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Background: Continuous intracoronary thermodilution with saline allows for the accurate measurement of volumetric blood flow (Q) and absolute microvascular resistance (R μ ). However, this requires repositioning of the temperature sensor by the operator to measure the entry temperature of the saline infusate, denoted as T i ., Aims: We evaluated whether Ti could be predicted based on known parameters without compromising the accuracy of calculated Q. This would significantly simplify the technique and render it completely operator independent., Methods: In a derivation cohort of 371 patients with Q measured both at rest and during hyperaemia, multivariate linear regression was used to derive an equation for the prediction of T i . Agreement between standard Q (calculated with measured T i ) and simplified Q (calculated with predicted T i ) was assessed in a validation cohort of 120 patients that underwent repeat Q measurements. The accuracy of simplified Q was assessed in a second validation cohort of 23 patients with [ 15 O]H 2 O positron emission tomography (PET)-derived Q measurements., Results: Simplified Q exhibited strong agreement with standard Q (r=0.94, confidence interval [CI]: 0.93-0.95; intraclass correlation coefficient [ICC] 0.94, CI: 0.92-0.95; both p<0.001). Simplified Q exhibited excellent agreement with PET-derived Q (r=0.86, CI: 0.75-0.92; ICC=0.84, CI: 0.72-0.91; both p<0.001). Compared with standard Q, there were no statistically significant differences between correlation coefficients (p=0.29) or standard deviations of absolute differences with PET-derived Q (p=0.85)., Conclusions: Predicting T i resulted in an excellent agreement with measured T i for the assessment of coronary blood flow. It significantly simplifies continuous intracoronary thermodilution and renders absolute coronary flow measurements completely operator independent.

Background: In 5%-25% of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients, coronary angiography reveals no obstructive coronary arteries (MINOCA). Coronary microvascular disease (CMD) is a potential causal pathophysiological mechanism in these patients and can be diagnosed by continuous thermodilution assessment. Recently, the microvascular resistance reserve (MRR) has been introduced as a novel index to assess the vasodilatory capacity of the microcirculation. However, continuous thermodilution and MRR have never been investigated in the acute setting in MINOCA patients and invasive assessment of the microcirculation in these patients are currently lacking., Aims: The objectives of the study were to investigate the incidence of CMD (MRR ≤ 2.7) in patients with MINOCA and to evaluate the feasibility and safety of continuous thermodilution-based assessment during index coronary angiography in the acute setting., Methods: This study was a prospective, observational, pilot study investigating coronary physiology in the acute setting in MINOCA patients. Patients admitted with a diagnosis of NSTE-ACS were eligible for inclusion., Results: In total, 19 MINOCA patients were included in this analysis; the mean age was 70 ± 9 years, and 79% were females. CMD was present in 6 patients (32%). Q rest was significantly higher in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (0.076 [0.057-0.100] vs. 0.049 [0.044-0.071] L/min, p = 0.03). R µ,rest was significantly lower in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (1083 [710-1510] vs. 1563 [1298-1970] WU, p = 0.04). No periprocedural complications or hemodynamic instability have occurred during continuous thermodilution assessment during the index coronary angiography., Conclusion: In patients admitted for MINOCA undergoing immediate coronary angiography, continuous thermodilution assessment and MRR are feasible and safe in the acute setting, and evidence of functional CMD could be observed in one-third of the MINOCA patients., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Diagnosing coronary microvascular dysfunction remains challenging, primarily due to the lack of direct measurements of absolute coronary blood flow (Q) and microvascular resistance (R μ ). However, there has been recent progress with the development and validation of continuous intracoronary thermodilution, which offers a simplified and validated approach for clinical use. This technique enables direct quantification of Q and R μ , leading to precise and accurate evaluation of the coronary microcirculation. To ensure consistent and reliable results, it is crucial to follow a standardized protocol when performing continuous intracoronary thermodilution measurements. This document aims to summarize the principles of thermodilution-derived absolute coronary flow measurements and propose a standardized method for conducting these assessments. The proposed standardization serves as a guide to ensure the best practice of the method, enhancing the clinical assessment of the coronary microcirculation., Competing Interests: Funding Support and Author Disclosures Drs Belmonte, Bertolone, and Viscusi are supported by a research grant from the CardioPaTh PhD Program. Dr Pijls has received institutional research grants from Abbott; has consulting relationships with and receives fees from Abbott and Coroventis; has equity in ASML, General Electric, HeartFlow, and Philips; is a member of the Scientific Advisory Board of Heartflow; and has patents pending in the field of the coronary microcirculation and aortic valve stenosis. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and has received speaker fees from Abbott Vascular. Dr Barbato has received speaker fees from Abbott Vascular, Boston Scientific, and GE. Dr Dannab has received grants from Philips, Abbott, and AstraZeneca; and has received consulting fees from Philips. Dr Keeble has received honoraria and institutional research funding from Abbott Vascular, Medtronic, Terumo, Zoll, and Shockwave; has received consulting fees from BD; has received speaker fees from Cardionovum, Abbott Vascular, and AstraZeneca; is on the steering group for the ORBITA-2 trial; and is on the committee for the National Institute for Health and Care Research Invention for Innovation (i4i), British Cardiovascular Intervention Society and Resuscitation Council. Dr Kern is a speaker for Abbott Vascular, Boston Scientific, Acist, Opsens, and Zoll. Dr Fearon has received institutional research support from Abbott, Boston Scientific, and Medtronic; has a consulting relationship with CathWorks and Siemens; and has stock options with HeartFlow. Dr Collet has received research grants from Biosensors, HeartFlow, and Abbott Vascular; and has received consultancy fees from HeartFlow, Abbott Vascular, Boston Scientific, Opsens, and Philips Volcano. Dr De Bruyne has consulting relationships with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; has received research grants from Abbott Vascular, Coroventis Research, Cathworks, and Boston Scientific; and holds minor equities in Philips Volcano, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Opsens, Sanofi, and Celiad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Single-center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute rejection., Objectives: The goal of this study was to validate whether IMR measured early after transplantation can predict subsequent acute rejection and long-term outcome in a large multicenter cohort., Methods: From 5 international cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was acute allograft rejection (AAR) within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE) (the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission) at 10 years., Results: IMR was measured at a median of 7 weeks (interquartile range: 3-10 weeks) post-transplantation. At 1 year, the incidence of AAR was 14.4%. IMR was associated proportionally with the risk of AAR (per increase of 1-U IMR; adjusted hazard ratio [aHR]: 1.04; 95% confidence interval [CI]: 1.02-1.06; p < 0.001). The incidence of AAR in patients with an IMR ≥18 was 23.8%, whereas the incidence of AAR in those with an IMR <18 was 6.3% (aHR: 3.93; 95% CI: 1.77-8.73; P = 0.001). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-U IMR; aHR: 1.02; 95% CI: 1.01-1.04; P = 0.005)., Conclusions: IMR measured early after heart transplantation is associated with subsequent AAR at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized posttransplantation management., Competing Interests: Funding Support and Author Disclosures Dr Angerås has received research grant, speaker fees, and personal fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10 mL/min (rest) and 20 mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r = 0.88; 95% confidence interval: 0.72-0.93; P < 0.001). MRR was independent from the epicardial resistance, the lower the FFR value, the greater the difference between MRR and CFR. Therefore, MRR is proposed as a specific, quantitative, and operator-independent metric to quantify coronary microvascular dysfunction., Competing Interests: Funding Support and Author Disclosures Dr De Bruyne has had a consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; has received research grants from Abbott Vascular, Coroventis Research, Cathworks, and Boston Scientific; and holds minor equities in Philips-Volcano, Siemens, GE Healthcare, Edwards Life Sciences, HeartFlow, Opsens, and Celiad. Dr Pijls has received institutional grants from Abbott Vascular and Hexacath; has served as a consultant for Abbott Vascular, GE, and Opsens; and has minor equities in Philips, GE, ASML, and HeartFlow. Dr Collet has received research grants from Biosensor, GE Healthcare, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and has received consultancy fees from Heart Flow Inc, Opsens, Pie Medical Imaging, Abbott Vascular, and Philips-Volcano. Dr Barbato has received speaker’s fees from Abbott Vascular, Boston Scientific, and GE. Dr Fearon has received institutional research support from Abbott Vascular, Medtronic, and Edwards Lifesciences; has had a consulting relationship with CathWorks; and holds minor stock options with HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Coronary microvascular dysfunction is a highly prevalent condition in both obstructive and nonobstructive coronary artery disease. Intracoronary thermodilution is a promising technique to investigate coronary microvascular (dys)function in vivo and to assess its most important metric: microvascular resistance. Here, the authors provide a practical review of bolus and continuous thermodilution for the measurement of coronary flow and microvascular resistance. The authors describe the basic principles of indicator-dilution theory and of coronary thermodilution and detail the practicalities of their application in the catheterization laboratory. Finally, the authors discuss contemporary clinical applications of coronary thermodilution-based microvascular assessment in humans and future perspectives., Competing Interests: Funding Support and Author Disclosures Drs. Kodeboina, Fournier, Di Gioia, and Sonk are supported by a research grant from CardioPaTh. Dr. Di Gioia is supported by the STAR program of Compagnia di San Paolo. Dr. Collet has received institutional consultancy fees from HeartFlow and Philips Volcano. Dr. van ’t Veer has received speaker fees from Abbott. Dr. Pijls has received institutional research grants from Abbott and Hexacath; has received consultancy fees from Abbott, Opsens, and GE; and holds minor equity positions in Philips, ASML, and HeartFlow. Dr. De Bruyne has received institutional consulting fees from Abbott Vascular, Boston Scientific, Opsens, and Siemens; has received institutional grant support from Abbott Vascular, Boston Scientific, Biotronik, and Medtronic; and holds equity positions in Philips, Siemens, GE, Bayer, HeartFlow, Edwards Lifesciences, and Ceyliad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

During the last two decades, there has been a sharp increase in both interest and knowledge about the coronary microcirculation. Since these small vessels are not visible by the human eye, physiologic measurements should be used to characterize their function. The invasive methods presently used (coronary flow reserve (CFR) and index of microvascular resistance (IMR)) are operator-dependent and mandate the use of adenosine to induce hyperemia. In recent years, a new thermodilution-based method for measurement of absolute coronary blood flow and microvascular resistance has been proposed and initial procedural problems have been overcome. Presently, the technique is easy to perform using the Rayflow infusion catheter and the Coroventis software. The method is accurate, reproducible, and completely operator-independent. This method has been validated noninvasively against the current golden standard for flow assessment: Positron Emission Tomography-Computed Tomography (PET-CT). In addition, absolute flow and resistance measurements have proved to be safe, both periprocedurally and at long-term follow-up. With an increasing number of studies being performed, this method has great potential for better understanding and quantification of microvascular disease., Competing Interests: Nico H. J. Pijls reports institutional grant from Abbott and Hexacath, consulting for Abbott and Opsens, minor equities in Philips, GE, ASML, and Heartflow, and consulting for GE and personal fees for GE. All other authors report no conflicts of interest., (Copyright © 2020 Daniëlle C. J. Keulards et al.)

With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and define severity. A better understanding of the microvasculature in AS could improve clinical care by predicting left ventricular remodeling or anticipate the interplay between epicardial stenosis and myocardial dysfunction. In this review, we combine five decades of literature regarding microvascular, coronary, and aortic valve physiology with emerging insights from newly developed invasive tools for quantifying microcirculatory function. Furthermore, we describe the coupling between microcirculation and epicardial stenosis, which is currently under investigation in several randomized trials enrolling subjects with concomitant AS and coronary disease. To clarify the physiology explained previously, we present two instructive cases with invasive pressure measurements quantifying coexisting valve and coronary stenoses. Finally, we pose open clinical and research questions whose answers would further expand our knowledge of microvascular dysfunction in AS. These trials were registered with NCT03042104, NCT03094143, and NCT02436655., Competing Interests: JMZ reports no support or industry relationships. PALT, NHJP, RLK, KLG, and NPJ have a patent pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology. PALT reports no additional support or industry relationships. NHPJ receives institutional grant support from Abbott, serves as a consultant for Abbott and Opsens, and possesses equity in Philips, GE, ASML, and Heartflow. BDB has received institutional research grants and consulting fees from Abbott Vascular (formerly St. Jude Medical), Boston Scientific, and Opsens. BDB, RLK, KLG, and NPJ have a patent pending on correcting pressure signals from fluid-filled catheters. RLK reports no additional support or industry relationships. KLG is the 510(k) applicant for CFR Quant (K113754) and HeartSee (K143664 and K171303), software packages for cardiac positron emission tomography image processing, analysis, and absolute flow quantification. NPJ receives internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis, has an institutional licensing and consulting agreement with Boston Scientific for the smart minimum FFR algorithm (commercialized under 510(k) K191008), and has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano Corporation (DEFINE-FLOW, NCT02328820), studies using intracoronary pressure and flow sensors., (Copyright © 2020 Jo M. Zelis et al.)

Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short-term follow-up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow-up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow-up ( P <0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow-up ( P =0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow-up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time.

Objectives: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI)., Background: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation., Methods: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months., Results: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01)., Conclusions: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution., (© 2019 Wiley Periodicals, Inc.)

Background: The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans., Methods and Results: Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (ρ=0.841, P <0.001; intraclass correlation coefficient=0.89, P <0.001) and R (ρ=0.780, P <0.001; intraclass correlation coefficient=0.89, P <0.001). In Bland-Altman plots, there was no significant bias or asymmetry., Conclusions: Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation., (© 2018 American Heart Association, Inc.)

Objectives: This work compares the diagnostic performance of adenosine-free coronary pressure wire indices based on lesion location., Background: Several adenosine-free coronary pressure wire indices have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that lesion location and the mass of perfused myocardium may affect diagnostic performance., Methods: A total of 763 patients were prospectively enrolled from 12 institutions. Fractional flow reserve (FFR) and contrast-based FFR (cFFR) were obtained during adenosine-induced maximal hyperemia and contrast-induced submaximal hyperemia respectively, whereas the instantaneous wave-free ratio (iFR) and distal pressure/aortic pressure (Pd/Pa) were obtained at rest. Using an FFR of ≤0.80 as a reference standard, the diagnostic accuracy of each index was compared based on lesion location (left main or proximal left anterior descending artery [LM/pLAD] compared with other lesion locations)., Results: The median FFR, cFFR, iFR, and Pd/Pa were 0.81 (interquartile range [IQR]: 0.74 to 0.87), 0.86 (IQR: 0.79 to 0.91), 0.90 (IQR: 0.85 to 0.94), and 0.92 (IQR: 0.88 to 0.95), respectively. The cFFR, iFR, and Pd/Pa were less accurate in LM/pLAD compared with other lesion locations (cFFR: 80.3% vs. 87.8%; iFR: 73.3% vs. 81.8%; Pd/Pa: 71.4% vs. 81.1%, respectively). By receiver-operating characteristics curve analysis, cFFR provided better diagnostic accuracy than resting indices regardless of lesion location (p ≤0.0001 vs. iFR and Pd/Pa for both groups)., Conclusions: The cFFR, iFR, and Pd/Pa are less accurate in LM/pLAD compared with other lesion locations, likely related to the larger amount of myocardium supplied by LM/pLAD. Nevertheless, cFFR provides the best diagnostic accuracy among the adenosine-free indices, regardless of lesion location., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)