Advanced Heart Failure: My ApproachAdvanced Heart Failure: My Approach

J.L. Mehta, MD, PhDJ.L. Mehta, MD, PhD

Stebbins Chair in CardiologyStebbins Chair in Cardiology

Professor of Internal Medicine, Physiology and BiophysicsProfessor of Internal Medicine, Physiology and Biophysics

University of Arkansas for Medical SciencesUniversity of Arkansas for Medical Sciences

Little Rock, ARLittle Rock, AR

Feb 4, 2011Feb 4, 2011

Topics to be Discussed

Burden of heart failure

Causes of heart failure, morbidity and mortality

Pathophsiology

Role of RAAS and SNS blockers, and diuretics

When to use defibrillators/biventricular pacing

CHF affects more than 4.5 million people in the USA

and 0.5 million new cases are diagnosed each year

1.2-2% of the population has CHF, with 75-80% of the

group are above the age of 65 years

Nearly 20 million people have unsuspected disease

and likely to develop CHF in the next 1- 5 years

CHF is responsible for >11 million visits to a

physician's office and result in 3.5 million

hospitalizations per year

Median survival following onset is 1.7 years for men

and 3.2 years for women- worse than lung cancer

Burden of Heart Failure

Causes of Heart Failure, Morbidity and Mortality

Causes of heart failure- Ischemic heart disease

- Hypertension

- Cardiomyopathies (viral, alcohol)

Causes of Hospitalization

- Non-compliance with drugs

- Excessive salt and alcohol intake

- Infections

- Anemia

- Co-morbidity (e.g. renal dz, Liver dz,

depression)

Angiotensin - Angiotensin - Angiotensin

Myocardial ischemia and Low Cardiac Output StateMyocardial ischemia and Low Cardiac Output State

InflammationInflammation

Release of MMPs Release of MMPs and collagen and collagen degradationdegradation

Myocyte slippageMyocyte slippage

Wall thinning Wall thinning and regional and regional dilatationdilatation

Wall stress Wall stress

Local Ang II releaseLocal Ang II release

Release of Release of Catecholamines, Catecholamines,

ANP, BNP and ET-1ANP, BNP and ET-1

TGFTGF1, PAI-1, 1, PAI-1, ROS expressionROS expression

Myocyte apoptosis, Myocyte apoptosis, Fibroblast growthFibroblast growth

Collagen Collagen formationformation

Myocyte Myocyte hypertrophyhypertrophy

Cardiac Cardiac enlargement enlargement and fibrosisand fibrosis

Early Stage Intermediate Stage Late Stage

Mehta JL, 2010

RAS, renin-angiotensin system; SNS, sympathetic nervous system.

Myocardial injury to the heart

Morbidity and mortalityArrhythmiasPump failureRenal dysfn

Peripheral vasoconstrictionHemodynamic alterations

CHF symptoms

Remodeling and progressive

worsening of LV function

Initial fall in LV performance, wall stress

Activation of SNS

Fibrosis, apoptosis,

hypertrophy, cellular,

alterations,myotoxicity

FatigueChest congestionEdemaSOB

Neurohormonal Activation in Heart Failure

Mortality by Baseline Plasma Norepinephrine Level

Francis G et al. Circulation. 1993;87(suppl VI):VI-40 - VI-48.

100

80

60

40

20

0 6 12 18 24 30 36 42 48 54 60

Months

Cu

mu

lati

ve M

ort

alit

y (%

)

> 900 pg/mL

> 600 and < 900 pg/mL

< 600 pg/mL

OverallP < .0001

0

When to Use ß-blockers and RAS Inhibitors

It dose not matter which agent is started first, but early ß-blockade reduces the risk of sudden death in the first year

The usual practice of starting the ACE inhibitor first may lead to under-treatment with ß-blockers

Willenheimer, Eur Heart J Suppl 2009;11:A15-A20

The CIBIS III trial

Treatment of Advanced of Heart Failure Part 1

Hospitalize early Treat first with usual drugs- if patient not

responsive, then change Rx Limit salt intake Treat hypertension Treat infections- usually UTI or pulmonary Treat anemia to hemoglobin to ~10 g/100 ml Treat co-morbidity (e.g. renal dz- may need fluids) Treat abnormal thyroid function If patient has angina, use anti-ischemic therapy If patient has valvular dz, may consider surgery

when patient is stable

Treatment of Advanced Heart Failure Part 2

ACE inhibitors, ARBs, Hydralazine and Nitrates

Use maximal dose of ACE inhibitors, if not

tolerated then use ARBs May combine the two groups of drugs If patient is already taking ACE inhibitors/ARBs,

switch to hydralazine + nitrates- use adequate

dose, response is quick Dose of hydrazine- 50-100 mg TID and ISD- 40

mg TID

Diuretics

Excessive diuresis can cause metabolic alkalosis

and poor renal perfusion- if present hold diuretics If no alkalosis, use IV lasix or metalazone If alkalosis present, use K+ and Mg+

supplementation Patient may have acute renal failure from excessive

diuresis, consider gentle fluid administration If patient has hyponatremia, consider half or normal

saline (250 ml per hr until urine output improves or

patient develops rales when diuresis may be begun)

Treatment of Advanced Heart Failure Part 3

RALES: Probability of Survival

Patients with Class II-IV CHF

30% reduction in risk of death

31% reduction in cardiac death,

P<0.001

Pitt, B. et al. N Engl J Med 1999;341:709-717

Eplerenone in Mild CHF- EMPHASIS-HF

Zannad F et al. N Engl J Med 2011;364:11-21.

Patients with class I-II CHF

NNT-19

Other therapies

Digitalis- increases CO and makes patient feel

better Dobutamine / milrinone- use short course only-

no long tem benefit Nasiritide - no role in the therapy of CHF CCBs – no role in the therapy of CHF Ultra-filtration - no better than diuresis

Treatment of Advanced Heart Failure Part 4

CRT improves functional capacity, quality of life, and reduces hospitalization in patients with advanced symptomatic CHF, and evidence of a ventricular conduction abnormality.

Appropriate method patient selection for CRT is not clear.

Issues about the placement of LV lead remain.

Cardiac Resynchronization Therapy:Treatment of Advanced Heart Failure

Part 5

Implantable defibrillators reduce the risk of sudden death in patients with CHF, with and without prolonged QRS duration

Patients with Class II-III benefit more than Class IV patients

Issues:

- Who are the best candidates for defibrillators?

- Is the cost of implanting and maintaining these devices worth the benefit?

- How can side effects and risks be minimized?

ICD Therapy:Treatment of Advanced Heart Failure

Part 6

CRT / ICD and Death or Hospitalization for CHF

Tang AS et al. N Engl J Med 2010;363:2385-2395.

In class II or III CHF patients, with wide QRS complex, and EF <30%, the addition of CRT to ICD reduced rates of death and hospitalization for CHF. This improvement was accompanied by more adverse events in 1 month (pneumothorax, hematoma and infections).

Thank you