Clin Res Cardiol (2022).

Single center experience of baroreflex activation therapy in heart failure with reduced ejection fraction.
C. Blanco1, E. B. Winzer1, N. Mangner1, K. M. Sveric1, S. Grimm1, M. Flechsig1, T. Madej2, M. Knaut2, A. Linke1
1Klinik für Innere Medizin, Kardiologie und Intensivmedizin, Herzzentrum Dresden GmbH an der TU Dresden, Dresden; 2Klinik für Herzchirurgie, Herzzentrum Dresden GmbH an der TU Dresden, Dresden;

Background: In heart failure with reduced ejection fraction (HFrEF) chronic sympathoexcitation and diminished baroreflex sensitivity are associated with higher mortality. Baroreflex activation therapy (BAT) in HFrEF patients was shown to reduce natriuretic peptide levels (NT-proBNP), to increase six minute walking distance, and to improve quality of life, at least in patients with NT-proBNP levels below 1600 pg/mL at baseline. The impact of BAT on heart failure hospitalizations and mortality is currently unknown. Experience with BAT in routine clinical practice is very limited.

Methods: We report on patient characteristics and clinical results after 12 months of treatment in a single centre experience of BAT in HFrEF. Due to small numbers, open-label design, and missing control group results are descriptive. Data are reported as absolute numbers and % or median with interquartile range.

Results: Since 2014, 30 patients with chronic HFrEF were treated with BAT (BarostimTM, CVRX Inc., Minneapolis, MN, USA).  Median age was 67 (63-77) years, 27 patients (90%) were male, median BMI was 29 (26-35). Eighteen patients (60%) suffered from ischemic heart disease. Four patients (18%) were in NYHA class IV at baseline, all others in NYHA class III, 25 patients (83%) were previously hospitalized due to decompensated heart failure. Renal function was impaired, eGFR 55 mL/min (34-70). Disease modifying drugs were used frequently and 10 patients (33%) were treated with Cardiac Resynchronization Therapy.
Complications associated with device implantation were rare: device pocket bleeding and red blood cell transfusion in 2 patients, transient nerve injury in 2 patients.
After 12 months of BAT blood pressure and heart rate remained stable. NYHA class significantly improved and left ventricular ejection fraction (LV-EF) increased (bsl. 25.5% (20.0-30.5), 12 months 30.0% (25.0-36.0), p<0.05). Left ventricular enddiastolic diameter and NT-proBNP levels (bsl. 3165 pg/mL (880-8085) vs. 1001 pg/mL (599-3820) did not change significantly.

Median follow-up was 16 (10-33) months. During this time 10 patients died. Mortality at 1 and 3 years was exactly as expected by MAGGIC risk score, and numbers of death/100 pt. years was 16.8, which was comparable to the findings in the placebo group of the VICTORIA trial (Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction) with 16.9 death/100 pt. years. VICTORIA included a similar patient population. However, the number of first and recurrent heart failure hospitalizations was 28.5/100 pt. years in our cohort, lower than what was seen in VICTORIA with 40.4 events/100 pt. years.
NYHA class IV, NT-proBNP levels > 1600 pg/mL, and eGFR < 30 ml/min at baseline but not Cardiac Resynchronization Therapy significantly predicted heart failure hospitalizations and death.

Conclusion: HFrEF patients in this single centre cohort treated with baroreflex activation therapy are clearly in a state of advanced heart failure. BAT was safe in an experienced centre. Results are promising since LV-EF and NYHA class improved after 12 months. NYHA class IV, NT-proBNP levels > 1600 pg/mL, and eGFR < 30 ml/min at baseline are predictors of worse outcome. Further studies are necessary to identify optimal candidates for BAT and clinical impact in HFrEF.