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Abstract-To investigate the cellular mechanisms for altered Ca 2ϩ homeostasis and contractility in cardiac hypertrophy, we measured whole-cell L-type Ca 2ϩ currents (I Ca,L ), whole-cell Ca 2ϩ transients ([Ca 2ϩ ] i ), and Ca 2ϩ sparks in ventricular cells from 6-month-old spontaneously hypertensive rats (SHRs) and from age-and sex-matched Wistar-Kyoto and Sprague-Dawley control rats. By echocardiography, SHR hearts had cardiac hypertrophy and enhanced contractility (increased fractional shortening) and no signs of heart failure. C ardiac hypertrophy is associated with marked changes in myocardial contractility. Peak active tension increases, 1-4 and the rates of both contraction and relaxation are slowed. 3,[5][6][7][8] These contractile abnormalities are associated with alterations in the whole-cell calcium transient ([Ca 2ϩ ] i ). In the hypertrophied myocardium, the amplitude of [Ca 2ϩ ] i increases, 9 whereas in failing myocardium, the amplitude of [Ca 2ϩ ] i decreases. 10 -13 In most animal models of hypertrophy 8,10,11,[13][14][15] and in failing human hearts, 12,16 the duration of the whole-cell [Ca 2ϩ ] i is also prolonged. However, the precise cellular mechanisms that are responsible for changes in contractility and alterations in [Ca 2ϩ ] i are largely unknown. Identification of the cellular mechanisms that underlie altered excitation-contraction coupling in cardiac hypertrophy and heart failure is complicated by several issues, including differences in experimental animal models and disease progression. In addition, it has only recently proved possible using confocal microscopy to measure local nonpropagating elevations of Ca 2ϩ (Ca 2ϩ sparks) at the level of individual sarcomeres. [17][18][19][20][21][22] The ability to measure Ca 2ϩ sparks provides an opportunity to evaluate directly the role of sarcoplasmic reticulum (SR) Ca 2ϩ release in muscle cells from animal models associated with cardiac hypertrophy.In this study, we used laser scanning confocal microscopy and Ca 2ϩ -sensitive fluorescent indicators to detect Ca 2ϩ sparks evoked by electrical field stimulation in ventricular cells from normal rats and from spontaneously hypertensive rats (SHRs) with cardiac hypertrophy. By quantitative analysis of the kinetic characteristics of Ca 2ϩ sparks, we identify enhanced SR Ca 2ϩ release from hypertrophied SHR cells. In

Cardiovascular abnormalities are important features of Costello syndrome and other Ras/MAPK pathway syndromes (“RASopathies”). We conducted clinical, pathological and molecular analyses of 146 patients with an HRAS mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%) HRAS mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients (44%), usually non‐progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow‐up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one‐fourth of those with arrhythmia, but is generally self‐limited in the remaining three‐fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated. © 2011 Wiley‐Liss, Inc.

Background-Diastolic run off into the pulmonary circulation and labile coronary perfusion are thought to contribute to morbidity and mortality after the Norwood procedure (NP). We compared outcomes from the use of a RV to PA conduit (RV/PA) or a modified Blalock-Taussig shunt (BTS), physiologically distinct sources of pulmonary blood flow.