A CASE OF DYSPNOEA

Mrs.muniammal 35 f Residing at

chetpet Household maid by

occupation

Admitted in our unit on 14.10.11 with complaints of

Breathlessness-5 months,gradually progressed to grade 3 Swelling of legs-2 months, Insidious,gradually progressive

Abdominal distension-1 monthh/o reduced urine output

No h/oChest painPalpitationsLocFacial puffinessFeverHigh coloured urineAbdominal painVomiting,loose stoolsHiccoughs,altered sensorium

no h/o Oral ulcers, alopecia, photosensitivity, Arthralgia Skin pigmentation Raynaud’s Dysphagia,skin tightening Intolerance to cold, altered bowel

habits

Past h/o: no similar illness in the past. not a K/C/O DM/SHT/CAD/PT/BA

Personal h/o: takes mixed dietNot an alcoholic,smoker.No h/o substance abuse.

Marital,Obstetric h/o:married with 2 children.lcb-12 yrs ago, antenatal h/o uneventful.

No h/o promiscual sexual activity.

Menstrual h/o:regular 3/30 menstrual cycles

No h/o heavy flow,clots.

Pt consciousOrientedAfebrileHyd-fairMuddy conjunctiva +Clubbing-gr 1b/l pitting pedal edemaNo pallor/cyanosis/lymphadenopathy

Jvp-elevated,a and v waves prominent Pulse rate-80/min regular BP-110/70 mm hg

Cvs- apical impulse left 5th ics 2.5cm lat to MCL,normal character

Grade 3 parasternal heave Palpable p2 Tricuspid area- psm+ 3/6 Pulmonary area-loud p2,esm+ 2/6

Respiratory system- nvbs+

Per abdomen-liver palpable 2cm below rcm,non tender,non pulsatile

Free fluid +No spleenomegaly.Bowel sounds+

Cns-nfnd.

PULMONARY HYPERTENSION ? CAUSE

RV FAILURE

Urine alb,sugar nil,1-2 pus cells

RBS-111 RFT-U 15 CR 0.8

CBC Hb 11 Tc 6100 Dc p40l57e3 Pcv 33.7 Rbc 3.8 Platelets 1,80,000

Lft Tb : 1 Db : 0.2 Sgot :34 Sgpt :42 Sap :57 S proteins:5.6 Albumin :3.0 Globulin :2.6

Ecg -RAE,RAD

CARDIOMEGALY PULMONARY

TRUNK DILATATION WITH PERIPHERAL PRUNING

PERIPHERAL SMEAR STUDY:microcytic,hypochromic anemia

Coagulation profile- normal Bt 3’30” Ct 4’45” Pt :14 s Aptt: 27 s Inr :1.o

HIV- non reactive

RA factor- negative

TFT: free T3 2.90pg/ml(2-4.4) freeT4 1.38ng/dl(0.93-1.7)TSH 3.43mIU/ml(0.27-4.2)

Usg abdomennormal study

IMPRESSION: SEVERE PULMONARY

HYPERTENSION ?CAUSE

Pht ? IdiopathicSuggested sputum analysis,ct chest

Mantoux- negativeSputum afb-negativeSputum c/s-negative for pathogens

Ph :7.39PaO2 : 92 mm hgPaCO2 :41 mm hgHCO3 :22 mmol/l

Ra / rv dilatedPulmonary artery dilatedCardiomegalyVisualised lung Parenchyma-normal

Doppler study of lower limbsNormal studyNo stenosis,narrowing

MR ANGIO CHEST-NORMAL

IDIOPATHICPULMONARY

HYPERTENSION

. It was first identified by Dr. Ernst von Romberg in 1891.

Epidemiology: IPAH is a rare disease with an incidence of about 2-3 per million per year and a prevalence of about 15 per million.

Adult females are almost three timesmore likely.

Typically younger women of childbearing age . However, IPAH can also affect individuals in their fifth and sixth decade .

Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

McLaughlin, V. V. et al. J Am Coll Cardiol 2009;53:1573-1619

Relevant Pathways in the Pathogenesis of Pulmonary Arterial Hypertension

vasoconstriction or tightening of blood vessels

Over time, the affected blood vessels become both stiffer and thicker-fibrosis

the increased workload of the heart causes hypertrophy of the right ventricle, ultimately causing right heart failure

At least 15-20% of patients previously thought to have IPAH actually have a familial form of PAH involving at least one genetic defect.

The most common genetic defect in these cases involves the BMPR-II gene.

Definition Characteristics Clinical group(s)b

Pulmonaryhypertension

Mean PAP25 mmHg

All

Pre-capillary PH Mean PAP25 mmHgPWP 15 mmHgCO normal orreduced

1. Pulmonary arterialHypertension3. PH due to lung diseases4. ChronicThromboembolic PH5. PH with unclear and/orMultifactorial mechanisms

Post-capillary PH Passive TPG 12 mmHgReactive (out ofproportion)TPG .12 mmHg

Mean PAP25 mmHgPWP .15 mmHgCO normal orreducedc

2. PH due to left heartdisease

increase in meanpulmonary arterial pressure (PAP) 25

mmHg at rest † mean PAP .30 mmHg at exerciseassessed by right heart

catheterization

1. PULMONARY ARTERIAL HYPERTENSION (PAH) 1.1. Idiopathic (IPAH)     1.2. Familial (FPAH)     1.3. Associated with (APAH):     1.3.1. Connective tissue disorder         1.3.2. Congenital systemic-to-pulmonary shunts         1.3.3. Portal hypertension         1.3.4. HIV infection         1.3.5. Drugs and toxins         1.3.6. Other (thyroid disorders, glycogen storage

disease,         Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, chronic myeloproliferative disorders, splenectomy)

1.4. Associated with significant venous or capillary involvement 1.4.1. Pulmonary veno-occlusive disease (PVOD)         1.4.2. Pulmonary capillary hemangiomatosis

(PCH)         1.5. Persistent pulmonary hypertension of the newborn    

2. Pulmonary hypertension with left heart disease 2.1. Left-sided atrial or ventricular heart

disease     2.2. Left-sided valvular heart disease

     3. Pulmonary hypertension associated with lung

diseases and/or hypoxemia 3.1. Chronic obstructive pulmonary disease     3.2. Interstitial lung disease     3.3. Sleep disordered breathing     3.4. Alveolar hypoventilation disorders     3.5. Chronic exposure to high altitude     3.6. Developmental abnormalities

4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease (CTEPH)

4.1. Thromboembolic obstruction of proximal pulmonary     arteries

4.2. Thromboembolic obstruction of distal pulmonary     arteries

4.3. Nonthrombotic pulmonary embolism (tumor, parasites, foreign  material)

5. Miscellaneous Sarcoidosis, histiocytosis X, lymphangiomatosis,

compression of     pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)

DyspnoeaFatigueNon productive coughAnginaSyncopePedal edema

Cardiovascular examination P2is usually increased, which may

demonstrate fixed or paradoxic splitting in the presence of severe right ventricular dysfunction;

Pulmonic regurgitation (Graham Steell murmur) may be apparent.

A murmur of tricuspid regurgitation can be present, and a right ventricular lift (heave) may be noted.

Jvp elevated – v waves ( TR)

ELECTROCARDIOGRAPHY RAE,RAD, RVH ST DEPRESSION T INVERSION V1-V3

ECHOCARDIOGRAPHY for assessing right and left ventricular

function, estimating pulmonary systolic arterial pressure, and excluding congenital anomalies and valvular disease.

. Findings include central pulmonary arterial dilation which contrasts with “pruning” (loss) of the peripheral bloodvessels.

Right atrial and ventricular enlargement may

be seen and it progresses in more advanced cases.

Chest radiography is useful for excluding interstitial and alveolar processes that may cause hypoxia-mediated pulmonary vasoconstriction.

PULMONARY FUNCTION TESTS AND ARTERIAL BLOOD GAS

ANALYSIS.. usually have decreased lung diffusion

capacity for carbon monoxide (DLCO)

The arterial oxygen tension is normal or only

slightly lower than normal and arterial carbon dioxide tension is decreased as a result of alveolar hyperventilation.

Ventilation and perfusion lung scan.

ventilation and perfusion (V/Q) scans may be entirelynormal.

However they may also show small peripheral

non-segmental defects in perfusion. These are normally ventilated and thus represent V/Q mismatch

High-resolution computed tomography of the lungs.

HRCT provides detailed views of the lung parenchyma and facilitates the diagnosis of interstitial lung diseaseand emphysema.

Contrast-enhanced spiral computed tomography of

the lungs and pulmonary angiography. in PAH patients when the V/Q lung scintigraphy

shows segmental or subsegmental defects of perfusion with normal ventilation,

BLOOD TESTS AND IMMUNOLOGY. Routine biochemistry,hematology and thyroid function tests

CTD are diagnosed primarily on clinical and laboratory criteria and an autoimmune screen consists of

antinuclear antibodies, including anti-centromere antibody,anti-

SCL70 and RNP.

About one third of patients with idiopathic PAH have positive but low antinuclear antibody titers (≥ 1:80 dilutions.

HIV Testing HIV-positive patients have a higher rate of IPAH than

the general population

Antinuclear Antibody Excluding autoimmune disorders is an important

part of the workup in a patient with suspected pulmonary hypertension. Reportedly, up to 40% of patients with IPAH have a positive finding on an antinuclear antibody (ANA) assay but no other clinical manifestations of autoimmune disease.

Thyrotropin Screen for thyroid abnormalities during the initial

workup for IPAH because these abnormalities are common in patients with IPAH. Thyroid abnormalities may be the cause of or contribute to symptoms similar to IPAH. In addition, hyperthyroidism itself may lead to an elevation in pulmonary artery pressure.

Abdominal ultrasound scan. Liver cirrhosis and/or portal

hypertension can be reliably excluded by the use of abdominal ultrasound scan..

Exercise Testing Six-minute walk testing

Cardiopulmonary Exercise Testing Assessment of aerobic capacity and

ventilatory efficiency can help identify a pulmonary vascular limit to exercise and can be used to differentiate intrinsic pulmonary vascular disease from cardiac deconditioning and restrictive or obstructive lung disease or left-sided cardiac dysfunction.

-TYPE NATRIURETIC PEPTIDELevels of B-type natriuretic peptide (BNP) and N-terminal BNP have been shown to be elevated in patients with IPAH, and levels appear to be prognostic.

Sleep Study Sleep apnea must be excluded as a contributor or cause

of pulmonary hypertension if the patient's history suggests so.

Cardiac Catheterization This is the criterion standard test to definitively confirm

any form of PAH, including IPAH. Excluding left-sided heart disease, including diastolic

dysfunction to determine pulmonary vasoreactivity, which may

have implications in the initiation and titration of ccb

Lung Biopsy When the etiology of pulmonary hypertension is still in

doubt

Low probability for PAH diagnosis

Echocardiographic diagnosis of ‘PH unlikely’, no symptoms: no additional work-up is Recommended

Echocardiographic diagnosis of ‘PH unlikely’, presence of symptoms and of associated conditions or risks factors for group 1—PAH: echocardiographic follow-up is recommended

Echocardiographic diagnosis of ‘PH unlikely’, presence of symptoms, and absence of associated conditions or risks factors for group 1—PAH: evaluation of other causes for the symptoms is recommended

High probability for PAH Echocardiographic diagnosis of ‘PH likely’,

with symptoms and presence/absence of

associated conditions or risks factors for group 1—PAH: RHC is recommended

Echocardiographic diagnosis of ‘PH likely’, without

symptoms and presence/absence of associated

conditions or risks factors for group 1—PAH: RHC should be considered

Class I Patients with pulmonary hypertension but without resulting limitation of physical activity

Class II Patients with pulmonary hypertension resulting in slight

limitation of physical activity. They are comfortable at Rest

Class III Patients with pulmonary hypertension resulting in marked

limitation of physical activity. They are comfortable at rest.

Class IV Patients with pulmonary hypertension with inability to

carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or fatigue may even be present at rest

Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

McLaughlin, V. V. et al. J Am Coll Cardiol 2009;53:1573-1619

Treatment Algorithm for PAH

act on the vascular smooth muscle, dilating the pulmonary resistance vessels and lowering the pulmonary artery pressure.

CCBs are used at high doses

limited to patients without overt evidence of right heart failure.

Parenteral Vasodilators Parenteral vasodilators are used for patients

whose IPAH fails to respond to calcium channel blockers or who cannot tolerate these agents and who have New York Heart Association (NYHA) type III or IV right-sided heart failure. PGI2 ANALOGUES

  Epoprostenol In addition ,this agent also

contributes to inhibition of platelet aggregation n inhibition of smooth muscle proliferation.

  Treprostinil

Inhaled Vasodilators Inhaled prostacyclin (PGI2) synthetic

analogues are an alternative to parenteral administration. They are used in an attempt to limit systemic adverse effects.

Iloprost  

Treprostinil 

Inhibition of the antiproliferative effects of the PDE-5 pathway, which regulates cyclic guanosine monophosphate hydrolysis

Sildenafil  Tadalafil  

Endothelin receptor antagonists (ERAs) are therapeutic alternatives to parenteral prostacyclin agents. Given orally, they competitively bind to endothelin 1 (ET-1) receptors endothelin-A and endothelin-B,

causing a reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP).

This agent is indicated for treatment of PAH in patients with WHO class III or IV symptoms to improve exercise ability and decrease the rate of clinical deterioration.

Bosentan   Ambrisentan  

Diuretics Diuretics are used in pulmonary

hypertension to manage peripheral edema.

Furosemide  

Bumetanide 

Spironolactone 

Anticoagulants survival in IPAH, regardless of histopathologic

subtype, is increased when patients are treated with anticoagulant therapy..

Warfarin should be used, provided the patient has no contraindications to anticoagulation.

Maintain an international normalized ratio (INR) of 1.5 to 2.

Cardiac Glycosides Digoxin therapy can be used to improve right

ventricular function in patients with right ventricular failure.

Surgical Care A single- or double-lung transplant is

indicated for patients who do not respond to medical therapy.

Atrial septostomy is a palliative

procedure allowing interatrial right-to-left shunting to occur, thus delivering more overall oxygen content to the respiring tissues, albeit with a lower overall saturation.

Future Therapies

TYROSINE KINASE INHIBITORS

CINACIGUAT,RIOCIGUAT-ACTIVATORS OF GUANYLYL CYCLASE

PrognosisThe NIH IPAH registry

For untreated IPAH, the estimated 3-year survival rate is approximately 41