Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris.
ABSTRACT: Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61?±?10 years) who underwent cardiac catheterization for stable coronary artery disease (n?=?10) or acute myocardial infarction (n?=?44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia. Three independent measurements of microvascular function were assessed, using predefined dichotomous thresholds: (1) coronary flow reserve (CFR), the average value of Doppler- and thermodilution-derived CFR; (2) cardiovascular magnetic resonance (CMR) derived myocardial perfusion reserve index; and (3) CMR-derived microvascular obstruction. hMR correlated with IMR (rho?=?0.41, p?<0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve [AUC] 0.82 vs 0.58, p?<0.001, sensitivity and specificity 77% and 77% vs 51% and 71%) and myocardial perfusion reserve index (AUC 0.85 vs 0.72, p?=?0.19, sensitivity and specificity 82% and 80% vs 64% and 75%). In patients with acute myocardial infarction, the AUCs of hMR and IMR at predicting extensive microvascular obstruction were 0.83 and 0.72, respectively (p?=?0.22, sensitivity and specificity 78% and 74% vs 44% and 91%). We conclude that these 2 invasive indices of coronary microvascular resistance only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and noninvasive measurements of microvascular function was better with hMR than with IMR.
Project description:BACKGROUND:Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS:IMR (n = 288) and CFR (n = 283; mean age [SD], 60  years) were measured acutely using guide wire-based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS:Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0-33.0] vs. 17 [13.0-39.0] vs. 37 [21.0-63.0], P < 0.001; CFR: 1.7 [1.4-2.5] vs. 1.5 [1.1-1.8] vs. 1.4 [1.0-1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS:IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION:NCT02072850. FUNDING:A British Heart Foundation Project Grant (PG/11/2/28474), the National Health Service, the Chief Scientist Office, a Scottish Funding Council Senior Fellowship, a British Heart Foundation Intermediate Fellowship (FS/12/62/29889), and a nonfinancial research agreement with Siemens Healthcare.
Project description:BACKGROUND:Primary percutaneous coronary intervention is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment-elevation myocardial infarction; however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an IMR>40, alone or in combination with a coronary flow reserve (CFR?2.0), in the culprit artery after emergency percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction. METHODS:Patients with acute ST-segment-elevation myocardial infarction were prospectively enrolled during emergency percutaneous coronary intervention and categorized according to IMR (?40 or >40) and CFR (?2.0 or >2.0). Cardiac magnetic resonance imaging was acquired 2 days and 6 months after myocardial infarction. All-cause death or first heart failure hospitalization was a prespecified outcome (median follow-up, 845 days). RESULTS:IMR and CFR were measured in the culprit artery at the end of percutaneous coronary intervention in 283 patients with ST-segment-elevation myocardial infarction (mean±SD age, 60±12 years; 73% male). The median IMR and CFR were 25 (interquartile range, 15-48) and 1.6 (interquartile range, 1.1-2.1), respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio, 2.10; 95% confidence interval, 1.03-4.27; P=0.042). An IMR>40 was closely associated with microvascular obstruction. Symptom-to-reperfusion time, TIMI (Thrombolysis in Myocardial Infarction) blush grade, and no (?30%) ST-segment resolution were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in left ventricular ejection fraction (coefficient, -2.12; 95% confidence interval, -4.02 to -0.23; P=0.028) and left ventricular end-diastolic volume (coefficient, 7.85; 95% confidence interval, 0.41-15.29; P=0.039) at 6 months independently of infarct size. An IMR>40 (odds ratio, 4.36; 95% confidence interval, 2.10-9.06; P<0.001) was a multivariable associate of all-cause death or heart failure. Compared with an IMR>40, the combination of IMR>40 and CFR?2.0 did not have incremental prognostic value. CONCLUSIONS:An IMR>40 is a multivariable associate of left ventricular and clinical outcomes after ST-segment-elevation myocardial infarction independently of the infarction size. Compared with standard clinical measures of the efficacy of myocardial reperfusion, including the ischemic time, ST-segment elevation, angiographic blush grade, and CFR, IMR has superior clinical value for risk stratification and may be considered a reference test for failed myocardial reperfusion. CLINICAL TRIAL REGISTRATION:URL: https//www.clinicaltrials.gov. Unique identifier: NCT02072850.
Project description:BACKGROUND AND OBJECTIVES:Recent guideline recommends evaluation using of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with functionally insignificant stenosis. We evaluated clinical implications of CFR and IMR in patients with high fractional flow reserve (FFR) and deferred revascularization. METHODS:A total of 867 patients (1,152 vessels) consigned to deferred revascularization who underwent comprehensive physiologic assessments were enrolled. Patients with high FFR (>0.80) were categorized by CFR (?2) and IMR (?23 U). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction (MI), and revascularization at 5 years. RESULTS:Patients with low CFR (?2) showed significantly greater risk of POCO than those with high CFR (>2) in both high-FFR (p=0.024) and low-FFR (p=0.034) groups. In patients with high FFR, those with low CFR and high IMR (overt microvascular disease) displayed the greatest risk of POCO overall (p=0.015), surpassing those with high CFR and low IMR (HR, 2.873; 95% CI, 1.476-5.594; p=0.002) and showing significantly greater risk of cardiac death or MI (HR, 5.662; 95% CI, 1.984-16.154; p=0.001). Overt microvascular disease was independently associated with POCO in the high-FFR population (HR, 2.282; 95% CI, 1.176-4.429; p=0.015). CONCLUSION:Among patients with deferred revascularization, those with low CFR showed significantly greater risk of POCO than those with high CFR, regardless of FFR. In patients with high FFR, those with overt microvascular disease showed significantly greater risk of POCO and cardiac death or MI at 5-year, compared with the others. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03690713.
Project description:BACKGROUND:The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance. RRR measures the vasodilatory capacity of the microcirculation. We compared RRR, index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) for predicting microvascular obstruction (MVO), myocardial hemorrhage, infarct size, and clinical outcomes, after ST-segment-elevation myocardial infarction. METHODS:In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute ST-segment-elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. MVO extent (% left ventricular mass) was determined by cardiovascular magnetic resonance imaging at 2 to 7 days. Infarct size was determined at 3 months. One-year major adverse cardiac events, heart failure hospitalizations, and all-cause death/heart failure hospitalizations were assessed. RESULTS:In these 144 patients (mean age, 59±11 years, 80% male), median IMR was 29.5 (interquartile range: 17.0-55.0), CFR was 1.4 (1.1-2.0), and RRR was 1.7 (1.3-2.3). MVO occurred in 41% of patients. IMR>40 was multivariably associated with more MVO (coefficient, 0.53 [95% CI, 0.05-1.02]; P=0.031), myocardial hemorrhage presence (odds ratio [OR], 3.20 [95% CI, 1.25-8.24]; P=0.016), and infarct size (coefficient, 5.05 [95% CI, 0.84-9.26]; P=0.019), independently of CFR?2.0, RRR?1.7, myocardial perfusion grade?1, and Thrombolysis in Myocardial Infarction frame count. RRR was multivariably associated with MVO extent (coefficient, -0.60 [95% CI, -0.97 to -0.23]; P=0.002), myocardial hemorrhage presence (OR, 0.34 [95% CI, 0.15-0.75]; P=0.008), and infarct size (coefficient, -3.41 [95% CI, -6.76 to -0.06]; P=0.046). IMR>40 was associated with heart failure hospitalization (OR, 5.34 [95% CI, 1.80-15.81] P=0.002), major adverse cardiac events (OR, 4.46 [95% CI, 1.70-11.70] P=0.002), and all-cause death/ heart failure hospitalization (OR, 4.08 [95% CI, 1.55-10.79] P=0.005). RRR was associated with heart failure hospitalization (OR, 0.44 [95% CI, 0.19-0.99] P=0.047). CFR was not associated with infarct characteristics or clinical outcomes. CONCLUSIONS:In acute ST-segment-elevationl infarction, IMR and RRR, but not CFR, were associated with MVO, myocardial hemorrhage, infarct size, and clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02257294.
Project description:<h4>Background</h4>In patients with angina undergoing invasive management, no obstructive coronary artery disease (NOCAD) is a common finding, and angina may persist following percutaneous coronary intervention (PCI). Coronary microvascular dysfunction may be relevant. We aimed to assess the proportion of patients presenting with suspected CAD who had coronary microvascular dysfunction.<h4>Methods</h4>Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC 2) was a prospective multicenter randomised controlled trial of functional imaging versus guideline-based management in patients with suspected CAD. Invasive coronary angiography was protocol-directed. Fractional flow reserve (FFR) and parameters of microvascular function (coronary flow reserve (CFR), index of microcirculatory resistance (IMR), resistance reserve ratio (RRR)) were measured in major epicardial coronary arteries with ?40-?90% diameter stenosis. An FFR value ?0.80 indicated the presence of obstructive CAD.<h4>Results</h4>267/1202 (22.2%) patients underwent angiography and 81 (30%) patients had FFR measured. 63 (78%) of these patients had microvascular function assessed in 85 arteries (mean age 58.5?±?8.2?years; 47 (75%) male). 25/63 (40%) patients had NOCAD, and of these, 17 (68%) had an abnormality ?1 parameter of microvascular function (abnormal IMR (?25), abnormal CFR (<2.0), and abnormal RRR (<2.0) occurred in 10 (40%), 12 (48%), and 11 (44%), respectively). 38/63 (60%) patients had obstructive epicardial CAD. Of these patients, 15/38 (39%), 20/38 (53%), and 12/38 (32%) had an abnormal IMR, CFR and RRR, respectively.<h4>Conclusions</h4>Coronary microvascular dysfunction is common in patients with angina. Invasive assessment of microvascular function may be informative and relevant for decision-making in patients with both NOCAD and obstructive epicardial CAD.<h4>Clinical trial registration</h4>ClinicalTrials.gov Identifier: NCT01664858.
Project description:Background Invasive measures of microvascular resistance in the culprit coronary artery have potential for risk stratification in acute ST-segment-elevation myocardial infarction. We aimed to investigate the pathological and prognostic significance of coronary thermodilution waveforms using a diagnostic guidewire. Methods and Results Coronary thermodilution was measured at the end of percutaneous coronary intervention, (PCI) and contrast-enhanced cardiac magnetic resonance imaging (MRI) was intended on day 2 and 6 months later to assess left ventricular (LV) function and pathology. All-cause death or first heart failure hospitalization was a pre-specified outcome (median follow-up duration 1469 days). Thermodilution recordings underwent core laboratory assessment. A total of 278 patients with acute ST-segment elevation myocardial infarction EMI (72% male, 59±11 years) had coronary thermodilution measurements classified as narrow unimodal (n=143 [51%]), wide unimodal (n=100 [36%]), or bimodal (n=35 [13%]). Microvascular obstruction and myocardial hemorrhage were associated with the thermodilution waveform pattern ( P=0.007 and 0.011, respectively), and both pathologies were more prevalent in patients with a bimodal morphology. On multivariate analysis with baseline characteristics, thermodilution waveform status was a multivariable associate of microvascular obstruction (odds ratio [95% confidence interval]=5.29 [1.73, 16.22];, P=0.004) and myocardial hemorrhage (3.45 [1.16, 10.26]; P=0.026), but the relationship was not significant when index of microvascular resistance (IMR) >40 or change in index of microvascular resistance (5 per unit) was included. However, a bimodal thermodilution waveform was independently associated with all-cause death and hospitalization for heart failure (odds ratio [95% confidence interval]=2.70 [1.10, 6.63]; P=0.031), independent of index of microvascular resistance>40, ST-segment resolution, and TIMI (Thrombolysis in Myocardial Infarction) Myocardial Perfusion Grade. Conclusions The thermodilution waveform in the culprit coronary artery is a biomarker of prognosis and may be useful for risk stratification immediately after reperfusion therapy.
Project description:Background Resistive reserve ratio is a thermodilution-based index which integrates both coronary flow and pressure. Resistive reserve ratio represents the vasodilatory capacity of interrogated vessels including both epicardial coronary artery and microvascular circulation. We evaluated the prognostic potential of resistive reserve ratio compared with pressure-derived index (fractional flow reserve [FFR]) or flow-derived index (coronary flow reserve [CFR]). Methods and Results A total of 1245 patients underwent coronary pressure and flow measurement using pressure-temperature wire. Resistive reserve ratio was calculated by CFR adjusted using the ratio between resting and hyperemic distal coronary pressure ([resting mean transit time/hyperemic mean transit time]×[resting distal coronary pressure/hyperemic distal coronary pressure]). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction, and revascularization at 5 years. At 5 years, the cumulative incidence of POCO was significantly different according to quartiles of resistive reserve ratio (9.9%, 11.3%, 17.2%, and 22.7% in quartiles 1 to 4, respectively, log rank P<0.001). Among patients with deferred revascularization, those with depressed resistive reserve ratio (<3.5) showed a significantly higher risk of POCO than those with preserved resistive reserve ratio (?3.5) in patients with FFR>0.80 or patients with CFR>2.0. (FFR>0.80 group: 14.8% versus 6.0%; log rank P=0.001; CFR>2.0 group: 13.5% versus 7.1%; log rank P=0.045). Adding resistive reserve ratio into the model for 5-year POCO showed significantly higher global Chi square value than FFR or CFR (P<0.001, respectively, for FFR and CFR). Resistive reserve ratio <3.5 was significantly associated with the risk of POCO at 5 years in multivariable model (adjusted hazard ratio 1.597, 95% CI, 1.098-2.271, P=0.014). Conclusions Resistive reserve ratio, which integrated both coronary flow and pressure, showed incremental prognostic implications in patients with coronary artery disease undergoing elective percutaneous coronary intervention guided by invasive physiologic evaluation. Registration URL: https://www.clini?caltr?ials.gov; Unique identifier: NCT03690713.
Project description:Aims:Coronary microvascular ischaemia, cardiomyocyte injury and stiffness may play an important role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). To date, the relationship between coronary flow reserve (CFR), myocardial injury, diastolic dysfunction, and future HFpEF risk is unknown. Methods and results:Consecutive patients (n = 201) undergoing evaluation for suspected coronary artery disease (CAD) with stress myocardial perfusion positron emission tomography, serum troponin, and transthoracic echocardiography who did not have flow-limiting CAD or reduced left ventricular ejection fraction were identified. Patients were followed up (median 4.1 years) for cardiovascular death and hospitalization for non-fatal myocardial infarction or heart failure. Coronary flow reserve was quantified as stress/rest myocardial blood flow. Early diastolic flow (E) and relaxation (e') velocities were obtained via transmitral and tissue Doppler, respectively. Patients with impaired CFR (<2, n = 108) demonstrated linearly decreasing e' and increasing E/e' consistent with worsening diastolic function (P for trend <0.0001). A detectable troponin was associated with diastolic dysfunction only in the presence of impaired CFR (interaction P = 0.002). In adjusted analyses, impaired CFR was independently associated with diastolic dysfunction (E/e'septal > 15, adjusted OR 2.58, 95%CI 1.22-5.48) and composite cardiovascular outcomes or HFpEF hospitalization alone (adjusted HR 2.47, 95%CI 1.09-5.62). Patients with both impaired CFR and diastolic dysfunction demonstrated >five-fold increased risk of HFpEF hospitalization (P < 0.001). Conclusion:In symptomatic patients without overt CAD, impaired CFR was independently associated with diastolic dysfunction and adverse events, especially HFpEF hospitalization. The presence of both coronary microvascular and diastolic dysfunctions was associated with a markedly increased risk of HFpEF events.
Project description:BACKGROUND:Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT. OBJECTIVES:This study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT. METHODS:In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year. RESULTS:Plaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm3 vs. 177.3 ± 94.3 mm3, respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group. CONCLUSIONS:Ramipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT. (Angiotensin Converting Enzyme [ACE] Inhibition and Cardiac Allograft Vasculopathy; NCT01078363).
Project description:Adenosine-assisted transthoracic Doppler-derived coronary flow reserve (TDE-CFR) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE-CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied.Three hundred seventy-one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE-CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow-up time of 4.5 years. A TDE-CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow-up in 60 patients (16.2%). A reduced TDE-CFR was detected in 76 patients (20.5%). Patients with reduced TDE-CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE-CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78-7.69; P<0.001). In a multivariate model, TDE-CFR remained a significant independent predictor of major cardiovascular events. The major cardiovascular events rate was 7.5% in patients without myocardial perfusion scintigraphy-detected myocardial ischemia and normal TDE-CFR (n=200), 24.2% in patients without ischemia but with reduced TDE-CFR (n=33), and 46.5% in patients with both myocardial perfusion scintigraphy-detected myocardial ischemia and a reduced TDE-CFR (n=43; P<0.001).Coronary microvascular dysfunction, as determined by TDE-CFR, is a strong independent predictor of cardiovascular events and adds incremental prognostic value compared with myocardial perfusion scintigraphy. The current study supports routine assessment of CFR in patients with suspected ischemic heart disease.