Deep Learning Algorithms to Detect Murmurs Associated With Structural Heart Disease.

Background The success of cardiac auscultation varies widely among medical professionals, which can lead to missed treatments for structural heart disease. Applying machine learning to cardiac auscultation could address this problem, but despite recent interest, few algorithms have been brought to clinical practice. We evaluated a novel suite of Food and Drug Administration-cleared algorithms trained via deep learning on >15 000 heart sound recordings. Methods and Results We validated the algorithms on a data set of 2375 recordings from 615 unique subjects. This data set was collected in real clinical environments using commercially available digital stethoscopes, annotated by board-certified cardiologists, and paired with echocardiograms as the gold standard. To model the algorithm in clinical practice, we compared its performance against 10 clinicians on a subset of the validation database. Our algorithm reliably detected structural murmurs with a sensitivity of 85.6% and specificity of 84.4%. When limiting the analysis to clearly audible murmurs in adults, performance improved to a sensitivity of 97.9% and specificity of 90.6%. The algorithm also reported timing within the cardiac cycle, differentiating between systolic and diastolic murmurs. Despite optimizing acoustics for the clinicians, the algorithm substantially outperformed the clinicians (average clinician accuracy, 77.9%; algorithm accuracy, 84.7%.) Conclusions The algorithms accurately identified murmurs associated with structural heart disease. Our results illustrate a marked contrast between the consistency of the algorithm and the substantial interobserver variability of clinicians. Our results suggest that adopting machine learning algorithms into clinical practice could improve the detection of structural heart disease to facilitate patient care.

D-ribose-L-cysteine supplementation enhances wound healing in a rodent model.

BACKGROUND: Wound healing and chronic wounds are serious public health issues. While wounds heal, cellular stores of antioxidants are depleted. d-ribose-l-cysteine (DRLC) is a precursor to the antioxidant glutathione. The effect of oral supplementation with DRLC on wound healing was studied in rats. METHODS: A rodent model of calibrated wounding was used. Group A rats were given DLRC for 1 week before wounding and for 3, 7, or 14 days after wounding. Group B rats were given DRLC only after wounding. Control animals were given no supplement. Photographic comparisons were made to study wound edema and inflammation. Wound strength was determined by using a laser-vacuum device. RESULTS: During healing, both Group A and B animals showed less edema and inflammation than Control. Group A animals had the weakest wounds at 3 days after surgery, but the strongest wounds after 14 days. Group B animals had similar wound strength to Control animals at 7 days, but stronger wounds after 14 days. CONCLUSIONS: DRLC supplementation appears to reduce wound inflammation early after wounding and enhance wound strength by 14 days. This suggests that increased intracellular glutathione levels may improve and enhance wound healing.

Cardima Surgical Ablation System: a novel tool for cardiac ablation in the treatment of atrial fibrillation.

Atrial fibrillation is a pervasive and difficult heart rhythm problem for more than 3 million Americans. Patients are plagued by myriad symptoms and are exposed to the risk of stroke. Attempts to restore normal rhythm with drug therapy have been largely unsuccessful and the complications associated with long-term anticoagulation to reduce stroke risk are appreciable. Much interest has therefore developed in nonpharmacological treatments, such as ablation. At present, the optimal ablation device and technique have yet to be found. The Cardima Surgical Ablation System is a newly developed apparatus delivering radiofrequency energy to the outside of the beating heart within a shielded, lighted, irrigated, suction sheath. It advances the field of surgical ablation by addressing many of the shortcomings of older ablating devices, such as target fixation, controlled energy delivery, prevention of collateral tissue damage and device conformability. In this publication we present the specific advantages and disadvantages of the system, discuss its possible role in atrial fibrillation treatment and compare its characteristics with other currently available devices.

Surgical approaches for atrial fibrillation.

For cardiac surgery patients presenting with atrial fibrillation (AF), surgeons offer an operation that corrects the structural heart disease and the AF. With this approach, it is estimated that surgeons will perform more than 10,000 ablation procedures in 2008. Surgeons are developing minimally invasive techniques for stand-alone, epicardial ablation of AF. This article reviews the rationale for surgical ablation of AF, describes the classic maze procedure and its results, details new approaches to surgical ablation of AF, emphasizes the importance of management of the left atrial appendage, and considers challenges and future directions in the ablation of AF.

Completely endoscopic microwave ablation of atrial fibrillation on the beating heart using bilateral thoracoscopy.

The pharmacological treatment of atrial fibrillation (AF) has proven to be wholly inadequate. Although highly successful, the surgical approach is too invasive and has not been widely adopted. Progress has been made with breathtaking speed over the last decade toward the creation of an ablative surgical procedure that retains a high cure rate yet solves the problem of invasiveness. This chapter will describe a procedure that uses microwave energy delivered via a thin, long, and flexible catheter through endoscopic ports to treat AF. As energy delivery methods, surgical techniques, and assessment procedures continue to improve, treatments such as this one will hopefully attract the largest number of patients who suffer with this arrhythmia to seek a safe and effective cure.

Histopathological evaluation of a novel radiofrequency surgical ablation system.

PURPOSE: : Using a porcine model, this feasibility study was undertaken to evaluate the histopathological characteristics of lesions created in the proximity of the pulmonary veins after ablation with a new endoscopic-guided radiofrequency device. METHODS: : Five adult female swine underwent endoscopic surgical ablation on the epicardial surface of the beating heart. Histologic sections taken from around the pulmonary vein pedicle, representing 10 separate anatomic sites, underwent independent qualitative histopathological evaluation as well as quantitative histomorphometric measurement of lesion depth and section thickness. RESULTS: : Sections from all five animals had histologically identical lesions, with the majority of ablation foci having pronounced thermal injury characterized by deep and extensive zones of acute myocardial necrosis in the absence of tissue charring. Fifty-seven percent (13 of 23) of the lesions were completely transmural and 91% (21 of 23) of the sections demonstrated ≥70% transmurality. No collateral injuries were noted. CONCLUSIONS: : This irrigated, suction-stabilized unipolar radiofrequency device can produce histologically transmural lesions around the pulmonary veins and is amenable to endoscopic-guided application on the beating heart.

Surgical approaches for atrial fibrillation.

For cardiac surgery patients presenting with atrial fibrillation (AF), surgeons offer an operation that corrects the structural heart disease and the AF. With this approach, it is estimated that surgeons will perform more than 10,000 ablation procedures in 2007. Surgeons are developing minimally invasive techniques for stand-alone, epicardial ablation of AF. This article (1) reviews the rationale for surgical ablation of AF, (2) describes the classic maze procedure and its results, (3) details new approaches to surgical ablation of AF, (4) emphasizes the importance of management of the left atrial appendage, and (5) considers challenges and future directions in the ablation of AF.

Ablation of atrial fibrillation with concomitant cardiac surgery.

Atrial fibrillation is present in approximately 35% of patients presenting for mitral valve surgery and in 1 to 6% of adult patients undergoing other forms of cardiac surgery. If left untreated, atrial fibrillation is associated with increased morbidity, and, in some subgroups, increased mortality. Therefore, concomitant management of the arrhythmia is indicated in most cardiac surgery patients with preexisting atrial fibrillation. Although the cut-and-sew Cox-maze III procedure is extremely effective, it has been supplanted by newer operations that rely on alternate energy sources to create lines of conduction block. Early and mid-term results are good with a variety of technologies. Choice of lesion set remains a matter of debate, but results of ablation appear to be enhanced by a biatrial lesion set. Targeted areas for improvement in concomitant ablation include acceptance of uniform standards for reporting results, development of improved technology for ablation and intraoperative assessment, and creation of instrumentation that facilitates minimally invasive approaches.

Minimally invasive surgery for atrial fibrillation.

Although the surgical treatment of atrial fibrillation has become technically simpler and faster with the advent of new ablative technologies, the ultimate goal of treating large numbers of patients for lone AF remains elusive. The ideal procedure would be performed epicardially, on the beating heart, with minimal risk to and impact on the patient, a rapid recovery and high cure rates. As minimal access techniques improve along with device designs and our understanding of pathophysiology, the field continues to move toward this objective. This article provides a brief overview of the progress made, questions yet unanswered and possible future directions.

The use of extracellular matrix as an inductive scaffold for the partial replacement of functional myocardium.

Regenerative medicine approaches for the treatment of damaged or missing myocardial tissue include cell-based therapies, scaffold-based therapies, and/or the use of specific growth factors and cytokines. The present study evaluated the ability of extracellular matrix (ECM) derived from porcine urinary bladder to serve as an inductive scaffold for myocardial repair. ECM scaffolds have been shown to support constructive remodeling of other tissue types including the lower urinary tract, the dermis, the esophagus, and dura mater by mechanisms that include the recruitment of bone marrow-derived progenitor cells, angiogenesis, and the generation of bioactive molecules that result from degradation of the ECM. ECM derived from the urinary bladder matrix, identified as UBM, was configured as a single layer sheet and used as a biologic scaffold for a surgically created 2 cm2 full-thickness defect in the right ventricular free wall. Sixteen dogs were divided into two equal groups of eight each. The defect in one group was repaired with a UBM scaffold and the defect in the second group was repaired with a Dacron patch. Each group was divided into two equal subgroups (n = 4), one of which was sacrificed 15 min after surgical repair and the other of which was sacrificed after 8 weeks. Global right ventricular contractility was similar in all four subgroups groups at the time of sacrifice. However, 8 weeks after implantation the UBM-treated defect area showed significantly greater (p < 0.05) regional systolic contraction compared to the myocardial defects repaired with by Dacron (3.3 +/- 1.3% vs. -1.8 +/- 1.1%; respectively). Unlike the Dacron-repaired region, the UBM-repaired region showed an increase in systolic contraction over the 8-week implantation period (-4.2 +/- 1.7% at the time of implantation vs. 3.3 +/- 1.3% at 8 weeks). Histological analysis showed the expected fibrotic reaction surrounding the embedded Dacron material with no evidence for myocardial regeneration. Histologic examination of the UBM scaffold site showed cardiomyocytes accounting for approximately 30% of the remodeled tissue. The cardiomyocytes were arranged in an apparently randomly dispersed pattern throughout the entire tissue specimen and stained positive for alpha- sarcomeric actinin and Connexin 43. The thickness of the UBM graft site increased greatly from the time of implantation to the 8-week sacrifice time point when it was approximately the thickness of the normal right ventricular wall. Histologic examination suggested complete degradation of the originally implanted ECM scaffold and replacement by host tissues. We conclude that UBM facilitates a constructive remodeling of myocardial tissue when used as replacement scaffold for excisional defects.

Inflammation effects on the electrical properties of atrial tissue and inducibility of postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common complication after cardiac surgery. Postoperative atrial fibrillation (PAF) has been shown to increase length of stay, morbidity, and mortality. Because the clinical behavior of PAF parallels that of inflammation following surgery, we investigated the effect of the inflammatory mediator arachidonic acid on the electrical behavior of normal atrial tissue in vitro and assessed the efficacy of the topical application of anti-inflammatory drugs at suppressing PAF in an animal model. METHODS: To study changes in electrical behavior from inflammation, the conduction properties of six normal canine right atrial appendages were quantified as a function of the direction of impulse propagation with and without 80 mum arachidonic acid. To study the effect of topical anti-inflammatory drugs, 24 adult mongrel dogs were prepared according to the model of sterile talc pericarditis. Nine dogs received talc alone (T), seven received talc combined with 600 mg ibuprofen (T + I), and eight received talc combined with 10 mg methylprednisolone (T + M). Three days following preparation, programmed electrical stimulation was performed to quantify conduction characteristics and to attempt the induction of atrial fibrillation (AF). RESULTS: In vitro, arachidonic acid produced an anisotropic and rapidly reversible 36.1 +/- 3.4% (P = 0.01) decrease in conduction velocity transverse to the long axis only. In vivo, both ibuprofen and methylprednisolone significantly reduced the incidence of sustained AF (from 56 to 0% T + I and 12% T + M, respectively, P = 0.02). No differences in conduction velocities or refractory periods were seen during sinus rhythm among the groups. CONCLUSIONS: Acute inflammation as mimicked by arachidonic acid slows conduction anisotropically, mainly transverse to the long axis of the atrial myocardial fibers. This may set the stage for reentry. Preventing inflammation in vivo by the topical application of anti-inflammatory drugs supports this hypothesis, suggesting a possible role for inflammation in the genesis of postoperative atrial fibrillation and shedding light on the mechanism underlying PAF.

Thrombogenic performance of a st. Jude bileaflet mechanical heart valve in a sheep model.

The sheep model is preferred for chronic evaluation of prosthetic heart valves, surgical techniques, and endocardiographic studies. A bileaflet mechanical heart valve (MHV) was implanted into a sheep model to study its in vivo performance and to evaluate the thrombogenic potential of the valve. Transesophageal echocardiography and transcranial Doppler ultrasonography measurements were conducted before and after the valve implantation. Platelet activity state (PAS) assay measurements were also conducted before and after the implantation surgery. After sheep euthanasia, the MHV was explanted and scanning electron microscopy (SEM) was performed on the explanted valve to examine changes to the MHV surface. Tissue blocks were taken from the sheep brain, left ventricle, aorta, spleen, and lung lobes for histological examination. Our results indicated that after the MHV implantation, more embolic signals were detected in the sheep carotid artery, increasing monotonously as a function of implantation time. Echocardiographic parameters including blood aortic velocity, transvalvular pressure gradient, and velocity time integral increased. PAS increased significantly after valve implantation. SEM pictures demonstrated calcium and phosphate deposition on the valve surfaces. Histological examination demonstrated hemorrhage in the lung tissue, pulmonary thrombosis, and osteogenesis in heart tissue.

High resolution mechanical function in the intact porcine heart: mechanical effects of pacemaker location.

The necessity to quantify the mechanical function with high spatial resolution stemmed from the advancement of myocardial salvaging techniques. Since these therapies are localized interventions, a whole field technique with high spatial resolution was needed to differentiate the normal, diseased, and treated myocardium. We developed a phase correlation algorithm for measuring myocardial displacement at high spatial resolution and to determine the regional mechanical function in the intact heart. Porcine hearts were exposed and high contrast microparticles were placed on the myocardium. A pressure transducer, inserted into the left ventricle, synchronized the pressure (LVP) with image acquisition using a charge-coupled device camera. The deformation of the myocardium was measured with a resolution of 0.58+/-0.04 mm. Within the region of interest (ROI), regional stroke work (RSW), defined as the integral of LVP with respect to regional area, was determined on average at 21 locations with a resolution of 27.1+/-2.7 mm2. To alter regional mechanical function, the heart was paced at three different locations around the ROI. Independent of the pacemaker location, RSW decreased in the ROI. In addition, a gradient of increasing RSW in the outward direction radiating from the pacemaker was observed in all pacing protocols. These data demonstrated the ability to determine regional whole field mechanical function with high spatial resolution, and the significant alterations induced by electrical pacing.

Multichannel data acquisition system for mapping the electrical activity of the heart.

BACKGROUND: Details of the electrical conduction pattern of the heart are revealed to the electrophysiologist when multichannel data are used for activation mapping. Commercial electronic systems are available for simultaneous acquisition of many surface electrograms; however, the cost of these systems may be prohibitive and they can be mostly inflexible for adaptation to other research projects. Furthermore, the hardware and software design is often proprietary. In this article we describe the in-house design and implementation of a 320-multichannel acquisition system for animal electrophysiologic research. METHOD AND RESULTS: Several modules comprise this system. The multichannel data are first preprocessed by amplification, filtering, and analog multiplexing. An algorithm for automatic adjustment of signal gains is implemented to maximize the voltage resolution and minimize noise pickup. Signals are then digitized, and sequenced to order the multichannel data and to add markers required for analysis. The digital data are streamed to archival storage media. Additionally, the electrocardiogram (ECG), blood pressure, and stimulus channel signals are stored simultaneously. Selected signals are then displayed in real-time for measurement and analysis and as a check of the system integrity. Examples of multielectrode arrays and surface recordings are provided. Costs for building such a system are estimated. CONCLUSIONS: Multichannel data acquisition systems that are designed and constructed in-house have several advantages over turnkey commercial systems, including the potential for considerable cost savings, flexibility in acquiring data, and the ability to subsequently add additional components.

Effects of ischemia on epicardial deformation in the passive rabbit heart.

BACKGROUND: Surgically induced ischemia in the arrested heart can result in changes in the mechanical properties of the myocardium. Regions of ischemia may be characterized based on the amount of epicardial deformation for a given load. Computer aided speckle interferometry (CASI), which tracks the movement of clusters of particles, is developed as a technique for measuring epicardial deformation, thereby determining the perfusion status of the passive heart. MATERIALS AND METHODS: Silicone carbide particles and retroreflective beads were dispersed randomly onto the epicardial surface of 11 isolated rabbit hearts to form speckle images. The hearts were arrested with hyperkalemic Krebs-Henseleit buffered solution. Each heart was then exposed to a series of intracavitary pressures, and at each pressure speckle images were acquired with a charge-coupled device (CCD) camera. Nine hearts were exposed to global ischemia, and two hearts were exposed to regional ischemia by occluding the second diagonal branch of the left anterior descending artery (LAD). The hearts were again loaded and the speckle images were acquired. CASI was used to determine the distribution of deformation field. RESULTS: CASI was able to determine displacements with a spatial resolution of about 50 microns. Global ischemia resulted in a significant increase in the maximum principle strain and the first invariant of the 2-D strain tensor. In the regionally ischemic heart, a large difference in deformation between the ischemic and perfused regions was clearly observed. CONCLUSION: Based on epicardial deformation, CASI is able to distinguish between perfused and ischemic myocardium, with a spatial resolution of 50 microns.