A case of catastrophic antiphospholipid syndrome: first report with advanced cardiac imaging using MRI.

This present case pertains to a 48-year-old woman with a history of antiphospholipid syndrome, who presented with progressive fatigue, generalized weakness, and orthopnea acutely. She had a prior diagnosis of antiphospholipid syndrome with recurrent deep vein thromboses (DVTs) and repeated demonstration of lupus anticoagulants. She presented in cardiogenic shock with markedly elevated troponin and global myocardial dysfunction on echocardiography, and cardiac catheterization revealed minimal disease. Cardiac magnetic resonance imaging was performed, which revealed findings of perfusion defects and microvascular obstruction, consistent with the pathophysiology of catastrophic antiphospholipid syndrome (CAPS). Diagnosis was made based on supportive imaging, including head magnetic resonance imaging (MRI) revealing multifocal, acute strokes; microvascular thrombosis in the dermis; and subacute renal infarctions. The patient was anticoagulated with intravenous unfractionated heparin and received high-dose methylprednisolone, plasmapheresis, intravenous immunoglobulin, and one dose each of rituximab and cyclophosphamide. She convalesced with eventual myocardial recovery after a complicated course. The diagnosis of CAPS relies on the presence of (1) antiphospholipid antibodies and (2) involvement of multiple organs in a microangiopathic thrombotic process with a close temporal association. The myocardium is frequently affected, and heart failure, either as the presenting symptom or cause of death, is common. Despite echocardiographic evidence of myocardial dysfunction in such patients, MRIs of CAPS have not previously been reported. This case highlights the utility in assessing the involvement of the myocardium by the microangiopathic process with MRI. Because the diagnosis of CAPS requires involvement in multiple organ systems, cardiac MRI is likely an underused tool that not only reaffirms the pathophysiology of CAPS, but could also clue clinicians in to the possibility of a diffuse thrombotic process.

Effect of enhanced external counterpulsation on circulating CD34+ progenitor cell subsets.

BACKGROUND: Enhanced external counterpulsation (EECP) is associated with improvement in endothelial function, angina and quality of life in patients with symptomatic coronary artery disease, although the mechanisms underlying the observed clinical benefits are not completely clear. The purpose of this study was to examine the effects of EECP on circulating haematopoietic progenitor cells (HPCs) and endothelial progenitor cells (EPCs) in patients with refractory angina. We compared HPC and EPC counts between patients scheduled for EECP and patients with normal angiographic coronary arteries, with and without coronary endothelial dysfunction. We hypothesized that an increase in circulating bone marrow derived progenitor cells in response to EECP may be part of the mechanism of action of EECP. METHODS: Thirteen consecutive patients scheduled to receive EECP treatment were prospectively enrolled. Clinical characteristics were recorded and venous blood (5 ml) was drawn on day 1, day 17, day 35 (final session) and one month post completion of EECP therapy. Buffy coat was extracted and HPCs and EPCs were counted by flow cytometry. RESULTS: Median Canadian Cardiovascular Society (CCS) angina class decreased and Duke Activity Status Index (DASI) functional score increased significantly (both, p < 0.05) in response to EECP, an effect that was maintained at one month after termination of treatment. Flow cytometric analysis revealed an accompanying significant increase in CD34+, CD133+ and CD34+, CD133+ CPC counts over the course of treatment (p < 0.05). DASI scores correlated significantly with CD34+ (R = 0.38 p = 0.02), CD133+ (R = 0.5, p = 0.006) and CD34+, CD133+ (R = 0.47, p = 0.01) CPC counts. CONCLUSION: This study shows that HPCs, but not EPCs are significantly increased in response to EECP treatment and correlate with reproducible measures of clinical improvement. These findings are the first to link the functional improvement observed with EECP treatment with increased circulating progenitor cells.

Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis is associated with necrotic core plaques.

BACKGROUND/OBJECTIVE: Endothelial dysfunction and atherosclerosis are systemic disorders, but are often characterised by segmental involvement and complications. A potential mechanism for local involvement early in the disease process may be related to plaque composition. This study was designed to test the hypothesis that in patients with minimal coronary atherosclerosis, coronary artery segments with abnormal endothelial function have specific plaque characteristics. METHODS: Intravascular ultrasound (IVUS) images were obtained from 30 patients who underwent coronary endothelial function assessment. Spectral analysis of the IVUS radiofrequency data was used for assessment of plaque composition. IVUS findings of the coronary sections were compared according to the corresponding endothelial response to acetylcholine. RESULTS: Sections with a decrease epicardial coronary arterial diameter in response to acetylcholine had smaller baseline lumen (7.5 (2.4) mm(2) vs 8.8 (3.3) mm(2), p = 0.006) but larger plaque burden (37.1% (9.4%) vs 31% (7%), p = 0.003) than sections with normal endothelial response. Sections with endothelial dysfunction had larger necrotic core plaques: 0.13 (0.03-0.33) mm(2) vs 0.0 (0.0-0.07), p<0.001 and more dense calcium: 0.03 (IQR 0.0-0.13) mm(2) vs 0.0 (0.0-0.10) mm(2), p<0.01), than those with normal endothelial response. Only necrotic core area was associated with endothelial dysfunction (p<0.001) after adjusting for other measures. CONCLUSIONS: This study suggests that local coronary endothelial dysfunction in patients with minimal coronary atherosclerosis is associated with plaque characteristics that are typical of vulnerable plaques.

Comparative outcomes of percutaneous coronary interventions in diabetics vs non-diabetics with prior coronary artery bypass grafting.

AIMS: To determine the influence of diabetes on outcome after percutaneous coronary intervention in patients with prior coronary artery bypass grafting. METHODS AND RESULTS: Patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention from 1 January 1996, to 31 August 2000, were divided into two groups based on whether or not they had diabetes, excluding patients with acute infarction or shock. Cox proportional hazards models were utilized to estimate the association between diabetes and adverse events. One thousand one hundred and fifty-three post-coronary artery bypass grafting percutaneous coronary intervention patients were identified (326 diabetics and 827 non-diabetics). Diabetics were younger, more likely to have hypertension, heart failure, and lower ejection fraction. Procedural characteristics and angiographic and procedural success rates were similar. Diabetes was associated with increased mortality (hazard ratio 1.58, 95% confidence intervals 1.10-2.27). Diabetes did not have a significant effect on mortality in patients treated for single-territory coronary disease (hazard ratio 1.44, 95% confidence intervals 0.69-3.02), but did in patients with multi-territory disease (hazard ratio 1.79, 95% confidence intervals 1.16-2.76). However, in diabetics with multi-territory disease who were completely revascularized with percutaneous coronary intervention, mortality was comparable to non-diabetics (hazard ratio 1.32, 95% confidence intervals 0.57-3.03). CONCLUSION: Among percutaneous coronary intervention patients with prior coronary artery bypass grafting, diabetes portends an adverse prognosis.

Effectiveness and safety of abciximab after failed thrombolytic therapy.

Among 214 patients treated with abciximab within 24 hours of full-dose thrombolytic therapy, major bleeding occurred in 50 patients (23%; 95% confidence interval [CI] 18% to 30%) and intracranial hemorrhage occurred in 3 patients (1.4%; 95% CI 0.3% to 4%). The independent multivariate predictors of major bleeding were age (odds ratio [OR] 1.53/10 years, 95% CI 1.05 to 2.21, p = 0.03), time from thrombolytic to abciximab (OR 0.91/hour, 95% CI 0.83 to 0.99, p = 0.03), and intra-aortic balloon pump insertion (OR 4.42, 95% CI 2.00 to 9.72, p = 0.0002).

Effect of abciximab on late adverse events in patients with diabetes mellitus undergoing stent implantation.

Percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with higher rates of adverse cardiac events. Recent data suggest that adverse events are reduced in DM after PCI using stents with abciximab. We performed a retrospective analysis of a prospective PCI registry for all patients with DM who underwent stent placement at the Mayo Clinic from 1995 to 1997 (n = 570), and divided them into 2 groups based on whether abciximab was administered. Characterization and comparison of the clinical and angiographic variables, procedural outcomes, and short- and long-term event rates between groups was performed. The baseline clinical characteristics of the groups were similar, but patients treated with abciximab were more likely to be men with a lower left ventricular ejection fraction. Patients treated with abciximab had more multivessel intervention, saphenous vein graft intervention, and thrombus before intervention. The 30-day mortality rate (0.6% vs 3.0%, p = 0.03) and repeat PCI (0% vs 1.1%, p = 0.03) was lower in patients treated with abciximab. The 30-day rates of bypass surgery, myocardial infarction (MI), and a composite of death, MI, and revascularization were similar. The 1-year event rates did not differ significantly between patients taking and not taking abciximab for the end points of death (8.9% vs 8.8%, p = 0.97), MI (13.3% vs 11.4%, p = 0.57), bypass surgery (10.3% vs 6.2%, p = 0.20), repeat PCI (14.7% vs 15.9%, p = 0.76), and a composite of death, MI, and revascularization (30.4% vs 26.7%, p = 0.43). After adjusting for baseline variables, abciximab did not influence the occurrence of late adverse events.

Noninvasive revascularization by enhanced external counterpulsation: a case study and literature review.

Nearly 8 million people in the United States suffer from symptoms of coronary artery disease (CAD). Unfortunately, the population of patients with ischemic coronary disease that is not readily amenable to surgical or percutaneous revascularization continues to grow. For patients who are not candidates for standard revascularization procedures and in whom aggressive medical therapy fails to control symptoms, enhanced external counterpulsation (EECP) is a new, noninvasive outpatient method to improve quality of life by decreasing ischemic symptoms and permit increased activity. We report the case of a 56-year-old woman with severe, symptomatic CAD receiving maximal medical therapy who underwent a course of EECP therapy because she was not a good candidate for other forms of revascularization. She demonstrated dramatic improvement in her anginal symptoms and complete resolution of myocardial ischemia on repeat nuclear stress imaging. This case suggests that EECP is a safe and effective method for reducing symptoms of myocardial ischemia in patients for whom standard percutaneous or surgical revascularization is not suitable treatment.

Issues and challenges with antithrombotic therapy in diabetic patients with acute coronary syndromes.

Diabetes mellitus is associated with significant morbidity and mortality in the setting of acute coronary syndromes. This increased risk is attributable, in large part, to the derangements in coagulation that can accompany the diabetic disease state. Patients with diabetes mellitus have disturbances in endothelial function, platelet function, and coagulation factors. Until recently, there has been little direct exploration of therapeutic measures to improve outcome specifically among diabetic patients with acute coronary syndromes. Fortunately, antithrombotic therapies that have proven benefit in the general population also seem to be beneficial among patients with diabetes, although optimal dosing for improved safety and efficacy in this population has yet to be established for many of these agents. Primary prevention strategies and strict attention to risk factor modification hold the greatest promise for improving long-term outcome.

Application of the New York State PTCA mortality model in patients undergoing stent implantation.

BACKGROUND: This study applied the New York State conventional coronary angioplasty (PTCA) model of clinical outcomes to evaluate whether it has relevance in the current era of stent implantation. The model was developed in 62 670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust mortality and bypass surgery after PTCA. Since then, stents have become the dominant form of intervention. Whether that model remains relevant is uncertain. METHODS AND RESULTS: All patients undergoing stenting at the Mayo Clinic from 1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed after attempted stenting, and longer-term mortality. No patients were excluded. The New York model was used to risk adjust and predict in-hospital and follow-up mortality. There were 3761 patients with 4063 procedural admissions for stenting; 6,472 target vessel segments were attempted, and 96.1% of procedures were successful. With the New York multivariable risk factor equation, 79 in-hospital deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model risk score in a logistic regression model was the most significant factor associated with in-hospital mortality (OR, 1.86; P<0.001). During a mean follow-up of 1.2+/-1.0 years, there were 154 deaths. Multivariable analysis documented 6 factors associated with subsequent mortality; New York risk score was the most significant (chi(2)=16.64, P=0.0001). CONCLUSIONS: Although the New York mortality model was developed in an era of conventional angioplasty, it remains relevant in patients undergoing stenting. The risk score derived from that model is the variable most significantly associated with not only in-hospital but also longer-term outcome.

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts.

BACKGROUND: Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. METHODS: We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had >/=60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. RESULTS: Median percent diameter stenosis improved from 69% to 45% (P =.0001) after local delivery, and TIMI thrombus grade >/=1 incidence reduced from 68% to 34% (P =.0001). TIMI flow grade was not significantly affected (P =.12). All patients had a successful intervention (

Local delivery of heparin post-PTCA: a multicenter randomized pilot study.

Bailout stenting for major dissection and threatened closure has high rates of ischemic complications. We performed a randomized trial of local heparin delivery using the infusion sleeve before bailout stenting for suboptimal angioplasty results. In phase I, 20 patients were randomized to local delivery with either 40- or 100-psi infusion pressure. In phase II, 37 patients were randomized to local delivery at 100 psi or standard therapy. Local delivery succeeded in all but one patient; overall there was no significant worsening of intimal dissection. One patient treated with 100-psi drug infusion suffered a perforation after stent placement. There were no significant differences in the composite endpoint of death, MI, CABG, urgent repeat angioplasty, and stent thrombosis at 30 days (21% vs. 0%; P = 0.18). At 6 months, the rates of myocardial infarction in phase II were 27% with local delivery vs. 10% with standard treatment (P = 0.4). Local heparin delivery in dissected vessels may be associated with increased complications and should be approached with caution.

Prognostic value of congestive heart failure history in patients undergoing percutaneous coronary interventions.

OBJECTIVES: We sought to determine the prognostic significance of a history of congestive heart failure above that provided by baseline ejection fraction in patients undergoing percutaneous coronary interventions. BACKGROUND: Left ventricular function is a known predictor of survival in patients with coronary artery disease, as is a history of congestive heart failure. The contribution of heart failure history independent of left ventricular function is unknown. METHODS: Data were pooled from four interventional trials and the Duke University database. The combined dataset included 5,260 patients undergoing percutaneous interventions, 334 with and 4,926 without a history of heart failure. Patients were defined by the treating physician as having a clinical history of heart failure at the time of enrollment. RESULTS: The 30-day and 6-month mortality were higher in patients with a clinical history of congestive heart failure than in those without such a history (2% vs. <1%, p=0.002 at 30 days, 5% vs. 1%, p=0.001 at 6 months). Heart failure history did not influence the incidence of myocardial infarction, use of angioplasty or the use of bypass surgery during follow-up. Multivariable analysis revealed that heart failure history added significantly to ejection fraction in predicting intermediate-term (6-month) mortality (p=0.01). Stepwise logistic regression also revealed heart failure history to be an independent predictor of 6-month mortality (odds risk 1.9, 95% confidence interval 1.1 to 3.5). CONCLUSIONS: A clinical history of congestive heart failure is associated with increased early and intermediate-term mortality in patients undergoing percutaneous revascularization. Congestive heart failure history appears to provide prognostic information independent of that available from a patient's left ventricular function. These findings suggest that patients with a clinical history of congestive heart failure who undergo a percutaneous intervention should be closely monitored, especially those with the lowest ejection fractions.

Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty.

BACKGROUND: Recent subgroup analyses of randomized trials have suggested that percutaneous intervention in diabetic patients with multivessel disease results in higher mortality than coronary artery bypass graft surgery (CABG). We studied the relationship between diabetes and survival after revascularization in a large prospective cohort of patients with multivessel coronary artery disease. METHODS AND RESULTS: By analyzing data for 3220 patients (24% diabetic) with symptomatic two- or three-vessel coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA) or CABG at Duke University Medical Center between 1984 and 1990, we found that at 5 years, unadjusted survival in the group of patients undergoing CABG was 74% in diabetics and 86% in nondiabetics. Similarly, 5-year survival among PTCA patients was 76% in diabetics and 88% in patients without diabetes. After adjustment for baseline characteristics, diabetic patients receiving either PTCA or CABG had significantly poorer survival than nondiabetics (chi2=43.56, P<.0001). Unlike previous studies, however, there was no significant differential effect of diabetes on outcome between patients treated with PTCA and those treated with CABG (chi2=0.01, P=.91). CONCLUSIONS: Although diabetes was associated with a worse long-term outcome after both PTCA and CABG in patients with multivessel coronary artery disease, the effect of diabetes on prognosis was similar in both treatment groups. Thus, our findings support the concept that the choice of initial revascularization strategy should not be based exclusively on a history of diabetes but rather should rely on other factors, such as angiographic suitability and clinical status.