Association of disproportionate liver fat with markers of heart failure: The multi-ethnic study of atherosclerosis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) has been linked to heart failure with preserved ejection fraction (HFpEF). We sought to understand association between individuals with amounts of liver adiposity greater than would be predicted by their body mass index (BMI) in order to understand whether this disproportionate liver fat (DLF) represents a proxy of metabolic risk shared between liver and heart disease. METHODS: We studied 2,932 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who received computed tomography (CT) measurements of hepatic attenuation. Quartiles of DLF were compared and multivariable linear regression was performed to evaluate the association of DLF with clinical, echocardiographic, and quality of life metrics. RESULTS: Compared to the lowest quartile of DLF, individuals in the highest quartile of DLF were more likely to be male (52.0% vs 47.1%, P < .001), less likely to be Black or African American (14.8 % vs 38.1% P < .001), have higher rates of dysglycemia (31.9% vs 16.6%, P < .001) and triglycerides (140 [98.0, 199.0] vs 99.0 [72.0, 144.0] mg/dL, P > .001). These individuals had lower global longitudinal strain (-0.13 [-0.25, -0.02], P = .02), stroke volumes (-1.05 [-1.76, -0.33], P < .01), lateral e' velocity (-0.10 [-0.18, -0.02], P = .02), and 6-minute walk distances (-4.25 [-7.62 to -0.88], P = .01). CONCLUSION: DLF is associated with abnormal metabolic profiles and ventricular functional changes known to be associated with HFpEF and may serve as an early metric to assess for those that may progress to clinical HFpEF.

Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

Activation of enamine by photoexcited organocatalyst assisted singlet oxygen: synthesis of oxazoles and quinoxalines.

Herein, a novel transition-metal-free thiol-based donor-acceptor organophotocatalyst-assisted, singlet-oxygen-mediated tandem oxidative cyclization for the synthesis of substituted oxazoles in moderate-to-good yields is described. The developed method demonstrates applicability for the synthesis of various substituted quinoxalines in good-to-excellent yields. The metal-free methodology shows a practical route for the synthesis of oxazole and quinoxaline derivatives, which are privileged moieties prevalent in various biologically active compounds and natural products. To the best of our knowledge, both the thiol photocatalyst and synthesis of oxazoles by visible-light irradiation are reported for the first time.

Missense Genetic Variation of ICAM1 and Incident Heart Failure.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF. METHODS AND RESULTS: We identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in the Atherosclerosis Risk in Communities (ARIC) study. Of the 3 missense variants, rs5491 was common in Black participants (minor allele frequency [MAF] > 20%) and rare in other race/ethnic groups (MAF < 5%). In Black participants, the presence of rs5491 was associated with higher levels of circulating ICAM-1 at 2 timepoints separated by 8 years. Among Black participants in MESA (n = 1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HR = 2.30; [95% CI 1.25-4.21; P = 0.007]). The other ICAM1 missense variants (rs5498 and rs1799969) were associated with ICAM-1 levels, but there were no associations with HF. In ARIC, rs5491 was significantly associated with incident HF (HR = 1.24 [95% CI 1.02 - 1.51]; P = 0.03), with a similar direction of effect for HFpEF that was not statistically significant. CONCLUSIONS: A common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.

Optimizing Flow Cytometric Analysis of Immune Cells in Samples Requiring Cryopreservation from Tumor-Bearing Mice.

Most shared resource flow cytometry facilities do not permit analysis of radioactive samples. We are investigating low-dose molecular targeted radionuclide therapy (MTRT) as an immunomodulator in combination with in situ tumor vaccines and need to analyze radioactive samples from MTRT-treated mice using flow cytometry. Further, the sudden shutdown of core facilities in response to the COVID-19 pandemic has created an unprecedented work stoppage. In these and other research settings, a robust and reliable means of cryopreservation of immune samples is required. We evaluated different fixation and cryopreservation protocols of disaggregated tumor cells with the aim of identifying a protocol for subsequent flow cytometry of the thawed sample, which most accurately reflects the flow cytometric analysis of the tumor immune microenvironment of a freshly disaggregated and analyzed sample. Cohorts of C57BL/6 mice bearing B78 melanoma tumors were evaluated using dual lymphoid and myeloid immunophenotyping panels involving fixation and cryopreservation at three distinct points during the workflow. Results demonstrate that freezing samples after all staining and fixation are completed most accurately matches the results from noncryopreserved equivalent samples. We observed that cryopreservation of living, unfixed cells introduces a nonuniform alteration to PD1 expression. We confirm the utility of our cryopreservation protocol by comparing tumors treated with in situ tumor vaccines, analyzing both fresh and cryopreserved tumor samples with similar results. Last, we use this cryopreservation protocol with radioactive specimens to demonstrate potentially beneficial effector cell changes to the tumor immune microenvironment following administration of a novel MTRT in a dose- and time-dependent manner.

Challenges of Cardio-Kidney Composite Outcomes in Large-Scale Clinical Trials.

Patients with chronic cardiovascular or metabolic diseases, including diabetes, hypertension, obesity, and heart failure, often have comorbid kidney disease. Long-term outcomes are worse in the setting of both cardiac and kidney disease compared with either disease in isolation. In addition, the clinical presentations of certain acute cardiovascular events (such as heart failure) and worsening kidney function overlap and may be challenging to distinguish. Recently, certain novel treatments have demonstrated beneficial effects on both cardiac and kidney outcomes. Sodium-glucose cotransporter-2 inhibitors have exhibited concordant risk reduction and clinically important benefits in chronic kidney disease with and without diabetes, diabetes and established cardiovascular disease or multiple atherosclerotic vascular disease risk factors, and heart failure with reduced ejection fraction with and without diabetes. Primary trial results have revealed that sacubitril-valsartan therapy improves cardiovascular outcomes in patients with chronic heart failure with reduced ejection fraction and post hoc analyses suggest favorable kidney effects. A concordant pattern of kidney benefit with sacubitril-valsartan has also been observed in chronic heart failure with preserved ejection fraction. Given the complex interplay between cardiac and kidney disease and the possibility that treatments may show concordant cardio-kidney benefits, there has been recent interest in formally acknowledging, defining, and using composite cardio-kidney outcomes in future cardiovascular trials. This review describes potential challenges in use of such outcomes that should be considered and addressed before their incorporation into such trials.

Drug Targets for Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach and Review of Contemporary Clinical Trials.

Heart failure with preserved ejection fraction (HFpEF) accounts for over half of prevalent heart failure (HF) worldwide, and prognosis after hospitalization for HFpEF remains poor. Due, at least in part, to the heterogeneous nature of HFpEF, drug development has proved immensely challenging. Currently, there are no universally accepted therapies that alter the clinical course of HFpEF. Despite these challenges, important mechanistic understandings of the disease have revealed that the pathophysiology of HFpEF is distinct from that of HF with reduced ejection fraction and have also highlighted potential new therapeutic targets for HFpEF. Of note, HFpEF is a systemic syndrome affecting multiple organ systems. Depending on the organ systems involved, certain novel therapies offer promise in reducing the morbidity of the HFpEF syndrome. In this review, we aim to discuss novel pharmacotherapies for HFpEF based on its unique pathophysiology and identify key research strategies to further elucidate mechanistic pathways to develop novel therapeutics in the future.

Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22.

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.

Atrial fibrillation and atrial cardiomyopathies.

Atrial fibrillation (AF) is the most common arrhythmia among adults. While there have been incredible advances in the management of AF and its clinical sequelae, investigation of atrial cardiomyopathies (ACMs) is becoming increasingly more prominent. ACM refers to the electromechanical changes-appreciated subclinically and/or clinically-that underlie atrial dysfunction and create an environment ripe for the development of clinically apparent AF. There are several subtypes of ACM, distinguished by histologic features. Recent progress in cardiovascular imaging, including echocardiography with speckle-tracking (e.g., strain analysis), cardiovascular magnetic resonance imaging (CMR), and atrial 4-D flow CMR, has enabled increased recognition of ACM. Identification of ACM and its features carry clinical implications, including elevating a patient's risk for development of AF, as well as associations with outcomes related to catheter-based and surgical AF ablation. In this review, we explore the definition and classifications of ACM, its complex relationship with clinical AF, imaging modalities, and clinical implications. We propose next steps for a more unified approach to ACM recognition that can direct further research into this complex field.

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF. METHODS AND RESULTS: Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes. CONCLUSIONS: In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

First-degree atrioventricular block is significantly associated with incident atrial fibrillation in the population predominantly including participants aged ≥ 60 years.

Some previous studies demonstrated that first-degree atrioventricular block (f-AVB) was associated with incident atrial fibrillation (AF), while evidence is scarce regarding the association between f-AVB and incident AF in older populations. Therefore, we sought to investigate the association of f-AVB with incident AF in the population predominantly including participants aged ≥ 60 years. Eligible participants were residents in Kanazawa City, Japan aged ≥ 40 years who underwent 12-lead ECG at the National Japanese Health Check-up in 2013. Participants with AF detected at the baseline exam and those without adequate follow-up were excluded. f-AVB was defined as PR interval ≥ 220 ms based on the Minnesota code (6-3). The cumulative incidence of AF was estimated by the Kaplan-Meier curve analysis, and statistical significance was evaluated by the Log-rank test. Unadjusted and adjusted hazard ratios (HRs) were computed by Cox proportional hazard models. HRs were adjusted for conventional risk factors for AF. 37,730 participants (mean age, 72.3 ± 9.6 years; male, 37%) were included. Baseline f-AVB was observed in 667 (1.8%) participants. During the median follow-up period of 5 years (interquartile range, 4.0-5.0 years), 691 cases of incident AF were observed. A 5-year cumulative incidence of AF was significantly higher in f-AVB (+) group compared with f-AVB (-) group (6.8% vs 2.1%, p < 0.01). In the fully adjusted model, f-AVB was significantly associated with incident AF (HR, 1.75; 95% confidence interval 1.25-2.45; p value < 0.01). f-AVB was independently associated with incident AF in the population predominantly including participants aged ≥ 60 years.

Depressive Symptoms Are Associated with Reduced Cardiac Function Among Hispanics: Results from the PREVENCION Study.

BACKGROUND: Depressive symptoms are common among patients with heart failure and are often associated with adverse outcomes, including re-hospitalization and mortality. However, little is known about the association between depressive symptoms and subclinical markers of heart failure and cardiac function in community-based samples and little research has focused on South American Hispanics. The current study examined the cross-sectional association between depressive symptoms and cardiac function in South American Hispanic community-based adults. METHODS: Participants included 527 adults enrolled in the Peruvian Study of Cardiovascular Disease (PREVENCION). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). Markers of cardiac function were assessed by impedance cardiography and included cardiac output, cardiac index, stroke volume, and stroke volume index. Several multiple regression analyses were used to examine the association between depressive symptoms and markers of cardiac function. RESULTS: In adjusted analyses, depressive symptoms were associated with reduced cardiac output, cardiac index, stroke volume, and stroke volume index. These associations remained significant between depressive symptoms and cardiac output (ß = - 0.106, p = 0.014), cardiac index (ß = - 0.099, p = 0.029), and stroke volume (ß = - 0.095, p = 0.022), and a trend was still observed between depressive symptoms and stroke index (ß = - 0.083, p = 0.061), even after having controlled for demographic factors (age, gender, education), cardiovascular risk factors (smoking status, body mass index, low- and high-density lipoprotein cholesterol, triglycerides, fasting glucose, serum creatinine), and comorbidities (diabetes mellitus, hypertension, hypercholesterolemia). CONCLUSIONS: In the PREVENCION sample tested, depressive symptoms were independently associated with cardiac function among Hispanic adults, even above and beyond pertinent factors such as demographic factors, cardiovascular risk factors, and comorbidities. Future studies should determine whether depressive symptoms are prospectively associated with systolic dysfunction, and examine the bio-behavioral pathways of this association.

Left Atrial Myopathy in Atrial Fibrillation and Heart Failure: Clinical Implications, Mechanisms, and Therapeutic Targets.

PURPOSE OF REVIEW: This review discusses the mechanisms, clinical implications, and treatments of left atrial (LA) myopathy in comorbid atrial fibrillation (AF) and heart failure (HF) across the spectrum of ejection fraction. RECENT FINDINGS: AF and HF are highly comorbid conditions. Left atrial (LA) myopathy, characterized by impairments in LA structure, function, or electrical conduction, plays a fundamental role in the development of both AF and HF with preserved ejection fraction (AF-HFpEF) along with AF and HF with reduced ejection fraction (AF-HFrEF). While the nature of LA myopathy in AF-HFpEF is unique from that of AF-HFrEF, LA myopathy also leads to progression of both of these conditions. There may be a vulnerable cohort of AF-HF patients who have a disproportionate degree of LA myopathy compared with left ventricular (LV) dysfunction. Further investigations are required to identify therapies to improve LA function in this cohort.

Renal Dysfunction in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status. METHODS AND RESULTS: Among 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m2) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO2) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (ß coefficient per 1 SD decrease in eGFR: -0.61, 95% CI: -1.01, -0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (ß coefficient: -0.26, 95% CI: -0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO2. Sildenafil therapy was independently associated with worsening eGFR over the trial (ß coefficient: -2.79, 95% CI: -5.34, -0.24, P = .03). CONCLUSION: Renal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.

Biomarker Profile of Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial.

BACKGROUND: Although left atrial (LA) mechanical dysfunction in heart failure with preserved ejection fraction (HFpEF) is associated with poor clinical outcomes, the influence of LA myopathy on temporal changes in cardiovascular biomarkers is unclear. METHODS AND RESULTS: We evaluated biomarker correlates of LA myopathy, as defined by reduced LA strain, and the associations of LA strain with longitudinal changes in biomarkers among participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. LA speckle-tracking was performed on baseline echocardiograms of RELAX participants to measure LA reservoir and LA contractile strain. Of the 216 RELAX participants, 169 (78%) had measurable LA strain and biomarker data. Participants with LA reservoir strain below median (13.5%, interquartile range: 10%-22.5%) were older, more likely to have atrial fibrillation, and had higher jugular venous pressure (P < .05 for all). At baseline, higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin I were independently associated with lower LA reservoir and contractile strain (Padjusted < .05 for all comparisons). Higher LA reservoir strain (ß coefficient per 1-unit increase: -21.2, 95% CI: -38.8, -3.7; P = .02) was independently associated with reduction in NT-proBNP at 24 weeks. CONCLUSION: In HFpEF, LA myopathy is characterized by elevation in biomarkers of neurohormonal activation and myocardial necrosis. Lower LA function is associated with continued elevation in NT-proBNP over time, suggesting that LA myopathy is associated with persistent congestion in HFpEF.

Addressing Comorbidities in Heart Failure: Hypertension, Atrial Fibrillation, and Diabetes.

Heart failure (HF) is a growing global epidemic and an increasingly cumbersome burden on health care systems worldwide. As such, optimal management of existing comorbidities in the setting of HF is particularly important to prevent disease progression, reduce HF hospitalizations, and improve quality of life. In this review, the authors address 3 key comorbidities commonly associated with HF: hypertension, atrial fibrillation, and diabetes mellitus. They comprehensively describe the epidemiology, management, and emerging therapies in these 3 disease states as they relate to the overall HF syndrome.

Availability and Use of Shared Data From Cardiometabolic Clinical Trials.

BACKGROUND: Sharing of patient-level clinical trial data has been widely endorsed. Little is known about how extensively these data have been used for cardiometabolic diseases. We sought to evaluate the availability and use of shared data from cardiometabolic clinical trials. METHODS: We extracted data from ClinicalStudyDataRequest.com, a large, multisponsor data-sharing platform hosting individual patient-level data from completed studies sponsored by 13 pharmaceutical companies. RESULTS: From January 2013 to May 2017, the platform had data from 3374 clinical trials, of which 537 (16%) evaluated cardiometabolic therapeutics (phase 1, 36%; phase 2, 17%; phase 2/3, 1%; phase 3, 42%; phase 4, 4%). They covered 74 therapies and 398 925 patients. Diabetes mellitus (60%) and hypertension (15%) were the most common study topics. Median time from study completion to data availability was 79 months. As of May 2017, ClinicalStudyDataRequest.com had received 318 submitted proposals, of which 163 had signed data-sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 79 unique studies (15% of all trials, 29% of phase 3/4 trials). Most (96%) data requesters of cardiometabolic clinical trial data were from academic centers in North America and Western Europe, and half the proposals were unfunded. Most proposals were for secondary hypothesis-generating questions, with only 1 proposed reanalysis of the original study primary hypothesis. To date, 3 peer-reviewed articles have been published after a median of 19 months (9-32 months) from the data-sharing agreement. CONCLUSIONS: Despite availability of data from >500 cardiometabolic trials in a multisponsor data-sharing platform, only 15% of these trials and 29% of phase 3/4 trials have been accessed by investigators thus far, and a negligible minority of analyses have reached publication.

Mental Health and Tobacco Use Are Correlated With Physical Function Outcomes in Patients With Knee Pain and Injury.

PURPOSE: To examine the relation between the Patient-Reported Outcomes Measurement Information System (PROMIS) domains of Pain Interference (PROMIS-PI), Depression (PROMIS-D), and Physical Function (PROMIS-PF) for nonoperative patients presenting to our ambulatory sports orthopaedic clinic with knee complaints and to determine whether patient demographic characteristics influence PROMIS scores, particularly tobacco use. METHODS: All patients treated nonoperatively for a primary complaint of knee pain were recruited for participation. Patients were included if they completed all 3 PROMIS questionnaires prior to their clinical evaluation. Patients were excluded if their treatment plan determined that surgical intervention was warranted. Survey results were compiled, and statistical correlations were run between PROMIS domains and patient demographic characteristics. RESULTS: A total of 527 PROMIS questionnaire sets were included. PROMIS-PF had a strong negative correlation with PROMIS-PI (R = -0.75, P < .001) and a nearly moderate negative correlation with PROMIS-D (R = -0.47, P < .001). When evaluating patient demographic characteristics, we found a significant decrease in physical function scores and increases in pain and depression scores in both current and former tobacco users compared with nonsmokers. Differences in all PROMIS domains between smokers and nonsmokers exceeded minimal clinically important differences. CONCLUSIONS: Our study showed an inverse correlation between PROMIS-PI and PROMIS-PF, as well as between PROMIS-D and PROMIS-PI, in patients seen in the ambulatory setting for knee complaints treated nonoperatively. A positive correlation was found between PROMIS-PI and PROMIS-D. Tobacco use was a patient demographic factor found to significantly impact PROMIS scores leading to minimal clinically important differences across all 3 PROMIS domains. The findings of this study may be used to identify patients at high risk of poor outcomes. LEVEL OF EVIDENCE: Level III, observational study.

Abnormal tibial alignment is a risk factor for lateral meniscus posterior root tears in patients with anterior cruciate ligament ruptures.

PURPOSE: The purpose of this study was to identify if abnormal tibial alignment was a risk factor for lateral meniscus posterior root tears (LMPRT) in patients with acute anterior cruciate ligament (ACL) ruptures. METHODS: The medical charts of 200 patients treated for ACL ruptures between 2013 and 2016 were retrospectively reviewed and evaluated. MRI images and reports were assessed for concurrent meniscal tears. Radiographs were reviewed for tibia vara and tibial slope angles and MRI reports identifying lateral root tears were compared to intraoperative reports to determine accuracy. Multiple logistic regression models were constructed to identify potential risk factors for LMPRTs. RESULTS: Of the 200 patients reviewed, a total of 97 individuals with concurrent meniscal injuries were identified. In patients sustaining a concurrent meniscal injury, there was a 4% incidence of medial meniscus posterior root tears and a 10.3% incidence of LMPRTs. Patients sustaining an ACL injury with an LMPRT were found to have greater tibia vara angles (4.2 ± 1.0 vs. 2.9 ± 1.7; p = 0.024), increased tibial slopes (12.6 ± 1.5 vs. 10.7 ± 2.9; p = 0.034), and higher BMIs (27.3 ± 2.9 vs. 25.3 ± 5.9; p = 0.034) when compared to patients without meniscus tears. There was low agreement between MRI and arthroscopic findings (kappa rate = 0.54). Multiple logistic regression analysis demonstrated that a tibia vara angle > 3 was associated with a 5.2-fold increase (95% CI 0.99-27.01; p = 0.050), and a tibial slope > 12 with a 5.4-fold increase (95% CI 1.03-28.19; p = 0.046) in LMPRTs. CONCLUSIONS: Patients with greater tibia varus angles, increased tibial slopes, and higher BMIs were found to have an increased risk of LMPRTs when sustaining an ACL rupture. There was a low rate of agreement between MRI and arthroscopy in identifying LMPRTs. In patients with ACL ruptures who have abnormal tibial alignment or increased BMI, physicians should be watchful for lateral meniscus posterior root tears. LEVEL OF EVIDENCE: 3.