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William F Fearon - One of the best experts on this subject based on the ideXlab platform.

  • assessing the Coronary microcirculation in patients after primary percutaneous Coronary intervention
    Journal of the American Heart Association, 2018
    Co-Authors: A Yong, William F Fearon
    Abstract:

    The primary management goal in patients with ST‐elevation myocardial infarction (STEMI) is to restore blood flow to the myocardium subtended by the occluded epicardial artery using pharmacologic and mechanical means. However, despite contemporary approaches with primary percutaneous Coronary intervention (PCI) and subsequent medical therapy, the morbidity and mortality of patients with STEMI have not changed significantly over recent years.1 Moreover, 10% to 20% of patients who survive to 5 years after STEMI will develop heart failure.2 There is therefore a need to develop and validate methods that can identify patients early who are at risk of subsequent adverse events that might be reduced by targeted adjunctive therapies. Microvascular impairment at the time of STEMI is an important determinant of subsequent prognosis. Cardiac magnetic resonance imaging (CMR) is considered to be the criterion standard for assessing the Coronary microcirculation. Microvascular obstruction on CMR is a strong predictor of subsequent cardiovascular events even after controlling for infarct size, and may even be a more potent prognostic marker than patency status of the culprit epicardial artery.3 However, it is currently not realistic to incorporate CMR into the routine care of patients with STEMI. Angiographic methods for assessing microvascular dysfunction in the cardiac catheterization laboratory at the time of STEMI include Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI frame count, and TIMI myocardial perfusion grade.4 In a study of 456 patients with STEMI undergoing primary PCI, 50% of patients had evidence of impaired myocardial blush grade after reopening of the epicardial artery,5 and patients with abnormal blush grade had a 3‐fold increase in 1‐year mortality. However, these methods are qualitative, not very reproducible outside of core laboratories, and difficult to apply to an individual patient. More recently, Coronary wire‐based methods such as the index of microcirculatory resistance (IMR) have been developed to interrogate the Coronary microcirculation. The IMR is measured using a 0.014‐inch pressure–temperature sensor guidewire and represents the minimal Coronary microcirculatory resistance of the myocardial territory being interrogated.6 To measure IMR, 3 mL of room temperature saline is injected down the Coronary artery during maximal hyperemia. A thermodilution curve is created after each injection by the temperature change, which allows quantification of the mean transit time, which is inversely proportional to Coronary flow. The distal Coronary pressure is measured simultaneously with the same wire and when divided by the inverse of the mean transit time, IMR is calculated. IMR is more quantitative and reproducible than angiographic parameters and easier to obtain in the acute setting than CMR. IMR corresponds with the extent of Coronary Microvasculature disruption in humans,6 and is stable and reproducible in the presence of varying hemodynamic conditions.7 In earlier studies, IMR measured immediately after primary PCI correlated with myocardial infarct size as measured by peak creatine kinase, whereas other less quantitative or specific measures of the microcirculation (including TIMI myocardial perfusion grade, TIMI frame count, Coronary flow reserve, and ST‐segment resolution) did not.8 An IMR >32 U has also been associated with worse wall motion score on echocardiogram 3 months post STEMI. IMR after primary PCI has a strong inverse relationship with myocardial viability, as assessed by fluorine‐18 fluorodeoxyglucose positron emission tomography9 and predicts infarct size, left ventricular ejection fraction, myocardial salvage, and the presence and extent of microvascular obstruction and myocardial hemorrhage as determined by CMR.10 In a multicenter study involving 253 patients with STEMI treated with primary PCI and with a median follow‐up of 2.8 years, it was found that an IMR >31 was an independent predictor of death or rehospitalization, and an IMR >40 was an independent predictor of death. In this issue of the Journal of the American Heart Association, Yew and colleagues undertook an elegant study by following 278 patients with STEMI and treated with primary PCI who underwent measures of microcirculatory function including IMR and TIMI blush grade, and compared these with the waveform of the thermodilution curves created when measuring IMR with respect to their ability to predict CMR‐determined myocardial hemorrhage and microvascular obstruction, as well as subsequent death or heart failure.11 The median follow‐up was a little over 4 years. The current study corroborated the findings of a previous smaller study involving 88 patients, which demonstrated that abnormal thermodilution wave morphology was associated with microvascular impairment, as assessed by IMR and CMR, and was predictive of subsequent adverse clinical outcome.12 The current study is considerably larger and had a significantly longer follow‐up period compared with its predecessor, and serves as an important validation of the previous results. The comprehensive multivariable analysis using several different models demonstrated that infarct size, as assessed by CMR, was the best predictor of clinical outcome. However, when considering a method that can be used in the cardiac catheterization laboratory, either a bimodal waveform of the thermodilution curve or IMR could be used to predict poor prognosis. A bimodal thermodilution waveform was associated with very high IMR (median 54, interquartile range 32–101). It is therefore not surprising that the bimodal waveform was a stronger predictor when included in the model with IMR >40 to predict death or heart failure, as it is likely to reflect greater microcirculatory disruption. Only 13% of patients had a bimodal waveform, potentially limiting its use as a clinical target. The strengths of this study include its large size, reasonably long follow‐up, and clinical outcome data. In addition, it provides support for an adjunctive method in the catheterization laboratory beyond IMR alone for further discriminating patients at risk for adverse outcome after successful primary PCI. There are a few limitations in the current study that are worth noting. First, the study originated from a single center and thermodilution wave morphology was analyzed by experienced analysts. It therefore remains uncertain whether accurate discrimination between the different waveforms can be achieved by other less experienced centers. In addition, it is not clear how to classify a patient if 1 of the 3 waveforms is bimodal, but the others are not. Second, the mechanism underlying waveform abnormalities such as the bimodal pattern remains unexplained. Last, the authors did not present data such as symptom to reperfusion or “door to balloon” time, and these factors could have interacted with the measures of microcirculatory disruption. This article adds to the growing evidence that assessment of the Coronary microcirculation after primary PCI can identify an at‐risk population that could be the target of additional treatments. Several adjunctive therapies have been investigated in an attempt to improve STEMI outcomes but have had disappointing results. However, a small study by Sezer et al reported that patients randomized to receive low‐dose intraCoronary thrombolysis after primary PCI had improved microvascular reperfusion, as indicated by lower IMR values, than those randomized to placebo.13 Moreover, the authors of the current study will soon report the results of a randomized clinical trial investigating the effect of intraCoronary alteplase on CMR and invasive Coronary physiology surrogate markers (T‐TIME http://ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02257294","term_id":"NCT02257294"}}NCT02257294). In addition, a clinical trial randomizing patients with IMR >32 to a low‐dose intraCoronary thrombolytic or to placebo with clinical outcome end points is currently under way (RESTORE‐MI http://anzctr.org.au identifier ACTRN12618000778280). Hopefully, with readily obtainable markers such as IMR and Coronary thermodilution waveform analysis and validation of adjunctive methods to improve myocardial reperfusion beyond primary PCI, patients with STEMI can enjoy improved long‐term outcomes.

  • response by kobayashi et al to letter regarding article three vessel assessment of Coronary microvascular dysfunction in patients with clinical suspicion of ischemia prospective observation study with the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2018
    Co-Authors: Yuhei Kobayashi, William F Fearon, Takeshi Nishi, Dong Hyun Choi, Frederik M Zimmermann, Ji Hyun Jung, Eunseok Shin
    Abstract:

    We thank Dr. Smilowitz for his interest in our study.1 In previous studies examining the invasive assessment of the Coronary Microvasculature, the left anterior descending artery was selected for practical purposes, either because it was the culprit vessel in an acute Coronary syndrome or because the anterior wall was felt to be the most important territory.2 As shown in the present study, we do not advocate interrogating only the left anterior descending artery because Coronary microvascular dysfunction may occur in …

  • invasive assessment of the Coronary Microvasculature the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: William F Fearon, Yuhei Kobayashi
    Abstract:

    Traditionally, invasive Coronary physiological assessment has focused on the epicardial Coronary artery. More recently, appreciation of the importance of the Coronary Microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived Coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the Microvasculature but interrogates the entire Coronary circulation. The index of microcirculatory resistance—a thermodilution-derived measure of the minimum achievable microvascular resistance—is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial Coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment–elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive Coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the Microvasculature in clinical trials.

  • invasive assessment of the Coronary Microvasculature the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: William F Fearon, Yuhei Kobayashi
    Abstract:

    Traditionally, invasive Coronary physiological assessment has focused on the epicardial Coronary artery. More recently, appreciation of the importance of the Coronary Microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived Coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the Microvasculature but interrogates the entire Coronary circulation. The index of microcirculatory resistance-a thermodilution-derived measure of the minimum achievable microvascular resistance-is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial Coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment-elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive Coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the Microvasculature in clinical trials.

  • three vessel assessment of Coronary microvascular dysfunction in patients with clinical suspicion of ischemia prospective observational study with the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: Yuhei Kobayashi, William F Fearon, Takeshi Nishi, Dong Hyun Choi, Frederik M Zimmermann, Ji Hyun Jung, Eunseok Shin
    Abstract:

    Background— Difficulty directly visualizing the Coronary Microvasculature as opposed to the epicardial Coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major Coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR. Methods and Results— Ninety-three patients who underwent Coronary physiological assessment in all 3 major Coronary vessels were prospectively enrolled (59.8±9.4 years with 77.4% men). IMR was corrected using Yong’s formula and Coronary microvascular dysfunction (CMD) was defined using vessel-specific cutoffs. A global IMR was calculated as the sum of the IMR in all 3 major epicardial vessels. Angiographic epicardial disease severity was assessed with vessel-specific and overall SYNTAX score. Median IMR and fractional flow reserve was 17.2 (Q1–Q3: 13.3–22.9) and 0.92 (0.85–0.97). The majority of patients (59.1%) had no CMD, 23.7% had 1-vessel CMD, 14.0% had 2-vessel CMD, and 3.2% had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major Coronary vessels (left anterior descending Coronary artery 28.0%, left circumflex artery 19.4%, and right Coronary artery 23.7%; P =0.39). Fractional flow reserve had a weak, positive correlation with IMR (ρ=0.16; P P =0.99) and a vessel-specific level (ρ=−0.06; P =0.36). By multivariable ordinal logistic regression analysis, no variable was left as an independent predictor of an abnormal IMR. Conclusions— Clinical factors and epicardial Coronary disease severity are not predictors of the extent of CMD. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Yuhei Kobayashi - One of the best experts on this subject based on the ideXlab platform.

  • response by kobayashi et al to letter regarding article three vessel assessment of Coronary microvascular dysfunction in patients with clinical suspicion of ischemia prospective observation study with the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2018
    Co-Authors: Yuhei Kobayashi, William F Fearon, Takeshi Nishi, Dong Hyun Choi, Frederik M Zimmermann, Ji Hyun Jung, Eunseok Shin
    Abstract:

    We thank Dr. Smilowitz for his interest in our study.1 In previous studies examining the invasive assessment of the Coronary Microvasculature, the left anterior descending artery was selected for practical purposes, either because it was the culprit vessel in an acute Coronary syndrome or because the anterior wall was felt to be the most important territory.2 As shown in the present study, we do not advocate interrogating only the left anterior descending artery because Coronary microvascular dysfunction may occur in …

  • invasive assessment of the Coronary Microvasculature the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: William F Fearon, Yuhei Kobayashi
    Abstract:

    Traditionally, invasive Coronary physiological assessment has focused on the epicardial Coronary artery. More recently, appreciation of the importance of the Coronary Microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived Coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the Microvasculature but interrogates the entire Coronary circulation. The index of microcirculatory resistance—a thermodilution-derived measure of the minimum achievable microvascular resistance—is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial Coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment–elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive Coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the Microvasculature in clinical trials.

  • invasive assessment of the Coronary Microvasculature the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: William F Fearon, Yuhei Kobayashi
    Abstract:

    Traditionally, invasive Coronary physiological assessment has focused on the epicardial Coronary artery. More recently, appreciation of the importance of the Coronary Microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived Coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the Microvasculature but interrogates the entire Coronary circulation. The index of microcirculatory resistance-a thermodilution-derived measure of the minimum achievable microvascular resistance-is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial Coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment-elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive Coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the Microvasculature in clinical trials.

  • three vessel assessment of Coronary microvascular dysfunction in patients with clinical suspicion of ischemia prospective observational study with the index of microcirculatory resistance
    Circulation-cardiovascular Interventions, 2017
    Co-Authors: Yuhei Kobayashi, William F Fearon, Takeshi Nishi, Dong Hyun Choi, Frederik M Zimmermann, Ji Hyun Jung, Eunseok Shin
    Abstract:

    Background— Difficulty directly visualizing the Coronary Microvasculature as opposed to the epicardial Coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major Coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR. Methods and Results— Ninety-three patients who underwent Coronary physiological assessment in all 3 major Coronary vessels were prospectively enrolled (59.8±9.4 years with 77.4% men). IMR was corrected using Yong’s formula and Coronary microvascular dysfunction (CMD) was defined using vessel-specific cutoffs. A global IMR was calculated as the sum of the IMR in all 3 major epicardial vessels. Angiographic epicardial disease severity was assessed with vessel-specific and overall SYNTAX score. Median IMR and fractional flow reserve was 17.2 (Q1–Q3: 13.3–22.9) and 0.92 (0.85–0.97). The majority of patients (59.1%) had no CMD, 23.7% had 1-vessel CMD, 14.0% had 2-vessel CMD, and 3.2% had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major Coronary vessels (left anterior descending Coronary artery 28.0%, left circumflex artery 19.4%, and right Coronary artery 23.7%; P =0.39). Fractional flow reserve had a weak, positive correlation with IMR (ρ=0.16; P P =0.99) and a vessel-specific level (ρ=−0.06; P =0.36). By multivariable ordinal logistic regression analysis, no variable was left as an independent predictor of an abnormal IMR. Conclusions— Clinical factors and epicardial Coronary disease severity are not predictors of the extent of CMD. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01621438.

  • invasive Coronary microcirculation assessment current status of index of microcirculatory resistance
    Japanese Circulation Journal-english Edition, 2014
    Co-Authors: Yuhei Kobayashi, William F Fearon
    Abstract:

    Assessment of the Coronary Microvasculature in the clinical setting is a key issue, given that microvascular dysfunction itself has a predictive value for cardiovascular events. The index of microcirculatory resistance (IMR) is an invasive method of interrogating the Microvasculature and provides further insight into the physiology of cardiovascular diseases. It is simple and readily applicable in the cardiac catheterization laboratory where many patients first present for evaluation of their Coronary circulation. In contrast to other invasive and non-invasive tests, this method is known to be stable and reproducible under various hemodynamics and even in the presence of epicardial Coronary artery stenosis. IMR has been shown to have prognostic value in patients with ST-segment elevation myocardial infarction; therefore it can be a surrogate marker of cardiovascular events. At the same time, it has the potential to be a therapeutic as well as an investigational tool in the physiology of cardiovascular diseases. This review summarizes the development of IMR, tips and tricks for its measurement, and its usefulness in various clinical settings.

Csilla Czimbalmos - One of the best experts on this subject based on the ideXlab platform.

  • in vivo mri and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning postconditioning and remote conditioning in a closed chest porcine model of reperfused acute myocardial infarction importance of microvasculat
    Journal of Translational Medicine, 2017
    Co-Authors: Tamas Baranyai, Zoltan Giricz, Zoltan Varga, Gabor Koncsos, Dominika Lukovic, Andras Makkos, Marta Sarkozy, Noemi Pavo, Andras Jakab, Csilla Czimbalmos
    Abstract:

    Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI‚ may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending Coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. We conclude that IPostC and RIC interventions may protect the Coronary Microvasculature even without reducing myocardial necrosis.

Pamela A Lucchesi - One of the best experts on this subject based on the ideXlab platform.

  • the angiotensin receptor blocker losartan reduces Coronary arteriole remodeling in type 2 diabetic mice
    Vascular Pharmacology, 2016
    Co-Authors: Kathryn E Husarek, Paige S Katz, Aaron J Trask, Maarten L Galantowicz, Mary J Cismowski, Pamela A Lucchesi
    Abstract:

    Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on Coronary microvascular structural remodeling. The renin–angiotensin–aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies Coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that Coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and Coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved Coronary flow reserve. Our data suggest that Ang II–AT1R signaling mediates, at least in part, Coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the Coronary Microvasculature in T2DM may help reduce cardiac ischemic events.

Kenshi Fujii - One of the best experts on this subject based on the ideXlab platform.

  • alternation in the Coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction
    Circulation, 1996
    Co-Authors: Katsuomi Iwakura, Shin Takiuchi, Yoshiaki Taniyama, Yoshiaki Nakatsuchi, Shinji Negoro, Yorihiko Higashino, Atsunori Okamura, Tohru Masuyama, Masatsugu Hori, Kenshi Fujii
    Abstract:

    Background Experimental and clinical evidence indicates that myocardial ischemia often damages the Coronary Microvasculature (“no-reflow” phenomenon). In this study, we examined the effect of this phenomenon on the Coronary blood flow velocity pattern in patients with reperfused acute myocardial infarction. Methods and Results We measured Coronary blood flow velocity after Coronary angioplasty in 42 patients with acute myocardial infarction using a Doppler guidewire. Myocardial contrast echocardiography (MCE) was also performed before and after angioplasty. Thirty-one patients showed good contrast reperfusion (MCE reflow), whereas the other 11 showed no reflow (MCE no reflow). Peak velocity and duration of systolic Coronary flow were significantly less in patients with MCE no reflow than in those with MCE reflow (8±4 versus 17±10 cm/s and 207±79 versus 289±55 ms, respectively; P<.01). Early systolic retrograde flow was frequently observed in patients with MCE no reflow, whereas it was observed in only 1 p...