Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Elevated Coronary Artery Calcium Quantified by a Validated Deep Learning Model From Lung Cancer Radiotherapy Planning Scans Predicts Mortality.

PURPOSE: Coronary artery calcium (CAC) quantified on computed tomography (CT) scans is a robust predictor of atherosclerotic coronary disease; however, the feasibility and relevance of quantitating CAC from lung cancer radiotherapy planning CT scans is unknown. We used a previously validated deep learning (DL) model to assess whether CAC is a predictor of all-cause mortality and major adverse cardiac events (MACEs). METHODS: Retrospective analysis of non-contrast-enhanced radiotherapy planning CT scans from 428 patients with locally advanced lung cancer is performed. The DL-CAC algorithm was previously trained on 1,636 cardiac-gated CT scans and tested on four clinical trial cohorts. Plaques ≥ 1 cubic millimeter were measured to generate an Agatston-like DL-CAC score and grouped as DL-CAC = 0 (very low risk) and DL-CAC ≥ 1 (elevated risk). Cox and Fine and Gray regressions were adjusted for lung cancer and cardiovascular factors. RESULTS: The median follow-up was 18.1 months. The majority (61.4%) had a DL-CAC ≥ 1. There was an increased risk of all-cause mortality with DL-CAC ≥ 1 versus DL-CAC = 0 (adjusted hazard ratio, 1.51; 95% CI, 1.01 to 2.26; P = .04), with 2-year estimates of 56.2% versus 45.4%, respectively. There was a trend toward increased risk of major adverse cardiac events with DL-CAC ≥ 1 versus DL-CAC = 0 (hazard ratio, 1.80; 95% CI, 0.87 to 3.74; P = .11), with 2-year estimates of 7.3% versus 1.2%, respectively. CONCLUSION: In this proof-of-concept study, CAC was effectively measured from routinely acquired radiotherapy planning CT scans using an automated model. Elevated CAC, as predicted by the DL model, was associated with an increased risk of mortality, suggesting a potential benefit for automated cardiac risk screening before cancer therapy begins.

Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy.

PURPOSE: Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy. METHODS AND MATERIALS: The coefficient of determination for MHD and LAD V15Gy was calculated in this retrospective analysis of 701 patients with locally advanced NSCLC treated with radiation therapy. Four groups were defined on the basis of high or low MHD (≥10 Gy vs <10 Gy) and LAD V15Gy (≥10% vs <10%). MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) cumulative incidence was estimated, and Fine and Gray regressions were performed. RESULTS: The proportion of variance in LAD V15Gy predictable from MHD was only 54.5% (R2 = 0.545). There was discordance (where MHD was high [≥10 Gy] and LAD low [V15Gy < 10%], or vice versa) in 23.1% of patients (n = 162). Two-year MACE estimates were 4.2% (MHDhigh/LADlow), 7.6% (MHDhigh/LADhigh), 1.8% (MHDlow/LADlow), and 13.0% (MHDlow/LADhigh). Adjusting for pre-existing coronary heart disease and other prognostic factors, MHDhigh/LADlow (subdistribution hazard ratio [SHR], 0.34; 95% CI, 0.13-0.93; P = .036) and MHDlow/LADlow (SHR, 0.24; 95% CI, 0.10-0.53; P < .001) were associated with a significantly reduced risk of MACE. CONCLUSIONS: MHD is insufficient to predict LAD V15Gy with confidence. When MHD and LAD V15Gy dose exposure is discordant, isolated low LAD V15Gy significantly reduces the risk of MACE in patients with locally advanced NSCLC after radiation therapy, suggesting that the validity of whole heart metrics for optimally predicting cardiac events should be reassessed.

Statin Use, Heart Radiation Dose, and Survival in Locally Advanced Lung Cancer.

PURPOSE: Patients with locally advanced non-small cell lung cancer (LA-NSCLC) have a high prevalence of pre-existing coronary heart disease and face excess cardiac risk after thoracic radiation therapy. We sought to assess whether statin therapy is a predictor of overall survival (OS) after thoracic radiation therapy. METHODS AND MATERIALS: We performed a retrospective analysis of 748 patients with LA-NSCLC treated with thoracic radiation therapy, using Kaplan-Meier OS estimates and Cox regression. RESULTS: Statin use among high cardiac risk patients (Framingham risk ≥20% or pre-existing coronary heart disease; n = 496) was 51.2%. After adjustment for baseline cardiac risk and other prognostic factors, statin therapy was associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio, 1.39; 95% confidence interval [CI], 1.00-1.91; P = .048) but not major adverse cardiac events (adjusted hazard ratio, 1.18; 95% CI, 0.52-2.68; P = .69). Among statin-naïve patients, mean heart dose ≥10 Gy versus <10 Gy was associated with a significantly increased risk of all-cause mortality (hazard ratio, 1.32; 95% CI, 1.04-1.68; P = .022), with 2-year OS estimates of 46.9% versus 60.0%, respectively. However, OS did not differ by heart dose among patients on statin therapy (hazard ratio, 1.00; 95% CI, 0.76-1.32; P = 1.00; P-interaction = .031), with 2-year OS estimates of 46.9% versus 50.3%, respectively. CONCLUSIONS: Among patients with LA-NSCLC, only half of statin-eligible high cardiac risk patients were on statin therapy, reflecting the highest cardiac risk level of our cohort. Statin use was an independent predictor of all-cause mortality but not major adverse cardiac events. Elevated mean heart dose (≥10 Gy) was associated with increased risk of all-cause mortality in statin-naïve patients but not among those on statin therapy, identifying a group of patients in which early intervention with statins may mitigate the deleterious effects of high heart radiation therapy dose. This warrants evaluation in prospective trials.

Upper reference limits of transient ischemic dilation ratio for different protocols on new-generation cadmium zinc telluride cameras: A report from REFINE SPECT registry.

BACKGROUND: Upper reference limits for transient ischemic dilation (TID) have not been rigorously established for cadmium-zinc-telluride (CZT) camera systems. We aimed to derive TID limits for common myocardial perfusion imaging protocols utilizing a large, multicenter registry (REFINE SPECT). METHODS: One thousand six hundred and seventy-two patients with low likelihood of coronary artery disease with normal perfusion findings were identified. Images were processed with Quantitative Perfusion SPECT software (Cedars-Sinai Medical Center, Los Angeles, CA). Non-attenuation-corrected, camera-, radiotracer-, and stress protocol-specific TID limits in supine position were derived from 97.5th percentile and mean + 2 standard deviations (SD). Reference limits were compared for different solid-state cameras (D-SPECT vs. Discovery), radiotracers (technetium-99m-sestamibi vs. tetrofosmin), different types of stress (exercise vs. four different vasodilator-based protocols), and different vasodilator-based protocols. RESULTS: TID measurements did not follow Gaussian distribution in six out of eight subgroups. TID limits ranged from 1.18 to 1.52 (97.5th percentile) and 1.18 to 1.39 (mean + 2SD). No difference was noted between D-SPECT and Discovery cameras (P = 0.71) while differences between exercise and vasodilator-based protocols (adenosine, regadenoson, or regadenoson-walk) were noted (all P < 0.05). CONCLUSIONS: We used a multicenter registry to establish camera-, radiotracer-, and protocol-specific upper reference limits of TID for supine position on CZT camera systems. Reference limits did not differ between D-SPECT and Discovery camera.

Post-pericardiotomy Syndrome.

Post-pericardiotomy syndrome (PPS) occurs in a subgroup of patients who have undergone cardiothoracic surgery and is characterized by fever, pleuritic pain, pleural effusion, and pericardial effusion. It is associated with significant morbidity, and the leading complications include tamponade and constrictive pericarditis. Epidemiologic studies have found that PPS often occurs among younger patients; however, there is a lack of comprehensive risk stratification. It is therefore important to be able to identify patients who are at high risk for developing this disease. The diagnosis is made if patients present with 2 out of the following 5 criteria; fever, pericardial or pleuritic chest pain, pericardial or pleural friction rub, pericardial effusion, and pleural effusion with elevated C-reactive protein (CRP). Pericardial effusion associated with PPS is detected by echocardiography, and cardiac MRI is used for evaluation of pericardial thickening as well as inflammation associated with PPS. These imaging modalities have been invaluable for monitoring the efficacy of treatment in PPS. Aspirin, nonsteroidal anti-inflammatory agents (NSAID), and colchicine are the mainstay of the current treatment for PPS. Although steroids are used for refractory cases of PPS, they are associated with significant side effects when used for long-term treatment of this disease. It is important for future research to focus on identification of clinical, serologic, and genetic markers that may predispose patients to PPS. There is also a need for clinical trials to address the use of targeted immunomodulatory treatment for this disease.

Clinical features associated with adverse events in patients with post-pericardiotomy syndrome following cardiac surgery.

Postpericardiotomy syndrome (PPS) may be associated with tamponade and pericardial constriction that may require procedural intervention. The aim of this study was to identify clinical features associated with adverse events requiring procedural intervention in patients with PPS. A total of 239 patients who developed PPS after cardiac surgery were monitored for 12 months. PPS was diagnosed if 2 of the 5 following findings were present: fever without infection, pleuritic pain, friction rub, pleural effusion, and pericardial effusion (<60 days after surgery). The primary end point was the development of pericardial effusion or pericardial constriction requiring procedural intervention. Among 239 patients with PPS, 75 (31%) required procedural intervention. In a univariate analysis, the odds of a procedural intervention were decreased with older age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96 to 0.99) and with colchicine used in combination with anti-inflammatory agents (OR 0.45, 95% CI 0.26 to 0.79). However, the odds were increased in patients with preoperative heart failure (OR 1.84, 95% CI 1 to 3.39) and early postoperative constrictive physiology (OR 5.77, 95% CI 2.62 to 12.7). After multivariate adjustment, treatment with colchicine along with anti-inflammatory agents was associated with lower odds of requiring intervention (OR 0.43, 95% CI 0.95 to 0.99). Independent positive predictors of procedural intervention included age (OR 0.97, 95% CI 0.95 to 0.99), time to PPS (OR 0.97, 95% CI 0.95 to 0.99), and early postoperative constrictive physiology (OR 6.23, 95% CI 2.04 to 19.07). In conclusion, younger age, early-onset PPS, and postoperative constrictive physiology were associated with the need for procedural intervention in patients with PPS, whereas colchicine was associated with reduced odds of adverse events and procedural intervention.

Assessment of left ventricular regional wall motion and ejection fraction with low-radiation dose helical dual-source CT: comparison to two-dimensional echocardiography.

BACKGROUND: Electrocardiographic (ECG)-based tube current modulation during cardiac CT reduces radiation exposure but significantly increases noise in parts of the cardiac cycle where tube current is minimized. OBJECTIVE: We evaluated the effect of maximal ECG-based tube current reduction on left ventricular (LV) regional wall motion assessment and ejection fraction (EF) by comparing low-radiation helical dual-source CT (DSCT) to 2-dimensional transthoracic echocardiography (2D-TTE). METHODS: We studied 83 consecutive patients (15 with prior myocardial infarction) who underwent helically acquired DSCT coronary angiography with maximal ECG-based tube current modulation (low-radiation helical DSCT) and 2D-TTE within a 6-month period (median, 1 day), without any change in clinical status between the studies. In all patients, full tube current was applied only at 70% of the R-R interval, with minimal tube current (4% of maximum) in all other parts of the cardiac cycle. Reduced tube voltage (100 kVp) was combined with the maximal dose modulation in 34 patients. DSCT datasets were evaluated by a blinded, experienced cardiologist. Regional wall motion was assessed with the standard 17-segment model, with each segment scored as normal, hypokinetic, akinetic, and dyskinetic. RESULTS: Mean effective radiation dose for the low-radiation helical DSCT was 5.2 ± 1.7 mSv. Regional wall motion was evaluable in all segments on low-radiation helical DSCT. There was excellent agreement of wall motion scoring by low-radiation helical DSCT and 2D-TTE in 1382 of 1411 segments (98%; Cohen's κ value 0.83; 95% confidence interval, 0.76-0.89; P < 0.0001). Mean LVEF was 67.6% ± 10.3% on low-radiation helical DSCT and 61.8% ± 10.3% on 2D-TTE (P < 0.0001). CONCLUSION: Low-radiation dose helical coronary CT angiography with maximal ECG-based tube current modulation is comparable to 2D-TTE for regional wall motion and EF assessment.

Comparison of the extent and severity of myocardial perfusion defects measured by CT coronary angiography and SPECT myocardial perfusion imaging.

OBJECTIVES: We compared electrocardiogram-gated computed tomography (CT) myocardial perfusion imaging (MPI) based on quantification of the extent and severity of perfusion abnormalities to that measured with single-photon emission computed tomography (SPECT) MPI. BACKGROUND: Contrast-enhanced CT-MPI has been used for the identification of myocardial ischemia. METHODS: We performed CT-MPI during intravenous adenosine infusion in 30 patients with perfusion abnormalities on rest/adenosine stress SPECT-MPI acquired within 60 days (18 stress-rest CT-MPI and 12 stress CT-MPI only). The extent and severity of perfusion defects on SPECT-MPI were assessed on a 5-point scale in a standard 17-segment model, and total perfusion deficit (TPD) was quantified by automated software. The extent and severity of perfusion defects on CT-MPI was visually assessed by 2 observers using the same grading scale and expressed as summed stress score and summed rest score; visually quantified TPD was given by summed stress score/(maximal score of 68) and summed rest score/68. The magnitude of perfusion abnormality on CT-MPI in regions of the myocardium was defined. RESULTS: On a per-segment basis, there was good agreement between CT-MPI and SPECT-MPI with a kappa of 0.71 (p < 0.0001) for detection of stress perfusion abnormalities. Automated TPD on SPECT-MPI was similar to visual TPD from CT-MPI (p = 0.65 stress TPD, and p = 0.12 ischemic TPD stress-rest) with excellent agreement (bias = -0.3 for stress TPD, and bias = 1.2 for ischemic TPD) on Bland-Altman analysis. Software-based quantification of the magnitude of stress perfusion deficit and ischemia on CT-MPI were similar to that for automated TPD measured by SPECT (p = 0.88 stress, and p = 0.48 ischemia), with minimal bias (bias = 0.6, and bias = 1.2). CONCLUSIONS: Stress and reversible myocardial perfusion deficit measured by CT-MPI using a visual semiquantitative approach and a visually guided software-based approach show strong similarity with SPECT-MPI, suggesting that CT-MPI-based assessment of myocardial perfusion defects may be of clinical and prognostic value.