Developing a Vaccine for Rheumatic Fever and Rheumatic Heart Disease: A Review of Current Research Strategies and Challenges

Rheumatic heart disease (RHD) is an auto immune sequelae of rheumatic fever (RF) caused by Group A Streptococcal (GAS) pharyngitis, rather than the direct bacterial infection of the heart, which leads to chronic heart valve damage. Although antibiotics like penicillin are effective against GAS infection, improper medical care such as poor patient compliance, overcrowding, poverty, and repeated exposure to GAS, leads to acute rheumatic fever and RHD. Thus, effort to design a vaccine based on emm gene identification of GAS, M-protein going on for more than 40 years, is unlikely to succeed. M-protein is strain specific. Infection with one strain does not provide immunity from infection with another strain. Based on the emm gene identification, of 250 or more identified strains of GAS, the distribution is heterogenous and keeps changing. The M-protein gene sequence of the organism tends to mutate. A vaccine prepared from available strains may not be effective against a strain following mutation.

Assessment of Mechanical and Electrical Dyssynchrony in Cardiomyopathy.

Background: Cardiac resynchronization therapy (CRT) had shown great promise in improving hospitalization and mortality of the patients suffering from refractory heart failure (HF) inspite of optimal medical management. The goal of CRT is to reduce cardiac mechanical dyssynchrony, thereby enabling the heart to contract more efficiently. Mechanical ventricular dyssynchrony as estimated by electrical dyssynchrony, is assessed with the QRS duration. But electrical and mechanical dyssynchrony are not well correlated in all HF patients. The dyssynchrony might have been related to the underlying etiology of HF. Objective: To compare the concordance of mechanical and electrical dyssynchrony in both ischemic and nonischemic cardiomyopathy patients. Methods: Doppler echocardiography and strain echocardiography was performed in 76 patients presenting with heart failure due to ischemic cardiomyopathy (n=40) or nonischemic cardiomyopathy (n=36) with left ventricular ejection fraction<35% & New York Heart Association class III–IV, regardless of their QRS duration. Interventricular dyssynchrony was assessed by the time interval between preaortic and prepulmonary ejection times. Intra-ventricular dyssynchrony was assessed by using conventional Doppler and strain echocardiograpy. Obtained from the three standard apical view (TMinMax) and (2) the standard deviation of the averaged time-to-peak strain (TPS-SD, ms) and (3) time to peak myocardial systolic velocity (Ts-SD) of same segments. Result: The correlation coefficient between QRS duration and mechanical interventricular dyssynchrony was significant (r=0.57, P=0.001) in patients with non-ischemic cardiomyopathy and insignificant (r=0.175, p=0.281) in patients with ischemic cardiomyoparhy. The correlation coefficient between QRS duration and mechanical intraventricular dyssynchrony was significant in patients with nonischemic cardiomyopathy (r= 0.69, P = 0.001 for TMin Max; r=0.57, P= 0.001 for TPS-SD; r=0.48, p=0.003 for TS-SD) and insignificant in patients with ischemic cardiomyopathy (r=0.153; p=0.345 for TMin Max; r=0.178; p=0.273 for TPS-SD r=0.139; p=0.392 for TS-SD). Conclusion: This study showed that the relationship between electrical and mechanical dyssynchrony is dependent on the underlying etiology of heart failure.