Dwight D. Stapleton

A Comparison of Contemporary Definitions of Contrast Nephropathy in Patients Undergoing Percutaneous Coronary Intervention and a Proposal for a Novel Nephropathy Grading System

Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) has multiple definitions. We attempted to identify the optimal definition of CIN. In 985 patients undergoing PCI (derivation group), we assessed the prognostic significance of 4 commonly used contemporary definitions of CIN (increases in serum creatinine after PCI [deltaCr] >1.0 mg/dl, >0.5 mg/dl, and >25% after PCI; and the American College of Cardiology National Cardiovascular Data Registry definition) with respect to 6-month major adverse cardiovascular events (MACEs) and all-cause mortality (at 863 +/- 324 days). Incidence of CIN ranged widely (2.0% to 15%) depending on the definition used. Only 2 definitions (deltaCr >0.5 mg/dl, >25%) consistently correlated with study outcomes. Using these 2 definitions, we devised a new grading system (grade 0 deltaCr <or=25% and <or=0.5 mg/dl; grade 1 deltaCr >25% but <or=0.5 mg/dl; and grade 2 deltaCr >0.5 mg/dl). Nephropathy grades (0 vs 1 vs 2) showed significant correlation with 6-month MACEs (12.4 vs 19.4 vs 28.6%, p = 0.003) and all-cause mortality (10.2 vs 10.4 vs 40.9%, p <0.0001). In multivariate analyses, the grading system showed an independent association with MACEs and mortality. The prognostic value of nephropathy grades was prospectively confirmed in an independent validation group of 539 patients. In conclusion, of the 4 contemporary definitions of CIN, only deltaCr >25% and >0.5 mg/dl consistently predicted adverse events after PCI. By unifying these 2 definitions, we devised a novel nephropathy grading system that is predictive of 6-month MACEs and all-cause mortality after PCI.

Cardiac allograft vasculopathy: current concepts.

The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in 15% to 20% of transplant recipients. It differs from traditional atherosclerosis in that it is a concentric and diffuse intimal hyperplastic process; the internal elastic lamina remains intact; calcification is rare; and the disease tends to develop rapidly. Although no definitive reason for cardiac allograft vasculopathy has been established, it has been suggested that it may be caused by a combination of immunologic and nonimmunologic damage to endothelial cells that results in myointimal proliferation. Intravascular ultrasound and coronary angioscopy are more sensitive diagnostic measures of cardiac allograft vasculopathy than coronary angiography. Although retransplantation currently seems to be the only definitive therapy for cardiac allograft vasculopathy, it has shown only fair results.

Predictive model to assess risk for cardiac allograft vasculopathy: an intravascular ultrasound study.

OBJECTIVES This study was performed to assess the influence and interdependence of immunologic and nonimmunologic risk factors in the development of cardiac allograft vasculopathy. Another primary objective was to establish a clinically useful model for risk assessment of cardiac allograft vasculopathy that would facilitate identifying those heart transplant recipients likely to have severe intimal proliferation and thereby at greater risk for adverse clinical events. BACKGROUND To our knowledge, no comprehensive intravascular ultrasound study has assessed the relative influences of both nonimmunologic and immunologic factors in the development of cardiac allograft vasculopathy, currently the major limitation to long-term cardiac allograft survival. METHODS Using a computer-assisted model of stepwise logistic regression, immunologic and nonimmunologic risk factors were evaluated to help identify the development of severe intimal thickening in 101 subjects who underwent intravascular ultrasound. Prospective validation of the findings was performed in a separate consecutive cohort of 37 heart transplant recipients, and the accuracy of this model to predict a relative risk > 1 for the development of severe intimal hyperplasia was assessed. RESULTS Significant independent predictors of severe intimal hyperplasia in this model included a donor age > 35 years, a first-year mean biopsy score > 1 (a measure not only of severity of rejection, but also of frequency of insidious rejection) and hypertriglyceridemia at two incremental levels of risk (150 to 250 mg/dl [1.70 to 2.83 mmol/liter] and > 250 mg/dl [2.83 mmol/liter]). Based on the absence (0) or presence (1) of these factors, 12 individual categories of risk were ascertained with increasing relative risks and predicted probabilities for severe intimal hyperplasia. Prospective validation of this model revealed a sensitivity and specificity of 70% and 90%, respectively, and the positive and negative predictive values were 85% and 80%, respectively. Additionally, subjects with severe intimal thickening had a four-fold higher cardiac event rate than those without severe intimal proliferation on intravascular ultrasound. CONCLUSIONS This study establishes a clinically useful predictive model that can be applied to individual heart transplant recipients to assess their risk for developing significant cardiac allograft vasculopathy and, thus, aids in the identification of patients at risk for cardiac events in whom closer surveillance and risk factor modification may be warranted.

An intravascular ultrasound study of the influence of angiotensin-converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculopathy.

In conclusion, this intravascular ultrasound study suggests that treatment of cardiac transplant recipients with either ACE inhibitors or CEBs is associated with a decrease in the degree of vascular intimal hyperplasia at 1 year after transplantation. Thus, early intervention with CEBs or ACE inhibitors offers a preventive option for the devastating consequences of cardiac allograft vasculopathy.

Cardiac allograft vasculopathy assessed by intravascular ultrasonography and nonimmunologic risk factors

The genesis of cardiac allograft vasculopathy has been linked to nonimmunologic endothelial injury. Studies evaluating the role of nonimmunologic risk factors have thus far been limited to angiographic assessment. Intravascular ultrasound can detect cardiac allograft vasculopathy before it becomes angiographically evident. To assess the influence of nonimmunologic risk factors in the development of cardiac allograft vasculopathy, we studied 101 consecutive cardiac transplant recipients who underwent intracoronary ultrasound imaging during routine, annual coronary angiography. Based on the severity of intimal thickening, patients were divided into 2 groups: group 1 = minimal, mild, or moderate intimal thickness; and group 2 = severe intimal thickness. Cardiac transplant recipients with severe intimal thickness had higher levels of total cholesterol (267 +/- 70 vs 227 +/- 41 mg/dl, p = 0.0008), low-density lipoprotein cholesterol (187 +/- 47 vs 139 +/- 31 mg/dl, p = 0.0001), and triglycerides (237 +/- 75 vs 182 +/- 88 mg/dl, p = 0.0004), a higher percentage of weight gain (12 +/- 4% vs 8 +/- 5%, p = 0.0001), a larger body mass index (30 +/- 4 vs 25 +/- 3, p = 0.0001), and older donor age (27 +/- 5 vs 23 +/- 7 years, p = 0.005) than recipients with mild or moderate intimal thickness. Multiple regression analysis established that total cholesterol, low-density lipoprotein cholesterol, triglyceride levels, obesity indexes, donor age, and years following cardiac transplantation (p < 0.01) were independent predictors of the severity of intimal thickening, and thus the severity of cardiac allograft vasculopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of hypertension in cardiac transplantation and the role of cyclosporine.

&NA; The use of cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Several mechanisms, including endothelin‐mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in nitric oxide, and altered cytosolic calcium translocation, have been proposed to underlie cyclosporine‐induced hypertension. In addition, other studies have shown activation of the sympathetic nervous system and the renin‐angiotensin system, as well as abnormalities in prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of cyclosporine‐induced hypertension consist of elevated peripheral vascular resistance, ventricular vascular uncoupling contributing to left ventricular hypertrophy, and abnormalities in the diastolic function of the allograft. Combined calcium‐channel blockers and angiotensin‐converting enzyme inhibitors have been used for the treatment of this clinical problem, and they achieve blood pressure control in 65% of patients. Moreover, these agents may also be beneficial in preventing development of cardiac allograft vasculopathy, a long‐term nemesis in cardiac transplantation.

Metabolic Syndrome: Definition and Therapeutic Implications

Abstract The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the worlds population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndromes individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low–fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.

Safety and clinical utility of long-term intravenous milrinone in advanced heart failure

Few data are available on the long-term safety or clinical utility of the inodilator agent milrinone. We designed a prospective, nonrandomized, observational trial in a cohort of 71 patients who had demonstrated dependence on inotropic therapy, had been clinically stable on an inotropic regimen (milrinone, dobutamine, or both) for > or = 72 hours, and had been given intravenous milrinone for > 72 hours. Group I (n = 22) patients required treatment with both milrinone and dobutamine to achieve stability; group II (n = 49) patients attained stability initially with either milrinone (subgroup IIA) or dobutamine (subgroup IIB), but later required adjunctive therapy with the other inotropic agent for continued hemodynamic support. Of the 71 patients, 38% required mechanical intervention to achieve hemodynamic stability, and 68% were successfully bridged to heart transplantation. Patients were maintained on milrinone therapy for as long as 8 weeks and demonstrated a low incidence of adverse cardiac (7%) or noncardiac (4%) events. Subgroup IIA (28%) had significantly less need than subgroup IIB (52%) for mechanical intervention using an intraaortic balloon pump (p = 0.05), although mortality rates while awaiting transplantation were statistically similar in subgroups IIA (28%) and IIB (35%). Significant improvements from baseline values were noted at the time of transplantation for all aspects of systemic hemodynamics, indicating sustained long-term hemodynamic effects. Long-term intravenous milrinone therapy is safe and well tolerated, and it provides hemodynamic and metabolic support as a pharmacologic bridge to transplantation. The findings also suggest that milrinone as primary inodilator therapy may be associated with less need for mechanical ventricular support.

Usefulness of Peak Oxygen Consumption in Predicting Outcome of Heart Failure in Women Versus Men

This investigation finds that percent of predicted maximum oxygen consumption, an age- and gender-adjusted measurement of exercise, capacity, describes the degree of functional impairment in women more accurately than peak oxygen consumption. This evidence must be considered when cardiopulmonary metabolic parameters are used for prognostic stratification of women with heart failure.

Implications for the vascular surgeon with prolonged (3 to 89 days) intraaortic balloon pump counterpulsation

PURPOSE The intraaortic balloon pump (IABP) is useful in the treatment of failing hearts. Although most experience with IABPs has been with acute short-term use, the safe duration of therapy and possible complications of long-term IABP use are uncertain. We evaluated the feasibility, management, and complications associated with long-term IABP therapy. METHODS Fifty consecutive patients with 87 IABPs were evaluated retrospectively. All patients had IABP support for greater than 72 hours. Results and complications were evaluated. RESULTS The mean duration of IABP support was 23.2 days. There were 21 IABP-related complications in 16 patients: (16 ischemic, three infections, two hemorrhage). The rate of complications was 0.13 per patient-week of support. Significant predictors of complications were total days of IABP support (p < 0.0001), use of multiple IABPs (p < 0.0001), and attempted but unsuccessful percutaneous insertions (p < 0.001). Complications led to 14 vascular procedures (five patch angioplasties, four bypass procedures, two major amputations, one fasciotomy, one groin exploration for hemorrhage, and one removal of an infected Dacron patch). Percutaneous removals had a 14% complication rate compared with none after operative removal (p = 0.02). Thirty-two patients survived (64%). Of the survivors, 27 underwent transplant. CONCLUSIONS Prolonged IABP therapy is feasible and is associated with an acceptable rate of complications. Operative removal is superior to percutaneous removal. Percutaneous removal should be limited to short-term therapy. There is no need for mandatory removal or site rotation based solely on indwelling time.