Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first‐in‐human clinical trial

Málek, Filip; Gajewski, Piotr; Zymliński, Robert; Janczak, Dariusz; Chabowski, Mariusz; Fudim, Marat; Martinča, Tomáš; Neužil, Petr; Biegus, Jan; Mates, Martin; Krüger, Andreas; Skalský, Ivo; Bapna, Anisha; Engelman, Zoar J.; Ponikowski, Piotr

doi:10.1002/ejhf.2209

Cited by 41 publications

(35 citation statements)

References 46 publications

(54 reference statements)

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“…Therefore, this study proposes the long-term effects of RIC on CHF and the reduced ejection fraction of a failing myocardium. Via this study, the myocardial expression of the somatotropic axis, adrenergic signaling, and calcium handling genes during HF with preserved ejection fraction and HF with reduced ejection fraction have been successfully demonstrated, thus, emphasizing the reciprocal organ interactions during HF, a position paper from the ESC working group on myocardial function, and highlighting the importance of surgical ablation of the right greater splanchnic nerve for the treatment of HF with preserved ejection fraction ( Ciccarelli et al, 2021 ; D’Assante et al, 2021 ; Málek et al, 2021 ). Previous study has shown that cardiomyocytes derived EVs injected into the hearts have been shown to promote cardiac recovery, and in this study, we showed that exosome released from the skeletal muscle contains musclin harboring exosomes that can protect the heart against the HF phenotype such as the CHF.…”

Section: Discussionmentioning

confidence: 79%

Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure

et al. 2021

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During acute heart failure (HF), remote ischemic conditioning (RIC) has proven to be beneficial; however, it is currently unclear whether it also extends benefits from chronic congestive, cardiopulmonary heart failure (CHF). Previous studies from our laboratory have shown three phases describing CHF viz. (1) HF with preserved ejection fraction (HFpEF), (2) HF with reduced EF (HFrEF), and (3) HF with reversed EF. Although reciprocal organ interaction, ablation of sympathetic, and calcium signaling genes are associated with HFpEF to HFrEF, the mechanism is unclear. The HFrEF ensues, in part, due to reduced angiogenesis, coronary reserve, and leakage of endocardial endothelial (EE) and finally breakdown of the blood-heart barrier (BHB) integrity. In fact, our hypothesis states that a change in phenotype from compensatory HFpEF to decompensatory HFrEF is determined by a potential decrease in regenerative, proangiogenic factors along with a concomitant increase in epigenetic memory, inflammation that combinedly causes oxidative, and proteolytic stress response. To test this hypothesis, we created CHF by aorta-vena-cava (AV) fistula in a group of mice that were subsequently treated with that of hind-limb RIC. HFpEF vs. HFrEF transition was determined by serial/longitudinal echo measurements. Results revealed an increase in skeletal muscle musclin contents, bone-marrow (CD71), and sympathetic activation (β2-AR) by RIC. We also observed a decrease in vascular density and attenuation of EE-BHB function due to a corresponding increase in the activity of MMP-2, vascular endothelial growth factor (VEGF), caspase, and calpain. This decrease was successfully mitigated by RIC-released skeletal muscle exosomes that contain musclin, the myokine along with bone marrow, and sympathetic activation. In short, based on proteome (omics) analysis, ∼20 proteins that appear to be involved in signaling pathways responsible for the synthesis, contraction, and relaxation of cardiac muscle were found to be the dominant features. Thus, our results support that the CHF phenotype causes dysfunction of cardiac metabolism, its contraction, and relaxation. Interestingly, RIC was able to mitigate many of the deleterious changes, as revealed by our multi-omics findings.

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Section: Discussionmentioning

confidence: 79%

Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure

et al. 2021

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“…Excess blood volume redistribution from splanchnic veins leads to increased cardiac filling pressures and exercise intolerance in patients with HF, and therapies aimed at reducing stressed blood volume, such as splanchnic nerve modulation, might be effective in HFpEF. 30,31 Assessment of PVP may be useful for identifying subjects who have a rapid rise of venous pressure during exercise and who might be candidates for such therapies.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Venous Pressure-Assisted Exercise Stress Echocardiography in the Evaluation of Pulmonary Hypertension During Exercise in Patients With Suspected Heart Failure With Preserved Ejection Fraction

Yang

Harada²,

Choi

et al. 2022

Circ: Heart Failure

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Background: Identification of elevated pulmonary artery (PA) pressures during exercise may provide diagnostic, prognostic, and therapeutic implications in heart failure with preserved ejection fraction. Although widely performed, exercise stress echocardiography may underestimate true PA pressures due to the difficulty in estimating right atrial pressure (RAP) during exercise. We hypothesized that peripheral venous pressure (PVP) could allow for reliable estimation of RAP, and thus PA pressures during exercise stress echocardiography. Methods: In protocol 1, we investigated the accuracy of PVP compared with simultaneously measured RAP at rest and during exercise right heart catheterization in 19 subjects. In protocol 2, we examined whether the addition of PVP to Doppler exercise echocardiography (tricuspid regurgitant velocity) would increase the ability to identify exercise-induced pulmonary hypertension compared with inferior vena cava-based RAP estimation in 60 patients with dyspnea. Results: In protocol 1, PVP was strongly correlated with simultaneously measured RAP at rest and during exercise ( r =0.77 and 0.90), with little overestimation of invasively measured RAP (bias 3.4 mm Hg at rest and 1.7 mm Hg during exercise). In protocol 2, PVP increased dramatically during exercise echocardiography (14±5 mm Hg) while an increase in inferior vena cava-based RAP was modest (6±4 mm Hg). Exercise PA pressures calculated from PVP and tricuspid regurgitant velocity were significantly higher than those estimated from inferior vena cava and the use of PVP increased the proportion of patients with exercise-induced pulmonary hypertension from 40% to 68%. Conclusions: PVP may prevent underestimation of PA pressures during exercise echocardiography and could be a preferred approach to identify exercise-induced pulmonary hypertension in patients with suspected heart failure with preserved ejection fraction.

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“…Permanent surgical ablation of the right-side GSN confirmed the long-term safety and efficacy of unilateral GSN ablation through at least 12 months in an open-label study. 4 There was no change in arterial blood pressure, resting heart rate, and serum creatinine. Similarly to temporary GSN block, at 3 months of follow-up, permanent GSN ablation reduced the mean PCWP by −4.5 mm Hg (95% CI: −14 to −2; P = 0.006) at 20 W exercise compared with baseline, and the effect carried over to peak exercise with a −5 mm Hg (95% CI: −11 to 0; P = 0.016) reduction.…”

mentioning

confidence: 90%

Splanchnic Nerve Ablation for Volume Management in Heart Failure

Fudim¹,

Engelman²,

Reddy³

et al. 2022

JACC: Basic to Translational Science

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Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first‐in‐human clinical trial

Cited by 41 publications

References 46 publications

Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure

Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure

Peripheral Venous Pressure-Assisted Exercise Stress Echocardiography in the Evaluation of Pulmonary Hypertension During Exercise in Patients With Suspected Heart Failure With Preserved Ejection Fraction

Splanchnic Nerve Ablation for Volume Management in Heart Failure

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