© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. in the clinic Heart Failure With Preserved Ejection Fraction (Diastolic Dysfunction)

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Terms of Use  The In the Clinic ® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for- profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets constitutes copyright infringement.

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What is the difference between HFpEF, diastolic dysfunction, and diastolic HF?  Heart failure with preserved ejection fraction (HFpEF)  Preferred term (ACC/AHA)  Most often have abnormalities in diastolic function (non-diastolic abnormalities in CV function also)  Diastolic heart failure / Diastolic dysfunction  Other common terms for HFpEF but less specific

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What’s the difference between HFpEF & HFrEF?  Left ventricle doesn’t dilate in HFpEF  Some treatments for HFrEF aren’t effective in HFpEF  HFpEF:  Older and more often female  Higher frequency of hypertension; lower CAD  Prevalence HFpEF rising 1% / yr relative to HFrEF

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.  Similar functional decline, hospital readmission rates, economic costs as HFrEF HFpEF is not “benign”

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What are the risk factors for HFpEF?  For HF in general  Age  Hypertension  Obesity  Dyslipidemia  Insulin resistance  For HFpEF  Older, more hypertensive, and higher prevalence of AF (than in HFrEF)  CAD prevalence comparatively lower  More common in women (by 2:1)

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Are any interventions effective for primary prevention of HFpEF?  Control hypertension  Main factor in development and progression  Lower systolic & diastolic according to guidelines  Treat hyperlipidemia and hyperglycemia  Reduces risk for HFpEF and HFrEF  Encourage smoking cessation, exercise, healthy diet  Moderate alcohol consumption among patients who drink  Weight reduction can prevent diabetes, AF, obstructive sleep apnea, hypertension

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Prevention…  Reduce risk for HF  Reduce systolic & diastolic BP <140/90 mm Hg (<130/80 mm Hg if htn + diabetes or renal disease)  Use diuretic-based antihypertensive therapy, ACE inhibitors, and beta-blockers  Glycemic control helps to prevent HF in diabetes mellitus  Treat hyperlipidemia in patients with Hx of MI  Encourage weight loss, smoking cessation; regular exercise; healthy diet

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Which presenting features help to distinguish HFpEF from HFrEF?  Both often present with…  Dyspnea, impaired exercise tolerance, orthopnea, paroxysmal nocturnal dyspnea  HFpEF  Hx hypertension & AF slightly more prevalent  Rapid onset of dyspnea with marked hypertension, particularly in elderly women  AF or LV hypertrophy on ECG  HFrEF  Cardiac output somewhat lower, CAD more prevalent  Slower-onset HF with Hx coronary disease, particularly in middle-aged men  LBBB or evidence prior ischemic injury

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Which diagnostic tests should the clinician order for patients with suspected HF?  Electrocardiography  Radiography  Echocardiography  Laboratory tests  Plasma BNP or NT-proBNP  CBC: ? anemia, serum electrolytes, creatinine, glucose, liver function, urinalysis  Renal function and electrolytes

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What additional tests should clinicians consider for patients with suspected HFpEF?  Cardiac catheterization (for new-onset HF)  Left heart: measure LVEDP + coronary arteriography  Right heart: if needed to evaluate valvular heart disease suggested by echo, or if pulmonary hypertension not explained by left heart disease  When abnormal myocardial function present (? Infiltrative processes, constriction, others), consider:  Myocardial or fat pad tissue CT or MRI

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What are the criteria for establishing the diagnosis?  History and physical examination  Radiography  BNP levels  Echocardiography Requirements for Diagnosis Presence of signs and/or symptoms of HF Preserved systolic LV function (EF ≥45%–50%) Evidence of diastolic LV dysfunction, elevated LV filling pressures, or surrogate markers of diastolic LV dysfunction

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.  Levels usually lower in HFpEF than HFrEF  When elevated: strong independent predictors of clinical events in HFpEF  No consensus on use to guide medical therapy What is the role of BNP in diagnosis and management?  NT-proBNP  Superior for evaluating suspected acute HFpEF  Sensitive & specific for Dx acute HF in emergency dept: >450 pg/mL ( 900 pg/mL (≥50y)  BNP  Falsely negative in up to 20% with HFpEF  Doesn’t correlate with symptoms

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Diagnosis…  Signs and symptoms  Impaired exercise tolerance, orthopnea, dyspnea, and signs suggestive of HF  History may include hypertension and atrial fibrillation  Diagnosed based on H&P exam, x-rays, BNP levels, & ECHO  Criteria for diagnosing HFpEF  Signs / sxs of HF  Preserved systolic LV function (EF ≥45%–50%)  Evidence of: diastolic LV dysfunction, elevated LV filling pressures or surrogate markers of diastolic LV dysfunction

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should HFpEF be treated?  Reduce preload  Use diuretics and vasodilators  BUT NOTE: Assess Volume Status carefully as aggressive reduction may cause hypotension if hypertensive & normovolemic  Consider control of hypertension with vasodilators alone  Treat acute HFpEF  First-line therapy: Vasodilators  I.V. nitrates + furosemide (improve cardiac output and reduce the symptoms)  Nitroglycerin to relieve acute pulmonary edema  Avoid aggressive diuresis (may cause hypotension)  Heart rate control, with particular attention in rapid AF

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.  Provide long-term treatment of hypertension  Improves diastolic tissue velocity in hypertension w/o HF  If no comorbid conditions: thiazide diuretics  If coronary atherosclerosis or AF: beta-blocker  Reduce / reverse adverse remodeling: ARBs  Manage Atrial Fibrillation  In HFpEF + AF: restore normal HR and NSR to improve symptoms (maybe not outcomes)  Rate control first: AV nodal blocking agents + β-blockers  Rhythm control: when rate control not achieved or when symptoms persist despite rate control  Immediate electrical cardioversion: new-onset AF and myocardial ischemia, symptomatic hypotension, or pulmonary congestion or rapid ventricular response uncontrolled by appropriate pharmacologic measures  Anticoagulation: to reduce thromboembolism risk

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should inotropic agents be considered?  Not indicated  Increase inotropy and heart rate  Have no lusitropic effects  Studies on digoxin showed no significantly positive result

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How does drug therapy for HFpEF differ from that of HFrEF?  Many of the same drugs are used… but evidence differs  HFrEF: Improved mortality and morbidity with ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists  HFpEF: No similar improvements found from the therapies  HFpEF focus: symptom relief, BP and heart rate control

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Are any novel drug therapies being investigated for HFpEF?  Spirinolactone  Proven therapy for HFrEF  Under investigation for HFpEF (TOPCAT study)  Sildenafil (phosophodiesterase-5 inhibition)  In small study: Reduced pulmonary arterial pressure, improved right ventricular systolic function, reduced right atrial pressure, improved QOL  Efficacy being studied in larger RELAX trial Requires further / completion of studies

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What are potential triggers of decompensation?  Dietary indiscretion  Use of NSAIDs  Medication nonadherence  Dysrhythmias (particularly AF)  Ischemia or infarction  Hypertension  Worsening renal function  Valvular cardiac disease  Alcohol abuse  Infection

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What is the role of diet and monitoring weight?  Advise patients to weigh themselves daily  Unexpected weight gain may warrant prompt action  If weight gain, increased edema, other HF symptoms occur, patient should promptly call health care provider  Sodium restriction recommended in symptomatic HF  To prevent fluid retention  Fluid restriction (≤1.5-2 L/day)  For severe symptoms of HF, especially hyponatremia

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What should clinicians advise patients with HFpEF about exercise?  Advise regular, moderate daily activity  Aerobic exercise especially beneficial  Improve CV performance  Lowers blood pressure  Prevents or reverses deconditioning  Increases energy levels  Reduces symptoms of HF

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians assess the response to therapy for HFpEF?  ? Symptom alleviation  ? Functional capacity improvement  ? Hospitalizations for decompensated HFpEF decreased  Other treatment targets…  Optimal blood pressure control  Adequate heart rate control in AF

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What is the prognosis of HFpEF?  Annual death rate ≈5%  ≈50% die of noncardiovascular diseases  Risk factors for mortality in HFpEF  Increasing age, male gender  Higher natriuretic peptide levels, higher NYHA class  Coronary artery or peripheral vascular disease  Diabetes mellitus, chronic renal insufficiency  Lower EF, restrictive filling pattern on Doppler ECHO  Low and very high BMI (in HFpEF)

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should patients with HFpEF be followed?  Educate patients on signs of fluid retention  Provide guidelines for using a flexible diuretic regimen  Provide telephone access to health care providers  Emphasize low-salt diet + medical regimen compliance  Frequency of follow-up visits depends stability of patient  See w/in 7d of hospital discharge for decompensated HF  See well-compensated patient every 4 to 6 months

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should patients with HFpEF be hospitalized?  Respiratory failure secondary to pulmonary edema  Moderate to severe volume overload  Atrial fibrillation with rapid ventricular response  Severe hypotension or hypertension  Need for close monitoring during therapy (e.g., of renal function, electrolytes)

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should clinicians consider consulting a cardiologist?  Diagnosis of HFpEF uncertain  Cause of HFpEF unclear  Patient symptomatic despite treatment  Frequent hospitalizations for decompensation  Comorbid cardiac conditions complicate management (CAD or dysrhythmia)

© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Treatment…  Treating the triggers of HF decompensation  Relieve acute pulmonary congestion and intravascular and interstitial volume excess  Alleviate symptoms, improve functional capacity, and decrease hospitalizations  Aim for optimal BP & adequate heart rate control in AF  Educate patients to recognize the signs of fluid retention  Use flexible diuretic regimen if needed  Emphasize low-salt diet + medical regimen compliance  Consult cardiologist when…  Diagnosis uncertain or cause unclear  Patient symptomatic despite treatment