Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

INTRODUCTION: Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. METHODS: We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 µg, with dose doubling at each step). RESULTS: We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. CONCLUSION: This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Hybrid Assessment of Myocardial Ischemia Using Stress-Only Nuclear Myocardial Perfusion Imaging and Rest Computed Tomography Perfusion Imaging.

BACKGROUND: Sequential assessment using CT coronary angiography (coronary CT) and nuclear myocardial perfusion imaging (MPI) is considered an anatomical and functional evaluation of coronary artery disease (CAD). However, there can be unexpected radiation exposure. Hybrid MPI with stress-only nuclear MPI and rest CT-MPI using coronary CT may contribute to reducing the radiation dose in sequential assessment with nuclear MPI after coronary CT. We analyzed the diagnostic performance and total radiation dose of hybrid MPI for detection of significant CAD compared with sequential assessment using nuclear MPI after coronary CT.Methods and Results:The results for 101 patients who underwent coronary CT, nuclear MPI and invasive coronary angiography within 3 months of all imaging were analyzed. We calculated the summed difference score (SDS) from standard nuclear MPI and hybrid SDS from hybrid MPI, which revealed myocardial ischemia. The diagnostic performance of SDS and hybrid SDS for detecting significant CAD was analyzed using receiver-operating characteristic (ROC) curve analysis. We also compared the total radiation dose of both methods. The area under the ROC curve was not different between SDS and hybrid SDS (0.901 and 0.815, P=0.079). Total radiation dose of hybrid MPI was significantly lower than standard nuclear MPI with CT angiography (4.62 mSv vs. 9.72 mSv, P<0.0001). CONCLUSIONS: Hybrid MPI showed a precise diagnostic accuracy for significant CAD detection.

Comparability of compressed sensing-based gradient echo perfusion sequence SPARSE and conventional gradient echo sequence in assessment of myocardial ischemia.

PURPOSE: Stress perfusion imaging plays a major role in non-invasive detection of coronary artery disease. We compared a compressed sensing-based and a conventional gradient echo perfusion sequence with regard to image quality and diagnostic performance. METHOD: Patients sent for coronary angiography due to pathologic stress perfusion CMR were recruited. All patients underwent two adenosine stress CMR using conventional TurboFLASH and prototype SPARSE sequence as well as quantitative coronary angiography with fractional flow reserve (FFR) within 6 weeks. Coronary angiography was considered gold standard with FFR < 0.75 or visual stenosis >90 % for identification of myocardial ischemia. Diagnostic performance of perfusion imaging was assessed in basal, mid-ventricular and apical slices by quantification of myocardial perfusion reserve (MPR) analysis utilizing the signal upslope method and a deconvolution technique using the fermi function model. RESULTS: 23 patients with mean age of 69.6 ± 8.9 years were enrolled. 46 % were female. Image quality was similar in conventional TurboFLASH sequence and SPARSE sequence (2.9 ± 0.5 vs 3.1 ± 0.7, p = 0,06). SPARSE sequence showed higher contrast-to-noise ratio (52.1 ± 27.4 vs 40.5 ± 17.6, p < 0.01) and signal-to-noise ratio (15.6 ± 6.2 vs 13.2 ± 4.2, p < 0.01) than TurboFLASH sequence. Dark-rim artifacts occurred less often with SPARSE (9 % of segments) than with TurboFLASH (23 %). In visual assessment of perfusion defects, SPARSE sequence detected less false-positive perfusion defects (n = 1) than TurboFLASH sequence (n = 3). Quantitative perfusion analysis on segment basis showed equal detection of perfusion defects for TurboFLASH and SPARSE with both upslope MPR analysis (TurboFLASH 0.88 ± 0.18; SPARSE 0.77 ± 0.26; p = 0.06) and fermi function model (TurboFLASH 0.85 ± 0.24; SPARSE 0.76 ± 0.30; p = 0.13). CONCLUSIONS: Compressed sensing perfusion imaging using SPARSE sequence allows reliable detection of myocardial ischemia.

Pulmonary vein antral isolation causes depolarization of vein sleeves: Implications for the assessment of isolation.

PURPOSE: Pulmonary vein isolation (PVI) for atrial fibrillation has been shown to result in inexcitability of a large fraction of pulmonary veins (PVs), but the mechanism is unknown. We investigated the mechanism of PV inexcitability by assessing the effects of PVI on the electrophysiology of PV sleeves. METHODS: Patients undergoing first-time radiofrequency PVI were studied. Capture threshold, effective refractory period (ERP), and excitability were measured in PVs and the left atrial appendage (LAA) before and after ablation. Adenosine was used to assess both transient reconnection and transient venous re-excitability. RESULTS: We assessed 248 veins among 67 patients. Mean PV ERP (249.7 ± 54.0 ms) and capture threshold (1.4 ± 1.6 mA) increased to 300.5 ± 67.1 and 5.7 ± 5.6 mA, respectively (P < .0001 for both) in the 26.9% PVs that remained excitable, but no change was noted in either measure in the LAA. In 16.3% of the 73.1% inexcitable veins, transient PV re-excitability (as opposed to reconnection) was seen with adenosine administration. CONCLUSIONS: Antral PVI causes inexcitability in a majority of the PVs, which can transiently be restored in some with adenosine. Among PVs that remain excitable, ERP and capture threshold increase significantly. These data imply resting membrane potential depolarization of the of PV myocardial sleeves. As PV inexcitability hampers the assessment of entrance and exit block, demonstrating transient PV re-excitability during adenosine administration helps ensure true isolation.

Impact of baseline calibration on semiquantitative assessment of myocardial perfusion reserve by adenosine stress MRI.

In this study, we sought to investigate the impact of baseline calibration, which is used in quantitative cardiac MRI perfusion analysis to correct for surface coil inhomogeneity and noise, on myocardial perfusion reserve index (MPRI) and its contribution to previously reported paradoxical low MPRI < 1.0 in patients with unobstructed coronary arteries. Semiquantitative perfusion analysis was performed in 20 patients with unobstructed coronary arteries undergoing stress/rest perfusion CMR and in ten patients undergoing paired rest perfusion CMR. The following baseline calibration settings were compared: (1) baseline division, (2) baseline subtraction and (3) no baseline calibration. In uncalibrated analysis, we observed ~ 20% segmental dispersion of signal intensity (SI)-over-time curves. Both baseline subtraction and baseline division reduced relative dispersion of t0-SI (p < 0.001), but only baseline division corrected for dispersion of peak-SI and maximum upslope also (p < 0.001). In the assessment of perfusion indices, however, baseline division resulted in paradoxical low MPRI (1.01 ± 0.23 vs. 1.63 ± 0.38, p < 0.001) and rest perfusion index (RPI 0.54 ± 0.07 vs. 0.94 ± 0.12, p < 0.001), respectively. This was due to a reversed ratio of blood-pool and myocardial baseline-SI before the second perfusion study caused by circulating contrast agent from the first injection. In conclusion, baseline division reliably corrects for inhomogeneity of the surface coil sensitivity profile facilitating comparisons of regional myocardial perfusion during hyperemia or at rest. However, in the assessment of MPRI, baseline division can lead to paradoxical low results (even MPRI < 1.0 in patients with unobstructed coronary arteries) potentially mimicking severely impaired perfusion reserve. Thus, in the assessment of MPRI we propose to waive baseline calibration.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

BACKGROUND: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. METHODS: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. RESULTS: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. CONCLUSIONS: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Adenosine intracoronary bolus dose escalation versus intravenous infusion to induce maximum coronary hyperemia for fractional flow reserve assessment.

BACKGROUND: Achievement of maximal hyperemia is mandatory for an accurate calculation of fractional flow reserve (FFR) and it is obtained with adenosine given either as an intravenous infusion or as an intracoronary bolus. AIMS: The purpose of this study was to compare the infusion of adenosine with intracoronary adenosine bolus dose escalation in the optimal assessment of peak FFR. METHODS: We enrolled consecutive patients with borderline coronary lesions that were assessed by FFR with the use of adenosine intracoronary boluses (100, 200, 400 and 600 µg) and intravenous infusion of 140 µg/kg/min and 280 µg/kg/min. FFR values were assessed and compared. RESULTS: Fifty patients with 125 borderline coronary artery stenoses were enrolled. Physiological severity assessed with: intravenous adenosine infusion at 140 µg/kg/min was mean 0.82 ± 0.09; infusion at 280 µg/kg/min - 0.81 ± 0.09; intracoronary bolus of 100 µg, 200 µg, 400 µg and 600 µg - 0.83 ± 0.09; 0.83 ± 0.09, 0.83 ± 0.09; and 0.83 ± 0.09, respectively. There was a strong linear correlation between FFR values obtained from 140 µg/kg/min infusion and adenosine intracoronary 100, 200, 400 and 600 µg bolus injection (r = 0.989, r = 0.99, r = 0.993, r = 0.994, respectively, p < 0.001 for all). CONCLUSIONS: FFR values achieved with intracoronary boluses of adenosine are very similar, but not identical to those obtained using intravenous adenosine administration. The values of FFR may vary between escalating doses of intracoronary boluses and intravenous infusion.

Impact of increasing dose of intracoronary adenosine on peak hyperemia duration during fractional flow reserve assessment.

BACKGROUND: Fractional Flow Reserve (FFR) is currently indicated as a first line strategy for the functional assessment of intermediate coronary stenoses. However, the protocol for inducing hyperemia still lacks standardization. Intracoronary adenosine boli, with a progressive increase to high-dosage, have been proposed as a sensitive and accurate strategy for the classification of coronary stenoses, although being potentially affected by the achievement of plateau of the effect and by a less prolonged and stable hyperemia as compared to intravenous administration. Therefore, the aim of the present study was to define the conditioning parameters and assess the impact of increasing-dose intracoronary adenosine on peak hyperemia duration in patients undergoing FFR for intermediate coronary stenoses. METHODS: FFR was assessed in patients with intermediate (40 to 70%) lesions by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Hyperemic duration was defined as the time for the variation form minimum FFR ±â€¯0.02 and time to recovery till baseline values. RESULTS: We included 87 patients, undergoing FFR evaluation of 101 lesions. Mean peak hyperemia duration and time to recovery significantly increased with adenosine doses escalation (p = 0.02 and p < 0.001). Peak hyperemia duration and time to recovery with 1440 µg adenosine were 14.5 ±â€¯12.6 s and 45.2 ±â€¯30.7 s, respectively. Hyperemia duration was not related to Quantitative Coronary Angiography (QCA) parameters or FFR values. In fact, a similar increase in the time of hyperemic peak was noted when comparing patients with positive or negative FFR (pbetween = 0.87) or patients with lesions < or ≥20 mm (pbetween = 0.92) and lesions involving left main coronary or proximal left anterior descending artery (LAD) (pbetween = 0.07). A linear relationship was observed between time to recovery and FFR variations, with a greater time to baseline required in patients with FFR ≤ 0.80 (p = 0.003) and in lesions ≥ 20 mm (p = 0.006), but not in LAD/LM lesions (p = 0.55). CONCLUSIONS: The present study shows a progressive raise in the duration of peak hyperemia and time to recovery, after the administration of increasing doses of intracoronary adenosine for the assessment of FFR. Therefore, considering the potential advantages of a high-dose adenosine protocol, allowing a more prolonged hyperemia and a more precise and reliable measurement of FFR, further larger studies with such FFR strategy should certainly be advocated to confirm its safety and benefits, before its routinely use recommendation.

Validation and comparison of non-hyperemic pressure reserve to fractional flow reserve for assessment of coronary artery stenosis: A real world study.

BACKGROUND: The visual interpretation of an angiographic stenosis may not always reflect the physiological significance of a lesion. Fractional Flow Reserve (FFR) is a reliable index to assess the significance of a lesion during hyperemia. However, there are pitfalls that can lead to significant misinterpretation and adverse events. OBJECTIVE: This study sought to evaluate the accuracy and predictability of the non-hyperaemic pressure ratio (NHPR) without hyperemic stimuli, compared to hyperemic FFR. METHODS: We conducted a retrospective, multicenter study of 700 patients who underwent a pressure recording during coronary angiography using NHPR and FFR measurements. Receiver operator characteristic (ROC) curve was constructed. NHPR sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy test were calculated. The most accurate NHPR cutoff was determined. RESULTS: Of the 700 procedures, 449 cases were included. By ROC analysis, the optimal cut-point for NHPR was 0.93 to predict an FFR of ≤0.80 with an overall diagnostic accuracy of 78.84%. The sensitivity of this NHPR cutoff was 85.06%, specificity of 75.59%, PPV of 64.53% and a NPV of 90.65%. There was an overall accuracy of about 80% for predicting non-hyperemic index (FFR < 0.80) using a cutoff of NHPR ≤ 0.93. CONCLUSIONS: The use of NHPR can be considered in certain clinical scenarios where adenosine is contraindicated or there are other challenges; with the knowledge that hyperemia might be necessary if there is any high clinical suspicion as it still remains the reference standard for diagnostic certainty.

Assessment with intracoronary pressure and flow guidewire, at baseline and after intracoronary adenosine infusion, in a patient with Takotsubo syndrome.

We present the case of a patient with Takotsubo syndrome assessed by intracoronary flow and pressure guidewire, showing elevation of intracoronary pressures at the level of the anterior descending artery, and thus demonstrating a new therapeutic target in a still little understood etiopathogenic entity. The results of this test have never been previously reported in Takotsubo patients.

Assessment of Systemic Adenosine Effect Using Color Doppler Ultrasound of the Splenic Artery-Feasibility and Potential Clinical Utility for Coronary Interventions.

Adenosine induces coronary vasodilation and simultaneously reduces splanchnic perfusion. This effect can be absent in adenosine non-responders. Imaging of splanchnic arteries under adenosine assessing this effect has not been performed in humans previously. In 26 patients, splenic artery color Doppler was performed during an infusion of adenosine. Peak velocity in the splenic artery was measured before the infusion and at 2 min. Results were compared qualitatively with perfusion imaging in magnetic resonance. A total of 24 patients showed a drop of splenic artery peak velocity from 62.3 ± 18.1 to 40.4 ± 15.7 cm/s (p <0.001), which corresponded to perfusion restriction in magnetic resonance. Two patients with constant splenic artery velocity did not show perfusion restriction. We showed feasibility of assessing changes in splenic artery velocity under adenosine for the first time in humans. Further studies are needed to investigate whether this novel application is a robust tool to rule out inadequate adenosine effect during measurement of fractional flow reserve in coronary catheterization.

An Evaluation of the Cost-effectiveness of Comprehensive MTM Integrated with Point-of-Care Phenotypic and Genetic Testing for U.S. Elderly Patients After Percutaneous Coronary Intervention.

BACKGROUND: Poor health outcomes after percutaneous coronary intervention (PCI) in elderly patients is an area of concern among policymakers and administrators. In an effort to determine the best strategy to improve outcomes among elderly patients who underwent PCI, several studies have evaluated the cost-effectiveness of genotype-guided antiplatelet therapy compared with universal use of any one of the antiplatelet drugs indicated for patients with acute coronary syndrome (ACS) who underwent PCI. The results have either been in favor of genotype-guided antiplatelet therapy or universal use of ticagrelor. However, no study has yet evaluated the cost-effectiveness of pharmacist-provided face-to-face medication therapy management (MTM) combined with point-of-care genotype-guided antiplatelet therapy (POCP) when compared with universal use of ticagrelor or clopidogrel for the elderly after PCI. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacist integration of MTM with POCP (MTM-POCP) when compared with universal use of ticagrelor or clopidogrel combined with MTM (MTM-ticagrelor or MTM-clopidogrel). METHODS: We conducted a cost-effectiveness analysis from the perspective of the U.S. health care system. A hybrid model, consisting of a 1-year decision tree and a 20-year Markov model, was used to simulate a cohort of elderly patients (aged at least 65 years) with ACS who underwent PCI. Treatment strategies available to patients were POCP, POCP-MTM, MTM-clopidogrel, or MTM-ticagrelor. Data used to populate the model were obtained from the PLATO trial and other published studies. Outcome measures were costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained. A deterministic and probabilistic sensitivity analysis was conducted to account for the joint uncertainty around the key parameters of the model. Finally, a benchmark willingness to pay of $50,000-200,000 was considered. RESULTS: The use of PCOP (with dual antiplatelet therapy) resulted in 5.29 QALYs, at a cost of $50,207. MTM-clopidogrel resulted in 5.34 QALYs, at a cost of $50,011. The use of POCP-MTM resulted in 5.36 QALYs, at a cost of $50,270. Finally, MTM-ticagrelor resulted in 5.42 QALYs, at a cost of $53,346. MTM-ticagrelor was found to be cost-effective compared with MTM-clopidogrel or MTM-POCP, irrespective of the willingness to pay. The deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case analysis. CONCLUSIONS: The combination of MTM-ticagrelor was cost-effective when compared with MTM-POCP or MTM-clopidogrel. The transitional probabilities, however, were mostly based on published studies. Analysis based on a prospective randomized clinical study, comparing all the treatment strategies included in this study, is warranted to confirm our findings. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to declare. Study concept and design were contributed by Okere and Diaby. Ezendu took the lead in data collection, along with Okere. Data interpretation was performed by all the authors. The manuscript was written by Okere, Diaby, and Berthe and revised by Okere and Diaby.

Combined Assessment of Stress Myocardial Perfusion Cardiovascular Magnetic Resonance and Flow Measurement in the Coronary Sinus Improves Prediction of Functionally Significant Coronary Stenosis Determined by Fractional Flow Reserve in Multivessel Disease.

BACKGROUND: Recent studies using stress-rest perfusion cardiovascular magnetic resonance (CMR) demonstrated a close correlation between myocardial ischemia and reduced fractional flow reserve (FFR). However, its diagnostic concordance may be reduced in patients with multivessel disease. We sought to evaluate the concordance of adenosine stress-rest perfusion CMR for predicting reduced FFR, and to determine the additive value of measuring global coronary flow reserve (CFR) in the coronary sinus in multivessel disease. METHODS AND RESULTS: Ninety-six patients with angiographic luminal narrowing >50% underwent comprehensive CMR study and FFR measurements in 139 coronary vessels. FFR <0.80 was considered hemodynamically significant. Global CFR was quantified as the ratio of stress-rest coronary sinus flow measured by phase-contrast cine CMR. In 25 patients with single-vessel disease, visual assessment of perfusion CMR yielded high diagnostic concordance for predicting flow-limiting stenosis, with the area under receiver operating characteristic curve of 0.93 on a per-patient basis. However, in 71 patients with multivessel disease, perfusion CMR underestimated flow-limiting stenosis, resulting in the reduced area under receiver operating characteristic curve of 0.74. When CFR of <2.0 measured in the coronary sinus was considered as global myocardial ischemia, combined assessment provided correct reclassifications in 7 patients with false-negative myocardial ischemia, and improved the diagnostic concordance to 92% sensitivity and 73% specificity with the area under receiver operating characteristic curve of 0.88 (95% confidence interval, 0.80%-0.97%, P=0.002). CONCLUSIONS: Visual analysis of stress-rest perfusion CMR has limited concordance with FFR in patients with multivessel disease. Multiparametric CMR integrating stress-rest perfusion CMR and flow measurement in the coronary sinus is useful for detecting reduced FFR in multivessel disease.

Ninety-Day Readmission and Long-Term Mortality in Medicare Patients (≥65 Years) Treated With Ticagrelor Versus Prasugrel After Percutaneous Coronary Intervention (from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium).

Ticagrelor and prasugrel were found to be superior to clopidogrel for the treatment of acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI); however, the comparative effectiveness of these 2 drugs remains unknown. We compared postdischarge outcomes among older patients treated with ticagrelor versus prasugrel after PCI for ACS. We linked clinical data from PCIs performed in older patients (age ≥65) for ACS at 47 Michigan hospitals to Medicare fee-for-service claims from January 1, 2013, to December 31, 2014, to ascertain rates of 90-day readmission and long-term mortality. We used propensity score matching to adjust for the nonrandom use of ticagrelor and prasugrel at discharge. Logistic regression and Cox proportional hazards models were used to compare rates of 90-day readmission and long-term mortality, respectively. Patients discharged on ticagrelor (n = 1,243) were more frequently older, female, had a history of cerebrovascular disease, and presented with ST- or non-ST-elevation myocardial infarction compared with prasugrel (n = 1,014). After matching (n = 756 per group), there were no significant differences in the rates of 90-day readmission (16.7% ticagrelor vs 14.6% prasugrel; adjusted odds ratio 1.15, 95% confidence interval 0.86 to 1.55, p = 0.35) or 1-year mortality (5.4% ticagrelor vs 3.7% prasugrel; hazard ratio 1.3, 95% confidence interval 0.8 to 2.2, p = 0.31). In conclusion, we found no significant differences in the rates of 90-day readmission or long-term mortality between older patients treated with ticagrelor and patients treated with prasugrel after PCI for ACS. In the absence of randomized data to the contrary, these 2 treatments appear similarly effective.

Nitroglycerin-Derived Pd/Pa for the Assessment of Intermediate Coronary Lesions.

OBJECTIVES: To assess the predictive value of Pd/Pa after nitroglycerin administration (Pd/Pa[N]) as compared with standard fractional flow reserve (FFR). METHODS: Consecutive patients with intermediate coronary lesions assessed by FFR between January 2014 and October 2015 were included. We measured Pd/Pa at baseline, Pd/Pa(N), and Pd/Pa after incremental doses of intracoronary adenosine. RESULTS: A total of 134 patients (27% females; mean age, 65 years) were included. The diagnostic performance of Pd/Pa(N) and identification of cut-off value for Pd/Pa(N) compared with FFR threshold of 0.8 using receiver-operating characteristic (ROC) area under the curve analysis was between 0.98 (95% confidence interval, 0.95-1.00; P<.05) for 48 µg and 0.86 (95% confidence interval, 0.79-0.94; P<.05) for 240 µg adenosine. Pd/Pa(N) ≤0.8 had 100% positive predictive value. Pd/Pa(N) ≥0.94 provided 100% negative predictive value with a high sensitivity (>92%). Optimal diagnostic accuracy of Pd/Pa(N) was achieved for values ≤0.84. The Pearson's correlation between Pd/Pa(N) and FFR varied between 0.89 for 24 µg adenosine and 0.77 for 240 µg (P<.01). CONCLUSION: Pd/Pa(N) values can be used for diagnosis of hemodynamically significant lesions. Pd/Pa(N) correlates well with standard FFR. Pd/Pa(N) cut-off of ≤0.8 can be considered significant without need for adenosine injection. The value of using adenosine whenever Pd/Pa(N) is ≥0.94 is limited.

Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial Infarction: Results From the PEGASUS-TIMI 54 Trial.

BACKGROUND: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. OBJECTIVES: The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. METHODS: The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily). RESULTS: Hospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained). CONCLUSIONS: For patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Meta-Analysis of Head-to-Head Comparison of Intracoronary Versus Intravenous Adenosine for the Assessment of Fractional Flow Reserve.

Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100 µg) or high-dose IC adenosine (≥100 µg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80 µg) and 5 studies high-dose boluses (120 to 600 µg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p = 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p = 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifying hemodynamically significant coronary stenosis and is better tolerated by the patients.