The in situ diagnosis of cardiac activities with simultaneous therapeutic electrical stimulation of the heart is key to preventing cardiac arrhythmia. Here, we present an unconventional single-device platform that enables in situ monitoring even in a wet condition and control of beating heart motions without interferences to the recording signal. This platform consists of the active-matrix array of pressure-sensitive transistors for detecting cardiac beatings, biocompatible, low-impedance electrodes for cardiac stimulations, and an alginate-based hydrogel adhesive for attaching this platform conformally to the epicardium. In contrast to conventional electrophysiological sensing using electrodes, the pressure-sensitive transistors measured mechanophysiological characteristics by monitoring the spatiotemporal distributions of cardiac pressures during heart beating motions. In vivo tests show mechanophysiological readings having good correlation with electrocardiography and negligible interference with the electrical artifacts caused during cardiac stimulations. This platform can therapeutically synchronize the rhythm of abnormal heartbeats through efficient pacing of cardiac arrhythmia.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal’s sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.

Pulmonary arterial hypertension (PAH) related to an atrial septal defect (ASD) poses a challenge to transcatheter closure of an ASD (tcASD). We aimed to determine the predictors for remaining PAH (rPAH) post-tcASD. This retrospective study was conducted at a single tertiary university hospital. Adult patients with an ASD and PAH were divided into three groups according to pulmonary vascular resistance (PVR). Normalization of pulmonary atrial systolic pressure (PASP) was defined as an estimated right ventricular systolic pressure < 40 mmHg and was determined using transthoracic echocardiography. Among 119 patients, 80% showed PAH normalization post-tcASD. Normalization of PAH post-tcASD was observed in 100%, 56.2%, and 28.6% of patients in mild, moderate, and severe PVR groups, respectively. The patients’ New York Heart Association functional class improved. Multivariate logistic regression analysis showed that age and high PVR were significant risk factors for rPAH. A receiving operator curve analysis showed a PASP cutoff value > 67.5 mmHg to be predictive of rPAH post-tcASD, with an area under the curve value of 0.944 (sensitivity, 0.922; specificity 0.933). Most patients, including moderate-to-severe PAH patients, improved hemodynamically and clinically with tcASD. Since patients with severe PAH are at a risk of rPAH, tcASD should be performed by selecting the patient carefully based on pre-procedure medication, a vasoreactivity test, and a balloon occlusion test.

(2000). On exchange rings with primitive factor rings artinian. Communications in Algebra: Vol. 28, No. 10, pp. 4989-4993.