Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

AIMS: Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. METHODS AND RESULTS: We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12 months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12 months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P < 0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12 months (P = 0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P = 0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n = 6, 20%) and 3 years (n = 10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600 pg/mL, or estimated glomerular filtration rate (eGFR) <30 mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. CONCLUSIONS: Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

Peak O2 -pulse predicts exercise training-induced changes in peak V̇O2 in heart failure with preserved ejection fraction.

AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2 -pulse (V̇O2  × HR-1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2 , is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2 , peak O2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2 -pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2 -pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2 -pulse was associated with a decreased mean change in peak V̇O2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O2 -pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2 -pulse, patients with high O2 -pulse may need to use additional therapies to significantly increase peak V̇O2 .

Treatment of failed aortic bioprostheses: An evaluation of conventional redo surgery and transfemoral transcatheter aortic valve-in-valve implantation.

BACKGROUND: The use of bioprostheses for surgical aortic valve replacement increased substantially within the last years. In case of prosthesis failure, re-SAVR is standard of care, whereas valve-in-valve deployment of a transfemoral transcatheter aortic valve prosthesis (VinV-TFAVI) has recently emerged as an alternative. We sought to evaluate early safety, clinical efficacy, and all-cause 1-year-mortality of VinV-TFAVI and redo surgery for failing aortic bioprostheses (re-SAVR). METHODS AND RESULTS: Patients receiving either VinV-TFAVI (n = 147) or re-SAVR (n = 111) for a degenerated aortic bioprosthesis between 01/2006 and 05/2017 were included in this analysis. All-cause 1-year mortality was the primary outcome measure. Early safety and clinical efficacy according to VARC-2 endpoint definitions were evaluated at 30 days. Baseline characteristics differed significantly between both groups including age, STS-PROM, and incidence of relevant comorbidities. Re-stenosis was the predominant mode of failure in 45.9% of re-SAVR and 63.1% of VinV-TFAVI patients. The rate of "early safety" endpoints was lower with VinV-TFAVI (17.7% vs. 64.9%, p < 0.01), the rate of "clinical efficacy" endpoints was lower, e.g. better with re-SAVR (53.1% vs. 32.4%, p < 0.01). All-cause 1-year-mortality (VinV-TFAVI 8.8% vs re-SAVR 9.9%, p = 0.84) was not different. Treatment strategy was not associated with 1-year-mortality in a Cox regression analysis. The incidence of prosthesis-patient-mismatch was higher in VinV-TFAVI compared to re-SAVR. CONCLUSION: VinV-TFAVI represents a viable alternative for treatment of degenerated aortic bioprostheses in patients at increased surgical risk. However, in patients at low risk for reoperation, a better clinical efficacy and acceptable safety may favour re-SAVR.

Outcome of patients with previous coronary artery bypass grafting and severe calcific aortic stenosis receiving transfemoral transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the impact of previous coronary artery bypass grafting (CABG) on early safety at 30 days and 1-year mortality in patients receiving transcatheter aortic valve replacement (TAVR). BACKGROUND: The use of TAVR in patients with previous CABG suffering from severe aortic stenosis has increased in the last years. METHODS: Consecutive TAVR patients were stratified according to previous CABG versus no previous cardiac surgery (control). All-cause 1-year mortality and early safety at 30 days were evaluated. RESULTS: In the unmatched cohort and compared to control (n = 2,364), CABG (n = 260) were younger, more often male and suffered more often from comorbidities leading to an increased STS-score (p < .001). The rate of early safety events at 30 days was comparable between CABG and control (21.2% vs. 24.6%, p = .22) with a higher mortality in CABG (9.6% vs. 5.3%, p = .005). All-cause 1-year mortality was higher in CABG compared to controls (HR 1.51 [95%-CI 1.15-1.97], p = .003). Applying Cox regression analysis, both 30-day (HR 1.57 [95%-CI 0.97-2.53], p = .067) and all-cause 1-year mortality (HR 1.24 [95%-CI 0.91-1.70], p = .174) were not significantly different between groups. After propensity-score matching, the rate of early safety events at 30 days was lower in CABG compared to controls (21.6% vs. 31.7%, p = .02). Thirty-day (9.1% vs. 7.7%, p = .596) and all-cause 1-year mortality (24.0% vs. 23.1%, p = .520, HR 1.14 [95%-CI 0.77-1.69], p = .520) were not different between groups. CONCLUSION: In patients receiving TAVR, previous CABG was not associated with an increase in periprocedural complications and all-cause 1-year mortality when adjusted for other comorbidities.

Cardiac Surgery Compared With Antibiotics Only in Patients Developing Infective Endocarditis After Transcatheter Aortic Valve Replacement.

Background Infective endocarditis ( IE ) after transcatheter aortic valve replacement is a devastating complication associated with a high mortality. Our objective was to determine the impact of cardiac surgery (CS) and antibiotics ( IE - CS ) compared with medical treatment with antibiotics only ( IE - AB x) on 1-year mortality in patients developing IE after transcatheter aortic valve replacement. Methods and Results Patients developing IE after transcatheter aortic valve replacement were included in this retrospective analysis. All-cause 1-year mortality was the primary end point. A total of 20 patients underwent IE - CS compared with 44 patients treated by IE - AB x. In this unmatched cohort, patients treated by IE - AB x were older ( P=0.006), had a higher Society of Thoracic Surgeons score ( P=0.029), and more often had severe chronic kidney disease ( P=0.037). One-year mortality was not different between groups ( IE -CS versus IE-ABx, 65% versus 68.2%; P=0.802). The rate of any complication during treatment was higher in the IE - CS group ( P=0.024). In a matched cohort, baseline characteristics were not significantly different. All-cause 1-year mortality was not different between groups ( IE -CS versus IE-ABx, 65% versus 75%; P=0.490). A Cox regression analysis revealed any indication for surgery (hazard ratio, 6.20; 95% confidence interval, 1.80-21.41; P=0.004), sepsis on admission (hazard ratio, 4.03; 95% confidence interval, 1.97-8.24; P<0.001), and mitral regurgitation ≥2 (hazard ratio, 2.91; 95% confidence interval, 1.33-6.37) as factors associated with 1-year mortality. Conclusions In patients developing IE after transcatheter aortic valve replacement, mortality was predicted by the severity of IE and concomitant mitral regurgitation. In this small, and therefore statistically limited, but high-risk patient cohort, CS provided no significant mortality benefit compared with medical therapy. Individual decision making by a "heart and endocarditis team" is necessary to offer those patients the most reasonable treatment option.