Echocardiographic derived pulmonary artery wedge pressure is associated with mortality, heart hospitalizations, and functional capacity in chronic systolic heart failure: insights from the HF-ACTION trial.

BACKGROUND: Heart Failure (HF) is associated with increased morbidity and mortality. Identification of patients at risk for adverse events could lead to improved outcomes. Few studies address the association of echocardiographic-derived PAWP with exercise capacity, readmissions, and mortality in HF. METHODS: HF-ACTION enrolled 2331 outpatients with HF with reduced ejection fraction (HFrEF) who were randomized to aerobic exercise training versus usual care. All patients underwent baseline echocardiography. Echocardiographic-derived PAWP (ePAWP) was assessed using the Nagueh formula. We evaluated the relationship between ePAWP to clinical outcomes. RESULTS: Among the 2331 patients in the HF-ACTION trial, 2125 patients consented and completed follow-up with available data. 807 of these patients had complete echocardiographic data that allowed the calculation of ePAWP. Of this cohort, mean age (SD) was 58 years (12.7), and 255 (31.6%) were female. The median ePAWP was 14.06 mmHg. ePAWP was significantly associated with cardiovascular death or HF hospitalization (Hazard ratio [HR] 1.02, coefficient 0.016, CI 1.002-1.030, p = 0.022) and all-cause death or HF hospitalization (HR 1.01, coefficient 0.010, CI 1.001-1.020, p = 0.04). Increased ePAWP was also associated with decreased exercise capacity leading to lower peak VO2 (p = < 0.001), high Ve/VCO2 slope (p = < 0.001), lower exercise duration (p = < 0.001), oxygen uptake efficiency (p = < 0.001), and shorter 6-MWT distance (p = < 0.001). CONCLUSIONS: Among HFrEF patients, echocardiographic-derived PAWP was associated with increased mortality, reduced functional capacity and heart failure hospitalization. ePAWP may be a viable noninvasive marker to risk stratify HFrEF patients.

Identifying Disease of Interest With Deep Learning Using Diagnosis Code.

BACKGROUND: Autoencoder (AE) is one of the deep learning techniques that uses an artificial neural network to reconstruct its input data in the output layer. We constructed a novel supervised AE model and tested its performance in the prediction of a co-existence of the disease of interest only using diagnostic codes. METHODS: Diagnostic codes of one million randomly sampled patients listed in the Korean National Health Information Database in 2019 were used to train, validate, and test the prediction model. The first used AE solely for a feature engineering tool for an input of a classifier. Supervised Multi-Layer Perceptron (sMLP) was added to train a classifier to predict a binary level with latent representation as an input (AE + sMLP). The second model simultaneously updated the parameters in the AE and the connected MLP classifier during the learning process (End-to-End Supervised AE [EEsAE]). We tested the performances of these two models against baseline models, eXtreme Gradient Boosting (XGB) and naïve Bayes, in the prediction of co-existing gastric cancer diagnosis. RESULTS: The proposed EEsAE model yielded the highest F1-score and highest area under the curve (0.86). The EEsAE and AE + sMLP gave the highest recalls. XGB yielded the highest precision. Ablation study revealed that iron deficiency anemia, gastroesophageal reflux disease, essential hypertension, gastric ulcers, benign prostate hyperplasia, and shoulder lesion were the top 6 most influential diagnoses on performance. CONCLUSION: A novel EEsAE model showed promising performance in the prediction of a disease of interest.

Positional obstructive sleep apnea in patients with atrial fibrillation.

PURPOSE: Obstructive sleep apnea (OSA) is a common, potentially modifiable condition implicated in the pathogenesis of atrial fibrillation (AF). The presence and severity of OSA is largely sleep position-dependent, yet there is high variability in positional dependence among patients with OSA. We investigated the prevalence of positional OSA (POSA) and examined associated factors in patients with AF. METHODS: We recruited an equal number of patients with and without AF who underwent diagnostic polysomnography. Patients included had ≥ 120 min of total sleep time with 30 min of sleep in both supine and lateral positions. POSA was defined as an overall apnea hypopnea index (AHI) ≥ 5/h, supine AHI (sAHI) ≥ 5/h, and sAHI greater than twice the non-supine AHI. POSA prevalence was compared in patients with and without AF adjusting for age, sex, OSA severity, and heart failure. RESULTS: A total of patients (male: 56%, mean age 62 years) were included. POSA prevalence was similar between the two groups (46% vs. 39%; p = 0.33). Obesity and severe OSA (AHI ≥ 30/h) were associated with low likelihood of POSA (OR [CI] of 0.17 [0.09-0.32] and 0.28 [0.12-0.62]). In patients with AF, male sex was associated with a higher likelihood of POSA (OR [CI] of 3.16 [1.06-10.4]). CONCLUSION: POSA is common, affecting more than half of patients with AF, but the prevalence was similar in those without AF. Obesity and more severe OSA are associated with lower odds of POSA. Positional therapy should be considered in patients with mild OSA and POSA.

Right atrial volume index to left atrial volume index ratio is associated with adverse clinical outcomes in cardiogenic shock.

BACKGROUND: Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Our objective was to test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS. METHODS: Patients in this cohort were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure > 15) and cardiogenic shock (cardiac index < 2.2, systolic blood pressure < 90 mmHg, and clinical evidence supporting CS) and had an echocardiogram at the time of admission. RAVI was measured using Simpson's method in the apical four-chamber view, while LAVI was measured using the biplane disc summation method in the four and two-chamber views by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD). RESULTS: Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD. Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p ≤ 0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11-2.64, chi square 5.91, p = 0.010) even after adjustment for patient characteristics, echocardiographic and hemodynamic variables. CONCLUSION: RAVI/LAVI is an easily assessed novel echocardiographic parameter strongly associated with the survival and or the need for mechanical circulatory support in patients with CS.

Continuous Noninvasive Blood Pressure Monitoring of Beat-By-Beat Blood Pressure and Heart Rate Using Caretaker Compared With Invasive Arterial Catheter in the Intensive Care Unit.

OBJECTIVE: To examine the accuracy of noninvasively-derived peripheral arterial blood pressure (BP) by the Caretaker device (CT) against invasively measured arterial BP and the fidelity of heart rate variability by CT compared with electrocardiogram (ECG)-derived data. DESIGN: Prospective cohort study. PARTICIPANTS: Adult surgical and trauma patients admitted to the intensive care unit. SETTING: Academic tertiary care medical center. INTERVENTIONS: In a prospective manner, beat-by-beat BP by CT was recorded simultaneously with invasive arterial BP measured in patients in the intensive care unit. Invasive arterial BPs were compared with those obtained by the CT system. All comparisons among the CT data, arterial catheter data, and ECG data were postprocessed. MEASUREMENTS AND MAIN RESULTS: From 37 enrolled patients, 34 were included with satisfactory data that overlapped between arterial catheter and CT. A total of 87,757 comparative data points were obtained for the 40-minute time window comparisons of the 34 patients, spanning approximately 22.5 hours in total. Systolic BP and diastolic BP correlations (Pearson coefficient), as well as the mean difference (standard deviation), were 0.92 and -0.36 (7.57) mmHg and 0.83 and -2.11 (6.00) mmHg, respectively. The overall interbeat correlation was 0.99, with the mean difference between interbeats obtained with the arterial BP and the CT of -0.056 ms (6.0). CONCLUSIONS: This study validated the noninvasive tracking of BP using the CT device, and the pulse decomposition analysis approach is possible within the guidelines of the standard.

Tracking of the beat-to-beat blood pressure changes by the Caretaker physiological monitor against invasive central aortic measurement.

OBJECTIVE: There is an unmet need for noninvasive continuous blood pressure (BP) monitoring technologies in various clinical settings. Continuous and noninvasive central aortic BP monitoring is technically not feasible currently, but if realized, would provide more accurate and real-time global hemodynamic information than any form of peripheral arterial BP monitoring in an acute care setting. As part of our efforts to develop such, herein we examined the tracking correlation between noninvasively-derived peripheral arterial BP by Caretaker device against invasively measured central aortic BP. METHODS: Beat-to-beat BP by Caretaker was recorded simultaneously with central aortic BP measured in patients undergoing cardiac catheterization. Pearson's correlation was also derived for SBP and DBP. A trend comparison analysis of the beat-to-beat BP change was performed using a four-quadrant plot analysis with the exclusion zones of 0.5 mmHg/s to determine concordance, (i.e. the direction of beat-to-beat changes in SBP and DBP). RESULTS: A total of 47 patients were included in the study. A total of 31 369 beats representing an average of 17.3 min of recording were used for analysis. The trend analysis yielded concordances of 84.4 and 83.5% for SBP and DBP, respectively. Respective correlations (Pearson's r) for SBP and DBP trends were 0.87 and 0.86 (P < 0.01). Tracking of beat-to-beat BP by Caretaker showed excellent concordance and correlation in the direction and the degree of BP change with central aortic BP, respectively. CONCLUSION: This study supports the satisfactory performance of the Caretaker device in continuous tracking of central aortic BP beat-to-beat BP and provides a basis to develop an algorithm for absolute central aortic BP estimation in the future.

Elucidation of obstructive sleep apnoea related blood pressure surge using a novel continuous beat-to-beat blood pressure monitoring system.

BACKGROUND: Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD: We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS: Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P < 0.001). In eight patients undergoing split-night sleep studies, the number of BP surge events (≥10 mmHg/h) decreased during continuous positive airway pressure in all but one patient. CONCLUSION: We demonstrated highly variable OSA-related BP surge patterns using the Caretaker's b-b BP monitoring technology that has the potential to be integrated into sleep studies.

Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction.

BACKGROUND: The prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. OBJECTIVE: To evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. METHODS: Analyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. RESULTS: Among 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10-16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. CONCLUSION: Although LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.

The Influence of Obesity on the Association of Obstructive Sleep Apnea and Atrial Fibrillation.

BACKGROUND AND OBJECTIVE: The association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) has been closely studied. However, obesity is a powerful confounder in the causal relationship between OSA and cardiovascular disease. The contribution of obesity in the relationship between OSA and AF remains unclear. METHODS: We recruited 457 consecutive patients equally with and without AF who underwent clinically indicated diagnostic polysomnography at a single academic sleep center. Multivariable logistic regression adjusting for age, sex, hypertension, and heart failure was performed to study the independent association between OSA and AF stratified by obesity. RESULTS: A total of 457 patients (male: 56.2%, mean age 63.1 ± 13.3 years) was included. OSA prevalence was similar between those with and without AF (52.6% vs. 47.4%, respectively; p = 0.24). In multivariable analysis, no association was found between AF and OSA regardless of obesity status. When severe OSA (vs. non-severe OSA) was modeled as a dependent variable, AF was associated with a higher likelihood of severe OSA in non-obese patients [odds ratio (OR): 2.29, 95% confidence interval (CI): 1.23-4.35, p = 0.01], but not in obese patients (OR: 0.95, 95% CI: 0.48-1.90, p = 0.89). CONCLUSION: The association of OSA with AF was present only in the non-obese and was limited to severe OSA patients. In contrast, no association was found in obese patients. The association between OSA and AF is partly dependent on the body habitus.

Atrial fibrillation is associated with central sleep apnea in clinic patients undergoing diagnostic polysomnography.

INTRODUCTION: Sleep apnea is highly prevalent in patients with atrial fibrillation (AF). Obstructive sleep apnea (OSA) is the most common type, and best studied in the context of AF. However, recent investigations have indicated that central sleep apnea (CSA) may be a risk factor for incident AF. We evaluated the burden of CSA events in patients referred for diagnostic polysomnography (PSG) and whether AF is associated with CSA. METHODS: We identified patients with and without a history of AF who underwent clinically indicated PSG in a matched manner. OSA was defined as obstructive apnea-hypopnea index (AHI) ≥15/h, and CSA was defined as central apnea index (CAI) ≥5/h. The association between AF and CSA was evaluated using multivariable logistic regression. RESULTS: Among 465 patients included, mean AHI was 25.5/h, and mean CAI was 1.7/h. OSA prevalence was 53.3%, while CSA prevalence was 8.4%. The prevalence of OSA in the AF and non-AF groups (54.7% vs 52.0%, P = .56) was similar. CSA was more common in the AF group (12.3% vs 4.4%, P = .002). In multivariable analysis, AF (OR: 2.19 [1.02, 5.03], P = .05), male gender (OR: 2.5 [1.17, 5.84], P = .02), and older age (OR: 2.44, [1.16, 5.46], P = .02) were associated with CSA. CONCLUSION: Though CSA is much less common than OSA in patients with AF, the presence of AF is independently associated with CSA.

Daytime QT by Routine 12-Lead ECG Is Prolonged in Patients with Severe Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to sudden cardiac death (SCD). Prolonged QT is a recognized electrocardiographic (ECG) marker of abnormal ventricular repolarization linked to increased risk of SCD. We hypothesized that individuals with OSA have more pronounced abnormality in daytime QT interval. METHODS: We reviewed consecutive patients who underwent clinically indicated polysomnography with 12-lead ECG within 1 year at a single center. Heart rate-corrected QT interval (QTc) was compared by OSA severity class (normal/mild: apnea-hypopnea index (AHI) < 15/hr (n = 72); moderate: 15-30 (n = 72); moderate: 15-30 (n = 72); moderate: 15-30 (. RESULTS: A total of 249 patients were included. QTc was similar between the normal/mild and moderate groups, and the overall QTc trend increased across OSA (normal/mild: 435.6 ms; moderate: 431.36; severe: 444.4; p trend = 0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0), p trend = 0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0), p trend = 0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0), p trend = 0.03). Abnormal QTc was found amongst 34% of male and 31% of female patients. Patients with severe OSA had longer QTc compared with normal/mild OSA (mean difference (95% CI): 10.0 ms (0.5, 19.0). CONCLUSIONS: In a sleep clinic cohort, severe OSA was associated with higher QTc and clinically defined abnormal QTc compared with nonsevere OSA.

Blood pressure monitoring in sleep: time to wake up.

Hypertension is a highly common condition with well-established adverse consequences. Ambulatory blood pressure monitoring has repeatedly been shown to better predict cardiovascular outcomes and mortality, compared to single office visit blood pressure. Non-dipping of sleep-time blood pressure is an independent marker for increased cardiovascular risk. We review blood pressure variability and the challenges of blood pressure monitoring during sleep. Although pathological sleep such as obstructive sleep apnea has been associated with non-dipping of sleep-time blood pressure, blood pressure is not routinely measured during sleep due to lack of unobtrusive blood pressure monitoring technology. Second, we review existing noninvasive continuous blood pressure monitoring technologies. Lastly, we propose including sleep-time blood pressure monitoring during sleep studies and including sleep studies in patients undergoing ambulatory blood pressure monitoring.

Sleep Apnea and Sudden Cardiac Death.

Sleep plays an integral role in maintaining health and quality of life. Obstructive sleep apnea (OSA) is a prevalent sleep disorder recognized as a risk factor for cardiovascular disease (CVD) and arrhythmias. Sudden cardiac death (SCD) is a common and devastating event. Out-of-hospital SCD accounts for the majority of deaths from cardiac disease, which is the leading cause of death globally. A limited but emerging body of research have further elaborated on the link between OSA and SCD. In this article, we aim to provide a critical review of the existing evidence by addressing the following: What epidemiologic evidence exists linking OSA to SCD? What evidence exists for a pathophysiologic connection between OSA and SCD? Are there electrocardiographic markers of SCD found in patients with OSA? Does heart failure represent a major effect modifier regarding the relationship between OSA and SCD? What is the impact of sleep apnea treatment on SCD and cardiovascular outcomes? Finally, we elaborate on ongoing research to enhance our understanding of the OSA-SCD association.

Intra-abdominal Hypertension and Postoperative Kidney Dysfunction in Cardiac Surgery Patients.

OBJECTIVE: To determine the incidence of intra-abdominal hypertension (IAH) in adult cardiac surgery patients and its association with postoperative kidney dysfunction. DESIGN: Prospective cohort study. SETTING: Single tertiary-care university hospital. PARTICIPANTS: Forty-two adult patients having cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Intra-abdominal pressure (IAP) was measured preoperatively, immediately after surgery, and at the following time points after surgery: 3 hours, 6 hours, 12 hours, and 24 hours. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels were measured as a marker of kidney dysfunction at the following time points: prior to surgery, immediately after surgery, 4 to 6 hours after surgery, and 16-to-18 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-two IAPs were measured, and 90 (35.7%) showed IAH. Thirty-five of 42 patients (83.3%) had IAH at 1 time point or more. Peak urine NGAL levels were lower in patients with normal IAP (mean difference = -130.6 ng/mL [95% CI = -211.2 to -50.1], p = 0.002). There was no difference in postoperative kidney dysfunction by risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria in patients with normal IAP (mean difference = -31.4% [95% CI = -48.0 to 6.3], p = 0.09). IAH was 100% sensitive for predicting postoperative kidney dysfunction by RIFLE criteria, but had poor specificity (54.8%). CONCLUSIONS: IAH occurs frequently during the perioperative period in cardiac surgery patients and may be associated with postoperative kidney dysfunction.

Undersized Rigid Nonplanar Annuloplasty: The Key to Effective and Durable Repair of Functional Tricuspid Regurgitation.

BACKGROUND: Previous clinical experiences have demonstrated high early and late recurrence rates after repair of functional tricuspid regurgitation (TR). We investigated the results of functional TR repair with undersized rigid nonplanar annuloplasty rings. METHODS: From January 2007 to December 2013, 216 consecutive patients with moderate or greater functional TR were treated with undersized (size 26 mm or 28 mm) rigid nonplanar annuloplasty rings. RESULTS: The mean age was 69 ± 13 years. There was a previous history of cardiac operation in 25% (54 of 216 patients). Tricuspid regurgitation was graded as severe in 47% (102 of 216) and moderate in 53% (114 of 216). Concomitant operations included mitral valve procedures in 92% (198 of 216), coronary artery bypass grafting in 21% (45 of 216), aortic valve procedures in 9% (20 of 216), and cryomaze procedures in 35% (76 of 216). Size 26 mm rings were used in 38% of patients (81 of 216), and size 28 mm in 62% (135 of 216). The perioperative mortality rate was 6% (14 of 216). On predischarge echocardiography, TR grade was none or mild in 94% (176 of 187 patients), moderate in 4% (7 of 187), and severe in 2% (4 of 187). At a mean follow-up of 33.0 ± 24.0 months, TR grade was none or mild in 81% of patients (130 of 160), moderate in 16% (26 of 160), and severe in 2% (4 of 160). There were no reoperations for recurrent TR, and no patients have had tricuspid stenosis or annuloplasty ring dehiscence. CONCLUSIONS: Treatment of functional TR with undersized (26 mm or 28 mm) nonplanar rigid annuloplasty rings is safe and highly effective, with a near absence of recurrent severe TR at midterm follow-up.

Muscle fibers are injured at the time of acute and chronic rotator cuff repair.

BACKGROUND: Rotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain. QUESTIONS/PURPOSES: We hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury? METHODS: We used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey's post hoc sorting. RESULTS: Chronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers. CONCLUSIONS: In a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint. CLINICAL RELEVANCE: In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.

Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.

Full-thickness tears to the rotator cuff can cause severe pain and disability. Untreated tears progress in size and are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of rotator cuff tears, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential. Using a rat model of rotator cuff injury, we measured the force generating capacity of individual muscle fibers and determined changes in muscle fiber type distribution that develop after a full thickness rotator cuff tear. We also measured the expression of mRNA and miRNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of rotator cuff muscle fibers, an accumulation of type IIb fibers, and an upregulation in fibrogenic, adipogenic, and inflammatory gene expression occur in torn rotator cuff muscles. Thirty days following rotator cuff tear, we observed a reduction in muscle fiber force production, an induction of fibrogenic, adipogenic, and autophagocytic mRNA and miRNA molecules, and a dramatic accumulation of macrophages in areas of fat accumulation.