Skip to main content
Volume 4, Supplement 3, 2003

Volume 4, Supplement 3, 2003

Table of Contents

Beyond Serum Creatinine: Defining the Patient with Renal Insufficiency and Why?
Chronic kidney disease is the most important factor in predicting adverse short- and long-term outcomes after percutaneous coronary intervention. Most studies of cardiovascular outcomes have found that a break point for the development of radiocontrast nephropathy (RCN), later restenosis, recurrent myocardial infarction, congestive heart failure, and cardiovascular death, occurs below an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2, which roughly corresponds to a serum creatinine (Cr) of > 1.5 mg/dL in the general population. Renal dysfunction is accurately recognized by calculating the eGFR from the age, serum creatinine, gender, race, and weight, and not from the serum creatinine alone. The pathogenesis of RCN goes beyond serum Cr and involves a unique vascular pathobiology that interrelates both the renal and cardiovascular disease outcomes. [Rev Cardiovasc Med. 2003;4(suppl 1):S2–S6]
Cardiac Natriuretic Peptides: A Proteomic Window to Cardiac Function
Congestive heart failure (CHF) is a leading cause of adult hospitalization in the United States, and despite advancements in treatment, the disease remains a major clinical challenge. The chief symptom of CHF is dyspnea, but in the urgent-care setting, it is often difficult to distinguish between cardiac and pulmonary causes of this symptom. B-type natriuretic peptide (BNP) is mainly synthesized, stored, and released in the ventricular myocardium and is strongly induced during ventricular-wall tension or stretch. It can be measured rapidly at the point of care and can be used to differentiate cardiac from pulmonary etiologies of dyspnea. In addition to its diagnostic utility, it also has prognostic value and may help guide the treatment of patients with CHF. Thus, it is likely that future algorithms incorporating BNP levels and other clinical indicators will become available to guide critical-care physicians in making management decisions for their CHF patients. [Rev Cardiovasc Med. 2003;4(suppl 4):S3-S12]
Ventricular Resynchronization: Pathophysiology and Identification of Responders
Patients with dilated cardiomyopathy and discoordinate wall motion due to intraventricular conduction delay are at increased risk for exacerbated pump failure and arrhythmias and suffer higher mortality rates. Biventricular and left ventricular resynchronization pacing therapies acutely improve systolic ventricular function and energetic efficiency in patients with heart failure and left-bundle–type intraventricular conduction delay. Sustained therapy can further inhibit or reverse chronic chamber dilation and remodeling. As with all therapies for heart failure, individual subject responses are variable; however, the invasive nature and expense of resynchronization therapy has particularly highlighted the need to prospectively identify optimal candidates. Although QRS duration has been principally used to date, increasing evidence shows this to have poor acute and chronic correlations with patient response. In contrast, direct measures of mechanical dyssynchrony based on simple echo imaging and more complex tissue Doppler and magnetic resonance imaging–based approaches appear to afford better predictive accuracy. [Rev Cardiovasc Med. 2003;4(suppl 2):S3–S13]
New Concepts in Post-Infarction Ventricular Remodeling
An understanding of the process of left ventricular (LV) remodeling has led to greater knowledge of the pathophysiology of heart failure syndrome. This article examines the relationship between LV remodeling and clinical outcomes of heart failure syndrome from several different perspectives. The studies cited suggest that the post–myocardial infarction process is related to and associated with long-term progression of LV dysfunction, heart failure symptoms, and mortality. It is also demonstrated that drug therapies that slow or reverse the remodeling process appear to have favorable natural history effects in the short term as well as during long-term therapy. [Rev Cardiovasc Med. 2003;4(suppl 3):S3-S12]
Radiocontrast Nephropathy: Identifying the High-Risk Patient and the Implications of Exacerbating Renal Function
Radiographic procedures using contrast media are widely performed throughout the world. This necessitates physicians’ awareness of radiocontrast nephropathy—the disorder that develops as a result of exposure to contrast agents. Although in the general population the risk of radiocontrast nephropathy is rather low, it may be very high in selected subsets of patients. This article focuses on the incidence, pathogenesis, risk factors, and prognosis of radiocontrast nephropathy and provides important insights on its prevention. [Rev Cardiovasc Med. 2003;4(suppl 1):S7–S14]
Sorting Out the Evidence on Natriuretic Peptides
B-type natriuretic peptide (BNP) is a cardiac neurohormone released as pre-proBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP have been used to identify patients with heart failure (HF). Clinical considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, interpretation of their units of measure, and the rapid availability of the test results. The BNP assay is currently used as a diagnostic and prognostic aid in HF and as a prognostic marker in acute coronary syndromes (ACS). In general, a BNP level less than 100 pg/mL excludes acutely decompensated HF. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in HF, related to HF severity, predictive of sudden death, and prognostic for death in ACS. This article will sort out the literature concerning the use of these peptides in a variety of clinical scenarios. [Rev Cardiovasc Med. 2003;4(suppl 4):S13–S19]
Reappraisal of Beta-Blocker Therapy in the Acute and Chronic Post-Myocardial Infarction Period
In patients presenting with acute myocardial infarction (MI), the early use of intravenous ß-blockade followed by short-term oral administration in the absence of reperfusion therapy has shown a modest reduction in mortality. In contrast, major reductions in mortality and reinfarction have been shown when ß-blockers have been used soon after an acute MI and continued long-term. These benefits were observed in trials conducted in the 1970s and 1980s, prior to the widespread use of reperfusion therapies, antiplatelet agents, and angiotensin-converting enzyme inhibitors; those trials excluded patients with postischemic heart failure. Recently, the CAPRICORN trial has shown a significant reduction in all-cause mortality and reinfarction in post-MI patients with systolic dysfunction, in response to carvedilol. In spite of compelling evidence supporting the use of ß-blockers in the post-MI setting, data published by the National Cooperative Cardiovascular Project have shown that fewer than half of all post-MI patients receive ß-blockers as long-term therapy. It appears that post-MI patients with perceived contraindications, such as advanced age, diabetes, heart failure, peripheral vascular disease, and/or chronic pulmonary obstructive disease, may derive a substantial benefit from the use of ß-blockers. Given the considerable evidence from randomized clinical trials, the use of ß-blockers is recommended in all post-MI patients without a contraindication, particularly in those with left ventricular systolic dysfunction. [Rev Cardiovasc Med. 2003;4(suppl 3):S13-S24]
Pathophysiology of Congestive Heart Failure
Heart failure is a clinical syndrome characterized by impaired structure and/or function of the heart, leading to dyspnea and fatigue at rest or with exertion. The pathophysiology of heart failure is complex, and there is no single lesion. Any form of heart disease can lead to heart failure. Most heart failure can be explained by well-recognized etiologic factors, though ostensibly healthy patients may harbor risk factors for the later development of heart failure. A fundamental response to myocardial injury or altered loading conditions includes “remodeling” of the heart, so that the size, shape, and function of the affected chamber is grossly distorted. This is accompanied by a constellation of biologic changes, best recognized in advanced cases of heart failure. These multiple alterations may be primary or secondary events but, nonetheless, add importantly to the morbidity and mortality of the patients. More emphasis should be placed on recognition and correction of risk factors related to the development of heart failure. [Rev Cardiovasc Med. 2003;4(suppl 2):S14–S20]
A Review of Contemporary Prevention Strategies for Radiocontrast Nephropathy: A Focus on Fenoldopam and N-Acetylcysteine
The mechanism most likely responsible for the development of radiocontrast nephropathy (RCN) is contrast-induced renal tubular ischemia. At this time, intravenous hydration remains the mainstay for preventing RCN. The antihypertensive agent fenoldopam has been shown in a canine model, as well as in small, retrospective, prospective, and randomized human evaluations, to be effective for preventing RCN. In addition, studies have reported the ability of the free radical scavenger N-acetylcysteine (NAC) to prevent RCN. The clinical trial data for NAC, however, are not consistent regarding this effect, which, if present, appears to be modest and perhaps restricted to lower-risk clinical scenarios. [Rev Cardiovasc Med. 2003;4(suppl 1):S15–S20]
Combining Natriuretic Peptides and Necrosis Markers in Determining Prognosis in Heart Failure
Despite significant advances in medical therapy, patients with heart failure remain at increased risk of overall mortality, progressive ventricular dysfunction, and sudden cardiac death. Although a number of individual clinical and laboratory variables have been identified as being associated with increased mortality risk in heart failure, there remains a clear need for an integrated, accurate method of determining prognosis. Elevated plasma B-type natriuretic peptide (BNP) has been demonstrated to be a powerful marker for prognosis and risk stratification in the setting of heart failure. Patients with elevated BNP levels have been shown to be at significantly higher risk for heart failure admission or death, and higher BNP levels are associated with progressively worse prognosis. Although cardiac troponins are a well-established diagnostic and prognostic marker in acute coronary syndromes, emerging data suggest that cardiac troponins also provide independent prognostic information in heart failure. Detection of cardiac troponins in the serum of patients with heart failure has been shown to be associated with an impaired hemodynamic profile, progressive decline in left ventricular systolic function, and shortened survival. Combining a marker of myocyte injury—cardiac troponin—with BNP in a multimarker strategy appears to be a useful tool for improving risk assessment and triage in patients with heart failure. Heart failure patients with detectable cardiac troponin I and high BNP levels have been shown to have a 12-fold increased mortality risk compared with those with both undetectable cardiac troponin I and lower BNP. Integrating this multimarker approach into the routine assessment of heart failure patients will allow clinicians to more accurately identify high-risk patients who may derive increased benefit from intensive management strategies. [Rev Cardiovasc Med. 2003;4(suppl 4):S20-S28]
Contemporary Strategies to Preserve Renal Function During Cardiac and Vascular Surgery
Mortality rates associated with perioperative acute renal failure (ARF) range from 60% to 90%. The major causes of ARF are prerenal factors that decrease renal blood flow; intrarenal factors that have a direct effect on tubules, interstitium, or glomeruli; and postrenal factors that obstruct urine outflow. Current strategies to provide perioperative renal protection include maintaining adequate renal O2 delivery, suppressing renovascular vasoconstriction, renovascular vasodilatation, maintaining tubular flow, decreasing renal cellular O2 consumption, and attenuating reperfusion injury. A study of patients undergoing elective repair of a thoracoabdominal aortic aneurysm (TAAA) found that the use of the selective dopamine-1 receptor agonist fenoldopam was associated with reductions in mortality, dialysis requirements, and lengths of stay in the hospital and intensive care unit. The study authors suggest that the improved patient outcomes and hospital-utilization data resulting from the use of fenoldopam were directly related to the protection of renal function during surgery and a reduction of postoperative renal complications. [Rev Cardiovasc Med. 2003;4(suppl 1):S21–S28]
Limitations of Current Medical Therapies for the Treatment of Heart Failure
The medical treatment of heart failure has evolved over the past 40 years, from the primary use of diuretics and digitalis in the 1960s to the use of inotropic agents and vasodilators in the 1970s. More recently, the focus has been on the neurohormonal system, specifically the renin-angiotensin-aldosterone system and the sympathetic nervous system. Drugs that inhibit or block these systems (eg, angiotensin-converting enzyme inhibitors and ß-blocking drugs) are the primary agents recommended in recent heart failure guidelines. However, the actual percent reduction in mortality associated with the use of these agents has been relatively modest. This article will review the results and limitations of medical therapy for heart failure. Our understanding of the pathogenesis of heart failure may be incomplete, and alternative strategies, including mechanical devices, may play an increasing role in the treatment of heart failure in the future. [Rev Cardiovasc Med. 2003;4(suppl 2):S21-S29]
New Evidence from the CAPRICORN Trial: The Role of Carvedilol in High-Risk, Post-Myocardial Infarction Patients
The CAPRICORN (Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction) trial established that the ß-blocker carvedilol reduces the risk of death in patients with left ventricular dysfunction post myocardial infarction, whether or not the infarct is complicated by clinical heart failure. Thus, the utility of the ß-blocker carvedilol is confirmed in the modern era as an adjunct to revascularization, angiotensin-converting enzyme inhibitors, aspirin, and statins. In addition, the results prompt us to review the prior studies of ß-blockers postinfarction. Critical review of CAPRICORN and earlier ß-blocker studies suggests that specific ß-blockers should be matched to specific clinical scenarios. The COMET (Carvedilol or Metoprolol European Trial) study reinforces this view by establishing that ß-blockers are not simply interchangeable agents. [Rev Cardiovasc Med. 2003;4(suppl 3):S25–S29]
Improving Perioperative Outcomes in Patients with End-Stage Heart Failure
In the United States alone, more than 4.5 million people are affected by heart failure, with more than 500,000 new cases diagnosed each year. Although cardiac transplantation remains the “gold-standard” surgical treatment for heart failure unresponsive to maximal medical therapy, the chronic shortage of donor hearts has necessitated clinical trials of other surgical options. Over the past two decades, research, technological progress, and extensive clinical experience have resulted in the application of ventricular assist device (VAD) technology to a broader population of heart-failure patients, as these devices have proven to be viable therapeutic alternatives for therapy of end-stage heart failure. All patients undergoing cardiac transplantation or VAD insertion have multiorgan dysfunction as a result of irreversible, severe ventricular dysfunction resulting in low cardiac output. Recently, fenoldopam has been described as a vasodilator that might be useful in patients with decompensated heart failure, particularly in the perioperative setting. As a selective dopamine-1 receptor agonist, fenoldopam causes vasodilation in the systemic, renal, mesenteric, coronary, and pulmonary vasculature. Potentially, the pharmacologic properties of fenoldopam could be successfully exploited in patients undergoing medical or surgical treatment of end-stage heart failure. Controlled randomized trials are needed to demonstrate improvement in cardiopulmonary or renal outcomes in such patients. [Rev Cardiovasc Med. 2003;4(suppl 1):S29–S34]
Neurohormonal Regulation and the Overlapping Pathology Between Heart Failure and Acute Coronary Syndromes
An understanding of the dynamic relationship between the coronary artery and left ventricular (LV) function is important in diagnosing and treating acute coronary disease. Measurement of B-type natriuretic peptide (BNP) provides rapid and accurate identification of patients with impaired LV function, which has proven valuable in differentiating between congestive heart failure (CHF) and symptoms attributable to pulmonary etiologies. Coronary artery and ventricular pathophysiology both are characterized by injury, functional aberrations, and subsequent remodeling. Ischemia occurs in both and accounts for virtually all significant adverse outcomes. The difference in BNP elevations seen in acute ischemia compared with those observed in chronic CHF is striking: Although even small BNP elevations in acute coronary syndromes have powerful prognostic value, it is not likely that they can be effectively used as a diagnostic marker for ischemia. [Rev Cardiovasc Med. 2003;4(suppl 4):S29–S36]