Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95% CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies

Proprotein convertase subtilisin kexin type 9 inhibitors reduce platelet activation modulating ox-LDL pathways

Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients

Meta-analysis: The Placebo Rate of Abdominal Pain Remission in Clinical Trials of Chronic Pancreatitis.

OBJECTIVES: Treatment of the pain caused by chronic pancreatitis (CP) is not standardized. Knowledge of the response to placebo in this setting may aid the design of future trials. We aimed at investigating the placebo effect on abdominal pain remission rates in patients with CP. METHODS: MEDLINE, EMBASE, and Scopus were searched, and randomized placebo-controlled trials in CP providing data on abdominal pain remission rates in placebo arms were included. Pooled estimates of the placebo rate were calculated using random-effects logistic regression analysis. Stratum-specific rates for different patients and study-level covariates were calculated to account for heterogeneity. RESULTS: Seven randomized controlled trials (202 placebo-treated patients) met the predefined criteria. The pooled estimate of the placebo rate for pain remission was 19.9\% (95\% confidence interval, 9\%-36\%). There was a statistically significant heterogeneity among the studies (I = 76\%; P < 0.001). A multicenter design, a run-in period of less than 2 weeks, and absence of a washout in crossover trials were all significant sources of heterogeneity associated with higher placebo responses. CONCLUSIONS: This meta-analysis identifies for the first time the efficacy of placebo for pain in CP and variables determining it. These data provide a sound basis for designing future placebo-controlled randomized clinical trials for the treatment of pain in CP

P4163Long term comparison between homograft vs stented bio-prostheses for pulmonary valve replacement in tetralogy of Fallot patients

Abstract Background Tetralogy of Fallot (TOF) repair results in long term chronic pulmonary regurgitation requiring pulmonary valve replacement (PVR). Homograft and stented bio-prosthesis are currently used for PVR but whether one should be considered superior to another remains unknown. Aim To compare echocardiographic and clinical outcomes after PVR with Homograft vs stented bioprosthesis in patients with previous TOF repair. Methods 137 patients who underwent PVR with stented bioproshesis were compared with 80 patients who received an homograft using Mixed linear model and multivariate Cox regression. Results Homograft were associated with a significantly lower transpulmonary gradient postoperatively (P=0.04) and after a mean follow-up 6 years (table). Homograft were associated with a significantly lower risk of reintervention (HR 0.24; 95% CI 0.07–0.85, p=0.026) while long term mortality was comparable between the two groups (P=0.1). Echocardiographic findings BIO HOMOGRAFT P N 137 80 Preoperatively   TV regurgitation (mean, sd) 1.80 (0.63) 1.94 (0.81) 0.353   TV regurgitation pressure drop (mean,sd) 35.15 (15.49) 45.34 (25.24) 0.009   PV regurgitation (mean,sd) 3.63 (0.52) 3.34 (0.64) 0.004   PV systolic peak gradient (mean, sd) 25.07 (17.05) 30.68 (21.70) 0.138 Early postoperatively   TV regurgitation (mean,sd) 1.52 (0.54) 1.54 (0.55) 0.858   TV regurgitation pressure drop (mean,sd) 30.10 (13.82) 29.13 (13.98) 0.733   PV regurgitation (mean,sd) 1.50 (0.54) 1.64 (0.53) 0.224   PV systolic peak gradient (mean,sd) 24.05 (11.10) 20.16 (14.19) 0.045 Latest follow_up   TV regurgitation (mean,sd) 1.63 (0.61) 1.83 (0.80) 0.195   TV regurgitation pressure drop (mean,sd) 37.46 (18.84) 32.58 (13.47) 0.233   PV regurgitation (mean,sd) 2.06 (0.77) 2.07 (0.94) 0.982   PV systolic peak gradient (mean,sd) 32.22 (18.17) 21.25 (13.47) 0.001 TAPSE: Tricuspid annular plane systolic excursion; TV: tricuspid valve; PV: pulmonary valve. PV re-intervention Conclusions When compared to stented bio-prostheses, homografts were associated better early and late hemodynamic profile and a significantly lower risk of re-intervention. Homograft should be considered the first choice in patients undergoing PVR after TOF repair. </jats:sec

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p &lt; 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95% CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p &lt; 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p &lt; 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies