Beneficial and harmful effects of sacubitril/valsartan in patients with heart failure: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

Current guidelines recommend angiotensin receptor blocker neprilysin inhibitors (ARNI) (sacubitril/valsartan) as a replacement for angiotensin-converting-enzymeinhibitor (ACE-I) in heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy. The effects of ARNIs have not previously been assessed in a systematic review. We searched for relevant trials until October 2019 in CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, CNKI, VIP, WanFang and CBM. Our primary outcomes were all-cause mortality and serious adverse events. We systematically assessed the risks of random errors and systematic errors. PROSPERO registration: CRD42019129336. 48 trials randomising 19 086 participants were included. The ARNI assessed in all trials was sacubitril/valsartan. ACE-I or ARB were used as control interventions. Trials randomising HFrEF participants (27 trials) and heart failure with preserved ejection fraction (HFpEF) participants (four trials) were analysed separately. In HFrEF participants, meta-analyses and Trial Sequential Analyses showed evidence of a beneficial effect of sacubitril/valsartan when assessing all-cause mortality (risk ratio (RR), 0.86; 95% CI, 0.79 to 0.94) and serious adverse events (RR, 0.89; 95% CI, 0.86 to 0.93); and the results did not differ between the guideline recommended target population and HFrEF participants in general. We found no evidence of an effect of sacubitril/valsartan in HFpEF participants. Sacubitril/valsartan compared with either ACE-I or ARB seems to have a beneficial effect in patients with HFrEF. Our results indicate that sacubitril/valsartan might be beneficial in a wider population of patients with heart failure than the guideline recommended target population. Sacubitril/valsartan does not seem to show evidence of a difference compared with valsartan in patients with HFpEF.

Left Ventricular Mass Assessment by 1- and 2-Dimensional Echocardiographic Methods in Hemodialysis Patients: Changes in Left Ventricular Volume Using Echocardiography Before and After a Hemodialysis Session.

RATIONALE & OBJECTIVE: Left ventricular (LV) mass (LVM) is a predictor of cardiovascular morbidity and mortality and commonly calculated using 1-dimensional (1D) echocardiographic methods. These methods are vulnerable to small measurement errors and LVM may wrongly change according to changes in LV volume (LVV). Less commonly used 2-dimensional (2D) methods can accommodate to the changes in LVV and may be a better alternative among patients receiving hemodialysis (HD) with large fluid fluctuations. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease receiving HD. EXPOSURE: One HD session. ANALYTICAL APPROACH: Transthoracic echocardiography was performed right before and after HD. LVM was calculated using 1D (Devereux, Penn, and Teichholz) and 2D methods (truncated ellipsoid and area-length). OUTCOMES: Significant differences in LVM after HD. RESULTS: We compared dimensions, LVV and LVM, in 53 patients (mean age, 63 ± 15 years; 66% men). For each 1-L increase in ultrafiltration volume (UFV), LV internal diameter decreased 1.1 mm (95% CI, 0.5-1.7 mm; P = 0.001). Patients were divided into 2 groups by the median UFV of 1.6 L. Patients with UFV > 1.6 L had significant smaller LVV and LV internal diameter after HD. LVM calculated using 1D methods decreased according to changes in LVV. Conversely, LVM calculated using 2D methods was not significantly different after HD. No significant change in differences between diastolic - systolic myocardial thickness or LVM as assessed using 1D and 2D methods was observed before and after HD, indicating that LVM remained constant despite HD. LIMITATIONS: We did not use contrast enhancement, 3-dimensional methods, or cardiac magnetic resonance. CONCLUSIONS: LVM calculated using 2D methods, truncated ellipsoid and area-length, is less affected by fluctuations in fluid and LVV, in contrast to 1D methods. Complementary LVM calculation using 2D methods is encouraged, especially in patients with large fluid fluctuations in which increased LVM using a 1D method has been detected.

The effects of adding angiotensin receptor neprilysin inhibitors to usual care in patients with heart failure: a protocol for a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

BACKGROUND: Heart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldosterone system. However, new drugs are currently being added to the recommended guideline therapy. The latest drug to be added combines inhibition of the renin-angiotensin-aldosterone system pathway with inhibiting the neprilysin enzyme and is therefore classified as an ARNI. Our objective is to identify the beneficial and harmful effects of ARNIs in the treatment of patient with heart failure. METHODS: This protocol for a systematic review was undertaken using the recommendations of the Cochrane, the Preferred Report Items of Systematic reviews with Meta-Analysis Protocols, and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ARNIs in the treatment of patients with heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS to identify relevant trials. We will also search for grey literature and unpublished trials. Extracted data will be analysed using Review Manager 5, STATA 5, and Trial Sequential Analysis. Our primary outcomes will be all-cause mortality and serious adverse events. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the GRADE assessment. DISCUSSION: The present systematic review will have the potential to aid clinicians in decision-making and thereby, benefit patients with heart failure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019129336.

Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure.

BACKGROUND: The value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in terms of diagnosis and prognosis in congestive heart failure (CHF) and left ventricular systolic dysfunction (LVSD) has been demonstrated previously in various populations, but data on primary care patients are sparse. The aim of this study was to evaluate the diagnostic and prognostic performance of NT-proBNP in primary care patients with suspected CHF. METHODS AND RESULTS: Three hundred sixty-seven consecutive patients (mean age, 68.8 years; range, 39.0-84.0 years) who had been referred by their general practitioner for echocardiographic evaluation because of suspected CHF. In all patients, NT-proBNP was measured at baseline and left ventricular ejection fraction (LVEF) was estimated with echocardiography. LVSD (LVEF < or =0.40) was found in 9% of the patients. NT-proBNP was significantly higher in patients with LVSD (P < .0001). With predefined cut off values for NT-proBNP (125 pg/mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of LVSD were 0.97, 0.46, 0.15 and 0.99, respectively. Area under the receiver operating characteristic curve was 0.87. The application of an age-differentiated cut-off value for NT-proBNP (125 pg/mL for <75 years old and 450 pg/mL for > or =75 years old) did not increase diagnostic performance. Patients were followed for a median of 778 days; 8% of the patients died during the follow-up period. The mortality rate was higher in patients with NT-proBNP of >125 pg/mL than in patients with normal values (P < .002, log rank), and the difference persisted after controlling for age, gender, and LVEF (hazard ratio per unit increase in log NT-proBNP, 2.2; range, 1.2-4.1; P = .015). CONCLUSION: In primary care patients who were referred for echocardiography because of suspected CHF, NT-proBNP values <125 pg/mL effectively rule out LVSD. Furthermore low NT-proBNP values are associated with a lower risk of death, independently of age, gender, and LVEF.

Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, double-blind study.

OBJECTIVE: To characterise the effect of long-term low-dose growth hormone (GH) treatment on cardiac anatomy and function. METHODS: 20 patients with multiple pituitary hormone deficiencies, including severe acquired GH deficiency (GHD), were randomly assigned to GH or placebo (P) for 18 months. Echocardiographic measurements were performed at baseline and after 6, 12 and 18 months. RESULTS: At baseline, 8 of 20 patients had diastolic dysfunction (6 severe and 2 borderline), while only 1 had systolic dysfunction. None of the investigated parameters of diastolic or systolic function changed during treatment. CONCLUSION: In adult onset GHD, diastolic dysfunction was present in 40% of the patients. None of the investigated values were different after 18 months of GH compared to placebo.