Cardiopulmonary Exercise Testing Variables Reflect …

1 Cardiopulmonary Exercise Testing Variables Reflect the Degree of Diastolic Dysfunction in Patients With Heart Failure Normal Ejection Fraction Marco Guazzi, MD, PhD, Jonathan Myers, PhD, Mary Ann Peberdy, MD, Daniel Bensimhon, MD, Paul Chase, MEd, and Ross Arena, PhD, PT. PURPOSE: Previous investigations have reported a relationship between K E Y W O R D S. Variables obtained from echocardiography with tissue Doppler imaging (TDI) and Cardiopulmonary Exercise Testing (CPX) in systolic diastolic function heart failure (HF) cohorts. The purpose of the present investigation was to perform a comparative analysis between echocardiography heart rate recovery with TDI and CPX in patients with HF and normal ejection fraction ventilatory expired gas (NEF).

2 METHODS: Patients with HF-NEF (N 32) underwent echocardiography with TDI and CPX to determine the following Variables : (1) the ratio between mitral early velocity (E ) and mitral annular velocity (E ), (2) Author Affiliations: Cardiology ejection fraction, (3) left ventricular (LV) mass, (4) left ventricular end Division, University of Milano, San systolic volume, (5) peak oxygen uptake ( V O2), (6) ventilatory efficien- Paolo Hospital, Milano, Italy cy, (7) the partial pressure of end-tidal carbon dioxide (PET CO2) at rest (Dr Guazzi); Cardiology Division, VA. and peak Exercise , and (8) heart rate recovery at 1 minute (HRR1). Palo Alto Health Care System, Stanford University, Palo Alto, California RESULTS: Pearson correlation revealed that E/E was significantly correlated (Dr Myers); Departments of Internal with peak oxygen uptake (r , P.)

3 001), the ventilatory effi- Medicine (Drs Peberdy and Arena) and ciency slope (r , P .001), resting PETCO2 (r , P .03), Physical Therapy (Dr Arena), Virginia peak PETCO2 (r , P .004), and HRR1 (r , P .001). Commonwealth University, Richmond, Left ventricular mass and left ventricular end systolic volume were not Virginia; and LeBauer Cardiovascular correlated with any CPX variable. Ejection fraction was correlated with Research Foundation, Greensboro, North Carolina (Dr Bensimhon and HRR1 (r , P .001). An HRR1 threshold of less than 16 and/or Mr Chase). 16 or more beats per minute (higher value positive) effectively identi- fied subjects with an E/E 10 (positive likelihood ratio: 13:2). Corresponding Author: Corresponding Author: Ross Arena, PhD, PT, DISCUSSION: E/E provides an accurate reflection of LV filling pressure Department of Physical Therapy, Box and thus, insight into diastolic function.

4 The results of the present 980224, Virginia Commonwealth investigation indicate CPX provides insight into cardiac dysfunction in University, Health Sciences Campus, patients with HF-NEF and thus, may eventually prove to be a valu- Richmond, VA 23298 able and accepted clinical assessment. edu). Cardiopulmonary Exercise Testing (CPX) and echocar- patients with HF and normal ejection fraction (NEF). diography are cornerstones in the clinical evaluation is not established. While initial evidence indicates that in patients with systolic heart failure (HF).1,2 Both CPX provides prognostic information in patients with assessment techniques provide complementary infor- NEF,3 additional diagnostic and prognostic investiga- mation, allowing for a more complete assessment of tions are required to gain clinical acceptance.

5 For disease severity and functional impairment. However, example, we are unaware of any previous investiga- unlike echocardiography, the clinical value of CPX in tion that has assessed the ability of CPX to Reflect the Exercise and Diastolic Function / 165. degree of disease severity in the HF-NEF population of the study. Seventy-two percent, 59%, and 38% of (ie, diagnostic potential), an area that has been stud- the subjects were prescribed an angiotensin-convert- ied extensively in patients with systolic ing enzyme inhibitor, (-blocker, and antialdosterone Tissue Doppler imaging (TDI) allows for the quan- agent, respectively. At a maximum, echocardiography tification of additional Variables during echocardiog- with TDI and CPX were performed within 1 week of raphy, which appear to provide valuable clinical each other.)

6 In 80% of the cohort, both evaluations information, particularly with respect to diastolic were performed on the same day. In the minority of function and hence, in the case of HF-NEF, disease cases where assessments were performed on separate 7 Of the Variables obtained from echocar- days, clinical status and pharmacological regimen diography with TDI, the ratio between mitral peak remained stable. Inclusion criteria consisted of a left early (E) and annular (E ) flow velocity, a reflection ventricular ejection fraction (LVEF) 50% or more by of left ventricular filling pressure, appears to be par- echocardiography, a previous diagnosis of HF16 with ticularly valuable. Given the established value of at least 1 previous hospital admission for acute car- echocardiography with TDI in those with HF-NEF, diac decompensation, and the ability to perform max- determination of its relationship to CPX, a well-estab- imal Exercise Testing on an outpatient basis.

7 Informed lished clinical assessment technique in its own right, consent and institutional review board approval was is warranted. Initial research indicates that, in patients obtained prior to study initiation. with systolic HF, Variables obtained from echocardio- graphy with TDI relating to diastolic function are sig- nificantly correlated with peak oxygen uptake (V O2).8 ECHOCARDIOGRAPHY. While peak V O2 is historically the CPX variable with the greatest degree of clinical recognition, there are a Standard M-mode and 2-dimensional echocardiogra- host of other Variables demonstrating robust diagnos- phy and Doppler blood flow measurements were tic and(or prognostic value, including the minute ven- performed in agreement with the American Society of tilation(carbon dioxide production (V E/V CO2) slope,9 Echocardiography Septal and posterior the partial pressure of end-tidal carbon dioxide left ventricular (LV) wall thickness was obtained from (PETCO2),10,11 Exercise oscillatory ventilation (EOV),12 the parasternal long-axis view.))

8 Left ventricular end- heart rate recovery (HRR),13 and dyspnea on exer- systolic volumes were obtained from 2-dimensional These latter Variables , individually or as a apical images. Left ventricular end-systolic volume group, have been scarcely assessed for their diagnos- was calculated according to Simpson's method from tic or prognostic potential in patients with HF-NEF. 2-dimensional apical images. Left ventricular mass The purpose of the present investigation was to was calculated according to the formula proposed by examine the ability of CPX to Reflect disease severity Devereux et in patients with HF-NEF, an area that has been thor- oughly studied in the systolic HF population. This Conventional Doppler and TDI Measurements type of research is needed to determine the value of Mitral inflow measurements included peak early (E).

9 CPX in HF-NEF, and if results are promising, begin to and peak late (A) flow velocities and the E /A ratio. establish the evidence needed to support utilization The TDI of the mitral annulus was obtained from the in clinical practice. We hypothesize that CPX vari- apical 4-chamber view. A sample was placed ables, some of which have been shown to Reflect car- sequentially at the lateral and septal annular sites. diac4 and pulmonary15 function in those with systolic Analysis was performed for the early (E ) diastolic HF, will likewise Reflect the degree of cardiac dys- peak velocity. The ratio of early transmitral flow function as assessed by measures obtained from velocity to annular mitral velocity of the lateral LV. echocardiography with TDI in subjects with HF-NEF.

10 Wall (E /E ) was taken as an estimate of LV filling METHODS Cardiopulmonary Exercise Testing Each patient performed a supervised progressively Thirty-two consecutive subjects with HF-NEF (22 increasing (individualized ramp protocol) CPX to male/10 female, mean age: ( years, New York maximum tolerance on an electromagnetically braked Heart Association class I III), undergoing evaluation cycle ergometer. Ventilatory expired gas analysis was at San Paolo Hospital in Milano, Italy, were enrolled obtained using a metabolic cart (Medgraphics CPX-D, in this study. Sixty-nine percent of subjects had a his- Minneapolis, Minnesota). The oxygen and carbon tory of coronary artery disease. All were receiving sta- dioxide sensors were calibrated prior to each test ble pharmacological management prior to initiation using gases with known oxygen, nitrogen, and 166 / Journal of Cardiopulmonary Rehabilitation and Prevention 2010;30:165 172 carbon dioxide concentrations per manufacturer spec- determine variable ability (in this case CPX) to ifications.)