Acute Efficacy of a Traditional Chinese Medicine for Treatment of Frequent Premature Ventricular Contractions in Patients with Concomitant Sinus Bradycardia: Results from a Double-Blind, Placebo-Controlled, Multicentre, Randomized Clinical Trial.

Pharmacological antiarrhythmic therapy such as beta-blockers in patients with frequent premature ventricular contractions (PVCs) and concomitant bradycardia is challenging. A traditional Chinese medicine, Shensong Yangxin (SSYX), has been effective in treatment of frequent PVCs and sinus bradycardia (SB) in separate patient cohorts. This double-blind, placebo-controlled, multicentre, randomized clinical trial investigates the acute efficacy of SSYX in reducing PVCs burden in patients with concomitant SB. Patients with symptomatic, frequent PVCs, and SB, defined as mean heart rate (MHR) of 45 to 59 beats per min (bpm), were recruited at 33 medical centres in mainland China and randomly assigned by computer to either SSYX or matching placebo for eight weeks. Patients, investigators, and trial personnel were masked to treatment allocation. Primary endpoints were changes in PVCs burden and MHR as assessed by 24-hour Holter monitoring relative to baseline. Secondary efficacy endpoints were subjective symptom score, ECG, and biochemical parameters. Analysis was based on intention-to-treat principles. 333 patients were randomized, of which 166 received SSYX and 167 placebo. Baseline characteristics did not differ. SSYX reduced PVCs burden by 68.2% (p < 0.001) and increased MHR by 10.9% (p < 0.001) compared to 32.2% and 4.7%, respectively, in the placebo group. SSYX group experienced greater symptomatic improvement (p < 0.001). No differences in reported adverse events were seen (20 versus 23). SSYX is an effective antiarrhythmic therapy for symptomatic, frequent PVCs uniquely suited patients with concomitant SB. Clinical trial number was NCT01750775.

Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-ß1-mediated hypertrophic signaling in vitro and in vivo.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Transforming growth factor-ß1 (TGF-ß1) signaling has been considered as a trigger causally contributing to pathological cardiac hypertrophy. Asiatic acid (AA) is a triterpenoid compound extracted from Centella asiatica and exhibits a variety of pharmacological effects. In this study, we investigated the anti-hypertrophic effects and mechanisms of action of AA in a TGF-ß1-stimulated hypertrophic response using cultured neonatal cardiomyocytes in vitro and in a mouse model of cardiac hypertrophy induced by pressure overload in vivo. Treatment with AA markedly attenuated the TGF-ß1-induced hypertrophic responses of cardiomyocytes as reflected by reduction in the cardiomyocyte surface area and the inhibition of atrial natriuretic peptide (ANP) mRNA expression. The protective effects of AA on hypertrophic cardiomyocytes were associated with the blocking of p38 and extracellular signal­regulated kinase (ERK)1/2 phosphorylation and the reduction of nuclear factor-κB (NF-κB) binding activity. In vivo experiments indicated that the administration of AA prevented cardiac hypertrophy and dysfunction induced by pressure overload. It was found that AA markedly reduced the excessive production of TGF-ß1 in the hypertrophic myocardium, blocked the phosphorylation of p38 and ERK1/2 and inhibited the activation of NF-κB. Our data suggest that AA may be a novel therapeutic agent for cardiac hypertrophy. The inhibition of TGF-ß1­mediated hypertrophic signaling may be the mechanism through which AA prevents cardiac hypertrophy.