PREVALANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH CREATININE CLEARANCE LESS THAN 30ML/MIN PER 1.73 METER
SQUARE ON DIALYSIS Dissertation submitted to
The Tamil Nadu Dr. M.G.R Medical University, Chennai In fulfilment of the requirements for the award of the degree of
Doctor of Medicine in General Medicine
Under the guidance of Dr. R. Tolstoy M.D.,
DEPARTMENT OF GENERAL MEDICINE
PSG INSTITUTE OF MEDICAL SCIENCES & RESEARCH, COIMBATORE
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This is to certify that the dissertation entitled “PREVALANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH CREATININE CLEARANCE LESS THAN 30ML/MIN PER 1.73 METER SQUARE ON DIALYSIS ” is the bonafide original work of Dr .VIGNESH .S done under my direct guidance and supervision in the Department of General Medicine, PSG Institute of Medical Sciences and Research, Coimbatore in fulfilment of the regulations by The Tamil Nadu Dr. MGR Medical University, Chennai for the degree of Doctor of Medicine in General Medicine.
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This is to certify that the dissertation entitled, “PREVALANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH CREATININE CLEARANCE LESS THAN 30ML/MIN PER 1.73 METER SQUARE ON DIALYSIS” is the bonafide original research work of Dr. VIGNESH.S under the guidance of Dr. R. Tolstoy M.D., Professor of Medicine, PSG IMS&R, Coimbatore in partial fulfilment of the requirements for the degree of Doctor of Medicine in General Medicine.
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I hereby declare that this dissertation entitled “PREVALANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH CREATININE CLEARANCE LESS THAN 30ML/MIN PER 1.73 METER SQUARE ON DIALYSIS” is a bonafide and genuine research work carried out by me under the guidance of Dr. R.Tolstoy M.D., Professor of Medicine, PSG IMS&R, Coimbatore. This dissertation is submitted to The Tamil Nadu Dr. M.G.R Medical University in fulfilment of the university regulations for the award of MD degree in General Medicine. This dissertation has not been submitted for award of any other degree or diploma.
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ACKNOWLEDGEMENT
I would like to express my deep sense of gratitude to my respected guide and teacher Dr. R. TOLSTOY M.D., Professor, Department of General Medicine for her valuable advice and guidance. I am very much thankful for her constant inspiration and timely suggestions without which this study would have not been completed.
I would also extend my gratitude to Dr.K.Jayachandran, Professor and Head of Department, Department of General Medicine, for his constant encouragement and structural support in carrying out this study.
I also thank Dr.Sujithkumar M.D, Dr.Murali M.D, Dr.Saravanan M.D, Dr.Sujaya Menon, and Dr.L.S.Somasundaram M.D, Professors in Department of General Medicine for their constant support and encouragement.
My heartful thanks to Dr.Anithkumar M.D, MRCP, Dr.DeneshNarasimham M.D, Dr.Jagadeeshwaran, Associate Professors, Department of General Medicine for their support and guidance.
My heartful thanks to Dr.Santhni, Dr.Zeya Ansari, Dr.Velammal, Dr.Yoganathan Assistant professors, Department of general medicine for their support.
I also extend my thanks to all the staff of Department of General Medicine, for their help in carrying out the study.
Last but not the least, I am very much thankful to the all the patients involved in the study without which my study would not have been possible.
CONTENTS
1. INTRODUCTION 2
2. AIM AND OBJECTIVES 6
3. MATERIALS AND METHODS 8
4. REVIEW OF LITERATURE 11
5. RESULTS 57
6. DISCUSSION 82
7. CONCLUSION 85
8. BIBLIOGRAPHY 9. ANNEXURES
i. PROFORMA ii. ABBREVIATIONS iii. CONSENT FORM
iv. LIST OF FIGURES v. LIST OF TABLES
TITLE
PREVALANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH CREATININE CLEARANCE LESS THAN 30ML/MIN PER 1.73 METER
SQUARE ON DIALYSIS
INTRODUCTION
Inspire of having advancement in field which helps in diagnosing pulmonary hypertension, it remains the disease that takes lot of time for diagnosis from the presence of first symptom, many patients are diagnosed only in advanced stage of disease.1 Normal pressure in pulmonary artery is 25/10mmHg if the pulmonary artery pressure exceeds 40/20mmhg or average pressure exceeds 25mmHg, then the pulmonary hypertension is present. If the pressure in the pulmonary artery is persistently high then the right ventricle of the heart, from which the pulmonary artery arises, will not be able to pump properly and then the symptoms of right heart failure will occur2. Pulmonary artery pressure is increased by many conditions and pulmonary hypertension was classified accordingly. Prevalence of pulmonary artery hypertension of WHO class1 which is caused mainly by connective tissue disorder, drug, and toxic agents is 15 cases/million adult population3, 4.Prevalence of idiopathic pulmonary artery hypertension 5.9cases/million adult population5, 6, 7, 8.
Pulmonary hypertension due to systemic sclerosis is 7-12% 9, 10 Pulmonary hypertension due to portal hypertension is 2-16%11, 12 Pulmonary hypertension due to congenital heart disease is 30%13
Up to 60%,70% of the patients with severe left ventricular systolic dysfunction, heart failure with preserved ejection fraction may present with pulmonary hypertension respectively. Almost all the patient’s mitral value diseases have pulmonary hypertension and 65% of those with symptomatic aortic stenosis also will have pulmonary hypertension15, 16, and 17
.
Chronic thrombo embolic pulmonary hypertension (CTEPH) prevalence was 3.2cases/million/year and incidents were 0.9cases/million/year. Severe pulmonary hypertension is uncommon in this conditions, severe pulmonary hypertension is only present in combined emphysema/fibrosis syndrome. A large survey that is conducted in united states that registered information from all form of pulmonary hypertension from 1980-2002 documented that death rate in patients with pulmonary hypertension during these time were stable and ranging from 5.2-5.4deaths/1,00,00018, 19, 20, 21
.
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR) 1
CKD is classified based on GFR category (G1-G5) and albuminuria category (A1-A3) G1 – ≥ 90
G2 – 60-89 G3 – 45-54 G3b – 30-44
G4 – 15-29 G5 – < 15
A1 – <30mg/g, <3mg/mmol A2 – 30-300mg/g, 3-30mg/mmol A3 – >300mg/g, >30mg/mmol22
CKD is the global health burden with high economic cost to health system and is an independent risk factor for coronary vascular disease. All stages of CKD are associated with increased risk of cardio vascular premature mortality, morbidity and decreased quality of life.
A symptomatic review and meta-analysis of observational study estimating CKD prevalence in general population was conducted through literature searches in 8 databases. Assessed pooled data using a random effect model of 5842 potential articles, 100 studies of diverse quality were included comprising 6,908,440 patients.
CKD prevalence of stage 5 13.4% (11.7-15.1%) and stage 3.5 was 10.6% (9.2-12.2%).
Stage1 (eGFR>90 + ACR>30) prevalence was 3.5% (2.8-4.2%).
Stage2 (eGFR>60-89 +ACR>30) prevalence was 3.9% (2.7-5.3%).
Pulmonary artery hypertension in renal disease is an on-going research topic since it has very limited data.
Prevalence of pulmonary hypertension ranges from 9-39% in stage5 CKD.
Prevalence of pulmonary hypertension in haemodialysis patients range from 18.8-68.8%
Prevalence was 0-4.2% in patients with peritoneal dialysis; no epidermological data are available yet for early stages of CKD3.
Pulmonary hypertension has direct association with mortality in end stage renal disease.
ESRD increases cardio vascular disease & use of hospitalization in advanced centres.
Pulmonary hypertension in end stage renal disease is associated with the worst outcomes24-33.
Pulmonary hypertension should be prevented in patient with ESRD and it’s important because even kidney transplantation may not reverse. The high risk of mortality associated with established pulmonary hypertension3.
Finding prevalence of pulmonary hypertension in early stages of chronic kidney disease is important because it has a large population and bears a very high burden of cardio vascular mortality and morbidity24.
AIMS AND OBJECTIVES
To find the prevalence of pulmonary hypertension in patients with glomerular filtration rate less than 30ml/min per 1.73 meter square on dialysis in PSGIMSR To find the significance of volume overload association with pulmonary
hypertension
To find the significance of mild left ventricular dysfunction association with pulmonary hypertension
To find the significance of arterial venous fistula association with pulmonary hypertension
To find the significance of duration of dialysis association With pulmonary hypertension
To find the significance of left ventricular diastolic dysfunction association with pulmonary hypertension
To find the significance of diabetic mellitus association with pulmonary hypertension
To find the significance of systemic hypertension association with pulmonary
To find the distribution of the pulmonary hypertension among different age groups
To find the significance of superimposed infection association with pulmonary hypertension
To find the significance of creatinine clearance association with pulmonary hypertension
MATERIALS AND METHODS
Type of study: hospital based prospective observational study Duration of Study: One year (august 2016 – august 2017) Sample size: 50
Study volunteers / participants are (specify population group & age group):
Patients with age more than 18 years of age whose creatinine clearance less than 30ml/min per 1.73 meter square on dialysis
Location: PSG Hospitals, PSGIMS&R, and Coimbatore.
Inclusion Criteria Age>18years
Patients with GFR less than 30 ml/min per 1.73 meter square Exclusion Criteria
Patients who has ejection fraction less than 45%
Patients who are known case of chronic lung disease
Patients who are known case of connective tissue disorder Patients who are known case of sleep disordered breathing Patients who are already diagnosed with portal hypertension Patients who are known case of congenital heart disease
METHODOLOGY
The study is based on the prospective collection of patients aged more than 18 years who fulfilled the inclusion criteria stated above with GFR less than 30 ml/min per 1.73 meter square on dialysis, who were admitted in tertiary care centre (PSGIMSR) and found to have pulmonary hypertension on echo during the study period of one year between august 2016 to august 2017, are taken in to consideration for the study , where systemic computer coding for registry is used. A Performa was made which included the detailed history clinical examination requisite investigations available in the hospital. After taking informed consent from the patient, history and risk factor attributed to pulmonary hypertension in our study group are collected in detail. Investigations like complete hemogram, routine urine analysis, blood sugar, serum electrolyte, serum creatinine, blood urea, thyroid profile, liver function test, ultrasound abdomen and pelvis, retroviral serology, hepatitis B and C serology, chest X-ray, echocardiogram, electrocardiogram were done. GFR is calculated with the help of Cockcroft-gault formula. Diagnosis of pulmonary hypertension is made with the help of echocardiogram (if RVSP more than 50). Finally the prevalence of pulmonary hypertension and the significance of risk factor
association with pulmonary hypertension is calculated, descriptive and statistical analysis and interpretation of the data collected is done.
STATISTICAL TOOLS:
The data collected from the patients is tabulated using Microsoft Excel. The data are reported as the mean +/- SD or the median, depending on their distribution. The differences in quantitative variables between groups were assessed by means of the unpaired t test. Comparison between groups was made by the non-parametric Mann- Whitney test. ANOVA was used to assess the variables. The chi square test was used to assess the difference in categorical variables between groups.
Descriptive analysis is done using chi square test and statistical analysis and interpretation of the data collected is done by using SPSS version 20. p value of
<0.05 using two tailed test was taken as being of significance for all statistical tests. All data were analysed with a statistical software package (SSPS version 16.0 for windows)
REVIEW OF LITERATURE
Pulmonary trunk gives origin to the pulmonary artery that brings deoxygenated blood from the right ventricle just below vertebral level T4 pulmonary trunk bifurcates trachea lies just in front of that left pulmonary artery is smaller than the right pulmonary artery.
Pulmonary artery passes through the mediastinum horizontally. pulmonary artery lies just anterior to the right main bronchus and slightly inferior to the tracheal bifurcation after entering the root of the lung pulmonary artery gives branch to the superior lobe of the lung. Second branch originate from the main pulmonary artery after the main vessel passes through the hilum of the lung. Superior lobe of the lung was applied by the second branch of the main pulmonary artery then the main pulmonary artery supply the middle and inferior lobes of the lung by dividing in to two branches just anterior to the descending aorta left pulmonary artery will be present and it’s lies posterior to the superior pulmonary vein and it gives of branches within the lung after passing through the root and hilum34.
The load on the right side of the heart is increased by constriction of pulmonary arteries.
Pulmonary blood flow is affected by various factors. There are lot of autonomic innervation in the pulmonary vessels, and their sympathetic stimulation reduces pulmonary blood flow. The vessels will also respond to several circulating molecules.
Different receptors have different effect on pulmonary smooth muscle. Pulmonary vascular dilation is caused by number of circulating molecules but dilation occurs mainly in response to release of nitric oxide (NO). Pulmonary blood flow is also influenced by
cardiac output and gravitational forces. Pulmonary arterial pressure increases in response to exercise with no or minimal vasodilation. O2 saturation of the haemoglobin in the red cells is not reduced while passing through the lung, that in turn increased the amount of oxygen delivered to the systemic circulation. These leads to dilation of capillaries, so previously non-functioning Capillaries will also become functional, so finally there will be increase in blood flow to the pulmonary vessels. If an air way get obstructed ventilation of alveoli will be reduced leading to hypoxia, this hypoxic state acts on the vascular smooth muscle leading to vasoconstriction of the pulmonary vessels supplying the particular area that gets obstructed and there will be shunting of blood away from the hypoxic area. In obstructed area there will be accumulation of co2 that leads to fall in pH, which causes vasoconstriction in the lungs (but in other parts of the body fall in pH causes vasodilation). Conversely, if there is a reduction in flow to a part of the lung there will be reduction in pco2 in that particular area which in turn leads to vasoconstriction of the bronchi supplying it, shifting the ventilation away from that area. Systemic hypoxia can also cause pulmonary arterial hypertension due to constriction of pulmonary arterioles. Following are the autonomic and humoral agents that affect the receptors in the pulmonary artery smooth muscles35
Table 135
Receptors affecting smooth muscle in pulmonary arteries and veins Autonomic
Receptor Sub type Response Endothelium dependency Adrenergic α1
α2 β2
Contraction Relaxation Relaxation
No Yes Yes
Muscarinic M3 Relaxation Yes
Purinergic P2x P2y
Contraction Relaxation
No Yes Tachykinin NK1
NK2
Relaxation Contraction
Yes No
VIP ? Relaxation ?
CGRP ? Relaxation No
Humoral
Receptor Sub type Response Endothelium dependency
Adenosine A1
A2
Contraction Relaxation
No No
Angiotensin -2 AT1 Contraction No
ANP ANPA
ANPB
Relaxation Relaxation
No No
Bradykinin B1
B2
Relaxation Relaxation
Yes Yes
Endothelin ETA
ETB
Contraction Relaxation
No Yes
Histamine H1
H2
Relaxation Relaxation
Yes No
5-HT 5-HT1
5-HT1c
Contraction Relaxation
No Yes
Thromboyane TP Contraction No
DEFINITION
proper way measuring pulmonary artery pressure is by doing right heart catheterization for the patient, pulmonary artery hypertension is defined as (PAPm) pulmonary artery pressure more than or equal to 25mmHg at rest & the normal PAPm at rest should be between 11 & 17. There is lack of data to define PH on exercise
pulmonary hypertension is hemodynamically classified into pre capillary ,
post capillary,
isolated post capillary,
combined pre &post capillary
with the help of pulmonary artery pressure PAP, pulmonary artery wedge pressure PAWP,pulmonary vascular resistance PVR, diastolic pressure gradient DPG.
Table2
Haemodynamic definition of pulmonary hypertension
Definition Charecteristics Clinical group
PH PAPm ≥ 25 mmHg All
Pre-capillary PH PAPm ≥ 25mmHg PAPm ≤ 15mmHg
pulmonary arterial hypertension
PH due to lung diseases Chronic thromboembolic PH
PH with unclear andior multifactorial mechanisms Post-capillary PH
Isolated post-capillary PH(Ipc-PH)
Combined post- capillary and pre- capillary PH (Cpc-PH)
PAPm ≥25mmHg PAPm > 15mmHg DPG<7mmHg andior PVR ≤ 3 WU
DPG ≥7 mmHg andior PVR>3WU
PH due to left heart disease
PH with unclear andior multifactorial machanisms
TABLE 3
Drugs & toxins that causes pulmonary artery hypertension
Definite Likely Possible
Aminorex
Fenfluramine
Dexfenfluramine
Toxic rapeseed oil
Benfluorex
Selective serotonin reuptake inhibitors
Amphetamines
Dasatinib
L-tryptophan
methamphetamines
cocaine
phenylpropanolamine st john’s wort
amphetamine-like drugs interferon α andβ
some chemotherapeutic agents such as alkylating agents (mytomycine C, cyclophosphamide)b
GENETICS
Heterogeneous BMPR2 mutation ,
mutation of genes coding for action receptor like kinase 1 & endoglin, mutations in BMPR1B & SMAD9,
rarely mutations in genes coding for protein such as caveolin 1 & KCNK3 can be the causative agent for group 1 PAH.
other possibilities that causes group 1 PAH includes recessive transmission from consanguineous marriages, bi-allelic mutation in EIF2AK4.
There is no association of genetic mutation with group 2 &group 4 pulmonary hypertension.
Among group 3,gene polymorphism is associated with severity of pulmonary hypertension in COPD38-42.
TABLE 4:-CLASSIFICATION OF PH46-50 1.Pulmonary arterial hypertension
1.1 Idiopathic 1.2 heritable
BMPR2 mutation
Other mutations 1.3 drugs and toxin induced 1.4 associated with:
connective tissue disease
HIV infection
Portal hypertension
Congential heart disease
Schistosomiasis
1’. Pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis 1’.1 idiopathic
1’.2 heritable
EIF2AK4 mutation
Other mutations
1’.3 drugs, toxins and radiation induced 1’.4 associated with
Connective tissue disorder
HIV infection
1”. Persistent pulmonary hypertension of the new born 2. pulmonary hypertension due to left heart disease 2.1 left ventricular systolic dysfunction
2.2 left ventricular diastolic dysfunction
2.3 valvular disesase
2.4 congential/ acquired left heart inflow/ outflow tract obstruction and congenital cardiomyopathies
2.5 congenital / acquired pulmonary veins stenosis
3. pulmonary hypertension due to lung disease and/or hypoxia 3.1 chronic obstructive pulmonary disease
3.2 interstitial lung disease
3.3 other pulmonary disease with mixed restrictive and obstructive pattern 3.4 sleep-disordered breathing
3.5 alveolar hypoventilation disorder 3.6 chronic exposure to high altitude 3.7 developmental lung disease
4. chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
4.1 chronic thromboembolic pulmonary hypertension 4.2 other pulmonary artery obstructions
Angiosarcoma
Other intravascular tumors
Arteritis
Congential pulmonary arteries stenosis
Parasites
5.pulmonary hypertension with unclear and multifactorial mechanism 5.1 haematological disorders
Pulmonary histiocytosis
Lymphangioleiomyomatosis
Neurofibromatosis 5.3 metabolic disorders
Glycogen storage disease
Gaucher disease
Thyroid disorder 5.4 others
Pulmonary tumoral thrombothic microamgiopathy
Fibrosing mediatinitis
Chronic renal failure
Segmental pulmonary hypertension
PATHOGENESIS
Pulmonary vascular resistance can be present in all PH irrespective of type, which leads to vasoconstriction, vascular remodelling, in situ thrombus & increased wall stiffness.
Pulmonary artery constriction occurs mainly by increase in cytosolic concentration of calcium in pulmonary vascular smooth muscles, this in turn prompt the vascular smooth muscle proliferation & migration.
Following are the mechanism that leads to PH
Passive obstruction to the outflow pulmonary veins,
Increased flow in pulmonary arteries leading to hyperactivity , for example , in case of left to right shunt,
damage to pulmonary vascular bed due to parenchymal disease, hypoxia induced vasoconstriction,
Different groups of pulmonary hypertension has different pathological features , in case of pulmonary artery hypertension distal arteries of diameter less than 500 mm in diameter are more commonly involved.
Adventitialthickening,
intimal proliferative & fibrotic changes,
moderate perivascular inflammatory infiltrates, complex lesions,
medial hypertrophy and
thrombotic lesions are the main pathological findings.
Pulmonary veins are involved only in case of pulmonary vent occlusive disease. Septal&
preseptal veins are mainly involved. Following are the main pathological findings in case of venoocclussive disease
occlusive fibrotic lesions,
inflammatory infiltrations &
lymphatic dilation with lymph node enlargement.
In this condition distal pulmonary arteries are involved due to medial hypertrophy, intimal fibrosis, & uncommon complex lesions.
Pathological findings in left sided heart disease induced pulmonary hypertension include enlarged & thickened pulmonary veins,
pulmonary capillary dilation, interstitial edema,
alveolar haemorrhage and lymphatic vessels
& lymph node enlargement.
Medial hypertrophy & intimal fibrosis are the reason behind pulmonary artery involvement.Pulmonary hypertension due to lung disease causes medial hypertrophy &
intimal obstructive proliferation of distal pulmonary arteries. There will be damage to vascular bed around the involved parenchyma.
Thrombi that are formed from chronic thrombi embolic pulmonary hypertension will firmly clinch to medial layer of pulmonary artery causing partial or complete occlusion, collateral will originate from other systemic circulation
Group 5 PH has lot of causes hence pathogenesis also variable43-45.
Diagram1
Features of plexogenic pulmonary arteriopathy are shown in this diagram1
Table 5: Components of the Pathogenesis of Pulmonary Arterial Hypertension Alteration in regulators of proliferation
Growth factors
Platelet-derived growth factor Fibroblast growth factor
Vascular endothelial growth factor Transforming growth factor β Bone morphogenetic protein Transcription factors
Matrix metalloproteinase Cytokines
Chemokine’s Mitochondria
Alteration in inflammatory mediators Altered T cell subsets
Monocytes and macrophages Interleukin
IL-6 MCP-1 RANTES Fractalkine
Alteration in vascular tone Endothelin
Nitric acid Serotonin
Prostaglandin K-channels Ca2-channels
Hypoxia induced remodelling HIF-1a
ROS
Mitochondria TGF-β signalling
BMPR2 ALK1 Endoglin Smad9 TGF-β1
CLINICAL MANIFESTATIONS
Dyspnea is the most common symptom of PH; this is nonspecific because it can be caused by variety of other conditions like
acute coronary syndrome, bronchial asthma, and other cardiac diseases.
other symptoms that are presenting PH includes edema,
chest pain, pre syncope, Frank syncope
But these complaints have direct association with severity of the disease.
Dry cough can also occur in case of PH. fatigue can also occur in PH.
In some cases leg swelling, abdominal distension, are the main symptoms, these symptoms occurs only if there is advanced disease with right heart failure.
Mechanical complication of ph. produces some symptoms those includes haemoptysis,
hoarseness of voice, wheeze,
angina,
haemoptysis occurs secondary to obstruction rupture of hypertrophied artery, left laryngeal nerve compression by dilated pulmonary artery causes hoarseness of voice,
compression to large airway causes wheeze,
compression of left main pulmonary artery causes myocardial ischemia,
signs & symptoms of cardiac tamponade occurs in case of rupture of pulmonary artery.
Signs of right heart failure like elevated JVP, pedal edema & ascites will be there in case of right heart failure.
Pulmonary stenosis murmur, tricuspid regurgitation murmur can be heard there will be loud second heart sound especially p2 component. Parasternal heave may be present.Clubbing cyanosis, sclerodactyly, Raynaud’s phenomenon, splenomegaly, palmar erythema, icterus, and ascites may be present143,5.
Table 6: Physical sign that suggest a possible underlying cause or associations of pulmonary hypertension
Sign Implication
Central cyanosis Abnormal ventilation-perfusion ratio, intrapulmonary shunt, hypoxemia, pulmonary-to-systemic shunt
Clubbing CHD, pulmonary venopathy
Cardiac auscultatory findings, including systolic murmurs, diastolic murmurs, opening snap, and gallop
Congenital or acquired heart or valvular disease
Rales, dullness, or decreased breath sounds Pulmonary congestion, effusion or both Fine rales, accessory muscle use,
wheezing, protracted expiration, productive cough
Pulmonary parenchymal disease
Obesity, kyphoscoliosis, enlarged tonsils Possible substrate for disordered ventilation
Sclerodactyly, arthritis, telangiectasia, Raynaud phenomenon, rash
Connective tissue disorder
Peripheral venous insufficiency or obstruction
Possible venous thrombosis
Venous stasis ulcers Possible SCD
Pulmonary vascular bruits Chronic thromboembolic PH Splenomegaly, spider angiomas, palmar
erythema, icterus, caput medusa, ascites
Portal hypertension
Table 6: Physical sign that reflect severity of pulmonary hypertension
Sign Implication
Accentuated pulmonary
component of s2 (audible at the apex in>90%)
High pulmonary pressure increase the force of pulmonic valve closure
Early systolic click Sudden interruption of opening of the pulmonary valve in to high pressure artery
Midsystolic ejection murmur Turbulent transvalvular pulmonary outflow
Left parasternal lift High right ventricular pressure and hypertrophy present
Right ventricular s4(in 38%) High right ventricular pressure and hypertrophy present
Increased jugular a wave Poor right ventricular compliance
Physical signs that suggest moderate to severe pulmonary hypertension Moderate to severe PH
Sign Implication
Holosystolic murmur that increase with inspiration Tricuspid regurgitation Increased jugular v waves
Pulsatile liver
Diastolic murmur Pulmonary regurgitation
Hepatojugular reflux High central venous pressure
Advanced PH with right ventricular failure
Sign Implication
Right ventricular s3(in 23%) Right ventricular dysfunction
Distention of jugular veins Right ventricular dysfunction, tricuspid regurgitation, or both
Hepatomegaly Right ventricular dysfunction, tricuspid regurgitation, or both
Peripheral edema (in 32%) Ascites
Low blood pressure, diminished pulse pressure, cool extremities
Reduced cardiac output, peripheral vasoconstriction
INVESTIGATIONS
Apart from routine biochemistry and haematology, liver function testing, hepatitis serology & ultrasound abdomen should be done to rule out portal hypertension. Thyroid disorder can cause pulmonary hypertension hence thyroid profile should be done.
ANA profile, ANA IF, ANCA should be done if there is suspicion of connective tissue
ECG finding that are present in patients with pulmonary hypertension are P pulmonale,
right axis deviation,
RV hypertrophy, RV strain, right bundle branch block, QTc prolongation.
Right ventricular strain pattern has more sensitivity & specificity compared to right ventricular hypertrophy.in advanced pulmonary hypertension,supraventricular tachyarrhythmia can occur especially when the patient has the disease for more than 5 years1, 43, 51-54.
There may be no change in chest X-ray in PH patients, but findings that can be present includes
pruning that is loss of peripheral blood vessels due to dilation of main pulmonary artery .
Right atrium & ventricular hypertrophy is present mainly if there is right heart failure. Pulmonary artery vein ratio helps in differentiating arterial from venous pulmonary hypertension.
Signs of obstructive airway disease may be present, plural effusion may be present in few patients1, 43, 55, 56.
Lung volume will be reduced in patient with pulmonary hypertension & has association with disease stage. Lung diffusion capacity for carbon monoxide will be low in many patients with PH, but it can be normal. Abnormally low DLCO is associated with poor outcome.PVOD, PAH associated with connective tissue disorder usually has low DCLO.COPD has low DLCO, increased residual volume & irreversible airway obstruction. Decrease in lung volume & DCLO indicate interstitial lung disease1, 43, 57-63
. Ventilation/perfusion lung scan should be performed in all patients with PH who were suspected to have chronic thrombi embolism. V/Q scan has a sensitivity & specificity of 90-100% & 94-100% respectively in ruling out CTEPH.
Findings that has high specificity in finding out pulmonary hypertension includes pulmonary artery diameter of more than 29mm
Pulmonary to ascending aorta diameter ratio more than or equal to 1.0.
A segmental artery: bronchus ratio >1 : 1 in three or four lobes has been reported to have high specificity for PH
CT will also find the evidence that support PH, it can also find out features of the condition that leads to pulmonary hypertension like congenital defects in
suspected with diffuse bilateral thickening of the interlobular septa and the presence of small, centrilobular, poorly circumscribed nodular opacities
Contrast angiography can be helpful in diagnosing & finding out surgical accessibility of CTEPH. Traditional angiography can find out the patients who benefit from pulmonary endarterectomy.
Both traditional & contrast angiography can also be helpful in finding vasculitis&
pulmonary arteriovenous malformations1, 43, 68-78
.
Contrast MRI cannot exclude PAH, it helps in measuring stroke volume,cardiac output, pulmonary artery distensibility79-86.
Diagram21
Chest x-ray AP and lateral view showing pulmonary artery enlargement
Diagram31
Pulmonary artery enlargement is highlighted in this CT picture
ECHO
Diagram41: A:- right atrium and ventricle enlargement with compression to left side of the heart. B:- normal echo
Table 7
Echocardiographic probability of pulmonary hypertension in symptomatic patients with a suspicion of pulmonary hypertension1, 5, 43, 64, 65
Peak tricuspid regurgitation velocity(m/s)
Presence of other echo PH signs
Echocardiographic probability of pulmonary hypertension
Less than or equal to 2.8 or not measurable
No Low
Less than or equal to 2.8 or not measurable
Yes Intermediate
2.9-3.4 No Intermediate
2.9-3.4 Yes High
>3.4 Not required High
Table 8
Echocardiographic signs suggesting pulmonary hypertension used to assess the probability of pulmonary hypertension in addition to tricuspid regurgitation velocity measurement in table61, 5, 43, 64, and 65
A: the ventricles B: pulmonary artery C: inferior vena cava and right atrium
Right ventricle/left ventricle basal diameter ratio >1.0
Right ventricular outflow Doppler acceleration time
<105msec and/or midsystolic notching
Inferior cava diameter >21 mm with decreased
inspiration collapse (<50%
with a sniff or <20% with quiet inspiration)
Flattening of the
interventricular septum (left ventricular eccentricity index
>1.1 in systole and/or diastole
Early diastolic
pulmonary regurgitation velocity >2.2m/sec
Right atrial area (end- systole) >18 cm2
PA diameter > 25mm
Table 9: Distinguishing Pulmonary Arterial Hypertension from Heart Failure with Preserved Ejection Fraction
Characteristic Pah more likely Hepef more likely
Age Younger Older
Comorbid conditions- DM, HTN, CAD, obesity
Often absent Often present
Symptoms-PND, ORTHOPNEA
Often absent Often present
Cardiac examination RV heave, loud p2, TR murmur
Sustained LV impulse, LS4
CXR Clear lung fields Pulmonary vascular congestion, pleural effusions, pulmonary edema Chest CT Often clear lungs Mosaic perfusion pattern, ground
class opacities consistent with chronic interstitial edema
ECG RAD, RVE LAE, LVE, atrial fibrillation
Natriuretic peptides Often elevated Often elevated
Echo –LAE, LVH Absent Often present
Echo- diastolic dysfunction
Grade 1 common Grade 2, 3 common
Echo –right ventricle Often enlarged, may share the apex
Often normal, mildly enlarged
Echo –pericardial effusion
Sometimes Rare
Recommendation for right heart catheterization in pulmonary hypertension
RHC is recommended to confirm the diagnosis of pulmonary arterial hypertension (group 1) and to support treatment decisions
In a patient with PH , it is recommended to perform RHC in expert centres as it technically demanding and may be associated with serious complications
RHC should be considered in pulmonary arterial hypertension(group 1) to access the treatment effect of drugs
RHC is recommended in the patients with congenital cardiac shunts to support decisions on correction
RHC is recommended in patients with PH due to left heart disease(group 2) or lung disease (group 3) if organ transplantation is considered
When measurement of PAWB is unreliable, left heart catheterization should be considered to measure LVEDP
RHC may be considered in patients with suspected PH and left heart disease or lung disease to assist in the differential diagnosis and support treatment decisions RHC is indicated in patients with CTEPH (group 4) to confirm the diagnosis and
Recommendations for vasoreactivity testing
Vasoreactivity testing is indicated only in expert centres
Vasoreactivity testing is recommended in patients with IPAH, HPAH and PAH associated with drugs use to detect patients who can be treated with high doses of a CCB.
A positive response to the vasoreactivity testing is defined as a reduction of mean PAP≥ 10mmHg to reach an absolute value of mean PAP ≤ 40mmHg with an increased or unchanged cardiac output.
Nitric oxide is recommended for performing vasoreactivity testing.
Intravenous epoprostenol is recommended for performing vasoreactivity testing as an alternative.
Adenosine should be considered for performing vasoreactivity testing as an alternative.
Inhaled iloprost may be considered or performing vasoreativity testing as an alternative.
The use of oral or intravenous CCBs in acute vasoreativity testing is not recommended
Vasoreactivity testing to detect patients who can be safely treated with high doses of a CCB is not recommended in patients with PAH other than IPAH,HPAH and
PAH associated with drugs use and is not recommended in PH groups 2,3,4 and 51,
5, 43.
TREATMENT
Recommendation for general measures
It is recommended that PAH patients avoid pregnancy.
Immunization of PAH patients against influenza and pneumococcal infection is recommended
Psychosocial support is recommended in PAH patients
Supervised exercise training should be considered in physically deconditioned PAH patients under medical therapy .
In-flight o2 administration should be considered for patients in WHO-FC3 AND 4 and those with arterial blood o2 pressure consistently <8kpa(60mmHg)
In elective surgery, epidural rather than general anaesthesia should be performed whenever possible
Exercise physical activities that leads to distressing symptoms is not recommended in PAH patients5.
Recommendation for supportive therapy
Diuretic treatment is recommended in PAH patients with signs of RV failure and fluid retention.
Continuous long term o2 therapy is recommended in PAH patients when arterial blood o2 pressure is consistently <8kpa(60mmhg)d.
Oral anticoagulant treatment may be considered in patients wih IPAH, HPAH and PAH due to the use of anorexigens.
Correction of anaemia and iron status may be considered in PAH patients.
The use of angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists, beta-blockers and ivabradine is not recommended in patients with PAH unless required by co-morbidities( i.e. high blood pressure, coronary artery disease or left heart failure)
TABLE10
FDA approveddrugs for treatment of PH Generic
name
Route of administration
Drug class Indication
Epoprostenol Iv Prostacyclin derivative
Treatment of PAH to improve exercise capacity
Lloprost Inhaled Prostacyclin derivative
Treatment of PAH to improve a composite end point consisting of exercise tolerance,
symptoms(NYHA class), and lack of deterioration
Treprostinil Iv or SC Prostacyclin derivative
Treatment of PAH to diminish symptoms associated with exercise Treprostinil Inhaled Prostacyclin
derivative
Treatment of PAH to improve exercise ability
Treprostinil Oral Prostacyclin derivative
Treatment of PAH to improve exercise ability
Bosentan Oral Non-selective
endothelin Receptor antagonist
Treatment of PAH to improve exercise capacity and delay clinical worsening
Ambrisentan Oral Endothelin Treatment of PAH to improve
Sildenafil Oral PDE5 inhibitor Treatment of PAH to improve exercise capacity and delay clinical worsening
Tadalafil Oral PDE5 inhibitor Treatment of PAH to improve exercise ability
Riociguat Oral Solubleguanylyl cyclase
stimulator
Treatment of PAH to improve exercise capacity and delay clinical worsening
SEVERITY
Episodes of chest pain, haemoptysis, and syncope are the symptoms that are used to evaluate the severity of the disease. Change in exercise capacity, presence of symptom of arrhythmias,change in medication & whether patient is regularly taking the drug are the important part of history taking.
Following has direct association with severity of disease Peripheral or central cyanosis,
Enlarged jugular veins, Edema,
Ascites,
Pleural effusion
World health organization functional class definition of patient status is important in accessing severity of patient & is helpful in follow up to find out progression of disease.
Even though systolic pulmonary artery pressure is not used as a prognostic tool according to some study, echo is the important tool in finding severity of the disease.
Table 11: WHO class
WHO class 1
Patients with pulmonary hypertension but without resulting limitation of physical activity, ordinary physical activity does not cause undue dyspnoea or fatigue, chest pain, or near syncope
WHO class 2
Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope
WHO class 3
Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope
WHO class 4
Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea or fatigue may be present even at rest. Discomfort is
Echo finds out chamber size, RA,
RV area,
magnitude of tricuspid regurgitation, LV eccentricity index &
RV contractility
but CMR is more exact in finding RV morphology & function. Follow-up CMR can be used.
Right heart catheterization also gives prognostic information about the patient both during admission & during follow up. the indicator that gives prognostic information during right heart catheterization are
RA pressure, cardiac index &
mixed venous oxygen saturation.
6 minutes walking test is the most commonly used test to find exercise capacity of the patient.
6MWT is influenced by following sex,
age, height, weight,
co-morbidities, need for O2, learning curve and motivation
Borg score is useful in evaluating effort level at the end of test. Peripheral oxygen &
heart rate should also be measured to improve the prognostic relevance
One way to gauge how hard you are exercising is to use the Borg Scale of Perceived Exertion. The Borg Scale takes into account your fitness level: It matches how hard you feel you are working with numbers from 6 to 20; thus, it is a “relative” scale. The scale starts with “no feeling of exertion,” which rates a 6, and ends with “very, very hard,” which rates a 20. Moderate activities register 11 to 14 on the Borg scale (“fairly light” to “somewhat hard”), while vigorous activities usually rate a 15 or higher (“hard”
Table12 Borg scale137
Percelved exertion Breathlessness Discomfort/pain fatigue 0 Nothing at all Nothing at all Nothing at all Nothing at all 0.5 Very very weak Very very light Very very light Very very light
1 Very weak Very light Very weak Very light
2 Weak Light Weak light
3 Moderate Moderate Moderate Moderate
4 Somewhat strong Somewhat hard Somewhat strong Somewhat hard
5 Strong Hard Strong hard
6
7 Very strong Very heavy Very strong Very heavy
8 9
10 Very very strong Very very hard Very very strong Very very hard
maximal Maximal Maximal Maximal
Cardiopulmonary testing can add more information to 6MWT diagnostically &
prognostically. It gives information on exercise capacity,
exchange,
ventilator efficacy
And cardiac function during exercise.
Following are the typical findings that are present in patients with pulmonary artery hypertension
a low end-tidal partial pressure of carbon dioxide (pCO2), high ventilator equivalents for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/HR) &
Low peak oxygen uptake (peak VO2).
List of markers that have association with pulmonary artery hypertension are
Markers of vascular dysfunction includes asymmetric dimethylarginine (ADMA), endothelin-1, angiopoeitins, von Willebrand factor132-137,
Markers of inflammation includes C-reactive protein, interleukin 6, chemokines126-
129,
Markers of secondary organ damage (creatinine, bilirubin)138, 131.
Even though there are lot of markers for PH, there is no specific marker. The most commonly used marker that have direct association with myocardial dysfunction are BNP & NT-pro BNP. Hence it can be used as a prognostic marker during admission &
during follow up in patients with PH. it can be elevated in other heart diseases also. NT- pro BNP is more reliable compared with BNP when it comes to prognosis.
Table 13
Risk assessment in pulmonary arterial hypertension Determinants of
prognosis
(estimated 1-year mortality)
Low risk >5% Intermediate risk 5-10%
High risk>10%
Clinical signs of right heart failure
Absent Absent Present
Progression of symptoms
No Slow Rapid
Syncope No Occasional
syncope
Repeated syncope
WHO functional class 1,2 3 4
6MWD >440m 165-440 m <165m
Cardiopulmonary exercise testing
Peak VO,
>15ml/min/kg(>65%) VE/VCO; slope <36
Peak VO, 11-15
ml/min/kg(35- 65% pred ) VE/VCO, slope 36-44.9
Peak VO,
<11ml/min/kg (<35% pred) VE/VCO, slope
≥ 45 NT-pro BNP plasma
levels
BNP <50ng/l
NT-pro8NP <300ng/l
BNP 50-300ng/l NT-pro BNP 300-1400ng/l
BNP >300ng/l NT-pro BNP
>1400ng/l Imaging
(echocardiography, CMR imaging)
RA area <18 cm
No pericardial effusion
RA area 18-26 cm2
No or minimal pericardial effusion
RA area >26 cm2
Pericardial effusion
Table 14
Suggested assessment and timing for the follow-up of patients with pulmonary arterial hypertension
At baseline
Every 3- 6 months
Every 6- 12 months
3-6 months after
changes in therapy
In case of clinical worsening Medical assessment
and determination of functional class
+ + + + +
ECG + + + + +
6MWT/ Borg dyspnoea score
+ + + + +
CPET + + +
Echo + + + +
Basic lab + + + + +
Extended lab + + +
Blood gas analysis + + + +
Right heart catheterization
+ + + +
Low risk patients categorize have an estimated 1-year mortality <5%. Estimated 1-year mortality in the intermediate-risk group is 5–10%. Patients in the high-risk group have an estimated 1-year mortality >10%.
Treatment goal in all patients with PH is achieving low risk status. once they achieve low risk status the patient will have good exercise capacity, good quality of life, good RV function and a low mortality risk88-131
RESULTS
In this prospective observational study conducted in PSGIMSR during the period of august 2016 to august 2017 we included total of 50 patients who were admitted in medical, nephrology ward and intensive care unit fulfilling inclusion criteria and in whom echo was done during the admission. Prevalence of PH in patients with GFR less than 30 is 22 percentage.
Table15: Distribution Of PH Among Various Age Group
Age PULMONARY HTN
Total
P value
Yes No
<=40 yrs No 3 3 6
0.241
% 50.0% 50.0% 100.0%
41 - 50 yrs No 0 7 7
% .0% 100.0% 100.0%
51 - 60 yrs No 6 18 24
% 25.0% 75.0% 100.0%
61 - 70 yrs No 1 8 9
% 11.1% 88.9% 100.0%
>70 yrs No 1 3 4
% 25.0% 75.0% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table, we have mentioned the pulmonary hypertension distribution among various age groups. In our study among the total of 50 patients 6(12%) patients were less than 40 years of age, 7(14%) patients were between 41-50 years of age, 24(48%) patients were between 51-60 years of age, 9 (18%) patients were between 61-70 years of age and
Diagram 5
0 5 10 15 20 25
<=40 yrs 41 - 50 yrs 51 - 60 yrs 61 - 70 yrs >70 yrs Age
3
0
6
1 1
3
7
18
8
3
PULMONARY HTN No PULMONARY HTN Yes
Table16: Association of Sex and Pulmonary Hypertension
SEX PULMONARY HTN
Total
P value
Yes No
Male No 5 23 28
0.503
% 17.9% 82.1% 100.0%
Female No 6 16 22
% 27.3% 72.7% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table the compared the PH distribution among male and female population, in which total of 28(56%) male and 22 (44%) female were there . Among males 5(17.9%) patients are found to have pulmonary hypertension and among females 6 (27.3%) patients had pulmonary hypertension. There were no significant association of pulmonary
Diagram 6
0 5 10 15 20 25 30
Male Female
SEX
5 6
23 16
PULMONARY HTN Yes PULMONARY HTN No
Table17: Association of DM and Pulmonary hypertension
DM PULMONARY HTN
Total
P value
Yes No
Yes No 7 24 31
0.595
% 22.6% 77.4% 100.0%
No No 4 15 19
% 21.1% 78.9% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of diabetic mellitus with pulmonary hypertension. In total of 50 patients, 31(62%) patients were found to have DM, and among them 7(22.6%) patients were found to have PH. P value was 0.595,
Diagram 7
0 10 20 30 40
Yes No
DM
7 4
24 15
PULMONARY HTN Yes PULMONARY HTN No
Table 18: Association of SHTN and Pulmonary hypertension
SHTN PULMONARY HTN
Total
P value
Yes No
Yes No 9 37 46
0.206
% 19.6% 80.4% 100.0%
No No 2 2 4
% 50.0% 50.0% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of systemic hypertension with pulmonary hypertension. In total of 50 patients, 46(92%) patients were found to have SHTN, and among them 9(19.6%) patients were found to have PH. P value was
Diagram 8
0 10 20 30 40 50
Yes No
SHTN
9 2
37 2
PULMONARY HTN Yes PULMONARY HTN No
Table19: Association of MILD LVD and pulmonary hypertension
MILD LVD PULMONARY HTN
Total
P value
Yes No
Yes No 2 5 7 0.641
% 28.6% 71.4% 100.0%
No No 9 34 43
% 20.9% 79.1% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of mild LVD dysfunction with pulmonary hypertension. In total of 50 patients, 7(14%) patients were found to have mild LVD, and among them 2(28.6%) patients were found to have PH. P value was 0.641, hence there was no significance of mild LVD association with PH. (by mild LVD,
Diagram 9
0 5 10 15 20 25 30 35 40 45
Yes No
MILD LVD 2
9 5
34
PULMONARY HTN No PULMONARY HTN Yes
Table 20: Association of AV F and pulmonary hypertension
MILD LVD PULMONARY HTN
Total
P value
Yes No
Yes No
11 38 49
0.780
% 22.4% 77.6% 100.0%
No No
0 1 1
% .0% 100.0% 100.0%
Total No
11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of AVF with pulmonary hypertension. In total of 50 patients, 49(98%) patients were on AVF and one patient was on peritoneal dialysis, and among patients on arterial venous fistula 11(22.4%) patients were found to have PH, and on one patient who was on peritoneal dialysis there was no
Diagram 10
0 5 10 15 20 25 30 35 40
Yes No
AV F 0
14 11
25
PULMONARY HTN No PULMONARY HTN Yes
Table21: Association of superimposed infection and pulmonary hypertension
SUPERIMPOSED INFECTION
PULMONARY HTN
Total
P value
Yes No
Yes No 7 14 21
% 33.3% 66.7% 100.0%
No No 4 25 29
% 13.8% 86.2% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of super imposed infection with pulmonary hypertension. In total of 50 patients, 21(42%) patients were found to have super imposed infection, and among them 7(33.3%) patients were found to have PH. P
Diagram 11
0 5 10 15 20 25 30
Yes No
SUPERIMPOSED INFECTION
7 4
14 25
PULMONARY HTN Yes PULMONARY HTN No
Table22: Association of VOLUME OVERLOAD and pulmonary hypertension VOLUME
OVERLOAD
PULMONARY HTN
Total
P value
Yes No
Yes No 6 20 26
0.560
% 23.1% 76.9% 100.0%
No No 5 19 24
% 20.8% 79.2% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of volume overload with pulmonary hypertension. In total of 50 patients, 26(52%) patients were found to have volume overload, and among them 6(23.1%) patients were found to have PH. P value was 0.560,
DIAGRAM 12
0 5 10 15 20 25 30
Yes No
VOLUME OVERLOAD
6 5
20 19
PULMONARY HTN Yes PULMONARY HTN No
Table 23: Association of ANAEMIA and pulmonary hypertension
ANAEMIA PULMONARY HTN
Total
P value
Yes No
Yes No 11 38 49
0.780
% 22.4% 77.6% 100.0%
No No 0 1 1
% .0% 100.0% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of anaemia with pulmonary hypertension. In total of 50 patients, 49(98%) patients were found to have anaemia, and among them 11(22.4%) patients were found to have PH. P value was 0.780, hence there
Diagram 13
0 5 10 15 20 25 30 35 40 45 50
Yes No
ANAEMIA 11
0 38
1
PULMONARY HTN No PULMONARY HTN Yes
Table 24: Association of LVDD and pulmonary hypertension
LVDD PULMONARY HTN
Total
P value
Yes No
Yes No 10 31 41
0.662
% 24.4% 75.6% 100.0%
No No 1 8 9
% 11.1% 88.9% 100.0%
Total No 11 39 50
% 22.0% 78.0% 100.0%
In this table we analysed significance of association of LVDD with pulmonary hypertension. In total of 50 patients, 41(82%) patients were found to have LVDD, and among them 10(24.4%) patients were found to have PH. P value was 0.662, hence there
Diagram 14
0 10 20 30 40 50
Yes No
LVDD
10 1
31 8
PULMONARY HTN Yes PULMONARY HTN No
