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Quale terapia nell’HFpEF?
Plinio Fabiani (Lido di Camaiore)
Definition of heart failure with preserved (HFpEF), mid-
range (HFmrEF) and reduced ejection fraction
(HFrEF)
European Heart Journal (2016) 37, 2129–2200
The Changing Landscape of Heart Failure:
The Projected Trajectory of HFpEF in
Hospitalized Heart Failure Patients.
Curr Heart Fail Rep. 2013 Dec;10(4):401-10Oktay AA, Rich JD, Shah SJ
HFpEF & HFrEF: Similarly high mortality
• 1. Owan et al. N Engl J Med 2006;355:251–9
2. Blanche et al. Swiss Med Wkly 2010;140:66–72
• 3. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). Eur Heart J 2012;33:1750–7
Survival
1.0
0.8
0.6
0.4
0.2
0
0 1 2 3 4 5Year
HFrEF (LVEF <50%)
HFpEF (LVEF ≥50%)
p=0.03
 Survival rate among patients with a discharge diagnosis of HF in the USA was slightly higher among
patients with HFpEF than those with HFrEF between 1987–20011
 Respective mortality rates were 29% and 32% at 1 year and 65% and 68% at 5 years
 HFpEF is associated with significant morbidity and mortality, despite having a slightly higher survival
rate compared with HFrEF2,3
Shah JS et Al.
Circulation. 2016;134:73-90
Chest wall restriction, reduced vital capacity,
impaired ventilation and diffusion
Obstructive sleep apnea
Pulmonary hypertension
Direct and indirect myocardial lipotoxicity
Worsened cardiac mechanics
Diastolic dysfunction; increased filling pressures/
volume overload, increased afterload
Non-alcoholic fatty liver disease
Promotes generalized
inflammatory stat
Inflammatory cytokines
Adverse neurohormones
Insulin resistance
Increased BNP clearance
Direct toxic effects of perinephric fat
Glomerulomegaly with
glomerular dysfunction
Increased adipose infiltration
Altered insulin signaling
Decreased capillary density; impaired perfusion
Decreased diffusive O2 transport
Mitochondrial dysfunction
The HFpEF Obesity Phenotype
The Elephant in the Room
Kitzman DW, Shah SJ
JACC 68(2): 200; 2016
Ponikowski EHJ (2016) 37, 2129–200
Cyclic GMP Pathway has been
Proposed as a Potential Mediator of HFpEF
PDE5 Inhibitors
RELAX Trial
Neprilysin
Inhibitor
PARAMOUNT
Nitrates
NEAT-HFpEF
sGC Stimulators
sGC Activators
LEPHT Trial
Pandey J Am Coll Cardiol 2017;69:1129–42
HFrEF
HFpEF

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Scompenso cardiaco a frazione di eiezione preservata - Heart failure with preserved ejection fraction

  • 1. Quale terapia nell’HFpEF? Plinio Fabiani (Lido di Camaiore)
  • 2. Definition of heart failure with preserved (HFpEF), mid- range (HFmrEF) and reduced ejection fraction (HFrEF) European Heart Journal (2016) 37, 2129–2200
  • 3. The Changing Landscape of Heart Failure: The Projected Trajectory of HFpEF in Hospitalized Heart Failure Patients. Curr Heart Fail Rep. 2013 Dec;10(4):401-10Oktay AA, Rich JD, Shah SJ
  • 4. HFpEF & HFrEF: Similarly high mortality • 1. Owan et al. N Engl J Med 2006;355:251–9 2. Blanche et al. Swiss Med Wkly 2010;140:66–72 • 3. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). Eur Heart J 2012;33:1750–7 Survival 1.0 0.8 0.6 0.4 0.2 0 0 1 2 3 4 5Year HFrEF (LVEF <50%) HFpEF (LVEF ≥50%) p=0.03  Survival rate among patients with a discharge diagnosis of HF in the USA was slightly higher among patients with HFpEF than those with HFrEF between 1987–20011  Respective mortality rates were 29% and 32% at 1 year and 65% and 68% at 5 years  HFpEF is associated with significant morbidity and mortality, despite having a slightly higher survival rate compared with HFrEF2,3
  • 5.
  • 6. Shah JS et Al. Circulation. 2016;134:73-90
  • 7. Chest wall restriction, reduced vital capacity, impaired ventilation and diffusion Obstructive sleep apnea Pulmonary hypertension Direct and indirect myocardial lipotoxicity Worsened cardiac mechanics Diastolic dysfunction; increased filling pressures/ volume overload, increased afterload Non-alcoholic fatty liver disease Promotes generalized inflammatory stat Inflammatory cytokines Adverse neurohormones Insulin resistance Increased BNP clearance Direct toxic effects of perinephric fat Glomerulomegaly with glomerular dysfunction Increased adipose infiltration Altered insulin signaling Decreased capillary density; impaired perfusion Decreased diffusive O2 transport Mitochondrial dysfunction The HFpEF Obesity Phenotype The Elephant in the Room Kitzman DW, Shah SJ JACC 68(2): 200; 2016
  • 8. Ponikowski EHJ (2016) 37, 2129–200
  • 9.
  • 10.
  • 11. Cyclic GMP Pathway has been Proposed as a Potential Mediator of HFpEF PDE5 Inhibitors RELAX Trial Neprilysin Inhibitor PARAMOUNT Nitrates NEAT-HFpEF sGC Stimulators sGC Activators LEPHT Trial
  • 12. Pandey J Am Coll Cardiol 2017;69:1129–42 HFrEF HFpEF

Notas do Editor

  1. HFpEF & HFrEF: Similarly high mortality Trends in the survival of HFpEF compared with those with HFrEF were investigated among patients hospitalized with acute HF at Mayo Clinic Hospitals, Minnesota over a 15-year period between 1987 and 2001. Data on LVEF were available for 4,596 patients and 47% were found to have HFpEF. Survival data were available for 4,594 patients with a mean follow-up period of 10.0±4.2 years. The survival rate was higher among patients with HFpEF compared with HFrEF, although the difference was small. The respective mortality rates were 29% for HFpEF and 32% for HFrEF at one year, and 65% for HFpEF and 68% for HFrEF at 5 years. The unadjusted HR for 5-year death in the HFpEF group versus the HFrEF group was 0.96 (95% CI, 0.93 to 1.00; p=0.03). After adjustment for differences in baseline characteristics and the year of admission, the likelihood of survival was still slightly higher among patients with HFpEF than in those with HFrEF (HR 0.96; 95% CI 0.92 to 1.00).1 Even though HFpEF is associated with improved survival rates compared with HFrEF, the difference is small, and levels of mortality and morbidity associated with HFpEF are high.2,3 1. Owan et al. N Engl J Med 2006;355:251–9 2. Blanche et al. Swiss Med Wkly 2010;140:66–72 3. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). Eur Heart J 2012;33:1750–7 Key communication point Both HFpEF and HFrEF are associated with high levels of mortality Abbreviations CI=confidence interval; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HR=hazard ratio; LVEF=left ventricular ejection fraction
  2. Restricted cubic splines showing continuous adjusted association between BMI and risk of HFrEF (top panel) and HFpEF (bottom panel). The shaded area shows the 95% confidence interval for the hazard ratio point estimates associated with different LTPA levels. Abbreviations as in Figures 2 and 3. There was no significant association between higher levels of physical activity and risk of heart failure with reduced ejection fraction (red line) at any doses. In contrast, there was a significant dose-dependent association between higher levels of physical activity and risk of heart failure with preserved ejection fraction (green line), particularly at greater than guideline-recommended minimum physical activity doses. HFpEF ¼ heart failure with preserved ejection fraction; HFrEF ¼ heart failure with reduced ejection fraction; MET ¼ metabolic equivalent task; PA ¼ physical activity.