Heart Failure : An Introduction Pathophysiology and Treatment

Allen S. Anderson, MD Medical Director, Bluhm Center for Heart Failure Professor of Medicine, Feinberg School of Medicine

Case example • 76 year old attorney. 1 week PTA developed

SOB, edema and orthopnea. No chest pain. • Elevated JVP, bilateral rales, ankle edema,

pleural effusions, and a heart rate of 140 BPM. No murmur, rub or gallop. BP 130/80.

• CXR showed CHF. Spiral CT of chest negative for PE. Cardiac enzymes mildly elevated.

• EKG read as sinus tachycardia and poor r progression −> cardiology consult.

1/29/01

76-year-old attorney with effort dyspnea for 1 week:

1/29/01

76-year-old attorney with effort dyspnea for 1 week:

1/30/01 Monitor strip

Right CSM 1/30/01

Case example (continued)

• Treatment – I.V. digoxin & furosemide, oral Lopressor,

nasal O2, ASA, nitrates −> rate slowed −> later atrial fibrillation with pauses.

• Emergency Doppler echocardiogram – Global hypokinesis with EF 15%.

• Continued medical therapy for 3 days until stable with controlled heart rate.

What would you do next?

• A dobutamine stress echo showed significant ischemia and viability.

• A cardiac cath was done next.

Dobutamine Stress Echo showing myocardial viability

Coronary angiogram

Main left: 80%

LAD: 70% diagonal 1

RCA 60% stenosis mid RCA

LV gram: systolic global hypokinesis; EF 35%

To OR CABG

Post op EF = 55% Normal LV

Key Areas of Interest • Is the patient in heart failure? • What is the underlying heart disease? • What caused the heart to fail at this time? • What is the best therapy to correct the

underlying pathophysiology? • And how do we keep the patient out of the

hospital?

Heart Failure Defined

A clinical syndrome characterized by the inability of the heart to generate sufficient cardiac output to meet the metabolic demands of the end organs (despite adequate venous return) or to do so only with increased cardiac filling pressures.

“Congestive” Heart Failure Defined

A clinical syndrome of sodium and water retention leading to breathlessness

caused by neurohormonal activation in the setting of cardiac disease

How long does the physician wait before interrupting a patient giving a medical history?

Answer: 23 seconds

Patient-Physician Communication: Why and How Traveline JM, Ruchinskas R, D’Alonzo Jr GE JAOA. 2005. 105 (No. 1): 13-18

BUN ( Creatinine )

20(1)

Neck Veins Go to YouTube and search for audio version of Dr. Heywood’s neck vein video. Also check out a search for S3 and S4 to see a

video of how to pick up certain sounds and murmurs.

CC: Chest pressure for 2 hours HPI: 50 YO diabetic businessman had CABG 9 years ago & 2 hrs ago awoke at 2 AM with new substernal chest pressure 5/10 with SOB but no dizziness, nausea, vomiting or sweating. Pressure increased despite sitting up & 1 TNG and he called 911. He also has HTN, high chol & smokes 1 PPD. In the ED he had positive markers and EKG changes of an anterior STEMI and a new murmur typical for a VSD. CXR showed HF.

CC

HPI

Risk Factors Pertinent Positives

Pertinent Negatives

Target Organ Involvement Complications

CC: Chest pressure for 2 hours HPI: 50 YO diabetic businessman had CABG 9 years ago & 2 hrs ago awoke at 2 AM with new substernal chest pressure 5/10 with SOB but no dizziness, nausea, vomiting or sweating. Pressure increased despite sitting up & 1 TNG and he called 911. He also has HTN, high chol & smokes 1 PPD. In the ED he had positive markers and EKG changes of an anterior STEMI and a new murmur typical for a VSD. CXR showed HF.

In the diagram the parts of the HPI are in darker blue and are really elaboration of the CC. The illustrated story (yellow text box) is condensed but includes his coronary risk factors, pertinent positive and negative symptoms, target organ involvement (acute MI) and two complications (VSD and heart failure). In a full illustration there would be much more detail: “Little things are infinitely the most important.” Also note the HPI clearly begins years before the CC and is written in chronological order.

4 basic clinical principles will help lead to the correct diagnosis and treatment

• Don’t take the history from the patient; allow the person to tell his or her story.

• Observe. Selective attention is the heart of the physical examination.

• When ordering a laboratory test, know what question you want answered and be sure to check on the results.

• If an organ or an organ system fails, look for a precipitating cause.

With experience, one day you will be able to select from the myriad of details in the H&P what is relevant, pertinent or critical from what is not.

Cardiac Physiology

Circulatory System

Heart: Generates pressure and flow Blood vessels: Conduit plus

•Large arteries: distribution, elastic recoil •Arterioles: resistance •Capillaries: exchange •Veins: capacitance (storage)

Blood: an anticoagulated pick up and delivery system

Prime Determinants of LV Function (and MVO2)

• Heart rate • Contractility • Preload • Afterload

.

Load = Wall Stress

• Wall stress ~ Pressure x Volume • Preload is mostly volume • Afterload is mostly pressure

A B

C D

Load = Wall Stress = ∆P x R LaPlace

R R

Pathophysiology of heart failure

LV DYSFUNCTION

• Systolic –Trouble emptying –Inotropy

• Diastolic –Trouble filling –Lusitropy

Systolic and Diastolic Dysfunction

EF decreased EF normal or increased

Normal Systolic Dysfunction

Diastolic Dysfunction

Myocardial injury

Cardiac function

Activation of Neurohormonal systems (SNS, RAAS, etc.)

Acute

(Adaptive) Chronic

(Maladaptive)

CURRENT PARIDIGM FOR HEART FAILURE

Adapted from E. Braunwald. 1999

Myocardial injury

Cardiac function

Activation of Neurohormonal systems (SNS, RAAS, etc.)

Acute

(Adaptive) Chronic

(Maladaptive)

CURRENT PARIDIGM FOR HEART FAILURE

Blockers

Adapted from E. Braunwald. 1999

Frank-Starling Mechanism Normal and Heart Failure

ACC/AHA Recommendations Class I

• History & Physical – family history – functional capacity – Labs

• Echocardiogram—2D/doppler • Chest X-Ray • ECG • Cardiac Catheterization

– Angina, if candidate for revascularization

History

• Previous cardiac disease, including childhood • Other medical diseases • Exposure to cardiotoxins

– ETOH, illicit drugs, chemotherapy, chest XRT • Pregnancies/complications • Syncope • Embolic events

Heart Failure Symptoms & Signs

• Dyspnea • Orthopnea • PND • Wheezing • Edema • Abdominal discomfort • Anorexia/early satiety • Fatigue

• Rales or Clear Lungs • S3 Gallop • Displaced PMI/LV heave • Audible wheezing • Hepatic congestion • Cool extremities • Oliguria • Altered mental status

Facial Urination due to Congestive Heart Failure

To the Editor.—We recently saw a patient in congestive heart failure whose main complaint was wetting his face every time he urinated. This case report describes this unusual presentation.

Comment.—Severe angulation of the penis, due to congestive heart failure, is a very unusual finding. A review of standard urological texts does not mention such a complication.

Gould L, Martinucci L, Patel C. JAMA. 1986:255:2448.

“An 87-year old man was admitted to the hospital because of swelling of his legs and his urine hitting him in the face….The scrotum was edematous and the penis was folded on itself and directed at the patient’s head.”

Classification of Heart Failure The New York Heart Association (NYHA) classification system1-3 Functional Capacity Objective Assessment Class I: No limitation A. No CV disease Class II: Slight limitation B. Minimal CV disease Class III: Marked limitation C. Moderate CV disease Class IV: Symptoms at rest D. Severe CV disease

1. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure. 2001. Available at: http://www.acc.org/clinical/guidelines/failure/hf_index.htm. Accessed September 18, 2003; 2. Gomberg-Maitland et al. Arch Intern Med. 2001;161:342-352; 3. Packer and Cohn, eds. Am J Cardiol. 1999;83(suppl 2A):1A-38A.

High risk with no symptoms

Structural heart disease with no

symptoms

Structural heart disease with symptoms

(dyspnea, fatigue, reduced exercise

tolerance)

Refractory symptoms

requiring special interventions

A B C D

Evolution of HF Therapy

Period Clinical Endpoint Pathophysiology Therapy

Pre-1970 Edema Na+ retention Diuretics

1970-1985 Symptoms Hemodynamics Inotropes Vasodilators Diuretics

1985-1995 Survival Neurohormonal Activation

ACE I’s β-blockers

1995- Cellular mechanism

Apoptosis Antioxidants Cytokine antagonists NO-regulators

Non- cardiac factors

Low ejection fraction

Arrhythmia

Death

Pump failure

Symptoms: Dyspnea Fatigue Edema

Chronic heart failure

• Neurohormonal stimulation

• Endothelial dysfunction

• Vasoconstriction • Renal sodium retention

Adapted from: Cohn JN. N Engl J Med. 1996;335:490-498.

Pathogenesis of Systolic Heart Failure HFrEF

Remodeling

Left ventricular dysfunction

• Coronary artery disease

• Hypertension • Cardiomyopathy • Valvular disease

Stages, Phenotypes and Treatment of HF

Major Therapeutic Options for HFrEF

•ACE inhibitor

•Aldosterone receptor blocker

•Angiotensin receptor blocker (if ACE-I intolerant)

•Beta-blocker

•Diuretic

•Digoxin

Adapted from: ESC Task Force; 2001 ACC/AHA Guidelines.

Trial ACE-I (%) RR (95% CI)

Mortality

CONSENSUS I

SOLVD (Treatment)

SOLVD (Prevention)

Heart Failure

Post-MI

TRACE (trandolapril)

0.56 (0.34–0.91)

0.82 (0.70–0.97)

0.92 (0.79–1.08)

0.81 (0.68–0.97)

0.73 (0.60–0.89)

SMILE (zofenopril) 0.75 (0.40–1.11)

Totals

0.78 (0.67–0.91)

39

35

15

20

17

5

35

21

Controls (%)

54

40

16

25

23

6.5

42

25

Effect of ACE Inhibitors on Mortality in Heart Failure Patients

SAVE (captopril)

AIRE (ramipril)

RAAS in Heart Failure Angiotensinogen

( Liver )

Angiotensin I

Angiotensin II

AT1 AT2

AT1 Receptor Blocker

ACE Inhibitor

Renin Inhibitor -

- -

JG cells: Renin

ACE

Hypokalemia, Hypomagnesemia,

arrhythmias

Pathologic LVH/myocardial

fibrosis

The Renin Angiotensin Aldosterone System

Elevated ALDOSTERONE

Fluid retention And edema

Morbidity Mortality

Angiotensinogen

Angiotensin I

Angiotensin II

Heart Failure

Renin

ACE ACEI reduces Angiotensin II levels

ACTH

Other

K+ ↑

Na+ ↓

ACE INHIBITORS

• Approximately 7000 patients enrolled in clinical trials

• Improvement in cardiac function, symptoms, and clinical status

• Decrease in all cause mortality by 20%-25% • Decrease in combined risk of death or

hospitalization by 25%-30%

Myth: ARBs are ACE inhibitors that do not cause a cough.

I. M. Grais, M.D.

ACE Inhibitor plus Spironolactone 25 mg/day Further Reduces Mortality

0 6 12 18 24 30 36

Months

Risk reduction 30% P <0.0001

Spironolactone

Placebo

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Prob

abili

ty o

f sur

viva

l

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

↑ CNS sympathetic outflow

↑ Cardiac sympathetic activity ↑ Renal sympathetic activity

Sodium retention Myocyte hypertrophy

Myocyte injury Increased arrhythmias

Disease progression

α1 β1 β1 β2 α1

↑ Vascular sympathetic activity

Vasoconstriction

α1

Activation of RAS

Adrenergic Pathway in Heart Failure Progression

Effect of Beta-Blockers on Mortality in Heart Failure Patients

34% lower risk (0.53–0.81) P=0.0062 after adjusted interim analysis

MERIT-HF (metoprolol)

34% lower risk P< 0.0001

CIBIS-II (bisoprolol)

38% lower risk (18%-53%) P< 0.001

US Carvedilol

35% lower risk*

COPERNICUS (carvedilol)

8.5% lower risk P=NS

BEST (bucindolol)

Clinical Trial

All-cause mortality

All-cause mortality

Combined end point: risk of hospitalization or death

All-cause mortality

All-cause mortality

Trial End Point Risk Reduction, % (95% CI)

*Preliminary data from XXII Congress of the European Society of Cardiology

Effectiveness of Individual Therapies in Preventing Events

From Evidence-Based Trials

DIG trial / 3 years

-

40

Digoxin

RALES trial / 2 years

57

138

Spironolactone

MERIT-HF study / 1 year

38

65

Beta-Blockers

Treatment arm of the SOLVD trial / 3.5 years

13

99

ACE-I

Evidence-Based Trial / Average Follow-Up

Deaths (prevented)

Hospital Admissions (prevented)

Therapy

Adapted from: Remme WJ et al. Eur. Heart J. 2001;22:1527-1560.

Events prevented per 1000 patient-hours of treatment

HF Preserved Systolic Fxn HFpEF

Diastolic Dysfunction: “The Devil is in Diastole”

• Fibrosis • Hypertrophy • Ischemia • Restrictive cardiomyopathy • Myocardial infarction

Treatment of HFpEF Recommendations COR LOE

Systolic and diastolic blood pressure should be controlled according to published clinical practice guidelines I B

Diuretics should be used for relief of symptoms due to volume overload I C

Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite GDMT

IIa C

Management of AF according to published clinical practice guidelines for HFpEF to improve symptomatic HF

IIa C

Use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF IIa C

ARBs might be considered to decrease hospitalizations in HFpEF IIb B

Nutritional supplementation is not recommended in HFpEF

III: No Benefit C

Acute Heart Failure

Diagnosis and Treatment

Diagnosis of CHF: Clinical Challenge

• Symptoms and signs of heart failure like shortness of breath and edema have a broad differential diagnosis

• Physical exam is neither sensitive nor specific for CHF and, even in good hands, there are often errors

• CXR findings have limited accuracy for CHF • One-third to one-half of patients with CHF have

normal systolic function Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85

The Physical Exam As A Diagnostic Test

PCWP>20- 22 mmHg Sensitivity Specificity Can’t tell

Orthopnea 90% 95% JVP inc. 80% 98% 15% Valsalva 90% 90% 25% HJ Reflux 92% 81% ? Perip edema 25% 95% 5% Rales 15% 95%

From Ewy, McIntyre et al, Stevenson & Perloff, Zema et al.

Invasive Hemodynamic Assessment

• Invasive • Significant Complications • Expensive • Requires ICU or Cath Lab setting • Data sometimes difficult to interpret

Goals of Acute HF Therapy

• Alleviate symptoms • Treat volume overload • Preserve/improve end organ function • Limit hospitalization • Initiate/optimize chronic therapy • Prevent readmission • Improve long-term outcomes

Rapid Assessment of Hemodynamic Status

Congestion at Rest

Low Perfusion

at Rest C

NO

NO YES

YES

L

A B Warm &

Dry Warm &

Wet

Cold & Wet Cold & Dry

(Complex) (Low Profile)

Signs/Symptoms of Congestion:

Orthopnea / PND JV Distension Hepatomegaly Edema Rales (rare in chronic

heart failure) Elevated est. PA

systolic Valsalva square wave

Possible Evidence of Low Perfusion: Narrow pulse pressure Cool extremities Sleepy / obtunded Hypotension with ACE inhibitor Low serum sodium Renal Dysfunction (one cause)

Current Treatment of Acute Heart Failure

Diuretics Aquaretics

Ultrafiltration

Reduce fluid

Volume Na+

& H20

Vasodilators

Decrease Preload

And Afterload

Inotropes

Augment Contract-

ility

Diuretic Resistance • Poor oral absorption due to gut edema • Decreased perfusion of kidney results in decreased delivery

of loop diuretics • Decreased GFR results in decreased filtered load of sodium • Volume depletion activates plasma renin activity and

stimulates SNS • Increased proximal tubule reabsorbtion of sodium,

particularly in setting of elevated AII and elevated catecholamine levels

• Increased distal reabsorbtion of sodium, stimulated by aldosterone

• Associated with tubular hypertrophy: resetting basal rates of sodium reabsorbtion.

Diuretic Principles

• The right dose is what it takes to effect diuresis – as high as it takes – as low as you can

• High dose loop vs loop+metolazone • Continuous IV infusion of loop diuretic • Flexible dosing • Daily weights

Most Common IV Medications All Enrolled Discharges (n=105,388) October 2001-January 2004

0 10 20 30 40 50 60 70 80 90

100

Patie

nts

(%)

IV Diuretic Dobutamine Dopamine Milrinone Nesiritide Nitroglycerin Nitroprusside

IV Vasoactive Meds

88%

6% 6% 10% 3% 1%

10%

Colors of Salt

• White • Black • Red • Yellow • Green • Brown • Clear

• Table salt • Soy sauce • Catsup • Mustard • Pickles • Soups & gravies • Saline

Profiles and Therapies of Advanced Heart Failure

Yes

R. Bourge, UAB Cardiology (adapted from L. Stevenson) Stevenson LW. Eur J Heart Failure 1999;1:251-257

No Warm and Dry PCW and CI

normal

Warm and Wet PCW elevated

CI normal

Cold and Wet PCW elevated CI decreased

Cold and Dry PCW low/normal

CI decreased

Vasodilators Nitroprusside Nitroglycerine

Nesiritide Relaxin

Inotropic Drugs Dobutamine

Milrinone Calcium Sensitizers

Nl SVR High SVR

Congestion at Rest

Low Perfusion

at Rest

No

Yes

Preload: diuretics-thiazides, loop, aldosterone antagonists, RAAS inhibition Afterload: vasodilators, nitrates, hydralazine, RAAS inhibition (ACEI, ARBs), recombinant B-type natriuretic peptide, now new LCZ696 which raises natriuretic peptides in combination with enalapril Contractility: digitalis, Beta-blockers, phosphodiesterase inhibitor Heart Rate: digitalis, Beta-blockers

A man with known ischemic cardiomyopathy and an ejection fraction of 0.15% on good therapy entered the ED with newly increased heart failure. His B-type natriuretic peptide (BNP) level was 2,000 pg/mL.

What is the key question the cardiologist asks the resident?

The attending asked the ED resident, “Why is he in heart failure?” When the medical resident said that he didn’t know, the attending asked, “Has anything changed in recent weeks?”

80 YO man with dementia & Parkinson’s was admitted with pneumonia and a fever of 103F. Rx: I.V. fluids and antibiotics. He developed severe dyspnea due to pulmonary edema. EKG showed sinus rhythm at 60 BPM but no acute changes.

What key question did the consulting cardiologist ask?

Why, he wondered, would an elderly man with pneumonia, a high fever, and pulmonary edema not have sinus tachycardia?

Two common causes for such a paradoxical finding would be sick sinus syndrome and hypothyroidism. TFTs confirmed the suspected severe hypothyroidism.

Gregory: “Is there any point to which you would wish to draw my attention?” Holmes: “To the curious incident of the dog in the nighttime.” Gregory: “The dog did nothing in the nighttime.” Holmes: “That was the curious incident.”

The Dog in the Nighttime Syndrome

“It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has.”

Sir William Osler

“The art of the practice of medicine is to be learned only by experience; ‘tis not an inheritance; it cannot be revealed. Learn to see, learn to hear, learn to feel, learn to smell, and know that by practice alone can you become expert.”

Osler, The Teacher, p. 198

Fini

Therapy CO PCWP BP HR Arrhy thmia

Shorter Onset

Longer Offset

Dopamine (ng/kg/min) Low (<3) Mod (3–7) High (7–15)

↔ ↑

↑↑

↔ ↔ ↔

↔ ↑

↑↑

↔ ↑

↑↑

↔ ↑↑

↑↑↑

+++ +++ +++

0 0 0

Dobutamine ↑↑↑ ↓ ↔ ↑ ↑↑ +++ 0

Milrinone ↑↑ ↓ ↓ ↑ ↑↑ + ++

Nitroglycerin ↑ ↓↓ ↓↓ ↔ ↔ +++ 0

Nesiritide ↑ ↓↓ ↓ ↔ ↔ ++ ++

Nitroprusside ↑ ↓↓ ↓↓↓ ↔ ↔ ++++ 0 ↑ increase; ↓ decrease; + effect (number of and qualitatively associated with degree of effect); 0 no effect

Intravenous Agents for Heart Failure

Reference: Adapted from Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19.