Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and meta-analysis.

Background: Penicillin is essential for secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). However, the incidences of ARF recurrence and RHD progression remain high, particularly in endemic countries. This meta-analysis evaluated the effectiveness of penicillin adherence in secondary prevention of ARF recurrence and RHD progression. Methods: The authors included original articles employing an observational study design in which the study population included patients with ARF or RHD and documented adherence to secondary prophylaxis with penicillin for secondary prevention. Systematic searches of the PubMed, Scopus, and Cochrane databases were performed. Moreover, the authors also conducted a snowballing literature search from Europe PMC to expand the included studies. The quality of each study was assessed using the National Institute of Health Quality Assessment Tool. The statistical analyses were conducted using Review Manager 5.4.1 software developed by Cochrane. In addition, the authors utilized pooled odds ratios (ORs) to compare the adherence techniques. Results: A total of 310 studies were identified, of which 57 full-text articles were assessed for eligibility. The authors included six studies with 1364 patients for the qualitative synthesis and meta-analysis. Good adherence to penicillin for the secondary prophylaxis of ARF and RHD, significantly reduced the odds of ARF recurrence or RHD progression by up to 71% compared to that associated with poor adherence [pooled OR 0.29 (0.21-0.40); I²=0% (p=0.56); Z=7.64 (p <0.00001)]. Conclusion: Good adherence to penicillin for secondary prophylaxis in patients with ARF or RHD is essential for reducing the risk of ARF recurrence or RHD progression.

The effect of external counterpulsation on intrinsic myocardial function evaluated by speckle tracking echocardiography in refractory angina patients: a randomized controlled trial.

External Counterpulsation (ECP) is one of the therapeutic options in patients with refractory angina inadequately controlled by medical, interventional, or surgical therapy. The 2D Speckle Tracking Echocardiography (2D-STE) method is considered superior in assessing clinical improvement. We would like to evaluate any improvement of myocardial intrinsic function using 2D-STE in patients underwent standard ECP protocol (35 sessions). We conducted a double-blind randomized controlled trial. Patients with refractory angina who could not be revascularized conventionally were randomized into two groups: (1) the ECP group (300 mmHg) and (2) the Sham/control group (75 mmHg). ECP standard therapy was given for 35 sessions (1 h/day/session). The 2D-STE data, including longitudinal strain and post systolic index (PSI) were obtained before and after therapy. 43 subjects were analyzed, with 22 subjects in ECP group and 21 control subjects (Sham group). A homogenous baseline strain was found either globally (12.42 ± 4.55 vs 12.00 ± 4.92 [- %]; P = 0.774) or segmentally/regionally (12.63 (0.01-25.16) vs 12.43 (0.01-27.20) [- %]; P = 0.570). There was no statistically significant improvement between groups in the left ventricle longitudinal strain globally (P = 0.535) and segmentally/regionally (P = 0.434). PSI parameters showed improvement in the ECP group (P = 0.049), and segments with PSI ≥ 20% seemed to improve longitudinal strains in the ECP group after therapy (P = 0.042). In conclusion, 35 ECP therapy sessions did not improve either global or segmental/regional left ventricular mechanical function in patients with refractory angina. However, the mechanical function of myocardial segments with PSS tends to improve after ECP therapy.

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2.

Rheumatic heart disease (RHD) is common in developing countries and poses a big medical challenge and burden. The pathogenesis of RHD is influenced by the triad of host, agent, and environment. Autoantigens generated from Group A Streptococcus (GAS) infection are captured by the resident dendritic cells (DCs) in the heart's valvular endothelium. DCs differentiate into antigen presenting cells (APC) in the valve interstices. APC induces activation of autoreactive T cells, which triggers inflammation and tissue fibrosis. Cardiac fibrosis is promoted through the activation of Mitogen activated protein kinases (MAPKs) and its downstream signaling, including its interaction with transforming growth factor-ß (TGF-ß) and Smad proteins. TGF-ß-induced phosphorylation of Smad2 complexes with Smad3 and Smad4, and translocates into the nucleus. Angiotensin II enhances the migration, maturation, and presentation of DC. In RHD, Angiotensin II induces fibrosis via the stimulation of TGF-ß, which further increases the binding of IL-33 to sST2 but not ST2L, resulting in the upregulation of Angiotensin II and progression of cardiac fibrosis. This cascade of inflammation and valvular fibrosis causes calcification and stiffening of the heart valves in RHD. Angiotensin converting enzyme inhibitors (ACEIs) inhibit Angiotensin II production, which in turn decreases TGF-ß expression and the onset of overt inflammatory response. This condition leads to a reduction in the sST2 as the decoy receptor to "steal" IL-33, and IL-33 binds to ST2L and results in cardioprotection against cardiac fibrosis in the pathogenesis of RHD.