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.

Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm-more similarities than differences?

Coronary spasm is an established cause for angina pectoris. Ethnic differences have been suggested among Asian compared to Caucasian patients regarding prevalence, gender distribution, and angiographic patterns of coronary spasm. The aim of this study was to compare contemporary German and Japanese patients with coronary spasm. Between 2011 and 2015, 149 patients with resting angina and unobstructed coronary arteries with acetylcholine-induced epicardial spasm were enrolled in Stuttgart, Germany (n = 69) and Sendai, Japan (n = 80). All patients underwent intracoronary acetylcholine testing according to a standardized protocol. Comprehensive analysis included type of spasm (focal/diffuse), dose of acetylcholine leading to spasm, and frequency of multivessel spasm. Patients in this study were 61 ± 11 years old, predominantly female (54%), and had normal left ventricular ejection fraction (73 ± 9%). Diffuse spasm was the most prevalent type of spasm (85%) whereas focal spasm was found in the remaining 15% of patients. 31% of patients had multivessel spasm. Comparing the German with the Japanese patients, distribution of spasm type (focal/diffuse, p = 0.19) and frequency of multivessel spasm (p = 0.22) were comparable. Moreover, when Japanese patients were compared with German patients and diffuse spasm with focal spasm patients, respectively, no significant differences were observed regarding the acetylcholine dose required to induce spasm (p = 0.078 and p = 0.46, respectively). In conclusion, diffuse epicardial coronary spasm is the most frequent finding among German and Japanese patients with resting angina, unobstructed coronary arteries, and epicardial spasm on acetylcholine testing. Japanese and German patients share several similarities including comparable types of spasm and frequency of multivessel spasm.

Quantitative Assessment of the Hemodynamic Effects of Intra-Arterial Nitroglycerin on Hepatocellular Carcinoma using Two-Dimensional Perfusion Angiography.

PURPOSE: To determine the hemodynamic effects of intra-arterial nitroglycerin on hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography. MATERIALS AND METHODS: Two-dimensional perfusion angiograms obtained prior to radioembolization from September 2019 to February 2020 were retrospectively reviewed. The inclusion criteria were the presence of Liver Imaging Reporting and Data System-5 tumors and angiographically distinguishable tumor and background liver. The exclusion criteria were previously treated tumors and motion-degraded studies. Thirteen patients with 2D perfusion angiograms obtained before and 2 minutes ± 1 after the administration of intra-arterial nitroglycerin were analyzed. The mean patient age was 72 years ± 9 and 11 of 13 (85%) had cirrhosis. The mean maximum tumor dimension was 4.6 cm ± 2.1. Eight tumors were in the right lobe and 5 were in the left lobe. The tumor and background liver 2D perfusion data were processed and the areas under the time-density curves were calculated. The relative perfusion of HCC to background liver was compared before and after nitroglycerin administration using a 2-tailed paired t-test. RESULTS: The mean rate of contrast administration was 1.4 mL/s ± 0.7 and the mean volume administered was 7.1 mL ± 3.3. The mean nitroglycerin dose was 281 µg ± 69. Ten of 13 patients (77%) demonstrated a relative increase in tumor perfusion. The mean HCC to background liver area under the curve ratio was 1.94 ± 0.76 before and 2.40 ± 0.89 after nitroglycerin administration (P < .05). CONCLUSIONS: Intra-arterial nitroglycerin increases previously untreated HCC perfusion relative to background liver as measured by 2D perfusion angiography, but this effect is variable among patients and should be validated with 3-dimensional imaging techniques.

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.

Inhaled Pulmonary Vasodilators and Thoracic Organ Transplantation: Does Evidence Support Its Use and Cost Benefit?

In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of perioperative morbidity and mortality. In lung transplantation, primary graft dysfunction remains a major obstacle because it can cause bronchiolitis obliterans and mortality. Pulmonary vasodilators have been used as an adjunct therapy for heart or lung transplantation, mainly to treat pulmonary hypertension, right ventricular failure, and associated refractory hypoxemia. Among pulmonary vasodilators, inhaled nitric oxide is unique in that it is selective in pulmonary circulation and causes fewer systemic complications such as hypotension, flushing, or coagulopathy. Nitric oxide is expected to prevent or attenuate primary graft dysfunction by decreasing ischemia-reperfusion injury in lung transplantation. However, when considering the long-term benefit of these medications, little evidence supports their use in heart or lung transplantation. Current guidelines endorse inhaled vasodilators for managing immediate postoperative right ventricular failure in lung or heart transplantation, but no guidance is offered regarding agent selection, dosing, or administration. This review presents the current evidence of inhaled nitric oxide in lung or heart transplantation as well as comparisons with other pulmonary vasodilators including cost differences in consideration of economic pressures to contain rising pharmacy costs.

Optimizing the Assessment of Patient Clinical Risk at the Time of Cardiac Stress Testing.

Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patient symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, the authors propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results.

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.

Effectiveness, Safety, and Economic Comparison of Inhaled Epoprostenol Brands, Flolan and Veletri, in Acute Respiratory Distress Syndrome.

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O2/fraction of inspired O2 (PaO2/FiO2) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy (P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO2/FiO2 ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

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.

Use and costs of inhaled nitric oxide and inhaled epoprostenol in adult critically ill patients: A quality improvement project.

PURPOSE: Inhaled epoprostenol and inhaled nitric oxide are pulmonary vasodilators commonly used in the management of acute respiratory distress syndrome and right ventricular failure; however, they have vastly different cost profiles. The purpose of the project was to transition from nitric oxide to epoprostenol as the inhaled pulmonary vasodilator (IPV) of choice in adult critically ill patients and evaluate the effect of the transition on associated usage and costs. METHODS: A single-center, prospective, before and after quality improvement project including adult patients receiving inhaled nitric oxide, inhaled epoprostenol, or both was conducted in 7 adult intensive care units, operating rooms, and postanesthesia care units of a tertiary care academic medical center. The total number of patients, hours of therapy, and costs for each agent were compared between stages of protocol implementation and annually. RESULTS: Seven hundred twenty-nine patients received inhaled nitric oxide, inhaled epoprostenol, or both during the study period. The monthly inhaled nitric oxide use in number of patients, hours, and cost decreased during all stages of the project (p < 0.01). The monthly inhaled epoprostenol use in number of patients, hours, and cost increased during all stages (p < 0.01). Overall, total IPV use increased during the study. However, despite this increase in usage, there was a 47% reduction in total IPV cost. CONCLUSION: Implementation of a staged protocol to introduce and expand inhaled epoprostenol use in adult critically ill patients resulted in decreased use and cost of inhaled nitric oxide. The total cost of all IPV was decreased by 47% despite increased IPV use.

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 sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues.

Microvascular capillary assessment in relation to forearm blood flow.

OBJECTIVE: To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. METHODS: Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. RESULTS: This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0·57; P<0·05). CONCLUSIONS: Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.

The value of a simplified approach to end-systolic volume measurement for assessment of left ventricular contractile reserve during stress-echocardiography.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Prognostic Value of Vasodilator Stress Cardiac Magnetic Resonance Imaging: A Multicenter Study With 48 000 Patient-Years of Follow-up.

Importance: Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. Objective: To determine whether stress CMR is associated with patient mortality. Design, Setting, and Participants: Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. Main Outcomes and Measures: All-cause patient mortality. Results: Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P < .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P < .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P < .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P < .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P < .001). Conclusions and Relevance: Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.

Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database.

BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.

Sodium Nitrite-Mediated Cardioprotection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Cost-Effectiveness Analysis.

OBJECTIVES: In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI), we found a reduction in the incidence of major adverse cardiac events (MACEs). Specifically, MACE rates were 5.2% versus 25.0% with placebo at 3 years ( P = .013). Such MACE reductions should also be associated with economic benefit. Thus, we assessed the cost utility of sodium nitrite therapy versus standard primary PCI only. METHODS AND RESULTS: We developed a model to simulate costs and quality-adjusted life years (QALYs) over the first 36 months after ST-Segment Elevation Myocardial Infarction (STEMI). Decision tree analysis was used to assess different potential cardiovascular outcomes after STEMI for patients in both treatment groups. Model inputs were derived from the NITRITE-AMI study. Cost of comparative treatments and follow-up in relation to cardiovascular events was calculated from the United Kingdom National Health Service perspective. Higher procedural costs for nitrite treatment were offset by lower costs for repeat revascularization, myocardial infarction, and hospitalization for heart failure compared to primary PCI plus placebo. Nitrite treatment was associated with higher utility values (0.91 ± 0.19 vs 0.82 ± 0.30, P = .041). The calculated incremental cost-effectiveness ratio of £2177 per QALY indicates a cost-effective strategy. Furthermore, positive results were maintained when input parameters varied, indicating the robustness of our model. In fact, based on the difference in utility values, the cost of nitrite could increase by 4-fold (£2006 per vial) and remain cost-effective. CONCLUSION: This first analysis of sodium nitrite as a cardioprotective treatment demonstrates cost-effectiveness. Although more comparative analysis and assessment of longer follow-up times are required, our data indicate the considerable potential of nitrite-mediated cardioprotection.

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.