Heart Failure With Preserved Ejection

Fraction Prof.M.Khalilullah

New Delhi, IndiaFormer Prof. & Head of Cardiology,

Director, G.B.Pant Hospital, New DelhiDirector, The Heart Centre, New Delhi

Ist Pulmonary Balloon Valvuloplasty

23rd March, 1985

Percutaneous Catheter Commissurotomy in Rheumatic Mitral Stenosis. N Engl J Med 1985; 313:1515-1518

27th March 1985 28th March 1985

July 1985

19871st Balloon Renal Angioplasty 1986

Before After

Double-balloon valvuloplasty of tricuspid stenosis.Am Heart J. 1987 Nov;114(5):1232–1233 Balloon dilatation of valv. AS , 1986

PDA Closure 1988 ASD Closure 1991

VSD Closure,1995

PTCA 1987

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

HFpEF is not “benign”

• Similar functional decline, hospital readmission rates, economic costs as HFrEF

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)

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 Weight reduction can prevent diabetes, AF, obstructive sleep apnea,

hypertension

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

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

What additional tests should clinicians consider for patients with suspected HFpEF?

Cardiac catheterization (for new-onset HF) Left heart: measure LVEDP + coronary angiography

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

What is the role of BNP in diagnosis and management?

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

NT-proBNP

Superior for evaluating suspected acute HFpEF Sensitive & specific for Dx acute HF in emergency dept: >450 pg/mL

(<50y); >900 pg/mL (≥50y)

BNP Falsely negative in up to 20% with HFpEF Doesn’t correlate with symptoms

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

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

When should inotropic agents be considered?

Not indicated Increase inotropy and heart rate Have no lusitropic/diastolic relaxation effects Studies on digoxin showed no significantly positive result

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

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

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

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

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

What is the prognosis of HFpEF?

Annual death rate ≈5%≈50% die of noncardiovascular diseasesRisk 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)

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

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)

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)

Ivabradine

Ivabradine is a highly selective blocker of inward “funny” channels, which are central regulators of spontaneous depolarization in pacemaker cells.

Thus ivabradine selectively decreases heart rate without having negative inotropic or lusitropic effects, as can occur with beta-blockers.

Furthermore, animal and human studies have shown that ivabradine can decrease heart rate while simultaneously improving stroke volume and cardiac output.

Ivabradine –If channel inhibition

Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction.

Genetic mouse model of HFpEF (db/db) Invasive hemodynamics with Ivabradine Ivabradine improved diastolic function

(Reil et al, Eur Heart J, 2012:1-11)

An elegant study, which used a novel HFpEF animal model, the db/db (leptin-receptor deficient) mouse, found that heart rate lowering with ivabradine had several beneficial effects, including reduced effective arterial elastance (Ea), increased aortic distensibility and decreased LV end-systolic elastance (Ees).

In addition, ivabradine accelerated myocardial relaxation by increased phosphorylation of phospholamban, reversing the SERCA2a inhibition that was present in the db/db mouse.

Ivabradine phase II study in HFpEFPrimary objective

Ivabradine vs placebo on diastolic function, exercise capacity and neuroendocrine activation over an 8-month treatment period in patients with chronic HF-PEF.

Primary endpointCo-primary endpoint based on echocardiography (E/e'), neuroendocrine activation (NT-proBNP) and six-minute walk test evaluated at 8 months.

Secondary objectives - To evaluate the effects of ivabradine compared to placebo on cardiac function and structural parameters, quality of life (KCCQ), NYHA classification and other biomarkers.

- To evaluate the safety and tolerance profile of ivabradine compared to placebo. (Start: May 2013 !)

Ivabradine - conclusion

• In conclusion, Kosmala, Marwick and colleagues should be congratulated for carrying out a carefully conduced and detailed exercise hemodynamic study in HFpEF patients, By taking ivabradine, a blocker of the inward “funny” current and matching it with the right type of HFpEF patient, coupled with appropriate endpoints (peak VO2 and exercise E/e), the authors were successful matchmakers and may have found a novel therapy for an otherwise difficult-to-manage patient population.

SUMMARY• HFpEF constitute about 50% of all Pts of HF. • More common in females, with elderly age, HTN,

DM,COPD, AF.• Comorbidities contribute to progress of disease.• Accurate diagnosis & proper Rx may prolong life, reduce hospital re admissions and improve QOL.• Newer drugs like ivabradine, sidnofil, neprilysin

inhibitions, MR antagonist are under trial.• New devices & interventions to be developed.

- Renal denervation, interatrial shunting, vagus / baroreceptor stimulation