EDEMA due to Cardiac Cause

Prof. A. George Koshy

Anatomy and pathophysilolgy

1/3 of total body water is extracellular space, and 2/3 is intracellular space;  Extracellular space is composed of the intravascular plasma volume (25%) and the extravascular interstitial spaces (75%);


EDEMA
Edema is defined as a clinically apparent increase in the interstitial fluid volume  Weight gain precedes overt edema  Anasarca refers to gross, generalized edema.  Ascites and hydrothorax refer to accumulation of excess fluid in the peritoneal and pleural cavities, respectively, and are considered to be special forms of edema.


Edema

Pitting edema

Non-pitting edema

Five factors contribute to the formation of edema: edema:  by increased hydrostatic pressure  reduced oncotic pressure within blood vessels;  by increased blood vessel wall permeability as in inflammation; inflammation;  by obstruction of fluid clearance via the lymphatic system; system;  by changes in the water retaining properties of the tissues

Approach to the patient with Edema

Generalized
Heart Liver Kidney Nutritional

or
Venous obstruction Lymphatic obstruction

Localized

Systemic Edema
Congestive heart failure

Congestive heart failure

Left-sided heart failure: shortness of breath with Left-

exertion and when lying down at night (orthopnea) (orthopnea) PND, pulmonary edema

RightRight-sided heart failure: swelling in the legs and feet. Ascites. Right sided Pleural effusion. Ascites.

Differential diagnosis
Heart Failure
Edema initially occurs at lower part of the body (lower extremities). Symmetric location. Painless, Pitting The presence of heart diseases
Dyspnoea cardiac enlargement gallop rhythm basilar rales venous distention hepatomegaly

Noninvasive tests may be helpf

CXR ECG echocardiography

Heart Failure


Elevated JVP  Tender hepatomegaly

Heart Failure


Systolic HF  Diastolic HF/ HF with preserved LV systolic function. Near normal LVEF.  Combination

CME Cardio 2003 MCH Trivandrum

Edema in CHF
Multi factorial  Renal vasoconstriction  Increased aldosterone & vasopressin activity  Increased sympathetic tone  Increased venous pressure  Even with asymptomatic LVD, renal avidity for Na &H2O is enhanced


Thiazides

Cortex

Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle

K-sparing
Inhibit reabsorption of Na in the distal convoluted and collecting tubule

Medulla
Loop of Henle

Loop diuretics
Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle

Collecting tubule

Loop diuretics preferred

More powerful natriuretic agents.  Effective even with renal impairment  High ceiling diuretics  Increase in vasodilatory ANP


Loop diuretics
Furosemide  Bumetanide  Torsemide  Ethacrynic acid


Loop diuretics Furosemide

Oral BioavailabilityBioavailability-50%, Onset- 30-60 mts Onset- 30PeaksPeaks1-2 hrs, Half life 50 mts LAsts LAsts for SIX hrs. Intravenous Onset 15 mts, Peaks 30-60 mts 30Duration 2 hrs . Transient venodilatation in acute pulmonary edema - vasodilator prostaglandin

Loop diuretics Torsemide

    

Longer duration of action IV dose 10 to 20mgms in HF 80 % hepatic metabolism, 20 % excreted unchanged in urine 80-90% Bioavailability, Peaks in 2 hrs, HL in 3.3 hrs, 80prolonged in cirrhosis In CHF, absorption is unimpaired and less variable than furosemide

Loop diuretics
Rebound phenomenon- a decrease in sodium phenomenonexcretion below baseline after the effect of the loop diuretic has worn off. Volume depletion activates the sodium retaining mechanisms  Braking phenomenon increase in sodium reabsorption by the distal tubule that occurs with chronic diuretic therapy


Diuretics. Indications


Symptomatic HF, with fluid retention  Edema  Dyspnea  Lung Rales  Jugular distension  Hepatomegaly  Pulmonary edema (Xray) (Xray)

Diuretic Resistance
      

Neurohormonal activation Rebound Na+ uptake after volume loss Hypertrophy of distal nephron Reduced tubular secretion (renal failure, NSAIDs) Decreased renal perfusion (low output) Altered absorption of diuretic Noncompliance with drugs

Managing Resistance to Diuretics

  

Restrict sodium and water intake Increase dose (individual dose, frequency, i.v.) Combine: furosemide + thiazide/spironolactone/metolazone Dopamine (increase cardiac output) Reduce dose of ACEI Ultrafiltration

  

Sequential Nephron Blockade

Combination of diuretics acting at different sites, by differing modes of action provides synergistic benefits

Aldosterone Inhibitors

Spironolactone
Competitive antagonist of the aldosterone receptor (myocardium, arterial walls, kidney)

ALDOSTERONE

Collagen

Retention Na+ Retention H2O Excretion K+ Excretion Mg2+

Edema

deposition

Fibrosis Arrhythmias
- myocardium - vessels

Spironolactone
RALES
NEJM 1999;341:709

1.0

Annual Mortality Aldactone 18%; Placebo 23%

0.9

0.8

Survival

0.7

Aldactone

0.6

p < 0.0001

N = 1663 NYHA III-IV Mean follow-up 2 y

0.5 months 0 6 12 18 24

Placebo
30 36

Spironolactone. Indications


Recent or recurrent symptoms despite ACEI, diuretics, digoxin and F-blockers

AHA / ACC HF guidelines 2001

Recommended in advanced heart failure (III-IV), in (IIIaddition to ACEI and diuretics Hypokalemia
ESC HF guidelines 2001

EPHESUS

Special precautions
Elderly  Diastolic dysfunction  RVMI  Pregnancy  Electrolyte abnormalities  Combination therapy


Digitalis

DIGOXIN
HEMODYNAMIC EFFECTS

Cardiac output LV ejection fraction LVEDP Exercise tolerance

DIGOXIN
NEUROHORMONAL EFFECTS

Plasma Noradrenaline Natriuresis RAAS activity Vagal tone Normalizes arterial baroreceptors

50
N=6800

40

NYHA II-III

Mortality % 30
Placebo 20 10 0 0
n=3403 p = 0.8

Digoxin
n=3397

DIG
NEJM 1997;336:525

12

24 Months

36

48

Death or hospitalization due to worsening HF

DIG
NEJM 1997;336:525

CME Cardio 2003 MCH Trivandrum

Only inotropic agent than does not increase HR Only inotropic agent that does not increase mortality

Indications
Out patient treatment of all patients who have persistent symptoms NYHA class 2 to 4 despite conventional therapy with diuretics, ACEI, beta blockers  AF with fast ventricular response


Bat wing appearance

Doppler evaluation MV inflow

The Past
 Haemodynamic hypothesis Damaged pump causes low blood pressure. Back pressure causes oedema.  Liberal

use of diuretics and Digoxin.

Hemodynamic --> approach Diuretics Inotropes Vasodilators

Neurohormonal approach RAAS SNS

Drugs improving Survival

Drugs acting on RAAS. ACEI. ARB. ARA Spironolactone, Eplerenone.  Beta blockers.  ISDN + Hydralazine.  Amiodarone ?  Statins ?


Major Trials of Beta-Blockade in HF

Patients

Mean Follow-up

NYHA Class

LVEF (%)

Effects on all-cause mortality

HF CIBIS CIBIS-II MERIT-HF US Carvedilol HF Study COMET Post-MI HF CAPRICORN 1959 1.25yrs N/A 40 All-cause mortality: q23%(p=0.03) 641 2647 3991 1094 3029 1.9yrs 1.3yrs 1yr 6.5mths III-IV III-IV IIIV IIIV II-IV <40
e35 e40 e35

All-cause mortality: q 20% (p=0.22) All-cause mortality: q 34% (p 0.0001) All-cause mortality: q 34% (p=0.0062) All-cause mortality: q 65% (p<0.001) All-cause mortality: q 17%(p=0.0017)

4.9yrs

<35

CIBIS Investigators and Committees. Circulation 1994; 90: 1765-1773. CIBIS-II Investigators and Committees. Lancet 1999; 353: 9-13. MERIT-HF Study Group. Lancet. 1999; 353:20012007. Packer M, Bristow MR, Cohn JN et al. US Carvedilol Heart Failure Study Group. N Eng J Med 1996; 334: 1349-1355. Poole-Wilson PA et al Lancet 2003; 362: 7-13. Capricorn Investigators. Lancet 2001; 357: 1385-1390.

Major Trials of ACE-Inhibitors in HF

Patients (n) HF CONSENSUS SOLVDTreatment SOLVDPrevention Post-MI HF SAVE AIRE TRACE 2231 2006 1749 3.5yrs 1.25yrs 2-4.2yrs N/A IIII N/A
e40

Mean Follow-up

NYHA Class

LVEF (%)

Effects on all-cause mortality

253 2569 4228

188 days 3.4yrs 3.1yrs

IV IIIII N/A

N/A
e35 e35

All-cause mortality: At 6 monthsq 40%(p=0.002) All-cause mortality: q 16% (p<0.0036) All-cause mortality q8% (p=0.30)

All-cause mortality: q 19%(p=0.019) All-cause mortality: q 27%(p=0.002) All-cause mortality: q 22%(p=0.001)

N/A
e 35

The CONSENSUS Trial Study Group. N Eng J Med 1987; 316: 1429-1435., The SOLVD Investigators. N Eng J Med 1991; 325: 293-302. The SOLVD Investigators. N Eng J Med 1992; 327: 685-691., Pfeffer MA, Braunwald E, Moye LA et al. The SAVE Investigators. N Eng J Med 1992; 327: 669-677., The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet 1993; 342: 821-828., Kber L, Torp-Pedersen C, Carlsen JE et al. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Eng J Med 1995; 333: 1670-1676.

THANK YOU