Background The role of the dysfunction of left atrium in the occurrence and development of cardiovascular disease has been gradually recognized. We aim to compare the impact on left atrial (LA) function between patients with hypertrophic cardiomyopathy (HCM) and hypertension (HTN) without LA enlargement using cardiovascular magnetic resonance feature tracking (CMR-FT), and if possible, explore the capability of LA function for providing clinical implication and predicting clinical adverse events in the early stage of cardiovascular disease. Methods Consecutive 60 HCM patients and 60 HTN patients with normal LA size among 1413 patients who underwent CMR were retrospectively analyzed as well as 60 controls. Left atrial and ventricular functions were quantified by volumetric and CMR-FT derived strain analysis from long and short left ventricular view cines. The primary endpoint was a composite of all-cause death, stroke, new-onset or worsening heart failure to hospitalization, and paroxysmal or persistent atrial fibrillation. Results Compared to the controls, both HTN and HCM participants had impaired LA reservoir function (εs) and conduit function (εe) with the different stage of LA booster pump dysfunction (εa). LA strain was more sensitive than LV longitudinal strain (GLS) for evaluate primary endpoint (εs: 33.9% ± 7.5 vs. 41.2% ± 14.3, p = 0.02; εe: 13.6% ± 6.2 vs. 17.4% ± 10.4, p = 0.03; εa: 20.2% ± 6.0 vs. 23.7% ± 8.8, p = 0.07; GLS: -19.4% ± 6.4 vs. -20.0% ± 6.8, p = 0.70, respectively). After a mean follow-up of 6.8 years, 23 patients reached primary endpoint. Cox regression analyses indicated impaired LA reservoir and booster pump strain were associated with clinical outcomes in patients at the early stage of HTN and HCM (p < 0.05). Conclusions CMR-FT-derived strain is a potential and robust tool in demonstrating impaired LA mechanics, quantifying LA dynamics and underlining the impacts on LA-LV coupling in patients with HTN and HCM without LA enlargement. The corresponding LA dysfunction is a promising metric to assess clinical implication and predict prognosis at the early stage, superior to GLS.
425126 Background: Adjuvant and neoadjuvant immunotherapy have been approved by US FDA to treat early-stage NSCLC. However, the optimal neoadjuvant and adjuvant treatment, including duration of treatment, are unknown. We present the interim results of a randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy in resectable stage III NSCLC. Methods: Patients with stage II/III resectable NSCLC, without EGFR/ALK alterations for non-squamous NSCLC, were randomly assigned 1:1 to receive 240 mg toripalimab or placebo combined with chemotherapy Q3W for 3 cycles before surgery and one cycle after surgery, followed by toripalimab or placebo monotherapy Q3W for 13 cycles. Stratification variables for randomization included disease stage, histopathologic subtype, PD-L1 expression and surgical procedure. Primary endpoints were EFS by investigator and major pathological response (MPR) rate by a blinded independent pathologic review (BIPR) in the stage III and the ITT populations. Secondary endpoints included overall survival (OS), pathologic complete response (pCR) rate, EFS by independent review committee (IRC), and safety. A planned interim analysis was performed on the primary endpoint of EFS in the stage III subjects. Results: A total of 404 patients with stage III NSCLC were randomly assigned to toripalimab (n=202) or placebo (n=202). By the data cutoff date (November 30, 2022), the median follow-up was 18.3 months. Baseline characteristics were well balanced between the two arms. EFS was significantly improved in the toripalimab arm, HR=0.40, 95% CI (0.277-0.565), P<0.0001, and crossed the pre-specified efficacy boundary. The median EFS was not reached in the toripalimab arm and 15.1 months in the placebo arm. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups. The MPR and pCR rates per BIPR were also higher in the toripalimab arm, 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The OS results showed a trend favoring toripalimab. The incidence of Grade ≥3 adverse events (AEs) (63.4% vs 54.0%), fatal AEs related to toripalimab/placebo (0.5% vs 0%) and AEs leading to discontinuation of toripalimab/placebo (9.4% vs 7.4%) were comparable between the two arms. However, the incidence of immune-related AEs (42.1% vs 22.8%) was more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to perioperative chemotherapy showed statistically significant improvements in EFS for patients with stage III NSCLC with a manageable safety profile. Patients will be followed for overall survival. Clinical trial information: NCT04158440 .
BackgroundDespite current recommendations for heart failure with preserved ejection fraction (HFpEF), few studies have demonstrated the ability of MRI to identify subtle functional differences between HFpEF with essential hypertension (HFpEF‐HTN) patients and hypertension patients (HTN).PurposeThis study aimed to detect and evaluate HFpEF in patients with HTN using feature‐tracking (FT) and to ascertain optimal strain cutoffs for the diagnosis of HFpEF‐HTN.Study TypeRetrospective study.PopulationThree groups (84 with HFpEF‐HTN; 72 with HTN; and 70 healthy controls).Field Strength1.5T, steady‐state free precession (SSFP), and half‐Fourier single‐shot turbo spin‐echo (HASTE) sequences.AssessmentAll patients underwent laboratory testing and imaging protocols (echocardiography and MRI). FT‐derived left ventricular (LV) strain and strain rate (SR) were measured and compared among the three groups with adjustment for confounding factors.Statistical TestsKolmogorov–Smirnov's test, independent‐sample t‐tests, one‐way analysis of variance (ANOVA), Pearson's correlation coefficient, area under the receiver‐operator characteristic (ROC) curve (AUC), and logistic regression.ResultsCompared to 72 HTN patients and 70 healthy controls, HFpEF‐HTN patients (84 patients) demonstrated significantly impaired LV strains (except for global peak systolic radial strain, GRS, P < 0.05 for all). Only LV global peak systolic longitudinal strain (GLS) was significantly impaired in HTN patients vs. controls (P < 0.05). The global peak systolic circumferential SR (sGCSR) showed the highest diagnostic value for the differentiation of HFpEF‐HTN patients from HTN patients (AUC, 0.731; cutoff value, −1.11/s; sensitivity, 56.0%; specificity, 84.7%). Only global peak early diastolic longitudinal SR (eGLSR) remained independently associated with a diagnosis of HFpEF‐HTN in multilogistic analysis. The major strain parameters significantly correlated with LV ejection fraction, end‐systolic volume index, and N‐terminal pro‐brain natriuretic peptide (P < 0.05 for all) and also demonstrated differences between NYHA functional class.Data ConclusionHFpEF‐HTN patients suffer from both systolic and diastolic cardiac dysfunction. FT‐derived strain parameters have potential value for the diagnosis and risk stratification of HFpEF‐HTN patients.Level of Evidence 3.Technical Efficacy Stage 2.
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