Plasma angiotensin peptides represent a dynamic network that is altered in HF and in response to rhACE2. An increased plasma Ang-(1-7) level is linked to ACE inhibitor use, whereas acute HF reduced Ang-(1-7) levels and suppressed the Ang-(1-7)/Ang II ratio. Increased chymase activity elevated Ang II levels in failing human hearts. Use of rhACE2 effectively normalized elevated Ang II while increasing Ang-(1-7) and Ang-(1-9) levels.

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Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

AimsThis study aims to assess long-term changes in left ventricular ejection fraction (LVEF) together with echocardiographic markers of cardiac remodelling and their association with prognosis and patient-reported quality of life (QoL). Methods and resultsWe conducted a retrospective analysis of serial echocardiograms performed between January 2009 and December 2019 in 1089 patients (median age 63 years, 71.0% men) enrolled in the Mazankowski Heart Function Clinic Registry who had at least two echocardiograms separated by ≥12 months. We classified the patients into four subgroups by their baseline and LVEF trajectories: persistent heart failure with reduced ejection fraction (persistent HFrEF, n = 364), recovered ejection fraction (HFrecEF, n = 325), transient recovery in ejection fraction (HFtrecEF, n = 117), and preserved ejection fraction (HFpEF, n = 283); 4490 echocardiograms were included in the present analysis, with 4.1 ± 1.8 echocardiograms available per patient during follow-up. Reductions in echocardiographic markers of cardiac remodelling, including LVIDd [adjusted odds ratio (aOR): 2.22, 95% confidence interval (CI) 1.75-2.86], LVIDs (aOR: 2.44, 95% CI 2.00-2.94), left ventricular mass index (aOR: 1.15, 95% CI 1.09-1.22), E/e0 ratio (aOR: 1.15, 95% CI 1.02-1.30), left atrial volume index (aOR: 1.10, 95% CI 1.03-1.16), along with an increase in the maximum recommended daily dose of renin-angiotensin system inhibitors (aOR: 1.04, 95% CI 1.01-1.07) and mineralocorticoid-receptor antagonists (aOR: 1.06, 95% CI 1.01-1.11) at 2 years, strongly predicted the HFrecEF classification, which was further sustained at 5 years of follow-up. However, changes in these parameters were mostly absent in patients experiencing only a transient recovery in LVEF (HFtrecEF), closely resembling patients with persistent HFrEF. In the multivariable analysis, HFrecEF patients had lower risk of all-cause mortality alone [adjusted hazard ratio (aHR): 0.46, 95% CI 0.23-0.93], and composite all-cause (aHR: 0.59, 95% CI 0.49-0.73), cardiovascular (aHR: 0.47, 95% CI 0.36-0.61), and heart failure (aHR: 0.50, 95% CI 0.35-0.70) related hospitalizations with mortality than patients with persistent HFrEF. QoL assessed through the shortened Kansas City Cardiomyopathy Questionnaire-12 at the end of follow-up was greater in patients with HFrecEF by 5.2, 12.4, and 9.4 points than persistent HFrEF, HFtrecEF, and HFpEF, respectively. Conclusions Patients with HFrecEF experienced progressive normalization in echocardiographic markers of cardiac remodelling characterized by reductions in left ventricular dimensions and mass in tandem with reductions in left atrial volume and E/e0 ratio, which is associated with better prognosis and QoL.

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