SummaryWhen pluripotency factors are removed, embryonic stem cells (ESCs) undergo spontaneous differentiation, which, among other lineages, also gives rise to cardiac sublineages, including chamber cardiomyocytes and pacemaker cells. Such heterogeneity complicates the use of ESC-derived heart cells in therapeutic and diagnostic applications. We sought to direct ESCs to differentiate specifically into cardiac pacemaker cells by overexpressing a transcription factor critical for embryonic patterning of the native cardiac pacemaker (the sinoatrial node). Overexpression of SHOX2 during ESC differentiation upregulated the pacemaker gene program, resulting in enhanced automaticity in vitro and induced biological pacing upon transplantation in vivo. The accentuated automaticity is accompanied by temporally evolving changes in the effectors and regulators of Wnt signaling. Our findings provide a strategy for enriching the cardiac pacemaker cell population from ESCs.

PRESENCE OF PACEMAKER and intracardiac defibrillator leads as well as tricuspid annuloplasty ring or bioprosthetic tricuspid valve by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), due to reverberation artifact produced by the catheter and prosthetic valve material.Identification of location of the vegetation on the lead versus prosthetic valve has therapeutic implications, particularly in patients with multiple prior cardiac surgeries in whom repeat surgery is not desirable. Cardiac magnetic resonance is currently not a feasible imaging option in patients with prosthetic devices. Real-time 3-dimensional transesophageal echocardiography (RT3D TEE) is able to demonstrate precise relationships among various anatomical structures and is also able to visualize intracardiac catheters, including catheter tip, without artifact associated with TTE and conventional TEE.The utility of RT3D TEE in suspected right-sided endocarditis in patients with pacemaker or intracardiac leads and bioprosthetic tricuspid valve or a tricuspid annuloplasty ring is described in this report. It is to be emphasized that lack of demonstrable vegetations by RT3D TEE may not necessarily imply lack of infection of the device.RT3D TEE allows evaluation of precise location of vegetation on prosthetic devices such as intracardiac defibrillator (ICD) leads, pacemakers, or tricuspid valve prostheses. Precise delineation of location of vegetation in these patients allows therapeutic medical and surgical treatment decisions. Absence of demonstrable vegetations by RT3D TEE however does not entirely exclude endocarditis, which ultimately remains a clinical diagnosis.

BackgroundBiventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.MethodsBlinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 ± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 ± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.ResultsSignificant improvement post optimization was achieved in LV ET (286.9 ± 37.3 to 299 ± 34.6 ms, p < 0.001), LV VTI (15.9 ± 4.8 cm to 18.4 ± 5.1 cm, p < 0.001) and MPI (0.57 ± 0.2 to 0.45 ± 0.13, p < 0.001) and in PEP (246.7 ± 36.1 ms to 234.7 ± 35.5 ms, p = 0.003), PEP/ET (0.88 ± 0.21 to 0.79 ± 0.17, p < 0.001), and PEP/VTI (17.3 ± 7 to 13.78 ± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 ± 0.8 to 2.0 ± 0.9 (p = 0.004) at 1.8 ± 1.4 months.ConclusionAn acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.

In spite of improvements in heart failure management and increasing utilization of cardiac resynchronization therapy (CRT), approximately 30-40% of CRT patients remain nonresponders and 50% or more are echocardiographic nonresponders (defined as less than 15% reduction in left ventricular end systolic volume post-CRT). Optimization guided by echocardiography has been studied as one of the methods to improve the nonresponder rate to CRT. Echo-guided biventricular (Biv) pacemaker optimization has been associated with improvement in acute cardiac hemodynamics and improvement in functional class. In this review, the authors discuss various methods to optimize Biv pacemaker by echocardiography, recent advances in pacemaker optimization and the limitations of echocardiography. The authors also demonstrate complex hemodynamic derangements in heart failure via multiple case examples highlighting the role of comprehensive echo Doppler in elucidating cardiac hemodynamics encountered in CRT nonresponders, as well as tailoring of Biv pacemaker optimization to the underlying physiologic derangement.