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CLINICAL RESEARCH: HEART FAILURE

Applicability and Clinical Relevance of the Transfer Function Method in the Assessment of Baroreflex Sensitivity in Heart Failure Patients

Department of Cardiology and Biomedical Engineering, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Montescano, Montescano (PV), Italy

Manuscript received December 13, 2004; revised manuscript received June 16, 2005, accepted June 21, 2005.

^_* Reprint requests and correspondence: Dr. Gian Domenico Pinna, Servizio di Bioingegneria, Fondazione S. Maugeri, IRCCS, Istituto Scientifico di Montescano, 27040 Montescano (PV), Italy (Email: gdpinna{at}fsm.it).

OBJECTIVES: We sought to assess applicability, clinical correlates, and prognostic value of the transfer function method for measuring baroreflex sensitivity (TF-BRS).

BACKGROUND: Abnormalities in autonomic reflexes play an important role in the development and progression of chronic heart failure (CHF). Simple and non-invasive techniques for clinical measurement of such reflexes are desirable.

METHODS: In 317 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 years [48 to 59 years], New York Heart Association [NYHA] functional class II to III: 88%, left ventricular ejection fraction [LVEF]: 27% [22% to 33%]) we recorded electrocardiograms and non-invasive arterial pressure during paced breathing to measure TF-BRS.

RESULTS: Owing to a high number of ectopic beats, TF-BRS could be computed in 72% of the patients; TF-BRS was lower in NYHA functional class III to IV and mitral regurgitation 2 to 3 (p < 0.0005 for both). Correlation with LVEF and standard deviation of all normal-to-normal intervals was 0.18 and 0.31 (p < 0.001 for both). During a mean follow-up of 26 months, 23% of the patients experienced a cardiac event. A depressed TF-BRS (3.1 ms/mm Hg) was significantly associated with the outcome (hazard ratio 3.2, 95% confidence interval [CI] 1.7 to 6.0, p = 0.0003). Patients with a missing TF-BRS had a high event rate (36%). Combining this information with available TF-BRS measurements, a new prognostic index could be computed in 97% of the patients that significantly predicted the outcome after adjustment for clinical and functional variables (hazard ratio 2.5, 95% CI 1.3 to 4.6 p = 0.004).

CONCLUSIONS: In CHF patients in sinus rhythm, TF-BRS conveys relevant clinical and prognostic information, but its measurability is markedly affected by ectopic activity. Nevertheless, a TF-BRS–based risk index carrying significant and independent prognostic information can be computed in almost all patients.

Abbreviations and Acronyms   AUC = area under the curve   BRS = baroreceptor-heart rate reflex sensitivity   CHF = chronic heart failure   ICD = implantable cardioverter-defibrillator   LF = low frequency   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   ROC = receiver-operating characteristic   SAP = systolic arterial pressure   SDNN = standard deviation of all normal-to-normal intervals   TF = transfer function

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