Cary Ward

STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to show SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide insight into the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells.

Extra-cardiac manifestations of adult congenital heart disease

Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations.

The utility of modified Butler-Leggett criteria for right ventricular hypertrophy in detection of clinically significant shunt ratio in ostium secundum-type atrial septal defect in adults.

BACKGROUND This study was performed to test the hypothesis that there exists a correlation between the Butler-Leggett (BL) criterion for right ventricular hypertrophy on the electrocardiogram and the Qp/Qs shunt ratio in adults with ostium secundum atrial septal defects (ASDs). METHODS Demographic, cardiac catheterization, ASD closure, and electrocardiographic data were acquired on 70 patients with secundum ASDs closed percutaneously. Simple linear regression and logistic regression models were created to test the hypothesis. RESULTS The mean Qp/Qs ratio and BL criterion value were 1.61 +/- 0.46 and 0.11 +/- 0.41, respectively. The BL criterion values correlated with shunt ratios (r(2) = 0.11 and P = .004). A BL criterion value greater than 0 mV predicted a significant shunt ratio (Qp/Qs > or = 1.5) (odds ratio, 4.8; 95% confidence interval, 1.3, 18.1; P = or <.0001) with a sensitivity of 0.68 and specificity of 0.65. CONCLUSION Our results indicate that there is limited utility of the BL criterion at detecting right ventricular volume overload, although a BL criterion value greater than 0 mV being used to identify patients with significant intracardiac shunts yielded a sensitivity of 0.68 and specificity of 0.65.

Congenital and Acquired Valvular Heart Disease in Pregnancy

Purpose of ReviewThe number of pregnancies complicated by valvular heart disease is increasing. This review describes the hemodynamic effects of clinically important valvular abnormalities during pregnancy and reviews current guideline-driven management strategies.Recent FindingsValvular heart disease in women of childbearing age is most commonly caused by congenital abnormalities and rheumatic heart disease. Regurgitant lesions are well tolerated, while stenotic lesions are associated with a higher risk of pregnancy-related complications. Management of symptomatic disease during pregnancy is primarily medical, with percutaneous interventions considered for refractory symptoms.SummaryMost guidelines addressing the management of valvular heart disease during pregnancy are based on case reports and observational studies. Additional investigation is required to further advance the care of this growing patient population.

The Use of Implantable Cardioverter-defibrillators in the Prevention of Sudden Cardiac Death: A Focus on Congenital Heart Disease and Inherited Arrhythmia Syndromes

Some congenital heart diseases (CHDs) and inherited arrhythmia syndromes are associated with an increased risk of sudden cardiac death (SCD). Appropriate selection criteria for implantable cardioverter-defibrillator (ICD) implantation in these patients are poorly defined due to a paucity of data available from randomized clinical trials, leading to current guidelines relying more on non-randomized studies and expert opinions to make their recommendations. This review describes available evidence-based risk stratification methods for identifying patients at risk for SCD, as well as current guideline-driven management strategies for the use of ICDs in patients with CHD and inherited arrhythmia syndromes.

Pre-existing Medical Conditionsamong Pregnant Women withCardiomyopathy

Pre-existing Medical Conditions among Pregnant Women with Cardiomyopathy Background: The purpose of this study was to identify medical conditions and obstetric complications associated with all forms of cardiomyopathy in pregnancy. Study Design: The Nationwide Inpatient Sample (NIS) for the years 2000-2007 was queried for all pregnancy-related discharges. The ICD-9 codes for cardiomyopathy were used to identify cases and were compared to women without cardiomyopathy. Results: During the 8-year period 2000-2007, there were 36,930 records with a diagnosis of cardiomyopathy in pregnancy for a rate of 0.98 per 1000 pregnancy-related discharges. At an admission for delivery, multivariable logistic regression demonstrated that chronic hypertension and preexisting heart disease were the pre-existing conditions that best predicted cardiomyopathy (OR 2.9, 95% CI 2.6, 3.3 for hypertension, OR 71.3, 95% CI 62.2, and 81.8 for pre-existing heart disease). Cardiac and pulmonary events that occurred during a delivery hospitalization were the two types of acute events most associated with cardiomyopathy in pregnancy (OR 34.7, 95% CI 28.8, 41.9 for cardiac event and OR 29.4, 95% CI 25.1, 34.4 for pulmonary events). Conclusions: Women with pre-existing cardiac disease and hypertension are at significantly increased risk for developing cardiomyopathy in pregnancy. Hypertension is a potentially modifiable risk factor that may ultimately decrease the risk for cardiomyopathy in pregnancy.