Virtual Care With Digital Technologies for Rural Canadians Living With Cardiovascular Disease.

Canada is a wealthy nation with a geographically diverse population, seeking health innovations to better serve patients in accordance with the Canada Health Act. In this country, population and geography converge with social determinants, policy, procurement regulations, and technological advances with the goal to achieve equity in the management and distribution of health care. Rural and remote patients are a vulnerable population; when managing chronic conditions like cardiovascular disease, there is currently inequity to accessing specialist physicians at the recommended frequency-increasing the likelihood of poor health outcomes. Ensuring equitable care for this population is an unrealized priority of several provincial and federal government mandates. Virtual care technology might provide practical, economical, and innovative solutions to remedy this discrepancy. We conducted a scoping review of the literature pertaining to the use of virtual care technologies to monitor patients living in rural areas of Canada with cardiovascular disease. A search strategy was developed to identify the literature specific to this context across 3 bibliographic databases. Two hundred thirty-two unique citations were ultimately assessed for eligibility, of which 37 met the inclusion criteria. In our assessment of these articles, we provide a summary of the interventions studied, their reported effectiveness in reducing adverse events and mortality, the challenges to implementation, and the receptivity of these technologies among patients, providers, and policy-makers. Furthermore, we glean insight into the barriers and opportunities to ensure equitable care for rural patients and conclude that there is an ongoing need for clinical trials on virtual care technologies in this context.

Le Canada, pays riche dont la population est répartie dans des régions géographiquement diversifiées, reste à l'affût des innovations en matière de santé pour mieux servir les patients conformément à la Loi canadienne sur la santé. Dans ce pays, la population et la géographie ainsi que les déterminants sociaux, les politiques, la réglementation des marchés publics et les progrès technologiques convergent vers un objectif d'équité dans la gestion et la distribution des soins de santé. Les patients des régions rurales et éloignées constituent une population vulnérable; la prise en charge de maladies chroniques comme les maladies cardiovasculaires est marquée par des inégalités en ce qui concerne l'accès aux médecins spécialistes à la fréquence recommandée ­ ce qui augmente le risque de problèmes de santé. La garantie d'un accès équitable aux soins de santé pour cette population constitue une priorité non concrétisée pour plusieurs gouvernements provinciaux et fédéraux. Les technologies des soins virtuels pourraient offrir des solutions pratiques, économiques et novatrices afin de remédier à la disparité qui persiste. Nous avons effectué une revue exploratoire de la littérature relative à l'utilisation des technologies des soins virtuels pour le suivi des patients atteints de maladies cardiovasculaires vivant dans les régions rurales du Canada. Une stratégie de recherche a été élaborée pour recenser les articles visant spécifiquement ce contexte dans trois bases de données bibliographiques. Au terme de la recherche, 232 références uniques ont été évaluées en fonction des critères d'admissibilité; 37 y répondaient. Dans notre évaluation des articles, nous résumons les interventions étudiées, leur efficacité rapportée quant à la réduction des événements indésirables et de la mortalité, les difficultés de mise en œuvre et la réceptivité des patients, des fournisseurs de soins et des décideurs politiques aux technologies utilisées. En outre, nous offrons un aperçu des obstacles à surmonter et des occasions à saisir pour garantir un accès équitable aux soins de santé dans les régions rurales et nous concluons que des études cliniques sur les technologies des soins virtuels demeurent nécessaires dans ce contexte.

The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.

Ex situ heart perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the heart and may negatively affect the functional preservation of the heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode perfusion in supported position = 94.77% versus nonworking mode perfusion in supported position = 62.80%, working mode perfusion in H position = 36.18%, nonworking mode perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H heart groups. The hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H hearts in non-S position. Optimizing the positional support for the ex situ-perfused hearts may improve myocardial preservation during ESHP.

Immunity and Stress Responses Are Induced During Ex Situ Heart Perfusion.

BACKGROUND: Ex situ heart perfusion (ESHP) preserves the donated heart in a perfused, beating condition preventing cold storage-related ischemia and provides a platform to evaluate myocardial viability during preservation. However, myocardial function declines gradually during ESHP. Extracorporeal circulation systems are associated with the induction of systemic inflammatory and stress responses. Our aim was to evaluate the incidence of inflammation and induction of endoplasmic reticulum stress responses during an extended period of ESHP. METHODS: Cardiac function, myocardial tissue injury, markers of inflammation, oxidative stress, and endoplasmic reticulum stress were assessed in healthy pig hearts, perfused for 12 hours either in nonworking mode (non-WM=7) or working mode (WM, n=6). RESULTS: Cardiac function declined during ESHP but was significantly better preserved in the hearts perfused in WM (median 11-hour cardiac index/1-hour cardiac index: WM=27% versus non-WM=9.5%, P=0.022). Myocardial markers of endoplasmic reticulum stress were expressed higher in ESHP hearts compared with in vivo samples. The proinflammatory cytokines and oxidized low-density lipoprotein significantly increased in the perfusate throughout the perfusion in both perfusion groups. The left ventricular expression of the cytokines and malondialdehyde was induced in non-WM, whereas it was not different between WM and in vivo. CONCLUSIONS: Myocardial function declines during ESHP regardless of perfusion mode. However, ESHP in WM may lead to superior preservation of myocardial function and viability. Both inflammation and endoplasmic reticulum stress responses are significantly induced during ESHP and may contribute to the myocardial functional decline, representing a potential therapeutic target to improve the clinical donor heart preservation.

A Minimally Invasive Approach to HeartMate 3 Implantation for Systemic Ventricular Failure Following the Mustard Procedure for Transposition of the Great Arteries.

Late systemic (right) ventricular failure is common after the Mustard procedure for transposition of the great arteries (TGA), and mechanical circulatory support may be required for patients presenting with refractory heart failure; however, clinical experience with this approach is limited. We describe the use of the Impella 5.0 (Abiomed Inc., Danvers, Massachusetts) as a bridge to HeartMate 3 implantation in a highly sensitized patient with severe pulmonary hypertension following the Mustard procedure for TGA.

Heart Transplantation With Donation After Circulatory Death.

Heart transplantation remains the preferred option for improving quality of life and survival for patients suffering from end-stage heart failure. Unfortunately, insufficient supply of cardiac grafts has become an obstacle. Increasing organ availability with donation after circulatory death (DCD) may be a promising option to overcome the organ shortage. Unlike conventional donation after brain death, DCD organs undergo a period of warm, global ischemia between circulatory arrest and graft procurement, which raises concerns for graft quality. Nonetheless, the potential of DCD heart transplantation is being reconsidered, after reports of more than 70 cases in Australia and the United Kingdom over the past 3 years. Ensuring optimal patient outcomes and generalized adoption of DCD in heart transplantation, however, requires further development of clinical protocols, which in turn require a better understanding of cardiac ischemia-reperfusion injury and the various possibilities to limit its adverse effects. Thus, we aim to provide an overview of the knowledge obtained with preclinical studies in animal models of DCD heart transplantation, to facilitate and promote the most effective and efficient advancement in preclinical research. A literature search of the PubMed database was performed to identify all relevant preclinical studies in DCD heart transplantation. Specific aspects relevant for DCD heart transplantation were analyzed, including animal models, graft procurement and storage conditions, cardioprotective approaches, and graft evaluation strategies. Several potential therapeutic strategies for optimizing graft quality are identified, and recommendations for further preclinical research are provided.

Myocardial Functional Decline During Prolonged Ex Situ Heart Perfusion.

BACKGROUND: Myocardial function declines in a time-dependent fashion during ex situ heart perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe perfusion period and the potential of ex situ heart perfusion to expand the donor pool. Our aim was to investigate the etiology of myocardial functional decline in ex situ perfused hearts. METHODS: Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig hearts perfused for 12 hours. These hearts were perfused in nonworking mode or working mode. RESULTS: Cardiac function declined during ex situ heart perfusion regardless of perfusion mode but was significantly better preserved in the hearts perfused in working mode (11-hour cardiac index/1-hour cardiac index: working mode, 33%; nonworking mode, 10%; p = 0.025). The rate of apoptosis was higher in the ex situ perfused hearts compared with in vivo samples (apoptotic cells: in vivo, 0.13%; working mode, 0.54%; nonworking mode, 0.88%; p < 0.001), but the absolute values were low and out of proportion to the decline in function in either group. Myocardial dysfunction at the end of the perfusion interval was partially rescued by delivery of a pyruvate bolus. CONCLUSIONS: A significant decline in myocardial function occurs over time in hearts preserved ex situ that is out of proportion to the magnitude of myocyte cell death present in dysfunctional hearts. Alterations in myocardial substrate utilization during prolonged ex situ heart perfusion may contribute to this phenomenon and represent an avenue to improve donor heart preservation.

Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism.

The current standard method for organ preservation (cold storage, CS), exposes the heart to a period of cold ischemia that limits the safe preservation time and increases the risk of adverse post-transplantation outcomes. Moreover, the static nature of CS does not allow for organ evaluation or intervention during the preservation interval. Normothermic ex situ heart perfusion (ESHP) is a novel method for preservation of the donated heart that minimizes cold ischemia by providing oxygenated, nutrient-rich perfusate to the heart. ESHP has been shown to be non-inferior to CS in the preservation of standard-criteria donor hearts and has also facilitated the clinical transplantation of the hearts donated after the circulatory determination of death. Currently, the only available clinical ESHP device perfuses the heart in an unloaded, non-working state, limiting assessments of myocardial performance. Conversely, ESHP in working mode provides the opportunity for comprehensive evaluation of cardiac performance by assessment of functional and metabolic parameters under physiologic conditions. Moreover, earlier experimental studies have suggested that ESHP in working mode may result in improved functional preservation. Here, we describe the protocol for ex situ perfusion of the heart in a large mammal (porcine) model, which is reproducible for different animal models and heart sizes. The software program in this ESHP apparatus allows for real-time and automated control of the pump speed to maintain desired aortic and left atrial pressure and evaluates a variety of functional and electrophysiological parameters with minimal need for supervision/manipulation.

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs.

Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty-nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI-related genes was measured and correlated with function and histology. Twenty-eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas downregulated 6-gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6-gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.

Metabolically stabilized double-stranded mRNA polyplexes.

The metabolic instability of mRNA currently limits its utility for gene therapy. Compared to plasmid DNA, mRNA is significantly more susceptible to digestion by RNase in the circulation following systemic dosing. To increase mRNA metabolic stability, we hybridized a complementary reverse mRNA with forward mRNA to generate double-stranded mRNA (dsmRNA). RNase A digestion of dsmRNA established a 3000-fold improved metabolic stability compared to single-stranded mRNA (ssmRNA). Formulation of a dsmRNA polyplex using a PEG-peptide further improved the stability by 3000-fold. Hydrodynamic dosing and quantitative bioluminescence imaging of luciferase expression in the liver of mice established the potent transfection efficiency of dsmRNA and dsmRNA polyplexes. However, hybridization of the reverse mRNA against the 5' and 3' UTR of forward mRNA resulted in UTR denaturation and a tenfold loss in expression. Repeat dosing of dsmRNA polyplexes produced an equivalent transient expression, suggesting the lack of an immune response in mice. Co-administration of excess uncapped dsmRNA with a dsmRNA polyplex failed to knock down expression, suggesting that dsmRNA is not a Dicer substrate. Maximal circulatory stability was achieved using a fully complementary dsmRNA polyplex. The results established dsmRNA as a novel metabolically stable and transfection-competent form of mRNA.

Transplantation of Hearts Donated after Circulatory Death.

Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement. The availability of a clinically approved ex situ heart perfusion device now allows DCD heart preservation in a normothermic beating state and minimizes exposure to incremental cold ischemia. This technology also facilitates assessments of organ viability to be undertaken prior to transplantation, thereby minimizing the risk of primary graft dysfunction. The application of a tailored approach to DCD heart transplantation that focuses on organ resuscitation at the time of procurement, ex situ preservation, and pre-transplant assessments of organ viability has facilitated the successful clinical application of DCD heart transplantation. The transplantation of hearts from DCD donors is now a clinical reality. Investigating ways to optimize the resuscitation, preservation, evaluation, and long-term outcomes is vital to ensure a broader application of DCD heart transplantation in the future.

Steroids Limit Myocardial Edema During Ex Vivo Perfusion of Hearts Donated After Circulatory Death.

BACKGROUND: Normothermic ex vivo heart perfusion (EVHP) has been shown to improve the preservation of hearts donated after circulatory arrest and to facilitate clinical successful transplantation. Steroids are added to the perfusate solution in current clinical EVHP protocols; however, the impact of this approach on donor heart preservation has not been previously investigated. We sought to determine the impact of steroids on the inflammatory response and development of myocardial edema during EVHP. METHODS: Thirteen pigs were anesthetized, mechanical ventilation was discontinued, and a hypoxemic cardiac arrest ensued. A 15-minute warm-ischemic standoff period was observed, and then hearts were resuscitated with a cardioplegic solution. Donor hearts were then perfused ex vivo in a normothermic beating state for 6 hours with 500 mg of methylprednisolone (steroid: n = 5) or without (control: n = 8). RESULTS: The addition of steroids to the perfusate solution reduced the generation of proinflammatory cytokines (interleukin-6, -8, -1ß, and tumor necrosis factor-α) and the development of myocardial edema during EVHP (percentage of weight gain: control = 26% ± 7% versus steroid = 16% ± 10%, p = 0.049). Electron microscopy suggested less endothelial cell edema in the steroid group (injury score: control = 1.8 ± 0.2 versus steroid = 1.2 ± 0.2, p = 0.06), whereas perfusate troponin-I (control = 11.9 ± 1.9 ng/mL versus steroid = 9.5 ± 2.4 ng/mL, p = 0.448) and myocardial function were comparable between the groups. CONCLUSIONS: The addition of methylprednisolone to the perfusion solution minimizes the generation of proinflammatory cytokines and development of myocardial edema during normothermic ex vivo perfusion of hearts donated after circulatory arrest.

Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion.

BACKGROUND: Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. METHODS: Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC). The impact of ventilation strategy on the preservation of 6 unutilized human donor lungs was also evaluated. Physiologic parameters, cytokine profiles, lung injury, bullae and edema formation were compared between treatment groups. RESULTS: Perfused lungs demonstrated acceptable oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiologic parameters. However, there was less generation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-8) in human and pig lungs perfused, irrespective of perfusate solution used, when comparing NPV with PPV (p < 0.05), and a reduction in bullae formation with an NPV modality (p = 0.02). Pig lungs developed less edema with NPV (p < 0.01), and EVLP using an acellular perfusate solution had greater edema formation, irrespective of ventilation strategy (p = 0.01). Interestingly, human lungs perfused with NPV developed negative edema, or "drying" (p < 0.01), and lower composite acute lung injury (p < 0.01). CONCLUSIONS: Utilization of an NPV strategy during extended EVLP is associated with significantly less inflammation, and lung injury, irrespective of perfusate solution composition.

A Leukocyte Filter Does Not Provide Further Benefit During Ex Vivo Lung Perfusion.

Normothermic ex vivo lung perfusion (EVLP) allows for assessment and reconditioning of donor lungs. Although a leukocyte filter (LF) is routinely incorporated into the EVLP circuit; its efficacy remains to be determined. Twelve pig lungs were perfused and ventilated ex vivo in a normothermic state for 12 hours. Lungs (n = 3) were allocated to four groups according to perfusate composition and the presence or absence of a LF in the circuit (acellular ± LF, cellular ± LF). Acceptable physiologic lung parameters were achieved during EVLP; however, increased amounts of pro-inflammatory cytokines (TNF-α and IL-6) and leukocytes in the perfusate were observed despite the presence or absence of a LF. Analysis of cells washed off the LF demonstrates that it trapped leukocytes although being ineffective throughout perfusion as it became saturated over 12 hours of EVLP. We conclude that there is no objective evidence to support the routine incorporation of a LF during EVLP as it does not provide further benefit and its removal does not appear to cause harm. The lack of hypothesized benefit to a LF may be because of the saturation of the LF with donor leukocytes, leading to similar amounts of circulating leukocytes still present in the perfusate with and without a LF.

Functional assessment and transplantation of the donor heart after circulatory death.

BACKGROUND: After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. METHODS: Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. RESULTS: NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. CONCLUSIONS: NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

Structure-Activity Relationship of PEGylated Polylysine Peptides as Scavenger Receptor Inhibitors for Non-Viral Gene Delivery.

PEGylated polylysine peptides of the general structure PEG30 kDa-Cys-Trp-LysN (N = 10 to 30) were used to form fully condensed plasmid DNA (pGL3) polyplexes at a ratio of 1 nmol of peptide per µg of DNA (ranging from N:P 3:1 to 10:1 depending on Lys repeat). Co-administration of 5 to 80 nmols of excess PEG-peptide with fully formed polyplexes inhibited the liver uptake of (125)I-pGL3-polyplexes. The percent inhibition was dependent on the PEG-peptide dose and was saturable, consistent with inhibition of scavenger receptors. The scavenger receptor inhibition potency of PEG-peptides was dependent on the length of the Lys repeat, which increased 10-fold when comparing PEG30 kDa-Cys-Trp-Lys10 (IC50 of 20.2 µM) with PEG30 kDa-Cys-Trp-Lys25 (IC50 of 2.1 µM). We hypothesize that PEG-peptides inhibit scavenger receptors by spontaneously forming small 40 to 60 nm albumin nanoparticles that bind to and saturate the receptor. Scavenger receptor inhibition delayed the metabolism of pGL3-polyplexes, resulting in efficient gene expression in liver hepatocytes following delayed hydrodynamic dosing. PEG-peptides represent a new class of scavenger inhibitors that will likely have broad utility in blocking unwanted liver uptake and metabolism of a variety of nanoparticles.

Dual antiplatelet therapy use by Canadian cardiac surgeons.

BACKGROUND: Dual antiplatelet therapy is the cornerstone treatment for patients with acute coronary syndrome. Recent Canadian Guidelines recommend the use of dual antiplatelet therapy for 1 year after coronary artery bypass grafting in patients with acute coronary syndrome, but considerable variability remains. METHODS: We performed a survey of 75 Canadian cardiac surgeons to assess the use of dual antiplatelet therapy. RESULTS: Whereas 58.6% of respondents indicated that the benefits of dual antiplatelet therapy were seen irrespective of how patients were managed after acute coronary syndrome, 36.2% believed that the benefits of dual antiplatelet therapy were limited to those treated medically or percutaneously. In regard to the timing of dual antiplatelet therapy administration, 57% of respondents indicated that dual antiplatelet therapy should be given upstream in the emergency department, whereas 36.2% responded that dual antiplatelet therapy should be given only once the coronary anatomy has been defined. The majority surveyed (81%) weighed bleeding risk as being more important than ischemic risk reduction. In stable patients after acute coronary syndrome, the majority of surgeons would wait approximately 4 days after the last dose of P2Y12 antagonist before coronary artery bypass grafting. Only 44.6% indicated that they routinely use dual antiplatelet therapy postrevascularization in the setting of acute coronary syndrome. Rather, most surgeons use dual antiplatelet therapy for select patients, such as those with a stented vessel without a bypass graft, endarterectomy, or off-pump coronary artery bypass grafting. CONCLUSIONS: Cardiac surgeons exhibit variation in their attitudes and practice patterns toward dual antiplatelet therapy after coronary artery bypass grafting, and in approximately half of cases, their practice does not adhere to current guideline recommendations. New trials focusing on coronary artery bypass grafting cases in their primary analysis and educational initiatives for surgeons that focus on guideline recommendations may be warranted.

Assessment of donor heart viability during ex vivo heart perfusion.

Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor hearts and expand the donor pool; however, a reliable means of demonstrating organ viability prior to transplantation is required. Therefore, we sought to identify metabolic and functional parameters that predict myocardial performance during EVHP. To evaluate the parameters over a broad spectrum of organ function, we obtained hearts from 9 normal pigs and 37 donation after circulatory death pigs and perfused them ex vivo. Functional parameters obtained from a left ventricular conductance catheter, oxygen consumption, coronary vascular resistance, and lactate concentration were measured, and linear regression analyses were performed to identify which parameters best correlated with myocardial performance (cardiac index: mL·min(-1)·g(-1)). Functional parameters exhibited excellent correlation with myocardial performance and demonstrated high sensitivity and specificity for identifying hearts at risk of poor post-transplant function (ejection fraction: R(2) = 0.80, sensitivity = 1.00, specificity = 0.85; stroke work: R(2) = 0.76, sensitivity = 1.00, specificity = 0.77; minimum dP/dt: R(2) = 0.74, sensitivity = 1.00, specificity = 0.54; tau: R(2) = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic parameters were limited in their ability to predict myocardial performance (oxygen consumption: R(2) = 0.28; coronary vascular resistance: R(2) = 0.20; lactate concentration: R(2) = 0.02). We concluded that evaluation of functional parameters provides the best assessment of myocardial performance during EVHP, which highlights the need for an EVHP device capable of assessing the donor heart in a physiologic working mode.

The utility of cardiac biomarkers and echocardiography for the early detection of bevacizumab- and sunitinib-mediated cardiotoxicity.

The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ- and SNT-mediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ- or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes.

Vocal Cord Paralysis After Thoracic Aortic Surgery: Incidence and Impact on Clinical Outcomes.

BACKGROUND: Vocal cord paralysis (VCP) is a serious complication associated with thoracic aortic surgery; however, there is a paucity of literature regarding the incidence and impact of VCP on postoperative outcomes. We sought to determine the incidence of VCP and its impact on clinical outcomes in patients who underwent thoracic aortic repair at our center. METHODS: A retrospective chart review was conducted on all patients who underwent thoracic aortic surgery between January 2009 and September 2012. RESULTS: A total of 259 patients underwent a thoracic aortic procedure during the study period. Vocal cord paralysis was diagnosed in 12 (5%) patients, a median of 6 [3 to 21] days after extubation. The incidence was 1%, 0%, 20%, and 25% in those undergoing an open ascending, hemiarch, total arch, or descending aortic procedure, respectively. Patients with VCP had an increased incidence of pneumonia (58% vs 17%, p = 0.003), readmission to the intensive care unit for respiratory failure (17% vs 2%, p = 0.047), and longer hospital length of stay (18 [11 to 43] days versus 9 [6 to 15] days, p = 0.002). A propensity-matched analysis confirmed a higher incidence of pneumonia (58% vs 17%, p = 0.020) and longer hospital length of stay (18 [11 to 43] vs 10 [7 to 14] days, p = 0.015) in patients suffering VCP. CONCLUSIONS: Vocal cord paralysis is a common complication in patients undergoing open surgery of the aortic arch and descending aorta, and is associated with significant morbidity. Further research may be warranted to determine if early fiberoptic examination and consideration of a vocal cord medialization procedure may mitigate the morbidity associated with VCP.