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INTRODUCTION: The interaction between the cardiovascular and respiratory systems in healthy subjects is determined by the autonomic nervous system and reflected in respiratory sinus arrhythmia. Recently, another pattern of cardio-respiratory coupling (CRC) has been proposed linking synchronization of heart and respiratory system. However, CRC has not been studied precisely in heart failure (HF) with reduced ejection fraction (EF) (HFrEF) according to the myocardial recovery. METHODS: 10-min resting electrocardiography measurements were performed in persistent HFrEF patients (n=40) who had a subsequent left ventricular EF (LVEF) of ≤ 40â¯%, HF with recovered EF patients (HFrecEF) (n=41) who had a subsequent LVEF of > 40â¯% and healthy controls (n=40). Respiratory frequency, respiratory rate, CRC index, time-domain, frequency-domain and nonlinear heart rate variability indices were obtained using standardized software-Kubios™. CRC index was defined as respiratory high-frequency peak minus heart rate variability high-frequency peak. RESULTS: Respiratory rate was positively correlated with high-frequency (HF) peak (Hz) in both persistent HFrEF group (p<0.001) and HFrecEF group (p<0.001), while respiratory rate was negatively correlated with HF power (ms2) in the healthy controls (p<0.05). CRC index was lowest in the persistent HFrEF group followed by HFrecEF and was high in healthy controls (0.008 vs 0.012 vs 0.056â¯Hz, p=0.03). CONCLUSION: CRC index was lowest in patients with impaired myocardial recovery, which indicates that cardio-respiratory synchrony is stronger in persistent HFrEF. This may represent a higher HF peak (Hz)/lower HF power (ms2) and abnormal sympathovagal balance in persistent HFrEF group compared to healthy controls. Further work is underway to tests this hypothesis and determine the utility of CRC index in HF phenotypes and its utility as a potential biomarker of response with neuromodulation.
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Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.
RESUMEN
OBJECTIVES: Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD. CTRCD is preceded by increased activation of the sympathetic nervous system and abnormal left ventricular mechanical deformation as measured by abnormal global longitudinal strain (GLS). Low-level tragus stimulation (LLTS) is a new, safe, noninvasive technique that offers great potential to reduce increased sympathetic activation and improve GLS. Here, we describe a study method to examine the effects of LLTS on autonomic balance and cardiac function in breast cancer or lymphoma patients treated with anthracyclines. METHODS: A first-in-human pilot, randomized, double-blind feasibility study will evaluate 104 patients (age >50 y) with breast cancer or lymphoma who receive anthracyclines with one additional CTRCD risk factor. Patients undergo 2 weeks of LLTS daily (1 h/d). Autonomic balance will be measured using heart rate variability metrics. Strain imaging using GLS will be performed pre and post-LLTS. Endothelial inflammation and oxidative stress measures will be performed using in vitro assays at baseline and after 2 weeks. CONCLUSION: We hypothesize that LLTS stabilizes sympathovagal imbalance and improves cardiac performance in anthracycline-treated patients with breast cancer or lymphoma.