Meta-Analysis of Studies Comparing Dual- Versus Mono-Antiplatelet Therapy Following Transcatheter Aortic Valve Implantation.

Current guidelines recommend dual-antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI), although some studies suggest mono-antiplatelet therapy is equally efficacious with an improved safety profile. We performed a meta-analysis of studies comparing DAPT with mono-antiplatelet therapy after TAVI. Study quality and heterogeneity were assessed using Jadad score, Newcastle-Ottawa Scale, and Cochran's Q statistics. Mantel-Haenszel odds ratios (ORs) were calculated using fixed effect models as the primary analysis. Eight studies including 2,439 patients met the inclusion criteria. At 30 days, DAPT was associated with an increased risk of all-cause mortality (OR 2.06, 95% confidence interval [CI] 1.34 to 3.18, p = 0.001), major or life-threatening bleeding (OR 2.04, 95% CI 1.60 to 2.59, p <0.001), and major vascular complications (OR 2.15, 95% CI 1.51 to 3.06, p <0.001). There was no difference in the rate of the combined end point of stroke or transient ischemic attack, or myocardial infarction. Outcome data up to 6 months were available in 5 studies; all-cause mortality and stroke were similar between groups, although major or life-threatening bleeding was more frequent with DAPT. In conclusion, in patients undergoing TAVI, DAPT is associated with increased risk at 30 days of all-cause mortality, major or life-threatening bleeding, and major vascular complications without a decrease in ischemic complications; at 6 months, the excess bleeding risk persisted. These data suggest a safety concern with DAPT and justify further investigation of the optimal antiplatelet therapy regimen after TAVI.

Increase in cardiac myosin binding protein-C plasma levels is a sensitive and cardiac-specific biomarker of myocardial infarction.

Earlier studies have shown that cardiac myosin binding protein-C (cMyBP-C) is easily releasable into the circulation following myocardial infarction (MI) in animal models and patients. However, since its release kinetics has not been clearly demonstrated, no parameters are available to judge its efficacy as a bona fide biomarker of MI in patients with MI. To make this assessment, plasma levels of cMyBP-C and six known biomarkers of MI were determined by sandwich enzyme-linked immunosorbent assay in patients with MI who had before and after Percutaneous Transcoronary Angioplasty (PTCA), as well as healthy controls. Compared to healthy controls (22.3 ± 2.4 ng/mL (n=54)), plasma levels of cMyBP-C were significantly increased in patients with MI (105.1 ± 8.8 ng/mL (n=65), P<0.001). Out of 65 patients, 24 had very high levels of plasma cMyBP-C (116.5 ± 13.3 ng/mL), indicating high probability of MI. Importantly, cMyBP-C levels were significantly decreased in patients (n=40) at 12 hours post-PTCA (41.2 ± 9.3 ng/mL, P<0.001), compared to the patients with MI. Receiver operating characteristic analysis revealed that a plasma cMyBP-C reading of 68.1 ng/mL provided a sensitivity of 66.2% and a specificity of 100%. Also, myoglobin, carbonic anhydrase and creatine kinase-MB levels were significantly increased in MI patients who also had higher cMyBP-C levels. In contrast, levels of cardiac troponin I, glycogen phosphorylase and heart-type fatty acid binding protein were not significantly changed in the samples, indicating the importance of evaluating the differences in release kinetics of these biomarkers in the context of accurate diagnosis. Our findings suggest that circulating cMyBP-C is a sensitive and cardiac-specific biomarker with potential utility for the accurate diagnosis of MI.

Long-term outcomes of plaque debulking with rotational atherectomy in side-branch ostial lesions to treat bifurcation coronary disease.

BACKGROUND: The prognosis after rotational atherectomy of a side-branch ostium to treat bifurcation coronary lesions is unknown. METHODS: This was a retrospective case-review study of 40 consecutive patients who underwent rotational atherectomy of the sidebranch ostium to treat symptomatic bifurcation coronary lesions meeting the Medina classification (1,1,1) at our institution between 2003 and 2007. RESULTS: Twenty-two (55.0%) patients underwent rotational atherectomy of the side-branch ostium alone and 18 (45.0%) underwent rotational atherectomy of the both the main vessel and the sidebranch ostium. Most of the patients (n = 37, 92.5%) had a drug-eluting stent placed in the main vessel after rotational atherectomy. Only 8 patients (20.0%) required side-branch stents, and 2 patients (5.0%) underwent a final kissing-balloon technique. No acute closure of the side branch or coronary perforation were observed. Major adverse cardiac events included cardiac death (n = 1; 2.5%), nonfatal myocardial infarction (n = 1; 2.5%), target vessel revascularization (n = 2; 5.0%) and target lesion revascularization (n = 0; 0.0%) during the mean follow-up period of 21.3 +/- 18.5 months. CONCLUSIONS: The study demonstrated safety and feasibility of rotational atherectomy and provisional side-branch stenting to treat side-branch ostial lesions of true severe bifurcation coronary artery disease. The study results suggest that rotational atherectomy of a side-branch ostium prior to main-vessel stenting may be an option in selected patients undergoing complex bifurcation lesion angioplasty.

Usefulness of wide pulse pressure as a predictor of poor outcome after renal artery angioplasty and stenting.

Renal artery stenosis is a common cause of secondary hypertension and ischemic nephropathy. Percutaneous angioplasty and stent placement has allowed select patients with renal artery stenosis to use fewer antihypertensive agents and improve or stabilize renal function. The associations of baseline systolic, diastolic, and pulse pressures (PPs) with outcomes of blood pressure (BP) and renal function were examined in 243 patients who underwent renal angioplasty and stent placement. The average PP before the procedure in patients with improvements or stabilizations in renal function was 53 +/- 20 mm Hg, compared to 107 +/- 18 mm Hg (p <0.05) in those with poorer outcomes. The average PPs before procedure were 47 +/- 15 mm Hg in those with improvements in BP, 82 +/- 10 mm Hg in those with stabilizations of BP, and 111 +/- 14 mm Hg in those with worsening BP. All findings were statistically significant (p <0.05). In conclusion, wide PP may reflect more advanced vascular stiffness and renal disease distinguishing patients less likely to benefit from revascularization.

Prospective study of cardiac sarcoid mimicking arrhythmogenic right ventricular dysplasia.

INTRODUCTION: Case studies indicate that cardiac sarcoid may mimic the clinical presentation of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C); however, the incidence and clinical predictors to diagnose cardiac sarcoid in patients who meet International Task Force criteria for ARVD/C are unknown. METHODS AND RESULTS: Patients referred for evaluation of left bundle branch block (LBBB)-type ventricular arrhythmia and suspected ARVD/C were prospectively evaluated by a standardized protocol including right ventricle (RV) cineangiography-guided myocardial biopsy. Sixteen patients had definite ARVD/C and four had probable ARVD/C. Three patients were found to have noncaseating granulomas on biopsy consistent with sarcoid. Age, systemic symptoms, findings on chest X-ray or magnetic resonance imaging (MRI), type of ventricular arrhythmia, RV function, ECG abnormalities, and the presence or duration of late potentials did not discriminate between sarcoid and ARVD/C. Left ventricular dysfunction (ejection fraction <50%) was present in 3/3 patients with cardiac sarcoid, but only 2/17 remaining patients with definite or probable ARVD/C (P = 0.01). CONCLUSIONS: In this prospective study of consecutive patients with suspected ARVD/C evaluated by a standard protocol including biopsy, the incidence of cardiac sarcoid was surprisingly high (15%). Clinical features, with the exception of left ventricular dysfunction and histological findings, did not discriminate between the two entities.

Paradoxical embolism to the central nervous system after sexual intercourse in a young woman with a complex atrial septal abnormality.

Ischemic stroke during sexual intercourse is an unusual occurrence. We report the evaluation and treatment of a young woman on oral contraceptives, with a complex atrial septal abnormality and right lower extremity deep vein thrombus, who had an ischemic stroke during sexual intercourse. Successful treatment was accomplished with administration of intra-arterial tissue plasminogen activator and subsequent transvascular occlusion of the atrial septal abnormality.

Stroke and myocardial infarction as late complications of lung transplantation.

A 64-year-old man who had received a lung transplant later presented with an air embolism that caused ST-segment elevation myocardial infarction, multiple strokes, and death. Transesophageal echocardiography was used to document air bubbles crossing from a bronchial fistula to a pulmonary vein and into the left atrium. Spontaneous air was seen entering a pulmonary vein during positive-pressure ventilation and exiting through the left ventricular outflow tract. Autopsy confirmed the presence of a probe-patent bronchial-to-pulmonary vein fistula within a focus of necrosis and infection with Aspergillus flavus, an angioinvasive organism. The potential for intravascular gas arising from the anastomotic site should be considered when transplant recipients who present with myocardial or peripheral arterial infarction are evaluated.

Safety and efficacy of the 2.25-mm sirolimus-eluting Bx Velocity stent in the treatment of patients with de novo native coronary artery lesions: the SIRIUS 2.25 trial.

Smaller reference vessel diameter is a recognized determinant of in-stent restenosis. The SIRIUS 2.25 trial was a prospective, nonrandomized study including 100 patients (mean age 63.4 years; 64% men, 40% with diabetes mellitus) assessing the safety and efficacy of the 2.25-mm sirolimus-eluting Bx Velocity stent in patients with de novo native coronary lesions. Using propensity score matching for gender, diabetes mellitus, left anterior descending artery target vessel, lesion length, and reference vessel diameter, the outcomes were compared with historical control groups (angioplasty and Palmaz-Schatz stent arms from the STRESS/BENESTENT I/II trials and the Bx Velocity bare metal stent arm from the RAVEL and SIRIUS trials having a reference vessel diameter <3 mm). Use of the 2.25-mm sirolimus-eluting Bx Velocity stent was associated with a high rate of procedural success (97%) and a low rate of in-hospital major adverse cardiac events (2%). The primary end point, 6-month in-lesion binary angiographic restenosis, occurred less frequently in patients treated with the 2.25-mm sirolimus-eluting Bx Velocity stent than in each of 3 historical controls (16.9% vs 30.6%, p = 0.12; 36.5%, p <0.001; 45.9%, p <0.001, respectively). This translated into lower rates of 6-month target lesion revascularization in the 2.25-mm sirolimus-eluting Bx Velocity stent group (4.0% vs 15.0% in each of 3 control groups, p = 0.01 to <0.001). By multivariate analysis, in-lesion binary restenosis was predicted by multiple implanted stents (odds ratio 10.4, p = 0.002). Four of 13 patients who developed restenosis (30.8%) had a diffuse pattern of restenosis. In the long lesion tertile (mean lesion length 19.5 mm), the in-lesion binary restenosis rate was 27.6%. In conclusion, use of the 2.25-mm sirolimus-eluting Bx Velocity stent was safe and provided favorable 6-month clinical outcomes. Use of multiple stents (in longer lesions) was an independent predictor of in-lesion restenosis.

Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia.

STUDY OBJECTIVES: We investigated the effects of the direct thrombin inhibitor argatroban, patient demographics, and the platelet count on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding. DESIGN: We retrospectively analyzed thrombotic outcomes in 882 HIT patients (697 patients receiving mean argatroban doses of 1.7 to 2.0 mug/kg/min for 5 to 7 days, plus 185 historical control subjects) from previously reported prospective studies. Time-to-event analyses of our primary end point-a thrombotic composite of death due to thrombosis, amputation secondary to HIT-associated thrombosis, or new thrombosis within 37 days-and the individual components were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, gender, race, weight, and baseline platelet count. MEASUREMENTS AND RESULTS: Argatroban, vs control, significantly reduced the thrombotic composite risk (HIT: hazard ratio, 0.33; 95% confidence interval [CI], 0.20 to 0.54, p < 0.001; HIT with thrombosis: hazard ratio, 0.39; 95% CI, 0.25 to 0.62, p < 0.001), regardless of covariate adjustments. More argatroban-treated patients than control subjects remained thrombotic event free during follow-up, regardless of whether baseline thrombosis was absent (91% vs 73%) or present (72% vs 50%). Argatroban significantly reduced new thrombosis (p < 0.001) and death due to thrombosis (p

Amelioration of hypertrophic cardiomyopathy using nonsurgical septal ablation in a cirrhotic patient prior to liver transplantation.

A 53-year-old male with hepatitis C cirrhosis, who had been refused liver transplantation because of hypertrophic cardiomyopathy (HC), underwent nonsurgical septal ablation using alcohol with resolution of his ventricular outflow obstruction. This patient was able to subsequently undergo a successful deceased donor liver transplantation. This is the first reported case of alcohol induced septal ablation being performed in a cirrhotic patient with HC. Such nonsurgical procedures may be attractive in cirrhotic patients who are refused access to liver transplantation because of high surgical risk.

Antiplatelet agents: current drugs and future trends.

Antiplatelet drugs in clinical use are discussed in terms of their mechanisms of action and the relevancy of that to the physiology of platelets and the pathophysiology of arterial thrombosis. Current clinical usage is outlined in detail for each drug. Experimental antiplatelet drugs also are discussed.

New catheter design for cannulation of the anomalous right coronary artery arising from the left sinus of valsalva.

Cannulation of an anomalous right coronary artery during coronary angiography and percutaneous intervention poses significant technical difficulties using currently available catheter shapes. We describe a new catheter design and the cannulation technique for application of this catheter. The initial experience with this catheter in cases is reported.

Argatroban anticoagulation in patients with heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an intensely prothrombotic syndrome managed by discontinuation of heparin therapy and substitution of an alternative inhibitor of thrombin. We describe our experience with argatroban, a direct thrombin inhibitor, in patients with HIT or HIT with thrombosis (HITTS). METHODS: In this multicenter, nonrandomized prospective study, 418 patients with HIT were administered intravenous argatroban, 2 micro g/kg per minute, adjusted to maintain the activated partial thromboplastin time at 1.5 to 3 times the baseline value for a mean of 5 to 7 days. Comparisons were made with a historical control cohort (n = 185). The prospectively defined, primary efficacy end point was a composite of all-cause death, all-cause amputation, or new thrombosis in 37 days. Other end points included the components of the composite, death due to thrombosis, increased platelet count, and bleeding. RESULTS: In the HIT arm, the composite end point was significantly reduced in argatroban-treated patients vs controls (28.0% vs 38.8%; P =.04). In the HITTS arm, the composite end point occurred in 41.5% of argatroban-treated patients vs 56.5% of controls (P =.07). By time-to-event analysis of the composite end point, argatroban therapy was significantly better than historical control therapy in HIT (P =.02) and HITTS (P =.008). Argatroban therapy also significantly reduced new thrombosis in HIT and HITTS and death due to thrombosis in HITTS. There were no significant between-group differences in all-cause death or amputation. Platelet counts recovered more rapidly in argatroban-treated patients than in controls. Bleeding rates were similar between groups. CONCLUSION: Argatroban therapy, compared with historical control, improves outcomes, particularly new thrombosis and death due to thrombosis, in patients with heparin-induced thrombocytopenia.

Evaluation of a novel point-of-care enoxaparin monitor with central laboratory anti-Xa levels.

BACKGROUND: Measurement of enoxaparin's anticoagulant activity has been limited to specialized coagulation laboratories and has been impractical for areas needing rapid results, such as during coronary angioplasty. A new point-of-care device, Rapidpoint ENOX, was recently developed to measure clotting times with enoxaparin use. OBJECTIVES: To correlate ENOX times with anti-Xa levels among patients receiving enoxaparin. METHODS: A total of 166 patients receiving enoxaparin for the prevention of deep venous thrombosis or as treatment during acute coronary syndromes or angioplasty were prospectively studied. Citrated and non-citrated whole-blood (CWB and NCWB) samples were obtained at baseline and peak enoxaparin activity. ENOX times were measured with whole-blood, and the Stachrom anti-Xa assay was performed on the plasma from the remainder of the samples. The Pearson correlation coefficient was used to assess the relationship between these two assays. RESULTS: There was a strong linear correlation between the ENOX times and the anti-Xa activities for both CWB (r=0.89, p<0.001) and NCWB (r=0.82, p<0.001) when considering all 332 samples (baseline and peak). When baseline samples were excluded, the correlation remained strong for CWB ENOX times and anti-Xa levels (r=0.84, p<0.001), but was only moderate for NCWB (r=0.73, p<0.001). A CWB ENOX time of /=200 s corresponded to anti-Xa levels >/=0.8 IU/ml in 96% (93/96) of patients. CONCLUSIONS: Rapidpoint ENOX times correlate strongly to anti-Xa activities measured by the Stachrom Heparin Assays for citrated whole-blood samples. This novel test can be used for rapid bedside measurements of enoxaparin anticoagulant activity.

Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome associated with thrombosis. Alternative anticoagulation to heparin is needed for HIT patients during percutaneous coronary intervention (PCI). We evaluated argatroban, a direct thrombin inhibitor, for anticoagulation in this setting. Ninety-one HIT patients underwent 112 PCIs while on intravenous argatroban (25 microg/kg/min [350 microg/kg initial bolus], adjusted to achieve an activated clotting time of 300-450 sec). Primary efficacy endpoints were subjective assessments of the satisfactory outcome of the procedure and adequate anticoagulation during PCI. Among patients undergoing initial PCIs with argatroban (n = 91), 94.5% had a satisfactory outcome of the procedure and 97.8% achieved adequate anticoagulation. Death (zero patients), myocardial infarction (four patients), or revascularization (four patients) at 24 hr after PCI occurred in seven (7.7%) patients overall. One patient (1.1%) experienced periprocedural major bleeding. For patients who had subsequent hospitalizations (mean separation of 150 days) for repeat PCI using argatroban anticoagulation (n = 21), there were no unsatisfactory outcomes. Overall, outcomes were comparable with those historically reported for heparin. Argatroban therefore is a reasonable anticoagulant option in this setting, where current options are limited.