Diastolic heart failure

Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology Classification

Prevention
Primary Screening Secondary

Diagnosis
History & examination Tests Differential Step-by-step Criteria Guidelines Case history

Treatment
Details Step-by-step Emerging Guidelines Evidence

Follow Up
Recommendations Complications Prognosis

Resources
References Images Online resources Patient leaflets Credits

History & exam

Key factors
presence of risk factors exertional dyspnoea

Other diagnostic factors

orthopnoea paroxysmal nocturnal dyspnoea abdominal fullness

rales jugular venous distention hepatojugular reflux congestive hepatomegaly lower extremity oedema laterally displaced apical impulse gallop sounds History & exam details

Diagnostic tests
1st tests to order
serum electrolytes renal function tests liver enzymes B-natriuretic peptide (BNP)/N-terminal prohormone B-natriuretic peptide (NT-pro-BNP) 12-lead ECG CXR Doppler echocardiography tissue Doppler imaging (TDI)

Tests to consider
radionuclide ventriculography (MUGA scan) CT angiography cardiac MRI stress testing cardiac catheterisation and coronary angiography Diagnostic tests details

Treatment details
Acute
acute decompensated DHF diuretic oxygen ACE inhibitor or angiotensin-II receptor blocker nesiritide oxygen ACE inhibitor or angiotensin-II receptor blocker

 o o o o o o o o

with hypertensive emergency intravenous vasodilator with atrial fibrillation beta-blocker or calcium-channel blocker or digoxin anticoagulants amiodarone with sinus tachycardia beta-blocker or calcium-channel blocker with myocardial ischaemia, previous MI, or HTN beta-blocker aspirin revascularisation

Ongoing
chronic DHF ACE inhibitor or angiotensin-II receptor blocker beta-blocker management of risk factors diuretic

Treatment details

Summary
Refers to the clinical syndrome of heart failure with symptoms of pulmonary and peripheral congestion in the presence of normal left-ventricular systolic function and increased diastolic filling pressures. Accounts for about 50% of all patients with heart failure, and carries a similar prognosis. The most common risk factors are advanced age, female gender, hypertension, obesity, chronic kidney disease, diabetes mellitus, and coronary artery disease. Patients may present with acute decompensated heart failure and are generally managed with diuresis, blood pressure control, and treatment of ischaemia and tachyarrhythmia, when present. No therapy has been shown to improve survival in randomised control trials. Risk factor modification is still the cornerstone of long-term management.

Epidemiology
DHF accounts for 55% of heart failure cases and is associated with older age, female gender, and HTN. [4] Based on data from prospective studies, the average age of patients ranges from 73 years to 79 years and the percentage of patients that are female ranges from 61% to 76%. Around 47%

of patients discharged with heart failure have a preserved ejection fraction (EF). [5]EF has been used as an indicator of systolic function. [6] [7] Although some trials have used other cut-offs, expert consensus and several registries have used >50% as the definition of normal EF or preserved systolic function. In population-based echocardiogram studies, the prevalence of DHF ranges from 40% to 71%. The wide variation is probably due to methodological differences (sample size, mean age of the studied population, diagnostic criteria for heart failure, and preserved systolic function). [8] Isolated diastolic dysfunction (with preserved EF) is present in about 42% to 44% of heart failure patients. [4] [9] In the general population, it occurs in 0.85% of males and 0.54% of females. [10] The prevalence of diastolic abnormalities varies from 2.8% in individuals aged 25 to 35 years to 15.8% in those >65 years. [11]

Aetiology
The most common causes of DHF are hypertension, coronary artery disease, and diabetes mellitus. Less commonly, cardiomyopathy (hypertrophic, infiltrative, genetic, post-partum, viral, radiation-induced or chemotherapyinduced) is the immediate cause. [12] Common precipitating factors of heart failure exacerbation include: [12]
Volume overload (e.g., in valvular heart disease) Tachycardia Uncontrolled hypertension Ischaemia Arrhythmia (e.g., atrial fibrillation) Systemic stressors (e.g., anaemia, fever, infection, thyrotoxicosis) Use of NSAIDs.

Myocardial and pericardial disorders are uncommon causes of diastolic dysfunction. [13]These conditions decrease left ventricular compliance and impair relaxation, thus increasing left ventricle filling pressures.

Pathophysiology
Diastole is a dynamic process that begins at the termination of contraction and occurs during isovolumetric relaxation and early ventricular filling.

Diastolic dysfunction can arise from the impairment of relaxation or from altered ventricular filling, although it is not uncommon to find both. Ventricular relaxation is an active process mediated by ATP and controlled primarily by calcium uptake by the sarcoplasmic reticulum. Ventricular filling is affected by elasticity, compliance, and stiffness, which are generally measured in end-diastole. An increase in chamber stiffness may occur secondary to any combination of the following: [1]
A rise in filling pressures due to volume overloaded states, such as valvular regurgitation and dilated cardiomyopathy A steeper pressure-volume curve, whether from ventricular hypertrophy/concentric remodelling (from hypertension, aortic stenosis, etc.) or from increased extracellular matrix leading to myocardial restriction (amyloidosis, endomyocardial fibrosis, etc.) A decrease in ventricular distensibility caused by extrinsic compression of the ventricles, as seen in tamponade or constrictive pericarditis.

The resulting elevation in LV filling pressures causes elevation in the pulmonary capillary pressures, causing symptoms of pulmonary congestion. Elevation of pressures in the left atrium may predispose to complications such as atrial arrhythmias.

Classification
Stages of diastolic dysfunction [3] The severity of diastolic dysfunction in DHF is based on findings on echocardiogram. Stage I (mild):
Also known as impaired relaxation Can be detected via a decrease in early diastolic flow velocity (E wave) and a greater contribution of atrial contraction (A wave) to left ventricular (LV) filling (E/A <1.0). View image

Stage II (moderate):
Also known as pseudo-normalisation Reflects increasing left atrial (LA) pressure at the onset of diastole and an increase in early diastolic flow velocity to a level near that of normal filling (E/A 1.0-1.5)

Increase in LA pressure largely due to reduced LV compliance Reduction in preload with the Valsalva manoeuvre can change a pseudo-normalised pattern to an abnormal relaxation pattern, or a restrictive pattern to a pseudo-normalised pattern

E/A is normal, but E/A reversal (ratio <1.0) occurs with Valsalva. View imageView image

Stage III (severe):

Also known as restrictive filling that reverses with the Valsalva manoeuvre Occurs when LA pressure is further elevated such that early diastolic flow is extremely rapid and LA and LV pressures equalise quickly during early diastole (E) E/A >2.0 and reverses with the Valsalva manoeuvre. View image

Stage IV:
Irreversible restrictive filling E/A >2.0 and remains fixed with the Valsalva manoeuvre.

Primary prevention
Involves the control of risk factors that predispose to impairment of myocardial relaxation and to increased LV filling pressures. These include:
BP control Weight management Coronary artery disease prevention Strict diabetes management Management of sleep apnoea.

Screening
There is no evidence to support screening in the general asymptomatic population. Echocardiogram needs to be obtained only in the appropriate clinical scenario when signs and symptoms of heart failure are present.

Risk factors
Screening for risk factors such as hypertension, diabetes, and obesity should be done in accordance with individual guidelines for these conditions. Since risk factor modification is crucial to the management of DHF, aggressive screening for these risk factors is encouraged.

Secondary prevention
Risk factor modification is the key to preventing or delaying the onset of overt clinical heart failure. Physicians are advised to:
Monitor BP as closely as necessary to meet targets based on the latest guidelines [NHLBI-NIH JNC-7 website] (external link) Monitor volume status (daily weights and adjustment of diuretic dose as necessary) Pursue revascularisation in patients with CAD, when appropriate; aggressive medical management of ischaemia is advised Maintain adequate rate control in patients with tachyarrhythmias (e.g., atrial fibrillation); if there is difficulty in achieving rate control or there is substantial symptom burden from the arrhythmia, rhythm control, and maintenance of sinus rhythm should be considered Strictly monitor glucose control with haemoglobin A1c every 3 to 6 months Treat obstructive sleep apnoea if present Promote weight loss in overweight patients. Surgically induced weight loss may be considered in morbidly obese patients Encourage tobacco and alcohol discontinuation Encourage regular aerobic exercise and consider cardiac rehabilitation when appropriate.

Monitoring
During the acute phase all patients require cardiac monitoring. Once stabilised, they can be transferred to a non-cardiac monitoring ward. Clinicians are advised to:
Monitor BP as closely as necessary to meet targets based on the latest guidelines [NHLBI-NIH JNC-7 website] (external link) Monitor volume status (daily weights and adjustment of diuretic dose as necessary) Screen for diabetes (annually); if the patient is diabetic, strict glucose control with haemoglobin A1c every 3 to 6 months should be performed Screen for coronary artery disease (CAD) when appropriate Screen for sleep apnoea when appropriate

Screen for chronic kidney disease.

Patient Instructions
Patients should be advised to:
Monitor BP closely Perform daily weights to monitor volume status Manage weight through diet and exercise Limit the intake of sodium, fat, and concentrated sweets Exercise regularly Discontinue tobacco and alcohol Have at least annual follow-up visits with the primary care physician for screening tests.

Prognosis
Risk factor modification is the key in preventing or delaying the onset of overt clinical heart failure. Once heart failure has been diagnosed, the prognosis of patients with preserved ejection fraction (EF) appears to be similar to that of patients with impaired EF. The reported rates of mortality (1 year and 5 years), re-admission for heart failure, and in-hospital complications are similar between the 2 groups. [5] [65] Higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with increased risk of all cause mortality and heart failure hospitalisations. [66] Presence of anaemia might be an indicator for poor prognosis and/or increased mortality. [67] Depression is prevalent in heart failure patients and associated with higher hospitalisation rates. Therefore, there is a need for screening and early intervention when depression is present. [68] A meta-analysis suggests that even a pseudo-normal diastolic filling pattern is associated with an increased risk of death compared with abnormal relaxation or a normal pattern, and the risk is similar to that noted with a restrictive filling pattern. [69] No treatment has been shown to decrease mortality rates in patients with preserved EF. Survival over time seems to be improving in patients with impaired EF but not for patients with preserved EF. [5]

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Stage I diastolic dysfunction: impaired relaxation From the collection of Dr Del Rosario

Stage II diastolic dysfunction: pseudo-normalisation From the collection of Dr Del Rosario

Stage II diastolic dysfunction: pseudo-normalisation with Valsalva From the collection of Dr Del Rosario

Stage III or IV diastolic dysfunction: restrictive filling From the collection of Dr Del Rosario

E/E' is the ratio of peak velocity across the mitral valve during early diastolic filling on routine Doppler echocardiography and the mitral annular velocity on tissue Doppler imaging (TDI) From the collection of Dr Del Rosario

Mitral annular velocity (E') From the collection of Dr Del Rosario

History & examination

Key diagnostic factorshide all
presence of risk factors (common)

Key risk factors include hypertension, female sex, age >70 years, obesity, coronary artery disease (CAD)/ischaemia, diabetes mellitus, and chronic kidney disease.

exertional dyspnoea (common)

Patients with anatomical or physiological abnormalities but who have no symptoms are considered, according to the New York Heart Association (NYHA) classification, to be in class I heart failure. Dyspnoea with moderate to severe exertion, including normal daily activities, is considered class II. Dyspnoea with minimal exertion, such as walking very short distances, is class III. Dyspnoea at rest is class IV.

Other diagnostic factorshide all

orthopnoea (common)

Defined as dyspnoea in the recumbent position that usually occurs within a few minutes after recumbency while the patient is awake.

A non-specific symptom, as it may occur in any condition that causes a decreased vital capacity. paroxysmal nocturnal dyspnoea (common)

Dyspnoea that occurs while a patient is asleep, waking up suddenly with a feeling of suffocation.

It is more specific to heart failure than orthopnoea. abdominal fullness (common) Related to congestion. rales (common)

Usually bilateral and in the basal segments. If unilateral, it is usually on the right side and associated with pleural effusion.

jugular venous distention (common)

Usually measured at a 45-degree angle, jugular venous pressure above 5 cm from the sternal angle is considered elevated, and roughly corresponds to a right atrial pressure of 10 cmH20.

hepatojugular reflux (common)

Jugular venous pressure may be normal at rest, but rises to abnormal levels with increased right upper quadrant pressure by the manoeuvre of firm pressure over the liver for 1 minute.

congestive hepatomegaly (common) Usually develops before overt oedema occurs. [1] lower extremity oedema (common)

Usually bilateral and pitting. Overt oedema usually denotes a gain of about 4 litres of extracellular fluid. [1]

laterally displaced apical impulse (common) A laterally displaced apical impulse on physical examination suggests cardiomegaly. gallop sounds (uncommon)

An S3 gallop, which occurs after the second heart sound, has been shown to be an independent predictor of death and hospitalisation due to heart failure. An S4 is heard in patients with hypertensive heart disease, which is usually the setting for diastolic dysfunction. However, it is nonspecific, as it may be heard in a variety of other conditions, including CAD.

Risk factorshide all

Strong hypertension

Hypertension is more common in heart failure patients with preserved systolic function than in those with reduced systolic function. [14] Abnormalities of left ventricular (LV) diastolic filling have been noted in adult patients with isolated diastolic, isolated systolic, and combined systolic and diastolic hypertension. [15]Changes in intrinsic myocardial stiffness, myocardial fibrosis with interstitial collagen deposition, and altered chamber geometry are other possible mechanisms for diastolic dysfunction in patients with hypertension. [15]

Hypertension is associated with left atrial enlargement, depression of atrial contractile function, and increased risk for atrial fibrillation. Atrial systole contributes up to 40% of diastolic filling, so atrial fibrillation with a resultant loss of 'atrial kick' can precipitate overt heart failure in patients with underlying ventricular diastolic dysfunction. [15]

female sex

DHF is more common in women (79%); reduced systolic function is equally common in women and men.[14] [16] However, there have been reports of higher prevalence of isolated diastolic dysfunction in men. [11]

age >70 years

Patients >70 years of age are more likely to have a normal ejection fraction (EF). [17] The mean age of heart failure patients with preserved systolic function ranges from 60 to 78 years. [8] In the general population, the proportion with diastolic dysfunction sharply increases after age 65 years in both sexes. [10]

obesity

Echocardiogram-based cohort studies have shown that higher BMI is associated with diastolic abnormalities.[11] Obesity is more prevalent in heart failure patients with normal EF compared with controls. [18] One study has shown impaired diastolic function in obese patients (BMI >30) <16 years of age compared with age-matched lean controls. [19] Central obesity, as measured by waist-hip ratio, is more correlated with diastolic function and mortality than BMI. [20]

coronary artery disease/ischaemia

Reported as an independent predictor of diastolic abnormalities, and is more prevalent in patients with heart failure with normal EF compared with controls. [11][18]

diabetes mellitus

Reported as an independent predictor of diastolic dysfunction. DM is more prevalent in patients with heart failure with normal EF compared with controls. [11] [18][21] Other studies in heart failure patients have reported similar prevalence rates in patients with preserved and impaired systolic function. [8]

chronic kidney disease

Echocardiogram-based population cohort studies have shown that chronic kidney disease does not differ between heart failure patients with preserved systolic function and those with impaired systolic function. [8]Patients with DHF have a higher baseline creatinine compared with controls and patients with hypertension without heart failure. [18] Patients with severe chronic kidney disease (creatinine clearance <30 mL/minute) have more impaired diastolic parameters on tissue Doppler imaging than both healthy controls and patients with mild chronic kidney disease. [22]

Weak myocardial and pericardial disorders

These conditions decrease LV compliance and impair relaxation, thus increasing LV filling pressures.

obstructive sleep apnoea

About 55% of patients with symptomatic DHF have sleep-disordered breathing, mostly obstructive sleep apnoea. [23] Patients with obstructive sleep apnoea have more impaired diastolic parameters as measured by tissue Doppler velocity. [24] [25]

Diagnostic tests
1st tests to orderhide all
Test

serum electrolytes Hypervolaemic hyponatraemia is common in severe heart failure due to expansion of extracellular volume. Potassium levels are usually normal, but thiazide and loop diuretics may result in hypokalaemia. renal function tests dysfunction.

Renal failure may be the aetiology of fluid overload, or chronic kidney disease may be a risk factor leading to dia

liver enzymes Marker of passive liver congestion. B-natriuretic peptide (BNP)/N-terminal prohormone B-natriuretic peptide (NT-pro-BNP) between systolic and DHF. Causes of elevated BNP other than heart failure include left ventricular hypertrophy, age >70 years, and cirrhosis. BNP <100 nanogram/L (<100 picogram/mL) suggests a non-cardiac aetiology of dyspnoea.

BNP >400 nanogram/L (>400 picogram/mL) may be indicative of heart failure. However, BNP does not distinguis

myocardial ischaemia, tachycardia, right ventricular overload, hypoxaemia, renal dysfunction, sepsis, COPD, dia

12-lead ECG May reveal evidence of prior MI, conduction defects, and arrhythmias common to DHF, such as atrial fibrillation. CXR The finding of cardiomegaly is helpful in the diagnosis.

CXR also helps evaluate for pulmonary causes of dyspnoea. In the presence of fluid overload, pulmonary oedem pleural effusion is a typical finding. Doppler echocardiography transmitral flow during atrial contraction and corresponds to the A wave.

E is the peak velocity across the mitral valve during early diastolic filling and corresponds to the E wave. A is the

Stage I or mild DHF: E/A ratio <1.0 due to impaired relaxation and significant contribution of atrial contraction to L filling. View image

Stage II or moderate DHF: E/A is normal, but E/A reversal (ratio <1.0) occurs with Valsalva manoeuvres. Also ca imageView image compliance, causing further increase in LA pressure. View image Stage IV: abnormal E/A ration (>2.0) and remains fixed with Valsalva manoeuvres.

pseudo-normalisation. This is due to reduced LV compliance, resulting in increased left atrial (LA) pressure. View

Stage III or severe DHF: abnormal E/A ratio (>2.0), but changes with Valsalva manoeuvres. Due to severe decre

E- and A-wave velocities are affected by volume status, mitral valve dysfunction, and the presence of atrial fibrilla making Doppler echocardiography a less reliable diagnostic tool. tissue Doppler imaging (TDI)

Measures the change in velocity of the myocardial tissue itself during different phases of the cardiac cycle. Mitral

velocity (E') View imagehas been used as a marker of diastolic function, and it seems to be less preload-depend and the mitral annular velocity on TDI.

E/E' View image is the ratio of peak velocity across the mitral valve during early diastolic filling on routine Dopple

Tests to considerhide all

Test

radionuclide ventriculography (MUGA scan)

In patients where image quality is poor on echocardiogram, radionuclide ventriculography can provide highly acc cardiac hypertrophy. CT angiography

measurements of LV function and right ventricular EF. However, it is unable to directly assess valvular abnormal

May be useful in evaluating chamber size and ventricular mass, detecting right ventricular dysplasia, or recognis

presence of pericardial disease. May diagnose CAD. cardiac MRI presence of pericardial disease.

May be useful in evaluating chamber size and ventricular mass, detecting right ventricular dysplasia, or recognis

Studies have shown that this technique has a high concordance with echocardiography in measuring mitral inflow and myocardial tissue velocities, in both patients and controls. [31] [32] stress testing preserved LVEF. [33]

Evaluation for ischaemic heart disease and inducible myocardial ischaemia is indicated in patients with heart failu

May be done using exercise (e.g., treadmill, bicycle) or pharmacological (e.g., adenosine, dobutamine) methods. Imaging modalities, such as echocardiography and single photon emission computerised tomography (SPECT), sensitivity of the test. cardiac catheterisation and coronary angiography May diagnose CAD.

Its invasive nature limits its clinical utility for exclusively diagnosing DHF in day-to-day clinical practice. However, done if the likelihood of CAD is high. Decision to perform this test should be made by a cardiologist.

Step-by-step diagnostic approach

Signs and symptoms of DHF are similar to those of heart failure with systolic dysfunction. Therefore, distinguishing between systolic and isolated DHF on physical examination alone is difficult. Identification of the structural abnormality leading to heart failure generally requires imaging of the cardiovascular system. [26]

History
A thorough history should be obtained in patients who present with signs and symptoms of heart failure to identify comorbidities and risk factors for DHF, and behaviours that might precipitate or accelerate the course of heart failure.

The initial history should include symptomatology and an accurate assessment of the patient's functional capacity. Common symptoms elicited are shortness of breath (SOB) with exertion, orthopnoea, paroxysmal nocturnal dyspnoea, abdominal fullness, and lower extremity swelling. Particular attention should also be made to the patient's diet, past and current medications, and habits (e.g., smoking, alcohol, illicit drug use).

Physical examination
Vital signs such as heart rate, BP, respiration rate, and oxygen saturation, should be measured and monitored. On physical examination, patients present with pulmonary rales, distended neck veins, a positive hepatojugular reflux, and lower extremity oedema. Occasionally, an S3 or S4 gallop and/or hepatomegaly may be appreciated. Distinguishing between systolic and isolated DHF on physical examination alone is difficult. Although the hx and examination may provide important clues about the nature of the underlying cardiac abnormality, identification of the structural abnormality leading to heart failure generally requires invasive or non-invasive imaging of the cardiovascular system. [26]

Initial investigations
The first tests to perform in patients presenting with suspected DHF are ECG, echocardiogram coupled with Doppler flow studies, CXR, B-natriuretic peptide (BNP) and N-terminal prohormone B-natriuretic peptide (NT-proBNP) levels, serum electrolytes, and renal and liver function tests.
12-lead ECG may reveal left ventricular (LV) hypertrophy, evidence of prior MI, conduction defects, and arrhythmias common to DHF, such as atrial fibrillation. The initial echocardiographic evaluation should include a comprehensive 2-dimensional echocardiogram coupled with Doppler flow studies to assess cardiac structure and function. Three fundamental questions must be addressed: [26] o o o Is the left ventricular ejection fraction (LVEF) preserved or reduced? Is the structure of the LV normal or abnormal? Are there other structural abnormalities such as valvular, pericardial, or right ventricular abnormalities that could account for the clinical presentation?

Patients with DHF usually have left atrial enlargement, elevated LV mass, and increased LV relative wall thickness. Doppler echocardiography is used to evaluate the characteristics of diastolic transmitral and pulmonary venous flow pattern that are used to assess diastolic function. Tissue Doppler imaging seems to be less dependent on volume status compared with routine Doppler, and has been used to aid in the diagnosis of diastolic dysfunction. Referral to a cardiologist is warranted when diastolic abnormalities are seen on echocardiogram and when signs and symptoms of heart failure are present. CXR may show cardiomegaly. In the presence of fluid overload, pulmonary oedema or pleural effusions are typical findings.
B-natriuretic peptide (BNP) is a sensitive marker of heart failure and can help differentiate the aetiology of dyspnoea between heart failure and a non-cardiac cause. However, BNP alone is unable to distinguish between systolic and DHF. [27] If heart failure is suspected, BNP may be ordered to aid in the diagnosis. Elevated BNP and N-terminal pro-BNP levels are associated with higher cardiovascular events in heart failure patients. [28] One study reported that BNP is predictive of cardiovascular mortality and early re-admission after 6 months of follow-up in patients with isolated DHF. [29] However, in another study, NT-proBNP-guided heart failure therapy failed to achieved mortality benefit, thus casting doubt on the usefulness of biomarker-guided therapy in the outpatient setting. [30] (Causes of elevated BNP other than heart failure include left ventricular hypertrophy, myocardial ischaemia, tachycardia, right ventricular overload, hypoxaemia [including from pulmonary embolism], renal dysfunction [estimated GFR <60 mL/minute], sepsis, COPD, diabetes, age >70 years, and cirrhosis. Causes of a low BNP include obesity and treatment with diuretics, ACE inhibitors, betablockers, or angiotensin receptor blockers.) Serum electrolytes may show hypervolaemic hyponatraemia, which is common in severe heart failure due to expansion of extracellular volume. Potassium levels are usually normal, but thiazide diuretics may result in hypokalaemia. Renal function tests may show increased creatinine and decreased estimated glomerular filtration rate (GFR) if renal failure is the aetiology of fluid overload, or if chronic kidney disease is responsible for the DHF.

Liver aminotransaminases (AST/ALT) will be elevated if there is passive liver congestion.

Subsequent investigations
If image quality is poor on echocardiography, radionuclide ventriculography (MUGA scan) can provide highly accurate measurements of LV function and right ventricular EF. However, it is unable to directly assess valvular abnormalities and cardiac hypertrophy. Other techniques such as CT

angiography may show coronary artery disease (CAD) or pericardial disease. Cardiac MRI may assess abnormal cardiac systolic and diastolic function. Patients who exhibit chest pain with exertion or any symptom that is suspicious (e.g., an anginal equivalent) should be screened for CAD, as ischaemia may contribute to abnormalities in systolic and diastolic function.
Stress testing may be done using exercise (e.g., treadmill, bicycle) or pharmacological (e.g., adenosine, dobutamine) methods. Exercise testing is preferred as it provides diagnostic and prognostic information from the patient's exercise capacity. Imaging techniques add to the sensitivity of the test. Stress echocardiogram and nuclear myocardial perfusion imaging with single photon emission computerised tomography (SPECT) are 2 of the most commonly used forms of stress tests. Cardiac catheterisation and coronary angiography remain the diagnostic standard in diagnosing CAD. It may be performed in patients who have a high pretest likelihood of CAD and those who have stress test showing ischaemia. Coronary revascularisation is reasonable in patients with heart failure and normal LVEF and CAD in whom symptomatic or demonstrable myocardial ischaemia is thought to be having an adverse effect on cardiac function. [26]
Click to view diagnostic guideline references.

Diagnostic criteria

Proposed criteria for DHF according to diagnostic certainty [2]

Possible DHF:
Signs and symptoms of heart failure, with supporting laboratory tests (including CXR and B-natriuretic peptide (BNP)), and response to diuretics Left ventricular ejection fraction (LVEF) 50%, but not measured at the time of the heart failure event No objective evidence of LV diastolic dysfunction (abnormal LV relaxation/filling/distensibility).

Probable DHF:
Similar to possible DHF, but LVEF 50% measured within 72 hours of the heart failure event.

Definite DHF:
Similar to probable DHF but with objective evidence of LV diastolic dysfunction.

Consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction [34]
According to the Heart Failure and Echocardiography Associations of the European Society of Cardiology, the diagnosis of DHF requires the following conditions to be satisfied:
Signs or symptoms of heart failure Normal or mildly abnormal systolic LV function Evidence of diastolic LV dysfunction.

Algorithm for the diagnosis of DHFAdapted from Paulus WJ, et al. Eur Heart J. 2007;28:2539-2550

Normal or mildly abnormal systolic LV function implies both an LVEF >50% and a left ventricular end-diastolic volume index (LVEDVI) <97 mL/m^2. Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (left ventricular end-diastolic pressure (LVEDP) >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E'>15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15>E/E'>8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation.

Case history #1
A 76-year-old female presents to the outpatient clinic with a complaint of shortness of breath with moderate exertion that has been gradually worsening over the past 6 months. She is a fairly active and healthy person except for a history of hypertension that her primary care physician has been treating for about 20 years with lisinopril and hydrochlorothiazide. She denies any chest pain with exertion. On physical examination, she has normal jugular venous pressure, no hepatojugular reflux, and no lower extremity oedema. Her cardiac examination reveals a non-displaced apical impulse, normal S1 and S2, and a fairly loud S4 with no murmurs.

Case history #2
A 56-year-old female presents to the emergency department with shortness of breath at rest, orthopnoea, and paroxysmal nocturnal dyspnoea that developed in the last 5 days. Her past medical history includes obesity, hypertension, diabetes mellitus, and chronic kidney disease stage II. She had a cardiac catheterisation done 2 years ago due to exertional chest pain that revealed non-obstructive coronary artery disease. On examination she is tachycardic with a heart rate of 110 bpm and her blood pressure is 192/98 mmHg. She has jugular venous distention up to her jaws, trace lower extremity oedema, and bi-basal crackles. She has a normal S1 and S2, but has a summation gallop with no murmurs.

Treatment Options

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

Treatment Patient group acute decompensated DHF line 1st Treatmenthide all

diuretic

Loop diuretics (e.g., furosemide, bumetanide, torasemide) have been shown to reduce preload, thus reducing ventricular filling, and improve pulmonary vascular congestion by decreasing filling pressures. Diuretics have the potential for decreasing cardiac output and causing hypotension. However, this is offset by a decrease in right ventricular (RV) diastolic pressure causing unloading of the interventricular septum and subsequent improvement in left ventricular (LV) distensibility. [52]

Diuretics must be used with caution as a sudden drop in LV filling can result in decreased cardiac output and hypotension.

Non-loop diuretics (e.g., metolazone) may be used in addition to loop diuretics when loop diuretics are not sufficient to achieve desired diuresis.

Doses should be started low and increased gradually according to response. Primary Options furosemide : 20-40 mg intravenously/intramuscularly every 1-2 hours initially, increase by 20 mg/dose increments every 2 hours according to response; 20-80 mg orally initially, increase by 20-40 mg increments every 6-8 hours according to response, maximum 600 mg/day OR bumetanide : 0.5 to 1 mg intravenously/intramuscularly every 2-3 hours, maximum 10 mg/day; 0.5 to 2 mg orally once or twice daily initially, increase according to response, maximum 10 mg/day OR torasemide : 10-20 mg orally/intravenously once daily initially, increase according to response,

La

Differential diagnosis
Condition Systolic heart failure Differentiating signs/symptoms Differentiating tests

No differentiating signs or symptoms.

Echocardiogram allows for the measurement of the left v fraction (LVEF).

Obstructive lung disease

Dyspnoea and orthopnoea may be present, but usually not paroxysmal nocturnal dyspnoea. Usual precipitants are allergens, environmental triggers, and respiratory infection.

Pulmonary function testing will show an obstructive lung without improvement after using bronchodilators.

Idiopathic pulmonary arterial hypertension

Usually causes more prominent 'right-sided' heart failure symptoms, such as jugular venous distention and oedema. Rales usually absent.

Pulmonary pressures may be indirectly measured by Dop On echocardiogram, left ventricular function is normal.

The established standard for diagnosis of pulmonary hyp catheterisation.

Pulmonary hypertension secondary to pulmonary

Dyspnoea is

Pulmonary pressures may be indirectly measured by Dop

disease

present due to lung pathology. Wheezing, rales, or rhonchi may be auscultated. 'Right-sided' heart failure symptoms such as jugular venous distention and oedema may also be present.

On echocardiogram, LV function is normal.

The gold standard for diagnosis of pulmonary hypertensio catheterisation.

High-resolution CT scan may diagnose interstitial lung pa

CT angiography may diagnose pulmonary emboli up to th thromboembolic phenomena.

branch of the pulmonary arteries. Ventilation/perfusion sc

Pulmonary function tests and sleep studies may diagnose

restrictive lung diseases that may lead to pulmonary hype

Heart failure from high metabolic demand

Hx or physical manifestations of precipitating conditions (e.g., anaemia, arteriovenous fistulas, thyrotoxicosis, sepsis).

Investigations may include FBC, thyroid function tests, an

Non-cardiogenic pulmonary oedema

No differentiating signs or symptoms. Hx of high altitude, neurological event, posttransfusion or pulmonary embolism

Echocardiogram shows normal LV function. CXR shows

Treatment approach
Acute treatment of decompensated heart failure is essentially similar for both systolic and diastolic dysfunction. The main goal of initial therapy is to relieve symptoms of SOB and oedema through diuresis. Patients with DHF typically present in a decompensated state with one or more of the following precipitating or comorbid factors: hypertensive crises, tachycardia or tachyarrhythmia, or ischaemia. These factors should be addressed to effectively manage patients in their decompensated state. Hypotension or cardiogenic shock are not typical presentations of DHF, but may be seen with systolic heart failure. The mainstays of chronic treatment are ACE inhibitors or angiotensin-II receptor blockers, and beta-blockers. Management of risk factors (e.g., diabetes, hypertension) is also key to preventing and treating chronic DHF. In patients with persistent signs of fluid overload, diuretics may be necessary.

Acute decompensated DHF

All patients with signs or symptoms of decompensated heart failure should be admitted to the hospital. Oxygen:
Adequate oxygenation should be maintained in all patients. Supplemental oxygen should be provided via nasal cannula, face mask, or mechanical ventilation to achieve oxygen saturation of >90%.

Diuresis:
Loop diuretics (e.g., furosemide) should be started. A thiazide diuretic (e.g., metolazone) may be used in addition to loop diuretics to achieve diuresis if a loop diuretic alone is not sufficient. Diuretic agents must be used cautiously and patients must be monitored closely as a sudden drop in left ventricular (LV) filling can result in decreased cardiac output and hypotension. The vasodilator nesiritide (a human B-type natriuretic peptide (hBNP) has been used as an alternative to diuretics in patients who have elevated filling pressures and require diuresis. There is limited evidence of its efficacy in the treatment of DHF, and its use is somewhat controversial. Results from a pooled analysis suggest an increase in short-term mortality and renal dysfunction associated with the use of nesiritide. [35] However, subsequent analyses and smaller studies have shown its safety. A large-scale, multi-centre randomised control trial is ongoing to establish its efficacy and safety in acute decompensated heart failure. [36] According to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, nesiritide is recommended

in patients who do not respond to diuretics alone and/or with evidence of severely symptomatic fluid overload in the absence of systemic hypotension when added to diuretics. [37] Authors recommend using nesiritide as a second-line treatment. Caution is advised in patients with renal insufficiency. Renal function should be monitored closely. It is contraindicated in hypotensive patients, patients with low cardiac filling pressures, or those with conditions that depend on venous return including significant valvular stenosis. Sodium intake should be restricted in these patients to <2 g/day.

Control of blood pressure:

ACE inhibitors or angiotensin-II receptor blockers should be added to diuretic therapy to control BP, which in turn improves diastolic performance. There is no evidence to favour the use of one over the other. Angiotensin-II slows the relaxation time in hypertrophic myocardium and failing myocardium. ACE inhibitors and angiotensin-II receptor blockers theoretically increase the rate of LV relaxation. [38] Patients hospitalised for heart failure have a significant decrease in 30-day death or re-admission if they are discharged on an ACE inhibitor. [39] In patients with controlled hypertension, ACE inhibitors or angiotensin-II receptor blockers minimise the symptoms of heart failure. [37]

The next step in treating acute decompensated DHF is to address any underlying precipitating factor for the acute decompensation. This includes, for example, control of hypertension, treatment and prevention of ischaemia, control of heart rate and/or maintenance of sinus rhythm, and treatment of concomitant infection or pulmonary disease if present.

Acute decompensated DHF: hypertensive urgency/emergency

Severe hypertension or hypertensive urgency, often defined as systolic BP greater or equal to 180 mmHg and/or diastolic BP greater or equal to 120 mmHg, can lead to elevation in LV filling pressures and precipitate decompensation in a stable heart failure patient. In the setting of acute, life-threatening complications such as hypertensive encephalopathy, retinal haemorrhages, papilloedema, or acute renal failure, this clinical scenario is known as a hypertensive emergency. Vasodilators are a broad and heterogeneous group of medications, and their use in the setting of HF depends on the haemodynamic effect desired. Intravenous vasodilators such as nitroprusside or glyceryl trinitrate are used in decompensated DHF for their blood pressure-lowering effect. Vasodilators cause similar preload unloading as diuretics, thereby causing a reduction in LV filling pressures, and may affect the myocardium causing release of nitric oxide thus improving LV distensibility. [40]

Acute decompensated DHF: tachycardia/tachyarrhythmia

Patients presenting with sinus tachycardia or a tachyarrhythmia should receive additional therapy to decrease myocardial oxygen demand and provide for adequate diastolic filling time.
In the setting of atrial fibrillation, agents such as beta-blockers, calcium-channel blockers, or digoxin are used to control the heart rate to increase diastolic filling time, and enhance cardiac output. There is no evidence to support the use of one drug class over the other in patients with acute decompensated DHF. Anticoagulation with warfarin (target INR of 2 to 3, or 2.5 to 3.5 in patients with prosthetic valves) is the accepted standard for treatment either in preparation for electrical or pharmacological cardioversion, or for persistent atrial fibrillation. It is particularly important in patients with identified moderate to high risk for stroke. Generally, in patients with no risk factors, aspirin is recommended. For patients with one moderate risk factor (i.e., age >75 years, HTN, heart failure, left ventricular ejection fraction of 35% or less, or diabetes) either aspirin or warfarin (target INR of 2 to 3) is recommended. For high-risk patients (i.e., prior cerebrovascular event, mitral stenosis, or prosthetic valve) warfarin (target INR of 2 to 3.5) is recommended, with the higher INR recommended for prosthetic valves. [41] Dabigatran is a direct thrombin inhibitor that has been approved in some countries for the prevention of stroke in patients with non-valvular atrial fibrillation as an alternative to warfarin. It is not recommended in patients with mechanical prosthetic heart valves. Amiodarone can be added to the treatment in patients with severe supra-ventricular tachyarrhythmia. It has both sympatholytic and calcium antagonistic properties, depresses AV conduction, and is effective in controlling the ventricular rate in patients with atrial fibrillation. It should be noted that although atrial fibrillation may be the tachyarrhythmia that is most commonly encountered, any tachyarrhythmia with a rapid ventricular rate can precipitate decompensation in HF. Intravenous amiodarone is effective and well tolerated in critically unwell patients who develop rapid atrial tachyarrhythmias refractory to conventional treatment, but has not been sufficiently evaluated in this indication. [41] Because tachycardia can shorten the time available for ventricular filling and coronary perfusion, drugs that slow the heart rate or the ventricular response to atrial arrhythmias, can provide symptomatic relief in patients with DHF. There may be situations where sinus tachycardia is a secondary response (e.g., hyperthyroidism, pulmonary disease) leading to HF decompensation due to inadequate ventricular filling time and increased myocardial demand. Treatment with beta-blockers or calcium-channel blockers may help in such situations. However, there is limited evidence to support their use in this setting and recommendation is based on expert opinion. In the acute decompensated state, these agents may have a potentially harmful effect on diastolic function due to their negative inotropic effect, and slowing of the rate of LV relaxation. Therefore, caution is advised.

Acute decompensated DHF: myocardial ischaemia

If a patient presents with acute coronary syndrome, [42] evaluation and treatment should be initiated according to guidelines. Aspirin should be given on clinical suspicion or diagnosis of acute coronary syndrome. [43]

Beta-blockers help decrease myocardial oxygen demand, and should be a mainstay of therapy if the patient's heart rate and BP tolerate the medication.

Revascularisation should be pursued when indicated. In the setting of acute ischaemia, early revascularisation is recommended.

In patients without known coronary heart disease but with cardiovascular risk factors and chest pain, a diagnostic workup for ischaemic heart disease may be necessary.

Maintenance therapy in patients with chronic DHF

ACE inhibitors or angiotensin-II receptor blockers are considered the mainstays of treatment in DHF. A sub-group analysis on patients with diastolic dysfunction from large heart failure trials suggests that ACE inhibitors and angiotensin-II receptor blockers decrease the rate of hospitalisation and long-term mortality. [44] [45] There is no evidence to favour the use of one over the other. However, combination therapy is not recommended due to the risk of hyperkalaemia. Beta-blockers are added to ACE inhibitors or angiotensin-II receptor blockers. Use in the chronic setting may cause regression of LV hypertrophy, reversal of adverse remodelling, and improved LV relaxation and distensibility. [46] [47] Treatment with a beta-blocker is recommended in patients with prior MI, HTN, and atrial fibrillation. [33] There is limited evidence regarding the routine use of calcium-channel blockers. Patients who have persistent signs of fluid overload require a maintenance dose of diuretic.

Maintenance therapy in patients with chronic DHF: risk factor modification

BP should be maintained at recommended targets. [NHLBI-NIH JNC-7 website] (external link)Controlling hypertension allows the LV to eject to a smaller end-systolic volume, so it can operate on a smaller diastolic volume and lower left atrial pressure. Lowering BP also allows for a rapid relaxation time, enhancing early filling. LV hypertrophy may also be reversed. Revascularisation is likely to be indicated, because ischaemia slows the LV relaxation rate and causes an increase in end-diastolic pressure. However, one study showed that revascularisation alone did not decrease the re-occurrence of pulmonary oedema in patients who presented with DHF and CAD. [48] Weight loss should be promoted in overweight patients. Surgically induced weight loss in morbidly obese individuals has been shown to reverse LV hypertrophy and restore diastolic function. [49]

Elevated right ventricular (RV) diastolic pressures of any cause can impair LV filling. Correction of factors that can increase RV and pulmonary artery diastolic pressures may theoretically improve LV filling pressures in an indirect manner.

Diabetic cardiomyopathy may be a distinct entity that causes worsening of LV diastolic function. Optimisation of glycaemic control is recommended. The American Diabetes Association (ADA) recommends to target an A1C of <7.0% but suggests targeting an A1C as close to normal (<6%) as possible if this can be achieved without causing significant hypoglycaemia. These recommendations are largely based on epidemiological studies that suggest that each 1% increase in A1C is associated with a 15% and 18% increase in the relative risk of cardiovascular disease (CVD) for patients with type 1 and type 2 diabetes, respectively. [50] The effect of tight glycaemic control on CVD outcomes is debated. However, there are no randomised clinical trials for cardiovascular outcomes in patients with heart failure. There are smaller studies using echocardiographic methods that support tight glycaemic control in patients with DHF. Augmented metabolic control has been shown to improve myocardial diastolic function and perfusion in non-insulindependent diabetes. [51]

There is no defined role for statins or aspirin in the treatment of chronic DHF. Nevertheless, these agents are used in the treatment of patients with associated CAD or ischaemia.

Tobacco and alcohol discontinuation, and regular aerobic exercise should be encouraged in these patients.

Emerging treatments
Ultrafiltration There is emerging evidence that ultrafiltration is a safe and effective alternative to intravenous diuretics in sodium and fluid removal in the setting of decompensated heart failure. One study performed in heart failure patients hospitalised for hypervolaemia showed that after 48 hours of treatment, weight and net fluid loss were greater in the ultrafiltration group compared with the intravenous diuretics group. The ultrafiltration group had fewer rehospitalisations due to heart failure, shorter re-hospitalisation stays per patient, and fewer unscheduled visits. [58] There were no differences in renal haemodynamics between the 2 groups. [59] This approach seems to be reasonable, particularly in patients who have a poor response to diuretics due to chronic kidney disease or repeated diuretic use. However, there have been no long-term studies with cardiovascular outcomes. Alagebrium Alagebrium is an advanced glycosylated end-product cross-links breaker. A 16-week pilot study involving 23 elderly patients with DHF showed that

treatment with alagebrium results in decreased left ventricular mass and increased Doppler early diastolic mitral annular velocity (E'). [60] A multicentre trial is in progress. Aldosterone antagonists Aldosterone antagonists cause regression of left ventricular hypertrophy in patients with hypertension and improves echocardiographical diastolic parameters. [61] Study is ongoing on the effect of spironolactone on clinical outcomes in heart failure patients with preserved systolic function. [TOPCAT study ] (external link) Digoxin Based on the DIG (Digitalis Investigation Group) ancillary study in patients with normal ejection fraction (EF >45%), there was no decrease in mortality, but there was a trend towards reduction in hospitalisations for worsening heart failure. [62] The literature indicates that digoxin may have a useful role for patients who are in normal sinus rhythm. Further trials are needed to clarify its role. [63] Calcium-channel blockers In studies of patients with heart failure with preserved EF, verapamil improved exercise tolerance. [55] [64]