overview · • HF is the final common pathway for all cardiac disease COP YRIGHT. symptoms...

overview• pathophysiology

• management of chronic HF (dilated LV and reduced LVEF)

• management of ADHF

• mitral regurgitation

• HFpEF (diastolic HF) nondilated LV with preserved LVEF

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definition• syndrome resulting from pathological

reduction of cardiac output or elevation of ventricular filling pressures or both

• LV dysfunction (systolic or diastolic) ≠heart failure

• HF is not a diagnosis made by echocardiography (although echo helps!)

• HF is the final common pathway for all cardiac disease

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symptoms• effort intolerance

• dyspnea, orthopnea, PND

• edema

• GI (anorexia, malabsorption, diarrhea, cardiac cachexia, visceral congestion, cirrhosis)

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physical findings• jugular venous distention (Kussmaul sign)

• peripheral edema

• S3, prominent P2, displaced LV/RV PMI

• pulmonary vascular congestion

• ascites, abdominojugular reflux

• weak arterial pulsations, reduced BP

• reduced skin perfusion

• reduced mental status

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echocardiography• reduced LVEF/SV

• LV chamber enlargement/LVH

• LA/RA enlargement

• valve dysfunction (MR/AS/AR/MS/TR)

• pulmonary hypertension

• diastolic filling abnormality (ranging from delayed relaxation to restrictive filling)

• pericardial thickening/constraint

• elevated LV/RV filling pressure

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Scope of problem• DRG 127: heart failure & shock represents 6% of the

entire volume of all Medicare discharge diagnoses

• By far the highest volume Medicare DRG (next are pneumonia @ 3.9%, CVA @ 3.2%, and psychoses @ 3.2%)

• 5 million Americans have HF

• 550,000 new cases annually

• > 1 million hospitalizations/year for HF as 10 dx

• 2 million hospitalizations/year for HF as 20 dx

• $37 billion in direct and indirect costs per year in USA

• Mortality with HF is, respectively, 11%, 22%, and 42% at 30 days, 1 year, and 5 years post hospitalization for ADHF

• 30% readmission rate for ADHF within 3-6 months

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etiology• Coronary

• Hypertension

• Valvular

• Drugs and toxins

• Viral and other infectious

• pregnancy-assciated

• Idiopathic (contractile protein gene mutations)

• infiltrative

• radiation

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HFSA 2006 Practice Guideline (3.2)

HF Risk Factor Treatment Goals

Maximum 2-3 g/dayDietary Sodium

CessationSmoking

Men 2 drinks/day, women 1Alcohol

Weight reduction < 30 BMIObesity

20-30 min. aerobic 3-5 x wk.Inactivity

See NCEP guidelines2Hyperlipidemia

See ADA guidelines1Diabetes

Generally < 130/80Hypertension

GoalRisk Factor

Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive

Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

1. Diabetes Care 2006; 29: S4-S42.

2. JAMA 2001; 285:2486-97.

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pathophysiology• Initial insult (MI, HTN, valve, virus, toxin, etc)

causes reduced SV/CO or increased LV/RV filling pressure

• reduced CO triggers compensatory mechanisms (adrenergic, RAAS, inflammatory cytokines) are adaptive in the short-term

• Persistent hyperactivation of these compensatory mechanisms leads to deleterious remodelling of cardiac structure and function at the molecular and cellular level, and eventually of the entire circulatory system, leading to decompensation in the long-term

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medical therapy of HF

• diuretics (see ADHF)

• beta blockers/ivabradine

• vasodilators: ACE-inhibitors/ARBs/ARNI

• aldosterone antagonists

• digoxin

• antiarrhythmicsCOPYRIGHT


Loop Diuretics

6 hrs67%R-33%M200 mg25-50 mg qd

or bid

Ethacrynic

acid

12-16 hrs20%R-80%M200 mg10-20 mg qdTorsemide

6-8 hrs62%R/38%M10 mg0.5-1.0 mg

qd or bid

Bumetanide

4-6 hrs65%R-35%M600 mg20-40mg qd

or bid

Furosemide

Duration of

Action

Elimination:

Renal – Met.

Max Total

Daily Dose

Initial Daily

Dose

Agent

Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive


absorption

+

+++

+

+

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HFSA 2006 Practice Guideline (7.3, 7.4)

Pharmacologic Therapy: Beta Blockers

Beta blockers shown to be effective in clinical trials are recommended for symptomatic and asymptomatic patients with an LVEF 40%.

Strength of Evidence = A

Beta blockers are recommended as routine therapy for asymptomatic patients with an LVEF 40%.

§ Post MI Strength of Evidence = B

§ Non Post-MI Strength of Evidence = C



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Effect of Beta Blockade on Outcome

in Patients With HF and Post-MI LVD

23% mortality (p =.031)25 BIDpost-MI

LVD

carvedilolCAPRICORN5

35% mortality (p = .0014)25 BIDseverecarvedilolCOPERNICUS4

34% mortality (p = .0062)200 QDmild/

moderate

metoprolol

succinate

MERIT-HF3

34% mortality (p <.0001)10 QDmoderate/

severe

bisoprololCIBIS-II2

48% disease progression

(p= .007)

6.25-

25 BID

mild/

moderate

carvedilolUS Carvedilol1

Outcome

Target

Dose (mg)

HF

SeverityDrugStudy

1. Colucci WS et al. Circulation 1196;94:2800-6.

2. CIBIS II Investigators. Lancet 1999;353:9-13.

3. MERIT-HF Study Group. Lancet 1999;353:2001-7.

4. Packer M et al. N Engl J Med 2001;3441651-8.

5. The CAPRICORN Investigators. Lancet 2001;357:1385-90.

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Pharmacologic Therapy: Beta Blockers

RECENT DECOMPENSATION OR EXACERBATION

Beta blocker therapy is recommended for patients with a recent decompensation of HF after optimization of volume status and successful discontinuation of IV diuretics and vasoactive agents.

Whenever possible, beta blocker therapy should be initiated in the hospital at a low dose prior to discharge of stable patients.

Strength of Evidence = B

Continuation of beta blocker therapy is recommended in most patients experiencing a symptomatic exacerbation of HF during chronic maintenance treatment. Strength of Evidence = C

§ If necessary, consider temporary dose reduction

§ Avoid abrupt discontinuation

§ Reinstate or gradually increase before discharge



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metoprolol vs carvedilol: which one should I use?

• metoprolol (b1)

• carvedilol (b1, b2, a1)

• avoid carvedilol in patients with active bronchospasm or hypotension

• COMET: mortality (all-cause and CV) lower in carvedilol arm (34 and 29%, repectively) than in metoprolol arm (40 and 35%, respectively)

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Figure 3. Kaplan-Meier cumulative event curves for (A) the

primary composite endpoint of cardiovascular death or hospital admission for worsening heart failure, (B) hospital admission for worsening heart failure, and (C) cardiovascular death

Ivabradine and outcomes in chronic heart failure (SHIFT): a

randomised placebo-controlled study (Lancet (2010) 376, 875-885ProfKarlSwedbergMDaProfMichelKomajdaMDbProfMichaelBöhmMDcProfJeffrey

SBorerMDdProfIanFordPhDeArianeDubost-

BramaMDfGuyLereboursMDfProfLuigiTavazziMDgon behalf of the SHIFT

Investigators‡

IIa B-RIvabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤35%) who are receiving GDEM, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest(37–40).

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Pharmacologic Therapy: ACE Inhibitors

ACE inhibitors are recommended for symptomatic and asymptomatic patients with an LVEF 40%.


ACE inhibitors should be titrated to doses used in clinical trials (as tolerated during uptitration of other medications, such as beta blockers). Strength of Evidence = C

ACE inhibitors are recommended as routine therapy for asymptomatic patients with an LVEF 40%.

§ Post MI Strength of Evidence = B

§ Non Post-MI Strength of Evidence = C



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ACE Inhibitors in Heart Failure:

From Asymptomatic LVD to Severe HF

SOLVD Prevention

(Asymptomatic LVD)

20% death or HF hosp.

29% death or new HF

CONSENSUS

(Severe Heart Failure)

40% mortality at 6 mos.

31% mortality at 1 year

27% mortality at end of

study

§ No difference in incidence of

sudden cardiac death

SOLVD Investigators. N Engl J Med 1992;327:685-91.

SOLVD Investigators. N Engl J Med 1991;325:293-302.

CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35.

(Chronic Heart Failure)

SOLVD Treatment

16% mortality

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Pharmacologic Therapy:

Angiotensin Receptor Blockers

ARBs are recommended for routine

administration to symptomatic and

asymptomatic patients with an

LVEF 40% who are intolerant to

ACE inhibitors for reasons other than

hyperkalemia or renal insufficiency.




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ARBS in Patients Not Taking ACE Inhibitors:

Val-HeFT & CHARM-Alternative

Val-HeFT

Valsartan

Placebo

p = 0.017

Months

Su

rviv

al

%

CV

De

ath

or

HF

Ho

sp

%

Placebo

Candesartan

CHARM-Alternative

HR 0.77, p = 0.0004

Months

Maggioni AP et al. JACC 2002;40:1422-4.

Granger CB et al. Lancet 2003;362:772-6.

50

60

70

80

90

100

0 3 6 9 12 15 18 21 24 27

0

10

20

30

40

50

0 9 18 27 36 42

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Angiotensin Receptor–Neprilysin Inhibition (ARNI) versus Enalapril in Heart Failure

John J.V. McMurray, M.D., Milton Packer, M.D., Akshay S. Desai, M.D., M.P.H., Jianjian Gong, Ph.D., Martin P. Lefkowitz, M.D., Adel R. Rizkala, Pharm.D., Jean L. Rouleau, M.D., Victor C. Shi, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., Michael R. Zile, M.D., for the PARADIGM-HF Investigators and Committees

N Engl J MedVolume 371(11):993-1004

September 11, 2014

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Study Overview

• The ARNI LCZ696 was compared with the ACE inhibitor enalapril in patients with advanced heart failure.

• LCZ696 was superior to enalapril in all outcomes.

• Neprilysin inhibition may replace ACE inhibition for the treatment of heart failure.

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Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.

McMurray JJV et al. N Engl J Med 2014;371:993-1004

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Pharmacologic Therapy:Hydralazine and Oral Nitrates

A combination of hydralazine and isosorbide dinitrate is recommended as part of standard therapy, in addition to beta-blockers and ACE-inhibitors, for African Americans with LV systolic dysfunction:

§ NYHA III or IV HF Strength of Evidence = A

§ NYHA II HF Strength of Evidence = B



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A-HeFT All-Cause MortalityS

urv

iva

l %

Days Since Baseline Visit

43% Decrease in Mortality

Fixed Dose ISDN/HDZN

Placebo

P = 0.01

Taylor AL et al. N Engl J Med 2004;351:2049-57.

85

90

95

100

0 100 200 300 400 500 600

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aldosterone• Promotes sodium retention and potassium

excretion in the collecting tubule

• Promotes myocardial fibrosis and triggers inflammatory cell signaling in the myocardium in animal models of HF

• Is not completely blocked by ACE-I due to incomplete supression of angiotensin II production as well as non-angiotensin II-triggered production

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HFSA 2006 Practice Guideline (7.14-7.15)

Pharmacologic Therapy:

Aldosterone Antagonists

An aldosterone antagonist is recommended for

patients on standard therapy, including diuretics,

who have:

§ NYHA class IV HF (or class III, previously class IV)

due to LV systolic dysfunction (LVEF 35%)

One should be considered in patients post-MI

with clinical HF or diabetes and an LVEF < 40%

who are on standard therapy, including an ACE

inhibitor or an ARB. Strength of Evidence = A



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Aldosterone Antagonists in HF

RALES (Advanced HF) EPHESUS (Post-MI)

Spironolactone

Placebo

Months

RR = 0.70

P < 0.001

Epleronone

Placebo

RR = 0.85

P < 0.008

Pitt B. N Engl J Med 1999;341:709-17.

Pitt B. N Engl J Med 2003;348:1309-21.

Pro

ba

bilit

y o

f S

urv

ival

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 3 6 9 12 15 18 21 24 27 30 33 36

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 3 6 9 12 15 18 21 24 27 30 33 36

Months

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HFSA 2006 Practice Guideline (7.16-7.18)

Aldosterone Antagonists and Renal Function

Aldosterone antagonists are not recommended when:

§ Creatinine > 2.5mg/dL (or clearance < 30 mL/min)

§ Serum potassium> 5.0 mmol/L

§ Therapy includes other potassium-sparing diuretics


It is recommended that potassium be measured at baseline, then 1 week, 1 month, and every 3 months


Supplemental potassium is not recommended unless potassium is < 4.0 mmol/L Strength of Evidence = A



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MADIT II: Prophylactic ICD in

Ischemic LVD (LVEF 30%)

365 (.69)170 (.78)329 (.90)490Conventional

9110 (.78)274 (.84)503 (.91)742Defibrillator

Number at Risk

0 1 2 3

.7

.8

.9

1.0P

rob

ab

ilit

y o

f S

urv

ival

Conventional

Therapy

Defibrillator

Year

.6

04

Moss AJ et al. N Engl J Med 2002;346:877-83.

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ICD Therapy in the SCD-HeFT Trial:

Mortality by Intention-to-Treat

.007.62-.96.77ICD vs Placebo

.53.86-1.301.06Amiodarone vs Placebo

P Value97.5% ClHR

Months of Follow-Up

Mo

rtality

0 6 12 18 24 30 36 42 48 54 600

.1

.2

.3

.4

Amiodarone

ICD Therapy

Placebo

17%

22%

Bardy GH et al. N Engl J Med 2005;352:225-37.

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cardiac resynchronization therapy (CRT)

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Device Therapy:

Biventricular Pacing

Biventricular pacing therapy should be consideredfor patients with all of the following:

§ Sinus rhythm

§ A widened QRS interval ( 120 ms)

§ Severe LV systolic dysfunction (LVEF 35% with LV dilation > 5.5 cm)

§ Persistent, moderate-to-severe HF (NYHA III) despite optimal medical therapy.




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CRT Improves Quality of Life and

NYHA Functional Class

(%)

Abraham WT et al. Circulation 2003;108:2596-2603.

Average Change in Score

(MLWHF)

-20

-15

-10

-5

0

MIR

AC

LE

MU

STIC

SR

CO

NTA

K C

D

MIR

AC

LE

IC

D

* P < .05Control CRT

* **

*

NYHA: Proportion Improving

by 1 or More Class

0

20

40

60

80

MIRACLE CONTAK

CD

MIRACLE

ICD

**

*

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Effect of CRT Without an ICD on

All-Cause Mortality: CARE-HF

571192321365404Medical Therapy

889213351376409CRT

Number at risk

0 500 1,000 1,500

25

50

75

100

% E

ven

t-F

ree S

urv

ival

Medical

Therapy

CRT

Days

0

HR = 0.64 (95% CI = .48-.85)

p = .0019

Cleland JG et al. N Engl J Med 2005;352:1539-49.

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dilated cardiomyopathyLBBB

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LBBB pre-CRT

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LBBB post-CRT

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Management of acutely decompensated heart

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Volume unloading does not necessarily result in reduced cardiac output

• decreasing MR/TR improves antegrade stroke volume

• shrinking the RV (by reducing pericardial constraint and ventricular interaction) allows improved LV filling

• Reduced myocardial edema improves systolic and diastolic function

• decreasing wall stress reduces myocardial oxygen demand and ischemia

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Diuretics (thiazides)

• When thiazide diuretics are added to loop diuretics, synergistic diuresis often results, and can often overcome “diuretic resistance” through sequential nephron blockade

• Metolazone (Zaroxolyn) and HCTZ (Hydrodiuril) are the two most commonly used thiazides

• Diuril is the IV form of HCTZ ($200/dose)!

• 5 mg metolazone = 50 mg HCTZ

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Theoretical advantages of continuous infusion over intermittent bolus dosing

• less ototoxicity

• increased sodium excretion due to elimination of drug-free intervals

• Continuous maintenance of a moderate drug level allowing for continuous translocation of extravascular fluid back into the circulation (plasma refill)

• less hypotension and azotemia

• typical regimen consists of furosemide at 7-20 mg/h IV (max 100 mg/h) continuous infusion with or without an oral thiazide (metolazone or HCTZ) – make sure to give an initial loading dose!

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HFSA 2006 Practice Guideline (12.3, Table 12.3)

Acute Decompensated Heart Failure (ADHF)—

Treatment Goals for Hospitalized Patients

• Improve symptoms, especially congestion and low-output symptoms

• Optimize volume status

• Identify etiology

• Identify precipitating factors

• Optimize chronic oral therapy; minimize side effects

• Identify who might benefit from revascularization

• Educate patients concerning medication and HF self-assessment

• Consider enrollment in a disease management program

Strength of Evidence = C



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Heart Failure Disease Management

Patients recently hospitalized for HF

and other patients at high risk

should be considered for referral

to a comprehensive HF disease

management program that delivers

individualized care.




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HF Disease Management and the

Risk of Readmission

Risk

Ratio

Summary RR = 0.76 (95% CI .68-.87)

Summary RR for randomized only = 0.75 (CI = .60-.95)

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Mitral regurgitation

treatment target in advanced HFCOPYRIGHT

Otto et al, NEJM 2001

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Romano and Bolling (2004) J Card Surg

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Grigioni et al (2001) Circulation (103) 1759-1764

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Natural history of MR

• Chronic severe MR can persist for a number of years without overt symptoms

• Progressive LV and LA chamber dilation

• Symptoms: fatigue, DOE, PND, orthopnea

• Secondary consequences include pHTN and AF

• MVR/HF/death is essentially unavoidable within 10 years

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Otto et al NEJM 2001

AHA/ACC guidelines for management of chronic severe MR

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Adherence to guidelines works!

Rosenchek et al (2006) Circulation (113) 2238

132 asymptomatic patients with severe MR from MVP or flail followed until a conventional endpoint indicating MV surgery occurred (HF, LVE, EF, pHTN, AF)

35 patients underwent MV surgery:29 repairs6 replacements

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HFpEF (diastolic HF)

• acute and chronic management of volume overload same as in systolic HF but (by definition) more preload sensitivity

• chronic management consists primarily of: (A) managing volume overload, and (B) addressing the underlying process leading to stiff LV and HF (aortic stenosis, HTN, infiltrative processes, pericardial disease)

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There is a lot of DD out there

28%

8%

Redfield et al (2003) JAMA

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DD predicts all-cause mortality...


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...but only severe DD predicts HF


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Effects of candesartan in patients with chronic

heart failure and preserved left-ventricular ejection

fraction: the CHARM-Preserved Trial , By: Yusuf, Salim, Pfeffer, Marc A., Swedberg, Karl, Granger, Christopher B., Held, Peter, McMurray, John J. V., Michelson, Eric L., Olofsson, Bertil, ostergren, Jan, Lancet, 0099-5355, September 6, 2003, Vol. 362,

Issue 9386

pharmacologic therapy for HFpEF

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no difference in CV death between candesartan and placebo

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cardiac transplantation and mechanical circulatory support

• Is the HF truly at end-stage?

– medical

– coronary

– valve

– rhythm

– resynchronization

– pericardium

• Are there contraindications?

– irreversible pulmonary hypertension

– active infection

– cancer

– nonadherent or unsupported patient

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HF overview: conclusions (1)

• HF management increasingly guideline-driven

• sticking to the guidelines reduces morbidity and mortality

• guideline adherence is low (<33% for guideline-recommended use of aldosterone antagonists)

• Consider continuous IV infusion of furosemide in patients who are difficult to diurese

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HF overview: conclusions (2)

• Mitral regurgitation is a common problem in sHF, and its presence confers significant incremental mortality and morbidity. However, when managed in accordance with AHA guidelines, the outcome is excellent

• DD is an echocardiographic/hemodynamic finding, and neither a diagnosis nor a disease. It is highly prevalent in the general population, especially in the aged, but not necessarily associated with or causative of HF

• HFpEF (DHF) is generally more difficult to treat than is HFrEF (SHF), due to the high preload-dependence that defines DHF and to the absence of proven efficacious therapies for DHF (unlike for SHF)

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overview · • HF is the final common pathway for all cardiac disease COP YRIGHT. symptoms...

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