Exercise
Diego Medvedofsky 2/2012
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Background
• ~50% of pts with symptomatic HF
experience HFpEF
• Morbi-mortality is high and comparable to
HF with reduced LVEF (HFrEF)
• In HFpEF no effective therapeutic
strategies shown to be effective in large
clinical trials
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Background
• In HFrEF exercise training (ET) improves
exercise capacity and reduces morbidity
(Van Tol, Eur J Heart Fail 2006)
• HF-ACTION also demonstrated a benefit
with ET in HFrEF (Piepoli, BMJ 2004, O’Connor, JAMA 2009)
• Conditions associated with HFpEF
(endothelial dysfunction, systemic
inflammation, metabolic sme) are
improved by ET (Adamopoulos, Eur Heart J 2001, Boulé,
JAMA 2001, Linke, JACC 2001)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Objectives
To determine whether structured exercise
training (ET) improves
– Exercise performnce
– LV diastolic FC
– Quality of life (QoL)
in pts with HF with preserved ejection
fraction (HFpEF)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods
• Prospective, multicenter, blind, RCT in
HFpEF
•
•
•
•
NYHA II/III
LVEF≥50%
Sinus
At least 1 of: overweight, DM, HTN,
hyperlipidemia, smoking
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods: Exclusion criteria
• Significant valvular disorders, pulmonary
disease, angina, untreated CAD>50%, S/P
MI, anemia, BP>150/100 mmHg, relevant
arrhythmia, change in CV cardiovascular
medication in previous 4 weeks
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods
• 64 pts (age 65±7, 56% female) with
HFpEF were prospectively randomized
(2:1) to
– From 1/2007-8/2007
– Supervised endurance/resistance training in
addition to usual care (ET, n=44)
– Usual care alone (UC) (n=20)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Intervention
• Supervised, facility based training program
• Endurance and resistance (32 sessions)
• Weeks 1-4: aerobic endurance (cycling)
– Target HR of 50-60% of peak oxygen
uptake (peak VO2) baseline
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Intervention
• From week 5:
– ↑ training freq and workload
– Added resistance training (bench press,
leg press, leg curl, rowing machine,
triceps dip, latissimus pull down)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods
• Primary endpoint
– Change in peak VO2 after 3 months
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods
• Secondary endpoints
– Systolic and diastolic function
– Effects on cardiac structure [LV mass index
(LVMI) and LA volume index (LAVI)]
– QoL [Health Survey (SF-36) and Minnesota
Questionnaire (MLWHFQ)]
– Serum biomarkers:
• NT-proBNP
• PINP (serum procollagen type I-NP)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Results
• Peak VO2
– The mean benefit of ET was 3.3
ml/min/kg (95% CI: 1.8 to 4.8, p<0.001),
NNT 3.5
– Increase in 6 min walk of 24 m (<0.001)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Results
• E/e' and LA volume index
– ↓ with ET, unchanged with UC
• The physical functioning score (36-Item
Short-Form Health Survey)
– ↑ with ET, unchanged with UC
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Safety
• Brief episodes of palpitations (2)
• Dyspnea (3)
• Mild musculoskeletal discomfort (9)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Compliance
• Training group - exercise sessions
– N=15 (34%) participated in >90%
– N=23 (52%) in 70% to 90%
– N=6 (14%) in <70%
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Conclusions
• 1ST multicenter, prospective RCT
• Effects of supervised, structured ET on HFpEF pts
– exercise capacity
– diastolic function (atrial reverse remodeling and
improved LV diastolic function)
– QoL
• Endurance/resistance ET over 3 months was
a feasible, safe, and effective intervention
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Limitations
• Nature of ET interventions prohibits pure
blinding
• Small number of younger and middle aged
pts in short-term follow-up
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Background
• Adults with congenital heart disease
(CHD) are at increased risk of mortality
and morbidity
• Parameters of cardiopulmonary exercise
testing (CPX) identified as strong
predictors of mortality in adults with CHD
– guide clinicians in assessing prognosis
and planning interventions
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Investigation
• Relation between CPX parameters
and their combination
• may provide optimal prognostic info
on midterm survival in this population
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Methods
• 1375 pts w/adult (>14y) CHD (33±13 y)
– Retrospectively
– CPX
– Single center, 10 years (1999-2008)
– All cause mortality
• Measured:
– Peak oxygen consumption (peak VO2)
– Ventilation/CO2 (VE/VCO2 slope)
– HR reserve (peak - resting HR)
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Cardiopulmonary Exercise Testing
• On a treadmill - modified Bruce protocol
• All patients were encouraged to exercise
to exhaustion
• Respiratory mass spectrometer:
ventilation, VO2, VCO2
• ECG: HR
• Manually sphygmomanometry: BP
• Pulse oximetry: O2 saturation
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
SO2<
90%
16%
I 51%
II 39%
Simple:
ASD
VSD
PDA
AO coartat
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
BB, CCB,
AMIODAR
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Results
• Follow-up of 5.8 years
– 117 patients died:
• HF 41
• SCD 34
• Perioperative 12
• Inf 5
• PE 1
• Hemoptysis 1
• Brain hemorrhage 1
• Out of Hospital 21
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Results
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Results
• Risk of death ↑ with:
– ↓ peak VO2
– ↓ HR reserve
– ↑ VE/VCO2 slope in noncyanotic pts
• Not predictive in cyanotic pts
– Combination of peak VO2+HR reserve
• greatest predictive info
• ↓ in pts with peak respiratory exchange
ratio <1.0
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Sheba Medical Center
(Neg chronotropic
Tel Hashomer
agents)
The Leviev Heart Center
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Conclusions
• Peak VO2 and HR reserve data can be
used to generate estimates of 5-year
survival across a wide spectrum of adults
with CHD
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Conclusions
• CPX: strong prognostic info in adult pts
w/CHD
– Data useful for comparing the exercise
capacity of a particular patient vs pts in
the same diagnostic group
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
Limitations
•
•
•
•
Retrospective
Part of routine evaluation
Tertiary center
Ed: patients terminated exercise before
reaching their cardiovascular limit
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center
THANKS
THANKS
Sheba Medical Center
Tel Hashomer
The Leviev Heart Center