Heart Failure with Preserved Ejection Fraction (HFpEF) – NEJM

Notes from NEJM Review Article:  Redfield MM. (2016), Heart Failure with Preserved Ejection Fraction

Case:  73 yo woman seen for hospital f/u after admission for AF with RVR and pulm edema.  She c/o fatigue and DOE. Cr 1.4, eGFR 37, NT-proBNP 300.  Echo EF 70% with nl LV dimensions.  Elevated LA pressure and pulm arterial systolic pressure approx 52.


  • HF is about 50/50% – pEF vs rEF
  • Observationally, pEF have about the same prognosis as rEF, but in studies, pEF do better.
  • Non-cardiac deaths more common in pEF patients vs rEF.
  • The main problem:  left ventricular diastolic dysfunction, either baseline or induced by demand or rate.  EF does not increase as expected with stress.
  • Poor adaptability to load –> rapid pulmonary edema with increased load, rapid hypotension with decreased load.
  • Pathophysiology:  hypertension-induced remodeling (classic model), endothelial dysfunction –> myocardial inflammation/fibrosis, myocyte signaling derangement, etc. (new model)


  • Risk factors for heart failure:
    • >60 yr of age
    • Hypertension
    • Proinflammatory coexisting conditions
    • Previous hospitalization for heart failure
  • DDx considerations:
    • cardiac ischemia due to epicardial coronary disease
    • lung disease
    • pulmonary arterial hypertension that is unrelated to heart failure
    • hypertrophic or infiltrative cardiomyopathy
    • pericardial disease
    • uncorrected primary valve disease
    • can be very tough to differentiate DOE from HF vs DOE from non-cardiac causes or deconditioning!
  • Labs and Imaging:
    • In the outpatient setting, HF is less likely if BNP < 35 or NT-proBNP < 125 than in patients with higher levels
    • BUT…these can be normal in obese patients or in patients with only exertional sxs!  Normal in up to 30% of HFpEF patients.  Also, BNPs can be up in the elderly or those with AFib without HF.
    • EKG: LVH, LAE or AFib.
    • CXR: Cardiomegaly, pulmonary venous hypertension, interstitial or alveolar edema, pleural effusion
    • Echo (Doppler): cardiac remodeling, elevated LA pressure, abnormal relaxation, PA systolic > 35, RV enlargement or systolic dysfunction (25-30%, often also with AFib).
    • Echo evidence of diastolic dysfcn can be absent in well-treated patients, or in those with only exertional symptoms!


  • Stress testing, angiography or both:  pts with CAD risk factors, if candidate for antiischemic therapy or revascularization.
    • Stress testing can tell you about chronotropic insufficiency and exaggerated hypertensive response, as well as deconditioning, poor pulmonary function.
  • Pulm artery cath for patients to clarify severity of pulmonary hypertension if PA pressures on Doppler > 50.
    • Markedly elevated PA wedge pressures –> L atrial stiffness, hallmark of condition.
  • Cardiac MRI if infiltrative or inflammatory cardiomyopathy suspected (e.g., amyloidosis, sarcoidosis, respectively).
  • Cardiac scintigraphy with specific tracers: identify cardiac amyloidosis.
  • Consider renal artery stenosis in those with risk factors or repeated episodes of HFpEF.
  • If Cr not bad, but pt requiring high-dose diuretics, consider occult renal failure with alternative markers of eGFR (e.g., check cystatin C).


  • Goals:  relieve volume overload, treat co-existing conditions, increase exercise tolerance, manage chronic disease while decreasing hospitalizations.  No tx has improved outcomes overall.


  • ACEI/ARBs:  no improved outcomes
  • Spironolactone:  no improved outcome, and more hyperkalemia and renal dysfunction
  • Beta-blockers:  conflicting data, no clear patient-oriented benefit
  • So…use ACEI/ARB and B-blockers only when other reasons exist to use them! (e.g, CRF for ACEI/ARB)


  • Diuretics for volume overload:  Giving thiazide (eg, metazolone) prior to loop diuretic (furosemide) may work better in pts requiring high-dose loop diuretics.
  • Some requiring high-dose diuretics may require IV loop diuretics
  • Diuretic tx is obviously risky:  monitor closely for hypoK, hypoNa, ARF
  • Avoid fluctuations in Na intake, and low-Na diet MAY help (unclear), but high-Na diet definitely does not.


  • Hypertension:  In general, follow JNC-8.  There may be some benefit to lower targets, but trials did not include HF patients, so uncertain.
  • HTN + CKD:  Give an ACEI/ARB.
  • HTN:  thiazide + CCB + ACEI/ARB for non-blacks; thiazide + CCB for blacks
  • Statins:  Use according to usual guidelines.
  • CAD:  follow usual guidelines.  Select pts may benefit from revascularization for angina/ischemia.
  • AFib:  follow usual guidelines.  Rate > rhythm control.
  • Obesity:  lose weight.
  • OSA and lung disease:  treat aggressively.


  • Nitrates like isosorbide mononitrate:  meh.  No clear benefit in clinical outcomes.
  • Cardiac rehab:  may help, but insurers don’t cover it in HFpEF pts (but do for HFrEF).
  • Education:  self-monitoring!  (Weight, salt intake, symptoms, med compliance, etc.)


  • Clinical trials of sacubitril-valsartan ongoing.
  • ??? do defibrillators help
  • ??? how best to optimally manage co-morbid conditions



Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s