Angina pectoris with non-obstructive coronary arteries (ANOCA) is a prevalent condition, particularly affecting women, and is often associated with coronary microvascular dysfunction (CMD). CMD, the primary cause of ANOCA, is associated with a diminished quality of life and adverse clinical outcomes. Invasive coronary function testing (CFT) now provides a precise diagnosis of CMD through indices such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR), assessed using the bolus thermodilution technique. This comprehensive review outlines a systematic approach to evaluating CMD, emphasizing practical steps and troubleshooting strategies to ensure accurate measurements of CFR and IMR. CMD phenotypes, including structural, functional, and compensated CMD, are discussed, along with their distinct pathophysiological mechanisms. Common challenges encountered during CMD testing, such as improper guide or wire positioning, waveform artifacts, and injection errors, are addressed with practical solutions. While continuous thermodilution offers enhanced accuracy, bolus thermodilution remains cost-effective and widely utilized. Proficiency in the intricacies of CMD testing is crucial for accurate diagnosis and management, ultimately enhancing clinical outcomes for this underrecognized patient population.

Literature reports a 20 % discordance between hyperemic (FFR) and non-hyperemic indexes (NHi) of coronary stenosis lesions. This work aims to develop and test clinically, a formula relating FFR and NHi (including iFR, RFR and Pd/Pa) to study their discordance.

We conducted a prospective, single-center, clinical study enrolling all patients undergoing full coronary physiology assessment with Coroventis CoroFlow Cardiovascular System (Abbott Vascular, St. Paul, Minnesota) to validate the developed formula: [Formula: see text] where IMR(BMR) is the hyperemic (basal) microvascular resistance and HSR(BSR) is the hyperemic (basal) stenosis resistance.

A total of 51 patients were enrolled, 72 % male, average age 67.4 ± 8.9. Mean hemodynamic data were: FFR 0.87 ± 0.07, iFR 0.93 ± 0.05, RFR 0.91 ± 0.05, Pd/Pa 0.92 ± 0.05, BMR 76.6 ± 51.6 mmHg*s, IMR 28.4 ± 22.8 mmHg*s, BSR 5.5 ± 4.7 mmHg, HSR 3.8 ± 2.9 mmHg*s, coronary flow reserve (CFR) 2.9 ± 1.6, resistive reserve ratio (RRR) 3.3 ± 2.0. Lin's Concordance and Bland Altman analysis showed an optimal correlation between measured and estimated data. Sensitivity analysis showed that: (1) FFR can underestimate epicardial stenosis severity leading to FFR- vs NHi + discordance in case of elevated IMR, (2) NHi can overestimate epicardial stenosis severity leading to FFR- vs NHi + in the case of low BMR, (3) if BSR > HSR, FFR- vs NHi + discordance can occur, while if BSR < HSR, FFR+ vs NHi- discordance can occur.

(1) NHi can be more reliable in case of elevated IMR; (2) FFR-CFR combination can be more reliable for low BMR occurring to compensate an epicardial stenosis; (3) NHi-CFR combination can be more reliable when BSR > HSR, while FFR-CFR combination can be more reliable when BSR < HSR. The combination between pressure and flow indexes (FFR-CFR or NHi-CFR) is more reliable when compensatory mechanisms occur.

Impaired microcirculatory function after heart transplantation is associated with increased risk for acute cellular rejection. Microvascular resistance reserve (MRR) is a novel index for assessing microcirculatory function, irrespective of epicardial coronary artery stenosis, but it has not been validated in transplanted hearts.

The aim of this study was to investigate the prognostic impact of MRR in heart transplantation.

The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. Coronary microcirculatory dysfunction was defined as MRR ≤3.0. Elevated microcirculatory resistance was defined as an index of microcirculatory resistance ≥15. The presence of epicardial coronary stenosis was assessed by fractional flow reserve. The primary outcome was a composite of death or biopsy-proven acute cellular rejection of grade ≥ 2R after transplantation.

Among the total patients, 22.1% (34 of 154) had impaired microcirculatory function (MRR ≤3.0), and 77.9% (122 of 154) had preserved microcirculatory function (MRR >3.0). During median follow-up of 730 days (Q1-Q3: 730-730 days), patients with MRR ≤3.0 showed increased risk for a composite of death or acute cellular rejection (adjusted HR: 5.31; 95% CI: 2.65-10.64; P < 0.001), acute cellular rejection (adjusted HR: 4.83; 95% CI: 2.20-10.60; P < 0.001), and death (adjusted HR: 5.19; 95% CI: 1.24-21.62; P = 0.024). MRR was significantly associated with increased risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis (HR adjusted for fractional flow reserve: 1.89 per 1-U decrease in MRR; 95% CI: 1.46-2.46; P < 0.001) or elevated microcirculatory resistance (HR adjusted for index of microcirculatory resistance: 1.90 per 1-U decrease in MRR; 95% CI: 1.43-2.52; P < 0.001).

Impaired microcirculatory function, determined by MRR early after heart transplantation, identified patients at high risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis or elevated microcirculatory resistance. (Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731).

Coronary microvascular dysfunction (CMD) is an important clinical disease spectrum which has gained widespread attention due to chronic anginal symptoms, and worse clinical outcomes, with or without obstructive coronary artery disease (CAD). Coronary microcirculatory dysfunction is due to a wide array of mechanisms such as inflammation, platelet aggregation, vessel wall collagen deposition, imbalance of nitric oxide, free radicals, and sympathetic/parasympathetic simulation. As noted in this supplement, CMD can occur as a primary disease or co-exist with multi-array of diverse cardiac conditions such as CAD (old infarct), hypertrophic cardiomyopathy, Takotsubo cardiomyopathy, hypertension, or infiltrative diseases. CMD, which is often under diagnosed, leads to increase in medical expenses, decrease in quality of life, exacerbation of underlying conditions such as heart failure and even increased mortality. CMD presents a challenge for patients as well as physicians to manage. Here, we review CMD and focus on its endotypes, techniques for microcirculatory assessment, associated tips and tricks and available treatment options.

In this review article, we provide an overview of the definition and application of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), coronary flow reserve (CFR), and index of microvascular resistance (IMR) in the diagnosis, prognosis, and management of coronary microvascular dysfunction. We discuss their respective limitations as it relates to microvascular dysfunction. In each section, we review the most recent evidence supporting their use in microvascular and epicardial coronary artery disease. We also highlight specific clinical conditions with emerging indications for the use of these indices, including in the setting of microvascular dysfunction due to acute myocardial infarction, heart failure with preserved ejection fraction, and post-cardiac transplant.

Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) obtained through coronary bolus thermodilution are used to assess and treat patients with angina and no obstructive coronary artery disease. Previous studies demonstrate comparable results assessing epicardial ischemia by fractional flow reserve using intravenous (IV) or intracoronary (IC) adenosine. It is unknown if there is a similarity between IC and IV hyperemia with adenosine when performing coronary reactivity testing (CRT). We reviewed CRT data and baseline demographics in a cohort of patients who underwent CRT for ischemia and no obstructive coronary artery disease. We evaluated CFR and IMR in patients whereby maximal hyperemia was obtained by both IC and IV means using linear regression, one-way analysis of variance, Wilcoxon, and Bland-Altman analysis. We assessed 62 patients with a median age of 60.5 years (50 to 67), and 72% were females. The average CFR with IC adenosine was 3.12 (2.31 to 4.06) and 2.71 (2.0 to 3.88) with IV adenosine, with an R2 value of 0.50 (p <0.0001). The average IMR with IC adenosine was 28.23 (16.24 to 50.72) and 22.27 (14.79 to 37.0) with IV adenosine, with an R2 value of 0.33 (p <0.0001). Average intra-method variability between IC and IV adenosine was nonsignificant (p = 0.31 for CFR and p = 0.55 for IMR). Bland-Altman analysis showed reasonable agreement between IV and IC adenosine for CFR and IMR with slightly higher values using IC adenosine. Therefore, in CRT with bolus thermodilution, CFR and IMR values obtained with IC adenosine correlate well with those obtained with IV adenosine. This presents a potential alternative to IV adenosine for bolus thermodilution CRT.

This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool.

In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90 mg twice daily, n = 184) or clopidogrel (75 mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up.

Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039).

The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www.

gov (NCT05978726).

Coronary microvascular dysfunction (CMD) after percutaneous coronary intervention (PCI) is prognostically important and may also be a cause of persistent angina. The stent balloon inflation technique or material properties may influence the degree of CMD post-PCI.

Thirty-six patients with stable angina attending for elective PCI were randomized to either slow drug eluting stent (DES) implantation technique (DES slow group): +2 atm. every 5 s., maintained for a further 30 s or a standard stent implantation technique (DES std group): rapid inflation and deflation. PressureWire X with thermodilution at rest and hyperemia and optical coherence tomography (OCT) were performed pre- and post-PCI. Combined primary endpoints were changes in index of microvascular resistance (delta IMR) and coronary flow reserve (delta CFR) following PCI. The secondary endpoints included differences in cardiac troponin I (delta cTnI) at 6 h post-PCI, Seattle angina questionnaire (SAQ) at 1, 3, 6, and 12 months and OCT measures of stent results immediately post-PCI and at 3 months.

Both groups were well matched, with similar baseline characteristics and OCT-defined plaque characteristics. Delta IMR was significantly better in the DES slow PCI arm with a median difference of -4.14 (95% CI -10.49, -0.39, p = 0.04). Delta CFR was also numerically higher with a median difference of 0.47 (95% CI -0.52, 1.31, p = 0.46). This did not translate to improved delta median cTnI (1.5 (34.8) vs. 0 (27.5) ng/L, p = 0.75) or median SAQ score at 3 months, (85 (20) vs. 95 (17.5), p = 0.47).

Slow stent implantation is associated with less CMD after elective PCI in patients with stable angina.

Coronary artery disease represents a global health challenge. Accurate diagnosis and evaluation of hemodynamic parameters are crucial for optimizing patient management and outcomes. Nowadays a wide range of both non-invasive and invasive methods are available to assess the hemodynamic impact of both epicardial coronary stenosis and vasomotor disorders. In fact, over the years, important developments have reshaped the nature of both invasive and non-invasive diagnostic techniques, and the future holds promises for further innovation and integration. Non-invasive techniques have progressively evolved and currently a broad spectrum of methods are available, from cardiac magnetic resonance imaging with pharmacological stress and coronary computed tomography (CT) to the newer application of FFR-CT and perfusion CT. Invasive methods, on the contrary, have developed to a full-physiology approach, able not only to identify functionally significant lesions but also to evaluate microcirculation and vasospastic disease. The aim of this review is to summarize the current state-of-the-art of invasive and non-invasive hemodynamic assessment for CAD management.

Stentablation (SA) has been used as a bailout method for undilated, under-expanded stents, but one reason that SA is associated with a high rate of major adverse cardiac events may be its adverse effect on microcirculation. Consequently, appropriate lesion preparation should always be considered for heavily calcified lesions to avoid such complications.

Under-expansion of the coronary stent is associated with increased rates of in-stent restenosis and thrombosis. Stentablation (SA) with rotational atherectomy is used in the treatment of undilatable, under-expanded coronary stents; however, its effect on coronary microcirculatory function remains unclear. This novel report compares microcirculation indices before and after SA.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined.

This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR.

This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated.

The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable.

The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297).

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF).

The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements.

In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months.

In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ± 0.8 vs. 3.2 ± 0.8; P  < 0.001 and MFR 2.5 ± 0.8 vs. 3.4 ± 1.1; P  = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ± 0.20 vs. 0.91 ± 0.06 vs. 0.91 ± 0.07; P  < 0.001; CFR 2.4 ± 1.2 vs. 3.6 ± 1.9 vs. 3.6 ± 1.9; P  < 0.001, whereas IMR did not change significantly: 30.3 ± 22.9 vs. 30.1 ± 25.3 vs. 31.9 ± 25.2; P  = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r  = 0.732; P  < 0.001) and an increase in MFR ( r  = 0.499; P  = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r  = -0.616; P  = 0.004).

Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction.

The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events.

The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

Objective The index of microvascular resistance (IMR) is an invasive method for quantifying the coronary microvasculature independent of the presence and degree of epicardial stenosis during cardiac catheterization, whereas the Selvester QRS score, which is related to myocardial damage, is a relatively simple and non-invasive measurement procedure. We investigated the relationship between the QRS score and coronary microvascular dysfunction (CMD) assessed via IMR. Methods Data from 74 patients who underwent invasive coronary physiological measurements were retrospectively reviewed. Using a coronary wire, we measured IMR by the hyperemic mean transit time and distal coronary pressure. We also determined a simplified QRS score following the Selvester QRS score criteria by 12-lead electrocardiography. After determining the best cutoff value for the QRS score to predict IMR ≥25, which was defined as CMD by the Coronary Vasomotion Disorders International Study Group, patients were categorized into the QRS score ≥3 (n=16) and the QRS score 0-2 (n=58) groups. Results IMR in the QRS score ≥3 group was significantly higher in comparison to the QRS score 0-2 group (31; IQR: 19-57 vs. 20; IQR: 14-29, p<0.01). The percentage of patients with IMR ≥25 in the QRS score ≥3 group was significantly higher than that in the QRS score 0-2 group (69% vs. 34%, p=0.01). Conclusion A higher QRS score was associated with CMD, as estimated by IMR. The Selvester QRS score is noninvasive parameter that is potentially useful for predicting CMD.

Microvascular resistance (MR) has prognostic value in acute and chronic coronary syndromes following percutaneous coronary intervention (PCI), however anatomic and physiologic determinants of the relative changes of MR and its association to target vessel failure (TVF) has not been investigated previously. This study aims to evaluate the association between changes in MR and TVF.

This is a sub-study of the Inclusive Invasive Physiological Assessment in Angina Syndromes (ILIAS) registry which is a global multi-centre initiative pooling lesion-level coronary pressure and flow data.

Paired pre-post PCI haemodynamic data were available in n = 295 vessels out of n = 828 PCI treated patients and of these paired data on MR was present in n = 155 vessels. Vessels were divided according to increase vs. decrease % in microvascular resistance following PCI (ΔMR % ≤ 0 vs. ΔMR > 0%). Decreased microvascular resistance ΔMR % ≤ 0 occurred in vessels with lower pre-PCI fractional flow reserve (0.67 ± 0.15 vs. 0.72 ± 0.09 p = 0.051), coronary flow reserve (1.9 ± 0.8 vs. 2.6 ± 1.8 p < 0.0001) and higher hyperemic microvascular resistance (2.76 ± 1.3 vs. 1.62 ± 0.74 p = 0.001) and index of microvascular resistance (24.4 IQ (13.8) vs. 15. 8 IQ (13.2) p = 0.004). There was no difference in angiographic parameters between ΔMR % ≤ 0 vs. ΔMR > 0%. In a cox regression model ΔMR % > 0 was associated with increased rate of TVF (hazard ratio 95% CI 3.6 [1.2; 10.3] p = 0.018).

Increased MR post-PCI was associated with lesions of less severe hemodynamic influence at baseline and higher rates of TVF at follow-up.

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.

To assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease.

Patients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment. Rest and dipyridamole-induced stress myocardial blood flow (MBF) and MPR were quantified using 99mTc-SestaMIBI and a CZT camera. Fractional flow reserve (FFR), Thermodilution CFR, and IMR were assessed during ICA.

Between December 2016 and July 2019, 36 patients were included. 25/36 patients presented no obstructive coronary artery disease. A complete functional assessment was performed in 32 arteries. No territory presented a significant ischemia on CZT myocardial perfusion imaging. A moderate yet significant correlation was observed between regional CZT MPR and CFR (r = 0.4, P = .03). Sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT MPR versus the composite invasive criterion (impaired CFR and IMR) were 87 [47% to 99%], 92% [73% to 99%], 78% [47% to 93%], 96% [78% to 99%], and 91% [75% to 98%], respectively. All territories with a regional CZT MPR ≤ 1.8 showed a CFR < 2. Regional CZT MPR values were significantly higher in arteries with CFR ≥ 2 and IMR < 25 (negative composite criterion, n = 14) than in those with CFR < 2 and IMR ≥ 25 (2.6 [2.1 to 3.6] versus 1.6 [1.2 to 1.8]), P < .01).

Regional CZT MPR presented excellent diagnostic performances for the detection of territories with simultaneously impaired CFR and IMR reflecting a very high cardiovascular risk in patients without obstructive coronary artery disease.

In daily clinical practice, physicians often encounter patients with angina or those with evidence of myocardial ischemia from noninvasive tests but not having obstructive coronary artery disease. This type of ischemic heart disease is referred to as ischemia with nonobstructive coronary arteries (INOCA). INOCA patients often suffer from recurrent chest pain without adequate management and are associated with poor clinical outcomes. There are several endotypes of INOCA, and each endotype should be treated based on its specific underlying mechanism. Therefore, identifying INOCA and discriminating its underlying mechanisms are important issues and of clinical interest. Invasive physiologic assessment is the first step in the diagnosis of INOCA and discriminating the underlying mechanism; additional provocation tests help physicians identify the vasospastic component in INOCA patients. Comprehensive information acquired from these invasive tests can provide a template for mechanism-specific management for patients with INOCA.

The landscape of interventional cardiology is ever evolving. Contemporary practice has shifted from a stenosis-centred approach to the total characterisation of both the epicardial and microcirculatory vessels. Microcirculatory dysfunction plays an important role in the pathophysiology of acute and chronic coronary syndromes, and characterisation of the microcirculation has important clinical consequences. Accordingly, the invasive diagnosis of microcirculatory dysfunction is becoming a key feature of the interventional cardiologist's toolkit. This review focuses on the methodology underpinning the invasive diagnosis of microvascular dysfunction and highlights the indices that have arisen from these methodologies.

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 .

Microvascular resistance reserve (MRR) is a new index to assess coronary microvascular (dys)function, which can be easily measured invasively using continuous thermodilution. In contrast to coronary flow reserve (CFR), MRR is independent of epicardial coronary disease and hemodynamic variations. Its measurement is accurate, reproducible, and operator independent.

The aim of this study was to establish the range of normal values for MRR and to determine an optimal cutoff point.

In this exploratory study in 214 patients with angina and no obstructive coronary artery disease, after excluding significant epicardial disease, all physiological parameters, such as fractional flow reserve, index of microvascular resistance, CFR, absolute blood flow, absolute microvascular resistance, and MRR, were measured. On the basis of concordant positive or concordant negative results of index of microvascular resistance and CFR, subgroups of patients were defined with high probability of either normal (n = 122) or abnormal (n = 24) microcirculatory function, and MRR was studied in these groups.

Mean MRR in the "normal" group was 3.4 compared with a mean MRR of 1.9 in the "abnormal" group; these values were significantly different between the groups. MRR >2.7 ruled out coronary microvascular dysfunction (CMD) with a certainty of 96%, whereas MRR <2.1 indicated the presence of CMD with a similar high certainty of 96%.

MRR is a suitable index to distinguish the presence or absence of CMD in patients with angina and no obstructive coronary artery disease. The present data indicate that an MRR of 2.7 virtually excludes the presence of CMD, while an MRR value <2.1 confirms its presence.

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an "adrenergic storm" upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.