Cardiac failure is the pathophysiologic state in which thc heart fails to pump blood at a rate commensurate at the requirements of the met;ibolizing tissues, or pumps only from an abnormally elevated diastolic filling pressure. Heart failure may be caused by myocardial failure, but may also occur in the presence conditions of high demand. Cardiac failure always causes circulatory failure.
Pathophysiology
When myocardial contractility is decreased or when there is excessive burden placed of adaptive inechailisms for on the ventricle, or both, the hear1 depends on ~li~rnber maintenance of pump function. Thc impo~tant ones among them are:
1) The Frank - Starling mechanism in which the increased preload helps lo suslain cardiac performance.
2) Neurohumoral systems activation, release of Nor Epinephine (NE) by adrenagic cardiac nerves which augment the myocardial contractility.
3) Activation of Renin Angiotensin Aldosterone (RAAS) system to maintain arterial pressure and pel-fusion of vital organs.
4) Myocardial remodeling with or without cardiac chamber dilatalioil - the mass of contractile tissue is augmented.
The primary myocardial response to chronic wall stress includes myocyte hypertrophy usually of eccentric type. Concentric type of hypertrophy occurs due to pressure overload. The reduction in cardiac output as a result of myocardial injuiy causes hernodynamic and neuro hormonal derangements that provoke activation of neuro endocrine activity of adrenergic system and RAAS. The release of epinephrine,endothelin 1 (ET 1) and vasopressin (V) causes vasoconstriction. Increase in after load and through an increase in Cyclic Adenosine Monophosphate (CAMP) results in increase in calcium entry into the myocyte augmenting myocardial contractility.
However, the calciun~ over load may also induce an-hythmias and lead to sudden death and also causes abnormality in relaxation of myocardium. The increased contractility and abnormal relaxatihn increases energy expenditure and may lead to myocardial cell death, causing enhancement of heart failure. 111 addition, the activation of RAAS leads to salt and water retention resulling in increase in myocardial energy expenditure. Increase in rennin results in increase in Angiotcnsin I1 (Ang 11) level and aldesterone levels. This will result in vasoconstriction and salt and water retention.
Angiotensin I1 also increascs inyocardial cellular liypertrophy. Neuro hormonal factors also lead to myocyte hypertrophy and interstitial fibrosis, leading to increased myocardial mass and myocyte loss. These are the hallmarks of remodeling process which leads to early adaptive mechanisms, such as augmentation of contraction (Starling's mechanism) and decreased wall stress (Laplace mechanism). However, this leads later to maladaptive mechanism like increased rnyocal.dia1 oxygen demand,myocardial ischemia, impaired contractility and ai-rhythmias.When the heart failure advances, there are relative counter regulatory effects of endogenous vasodilators including Nitric Oxide (NO), Prostaglandins, Atrial Natriuretic Peptide (ANP) and B-Type Natriuretic Peptide (BNP).Both systolic and diastolic heart failure results in decrease in stroke volume. This results in activation of central baro reflexes and chemo reflexes which result in neuro ho~monal responses with elevation of Nor Epinephjne (NE) and its level colrelates with degree of failure.
The ANP and BNP are endogenously generated peptides activated in response Lo atrial and ventricular expansion and are released from the atrial and ventricles respectively.They reduce cardiac preload and after load. BNP in particular produces selective inhibition of sodium resorption in the proximal convoluted tubules. It inhibits renin and possibly adrenergic activation as well. In chronic heai-t failure, both ANP and BNP are elevated, and they are important in the diagnostic, progliostic and therapeutic aspects.
Other vaso active systems that play a role in the pathogenesis of CHF are endothelin receptors system'(~T), vasopressin (V) and tilmor nectross Factor-alpha (TNF -alpha). Elevated ET-I closely correlate with severity of heart failure. ET-I has vasoconstrictor effects in the renal vasculature reducing renal Filtration Rate (GFR) and sodium excretion, TNF-alpha has been implicated in response to The inflammatory conditions and its level has been col~elaled with the degree of myocardial dysfunction. It has toxic effect on myocardium, worsening the myocardial function.
In individuals with systolic dysfunction the neuro hormonal responses to decreased stroke volume, temporarily improve the systolic blood pressure and tissue perfusion However, these responses accelerate downward spiralling of systolic dysf~~nction in the long term. In case of diastolic failure the same patho physiologic processes to decreased cardiac output in heart failure occur, but they do so in response Lo a different set of hem0 dynatnic factors that depress cardiac output.In diastolic heart failure, altered relaxation of the ventricle (due to calciunl intake by sarcoplasmic reticulu~n and delayed calcium efflux from the myocyte) occurs in response to ventricular after load (pressure over load).An increase in the LV chamber stiffness occurs secondary to any of these following mechanisms:
1) A rise in filling pressure - as occurs in volume over load or acute left ventricular failure due to myocarditis,
2) A shift to the steeper ventricular pressure - volume curve as a result of increased ventricular mass and wall thickness as observed,
a) In long standing hypertension and in,
b) Infultrative disorder like anyloidosis, and
c) Myocardial ischemia.
3) A parallel upward displace~nent of diastolic filling curve referred to as a decrease in ventricular distensibility.
Frequency: CHF is a world wide problem. In pregnancy, rheumatic valvular disease,hypertension, cardiomyopathy are common causes in our country, contributiilg to CHE Overt heart failure may be precipitated by several precipitating causes. These causes are:
1) Arrhythmias
a) Tachy a]-rhythinias - most commonly atrial fibrillation
c) Atrio ventricular dissociation
2) Systemic infections, septic silock
3) Pulmonary embolisn~
4) Physical exertion
5) Cardiac infla~ntniltion e.g. Myocarditis, infective endocarditis, anemia, fever
6) Excess intake of salt and water
7) Administration of cardiac depressants or drugs that cause sdi retention
8) High output states - tllyrotroicosis, Paget's disease corpulinonale
9) Develop~nent of a second form of heart disease.
Important Causes
a) Dominant systolic heart failure
1) Periparlum cardiomyopathy
2) Other forms of cardiomyopathy - diabetic, idiopathic, alcoholic
3) Myocarditis
4) Valvular heart disease - specially rheumatic mitral, aortic, ticuspid valve diseases
5) Congenital heart diseases with severe pulmonzuy hype~~ension
6 ) Ischemic myocardial disease, coronary a-lery disease.
b) Dominant diastolic heart failure
1)Hypertension
2) Severe aortic stenosis
3) Hypertrophic. cardiomyopathy
4) Restrictive cardiomyopathy.
c)Acute heart failure
1) Acute mitral or aortic regurgitation
2) Rupture of valve leaflets or supporting sttuctures
3) Infective endocarditis with acute valve incompetence
4) Myocardial infarction.
d) High output fai1ui.e
1) Anemia
2) Hyperthyroidism
3) Systemic artelio-venous fistula
4) Pregnancy
5) Glomerulonephritis
6) Corpulmonale
7) Polycytheinia Vera
8) Carcinoid syndrome.
Symptoms
Clinical Preventative
1) Breathlessness - a cardinal symptom of LV failure, may manifest progressively increasing
a)Exel-lional dyspnea
b) O~thopnea i.e., dyspnea occurring in lying down posture
c) Paroxysmal nocturnal dyspnea
d) Dyspnea at rest.
2) Fatigue and wedmess : These symptoms are often accompanied by a feeling of heaviness in the limbs and are generally related to poor perfusion of the skeletal muscles due to lowered cardiac output.
3) Nocturia : May occur relatively early in the course of heart failure. This will affect the much needed sleep to the patients. Oliguria is a late finding in CHF and is found in patients with markedly reduced LV function.
4) Cerebral symptoms : Confusion, memory impainnent, anxiety, headache,insomnia, night mares, disorientation and delirium.Some Feature of dormant right sided heart failure i.e. ~ s c i t i s hepatomegaly,anasarea-due to elevated light sided h e m pressures. Gastro-intestinal symptoms, anorexia,bloating, nausea - due to inadequate bowel perfusion.The dyspnea - prominent LV failure symptom, becomes less prominent in isolated right sided failure in the absence of pulmonary congestion. However, in teinlinal situation, thrombo embolic dyspnea may occur.
Signs
With mild to moderate heart failure patients may not be in distress, but with moderate activity they become dyspneic. Edema in the legs and feet may be present. Cardiovascular examination may reveal increase in heart rate, elevated jugular venous pressure and hepatomegaly. The enlarged liver is usually tender. If the patient has inarked tricuspid regurgitation, systolic pulsation of liver may be present. Cardiac examination will reveal enlarged heart, presence of third heart sound and muinlurs depending on the cause of
heat failure. In rheuinatic heart disease the classical murmur of the valve involved is heard. Duiing pregnancy, especially in later pregnancy, palpation of liver may be difficult.When assessing the cardiac murnmurs, one should take into account the innocent murmurs that may be heard in normal pregnancy.
Laboratory Investigations
Serum electrolytes, blood urea aild creatinine levels are lo be assessed, including diabetic profile. Estimation of B-type ilatriuretic peptidc (BNP) is helpful in the diagnosis and prognosis of heart failure. T'he release of BNP appears to be in direct proportion to ventricular volume expansion and its level is an independent predictor oC high LV end diastolic pressure. BNP level co~relates closely with NYHA classification 0111Earl failure.BNP level of > 100 pg 1 in1 has high specificity lor diagnosis of heart hilure. Chest X-ray is to be avoided during pregnancy. Electrocardiography is useful in detecting left ventricular hypertrophy, arrhythmias, myocardial ischemia o r infarction.
Echocardiography is mosl useful non-invasive test and is helpf~il in assessiilg left ventricular function, chamber size, valvular disease, pericardial diseases and assessment of regional wall motion abnormalities. Trans esophageal echocarcliography inay be more helpful where trans thoracic echocardiogram was inadequate.
Treatment
Aims theTreatment
1) Relief of symptoms,
2) Improvement in quality of life,
3) Reduction or prevention of repeated hospital admissions, and
4) Reduction in mortality.
General Measures
1) Bed rest in severely sylnptomatic patients including cardiac bed rest. Restrictccl physical aclivity is advised in others.
2) Salt and water restiiclion is advised, specially in those patients who have edema,
3) Oxygen administration intermittently in severely ill patients and who have hypoxia.
Pharmacological Treatment
1) Diuretics: Diuretics are essential for synlptornatiL management of patients with Congestive Heart Failure (CHF) with peripheral edema and fluid retention.Although diurelics improve symptoms, they do not influence the na
a) Firrosemide: It is a loop diuretic-acting on the loop of I-Ienle inhibiting sodium, potassium and chloride co-transporter. Oral dose of 20-40 mg.Intravenous dose of 10-20 mg. Belongs to C category duriilg pregnancy.Torsemide beloilgs to B category during pregnancy.
b) Hyclrochlorthiazide: The usual dose is 25 mg orally initially. Not corninonly used in pregnancy for CHF, but useful to treat hypertension. Belongs to B category duiing pregnancy. It may prevent norinal physiologic volume expansion that occurs in pregnancy and may reduce uterine blood flow.
c) Spironolactone: It is an anti aldesterorie agent. Recent studies have shown reduction in inortality in patients with heart failure. Adults dose orally 25-100 mg per day in divided doses. However it is unsafe in praegnancy and belongs to D Category. (For categoiy classification-see section on pharn~acolheraphy i n pregnancy)
2) ACE Inhibitors: Angiotensin converting enzyme inhibitors and angiotensin I1 receptor bloclters have been shown to give survival benefits in patients with CHF. However,these agents are not indicated in pregnancy as the cause fetal renal failure and death.
3) Digoxin: Digitalis has been used to treat CHF for more than 200 years. Digitalis sti~nulates the myocardiuill while depressing sill0 atrial and atiio ventricular nodal functions. This disparate action matches the requirenlcnts for treating palients with atrial fibrillation and CHF. Digitalis inhibits sodiuin and potassium ATpase on the sarcolermial membrane of cardiac myocyte, resulting in increased availability of calcium which improves contractility. The results of Digitalis Investigation Group (DIG) have clearly shown that it reduces number of hospital adinissions and deaths due to worsening of heart failure. Usual dose is 0.25 mg tablets orally daily. Toxic effects include, nausea, vomiting arrhythmias, fatigue,muscle cramps and conduction disturbances. Tt is usually safe to use in pregnancy and belongs to C category and considcred safe in lactating mothers also.
4) Beta-blockers: Beta-blockers were contraindicated in CHF in the past. However recent studies have shown that these agents improve symptoms and henlodynamics and also decrease mortality rates. The beta-blockers of choice in treatment of CHF are carvedilol, bispprolol, metoprolol and atenolol. Carvedilol in particular has additional one blocking effect causing vasodilatation. In general beta-blockers reduce the heart rate, reduce plasma rennin activity and stimulate parasympathetic activity.They ase also anti-arrhythrnics, and also decrease illyocardial oxygen requirement.Carvedilol is usually started orally with a small dose of 3.125 mg and increase the dose 1-2 weeks later up to 12.5 mg to 25 ing maximum, monitoring the blood pressure and side effects. Mctoprolol50-100 mg, atenolol 50-1 00 mg.In general beta-blockers are relatively safe in pregnancy (belong to C category).
Preferable to use maximum dose. Preferable to discontinue 2 to 3 days before labor as they are Iikely to affect uterine contractions. The usual side effects of beta-blockers are bradycardia, atrio ventricular blocks and bronchospasm. They are contra indicated in patients with bronchial asthma.
5) Other Iizotropic Agents: Like Dobutamine, dopamine, phosphodiesterase inhibitors like amrinone, inilrenoile - are useful to tide over severely ill patients temporarily. The use of these agents during pregnancy and their safety or unsafety has been discussed in the section "Pharn~acotherapy during pregnancy".
6 ) Nasiritide: Belongs to human B-type natriuretic peptide group. It is effective in reducing pulmonary capillary wedge pressure and improving dyspnea in patients with CHF. Nasiritide serves as a second messenger to dilate veins and arteries. ~ a s i r i t i d e is peptide. It is administered by recombitant DNA form oI human B-type nat~i~uetic intravenous route - dosage 2 mg I kg IV bolus ovcr 60 seconds followed by 0.01 mg /kg I min infusion. Contraindicated in patients with documented hypersensitivity and systolic blood pressure < 90 rnm Hg, severe aortic or ~nitral stenosis. However, its use in pregnancy and safety has not been established and beloilgs to C category.
7 ) Other Drugs: Nitrogycerine infusion, hydralazine, tumor necrosis factor inhibitors and ancillary drugs like ainiodarone are also useful in selected patients with CI-IF. However, large data of their use in pregliancy with CHF is not available.
Pathophysiology
When myocardial contractility is decreased or when there is excessive burden placed of adaptive inechailisms for on the ventricle, or both, the hear1 depends on ~li~rnber maintenance of pump function. Thc impo~tant ones among them are:
1) The Frank - Starling mechanism in which the increased preload helps lo suslain cardiac performance.
2) Neurohumoral systems activation, release of Nor Epinephine (NE) by adrenagic cardiac nerves which augment the myocardial contractility.
3) Activation of Renin Angiotensin Aldosterone (RAAS) system to maintain arterial pressure and pel-fusion of vital organs.
4) Myocardial remodeling with or without cardiac chamber dilatalioil - the mass of contractile tissue is augmented.
The primary myocardial response to chronic wall stress includes myocyte hypertrophy usually of eccentric type. Concentric type of hypertrophy occurs due to pressure overload. The reduction in cardiac output as a result of myocardial injuiy causes hernodynamic and neuro hormonal derangements that provoke activation of neuro endocrine activity of adrenergic system and RAAS. The release of epinephrine,endothelin 1 (ET 1) and vasopressin (V) causes vasoconstriction. Increase in after load and through an increase in Cyclic Adenosine Monophosphate (CAMP) results in increase in calcium entry into the myocyte augmenting myocardial contractility.
However, the calciun~ over load may also induce an-hythmias and lead to sudden death and also causes abnormality in relaxation of myocardium. The increased contractility and abnormal relaxatihn increases energy expenditure and may lead to myocardial cell death, causing enhancement of heart failure. 111 addition, the activation of RAAS leads to salt and water retention resulling in increase in myocardial energy expenditure. Increase in rennin results in increase in Angiotcnsin I1 (Ang 11) level and aldesterone levels. This will result in vasoconstriction and salt and water retention.
Angiotensin I1 also increascs inyocardial cellular liypertrophy. Neuro hormonal factors also lead to myocyte hypertrophy and interstitial fibrosis, leading to increased myocardial mass and myocyte loss. These are the hallmarks of remodeling process which leads to early adaptive mechanisms, such as augmentation of contraction (Starling's mechanism) and decreased wall stress (Laplace mechanism). However, this leads later to maladaptive mechanism like increased rnyocal.dia1 oxygen demand,myocardial ischemia, impaired contractility and ai-rhythmias.When the heart failure advances, there are relative counter regulatory effects of endogenous vasodilators including Nitric Oxide (NO), Prostaglandins, Atrial Natriuretic Peptide (ANP) and B-Type Natriuretic Peptide (BNP).Both systolic and diastolic heart failure results in decrease in stroke volume. This results in activation of central baro reflexes and chemo reflexes which result in neuro ho~monal responses with elevation of Nor Epinephjne (NE) and its level colrelates with degree of failure.
The ANP and BNP are endogenously generated peptides activated in response Lo atrial and ventricular expansion and are released from the atrial and ventricles respectively.They reduce cardiac preload and after load. BNP in particular produces selective inhibition of sodium resorption in the proximal convoluted tubules. It inhibits renin and possibly adrenergic activation as well. In chronic heai-t failure, both ANP and BNP are elevated, and they are important in the diagnostic, progliostic and therapeutic aspects.
Other vaso active systems that play a role in the pathogenesis of CHF are endothelin receptors system'(~T), vasopressin (V) and tilmor nectross Factor-alpha (TNF -alpha). Elevated ET-I closely correlate with severity of heart failure. ET-I has vasoconstrictor effects in the renal vasculature reducing renal Filtration Rate (GFR) and sodium excretion, TNF-alpha has been implicated in response to The inflammatory conditions and its level has been col~elaled with the degree of myocardial dysfunction. It has toxic effect on myocardium, worsening the myocardial function.
In individuals with systolic dysfunction the neuro hormonal responses to decreased stroke volume, temporarily improve the systolic blood pressure and tissue perfusion However, these responses accelerate downward spiralling of systolic dysf~~nction in the long term. In case of diastolic failure the same patho physiologic processes to decreased cardiac output in heart failure occur, but they do so in response Lo a different set of hem0 dynatnic factors that depress cardiac output.In diastolic heart failure, altered relaxation of the ventricle (due to calciunl intake by sarcoplasmic reticulu~n and delayed calcium efflux from the myocyte) occurs in response to ventricular after load (pressure over load).An increase in the LV chamber stiffness occurs secondary to any of these following mechanisms:
1) A rise in filling pressure - as occurs in volume over load or acute left ventricular failure due to myocarditis,
2) A shift to the steeper ventricular pressure - volume curve as a result of increased ventricular mass and wall thickness as observed,
a) In long standing hypertension and in,
b) Infultrative disorder like anyloidosis, and
c) Myocardial ischemia.
3) A parallel upward displace~nent of diastolic filling curve referred to as a decrease in ventricular distensibility.
Frequency: CHF is a world wide problem. In pregnancy, rheumatic valvular disease,hypertension, cardiomyopathy are common causes in our country, contributiilg to CHE Overt heart failure may be precipitated by several precipitating causes. These causes are:
1) Arrhythmias
a) Tachy a]-rhythinias - most commonly atrial fibrillation
c) Atrio ventricular dissociation
2) Systemic infections, septic silock
3) Pulmonary embolisn~
4) Physical exertion
5) Cardiac infla~ntniltion e.g. Myocarditis, infective endocarditis, anemia, fever
6) Excess intake of salt and water
7) Administration of cardiac depressants or drugs that cause sdi retention
8) High output states - tllyrotroicosis, Paget's disease corpulinonale
9) Develop~nent of a second form of heart disease.
Important Causes
a) Dominant systolic heart failure
1) Periparlum cardiomyopathy
2) Other forms of cardiomyopathy - diabetic, idiopathic, alcoholic
3) Myocarditis
4) Valvular heart disease - specially rheumatic mitral, aortic, ticuspid valve diseases
5) Congenital heart diseases with severe pulmonzuy hype~~ension
6 ) Ischemic myocardial disease, coronary a-lery disease.
b) Dominant diastolic heart failure
1)Hypertension
2) Severe aortic stenosis
3) Hypertrophic. cardiomyopathy
4) Restrictive cardiomyopathy.
c)Acute heart failure
1) Acute mitral or aortic regurgitation
2) Rupture of valve leaflets or supporting sttuctures
3) Infective endocarditis with acute valve incompetence
4) Myocardial infarction.
d) High output fai1ui.e
1) Anemia
2) Hyperthyroidism
3) Systemic artelio-venous fistula
4) Pregnancy
5) Glomerulonephritis
6) Corpulmonale
7) Polycytheinia Vera
8) Carcinoid syndrome.
Symptoms
Clinical Preventative
1) Breathlessness - a cardinal symptom of LV failure, may manifest progressively increasing
a)Exel-lional dyspnea
b) O~thopnea i.e., dyspnea occurring in lying down posture
c) Paroxysmal nocturnal dyspnea
d) Dyspnea at rest.
2) Fatigue and wedmess : These symptoms are often accompanied by a feeling of heaviness in the limbs and are generally related to poor perfusion of the skeletal muscles due to lowered cardiac output.
3) Nocturia : May occur relatively early in the course of heart failure. This will affect the much needed sleep to the patients. Oliguria is a late finding in CHF and is found in patients with markedly reduced LV function.
4) Cerebral symptoms : Confusion, memory impainnent, anxiety, headache,insomnia, night mares, disorientation and delirium.Some Feature of dormant right sided heart failure i.e. ~ s c i t i s hepatomegaly,anasarea-due to elevated light sided h e m pressures. Gastro-intestinal symptoms, anorexia,bloating, nausea - due to inadequate bowel perfusion.The dyspnea - prominent LV failure symptom, becomes less prominent in isolated right sided failure in the absence of pulmonary congestion. However, in teinlinal situation, thrombo embolic dyspnea may occur.
Signs
With mild to moderate heart failure patients may not be in distress, but with moderate activity they become dyspneic. Edema in the legs and feet may be present. Cardiovascular examination may reveal increase in heart rate, elevated jugular venous pressure and hepatomegaly. The enlarged liver is usually tender. If the patient has inarked tricuspid regurgitation, systolic pulsation of liver may be present. Cardiac examination will reveal enlarged heart, presence of third heart sound and muinlurs depending on the cause of
heat failure. In rheuinatic heart disease the classical murmur of the valve involved is heard. Duiing pregnancy, especially in later pregnancy, palpation of liver may be difficult.When assessing the cardiac murnmurs, one should take into account the innocent murmurs that may be heard in normal pregnancy.
Laboratory Investigations
Serum electrolytes, blood urea aild creatinine levels are lo be assessed, including diabetic profile. Estimation of B-type ilatriuretic peptidc (BNP) is helpful in the diagnosis and prognosis of heart failure. T'he release of BNP appears to be in direct proportion to ventricular volume expansion and its level is an independent predictor oC high LV end diastolic pressure. BNP level co~relates closely with NYHA classification 0111Earl failure.BNP level of > 100 pg 1 in1 has high specificity lor diagnosis of heart hilure. Chest X-ray is to be avoided during pregnancy. Electrocardiography is useful in detecting left ventricular hypertrophy, arrhythmias, myocardial ischemia o r infarction.
Echocardiography is mosl useful non-invasive test and is helpf~il in assessiilg left ventricular function, chamber size, valvular disease, pericardial diseases and assessment of regional wall motion abnormalities. Trans esophageal echocarcliography inay be more helpful where trans thoracic echocardiogram was inadequate.
Treatment
Aims theTreatment
1) Relief of symptoms,
2) Improvement in quality of life,
3) Reduction or prevention of repeated hospital admissions, and
4) Reduction in mortality.
General Measures
1) Bed rest in severely sylnptomatic patients including cardiac bed rest. Restrictccl physical aclivity is advised in others.
2) Salt and water restiiclion is advised, specially in those patients who have edema,
3) Oxygen administration intermittently in severely ill patients and who have hypoxia.
Pharmacological Treatment
1) Diuretics: Diuretics are essential for synlptornatiL management of patients with Congestive Heart Failure (CHF) with peripheral edema and fluid retention.Although diurelics improve symptoms, they do not influence the na
a) Firrosemide: It is a loop diuretic-acting on the loop of I-Ienle inhibiting sodium, potassium and chloride co-transporter. Oral dose of 20-40 mg.Intravenous dose of 10-20 mg. Belongs to C category duriilg pregnancy.Torsemide beloilgs to B category during pregnancy.
b) Hyclrochlorthiazide: The usual dose is 25 mg orally initially. Not corninonly used in pregnancy for CHF, but useful to treat hypertension. Belongs to B category duiing pregnancy. It may prevent norinal physiologic volume expansion that occurs in pregnancy and may reduce uterine blood flow.
c) Spironolactone: It is an anti aldesterorie agent. Recent studies have shown reduction in inortality in patients with heart failure. Adults dose orally 25-100 mg per day in divided doses. However it is unsafe in praegnancy and belongs to D Category. (For categoiy classification-see section on pharn~acolheraphy i n pregnancy)
2) ACE Inhibitors: Angiotensin converting enzyme inhibitors and angiotensin I1 receptor bloclters have been shown to give survival benefits in patients with CHF. However,these agents are not indicated in pregnancy as the cause fetal renal failure and death.
3) Digoxin: Digitalis has been used to treat CHF for more than 200 years. Digitalis sti~nulates the myocardiuill while depressing sill0 atrial and atiio ventricular nodal functions. This disparate action matches the requirenlcnts for treating palients with atrial fibrillation and CHF. Digitalis inhibits sodiuin and potassium ATpase on the sarcolermial membrane of cardiac myocyte, resulting in increased availability of calcium which improves contractility. The results of Digitalis Investigation Group (DIG) have clearly shown that it reduces number of hospital adinissions and deaths due to worsening of heart failure. Usual dose is 0.25 mg tablets orally daily. Toxic effects include, nausea, vomiting arrhythmias, fatigue,muscle cramps and conduction disturbances. Tt is usually safe to use in pregnancy and belongs to C category and considcred safe in lactating mothers also.
4) Beta-blockers: Beta-blockers were contraindicated in CHF in the past. However recent studies have shown that these agents improve symptoms and henlodynamics and also decrease mortality rates. The beta-blockers of choice in treatment of CHF are carvedilol, bispprolol, metoprolol and atenolol. Carvedilol in particular has additional one blocking effect causing vasodilatation. In general beta-blockers reduce the heart rate, reduce plasma rennin activity and stimulate parasympathetic activity.They ase also anti-arrhythrnics, and also decrease illyocardial oxygen requirement.Carvedilol is usually started orally with a small dose of 3.125 mg and increase the dose 1-2 weeks later up to 12.5 mg to 25 ing maximum, monitoring the blood pressure and side effects. Mctoprolol50-100 mg, atenolol 50-1 00 mg.In general beta-blockers are relatively safe in pregnancy (belong to C category).
Preferable to use maximum dose. Preferable to discontinue 2 to 3 days before labor as they are Iikely to affect uterine contractions. The usual side effects of beta-blockers are bradycardia, atrio ventricular blocks and bronchospasm. They are contra indicated in patients with bronchial asthma.
5) Other Iizotropic Agents: Like Dobutamine, dopamine, phosphodiesterase inhibitors like amrinone, inilrenoile - are useful to tide over severely ill patients temporarily. The use of these agents during pregnancy and their safety or unsafety has been discussed in the section "Pharn~acotherapy during pregnancy".
6 ) Nasiritide: Belongs to human B-type natriuretic peptide group. It is effective in reducing pulmonary capillary wedge pressure and improving dyspnea in patients with CHF. Nasiritide serves as a second messenger to dilate veins and arteries. ~ a s i r i t i d e is peptide. It is administered by recombitant DNA form oI human B-type nat~i~uetic intravenous route - dosage 2 mg I kg IV bolus ovcr 60 seconds followed by 0.01 mg /kg I min infusion. Contraindicated in patients with documented hypersensitivity and systolic blood pressure < 90 rnm Hg, severe aortic or ~nitral stenosis. However, its use in pregnancy and safety has not been established and beloilgs to C category.
7 ) Other Drugs: Nitrogycerine infusion, hydralazine, tumor necrosis factor inhibitors and ancillary drugs like ainiodarone are also useful in selected patients with CI-IF. However, large data of their use in pregliancy with CHF is not available.
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