Novel algorithms improve arrhythmia detection accuracy in insertable cardiac monitors.

INTRODUCTION: Insertable cardiac monitors (ICMs) are commonly used to diagnose cardiac arrhythmias. False detections in the latest ICM systems remain an issue, primarily due to inaccurate R-wave sensing. New discrimination algorithms were developed and tested to reduce false detections of atrial fibrillation (AF), pause, and tachycardia episodes in ICMs. METHODS: Stored electrograms (EGMs) of AF, pause, and tachycardia episodes detected by Abbott Confirm Rx™ ICMs were extracted from the Merlin.net™ Patient Care Network, and manually adjudicated to establish independent training and testing datasets. New discrimination algorithms were developed to reject false episodes due to inaccurate R-wave sensing, P-wave identification, and R-R interval patterns. The performance of these new algorithms was quantified by false positive reduction (FPR) and true positive maintenance (TPM), relative to the existing algorithms. RESULTS: The new AF detection algorithm was trained on 5911 EGMs from 744 devices, resulting in 66.9% FPR and 97.8% TPM. In the testing data set of 1354 EGMs from 119 devices, this algorithm achieved 45.8% FPR and 97.0% TPM. The new pause algorithm was trained on 7178 EGMs from 1490 devices, resulting in 70.9% FPR and 98.7% TPM. In the testing data set of 1442 EGMs from 340 devices, this algorithm achieved 74.4% FPR and 99.3% TPM. The new tachycardia algorithm was trained on 520 EGMs from 204 devices, resulting in 57.0% FPR and 96.6% TPM. In the testing data set of 459 EGMs from 237 devices, this algorithm achieved 57.9% FPR and 96.5% TPM. CONCLUSION: The new algorithms substantially reduced false AF, pause, and tachycardia episodes while maintaining the majority of true arrhythmia episodes detected by the Abbott ICM algorithms that exist today. Implementing these algorithms in the next-generation ICM systems may lead to improved detection accuracy, in-clinic efficiency, and device battery longevity.

Reducing the electrogram review burden imposed by insertable cardiac monitors.

BACKGROUND: Insertable cardiac monitors (ICMs) are essential for ambulatory arrhythmia diagnosis. However, definitive diagnoses still require time-consuming, manual adjudication of electrograms (EGMs). OBJECTIVE: To evaluate the clinical impact of selecting only key EGMs for review. METHODS: Retrospective analyses of randomly selected Abbott Confirm Rx™ devices with ≥90 days of remote transmission history were performed, with each EGM adjudicated as true or false positive (TP, FP). For each device, up to 3 "key EGMs" per arrhythmia type per day were prioritized for review based on ventricular rate and episode duration. The reduction in EGMs and TP days (patient-days with at least one TP EGM), and any diagnostic delay (from the first TP), were calculated versus reviewing all EGMs. RESULTS: In 1000 ICMs over a median duration of 8.1 months, at least one atrial fibrillation (AF), tachycardia, bradycardia, or pause EGM was transmitted by 424, 343, 190, and 325 devices, respectively, with a total of 95 716 EGMs. Approximately 90% of episodes were contributed by 25% of patients. Key EGM selection reduced EGM review burden by 43%, 66%, 77%, and 50% (55% overall), while reducing TP days by 0.8%, 2.1%, 0.2%, and 0.0%, respectively. Despite reviewing fewer EGMs, 99% of devices with a TP EGM were ultimately diagnosed on the same day versus reviewing all EGMs. CONCLUSION: Key EGM selection reduced the EGM review substantially with no delay-to-diagnosis in 99% of patients exhibiting true arrhythmias. Implementing these rules in the Abbott patient care network may accelerate clinical workflow without compromising diagnostic timelines.

Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia.

OBJECTIVE: We assessed the impact of early enteral feeding introduction during therapeutic hypothermia on time to reach full enteral feeding (FEF) and other feeding related outcomes in infants born at ≥35 weeks gestational age and diagnosed with moderate to severe Hypoxic-Ischemic Encephalopathy. METHODS: A prospective cohort with historical control study, conducted on infants admitted to the Alberta Children's Hospital level III NICU in Calgary between January 2013 and December 2018. Infants were divided into 2 groups: (1) unfed group (UG), which was kept nil per os during the 72 h of therapeutic Hypothermia (TH), with subsequent introduction of feeding and gradual increase to FEF; (2) fed group (FG), which received feeding at 10 mL/kg/day during TH then increased gradually to FEF. Groups were compared for time to FEF and the type of milk they were being fed on discharge. Other gut related health risks such as NEC and sepsis were examined. RESULTS: During the study period, 146 infants received therapeutic hypothermia, of whom 75 in the UG and 71 in the FG. The FG compared to the UG received the first feed sooner after TH initiation (median 57 vs. 86.5 h, p < .001), reached FEF earlier (median 6 vs. 8 days, p = .012), had a higher rate of being fully fed in the first week of life (70 vs. 53%, p < .035), was kept NPO for shorter duration (median 2 vs. 4 days, p < .001), and had a higher rate of breast milk feeding at discharge (41 vs. 13%, p < .001). There were no cases of necrotizing enterocolitis or late onset sepsis in either group during the hospital stay. CONCLUSION: Minimal enteral feeding during therapeutic hypothermia appears to be safe and leads to a shorter time to FEF and higher rates of breast milk feeding at discharge.

Effectiveness of SharpSense™ algorithms in reducing bradycardia and pause detection: real-world performance in Confirm Rx™ insertable cardiac monitor.

PURPOSE: SharpSense™ technology is an upgradable software enhancement introduced to the Abbott Confirm Rx™ insertable cardiac monitor (ICM). This study aims to characterize the real-world performance of SharpSense algorithms by comparing device detected pause and bradycardia episodes before and after the SharpSense upgrade. METHODS: Confirm Rx devices with at least 90 days monitoring each before and after SharpSense upgrade were included in the study. Bradycardia and pause detections and subcutaneous electrocardiograms (SECGs) within 90 days before and after the upgrade were extracted from Merlin.net™ patient care network for evaluation and adjudicated by expert adjudicators. RESULTS: A total of 197 devices were included in the analysis. Devices were implanted for syncope (35.0%), atrial fibrillation (32.5%), cryptogenic stroke (16.8%), and other indications including palpitations (15.7%). The SharpSense upgrade significantly reduced the number of bradycardia detections by 86.8% and pause detections by 93.1%. In adjudicated SECGs, the upgrade significantly reduced false positive (FP) bradycardia episodes by 91.5% and FP pause episodes by 82.8%. The percentage of devices with at least one FP episode was reduced from 39 to 20% for bradycardia and from 52 to 35% for pause. The number of devices with FP rate greater than 1 episode per week was reduced from 23 to 8% for bradycardia and from 39 to 20% for pause. CONCLUSIONS: In this real-world performance evaluation, the algorithms incorporated in SharpSense software upgrade in Confirm Rx ICMs substantially reduced false positive bradycardia and pause detections and the number of transmitted SECGs for clinic review.

Oral Ondansetron Administration to Dehydrated Children in Pakistan: A Randomized Clinical Trial.

BACKGROUND: Ondansetron is an effective antiemetic employed to prevent vomiting in children with gastroenteritis in high-income countries; data from low- and middle-income countries are sparse. METHODS: We conducted a randomized, double-blind, placebo-controlled superiority trial in 2 pediatric emergency departments in Pakistan. Dehydrated children aged 6 to 60 months with ≥1 diarrheal (ie, loose or liquid) stool and ≥1 vomiting episode within the preceding 4 hours were eligible to participate. Participants received a single weight-based dose of oral ondansetron (8-15 kg: 2 mg; >15 kg: 4 mg) or identical placebo. The primary outcome was intravenous administration of ≥20 mL/kg over 4 hours of an isotonic fluid within 72 hours of random assignment. RESULTS: All 918 (100%) randomly assigned children completed follow-up. Intravenous rehydration was administered to 14.7% (68 of 462) and 19.5% (89 of 456) of those administered ondansetron and placebo, respectively (difference: -4.8%; 95% confidence interval [CI], -9.7% to 0.0%). In multivariable logistic regression analysis adjusted for other antiemetic agents, antibiotics, zinc, and the number of vomiting episodes in the preceding 24 hours, children administered ondansetron had lower odds of the primary outcome (odds ratio: 0.70; 95% CI, 0.49 to 1.00). Fewer children in the ondansetron, relative to the placebo group vomited during the observation period (difference: -12.9%; 95% CI, -18.0% to -7.8%). The median number of vomiting episodes (P < .001) was lower in the ondansetron group. CONCLUSIONS: Among children with gastroenteritis-associated vomiting and dehydration, oral ondansetron administration reduced vomiting and intravenous rehydration use. Ondansetron use may be considered to promote oral rehydration therapy success among dehydrated children in low- and middle-income countries.

Non-Nutritive Sweeteners and Their Implications on the Development of Metabolic Syndrome.

Individuals widely use non-nutritive sweeteners (NNS) in attempts to lower their overall daily caloric intake, lose weight, and sustain a healthy diet. There are insufficient scientific data that support the safety of consuming NNS. However, recent studies have suggested that NNS consumption can induce gut microbiota dysbiosis and promote glucose intolerance in healthy individuals that may result in the development of type 2 diabetes mellitus (T2DM). This sequence of events may result in changes in the gut microbiota composition through microRNA (miRNA)-mediated changes. The mechanism(s) by which miRNAs alter gene expression of different bacterial species provides a link between the consumption of NNS and the development of metabolic changes. Another potential mechanism that connects NNS to metabolic changes is the molecular crosstalk between the insulin receptor (IR) and G protein-coupled receptors (GPCRs). Here, we aim to highlight the role of NNS in obesity and discuss IR-GPCR crosstalk and miRNA-mediated changes, in the manipulation of the gut microbiota composition and T2DM pathogenesis.

Oral Ondansetron Administration to Nondehydrated Children With Diarrhea and Associated Vomiting in Emergency Departments in Pakistan: A Randomized Controlled Trial.

STUDY OBJECTIVE: We determine whether single-dose oral ondansetron administration to children with vomiting as a result of acute gastroenteritis without dehydration reduces administration of intravenous fluid rehydration. METHODS: In this 2-hospital, double-blind, placebo-controlled, emergency department-based, randomized trial conducted in Karachi Pakistan, we recruited children aged 0.5 to 5.0 years, without dehydration, who had diarrhea and greater than or equal to 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), through an Internet-based randomization service using a stratified variable-block randomization scheme, to single-dose oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of ≥20 mL/kg of an isotonic fluid during 4 hours) within 72 hours of randomization. RESULTS: Participant median age was 15 months (interquartile range 10 to 26) and 59.4% (372/626) were male patients. Intravenous rehydration use was 12.1% (38/314) and 11.9% (37/312) in the placebo and ondansetron groups, respectively (odds ratio 0.98; 95% confidence interval [CI] 0.60 to 1.61; difference 0.2%; 95% CI of the difference -4.9% to 5.4%). Bolus fluid administration occurred within 72 hours of randomization in 10.8% (34/314) and 10.3% (27/312) of children administered placebo and ondansetron, respectively (odds ratio 0.95; 95% CI 0.56 to 1.59). A multivariable regression model fitted with treatment group and adjusted for antiemetic administration, antibiotics, zinc prerandomization, and vomiting frequency prerandomization yielded similar results (odds ratio 0.91; 95% CI 0.55 to 1.53). There was no interaction between treatment group and age, greater than or equal to 3 stools in the preceding 24 hours, or greater than or equal to 3 vomiting episodes in the preceding 24 hours. CONCLUSION: Oral administration of a single dose of ondansetron did not result in a reduction in intravenous rehydration use. In children without dehydration, ondansetron does not improve clinical outcomes.

Localization of Activation Origin on Patient-Specific Epicardial Surface by Empirical Bayesian Method.

OBJECTIVE: Ablation treatment of ventricular arrhythmias can be facilitated by pre-procedure planning aided by electrocardiographic inverse solution, which can help to localize the origin of arrhythmia. Our aim was to improve localization accuracy of the inverse solution by using a novel Bayesian approach. METHODS: The inverse problem of electrocardiography was solved by reconstructing epicardial potentials from 120 body-surface electrocardiograms and from patient-specific geometry of the heart and torso for four patients suffering from scar-related ventricular tachycardia who underwent epicardial catheter mapping, which included pace-mapping. Simulations using dipole sources in patient-specific geometry were also performed. The proposed method, using dynamic spatio-temporal a priori constraints of the solution, was compared with classical Tikhonov methods based on fixed constraints. RESULTS: The mean localization error of the proposed method for all available pacing sites (n=78) was significantly smaller than that achieved by Tikhonov methods; specifically, the localization accuracy for pacing in the normal tissue (n=17) was [Formula: see text] mm (mean ± SD) versus [Formula: see text] mm reported in the previous study using the same clinical data and Tikhonov regularization. Simulation experiments further supported these clinical findings. CONCLUSION: The promising results of in vivo and in silico experiments presented in this study provide a strong incentive to pursuing further investigation of data-driven Bayesian methods in solving the electrocardiographic inverse problem. SIGNIFICANCE: The proposed approach to localizing origin of ventricular activation sequence may have important applications in pre-procedure assessment of arrhythmias and in guiding their ablation treatment.

The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome.

Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term "metabolic syndrome". Although many of these pathologies are associated with insulin resistance, the exact mechanisms are not well understood. One area of current interest is the possibility of G-protein-coupled receptors (GPCRs) influencing or regulating IR signaling. This concept is particularly significant, because GPCRs have been shown to participate in cross-talk with the IR. More importantly, GPCR signaling has also been shown to preferentially regulate specific downstream signaling targets through GPCR agonist bias. A novel study recently demonstrated that this GPCR-biased agonism influences the activity of the IR without the presence of insulin. Although GPCR-IR cross-talk has previously been established, the notion that GPCRs can regulate the activation of the IR is particularly significant in relation to metabolic syndrome and other pathologies that develop as a result of alterations in IR signaling. As such, we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism may perhaps mediate some of the downstream signaling effects that further exacerbate these diseases for which the mechanisms are currently not well understood.

Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.

OBJECTIVES: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease. CONCLUSIONS: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.

Insights from Novel Noninvasive CT and ECG Imaging Modalities on Electromechanical Myocardial Activation in a Canine Model of Ischemic Dyssynchronous Heart Failure.

INTRODUCTION: The interplay between electrical activation and mechanical contraction patterns is hypothesized to be central to reduced effectiveness of cardiac resynchronization therapy (CRT). Furthermore, complex scar substrates render CRT less effective. We used novel cardiac computed tomography (CT) and noninvasive electrocardiographic imaging (ECGI) techniques in an ischemic dyssynchronous heart failure (DHF) animal model to evaluate electrical and mechanical coupling of cardiac function, tissue viability, and venous accessibility of target pacing regions. METHODS AND RESULTS: Ischemic DHF was induced in 6 dogs using coronary occlusion, left bundle ablation and tachy RV pacing. Full body ECG was recorded during native rhythm followed by volumetric first-pass and delayed enhancement CT. Regional electrical activation were computed and overlaid with segmented venous anatomy and scar regions. Reconstructed electrical activation maps show consistency with LBBB starting on the RV and spreading in a "U-shaped" pattern to the LV. Previously reported lines of slow conduction are seen parallel to anterior or inferior interventricular grooves. Mechanical contraction showed large septal to lateral wall delay (80 ± 38 milliseconds vs. 123 ± 31 milliseconds, P = 0.0001). All animals showed electromechanical correlation except dog 5 with largest scar burden. Electromechanical decoupling was largest in basal lateral LV segments. CONCLUSION: We demonstrated a promising application of CT in combination with ECGI to gain insight into electromechanical function in ischemic dyssynchronous heart failure that can provide useful information to study regional substrate of CRT candidates.

Non-invasive electromechanical activation imaging as a tool to study left ventricular dyssynchronous patients: Implication for CRT therapy.

AIMS: Electromechanical de-coupling is hypothesized to explain non-response of dyssynchrony patient to cardiac resynchronization therapy (CRT). In this pilot study, we investigated regional electromechanical uncoupling in 10 patients referred for CRT using two non-invasive electrical and mechanical imaging techniques (CMR tissue tracking and ECGI). METHODS AND RESULTS: Reconstructed regional electrical and mechanical activation captured delayed LBBB propagation direction from septal to anterior/inferior and finally to lateral walls as well as from LV apical to basal. All 5 responders demonstrated significantly delayed mechanical and electrical activation on the lateral LV wall at baseline compared to the non-responders (P<.05). On follow-up ECGI, baseline electrical activation patterns were preserved in native rhythm and global LV activation time was reduced with biventricular pacing. CONCLUSIONS: The combination of novel imaging techniques of ECGI and CMR tissue tracking can be used to assess spatial concordance of LV electrical and mechanical activation to gain insight into electromechanical coupling.

Noninvasive electrocardiographic imaging of chronic myocardial infarct scar.

BACKGROUND: Myocardial infarction (MI) scar constitutes a substrate for ventricular tachycardia (VT), and an accurate delineation of infarct scar may help to identify reentrant circuits and thus facilitate catheter ablation. One of the recent advancements in characterization of a VT substrate is its volumetric delineation within the ventricular wall by noninvasive electrocardiographic imaging. This paper compares, in four specific cases, epicardial and volumetric inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium enhancement as a gold standard. METHODS: For patients with chronic MI, who presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body surface potential mapping (BSPM) data were acquired and 4 selected cases were later made available to a wider community as part of the 2007 PhysioNet/Computers in Cardiology Challenge. These data were used to perform patient-specific inverse solutions for epicardial electrograms and morphology-based criteria were applied to delineate infarct scar on the epicardial surface. Later, the Rochester group analyzed the same data by means of a novel inverse solution for reconstructing intramural transmembrane potentials, to delineate infarct scar in three dimensions. Comparison of the performance of three specific inverse-solution algorithms is presented here, using scores based on the 17-segment ventricular division scheme recommended by the American Heart Association. RESULTS: The noninvasive methods delineating infarct scar as three-dimensional (3D) intramural distribution of transmembrane action potentials outperform estimates providing scar delineation on the epicardial surface in all scores used for comparison. In particular, the extent of infarct scar (its percentage mass relative to the total ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the volumetric rendition of scar border provides better clues to potential targets for catheter ablation. CONCLUSIONS: Electrocardiographic inverse solution providing transmural distribution of ventricular action potentials is a promising tool for noninvasively delineating the extent and location of chronic MI scar. Further validation on a larger data set with detailed gold-standard data is needed to confirm observations reported in this study.

Transmural imaging of ventricular action potentials and post-infarction scars in swine hearts.

The problem of using surface data to reconstruct transmural electrophysiological (EP) signals is intrinsically ill-posed without a unique solution in its unconstrained form. Incorporating physiological spatiotemporal priors through probabilistic integration of dynamic EP models, we have previously developed a Bayesian approach to transmural electrophysiological imaging (TEPI) using body-surface electrocardiograms. In this study, we generalize TEPI to using electrical signals collected from heart surfaces, and we test its feasibility on two pre-clinical swine models provided through the STACOM 2011 EP simulation Challenge. Since this new application of TEPI does not require whole-body imaging, there may be more immediate potential in EP laboratories where it could utilize catheter mapping data and produce transmural information for therapy guidance. Another focus of this study is to investigate the consistency among three modalities in delineating scar after myocardial infarction: TEPI, electroanatomical voltage mapping (EAVM), and magnetic resonance imaging (MRI). Our preliminary data demonstrate that, compared to the low-voltage scar area in EAVM, the 3-D electrical scar volume detected by TEPI is more consistent with anatomical scar volume delineated in MRI. Furthermore, TEPI could complement anatomical imaging by providing EP functional features related to both scar and healthy tissue.

Inverse solution mapping of epicardial potentials: quantitative comparison with epicardial contact mapping.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is still one of the most challenging procedures in cardiac electrophysiology, limited, in part, by unmappable arrhythmias that are nonsustained or poorly tolerated. Calculation of the inverse solution from body surface potential mapping (sometimes known as ECG imaging) has shown tremendous promise and can rapidly map these arrhythmias, but we lack quantitative assessment of its accuracy in humans. We compared inverse solution mapping with computed tomography-registered electroanatomic epicardial contact catheter mapping to study the resolution of this technique, the influence of myocardial scar, and the ability to map VT. METHODS AND RESULTS: For 4 patients undergoing epicardial catheter mapping and ablation of VT, 120-lead body surface potential mappings were obtained during implantable defibrillator pacing, catheter pacing from 79 epicardial sites, and induced VT. Inverse epicardial electrograms computed using individualized torso/epicardial surface geometries extracted from computed tomography images were compared with registered electroanatomic contact maps. The distance between estimated and actual epicardial pacing sites was 13 ± 9 mm over normal myocardium with no stimulus-QRS delay but increased significantly over scar (P=0.013) or was close to scar (P=0.014). Contact maps during right ventricular pacing correlated closely to inverse solution isochrones. Maps of inverse epicardial potentials during 6 different induced VTs indicated areas of earliest activation, which correlated closely with clinically identified VT exit sites for 2 epicardial VTs. CONCLUSIONS: Inverse solution maps can identify sites of epicardial pacing with good accuracy, which diminishes over myocardial scar or over slowly conducting tissue. This approach can also identify epicardial VT exit sites and ventricular activation sequences.

CT for evaluation of myocardial cell therapy in heart failure: a comparison with CMR imaging.

OBJECTIVES: The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies. BACKGROUND: Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF). METHODS: Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions. RESULTS: MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001). CONCLUSIONS: This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

Using inverse electrocardiography to image myocardial infarction--reflecting on the 2007 PhysioNet/Computers in Cardiology Challenge.

The goal of the 2007 PhysioNet/Computers in Cardiology Challenge was to try to establish how well it is possible to characterize the location and extent of old myocardial infarcts using electrocardiographic evidence supplemented by anatomical imaging information. A brief overview of the challenge and how different challengers approached the competition is provided, followed by detailed response of the first author to integrate electrophysiologic and anatomical data. The first author used the provided 120-electrode body-surface potential mapping data and magnetic resonance imaging heart and torso images to calculate epicardial potentials on customized ventricular geometries. A method was developed to define the location and extent of scar tissue based on the morphology of computed epicardial electrograms. Negative Q-wave deflection followed by R-wave on the left ventricular surface seemed to correspond with the location of the scar as determined by the gadolinium-enhanced magnetic resonance imaging gold standard in the supplied data sets. The method shows promising results as a noninvasive imaging tool to quantitatively characterize chronic infarcts and warrants further investigation on a larger patient data set.