CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction.

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 ß-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.

A systematic review of perceived risks, psychological and behavioral impacts of genetic testing.

Genetic testing may enable early disease detection, targeted surveillance, and result in effective prevention strategies. Knowledge of genetic risk may also enable behavioral change. However, the impact of carrier status from the psychological, behavior, and perceived risk perspectives is not well understood. We conducted a systematic review to summarize the available literature on these elements. An extensive literature review was performed to identify studies that measured the perceived risk, psychological, and/or behavioral impacts of genetic testing on individuals. The search was not limited to specific diseases but excluded the impacts of testing for single gene disorders. A total of 35 articles and 30 studies were included. The studies evaluated hereditary nonpolyposis colorectal carcinoma, hereditary breast and ovarian cancer, and Alzheimer disease. For affective outcomes, the majority of the studies reported negative effects on carriers but these were short-lived. For behavioral outcomes, an increase in screening behavior of varying rates was demonstrated in carriers but the change in behaviors was less than expected. With respect to perceived risk, there were generally no differences between carriers and noncarriers by 12 months after genetic testing and over time risk perception decreased. Overall, predispositional genetic testing has no significant impact on psychological outcomes, little effect on behavior, and did not change perceived risk. It seems as though better patient education strategies are required. Our data would suggest better knowledge among carriers would not have significant psychological impacts and therefore, it is worth pursuing improved educational strategies.

Spironolactone for difficult to control hypertension in chronic kidney disease: an analysis of safety and efficacy.

Spironolactone is effective at treating difficult to control hypertension in the general population, and it is unknown if it is safe or effective for those with chronic kidney disease (CKD) and difficult-to-control hypertension. In a retrospective cohort design, 88 patients with difficult-to-control hypertension study were assessed for blood pressure (BP) response to spironolactone as well as for biochemical changes. In the CKD group (34 patients), the average systolic BP (SBP) fell from 153 ± 18 to 143 ± 20 mm Hg (P = .006) compared with a fall in SBP from 150 ± 17 to 135 ± 17 mm Hg (P < .0001) in the non-CKD group (P < .0001). In 44% of those with CKD and 59% of those without CKD, SBP decreased by >10 mm Hg (defined as responders; P = .22). Potassium rose by 0.5 ± 0.6 mmol/L in the CKD group and 0.3 ± 0.5 mmol/L in the non-CKD group (P = .12). The overall incidence of hyperkalemia was 5.7% in the CKD group and 0% in the non-CKD group (P = .07). Spironolactone is associated with a significant fall in BP among those with CKD and difficult-to-control BP. It is associated with a modest rise in serum potassium, which is more pronounced among those with glomerular filtration rate below 45 mL/minute.