Incidental coronary calcium in cancer patients treated with anthracycline and/or trastuzumab.

AIMS: Cancer patients are at increased risk of cardiovascular disease (CVD) after treatment with potentially cardiotoxic treatments. Many cancer patients undergo non-gated chest computed tomography (NCCT) for cancer staging prior to treatment. We aimed to assess whether coronary artery calcification on NCCT predicts CVD risk in cancer patients. METHODS AND RESULTS: Six hundred and three patients (mean age: 61.3 years, 30.8% male) with either breast cancer, lymphoma, or sarcoma were identified retrospectively. Primary endpoint was a major adverse cardiac event (MACE) composite including non-fatal myocardial infarction, new heart failure (HF) diagnosis, HF hospitalization, and cardiac death, with Fine-Gray analysis for non-cardiac death as competing risk. Secondary endpoints included a coronary composite and a HF composite. Coronary artery calcification was present in 194 (32.2%) and clinically reported in 85 (43.8%) patients. At a median follow-up of 5.3 years, 256 (42.5%) patients died of non-cardiac causes. Coronary artery calcification presence or extent was not an independent predictor of MACE [sub-distribution hazards ratio (SHR) 1.28; 0.73-2.27]. Coronary artery calcification extent was a significant predictor of the coronary composite outcome (SHR per two-fold increase 1.14; 1.01-1.28), but not of the HF composite outcome (SHR per two-fold increase 1.04; 0.95-1.14). CONCLUSION: Coronary artery calcification detected incidentally on NCCT scans in cancer patients is prevalent and often not reported. Coronary artery calcification presence or extent did not independently predict MACE. Coronary artery calcification extent was independently associated with increased risk of CAD events but not HF events.

Prognostic impact of identifying etiology of prosthetic valve dysfunction with CT.

BACKGROUND: In patients with prosthetic heart valves (PHV), there are distinct treatment implications based on prosthetic valve dysfunction (PVD) etiology. We investigated whether evaluation for PVD etiology on computed tomography (CT) has prognostic value for adverse clinical outcomes. METHODS: Consecutive patients with suspected PVD that had a clinically indicated contrast chest CT and echocardiogram done within 1 year of each other were identified retrospectively from the Prosthetic Heart Valve CT Registry at the University of Minnesota. CTs and echocardiograms were assessed for potential PVD etiologies of pannus, structural valve degeneration (SVD) and thrombus, as per standard guidelines. Kaplan-Meier and Cox regression analyses were performed to assess association with a composite outcome of reoperation and all-cause mortality. RESULTS: 132 patients (51.5% male, mean age 62.1 â€‹± â€‹19.3 years) with suspected PVD were included. There were 97 tissue valves, 31 mechanical valves and 4 transcatheter valves. The location of the valve was as follows: 72 aortic, 45 mitral, 8 tricuspid, and 7 pulmonic. A PVD etiology was diagnosed on CT in 80 (60.6%) patients, and on echocardiography in 45 (34.1%) patients, largely driven by a diagnosis of SVD on both modalities. Significant univariate predictors of the composite outcome included CT diagnosis of SVD (P â€‹< â€‹0.001), echocardiography diagnosis of SVD (P â€‹< â€‹0.001), degree of prosthetic stenosis (P â€‹< â€‹0.001) and degree of prosthetic regurgitation (P â€‹< â€‹0.001). On multivariable analyses adjusted for age, sex, left ventricular function, degree of prosthetic stenosis and degree of prosthetic regurgitation, CT diagnosis of SVD was significantly associated with the composite outcome (HR: 1.79, 1.09-2.95) whereas echocardiography diagnosis of SVD was not (HR: 1.56, 0.98-2.46). CONCLUSION: In patients with suspected PVD, CT assessment of SVD had prognostic significance for hard outcomes. CT should be considered in the diagnostic evaluation of patients with suspected PVD.

Prognostic Role of Paravalvular Spread on Computed Tomography in Suspected Prosthetic Valve Endocarditis.

We aimed to assess the prognostic value of computed tomography assessment of paravalvular spread in suspected prosthetic valve endocarditis.

Long-term prognostic value of right ventricular dysfunction on cardiovascular magnetic resonance imaging in anthracycline-treated cancer survivors.

AIMS: We aimed to determine the prevalence of right ventricular (RV) systolic dysfunction on cardiovascular magnetic resonance imaging (CMR) and its impact on long-term adverse outcomes in a large cohort of cancer survivors treated with anthracycline-based chemotherapy. METHODS AND RESULTS: Consecutive cancer survivors treated with anthracyclines who underwent clinical CMR for suspected anthracycline-related cardiomyopathy were studied. The primary endpoint was a composite of all-cause death or major adverse cardiac events (MACE): heart failure hospitalization, heart transplantation, ventricular assist device implantation, resuscitated cardiac arrest, or life-threatening ventricular arrhythmia. The secondary endpoints were all-cause death, and cardiac death or MACE. Among 249 survivors who underwent CMR at a median of 2.9 years after cancer treatment, RV systolic dysfunction was present in 54 (21.7%). Of these, 50 (92.6%) had an abnormal left ventricular ejection fraction (LVEF). At a median follow-up time after the CMR of 2.7 years, 105 survivors experienced the primary endpoint. On Kaplan-Meier analyses, the cumulative incidence of the primary endpoint was significantly higher in survivors with abnormal RVEF compared with those with normal RVEF (P = 0.002). However, on Cox multivariable analyses, RVEF was not associated with the primary endpoint (HR 1.04 per 5% decrease; 95% CI 0.93-1.17; P = 0.46) after adjustment for non-imaging variables and LVEF. RVEF was also not associated with the secondary endpoints. CONCLUSION: Among anthracycline-treated cancer survivors undergoing CMR for suspected cardiotoxicity, RV systolic dysfunction was present in one in five cases, accompanied by LV systolic dysfunction in nearly all cases, and was not independently associated with long-term outcomes.

Interplay of CT Coronary Plaque Characteristics and Ischemia to Predict Adverse Outcomes.

In 134 patients with stable coronary artery disease, high-risk plaque features at CT and physiologic stenosis were found to act in a synergistic fashion to predict adverse outcomes.

Sex Differences in Patients With Suspected Cardiac Sarcoidosis Assessed by Cardiovascular Magnetic Resonance Imaging.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P=0.010) and palpitations (39.3% versus 26.1%; P=0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P=0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P=0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P=0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P=0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P=0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P=0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77­2.43]; P=0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

Impact of 2016 SCCT/STR guidelines for coronary artery calcium scoring of noncardiac chest CT scans on lung cancer screening CT reporting.

The 2016 SCCT/STR guideline for coronary artery calcification (CAC) scoring on non-cardiac chest CT (NCCT) scans explicitly calls for the reporting of CAC. Whether the publication of the 2016 SCCT/STR guideline has had any impact on CAC reporting in lung cancer screening (LCS) scans has not been investigated. Consecutive patients with a LCS scan were identified from the University of Minnesota LCS registry and evaluated for CAC reporting in 3 separate cohorts: 6 months before, 6 months after, and 1 year after the publication of the 2016 SCCT/STR guideline. Scans were evaluated for CAC and quantified using the Agatston method. CAC reporting, downstream testing and initiation of preventive therapy were assessed. Among 614 patients (50% male, mean age 64.1 ± 6.0 years), CAC was present in 460 (74.9%) with a median Agatston score of 62 (IQR 0, 230). Of these, 196 (31.9%) had a CAC score of 1-100, 125 (20.4%) had 101-300, and 118 (19.2%) had > 300. Overall, CAC was reported in 325 (70.7%) patients with CAC present. CAC reporting relative to publication of the 2016 SCCT/STR guideline was as follows: 6 months prior-74.1%, 6 months after-64.6%, and 1 year after-77.5%. In the 308 patients with a new diagnosis of sub-clinical CAD based on CAC presence, 6 (1.9%) patients were referred to cardiology, and 15 (4.9%) patients underwent testing for obstructive CAD. Only 6 (1.9%) and 9 (2.9%) patients were newly started on aspirin and statin respectively. CAC detected incidentally on lung cancer screening CT scans is prevalent, and rarely acted upon clinically. CAC reporting is fairly high, and publication of the 2016 SCCT/STR guideline for CAC scoring on NCCT scans did not have any significant impact on CAC reporting.

Myocardial damage assessed by late gadolinium enhancement on cardiovascular magnetic resonance imaging in cancer patients treated with anthracyclines and/or trastuzumab.

AIMS: In cancer patients with cardiomyopathy related to anthracyclines and/or trastuzumab, data regarding late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging are confusing. The prevalence ranges from 0% to 30% and the patterns are ill-defined. Whether treatment with anthracyclines and/or trastuzumab is associated with LGE is unclear. We aimed to investigate these topics in a large cohort of consecutive cancer patients with suspected cardiotoxicity from anthracyclines and/or trastuzumab. METHODS AND RESULTS: We studied 298 patients, analysed the prevalence, patterns, and correlates of LGE, and determined their causes. We compared the findings with those from 100 age-matched cancer patients who received neither anthracyclines nor trastuzumab. Amongst those who received anthracyclines and/or trastuzumab, 31 (10.4%) had LGE. It had a wide range of extent (3.9-34.7%) and locations. An ischaemic pattern was present in 20/31 (64.5%) patients. There was an alternative explanation for the non-ischaemic LGE in 7/11 (63.6%) patients. In the age-matched patients who received neither anthracyclines nor trastuzumab, the prevalence of LGE was higher at 27.0%, while the extent of LGE and the proportion with ischaemic pattern were not different. CONCLUSION: LGE was present in only a minority. Its patterns and locations did not fit into a single unique profile. It had alternative explanations in virtually all cases. Finally, LGE was also present in cancer patients who received neither anthracyclines nor trastuzumab. Therefore, treatment with anthracyclines and/or trastuzumab is unlikely to be associated with LGE. The absence of LGE can help distinguish anthracycline- and/or trastuzumab-related cardiomyopathy from unrelated cardiomyopathies.

Computed Tomography Coronary Plaque Characteristics Predict Ischemia Detected by Invasive Fractional Flow Reserve.

PURPOSE: Coronary computed tomography angiography (CCTA) plaque quantification has been proposed to be of incremental value in the prediction of ischemia, although prior studies have shown conflicting results. We aimed to determine whether CCTA plaque features assessed on a commercial vendor platform predict invasive fractional flow reserve (FFR)/instantaneous wave-free ratio (IFR). METHODS: Consecutive patients who underwent CCTA for evaluation of suspected stable coronary artery disease followed by invasive coronary physiology testing within 60 days at a single academic center were identified retrospectively. Semiautomated plaque quantification of the vessel proximal to the location of FFR/IFR measurement was carried out in TeraRecon, along with simple visual assessment for high-risk plaque features of positive remodeling, spotty calcification, low-attenuation plaque (LAP), and lesion length. Ischemia was defined by FFR ≤0.80 or IFR ≤0.89. RESULTS: A total of 134 patients (62% male, mean age 62±10 y) were included in this study. On univariate logistic regression, the following visual plaque analysis parameters were predictive of ischemia: positive remodeling (odds ratio [OR] with 95% confidence interval [CI]: 4.96; 2.25-10.95; P<0.001), lesion length (OR for every 1 mm with 95% CI: 1.24; 1.14-1.34; P<0.001), spotty calcification (OR with 95% CI: 6.67; 1.67-26.64; P=0.007), and LAP (OR with 95% CI: 30; 3.78-246; P=0.001). None of the semiautomated plaque quantification parameters, such as noncalcified plaque volume or LAP volume, were predictive of ischemia. On stepwise multivariable logistic regression, lesion length (OR with 95% CI: 1.25; 1.14-1.37; P<0.0001) and LAP (OR with 95% CI: 43; 4.4-438; P=0.001) were significant predictors of ischemia, improving the area under the curve of CCTA from 0.53 to 0.87. CONCLUSIONS: Simple visual plaque assessment for high-risk plaque features improved the performance of CCTA to predict ischemia. Semiautomated plaque quantification performed on a commercial vendor platform was not predictive of ischemia.

Left ventricular thrombus on cardiovascular magnetic resonance imaging in non-ischaemic cardiomyopathy.

AIMS: Case reports have described left ventricular (LV) thrombus in patients with non-ischaemic cardiomyopathy (NICM). We aimed to systematically study the characteristics, predictors, and outcomes of LV thrombus in NICM. METHODS AND RESULTS: Forty-eight patients with LV thrombus detected on late gadolinium enhancement cardiovascular magnetic resonance imaging (LGE CMR) in NICM were compared with 124 patients with LV thrombus in ischaemic cardiomyopathy (ICM), and 144 matched patients with no LV thrombus in NICM. The performance of echocardiography for the detection of LV thrombus was compared between NICM and ICM. The 12-month incidence of embolism was compared between the three study groups. Independent predictors of LV thrombus in NICM were LV ejection fraction (LVEF) [hazard ratio (HR) 1.36 per 5% decrease; P = 0.002], LGE presence (HR 6.30; P < 0.001), and LGE extent (HR 1.33 per 5% increase; P = 0.001). Compared with patients with LV thrombus in ICM, those with LV thrombus in NICM had a 10-fold higher prevalence of thrombi in other cardiac chambers. The performance of echocardiography for the detection of LV thrombus was not different between NICM and ICM. The 12-month incidence of embolism associated with LV thrombus was not different between NICM and ICM (8.7% vs. 6.8%; P = 0.69) but both were higher compared with no LV thrombus in NICM (1.5%). CONCLUSION: Independent predictors of LV thrombus in NICM were lower LVEF, LGE presence, and greater LGE extent. The 12-month incidence of embolism associated with LV thrombus in NICM was not different compared with LV thrombus in ICM.

Utility of CT in the diagnosis of prosthetic valve abnormalities.

BACKGROUND: Patients with prosthetic heart valves (PHV) are at an increased risk of endocarditis and dysfunction. Knowledge about the etiology of dysfunction and extent of endocarditis can have distinct treatment implications. Echocardiography has limitations due to PHV-related artifacts. We hypothesized that computed tomography (CT) will have incremental value over echocardiography for evaluation of PHV abnormalities with surgical findings as the reference standard. METHODS: Consecutive patients with PHV that had a reoperation for valve replacement, had a contrast chest CT and echocardiogram within 1 year of the reoperation, between 2010 and 2018 at a single academic center formed the study cohort. CTs and echocardiograms were assessed for potential etiologies of dysfunction (valve degeneration, pannus and thrombus); and for extent of endocarditis (vegetation, abscess, and pseudoaneurysm). RESULTS: Seventy-three patients (65.8% male, mean age 62.1 ± 16.5 years) formed the study cohort. The indication for reoperation was PHV dysfunction in 51 and PHV endocarditis in 22. Compared to echocardiography, CT diagnosed the etiology of PHV dysfunction in 17 (33.3%) more patients (9 valve degeneration, 8 pannus). In the PHV endocarditis cohort, CT failed to detect one vegetation and one abscess, whereas echocardiography failed to detect 1 abscess. In combination, CT and echocardiography demonstrated all the vegetations and abscesses. CONCLUSION: CT may provide superior characterization in comparison to echocardiography for the identification of the cause of prosthetic valve dysfunction, and complementary information to echocardiography for the evaluation of prosthetic valve endocarditis.

Right Ventricular Abnormalities on Cardiovascular Magnetic Resonance Imaging in Patients With Sarcoidosis.

OBJECTIVES: This study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis. BACKGROUND: In patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE. METHODS: Consecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia. RESULTS: Among 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4 to 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024). CONCLUSIONS: In this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.

Double Rule In: Concomitant Acute Coronary Occlusion and Pulmonary Embolism.

Computed tomography angiography is frequently used for double rule out of obstructive coronary artery disease and pulmonary embolism in patients presenting to the emergency department with acute chest pain, but it is rare to see concomitant acute coronary occlusion and pulmonary embolism on the same computed tomography angiography scan.

Long-Term Embolic Outcomes After Detection of Left Ventricular Thrombus by Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Imaging: A Matched Cohort Study.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of intracardiac thrombus because of its unique ability to identify thrombus based on tissue characteristics related to avascularity. The long-term prognostic significance of left ventricular (LV) thrombus detected by LGE CMR is unknown. METHODS: We performed a matched cohort study of consecutive adult patients with LV thrombus detected by LGE CMR who were matched on the date of CMR, age, and LV ejection fraction to up to 3 patients without LV thrombus. We investigated the long-term incidence of a composite of embolic events: stroke, transient ischemic attack, or extracranial systemic arterial embolism. We also compared outcomes among patients with LV thrombus detected by LGE CMR stratified by whether the LV thrombus was also detected by echocardiography or not. RESULTS: Of 157 LV thrombus patients, 155 were matched to 400 non-LV thrombus patients. During a median follow-up of 3.3 years, the cumulative incidence of embolism was significantly higher in LV thrombus patients compared with the matched non-LV thrombus patients (P<0.001), with annualized rates of 3.7% and 0.8% for LV thrombus and matched non-LV thrombus patients, respectively. LV thrombus was the only independent predictor of the composite embolic end point (hazard ratio, 3.99 [95% CI, 1.54-10.35]; P=0.004). The cumulative incidence of embolism was not different in patients with LV thrombus that was also detected by echocardiography versus patients with LV thrombus not detected by echocardiography (P=0.25). CONCLUSIONS: Despite contemporary antithrombotic treatment, LV thrombus detected by LGE CMR is associated with a 4-fold higher long-term incidence of embolism compared with matched non-LV thrombus patients. LV thrombus detected by LGE CMR but not by echocardiography is associated with a similar risk of embolism as that detected by both LGE CMR and echocardiography.

Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis.

BACKGROUND: Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them. METHODS: We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index. RESULTS: In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point. CONCLUSIONS: We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.