Cardiology Core Curriculum - part 3 ppt

Intracoronary stents There is a wide variety of intracoronary stents available for deployment in the coronary arteries after PTCA. These will reduce the rate of restenosis, as compared with PTCA alone, when introduced into vessels of sufficiently large caliber. Two randomized trials compared Palmaz-Schatz stent placement following PTCA versus PTCA alone for elective procedures in large vessels (≥3·0 mm) and convincingly demonstrated that angiographic restenosis and need for repeat interventions were lower in stented patients. This benefit was derived at the cost of longer hospital stays and a greater incidence of vascular complications in the stented group because of the need for aggressive anticoagulation following stent placement. The incidence of stent thrombosis, for which a patient is at risk for approximately 30 days following the procedure, was less than 4% in those studies. Because stent deployment strategies now include only aspirin and clopidogrel for 1 month instead of a combination of aspirin and coumadin, there are currently no disadvantages to using stents, other than cost. Although the incidence of lesion recurrence is decreased with stenting, in-stent restenosis is a difficult situation to treat because of a high incidence (up to 70%) of a second restenosis, especially if the renarrowing involves the majority of the stent length. Intravascular radiation (brachytherapy) using either β or γ emitters have been demonstrated to reduce conclusively the incidence of recurrent in- stent restenosis, although at a greater risk for stent thrombosis. Consequently, patients receiving coronary brachytherapy are treated with aspirin and clopridogel for 6–9 months rather than the usual 30 days. A promising alternative is the use of coated stents, which locally release antiproliferative pharmaceuticals continuously over several weeks. Initial results using paclitaxel and sirolimus eluting stents have shown a marked reduction in in-stent restenosis, although further studies are needed. Coronary atherectomy Atherectomy refers to a procedure that employs a class of percutaneously introduced devices to actually remove or pulverize plaque within the coronary arteries. Like balloon angioplasty, a guide catheter and guidewire are used with all of these devices. Directional coronary atherectomy involves the use of a device with a windowed cylindrical housing that is compressed against the stenosis as the attached balloon is inflated against the opposite wall Cardiology Core Curriculum 116 of the artery. Once positioned, a rotating metal cutting blade inside the housing is advanced, shaving plaque from the vessel wall and depositing the shaved debris in the catheter’s nose cone. An increased luminal area is achieved by the dilating effect of the device itself, angioplasty effect from balloon inflation, and the removal of atherosclerotic material. When used for non-calcified stenoses, the incidence of initial success, abrupt closure, and restenosis with atherectomy is similar to that with PTCA. At present, atherectomy offers no obvious benefit as compared with PTCA. Transluminal extraction atherectomy is a different device that employs a rotating conical blade that is attached to a hollow shaft through which suction is applied. The contents of the vessel cut by the blade are liquefied and removed by the vacuum, which is transmitted to the tip of the device. It has been less well studied than directional atherectomy, and appears to have a role primarily in lesions with intracoronary thrombus or in old, degenerated saphenous vein grafts, which are usually lined with friable atheromatous material. Rotational atherectomy utilizes a high speed burr that pulverizes plaque as it is passed through the diseased vessel over the guidewire. Its utility is greatest in heavily calcified lesions, diffusely diseased vessels, and ostial stenoses. As with transluminal atherectomy, most lesions treated with the device are subjected to adjunctive balloon angioplasty or stenting to achieve an optimal result. Rotational atherectomy is utilized primarily in circumstances in which primary PTCA is an unattractive option because of high-risk lesion characteristics. Case studies Case 3.6 A 58-year-old diabetic hypertensive man with a several-year history of exertional angina presented to the hospital with a prolonged episode of pain at rest. He was admitted and was rendered pain-free with the addition of intravenous nitroglycerin and heparin to his regimen. A myocardial infarction was excluded with serial cardiac enzymes and electrocardiograms. He had several recurrent episodes of angina on hospital day 2 and, because of his refractory ischemia, he was sent to the cardiac catheterization laboratory. Medications: aspirin 325 mg/day, nitroglycerin 150 micrograms/min intravenously, heparin 1200 U/hour intravenously, metoprolol 100 mg twice per day, diltiazem 60 mg four times per day, and glyburide 5 mg/day. Cardiac catheterization 117 Examination. Physical examination: the patient appeared normal. Pulse: 54 beats/min, normal character. Blood pressure: 100/60 mmHg in right arm. Jugular venous pulse: 6 cm. Cardiac impulse: normal. First heart sound: normal. Second heart sound: split normally on inspiration. No added sounds or murmurs. Chest examination: normal air entry, no rales or rhonchi. Abdominal examination: soft abdomen, no tenderness, and no masses. Normal liver span. No peripheral edema. Femoral, popliteal, posterior tibial, and dorsalis pedis pulses: all normal volume and equal. Carotid pulses: normal, no bruits. Optic fundi: normal. Investigations. Hematology and biochemistry: normal. Electrocardio- gram: sinus bradycardia; PR interval 0·24 s; QRS duration 0·09 s. Flattened T waves in leads I and aVL. During anginal episodes, 1·5 mm of horizontal ST depression in these same leads. Chest x ray: normal cardiac silhouette, no pulmonary venous congestion. Cardiac catheterization. Aortic pressure: 98/60 mmHg. Left ventricular pressure: 98/20 mmHg. Normal left ventricular wall motion, ejection fraction 55%, no mitral regurgitation. Left ventricular systolic and diastolic volumes were within normal limits. The left main had a normal contour without stenoses. The left anterior descending artery had a 30% lesion in its mid-portion, there was a 90% lesion of the proximal left circumflex artery that measured 2·5 mm, and the right coronary artery had a 50% lesion in its distal segment. Questions 1. Is it reasonable to continue medical therapy alone? 2. What revascularization options can be offered to the patient? 3. Should stenting be considered as a primary modality for this patient? Answers Answer to question 1 Although many patients with unstable angina can successfully be treated with medications, this patient is experiencing ongoing ischemia despite an aggressive regimen. One of the objectives of medical therapy is to reduce myocardial oxygen demand by decreasing heart rate and blood pressure. This patient already exhibits excellent control of both parameters, and in addition has first-degree atrioventricular block on the electrocardiogram that may be drug induced. Increased doses of his calcium antagonist or β-blocker may result in bradyarrhythmias and/or hypotension. The Cardiology Core Curriculum 118 presence of electrocardiogram changes with pain also places this patient in a high-risk subgroup for adverse events, and so an aggressive approach in this case is most appropriate. Answer to question 2 Using the normal threshold of a lesion of 70% or greater as denoting a significant stenosis, this patient is classified as having single vessel coronary disease of the left circumflex artery. Because of his medically refractory symptoms, mechanical revascularization is indicated. Although bypass surgery is likely to offer symptomatic relief, in the case of single vessel disease the lower morbidity and mortality of PTCA make it the preferred approach in these circumstances. In the absence of the adverse lesion characteristics mentioned above, a success rate in excess of 90% can be expected with an approximately 30% risk of recurrent symptoms caused by restenosis over the ensuing 6 months (Figure 3.10). Answer to question 3 The use of intracoronary stents appears to diminish restenosis when used in de novo (i.e. not previously dilated) lesions. Because of the 2·5 mm caliber vessel in this case, stenting may not be the best option for this patient. Other lesion characteristics that may dissuade the use of stents (and that were excluded from the studies comparing stent with PTCA) include excessive length, marked vessel tortuosity, intracoronary thrombus, or lesion location at a branch point or in a diffusely diseased vessel. On the other hand there is growing evidence that in diabetic patients PTCA and stenting is preferred to PTCA alone because of the high rate of restenosis after PTCA. Cardiac catheterization 119 Figure 3.10 Cineangiographic frames revealing (a) a 90% stenosis in the proximal left circumflex coronary artery (arrow), which was (b) successfully dilated to a 10% residual stenosis. The left anterior descending artery is seen in the upper portion of this right anterior oblique view (a) (b) Further reading Bittl JA. Advances in coronary angioplasty. N Eng J Med 1996;335:1290–302. Boehrer JD, Lange RA Willard JE, Grayburn PA, Hillis LD. Advantages and limitations of methods to detect, localize, and quantitate intracardiac left-to-right shunting. Am Heart J 1992;124:448–55. Ellis SG, da Silva ER, Heyndrickx G, et al. Randomised comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction. Circulation 1994;90:2280–4. Grines RJ, Browne KF, Marco J, et al. A comparison of primary angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1994;331:673–9. Grossman WG, Baim DS, eds. Cardiac catheterization, angiography, and intervention, 4th ed. Philadelphia: Lea and Febiger, 1991. King SB, Lembo NJ, Weintraub WS, et al. A randomised trial comparing coronary angioplasty with coronary bypass surgery. N Engl J Med 1994;331:1044–50. Nobuyoshi M, Hamasaki N, Kimura T, et al. Indications, complications, and short term clinical outcome of percutaneous transvenous mitral commissurotomy. Circulation 1989;80:782–92. Serruys PW, Jaegere P, Kiemeneij F, et al. A comparision of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489–95. Shabetai R, Fowler NO, Guntheroth WG. The hemodynamics of cardiac tamponade and constrictive pericarditis. Am J Cardiol 1980:46:570–5. Topol EJ, Leya F, Pinkerton CA, et al. A comparison of directional atherectomy with coronary angioplasty in patients with coronary artery disease. N Engl J Med 1993; 329:221–7. Cardiology Core Curriculum 120 4: Hypertension SHARON C REIMOLD Hypertension is a major common cardiovascular disease, affecting up to 75% of the population by the eighth decade of life. Although hypertension is defined as a blood pressure exceeding 140/90 mmHg, the cardiovascular risk associated with elevated blood pressure forms a continuum. The primary reason for treating hypertension is to reduce the risk for vascular complications, including hemorrhagic and atherothrombotic stroke, congestive heart failure, coronary artery disease, aortic dissection, sudden death, nephrosclerosis, and peripheral vascular disease. The risks for these complications rise with increasing severity of hypertension. Definitions The Joint National Committee on the Detection and Treatment of Hypertension Guidelines 1 form the basis for diagnosis, classification (Table 4.1), 2 and treatment of hypertension. Although hypertension is defined as a blood pressure greater than 140/90 mmHg, the guidelines draw attention to the population of patients with systolic blood pressure ranging from 130 to 139 mmHg and diastolic blood pressure from 85 to 89 mmHg as a “high normal group”. This group is important because blood pressures in this range may be associated with increased risk for adverse outcomes. The most typical form of hypertension involves elevation in both the systolic and diastolic blood pressures. Systolic hypertension, or isolated elevation in systolic blood pressure to a level greater than 140 mmHg with normal diastolic pressure, is common in the elderly. It is now recognized that patients with increased pulse pressure (systolic blood pressure – diastolic blood pressure) are at higher risk for cardiovascular complications than are those with lower pulse pressure. 3 For example, a patient with a blood pressure of 180/90 mmHg has greater cardiovascular risk than does a patient with a blood pressure of 150/95 mmHg. Blood pressure is determined as the product of cardiac output and total peripheral resistance. Early in the course of the hypertensive disease process, cardiac output is elevated and total peripheral resistance is essentially normal. As the disease progresses, cardiac output normalizes but total peripheral resistance becomes elevated. 121 Blood pressure therapies can work by decreasing cardiac output or peripheral resistance, or both. In response to the elevated systolic arterial blood pressure, the myocardium hypertrophies. Several electrocardiographic criteria exist for the detection of hypertrophy. Voltage criteria are the most helpful (Table 4.2). Left ventricular hypertrophy may be detected on echocardiography as increased wall thickness and increased myocardial mass. Echocardiography is more sensitive for the detection of hypertrophy than is electrocardiography. Detection of left ventricular hypertrophy is a marker for end-organ damage from hypertension. This increased wall thickness may lead to systolic and/or diastolic dysfunction of the myocardium. Individuals who develop systolic dysfunction may have had an inadequate hypertrophic response of the ventricle and develop decreased myocardial contractile function in response to increased afterload. Systolic dysfunction in hypertension may be identified as a reduction in ejection fraction accompanied by a small increase in chamber volumes. Advanced cases of systolic dysfunction may present with a low cardiac output state. It is more common for patients with hypertension and left ventricular hypertrophy to develop diastolic dysfunction (Figure 4.1). 4 In these patients, the relaxation or compliance of the left ventricle is Cardiology Core Curriculum 122 Table 4.1 Classification of adult blood pressure Category Systolic pressure (mmHg) Diastolic pressure (mmHg) Optimal <120 <80 Normal <130 <85 High normal 130–139 85–89 Hypertension Stage I 140–159 90–99 Stage II 160–179 100–109 Stage III ≥180 ≥110 From the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 2 Table 4.2 Voltage criteria for left ventricular hypertrophy Lead Criteria Limb lead R amplitude in aVL >11 mm R wave in aVF >14 mm R wave in lead I plus S wave in lead III >25 mm Precordial lead R wave in V 5 –V 6 plus S wave in V 1 >35 mm R wave in V 5 or V 6 >26 mm abnormal. The ejection fraction may be normal or increased with normal chamber volumes. For these normal volumes, however, left ventricular filling pressures are elevated, leading to pulmonary venous congestion and symptoms of decreased exercise tolerance or dyspnea. Patients with systolic dysfunction also have underlying diastolic dysfunction of the ventricle. The hypertrophy produced by hypertension predisposes patients to the development of ventricular arrhythmias and sudden death. Approximately 95% of all patients with high blood pressure have essential hypertension. Essential hypertension may also be referred to as primary or idiopathic. Although no underlying etiology is identified for patients with essential hypertension, it is likely that multiple factors play a role in the development of hypertension. Up to 5% of patients have secondary hypertension. Secondary hypertension implies that a specific etiology for the elevated blood pressure has been identified. Treatment of secondary hypertension is based on the specific underlying etiology (see Secondary hypertension, below). The frequency of hypertension increases with age and varies by race. African-American and Hispanic patients are more likely to have hypertension before age 40 years than are Caucasian patients. Genetic abnormalities may be responsible for the development of hypertension in many of these patients. Only a few single gene mutations capable of producing hypertension have been identified. Abnormalities in the gene encoding aldosterone synthase/ 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase deficiency Hypertension 123 IBP LVH Ventricular arrhythmias Diastolic dysfunction Systolic dysfunction Ejection fraction ↓ End diastolic volume ↑ LV dilation Low cardiac output syndrome Ejection fraction → or ↑ End diastolic volume → or ↓ LV size normal LV filling pressure ↑ Pulmonary venous congestion Dyspnea Figure 4.1 Impact of elevated blood pressure on systolic and diastolic function of the left ventricle. IBP, arterial blood pressure; LVH, left ventricular hypertrophy. From Shepherd et al . 4 are examples of monogenic forms of hypertension. The development of hypertension may also be polygenic, requiring several genetic abnormalities to be present at one time. Multiple genes may contribute to the regulation of blood pressure, and the ultimate development of hypertension may relate to the interaction of a genetic substrate with environmental and dietary factors. Pathophysiology Several mechanisms underlie the development of hypertension. These mechanisms include sympathetic nervous system overactivity, renin–angiotensin excess, abnormal nephron number, genetic abnormalities, obesity, and endothelial abnormalities. The renin–angiotensin system is important in the development of hypertension (Figure 4.2). 5 The juxtaglomerular cells of the kidneys secrete renin. Renin works together with renin substrate to produce angiotensin I. Angiotensin-converting enzyme converts angiotensin I to angiotensin II. The biologic effect of angiotensin II is to directly produce vasoconstriction and to upregulate aldosterone synthesis. Aldosterone facilitates sodium retention. The combined effects of angiotensin II and aldosterone production lead to elevated blood pressure. Elevated blood pressure results in negative feedback on renin production by the juxtaglomerular cells. On the basis of this negative feedback loop, it would be expected that patients with essential hypertension would have low renin states. However, many of these patients may actually have elevated renin states. Several explanations for elevated renin have been suggested, including catecholamine mediated release of renin from the kidney. Patients with single or multiple genetic mutations may have abnormal enzymes or proteins, which alter either sodium and volume regulation in the kidney, sympathetic nervous system activity, or the vasculature. Reduced nephron number may be present in patients with low birth weight and prematurity. The reduced renal sodium excretion and decreased filtration surface of the kidney may predispose these patients to hypertension. Extrinsic and intrinsic stressors lead to sympathetic nervous overactivity. Activation of the sympathetic nervous system produces increased contractility of the ventricle and may lead to arterial and venous constriction. Elevated circulating catecholamine levels also lead to increased renin release. The association between hypertension and hyperinsulinemia is most pronounced in patients with truncal obesity. Patients who are obese or hypertensive may demonstrate augmented sympathetic Cardiology Core Curriculum 124 pressor activity and/or decreased vasodilatory response to insulin. These abnormalities may result in elevation of blood pressure in this patient population. Non-obese hypertensive persons may have abnormal vascular responses to circulating insulin. Increasing age is associated with the development of hypertension. This may be related to increased vascular stiffness that occurs with advancing age. Other growth factors and endothelial cell dysfunction may play a role in the control of blood pressure. Patients with high blood pressure may fail to synthesize sufficient nitric oxide, a substance that is important to the maintenance of vascular tone and smooth muscle cell relaxation. In addition, patients with hypertension have abnormal nitric oxide mediated vasodilatation. The absence of appropriate nitric oxide mediated vasodilatation may lead to abnormal vascular remodeling and promote vascular damage, predisposing the patient to atherosclerosis. Nitric oxide mediated forearm vasodilatation may be normalized by treatment with antihypertensive therapy. Endothelin and related factors produce vasoconstriction but have not been shown to have a role in human hypertension. Risk factors for the development of hypertension Genetic predisposition to hypertension is an extremely important risk factor for the development of hypertension. Although very few Hypertension 125 Renin substrate Renin J–G Angiotensin I converting enzyme Angiotensin II Vasoconstriction FEEDBACK BLOOD PRESSURE Sodium retention Aldosterone synthesis Figure 4.2 Renin–angiotensin system and its role in hypertension. J–G, renal juxtaglomerular cell. From Kaplan 5 [...]... 88/ 232 191 /34 7 147 /33 5 102/158 0·49 0·66 0·71 0·64 (0 39 –0·62) (0·55–0·78) (0·59–0·86) (0·50–0·82) 11 4 4 1 211 /33 1 215 /36 3 2 43/ 459 171/189 0·99 0·72 0· 93 0·90 6 /35 81/ 134 41/175 224 /38 2 514/7 13 3 83/ 700 34 9/419 0·88 0·90 0·95 0· 83 1·0 Treatment better Treatment worse 0·17 (0·07–0·41) 0·58 (0·44–0·76) 0·58 (0·40–0·84) 11 4 4 1 0·7 (0· 83 1·18) (0·61–0·85) (0·80–1·09) (0· 73 1·10) 9 3 2 0·4 (0·75–1· 03) ... β-Blockers β-Blockers, central α-agonists, reserpine β-Blockers, high dose diuretics β-Blockers (non-ISA), diuretics (high dose) ACE inhibitor (preferred), CCB Low dose diuretics α-Blockers β-Blockers (non-CS) Carvedilol, losartan potassium β-Blockers β-Blockers (non-CS), CCB (non-DHP) Diltiazem hydrochloride, verapamil hydrochloride Thiazides β-Blockers α-Blockers ACE inhibitor β-Blockers, CCB β-Blockers,... hydrochloride (G) Methyldopa (G) α-Blockers Doxazosin mesylate Prazosin hydrochloride (G) Terazosin hydrochloride β-Blockers Central α-agonists Drug Table 4.6 Continued 0·2–1·2 (2 3) 8 32 (2) 1 3 (1) 500 30 00 (2) Usual dose range, total mg/day (frequency/day) 1–16 (1) 2 30 (2 3) 1–20 (1) 200–800 (1) 25–100 (1–2) 5–20 (1) 2·5–10 (1) 2·5–10 (1) 50 30 0 (2) 50 30 0 (1) 40 32 0 (1) 10–20 (1) Catapres Wytensin... or resistant hypertension Thiazides and potassium-sparing agents 133 Cardiology Core Curriculum Outcome Drug Regimen Stroke Diuretics Diuretics β-Blockers HDFP Coronary heart Diuretics Diuretics β-Blockers HDFP Dose High Low High disease High Low High Congestive heart failure Diuretics High Diuretics Low β-Blockers Total mortality Diuretics Diuretics β-Blockers HDFP High Low High Number of trials Event,... doses or inappropriate combinations Coexisting use of non-steroidal anti-inflammatory agents, steroids, caffeine, cocaine, and various over 1 43 Cardiology Core Curriculum Lifestyle modifications Not at target blood pressure ( . 191 /34 7 0·66 (0·55–0·78) β-Blockers 4 147 /33 5 0·71 (0·59–0·86) HDFP High 1 102/158 0·64 (0·50–0·82) Coronary heart disease Diuretics High 11 211 /33 1 0·99 (0· 83 1·18) Diuretics Low 4 215 /36 3 0·72. 11 224 /38 2 0·88 (0·75–1· 03) Diuretics Low 4 514/7 13 0·90 (0·81–0·99) β-Blockers 4 38 3/700 0·95 (0·84–1·07) HDFP High 1 34 9/419 0· 83 (0·72–0·95) Treatment Treatment better worse Figure 4 .3 Influence. (0·61–0·85) β-Blockers 4 2 43/ 459 0· 93 (0·80–1·09) HDFP High 1 171/189 0·90 (0· 73 1·10) Congestive heart failure Diuretics High 9 6 /35 0·17 (0·07–0·41) Diuretics Low 3 81/ 134 0·58 (0·44–0·76) β-Blockers