All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular ...disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria-mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease.
Since the inception of the Canadian Cardiovascular Society heart failure (HF) guidelines in 2006, much has changed in the care for patients with HF. Over the past decade, the HF Guidelines Committee ...has published regular updates. However, because of the major changes that have occurred, the Guidelines Committee believes that a comprehensive reassessment of the HF management recommendations is presently needed, with a view to producing a full and complete set of updated guidelines. The primary and secondary Canadian Cardiovascular Society HF panel members as well as external experts have reviewed clinically relevant literature to provide guidance for the practicing clinician. The 2017 HF guidelines provide updated guidance on the diagnosis and management (self-care, pharmacologic, nonpharmacologic, device, and referral) that should aid in day-to-day decisions for caring for patients with HF. Among specific issues covered are risk scores, the differences in management for HF with preserved vs reduced ejection fraction, exercise and rehabilitation, implantable devices, revascularization, right ventricular dysfunction, anemia, and iron deficiency, cardiorenal syndrome, sleep apnea, cardiomyopathies, HF in pregnancy, cardio-oncology, and myocarditis. We devoted attention to strategies and treatments to prevent HF, to the organization of HF care, comorbidity management, as well as practical issues around the timing of referral and follow-up care. Recognition and treatment of advanced HF is another important aspect of this update, including how to select advanced therapies as well as end of life considerations. Finally, we acknowledge the remaining gaps in evidence that need to be filled by future research.
Depuis la parution des Lignes directrices sur l’insuffisance cardiaque (IC) de la Société canadienne de cardiologie en 2006, les soins aux patients atteints de ce trouble ont connu d’importants changements. Au cours de la dernière décennie, le Comité des lignes directrices sur l’IC a publié des mises à jour périodiques. Toutefois, en raison des changements importants qui sont survenus, le Comité des lignes directrices a jugé qu’il était nécessaire de procéder à une réévaluation exhaustive des recommandations sur la prise en charge de l’IC afin de produire un ensemble complet de lignes directrices à jour. Les membres des comités primaire et secondaire sur l’IC de la Société canadienne de cardiologie, ainsi que des spécialistes externes, ont passé en revue la littérature pertinente afin d’indiquer aux cliniciens la marche à suivre. Les lignes directrices de 2017 donnent des indications sur le diagnostic et la prise en charge (autosoins, traitements pharmacologiques et non pharmacologiques, dispositifs et orientation des patients) destinées à faciliter la prise de décisions quotidiennes en matière de soins aux patients atteints d’IC. Parmi les questions abordées figurent notamment les cotes de risque, les différences de prise en charge selon qu’il s’agit d’IC à fraction d’éjection préservée ou réduite, l’activité physique et la réadaptation, les dispositifs implantables, la revascularisation, la dysfonction ventriculaire droite, l’anémie et la carence en fer, le syndrome cardiorénal, l’apnée du sommeil, les cardiomyopathies, l’IC pendant la grossesse, la cardio-oncologie et la myocardite. Le comité a apporté une attention particulière aux stratégies et aux traitements visant à prévenir l’IC, à l’organisation des soins aux patients atteints d’IC, à la prise en charge des comorbidités, ainsi qu’à des questions pratiques concernant les délais d’orientation du patient et les soins de suivi. La reconnaissance et le traitement de l’IC au stade avancé, et notamment le choix des thérapies à ce stade et les considérations en matière de fin de vie, représentent un autre aspect important de cette mise à jour. Enfin, le comité reconnaît les lacunes dans les données probantes qui subsistent et devront être comblées par les recherches futures.
Over the past decade, mitochondria have emerged as critical integrators of energy production, generation of reactive oxygen species (ROS), multiple cell death, and signaling pathways in the ...constantly beating heart. Clarification of the molecular mechanisms, underlying mitochondrial ROS generation and ROS-induced cell death pathways, associated with cardiovascular diseases, by itself remains an important aim; more recently, mitochondrial dynamics has emerged as an important active mechanism to maintain normal mitochondria number and morphology, both are necessary to preserve cardiomyocytes integrity. The two opposing processes, division (fission) and fusion, determine the cell type-specific mitochondrial morphology, the intracellular distribution and activity. The tightly controlled balance between fusion and fission is of particular importance in the high energy demanding cells, such as cardiomyocytes, skeletal muscles, and neuronal cells. A shift toward fission will lead to mitochondrial fragmentation, observed in quiescent cells, while a shift toward fusion will result in the formation of large mitochondrial networks, found in metabolically active cardiomyocytes. Defects in mitochondrial dynamics have been associated with various human disorders, including heart failure, ischemia reperfusion injury, diabetes, and aging. Despite significant progress in our understanding of the molecular mechanisms of mitochondrial function in the heart, further focused research is needed to translate this knowledge into the development of new therapies for various ailments.
In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF ...with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a β-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.
Dans cette mise à jour des Lignes directrices de la Société canadienne de cardiologie sur l'insuffisance cardiaque (IC), nous fournissons des recommandations complètes et des conseils pratiques pour la gestion pharmacologique des patients atteints d'IC avec une fraction d'éjection réduite (ICFER). Depuis la mise à jour complète de 2017 des Lignes directrices de la Société canadienne de cardiologie pour la prise en charge de l'IC, de nouvelles indications substantielles sont apparues au bénéfice des soins de ces patients. Nous nous concentrons en particulier sur le rôle des nouvelles thérapies pharmacologiques pour le traitement de l'ICFER, notamment les inhibiteurs des récepteurs de l'angiotensine et de la néprilysine, les inhibiteurs du nœud sinusal, les inhibiteurs du cotransporteur sodium-glucose de type 2 et les activateurs de la guanylate cyclase soluble, en conjonction avec d'autres thérapies ciblant l'ICFER et établies de longue date. Des recommandations actualisées sont également fournies dans le contexte du cadre clinique pour lequel chacune de ces molécules pourrait être prescrite ; la valeur potentielle de chaque thérapie est examinée, le cas échéant, pour une IC chronique, pour une IC apparue récemment et pour une hospitalisation pour IC. Nous définissons une nouvelle norme de soins pharmacologiques pour l'ICFER qui intègre quatre classes de médicaments thérapeutiques clés comme traitement standard pour la plupart des patients : un inhibiteur du récepteur de l'angiotensine et de la néprilysine (comme traitement de première ligne ou après titrage de l'inhibiteur de l'enzyme de conversion de l'angiotensine/inhibiteur du récepteur de l'angiotensine); un β-bloquant; un antagoniste des récepteurs des minéralocorticoïdes; et un inhibiteur du cotransporteur sodium-glucose de type 2. En outre, de nombreux patients atteints d'ICFER présenteront des caractéristiques cliniques pour lesquelles nous avons recommandé d'autres thérapies clés pour améliorer le pronostic de l'IC, notamment des inhibiteurs du nœud sinusal, des stimulateurs de guanylate cyclase soluble, l'association hydralazine/nitrates et/ou la digoxine. Enfin, une approche de traitement qui intègre des thérapies pharmacologiques prioritaires avec des thérapies non pharmacologiques et invasives après un diagnostic d'ICFER est mise en évidence.
The diagnostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare ...resource use, and randomized evidence for utility of NT-proBNP was lacking.
We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure (P<0.00001). Knowledge of NT-proBNP results reduced the duration of ED visit by 21% (6.3 to 5.6 hours; P=0.031), the number of patients rehospitalized over 60 days by 35% (51 to 33; P=0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per patient; P=0.023) over 60 days from enrollment. Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 (P<0.00001).
In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes.
Abstract 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.
Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this ...population-based retrospective study was undertaken to study them systematically.
From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population.
Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (
< 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (
< 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 (
= 0.069), while for South Asians, it was 64/10,000 (
= 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (
< 0.001); South Asians was 40/10,000 (
= 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (
< 0.001), while it was lower in South Asians at 2.1% (
< 0.001).
Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.
Background Heart failure trials use a variety of measures of functional capacity and quality of life. Lack of formal assessments of the relationships between changes in multiple aspects of ...patient-reported health status and measures of functional capacity over time limits the ability to compare results across studies. Methods Using data from HF-ACTION (N = 2331), we used the Pearson correlation coefficients and predicted change scores from linear mixed-effects modeling to demonstrate the associations between changes in patient-reported health status measured with the EQ-5D visual analog scale and the Kansas City Cardiomyopathy Questionnaire (KCCQ) and changes in peak VO2 and 6-minute walk distance at 3 and 12 months. We examined a 5-point change in KCCQ within individuals to provide a framework for interpreting changes in these measures. Results After adjustment for baseline characteristics, correlations between changes in the visual analog scale and changes in peak VO2 and 6-minute walk distance ranged from 0.13 to 0.28, and correlations between changes in the KCCQ overall and subscale scores and changes in peak VO2 and 6-minute walk distance ranged from 0.18 to 0.34. A 5-point change in KCCQ was associated with a 2.50-mL kg−1 min−1 change in peak VO2 (95% CI 2.21-2.86) and a 112-m change in 6-minute walk distance (95% CI 96-134). Conclusions Changes in patient-reported health status are not highly correlated with changes in functional capacity. Our findings generally support the current practice of considering a 5-point change in the KCCQ within individuals to be clinically meaningful.
Introduction
In patients with heart failure (HF) and reduced ejection fraction, increased heart rate (HR) is an independent risk factor for adverse outcomes. In systolic HF treatment with the
If
...inhibitor ivabradine trial (SHIFT), Ivabradine improved survival when added to conventional treatment including β-blockers. However, the extent of benefit in the real world is unclear. We examined the characteristics of patients on guideline-directed therapy and determined who had SHIFT-like characteristics.
Methods
A total of 1096 patients with chronic HF were reviewed from June 2014 to April 2015 in two HF clinics in Toronto: an academic institution (AI), and a community hospital (CH) clinic. SHIFT-like characteristics left ventricular ejection fraction (LVEF) ≤35%; sinus rhythm; and HR ≥ 70 bpm were described.
Results
For all patients, mean age was 75 ± 13 years, overall LVEF was 44 ± 15%, AI less than CH (41.9 ± 14.0% vs. 45.7 ± 15.0%;
p
< 0.0001). More than two-thirds of patients in both groups were on β-blockers; with less than one-third at target dose. The proportion of patients with SHIFT-like characteristics was 8.4% AI and 11.7% CH, respectively (
p
= 0.0658).
Conclusion
In HF clinics from both academic and community hospitals in Toronto, up-titration in the dose of β-blockers and other guideline therapy can be improved on. A small proportion of patients with HF and SHIFT-like characteristics may potentially benefit from the addition of Ivabradine, just approved in Canada; this number will be further reduced if target dosage for β-blockers is achieved.
Funding
Servier Inc.
PDF
