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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. Résumé: 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 54-year-old woman presented to the emergency department with increasing shortness of breath over four days. She reported an increased cough over the previous two months and that her daughter recently had an upper respiratory tract infection. The patient had metastatic breast cancer (estrogen

Coronavirus disease 2019 (Covid-19) has resulted in public health measures and healthcare reconfigurations likely to impact chronic disease care. We aimed to assess the volume and characteristics of patients presenting to hospital with acute decompensated heart failure (ADHF) during the 2020 Covid-19 pandemic compared to a time-matched 2019 cohort. Patients presenting to hospital 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 two years. During the Covid-19 pandemic, a total of 1,106 Emergency Department (ED) visits for dyspnea or peripheral edema were recorded, compared to 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 to 2019. Patients presenting to hospital with ADHF (n=128) were similar in age, sex, and co-morbidities, compared to the 2019 cohort (n=186), however a higher proportion had a recent heart failure diagnosis. Upon ED presentation, the relative probability of hospitalization or intensive care admission was not statistically different. There was a trend towards 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., During the Covid-19 pandemic in March-April 2020, a decrease in acute decompensated heart failure-related Emergency Department visits and hospitalizations of 44% and 39%, respectively, was observed compared to a time-matched 2019 cohort. Probability of hospitalization or intensive care admission was not statistically different. There was a trend towards higher in-hospital mortality in 2020.

Chronic pulmonary regurgitation (PR) leads to RV dilatation and dysfunction, and can also induce LV failure through ventricular-ventricular (VV) interaction. Pulmonary valve replacement (PVR) is advocated to prevent this pathophysiology. A 51-year-old woman with a dysplastic pulmonary valve, severe

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.

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.

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

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.

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 (VEGF165) plasmid deoxyribonucleic acid was performed. Thirty-five animals received IM injections of VEGF165/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 VEGF165produced 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 VEGF165/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 VEGF165is 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.

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.

Ultrasound-mediated (UM) destruction of plasmid-bearing microbubbles targets gene delivery to the vascular endothelium, promoting therapeutic angiogenesis. We hypothesized that modulation of the ultrasound pulsing intervals (PI) would allow targeting of gene delivery to selective vascular compartments based upon blood flow velocities, allowing differential targeting of faster filling vessels (arterioles) versus slower vessels (capillaries). Methods: Unilateral hindlimb ischemia was produced by iliac artery ligation in 60 rats. At day 14 post-ligation, microvascular blood volume (MBV) and blood flow (MBF) in the proximal hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). UM-delivery of VEGF 165 /GFP plasmid (500 μg cDNA)-bearing microbubbles (1x10 9 ), was performed, at PIs of 2, 5 and 10 s (n=20 for each). Perfusion was re-assessed by CEU at days 17 and 28 (n=10 for each). Fluorescent microangiography (FMA) was performed at day 28 to assess vessel density. Transfection was localized using immunohistochemistry. PCR was used to quantify transgene expression. Results: VEGF 165 /GFP mRNA expression was greatest at day 17, and was similar for PI 5 and 10 s, however reduced for PI 2 s. Fluorescent microscopy demonstrated GFP transfection predominantly within arterioles for shorter PIs (PI 5 s >> PI 2 s), and more capillary expression with PI 10 s. Prior to delivery, normalized MBV and MBF in ischemic muscle were similarly reduced in all groups. By day 28, for PI 5 and 10 s, there was a significant increase in normalized MBV (1.4±0.2 vs 0.9±0.2, pvs 0.9±0.2, pvs 0.3±0.1, pvs 0.3±0.1, p Conclusions: Altering the PI during UM-gene delivery can result in targeted delivery to selective vascular compartments. For the purposes of gene therapy for angiogenesis in chronic ischemia, a strategy that selectively targets arterioles is more effective than one that targets capillaries.

Purpose Mortality after cardiac transplant is predicted by The Model for End-Stage Liver Disease (MELD) score. The score is derived from serum bilirubin, creatinine and International Normalized Ratio (INR); abnormalities in each occurs with advanced liver disease. Given the hemodynamic burden experienced during cardiac transplant, we hypothesized that markers of milder pre-transplant liver dysfunction also predict early mortality after cardiac transplant. Methods and Materials We conducted a retrospective cohort study of adult patients at our institution that underwent their first heart transplant from 2007 to 2012. We evaluated the utility of pre-transplant aspartate aminotransferase (AST), bilirubin, albumin, INR, platelets and imaging evidence of cirrhosis and splenomegaly in predicting 30-day mortality post transplant. We used univariable logistic regression to identify hepatic predictors of mortality post transplant. We then compared a risk score that integrated these predictors to the MELD score using receiver operating characteristic (ROC) curve analysis. Results The study population consisted of 126 heart transplant recipients (Age 49±13,male 66%,ischemic etiology 27%). Mortality rate was 10.3% at 30 days. Patients that died had more sternotomies, higher pre-transplant creatinine levels and were more likely to have congenital heart disease. Univariate hepatic predictors of 30-day post-operative mortality were pre-transplant: platelet count Conclusions In our cohort, pre-transplant spleen length and platelet count, parameters not included in the MELD score, predicted mortality post heart transplant. These markers of milder liver dysfunction enhanced the MELD score’s ability to predict early mortality after cardiac transplant.

See also page [510][1] and [www.cmaj.ca/lookup/doi/10.1503/cmaj.131742][2] Heart failure with reduced ejection fraction is a clinical syndrome of dyspnea, exercise intolerance and/or edema resulting from an impairment of ejection of blood, usually documented by a left ventricular ejection fraction

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.