Increased Mortality in Patients With Acutely Decompensated Heart Failure During the COVID-19 Pandemic in Toronto, Canada.

Background: Coronavirus disease 2019 (COVID-19) has resulted in a reduction in patients seeking timely consultation for illnesses that are not related to COVID-19. Previously, we reported a decline in the number of emergency department (ED) visits and hospitalizations for acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic vs that in 2019. We aimed to determine the consequences of these early trends on ADHF-patient morbidity and mortality. Methods: We compared consecutive patients presenting with ADHF to 3 academic medical centres in Toronto, Canada from March 1-September 28, 2020, vs those from the same time period in 2019. We used multivariate logistic regression models to evaluate whether the odds of hospitalization after presenting to the ED, recurrent ED visits or readmission within 30 days, and in-hospital all-cause mortality differed by timeframe. Results: We observed that, during the COVID-19 pandemic, a lower total number of patients presented to the hospital with ADHF, vs that in 2019. Despite this difference, the probability of being admitted to the hospital did not differ for patients seen in 2020 vs 2019. Among ADHF patients admitted to the hospital, however, we observed a significantly higher proportion being admitted to the intensive care unit, and a relative 66% increase in in-hospital mortality during the 2020 COVID-19 era, compared to that in 2019. Conclusions: Our findings suggest that improved messaging may be needed for patients living with chronic health conditions, including HF, during the pandemic, to educate and encourage them to present to hospital services when in need.

Contexte: La maladie à coronavirus 2019 (COVID-19) s'est traduite par une diminution du nombre de patients demandant des consultations médicales pour des états de santé sans lien avec la COVID-19. Nous avons précédemment décrit une diminution du nombre de consultations aux urgences et d'hospitalisations en raison d'une insuffisance cardiaque aiguë décompensée (ICAD) au cours de la pandémie de COVID-19 en 2020, par rapport à 2019. Nous avons voulu déterminer les conséquences de ces tendances précoces sur la morbidité et la mortalité chez les patients atteints d'ICAD. Méthodologie: Nous avons comparé les données pour les patients consécutifs atteints d'ICAD de trois centres médicaux hospitaliers de Toronto (Canada) traités entre le 1er mars et le 28 septembre 2020 et durant la même période en 2019. À l'aide de modèles de régression logistique multivariée, nous avons évalué les différences entre les probabilités d'hospitalisation après une consultation aux urgences, de consultations récurrentes aux urgences ou de réadmission dans les 30 jours suivant la visite initiale, ainsi que de mortalité hospitalière toutes causes confondues pour les patients vus durant ces deux périodes. Résultats: Durant la pandémie de COVID-19, le nombre total de patients atteints d'ICAD s'étant présentés à l'hôpital a été plus faible que celui relevé pour l'année 2019. Malgré cet écart, la probabilité d'admission à l'hôpital ne différait pas pour les patients vus en 2020 et en 2019. Parmi les patients atteints d'ICAD admis à l'hôpital, nous avons toutefois observé une proportion significativement plus élevée de séjours aux soins intensifs et une hausse relative de 66 % du taux de mortalité hospitalière, en comparant les données de 2020 (pandémie de COVID-19) et celles de 2019. Conclusions: Nos observations indiquent qu'il pourrait être nécessaire d'améliorer la communication avec les patients atteints de problèmes de santé chroniques (y compris l'IC) en situation de pandémie de façon à mieux les informer et à les encourager à consulter les services hospitaliers lorsque nécessaire.

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

Management of Frail and Older Homebound Patients With Heart Failure: A Contemporary Virtual Ambulatory Model.

BACKGROUND: Heart failure (HF) affects many patients who are older and frail, presenting multiple physical barriers to accessing specialty care in a traditional ambulatory clinic model. Here, we present an assisted virtual care model in which a home visiting nurse facilitated video visits with a HF cardiologist to follow homebound, frail, and older patients with HF. METHODS: This is a pragmatic, quasi-experimental, pre-post, single-centre study. It included homebound, frail, and older patients with HF from 2015 to 2019 who were followed for 1 year; in-person clinic visits were completely replaced by nurse-facilitated virtual video visits. Outcomes evaluated included annualized hospitalization rate, number of hospitalization days, and number of emergency department visits. RESULTS: A total of 49 patients were included, with a median age of 86 (83-93) years, and were followed for 1 year after enrollment. Among patients enrolled, HF with preserved ejection fraction was the most common subtype (57%). Compared to the year prior to enrollment, patients had a lower mortality-adjusted all-cause annualized hospitalization rate in the year following enrollment (2.57 vs 1.78, P < 0.0001). Compared to the year prior, the number of mortality-adjusted all-cause hospitalization days was significantly lower in the year following enrollment (27.2 vs 21.4, P < 0.0001). There was a reduction in the number of all-cause annualized emergency department visits (3.10 vs 2.27, P = 0.003). CONCLUSIONS: Nurse-assisted virtual visits may be a preferable strategy for homebound, frail, and older patients with HF to receive longitudinal care. This approach may represent a plausible strategy to care for other patients with significant barriers to accessing specialized cardiac care.

CONTEXTE: L'insuffisance cardiaque (IC) touche de nombreux patients âgés et fragiles, et dresse maints obstacles physiques à l'accès aux soins spécialisés au sein d'un modèle classique de soins cliniques ambulatoires. Dans le présent article, nous exposons un modèle de soins virtuels assistés où une infirmière visiteuse assure par vidéoconsultation, avec un cardiologue, le suivi de patients âgés et fragiles atteints d'IC confinés à la maison. MÉTHODOLOGIE: Une étude monocentrique et pragmatique, quasi expérimentale de type « avant-après ¼, a été menée de 2015 à 2019 auprès de patients âgés et fragiles atteints d'IC confinés à la maison. Les patients ont été suivis durant un an; les consultations en personne ont été entièrement remplacées par des vidéoconsultations effectuées par une infirmière. Les paramètres évalués comprenaient le taux annualisé d'hospitalisation, le nombre de jours d'hospitalisation et le nombre de consultations aux urgences. RÉSULTATS: Au total, 49 patients dont l'âge médian était de 86 ans (83-93 ans) ont été suivis durant un an à compter de leur admission à l'étude. L'IC à fraction d'éjection préservée était le sous-type d'IC le plus fréquent (57 %) chez les patients participant à l'étude. Par comparaison à l'année précédente, le taux annualisé d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été plus faible chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (2,57 vs 1,78, P < 0,0001). Toujours par comparaison à l'année précédente, le nombre de jours d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été significativement inférieur chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (27,2 vs 21,4, P < 0,0001). Le nombre annualisé de consultations aux urgences toutes causes confondues a quant à lui diminué (3,10 vs 2,27, P = 0,003). CONCLUSIONS: Les consultations virtuelles assistées par une infirmière peuvent constituer une stratégie à privilégier dans la prestation de soins longitudinaux à des patients âgés et fragiles atteints d'IC qui sont confinés à la maison. Cette approche pourrait représenter une stratégie plausible pour prodiguer des soins à d'autres patients qui sont confrontés à d'importants obstacles limitant leur accès à des soins spécialisés en cardiologie.

Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial.

INTRODUCTION: Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE-vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self-care materials, and health-related quality of life. METHODS AND ANALYSIS: Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes. ETHICS AND DISSEMINATION: The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care. TRIAL REGISTRATION NUMBER: NCT04966104.

Fate of the liver in the survivors of adult heart transplant for a failing Fontan circulation.

The Fontan circulation has inherent long-term vulnerabilities such that adult Fontan patients now comprise the largest, most rapidly growing subgroup of adult congenital heart disease referred for transplant assessment. Almost all have Fontan Associated Liver Disease (FALD). There is an absence of mid to late hepatic outcome data after heart transplant alone. Therefore, we analyzed outcomes of survivors of heart only transplant in patients with failing Fontan circulation. Including all 10 of our adult Fontan patients surviving >1 year after isolated heart transplant, we report evolution of their clinical features, bloodwork, hemodynamic data, and liver ultrasound findings over a median of 4.7 years. Nonprogression of FALD, resolution of ascites and freedom from hepatocellular carcinoma in the mid-term highlight the outcomes in this selected group once normal cardiac output and venous pressures are established by heart transplant.

Reduced Rate of Hospital Presentations for Heart Failure During the COVID-19 Pandemic in Toronto, Canada.

Coronavirus disease 2019 (COVID-19) has resulted in public health measures and health care reconfigurations likely to have impact on chronic disease care. We aimed to assess the volume and characteristics of patients presenting to hospitals with acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic compared with a time-matched 2019 cohort. Patients presenting to hospitals with ADHF from March 1, to April 19, 2020 and 2019 in an urban hospital were examined. Multivariable logistic-regression models were used to evaluate the difference in probability of ADHF-related hospitalization between the 2 years. During the COVID-19 pandemic, a total of 1106 emergency department (ED) visits for dyspnea or peripheral edema were recorded, compared with 800 ED visits in 2019. A decrease in ADHF-related ED visits of 43.5% (14.8%-79.4%, P = 0.002) and ADHF-related admissions of 39.3% (8.6%-78.5%, P = 0.009) was observed compared with 2019. Patients with ADHF presenting to hospitals (n = 128) were similar in age, sex, and comorbidities compared with the 2019 cohort (n = 186); however, a higher proportion had recent diagnoses of heart failure. Upon ED presentation, the relative probability of hospitalization or admission to intensive care was not statistically different. There was a trend toward higher in-hospital mortality in 2020. The decline in ADHF-related hospitalizations raises the timely question of how patients with heart failure are managing beyond the acute-care setting and reinforces the need for public education on the availability and safety of emergency services throughout the COVID-19 pandemic.

The Role of Ambulatory Heart Failure Clinics to Avoid Heart Failure Admissions.

BACKGROUND: There is a complex relationship between heart failure (HF) clinic services and health outcomes. We hypothesized that ambulatory clinic activity may be associated with both hospital admission and also with avoidance of admission. METHODS: A retrospective comparative cohort study was conducted examining activity in an ambulatory HF Clinic. Consecutive clinic visits in 2013 were recorded (n = 1728) and periods of high-intensity utilization (HIU) were identified (n = 128). A HIU period was defined by ≥2 consecutive clinic visits within 30 days, ending after 30 days passed without an additional clinic visit. For each HIU period identified, patient characteristics (n = 107) and all clinic visits (n = 324) were examined. HIU periods were then classified by association with hospital admission (±30 days). RESULTS: In 2013, 18.8% of all clinic visits occurred during HIU periods, involving 13.7% of the clinic population. Thirty-eight percent of HIU periods were associated with 62 total hospital admissions (±30 days), of which 58% (n = 36) were for a primary diagnosis of HF. In addition,17 HIU periods met criteria for admission avoided, and 7 HIU periods occurring after hospital discharge also met criteria for admission avoided. CONCLUSIONS: We identified periods of intensive ambulatory clinic activity dedicated to patients with high burdens of comorbidities and both HF and non-HF-related admissions. These periods were also associated with episodes of successful decongestion with oral diuretics, resulting in avoidance of admission. Identifying HF patients who can be treated successfully or who are likely to require admission may be helpful for allocating clinic resources.

CONTEXTE: Il existe un lien complexe entre les services cliniques relatifs à l'insuffisance cardiaque (IC) et les résultats liés à la santé. Nous avons posé l'hypothèse que l'activité dans les unités de soins ambulatoires pourrait avoir une influence à la fois sur les hospitalisations et sur l'évitement des hospitalisations. MÉTHODOLOGIE: Une étude de cohorte comparative rétrospective a été menée afin d'examiner l'activité dans une unité de soins ambulatoires auprès de patients atteints d'IC. Les visites consécutives effectuées à l'unité de soins en 2013 ont été compilées (n = 1728) et les périodes d'utilisation intensive des services (UIS) ont été relevées (n = 128). Une période d'UIS était définie par au moins 2 visites consécutives à l'unité de soins ambulatoires en l'espace de 30 jours; la période était considérée comme terminée après 30 jours sans nouvelle visite. Pour chaque période d'UIS relevée, les caractéristiques des patients (n = 107) et toutes les visites à l'unité de soins (n = 324) ont été examinées. Les périodes d'UIS ont ensuite été classées en fonction de leur association avec une hospitalisation (± 30 jours). RÉSULTATS: En 2013, 18,8 % de toutes les visites à l'unité de soins ambulatoires étaient rattachées à une période d'UIS et concernaient 13,7 % des patients de l'unité. Au total, 38 % des périodes d'UIS ont été associées à 62 hospitalisations (± 30 jours), dont 58 % (n = 36) étaient liées à un diagnostic primaire d'IC. En outre, 17 périodes d'UIS répondaient aux critères définissant une hospitalisation évitée, et 7 périodes d'UIS survenues après que le patient soit sorti de l'hôpital répondaient aussi aux critères définissant une hospitalisation évitée. CONCLUSIONS: Nous avons relevé des périodes d'activité intensive de l'unité de soins ambulatoires consacrées à des patients présentant un lourd fardeau de comorbidité, ainsi que les hospitalisations liées à l'IC et non liées à l'IC. Ces périodes étaient aussi associées à des épisodes de congestion soulagée grâce à des diurétiques oraux, ce qui a permis d'éviter des hospitalisations. Le repérage des patients atteints d'IC qui peuvent être traités efficacement en consultation externe et de ceux qui risquent de devoir être hospitalisés pourrait permettre d'optimiser l'affectation des ressources des unités de soins.

A Mobile Phone-Based Telemonitoring Program for Heart Failure Patients After an Incidence of Acute Decompensation (Medly-AID): Protocol for a Randomized Controlled Trial.

BACKGROUND: Patients with heart failure (HF) are at the highest risk for hospital readmissions during the first few weeks after discharge when patients are transitioning from hospital to home. Telemonitoring (TM) for HF management has been found to reduce mortality risk and hospital readmissions if implemented appropriately; however, the impact of TM targeted for patients recently discharged from hospital, for whom TM might have the biggest benefit, is still unknown. Medly, a mobile phone-based TM system that is currently being used as a standard of care for HF at a large Canadian hospital, may be an effective tool for the management of HF in patients recently discharged from hospital. OBJECTIVE: The objective of the Medly-After an Incidence of acute Decompensation (Medly-AID) trial is to determine the effect of Medly on the self-care and quality of life of patients with HF who have been recently discharged from hospital after an HF-related decompensation. METHODS: A multisite multimethod randomized controlled trial (RCT) will be conducted at 2 academic hospitals and at least one community hospital to evaluate the impact of Medly-enabled HF management on the outcomes of patients with HF who had been hospitalized for HF-related decompensation and discharged during the 2 weeks before recruitment. The trial will include 144 participants with HF (74 in each control and intervention groups). Control patients will receive standard of care, whereas patients in the intervention group will receive standard of care and Medly. Specifically, patients in the intervention group will record daily weight, blood pressure, and heart rate and answer symptom-related questions via the Medly app. Medly will generate automated patient self-care messages such as to adjust diuretic medications, based on the rules-based algorithm personalized to the individual patient, and send real-time alerts to their health care providers as necessary. All patients will be followed for 3 months. Primary outcome measures are self-care and quality of life as measured through the validated questionnaires Self-Care of Heart Failure Index, EQ-5D-5L, and the Kansas City Cardiomyopathy Questionnaire-12. Secondary outcome measures for this study include cost of health care services used and health outcomes. RESULTS: Patient recruitment began in November 2018 at the Sunnybrook Health Sciences Centre, with a total of 35 participants recruited by July 30, 2019 (17 in the intervention group and 18 in the control group). The final analysis is expected to occur in the fall of 2020. CONCLUSIONS: This RCT will be the first to assess the effectiveness of the Medly TM system for use following discharge from hospital after a HF-related decompensation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03358303; https://clinicaltrials.gov/ct2/show/NCT03358303. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15753.

Ethnic disparities in cardiac transplantation: opportunities to improve long-term outcomes in all cardiac transplant recipients.

Ethnic disparities in cardiovascular outcomes have been increasingly recognized in the medical literature. In a recent paper in this journal, Peled et al. provide evidence that Arab Israelis may have worse outcome after cardiac transplant than their Jewish counterparts. This commentary explores possible explanations for the differing outcomes and suggests potential solutions that may improve outcomes for cardiac transplant recipients regardless of ethnicity.

The Physiological Rationale for Incorporating Pulsatility in Continuous-Flow Left Ventricular Assist Devices.

Over the past few decades, left ventricular assist device (LVAD) support has extended the lives of many patients with end-stage heart failure. The most common devices are continuous-flow (CF) LVADs. The use of the CF-LVADs has required that clinicians learn the physiological and clinical consequences of long-term continuous blood flow. While this alteration in the normal physiology still offers advantages from mechanical circulatory support, the lack of pulsatility may also increase the likelihood of adverse events. However, it is currently unknown whether newly evolved devices should incorporate pulsatility. In this article, we discuss the possible benefits of incorporating pulsatility, while maintaining the benefits of the CF-LVAD, to maximize the treatment of patients.

Closing the Care Gap: A Primer on Quality Improvement for Heart Failure Clinicians.

Quality improvement (QI) initiatives have become an integral part of patient-centered care. In this primer, we outline 6 steps for initiating, implementing, and monitoring improvement in heart failure care. These steps include acknowledging that improvement is needed and setting a culture for improvement; forming a QI team; understanding the local problem; generating improvement strategies that will fit with the local problem; monitoring; testing; and refining improvements, analysis of data, and interpretation of run charts. This primer provides tools and resources for clinicians who want to learn how to perform QI specifically in the field of heart failure. We will illustrate the application of these steps using a hypothetical example for a congestive heart failure postdischarge clinic.

Experimental biomarkers in heart failure: an update.

Over the past 5 years, researchers have examined the utility of many experimental heart failure biomarkers that are not yet widely adopted clinically, to complement the role of B-type natriuretic peptide and its precursor. Candidate biomarkers have been identified from several different pathophysiologic categories, including markers of inflammation, myocyte necrosis, renal dysfunction, neurohumoral activation, oxidative stress and raised intracardiac pressure. Indeed, some biomarkers provide prognostic information that is independent of information obtained from conventional clinical and biomarker assessment. Moreover, some biomarkers studied help to identify dominant pathology that may predict responsiveness to specific therapies. Preliminary data also suggest a potential role for the development of comprehensive biomarker profiling models, integrating biomarkers from several categories to refine risk assessment.

Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle.

Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.

Comparison of gene delivery techniques for therapeutic angiogenesis ultrasound-mediated destruction of carrier microbubbles versus direct intramuscular injection.

OBJECTIVES: This study was designed to compare the efficacy of angiogenic gene delivery by ultrasound-mediated (UM) destruction of intravenous carrier microbubbles to direct intramuscular (IM) injections. BACKGROUND: Current trials of gene therapy for angiogenesis remain limited by suboptimal, invasive delivery techniques. METHODS: Hind-limb ischemia was produced by iliac artery ligation in 99 rats. In 32 rats, UM delivery of green fluorescent protein (GFP)/vascular endothelial growth factor-165 (VEGF(165)) plasmid deoxyribonucleic acid was performed. Thirty-five animals received IM injections of VEGF(165)/GFP plasmid. Remaining rats received no treatment. Before delivery (day 14 after ligation) and at days 17, 21, and 28 and week 8 after ligation, microvascular blood volume and microvascular blood flow to the proximal hind limbs were assessed by contrast-enhanced ultrasound (n = 8 per group). Total transfection was assessed by reverse transcriptase-polymerase chain reaction, and localization of transfection was determined by immunohistochemistry. RESULTS: By day 28, both IM and UM delivery of VEGF(165) produced significant increases in microvascular blood volume and microvascular blood flow. Whereas increases in microvascular blood volume were similar between treatment groups, microvascular blood flow was greater (p < 0.005) in UM-treated animals as compared with IM-treated animals, persisting to week 8. The VEGF(165)/GFP messenger ribonucleic acid expression was greater (p < 0.05) for IM-treated animals. A strong GFP signal was detected for both groups and was localized to focal perivascular regions and myocytes around injection sites for IM and to the vascular endothelium of arterioles/capillaries in a wider distribution for UM delivery. CONCLUSIONS: Despite lower transfection levels, UM delivery of VEGF(165) is as effective as IM injections. The UM delivery results in directed vascular transfection over a wider distribution, which may account for the more efficient angiogenesis.

Mitral stenosis and cardiogenic shock from an obstructive abscess of the mitral annulus.

A 48-year-old female hemodialysis patient with gram-positive mitral endocarditis developed progressive hemodynamic collapse. Echocardiography revealed a mitral annular abscess, which expanded rapidly due to connection with and pressure from the left ventricle. The mitral annular abscess had enlarged sufficiently to obstruct the mitral orifice, resulting in acute cardiogenic shock. The patient underwent and survived emergency surgical repair, and remained well on follow-up.

Saphenous vein graft aneurysm masquerading as a left atrial mass: diagnosis by contrast transesophageal echocardiography.

We describe the first reported case of a saphenous vein graft aneurysm mimicking a left atrial (LA) mass on echocardiographic imaging in a 62-year-old man 22 years after coronary bypass surgery. On presentation with worsening angina, a transthoracic echocardiogram revealed a LA mass. Coronary angiography showed severe native coronary artery and graft disease. The saphenous vein graft to the first obtuse marginal branch of the left circumflex coronary artery appeared ectatic and aneurysmal and was diffusely diseased. Transesophageal echocardiography demonstrated a well-circumscribed mass apparently within the LA, with an area of central echolucency and a surrounding crescentic region of increased echodensity, with absent flow by color and spectral Doppler techniques. After an intravenous bolus injection of Definity, the area of central echolucency within the mass was opacified compatible with a vascular origin. Pulsatile contrast flow was seen predominantly in diastole consistent with a coronary arterial flow pattern. Thus, contrast transesophageal echocardiography confirmed the diagnosis of a saphenous vein graft aneurysm invaginating the lateral aspect of the LA, mimicking a true LA mass, highlighting a novel use for this technology.