BY SUNNDEEP CHOPRA.
Pulmonary Hypertension is most commonly defined as and elevation or increase of the pulmonary arterial pressure with the same being well above the normal or prescribed value.
Pulmonary Hypertension or then an abnormal or far from ideal elevation or increase in pulmonary artery pressure is mainly attributed to or then may be the result of left heart failure, pulmonary parenchymal (associated with or pertaining to the lungs, lung related disorder or disease) or vascular disease, thromboembolism (formation of a clot within a blood vessel can occur both in arteries and veins), or then an amalgam or combination of the afore mentioned factors.
The same is widely perceived to be a feature or characteristic of advanced or virulent form of the disease irrespective of whether it has arisen form either a cardiac pulmonary or then intrinsic vascular disease.
The etiology (study of causation or origination of diseases) underlying or then causing the pulmonary hypertension needs to be clearly established and understood on account of the onset of pulmonary hypertension being attributed to a plethora of causes or reasons. Pulmonary hypertension has also been widely touted as the primary or most common cause of a condition christened as Cor Pulmonale or right ventricular enlargement secondary or subsequent to any emerging cardiac or pulmonary disease.
Pulmonary hypertension has also been defined or identified as a mean or median pulmonary pressure greater than or in excess of 25 mmHg at rest or then in a supine position or 30 mmHg after any exertion or exercise period.
CLINICAL FEATURES OR SYMPTOMS: The diagnosis or recognition of pulmonary thrombosis is generally made at a much later stage on account of the non-specific or common nature of the causal symptoms which include shortage of breath or breathlessness, pains in the chest region and syncope (temporary loss of consciousness; a common form of fainting). Significant or characteristic signs or manifestations include elevation or increase of the joint ventricular pressure (JVP) (characterized by a prominent ‘a’ wave if it is in sinus rhythm), a parasternal heave (or then right ventricle hypertrophy), accentuation or in crease in the pulmonary component or constituent of the secondary or second heart sound and the beginning of an early diastoilic murumur on account of pulmonary regurgitation (backwards or reverse flow of blood from the pulmonary artery).
ALLIED OR ADDITIONAL CLINICAL FEATURES INCLUDE:
Ø Haemoptysis or expectoration or then coughing up of blood.
Ø Fatigue, syncope and angina on account of reduced or diminished cardiac output or outflow.
Ø Peripheral Oedema (swelling or inflammation of the lower limbs on account of accumulation of fluid/liquids in the affected limbs), tender hepatomegaly (easily briken, cur or then crushed and enhanced or raised jugular veinous pressure on account of due to right ventricular pressure.
Cyanosis:
· Peripheral cyanosis (blue tint in fingers or extremities as result of inadequate circulation) due to reduced or diminished cardiac output and blood flow to the skin.
· Central cyanosis occurs exclusively when a patent foramen ovale permits or then facilitates right to left shunt or shift.
PULSE: Reduced or low pulse on account of reduced or diminished cardiac output and left ventricular stroke volume.
Blood Pressure: Narrow or constricted pulse pressure following from reduced or diminished cardiac output and left ventricular stroke volume.
JUGULAR VEINS:
· Prominent or then stand out ‘a’ waves.
· Jugular venous pressure is elevated or increased along with or in conjunction with right ventricular failure.
· Prominent or significant ‘v’ waves and rapid or increased ‘y’ descent with functional tricuspid regurgitation (disorder in which the heart’s tricuspid valve does not close or shut down adequately thereby causing the reverse flow of blood or then blood flowing in a backward direction).
Inspection and Palpation:
Ø Apical impulse (heartbeats) may be shifted or altered indicating or pointing towards right ventricular hypertrophy (increased volume of an organ or tissue) and dilatation (dilated or stretched beyond normal dimensions).
Ø Visible and palpable (felt with a finger) left parasternal heave (visible heartbeats) and epigastric pulsations (rapid heartbeats) indicationg or pointing towards right ventricular hypertrophy.
Ø Visible and palpable pulsations in the second left intercostal muscle (space) from or on account of an underlying dilated pulmonary artery.
Ø Palpable pulmonary component (P2) of second or subsidiary heart sound in the pulmonary area.
Auscultatory (listening to the internal signs of the body with the aid of a stethoscope) signs or manifestations in pulmonary hypertension:
Pulmonary Ejection Sound (ES) : is a high pitched, distinctly audible clicking sound heard in systole (phase of contraction during the cardiac cycle) and is most clearly heard in the pulmonary area during expiration (coming to a close; termination). A loud and distinct pulmonary ejection sound may radiate to the lower left sterna border or even the apex. The same results on account of the dilation of the pulmonary atery.
Abnormal Second Heart Sounds (s2):
· Loud or distinct/audible pulmonary component or constituent (p2) of second or subsidiary heart sound.
· Narrow splitting of the second heart sound.
Right Atrial fourth heart sound (S4):
· It is best or most clearly heard at the lower left sternal border and becomes louder and clearer during inspiration or inhalation.
Right Ventricular Third heart Sound (S3):
· The same is a low frequency or less clearly audible sound most clearly heard or distinguished at the lower left sterna border and becomes louder and clearer during inspiration
· The same has also been construed as a sign or indication of right ventricular failure.
Pulmonary Ejection Systolic Murmur (ESM):
· The same is an ejection systolic murmur clearly distinct at the pulmonary area.
· It results from or is consequent to the ejection or pumping in of blood into a dilated pulmonary artery.
Pulmonary Early Diastolic Murmur (Graham Steell Murmur):
· This is a high pitched, soft, blowing, decrescendo, early diastolic murmur that sets in immediately after or then begins with a loud P2. It is commonly confined or restricted to the second and third left intercostals spaces, in close proximity to the sternum.
· The murmur results from pulmonary regurgitation secondary to pulmonary valve ring dilation.
·
Tricuspid Pansystolic Murmur (PSM):
· This is a high pitched, pansystolic murmur best heard at the lower left sterna border. The same increases in intensity during active inspiration.
· The murmur results from/ on account of functional tricuspid regurgitation secondary to or subsidiary to/ following on from the dilatation of tricuspid valve ring in right ventricular dilatation.
TREATMENT: Pulmonary arterial hypertension (PAH) most commonly refers to a plethora of diseases including or then inclusive of all idiopathic diseases. Several or wide ranging treatments can be initiated or then taken recourse to for both adequate and timely treatment of the disease/condition. However, physicians and specialists must draw the right balance between the efficacy or effectiveness of a drug and it’s resultant side effects before recommending the ingestion of the same. Another inhibiting factor in the ingestion of drugs is that all the available or resorted to drugs might not have the same or then varied effects on pulmonary arterial hypertension.
Patients should also be exhorted to exercise due caution before embarking upon/initiating a strenuous exercise or activity programme as the same has been known to aggravate pulmonary artery pressure in cases of PAH dramatically. Adequate periods of rest and recuperation are as important as exercise periods in the case of PAH patients.
Diuretic (anything or then any measure that forces the formation of urine within the kidneys) therapy has proved to be of immense benefit in relieving peripheral or border line edema and has also been found to be useful in reducing or diminishing right ventricle volume overload in the presence of tricuspid regurgitation.
Resting and exercise pulse oximetry (rates) should be duly noted and recorded as oxygen supplementation or augmentation helps or then plays a crucial role in alleviating or considerably reducing dyspnea and right ventricle ischemia in those patients whose arterial oxygen saturation has been considerably lowered or then reduced over a period of time.
Retrospective (past studies) and prospective (present and future, predominantly future) studies have highlighted the fact that the ingestion of warfarin significantly or considerably increases the survival rate of patients with pulmonary arterial hypertension thereby leading to the widespread embracing of anti coagulant therapy as a favoured course of treatment.
Calcium channel Blockers: patients who have recorded or manifested substantial or major decrease or then reduction in pulmonary arterial pressure as a direct consequence of or in response to short acting or short term vasodilators at the time of cardiac catheterization ( a fall or reduction in mean pulmonary arterial pressure lesser than or then equivalent to 10 mmHg and a final mean or medial pressure not exceeding 40 mmHg) should be started off or then initially treated with calcium channel blockers or inhibitors. Most or then a significant majority of patients need or require high doses (e.g. nifedipine,240mg/d, or then amlodipine, 20mg/d). Patients who react favourably to the ingestion of these drugs have been known to experience dramatic or considerable reductions in pulmonary artery pressure and pulmonary vascular resistance associated or then synonymous with improved/better symptoms.
Alas, less than 20% of all patients respond favourably to calcium channel blockers in the long term or over a prolonged period and these drugs should not be persisted with in the case of unresponsive patients as they can result in or cause hypotension, hypoxemia, tachycardia or then worsening or deteriorating right heart failure. The above mentioned drugs are yet to be recognized as or accorded their due status as approved treatments of pulmonary arterial hypertension by the U.S. Food and Drug Administration.
Endothelin Receptor Antagonists: The nonselective endothelin (is found in the smooth muscle tissues of blood vessels) receptor antagonist bosentan is an approved treatment of pulmonary arterial hypertension in cases of patients who are NYHA functional classes iii and iv . Bosentan was found to considerably/significantly improve both symptoms and exercise tolerance when measure through or by requisite increases in the distance covered over 6 minutes (while walking) in the case of a select group of patients. Therapy is introduced at or then initiated at the 62.5 mg level for the first month and then subsequently increased to 125 mg.
Phosphodiesterase-5 Inhibitors: Sildenafil, a phopsphodiesterase-5 inhibitor is both approved and has been found to be beneficial in treating PAH patients who are functional classes II and III. Phosphodiesterase-5 is responsible for the hydrolysis of cyclic GMP in pulmonary vascular smooth muscle. Sildenafil has been of help in improving both symptoms and exercise tolerance in pulmonary arterial hypertension. The recommended or necessary dose is 20mg tid. The most commonly recorded side or contra effect is headaches.
Prostacyclins: Iloporost; a prostacyclin drug (analogue) is approved in the form of an inhalator for PAH patients who are NYHA functional classes III and IV. It has stereotypically been shown to improve both symptoms as well as exercise tolerance. Therapy can be initiated at either the 2.5 or then 5 mcg level per inhalation. The inhaler must only be used in conjunction with a dedicated nebulizer and the most commonly manifested side or contra effects are flushing and cough.
LUNG TRANSPLANTATION: Is often the last resort or then course of treatment in the case of those patients who continue to manifest or display signs of right heart failure despite being treated with an intravenous prostacyclin. Acceptable or mostly favourable results have been obtained with heart-lung, bilateral lung and single lung transplants. The ready availability of donor organs more often than not determines the choice of procedure.
PROGNOSIS: Treatment options for primary pulmonary hypertension are extremely limited or restricted and the prognosis continues to be anything but encouraging despite recent medical advances. The median/average survival rate beginning from when the disease was diagnosed is a dismal 2-3 years (without resorting to heart-lung transplantation). All patients without exceptions should be anticoagulated with warfarin as the same has proved to be of immense benefit in improving the prognosis in cases of acute/severe pulmonary hypertension.
CAUSES: The right ventricle responds favourably more often than not to a corresponding increase in resistance within the pulmonary circulation by gradually increasing right ventricle systolic pressure as required to ensure required cardiac output. Chronic/multifarious changes that ultimately result in the progressive/ongoing remodeling of the vasculature occur in the pulmonary circulation over a prolonged interval.
The same can either sustain/maintain or then promote/accelerate pulmonary hypertension in the conspicuous absence of the initiating or accommodating factor.
The ability of the right ventricle to adapt or then adjust to increased or enhanced vascular resistance is inextricably linked to several factors inclusive of the age, and the rapidity of pulmonary hypertension; for example a large and acute pulmonary thromboembolism can result in/ directly cause right ventricle failure and shock.
Whereas, chronic thromboembolic disease of equal if not greater severity or seriousness may result in mild or negligible exercise intolerance. Coexisting or conjoined hypoxemia can impair or inhibit the intrinsic ability of the ventricle to compensate.
Abnormalities or deviations from normal in molecular pathways regulating or controlling the pulmonary vascular endothelial and smooth muscle cells have been best described as underlying or dormant pulmonary arterial hypertension. These include or inclusive of inhibition of the voltage regulated or controlled potassium channel, mutations or abnormal changes in the bone morphogenetic protein 2 receptor, increased or enhanced serotonin uptake or absorption in the smooth-muscle cells, increased or enhanced angiopoietin expression in the smooth-muscle cells and excessive or unnecessary deposition related to or then linked with a procaoagulant state.
SICKLE CELL DISEASE: cardiovascular system related abnormalities or anomalies are prominent/significant in the clinical manifestations/spectrum of sickle cell disease including or then inclusive of pulmonary hnypertension. The reasons behind the onset/setting in of the disease are multi-factoral (caused by a multitude of reasons) and always include-hemolysis, impaired or restricted nitric oxide availability, hypoxemia, thromboembolism, chronic high cardiac output and last but not the least chronic liver disease. The presence or then signs of pulmonary hypertension in patients with sickle cell disease is inextricably associated/linked with a higher/increased morbidity and mortality rate irrespective of the causal reasons or mechanisms.
SARCOIDOSIS: can produce or cause severe or extremely virulent pulmonary hypertension as a consequence/result of both chronic and severe fibrocystic lung involvement or direct cardiovascular involvement. Patients with sarcoidosis who also show signs of or then present symptoms of progressive dyspnea and clinical features or manifestations of pulmonary hypertension should be subjected to a thorough and minute evaluation/examination.
SCHISTOSOMIASIS: Schistomioasis is the single most common cause of pulmonary hypertension worldwide with the notable exception of North America. The development or progress of pulmonary hypertension more often than not occurs in the backdrop of hepatosplenic disease and portal hypertension. Schistosome ova have been known to embolize or spread from the liver to the lungs and thereby cause or result in an inflammatory pulmonary vascular reaction and chronic changes.
HIV INFECTION: The mechanisms or tools through which HIV infections manifest or give rise to pulmonary hypertension remain shrouded by the mists of mystery. Though it is hugely uncommon nay extremely rare for HIV infections to progress to or then result in pulmonary hypertension, the significant/marked rise in the prevalence or incidence of HIV infections worldwide could supposedly have a significant or huge impact on the frequency or number of times that these distinct entities are seen in close conjunction with each other.
Commonly encountered or spotted causes of pulmonary hypertension are as under:
Ø Idiopathic or primary pulmonary hypertension (PPH) whose parentage/ancestry remains largely obscure.
Ø Valvular heart diseases, especially mitral stenosis.
Ø Congenital heart diseases, especially atrial septal defect (ASD), ventricular septal defect (VSD) and persistent ductus ateriosus (PDA).
Ø Any and every cause of left sided cardiac failure.
Ø Obstructive lung diseases like chronic bronchitis and emphysema.
Ø Pulmonary thromboembolism.
Ø Interstitial lung diseases.
Ø Conditions synonymous with arterial hypoxaemia and hypercapnia like high altitude and chronic alveolar hypoventilation.
Ø Chronic liver diseases like cirrhosis.
Ø Drugs like fenfluramine and aminorex fumarate.
Note: Substances/elements from the gastrointestinal tract are thought to escape or obfuscate hepatic metabolic pathways and subsequently reach or arrive at the pulmonary circulation mechanism thereby causing vasoconstriction that leads to pulmonary hypertension in cases of cirrhosis of the liver.
Pulmonary hypertension is also thought to make an appearance or then manifest itself on account of the two below mentioned reasons or attributes:
· Significant increase in pulmonary vascular resistance .
· Increase in pulmonary blood flow.
SECONDARY PULMONARY HYPERTENSION:
All the collagen vascular diseases are thought to be associated or then interlinked with pulmonary arterial hypertension (PAH). This complication occurs most commonly along with the CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly and in scleroderma, and less frequently in systemic lupus erythematosus, Sjogren’s syndrome, dermatomyositis, polymyositis and rheumatoid arthritis).
These patients would more often then not exhibit a few elements or symptoms of coexistent or conjoined interstitial pulmonary fibrosis even though the same may remain invisible on chest x-rays, CT scans or pulmonary function tests.
Congenital Systemic to Pulmonary Shunts: it is commonplace for large or gigantic tricuspid cardiac shunts (e.g. ventricular septal defect, patent ductus arteriosus) to produce or cause severe pulmonary arterial hypertension. Though far less common or prevalent the same may also occur or appear in pre-tricuspid shunts (e.g. atrial septal defect, anomalous pulmonary venous drainage).
Portal Hypertension: Portal Hypertension does have an affinity with or is then closely linked with PAH, but the methodology or mechanism that interlinks the two continues to remain obscure. Patients with advanced cirrhosis can/may have the combined or interlinked features/symptoms of a high-output cardiac state in association or conjunction with the features of pulmonary hypertension and right ventricle failure.
Anorexigens: A causal or reason related affinity has been conclusively established between the prolonged or recent exposure to several anorexigens, including aminorex and fenfluramines and the development/progression of pulmonary arterial hypertension. Though, the pulmonary hypertension can or has been known to manifest itself or make it’s presence felt years after the last exposure.
Pulmonary Venoocclusive Disease: Is a rare and distinct/obscure pathologic entity found or then manifested in less then 10% of patients who present symptoms of unexplicable pulmonary hypertension. The same manifests itself through intimal proliferation and fibrosis of the intrapulmponary veins and venules, sometimes even extending to the arteriolar bed.
Pulmonary Capillary Hemangiomatosis: Is an extremely are form or species of pulmonary hypertension. The same is often characterized or recognized through the presence of infiltrating thin-walled blood vessels throughout the pulmonary interstitium and walls of the pulmonary arteries and veins.
PULMONARY HYPERTENSION DUE TO THROMBOEMBOLIC DISEASE:
Patients appropriately or symptomatically treated for acute pulmonary thromboembolism with intravenous heparin and chronic oral warfarin therapy are often oblivious of the scourge of chronic pulmonary hypertension. A few patients may however develop impaired fibrinolytic resolution of the thromboembolism that consequently leads to the organization, incomplete recanalisation and chronic obstruction of the pulmonary vascular bed.
Diagnosis: The physical examination of the patient mimics pulmonary hypertension but may also include bruits (the unusual sound that blood makes while rushing past an obstruction) heard over and around the vicinity of the lungs, representing or then embodying the flowing of blood through vessels with a partial obstruction (occlusion) . A perfusion lung scan or contrast-enhanced spiral CT scan will almost always reveal multiple thromboemboli. The administration of pulmonary angiography is a pre-requisite when it comes to determining the precise or exact location and proximal extent of the thromboemboli and consequently the potential or chances of operability.
Ø Pulmonary thromboendarectomy is a widely established and resorted to surgical procedure in the case of patients whose thrombi (blood clots) are accessible or then can be removed through surgical interventions. The operative mortality or death of a patient during the course of the operation is alarmingly high and has been recorded at around the 12% mark in corporate hospitals and centres of excellence. Post-operative survivors can expect to realize an improvement in the quality of their lives and enhanced exercise tolerance depending upon the success or efficacy of the surgical procedure. Lifelong anticoagulation through the ingestion of warfarin is a necessary evil.
DIAGNOSIS: The most common visible symptom attributable to pulmonary hypertension is exertional dyspnea (gradually developing anaemia). Other common or closely linked symptoms are fatigue, angina pectoris that may or may not represent or manifest Right Ventricle ischemia, syncope in the vicinity of or then near the syncope and peripheral or boundary line edema.
The ensuing physical examination of a patient would more often than not reveal increased or considerably enhanced jugular venous pressure, a reduced or diminished carotid pulse and a palpable right ventricle impulse.
Laboratory Findings: The chest x-ray would immediately throw up considerably enlarged central pulmonary arteries while the lung fields may or may not show or highlight any other/further development of the disease. The electrocardiogram or ECG would always shed light on possible right axis deviation and right ventricle hypertrophy. The echocardiogram would commonly demonstrate right ventricle and right atrial enlargement, a reduction in the left ventricular cavity size and a tricuspid regurgitant jet that can play a major role in determining or establishing right ventricle systolic pressure.
Cardiac Catherization: This procedure is mandatory or then a must in the accurate measurement of pulmonary artery pressure, cardiac output and left ventricle filling pressure as well as for the exclusion or ruling out of an underlying cardiac shunt. Due care should be taken to measure pressures only at the extreme end of any development or manifestation of the disease/organs (end expiration).
IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION: Idiopathic pulmonary arterial hypertension (IPAH) formerly christened or nomenclatured as primary pulmonary hypertension is highly uncommon if not altogether rare with the rate of incidence of the same being a measly two cases per million. The same unfortunately displays a strong or almost lopsided female predominance with most patients between the 40 and 50 age bracket, though a few doctors believe that the disease can affect anybody from infancy to sixty plus.
Familial or genetic idiopathic pulmonary arterial hypertension accounts for upto 20% of all cases of the same and is characterized or highlighted by autosomal dominant inheritance, variable or vacillating age of onset or manifestation and last but not the least incomplete penetration. The clinical and pathological features or symptoms of familial and sporadic IPAH are almost identical twins.
Natural History: The natural history or then development of the same over/through the ages is extremely uncertain and dicey, and since the predominant or then almost only recognizable symptom is dyspnea that can have an insidious or internal onset or manifestation, the disease is normally diagnosed when it is well past it’s prime or then critical stage. A pithy mean survival rate of 2-3 years from the time of diagnosis onwards was the norm until recent medical developments in this field have succeeded in prolonging the lives of the hapless patients somewhat.
SHORT NOTES:
Ø Primary pulmonary hypertension (PPH) has been vacuously defined as an intrinsic, idiopathic and obstructive disease of the small pulmonary arteries and arterioles.
Ø The causes or reasons behind the manifestations of the disease remain largely unknown, however, pregnancy, usage or ingestion of oral contraceptives (commonly known as birth control pills) and familial occurrence are noteworthy and deserve a mention. Primary pulmonary hypertension is far more prevalent in females with the highly skewed female to male ratio being 5:1. The disease most commonly manifests itself in people between the ages of 20-30 and death most commonly occurs within five years of the onset of symptoms.
Ø Clinically manifestations like dyspnoea, weakness, fatigue, exercise induced syncope and chest pains in a biologically young woman with no prior history of heart disease or cardiac murmurs strongly indicate the presence of primary pulmonary hypertension.
Management:
· Highly restricted or necessary physical activities or exertions.
· Diuretics in cases of right ventricular failure and functional tricuspid regurgitation.
· Vasodilators are tried or initiated but with varying degrees of success.
· Calcium channel blockers may prove to be effective/are effective in the short term.
· Continuous intravenous infusion of prostacyclin (under clinical investigation).
· The ultimate answer or mode of treatment is a heart-lung transplantation.
