Camrelizumab-Related Lethal Arrhythmias and Myasthenic Crisis in a Patient with Metastatic Thymoma.

Immune checkpoint inhibitors (ICIs) have emerged in recent years as promising treatment options for several malignant tumors. However, ICI therapy has also been associated with various immune-related adverse events (irAEs), especially for patients with preexisting autoimmune status, which sometimes can be life-threatening. A 68-year-old woman diagnosed with metastatic thymoma was treated with camrelizumab, a new ICI, as her antitumor protocol. Eleven days after the first dose of camrelizumab, the patient was admitted to our hospital with symptoms of dyspnea, fatigue, and poor appetite. Workups on admission indicated dramatically elevated transaminase, troponin I, creatine kinase, and a new-onset conduction abnormality on electrocardiography. After detailed evaluation, ICI-related myocarditis, myositis, and hepatitis were diagnosed, and therapies including intravenous methylprednisolone were administered. Coronary angiography was performed to exclude acute coronary syndrome due to dynamic electrocardiography changes on day 3. She lapsed into a coma with respiratory muscle failure on the next day, which was highly suspected of myasthenic crisis. Mechanical ventilation and higher dose of methylprednisolone plus intravenous immunoglobulin were applied immediately. However, the third atrioventricular block occurred within the same day, and an urgent temporary pacemaker was placed. More seriously, refractory ventricular tachycardia (VT) occurred subsequently, and even multiple antiarrhythmic drugs used in combination failed to alleviate the VT storm. On day 5 of hospitalization, she suffered from ventricular fibrillation and died of cardiac arrest. In clinical practice, close follow-up should be conducted after ICI treatment, especially for patients already with or at high risk for autoimmune disorders. A multidisciplinary team approach is of importance for better management of patients with multiple organ involvement.

Selective Renal Denervation Guided by Renal Nerve Stimulation in Canine.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P<0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P<0.001 and R=0.927, P<0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.

The Impact of Renal Denervation on the Progression of Heart Failure in a Canine Model Induced by Right Ventricular Rapid Pacing.

Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson's trichrome staining and the expression of transforming growth factor-ß1 (TGF-ß1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin-angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure.

Autonomic nervous system plays a crucial role in maintaining and regulating vessel tension. Renal denervation (RDN) may induce renal artery vasodilation by damaging renal sympathetic fibers. We conducted this animal study to evaluate whether renal artery vasodilation could be a direct indicator of successful RDN. Twenty-eight Chinese Kunming dogs were randomly assigned into three groups and underwent RDN utilizing temperature-controlled catheter (group A, n = 11) or saline-irrigated catheter (group B, n = 11) or sham procedure (group C, n = 6). Renal angiography, blood pressure (BP) and renal artery vasodilation measurements were performed at baseline, 30-minute, 1-month, and 3-month after interventions. Plasma norepinephrine concentrations were tested at baseline and 3-month after intervention. Results showed that, in addition to significant BP reduction, RDN induced significant renal artery vasodilation. Correlation analyses showed that the induced renal artery vasodilation positively correlated with SBP reduction and plasma norepinephrine reduction over 3 months after ablation. Post hoc analyses showed that saline-irrigated catheter was superior to TC catheter in renal artery vasodilation, especially for the acute dilatation of renal artery at 30-minute after RDN. In conclusion, renal artery vasodilation, induced by RDN, may be a possible indicator of successful renal nerve damage and a predictor of blood pressure response to RDN.

The Effect of Catheter Ablation on Left Atrial Size and Function for Patients with Atrial Fibrillation: An Updated Meta-Analysis.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) is now an important therapeutic modality for patients with AF. However, data regarding changes in left atrial (LA) function after CA have indicated conflicting results depending on the AF types, follow-up period, and the analytical imaging tools. The objective of this review was to analyze the effect of CA on the LA size and function for patients with AF. METHODS: We searched for studies regarding LA size and function pre- and post-ablation in PubMed, Embase, the Cochrane Library, and Web of Knowledge through May 2014. LA function was measured by LA ejective fraction (LAEF), LA active ejective fraction (LAAEF), or both. Total and subgroup analyses were implemented using Cochrane Review Manager Version 5.2. Weighted mean differences with 95% confidence intervals were used to express the results of continuous outcomes using fixed or random effect models. I2 was used to calculate heterogeneity. To assess publication bias, Egger's test and Begg's funnel plot were performed using Stata 12.0. RESULTS: Twenty-five studies (2040 enrolled patients) were selected for this meta-analysis. The LA diameter (LAD), maximum LA volume, and minimal LA volume were significantly decreased post-ablation, as compared with those at a pre-ablation visit. Compared with the pre-ablation outcomes, we found no significant differences in LAEF/LAAEF at a post-ablation follow-up. Decreases in LA volume and LAEF remained significant post-ablation for paroxysmal AF (PAF); however, the LAEF was insignificant changes in persistent AF (PeAF). Heterogeneity was significant in spite which individual study was excluded. A publication bias was not found. In a meta-regression analysis, we did not find any factor that contributed to the heterogeneity. CONCLUSION: With CA, LA volumes and LAD were decreased significantly in patients with AF; LAEF was not significant changes in patients with PeAF but decreased in those with PAF.