Late Outcomes of Patients in the Emergency Department with Acute Chest Pain Evaluated with Computed Tomography-Derived Fractional Flow Reserve.

Computed tomography (CTA)-derived fractional flow reserve (FFRCT) guides the need for invasive coronary angiography (ICA). Late outcomes after FFRCT are reported in stable ischemic heart disease, but not in acute chest pain in the Emergency Department (ACP-ED). The objectives are to assess the risk of death, myocardial infarction (MI), revascularization, and ICA after FFRCT. From 2015-2018, 389 ACP-ED low-risk patients (negative biomarkers, no ECG ischemia) underwent CTA and FFRCT and were entered into a prospective institutional registry; patients were followed for 41 ± 10 months. CTA stenosis ≥ 50% was present in 81% of patients. Positive (FFRCT ≤0.80) and negative FFRCT were observed in 124 (32%) and 265 (68%) patients, respectively. ICA was performed in 108/124 (87%) patients with positive and 89/265 (34%) patients with negative FFRCT (p<0.00001). Revascularization was performed in 87/124 (70%) with positive FFRCT and in 22/265 (8%) with negative FFRCT (p<0.00001). Appropriateness of revascularization was established by blinded adjudication of ICA and invasive FFR using practice guidelines; revascularization was appropriate in 81/124 (65%) and 6/265 (2%) of FFRCT positive and negative patients, respectively (p<0.00001). At follow up, for positive versus negative FFRCT patients, the rates were 0.8% versus 0% for death (p=0.32) and 1.6% versus 0.4% for MI (p=0.24). In conclusion, low-risk ACP-ED patients undergoing CTA and FFRCT, the risk of late death (0.2%) and MI (0.7%) are low. Negative FFRCT is associated with excellent long-term prognosis, and positive FFRCT predicts obstructive disease requiring revascularization. FFRCT can safely triage ACP-ED patients, and reduce unnecessary ICA and revascularization.

Cardiotoxicity of Biological Therapies in Cancer Patients: An In-depth Review.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Valve-in-Mitral Annular Calcification Transcatheter Mitral Valve Replacement After Thrombosis of Extracardiac Valved Conduit.

We report a patient with severe mitral annular calcification, mitral stenosis/regurgitation, hypertrophic obstructive cardiomyopathy, and subaortic membrane treated with valved left atrium-left ventricle conduit, septal myectomy, and membrane resection. Subsequent thrombosis of the conduit prompted successful valve-in- mitral annular calcification transcatheter mitral valve replacement and laceration of the anterior mitral leaflet to prevent outflow obstruction. (Level of Difficulty: Advanced.).

Usefulness of Coronary Computed Tomographic Angiography to Evaluate Coronary Artery Disease in Radiotherapy-Treated Breast Cancer Survivors.

Breast cancer is the most commonly diagnosed cancer in women and radiotherapy is a widely used treatment approach. However, there is an increased risk of coronary artery disease and cardiac death in women treated with radiotherapy. The present study was undertaken to clarify the relation between radiotherapy and coronary disease in women with previous breast irradiation using coronary computed tomographic angiography (CCTA). We conducted a retrospective analysis of women with a history of right or left-sided breast cancer (RBC; LBC) treated with radiotherapy who subsequently underwent CCTA. RBC patients who had reduced radiation doses to the myocardium served as controls. Patients (n = 6,593) with a history of nonmetastatic breast cancer treated with radiotherapy were screened for completion of CCTA; 49 LBC and 45 RBC women were identified. Age and risk factor matched patients with LBC had higher rates of coronary disease compared with RBC patients; left anterior descending (LAD) coronary artery (76% vs 31% [p < 0.001]), left circumflex (33% vs. 6.7% [p = 0.004]), and right coronary artery (37% vs 13% [p = 0.018]). Mean LAD radiation dose and mean heart dose strongly correlated with coronary disease, with a 21% higher incidence of disease in the LAD per Gy for mean LAD dose and a 95% higher incidence of disease in the LAD per Gy for mean heart dose. In conclusion, LBC patients treated with radiotherapy have a significantly higher incidence of coronary disease when compared with a matched group of patients treated for RBC. Radiation doses correlated with the incidence of coronary disease.

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve.

BACKGROUND: Values of fractional flow reserve (FFRCT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFRCT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFRINV). METHODS: 1484 patients underwent FFRCT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25-50%, 50-70%, and >70% stenosis). The rates of positive FFRCT (≤0.8) were determined by measuring FFRCT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFRCT were calculated. Diagnostic performance of FFRCT relative to FFRINV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves. RESULTS: Positive FFRCT was identified in 24.9% of vessels using terminal vessel FFRCT and 10.1% using FFRCT distal-to-the-lesion (p â€‹< â€‹0.001). FFRCT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFRCT to negative FFRCT. Relative to FFRINV, there were improvements in specificity (50% to 86%, p â€‹< â€‹0.001), diagnostic accuracy (65% to 88%, p â€‹< â€‹0.001), positive predictive value (50% to 78%, p â€‹< â€‹0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p â€‹< â€‹0.001) when FFRCT was measured distal-to-the-lesion. CONCLUSION: FFRCT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFRCT measured distal-to-the-lesion improves the diagnostic performance of FFRCT relative to FFRINV, ensures that FFRCT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.

Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department.

OBJECTIVES: This study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography-derived fractional flow reserve (FFRCT) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)-based triage program. BACKGROUND: FFRCT is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied. METHODS: ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFRCT were studied. FFRCT ≤0.80 was considered positive for hemodynamically significant stenosis. RESULTS: Among 555 patients, 297 underwent coronary CTA and FFRCT (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFRCT was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFRCT groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFRCT results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFRCT when revascularization was deferred. Negative FFRCT was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFRCT (8.0%) and coronary CTA (22.9%) (p < 0.001). There was no difference in overall costs between the coronary CTA and FFRCT groups ($8,582 vs. $8,048; p = 0.550). CONCLUSIONS: In ACP, FFRCT is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFRCT, which is associated with higher nonobstructive disease on invasive angiography.

Assessment of lesion-specific ischemia using fractional flow reserve (FFR) profiles derived from coronary computed tomography angiography (FFRCT) and invasive pressure measurements (FFRINV): Importance of the site of measurement and implications for patient referral for invasive coronary angiography and percutaneous coronary intervention.

BACKGROUND: Fractional flow reserve (FFR)-derived from computed tomography angiography (CTA; FFRCT) and invasive FFR (FFRINV) are used to assess the need for invasive coronary angiography (ICA) and percutaneous coronary intervention (PCI). The optimal location for measuring FFR and the impact of measurement location have not been well defined. METHODS: 930 patients (age 60.7 + 10 years, 59% male) were included in this study. Normal and diseased coronary arteries were classified into stenosis grades 0-4 in the left anterior descending artery (LAD, n = 518), left circumflex (LCX, n = 112) and right coronary artery (RCA, n = 585). FFRCT (n = 1215 arteries) and FFRINV (n = 26 LAD) profiles were developed by plotting FFR values (y-axis) versus site of measurement (x-axis: ostium, proximal, mid, distal segments). The best location to measure FFR was defined relative to the distal end of the stenosis. FFR ≤0.8 was considered positive for ischemia. RESULTS: In normal and stenotic coronary arteries there are significant declines in FFRCT and FFRINV from the ostium to the distal vessel (p < 0.001), due to lesion-specific ischemia and to effects unrelated to the lesion. A reliable location (distal to the stenosis) is 10.5 mm [IQR 7.3-14.8 mm] for FFRCT and within 20-30 mm for FFRINV. Rates of positive FFR (from the distal vessel) reclassified to negative FFR (distal to the stenosis) are 61% (FFRCT) and 33% (FFRINV). CONCLUSION: FFRCT and FFRINV values are influenced by stenosis severity and the site of measurement. FFR measurements from the distal vessel may over-estimate lesion-specific ischemia and result in unnecessary referrals for ICA and PCI.

Plaque disruption by coronary computed tomographic angiography in stable patients vs. acute coronary syndrome: a feasibility study.

AIMS: This study was designed to determine whether coronary CT angiography (CTA) can detect features of plaque disruption in clinically stable patients and to compare lesion prevalence and features between stable patients and those with acute coronary syndrome (ACS). METHODS: We retrospectively identified patients undergoing CTA, followed by invasive coronary angiography (ICA) within 60 days. Quantitative 3-vessel CTA lesion analysis was performed on all plaques ≥25% stenosis to assess total plaque volume, low attenuation plaque (LAP, <50 HU) volume, and remodelling index. Plaques were qualitatively assessed for CTA features of disruption, including ulceration and intra-plaque dye penetration (IDP). ICA was employed as a reference standard for disruption. A total of 145 (94 ACS and 51 stable) patients were identified. By CTA, plaque disruption was evident in 77.7% of ACS cases. Although more common among those with ACS, CTA also detected plaque disruption in 37.3% of clinically stable patients (P < 0.0001). CONCLUSIONS: Clinically stable patients commonly manifest plaques with features of disruption as determined by CTA. Though the prevalence of plaque disruption is less than patients with ACS, these findings support the concept that some clinically stable patients may harbour 'silent' disrupted plaques. These findings may have implications for detection of 'at risk' plaques and patients.

CT dose reduction using prospectively triggered or fast-pitch spiral technique employed in cardiothoracic imaging (the CT dose study).

OBJECTIVES: To establish current radiation dose levels with contemporary scanners capable of prospectively triggered or high-pitch spiral scan modes to previous generation scanners among patients evaluated for coronary artery disease, pulmonary embolism, aortic disease, and "triple rule out" in a large population of patients at multiple centers. BACKGROUND: Previous small-scale studies with carefully controlled scan protocols report that CT scanners that facilitate prospectively triggered scanning and provide high-pitch spiral CT scan modes drastically lower radiation doses. However, diagnostic reference levels should be selected by medical bodies on the basis of large surveys of representative sites and reviewed at appropriate time intervals. METHODS: Scan data including dose and image quality parameters were collected retrospectively from 64 slice scanners (control) and prospectively after sites installed 128-slice dual-source scanners with high-pitch capability (study). Protocol selection was purposely not specified to survey "real world" results. Blinded quantitative image analysis was performed on every fifth scan. RESULTS: From April 2011 to March 2012, 2085 patients at 9 sites completed the study: 1051 coronary artery disease (509 control, 542 study), 528 pulmonary embolism (267 control, 261 study), 419 aortic disease (268 control, 151 study), and 87 triple rule out (53 control, 34 study). There was a significant reduction in median dose-length product (DLP) from 669 mGy ∙ cm (interquartile range [IQR]: 419-1026 mGy ∙ cm) in the control group to 260 mGy ∙ cm (IQR: 159-441 mGy ∙ cm) in the study group, a reduction by 61% (P < .0001) and was lower in all categories. No significant differences were noted in image quality. CONCLUSION: Use of advanced scanners facilitating prospectively triggered or high-pitch spiral scan modes results in marked dose reduction across a variety of cardiovascular studies, with no compromise in image quality. These findings may contribute to new target dose recommendations in societal guidelines.

Prospective radial artery study following induction of reactive hyperemia looking at degree of diameter growth in healthy subjects.

OBJECTIVES: This "proof of concept" study sought to determine the magnitude of radial artery diameter change in 20 healthy subjects by induction of flow mediation dilatation (FMD) via reactive hyperemia. BACKGROUND: Transradial access in the cardiac catheterization laboratory is becoming more commonplace due to lower bleeding complications and increase in patient comfort. However, access to the radial artery can be challenging due to small vessel size. We sought to examine whether FMD can be used to increase radial artery diameter, potentially allowing improved transradial access. METHODS: We obtained baseline radial artery diameter via a high frequency ultrasound probe on 20 healthy subjects. A standard reactive hyperemia protocol was employed in the right arm, followed by successive measurements of the subject's radial artery at pre-specified intervals. Radial artery diameter measurements were performed offline by the sonographer and also a blinded reader to which agreement was sought. RESULTS: We found a mean increase in radial artery size of 0.48 ± 0.13 mm at peak reactive hyperemic states. This correlated to a mean increase in overall radial artery diameter of 21.7 ± 6.7%. The median time to peak dilation was 30 seconds (95% CI; 15-45 seconds), and the median duration of maximal dilation was 60 seconds (95% CI; 45-75 seconds). CONCLUSIONS: Among healthy subjects, we demonstrated a mean maximal increase in radial artery diameter of 21.7 ± 6.7% via FMD. This finding supports the notion that radial artery diameter can be increased noninvasively via a reactive hyperemia protocol.