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InternalMed_Harrison. Metallic stents are also prone to stent thrombosis (1–3%), either acute (<24 h) or subacute (1–30 days), which can be ameliorated by greater attention to full initial stent deployment and the use of dual antiplatelet therapy (DAPT) (aspirin, plus a platelet P2Y12 receptor blocker [clopidogrel, prasugrel, or ticagrelor]). Late (30 days–1 year) and very late stent thromboses (>1 year) occur very infrequently with stents but are slightly more common with first-generation drug-eluting stents, necessitating DAPT for up to 1 year or longer. Use of the second-generation stents is associated with lower rates of late and very late stent thromboses, and shorter durations of DAPT may be possible. Premature discontinuation of DAPT, particularly in the first month after implantation, is associated with a significantly increased risk for stent thrombosis (threeto ninefold greater). Stent thrombosis results in death in 10–20% and myocardial infarction in 30–70% of patients. Elective surgery that


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InternalMed_Harrison. with a significantly increased risk for stent thrombosis (threeto ninefold greater). Stent thrombosis results in death in 10–20% and myocardial infarction in 30–70% of patients. Elective surgery that requires discontinuation of antiplatelet therapy after drug-eluting stent implantation should be postponed until after 6 months and preferably after 1 year, if at all possible.


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InternalMed_Harrison. Restenosis, or renarrowing of the dilated coronary stenosis, is the most common complication of angioplasty and occurs in 20–50% of patients with balloon angioplasty alone, 10–30% of patients with bare metal stents, and 5–15% of patients with drug-eluting stents within the first year. The fact that stent placement provides a larger acute luminal area than balloon angioplasty alone reduces the incidence of subsequent restenosis. Drug-eluting stents further reduce restenosis through a reduction in excessive neointimal growth over the stent. If restenosis does not occur, the long-term outcome is excellent (Fig. 296e-3). Clinical restenosis is recognized by recurrence of angina or symptoms within 9 months of the procedure. Less frequently, patients with restenosis can present with non-ST-segment elevation myocardial infarction (NSTEMI) (10%) or STEMI (2%) as well. Clinical restenosis requires confirmation of a significant stenosis at the site of the prior PCI. Target lesion


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InternalMed_Harrison. non-ST-segment elevation myocardial infarction (NSTEMI) (10%) or STEMI (2%) as well. Clinical restenosis requires confirmation of a significant stenosis at the site of the prior PCI. Target lesion revascularization (TLR) or target vessel revascularization (TVR) is defined as angiographic restenosis with repeat PCI or coronary artery bypass grafting (CABG). By angiography, the incidence of restenosis is significantly higher than clinical restenosis (TLR or TVR) because many patients have mild restenosis that does not result in a recurrence of symptoms. The management of clinical restenosis is usually to repeat the PCI with balloon dilatation and placement of a drug-eluting stent. Once a patient has had restenosis, the risk of a second restenosis is further increased. The risk factors for restenosis are diabetes, myocardial infarction, long lesions, small-diameter vessels, and suboptimal initial PCI result.


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InternalMed_Harrison. FIgUrE 296e-3 Long-term results from one of the first patients to receive a sirolimus-eluting stent from early Sao Paulo experience. (From: GW Stone, in D Baim [ed]: Cardiac Catheterization, Angiography and Intervention, 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2006; with permission.)


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InternalMed_Harrison. The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines extensively review the indications for PCI in patients with stable angina, unstable angina, NSTEMI, and STEMI and should be referred to for a comprehensive discussion of the indications. Briefly, the two principal indications for coronary revascularization in patients with chronic stable angina (Chap. 293) are (1) to improve anginal symptoms in patients who remain symptomatic despite adequate medical therapy and (2) to reduce mortality rates in patients with severe coronary disease. In patients with stable angina who are well controlled on medical therapy, studies such as the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials have shown that initial revascularization does not lead to better outcomes and can be safely delayed until symptoms worsen or evidence of severe ischemia on


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InternalMed_Harrison. Investigation 2 Diabetes (BARI 2D) trials have shown that initial revascularization does not lead to better outcomes and can be safely delayed until symptoms worsen or evidence of severe ischemia on noninvasive testing occurs. When revascularization is indicated, the choice of PCI or CABG depends on a number of clinical and anatomic factors (Fig. 296e-4). The Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial compared PCI with the paclitaxel drug-eluting stent to CABG in 1800 patients with three-vessel coronary disease or left main disease. The study found no difference in death or myocardial infarction at 1 year, but repeat revascularization was signifi-296e-3 cantly higher in the stent-treated group (13.5 vs. 5.9%), while stroke was significantly higher in the surgical group (2.2 vs. 0.6%). The primary endpoint of death, myocardial infarction, stroke, or revascularization was significantly better with CABG, particularly in those with the


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InternalMed_Harrison. higher in the surgical group (2.2 vs. 0.6%). The primary endpoint of death, myocardial infarction, stroke, or revascularization was significantly better with CABG, particularly in those with the most extensive coronary artery disease. The 3-year results confirm these findings. The Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial randomized 1900 patients with diabetes and multivessel disease and showed a significantly lower primary endpoint of death, myocardial infarction, or stroke with CABG than PCI. These studies support CABG for those with the most severe left main and three-vessel disease or those with diabetes. Lesser degrees of multivessel disease in patients with or without diabetes have an equal outcome with PCI.


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InternalMed_Harrison. The choice of PCI versus CABG is also related to the anticipated procedural success and complications of PCI and the risks of CABG. For PCI, the characteristics of the coronary anatomy are critically important. The location of the lesion in the vessel (proximal or distal), the degree of tortuosity, and the size of the vessel are considered. In addition, the Is there an increased risk for less favorable long-term outcome due to both stent thrombosis and restenosis concerns? Example: Diabetics with multivessel Yes disease, diffuse three vessel disease Is there a low risk for restenosis? Example: Large vessels, focal lesions Are there relative contraindications to DES? Example: • Medical noncompliance • Chronic oral anti-coagulation • Anticipated surgery • High risk for bleeding Consider BMSYesNoNo


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InternalMed_Harrison. FIgUrE 296e-4 In patients requiring revascularization, several factors need to be considered in choosing between bare metal stents, drug-eluting stents, or coronary artery bypass surgery. ACS, acute coronary syndrome; BMS, bare metal stent; CABG, coronary artery bypass grafting; DES, drug-eluting stent; IVUS, intravascular ultrasound; STEMI, ST-segment elevation myocardial infarction. (From AA Bavry, DL Bhatt: Circulation 116:696, 2007; with permission.)


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InternalMed_Harrison. PART 10 Disorders of the Cardiovascular System 296e-4 lesion characteristics, including the degree of the stenosis, the presence of calcium, lesion length, and presence of thrombus, are assessed. The most common reason to decide not to do PCI is that the lesion felt to be responsible for the patient’s symptoms is not treatable. This is most commonly due to the presence of a chronic total occlusion (>3 months in duration). In this setting, the historical success rate has been low (30–70%) and complications are more common. A lesion classification to characterize the likelihood of success or failure of PCI has been developed by the ACC/AHA. Lesions with the highest success are called type A lesions (such as proximal noncalcified subtotal lesions), and those with the lowest success or highest complication rate are type C lesions (such as chronic total occlusions). Intermediate lesions are classified as type B1 or B2 depending on the number of unfavorable characteristics. Approximately


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InternalMed_Harrison. complication rate are type C lesions (such as chronic total occlusions). Intermediate lesions are classified as type B1 or B2 depending on the number of unfavorable characteristics. Approximately 25–30% of patients will not be candidates for PCI due to unfavorable anatomy, whereas only 5% of CABG patients will not be candidates for surgery due to coronary anatomy. The primary reason for being considered inoperable with CABG is the presence of severe comorbidities such as advanced age, frailty, severe chronic obstructive pulmonary disease (COPD), or poor left ventricular function. Another consideration in choosing a revascularization strategy is the degree of revascularization. In patients with multivessel disease, bypass grafts can usually be placed to all vessels with significant steno-sis, whereas PCI may be able to treat only some of the lesions due to the presence of unfavorable anatomy. Assessment of the significance of intermediate lesions using fractional flow reserve (FFR)


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InternalMed_Harrison. whereas PCI may be able to treat only some of the lesions due to the presence of unfavorable anatomy. Assessment of the significance of intermediate lesions using fractional flow reserve (FFR) (Chap.


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InternalMed_Harrison. 272) can assist in determining which lesions should be revascularized. The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial showed a 30% reduction in adverse events when revascularization by PCI was restricted to those lesions that were hemodynamically significant (FFR ≤0.80) rather than when guided by angiography alone. Thus, complete revascularization of all functionally significant lesions should be favored and considered when choosing the optimal revascularization strategy. Given the multiple factors that need to be considered in choosing the best revascularization for an individual patient with multivessel disease, it is optimal to have a discussion among the cardiac surgeon, interventional cardiologist, and the physicians caring for the patient (so-called Heart Team) to properly weigh the choices.


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InternalMed_Harrison. Patients with acute coronary syndrome are at excess risk of short-and long-term mortality. Randomized clinical trials have shown that PCI is superior to intensive medical therapy in reducing mortality and myocardial infarction, with the benefit largely confined to those patients who are high risk. High-risk patients are defined as those with any one of the following: refractory ischemia, recurrent angina, positive cardiac-specific enzymes, new ST-segment depression, low ejection fraction, severe arrhythmias, or a recent PCI or CABG. PCI is preferred over surgical therapy in most high-risk patients with acute coronary syndromes unless they have severe multivessel disease or the culprit lesion responsible for the unstable presentation cannot be adequately treated. In STEMI, thrombolysis or PCI (primary PCI) are effective methods to restore coronary blood flow and salvage myocardium within the first 12 h after onset of chest pain. Because PCI is more effective in restoring flow than


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InternalMed_Harrison. or PCI (primary PCI) are effective methods to restore coronary blood flow and salvage myocardium within the first 12 h after onset of chest pain. Because PCI is more effective in restoring flow than thrombolysis, it is preferred if readily available. PCI is also performed following thrombolysis to facilitate adequate reperfusion or as a rescue procedure in those who do not achieve reperfusion from thrombolysis or in those who develop cardiogenic shock.


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InternalMed_Harrison. Interventional treatment for structural heart disease (adult congenital heart disease and valvular heart disease) is a significant and growing component of the field of interventional cardiology.


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InternalMed_Harrison. The most common adult congenital lesion to be treated with percutaneous techniques is closure of atrial septal defects (Chap. 282). The procedure is done as in a diagnostic right heart catheterization with the passage of a catheter up the femoral vein into the right atrium. With echo and fluoroscopic guidance, the size and location of the defect can be accurately defined, and closure is accomplished using one of several approved devices. All devices use a left atrial and right atrial wire mesh or covered disk that are pulled together to capture the atrial septum around the defect and seal it off. The Amplatzer Septal Occluder device (AGA Medical, Minneapolis, Minnesota) is the most commonly used in the United States. The success rate in selected patients is 85–95%, and the device complications are rare and include device embolization, infection, or erosion. Closure of patent foramen ovale (PFO) is done in a similar way. PFO closure may be considered in patients who have had recurrent


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InternalMed_Harrison. are rare and include device embolization, infection, or erosion. Closure of patent foramen ovale (PFO) is done in a similar way. PFO closure may be considered in patients who have had recurrent paradoxical stroke or transient ischemic attack (TIA) despite adequate medical therapy including anticoagulation or antiplatelet therapy. The benefit, however, has not been proven. The CLOSURE I trial randomized 909 patients with cryptogenic stroke or TIA who had a PFO. Closure did not reduce the primary endpoint of death within 30 days or death following a neurologic cause during 2 years of follow-up or stroke/TIA within 2 years. Other trials have confirmed these findings. The use in the treatment of migraine is under clinical investigation and is not an approved indication.


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InternalMed_Harrison. Similar devices can also be used to close patent ductus arteriosus and ventricular septal defects. Other congenital diseases that can be treated percutaneously include coarctation of the aorta, pulmonic stenosis, peripheral pulmonary stenosis, and other abnormal communications between the cardiac chambers or vessels.


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InternalMed_Harrison. The treatment of valvular heart disease is the most rapidly growing area in interventional cardiology. Until recently, the only available techniques were balloon valvuloplasty for the treatment of aortic, mitral, or pulmonic stenosis (Chap. 283). Mitral valvuloplasty is the preferred treatment for symptomatic patients with rheumatic mitral stenosis who have favorable anatomy. The outcome in these patients is equal to that of surgical commissurotomy. The success is highly related to the echocardiographic appearance of the valve. The most favorable setting is commissural fusion without calcification or subchordal fusion and the absence of significant mitral regurgitation. Access is obtained from the femoral vein using a transseptal technique in which a long metal catheter with a needle tip is advanced from the femoral vein through the right atrium and atrial septum at the level of the foramen ovale into the left atrium. A guidewire is advanced into the left ventricle, and a


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InternalMed_Harrison. needle tip is advanced from the femoral vein through the right atrium and atrial septum at the level of the foramen ovale into the left atrium. A guidewire is advanced into the left ventricle, and a balloon-dilatation catheter is negotiated across the mitral valve and inflated to a predetermined size to enlarge the valve. The most commonly used dilatation catheter is the Inoue balloon. The technique splits the commissural fusion and commonly results in a doubling of the mitral valve area. The success of the procedure in favorable anatomy is 95% and severe complications are rare (1–2%). The most common complications are tamponade due to puncture into the pericardium or the creation of severe mitral regurgitation.


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InternalMed_Harrison. For regurgitant valvular lesions, only severe mitral regurgitation can be effectively treated percutaneously using the MitraClip (Abbott, Abbott Park, Ill) device. The procedure involves the passage of a catheter into the left atrium using the transseptal technique. A special catheter with a metallic clip on the end is passed through the mitral valve and retracted to catch and clip together the mid portion of the anterior and posterior mitral valve leaflet. The clip creates a double opening in the mitral valve and thereby reduces mitral regurgitation similar to the surgical Alfieri repair. In the Endovascular Valve Edge-to-Edge Repair Study (EVEREST II) trial, the device was less effective than surgical repair or replacement but was shown to be safe. It is currently used for patients who are not good candidates for surgical repair, particularly when the regurgitation is due to functional causes.


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InternalMed_Harrison. Severe aortic stenosis can be treated with balloon valvuloplasty as well. In this setting, the valvuloplasty balloon catheter is placed retrograde across the aortic valve from the femoral artery and briefly inflated to stretch open the valve. The success is much less favorable, with only 50% achieving an aortic valve area of >1 cm2 and a restenosis rate of 25–50% after 6–12 months. This poor success rate has limited its use to patients who are not surgical candidates or as a bridge to surgery or transcatheter aortic valve replacement (TAVR). In this setting, the intermediate-term mortality rate of the procedure is high (10%). Repeat aortic valvuloplasty as a treatment for aortic valve restenosis has been reported.


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InternalMed_Harrison. Percutaneous aortic valve replacement (TAVR) has been shown to be an effective treatment for high-risk and inoperable patients with aortic stenosis. Currently, two valve models, the Edwards SAPIEN valve (Edwards Lifescience, Irvine, California) and the CoreValve ReValving system (Medtronic, Minneapolis, Minnesota) are available. In more than 10,000 cases worldwide, follow-up shows no evidence of restenosis or severe prosthetic valve dysfunction in the midterm. The CoreValve is self-expanding, while the Edwards valve is balloon expanded. The cannulas are large (14–22 French), and retrograde access via the femoral artery is most commonly chosen, if possible. In patients with peripheral artery disease, access via the subclavian artery or transapically through a surgical incision can be used. Following balloon valvuloplasty, the valve is positioned across the valve and deployed with postdeployment balloon inflation to ensure full contact with the aortic annulus. The success rate is


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InternalMed_Harrison. used. Following balloon valvuloplasty, the valve is positioned across the valve and deployed with postdeployment balloon inflation to ensure full contact with the aortic annulus. The success rate is 80–90%, and the 30-day mortality rate is 10–15%, not unexpectedly as only high-risk patients are undergoing the procedure currently. The Placement of Aortic Transcatheter Valve (PARTNER) randomized trial of the Edwards valve showed a 55% reduction in 1-year mortality and major adverse events in the extreme-risk group randomized to TAVR compared to medical therapy. In a separate randomized trial, high-risk patients had a similar outcome to surgical valve replacement at 1 year. As a result, this valve is approved for both high-risk and extreme-risk patients with severe aortic stenosis.


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InternalMed_Harrison. Pulmonic stenosis can also be effectively treated with balloon valvuloplasty and percutaneously replaced with the Melody stent (Medtronic). Tricuspid valve interventions remain experimental.


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InternalMed_Harrison. The use of percutaneous interventions to treat symptomatic patients with arterial obstruction in the carotid, renal, aortic, and peripheral vessels is also part of the field of interventional cardiology. Randomized clinical trial data already support the use of carotid stenting in patients at high risk of complications from carotid endarterectomy (Fig. 296e-5). Recent trials suggest similar outcomes with carotid stenting and carotid endarterectomy in patients at average risk, although depending on the patient’s risk for periprocedural stroke or myocardial infarction, one procedure may be preferred over the other. The success rate of peripheral artery interventional procedures has been improving, including for long segments of occlusive disease historically treated by peripheral bypass surgery (Fig. 296e-6). Peripheral intervention is increasingly part of the training of an interventional cardiologist, and most programs now require an additional year of training after the


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InternalMed_Harrison. bypass surgery (Fig. 296e-6). Peripheral intervention is increasingly part of the training of an interventional cardiologist, and most programs now require an additional year of training after the interventional cardiology training year. The techniques and outcomes are described in detail in the chapter on peripheral vascular disease (Chap. 302).


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InternalMed_Harrison. The use of circulatory support techniques is occasionally needed in order to safely perform PCI on hemodynamically unstable patients. It also can be useful in helping to stabilize patients before surgical interventions. The most commonly used device is the percutaneous intraaortic balloon pump developed in the early 1960s. A 7to 10-French, 25to 50-mL balloon catheter is placed retrograde from the femoral artery into the descending aorta between the aortic arch and the abdominal aortic bifurcation. It is connected to a helium gas inflation system that synchronizes the inflation to coincide with early diastole with deflation by mid-diastole. As a result, it increases early diastolic pressure, lowers systolic pressure, and lowers late diastolic pressure through displacement of blood from the descending aorta (counterpulsation). This results in an increase in coronary blood flow and a decrease in afterload. It is contraindicated in patients with aortic regurgitation, aortic dissection, or


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InternalMed_Harrison. descending aorta (counterpulsation). This results in an increase in coronary blood flow and a decrease in afterload. It is contraindicated in patients with aortic regurgitation, aortic dissection, or severe peripheral artery disease. The major complications are vascular and thrombotic. Intravenous heparin is given in order to reduce thrombotic complications.


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InternalMed_Harrison. Another potentially useful tool is the Impella device (Abiomed, Danvers, Massachusetts). The catheter is placed percutaneously from the femoral artery into the left ventricle. The catheter has a small microaxial pump at its tip that can pump up to 2.5–5 L/min from the left ventricle to the aorta. Other support devices include TandemHeart (CardiacAssist, Pittsburgh, Pennsylvania), which involves placement of a large 21-French catheter from the femoral vein through the right atrium into the left atrium using the transseptal technique and a catheter in the femoral artery. A centrifugal pump can deliver 5 L of blood per minute. It may be useful in patients in shock or with STEMI or very-high-risk PCI. Patients can also be placed on peripheral extracorporeal membrane oxygenation using large cannulas placed in the femoral artery and vein.


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InternalMed_Harrison. The treatment of deep vein thrombosis is intravenous anticoagulation, with placement of an inferior vena cava filter if recurrent pulmonary emboli occur. Postphlebitic syndrome is a serious condition due to chronic venous obstruction that can lead to chronic leg edema and venous ulcers. Preliminary studies suggest that mechanical treatments may have a role in treatment, and a large trial is ongoing.


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InternalMed_Harrison. Pulmonary emboli (PE) should be treated with fibrinolytic agents if massive and in some cases if submassive. Surgical pulmonary embolectomy is an option for the treatment of massive PE with hemodynamic instability in patients who have contraindications for systemic fibrinolysis or those in whom it has failed. Catheter-based therapies for submassive and massive PEs are still evolving, but studies have shown promise. The techniques employed include the use of aspiration of the clot with a large catheter (10 French), intraclot infusion of a thrombolytic agent followed by aspiration, ultrasound-assisted catheter-directed thrombolysis, and use of rheolytic thrombectomy. Success for these techniques has been reported to be 80–90%, with major complications occurring in 2–4% of patients.


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InternalMed_Harrison. The recent recognition of the importance of the renal sympathetic nerves in modulating blood pressure has led to a technique to selectively denervate renal sympathetic nerves in patients with refractory hypertension. The procedure involves applying low-power radiofrequency treatment via a catheter along the length of both renal arteries. In the randomized Symplicity HTN-2 trial,AB renal denervation significantly reduced blood FIgUrE 296e-5 An example of a high-risk patient who requires carotid revasculariza-pressure compared with medical therapy. The tion, but who is not a candidate for carotid endarterectomy. Carotid artery stenting Symplicity device (Medtronic) is approved in resulted in an excellent angiographic result. (From M Belkin, DL Bhatt: Circulation 119:2302, Europe, though the randomized and blinded U.S. 2009; with permission.) Symplicity HTN-3 trial showed no effect.


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InternalMed_Harrison. Interventional cardiology continues to expand its borders. Treatment for coronary artery disease, including complex anatomic subsets, continues to advance, encroaching on what has traditionally been treated by CABG. Technological advances such as drug-eluting stents, now already in their second generation, and manual thrombus aspiration devices are improving the A BC results of PCI. In particular, PCI has been shown to prevent future ischemic events in acute coronary syndromes. For patients with stable coronary disease, PCI has an important role in symptom alleviation. Treatment of peripheral and cerebrovascular disease has also benefited from the application of percutaneous techniques. Structural heart disease is increasingly being treated with percutaneous options, with a high likelihood that interventional approaches will compete with open-heart surgery in a significant proportion of cases in years to come.


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InternalMed_Harrison. FIgUrE 296e-6 Peripheral interventional procedures have become highly effective at treating anatomic lesions previously amenable only to bypass surgery. A. Complete occlusion of the left superficial femoral artery. B. Wire and catheter advanced into subintimal space. C. Intravascular ultrasound positioned in the subintimal space to guide retrograde wire placement through the occluded vessel. D. Balloon dilation of the occlusion. E. Stent placement with excellent angiographic result. (From A Al Mahameed, DL Bhatt: Cleve Clin J Med 73:S45, 2006; with permission.)


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InternalMed_Harrison. E. Stent placement with excellent angiographic result. (From A Al Mahameed, DL Bhatt: Cleve Clin J Med 73:S45, 2006; with permission.) Atlas of Percutaneous Revascularization Jane A. Leopold, Deepak L. Bhatt, David P. Faxon Percutaneous coronary intervention (PCI) is the most widely employed coronary revascularization procedure worldwide (Chap. 296e). It 297e is now applied to patients with stable angina; patients with acute coronary syndromes, including unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI); and as a primary treatment strategy in patients with ST-segment elevation myocardial infarction (STEMI). PCI is also applicable to patients with either single-vessel or multivessel disease.


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InternalMed_Harrison. In this chapter, the use of PCI will be illustrated in a variety of commonly encountered clinical and anatomic situations, such as chronic total occlusion of a coronary artery, bifurcation disease, acute STEMI, saphenous vein graft disease, left main coronary artery disease, multivessel disease, and stent thrombosis. In addition, the use of interventional techniques to treat structural heart disease will be shown, including closure of an atrial septal defect (ASD) and transcatheter aortic valve replacement (TAVR). CASE 1: CHRONIC TOTAL OCCLUSION (Videos 297e-1 to 297e-7) An 81-year-old male with angina, New York Heart Association (NYHA) class IV congestive heart failure and inferoapicoposterior ischemia on an exercise technetium-99m scan.


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InternalMed_Harrison. An 81-year-old male with angina, New York Heart Association (NYHA) class IV congestive heart failure and inferoapicoposterior ischemia on an exercise technetium-99m scan. Diagnostic cardiac catheterization revealed a left dominant system with a totally occluded left circumflex (LCx) artery. The distal LCx filled via collaterals from the left anterior descending (LAD) artery, indicating chronicity of the total occlusion. VIDEO 297e-1 Baseline left coronary angiogram shows an occluded LCx with left-to-left collaterals originating from LAD septal vessels. VIDEO 297e-2 Attempts to cross the total occlusion in the LCx using a hydrophilic wire and an antegrade approach were not successful with the wire tracking to the right of the trajectory.


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InternalMed_Harrison. VIDEO 297e-3 The LAD septal collateral is accessed with a guidewire 297e-1 that is directed toward the distal LCx to cross the total occlusion retrograde. VIDEO 297e-4 The total occlusion is crossed retrograde. The wire is snared in the guide, exteriorized, and used to provide antegrade access to the LCx. VIDEO 297e-5 Antegrade flow in the LCx is restored after balloon inflation. VIDEO 297e-6 Following stenting of the total occlusion, blood flow in the distal vessel is improved and a second significant stenosis is seen. VIDEO 297e-7 Final result after LCx stenting. Approximately 15–30% of all patients referred for cardiac catheterization will have a chronic total occlusion (CTO) of a coronary artery. CTO often leads to a surgical referral for complete revascularization. Incomplete revascularization due to an untreated CTO is associated with an increased mortality rate (hazard ratio = 1.36; 95% confidence interval [CI], 1.12–1.66, p <.05).


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InternalMed_Harrison. Incomplete revascularization due to an untreated CTO is associated with an increased mortality rate (hazard ratio = 1.36; 95% confidence interval [CI], 1.12–1.66, p <.05). Successful PCI of a CTO leads to a 3.8–8.4% absolute reduction in mortality, symptom relief, and improved left ventricular function. Newer techniques, such as the retrograde approach to crossing total occlusions, are useful when the antegrade approach fails or is not feasible and there are well-developed collateral vessels. (Case contributed with permission by Dr. Frederick G.P. Welt.) CASE 2: BIFURCATION STENTING (Fig. 297e-1; Videos 297e-8 to 297e-16) A 52-year-old male with an acute coronary syndrome and a troponin I = 0.18 (upper limit of normal, <0.04). Diagnostic cardiac catheterization showed single-vessel coronary artery disease with a significant stenosis in the mid-LAD and a bifurcation lesion involving a large diagonal branch.


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InternalMed_Harrison. Diagnostic cardiac catheterization showed single-vessel coronary artery disease with a significant stenosis in the mid-LAD and a bifurcation lesion involving a large diagonal branch. VIDEO 297e-8 Baseline angiogram of the left coronary circulation shows the significant stenosis in the mid-LAD and the bifurcation lesion involving a large diagonal branch. CHAPTER 297e Atlas of Percutaneous Revascularization


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InternalMed_Harrison. CHAPTER 297e Atlas of Percutaneous Revascularization FIGURE 297e-1 Schematic representation of one-stent and two-stent techniques to treat bifurcation lesions. PTCA, percutaneous transluminal coronary angioplasty 297e-2 VIDEO 297e-9 Both vessels are accessed with guidewires and pretreated with balloon angioplasty. VIDEO 297e-10 Result after balloon angioplasty. VIDEO 297e-11 Stent being positioned in the LAD. VIDEO 297e-12 LAD poststent result. VIDEO 297e-13 Stent deployed in the diagonal branch through the stent struts in the LAD using the “culotte” technique. VIDEO 297e-14 Diagonal branch poststent result. VIDEO 297e-15 Simultaneous inflation of two 2.5-mm “kissing” balloons. VIDEO 297e-16 Final postbifurcation stenting result. Approximately 15–20% of PCIs will involve the treatment of bifurcation lesions. Bifurcation lesions require consideration of PCI strategies that protect side-branch patency.


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InternalMed_Harrison. Approximately 15–20% of PCIs will involve the treatment of bifurcation lesions. Bifurcation lesions require consideration of PCI strategies that protect side-branch patency. There are both one-stent and two-stent techniques to treat bifurcation lesions; the selection of technique depends on anatomic considerations, including plaque burden, angle of side-branch take-off, plaque shift during angioplasty, and side-branch distribution. Rates of target lesion revascularization and stent thrombosis are similar between one-stent and two-stent procedures. CASE 3: INFERIOR MYOCARDIAL INFARCTION—THROMBUS AND MANUAL THROMBECTOMY PART 10 Disorders of the Cardiovascular System (Figs. 297e-2 to 297e-4; Videos 297e-17 to 297e-22) A 59-year-old male presented to the emergency room with 2 h of severe midsternal chest pressure. His systolic blood pressure was 100 mmHg, and he was tachycardic in sinus rhythm with a heart rate of 90–100 beats/min.


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InternalMed_Harrison. His systolic blood pressure was 100 mmHg, and he was tachycardic in sinus rhythm with a heart rate of 90–100 beats/min. His initial electrocardiogram (ECG) showed inferior ST-segment elevations with lateral ST-segment depressions. He was referred emergently to the cardiac catheterization laboratory for primary PCI. VIDEO 297e-17 The right coronary artery (RCA) is totally occluded with filling defects in the vessel after contrast injection, indicating thrombus is present in the vessel. VIDEO 297e-18 An angioplasty wire is threaded through the thrombotic lesion, but this does not restore blood flow to the distal vessel. VIDEO 297e-19 Result after manual thrombectomy and thrombus extraction. The “culprit” ruptured plaque and residual thrombus are now apparent in the vessel. FIGURE 297e-3 Example of an organized red thrombus retrieved by manual thrombectomy.


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InternalMed_Harrison. FIGURE 297e-3 Example of an organized red thrombus retrieved by manual thrombectomy. VIDEO 297e-20 After balloon angioplasty and stenting, thrombus is still present. VIDEO 297e-21 After repeat manual thrombectomy and expansion of the stent, the thrombus is no longer present. VIDEO 297e-22 Final result. An acute STEMI occurs following plaque rupture that promotes thrombotic occlusion of a coronary artery. Despite successful revascularization of the epicardial coronary artery, microemboli liberated during balloon angioplasty and stenting may lead to persistent microvascular dysfunction. When present, microvascular dysfunction is associated with a larger infarct size, heart failure, malignant ventricular arrhythmias, and death. Manual thrombectomy is used to aspirate or remove thrombus in the vessel and limit distal embolization during angioplasty and stenting. Manual thrombectomy in primary PCI is associated with improved myocardial perfusion and a reduction in mortality.


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InternalMed_Harrison. Manual thrombectomy in primary PCI is associated with improved myocardial perfusion and a reduction in mortality. Adjunctive antiplatelet and antithrombin agents are important to aid in the resolution of intracoronary thrombus. FIGURE 297e-2 Preprocedure ECG showing inferior ST-segment elevations and lateral ST-segment depressions. FIGURE 297e-4 Postprocedure ECG showing resolution of ST-segment elevations. FIGURE 297e-5 Distal protection device showing captured atherosclerotic debris liberated by initial balloon dilation. CASE 4: SAPHENOUS VEIN GRAFT INTERVENTION WITH DISTAL PROTECTION (Fig. 297e-5; Videos 297e-23 to 297e-26) A 62-year-old male with a history of chronic stable angina.


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InternalMed_Harrison. CASE 4: SAPHENOUS VEIN GRAFT INTERVENTION WITH DISTAL PROTECTION (Fig. 297e-5; Videos 297e-23 to 297e-26) A 62-year-old male with a history of chronic stable angina. A four-vessel coronary artery bypass grafting (CABG) surgery was performed 17 years earlier with a left internal mammary artery graft to the LAD, a right internal mammary artery graft to the right coronary artery (RCA), a saphenous vein graft to the first obtuse marginal branch, and a saphenous vein graft to the first diagonal branch. The patient had a recent increase in angina with exertion and was found to have lateral ischemia on an exercise technetium-99m scan. Diagnostic cardiac catheterization revealed a significant stenosis in the body of the saphenous vein graft to the first obtuse marginal branch.


InternalMed_Harrison

InternalMed_Harrison. Diagnostic cardiac catheterization revealed a significant stenosis in the body of the saphenous vein graft to the first obtuse marginal branch. VIDEO 297e-23 Saphenous vein graft to a first obtuse marginal branch with an 80% eccentric stenosis in the midgraft. VIDEO 297e-24 A distal protection device is deployed past the lesion. VIDEO 297e-25 Angioplasty balloon inflation with the distal protection device in place. VIDEO 297e-26 Final result after stent placement. Saphenous vein grafts have a failure rate of up to 20% after 1 year and as high as 50% by 5 years. Graft failure (after >1 month) results from intimal hyperplasia and atherosclerosis. Saphenous vein graft PCI is associated with distal embolization of 297e-3 atherosclerotic debris and microthrombi leading to microvascular occlusion, reduced antegrade blood flow (the “no-reflow” phenomenon), and myocardial infarction.


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InternalMed_Harrison. Embolic distal protection devices decrease the risk of distal embolization, as well as the incidence of no-reflow and myocardial infarction associated with saphenous vein graft interventions. CASE 5: UNPROTECTED LEFT MAIN PCI IN A HIGH-RISK PATIENT (Figs. 297e-6 and 297e-7; Videos 297e-27 to 297e-34) An 89-year-old woman presented with a NSTEMI associated with 5-mm ST-segment depression in the apical leads occurring 2 weeks after hospitalization for a NSTEMI that was treated conservatively. Chronic obstructive lung disease, elderly age, and the patient’s refusal to consider cardiac surgery restricted the choice of therapeutic options to medical and/or percutaneous interventions. Diagnostic catheterization revealed a left dominant circulation with a heavily calcified 80% distal left main coronary artery stenosis extending into the LAD and into the proximal LCx coronary arteries. A 70% proximal LAD lesion was also present.


InternalMed_Harrison

InternalMed_Harrison. After consultation with the patient, family, and a cardiac surgeon, PCI was performed with intraaortic balloon pump support and a temporary pacemaker in the right ventricle.


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InternalMed_Harrison. VIDEO 297e-27 Baseline left coronary artery injection in right anterior oblique (RAO) cranial projection shows a high-grade calcified stenosis in the left main coronary artery and a significant stenosis in the proximal LAD. VIDEO 297e-28 In the left anterior oblique (LAO) caudal view, the left main coronary artery lesion can be seen to extend into the ostia of both the LCx and the LAD. VIDEO 297e-29 Guidewires were placed into both the LCx and LAD. After the left main coronary artery and LCx are dilated with balloon angioplasty, the proximal LAD is dilated, and a long drug-eluting stent is placed to cover a lesion dissection that occurred with wiring of the vessel. VIDEO 297e-30 The bifurcation lesion in the left main coronary artery extending into the LCx and LAD ostia is treated using a “culotte” technique. First, a drug-eluting stent is placed in the left main coronary artery and into the proximal LCx. CHAPTER 297e Atlas of Percutaneous Revascularization


InternalMed_Harrison

InternalMed_Harrison. CHAPTER 297e Atlas of Percutaneous Revascularization FIGURE 297e-6 During chest pain, the ECG showed diffuse ST-segment depression of up to 5 mm in the inferior and lateral leads. PART 10 Disorders of the Cardiovascular System FIGURE 297e-7 Following resolution of the chest pain, the ST-segment depression is less marked. VIDEO 297e-31 Next, the LAD wire is removed and passed through the stent into the distal LAD. A second drug-eluting stent is deployed through the struts of the left main coronary artery/LCx stent. VIDEO 297e-32 Following rewiring of the LCx, both stents are re-dilated simultaneously (“kissing” balloons). VIDEO 297e-33 The final result in the LAO caudal view. VIDEO 297e-34 The final result in the RAO cranial view showing patent left main, LCx, and LAD coronary arteries. Left main coronary artery disease occurs in 5–10% of patients with symptomatic coronary artery disease.


InternalMed_Harrison

InternalMed_Harrison. Left main coronary artery disease occurs in 5–10% of patients with symptomatic coronary artery disease. In patients with left main coronary artery disease, revascularization with CABG has been shown to decrease mortality significantly over 5–10 years of follow-up. PCI with drug-eluting stents in selected cases has been shown to have equal in-hospital and 1-year death and myocardial infarction rates compared with CABG in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. Long-term outcome differences between the two treatment strategies are not known.


InternalMed_Harrison

InternalMed_Harrison. Indications for PCI of left main coronary artery lesions are high-risk surgical patients and patients with protected left main coronary artery disease (i.e., prior CABG with patent bypass grafts). Patients who are good candidates for bypass surgery may also undergo a stenting procedure, but discussion with the patient, the interventional cardiologist, and the cardiac surgeon should be undertaken to determine the best treatment option in an individual case. Outcomes are better for patients with an isolated lesion in the ostium and body of the left main coronary artery where a single stent can be placed compared to bifurcation lesions that involve the ostium of the LAD and LCx. CASE 6: MULTIVESSEL PCI IN A DIABETIC PATIENT (Videos 297e-35 to 297e-42) A 58-year-old man presented with a NSTEMI. The patient has hyperlipidemia and type 2 diabetes mellitus treated with oral hypoglycemic agents.


InternalMed_Harrison

InternalMed_Harrison. A 58-year-old man presented with a NSTEMI. The patient has hyperlipidemia and type 2 diabetes mellitus treated with oral hypoglycemic agents. Diagnostic catheterization revealed two-vessel disease with a total occlusion of the second obtuse marginal branch that was felt to be responsible for the patient’s symptoms (culprit lesion). In addition, there was a high-grade stenosis in a large ramus intermedius branch, and the RCA had a significant stenosis in the midsegment of the vessel.


InternalMed_Harrison

InternalMed_Harrison. VIDEO 297e-35 Baseline angiogram of the left coronary circulation in the RAO view shows the total occlusion of the second obtuse marginal branch with delayed retrograde filling via collateral vessels and a high-grade stenosis in the ramus intermedius. VIDEO 297e-36 A guidewire is passed through the total occlusion, and the lesion is pretreated with balloon angioplasty. VIDEO 297e-37 Following placement of a drug-eluting stent in the lesion, the vessel is widely patent. A third obtuse marginal vessel, not previously seen, now fills faintly (Thrombolysis in Myocardial Infarction [TIMI] grade 1 flow) with contrast but was not treated. VIDEO 297e-38 The ramus intermedius lesion was crossed with a guidewire and pretreated with balloon angioplasty. VIDEO 297e-39 A drug-eluting stent is placed across the ramus lesion and deployed. The final result shows no residual stenosis in either the ramus or second obtuse marginal vessels. VIDEO 297e-40 Baseline angiogram of the RCA shows a high-grade


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InternalMed_Harrison. across the ramus lesion and deployed. The final result shows no residual stenosis in either the ramus or second obtuse marginal vessels. VIDEO 297e-40 Baseline angiogram of the RCA shows a high-grade lesion in the midsegment of the vessel. VIDEO 297e-41 The lesion was pretreated with balloon dilation followed by stent deployment. VIDEO 297e-42 The final result shows no residual stenosis in the mid-RCA.


InternalMed_Harrison

InternalMed_Harrison. Multivessel PCI is performed commonly and may be done in one setting or staged with two or more procedures. Acute and long-term studies of multivessel PCI have shown comparable rates of death and myocardial infarction when compared to CABG, but a higher incidence of repeat revascularization as a result of restenosis is associated with PCI. In the randomized Bypass Angioplasty Revascularization Investigation (BARI) trial, diabetic patients treated with PCI had a worse long-term mortality than diabetic patients treated with CABG. However, the BARI registry found that in selected diabetic patients with favorable anatomy, PCI can result in outcomes equal to those observed with CABG. FIGURE 297e-8 Optical coherence tomography image following initial balloon dilation. Residual thrombus that is adherent to the stent struts is seen. CASE 7: VERY LATE STENT THROMBOSIS OF A PROXIMAL LAD DRUG-ELUTING STENT (Figs. 297e-8 and 297e-9; Videos 297e-43 to 297e-46)


InternalMed_Harrison

InternalMed_Harrison. CASE 7: VERY LATE STENT THROMBOSIS OF A PROXIMAL LAD DRUG-ELUTING STENT (Figs. 297e-8 and 297e-9; Videos 297e-43 to 297e-46) A 62-year-old male had a drug-eluting stent placed in a proximal LAD lesion to treat severe angina. He received dual antiplatelet therapy with aspirin and clopidogrel for 1 year and then discontinued clopidogrel per protocol. He remained asymptomatic until 15 months after the initial stent placement when he presented with severe chest pain due to an acute anterior STEMI. He was taken to the catheterization laboratory within 70 min of presentation, and his initial angiogram showed a total occlusion of the proximal LAD stent. VIDEO 297e-43 Baseline angiogram showing a total occlusion of the proximal LAD within the drug-eluting stent and a significant stenosis at the origin of the LCx.


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InternalMed_Harrison. VIDEO 297e-43 Baseline angiogram showing a total occlusion of the proximal LAD within the drug-eluting stent and a significant stenosis at the origin of the LCx. VIDEO 297e-44 The LAO view shows the LCx stenosis with a filling 297e-5 defect indicating that thrombus is present in the vessel lumen. VIDEO 297e-45 The LAD lesion was crossed with a guidewire, which resulted in slow filling of the mid-LAD (TIMI 2 flow) and revealed thrombus filling the stent. VIDEO 297e-46 The final result after LAD and LCx stenting. The LAD lesion was pretreated with balloon angioplasty, and a bare metal stent was deployed to cover the proximal lesion. The LCx ostial lesion was dilated with balloon angioplasty, and a bare metal stent was placed using a “V stenting” technique.


InternalMed_Harrison

InternalMed_Harrison. Stent thrombosis is an infrequent (1–2%) but serious complication of stent placement. It occurs most commonly within the first month, but rarely can occur as late as 1 year (0.2–0.6%) with bare metal stents. Very late stent thrombosis (VLST), which occurs after 1 year, is very rare with bare metal stents but can occur with drug-eluting stents. Premature discontinuation of dual antiplatelet therapy is the most common cause of early and late stent thrombosis; however, the etiology of VLST is not clear. The majority of patients with stent thrombosis present with acute coronary syndromes or STEMI; this presentation is associated with a high mortality rate (10%). Treatment is immediate PCI with balloon angioplasty or re-stenting. CASE 8: TRANSCATHETER AORTIC VALVE REPLACEMENT CHAPTER 297e Atlas of Percutaneous Revascularization (Figs. 297e-10 to 297e-14; Videos 297e-47 to 297e-50)


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InternalMed_Harrison. CASE 8: TRANSCATHETER AORTIC VALVE REPLACEMENT CHAPTER 297e Atlas of Percutaneous Revascularization (Figs. 297e-10 to 297e-14; Videos 297e-47 to 297e-50) A 75-year-old female with symptomatic aortic stenosis and a valve area of 0.58 cm2 by transthoracic echocardiogram. Chronic obstructive pulmonary disease (forced expiratory volume in 1 s [FEV1] = 0.54) and other comorbidities contributed to an unacceptably high cardiac surgical risk (calculated logistic Euroscore = 29.57%) for aortic valve replacement. She was referred for transcatheter aortic valve replacement (TAVR) as part of a clinical trial.


InternalMed_Harrison

InternalMed_Harrison. She was referred for transcatheter aortic valve replacement (TAVR) as part of a clinical trial. VIDEO 297e-47 Aortogram shows patent coronary arteries and minimal aortic insufficiency. VIDEO 297e-48 Balloon valvuloplasty is performed with rapid ventricular pacing at 180 beats/min. VIDEO 297e-49 A 26-mm Edwards SAPIEN valve is positioned using fluoroscopic and transesophageal echo guidance and deployed. VIDEO 297e-50 Aortogram after valve deployment shows a functional valve with mild aortic insufficiency and without impingement of the coronary ostia. FIGURE 297e-9 Pathologic specimen of late stent thrombosis obtained at autopsy. Thrombus is seen filling the LAD vessel lumen and extending into a diagonal branch (LD). Stent struts occupied the space denoted by the asterisk (*) (left). A magnified view of the vessel reveals thrombus around the stent strut and neointima formation (arrow) (right). Disorders of the Cardiovascular System


InternalMed_Harrison

InternalMed_Harrison. Disorders of the Cardiovascular System FIGURE 297e-10 Transesophageal echocardiogram shows a calcified trileaflet aortic valve (left) with reduced leaflet excursion and a narrowed orifice in peak systole (right). FIGURE 297e-11 Hemodynamically significant aortic (AO) steno-sis. Simultaneous recording of AO and left ventricle (LV) pressures shows an 82 mmHg peak-to-peak gradient and a 63.3 mmHg mean gradient between the LV (154/9 mmHg) and AO (72/29 mmHg) pres-sures. This is consistent with an aortic valve area of 0.58 cm2. FIGURE 297e-13 The Edwards SAPIEN transcatheter heart valve. (Reprinted with permission from A Zajarias, AG Cribier: J Am Coll Cardiol 53:1829, 2009.) FIGURE 297e-12 After balloon valvuloplasty, the LV-AO mean pres-sure gradient decreased to 37.3 mmHg, indicating that the aortic valve area increased to 0.95 cm2.


InternalMed_Harrison

InternalMed_Harrison. FIGURE 297e-12 After balloon valvuloplasty, the LV-AO mean pres-sure gradient decreased to 37.3 mmHg, indicating that the aortic valve area increased to 0.95 cm2. FIGURE 297e-14 Once the valve was deployed, the pressure gradi-ent between the LV and AO decreased to 11.6 mmHg, and the func-tional valve area is 1.34 cm2. The prevalence of calcific aortic stenosis is 2–3% in individuals age ≥75 years. Symptomatic aortic stenosis is associated with an average survival of 2–3 years and an increased risk of sudden death; aortic valve replacement improves both symptoms and survival. In high-risk patients with severe aortic stenosis who are not surgical candidates, 1and 5-year survival rates are ~62% and 38%, respectively. TAVR is approved in Europe and was recently approved in the United States as an alternative to surgical aortic valve replacement in high-risk patients. (Case contributed with permission by Dr. Andrew C. Eisenhauer.)


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InternalMed_Harrison. (Case contributed with permission by Dr. Andrew C. Eisenhauer.) CASE 9: ATRIAL SEPTAL DEFECT CLOSURE (Figs. 297e-15 to 297e-21; Videos 297e-51 to 297e-53) A 48-year-old female with increased shortness of breath, exercise intolerance, and an 18-mm secundum ASD. Echocardiogram showed a dilated right atrium (RA) and right ventricle (RV) with evidence of right ventricular volume overload.


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InternalMed_Harrison. Echocardiogram showed a dilated right atrium (RA) and right ventricle (RV) with evidence of right ventricular volume overload. FIGURE 297e-15 Anatomic location of common atrial septal defects (ASDs). The most common ASDs are the sinus venosus, ostium secundum, and ostium primum ASDs. The sinus venosus ASD is located at the junction of the superior vena cava (SVC) and the right atrium (RA). This ASD is often associated with anomalous drainage of the right-side pulmonary veins into the RA instead of the left atrium. The secundum ASD is located at the foramen ovale and allows blood to flow between the RA and the left atrium. The primum ASD, also known as an atrioventricular septal defect, connects the RA and right ventricle with the left atrium and ventricle. (Illustration by Justin E. Tribuna.) FIGURE 297e-17 Three-dimensional echocardiographic recon-struction of the secundum ASD. The ASD is round and has an acceptable margin of tissue to seat a septal occluder device.


InternalMed_Harrison

InternalMed_Harrison. FIGURE 297e-17 Three-dimensional echocardiographic recon-struction of the secundum ASD. The ASD is round and has an acceptable margin of tissue to seat a septal occluder device. CHAPTER 297e Atlas of Percutaneous Revascularization FIGURE 297e-18 ASD percutaneous closure devices. The Amplatzer® septal occluder (left) and the HELEX® septal occluder (right) are among the devices used for percutaneous closure of ASDs. The Amplatzer® septal occluder is a plug between two disks that are positioned on each side of the ASD to obstruct blood flow. The HELEX® Septal Occluder is positioned on each side of the ASD to allow circular rings covered with rapidly stretching polytetrafluoroethylene device to limit blood flow. The delivery catheters are detached and the devices are left in place. (Illustration by Justin E. Tribuna.)


InternalMed_Harrison

InternalMed_Harrison. FIGURE 297e-16 Transesophageal echocardiogram of a secundum ASD. The ASD is seen as “dropout” in the interatrial septum between the left atrium (LA) and RA (left). Doppler color flow imaging shows blue in the RA consistent with left-to-right flow (right). Disorders of the Cardiovascular System FIGURE 297e-19 Transesophageal echocardiogram showing sizing balloon (left) and no flow (right) across the atrial septal defect. FIGURE 297e-20 Amplatzer® septal occluder in place (left). There is no blood flow across the device (right). FIGURE 297e-21 Postprocedure lateral chest x-ray showing the Amplatzer® septal occluder in place. A shunt ratio (Qp/Qs) of 2.3:1 was determined at cardiac catheterization. Based on her symptoms, evidence of right-side chamber dilation, and a moderately sized ASD, the patient was referred for percutaneous closure of the ASD.


InternalMed_Harrison

InternalMed_Harrison. Based on her symptoms, evidence of right-side chamber dilation, and a moderately sized ASD, the patient was referred for percutaneous closure of the ASD. VIDEO 297e-51 A sizing balloon is placed across the ASD. VIDEO 297e-52 An Amplatzer® septal occluder is being positioned across the ASD. VIDEO 297e-53 The two disks of the device in place across the ASD. • Unrepaired ASDs lead to signs and symptoms of increased pulmonary blood flow and right heart failure, dyspnea, exercise intolerance, fatigue, palpitations and atrial arrhythmias, and pulmonary infections. Percutaneous closure of an ASD may be recommended for indi-297e-9 viduals with a secundum ASD and evidence of RA and RV enlargement with or without symptoms. Percutaneous closure is contraindicated in patients with irreversible pulmonary arterial hypertension and no left-to-right shunt. It is not recommended for closure of sinus venosus, coronary sinus, or primum ASDs.


InternalMed_Harrison

InternalMed_Harrison. After the atrial septal occluder device is placed, patients are treated with antiplatelet agents and use antibiotic prophylaxis for certain procedures for 6 months. Follow-up echocardiograms to assess for device migration or erosion, residual shunting, thrombus, or pericardial effusion are recommended at 1 day, 1 month, 6 months, 1 year, and periodically thereafter. (Case contributed with permission by Dr. Andrew C. Eisenhauer.) CHAPTER 297e Atlas of Percutaneous Revascularization


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InternalMed_Harrison. (Case contributed with permission by Dr. Andrew C. Eisenhauer.) CHAPTER 297e Atlas of Percutaneous Revascularization Hypertensive vascular Disease Theodore A. Kotchen Hypertension is one of the leading causes of the global burden of disease. Approximately 7.6 million deaths (13–15% of the total) and 92 million disability-adjusted life years worldwide were attributable to high blood pressure in 2001. Hypertension doubles the risk of cardio-298 vascular diseases, including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease. It often is associated with additional cardiovascular disease risk factors, and the risk of cardiovascular disease increases with the total burden of risk factors. Although anti-hypertensive therapy reduces the risks of cardiovascular and renal disease, large segments of the hypertensive population are either untreated or inadequately treated.


InternalMed_Harrison

InternalMed_Harrison. Blood pressure levels, the rate of age-related increases in blood pressure, and the prevalence of hypertension vary among countries and among subpopulations within a country. Hypertension is present in all populations except for a small number of individuals living in developing countries. In industrialized societies, blood pressure increases steadily during the first two decades of life. In children and adolescents, blood pressure is associated with growth and maturation. Blood pressure “tracks” over time in children and between adolescence and young adulthood. In the United States, average systolic blood pressure is higher for men than for women during early adulthood, although among older individuals the age-related rate of rise is steeper for women. Consequently, among individuals age 60 and older, systolic blood pressures of women are higher than those of men. Among adults, diastolic blood pressure also increases progressively with age until ~55 years, after which it tends to


InternalMed_Harrison

InternalMed_Harrison. age 60 and older, systolic blood pressures of women are higher than those of men. Among adults, diastolic blood pressure also increases progressively with age until ~55 years, after which it tends to decrease. The consequence is a widening of pulse pressure (the difference between systolic and diastolic blood pressure) beyond age 60.


InternalMed_Harrison

InternalMed_Harrison. 1612 In the United States, based on results of the National Health and Nutrition Examination Survey (NHANES), approximately 30% (ageadjusted prevalence) of adults, or at least 65 million individuals, have hypertension (defined as any one of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, taking antihypertensive medications). Hypertension prevalence is 33.5% in non-Hispanic blacks, 28.9% in non-Hispanic whites, and 20.7% in Mexican Americans. The likelihood of hypertension increases with age, and among individuals age ≥60, the prevalence is 65.4%. Recent evidence suggests that the prevalence of hypertension in the United States may be increasing, possibly as a consequence of increasing obesity. The prevalence of hypertension and stroke mortality rates are higher in the southeastern United States than in other regions. In African Americans, hypertension appears earlier, is generally more severe, and results in higher rates of morbidity and mortality


InternalMed_Harrison

InternalMed_Harrison. higher in the southeastern United States than in other regions. In African Americans, hypertension appears earlier, is generally more severe, and results in higher rates of morbidity and mortality from stroke, left ventricular hypertrophy, CHF, and end-stage renal disease (ESRD) than in white Americans. Both environmental and genetic factors may contribute to regional and racial variations in hypertension prevalence. Studies of societies undergoing “acculturation” and studies of migrants from a less to a more urbanized setting indicate a profound environmental contribution to blood pressure. Obesity and weight gain are strong, independent risk factors for hypertension. It has been estimated that 60% of hypertensives are >20% overweight. Among populations, hypertension prevalence is related to dietary NaCl intake, and the age-related increase in blood pressure may be augmented by a high NaCl intake. Low dietary intakes of calcium and potassium also may contribute to the risk of


InternalMed_Harrison

InternalMed_Harrison. related to dietary NaCl intake, and the age-related increase in blood pressure may be augmented by a high NaCl intake. Low dietary intakes of calcium and potassium also may contribute to the risk of hypertension. The urine sodium-to-potassium ratio (an index of both sodium and potassium intakes) is a stronger correlate of blood pressure than is either sodium or potassium alone. Alcohol consumption, psychosocial stress, and low levels of physical activity also may contribute to hypertension. Adoption, twin, and family studies document a significant heritable component to blood pressure levels and hypertension. Family studies controlling for a common environment indicate that blood pressure heritabilities are in the range 15–35%. In twin studies, heritability estimates of blood pressure are ~60% for males and 30–40% for females. High blood pressure before age 55 occurs 3.8 times more frequently among persons with a positive family history of hypertension. However, to date, only a


InternalMed_Harrison

InternalMed_Harrison. are ~60% for males and 30–40% for females. High blood pressure before age 55 occurs 3.8 times more frequently among persons with a positive family history of hypertension. However, to date, only a fraction of high heritability estimates are accounted for by specific genetic determinants.


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InternalMed_Harrison. Although specific genetic variants have been identified in rare Mendelian forms of hypertension (Table 298–5), these variants are not applicable to the vast majority (>98%) of patients with hypertension. For most individuals, it is likely that hypertension represents a polygenic disorder in which a combination of genes acts in concert with environmental exposures to make only a modest contribution to blood pressure. Further, different subsets of genes may lead to different phenotypes associated with hypertension, e.g., obesity, dyslipidemia, insulin resistance.


InternalMed_Harrison

InternalMed_Harrison. Several strategies are being used in the search for specific hypertension-related genes. Animal models (including selectively bred rats and congenic rat strains) provide a powerful approach for evaluating genetic loci and genes associated with hypertension. Comparative mapping strategies allow for the identification of syntenic genomic regions between the rat and human genomes that may be involved in blood pressure regulation. In association studies, different alleles (or combinations of alleles at different loci) of specific candidate genes or chromosomal regions are compared in hypertensive patients and normotensive control subjects. Current evidence suggests that genes that encode components of the renin-angiotensin-aldosterone system, along with angiotensinogen and angiotensin-converting enzyme (ACE) polymorphisms, may be related to hypertension and to blood pressure sensitivity to dietary NaCl. The alpha-adducin gene is thought to be associated with increased renal tubular


InternalMed_Harrison

InternalMed_Harrison. enzyme (ACE) polymorphisms, may be related to hypertension and to blood pressure sensitivity to dietary NaCl. The alpha-adducin gene is thought to be associated with increased renal tubular absorption of sodium, and variants of this gene may be associated with hypertension and salt sensitivity of blood pressure. Other genes possibly related to hypertension include genes encoding the AT1 receptor, aldosterone synthase, atrial natriuretic peptide, and the β2 adrenoreceptor. Genomewide association studies involve rapidly scanning markers across the entire genome to identify loci (not specific genes) associated with an observable trait (e.g., blood pressure) or a particular disease. This strategy has been facilitated by the availability of dense genotyping chips and the International HapMap. Results of candidate gene studies often have not been replicated, and in contrast to several other polygenic disorders, genomewide association studies have had limited success in identifying genetic


InternalMed_Harrison

InternalMed_Harrison. Results of candidate gene studies often have not been replicated, and in contrast to several other polygenic disorders, genomewide association studies have had limited success in identifying genetic determinants of hypertension.


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InternalMed_Harrison. Preliminary evidence suggests that there may also be genetic determinants of target organ damage attributed to hypertension. Family studies indicate significant heritability of left ventricular mass, and there is considerable individual variation in the responses of the heart to hypertension. Family studies and variations in candidate genes associated with renal damage suggest that genetic factors also may contribute to hypertensive nephropathy. Specific genetic variants have been linked to CHD and stroke. In the future, it is possible that DNA analysis will predict individual risk for hypertension and target organ damage and will identify responders to specific classes of antihypertensive agents. However, with the exception of the rare, monogenic hypertensive diseases, the genetic variants associated with hypertension remain to be confirmed, and the intermediate steps by which these variants affect blood pressure remain to be determined.


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InternalMed_Harrison. To provide a framework for understanding the pathogenesis of and treatment options for hypertensive disorders, it is useful to understand factors involved in the regulation of both normal and elevated arterial pressure. Cardiac output and peripheral resistance are the two determinants of arterial pressure (Fig. 298-1). Cardiac output is determined by stroke volume and heart rate; stroke volume is related to myocardial contractility and to the size of the vascular compartment. Peripheral resistance is determined by functional and anatomic changes in small arteries (lumen diameter 100–400 μm) and arterioles.


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InternalMed_Harrison. Sodium is predominantly an extracellular ion and is a primary determinant of the extracellular fluid volume. When NaCl intake exceeds the capacity of the kidney to excrete sodium, vascular volume may initially expand and cardiac output may increase. However, many vascular beds have the capacity to autoregulate blood flow, and if constant blood flow is to be maintained in the face of increased arterial pressure, resistance within that bed must increase, since


InternalMed_Harrison

InternalMed_Harrison. The initial elevation of blood pressure in response to vascular volume expansion may be related to an increase of cardiac output; however, over time, peripheral resistance increases and cardiac output reverts toward normal. Whether this hypothesized sequence of events occurs in the pathogenesis of hypertension is not clear. What is clear is that salt can activate a number of neural, endocrine/paracrine, and vascular mechanisms, all of which have the potential to increase arterial pressure. The effect of sodium on blood pressure is related to the provision of sodium with chloride; nonchloride salts of sodium have FIGURE 298-1 Determinants of arterial pressure.


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InternalMed_Harrison. FIGURE 298-1 Determinants of arterial pressure. little or no effect on blood pressure. As arterial pressure increases in response to a high NaCl intake, urinary sodium excretion increases and sodium balance is maintained at the expense of an increase in arterial pressure. The mechanism for this “pressure-natriuresis” phenomenon may involve a subtle increase in the glomerular filtration rate, decreased absorbing capacity of the renal tubules, and possibly hormonal factors such as atrial natriuretic factor. In individuals with an impaired capacity to excrete sodium, greater increases in arterial pressure are required to achieve natriuresis and sodium balance.


InternalMed_Harrison

InternalMed_Harrison. NaCl-dependent hypertension may be a consequence of a decreased capacity of the kidney to excrete sodium, due either to intrinsic renal disease or to increased production of a salt-retaining hormone (mineralocorticoid) resulting in increased renal tubular reabsorption of sodium. Renal tubular sodium reabsorption also may be augmented by increased neural activity to the kidney. In each of these situations, a higher arterial pressure may be required to achieve sodium balance. Conversely, salt-wasting disorders are associated with low blood pressure levels. ESRD is an extreme example of volume-dependent hypertension. In ~80% of these patients, vascular volume and hypertension can be controlled with adequate dialysis; in the other 20%, the mechanism of hypertension is related to increased activity of the reninangiotensin system and is likely to be responsive to pharmacologic blockade of renin-angiotensin.


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InternalMed_Harrison. Adrenergic reflexes modulate blood pressure over the short term, and adrenergic function, in concert with hormonal and volume-related factors, contributes to the long-term regulation of arterial pressure. Norepinephrine, epinephrine, and dopamine all play important roles in tonic and phasic cardiovascular regulation.


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InternalMed_Harrison. The activities of the adrenergic receptors are mediated by guanosine nucleotide-binding regulatory proteins (G proteins) and by intracellular concentrations of downstream second messengers. In addition to receptor affinity and density, physiologic responsiveness to catecholamines may be altered by the efficiency of receptor-effector coupling at a site “distal” to receptor binding. The receptor sites are relatively specific both for the transmitter substance and for the response that occupancy of the receptor site elicits. Based on their physiology and pharmacology, adrenergic receptors have been divided into two principal types: α and β. These types have been differentiated further into α1, α2, β1, and β2 receptors. Recent molecular cloning studies have identified several additional subtypes. α Receptors are occupied and activated more avidly by norepinephrine than by epinephrine, and the reverse is true for β receptors. α1 Receptors are located on postsynaptic cells in smooth muscle


InternalMed_Harrison

InternalMed_Harrison. α Receptors are occupied and activated more avidly by norepinephrine than by epinephrine, and the reverse is true for β receptors. α1 Receptors are located on postsynaptic cells in smooth muscle and elicit vasoconstriction. α2 Receptors are localized on presynaptic membranes of postganglionic nerve terminals that synthesize norepinephrine. When activated by catecholamines, α2 receptors act as negative feedback controllers, inhibiting further norepinephrine release. In the kidney, activation of α1-adrenergic receptors increases renal tubular reabsorption of sodium. Different classes of antihypertensive agents either inhibit α1 receptors or act as agonists of α2 receptors and reduce systemic sympathetic outflow. Activation of myocardial β1 receptors stimulates the rate and strength of cardiac contraction and consequently increases cardiac output. β1 Receptor activation also stimulates renin release from the kidney. Another class of antihypertensive agents acts by inhibiting β1


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InternalMed_Harrison. of cardiac contraction and consequently increases cardiac output. β1 Receptor activation also stimulates renin release from the kidney. Another class of antihypertensive agents acts by inhibiting β1 receptors. Activation of β2 receptors by epinephrine relaxes vascular smooth muscle and results in vasodilation.


InternalMed_Harrison

InternalMed_Harrison. Circulating catecholamine concentrations may affect the number of adrenoreceptors in various tissues. Downregulation of receptors may be a consequence of sustained high levels of catecholamines and provides an explanation for decreasing responsiveness, or tachyphylaxis, to catecholamines. For example, orthostatic hypotension frequently is observed in patients with pheochromocytoma, possibly due to the lack of norepinephrine-induced vasoconstriction with assumption of the upright posture. Conversely, with chronic reduction of neurotransmitter substances, adrenoreceptors may increase in number or be upregulated, resulting in increased responsiveness to the neurotransmitter. Chronic administration of agents that block adrenergic receptors may result in upregulation, and abrupt withdrawal of those agents may pro-1613 duce a condition of temporary hypersensitivity to sympathetic stimuli. For example, clonidine is an antihypertensive agent that is a centrally acting α2 agonist that inhibits


InternalMed_Harrison

InternalMed_Harrison. agents may pro-1613 duce a condition of temporary hypersensitivity to sympathetic stimuli. For example, clonidine is an antihypertensive agent that is a centrally acting α2 agonist that inhibits sympathetic outflow. Rebound hypertension may occur with the abrupt cessation of clonidine therapy, probably as a consequence of upregulation of α1 receptors.


InternalMed_Harrison

InternalMed_Harrison. Several reflexes modulate blood pressure on a minute-to-minute basis. One arterial baroreflex is mediated by stretch-sensitive sensory nerve endings in the carotid sinuses and the aortic arch. The rate of firing of these baroreceptors increases with arterial pressure, and the net effect is a decrease in sympathetic outflow, resulting in decreases in arterial pressure and heart rate. This is a primary mechanism for rapid buffering of acute fluctuations of arterial pressure that may occur during postural changes, behavioral or physiologic stress, and changes in blood volume. However, the activity of the baroreflex declines or adapts to sustained increases in arterial pressure such that the baroreceptors are reset to higher pressures. Patients with autonomic neuropathy and impaired baroreflex function may have extremely labile blood pressures with difficult-to-control episodic blood pressure spikes associated with tachycardia.


InternalMed_Harrison

InternalMed_Harrison. In both normal-weight and obese individuals, hypertension often is associated with increased sympathetic outflow. Based on recordings of postganglionic muscle nerve activity (detected by a microelectrode inserted in a peroneal nerve in the leg), sympathetic outflow tends to be higher in hypertensive than in normotensive individuals. Sympathetic outflow is increased in obesity-related hypertension and in hypertension associated with obstructive sleep apnea. Baroreceptor activation via electrical stimulation of carotid sinus afferent nerves lowers blood pressure in patients with “resistant” hypertension. Drugs that block the sympathetic nervous system are potent antihypertensive agents, indicating that the sympathetic nervous system plays a permissive, although not necessarily a causative, role in the maintenance of increased arterial pressure.


InternalMed_Harrison

InternalMed_Harrison. Pheochromocytoma is the most blatant example of hypertension related to increased catecholamine production, in this instance by a tumor. Blood pressure can be reduced by surgical excision of the tumor or by pharmacologic treatment with an α1 receptor antagonist or with an inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis.


InternalMed_Harrison

InternalMed_Harrison. The renin-angiotensin-aldosterone system contributes to the regulation of arterial pressure primarily via the vasoconstrictor properties of angiotensin II and the sodium-retaining properties of aldosterone. Renin is an aspartyl protease that is synthesized as an enzymatically inactive precursor, prorenin. Most renin in the circulation is synthesized in the renal afferent renal arteriole. Prorenin may be secreted directly into the circulation or may be activated within secretory cells and released as active renin. Although human plasma contains two to five times more prorenin than renin, there is no evidence that prorenin contributes to the physiologic activity of this system. There are three primary stimuli for renin secretion: (1) decreased NaCl transport in the distal portion of the thick ascending limb of the loop of Henle that abuts the corresponding afferent arteriole (macula densa), (2) decreased pressure or stretch within the renal afferent arteriole (baroreceptor mechanism),


InternalMed_Harrison

InternalMed_Harrison. ascending limb of the loop of Henle that abuts the corresponding afferent arteriole (macula densa), (2) decreased pressure or stretch within the renal afferent arteriole (baroreceptor mechanism), and (3) sympathetic nervous system stimulation of renin-secreting cells via β1 adrenoreceptors. Conversely, renin secretion is inhibited by increased NaCl transport in the thick ascending limb of the loop of Henle, by increased stretch within the renal afferent arteriole, and by β1 receptor blockade. In addition, angiotensin II directly inhibits renin secretion due to angiotensin II type 1 receptors on juxtaglomerular cells, and renin secretion increases in response to pharmacologic blockade of either ACE or angiotensin II receptors.


InternalMed_Harrison

InternalMed_Harrison. Once released into the circulation, active renin cleaves a substrate, angiotensinogen, to form an inactive decapeptide, angiotensin I (Fig. 298-2). A converting enzyme, located primarily but not exclusively in the pulmonary circulation, converts angiotensin I to the active octapeptide, angiotensin II, by releasing the C-terminal histidylleucine dipeptide. The same converting enzyme cleaves a number FIGURE 298-2 Renin-angiotensin-aldosterone axis. ACE, angiotensinconverting enzyme.


InternalMed_Harrison

InternalMed_Harrison. of other peptides, including and thereby inactivating the vasodilator bradykinin. Acting primarily through angiotensin II type 1 (AT1) receptors on cell membranes, angiotensin II is a potent pressor substance, the primary tropic factor for the secretion of aldosterone by the adrenal zona glomerulosa, and a potent mitogen that stimulates vascular smooth muscle cell and myocyte growth. Independent of its hemodynamic effects, angiotensin II may play a role in the pathogenesis of atherosclerosis through a direct cellular action on the vessel wall. The angiotensin II type 2 (AT2) receptor has the opposite functional effects of the AT1 receptor. The AT2 receptor induces vasodilation, sodium excretion, and inhibition of cell growth and matrix formation. Experimental evidence suggests that the AT2 receptor improves vascular remodeling by stimulating smooth muscle cell apoptosis and contributes to the regulation of glomerular filtration rate. AT1 receptor blockade induces an increase in AT2


InternalMed_Harrison

InternalMed_Harrison. AT2 receptor improves vascular remodeling by stimulating smooth muscle cell apoptosis and contributes to the regulation of glomerular filtration rate. AT1 receptor blockade induces an increase in AT2 receptor activity.


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InternalMed_Harrison. Renin-secreting tumors are clear examples of renin-dependent hypertension. In the kidney, these tumors include benign hemangiopericytomas of the juxtaglomerular apparatus and, infrequently, renal carcinomas, including Wilms’ tumors. Renin-producing carcinomas also have been described in lung, liver, pancreas, colon, and adrenals. In these instances, in addition to excision and/or ablation of the tumor, treatment of hypertension includes pharmacologic therapies targeted to inhibit angiotensin II production or action. Renovascular hypertension is another renin-mediated form of hypertension. Obstruction of the renal artery leads to decreased renal perfusion pressure, thereby stimulating renin secretion. Over time, possibly as a consequence of secondary renal damage, this form of hypertension may become less renin dependent.


InternalMed_Harrison

InternalMed_Harrison. Angiotensinogen, renin, and angiotensin II are also synthesized locally in many tissues, including the brain, pituitary, aorta, arteries, heart, adrenal glands, kidneys, adipocytes, leukocytes, ovaries, testes, uterus, spleen, and skin. Angiotensin II in tissues may be formed by the enzymatic activity of renin or by other proteases, e.g., tonin, chymase, and cathepsins. In addition to regulating local blood flow, tissue angiotensin II is a mitogen that stimulates growth and contributes to modeling and repair. Excess tissue angiotensin II may contribute to atherosclerosis, cardiac hypertrophy, and renal failure and consequently may be a target for pharmacologic therapy to prevent target organ damage.


InternalMed_Harrison

InternalMed_Harrison. Angiotensin II is the primary tropic factor regulating the synthesis and secretion of aldosterone by the zona glomerulosa of the adrenal cortex. Aldosterone synthesis is also dependent on potassium, and aldosterone secretion may be decreased in potassium-depleted individuals. Although acute elevations of adrenocorticotropic hormone (ACTH) levels also increase aldosterone secretion, ACTH is not an important tropic factor for the chronic regulation of aldosterone. Aldosterone is a potent mineralocorticoid that increases sodium reabsorption by amiloride-sensitive epithelial sodium channels (ENaC) on the apical surface of the principal cells of the renal cortical collecting duct (Chap. 332e). Electric neutrality is maintained by exchanging sodium for potassium and hydrogen ions. Consequently, increased aldosterone secretion may result in hypokalemia and alkalosis.


InternalMed_Harrison

InternalMed_Harrison. Cortisol also binds to the mineralocorticoid receptor but normally functions as a less potent mineralocorticoid than aldosterone because cortisol is converted to cortisone by the enzyme 11 β-hydroxysteroid dehydrogenase type 2. Cortisone has no affinity for the mineralocorticoid receptor. Primary aldosteronism is a compelling example of mineralocorticoid-mediated hypertension. In this disorder, adrenal aldosterone synthesis and release are independent of renin-angiotensin, and renin release is suppressed by the resulting volume expansion.


InternalMed_Harrison

InternalMed_Harrison. Mineralocorticoid receptors are expressed in a number of tissues in addition to the kidney, and mineralocorticoid receptor activation induces structural and functional alterations in the heart, kidney, and blood vessels, leading to myocardial fibrosis, nephrosclerosis, and vascular inflammation and remodeling, perhaps as a consequence of oxidative stress. These effects are amplified by a high salt intake. In animal models, high circulating aldosterone levels stimulate cardiac fibrosis and left ventricular hypertrophy, and spironolactone (an aldosterone antagonist) prevents aldosterone-induced myocardial fibrosis. Pathologic patterns of left ventricular geometry also have been associated with elevations of plasma aldosterone concentration in hypertensive patients. In patients with CHF, low-dose spironolactone reduces the risk of progressive heart failure and sudden death from cardiac causes by 30%. Due to a renal hemodynamic effect, in patients with primary aldosteronism, high


InternalMed_Harrison

InternalMed_Harrison. CHF, low-dose spironolactone reduces the risk of progressive heart failure and sudden death from cardiac causes by 30%. Due to a renal hemodynamic effect, in patients with primary aldosteronism, high circulating levels of aldosterone also may cause glomerular hyperfiltration and albuminuria. These renal effects are reversible after removal of the effects of excess aldosterone by adrenalectomy or spironolactone.


InternalMed_Harrison

InternalMed_Harrison. Increased activity of the renin-angiotensin-aldosterone axis is not invariably associated with hypertension. In response to a low-NaCl diet or to volume contraction, arterial pressure and volume homeostasis may be maintained by increased activity of the renin-angiotensinaldosterone axis. Secondary aldosteronism (i.e., increased aldosterone secondary to increased renin-angiotensin), but not hypertension, also is observed in edematous states such as CHF and liver disease.


InternalMed_Harrison

InternalMed_Harrison. Vascular radius and compliance of resistance arteries are important determinants of arterial pressure. Resistance to flow varies inversely with the fourth power of the radius, and consequently, small decreases in lumen size significantly increase resistance. In hypertensive patients, structural, mechanical, or functional changes may reduce the lumen diameter of small arteries and arterioles. Remodeling refers to geometric alterations in the vessel wall without a change in vessel volume. Hypertrophic (increased cell size, and increased deposition of intercellular matrix) or eutrophic vascular remodeling results in decreased lumen size and, hence, increased peripheral resistance. Apoptosis, low-grade inflammation, and vascular fibrosis also contribute to remodeling. Lumen diameter also is related to elasticity of the vessel. Vessels with a high degree of elasticity can accommodate an increase of volume with relatively little change in pressure, whereas in a semirigid vascular system, a


InternalMed_Harrison

InternalMed_Harrison. to elasticity of the vessel. Vessels with a high degree of elasticity can accommodate an increase of volume with relatively little change in pressure, whereas in a semirigid vascular system, a small increment in volume induces a relatively large increment of pressure.


InternalMed_Harrison

InternalMed_Harrison. Hypertensive patients may have stiffer arteries due to arteriosclerosis, and high systolic blood pressures and wide pulse pressures are a consequence of decreased vascular compliance. Due to arterial stiffness, central blood pressures (aortic, carotid) may not correspond to brachial artery pressures. Ejection of blood into the aorta elicits a pressure wave that is propagated at a given velocity. The forward travelling wave generates a reflected wave that travels backward toward the ascending aorta. Although mean arterial pressure is determined by cardiac output and peripheral resistance, pulse pressure is related to the functional properties of large arteries and the amplitude and timing of the incident and reflected waves. Increased arterial stiffness results in increased pulse wave velocity of both incident and reflected waves. Due to the timing of these waves, the consequence is augmentation of aortic systolic pressure and a reduction of aortic diastolic pressure, i.e., an increase


InternalMed_Harrison

InternalMed_Harrison. of both incident and reflected waves. Due to the timing of these waves, the consequence is augmentation of aortic systolic pressure and a reduction of aortic diastolic pressure, i.e., an increase in pulse pressure. The aortic augmentation index, an index of arterial stiffening, is calculated as the ratio of central arterial pressure-to-pulse pressure. Central blood pressure may be measured directly by placing a sensor in the aorta or noninvasively by radial tonometry using commercially available devices. Central blood pressure and the aortic augmentation index are strong, independent predictors of cardiovascular disease and all-cause mortality.


InternalMed_Harrison

InternalMed_Harrison. Ion transport by vascular smooth muscle cells may contribute to hypertension-associated abnormalities of vascular tone and vascular growth, both of which are modulated by intracellular pH (pHi). Three ion transport mechanisms participate in the regulation of pHi:


InternalMed_Harrison

InternalMed_Harrison. Na+-H+ exchange, (2) Na+-dependent HCO3−-Cl− exchange, and cation-independent HCO3−-Cl− exchange. Based on measurements in cell types that are more accessible than vascular smooth muscle (e.g., leukocytes, erythrocytes, platelets, skeletal muscle), activity of the Na+-H+ exchanger is increased in hypertension, and this may result in increased vascular tone by two mechanisms. First, increased sodium entry may lead to increased vascular tone by activating Na+-Ca2+ exchange and thereby increasing intracellular calcium. Second, increased pHi enhances calcium sensitivity of the contractile apparatus, leading to an increase in contractility for a given intracellular calcium concentration. Additionally, increased Na+-H+ exchange may stimulate growth of vascular smooth muscle cells by enhancing sensitivity to mitogens.


InternalMed_Harrison

InternalMed_Harrison. Vascular endothelial function also modulates vascular tone. The vascular endothelium synthesizes and releases several vasoactive substances, including nitric oxide, a potent vasodilator. Endotheliumdependent vasodilation is impaired in hypertensive patients. This impairment often is assessed with high-resolution ultrasonography before and after the hyperemic phase of reperfusion that follows 5 minutes of forearm ischemia. Alternatively, endothelium-dependent vasodilation may be assessed in response to an intra-arterially infused endothelium-dependent vasodilator, e.g., acetylcholine. Endothelin is a vasoconstrictor peptide produced by the endothelium, and orally active endothelin antagonists may lower blood pressure in patients with resistant hypertension.


InternalMed_Harrison

InternalMed_Harrison. Currently, it is not known if the hypertension-related vascular abnormalities of ion transport and endothelial function are primary alterations or secondary consequences of elevated arterial pressure. Limited evidence suggests that vascular compliance and endotheliumdependent vasodilation may be improved by aerobic exercise, weight loss, and antihypertensive agents. It remains to be determined whether these interventions affect arterial structure and stiffness via a blood pressure–independent mechanism and whether different classes of antihypertensive agents preferentially affect vascular structure and function. Hypertension is an independent predisposing factor for heart failure, coronary artery disease, stroke, renal disease, and peripheral arterial disease (PAD).


InternalMed_Harrison

InternalMed_Harrison. Hypertension is an independent predisposing factor for heart failure, coronary artery disease, stroke, renal disease, and peripheral arterial disease (PAD). Heart disease is the most common cause of death in hypertensive patients. Hypertensive heart disease is the result of structural and functional adaptations leading to left ventricular hypertrophy, CHF, abnormalities of blood flow due to atherosclerotic coronary artery disease and microvascular disease, and cardiac arrhythmias. Individuals with left ventricular hypertrophy are at increased risk for CHD, stroke, CHF, and sudden death. Aggressive control of hypertension can regress or reverse left ventricular hypertrophy and reduce the risk of cardiovascular disease. It is not clear whether different 1615 classes of antihypertensive agents have an added impact on reducing left ventricular mass, independent of their blood pressure–lowering effect.


InternalMed_Harrison

InternalMed_Harrison. CHF may be related to systolic dysfunction, diastolic dysfunction, or a combination of the two. Abnormalities of diastolic function that range from asymptomatic heart disease to overt heart failure are common in hypertensive patients. Approximately one-third of patients with CHF have normal systolic function but abnormal diastolic function. Diastolic dysfunction is an early consequence of hypertension- related heart disease and is exacerbated by left ventricular hypertrophy and ischemia. Cardiac catheterization provides the most accurate assessment of diastolic function. Alternatively, diastolic function can be evaluated by several noninvasive methods, including echocardiography and radionuclide angiography.


InternalMed_Harrison

InternalMed_Harrison. Stroke is the second most frequent cause of death in the world; it accounts for 5 million deaths each year, with an additional 15 million persons having nonfatal strokes. Elevated blood pressure is the strongest risk factor for stroke. Approximately 85% of strokes are due to infarction, and the remainder are due to either intracerebral or subarachnoid hemorrhage. The incidence of stroke rises progressively with increasing blood pressure levels, particularly systolic blood pressure in individuals >65 years. Treatment of hypertension decreases the incidence of both ischemic and hemorrhagic strokes.


InternalMed_Harrison

InternalMed_Harrison. Hypertension also is associated with impaired cognition in an aging population, and longitudinal studies support an association between midlife hypertension and late-life cognitive decline. Hypertension-related cognitive impairment and dementia may be a consequence of a single infarct due to occlusion of a “strategic” larger vessel or multiple lacunar infarcts due to occlusive small vessel disease resulting in subcortical white matter ischemia. Several clinical trials suggest that antihypertensive therapy has a beneficial effect on cognitive function, although this remains an active area of investigation.


InternalMed_Harrison

InternalMed_Harrison. Cerebral blood flow remains unchanged over a wide range of arterial pressures (mean arterial pressure of 50–150 mmHg) through a process termed autoregulation of blood flow. In patients with the clinical syndrome of malignant hypertension, encephalopathy is related to failure of autoregulation of cerebral blood flow at the upper pressure limit, resulting in vasodilation and hyperperfusion. Signs and symptoms of hypertensive encephalopathy may include severe headache, nausea and vomiting (often of a projectile nature), focal neurologic signs, and alterations in mental status. Untreated, hypertensive encephalopathy may progress to stupor, coma, seizures, and death within hours. It is important to distinguish hypertensive encephalopathy from other neurologic syndromes that may be associated with hypertension, e.g., cerebral ischemia, hemorrhagic or thrombotic stroke, seizure disorder, mass lesions, pseudotumor cerebri, delirium tremens, meningitis, acute intermittent porphyria, traumatic


InternalMed_Harrison

InternalMed_Harrison. hypertension, e.g., cerebral ischemia, hemorrhagic or thrombotic stroke, seizure disorder, mass lesions, pseudotumor cerebri, delirium tremens, meningitis, acute intermittent porphyria, traumatic or chemical injury to the brain, and uremic encephalopathy.


InternalMed_Harrison

InternalMed_Harrison. The kidney is both a target and a cause of hypertension. Primary renal disease is the most common etiology of secondary hypertension. Mechanisms of kidney-related hypertension include a diminished capacity to excrete sodium, excessive renin secretion in relation to volume status, and sympathetic nervous system overactivity. Conversely, hypertension is a risk factor for renal injury and ESRD. The increased risk associated with high blood pressure is graded, continuous, and present throughout the distribution of blood pressure above optimal pressure. Renal risk appears to be more closely related to systolic than to diastolic blood pressure, and black men are at greater risk than white men for developing ESRD at every level of blood pressure.


InternalMed_Harrison

InternalMed_Harrison. Atherosclerotic, hypertension-related vascular lesions in the kidney primarily affect preglomerular arterioles, resulting in ischemic changes in the glomeruli and postglomerular structures. Glomerular injury also may be a consequence of direct damage to the glomerular capillaries due to glomerular hyperperfusion. Studies of hypertension-related 1616 renal damage, primarily in experimental animals, suggest that loss of autoregulation of renal blood flow at the afferent arteriole results in transmission of elevated pressures to an unprotected glomerulus with ensuing hyperfiltration, hypertrophy, and eventual focal segmental glomerular sclerosis. With progressive renal injury there is a loss of autoregulation of renal blood flow and glomerular filtration rate, resulting in a lower blood pressure threshold for renal damage and a steeper slope between blood pressure and renal damage. The result may be a vicious cycle of renal damage and nephron loss leading to more severe hypertension,