The digitization of medical records ushered in a new era of big data to clinical science, and with it the possibility that data could be shared, to multiply insights beyond what investigators could abstract from paper records. The need to share individual-level medical data to accelerate innovation in precision medicine continues to grow, and has never been more urgent, as scientists grapple with the COVID-19 pandemic. However, enthusiasm for the use of big data has been tempered by a fully appropriate concern for patient autonomy and privacy. That is, the ability to extract private or confidential information about an individual, in practice, renders it difficult to share data, since significant infrastructure and data governance must be established before data can be shared. Although HIPAA provided de-identification as an approved mechanism for data sharing, linkage attacks were identified as a major vulnerability. A variety of mechanisms have been established to avoid leaking private information, such as field suppression or abstraction, strictly limiting the amount of information that can be shared, or employing mathematical techniques such as differential privacy. Another approach, which we focus on here, is creating synthetic data that mimics the underlying data. For synthetic data to be a useful mechanism in support of medical innovation and a proxy for real-world evidence, one must demonstrate two properties of the synthetic dataset: (1) any analysis on the real data must be matched by analysis of the synthetic data (statistical fidelity) and (2) the synthetic data must preserve privacy, with minimal risk of re-identification (privacy guarantee). In this paper we propose a framework for quantifying the statistical fidelity and privacy preservation properties of synthetic datasets and demonstrate these metrics for synthetic data generated by Syntegra technology.

When attempting to answer questions of interest, scientists often encounter hurdles that may stem from limited access to existing adequate datasets as a consequence of poor data sharing practices, constraining administrative practices. Further, when attempting to integrate data, differences in existing datasets also impose challenges that limit opportunities for data integration. As a result, the pace of scientific advancements is suboptimal. Synthetic data and virtual cohorts generated using innovative computational techniques represent an opportunity to overcome some of these limitations and consequently, to advance scientific developments. In this paper, we demonstrate the use of virtual cohorts techniques to generate a synthetic dataset that mirrors a deeply phenotyped sample of preclinical dementia research participants.

Recent advances in generative modeling, based on large scale deep neural networks, provide a novel approach for sharing individual-level datasets (micro-data) without privacy concerns. Unlike differential privacy, which enforces a specific query mechanism on data to ensure privacy, generative models can accurately learn the statistical patterns of such micro-data and then be used to generate "synthetic data" that accurately reflects these statistical patterns, yet contain none of the original data itself, and thus can be safely shared for analysis and modeling without compromising privacy. The successful application of these techniques to various industries including healthcare, finance, and autonomous vehicles is promising and results in continued investment in research and development of generative models in both academia and industry.

A total of 13 (4 .5%) of 290 patients with aborted sudden death had either documented (7 ; 54%) or strong pre.ampdve evidence of supraventricular tachycardia that deteriorated into ventricular fibrillation. Six (46%) of the 13 had an accessory conduction pathway and either atria[ fibrillation IS patients) or paroxysmal atrioventricular (AV) reentrant tachycardia it patient) that deteriorated into ventricular fibrillation . Three patients 00(1k AV node reentrant tachycardia and four with atria[ fibrillation and enhanced AV node conduction presented with supraventricular arrhythmias that deteriorated into ventricular fibrillation . Patients were treated with medical, surgical or catheterablative procedures designed to prevent recurrences of supraven-

Objective A project is now underway to implement a novel percutaneous mitral repair system for severe mitral regurgitation (MR). The initial phase of the project consists of proof-of-concept by testing device characteristics using open surgical implantation. When surgical proof-of-concept of the intended percutaneous design is completed, a second phase of the project will consist of in vivo testing of the percutaneous transseptal system. The device is currently being designed to fold into a 17F catheter system and to unfold within the left atrium where attachment is accomplished using a reversible anchoring system. The purpose of this study was to show functionality of the device in elimination of MR using the open surgical method. Methods We have performed surgical prototype device implantation in 5 acute and 7 chronic sheep preparations. We created a P2-flail model of severe (4+) MR in the 12 sheep. Via a minimally invasive left thoracotomy incision and open repair on cardiopulmonary bypass, the device was implanted to determine efficacy of elimination of severe MR. Implantation was considered successful if 4+ regurgitation was converted to 1+ MR or lower. Left ventriculography and epicardial 2-dimensional/3-dimensional echocardiography were used to assess repair; serial 2-dimensional/3-dimensional transthoracic echocardiography was used to assess long-term mitral repair status. Results Twelve sheep had surgical creation of severe (4+) MR by cutting all chordae to the P2 scallop of the mitral valve; this preparation was tested and was found to produce 100% acute fatality without repair of the mitral valve. Five sheep had acute implantation of the device with elimination of regurgitation in 5/5 sheep. Seven sheep had chronic (1–7 month) implantation of the device. The device was tested in the chronic model for clinical status, residual regurgitation, thrombosis, and histopathology. All sheep had mitigation of MR and survived to the intended date of death. Conclusions Proof-of-concept of a novel percutaneous mitral repair device has been completed using an ovine P2-flail severe MR model. The device has characteristics that will allow its use in posterior leaflet degenerative disease and functional/secondary MR. Open, minimally invasive, and robotic surgical implantation of the device can also be developed as an alternative to the percutaneous approach.

Experiments wereperformed invitro on sixnormalthinventricular epicardial tissue strips and 10strips removed fromtheinfarcted regions ofdogs21-60daysafter experimental myocardial infarction. Conduction was evaluated bymapping activation sequencesat40-45sites overan areaof1x2cm during pacing atabasic cycle length of2,000 msec.Theamplitude andlength ofrecorded electrograms werealsodetermined ateachsite. After control recordings, heptanol, whichincreases gap junctional resistance, was addedtothetissue bathatconcentrations ranging between 0.2and1.0mM.Incontrast toits effect on normal tissues, heptanol caused 75 of260previously active sites intheinfarcted tissues tobecomeinactive. Theaffected sites were located inareasofveryslowconduction and/or adjacent toareasofpreexisting conduction block. Inaddition, heptanol decreased thelength anddegree offractionation ofelectrograms recorded inslowly conducting regions oftheinfarcted tissues. Themagnitude ofthedecrease inelectrogram length following heptanol was related tothedegree ofelectrogram abnormality during control asreflected intheratio ofelectrogram length toamplitude. Heptanol shortened electrograms bycausing local conduction block, whicheliminated some components ofthe fractionated electrograms. Inan additional eight epicardial strips removed fromtheinfarcted region, 0.5mM heptanol hadonly a slight effect (10.7% decrease) on themaximumrateof membranedepolarization. Thus, heptanol doesnotactprimarily byway ofdepressing thefast inward current. We conclude fromheptanol's effects on conduction andelectrogram charac- teristics thatslowanddissociated conduction intheinfarcted region isduetoan abnormality ingapjunctional distribution between surviving cells and/or an abnormality inindividual gap junctional function. (Circulation Research 1990;66:202-217)

Background The pacing site has been shown to influence functional improvement with cardiac resynchronization therapy. We evaluated the effects of the pacing site on left ventricular (LV) function in an animal model. Methods and Results Equilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with ventricular pacing, from three pacing sites in seven normal and eight infarcted dogs. QRS duration, electrical activation pattern, wall motion, LV ejection fraction (EF), synchrony of ventricular contraction, and mean arterial pressure (MAP), were related to the pacing site and infarct size, during each of 120 episodes. Little changed during pacing in normals. In infarcted dogs, LV wall motion, and synchrony worsened, LVEF and MAP often fell. These changes related to altered activation patterns which were influenced by the pacing site but were not related to infarct size. Conclusions Hemodynamic and functional LV changes after infarction were found to vary with the pacing site and associated conduction and synchrony.

Background Phase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation. Objectives We sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both. Methods In 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites. Results In each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups. Conclusions A noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences.