Sean A. Virani

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Focus Update: Anemia, Biomarkers, and Recent Therapeutic Trial Implications

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides discussion on the management recommendations on 3 focused areas: (1) anemia; (2) biomarkers, especially natriuretic peptides; and (3) clinical trials that might change practice in the management of patients with heart failure. First, all patients with heart failure and anemia should be investigated for reversible causes of anemia. Second, patients with chronic stable heart failure should undergo natriuretic peptide testing. Third, considerations should be given to treat selected patients with heart failure and preserved systolic function with a mineralocorticoid receptor antagonist and to treat patients with heart failure and reduced ejection fraction with an angiotensin receptor/neprilysin inhibitor, when the drug is approved. As with updates in previous years, the topics were chosen in response to stakeholder feedback. The 2014 Update includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers to best manage patients with heart failure.

Heart failure and chronic obstructive pulmonary disease: the challenges facing physicians and health services.

Pulmonary disease is common in patients with heart failure, through shared risk factors and pathophysiological mechanisms. Adverse pulmonary vascular remodelling and chronic systemic inflammation characterize both diseases. Concurrent chronic obstructive pulmonary disease presents diagnostic and therapeutic challenges, and is associated with increased morbidity and mortality. The cornerstones of therapy are beta-blockers and beta-agonists, whose pharmacological properties are diametrically opposed. Each disease is implicated in exacerbations of the other condition, greatly increasing hospitalizations and associated health care costs. Such multimorbidity is a key challenge for health-care systems oriented towards the treatment of individual diseases. Early identification and treatment of cardiopulmonary disease may alleviate this burden. However, diagnostic and therapeutic strategies require further validation in patients with both conditions.

Canadian Cardiovascular Society Guidelines for Evaluation and Management of Cardiovascular Complications of Cancer Therapy

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice

The Canadian Cardiovascular Society Heart Failure (HF) Guidelines Program has generated annual HF updates, including formal recommendations and supporting Practical Tips since 2006. Many clinicians indicate they routinely use the Canadian Cardiovascular Society HF Guidelines in their daily practice. However, many questions surrounding the actual implementation of the Guidelines into their daily practice remain. A consensus-based approach was used, including feedback from the Primary and Secondary HF Panels. This companion is intended to answer several key questions brought forth by HF practitioners such as appropriate timelines for initial assessments and subsequent reassessments of patients, the order in which medications should be added, how newer medications should be included in treatment algorithms, and when left ventricular function should be reassessed. A new treatment algorithm for HF with reduced ejection fraction is included. Several other practical issues are addressed such as an approach to management of hyperkalemia/hypokalemia, treatment of gout, when medications can be stopped, and whether a target blood pressure or heart rate is suggested. Finally, elements and teaching of self-care are described. This tool will hopefully function to allow better integration of the HF Guidelines into clinical practice.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update: Focus on Rehabilitation and Exercise and Surgical Coronary Revascularization

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides focused discussions on the management recommendations on 2 topics: (1) exercise and rehabilitation; and (2) surgical coronary revascularization in patients with heart failure. First, all patients with stable New York Heart Association class I-III symptoms should be considered for enrollment in a tailored exercise training program, to improve exercise tolerance and quality of life. Second, selected patients with suitable coronary anatomy should be considered for bypass graft surgery. As in previous updates, the topics were chosen in response to stakeholder feedback. The 2013 Update also includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers manage their patients with heart failure.

Predicting heart failure decompensation using cardiac implantable electronic devices: a review of practices and challenges.

Cardiac implantable electronic devices include remote monitoring tools intended to guide heart failure management. The monitoring focus has been on averting hospitalizations by predicting worsening heart failure. However, although device measurements including intrathoracic impedance correlate with risk of decompensation, they individually predict hospitalizations with limited accuracy. Current ‘crisis detection’ methods involve repeatedly screening for impending decompensation, and do not adhere to the principles of diagnostic testing. Complex substrate, limited test performance, low outcome incidence, and long test to outcome times inevitably generate low positive and high negative predictive values. When combined with spectrum bias, the generalizability, incremental value, and cost‐effectiveness of device algorithms are questionable. To avoid these pitfalls, remote monitoring may need to shift from crisis detection to health maintenance, keeping the patient within an ideal physiological range through continuous ‘closed loop’ interaction and dynamic therapy adjustment. Test performance must also improve, possibly through combination with physiological sensors in different dimensions, static baseline characteristics, and biomarkers. Complex modelling may tailor monitoring to individual phenotypes, and thus realize a personalized medicine approach. Future randomized controlled trials should carefully consider these issues, and ensure that the interventions tested are generalizable to clinical practice.

Acute Heart Failure: Perspectives from a Randomized Trial and a Simultaneous Registry

Background—Randomized controlled trials (RCT) are limited by their generalizability to the broader nontrial population. To provide a context for Acute Study of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, we designed a complementary registry to characterize clinical characteristics, practice patterns, and in-hospital outcomes of acute heart failure patients. Methods and Results—Eligible patients for the registry included those with a principal diagnosis of acute heart failure (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) from 8 sites participating in ASCEND-HF (n=697 patients, 2007–2010). Baseline characteristics, treatments, and hospital outcomes from the registy were compared with ASCEND-HF RCT patients from 31 Canadian sites (n=465, 2007–2010). Patients in the registry were older, more likely to be female, and have chronic respiratory disease, less likely to have diabetes mellitus: they had a similar incidence of ischemic HF, atrial fibrillation, and similar B-type natriuretic peptide levels. Registry patients had higher systolic blood pressure (registry: median 132 mm Hg [interquartile range 115–151 mm Hg]; RCT: median 120 mm Hg [interquartile range 110–135 mm Hg]) and ejection fraction (registry: median 40% [interquartile range 27–58%]; RCT: median 29% [interquartile range 20–40 mm Hg]) than RCT patients. Registry patients presented more often via ambulance and had a similar total length of stay as RCT patients. In-hospital mortality was significantly higher in the registry compared with the RCT patients (9.3% versus 1.3%,P<0.001), and this remained after multivariable adjustment (odds ratio 6.6, 95% CI 2.6–16.8, P<0.001). Conclusions—Patients enrolled in a large RCT of acute heart failure differed significantly based on clinical characteristics, treatments, and inpatient outcomes from contemporaneous patients participating in a registry. These results highlight the need for context of RCTs to evaluate generalizability of results and especially the need to improve clinical outcomes in acute heart failure. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.Background— Randomized controlled trials (RCT) are limited by their generalizability to the broader nontrial population. To provide a context for Acute Study of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, we designed a complementary registry to characterize clinical characteristics, practice patterns, and in-hospital outcomes of acute heart failure patients. Methods and Results— Eligible patients for the registry included those with a principal diagnosis of acute heart failure (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) from 8 sites participating in ASCEND-HF (n=697 patients, 2007–2010). Baseline characteristics, treatments, and hospital outcomes from the registy were compared with ASCEND-HF RCT patients from 31 Canadian sites (n=465, 2007–2010). Patients in the registry were older, more likely to be female, and have chronic respiratory disease, less likely to have diabetes mellitus: they had a similar incidence of ischemic HF, atrial fibrillation, and similar B-type natriuretic peptide levels. Registry patients had higher systolic blood pressure (registry: median 132 mm Hg [interquartile range 115–151 mm Hg]; RCT: median 120 mm Hg [interquartile range 110–135 mm Hg]) and ejection fraction (registry: median 40% [interquartile range 27–58%]; RCT: median 29% [interquartile range 20–40 mm Hg]) than RCT patients. Registry patients presented more often via ambulance and had a similar total length of stay as RCT patients. In-hospital mortality was significantly higher in the registry compared with the RCT patients (9.3% versus 1.3%, P <0.001), and this remained after multivariable adjustment (odds ratio 6.6, 95% CI 2.6–16.8, P <0.001). Conclusions— Patients enrolled in a large RCT of acute heart failure differed significantly based on clinical characteristics, treatments, and inpatient outcomes from contemporaneous patients participating in a registry. These results highlight the need for context of RCTs to evaluate generalizability of results and especially the need to improve clinical outcomes in acute heart failure. Clinical Trial Registration— URL: . Unique identifier: [NCT00475852][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00475852&atom=%2Fcirchf%2F5%2F6%2F735.atom

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

PURPOSE The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. METHODS AND MATERIALS Between 1990 and 1998, 5334 women ≤ 80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. RESULTS The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). CONCLUSIONS There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.

Allosensitization in Heart Transplantation: An Overview

Transplant candidates might manifest circulating antibodies against human leukocyte antigens and nonhuman leukocyte antigens, a condition termed allosensitization. The presence of these antibodies decreases a given candidates possible donor pool, thereby prolonging the time to transplantation. They are also associated with poorer posttransplant outcomes including increased morbidity and mortality. With the increasing use of ventricular assist devices as a bridge to transplantation, the prevalence of allosensitized transplant candidates has increased. This has implications for transplant programs in terms of donor-recipient matching and managing transplant-related complications, which are more common in this high risk cohort. Controversy exists as to the best approach in managing sensitized patients, before and after transplantation. Transplant centres have used various strategies to reduce antibody loads with mixed results being reported; moreover, it remains unclear as to whether attempts at desensitization translate into better posttransplant outcomes. As an alternative management approach, some centres participate in large organ sharing strategies and allocate organs based on the probability of finding a successful donor-recipient match. In this article, the immunological basis of allosensitization, its causes, implications, and therapeutic strategies to manage sensitized patients are reviewed. The literature in relation to desensitization therapies in heart transplant candidates is also reviewed.

The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer Undergoing Androgen Deprivation Therapy in British Columbia, Canada.

Background. While androgen deprivation therapy (ADT) reduces the risk of prostate cancer-specific mortality in high-risk localized prostate cancer, it adversely affects cardiovascular (CV) risk factor profiles in treated men. Methods. We retrospectively reviewed the charts of 100 consecutive men with intermediate- or high-risk localized prostate cancer referred to the British Columbia Cancer Agency for ADT. Data on CV risk factors and disease were collected and Framingham risk scores were calculated. Results. The median age of the study cohort was 73 years. Established cardiovascular disease was present in 25% of patients. Among patients without established CV disease, calculated Framingham risk was high in 65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58% of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in 24%. Hypertension was more prevalent in the study cohort than in an age- and sex-matched population sample (OR 1.74, P = 0.006); diabetes had a similar prevalence (OR 0.93, P = 0.8). Conclusions. Patients receiving ADT have a high prevalence of cardiovascular disease and risk factors and are more likely to be hypertensive than population controls. Low rates of CV risk screening suggest opportunities for improved primary and secondary prevention of CV disease in this population.