Laboratory Evaluation of the Pivot-Shift Phenomenon with Use of Kinetic Analysis

Background: Currently, a suitable and reliable noninvasive method to evaluate rotational stability in vivo in anterior cruciate ligament-deficient knees, particularly during sports movements, does not exist. We speculated that if there is a rotational instability, the patient would avoid reaching a high pivoting moment during pivoting activities as a defense mechanism, and that the ground reaction moment, as registered by dynamometric platforms, would be reduced. On the basis of this hypothesis, we developed a study using kinetic analysis to evaluate rotational stability under dynamic loading. Methods: Thirty recreationally active athletes, including fifteen healthy subjects and fifteen with an anterior cruciate ligament-deficient knee, were recruited for this study. Patients performed jumping with pivoting with internal tibial rotation and external tibial rotation on the dynamometric platform with both the healthy and the injured limb. The quantitative results were graphically plotted, and the following parameters were evaluated: loading moment, pivoting moment, torque amplitude, loading slope, pivoting slope, percentage of pivoting with load, loading impulse, pivoting impulse, and maximum body rotation angle. Results: There were no significant differences between the dominant and nondominant knees in the control group during the jumping with pivoting and external tibial rotation test with regard to the pivoting moment (p = 0.805), pivoting slope (p = 0.716), pivoting impulse 2 (p = 0.858), and pivoting impulse 3 (p = 0.873). In patients with a chronic tear of the anterior cruciate ligament, there was a significant decrease of the pivoting moment (p = 0.02), pivoting slope (p = 0.005), pivoting impulse 2 (p = 0.006), and pivoting impulse 3 (p = 0.035) during the jumping with pivoting and external tibial rotation test in the anterior cruciate ligament-deficient knee compared with the healthy, contralateral knee. Conclusion: Kinetic analysis with use of a dynamic platform can objectively detect alterations of rotational stability in anterior cruciate ligament-deficient knees, which may allow this to be a useful research tool for evaluating treatment strategies in patients with anterior cruciate ligament injuries. Level of Evidence: Diagnostic Level IV. See Instructions to Authors for a complete description of levels of evidence.Sanchis Alfonso, V.; Baydal Bertomeu, JM.; Castelli ., A.; Montesinos Berry, E.; Marín Roca, S.; Garrido Jaen, JD. (2011). Laboratory Evaluation of the Pivot-Shift Phenomenon with Use of Kinetic Analysis. Journal of Bone and Joint Surgery, American Volume. 93(13):1256-1267. doi:10.2106/JBJS.J.00582S12561267931

Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction

BACKGROUND Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet b-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES This study aimed to evaluate the effect of b-blocker withdrawal on peak oxygen consumption (peak VO2) in patients with HFpEF and chronotropic incompetence. METHODS This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with b-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n ¼ 26) versus continuing (arm B: n ¼ 26) b-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak VO2 and percentage of predicted peak VO2 (peak VO2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. RESULTS The mean age was 72.6 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVO2 and peak VO2% were 12.4 2.9 mL/kg/min, and 72.4 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak VO2 and peak VO2% increased significantly after b-blocker withdrawal (14.3 vs 12.2 mL/kg/min [D þ2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [D þ11.7%]; P < 0.001, respectively). CONCLUSIONS b-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. b-blocker use in HFpEF deserves profound re-evaluation. (b-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39) (J Am Coll Cardiol 2021;78:2042–2056) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life and Natriuretic Peptides After Initiation of Dapagliflozin in Heart Failure With Reduced Ejection Fraction

Background: We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels. Methods: This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels. Results: At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively). Conclusions: In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.This work was supported in part by an unrestricted grant from Astra Zeneca (ESR-17-13447), Unidad de Investigación Clínica y Ensayos Clínicos INCLIVA Health Research Institute, Spanish Clinical Research Network (SCReN; PT17/0017/0003 y PT20/00100), and CIBER Cardiovascular [grant numbers 16/11/00420, 16/11/00403, and 16/11/00486]

Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Introduction and objectivesCarbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF.MethodsThe derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n=1583).ResultsIn the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was ConclusionsIn patients admitted with AHF, CA125 <23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring

Bending oxygen saturation index and risk of worsening heart failure events in chronic heart failure

Aims: Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients. Methods and results: We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO2). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥−3%. The agreement between BOSI ≥−3% and bendopnea was moderate (Gwet's AC 0.482, p < 0.001). At a median (p25%–p75%) follow-up of 2.17 years (0.88–3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p < 0.001). Compared to improvement/no change in SpO2 when bending (BOSI 0%), those with BOSI ≥−3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67–2.79; p < 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83–1.31; p = 0.705). Conclusions: In ambulatory and stable CHF patients, BOSI ≥−3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations

Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2): a randomized clinical trial

Aims This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). Methods and results In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2, 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th–75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889–2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14–2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07–2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. Conclusions Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)