Tricuspid Regurgitation: What is the impact of TTVR treatment on sympathetic stress?

Context and objectives: sympathetic tone in the face of tricuspid regurgitation

Hyperactivity of the sympathetic nervous system (SNS) constitutes a major pathophysiological pivot in numerous cardiovascular pathologies, notably chronic heart failure. While SNS activation is initially compensatory to maintain blood pressure and cardiac output, its chronic persistence becomes deleterious, promoting adverse cardiac remodeling and increasing the risk of arrhythmia. In this context, functional tricuspid regurgitation (FTR) is a frequent comorbidity, systematically associated with a poor prognosis. Although the hemodynamic benefits of tricuspid valve interventions are documented, their consequences on autonomic regulation remain largely unexplored.

This prospective study aimed to evaluate muscle sympathetic nerve activity (MSNA) by microneurography — the gold standard technique for direct measurement of sympathetic activity in humans — in patients suffering from severe functional tricuspid regurgitation. The primary objective was to quantify changes in autonomic regulation following valve repair.

The authors test the hypothesis that TRF directly contributes to the overexpression of the sympathetic system. Consequently, the interventional reduction of this regurgitation could attenuate sympathetic hyperactivity, thus offering a neurohormonal therapeutic benefit complementary to mechanical correction. This research provides new insight into the link between structural improvement of the valve and the normalization of sympathetic tone.

Study design and population

This prospective clinical study recruited 28 consecutive patients with symptomatic severe functional tricuspid regurgitation (TR) (grade ≥ III). The objective was to evaluate the impact of transcatheter tricuspid valve repair (TTVR) on sympathetic nerve activity (SNA). The protocol was approved by the Ethics Committee of the University of Bonn and conducted in accordance with the Declaration of Helsinki.

Experimental protocol and follow-up

The initial evaluation included transthoracic echocardiography (TTE), a six-minute walk test (6MWT), biological analyses (NT-proBNP assay), and SNA measurement by microneurography. A complete follow-up including these same parameters was performed 12 months after the TTVR procedure.

Evaluation of sympathetic nerve activity (SNA)

Muscle sympathetic nerve activity (MSNA) was measured by microneurography (ADInstruments, Neuro Amp EX) according to the following parameters:

• Insertion site: 200 µm tungsten needle inserted into the common peroneal nerve (nervus peroneus longus) near the fibular head.
• Conditions: Recording started after 5 minutes of relaxation to ensure ANS normalization.
• Signal processing: Amplification between 50,000 and 100,000, band-pass filtering from 300 to 3000 Hz and signal integration.
• Measured variables: Burst frequency (bursts/min) and burst incidence (bursts/100 beats).

Subgroup analysis

Although 28 patients were initially included, repeated MSNA measurements were technically feasible in only a subgroup of 10 patients. Consequently, autonomic modulation analyses are presented as exploratory for this restricted cohort.

Recruitment results and technical feasibility of microneurography

The study prospectively included 28 consecutive patients presenting with severe (grade ≥ III) and symptomatic functional tricuspid regurgitation (TR). The protocol allowed for the evaluation of clinical, echocardiographic, and biological parameters over a 12-month follow-up after the transcatheter tricuspid valve repair (TTVR) procedure.

Feasibility of sympathetic nervous system assessment

Muscle sympathetic nerve activity (MSNA) was measured by microneurography at the peroneal nerve. Although the entire cohort was initially included, repeat MSNA measurements at 12 months were technically feasible in only a subgroup of 10 patients. Consequently, analyses regarding autonomic modulation are presented as exploratory.

The study integrated systematic measurements of NT-proBNP and the six-minute walk test (6MWT) to complement the clinical assessment. The authors highlight that the direct assessment of MSNA by microneurography is a validated but demanding method, requiring a 5-minute acclimatization period after puncture to normalize nerve activity before recording.

Sympathetic activity: an undervalued prognostic lever

In heart failure, hyperactivation of the sympathetic nervous system (SNS) is an initial compensatory mechanism that becomes chronically deleterious, promoting cardiac remodeling, arrhythmogenicity, and mortality. This study specifically focuses on severe functional tricuspid regurgitation (FTR), a pathology frequently associated with poor clinical outcomes. The objective was to determine whether percutaneous correction of FTR (TTVR) could modulate this sympathetic discharge.

Methodological precision: the use of microneurography

The study prospectively recruited 28 patients presenting with symptomatic ITF (grade ≥ III). The originality lies in the evaluation of muscle sympathetic nerve activity (MSNA) via microneurography. This technique uses a 200 µm tungsten electrode inserted into the peroneal nerve (nervus peroneus longus) for direct recording of postganglionic activity. This methodological choice surpasses standard indirect measurements due to its reliability and clinical validation as an independent predictor of survival.

Limits and exploratory framework

A major point of vigilance: while 28 patients were included in the global protocol (TTE, 6-minute walk test, NT-proBNP), repeated MSNA measurements at 12 months were technically feasible in only a subgroup of 10 patients. This technical constraint reduces statistical power and requires the data on autonomic modulation to be considered as exploratory. The study therefore focuses on a proof of concept rather than massive statistical generalization.

Clinical significance of the initial results

The analysis seeks to fill a gap in the literature, which has so far focused on hemodynamic and structural gains after TTVR. By evaluating the frequency (burst/min) and incidence (burst/100 beats) of discharges, the study allows for the visualization of the systemic impact of the valve. If the intervention reduces sympathetic hyperactivity, it could offer a physiological benefit extending beyond the simple reduction of valvular regurgitation, acting directly on one of the drivers of heart failure progression.

Study summary

This prospective study included 28 patients with severe symptomatic functional tricuspid regurgitation (FTR) (grade ≥ III) to evaluate the impact of transcatheter tricuspid valve repair (TTVR) on autonomic regulation. Muscle sympathetic nerve activity (MSNA) was measured by microneurography (200 µm needle) with a 12-month follow-up including NT-proBNP and the 6-minute walk test (6MWT) for a subgroup of 10 patients.

In concrete terms, for the practitioner:

• Identify autonomic risk: Sympathetic hyperactivity is a marker of limited survival; its persistence despite treatment suggests a high residual risk of remodeling and arrhythmia.
• Evaluate beyond the image: The success of a TEER does not only depend on the reduction of the regurgitation grade, but must be accompanied by an improvement in biomarkers (NT-proBNP) and exercise tolerance.
• Exploratory approach: Microneurography confirms that severe ITF contributes to systemic sympathetic overdrive, a major therapeutic target in chronic heart failure.

Technical Lexicon

SNA (Sympathetic Nerve Activity): Sympathetic nerve activity whose elevation, although initially compensatory to maintain systemic blood pressure, becomes deleterious in the long term by contributing to cardiac remodeling and mortality.

MSNA (Muscle Sympathetic Nerve Activity): Muscle sympathetic nerve activity, used as an independent marker to assess prognosis and risks of limited survival in patients with heart failure.

Microneurography: Validated reference method allowing the direct assessment of sympathetic nerve activity in humans by intraneural recording.

FTR (Functional Tricuspid Regurgitation): Functional tricuspid regurgitation, a frequent pathology in patients suffering from chronic heart failure (ischemic or non-ischemic) and associated with unfavorable clinical outcomes.

NT-proBNP: Cardiac biomarker measured by biological analysis to assess the clinical status and follow-up of patients during the study.

6MWT (Six-Minute Walk Test): Six-minute walk test used to assess in a standardised manner the functional capacity and exercise tolerance of patients.

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