Incidence of atrial and ventricular arrhythmias in obese patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

AIM: To compare clinical outcomes among patients with heart failure and reduced ejection fraction (HFrEF) according to body mass index (BMI) after initiating treatment with an angiotensin-receptor neprilysin inhibitor (ARNI). METHODS: We gathered data from 2016 to 2020 at the University Medical Center Mannheim; 208 consecutive patients were divided into two groups according to BMI (< 30 kg/m2 ; n = 116, ≥ 30 kg/m2 ; n = 92). Clinical outcomes, including mortality rate, all-cause hospitalizations and congestion, were systematically analysed. RESULTS: At the 12-month follow-up, the mortality rate was similar in both groups (7.9% in BMI < 30 kg/m2 vs. 5.6% in BMI ≥ 30 kg/m2 ; P = .76). All-cause hospitalization before ARNI treatment was comparable in both groups (63.8% in BMI < 30 kg/m2 vs. 57.6% in BMI ≥ 30 kg/m2 ; P = .69). After ARNI treatment, the hospitalization rate was also comparable in both groups at the 12-month follow-up (52.2% in BMI < 30 kg/m2 vs. 53.7% in BMI ≥ 30 kg/m2 ; P = .73). Obese patients experienced more congestion compared with non-obese patients at follow-up, without statistical significance (6.8% in BMI < 30 kg/m2 vs. 15.5% in BMI ≥ 30 kg/m2 ; P = .11). Median left ventricular ejection fraction (LVEF) improved in both groups, but significantly more in non-obese compared with obese patients at the 12-month follow-up (from 26% [3%-45%] [min.-max.] vs. 29% [10%-45%] [min.-max.] [P = .56] to 35.5% [15%-59%] [min.-max.] vs. 30% [13%-50%] [min.-max.] [P = .03], respectively). The incidence of atrial fibrillation (AF), non-sustained (ns) and sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) was less in non-obese than in obese patients after initiation of sacubitril/valsartan at the 12-month follow-up (AF: 43.5% vs. 53.7%; P = .20; nsVT: 9.8% vs. 28.4%; P = .01; VT: 14.1% vs. 17.9%; P = .52; VF: 7.6% vs. 13.4%; P = .23). CONCLUSIONS: The incidence of congestion in obese patients was higher compared with non-obese patients. LVEF improved significantly more in non-obese compared with obese HFrEF patients. Furthermore, AF and the ventricular tachyarrhythmia rate were revealed more in obesity compared with those without obesity at the 12-month follow-up.

The impact of sacubitril/valsartan on outcome in patients suffering from heart failure with a concomitant diabetes mellitus.

BACKGROUND: Guidelines classify sacubitril/valsartan as a significant part of medical treatment of heart failure with reduced ejection fraction (HFrEF). Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes patients treated with sacubitril/valsartan on outcome and echocardiography parameters is not well studied yet. AIMS: The aim of the present study was to compare the impact of sacubitril/valsartan on life-threatening arrhythmias, atrial fibrillation, different echocardiography parameters and congestion rate in patients suffering from HFrEF according to the diagnosis diabetes mellitus or no diabetes mellitus. METHODS AND RESULTS: Consecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (n = 87, median age 68 years interquartile range (IQR) [32-87]) or no diabetes mellitus (n = 153, median age 66 year IQR [34-89]). Different comorbidities and outcome data were evaluated over a follow-up period of 24 months. Arterial hypertension (87% vs. 64%; P < 0.01) and coronary artery disease (74% vs. 60%; P = 0.03) were more often documented in patients with diabetes mellitus compared with patients without diabetes mellitus. Over the follow-up of 24 months several changes were noted in both subgroups: Median left ventricular ejection fraction (EF) increased significantly in non-diabetes (27% IQR [3-44] at baseline to 35% IQR [13-64]; P < 0.001), but not in diabetic patients (29% IQR [10-65] at baseline to 30% IQR [13-55]; P = 0.11). Accordingly, NT-proBNP and troponin-I levels decreased significantly in non-diabetes patients (NT-brain natriuretic peptide [NT-proBNP] from median 1445 pg/mL IQR [12.6-74 676] to 491 pg/mL IQR [13-4571]; P < 0.001, troponin-I levels from 0.099 ng/mL IQR [0.009-138.69] to 0.023 ng/mL IQR [0.006-0.635]; P < 0.001), but not in diabetic patients (NT-proBNP from 1395 pg/mL IQR [100-29 924] to 885 pg/mL IQR [159-4331]; P = 0.06, troponin-I levels from 0.05 ng/mL IQR [0.013-103.0] to 0.020 ng/mL IQR [0.015-0.514]; P = 0.27). No significant change of laboratory parameters e. g. glomerular filtration rate, potassium level and creatinine levels were found in diabetes or non-diabetes patients. Comparing further echocardiography data, left atrial surface area, right atrial surface area, E/A ratio did not show a significant change either in the diabetes or non-diabetes group. However, the tricuspid annular plane systolic excursion was significantly increased in non-diabetes mellitus patients (from 17 mm IQR [3-31] to 18 mm [2.5-31]; P = 0.04), and not in diabetic s patients (17.5 mm IQR [8-30] to 18 mm IQR [14-31]; P = 0.70); the systolic pulmonary artery pressure remained unchanged in both groups. During follow-up, a similar rate of ventricular tachyarrhythmias was observed in both groups. The congestion rate decreased significantly in both groups, in diabetes patients (44.4% before sacubitril/valsartan and 13.5% after 24 months treatment; P = 0.0009) and in non-diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24 months treatment; P = 0.0004). The all-cause mortality rate was higher in patients with diabetes mellitus as compared with those without diabetes (25% vs. 8.1%; P < 0.01). CONCLUSIONS: Sacubitril/valsartan reverses cardiac remodelling in non-diabetes patients. However, it reduces the congestion rate in diabetes and non-diabetes patients. The rates of ventricular tachyarrhythmias were similar in DM compared with non-DM over follow-up. The mortality rate remained to be over follow-up higher in diabetes patients compared with non-diabetes; however, it was lower compared with published data on diabetes and concomitant HFrEF not treated with sacubitril/valsartan.

Hemodynamic Effects of Sacubitril/Valsartan in Patients with Reduced Left Ventricular Ejection Fraction Over 24 Months: A Retrospective Study.

BACKGROUND: The effects of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction (HFrEF) were recently reported. However, the hemodynamic impact of this well-established treatment in patients with HFrEF has been poorly systematically researched. AIM: We aimed to investigate the hemodynamic effects of sacubitril/valsartan among patients with HFrEF. METHODS: Between 2016 and 2020, we retrospectively collected data for patients with HFrEF treated at the University Medical Center Mannheim, Germany. Data for 240 patients with HFrEF were available. We systematically analyzed echocardiographic parameters, all-cause hospitalization, and congestion rate. RESULTS: The left ventricular ejection fraction (LVEF) improved from a median (minimum; maximum) of 28% (3; 65) before initiation of sacubitril/valsartan to a median of 34% (13; 64) at 24-month follow-up (p < 0.001). Systolic pulmonary atrial pressure (PAPsys) decreased from a median of 30 mmHg (13; 115) to 25 mmHg (20; 80) at 24-month follow-up (p = 0.005). The median (minimum; maximum) tricuspid annular plane systolic excursion improved from 17 mm (3; 31) at baseline to 20 mm (9; 30) at 12-month follow-up (p = 0.007). The incidence of severe and moderate mitral, tricuspid, and aortic valvular insufficiency improved after treatment. Hospitalization and congestion rates reduced at 24-month follow-up. The mortality rate in echocardiographic and functional nonresponders was higher than in responders (12.1 vs. 5.2%; p = 0.1 and 11.3 vs. 3.1%; p = 0.01, respectively). CONCLUSION: Follow-up 24 months after starting treatment with sacubitril/valsartan revealed sustained improvements in echocardiographic parameters, including LVEF, PAPsys, and cardiac valvular insufficiency. Rates of all-cause hospitalization and congestion had decreased significantly at follow-up. The mortality rate was higher in echocardiographic and functional nonresponders.

Comparison of the prognosis and outcome of heart failure with reduced ejection fraction patients treated with sacubitril/valsartan according to age.

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).

Lay abstract Many patients still die from heart failure (HF). Better drugs for this condition were developed over the past 20 years. The drug combination sacubitril/valsartan improves heart function and might lower the risk of sudden cardiac death from a fast heart rate (ventricular arrythmia). More research is needed on the effect of sacubitril/valsartan on older patients with HF. We wanted to see how sacubitril/valsartan affects older patients with HF. Seventy-six patients above 65 years of age were compared with 51 patients below 65 years. A year later, the number of ventricular arrhythmias was similar in both groups. Side effects were more common in older patients. At 2 years, there were more deaths in the older group. In summary, side effects of sacubitril/valsartan could be an obstacle to treating older patients. Finding better concepts to treat older patients with a weak heart remains necessary.

Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy.

BACKGROUND: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. METHODS AND RESULTS: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). CONCLUSIONS: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

Impact of Sacubitril/Valsartan on the Long-Term Incidence of Ventricular Arrhythmias in Chronic Heart Failure Patients.

BACKGROUND: Sacubitril/valsartan decreased the risk of sudden cardiac death (SCD) in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, long-term data are sparse. OBJECTIVE: The aim of the present study was to compare the incidence of life-threatening arrhythmias consisting of ventricular tachycardia and/or ventricular fibrillation before and after initiation of sacubitril/valsartan treatment. METHODS: Out of 12,000 patients with HFrEF from 2016-2018, 148 patients were newly prescribed sacubitril/valsartan, but the long-term data of only 127 patients were available and included in this study. RESULTS: Patients with an average age of 66.8 ± 12.1 had a median left ventricular ejection fraction (LVEF) of 25% (interquartile range (IQR) 5.00-45.00) and 30% (IQR 10.00-55.00, p < 0.0005) before and after sacubitril/valsartan treatment, respectively. Systolic blood pressure decreased from 127.93 ± 22.01 to 118.36 ± 20.55 mmHg (p = 0.0035) at 6 months of follow-up. However, in 59 patients with a long-term outcome of 12 months, ventricular arrhythmias persistently increased (ventricular fibrillation from 27.6 to 29.3%, ventricular tachycardia (VT) from 12% to 13.8%, and nonsustained VT from 26.6 to 33.3%). CONCLUSIONS: Sacubitril/valsartan does not reduce the risk of ventricular tachyarrhythmias in chronic HFrEF patients over 12 months of follow-up.