Editorial comment
Renal denervation in heart failure: Modulating the sympathetic nervous system
Desnervação renal na insuficiência cardíaca: modular o sistema nervoso simpático
Joana Delgado Silva
Centro Hospitalar e Universitário de Coimbra, Hospital Geral, Coimbra, Portugal
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The terminology of HF has recently been redefined and patients with an ejection fraction (EF) of 40-49% (the so-called ‘gray area’) now being classified as having ‘heart failure with mid-range ejection fraction’, as opposed to ‘HF with reduced EF’ (<40%) and ‘HF with preserved EF’ (EF ≥50%).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathophysiology of HF is highly complex and involves the activation of compensatory mechanisms including the renin-angiotensin-aldosterone system, the sympathetic nervous system (SNS) and arginine vasopressin release, probably as a consequence of hemodynamic changes induced by a dysfunctional myocardium.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Activation of the SNS leads to excessive release and decreased uptake of norepinephrine. This autonomic hyperactivity has long been known to be directly related to the worsening of HF, by inducing myocyte enlargement and interstitial growth and remodeling, leading to increased myocardial mass and chamber dilatation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> The SNS thus became a therapeutic target, and there is evidence that continuing pharmacological beta-blockade has favorable prognostic implications in both ischemic and non-ischemic cardiomyopathies.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Renal denervation (RDN) is a percutaneous procedure which aims to achieve selective disruption of the sympathetic nerve endings in the renal arterial wall. It is currently under investigation as a promising technique for the treatment not only of hypertension (with varying treatment effects) but also of other clinical entities associated with an increased sympathetic drive such as advanced HF, sleep apnea and life-threatening cardiac arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> Two pilot studies have been published that aimed to prove the effectiveness of RDN in patients with HF. The REACH-Pilot was a first-in-man study which assessed the safety of RDN in seven patients with symptomatic chronic systolic HF (New York Heart Association [NYHA] class III or IV), EF of 45±15% and without hypertension. At six months all patients were symptomatically improved, there was an increase in the six-minute walk distance (Δ=27.1±9.7 m, p=0.03) and diuretics were reduced or stopped in four patients (p=0.046). No significant differences were observed in EF. This study had clear limitations (population and design, among others) and was underpowered for several parameters, but established the need for additional evidence.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Chen et al. conducted a randomized prospective pilot study which included 60 patients (30 in the RDN group and 30 in the optimal medical therapy group) in NYHA II-IV with EF ≤40%. Renal denervation was performed with a saline irrigated catheter. At six-month follow-up EF (from 31.1±5.7% to 41.9±7.9%, p<0.001), the six-minute walk distance (from 285.5±84.3 m to 374.9±91.9 m, p=0.043), NYHA classification (p<0.001) and NT-pro-BNP levels (p<0.001) were significantly improved in the RDN group. There were no safety concerns and there was no difference in blood pressure between the groups.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Again, this study had several limitations, such as sample size, and data from two randomized trials which are currently recruiting are eagerly awaited.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">As the relationship between HF and the SNS is robust and the available clinical data is promising, evaluation of the effects of RDN in patients with reduced EF is appropriate. Is this issue of the <span class="elsevierStyleItalic">Journal</span>, Gao et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> present the results of a prospective, open, single-arm study which included fourteen patients with an EF below 45% (eight with ischemic cardiomyopathy), in class NYHA III or IV and on optimized medical therapy. Patients with severe renal failure (glomerular filtration rate below 30 ml/min/1.73 m<span class="elsevierStyleSup">2</span>), type 1 diabetes or hypotension or in the acute phase of myocardial infarction or cerebrovascular accident were excluded. RDN was performed using a radiofrequency catheter with temperature control and 4-6 ablation points were delivered to each artery. At six-month follow-up improvements were observed in the six-minute walk distance (from 152.9±38.0 m to 334.3±94.4 m, p<0.001), EF (from 36±4.1% to 43.8±7.9%, p<0.003), NYHA functional class (p<0.001) and BNP levels (p<0.008). The recovery in EF was more significant in the group of hypertensive patients (34.5±4.3% to 52.3±6.1%, p<0.005) than in the non-hypertensive group (36.6±3.8% to 41±6.2%, p=0.07), a fact that the authors attribute to the blood-pressure lowering effect of RDN and suggesting a more beneficial effect of RDN in HF due to hypertensive disease. There were no safety issues. These results are different from those of the REACH-Pilot study in terms of change in EF, but are comparable to the results published by Chen et al., indicating a favorable effect of RDN in HF patients. However, several limitations must be taken into consideration such as the small sample size, the absence of a control group and non-randomization.</p><p id="par0025" class="elsevierStylePara elsevierViewall">To summarize, this article highlights the role of RDN in modulating autonomic tone in specific conditions, including HF, and emphasizes the importance of further investigation in this area. The authors should be encouraged to continue their research on RDN in various clinical settings, and perhaps in the future some light will be shed on RDN's ‘autonomic’ significance.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.P. 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 8 | 3 | 11 |
| 2024 Outubro | 46 | 22 | 68 |
| 2024 Setembro | 54 | 20 | 74 |
| 2024 Agosto | 65 | 28 | 93 |
| 2024 Julho | 48 | 35 | 83 |
| 2024 Junho | 42 | 25 | 67 |
| 2024 Maio | 40 | 19 | 59 |
| 2024 Abril | 47 | 30 | 77 |
| 2024 Maro | 35 | 24 | 59 |
| 2024 Fevereiro | 43 | 35 | 78 |
| 2024 Janeiro | 29 | 33 | 62 |
| 2023 Dezembro | 29 | 31 | 60 |
| 2023 Novembro | 37 | 20 | 57 |
| 2023 Outubro | 36 | 16 | 52 |
| 2023 Setembro | 22 | 22 | 44 |
| 2023 Agosto | 40 | 20 | 60 |
| 2023 Julho | 30 | 13 | 43 |
| 2023 Junho | 31 | 14 | 45 |
| 2023 Maio | 42 | 22 | 64 |
| 2023 Abril | 23 | 0 | 23 |
| 2023 Maro | 29 | 22 | 51 |
| 2023 Fevereiro | 25 | 16 | 41 |
| 2023 Janeiro | 16 | 16 | 32 |
| 2022 Dezembro | 28 | 16 | 44 |
| 2022 Novembro | 42 | 31 | 73 |
| 2022 Outubro | 24 | 18 | 42 |
| 2022 Setembro | 27 | 40 | 67 |
| 2022 Agosto | 31 | 35 | 66 |
| 2022 Julho | 28 | 34 | 62 |
| 2022 Junho | 24 | 27 | 51 |
| 2022 Maio | 22 | 29 | 51 |
| 2022 Abril | 35 | 33 | 68 |
| 2022 Maro | 30 | 38 | 68 |
| 2022 Fevereiro | 24 | 30 | 54 |
| 2022 Janeiro | 26 | 24 | 50 |
| 2021 Dezembro | 30 | 29 | 59 |
| 2021 Novembro | 34 | 36 | 70 |
| 2021 Outubro | 36 | 44 | 80 |
| 2021 Setembro | 31 | 40 | 71 |
| 2021 Agosto | 24 | 35 | 59 |
| 2021 Julho | 24 | 22 | 46 |
| 2021 Junho | 27 | 34 | 61 |
| 2021 Maio | 32 | 40 | 72 |
| 2021 Abril | 88 | 49 | 137 |
| 2021 Maro | 86 | 13 | 99 |
| 2021 Fevereiro | 75 | 24 | 99 |
| 2021 Janeiro | 48 | 16 | 64 |
| 2020 Dezembro | 52 | 15 | 67 |
| 2020 Novembro | 56 | 22 | 78 |
| 2020 Outubro | 42 | 11 | 53 |
| 2020 Setembro | 55 | 16 | 71 |
| 2020 Agosto | 37 | 13 | 50 |
| 2020 Julho | 37 | 12 | 49 |
| 2020 Junho | 36 | 9 | 45 |
| 2020 Maio | 46 | 8 | 54 |
| 2020 Abril | 39 | 28 | 67 |
| 2020 Maro | 48 | 6 | 54 |
| 2020 Fevereiro | 108 | 55 | 163 |
| 2020 Janeiro | 36 | 10 | 46 |
| 2019 Dezembro | 31 | 14 | 45 |
| 2019 Novembro | 30 | 11 | 41 |
| 2019 Outubro | 30 | 8 | 38 |
| 2019 Setembro | 22 | 4 | 26 |
| 2019 Agosto | 28 | 9 | 37 |
| 2019 Julho | 38 | 9 | 47 |
| 2019 Junho | 30 | 9 | 39 |
| 2019 Maio | 49 | 23 | 72 |
| 2019 Abril | 19 | 10 | 29 |
| 2019 Maro | 43 | 10 | 53 |
| 2019 Fevereiro | 48 | 10 | 58 |
| 2019 Janeiro | 25 | 7 | 32 |
| 2018 Dezembro | 42 | 12 | 54 |
| 2018 Novembro | 97 | 8 | 105 |
| 2018 Outubro | 128 | 17 | 145 |
| 2018 Setembro | 49 | 11 | 60 |
| 2018 Agosto | 27 | 12 | 39 |
| 2018 Julho | 25 | 10 | 35 |
| 2018 Junho | 37 | 5 | 42 |
| 2018 Maio | 54 | 14 | 68 |
| 2018 Abril | 52 | 2 | 54 |
| 2018 Maro | 67 | 13 | 80 |
| 2018 Fevereiro | 68 | 8 | 76 |
| 2018 Janeiro | 41 | 7 | 48 |
| 2017 Dezembro | 105 | 8 | 113 |
| 2017 Novembro | 51 | 13 | 64 |
| 2017 Outubro | 21 | 12 | 33 |
| 2017 Setembro | 23 | 8 | 31 |
| 2017 Agosto | 27 | 15 | 42 |
| 2017 Julho | 24 | 12 | 36 |
| 2017 Junho | 33 | 10 | 43 |
| 2017 Maio | 36 | 13 | 49 |
| 2017 Abril | 25 | 8 | 33 |
| 2017 Maro | 30 | 9 | 39 |
| 2017 Fevereiro | 57 | 25 | 82 |
| 2017 Janeiro | 75 | 63 | 138 |
| 2016 Dezembro | 5 | 28 | 33 |
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