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The carefully run RCTs CHARM (2003), Val-HeFT (2001), and TRANSCEND (2008) did not show a decrease in total mortality in heart failure (HF) subjects (see Chaps. 4 and 12). This surprising finding was observed in patients intolerant to ACE inhibitor administration. It is abundantly clear that ARBs are not as effective as ACE inhibitor therapy for HF, hypertension, or stroke. The salutary effects of ARBs are probably less than that observed with digoxin, yet these agents are used widely and excessively. In Val-HeFT valsartan when combined with a beta-blocker caused significantly more cardiac events.

Angiotensin-converting enzyme (ACE) inhibitors have been shown in large randomized controlled trials (RCTs) to prevent cardiovascular disease (CVD) outcomes significantly in patients with hypertension and heart failure (HF) and particularly in patients with LV dysfunction caused by acute myocardial infarction (MI). Some ARBs confer modest cardiovascular protection.

A meta-analysis (Lindholm et al. 2005) concluded that beta-blockers should not remain the first choice in the treatment of primary hypertension. Unfortunately, this analysis included randomized controlled trials (RCTs) with poor methodology.

Endocrine disorders are known to cause cardiovascular disturbances that have clinical implications. Acromegaly causes enlargement of the heart, premature coronary artery disease (CAD), heart failure, hypertension, intraventricular conduction defects, and cardiac arrhythmias may require management by a cardiologist. Mild hypertension occurs in more than 50 % of patients. Rarely acromegalic cardiomyopathy occurs. The defect in the myocardium causes arrhythmias, which weaken the myocardial force that leads to heart failure.

Most cardiovascular agents (like all other drugs) must be avoided in the first trimester of pregnancy because they may produce congenital malformations, especially from the 3rd to the 12th week of pregnancy. When used during the second and third trimesters, several cardiac drugs may affect growth and functional development of the fetus or cause toxic effects on fetal tissues. Also, some agents must be avoided just before parturition as they may have adverse effects on labor or in the newborn.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) play a pivotal role in the management of heart failure (HF) and hypertension. These agents are mildly cardioprotective and increase survival somewhat in patients with

Results that dictate a reduction in end points observed in a few hallmark and other recent randomized clinical trials (RCTs) are given. The appropriate reference source is given so that the reader can explore the details of the RCT if required. Because of the constraints of available space, only a brief comment is given in the text regarding the results and their implications.

Calcium antagonists without doubt cause an increased incidence of heart failure (HF) as observed in several well-run randomized controlled trials (RCTs)

Antiplatelet agents are used in virtually all patients with coronary heart disease (CHD). Aspirin, the pioneer hallmark agent, is of proven value for the management of

There are important, subtle differences among the available calcium antagonists that may affect the choice in treating individual patients. First generation dihydropyridines are short-acting agents that include felodipine, isradipine, nifedipine, and nitrendipine. These rapid-acting vasodilators are powerful antihypertensive agents, but their fast onset of action results in marked vasodilation that causes reflex stimulation of the sympathetic nervous system and hemodynamic adverse effects that include increased heart rate, increased cardiac workload, and an increased incidence of heart failure in patients with left ventricular dysfunction. The short-acting formulations of dihydropyridines, verapamil, and diltiazem are no longer recommended.

Oxygen is carried by hemoglobin in red blood cells to the tissues. The normal level of hemoglobin in circulating blood is 11.5–15.5 g/dl (115–155 g/L) in women and 15 to 17 g/dl in men. A normal structural heart with normal function can tolerate hemoglobin of 7 g/dl for approximately one year without causing cardiac damage or heart failure. Levels of 6 g/dl or less may cause cardiac dysfunction after approximately 6 months. In patients with angina, chest pain may be precipitated, because lack of oxygen to the myocardium produces myocardial ischemia that causes pain. Patients with sickle cell anemia commonly have hemoglobin in the range of 7–8 g/dl. In these individuals cardiac, enlargement with dilation occurs early in the course of the disease. Because of the anemia and poor delivery of oxygen to tissues, cardiac output increases to compensate and deliver the supply of nutrients. This entails more work for the heart. By age 40, these individuals manifest symptoms of poor cardiac function.

During a heart attack, large quantities of noradrenaline are released into the heart muscle, which can precipitate abnormal heart rhythms, particularly, ventricular fibrillation. Adrenaline causes an increase in heart rate and an increase in blood pressure, thus causing the heart to work harder. Because a coronary artery is blocked during a heart attack, the increased work with less available oxygen causes further damage to the heart muscle and increases the size of the muscle damage, causing a larger heart attack. Beta-blocking drugs were originally discovered by Sir James Black of Imperial Chemical Industries. Since the introduction of the prototype, propranolol, for the management of hypertension in 1964, more than 12 beta-blocking drugs have become available. Beta-adrenergic blocking drugs have become the cornerstone of cardiac drug therapy. Beta-blockers block beta-receptors. Structurally, they resemble the catecholamines (adrenaline and noradrenaline) and block the action of these catecholamines at their receptor sites. The beta receptors are situated on the cell membrane and are believed to be a part of the adenyl cyclase system. An agonist acting on its receptor site activates adenyl cyclase to produce cyclic adenosine-5-monophosphate, which is believed to be the intracellular messenger of beta stimulation.

Well-known anti-allergy medications may occasionally cause an increase in the pulse rate because they have an atropine-like effect. In some individuals, the heart rate may become rapid. These sensations, called palpitations caused by arrhythmia, subside over time and usually cause no harm. Patients with angina, however, should be cautious with the use of antihistamines, because an increase in heart rate may trigger an attack of angina. Blood pressure is usually not increased by antihistamine use, but many remedies containing antihistamines contain the decongestant phenylpropanolamine, which elevates blood pressure. This should be avoided by patients with hypertension and angina.

Cardiovascular disease is a much more common cause of death and disability in women than all forms of cancer, pneumonia, and AIDS. Women incorrectly perceive their risk of cancer of the breast and uterus as much greater than that of heart disease or stroke. Symptoms of a genuine heart attack are not significantly different in women and men. Some women suffer with shortness of breath or nausea instead of pain during a heart attack, but so do a few men. Diagnosis of a heart attack is similar in women and men. An ECG records the same information for both. The medical treatment for heart attack is virtually the same for both women and men, and the response is the same. All blood pressure lowering medications work equally well in women and men to prevent stroke or heart failure. Bypass surgery and angioplasty in the elderly carry a greater risk, and the results of angioplasty appear to be less impressive in women.

This chapter focuses on pulmonary arterial hypertension (PAH), which is primarily caused by primary pulmonary hypertension (PPH). The chapter also defines several disorders that cause PAH: pathophysiologic causes of severe chronic hypoxemia including alveolar hypoventilation disorders, such as chronic obstructive pulmonary disease (COPD); numerous restrictive lung diseases; chronic exposure to high altitude; sleep apnea drugs, such as appetite suppressants, pulmonary venous hypertension in which the pulmonary capillary wedge pressure is increased. The most publicized risk factor for PAH is appetite suppressant drugs. Aminorex fumarate was linked to an epidemic of PAH in Switzerland, Germany, and Austria in the sixties, and withdrawal of this agent was followed by a fall in incidence of the disorder.

Pericarditis can be caused by cancer chemotherapeutic agents, such as dantrolene, hydralazine, isoniazid, minoxidil, procainamide, phenytoin, and anticoagulants. Pericardium is defined as a double membrane that covers the heart and can be involved in infective and non-infective disorders. Pericarditis may cause severe chest pain in the retrosternal or left precordial area. Radiation to the chest may rarely cause pericarditis. Occasionally, the pain radiates to the trapezius ridge, a radiation that does not occur with angina, but it may also radiate to the neck or left arm and may stimulate angina or myocardial infarction. At times, the pain is localized to the upper epigastrium and left upper quadrant. Typical features of pain include a sharp, pleuritic pain that increases with deep inspiration, coughing, sneezing, or worsening of pain when lying down. The sharp pain that occurs in bed typically is relieved immediately by sitting and leaning forward or on standing; pain recurs with recumbency.

High-altitude pulmonary edema and severe shortness of breath due to accumulation of fluid in air sacs of the lungs may occur in young, healthy, susceptible adults who ascend rapidly to altitudes in excess of 2500 m. The first symptom is usually dyspnea on exertion and a reduced exercise tolerance, greater than expected for the altitude. Symptoms may become much worse when these individuals engage in strenuous exercise at such high altitudes before they become acclimatized. Cough, shortness of breath, and reduced effort tolerance may increase within hours and progress to fulminant pulmonary edema, which is heralded by extreme shortness of breath, including shortness of breath when the individual is lying in bed. Death may occur in young individuals who have no structural heart disease. The risk for pulmonary edema is related to the rapidity of ascent, the level of exertion, and individual susceptibility.

C-reactive protein (CRP) is an acute phase reactant produced by the liver in response to inflammatory cytokines (1L-1, 1L-6) and tumor necrosis factor-α (TNF-α). C-reactive protein has been identified as a marker of risk for coronary events, independent of other factors. The exact source of elevated CRP levels among patients with acute coronary syndromes remains unclear. In some studies, CRP has been found to have prognostic value among patients without evidence of myocardial necrosis. In patients with acute coronary syndromes and negative troponin-T, elevated CRP appears to be predictive of future adverse events. In addition, it has been observed that CRP is a strong independent predictor of short- and long-term mortality among patients treated with early revascularization.

Caffeine is a psychoactive drug that occurs naturally in many foods and beverages including coffee, tea, chocolate, and cocoa. It has found its way into many commercial soft drinks because of its proven mild stimulant effect and relative safety when consumed in small amounts. But caffeine can produce beneficial effects in one individual and potentially harmful effects in another. Caffeine is the most widely used psychoactive substance. This chapter starts with the biochemistry of caffeine, which is a xanthine derivative—1, 3, 7-trimethylxanthine. Caffeine is a powerful central nervous stimulant, and moderate doses of 200 mg contained in two cups of coffee, activate the cerebral cortex sufficiently to slow changes in an individual's electroencephalogram (EEG). Caffeine is also a mild cardiac stimulant. This chapter also discusses the effects that caffeine can generate. Caffeine has mild and variable effects on the heart rate, the heart muscle, blood pressure, blood flow, and blood cholesterol.

This chapter highlights erectile dysfunction (ED), which is a disorder of the blood supply to the penis. It is observed often in men with cardiovascular disease. Some investigators have suggested that ED may serve as a predictor for cardiovascular disease, because in both conditions, endothelial dysfunction is deranged. Endothelial dysfunction is a well-defined entity and is a major player in the pathogenesis of atherosclerosis, its complications, and symptomatology. Endothelial dysfunction shares many common risk factors with both atherosclerotic vascular disease and ED. The chapter claims that nitric oxide (NO) bioavailability is at the core of normal and abnormal erectile function. Nitric acid is synthesized from the amino acid L-arginine in response to sexual stimulation. Physical or emotional stimulation causes brain or neuronal NO synthase (bNOS) located in nonadrenergic, noncholinergic cavernous nerves of the penis to release NO.

A cardiac pacemaker is an electronic device that senses cardiac electrical activity and delivers electrical stimuli to the heart when needed. If the natural pacemaker is no longer working well or the electric current is blocked by disease of the conducting bundles, a pacemaker can be implanted. A cardiac pacemaker is inserted just under the skin and the pacemaker lead (electrode) is inserted into the right ventricle. The lead is then attached to the pacemaker. A small electrical current is passed through the lead at the rate set by the cardiologist. When the impulse reaches the heart muscle the muscle contracts in the same way it would as if the electrical impulse occurred naturally. The pacemaker generator can be visualized as an eye that stands guard over ventricular, and in some cases, atrial activity. If the eye sees ventricular activity, it inhibits its own output electrical pulse, but if it sees no activity, then it delivers an electrical stimulus to the ventricle to keep it beating at a programmed rate. This chapter explains the various types of pacemakers.

This chapter addresses the epidemiologic studies that strongly support the hypothesis that cigarette smoking increases the incidence of fatal and nonfatal heart attacks. Low-tar cigarettes and smokeless tobacco are shown to increase the risk of cardiovascular events in comparison to nonsmokers. Passive smoke is associated with about a 30% increase in risk of cardiac events compared with an 80% increase in active smokers. A smoke free environment in several cities has reportedly resulted in a decreased incidence of cardiac events. Cigarette smoke is divided into two phases: a tar phase and a gas phase. Tobacco smoke contains more than 4000 components. Some of these are nicotine, carbon monoxide, ammonia, benzene, nitrobenzene, phenol, 2,4,dimethylphenol, acetaldehyde, hydrogen cyanide, toluene, and O-cresol. Nicotine stimulates the adrenal glands to put out excessive adrenaline and noradrenaline. The higher the nicotine concentration inhaled, the greater the outpouring of adrenaline.

This chapter explains the alternative therapies with herbal, dietary, and vitamin supplements that have considerably escalated in the Western world during the past 10 years. Alternative therapies were used in more than 40% of adults in the United States during 1997, and a consumer poll in 1998 indicated that more than 30% of respondents use herbal remedies. It appears that of patients who take prescription medications, nearly 20% use herbal remedies, high-dose dietary supplements, or both. More importantly, adverse drug interactions involving prescribed medications and herbal remedies are common. Drugs such as ephedrine, chlorpheniramine, and testosterone are also contained in so-called herbal remedies. Because most herbal products are considered dietary supplements rather than medicines, they are not required to meet standards specified in the Federal Food, Drug, and Cosmetic Act. The manufacturer of a herbal or dietary supplement can market the product as long as there is no claim of effectiveness for the prevention and treatment of a specific disease.

This chapter discusses deep vein thrombosis that occurs in the veins of the legs, thigh, and pelvis. It can lead to a life-threatening condition called pulmonary embolism, and is a common problem worldwide. Thrombosis of veins that lie deep in the calf or thigh muscle is more dangerous than clots occurring in superficial veins just under the skin, because deep veins are much larger and communicate more directly with the lungs and the heart. A thrombus that is lodged in the femoral or iliac veins may break off and travel into the bloodstream, be carried to the right heart, and pumped into the lungs. This traveling clot is called an embolus, hence the term pulmonary embolism. Thrombi form in veins of the lower limbs and pelvis because of certain factors that increase the tendency of free-flowing blood to clot. A sudden increase in the tendency of the blood to clot commonly occurs soon after surgical operations or fractures that immobilize the lower limbs. Deep vein thrombosis occurring in the lower limbs is often difficult to diagnose from the history and physical examination. Some individuals present with pain and swelling of the calf muscle, whereas others are asymptomatic.

This chapter focuses on the epidemic of heart failure, which is usually the result of a diseased heart. Heart failure occurs when the heart is unable to eject enough blood from its chambers into the circulation to satisfy the needs of the body. The most common cause of heart failure is a very weak heart muscle. The heart muscle is the strongest muscle in the body. During an average life span, the heart beats about 2.5 billion times, pumping more than 227 million liters of blood. If the heart muscle is severely weakened and unable to adequately expel the blood brought to the left or right ventricle, blood backs up in the veins that drain into the left or right side of the heart. In heart failure, blood and fluid overdistend or congest the veins that bring blood into the failing muscular chambers.

This chapter is the clinical study related to chelation. Chelation, a method for clearing the obstruction, is analogous to using Drano to clean obstructed pipes. Chelation therapy using EDTA is an unproven, but widely used, alternative therapy for ischemic heart disease. The objective is to determine whether current EDTA protocols have a favorable impact on exercise ischemia threshold and quality of life measures in patients with stable ischemic heart disease.

This chapter focuses on diuretics, which are the water pills beneficial for the management of hypertension. A diuretic is the drug of choice for the initial treatment in individuals of African origin over age 60, because these agents have been shown to be more effective than the three other agents available for the management of hypertension. Diuretics are not as effective in the younger individuals of African origin. A diuretic is necessary for the management of hypertension in patients with heart failure or edema and in patients who have not responded adequately to one of the three antihypertensive agents, beta-blockers, Angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists. Diuretics, particularly loop diuretics such as furosemide and torsemide, are the mainstay of therapy for the millions of patients with moderate-to-severe heart failure.

Valve diseases are caused due to the damage to heart valves. This damage is caused by rheumatic fever, mitral valve prolapse, infections, such as bacterial endocarditis and syphilis, degenerative diseases, and complications of coronary artery disease and cardiomyopathy. The major symptoms of serious valve disease are increasing shortness of breath on mild exertion and on lying flat, cough, and occasional blood-tinged sputum. Damage to heart valves often occurs during an attack of rheumatic fever. Rheumatic fever is the most common between the ages of 5 and 25, and occurs in susceptible individuals after a beta-hemolytic streptococcal sore throat. The streptococcus bacterium sets up an allergic-like reaction on the valves and in the joints. There are usually fever and joint pains, and murmurs are heard over the swollen heart valves. A blood test to show a reaction to the streptococcus usually confirms the diagnosis.

Sudden cardiac death occurs most often within a few hours of wakening from sleep. Arousal from sleep causes circulatory, neural, and hormonal alterations that affect the heart and entire circulatory system. Arousal from sleep has profound influences on the cardiovascular system. Recently, sleep apnea and the arousal reaction are shown to play a role in increasing morbidity in patients with heart failure. It is explained that sleep apneas do not cause heart failure in individuals with normal hearts and normal ventricular function. Sleep apneas are not associated with the epidemic of atherothrombosis, which is the main cause for heart attack and stroke. This chapter outlines obstructive sleep apnea (OSA) and central sleep apnea (CSA), which are the two major recognized forms of sleep apnea. Obstructive sleep apneas and hypopneas are caused by complete or partial collapse of an abnormally narrowed pharynx.

Patent foramen ovale (PFO) is a failure of fusion of the two flaps that cause a less than 5-mm, slit-like valvular opening in the interatrial septum. With echocardiographic visualization of the left atrium and the septum, it became apparent that PFO is present in approximately 25% percent of a randomly selected population. During fetal development, PFO allows the necessary shunting of oxygenated blood from the right atrium to the left atrium; thus, oxygenated blood flows into the systemic circulation to organs and tissues. This right-to-left shunting of blood is crucial for fetal development, but it is also vital that no shunt should occur after birth, because the right side of the heart is no longer filled with oxygenated blood. A right-to-left shunt in individuals with congenital heart disease (CHD) causes cyanotic congenital heart disease, which is life-threatening.