Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices.

BACKGROUND: Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear. OBJECTIVE: The purpose of this study was to explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias compared to angiotensin inhibition in rEFHF patients with an implantable cardioverter-defibrillator (ICD) and remote monitoring. METHODS: We prospectively included 120 patients with ICD and (1) New York Heart Association functional class ≥II; (2) left ventricular ejection fraction ≤40%; and (3) remote monitoring. For 9 months, patients received 100% angiotensin inhibition with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blockers, and mineraloid antagonist. Subsequently, ACEi or ARB was changed to sacubitril-valsartan in all patients, who were followed for 9 months. Appropriate shocks, nonsustained ventricular tachycardia (NSVT), premature ventricular contraction (PVC) burden, and biventricular pacing percentage were analyzed. RESULTS: Patients were an average age of 69 ± 8 years and had mean left ventricular ejection fraction of 30.4% ± 4% (82% ischemic). Use of beta-blockers (98%), mineraloid antagonist (97%) and antiarrhythmic drugs was similar before and after sacubitril-valsartan. Sacubitril-valsartan significantly decreased NSVT episodes (5.4 ± 0.5 vs 15 ± 1.7 in angiotensin inhibition; P <.002), sustained ventricular tachycardia, and appropriate ICD shocks (0.8% vs 6.7% in angiotensin inhibition; P <.02). PVCs per hour decreased after sacubitril-valsartan (33 ± 12 vs 78 ± 15 in angiotensin inhibition; P <.0003) and was associated with increased biventricular pacing percentage (from 95% ± 6% to 98.8% ± 1.3%; P <.02). CONCLUSION: Angiotensin-neprilysin inhibition decreased ventricular arrhythmias and appropriate ICD shocks in rEFHF patients under home monitoring compared to angiotensin inhibition.

Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients.

INTRODUCTION: In critically ill patients sudden changes in glomerular filtration rate (GFR) are not instantly followed by parallel changes in serum creatinine. The aim of the present study was to analyze the utility of serum cystatin C as a marker of renal function in these patients. METHODS: Serum creatinine, serum cystatin C and 24-hour creatinine clearance (CCr) were determined in 50 critically ill patients (age 21-86 years; mean Acute Physiology and Chronic Health Evaluation II score 20 +/- 9). They did not have chronic renal failure but were at risk for developing renal dysfunction. Serum cystatin C was measured using particle enhanced immunonephelometry. Twenty-four-hour body surface adjusted CCr was used as a control because it is the 'gold standard' for determining GFR. RESULTS: Serum creatinine, serum cystatin C and CCr (mean +/- standard deviation [range]) were 1.00 +/- 0.85 mg/dl (0.40-5.61 mg/dl), 1.19 +/- 0.79 mg/l (0.49-4.70 mg/l), and 92.74 +/- 52.74 ml/min per 1.73 m2 (8.17-233.21 ml/min per 1.73 m2), respectively. Our data showed that serum cystatin C correlated better with GFR than did creatinine (1/cystatin C versus CCr: r = 0.832, P < 0.001; 1/creatinine versus CCr: r = 0.426, P = 0.002). Cystatin C was diagnostically superior to creatinine (area under the curve [AUC] for cystatin C 0.927, 95% confidence interval 86.1-99.4; AUC for creatinine 0.694, 95% confidence interval 54.1-84.6). Half of the patients had acute renal dysfunction. Only five (20%) of these 25 patients had elevated serum creatinine, whereas 76% had elevated serum cystatin C levels (P = 0.032). CONCLUSION: Cystatin C is an accurate marker of subtle changes in GFR, and it may be superior to creatinine when assessing this parameter in clinical practice in critically ill patients.