Heart Failure Master [Compatibility Mode]

8/12/2019 Heart Failure Master [Compatibility Mode]

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M AM AKK

2014

Learning goals

Definition

Epidemiology

Determinants of cardiac performance

Types of HF

Etiology of HF

Pathophysiology

Prognosis

Diagnosis

Management

Heart failure is a clinicalsyndrome characterized byinadequate systemicperfusion to meet the body'smetabolic demands as aresult of impaired cardiacpump function.

DefinitionDefinition

The overall prevalence of heart failure was est imated as 1.0% to 1.6%, rising

from 0.1% in the 30-39 age range to 4.2% at 70- 79.

Hospital admissionsPatients with HF account for about 1,000,000 hospital admissions annually.

Hospital Re-admissionsOne-third of these patients are re-admitted within 90 days for recurrentdecompensation.

Mortality Although much progress has been made in the treatment of HF, there is a20% overall annual mortality, particularly in patients with NYHA IV symptoms.

Approximately 50% of patients with severeheart failure due to LV dysfunction

will die within 2 years. Many patients die suddenly from malignant ventricular arrhythmias or MI.

Epidemiology


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1. Pre loadIs the stress on the myocardial wall in an intact ventricle at the endof diastole - just prior to ventricular contraction - this is related tothe end diastolic pressure and volume - which ultimatelyaffect themuscle fiber length.

22.. Afterload Is the tension or "wall stress" acting after the onset of

shortening/contraction - and is primari ly mediated by arter ialpressure. As arterial pressure/resistance rises, stroke volume falls- which can cause acute exacerbations of CHF in patients withfailing hearts, especially those with diastolic dysfunction .

33.. ContractilityContractilityIs also referred to as the inotropic state. When preload and afterload are

constant, increasing contractility (with drugs for example) can augment

the cardiac output .

4. Others Strokevolume(SV) - the amount of blood ejectedwith each systole Cardiac output (CO) - which is [SV]x [Heart Rate] (beats per min) =

CO(normal is~5-6 L/M)

End diastolic volume (EDV).

Ejection fraction (i.e., the portion of blood ejected with each systole)which is the [SVdivided by EDV] x 100 (normal is 55-65%.


1. Systolic Dysfunction (SHF) vs. Diastolic Dysfunction (DHF):

Systolic failureis a disorder of impaired myocardial contractility - leading to areduced ejection fraction and a reduced stroke volume. This is associated withan elevated end diastolic left ventricular volume and pressure.

Diastolic failure is a disorder of impaired myocardial relaxation leading toreduced filling in diastole and an elevated diastolic pressure. The ejectionfraction may be normal or reduced.

Types of HF Syndrome 2. Forward HF vs. Backward HF:Backward failure is characterised by increased systemic venous pressure in the right

heart side and increased pulmonary venous pressure in the left heart side. For example,

development of fluid retention raises the workload and thereby worsens backward

failure.

Types of HF Syndrome

Forward failure shows a reduced blood flow volume (ejection) into the aorta ( left heartside) and pulmonary artery (right heart side). Forward heart failure worsens by increasedvasoconstriction which further reduces the ejection. In contrast, vasodilators improve it.


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3. Left sided HF vs. Right sided HF:

Left sided HF

There is a reduction in the left ventricular output and/or an increase in the leftatrial or pulmonary venous pressure.

Right sided HF

There is a reduction in RV output. Causes of isolated r ight heart fai lureinclude chronic lung disease (cor pulmonale), multiple pulmonary emboli and

pulmonary valvular stenosis.

Bivent.HF

Failure of the left and right heart may develop because the disease process

(e.g. dilated cardiomyopathy or ischaemic heart disease) affects both ventricles,

or because disease of the left heart leads to chronic elevation of the left atrial

pressure, pulmonary hypertension and right heart failure.

5. Acute Vs chronic HF:

Acute HF means acute onset or decompansation of CHF characterized by signs ofpulmonary and /or per ipheral congestion, including pulmonary edema and/orperipheral edema with /or without sign of peripheral hyoperfusion.

4. High-output failure

A rare cause of heart failure caused by thyrotoxicosis, arteriovenous fistulae,

Paget's disease, pregnancy, or severe chronic anemia. In such cases,

additional causes of heart failure are often present.

Coronary artery diseaseMyocardial infarctionIschaemia

Hypertension

CardiomyopathyDilated (congestive)Hypertrophic/obstructiveRestrictivefor example, amyloidosis, sarcoidosis,haemochromatosisObliterative

Valvular and congenital heart diseaseMitral valve diseaseAortic valve disease

Atrial septal defect,ventricular septal defect

Arrhythmias

TachycardiaBradycardia (complete heart block, the sick sinussyndrome)Loss of atrial transportfor example, atrial fibrillation

Alcohol and drugs

AlcoholCardiac depressant drugs ( blockers, calciumantagonists)

High output failure

Anaemia, thyrotoxicosis, arteriovenous fistulae,Pagets diseasePericardial diseaseConstrictive pericarditisPericardial effusion

Primary right heart failure

Pulmonary hypertensionfor example, pulmonaryembolism, cor pulmonale, Tricuspid incompetence

Etiology of HF ACC/AHA GH F C

NYHA I NYHA II NYHA III NYHA IV

Slight limitation in physicalactivity. More strenuousactivity causes shortness of

breathexample, walkingon steep inclines and severalflights of steps. Patients inthis group can continue tohave analmost normal lifestyleand employment

No limitation in physical activitydespite presence of heartdisease.

This can be suspected only ifthere is a history of heart disease

which is confirmed byinvestigationsexample,echocardiography

More marked limitation ofactivity which interferes with

work.Walking on the flatproduces symptoms

Unable to carry out anyphysical activity without

symptoms. Patientsare breathless at rest .

ASYPTOMATIC MILD MODERATE SEVERE


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ACC/AHA GH F C

Stage AStage AAt high risk forAt high risk forHF but withoutHF but without

structural heart diseasestructural heart diseaseor symptoms of HFor symptoms of HF

Stage BStage BStructural heartStructural heart

disease but withoutdisease but withoutsymptoms of HFsymptoms of HF

Stage CStage CStructural heart diseaseStructural heart disease

with prior or currentwith prior or currentsymptoms of HFsymptoms of HF

Stage DStage DRefractory HFRefractory HF

requiring specializedrequiring specializedinterventionsinterventions

e.g., Patients with: Hypertension

Diabetes melliusor

Patients

Using cardiotoxins

With FHx CM

StructuralStructuralHeartHeartDiseaseDisease

e.g., Patients with: Previous MI

LV systolicdysfunction

Asymptomaticvalvular disease

SymptomsSymptomsof HFof HFdevelopdevelop

e.g., Patients with: Known structural

heart disease Shortness of

breath and fatigue,reduced exercisetolerance

RefractoryRefractorysymptomssymptomsof HF atof HF atrestrest

e.g., Patients whohave symptoms at restdespite maximalmedical therapy (e.g.,those who arerecurrentlyhospitalizedor cannot be safelydischarged fromhospital withoutspecializedinterventions)

In le ft ventr icular sys to lic dys func tion,regardless of the etiology, cardiac output islow and pulmonary pressures are high,

leading to pulmonary congestion.

I nit ia lly, as a d irect result of decreas ecardiac output and systemic perfusion, thebody activates several neurohormonalpathways in order to increase circulatingblood volume. This response is adaptive

and designed to preserve normal blood flowto systemic organs.

over t ime, these responses can becomemaladaptive or counterproductive, leadingto progression of the disease andworsening of symptoms.

Pathophysiology of HF


ReninRenin--angiotensin systemangiotensin system

VasopressinVasopressin

AldosteroneAldosterone

sympatheticsympatheticnervous systemnervous system

AdaptiveAdaptivemechanismmechanism

EndothelinEndothelin

CytokinesCytokines

MaladaptiveMaladaptivemechanismmechanism


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The sympathetic nervous system

Increases heart rate and contractility, both of which increase cardiac output.Circulating catecholamines also cause arteriolar vasoconstriction in nonessential vascular beds and stimulate secretion of renin. Unfortunately,catecholamines aggravate ischemia, potentiate arrhythmias, promote cardiacremodeling, and are directly toxic to myocytes.

ReninRenin--angiotensinangiotensin systemsystem:StimulationStimulation ofof thethe reninrenin--angiotensinangiotensin systems ystem asas aa resu ltresult o fof increasedincreasedsympatheticsympathetic stimulationstimulation andand decreaseddecreased renalrenal perfusionperfusion resultsresul ts inin fur therfurtherarteriolararteriolar vasoconstriction,vasoconstriction, sodiumsodium andand waterwater retention,retention, andand releaserelease ofof

aldosteronealdosterone..

AldosteroneAldosterone::IncreasedIncreased aldosteronealdosterone,, inin turn,turn, leadsleads toto sodiumsodium andand waterwater retention,retention, endothelialendothelialdysfunctiondysfunction andand organorgan fibrosisfibrosis..


VasopressinVasopressin: In heart failure,In heart failure, baroreceptorbaroreceptor and osmotic stimuli lead toand osmotic stimuli lead to

vasopressin release from the hypothalamus causingvasopressin release from the hypothalamus causing reabsorptionreabsorption of waterof waterin the renal collecting duct.in the renal collecting duct.

EndothelinEndothelin:: endolthellinendolthellin levels are elevated in heart failure and correlatelevels are elevated in heart failure and correlatewith severity of disease and prognosis.with severity of disease and prognosis. EndothelinEndothelin is an endogenousis an endogenous

vasoconstrictor and growth factor.vasoconstrictor and growth factor.

Cytokines:Cytokines: Levels of the proLevels of the pro--inflammatory cytokines also are elevated ininflammatory cytokines also are elevated inheart failure, and contribute to cardiacheart failure, and contribute to cardiac cachexiacachexia and apoptosis.and apoptosis.


Although these neurohormonal pathways initially are compensatory andbeneficial, eventually, they are deleterious, and neurohormonal modulation isthe basis for modern treatment for heart failure.

Enhanced neurohormonal stimulation of the myocardium also causes apoptosisor programmed cell death, worsening of ventricular contractility and death.

With continuous neurohormonal stimulation, the left ventr ic le undergoesremodeling consisting of left ventricular dilatation and hypertrophy.

Left ventricular chamber dilatation causes increased wall tension, worsens

subendocardial myocardial perfusion, and may provoke ischemia in patientswith coronary atherosclerosis.

Furthermore, left ventricular chamber dilatation may cause separation of the

mitral leaflets and mitral regurgitation leading to pulmonary congestion.



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Pathophysiology of HF Pathophysiology of HF

In contrast, natriuretic peptides are hormonesreleased by secretory granules incardiac myocytes. They have a beneficial influence in heart failure, includingsystemic and pulmonary vasodilation, enhanced sodium and water excretion,and suppression of other neurohormones.


500 pg/mL, then HF is highly likely (PPV = 90%)

100500 pg/mL, consider the baseline BNP is elevated due to stableunderlying dysfunction, right ventricular failure from cor pulmonale, acutepulmonary embolism, or renal failure

In diastolic dysfunction, the primary abnormality is impaired left ventricularrelaxation causing high diastolic pressures and poor filling of the ventricles. Inorder to increase diastolic fil ling, left atrial pressure increases until it exceedsthe hydros tatic and oncot ic pressures in the pulmonary capil laries and

pulmonary edema ensues. As a resul t, patients are often symptomatic withexert ion when increased heart rate reduces left ventr icular f il ling time andcirculating catecholamines worsen diastolic dysfunction.

Pathophysiology of diastolic HF


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1. Arrhythmias, especially atrial fibrillation2. Infections(especially pneumonia)3. Acute myocardial infarction4. Angina pectoris or recurrent myocardial ischaemia5. Anaemia6. Alcohol excess

7. Iatrogenic causefor example, postoperative fluid replacement oradministration of steroids or non steroidal anti inflammatory drugs

8. Poor drug compliance, especially in antihypertensive treatment9. Thyroid disordersfor example, thyrotoxicosis10. Pulmonary embolism11. Pregnancy

12. Administration of a drug with negative inotropic properties (e.g. -blocker) or f luid-retaining propert ies (e.g. non-steroidal anti-inflammatory drugs, corticosteroids)

13. Intravenous fluid overload, e.g. post-operative i.v. infusion

Precipitating causes of heart failure

11. ArrhythmiasAtrial fibrillation; ventricular arrhythmias (ventricular

tachycardia, VF); bradyarrhythmias

2. ThromboembolismStroke; peripheral embolism; deep venous

thrombosis; pulmonary embolism

3. GastrointestinalHepatic congestion and hepatic dysfunction; malabsorption

4. MusculoskeletalMuscle wasting

5. RespiratoryPulmonary congestion; respiratory muscle weakness;pulmonary hypertension (rare)

6. Renal failure due to : Low cardiac output- Diuretics (as side effect)7. Hypokalemia due to : High aldestrone levels- Potasium losing diuretics8. Hyperkalemia due to: Drugs such as Sprinolactone +ACEI- R. dysfunction9. Sudden death in 50% of Pt.s because of V.F

Complications of heart failure

Morbidi ty and mortal ity for all grades ofsymptomatic chronic heart failure are high,with a 20-30% one year mortality in mild tomoderate heart failure and a greater than50% one year mortal ity in sever e hear tfailure.

Prognosis of HF

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I

Initial investigations

x Chest radiographyx Electrocardiographyx Echocardiography, including Doppler studiesx Haematology testsx Serum biochemistry, including renal function and glucose concentrations,

liver function tests, and thyroid function testsx Cardiac enzymes (if recent infarction is suspected), BNP.

Other investigations

X Radionuclide imagingx Cardiopulmonary exercise testingx Cardiac catheterisationx Myocardial biopsyfor example, in suspected myocarditis

Investigations if heart failure is suspected

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Treatment objectives


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HFREF: D 2012

EuropeanHeart Journal (2012) 33, 17871847

doi:10.1093/eurheartj/ehs104


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20% .

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40% 6 .

31% 1

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SOLVD Investigators. N Engl J Med 1992;327:685-91SOLVD Investigators. N Engl J Med 1991;325:293-302CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35

(Chronic Heart Failure)

SOLVD Treatment

16% mortality

1. Angiotensin Converting EnzymeInhibitors (ACE-inhibitors)

Block the renin-aldosterone-angiotensin system by inhibiting the conversionof angiotensin I to angiotensin II vasodilation and Na+ retention

bradykinin degradation its levelPG secretion & NO

Decrease cardiac preload & afterload

Major anti-remodeling effectson myocardium and vessels

Mainstay in HF: they improve cardiac function, symptoms, and survival

Angiotensin Converting EnzymeInhibitors (ACE-inhibitors) M

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P ACEI

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Study Drug

HFSeverity

TargetDose (mg) Outcome

US Carvedilol1 carvedilol mild/moderate

6.25-25 BID

48% disease progression(p= .007)

CIBIS-II2 bisoprolol moderate/severe

10 QD 34% mortality (p


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I B

: A , O O ACEI ( )

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: NHA I I ( )

: M D I , N

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Use of best beta-blocker invarious settings

Aldosterone antagonists


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What about patients with mild HF?

EPHESUS

MRAs?

Severity of heart failurePost MI

P

HF 37%

Reductions were also seen in rates o f death from any cause (24%),

cardiovascular death (24%), hospitalization for any reason (23%),and HF hospitalization (42%).

Reductions were also seen in rates o f death from any cause (24%),

cardiovascular death (24%), hospitalization for any reason (23%),and HF hospitalization (42%).


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Aldosterone antagonists

Block aldosterone receptors

Can be used in advanced HF, to further inhibit the R-A-A system after

complete uptitration of ACE-inhibitors

Check often for risk of hyperkalemia

Available agents: spironolactone, eplerenone

C A I

S/E HF!!

O (25/)

:

S (> 5%)

N

10% ( 6.0 C I

E 25/

S


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Angiotensin II antagonists

1.1. Are ARBs more effective than ACEAre ARBs more effective than ACE--inhibitors?inhibitors?

2.2. Are ARBs as effective as ACE inhibitors?Are ARBs as effective as ACE inhibitors?

3.3. Is the combination of an ARB & an ACEIs the combination of an ARB & an ACE--inhibitors more effective than ACEinhibitors more effective than ACE--

inhibitor monotherapy?inhibitor monotherapy?

4.4. Are ARBs effective in patients who cannot tolerate ACEAre ARBs effective in patients who cannot tolerate ACE--inhibitors?inhibitors?

5.5. Are ARBs effective in patients with heart failure and preserved leftAre ARBs effective in patients with heart failure and preserved leftventricular function?ventricular function?

NO

PRO

YESYES

NOT SURE??

O EF

Diuretics

The most effective symptomatic reliefThe most effective symptomatic relief

Usually shortUsually short--term IV therapy followed by longterm IV therapy followed by long--term PO therapyterm PO therapy

ThiazidesThiazides::

HCTZ, chlorthalidone

Loop diuretics:Loop diuretics:

Furosemide, torasemide,, bumetanidebumetanide,, etacrynicetacrynic acidacid

Mixed agents:Mixed agents:

Metolazone, nesiritide


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D ( )

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Diuretics

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Aspirin/oral anticoagulants

Aspirin is recommended in all pat ients w ith coronary heart d isease,diabetes or any other established form of atherosclerotic disease, unlesscontraindicated by bleeding diathesis.

Oral anticoagulants are recommended in patients withparoxysmal/permanent atrial fibrillation, or those with previous embolicevents (eg in poor LVcontractilty) and hugely dilated LV.


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Antiarrhythmics

Most common cause of sudden cardiac death in HF is ventriculartachyarrhythmia

Antiarrhythmic drugs may suppress PVC but may induce VT or VF!!!

Only amiodarone has a reasonably safe profile in HF, but no impact ofamiodarone on prognosis.

Remember the many toxic effects of amiodarone:

lung, thyroid, eye, liver

Digitalis glycosides (digoxin, digitoxin)

Their role has declined in recent years (DIG Study)

Digitals does not affect mortality in CHF patients but causes significant:

Reduction in hospitalization

Reduction in symptoms of HF

Actions:

Positive inotropic effect

Arrhythmogenic effect

Vagotonic effect

Digoxin in high risk HF patients subgroup:HF hospitalization or HF mortality


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Digitalis glycosides (digoxin, digitoxin)

Digoxin levels should be 1.0 2.0 ng/dL, but narrow & variable therapeutic

window (check serum!)

Toxicity - non cardiac manifestations:

Anorexia, nausea, vomiting, headache, xanthopsia sotoma, disorientation

Toxicity - cardiac manifestations:

Sinus bradycardia and arrest, A/V block (usually 2nd degree), atrialtachycardia with A/V block, development of junctional rhythm in patients with

AF, PVC, VT/ VF (bi-directional VT)

S D

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0.125/

(Vaso) Dilators: nitrates & hydralazine

Reduction of afterload by arteriolar vasodilatation (hydralazin) LVEDP, O2consumption, myocardial perfusion, stroke volume and CO

Reduction of preload by venous dilation

(nitrates) venous return load on both ventricles

Usually maximum benefit achieved by using both agents, but currentlyapproved (in US).


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N/H

C ACEI

R

C

S

D ISDN 4060 TID

H 25100 TID QID


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S

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Should be considered to reduce the risk of HFhospitalization in patients in sinus rhythm with an EF 35%,a HR remaining 70 b.p.m., and persisting symptoms(NYHA class IIIV) despite treatment with an evidence-based dose of beta-blocker (or maximum tolerated dosebelow that), ACE inhibitor (or ARB), and an MRA (or ARB)


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Inotropes

Improve myocardial contractility (adrenergic agonists, dopaminergic

agents, phosphodiesterase inhibitors, calcium-channel sensitizers):dopamine, dobutamine, milrinone, amrinone, levosimendan

Most studies showed long-term mortality with inotropic agents.

Yet beneficial at short-term use for peripheral hypoperfusion +/- pulmonary

edema refractory to diuretics and vasodilators

Only use them in acute conditions such as cardiogenic shock, as bridge toanother lasting intervention (eg transplant).

Invasive Non-surgical treatment in HF

ImplantableImplantable cardiovertercardioverter debribillatorsdebribillators (ICD)(ICD)

Cardiac resynchronization therapy (CRT)Cardiac resynchronization therapy (CRT)

I (ICD)

P EF35% CHF ICD ()

P T SCD ICD ( )

P T EF 3040% ICD ( )

Angina, reversible ischaemia,Coronaryrevascularisation

(PTCA, CABG)

Significant valve disease (AS, MR)Valve replacement (or repair)

End stage heart failureCardiac transplantation

Short term ventricular supportegawaiting for transplantation

Ventricular assist devices

Stem cells- cardiac reconstructionNovel surgical techniques

Type of surgery Reason

Surgical management of HF


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2

C

I

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1 80% 90%

5 70%

10 50%

L .

Non-pharmacological measures

Compliance: give careful advice about disease, treatment, and self helpstrategies

Diet: ensure adequate general nutrition and, in obese patients, weightreduction

Salt: advise patients to avoid high salt content foods and not to add salt

(particularly in severe cases of CHF)

Fluid: Advice overloaded patients and those with severe CHF to res tricttheir fluid intake

Alcohol: advise moderate alcohol consumption.

Smoking: avoid smoking.

Exercise: regular exercise should be encouraged

Vaccination: patients should consider influenza and pneumococcal

vaccinations

TAILORED T

: 1. S, , (); 2.

M

(O, 2 2005)

M

I II III IV


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Control Volume Improve Clinical Outcomes

Diuretics

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD*

HDZN/ISDN*

*In selected patients

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HFPEF.

D

HFREF.

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AF.

T HFREF

HFPEF, CCB.

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()


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2

Spironolactone (25mg/d) improved diastolic function.

Did not improve exercise capacity, NYHA class, or quality of life

No significant differences in death or hospitalization rates.

Was safe and not associated with severe adverse events

Can be considered in patients with diastolic heart failure for

improving cardiac function and blood pressure control

Spironolactone (25mg/d) improved diastolic function.

Did not improve exercise capacity, NYHA class, or quality of life

No significant differences in death or hospitalization rates.

Was safe and not associated with severe adverse events

Can be considered in patients with diastolic heart failure for

improving cardiac function and blood pressure control

TOPCAT is a multi-center, international, randomized, double blindplacebo-controlled trial of the aldosterone antagonist,

spironolactone, in 3,445 adult subjects with heart failure and leftventricular ejection fraction of at least 45%, recruitedinternationally from over 200 clinical centers in the US, Canada,

Russia,Republic of Georgia, Argentina, and Brazil.

Enrollment started in August 2006 and recently ended on January31, 2012.

Potassium Spiro Placebo P (chi-sq)

Hyperkalemia(5.5 mmol/L)

322(18.7%)

157(9.1%)


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Spironolactone(N = 1722)

Placebo(N = 1723)

HR (95% CI)

Primary Outcome320 (18.6%)5.9/100pt-yr

351 (20.4%)6.6/100pt-yr

0.89 (0.77-1.04)P=0.138

Hospitalization for HeartFailure

206 (12.0%)3.8/100pt-yr

245 (14.2%)4.6/100pt-yr

0.83 ( 0.69-0.99)P=0.042

Multiple HF HospP


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Documents

Heart Failure Master [Compatibility Mode]