title: Influence of central apneas and chemoreflex activation on pulmonary artery pressure in chronic heart failure.
abstract: BACKGROUND
  Pulmonary artery hypertension (PH), associated with increased left ventricular (LV) diastolic pressure and pulmonary vasoconstriction, is frequently observed in heart failure (HF), where it holds prognostic significance. We hypothesized that Cheyne-Stokes respiration (CSR) may contribute to increased pulmonary arterartery pressure (PAP) and right ventricular (RV) remodeling in HF, via hypoxia/hypercapnia cycles and adrenergic activation by the chemoreflex stimulation.
  
  
  METHODS
  Seventy-two HF patients (57 males, aged 65.1 SD 12.3 years, LV ejection fraction<50%, 33.2 SD 7.5%), on guideline recommended pharmacological/device treatment underwent thorough clinical, echocardiographic and neurohormonal assessment, 24-hour cardiorespiratory screening for arrhythmias and CSR, and chemoreflex test for hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses.
  
  
  RESULTS
  Twenty patients (28%) showed significant CSR (24-hour apnea-hypopnea index, AHI≥15). Patients with CSR presented with: a) higher systolic pulmonary artery pressure (sPAP: 42.8 standard deviation-SD 10.1 vs 32.3 SD 5.7 mmHg, p<0.001), despite similar LV systolic and diastolic function; b) indexes of right chamber remodeling (all p<0.05); c) enhanced HVR (median 0.78, interquartile range-IR 0.46-1.22 vs 0.42, IR 0.18-0.67 L/min/%, p=0.01) and HCVR (1.17, IR 0.97-1.29 vs 0.72, IR 0.47-0.93 L/min/mmHg, p=0.02); d) increased plasma norepinephrine levels (690, IR 477-868 vs 366, IR 226-508 ng/L, p<0.001). Univariate predictors of sPAP>35 mmHg were AHI, HVR, HCVR; only AHI maintained its predictive value at multivariate analysis (p=0.017).
  
  
  CONCLUSIONS
  CSR may contribute to increased pulmonary artery pressure and right chamber remodeling in HF, independently of the severity of LV systolic and diastolic dysfunction, likely via recurrent hypoxia/hypercapnia cycles and chemoreflex mediated adrenergic discharge.
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. Electronic address: alberto.giannoni@gmail.com.
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannoni
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Raglianti
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Mirizzi
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Taddei
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Del Franco
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Iudice
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bramanti
authors.affiliation: Institute of Health Science, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Aimo
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Pasanisi
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy; Institute of Health Science, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.affiliation: Cardiovascular Medicine Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy; Institute of Health Science, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
mesh_terms: D000368:Aged; D015150:Echocardiography, Doppler; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011651:Pulmonary Artery / Q000503:physiopathology*; D011669:Pulmonary Wedge Pressure / Q000502:physiology*; D020182:Sleep Apnea, Central / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: Chemoreflex; Cheyne–Stokes respiration; Heart failure; Pulmonary artery hypertension