Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society

Tsutsui, Hiroyuki; Albert, Nancy M.; Coats, Andrew J.S.; Anker, Stefan D.; Bayés‐Genís, Antoni; Butler, Javed; Chioncel, Ovidiu; deFilippi, Christopher R.; Drazner, Mark H.; Felker, G. Michael; Filippatos, Gerasimos; Fiuzat, Mona; Ide, Tomomi; Januzzi, James L.; Kinugawa, Koichiro; Kuwahara, Koichiro; Matsue, Yuya; Mentz, Robert J; Metra, Marco; Rosano, Giuseppe; Saito, Yoshihiko; Sakata, Yasushi; Sato, Naoki; Seferović, Petar; Teerlink, John R.; Yamamoto, Kazuhide; Yoshimura, Michihiro

doi:10.1002/ejhf.2848

Cited by 51 publications

(18 citation statements)

References 134 publications

(293 reference statements)

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“…Hence, the increased serum levels of FGF21 and the decreased expression of KLB following MI may reflect a compensatory response to FGF21 resistance ( 5 ). Similarly, cardiac remodeling or HF is accompanied by the elevated expression of natriuretic peptides, suggesting that the intravenous injection of natriuretic peptides could also provide additional benefits to improve HF symptoms ( 33 ). The findings of the present study and those of other studies suggest that the targeted restoration of cardiac KLB expression significantly promotes the activation of FGF21 receptor-dependent pathways in rats post-MI, closely associated with improvements in cardiometabolic parameters, suggesting an increase in FGF21 sensitivity ( 5 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Yue,

Li,

et al. 2024

Int J Mol Med

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Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co-receptor β-klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound-targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post-acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post-infarction were determined using ELISA. Sprague-Dawley rats received the 3X UTMD-mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post-infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α-klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post-infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo , the UTMD technology-mediated delivery of KLB@ CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2-related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post-myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Yue,

Li,

et al. 2024

Int J Mol Med

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“…The role of natriuretic peptides to establish the diagnosis of HF is established in international HF guidelines 10–12 . A scientific statement by three HF Societies (Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society) provides a comprehensive and updated perspective for the use of natriuretic peptides in the prognostic stratification, management and treatment of HF 13 …”

Section: Natriuretic Peptidesmentioning

confidence: 99%

“…It has recently been observed that left ventricular ejection fraction (LVEF) may have a U‐shaped relationship with mortality with an increase in the risk of death also in patients with a LVEF >65% 15,16 . These patients with supranormal (sn) LVEF (HFsnEF) may have peculiar characteristics compared to those with preserved ejection fraction (HFpEF), with a higher risk of events and a lower response to medical treatment, namely neurohormonal antagonists 16–20 . A recent study included 621 patients with HFpEF, of whom 302 had HFsnEF.…”

Section: Pathophysiologymentioning

confidence: 99%

May 2023 at a glance: focus on pathophysiology, comorbidities and devices

Tomasoni

Adamo

Metra

2023

European J of Heart Fail

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Win ratio approachThe win ratio is increasingly used as a statistical tool to include multiple variables related both with outcomes as well as symptoms and quality of life and thus gain statistical power from smaller study groups. 1,2 The EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo in 530 patients with acute heart failure (HF) after initial stabilization using the stratified win ratio approach. 2 Based on the experience from the EMPULSE trial, Pocock et al. 3 elucidated how the win ratio method works and what it means, in order to favour its use in future trials. The investigators of the EMPULSE trial were able to integrate deaths, clinical events and patient-reported outcomes into a win ratio strategy, highlighting the most meaningful clinical findings related to patients' benefits. Natriuretic peptidesBiomarkers are foundation of current management of HF. [4][5][6][7][8][9] The role of natriuretic peptides to establish the diagnosis of HF is established in international HF guidelines. 10-12 A scientific statement by three HF Societies (Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society) provides a comprehensive and updated perspective for the use of natriuretic peptides in the prognostic stratification, management and treatment of HF. 13 Pathophysiology Giannoni et al. 14 reviewed recent evidence regarding chemoreflex physiology and pathophysiology with desensitization of hyperactive chemoreceptors that is emerging as a potential therapeutic option for patients with hypertension and HF. 14 It has recently been observed that left ventricular ejection fraction (LVEF) may have a U-shaped relationship with mortality with an increase in the risk of death also in patients with a LVEF >65%. 15,16 These patients with supranormal (sn) LVEF (HFsnEF) may have peculiar characteristics compared to those with preserved ejection fraction (HFpEF), with a higher risk of events and a lower response to medical treatment, namely

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“…Building on these promising outcomes, we subsequently conducted a single-arm, open-label, multicenter study to assess the e cacy of tranilast as an additional therapy for patients with MD and heart failure, with BNP levels > 100 pg/mL during standard cardiac protection therapy [12]. BNP is a standard cardiac function indicator that is highly correlated with the severity and prognosis of heart failure [13,14]. In MD, a BNP level ≥ 100 pg/mL is considered a predictive risk factor for death [15].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: A single-arm, open-label, multicenter study

Matsumura,

Fukudome,

Motoyoshi

et al. 2024

Preprint

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Background Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two patients with muscular dystrophy (MD) and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in MD patients. Results This study involved 18 MD patients with BNP levels > 100 pg/mL, despite receiving standard cardioprotective therapy. Tranilast was administered orally at a dose of 100 mg, three times daily. In the short-term period (28 weeks), the primary endpoint of change ratio in the logarithm of BNP level from baseline to 28 weeks was not significant in the full analysis set, but lower in the per set protocol compared with data from a previous beta-blocker treatment study. All 15 patients who completed the short-term treatment consented to be enrolled in long-term therapy for an additional 116 weeks. After all participants completed the long-term treatment, we analyzed all the data. TRPV2 expression on the peripheral blood mononuclear cell surfaces decreased throughout the study period, confirming that the TRPV2 inhibitory effect of tranilast was maintained over time. Despite the presence of progressive disease, cardiac indices such as BNP level, human atrial natriuretic peptide, and fractional shortening, remained stable, and only BNP levels at 144 weeks showed significant changes. The survival rate was 80.7%, and no cardiac deaths were reported. In terms of safety, no serious adverse events associated with tranilast were noted, except for recurrent diarrhea during the short-term period in one case. Conclusions The findings suggest that tranilast can inhibit TRPV2 expression for an extended period and is effective in preventing the worsening of cardiac function and subsequent death from heart failure. Clinical Trial Registration Details: The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/) [November 12, 2021]. Patient registration was initiated on December 19, 2018.

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Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society

Cited by 51 publications

References 134 publications

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction

May 2023 at a glance: focus on pathophysiology, comorbidities and devices

Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: A single-arm, open-label, multicenter study

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