Considerations for the use of porcine organ donation models in preclinical organ donor intervention research.

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation. Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury, organ preservation strategies, and future donor-based interventions. Important considerations include cost, public opinion regarding the conduct of animal research, translational value, and relevance of the animal model for clinical practice. We present an overview of two porcine models of organ donation: donation following brain death (DBD) and donation following circulatory death (DCD). The cardiovascular anatomy and physiology of pigs closely resembles those of humans, making this species the most appropriate for pre-clinical research. Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation. It is imperative to minimize animal loss during procedures that are surgically complex. We present our experience with these models and describe in detail the use cases, procedural approach, challenges, alternatives, and limitations of each model.

A Multidisciplinary Algorithm for the Evaluation of Acute Neurologic Deficits Improves Management of Cryptogenic Stroke or Transient Ischemic Attack.

The appropriate diagnosis and management of cryptogenic stroke and transient ischemic attack (TIA) is challenging and requires multidisciplinary involvement. Joint societal guidelines exist to guide the comprehensive evaluation of these entities. This study aimed to implement a standardized multidisciplinary diagnostic algorithm for cryptogenic stroke/TIA. We performed a retrospective analysis of patients admitted to the largest regional military healthcare center with stroke or TIA considered to be cryptogenic at the time of discharge. We abstracted baseline demographics and rates of extra- and intracranial imaging, transthoracic and transesophageal echocardiography, and event monitor orders at the time of discharge. The incidence of event monitor results at 30 days and six months were included. A diagnostic algorithm for evaluation of cryptogenic stroke/TIA was created and disseminated hospital-wide using increased compliance with neuroimaging, echocardiography, and cardiac rhythm monitoring as primary endpoints for our intervention. Post-intervention data abstraction revealed similar rates of extra- and intracranial imaging, but significantly greater rates of transthoracic echocardiography (70% vs. 87%, p 0.0073), inclusion of agitated saline study (41% vs. 65%, p 0.0024), and event monitors ordered at discharge (18% vs. 35%, p 0.0045). At six months there was a higher rate of event monitors obtained (24% vs. 45%, p 0.001). Our study showed implementation of an evidence-based diagnostic algorithm for evaluation of cryptogenic stroke/TIA increases appropriate use of echocardiography and event monitoring.

Cardiogenic shock and severe secondary mitral regurgitation successfully treated with transcatheter edge-to-edge repair: a case report.

Background: Cardiogenic shock (CS) associated with severe mitral regurgitation (MR) forebodes a high risk of morbidity and mortality. Transcatheter edge-to-edge repair (TEER) is a rapidly evolving technique for severe MR in haemodynamically stable patients. However, the safety and efficacy of TEER for severe MR in CS are not well established. Case summary: An 83-year-old male presented with dyspnoea and was hospitalized for heart failure. Chest X-ray revealed pulmonary oedema. Transthoracic echocardiography showed severely depressed ejection fraction (EF) with severe secondary MR. Right heart catheterization confirmed a low cardiac index. Diuretics and inotropes were administered. Due to persistent hypotension, we could not wean inotropes. The patient was deemed high risk for surgery by the heart team, and a decision was made to proceed with TEER with MitraClip. Under transoesophageal echocardiography and fluoroscopic guidance, two MitraClips were deployed sequentially. The MR grade was reduced to two mild jets subsequently. The patient was weaned off inotropes and eventually discharged. At the 30-day follow-up, he was participating in physical activities such as golf. Discussion: Cardiogenic shock complicated by severe MR carries high mortality. With severe MR, the forward stroke volume is lower than the stated EF leading to poor organ perfusion. Inotropes and/or mechanical circulatory support devices are paramount for initial stabilization; however, they do not treat underlying MR. Transcatheter edge-to-edge repair with MitraClip has been shown to improve survival in CS patients with severe MR in observational studies. However, prospective trials are lacking. Our case demonstrates the utility of MitraClip to treat severe secondary MR refractory to medical therapy in a CS patient. The heart team must evaluate risks and benefits of this therapy in CS patients.

Does Tracheostomy Improve Outcomes in Those Receiving Venovenous Extracorporeal Membrane Oxygenation?

Patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) often require extended periods of ventilation. We examined the role of tracheostomy on outcomes of patients supported with VV-ECMO. We reviewed all patients at our institution who received VV-ECMO between 2013 and 2019. Patients who received a tracheostomy were compared with VV-ECMO-supported patients without tracheostomy. The primary outcome measure was survival to hospital discharge. Secondary outcome measures included length of intensive care unit (ICU) and hospital stay and adverse events related to the tracheostomy procedure. Multivariable analysis was performed to identify predictors of in-hospital mortality. We dichotomized patients receiving tracheostomy into an "early" and "late" group based on median days to tracheostomy following ECMO cannulation and separate analysis was performed. One hundred and fifty patients met inclusion criteria, 32 received a tracheostomy. Survival to discharge was comparable between the groups (53.1% vs. 57.5%, p = 0.658). Predictors of mortality on multivariable analysis included Respiratory ECMO Survival Prediction (RESP) score (odds ratio [OR] = 0.831, p = .015) and blood urea nitrogen (BUN) (OR = 1.026, p = 0.011). Tracheostomy performance was not predictive of mortality (OR = 0.837, p = 0.658). Bleeding requiring intervention occurred in 18.7% of patients following tracheostomy. Early tracheostomy (<7 days from the initiation of VV-ECMO) was associated with shorter ICU (25 vs. 36 days, p = 0.04) and hospital (33 vs. 47, p = 0.017) length of stay compared with late tracheostomy. We conclude that tracheostomy can be performed safely in patients receiving VV-ECMO. Mortality in these patients is predicted by severity of the underlying disease. Performance of tracheostomy does not impact survival. Early tracheostomy may decrease length of stay.

A fast computational model for circulatory dynamics: effects of left ventricle-aorta coupling.

The course of diseases such as hypertension, systolic heart failure and heart failure with a preserved ejection fraction is affected by interactions between the left ventricle (LV) and the vasculature. To study these interactions, a computationally efficient, biophysically based mathematical model for the circulatory system is presented. In a four-chamber model of the heart, the LV is represented by a previously described low-order, wall volume-preserving model that includes torsion and base-to-apex and circumferential wall shortening and lengthening, and the other chambers are represented using spherical geometries. Active and passive myocardial mechanics of all four chambers are included. The cardiac model is coupled with a wave propagation model for the aorta and a closed lumped-parameter circulation model. Parameters for the normal heart and aorta are determined by fitting to experimental data. Changes in the timing and magnitude of pulse wave reflections by the aorta are demonstrated with changes in compliance and taper of the aorta as seen in aging (decreased compliance, increased diameter and length), and resulting effects on LV pressure-volume loops and LV fiber stress and sarcomere shortening are predicted. Effects of aging of the aorta combined with reduced LV contractile force (failing heart) are examined. In the failing heart, changes in aortic properties with aging affect stroke volume and sarcomere shortening without appreciable augmentation of aortic pressure, and the reflected pressure wave contributes an increased proportion of aortic pressure.

Enhanced central sympathetic tone induces heart failure with preserved ejection fraction (HFpEF) in rats.

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic functions. Mean arterial pressure, heart rate, left ventricular end-diastolic pressure (LVEDP), and ± dP/dt changes in responses to isoproterenol (0.5 µg/kg, iv) were measured. Central infusion of Ang II resulted in increased sympatho-excitation with a consequent increase in blood pressure. Although the ejection fraction was comparable between the groups, there was a decrease in the E/A ratio (saline: 1.5 ± 0.2 vs Ang II: 1.2 ± 0.1). LVEDP was significantly increased in the Ang II-treated group (saline: 1.8 ± 0.2 vs Ang II: 4.6 ± 0.5). The increase in +dP/dt to isoproterenol was not significantly different between the groups, but the response in -dP/dt was significantly lower in Ang II-infused rats (saline: 11,765 ± 708 mmHg/s vs Ang II: 8,581 ± 661). Ang II-infused rats demonstrated an increased heart to body weight ratio, cardiomyocyte hypertrophy, and fibrosis. There were elevated levels of atrial natriuretic peptide and interleukin-6 in the Ang II-infused group. In conclusion, central infusion of Ang II in rats induces sympatho-excitation with concurrent diastolic dysfunction, pathological cardiac concentric hypertrophy, and cardiac fibrosis. This novel model of centrally mediated sympatho-excitation demonstrates characteristic diastolic dysfunction in rats, representing a potentially useful preclinical murine model of HFpEF to investigate various altered underlying mechanisms during HFpEF in future studies.

Eight-year outcomes of aortic valve replacement with the Carpentier-Edwards PERIMOUNT Magna Ease valve.

INTRODUCTION: The Carpentier-Edwards PERIMOUNT Magna Ease valve is a third-generation bioprosthesis for aortic valve replacement (AVR). This is a postapproval study reporting on its 8-year outcomes. METHODS: Adults undergoing AVR with the Magna Ease valve between October 2007 and December 2012 were enrolled for this prospective, nonrandomized, single-arm, and multicenter study. Assessments occurred preoperatively, at hospital discharge, 6 months, 1 year, and annually thereafter for up to 8 years. Outcomes included safety endpoints, hemodynamic performance, and New York Heart Association (NYHA) functional class. RESULTS: Of the 258 study patients, 67.5% were in NYHA Class I or II, and 32.5% were in NYHA Class III or IV at baseline. Concomitant procedures were performed in 44.2%. Total follow-up was 1597.6 patient-years, and median follow-up was 7 years (interquartile range: 5.5-8.0 years). Eight years following AVR, the functional class remained improved from baseline with 93.9% in NYHA Class I/II and 6.1% in NYHA Class III; 38 deaths had occurred, 8 of which were valve related; freedom from all-cause mortality was 80.7% (95% confidence intervals: 74.9, 86.4); freedom from valve-related mortality was 95.8% (92.8, 98.8); freedom from reintervention, explant, major bleeding events, and structural valve deterioration was 89.8% (85.1, 94.6), 94.8% (91.7, 97.9), 85.1% (80.0, 90.1), and 90.1% (84.7, 95.4), respectively; effective orifice area was 1.5 ± 0.5 cm2 , the mean gradient was 14.8 ± 8.3 mmHg, and 88.6% of patients had no or trivial aortic regurgitation. CONCLUSIONS: This study demonstrated satisfactory safety and sustained hemodynamic and functional improvements at 8 years following AVR with the Magna Ease valve.

In a large-volume multidisciplinary setting individual surgeon volume does not impact LVAD outcomes.

BACKGROUND: In complex operations surgeon volume may impact outcomes. We sought to understand if individual surgeon volume affects left ventricular assist device (LVAD) outcomes. METHODS: We reviewed primary LVAD implants at an experienced ventricular assist devices (VAD)/transplant center between 2013 and 2019. Cases were dichotomized into a high-volume group (surgeons averaging 11 or more LVAD cases per year), and a low-volume group (10 or less per year). Propensity score matching was performed. Survival to discharge, 1-year survival, and incidence of major adverse events were compared between the low- and high-volume groups. Predictors of survival were identified with multivariate analysis. RESULTS: There were 315 patients who met inclusion criteria-45 in the low-volume group, 270 in the high-volume group. There was no difference in survival to hospital discharge between the low (91.9%) and high (83.3%) volume matched groups (p = .22). Survival at 1-year was also similar (85.4% vs. 80.6%, p = .55). There was no difference in the incidence of major adverse events between the groups. Predictors of mortality in the first year included: age (hazards ratio [HR]: 1.061, p < .001), prior sternotomy (HR: 1.991, p = .01), increasing international normalized ratio (HR: 4.748, p < .001), increasing AST (HR: 1.001, p < .001), increasing bilirubin (HR: 1.081, p = .01), and preoperative mechanical ventilation (HR: 2.662, p = .005). Individual surgeon volume was not an independent predictor of discharge or 1-year survival. CONCLUSION: There was no difference in survival or adverse events between high and low volume surgeons suggesting that, in an experienced multidisciplinary setting, low-volume VAD surgeons can achieve similar outcomes to their high-volume colleagues.

Clostridioides difficile-Associated Atypical Hemolytic-Uremic Syndrome Successfully Treated With Eculizumab: A Case Report and Literature Review.

Clostridioides difficile infection is a rare precipitant for patients to develop atypical hemolytic-uremic syndrome, of which the pathogenesis remains unclear. Previous reports suggest activation of cytokine storm from binding of cyotoxins A and B to colonic wall membranes. CASE SUMMARY: We present a case of a previously healthy 21-year-old woman who developed fulminant C. difficile colitis and atypical hemolytic-uremic syndrome requiring abdominal surgery and renal replacement therapy. She was ultimately treated with eculizumab without the use of plasmapheresis and remains in remission with full renal recovery. CONCLUSIONS: Our patient's significant response to terminal complement inhibitor, without the use of plasmapheresis, suggests that the underlying pathology is significantly driven by the alternative complement pathway. We propose that C. difficile-associated atypical hemolytic-uremic syndrome be defined as primary atypical hemolytic-uremic syndrome and strongly consider eculizumab as first-line therapy.

Combination plate and band fixation for primary closure in bilateral lung transplantation.

BACKGROUND: Sternal complications are common following transverse thoracosternotomy in patients undergoing bilateral lung transplantation. We present a single-institution experience using a next generation rigid fixation system for primary sternal closure following transverse sternotomy for bilateral lung transplantation. METHODS: Retrospective review was performed on all patients who had bilateral sequential lung transplants utilizing a transverse thoracosternotomy from 2016 to 2020. Demographics, baseline characteristics, peri-operative data, and outcomes were collected, reviewed and summarized. Two groups of patients were identified: wire cerclage (Group A), combination plate-and-band rigid fixation (Group B). The primary outcome was sternal complications, which were divided into mechanical and non-mechanical. RESULTS: Twenty-two patients met inclusion criteria. Three patients (13.6%) were in Group A, nineteen patients (86.4%) in Group B. Two patients in each Group A (66.6%) and Group B (10.5%) experienced a sternal complication. Sternal complications included sternal dehiscence (2), sternal malunion (1), and surgical site infection (1). One patient with plate-and-band fixation (5.2%) had a mechanical sternal complication. Three patients required reoperation secondary to sternal complication. CONCLUSIONS: The utilization of a combination plate-and-band rigid fixation system for primary closure is safe and may be an effective method to reduce sternal complications following transverse thoracosternotomy for lung transplantation.

A quantitative assessment of site-level factors in influencing Chukar (Alectoris chukar) introduction outcomes.

Chukar partridges (Alectoris chukar) are popular game birds that have been introduced throughout the world. Propagules of varying magnitudes have been used to try and establish populations into novel locations, though the relationship between propagule size and species establishment remains speculative. Previous qualitative studies argue that site-level factors are of importance when determining where to release Chukar. We utilized machine learning ensembles to evaluate bioclimatic and topographic data from native and naturalized regions to produce predictive species distribution models (SDMs) and evaluate the relationship between establishment and site-level factors for the conterminous United States. Predictions were then compared to a distribution map based on recorded occurrences to determine model prediction performance. SDM predictions scored an average of 88% accuracy and suitability favored states where Chukars were successfully introduced and are present. Our study shows that the use of quantitative models in evaluating environmental variables and that site-level factors are strong indicators of habitat suitability and species establishment.

A 21-Year-Old Man With a Cough.

CASE PRESENTATION: A 21-year-old male African American college student from Southern California, with no significant medical history, was visiting family in southwestern Texas when he presented to the hospital with 1 week history of cough, shortness of breath, lower back pain, and a 10-pound weight loss.

Postcardiotomy extracorporeal membrane oxygenator: No longer a bridge to no where?

BACKGROUND: Postcardiotomy extracorporeal membrane oxygenation (PC-ECMO) represents a unique subset of critically ill patients, with a paucity of data regarding long-term survival and correlated characteristics. We present a retrospective cohort of PC-ECMO patients, with outcomes at 1 and 3 years. METHODS: Data were collected retrospectively for all patients requiring ECMO within 72 hours of an index cardiac operation (excluding assist devices and transplants). Primary outcomes were the ability to wean from ECMO, hospital survival, and long-term survival. RESULTS: Thirty-one patients required PC-ECMO, representing a total of 172 days of ECMO support. Overall survival data were the ability to wean 58%, hospital survival 52%, 1-month survival 42%. The estimated 12- and 36-month survival for all PC-ECMO patients was 35% and 29%, respectively. Twelve and 36-month survival for all hospital survivors was 62% and 56%. Operative times, the Society of Thoracic Surgeons risk scores, type of operation, open chest status, hemorrhage, and cannulation location, and timing were all compared. Centrally cannulated patients were more likely to wean from ECMO (83% vs 44%; P = .03), and survive hospitalization (75% vs 36%; P = .04) and trended toward long-term survival benefit (67% vs 33%; P = .06). Otherwise, no statistically significant relationships were observed. CONCLUSIONS: Central cannulation may provide benefits in the postcardiotomy patient, compared to peripheral strategies. Twelve and 36-month survival for all PC-ECMO patients was 35% and 29%. For hospital survivors, 12 and 36-month survival 62% 56% at 36. These data support PC-ECMO as a reasonable salvage strategy, with midterm survival comparable to other surgically treated diseases.

Impaired Exercise Tolerance Early After Heart Transplantation Is Associated With Development of Cardiac Allograft Vasculopathy.

BACKGROUND: Exercise performance remains limited in some patients after heart transplantation (HTx). The goal of this study was to assess for association between cardiopulmonary exercise test performance at 1 year after HTx and future development of cardiac allograft vasculopathy (CAV). METHODS: Overall 243 HTx recipients performed cardiopulmonary exercise testing at 1 year after HTx. During the median follow-up period of 31 (interquartile range 19;61) months, 76 (32%) patients were diagnosed with CAV (CAV group). RESULTS: The CAV group patients had lower exercise capacity (5.2 ± 1.9 versus 6.5 ± 2.2 metabolic equivalents; P = 0.001) and duration (9.6 ± 3.5 versus 11.4 ± 4.8 min; P = 0.008), lower peak oxygen consumption (VO2) (18.4 ± 5.4 versus 21.4 ± 6.1 mL/kg/min; P = 0.0005), lower normalized peak VO2 (63% ± 18% versus 71% ± 19%; P = 0.007), and higher minute ventilation (VE)/carbon dioxide production (VCO2) (34 ± 5 versus 32 ± 5, P = 0.04). On Cox proportional hazards regression analysis, normalized peak VO2 ≤60%, and VE/VCO2 ≥34 were associated with a high hazard for CAV (HR = 1.8 [95% CI 1.10-4.53, P = 0.03] and 2.5 [95% CI 1.01-8.81, P = 0.04], respectively). The subgroup of patients with both normalized peak VO2 ≤60% and VE/VCO2 ≥34 was at highest risk for development of CAV (HR = 5.2, 95% CI 2.27-15.17, P = 0.001). CONCLUSIONS: Normalized peak VO2 ≤60% and VE/VCO2 ≥34 at 1 year after HTx are associated with the development of CAV.

Recurrent pump thrombosis is common after axial continuous-flow left ventricular assist device exchange.

In selected patients with left ventricular assist device-associated infection or malfunction, pump exchange may become necessary after conservative treatment options fail and heart transplantation is not readily available. We examined the survival and complication rate in patients (⩾19 years of age) who underwent HeartMate II to HeartMate II exchange at our institution from 1 January 2010 to 28 February 2018. Clinical outcomes were analyzed and compared for patients who underwent exchange for pump thrombosis (14 patients), breach of driveline integrity (5 patients), and device-associated infection (2 patients). There were no differences in 30-day mortality (p = 0.58), need for temporary renal replacement therapy (p = 0.58), right ventricular mechanical support (p = 0.11), and postoperative stroke (p = 0.80) among groups. Survival at 1 year was 90% ± 7% for the whole cohort and 85% ± 10% for those who underwent exchange for pump thrombosis. In patients exchanged for device thrombosis, freedom from re-thrombosis and survival free from pump re-thrombosis at 1 year were 49% ± 16% and 42% ± 15%, respectively. No association of demographic and clinical variables with the risk of recurrent pump thrombosis after the first exchange was identified. Survival after left ventricular assist device exchange compares well with published results after primary left ventricular assist device implantation. However, recurrence of thrombosis was common among patients who required a left ventricular assist device exchange due to pump thrombosis. In this sub-group, consideration should be given to alternative strategies to improve the outcomes.

Propagule pressure does not consistently predict the outcomes of exotic bird introductions.

Some have argued that the role of propagule pressure in explaining the outcomes of bird introductions is well-supported by the historical record. Here, we show that the data from a large published database (including 832 records with propagule information) do not support the conclusion that propagule pressure is the primary determinant of introduction success in birds. A few compendia of historical reports have been widely used to evaluate introduction success, typically by combining data from numerous species and introduction locations. Very few taxa, other than birds, have usable spatially explicit records of introductions over time. This availability of data inflates the perceived importance of bird analyses for addressing factors related to invasion success. The available data allow limited testing of taxonomic and site-level factors of introduction outcomes. We did find significant differences in effort and success probabilities among avian orders and across highly aggregated spatial regions. As a test of a standard and logical expectation of the propagule pressure hypothesis, we concentrated on introductions with the smallest propagules, because it is for these the hypothesis is most likely to be correct. We analyzed the effect of numbers released in small propagules (two through 10) for 227 releases. Weighted linear regression indicated no significant effect of propagule size for this range of release size. In fact, the mean success rate of 28% for propagules of 2-10 isn't significantly different than that of 34% for propagules of 11-100. Following the example of previous analyses, we expanded the statistical test of propagule pressure to include the full range of release numbers. No significant support for the propagule pressure hypothesis was found using logistic regression with either logit or complementary log-log link functions.

Can we expect improvements in outcomes with centrifugal vs axial flow left ventricular assist devices in patients transitioned from extracorporeal life support?

BACKGROUND: Several patient-related characteristics have been associated with inferior outcomes following durable left ventricular assist device (LVAD) implantation in patients transitioned from venoarterial extracorporeal membrane oxygenation (VA ECMO). The impact of LVAD pump type used is less well-known. METHODS: We compared outcomes between patents who received axial and centrifugal flow LVADs following stabilization with VA ECMO. RESULTS: From January 2011 to December 2018, we implanted 28 LVADs in patients transitioned from VA ECMO. This included 17 axial flow devices (HeartMate II LVAD, Abbott Laboratories, Chicago, IL) and 11 centrifugal flow pumps (eight HeartWare HVADs; Medtronic, Minneapolis, MN and three HeartMate 3 LVAS pumps; Abbott Laboratories, Chicago, IL). There was no difference in hospital mortality (23.5% vs 18.2%, P = .74) or 1-year survival (P = .31) between the devices. There were no differences in adverse event rates between the two pump types, apart from a higher rate of gastrointestinal bleeding in patients who received centrifugal flow pumps (1.44 events per 100 patient-months vs 14.67 events per 100 patient-months, P = .010). Preimplantation levels of alanine aminotransferase (hazard ratio [HR], 1.001; 95% confidence interval [CI], 1.000 to 1.002; P = .004) and elevated serum creatinine level (HR, 3.480; 95% CI, 1.121-10.807; P = .031) emerged as significant predictors of decreased 1-year survival. CONCLUSIONS: Preimplantation optimization of end-organ function is the single most important determinant of successful post-LVAD survival in patients transitioned from extracorporeal life support. There is no association of pump type with LVAD outcomes up to 1-year post implantation.

Modeling left ventricular dynamics with characteristic deformation modes.

A computationally efficient method is described for simulating the dynamics of the left ventricle (LV) in three dimensions. LV motion is represented as a combination of a limited number of deformation modes, chosen to represent observed cardiac motions while conserving volume in the LV wall. The contribution of each mode to wall motion is determined by a corresponding time-dependent deformation variable. The principle of virtual work is applied to these deformation variables, yielding a system of ordinary differential equations for LV dynamics, including effects of muscle fiber orientations, active and passive stresses, and surface tractions. Passive stress is governed by a transversely isotropic elastic model. Active stress acts in the fiber direction and incorporates length-tension and force-velocity properties of cardiac muscle. Preload and afterload are represented by lumped vascular models. The variational equations and their numerical solutions are verified by comparison to analytic solutions of the strong form equations. Deformation modes are constructed using Fourier series with an arbitrary number of terms. Greater numbers of deformation modes increase deformable model resolution but at increased computational cost. Simulations of normal LV motion throughout the cardiac cycle are presented using models with 8, 23, or 46 deformation modes. Aggregate quantities that describe LV function vary little as the number of deformation modes is increased. Spatial distributions of stress and strain change as more deformation modes are included, but overall patterns are conserved. This approach yields three-dimensional simulations of the cardiac cycle on a clinically relevant time-scale.

Left Ventricular Pseudoaneurysm Complicated With Very Late Rupture 5 Years After Myocardial Infarction.

This is a case of a chronic left ventricular pseudoaneurysm after inferior myocardial infarction that remained clinically silent for 5 years before presenting with sudden rupture, leading to hemopericardium and cardiac tamponade. We discuss the importance of surveillance for left ventricular pseudoaneurysms, the limitations of echocardiography, and the critical role of computed tomography angiography imaging to establish the diagnosis and guide therapy. (Level of Difficulty: Beginner.).

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration.

Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector-driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR-1, miR-133, miR-208, and miR-499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-ß, enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.