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Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age‐ and sex‐adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI , 25%–34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95% CI , 1.07–1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI , 27%–39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95% CI , 1.00–1.22]). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

Background The objective of this case cohort study was to describe our experience in the care of patients with immune checkpoint inhibitor–related acute interstitial nephritis (ICI-AIN) including rechallenge. Methods A descriptive case series of patients that received an ICI and had an AKI (defined as a ≥1.5-fold increase in serum creatinine) as an immune-related adverse event (irAE), with biopsy-proven or clinically suspected ICI-AIN from January 1, 2014 to December 1, 2018 at Mayo Clinic, Rochester. We studied details regarding diagnosis, clinical course, management, and outcomes of rechallenge of immunotherapy. Complete response (CR) was defined as return of kidney function back to baseline or <0.3 mg/dl above baseline creatinine; partial response (PR) was defined as creatinine >0.3 mg/dl from baseline, but less than twofold above the baseline by the end of steroid course. Results A total of 14 cases of biopsy-proven (35%) or clinically suspected (65%) ICI-AIN was identified. All patients had their ICI withheld and 12 patients received steroids. Steroid regimens were highly variable. The starting equivalent dose of prednisone was higher in those that had a CR versus a PR (median 0.77 mg/kg versus 0.66 mg/kg). Proton pump inhibitors (PPIs) were used in 11 patients and were stopped in eight (73%) patients at the time of the AKI event. A CR was seen in five (63%) of the eight patients who discontinued PPIs. Rechallenge was attempted in four of the 14 patients: three were successful with no recurrence of AKI, but one patient had recurrent AKI and fatal pneumonitis. Conclusions Careful review, withholding ICI and concomitant known AIN-inducing medications, along with prompt initial steroid management were the key in complete renal kidney recovery. A kidney biopsy should be strongly considered. Rechallenge of immunotherapy after a kidney irAE, although challenging, is possible and would need careful evaluation on an individual basis. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_01_30_KID0000152019.mp3

Background With lymphoma survival rates increasing and a growing population of long-term survivors, the development of cardiovascular disease (CVD) in this patient population is of increasing importance. Anthracyclines are critical in the management of many lymphoma subtypes. However, there is a risk of developing anthracycline-induced CVD. Here, we estimate the cumulative incidence of CVD in adult lymphoma survivors and investigate risk factors associated with post diagnosis CVD. Methods Participants were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). From 2002-2015, the MER offered enrollment to all patients with newly diagnosed lymphoma who are US residents and age &gt;18 years. Participants completed a risk factor questionnaire, and clinical and treatment data were abstracted from medical records. Patients were contacted every 6 months for the first 3 years after diagnosis and annually thereafter to assess disease status, re-treatment and new onset morbidity including CVD. CVD events, including congestive heart failure (CHF), coronary artery disease (CAD), valvular heart disease (VHD), and arrhythmia were identified and validated against medical records. CHF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. CAD, arrhythmia, and VHD were validated using clinical definitions. We calculated the cumulative incidence of CVD, with death modeled as a competing risk. The association of risk factors and treatments with risk of CVD was estimated using hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression with a competing risk of death. Risk factors included age, sex, diabetes, smoking, body mass index (BMI), and treatment with anthracyclines or radiation therapy. Results The study consisted of 3,063 lymphoma patients after excluding those with chronic lymphocytic leukemia and CVD prior to lymphoma diagnosis. The median age at diagnosis was 59 years (range 18-95), and 56% were males. At a median follow-up was 6.9 years (range 0.8-17.1), 640 patients (21%) had died without CVD and 485 patients self-reported CVD post lymphoma diagnosis, of which 280 (57.7%) were validated. Cardiovascular events included 86 CHF, 78 CAD, 40 VHD, and 164 arrhythmias. The cumulative incidence of CVD (Figure 1) at 5 and 10 years was 6.0% (95% 5.2%-7.0%) and 10.7% (95% CI 9.5%-12.1%), respectively. In multivariable analysis, increasing age (HR=3.93 per 5 years, p&lt;0.001), male sex (HR=1.33, p=0.03), former smoker (HR=1.04, p=0.77), current smoker (HR=1.96, p&lt;0.001), BMI&gt;30 kg/m2 (HR=1.50, p=0.01), and anthracycline treatment (HR=1.49. p&lt;0.001) were all significantly associated with risk of overall CVD, while there was no association with diabetes (HR=0.92, p=0.70) or radiation therapy (HR=1.05, p=0.78) in the multivariable model. Anthracycline use was significantly associated with increased risk of CHF (HR=2.64, p&lt;0.001) and arrhythmia (HR=1.51, p&lt;0.01), but not VHD (HR=0.83, p=0.56) or CAD (HR=1.23, p=0.31) after adjustment for the cardiac risk factors. The number of anthracycline cycles ranged from 0 to 12. 63.2% of individuals that received anthracyclines received 6 cycles. The 5-year cumulative incidence of CVD for 0, 1-5, 6, and &gt;6 anthracycline cycles was 5%, 6.9%, 7.4%, and 7.7%, respectively. Adjusting for cardiac risk factors, the number of anthracycline cycles was significantly associated with increased risk of CVD (1-5 cycles HR=1.34, p=0.11; 6 cycles HR=1.51, p&lt;0.01; &gt;6 cycles HR=2.04, p=0.03). Furthermore, the number of anthracycline cycles was associated with CHF (1-5 cycles HR=2.82, p&lt;0.001; 6 cycles HR=2.46, p&lt;0.001; &gt;6 cycles HR=5.33, p&lt;0.001) and arrhythmia (1-5 cycles HR=1.31, p=0.27; 6 cycles HR=1.60, p&lt;0.01; &gt;6 cycles HR=1.65, p=0.27). Conclusions In the modern treatment era, the risk of new onset CVD in patients with lymphoma without a history of CVD is approximately 1% per year after diagnosis. Arrhythmia and CHF were the most commonly occurring CVD events in this cohort. Both traditional CVD risk factors and treatment with anthracyclines was associated with an increased risk of developing CVD, and anthracyclines were a risk factor for arrhythmia and CHF in particular. Prevention of CVD in lymphoma patients will need to address both treatment and traditional lifestyle factors. Figure 1 Disclosures Maurer: Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Celgene: Research Funding. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

RXRA is an endothelial- and early stage–predominant therapeutic target for treating anthracycline-induced cardiotoxicity.

Aims Cardiovascular health metrics predict the risk not only of cardiovascular diseases but also of several types of cancers. Microvascular endothelial dysfunction can predict future cardiovascular adverse events, but the predictive value of microvascular endothelial dysfunction for future risk of solid-tumor cancer has not been characterized. Methods A total of 488 patients who underwent microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry were included in this study. Microvascular endothelial dysfunction was defined as a reactive hyperemia peripheral arterial tonometry index ≤2.0. Results Of 221 patients with a baseline reactive hyperemia peripheral arterial tonometry index ≤2.0, 21 patients (9.5%) were diagnosed with incident solid-tumor cancer during follow-up, whereas of 267 patients with a baseline reactive hyperemia peripheral arterial tonometry index >2.0, 10 patients (3.7%) were diagnosed with incident solid-tumor cancer during follow-up ( p = 0.009). Patients with a reactive hyperemia peripheral arterial tonometry index ≤2.0 had lower solid-tumor cancer-free survival compared to patients with a reactive hyperemia peripheral arterial tonometry index >2.0 (log-rank p = 0.017) (median follow-up 6.0 (3.0–9.1) years). Cox proportional hazard analyses showed that a reactive hyperemia peripheral arterial tonometry index ≤2.0 predicted the incidence of solid-tumor cancer, with a hazard ratio of 2.52 (95% confidence interval 1.17–5.45; p = 0.019) after adjusting for age, sex, and coronary artery disease, 2.83 (95% confidence interval 1.30–6.17; p = 0.009) after adjusting for diabetes mellitus, hypertension, smoking status, and body mass index >30 kg/m2, 2.79 (95% confidence interval 1.21–6.41; p = 0.016) after adjusting for fasting plasma glucose, systolic blood pressure, smoking status (current or former), and body mass index, and 2.43 (95% confidence interval 1.10–5.34; p = 0.028) after adjusting for Framingham risk score. Conclusion Microvascular endothelial dysfunction, as defined by a reactive hyperemia peripheral arterial tonometry index ≤2.0, was associated with a greater than two-fold increased risk of solid-tumor cancer. Microvascular endothelial dysfunction may be a useful marker to predict the future risk of solid-tumor cancer, in addition to its known ability to predict cardiovascular disease. Further research is necessary to develop adequate cancer screening strategies for patients with microvascular endothelial dysfunction.

Abstract Background Anthracyclines are one of the most effective chemotherapeutic agents but can lead to a decline in cardiac function. Two-dimensional (2D) speckle tracking echocardiography derived strain can predict cancer therapeutics-related cardiac dysfunction (CTRCD). However, little is known about the role of three-dimensional (3D) strain imaging in this setting. Purpose To evaluate different methods of Left Ventricular Ejection Fraction (LVEF) and strain, and to identify the best strain parameter for the prediction of CTRCD in this group of patients during treatment with anthracycline based chemotherapy. Methods Patients with Hodgkin's or non-Hodgkin's lymphoma receiving anthracycline based chemotherapy were enrolled. 2D-and 3D echocardiography was performed at 3 time points: baseline, at the completion of chemotherapy and at 1 year. 2D- and 3D LVEF (2D Modified Quinones, M-mode, 2D Biplane, 3D Philips, 3D GE and 3D TomTec), peak systolic left and right ventricular longitudinal, radial and circumferential strain and strain rate were measured. CTRCD was defined as a decrease in LVEF >10% to an absolute value of <53%. Lin's Concordance Correlation Coefficient (CCC) was calculated to compare LVEF methods. ANOVA, uni and multivariate analysis was performed. Results A total of 130 patients (79 males, mean age 57±16 years) were enrolled; 104 non-Hodgkin.3D Philips and GE (CCC 0.88 [0.84, 0.92]), 3D Philips and biplane (CCC 0.84 [0.79, 0.89]), 3D Philips and Modified Quinones (CCC 0.86 [0.82, 091]) as well as 3D Philips and M-mode (CCC 0.77 [0.70, 0.85]) showed strong correlation for LVEF. 15 patients (12%) developed CTRCD. Mean cumulative anthracycline dose was 263±65 mg/m2. 2D and 3D global longitudinal and circumferential peak systolic strain, 2D global longitudinal systolic and early diastolic strain rate, 2D global early diastolic strain rate, 2D right ventricular longitudinal peak systolic strain and systolic strain rate, 2D global radial peak systolic strain and systolic strain rate measured at the completion of chemotherapy were independent predictors of the development of CTRCD at 1 year post-chemotherapy. The strongest predictors of CTRCD were 3D global longitudinal and circumferential strain either individually (area under the curve, 0.90 and 0.95 respectively) or combined (area under the curve, 0.95) at the completion of chemotherapy; a cutoff value of <-18% in 3D global longitudinal strain had a sensitivity of 82% and specificity of 99%, while for 3D global circumferential peak systolic strain of <-24% had a sensitivity of 82% and specificity of 95%. Conclusions To our knowledge this is the first prospective trial that shows that 3D EF correlates well with other EF methods and 3D strain predicts cardiac toxicity in this group of patients with a very good sensitivity and specificity. Acknowledgement/Funding Department of Cardiovascular Medicine-Mayo Clinic Rochester MN

Abstract Background Cancer patients have a higher risk of thromboembolic events but it is not well known if these patients also have a higher risk of death, myocardial infarction (MI) or repeat revascularization after percutaneous coronary intervention (PCI) is unknown. Methods Cancer patients who underwent first-time single vessel PCI from January 1, 2003, through December 31, 2013 were identified by cross-matching of institutional cancer and PCI registries. These cancer patients were matched 4:1 to non-cancer patients, likewise undergoing first-time single vessel PCI in the time period. The combined primary endpoint was death, MI and revascularization at 5 year follow-up. Secondary endpoints were death and MI combined and the individual components of the primary endpoint. Both time dependent and non-time-dependent analyses were conducted. Results A total of 712 cancer patients were identified and matched to 2,848 non-cancer patients (one third women in either group). Bare-metal stents were used in one third of patients in both groups. The combined primary study endpoint was significantly more frequently encountered in the cancer than in the non-cancer group in both time-dependent (Figure 1) and non-time dependent analyses (5-year event rate 48.6% vs. 31.2%, p<0.001). This was driven by a higher 5-year event rate of death (39.0% vs. 20.1%) and MI (14.8% vs 4.86%) in the cancer group. The 5-year rate of revascularization did not differ significantly between the two groups (10.5% vs 10.3%). Figure 1. MI + revascularization-survival Conclusion Cancer patients have a two times higher rate of death and a three times higher rate of MI over the first 5 years after PCI. Future studies will need to define the etiology and factors accounting for this higher event rate in cancer patients, especially of these patients are predisposed to stent thrombosis and need longer term dual antiplatelet therapy.