Cardiac implantable electronic device-induced tricuspid regurgitation: Implications and management.

Tricuspid regurgitation (TR) secondary to cardiac implantable electronic devices (CIEDs) has been well documented and is associated with worse cardiovascular outcomes. A variety of mechanisms have been proposed including lead-induced mechanical disruption of the tricuspid valvular or subvalvular apparatus and pacing-induced electrical dyssynchrony. Patient characteristics such as age, sex, baseline atrial fibrillation, and pre-existing TR have not been consistent predictors of CIED-induced TR. While two-dimensional echocardiography is helpful in assessing the severity of TR, three-dimensional echocardiography has significantly improved accuracy in identifying the etiology of TR and whether lead position contributes to TR. Three-dimensional echocardiography may therefore play a future role in optimizing lead positioning during implant to reduce the risk of CIED-induced TR. Optimal lead management strategies in addition to percutaneous interventions and surgery in alleviating TR are very important.

Coronary Computed Tomographic Angiography With Fractional Flow Reserve in Patients With Type 2 Myocardial Infarction.

BACKGROUND: Type 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population. OBJECTIVES: The goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI. METHODS: In this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFRCT), and plaque volume analyses. RESULTS: Among 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFRCT was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFRCT excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%). CONCLUSIONS: Among individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119).

The healing arts.

ABSTRACT: Art asks of us some measure of curiosity and then rewards our curiosity with an affirmation of the desire to explore self, others, and the world. A psychiatric-mental health nurse practitioner describes his path into nursing and the nurse practitioner role, informed by and informing his art.

Clinical profiling of end-stage heart failure with preserved ejection fraction: The National Readmission Database.

BACKGROUND: End-stage (Stage D) heart failure with preserved ejection fraction (HFpEF) is a poorly characterized syndrome that has heterogeneous underlying pathophysiology. A better characterization of the various clinical profiles of Stage D HFpEF is needed. METHOD: 1066 patients with Stage D HFpEF were selected from National Readmission Database. A Bayesian clustering algorithm based on a Dirichlet process mixture model was implemented. Cox proportional hazard regression model was used to relate the risk of in-hospital mortality with each identified clinical cluster. RESULT: 4 distinct clinical clusters were recognized. Group 1 had a higher prevalence of obesity (84.5%) and sleep disorders (62.0%). Group 2 had a higher prevalence of diabetes mellitus (92%), chronic kidney disease (98.3%), anemia (72.6%), and coronary artery disease (59.0%). Group 3 had a higher prevalence of advanced age (82.1%), hypothyroidism (28.9%), dementia (17.0%), atrial fibrillation (63.8%) and valvular disease (30.5%) and Group 4 had a higher prevalence of liver disease (44.5%), right-sided HF (20.2%) and amyloidosis (4.5%). During 2019, 193 (18.1%) in-hospital mortality events occurred. Considering Group 1 (with mortality rate of 4.1%) as a reference, the hazard ratio of in-hospital mortality was 5.4 [95% confidence interval (CI): 2.2-13.6] for Group 2, 6.4 (95% CI: 2.6-15.8) for Group 3 and 9.1 (95% CI: 3.5-23.8) for Group 4. CONCLUSION: End-stage HFpEF presents with different clinical profiles with varied upstream causes. This may help provide evidence toward the development of targeted therapies.

Near Real-time Natural Language Processing for the Extraction of Abdominal Aortic Aneurysm Diagnoses From Radiology Reports: Algorithm Development and Validation Study.

BACKGROUND: Management of abdominal aortic aneurysms (AAAs) requires serial imaging surveillance to evaluate the aneurysm dimension. Natural language processing (NLP) has been previously developed to retrospectively identify patients with AAA from electronic health records (EHRs). However, there are no reported studies that use NLP to identify patients with AAA in near real-time from radiology reports. OBJECTIVE: This study aims to develop and validate a rule-based NLP algorithm for near real-time automatic extraction of AAA diagnosis from radiology reports for case identification. METHODS: The AAA-NLP algorithm was developed and deployed to an EHR big data infrastructure for near real-time processing of radiology reports from May 1, 2019, to September 2020. NLP extracted named entities for AAA case identification and classified subjects as cases and controls. The reference standard to assess algorithm performance was a manual review of processed radiology reports by trained physicians following standardized criteria. Reviewers were blinded to the diagnosis of each subject. The AAA-NLP algorithm was refined in 3 successive iterations. For each iteration, the AAA-NLP algorithm was modified based on performance compared to the reference standard. RESULTS: A total of 360 reports were reviewed, of which 120 radiology reports were randomly selected for each iteration. At each iteration, the AAA-NLP algorithm performance improved. The algorithm identified AAA cases in near real-time with high positive predictive value (0.98), sensitivity (0.95), specificity (0.98), F1 score (0.97), and accuracy (0.97). CONCLUSIONS: Implementation of NLP for accurate identification of AAA cases from radiology reports with high performance in near real time is feasible. This NLP technique will support automated input for patient care and clinical decision support tools for the management of patients with AAA. .

Inflammation across universal definition of heart failure stages: the CASABLANCA study.

AIM: We sought to investigate the association of inflammatory biomarkers with incident heart failure (HF) events in patients at different stages of HF. METHODS AND RESULTS: Overall, 1231 study participants undergoing diagnostic coronary and/or peripheral angiography were categorized by Universal Definition of HF (UDHF) stage A (at risk), stage B (pre-HF), and stages C or D (HF, including end-stage). Twenty-four inflammatory biomarkers were collected prior to angiography and unsupervised machine learning categorized levels of inflammation into three groups (low, medium, and high). Cox proportional hazard regression was implemented to assess the associations of inflammation level with incident HF hospitalization in each UDHF stage. Using machine learning, study participants were grouped into low (n = 443), medium (n = 570) and high inflammation categories (n = 230). Significantly higher concentrations of natriuretic peptide, troponin, and soluble ST2 were observed among those with high inflammation levels (p < 0.001). During 3.7 years of follow-up, 123 (15.1%) HF hospitalizations occurred in stage A/B and 180 (41.8%) HF hospitalizations occurred in stage C/D. In multivariable model considering low inflammation level as a reference, among patients with stage A/B, the hazard ratio (HR) (95% confidence interval [CI]) of incident HF was 2.31 (1.40-3.80) for moderate inflammation level, and 4.16 (2.35-7.37) for high inflammation level. Among patients with stage C/D, the corresponding HR (95% CI) of HF hospitalization was 1.98 (1.28-3.04) for moderate inflammation level, and 2.69 (1.69-4.28) for high inflammation level. CONCLUSION: Patterns of inflammation severity may have differing prognostic meaning across UDHF stages.

Age Differences in Effects of Sacubitril/Valsartan on Cardiac Remodeling, Biomarkers, and Health Status.

BACKGROUND: Sacubitril/valsartan (Sac/Val) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: In this study, the authors sought to explore age differences in effects of Sac/Val on biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores and cardiac remodeling. METHODS: After initiation and titration of Sac/Val, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-cTnT), and soluble suppressor of tumorigenicity 2 (sST2) were measured and KCCQ-23 scores obtained from baseline to 12 months. Left ventricular ejection fraction (LVEF), and indexed left ventricular end-systolic (LVESVi) and indexed left ventricular end-diastolic (LVEDVi) and left atrial volume index (LAVi) volumes were measured with the use of echocardiography. Safety end points were assessed. Age-stratified analysis was performed for groups aged <65, 65-74, and ≥75 years. RESULTS: Among 794 participants with HFrEF (mean age 65.1 years, 28.5% women), compared with patients aged <65 years (n = 369), 65-74 years (n = 237), and those aged ≥75 years (n = 188), had similar reductions in hs-cTnT and sST2, but less NT-proBNP reduction (-45.6% vs -40.2% vs -30.5%, respectively; P = 0.02). Gains in KCCQ-23 were smaller (+11.8 vs +11.4 vs +6.0 points; P = 0.03) in patients aged ≥75 years, although similar proportions of each age group achieved ≥10-point and ≥20-point increases in KCCQ-23 by month 12. Improvements in LVEF, LVEDVi, LVESVi, and LAVi were similar among age groups. Incidence of safety end points was also similar. CONCLUSIONS: Sac/Val resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories. Older study participants showed somewhat blunted reduction in NT-proBNP and less improvement in KCCQ-23 overall summary scores. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).

Optimal Echocardiographic Parameters to Improve the Diagnostic Yield of Tc-99m-Bone Avid Tracer Cardiac Scintigraphy for Transthyretin Cardiac Amyloidosis.

BACKGROUND: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy. METHODS: Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC). RESULTS: Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83; P=0.004). An inferolateral wall thickness of ≥14 mm (AUC: 0.73) was as accurate as the published cut-offs for transthyretin cardiac amyloidosis score and septal apex to base (AUC: 0.72 and 0.69, P=0.8 and P=0.1, respectively), and was superior to ejection fraction to global LS and relative apical sparing (AUC: 0.64 and 0.53, P<0.001, respectively). A cut-off of ≥-8% for average basal LS (AUC: 0.76, CI: 0.72-0.79) had a similar area under the curve to transthyretin cardiac amyloidosis score (TCAS) (P=0.2); outperforming the other indices (P<0.01). CONCLUSION: Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

Natural language processing for identification of hypertrophic cardiomyopathy patients from cardiac magnetic resonance reports.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging is important for diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM) patients. However, collection of information from large numbers of CMR reports by manual review is time-consuming, error-prone and costly. Natural language processing (NLP) is an artificial intelligence method for automated extraction of information from narrative text including text in CMR reports in electronic health records (EHR). Our objective was to assess whether NLP can accurately extract diagnosis of HCM from CMR reports. METHODS: An NLP system with two tiers was developed for information extraction from narrative text in CMR reports; the first tier extracted information regarding HCM diagnosis while the second extracted categorical and numeric concepts for HCM classification. We randomly allocated 200 HCM patients with CMR reports from 2004 to 2018 into training (100 patients with 185 CMR reports) and testing sets (100 patients with 206 reports). RESULTS: NLP algorithms demonstrated very high performance compared to manual annotation. The algorithm to extract HCM diagnosis had accuracy of 0.99. The accuracy for categorical concepts included HCM morphologic subtype 0.99, systolic anterior motion of the mitral valve 0.96, mitral regurgitation 0.93, left ventricular (LV) obstruction 0.94, location of obstruction 0.92, apical pouch 0.98, LV delayed enhancement 0.93, left atrial enlargement 0.99 and right atrial enlargement 0.98. Accuracy for numeric concepts included maximal LV wall thickness 0.96, LV mass 0.99, LV mass index 0.98, LV ejection fraction 0.98 and right ventricular ejection fraction 0.99. CONCLUSIONS: NLP identified and classified HCM from CMR narrative text reports with very high performance.

Relation of High-Sensitivity Cardiac Troponin I and Obstructive Coronary Artery Disease in Patients Without Acute Myocardial Infarction.

The relation of high-sensitivity cardiac troponin I (hs-cTnI) concentration and presence of obstructive coronary artery disease (CAD) in patients without myocardial infarction (MI) is unclear. Study participants selected from patients free of MI who underwent coronary angiography with or without intervention were enrolled, and hs-cTnI measured. A gradient boosting model was implemented to build a model for detection of CAD. Cox proportional hazard regression was used to assess the association of hs-cTnI and adverse cardiovascular (CV) outcome. Among 978 study participants, 607 patients (62%) had CAD. Higher concentrations of hs-cTnI were associated with chronic kidney disease, heart failure, CAD, male gender, current tobacco use, anemia, age, and low-density lipoprotein cholesterol. History of CAD, male gender, type 2 diabetes mellitus, hs-cTnI, anemia, age, and high-density lipoprotein cholesterol were the most influential factors for detection of CAD. The gradient boosting model had an area under the curve of 0.82, accuracy of 75%, sensitivity of 88%, specificity of 52%, positive predictive value of 76%, and negative predictive value of 72% for detection of CAD. Increase in 1 log unit of hs-cTnI was significantly associated with increased risk of incident MI (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47, p <0.001), CV mortality (HR 1. 24, 95% CI 1.11 to 1.39, p <0.001), and composite of incident MI or CV mortality (HR 1.29, 95% CI 1.20 to 1.40, p <0.001). In conclusion, among patients without acute MI and CAD, higher concentrations of hs-cTnI were associated with the presence of CAD and linked to increased risk of future CV events. ClinicalTrials.gov Identifier: NCT00842868.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BACKGROUND: Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. METHODS: We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. RESULTS: Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). CONCLUSION: Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF.

OBJECTIVES: This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. BACKGROUND: Through inhibition of neprilysin, Sac/Val may increase BNP concentrations. METHODS: In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. RESULTS: Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [-30% to +41%]; P = 0.36) or week 12 (+1% [-36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by -30% (-50% to -8%) and -32% (-54% to -1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34% to +115%]), unchanged (+34% [-15% to +205%]), or increased (+57% [-12% to +14%]). CONCLUSIONS: In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy.

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk. Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI. Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events. Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P < 0.001) and colitis (24.3% vs 16.7%; P = 0.045) in patients with autoimmune disease. Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI.

Building Culturally Competent Practice with Sexual and Gender Minorities Using Nonviolent Communication.

Psychiatric-Mental Health nurses can build cultural competence when caring for clients who are Sexual and Gender Minorities (LGBTQIA+) in the following ways: by learning how health care pathologized core aspects of Sexual and Gender Minorities' (SGM) identities; by understanding historical and current SGM minority stressors and consequent health disparities and inequities; and by framing health disparities and inequities as forms of cultural violence. To begin building trust among SGMs and health care providers, trust damaged by cultural violence and stigma, nurses can implement the Nonviolent Communication Process in clinical settings.

Immune checkpoint inhibitors for cancer and venous thromboembolic events.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. There are limited data on the risk for developing venous thromboembolism (VTE) among patients on an ICI. METHODS: This was a retrospective study of 2854 patients who received ICIs at a single academic centre. VTE events, defined as a composite of deep vein thrombosis or pulmonary embolism, were identified by individual chart review and blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an 'at-risk period' defined as the two-year period after and the 'control period', defined as the two-year before treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model. RESULTS: Of the 2854 patients, 1640 (57.5%) were men; the mean age was 64 ± 13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was > 4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65-8.59, p < 0.001). There was a 5.7-fold higher risk for deep vein thrombosis (HR 5.70, 95% CI 3.79-8.59, p < 0.001) and a 4.75-fold higher risk for pulmonary embolism (HR 4.75, 95% CI 3.20-7.10, p < 0.001). Comparing patients with and without a VTE event, a history of melanoma and older age predicted lower risk of VTE, while a higher Khorana risk score, history of hypertension and history of VTE predicted higher risk. CONCLUSIONS: The rate of VTE among patients on an ICI is high and increases after starting an ICI.

Association between incidental statin use and skeletal myopathies in patients treated with immune checkpoint inhibitors.

OBJECTIVES: Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies. METHODS: This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal). RESULTS: Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65-410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07-4.50; P = 0.033). CONCLUSION: In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies.

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. METHODS: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. RESULTS: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures. CONCLUSIONS: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.