Noninvasive techniques have assumed an increasingly important role in the management of patients with vascular disease. Both ultrasonic and plethysmographic instruments allow objective evaluation of vascular disorders by the measurement of segmental limb blood pressures, analysis of blood velocity disturbances, recording of digit or limb pulse waveforms, or imaging of vascular disease, with or without Doppler flow analysis or color-flow mapping. These techniques have been applied for screening asymptomatic individuals, diagnosis of symptomatic patients, monitoring of interventional or surgical procedures, and follow-up of the natural history or the efficacy of medical, interventional, or surgical therapy of vascular disease. This article reviews the clinical application of these modalities to patients with peripheral arterial disease and briefly discusses cost-effectiveness and potential abuses of noninvasive technology.

Treatment of complex cerebrovascular disorders, including intracranial aneurysms, carotid cavernous sinus fistulas, vertebral fistulas, arteriovenous malformations, atherosclerosis of brachiocephalic vessels, and arterial vasospasm, is being performed in selected cases by interventional neurovascular techniques. Recent advances in microballoon technology, permanent solidifying polymers, newer embolic agents, high-resolution digital subtraction angiography with road-mapping technique, and steerable micro-guide wires and catheters have greatly improved access in the distal intracranial circulation and markedly reduced the morbidity associated with these procedures. Interventional neuroradiology is emerging as an important adjunct to neurosurgery for selected cerebrovascular disorders.

The role of surgical revascularization in the management of patients with renal artery disease has changed in recent years. This has occurred due to the advent of percutaneous transluminal angioplasty as an effective method of treatment for certain patients, improved results of surgical revascularization in older patients with atherosclerosis, an enhanced appreciation of advanced atherosclerotic renal artery disease as a correctable cause of renal failure, and the development of more effective surgical techniques for patients with severe aortic atherosclerosis and branch renal artery disease. Surgical revascularization is currently the treatment of choice for patients with branch renal artery disease, ostial atherosclerotic renal artery disease, a renal artery aneurysm, and patients in whom renal percutaneous transluminal angioplasty has been unsuccessful. Excellent clinical results continue to be achieved with surgical revascularization in properly selected patients.

Nonoperative therapy includes conservative noninterventional modalities and the endovascular interventional modalities of percutaneous transluminal angioplasty and a variety of laser systems and atherectomy devices. The role and impact of all nonoperative treatments are considered in the perspectives of the natural history of lower-extremity arteriosclerosis and its present surgical (operative) treatment. Nonoperative treatments may replace and/or facilitate surgical treatment in operative candidates. Nonoperative methods may also justify treatment in patients who cannot or should not be subjected to surgery. Facts and opinions relating to these uses of nonoperative treatments are presented, and the qualifications and credentialing of individuals who should be treating patients with lower-extremity ischemia resulting from peripheral arteriosclerosis are discussed.

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)

The evidence that ETS increases risk of death from heart disease is similar to that which existed in 1986 when the US Surgeon General concluded that ETS caused lung cancer in healthy nonsmokers. There are 10 epidemiological studies, conducted in a variety of locations, that reflect about a 30% increase in risk of death from ischemic heart disease or myocardial infarction among nonsmokers living with smokers. The larger studies also demonstrate a significant dose-response effect, with greater exposure to ETS associated with greater risk of death from heart disease. These epidemiological studies are complemented by a variety of physiological and biochemical data that show that ETS adversely affects platelet function and damages arterial endothelium in a way that increases the risk of heart disease. Moreover, ETS, in realistic exposures, also exerts significant adverse effects on exercise capability of both healthy people and those with heart disease by reducing the body's ability to deliver and utilize oxygen. In animal experiments, ETS also depresses cellular respiration at the level of mitochondria. The polycyclic aromatic hydrocarbons in ETS also accelerate, and may initiate, the development of atherosclerotic plaque. Of note, the cardiovascular effects of ETS appear to be different in nonsmokers and smokers. Nonsmokers appear to be more sensitive to ETS than do smokers, perhaps because some of the affected physiological systems are sensitive to low doses of the compounds in ETS, then saturate, and also perhaps because of physiological adaptions smokers undergo as a result of long-term exposure to the toxins in cigarette smoke. In any event, these findings indicate that, for cardiovascular disease, it is incorrect to compute "cigarette equivalents" for passive exposure to ETS and then to extrapolate the effects of this exposure on nonsmokers from the effects of direct smoking on smokers. These results suggest that heart disease is an important consequence of exposure to ETS. The combination of epidemiological studies with demonstration of physiological changes with exposure to ETS, together with biochemical evidence that elements of ETS have significant adverse effects on the cardiovascular system, leads to the conclusion that ETS causes heart disease. This increase in risk translates into about 10 times as many deaths from ETS-induced heart disease as lung cancer; these deaths contribute greatly to the estimated 53,000 deaths annually from passive smoking. This toll makes passive smoking the third leading preventable cause of death in the United States today, behind active smoking and alcohol.

Although work on class III antiarrhythmics remains at an early stage, these agents still appear to possess greater efficacy and less proarrhythmia than conventional class I agents in those experimental arrhythmia models considered to be most representative of the clinical situation. Although prolongation of repolarization carries with its own tendency for pause-dependent arrhythmogenesis (i.e., torsade de pointes), available data suggest that this may be a function of nonspecificity in potassium channel block rather than a general characteristic of class III activity. The availability of new and more selective blockers of specific cardiac potassium channels under development as class III agents have already helped to clarify basic questions about the ionic mechanism of repolarization in the heart, and one hopes that a growing clinical data base will eventually determine the relative safety and efficacy of these agents in preventing symptomatic and life-threatening arrhythmias.

The evidence gained from both human and animal studies of chronic chagasic cardiomyopathy suggests that the disease occurs as a consequence of several discrete and progressive pathophysiological processes occurring after infection, the ultimate expression of which depends on a host of unidentified factors. Collectively, the infection-associated events compromise microvasculature function and result in hypoperfusion, with consequences indistinguishable from those observed in other, nonparasitological cardiomyopathic diseases secondary to hypoperfusion. Therefore, chronic chagasic cardiomyopathy may share similar pathophysiological abnormalities with other chronic congestive cardiomyopathic states.

With the limitations of currently available modalities for treating clinically important tachycardias, the role of implanted antitachycardia devices will continue to expand. The challenge of the future will not only involve continued technological advances but the socioeconomic impact of this efficacious but expensive mode of therapy in an era of increasing financial restraints. Further studies to definitively prove the efficacy of more widespread use of antitachycardia device therapy will be needed.

In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment.

Exercise trials in cardiology are often hindered by inconsistent approaches to exercise testing. These inconsistencies include the choice of exercise protocol, exercise end points, points of analysis, and absence or misuse of gas exchange data. Gas exchange techniques greatly enhance the accuracy with which cardiopulmonary function is assessed by exercise. Commonly used protocols are not always appropriate for all patients or all studies. Both cardiovascular disease and the exercise protocol can have an important impact on the relation between changes in work rate and oxygen uptake. Ramp protocols appear to offer the greatest promise for assessing cardiopulmonary function. Analyzing hemodynamic and gas exchange responses at several points submaximally, in addition to those at peak exercise, can add important information concerning the efficacy of a drug. A great deal of confusion continues to hinder the application of the gas exchange anaerobic threshold, and many of the commonly used testing end points are not reliable.