Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Ventricular-Arterial Coupling in Heart Failure with preserved Ejection Fraction – Importance of Sympathetic Tone – Insights from Computer Modeling.
K.-P. Rommel1, S. Pagoulatou2, K.-P. Kresoja1, S. Rosch1, A. Schöber1, M. von Roeder1, H. Thiele1, K. Fengler1, N. Stergiopulos2, P. Lurz1
1Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig - Universität Leipzig, Leipzig; 2Laboratory of Hemodynamics and Cardiovascular Technology, Institute of Bioengineering / Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH;

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with limited therapeutic options. Pathological ventricular-arterial coupling (VAC) contributes importantly to hemodynamic limitations with increased impedance to generated flow and excessive, as well as premature, wave reflections in the setting of elevated arterial stiffness. We recently demonstrated that attenuation of sympathetic tone is associated with favorable effects on left ventricular (LV) stroke work, LV filling pressures as well as aortic distensibility. Whether sympathetic tone impacts on arterial functional properties and thus LV pulsatile load remains controversial. We therefore sought to investigate changes in VAC before and after interventional sympathetic tone modulation (STM) in HFpEF.

Methods: HFpEF patients and patients without heart failure (NoHF) were identified according to ESC guideline recommendations and underwent STM at our center with clinical follow-up at three month. A recently developed complete 1-D computer model of the arterial tree, comprising 103 arterial segments, was applied and optimized using invasive aortic pressure tracings and pulse-wave velocity (PWV) measures. Brachial blood pressure, aortic flow curves, LV volumes and E/e’ ratio served as non-invasive inputs. Key parameters of pulsatile LV load were compared from baseline to follow up, including the characteristic impedance of the proximal aorta (Zc), the magnitude of wave reflections (reflection coefficient, RC, i.e. pulse pressure of backward/forward wave), the timing of wave reflections (backward transit time normalized to ejection time, BTT) and the total compliance of the arterial tree (TAC).

Results As compared to NoHF(n=30), HFpEF patients(n=30) were older (66[62,72]vs.61[53,67]years, p=0.02), were more often female (50vs.23%,p=0.03), had more often diabetes (60vs.30%,p=0.02), higher  HFA-PEF Scores (5[4,6]vs.3[1,4],p<0.01), while LV ejection fraction was normal in both groups (63[61,70]vs. 61[58,66]%,p=0.09). HFpEF patients demonstrated elevated invasive PWV (17[12,22]vs.13[11,16]m/s,p<0.01), lower TAC, higher Zc, a higher RC and a shorter BTT (p<0.01 for all, Figure 1), compatible with higher arterial stiffness and higher intensity/early return of the reflected pressure wave.

In response to STM day time systolic and diastolic blood pressure (-10[-3,-15]/-6[-3,-10]mmHg,p<0.01) andblood pressure variability (-2 [1,-6],p=0.01) on ambulatory blood pressure monitoring decreased in the overall cohort, indicating attenuation of sympathetic tone.

In HFpEF patients TAC (p<0.01) and BTT (p=0.01) increased , Zc (p<0.01) and RC (p=0.03) decreased after the intervention, suggesting a reduction in aortic stiffness and lower intensity as well as later return of the reflected wave. No alteration were observed in NoHF patients (Figure 1). These hemodynamic improvements were accompanied by a symptomatic benefit in HFpEF patients (NYHA≥II 100vs.63%,p<0.01) and a reduction in NT-pro-BNP (315[218, 592]vs.246[142, 446],p<0.01).

Conclusion: HFpEF is characterized by heightened aortic stiffness, increased LV pulsatile load and thus unfavorable VAC, which can readily be assessed using computer modeling. These abnormalities can partly be normalized by attenuation of sympathetic tone. Our findings imply an important contribution of sympathetic tone to arterial dysfunction in HFpEF and prompt further studies to investigate the clinical impact of STM in these patients.



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