Primary Right Heart Primary Right Heart FailureFailure

(Cor (Cor Pulmonale)Pulmonale)

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Cor PulmonaleCor Pulmonale (CP) (CP) defineddefined• Alteration of the right ventricular Alteration of the right ventricular

structure or function that is due to structure or function that is due to pulmonary hypertension (PHTn) pulmonary hypertension (PHTn) caused by diseases affecting the lung caused by diseases affecting the lung or its vasculature.or its vasculature.

• ExcludesExcludes– Left sided heart disease with 2Left sided heart disease with 2ndnd changes changes – Congenital heart diseaseCongenital heart disease

EtiologiesEtiologies

– Pulmonary Artery vasoconstrictionPulmonary Artery vasoconstriction• Alveolar hypoxiaAlveolar hypoxia

• Blood acidosisBlood acidosis

– Anatomic red’n of pulmonary vascular bedAnatomic red’n of pulmonary vascular bed• EmphysemaEmphysema

• Pulmonary emboliPulmonary emboli

– Increased blood viscosityIncreased blood viscosity• Erythrocytosis (Includes polycythemia)Erythrocytosis (Includes polycythemia)

• Sickle-cell diseaseSickle-cell disease

– Increased pulmonary blood flowIncreased pulmonary blood flow

Patients with COPDPatients with COPD

• Most frequent cause of cor pulmonaleMost frequent cause of cor pulmonale

• Right ventricular hypertrophy (RVH) inRight ventricular hypertrophy (RVH) in– 40% of patients with FEV1 < 1.0 L40% of patients with FEV1 < 1.0 L– 70% of patients with FEV1 < 0.6 L70% of patients with FEV1 < 0.6 L

• Independent predictors of RVHIndependent predictors of RVH– HypoxemiaHypoxemia– Hypercapnea Hypercapnea

– Erythrocytosis (Erythrocytosis (not Polycythemianot Polycythemia))

Prognosis of Cor PulmonalePrognosis of Cor Pulmonale

• When due to COPD, PHTn plus When due to COPD, PHTn plus peripheral edema peripheral edema – 5 year survival 30%, mean 3 years from 5 year survival 30%, mean 3 years from

dxdx– Pulmonary vascular resistance >550 Pulmonary vascular resistance >550

dynes-sec/cm rarely survive more than 3 dynes-sec/cm rarely survive more than 3 yearsyears

– May just reflect the degree of underlying May just reflect the degree of underlying COPDCOPD

Symptoms of CPSymptoms of CP• Directly attributable to PHTnDirectly attributable to PHTn

– Dyspnea on exertion, fatigue, lethargyDyspnea on exertion, fatigue, lethargy– Chest pain, syncope with exertionChest pain, syncope with exertion

• Typical exertional anginaTypical exertional angina– Occurs in patients with primary or secondary PHTn even Occurs in patients with primary or secondary PHTn even

in the absence of epicardial CADin the absence of epicardial CAD– Subendocardial RV ischemia induced by hypoxemia and Subendocardial RV ischemia induced by hypoxemia and

increased transmural wall tensionincreased transmural wall tension– Dynamic compression of left main coronary by enlarged Dynamic compression of left main coronary by enlarged

PAPA

• Less commonLess common– Cough, hemoptysis, hoarsenessCough, hemoptysis, hoarseness

• With severe right ventricular (RV) failureWith severe right ventricular (RV) failure– Passive hepatic congestionPassive hepatic congestion– Anorexia, right upper quadrant discomfortAnorexia, right upper quadrant discomfort

Physical FindingsPhysical Findings• Cardiac findingsCardiac findings

– RVHRVH•Prominent A wave in the jugular venous pulse. Prominent A wave in the jugular venous pulse.

with R sided 4with R sided 4thth heart sound heart sound

– RV failure leads to systemic venous HTnRV failure leads to systemic venous HTn•Elevated jugular venous pressure with a Elevated jugular venous pressure with a

prominent V waveprominent V wave

•RV S3RV S3

•High pitched tricuspid regurgitant (TR) High pitched tricuspid regurgitant (TR) murmurmurmur

– Extra cardiac changesExtra cardiac changes•Hepatomegaly, pulsatile liver Hepatomegaly, pulsatile liver

•peripheral edema-often related to hypercarbia peripheral edema-often related to hypercarbia and passive Na+ and water retentionand passive Na+ and water retention

Other Areas of Fluid Other Areas of Fluid RetentionRetention• Pleural effusion, often bilateralPleural effusion, often bilateral

– Right heart failure until proved otherwiseRight heart failure until proved otherwise– Also kidney and liverAlso kidney and liver

• Engorged inferior vena cavaEngorged inferior vena cava

• Hepatic congestionHepatic congestion

• AscitesAscites

• AnasarcaAnasarca

Right Atrial Pressure TracingRight Atrial Pressure Tracing

Jugular PulsationsJugular PulsationsA wave

•RAP transmitted to jugular veins (JV) during right atrial systole

V wave

•Rise in RA and JVP due to continued inflow of blood to the venous system during late ventricular systole when the tricuspid valve is still closed

•May also be elevated in heart failure and renal failure, but not cirrhosis.

Hepatojugular RefluxHepatojugular Reflux

• Assessed by applying firm sustained Assessed by applying firm sustained pressure over the upper abdomen pressure over the upper abdomen with pt. breathing quietly.with pt. breathing quietly.

• ResponseResponse– Transient elevation by approximately 1 Transient elevation by approximately 1

cm in normal responsecm in normal response– In RHF sustained elevationIn RHF sustained elevation– Low specificity and sensitivityLow specificity and sensitivity

DisorderPulmonary

edemaCentral venous

pressureAscites and/or

pedal edema

Left-sided heart failure

+ Variable -

Right-sided heart failure

- Variable +

Cirrhosis - Normal +

Renal disease Variable +

Nephrotic syndrome

- Variable +

Idiopathic edema

- -Normal +

Venous insufficiency

- Normal +, edema may be asymmetric

Major Physical Finding in Edematous States

Peripheral EdemaPeripheral Edema

• Edema formation requiresEdema formation requires– Alteration in capillary hemodynamics that Alteration in capillary hemodynamics that

favors the movement of fluid from the vascular favors the movement of fluid from the vascular space into the interstitium (IS)space into the interstitium (IS)

– The retention of dietary or IV administered The retention of dietary or IV administered sodium and water by the kidneys.sodium and water by the kidneys.

– Requires 2.5 to 3.0 liters of extra volumeRequires 2.5 to 3.0 liters of extra volume

• Sequence of eventsSequence of events– Movement of fluid from vascular space into the Movement of fluid from vascular space into the

IS reduces the plasma volume and IS reduces the plasma volume and consequently tissue perfusion consequently tissue perfusion

– The kidney then compensates by retaining The kidney then compensates by retaining sodium and watersodium and water

EvaluationEvaluation

• Laboratory CBC, chem 7, LFT’s, BNPLaboratory CBC, chem 7, LFT’s, BNP• Chest radiographChest radiograph• ElectrocardiogramElectrocardiogram• Two D and Doppler echocardiographyTwo D and Doppler echocardiography• Pulmonary function testsPulmonary function tests• Radionuclide ventriculographyRadionuclide ventriculography• Magnetic resonance imagingMagnetic resonance imaging• Right heart catheterizationRight heart catheterization• Lung biopsyLung biopsy

LaboratoryLaboratory

• CBC-depressed or elevated Hgb, HctCBC-depressed or elevated Hgb, Hct• Chem 7-relationship of BUN to CreatinineChem 7-relationship of BUN to Creatinine

– Normal ratio BUN/Cr approximates 20/1Normal ratio BUN/Cr approximates 20/1– Prerenal azotemia > 20/1Prerenal azotemia > 20/1– Intrinsic renal disease < 20/1Intrinsic renal disease < 20/1– Estimated glomerular filtration rate (eGFR)Estimated glomerular filtration rate (eGFR)

• Liver function testsLiver function tests– SGOTSGOT– SGPTSGPT

Brain Natriuretic Peptide Brain Natriuretic Peptide (BNP)(BNP)• A hormone released from myocardial A hormone released from myocardial

cellscells

• Both atria and both ventriclesBoth atria and both ventricles

• Inhibits weaklyInhibits weakly– Renin-angiotensin system (Angiotensin II)Renin-angiotensin system (Angiotensin II)– Endothelin secretionEndothelin secretion– Systemic and renal sympathetic activitySystemic and renal sympathetic activity– Plasma aldosterone productionPlasma aldosterone production

BNP ContinuedBNP Continued

• Higher inHigher in– Older >youngerOlder >younger– Women > menWomen > men– Normal weight > obeseNormal weight > obese– Renal failureRenal failure– Congestive heart failure (right and/or left)Congestive heart failure (right and/or left)

• Patient is his own reference pointPatient is his own reference point– BaselineBaseline– Post treatmentPost treatment

BNP Continued, PrognosisBNP Continued, Prognosis

• HF pts.- Highest quartile at baseline HF pts.- Highest quartile at baseline had higher mortality over 2 years at had higher mortality over 2 years at baseline (32.4 vs 9.7%) than lowest baseline (32.4 vs 9.7%) than lowest quartile.quartile.

• Following optimal medical treatment Following optimal medical treatment mortality increased proportionately mortality increased proportionately to the level of the BNP elevation.to the level of the BNP elevation.

Normal Chest Radiograph

Normal chest film

Radiograph in Cor Pulmonale

Radiograph and Cor Radiograph and Cor PulmonalePulmonale

• Enlargement of Central PA’sEnlargement of Central PA’s

• In 95% of Pts with PHTn from COPD In 95% of Pts with PHTn from COPD the diameter of the descending the diameter of the descending branch of the right PA is > 20 mm in branch of the right PA is > 20 mm in widthwidth

• Peripheral vessels are attenuated Peripheral vessels are attenuated leading to peripheral oligemialeading to peripheral oligemia

Normal ElectrocardiogramNormal Electrocardiogram

Right Atrial Enlargement on Right Atrial Enlargement on ECGECG

Right atrial enlargement

                                                                         

ECG in Cor PulmonaleECG in Cor Pulmonale

Normal

Cor Pulmonale

Two Dimensional Two Dimensional EchocardiogramEchocardiogram

Two D Echo, continuedTwo D Echo, continuedTricuspid Regurgitation (TR)

Doppler EchocardiographyDoppler Echocardiography

• Most reliable noninvasive estimate of Most reliable noninvasive estimate of the Pulmonary Artery Pressure (PAP)the Pulmonary Artery Pressure (PAP)

• Dependent on identifying an Dependent on identifying an adequate tricuspid regurgitant jetadequate tricuspid regurgitant jet

• More sensitive as PAP increasesMore sensitive as PAP increases

2D Echo with Color Flow 2D Echo with Color Flow DopplerDoppler

Pulmonary Function Testing (PFT’s)

•Primer and overview•Satisfactory effort•Obstruction •Restriction•Malingering

PFT Expiratory ManeuverPFT Expiratory Maneuver

Expiratory Flow/Volume Expiratory Flow/Volume LoopLoop

Right Sided Cardiac Right Sided Cardiac CatheterizationCatheterization

• When echo does not permit measurement of TRWhen echo does not permit measurement of TR

• When symptoms are exertional and left sided When symptoms are exertional and left sided pressures are unremarkablepressures are unremarkable

• When therapy will be determined by precise When therapy will be determined by precise measurement of pulmonary vascular resistance measurement of pulmonary vascular resistance (PVR) and the response to vasodilators(PVR) and the response to vasodilators

• When left heart catheterization is also required When left heart catheterization is also required (patients > 40 y/o and or with CAD)(patients > 40 y/o and or with CAD)

Lung BiopsyLung Biopsy

• Rarely, if ever requiredRarely, if ever required

• High risk procedure (elevated PVP, High risk procedure (elevated PVP, PAP)PAP)

• Transbronchial lung biopsy firstTransbronchial lung biopsy first

• Fiber optic thoracoscopyFiber optic thoracoscopy

• Never open thoracotomyNever open thoracotomy

Leading causes of Leading causes of disability-adjusted life disability-adjusted life years (DALYs) lost years (DALYs) lost worldwide, 1990 and worldwide, 1990 and 2020 (projected) 2020 (projected)

Disease or InjuryRank 1990

Percent of Total Daly's

Rank 2020

Percent of Total Daly's

Lower respiratory infections

1 8.2 6 3.1

Diarrheal diseases 2 7.2 9 2.7

Perinatal period conditions

3 6.7 11 2.5

Unipolar major depression

4 3.7 2 5.7

Ischemic heart disease

5 3.4 1 5.9

Cerebrovascular disease

6 2.8 4 4.4

Tuberculosis 7 2.8 7 3.1

Measles 8 2.6 25 1.1

Road traffic accidents

9 2.5 3 5.1

Congenital anomalies

10 2.4 13 2.2

Malaria 11 2.3 19 1.5

COPD 12 2.1 5 4.1

Trachea, bronchus, lung cancer

33 0.6 15 1.8

TreatmentTreatment• OxygenOxygen

– Relieves pulmonary vasoconstrictionRelieves pulmonary vasoconstriction•Decreases PVRDecreases PVR

• Increases RV Stroke volume and cardiac Increases RV Stroke volume and cardiac outputoutput

•Renal vasoconstriction may be relieved with Renal vasoconstriction may be relieved with increase in urinary sodium excretionincrease in urinary sodium excretion

– Improves arterial oxygen tension with Improves arterial oxygen tension with enhanced delivery toenhanced delivery to•HeartHeart

•BrainBrain

•Other vital organs (kidneys)Other vital organs (kidneys)

Survival benefit of LTOT in COPD

                                                               

Effects of O2 Therapy in COPD

Treatment-DiureticsTreatment-Diuretics

• Increasing RV filling volume using diureticsIncreasing RV filling volume using diuretics– Improve function of both RV and LVImprove function of both RV and LV

• As RV dilatation is reduced LV filling improvesAs RV dilatation is reduced LV filling improves• May improve cardiovascular performanceMay improve cardiovascular performance

• Monitor for excessive volume depletionMonitor for excessive volume depletion– BUN (blood urea nitrogen) “Prerenal”BUN (blood urea nitrogen) “Prerenal”– Creatinine “Renal”Creatinine “Renal”– Estimated glomerular filtration rate (eGFR)Estimated glomerular filtration rate (eGFR)

• Watch for metabolic alkalosisWatch for metabolic alkalosis– May suppress ventilationMay suppress ventilation

Complimentary Treatments Related to Complimentary Treatments Related to Severity of PHTn and its Systemic EffectsSeverity of PHTn and its Systemic Effects• Furosemide/Bumetanide/Torsemide Furosemide/Bumetanide/Torsemide

– loop diureticsloop diuretics

• Hydrochlorothiazide Hydrochlorothiazide – blocks sodium reabsorptionblocks sodium reabsorption

• Spironolactone/Eplerinone Spironolactone/Eplerinone – Blocks aldosterone effect on both kidney and heartBlocks aldosterone effect on both kidney and heart

• Angiotensin Converting Enzyme (ACE) Angiotensin Converting Enzyme (ACE) inhibitor/ACE Receptor Blockersinhibitor/ACE Receptor Blockers– Blocks Renin and Angiotensin Blocks Renin and Angiotensin

• Beta blockers (metroprolol, Atenolol, Carvedilol)Beta blockers (metroprolol, Atenolol, Carvedilol)– Blocks effect of norepinephrineBlocks effect of norepinephrine

Treatment, ContinuedTreatment, Continued

• Digoxin is Digoxin is NOTNOT indicated in pure CP indicated in pure CP

• These PA Vasodilators are of These PA Vasodilators are of NONO benefitbenefit– HydralazineHydralazine– NitratesNitrates– NifedipineNifedipine– VerapamilVerapamil

Theophylline/TerbutalineTheophylline/Terbutaline

• Has effects other than direct Has effects other than direct bronchial dilatation and diuresisbronchial dilatation and diuresis

• Improves myocardial contractilityImproves myocardial contractility

• Provides some degree of pulmonary Provides some degree of pulmonary vasodilatationvasodilatation

• Enhances diaphragmatic enduranceEnhances diaphragmatic endurance

• Narrow range of efficacyNarrow range of efficacy

PhlebotomyPhlebotomy

• When hematocrit > 55When hematocrit > 55

• Goal is hematocrit < 50Goal is hematocrit < 50

• Secondary Secondary ErythrocytosisErythrocytosis vs vs PolycythemiaPolycythemia

• Treat underlying conditionTreat underlying condition

Treatment, The Future?Treatment, The Future?

• The following is for completeness The following is for completeness and is not considered applicable for and is not considered applicable for most pts with PHTn due to most pts with PHTn due to – The route of administrationThe route of administration– CostCost– Side effectsSide effects– ? Long term efficacy? Long term efficacy

DrugDrug RouteRoute Dose rangeDose range Half-lifeHalf-life

EpoprostenolEpoprostenol**

IntravenousIntravenous 2 to 20 ng/kg/min2 to 20 ng/kg/min 3-5 min3-5 min

TreprostinilTreprostinil SubcutaneoSubcutaneousus

0.625 to 1.25 0.625 to 1.25 ng/kg/minng/kg/min

4-5 hr4-5 hr

IloprostIloprost InhaledInhaled 2.5 to 5 mcg2.5 to 5 mcg 1-2 hr1-2 hr

BosentanBosentan OralOral 62.5 to 125 mg62.5 to 125 mg 5 hr5 hr

AdenosineAdenosine IntravenousIntravenous 50 to 200 µg/kg/min50 to 200 µg/kg/min 5-10 sec5-10 sec

Nitric oxideNitric oxide InhaledInhaled 5 to 80 ppm5 to 80 ppm 15-30 sec15-30 sec

Nitric Oxide (INOmax)Nitric Oxide (INOmax)

• Initially in neonates with PHTnInitially in neonates with PHTn• Relaxes vascular smooth muscleRelaxes vascular smooth muscle• Binds to cytosolic guanylate cyclaseBinds to cytosolic guanylate cyclase• Activates guanylate cyclaseActivates guanylate cyclase• Increases intracellular levels of cyclic Increases intracellular levels of cyclic

quanosine 3’,5’-monophosphatequanosine 3’,5’-monophosphate• Produces vasodilatation Produces vasodilatation • Can only be used in inhalational formCan only be used in inhalational form• ½ life 15-30 seconds½ life 15-30 seconds

Epoprostenol (Flolan)Epoprostenol (Flolan)

• Also called Prostacyclin (PG 12)Also called Prostacyclin (PG 12)• Strong vasodilator of all vascular bedsStrong vasodilator of all vascular beds• Decreases platelet aggregation and Decreases platelet aggregation and

thrombogenesisthrombogenesis• Increases cyclic Adenosine MonophosphateIncreases cyclic Adenosine Monophosphate• Stimulates intracellular adenate cyclaseStimulates intracellular adenate cyclase• ½ Life elimination six minutes½ Life elimination six minutes• Requires continuous central line and pumpRequires continuous central line and pump• Cost to VA is $29,400/yearCost to VA is $29,400/year

Sildenafil (Viagra, Revatio)Sildenafil (Viagra, Revatio)

• Phosphodiesterase 5 enzyme Phosphodiesterase 5 enzyme inhibitor (PDE 5)inhibitor (PDE 5)

• 20-60 mgm TID oral dosing schedule20-60 mgm TID oral dosing schedule

• Yearly cost to VA $3180 to Yearly cost to VA $3180 to $9540/year$9540/year

• Same benefits do not occur with Same benefits do not occur with other PDE5 Inhibitorsother PDE5 Inhibitors

SummarySummaryCor PulmonaleCor Pulmonale• is an end stage manifestation of primary is an end stage manifestation of primary

right sided heart failure. right sided heart failure. • For the most part, treatment is supportive. For the most part, treatment is supportive. • In COPD, oxygen is a mainstay of therapy. In COPD, oxygen is a mainstay of therapy. • Diuretics, ACEI, ARB, beta blockers may Diuretics, ACEI, ARB, beta blockers may

add efficacy. add efficacy. • Better drug therapy, directed at Better drug therapy, directed at

pulmonary artery relaxation, may be on pulmonary artery relaxation, may be on the horizon. the horizon.

• Whatever the etiology the prognosis Whatever the etiology the prognosis remains poorremains poor

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Glossary

COPD Chronic Obstructive Pulmonary DiseaseCP Cor PulmonaleDALY’s Disability Adjusted Life Years EC(K)G ElectrocardiogrameGFR Estimated Glomerular Filtration RateHF Heart FailureHTn HypertensionIS InterstitiumJV Jugular VeinJVP Jugular Venous PressureLV Left VentriclePA Pulmonary ArteryPFT Pulmonary Function TestPHTn Pulmonary HypertensionPDE5 Phosphodiesterase-5 Enzyme InhibitorRAP Right Atrial PressureRV Right VentricleRVH Right Ventricular HypertrophyTR Tricuspid Regurgitation