Right ventricular and pulmonary vascular function indices for risk stratification of patients with pulmonary regurgitation

Background: We hypothesized that echocardiographic indices of right ventricular to pulmonary artery (RV‐PA) coupling were comparable to cardiac magnetic resonance imaging (CMRI)‐derived RV volumetric indices in predicting disease severity in chronic pulmonary regurgitation (PR).
Methods: Patients with ≥ moderate PR (2003‐2015) with and without prior CMRI scans were enrolled into the study cohort and validation cohort, respectively. Endpoint was to determine the association between noninvasive RV‐PA coupling in‐ dices (tricuspid annular plane systolic excursion/right ventricular systolic pressure [TAPSE/RVSP] and fractional area change [FAC]/RVSP ratio) and markers of disease severity, and compared this association to that of CMRI‐derived RV volumetric indi‐ ces and markers of disease severity (peak oxygen consumption [VO2], NT‐proBNP and atrial and/or ventricular arrhythmias).
Results: Of the 256 patients in the study cohort (age 33 ± 6 years), 187 (73%) had tetralogy of Fallot (TOF) while 69 (27%) had valvular pulmonic stenosis (VPS). TAPSE/ RVSP (r = 0.73, P < .001) and FAC/RVSP (r = 0.78, P < .001) correlated with peak VO2. Among the CMRI‐derived RV volumetric indices analyzed, only right ventricular end‐ systolic volume index correlated with peak VO2 (r = −0.54, P < .001) and NT‐proBNP (r = 0.51, P < .001). These RV‐PA coupling indices were tested in the validation cohort of 218 patients (age 37 ± 9 years). Similar to the study cohort, TAPSE/RVSP (r = 0.59, P < .001) and FAC/RVSP (r = 0.70, P < .001) correlated with peak VO2. TAPSE/RVSP (but not FAC/RVSP) was also associated with arrhythmia occurrence in both the study cohort and validation cohorts.
Conclusion: Noninvasive RV‐PA coupling may provide complementary prognostic data in the management of chronic PR. Further studies are required to explore this clinical tool.     

Nephroscope in the management of recurrent pyogenic cholangitis

Several minimally invasive procedures have been successfully used for removal of stones from the hepatobiliary system. We describe an innovative interventional radiologic procedure using rigid urologic instruments within the hepatobiliary system. Stones within the hepatic and bile ducts in a patient with recurrent pyogenic cholangitis were removed by a technique resembling percutaneous nephrolithotomy for renal stones.     

Efficacy of Communication DEALL—An Indigenous Early Intervention Program for Children with Autism Spectrum Disorders

Objective  

To establish the efficacy of Communication DEALL, an indigenous early intervention program; in the management of children with autism spectrum disorders (ASD).     

Modulation of left ventricular dilation remodeling with epicardial restraint devices in postmyocardial infarction heart failure

Myocardial infarction initiates progressive changes in the biology of the myocyte and nonmyocyte components of the myocardium, as well as the geometry of the left ventricle. Despite the use of evidence-based strategies to postmyocardial infarction, heart failure supervenes and is attended by an unacceptably high mortality rate. Given that left ventricular (LV) remodeling may contribute independently to disease progression, several innovative approaches have been designed to attenuate and reverse LV remodeling. This review discusses the emerging role of epicardial restraint devices in the treatment of postmyocardial cardiac remodeling.     

Abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel complex linked to exercise-induced sudden cardiac death

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic disorder associated with mutations in the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2) genes. Previous in vitro studies suggested that RyR2 and CASQ2 interact as parts of a multimolecular Ca(2+)-signaling complex; however, direct evidence for such interactions and their potential significance to myocardial function remain to be determined. We identified a novel CASQ2 mutation in a young female with a structurally normal heart and unexplained syncopal episodes. This mutation results in the nonconservative substitution of glutamine for arginine at amino acid 33 of CASQ2 (R33Q). Adenoviral-mediated expression of CASQ2(R33Q) in adult rat myocytes led to an increase in excitation-contraction coupling gain and to more frequent occurrences of spontaneous propagating (Ca2+ waves) and local Ca2+ signals (sparks) with respect to control cells expressing wild-type CASQ2 (CASQ2WT). As revealed by a Ca2+ indicator entrapped inside the sarcoplasmic reticulum (SR) of permeabilized myocytes, the increased occurrence of spontaneous Ca2+ sparks and waves was associated with a dramatic decrease in intra-SR [Ca2+]. Recombinant CASQ2WT and CASQ2R33Q exhibited similar Ca(2+)-binding capacities in vitro; however, the mutant protein lacked the ability of its WT counterpart to inhibit RyR2 activity at low luminal [Ca2+] in planar lipid bilayers. We conclude that the R33Q mutation disrupts interactions of CASQ2 with the RyR2 channel complex and impairs regulation of RyR2 by luminal Ca2+. These results show that intracellular Ca2+ cycling in normal heart relies on an intricate interplay of CASQ2 with the proteins of the RyR2 channel complex and that disruption of these interactions can lead to cardiac arrhythmia.