Fractional Flow Reserve Cardio-Oncology Effects on Inpatient Mortality, Length of Stay, and Cost Based on Malignancy Type: Machine Learning Supported Nationally Representative Case-Control Study of 30 Million Hospitalizations.

Background and Objectives: There are no nationally representative studies of mortality and cost effectiveness for fractional flow reserve (FFR) guided percutaneous coronary interventions (PCI) in patients with cancer. Our study aims to show how this patient population may benefit from FFR-guided PCI. Materials and Methods: Propensity score matched analysis and backward propagation neural network machine learning supported multivariable regression was performed for inpatient mortality in this case-control study of the 2016 National Inpatient Sample (NIS). Regression results were adjusted for age, race, income, geographic region, metastases, mortality risk, and the likelihood of undergoing FFR versus non-FFR PCI. All analyses were adjusted for the complex survey design to produce nationally representative estimates. Results: Of the 30,195,722 hospitalized patients meeting criteria, 3.37% of the PCIs performed included FFR. In propensity score adjusted multivariable regression, FFR versus non-FFR PCI significantly reduced inpatient mortality (OR 0.47, 95%CI 0.35−0.63; p < 0.001) and length of stay (LOS) (in days; beta −0.23, 95%CI −0.37−−0.09; p = 0.001) while increasing cost (in USD; beta $5708.63, 95%CI, 3042.70−8374.57; p < 0.001), without significantly increasing complications overall. FFR versus non-FFR PCI did not specifically change cancer patients' inpatient mortality, LOS, or cost. However, FFR versus non-FFR PCI significantly increased inpatient mortality for Hodgkin's lymphoma (OR 52.48, 95%CI 7.16−384.53; p < 0.001) and rectal cancer (OR 24.38, 95%CI 2.24−265.73; p = 0.009). Conclusions: FFR-guided PCI may be safely utilized in patients with cancer as it does not significantly increase inpatient mortality, complications, and LOS. These findings support the need for an increased utilization of FFR-guided PCI and further studies to evaluate its long-term impact.

Artificial intelligence-augmented analysis of contemporary procedural, mortality, and cost trends in carcinoid heart disease in a large national cohort with a focus on the "forgotten pulmonic valve".

Background: Carcinoid heart disease is increasingly recognized and challenging to manage due to limited outcomes data. This is the largest known cohort study of valvular pathology, treatment (including pulmonary and tricuspid valve replacements [PVR and TVR]), dispairties, mortality, and cost in patients with malignant carcinoid tumor (MCT). Methods: Machine learning-augmented propensity score-adjusted multivariable regression was conducted for clincal outcomes in the 2016-2018 U.S. National Inpatient Sample (NIS). Regression models were weighted by the complex survey design and adjusted for known confounders and the likelihood of undergoing valvular procedures. Results: Among 101,521,656 hospitalizations, 55,910 (0.06%) had MCT. Patients with MCT vs. those without had significantly higher inpatient mortality (2.93 vs. 2.04%, p = 0.002), longer mean length of stay (12.20 vs. 4.62, p < 0.001), and increased mean total cost of stay ($70,252.18 vs. 51,092.01, p < 0.001). There was a step-wise increased rate of TVR and PVR with each subsequent year, with significantly more TV (0.16% vs. 0.01, p < 0.001) and PV (0.03 vs. 0.00, p = 0.040) diagnosed with vs. without MCT for 2016, with comparable trends in 2017 and 2018. There were no significant procedural disparities among patients with MCT for sex, race, income, urban density, or geographic region, except in 2017, when the highest prevalence of PV procedures were performed in the Western North at 50.00% (p = 0.034). In machine learning and propensity score augmented multivariable regression, MCT did not significantly increase the likelihood of TVR or PVR. In sub-group analysis restricted to MCT, neither TVR nor PVR significantly increased mortality, though it did increase cost (respectively, $141,082.30, p = 0.015; $355,356.40, p = 0.012). Conclusion: This analysis reflects a favorable trend in recognizing the need for TVR and PVR in patients with MCT, with associated increased cost but not mortality. Our study also suggests that pulmonic valve pathology is increasingly recognized in MCT as reflected by the upward trend in PVRs. Further research and updated societal guidelines may need to focus on the "forgotten pulmonic valve" to improve outcomes and disparities in this understudied patient population.

Stress cardiomyopathy in hospitalized patients with cancer: machine learning analysis by primary malignancy type.

AIMS: Previous studies have shown that patients with stress (Takotsubo) cardiomyopathy (SC) and cancer have higher in-hospital mortality than patients with SC alone. No studies have examined outcomes in patients with active cancer and SC compared to patients with active cancer without SC. We aimed to assess the potential association between primary malignancy type and SC and their shared interaction with inpatient mortality. METHODS AND RESULTS: We analysed SC by primary malignancy type with propensity score adjusted multivariable regression and machine learning analysis using the 2016 United States National Inpatient Sample. Of 30 195 722 adult hospitalized patients, 4 719 591 had active cancer, of whom 568 239 had SC. The mean age of patients with cancer and SC was 69.1, of which 74.7% were women. Among patients with cancer, those with SC were more likely to be female and have white race, Medicare insurance, hypertension, heart failure with reduced ejection fraction, obesity, cerebrovascular disease, anaemia, and chronic obstructive pulmonary disease (P < 0.003 for all). In machine learning-augmented, propensity score multivariable regression adjusted for age, race, and income, only lung cancer [OR 1.25; 95% CI: 1.08-1.46; P = 0.003] and breast cancer [OR 1.81; 95% CI: 1.62-2.02; P < 0.001] were associated with a significantly increased likelihood of SC. Neither SC alone nor having both SC and cancer was significantly associated with in-hospital mortality. The presence of concomitant SC and breast cancer was significantly associated with reduced mortality (OR 0.48; 95% CI: 0.25-0.94; P = 0.032). CONCLUSIONS: This analysis demonstrates that primary malignancy type influences the likelihood of developing SC. Further studies will be necessary to delineate characteristics in patients with lung cancer and breast cancer which contribute to development of SC. Additional investigation should confirm lower mortality in patients with SC and breast cancer and determine possible explanations and protective factors.

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial.

PURPOSE: Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements. RESULTS: Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L. CONCLUSIONS: Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.

TAVR and cancer: machine learning-augmented propensity score mortality and cost analysis in over 30 million patients.

INTRODUCTION: Cardiovascular disease (CVD) and cancer are the top mortality causes globally, yet little is known about how the diagnosis of cancer affects treatment options in patients with hemodynamically compromising aortic stenosis (AS). Patients with cancer often are excluded from aortic valve replacement (AVR) trials including trials with transcatheter AVR (TAVR) and surgical AVR (SAVR). This study looks at how cancer may influence treatment options and assesses the outcome of patients with cancer who undergo SAVR or TAVR intervention. Additionally, we sought to quantitate and compare both clinical and cost outcomes for patients with and without cancer. METHODS: This population-based case-control study uses the most recent year available National Inpatient Sample (NIS (2016) from the United States Department of Health and Human Services' Agency for Healthcare Research and Quality (AHRQ). Machine learning augmented propensity score adjusted multivariable regression was conducted based on the likelihood of undergoing TAVR versus medical management (MM) and TAVR versus SAVR with model optimization supported by backward propagation neural network machine learning. RESULTS: Of the 30,195,722 total hospital admissions, 39,254 (0.13%) TAVRs were performed, with significantly fewer performed in patients with versus without cancer even in those of comparable age and mortality risk (23.82% versus 76.18%, p < 0.001) despite having similar hospital and procedural mortality. Multivariable regression in patients with cancer demonstrated that mortality was similar for TAVR, MM, and SAVR, though LOS and cost was significantly lower for TAVR versus MM and comparable for TAVR versus SAVR. Patients with prostate cancer constituted the largest primary cancer among TAVR patients including those with metastatic disease. There were no significant race or geographic disparities for TAVR mortality. DISCUSSION: Comparison of aortic valve intervention in patients with and without cancer suggests that interventions are underutilized in the cancer population. This study suggests that patients with cancer including those with metastasis have similar inpatient outcomes to patients without cancer. Further, patients who have symptomatic AS and those with higher risk aortic valve disease should be offered the benefit of intervention. Modern techniques have reduced intervention-related adverse events, provided improved quality of life, and appear to be cost effective; these advantages should not necessarily be denied to patients with co-existing cancer.

Percutaneous Coronary Intervention in Patients With Gynecological Cancer: Machine Learning-Augmented Propensity Score Mortality and Cost Analysis for 383,760 Patients.

BACKGROUND: Despite the growing number of patients with both coronary artery disease and gynecological cancer, there are no nationally representative studies of mortality and cost effectiveness for percutaneous coronary interventions (PCI) and this cancer type. METHODS: Backward propagation neural network machine learning supported and propensity score adjusted multivariable regression was conducted for the above outcomes in this case-control study of the 2016 National Inpatient Sample (NIS), the United States' largest all-payer hospitalized dataset. Regression models were fully adjusted for age, race, income, geographic region, cancer metastases, mortality risk, and the likelihood of undergoing PCI (and also with length of stay [LOS] for cost). Analyses were also adjusted for the complex survey design to produce nationally representative estimates. Centers for Disease Control and Prevention (CDC)-based cost effectiveness ratio (CER) analysis was performed. RESULTS: Of the 30,195,722 hospitalized patients meeting criteria, 1.27% had gynecological cancer of whom 0.02% underwent PCI including 0.04% with metastases. In propensity score adjusted regression among all patients, the interaction of PCI and gynecological cancer (vs. not having PCI) significantly reduced mortality (OR 0.53, 95%CI 0.36-0.77; p = 0.001) while increasing LOS (Beta 1.16 days, 95%CI 0.57-1.75; p < 0.001) and total cost (Beta $31,035.46, 95%CI 26758.86-35312.06; p < 0.001). Among gynecological cancer patients, mortality was significantly reduced by PCI (OR 0.58, 95%CI 0.39-0.85; p = 0.006) and being in East North Central, West North Central, South Atlantic, and Mountain regions (all p < 0.03) compared to New England. PCI reduced mortality but not significantly for metastatic patients (OR 0.74, 95%CI 0.32-1.71; p = 0.481). Eighteen extra gynecological cancer patients' lives were saved with PCI for a net national cost of $3.18 billion and a CER of $176.50 million per averted death. CONCLUSION: This large propensity score analysis suggests that PCI may cost inefficiently reduce mortality for gynecological cancer patients, amid income and geographic disparities in outcomes.

Socio-Economic Burden of Myocardial Infarction Among Cancer Patients.

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in noncancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013 to 2018 derived from publicly available United States datasets, the National Health Interview Survey , and economic data from the National Inpatient Sample , we compared the socio-economic outcomes in those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 National Health Interview Survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI in cancer survivors compared with noncancer patients (8.8% vs 3.2%, p <0.001). MI was associated with increased financial worry, food insecurity, and financial burden of medical bills (p <0.001, respectively); however, concurrent cancer did not seem to be an effect modifier (p >0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. MI continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly.

Comparative Assessment of Mitral Regurgitation Severity by Transthoracic Echocardiography and Cardiac Magnetic Resonance Using an Integrative and Quantitative Approach.

Although transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) are validated in quantitation of mitral regurgitation (MR), discrepancies may occur. This study assesses the agreement between TTE and CMR in MR and evaluates characteristics and clinical outcome of patients with discrepancy. From our institutional database, 70 subjects with MR underwent both TTE and CMR within 30 days (median 3 days). MR was evaluated semiquantitatively (n = 70) using a 4-grade scale and quantitatively (n = 60) with calculation of regurgitant volume (RVol) and regurgitant fraction (RF). Of the 70 subjects, qualitative assessment by TTE yielded 30 subjects with mild MR, 17 moderate, and 23 moderately severe or severe MR. Exact concordance in MR grade was seen in 50% and increased to 91% when considering concordance within one grade of severity (κ = 0.44). A modest correlation was observed for RVol and RF between both methods (r = 0.59 and 0.54, respectively, p <0.0001). Ten patients had a significant discrepancy in quantitative MR (difference in RF >20%); the frequency of secondary MR was higher (100% vs 46%; p = 0.003) in patients with discrepancy. Although interobserver variability in RF was higher with TTE compared with CMR (-5.5 ± 15% vs 0.1 ± 7.3%), patients with discrepancy were equally distributed by severity and clinical outcome without an overestimation by either method. In conclusion, there is a modest agreement between TTE and CMR in assessing MR severity. In patients with discrepancy, there is a higher prevalence of functional MR, without a consistent overestimation of MR severity by either method.