Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction.

OBJECTIVES: We surveyed the literature to estimate prediction values for five common tests for risk of major arrhythmic events (MAEs) after myocardial infarction. We then determined feasibility of a staged risk stratification using combinations of noninvasive tests, reserving an electrophysiologic study (EPS) as the final test. BACKGROUND: Improved approaches are needed for identifying those patients at highest risk for subsequent MAE and candidates for implantable cardioverter-defibrillators. METHODS: We located 44 reports for which values of MAE incidence and predictive accuracy could be inferred: signal-averaged electrocardiography; heart rate variability; severe ventricular arrhythmia on ambulatory electrocardiography; left ventricular ejection fraction; and EPS. A meta-analysis of reports used receiver-operating characteristic curves to estimate mean values for sensitivity and specificity for each test and 95% confidence limits. We then simulated a clinical situation in which risk was estimated by combining tests in three stages. RESULTS: Test sensitivities ranged from 42.8% to 62.4%; specificities from 77.4% to 85.8%. A three-stage stratification yielded a low-risk group (80.0% with a two-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk) and an unstratified group (8.2% with an 8.9% risk equivalent to a two-year incidence of 7.9%). CONCLUSIONS: Sensitivities and specificities for the five tests were relatively similar. No one test was satisfactory alone for predicting risk. Combinations of tests in stages allowed us to stratify 91.8% of patients as either high-risk or low-risk. These data suggest that a large prospective study to develop a robust prediction model is feasible and desirable.

Dysrhythmia hazard after hospitalization for myocardial infarction: two ECG prognostic methods compared.

We retrieved reports of heart rate variability and signal-averaged electrocardiograms (SAECG) used to predict risk of a dysrhythmic event. From each report the number of cases with and without events was extracted to establish accurate values for true positive rate (tpr = sensitivity) and false positive rate (fpr = 1 minus specificity). For all the heart rate variability reports, these values were collected and tpr values were plotted versus fpr. The (fpr,tpr) data were summarized by a meta ROC graph using the method of Moses and Shapiro. A composite weighted mean value and 95% confidence interval were also derived. A summary meta-ROC curve for the SAECG reports was similarly obtained., Meta-ROC analysis of multiple reports better summarizes the performances of different prognostic methods and allows the effect of combining tests for a larger population to be simulated.

Cryosurgery for recurrent prostate cancer following radiation therapy.

Patients with prostate cancer are commonly treated medically or undergo radical prostatectomy and/or radiation therapy. Radiation therapy is usually selected for patients with local or regional disease and patients for whom traditional surgery has failed. The local recurrence of cancer in patients treated with radiation therapy presents a difficult challenge regarding the selection of further treatment options. A commonly applied treatment is salvage prostatectomy, but it can be difficult and complicated, with positive surgical margins occurring in as many as 50 percent of patients and with significant postoperative morbidity. Hormonal therapy, which is not curative, has served as an alternative to surgery in patients who have failed to respond to radiation therapy. Cryosurgery, the destruction of diseased tissue by freezing, is increasingly used both as a first-line therapy and as a second-line therapy (salvage therapy) in patients for whom radiation therapy has failed. Recent reports suggest that cryosurgery may be a useful alternative procedure for treating some of these patients with recurrent cancers. Outcomes of cryosurgery are improving through better instrumentation, surgical technique, and experience. The available data suggest that some patients with radioresistant cancer appear to benefit from the use of cryosurgery as a salvage therapy. Use of this technique has resulted in biochemical disease-free survival for varying periods of some patients who had recurrent prostate carcinoma following radiation therapy; however, morbidity remains high and relatively few patients have had adequate followup. Salvage cryosurgery prospective clinical trials are warranted and would help determine long-term survival benefits and make possible the comparison of cryotherapy patient survival rates with those of untreated biopsy-positive patients.

Signal-averaged electrocardiography.

Signal-averaged electrocardiography (SAECG) is a technique involving computerized analysis of segments of a standard surface electrocardiogram. It is used for detecting small electrical impulses, termed ventricular late potentials, that follow the QRS segment. They are embedded in the electrocardiogram but ordinarily obscured by skeletal muscle activity and other extraneous sources of "noise" encountered in recording a standard electrocardiogram. Ventricular late potentials in patients with cardiac abnormalities, especially coronary artery disease or following an acute myocardial infarction, are associated with an increased risk of ventricular tachyarrhythmias and sudden cardiac death. Proponents of SAECG claim that it can obviate the need for invasive techniques commonly used to identify high-risk patients for interventions that treat or prevent ventricular tachyarrhythmia and sudden death. No randomized clinical trials evaluating SAECG have been completed; data from an ongoing National Institutes of Health-sponsored clinical trial are expected to be available in 3-4 years. The current data on SAECG show relatively consistent high negative predictive values, poor positive predictive values, and variable sensitivity and specificity when the technique is used on patients with cardiomyopathy or following a myocardial infarction. The available evidence also indicates that combining SAECG with other tests of cardiac function is superior to using any single test for risk. The utility of SAECG alone as an indicator of risk remains to be proven. SAECG combined with other standard tests of risk has been demonstrated to have clinical utility in patients following an acute myocardial infarction. Other patient populations have not been conclusively shown to benefit from its use.

Lung-volume reduction surgery for end-stage chronic obstructive pulmonary disease.

Lung-volume reduction surgery (LVRS) has been proposed as a palliative treatment for selected patients with diffuse emphysema and end-stage chronic obstructive pulmonary disease who have failed conventional therapy. A number of surgical techniques have been used that are designed to reduce lung volume by surgical resection or laser plication. These techniques are designed to restore previous compromised lung elastic recoil so that expiratory airflow obstruction is reduced, respiratory mechanics are improved, and disabling dyspnea is relieved. Preliminary data derived from both published and unpublished information indicate some favorable short-term benefits. However, objective postoperative data are available for only a small proportion of patients, and long-term followup data are not available. In addition, these surgeries are associated with significant morbidity (and a 6 percent [approximate] surgical mortality) and prolonged hospital stays in a substantial percentage of patients. Patient selection criteria are heterogeneous and in flux, and controversy continues concerning the most appropriate surgical techniques for various categories of patients. The current data do not permit a logical and scientifically defensible conclusion regarding the risks and benefits of LVRS.

Autologous peripheral stem-cell transplantation.

Autologous peripheral stem-cell transplantation (APSCT) has been extensively applied to support cancer patients who have undergone high-dose chemotherapy (HDCT) and suffer from the effects of otherwise prolonged or irreversible myelosuppression. The APSCT process involves harvesting of autologous progenitor cells from a patient's circulating blood (via leukapheresis), cryopreservation of the cells, and subsequent intravenous infusion for bone marrow hematopoietic reconstitution (HR). Although pluripotent stem cells, capable of multilineage differentiation, cannot be distinguished by morphologic criteria, they can be characterized as being CD34+ cells capable of indefinite self-renewal in situ and long-term self-renewal in cell cultures. Bone marrow and peripheral blood are common sources of autologous progenitor cells. Current techniques to identify and separate CD34+ cells for use in APSCT have resulted in fewer tumor cells being infused than if unseparated peripheral stem cells (PSC) were transplanted, with no differences noted in HR. Chemotherapy- and cytokine-induced mobilization results in increases in progenitor cells, necessitating fewer phereses to harvest sufficient numbers of progenitor cells for engraftment. This assessment addresses the safety, efficacy, and cost-effectiveness of the use of PSC for HR and improving patient outcome, as well as the indications and criteria for patient selection for the use of APSCT. Available information from study panels, research centers, institutions, and government agencies is reviewed; randomized clinical tests (or lack thereof) are discussed; and comparisons are made between APSCT and autologous bone marrow transplantation (ABMT), an accepted therapy in treatment of some malignancies (e.g., leukemia and lymphoma). The author concludes that existing evidence indicates that PSC can provide satisfactory HR, and the rate of HR via PSC does not seem consistently different from that of ABMT. The clinical importance of HR continues to be secondary to the primary issue of the patient benefits of HDCT in terms of antitumor response, palliation, or survival.

Magnetic resonance angiography: vascular and flow imaging.

Magnetic resonance angiography (MRA) techniques are increasingly being used in addition to or in place of conventional x-ray angiography (CA) methods for studies of blood flow and blood vessel morphology. MRA has evolved from magnetic resonance imaging (MRI) techniques for noninvasive visualization of blood flow and vasculature. MRI, aided by computers, generates images (angiograms) created by the contrast of flowing blood and the surrounding tissues; the magnetically depolarized flowing blood contrasts with the magnetically saturated stationary tissues, resulting in a differential high-signal intensity. MRA signals are MRI signals encoded with spatial data achieved by Fourier and echoplanar imaging, projection reconstruction, and spiral scanning. MRA's vasculature "flow map" incorporates both anatomic and physiologic information. This publication explores the history, principles, techniques (including time-of-flight and phase-contrast imaging), clinical applications, and indications and contraindications of MRA use. In addition, data on particular areas of study such as the head and neck and cerebral, thoracic, abdominal, and peripheral vasculature are provided. Two-and three-dimensional MRA methods are discussed, and comparisons are made between MRA and CA. Recommendations from several health service agencies and institutions are provided. Drawbacks, e.g., generally poorer resolution compared with CA, and restrictions of MRA use are discussed. Corollary studies with standard MRI or CA methods are sometimes advisable, and MRA alone is not always sufficient for comprehensive analysis of blood flow and blood vessel vasculature. MRA techniques have been developing in response to the hazards and limitations of CA; MRA involves no exposure to ionizing radiation and generally has a shorter information accrual time compared with conventional scans, in addition to being noninvasive and circumventing the systemic reactions sometimes caused by contrast agents in CA. Another advantage to MRA use is that it can be conducted in an outpatient setting, and many restrictions that apply to CA do not apply to MRA techniques. MRA is useful in detecting aneurysms, occlusions, and stenoses and is especially important in cases in which the use of contrast agents presents high risk. MRA is a promising technology for accurate and noninvasive evaluation of blood flow and blood vessel morphology. Though it cannot at present be considered a standard technique, it is gaining wider acceptance, especially in diagnoses of patients whose condition contraindicates standard angiography.

Intermittent positive pressure breathing (IPPB) therapy.

IPPB uses a mechanical respirator to deliver a controlled pressure of a gas to assist in ventilation or expansion of the lungs, thereby providing an increased tidal volume for patients with a variety of pulmonary conditions. IPPB machines are also used for the delivery of aerosol medications. The early widespread application of IPPB has dramatically diminished in response to published reports of more recent clinical trials that either question its utility or document its futility in the prophylaxis or treatment of the numerous conditions for which it was commonly prescribed. The effects of IPPB are short-lived, lasting approximately 1 hour, and the long-term consequences have not been adequately evaluated. In no study has IPPB been shown to have unequivocal clinical effectiveness, in terms of morbidity, mortality, or lung function, when used either alone or in combination with other modalities. In general, IPPB is not thought to offer any advantage over simpler therapies in the treatment of COPD or asthma or in preventing or treating postoperative atelectasis. However, IPPB may be useful in the following circumstances: 1) in patients at risk of respiratory failure because of decreased respiratory function secondary to kyphoscoliosis or neuromuscular disorders; 2) in patients with acute severe bronchospasm or exacerbated COPD, who fail to respond to other standard therapy; and 3) in the management of atelectasis that has not improved with simpler therapy (e.g., IS, postural drainage, aerosol therapy).

Diagnosis and treatment of impotence.

Among the common procedures used in the diagnosis of impotence, neither nocturnal penile tumescence testing nor inhome monitoring devices designed to measure tumescence or rigidity is regarded as reliable for evaluating impotence. Plethysmography as a nonspecific test of vascular competence is increasingly being supplanted by Doppler ultrasound as a safe and effective diagnostic modality. Arteriography, cavernosography, and cavernosometry are established techniques for evaluating penile vasculature. Intracavernosal injection of smooth muscle relaxing drugs, endocrine assays, and electrophysiological testing are widely used for the diagnosis of impotence. Excluding implanted devices, and intracavernosal injections. Aortoiliac reconstruction, endarterectomy, or arterial dilatations are regarded as safe and effective for the treatment of proximal occlusive lesions, and venous leakage surgery is regarded as investigational. Intracavernosal injections are widely employed in clinical environments and for self-injection at home. However, this currently represents the use of FDA-approved drugs for an unlabeled indication. The use of external vacuum devices has achieved widespread use and is regarded as being safe and effective for the treatment of impotence.

Implantation of the automatic cardioverter-defibrillator.

The automatic implantable cardioverter-defibrillator (AICD) is an electronic device that can be implanted in patients identified as being at high risk for sudden cardiac death (SCD) due to ventricular tachycardia or fibrillation (VT/VF). This device continuously monitors heart rhythm, senses malignant arrhythmias, and aborts them by means of an electronic shock. A previous assessment of the AICD concluded that the device is safe and clinically effective in patients selected on the basis of the demonstration of inducibile Vt/VF during baseline electrophysiological study (EPS). Recent clinical experience and data have indicated that the risk of recurrent VT/VF or SCD in survivors of prior episodes is significant and unpredictable, and that inducibility at baseline EPS cannot reliably discriminate all patients who might be at either high or low risk, or responders to any therapy. Although optimal treatment for noninducible patients remains controversial, the AICD is no longer regarded as a treatment of last resort and is frequently applied as the treatment of choice in patients who are resuscitated from SCD, unassociated with a concurrent myocardial infarction, and in whom a sustained monomorphic ventricular tachycardia cannot be induced in the electrophysiological laboratory.

Carotid endarterectomy.

Carotid endarterectomy is a surgical procedure to remove atherosclerotic occlusions from the carotid artery. The surgery is usually performed in patients with transient ischemic attacks (TIAs), asymptomatic stenosis, or stroke in order to reduce stroke risk and increase cerebral blood flow. Complication rates vary widely among surgeons and hospitals, and numerous studies testing the efficacy of carotid endarterectomy and documenting its associated morbidity and mortality have produced conflicting or inconclusive results. No properly designed prospective clinical trial has convincingly demonstrated this surgery to be superior or inferior to nonoperative management for any subset of patients with carotid artery disease. There has been no definitive study concluding that patients with TIA benefit from carotid endarterectomy. The benefits for asymptomatic patients are even less clear. Among the alternative surgical and medical treatments advocated for occlusive carotid disease, none has clearly demonstrated superior therapeutic results. It is generally agreed that current ongoing prospective, randomized, controlled clinical trials are likely to provide the data required for determination of optimal therapy and better identify subsets of patients who are most likely to benefit from carotid endarterectomy. Until the results of these clinical trials become available, the proposed benefits of carotid endarterectomy must be regarded as indeterminate.

Protein A columns for the treatment of patients with idiopathic thrombocytopenic purpura and other indications.

ECI using protein A columns has been designed to selectively remove circulating CICs and IgG from the plasma of patients in whom these substances are associated with their disease. The use of protein A columns appears to be a reasonable alternative to plasmapheresis in many autoimmune disorders for which plasma exchange is indicated. Although preliminary evidence suggests efficacy of plasma exchange, there is a paucity of data indicating that ECI would indeed provide comparable efficacious results. Although the role of ECI using protein A columns for the treatment of ITP continues to be poorly defined, its use in urgent and life-threatening situations in both ITP and HUS appears reasonable. The results of any treatment for chronic refractory ITP continue to be unsatisfactory. However, favorable responses have been achieved using protein A columns, suggesting the need for further investigation. The role of ECI in the treatment of other disorders, including AIDS, TTP, and the treatment of malignancies, where clinical effects are transient, continues to be investigational. The true clinical response rates and duration of responses to ECI using protein A in treating any disorder requires definition in studies involving a larger number of patients with longer followup. The demonstration of the ultimate clinical value of this therapy will require clinical trials comparing its efficacy to other therapies. Although more serious reactions have been reported, toxicities associated with the use of protein A columns are generally transient and mild.

Thermography for indications other than breast lesions.

Thermography is the measurement of self-emanating infrared radiation revealing temperature variations at the body surface. The two commonly employed methods demonstrating such changes are telethermographic infrared detector/imagers and heat-sensitive cholesterolic liquid crystal systems. Both methods sense body temperature and demonstrate areas of differing heat emission by producing brightly colored patterns. Each color represents a specific temperature level. Interpretation of color patterns in dermatomes or other anatomic distributions are proposed as an aid in diagnosing and evaluating a vast array of diseases. Information obtained from the literature, responses to a Federal Register notice of this assessment, PHS agencies and medical specialty groups failed to support claims of efficacy of thermography as a useful diagnostic modality for non-breast indications. Rather, it suggested that thermography lacks sensitivity, specificity, or predictive value. Unassailable data are lacking to indicate that thermography provides a useful guide to monitor the effect of treatment of any disease entity. The evidence suggests that thermography may only confirm the presence of a temperature difference, that other procedures are needed to reach a specific diagnosis, and that thermography may add little to what physicians already know based on history, physical examination, and other studies.

Real-time cardiac monitors.

Real-time cardiac monitors (RTCMs) are portable computerized devices that use programmed algorithms to perform rapid, readily available online analysis and processing of electrocardiographic (ECG) data. RTCMs are primarily applied for long-term monitoring of ambulatory cardiac outpatients for the purpose of detecting transient abnormal ECG events. A wide variety of RTCM devices is available ranging from limited capacity intermittent recorders that store only selected ECG data, to 24-hour full-disclosure systems that provide ECG complex and to replay this data for subsequent review. Critics of RTCMs suggest that the best algorithms are imperfect and may lead to errors involving potentially lethal arrhythmias, while proponents argue that real-time cardiac monitoring is sufficiently reliable for clinical use. Available data suggest that the devices are safe and particularly with regard to detecting ventricular arrhythmias, clinically reliable. Currently available algorithms cannot analyze atrial fibrillation, pacemaker rhythms, isolated P-waves, junctional rhythms, and atrial ventricular blocks. The advantages and limitations of RTCMs are well described. Their use can be applied to provide satisfactory results in the diagnosis, prognosis, and therapeutic amangement of selected patients.

Cardiac output by electrical bioimpedance.

Continuous CO measurement by EB is a highly technical issue requiring expert opinion for evaluation. At present, the NIH, American Society of Anesthesiologists, and the American College of Cardiology consider continuous CO monitoring by EB to be investigational. However, EB has numerous advantages when compared with other presently available techniques. Consequently, advances may require that the OHTA conduct another assessment in the near future. The NIH suggested that the use of EB on a noncontinuous basis in selected patients to measure changes in CO (but not the absolute value of CO) is reasonable. If the use of EB on a continuous basis is contemplated, then studies should be conducted to determine the safety of long-term electrical input into the thorax. Electrical bioimpedance should not be used in patients with pacemakers and may be inappropriate in patients with regurgitant valvular heart disease, intracardiac shunts, arrhythmias, ventricular asynchrony, tachycardia, hypertension, significant airway obstruction, or in patients undergoing therapy such as atropinization, all of which may change the shape of the dZ/dt waveform.

Apheresis in the treatment of chronic relapsing polyneuropathy.

As a distinct inflammatory demyelinating disease, chronic relapsing polyneuropathy can be extremely debilitating and cause respiratory failure leading to death. The cause of the disorder is unknown, although evidence suggests that immune dysfunction plays some role in its pathogenesis. Conventional treatment using steroids and immunosuppressants has been reported both as effective and ineffective in controlling the course of the disease. The rationale for apheresis, as a nonspecific therapy, is related to the removal and/or dilution of circulating cytotoxic factors, and some patients have achieved dramatic and sometimes prolonged remissions from such treatments. Existing evidence from a large and growing number of case reports suggests that apheresis is a reasonable treatment for patients with severe or life-threatening symptoms which fail to respond to conventional therapy. However, convincing data of its efficacy is lacking and must await the results of appropriate randomized clinical trials.