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Sympathetic neural overdrive in congestive heart failure and its correlates

systematic reviews and meta-analysis

Grassi, Guidoa,*; D’Arrigo, Graziellab,*; Pisano, Annab; Bolignano, Davideb; Mallamaci, Francescab; Dell’Oro, Raffaellaa; Quarti-Trevano, Foscaa; Seravalle, Ginoc; Mancia, Giuseppec,d; Zoccali, Carmineb

doi: 10.1097/HJH.0000000000002093

Background and objectives: Sympathetic neural activation occurs in congestive heart failure (CHF). However, the small sample size of the microneurographic studies, heterogeneity of the patients examined, presence of comorbidities as well as confounders (including treatment) represented major weaknesses not allowing to identify the major features of the phoenomenon, particularly in mild CHF. This meta-analysis evaluated 2530 heart failure (CHF) patients recruited in 106 microneurographic studies. It was based on muscle sympathetic nerve activity (MSNA) quantification in CHF of different clinical severity, but data from less widely addressed conditions, such as ischemic vs. idiopathic, were also considered.

Methods: Assessment was extended to the relationships of MSNA with venous plasma norepinephrine, heart rate (HR) and echocardiographic parameters of cardiac morphology [left ventricular (LV) end-diastolic diameter] and function (LV ejection fraction) as well.

Results: MSNA was significantly greater (1.9 times, P < 0.001) in CHF patients as compared with healthy controls, a progressive significant increase being observed from New York Heart Association classes I–IV in unadjusted and adjusted analyses. MSNA was significantly greater in both untreated and treated CHF (P < 0.001 for both), related to left ventricular (LV) end-diastolic diameter and to a lesser extent to LV ejection fraction (r = 0.24 and −0.05, P < 0.001 and <0.01, respectively), and closely associated with HR (r = 0.66, P < 0.001) and plasma norepinephrine (r = 0.68, P < 0.001).

Conclusion: CHF is characterized by sympathetic overactivity which mirrors the degree of LV dysfunction independently of the stage of CHF, its cause and presence of confounders or pharmacological treatment. plasma norepinephrine and HR represent potentially valuable surrogate markers of sympathetic activation in the clinical setting.

aClinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Monza

bConsiglio Nazionale delle Ricerche-Istituto di Fisiologia Clinica, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria

cUniversity of Milano-Bicocca, Milan

dPoliclinico di Monza, Monza, Italy

Correspondence to Guido Grassi, Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Via Pergolesi 33, 20052 Monza, Milano, Italy. Tel: +39 039 2333357; e-mail:

Abbreviations: CHF, congestive heart failure; HR, heart rate; MSNA, muscle sympathetic nerve activity

Received 27 January, 2019

Accepted 21 February, 2019

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