CHF AND ARRHYTHMIAS

ANTIARRHYTHMICS

Due to the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, and the proarrhythmic properties of many antiarrhythmic agents, including those in Class IA, the use of antiarrhythmic drugs should be reserved for patients with life-threatening ventricular arrhythmias.
Because of the differences in pharmacological activity of the various antiarrhythmic drugs, they are classified according to the mechanisms that they target.

CLASS I ANTIARRHYTHMICS 


-Block the transmembrane influx of sodium (Na⁺)
-Subdivided into three classes:


1) Class 1A (eg, quinidine, procainamide, disopyramide):


-Broad-spectrum antiarrhythmics
-Intermediate in binding kinetics to Na⁺ channel receptors
-Slow conduction velocity, prolong the refractory period, and decrease automaticity
-Indicated to treat ventricular and supraventricular arrhythmias


2) Class 1B (eg, mexiletine):


-Bind to and dissociate quickly from Na⁺ channel receptors
-Have little effect on conduction velocity
-Decrease refractory period and automatocity 
-More effective in treating ventricular arrhythmias


3) Class 1C (eg, flecainide, propafenone):


-Bind to and dissociate slowly from Na⁺ channel receptors
-Potent effects on slowing ventricular conduction
-Refractory period left unchanged
-Used to treat both ventricular and supraventricular arrhythmias
-Limited by the risk of proarrhythmias

CLASS II ANTIARRHYTHMICS 


-Composed of β-blockers (eg, acebutolol, propranolol)
-Inhibit β-adrenergic receptors in the heart
-Slow conduction velocity, prolong the refractory period, and decrease automaticity
-Useful in treating re-entrant arrhythmias involving the atrioventricular (AV) node and in controlling ventricular rates in atrial fibrillation or flutter

CLASS III ANTIARRHYTHMICS (eg, dofetilide, amiodarone, sotalol)


-Block potassium channels in the heart causing an increase in action potential duration (increased QT interval) and a reduction in normal automaticity 
-Increase in refractoriness makes them effective in treating re-entry
-Amiodarone and sotalol also have β-blocking properties that contribute to efficacy
-Used to treat ventricular arrhythmias (particularly life-threatening arrhythmias resistant to other treatments)

CLASS IV ANTIARRHYTHMICS 


-Composed of calcium channel blockers (eg, diltiazem, verapamil)
-Block calcium channels in slow response tissue of the sinus and AV nodes 
-Slow conduction velocity, prolong the refractory period, and decrease automaticity 
-Used to treat automatic or re-entrant tachycardias that arise from sinoatrial and AV nodes


CONGESTIVE HEART FAILURE (CHF)

CHF is a condition in which the heart fails to pump blood at a rate proportionate to the metabolic needs of the body. 

Goals of therapy:

-Improve patient's quality of life
-Reduce symptoms
-Reduce hospitalizations
-Slow the progression of the disease
-Prolong survival

RENIN-ANGIOTENSIN SYSTEM ANTAGONISTS


-Cause arterial vasodilation resulting in decreased afterload and increased stroke volume and cardiac output
-Prevent Na⁺ and water retention, potentiating the effect of diuretics 
-Decrease sympathetic nervous system activity

1) ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs) (eg, ramipril, lisinopril)


-Block angiotensin II and aldosterone production
-More potent arterial than venous dilators
-Reduce bradykinin degradation thereby increasing production of vasodilator substances (nitric oxide, prostaglandin I₂)
-"ACE escape" (an increase in circulating angiotensin II) can result with chronic therapy
-Start with low dose to avoid abrupt drop in blood pressure
-Bradykinin-mediated side effects: cough, angioedema

2) ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) (eg, candesartan, valsartan)


-Block angiotensin II receptor subtype AT₁
-May provide more potent reduction of the effects of angiotensin II than ACEIs
-Does not appear to affect bradykinin (however, angioedema has been reported with ARBs)
-Preferred alternative in patients who cannot tolerate ACEIs

DIURETICS (For more information on diuretics see the Edema section)


-Recommended for all patients with evidence of fluid retention
-Reduce extracellular fluid volume and ventricular filling pressure
-Response often impaired in patients with CHF
-The use of spironolactone, an aldosterone antagonist, has been beneficial in patients with moderate to severe heart failure

CARDIAC GLYCOSIDES (eg, digoxin)


-Positive inotropic effect due to inhibition of Na⁺,K⁺-ATPase
-Control ventricular rate response to atrial fibrillation
-Neurohumoral effects: block sympathetic activation and reduce renin release
-Narrow therapeutic index (monitor for toxicity)
-No longer considered first-line treatment 

β-BLOCKERS (eg, metoprolol, carvedilol)


-Improve left ventricular structure and function, decrease chamber size, and increase ejection fraction
-Reduce the incidence of sudden death
-Recommended therapy in patients with ejection fraction <35% in conjunction with ACEIs or ARBs, and diuretics
-Should be initiated at low doses and increased slowly because of the potential to worsen symptoms and ventricular function
-May be necessary to adjust diuretic regimen because of increased fluid retention
-Increase in exercise tolerance seen with metoprolol
NITRATES & HYDRALAZINE 


-Nitrates are venodilators that produce reductions in preload
-Hydralazine is a direct-acting vasodilator that reduces afterload and increases stroke volume and cardiac output
-Combination therapy (nitrate + hydralazine) should be considered in patients with renal dysfunction who cannot tolerate ACEIs