and 9.0% of the cases, respectively. In the remaining 21.1% of the patients, pb-CFR was "indeterminate". In this cohort, pb-CFR correlated poorly with thermodilution-derived coronary flow reserve (k=0.03, p=0.39). The IMR was significantly different across the pb-CFR subgroups. Similarly, significant differences were observed in MVO, myocardium area at risk and 48-hour infarct size (IS). A trend towards lower six-month IS was observed in patients with high (>2) post-PPCI pb-CFR. Nevertheless, pb-CFR was inferior to IMR in predicting MVO and the extent of IS. Pb-CFR can identify microvascular dysfunction in patients after STEMI. It provided superior diagnostic performance compared to thermodilution-derived CFR in predicting MVO. However, IMR was superior to both pb-CFR and thermodilution-derived CFR and, consequently, IMR was the most accurate in predicting all of the studied CMR endpoints of myocardial injury after PPCI.

Doppler Flow Velocity and Thermodilution to Assess Coronary Flow Reserve: A Head-to-Head Comparison With [15O]H2O PET

ObjectivesThis study sought to compare Doppler flow velocity reserve (CFRDoppl) and thermodilution-derived coronary flow reserve (CFRthermo) head-to-head with the gold standard for quantification of myocardial perfusion, [15O]H2O positron emission tomography (PET). BackgroundCoronary flow reserve (CFR) is an important parameter for assessing coronary vascular function. To date, 2 techniques are available for invasive assessment of CFR: Doppler flow velocity and thermodilution. Although these techniques have been compared with each other, neither has been compared with [15O]H2O PET perfusion imaging. MethodsCFR was assessed in 98 vessels of 40 consecutive stable patients with suspected coronary artery disease. Patients underwent [15O]H2O PET, followed by invasive angiography in conjunction with simultaneous measurements of fractional flow reserve, CFRDoppl, and CFRthermo. Both normal and obstructed arteries were included. ResultsThe quality of Doppler flow velocity traces was significantly lower than that of thermodilution curves (p < 0.001). A moderate correlation was observed between CFRDoppl and CFRthermo (r = 0.59; p < 0.001). CFRDoppl correlated well with PET-derived CFR (CFRPET) (r = 0.82; p < 0.001). In contrast, the correlation between CFRthermo and CFRPET was only modest (r = 0.55; p < 0.001). This difference in correlation with CFRPET was significant (t = 4.9; df = 95; p < 0.001). Bland-Altman analysis revealed a tendency of CFRthermo to overestimate flow reserve at higher values. ConclusionsCoronary flow reserve, determined using Doppler flow velocity, has superior agreement with [15O]H2O PET in comparison with CFRthermo.

Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris

Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61 ± 10 years) who underwent cardiac catheterization for stable coronary artery disease (n = 10) or acute myocardial infarction (n = 44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia. Three independent measurements of microvascular function were assessed, using predefined dichotomous thresholds: (1) coronary flow reserve (CFR), the average value of Doppler- and thermodilution-derived CFR; (2) cardiovascular magnetic resonance (CMR) derived myocardial perfusion reserve index; and (3) CMR-derived microvascular obstruction. hMR correlated with IMR (rho = 0.41, p <0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve [AUC] 0.82 vs 0.58, p <0.001, sensitivity and specificity 77% and 77% vs 51% and 71%) and myocardial perfusion reserve index (AUC 0.85 vs 0.72, p = 0.19, sensitivity and specificity 82% and 80% vs 64% and 75%). In patients with acute myocardial infarction, the AUCs of hMR and IMR at predicting extensive microvascular obstruction were 0.83 and 0.72, respectively (p = 0.22, sensitivity and specificity 78% and 74% vs 44% and 91%). We conclude that these 2 invasive indices of coronary microvascular resistance only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and noninvasive measurements of microvascular function was better with hMR than with IMR.

Invasive assessment of coronary flow reserve impairment in severe aortic stenosis and ecochadiographic correlations

Objectives and backgroundPatients with aortic stenosis (AS) may have impaired coronary flow reserve (CFR) despite angiographically normal coronary arteries. This is the first report of invasive thermodilution-derived CFR and IMR in patients with AS and their associations with echocardiographic parameters for AS assessment. MethodsThirty-six consecutive severe AS patients and ten patients without AS underwent prospectively cardiac catheterization and coronary physiological parameters were determined in the left anterior descending (LAD). Mean transit time (Tmn), a surrogate of absolute coronary flow, was obtained from the coronary thermodilution curve. ResultsIn AS patients we found a high LAD flow at rest (Tmn rest 0.55±0.3 vs 0.99±0.4, p=0.01) and a low flow at hyperemia (Tmnhyp 0.44±0.2 vs 27.7±0.1, p=0.02) and consequently a severe CFR impairment (1.4±0.4 vs 3.8±1.4, p<0.001) compared with controls. An elevated index of microvascular resistance (IMR) (32.7±16 vs 17.8±6.5, p=0.01) and a low baseline microvascular coronary resistance (48.1±29 vs 84±34, p=0.02) were also found.In AS patients there were significant correlations between CFR and left ventricular mass index (r=−0.32; p=0.02), and the ratio of acceleration time to ejection time (AT/ET) (r=−0.4; p=0.01) a non-flow dependent echocardiographic parameter for AS assessment. Multiple linear stepwise regression analysis showed that AT/ET (β=−0.441, p=0.019) was the only independently variable associated with CFR ConclusionsIn severe AS, invasive CFR shows a progressive decrease with AS severity and a good correlation with echocardiographic parameters of AS, especially with flow-independent ones.

Association of Inflammation and Endothelial Dysfunction with Coronary Microvascular Resistance in Patients with Cardiac Syndrome X

BackgroundAlthough a proportion of CSX patients have impaired brachial artery flow-mediated dilatation (FMD) in response to hyperemia, suggesting that endothelial dysfunction in these patients may be systemic and not just confined to the coronary circulation; the underlying mechanisms triggering endothelial dysfunction in these patients are still incompletely understood.ObjectivesTo assess the association of the index of Microcirculatory Resistance (IMR) with endothelial dysfunction and inflammation in patients with CSX.MethodsWe studied 20 CSX patients and 20 age and gender-matched control subjects. Thermodilution-derived coronary flow reserve (CFR) and IMR were measured using a pressure-temperature sensor-tipped guidewire. Brachial artery FMD was measured using high-resolution, two-dimensional ultrasound images obtained with a Doppler ultrasound device (HDI-ATL 5000, USA) with a 5 MHz to 12 MHz linear-array transducer.ResultsCompared with in control subjects, CFR was significantly lower (2.42 ± 0.78 vs. 3.59 ± 0.79, p < 0.001); IMR was higher (32.2 ± 8.0 vs. 19.5 ± 5.5, p < 0.001); the concentration of hs-CRP and FMD was higher (4.75 ± 1.62 vs. 2.75 ± 1.50; 5.24 ± 2.41 vs. 8.57 ± 2.46, p < 0.001) in CSX patients. The Duke treadmill score (DTS) was correlated positively to CFR and FMD (0.489 and 0.661, p < 0.001), it was negative to IMR and hsCRP (-0.761 and -0.087, p < 0.001) in CSX patients.ConclusionsThe main finding in this study is that the DTS measured in patients with CSX was associated to hsCRP and FMD. Moreover, the independent effects of exercise tolerance can significantly impair FMD and hsCRP in CSX patients; especially it is particularly important to whom where FMD was associated negatively with IMR.

Combination of the Thermodilution-Derived Index of Microcirculatory Resistance and Coronary Flow Reserve Is Highly Predictive of Microvascular Obstruction on Cardiac Magnetic Resonance Imaging After ST-Segment Elevation Myocardial Infarction.

The aim of this study was to investigate the predictive accuracy of invasive coronary microvascular indexes for identifying microvascular obstruction (MVO) on cardiac magnetic resonance imaging (CMR) in patients treated with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). We hypothesized that a combination of the index of microcirculatory resistance (IMR) and the thermodilution-derived coronary flow reserve (CFRthermo) will enhance the predictive accuracy of detecting MVO compared with either index alone. The IMR and CFRthermo were measured using a single pressure sensor/thermistor-tipped guidewire in 40STEMI patients immediately after PCI and related to MVO assessed by CMR day 7. The primary endpoint was the predictive accuracy of the IMR for detecting MVO. Patients with an IMR >36 (upper tertile) had a higher rate of MVO compared with those with an IMR≤36 (93% vs. 39%; p= 0.001). MVO occurred in all patients with an IMR >36 and a CFRthermo≤1.7 and in no patients with an IMR≤36 and a CFRthermo >1.7. The IMR remained an independent predictor of MVO (odds ratio: 1.212, 95% confidence interval [CI]: 1.004 to 1.464; p= 0.045) after adjustment for age, creatine kinase-myocardial band, myocardial blush grade, thrombus burden, and CFRthermo. Both the IMR (area under the curve, 0.868, 95% CI: 0.719 to 0.956; p= 0.001) and the CFRthermo (area under the curve, 0.706, 95% CI: 0.536 to 0.842; p= 0.03) were predictive of MVO. Combined IMR and CFRthermo increased the area under the curve for MVO to 0.941. In patients who underwent primary PCI for STEMI, an increased IMR has an independent predictive value for MVO detection, and combined high IMR and low CFRthermo are highly predictive of MVO. These indexes could be used to further risk-stratify patients and guide regional and systemic therapies.

Thermodilutional Confirmation of Coronary Microvascular Dysfunction in Patients With Recurrent Angina After Successful Percutaneous Coronary Intervention

BackgroundRecurrent angina (RA) after percutaneous coronary intervention (PCI) remains a challenging problem that confronts cardiologists in routine clinical practice. In patients without epicardial coronary causes, RA is commonly speculated as resulting from coronary microvascular dysfunction. The aim of this study was to investigate the coronary microvascular function in patients with RA late after successful PCI and without epicardial stenosis at the time of repeat angiography. MethodsWe studied 39 consecutive patients with RA in whom PCI was successfully performed 6 to 12 months previously because of angina and single-vessel disease and without restenosis and disease progression at the time of repeat angiography. Twelve subjects without RA were recruited as the control group. Thermodilution-derived coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured using a pressure-temperature sensor-tipped coronary wire. The exercise treadmill test was performed according to the Bruce protocol. ResultsPatients with RA showed significantly higher IMR and lower CFR than control subjects, in the target arteries and in the reference vessels (P < 0.05). The hyperemic IMR was more remarkably increased in the target arteries than in the reference vessels (29.3 ± 11.7 vs 24.4 ± 9.7; P = 0.008). The hyperemic IMR was increased and the CFR was impaired more significantly in patients with a positive exercise treadmill test (P < 0.05). ConclusionsUsing an intracoronary thermodilution method, to our knowledge, we have for the first time confirmed that, in patients who underwent successful coronary stenting and without epicardial stenosis at repeat angiography late after PCI, coronary microvascular dysfunction was responsible for the RA.

Thermodilution-Derived Coronary Microvascular Resistance and Flow Reserve in Patients With Cardiac Syndrome X

Although increased coronary microvascular resistance (CMR), resulting in coronary microvascular dysfunction, is speculated to be responsible for myocardial ischemia in patients with cardiac syndrome X (CSX), it has never been directly demonstrated, and the correlation between CMR and severity of myocardial ischemia has not been elucidated in this setting. This study aimed to ascertain the increased CMR directly and to explore the relationship between CMR and severity of ischemia in patients with CSX. We studied 18 patients with CSX and 18 age- and sex-matched control subjects. Thermodilution-derived coronary flow reserve and index of microvascular resistance were measured using a pressure-temperature sensor-tipped coronary wire. Exercise treadmill test was performed by the Bruce protocol for calculating Duke treadmill score. Coronary flow reserve was significantly lower (2.37±0.81 versus 3.68±0.72; P<0.001) and index of microvascular resistance was higher (33.1±7.9 versus 18.8±5.6 U; P<0.001) in patients with CSX compared with those in control subjects. The Duke treadmill score was correlated positively to coronary flow reserve (r=0.539; P=0.021) and negatively to index of microvascular resistance (r=-0.742; P<0.001) in patients with CSX. Using an intracoronary thermodilution method, we for the first time directly demonstrated an increased microvascular resistance in patients with CSX. Furthermore, severity of ischemia was found to be intimately associated with CMR in this setting.

TCT-472 Prognosis of Patients Presenting with Non ST-Segment Elevation Myocardial Infarction and Non-obstructive Coronary Artery Disease: Propensity Score Matched Cohort from the ACUITY Trial

Methods: 41consecutive patients (38 men and 3 women; age 52 � 9 years) with anterior STEMI were enrolled. All patients were randomized into two groups and underwent primary PCI for anterior STEMI: stenting after manual thrombectomy (aspiration group, n�22) and stenting without manual thrombectomy (conventional group, n�19). The thermodilution-derived coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured by using the pressure-temperature sensor-tipped coronary wire at the left anterior descending artery (LAD) after primary PCI. Baseline echocardiography was performed before discharge and follow-up echocardiography was performed 6 months later. Results: There was no significant difference in reperfusion time (onset to balloon time) and CFR (2.01 � 1.1 vs. 2.08 � 1.1, p � 0.831), baseline ejection fraction (EF, 44.5 � 7.5% vs. 48.0 � 8.0%, p � 0.15), baseline wall motion score index (WMSI, 1.52 � 0.32 vs. 1.46 � 0.31, p � 0.59) between two groups. But, there was significant difference in IMR (22.3 � 8.7 vs. 29.5 � 11.9, p � 0.037), �EF (follow up EF ‐ baseline EF, 5.86 � 7.2 vs. 1.29 � 2.5, p � 0.011), �WMSI (baseline WMSI ‐ follow up WMSI, �0.199 � 0.242 vs. 0.003 � 0.075, p � 0.001) between two groups. Conclusions: Compared with conventional PCI, manual thrombectomy before stenting for patients with anterior STEMI seems to preserve microvascular integrity. Manual thrombectomy as an adjunctive method of primary PCI for acute anterior STEMI might have beneficial efficacy on myocardial microcirculation.

Increased basal coronary blood flow as a cause of reduced coronary flow reserve in diabetic patients

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (T(mn)); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic T(mn). We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4-3.2) vs. 4.1 (2.7-4.4); P = 0.02]. Basal T(mn) was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25-0.71) vs. 0.64 (0.50-1.17); P = 0.04], while hyperemic T(mn) and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index (r(2) = 0.35; P = 0.0005) and between basal T(mn) and the HOMA index (r(2) = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.

Intracoronary Autologous Bone Marrow−Derived Mononuclear Cell Transplantation Improves Coronary Collateral Vessel Formation and Recruitment Capacity in Patients With Ischemic Cardiomyopathy: A Combined Hemodynamic and Scintigraphic Approach

This study investigated the effects of intracoronary autologous bone marrow-derived mononuclear cell (BMC) transplantation on coronary microcirculation. Fifteen patients with ischemic cardiomyopathy were treated by intracoronary infusion of BMCs via the patent infarct-related artery. The thermodilution-derived coronary flow reserve, index of microvascular resistance, pressure-derived collateral flow index, and coronary wedge pressure were measured at baseline and at 6 months. Successive balloon inflations during BMC transplantation were performed to observe the recruitment in pressure-derived collateral flow index and coronary wedge pressure, and the percentage changes between baseline and 6 months were calculated. The mean (SD) coronary flow reserve increased from 1.3 (0.4) to 2.1 (0.5), and the mean (SD) index of microvascular resistance decreased from 44.9 (24.4) to 21.2 (14.1) (P = .001 for both). The mean (SD) improvement in pressure-derived collateral flow index (from 0.14 [0.05] to 0.22 [0.08]) was also statistically significant (P = .001). Similarly, the percentage improvements in pressure-derived collateral flow index and coronary wedge pressure were statistically significant (P = .01 for both). The percentage improvement in perfusion assessed by single-photon emission computed tomography strongly correlated with the percentage changes in pressure-derived collateral flow index (r = 0.88, P = .001) and coronary wedge pressure (r = 0.69, P = .01). These results demonstrate for the first time (to our knowledge) that intracoronary autologous BMC transplantation improves coronary collateral vessel formation and recruitment capacity in human subjects.