Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II).

OBJECTIVES: The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial evaluated the safety and efficacy of the coronary Orbital Atherectomy System (OAS) to prepare de novo, severely calcified coronary lesions for stent placement. BACKGROUND: Despite advances in interventional techniques, treatment of calcified coronary lesions remains a challenge. Stent placement in these lesions may result in stent underexpansion, malapposition, and procedural complications. METHODS: ORBIT II is a prospective, multicenter, nonblinded clinical trial that enrolled 443 consecutive patients with severely calcified coronary lesions at 49 U.S. sites from May 25, 2010, to November 26, 2012. Investigators used the centrifugal action of the OAS diamond-coated crown to modify calcified lesions prior to stent placement. RESULTS: The pre-procedure mean minimal lumen diameter of 0.5 mm increased to 2.9 mm after the procedure. The primary safety endpoint was 89.6% freedom from 30-day major adverse cardiac events compared with the performance goal of 83%. The primary efficacy endpoint (residual stenosis <50% post-stent without in-hospital major adverse cardiac events) was 88.9% compared with the performance goal of 82%. Stent delivery occurred successfully in 97.7% of cases with <50% stenosis in 98.6% of subjects. Low rates of in-hospital Q-wave myocardial infarction (0.7%), cardiac death (0.2%), and target vessel revascularization (0.7%) were reported. CONCLUSIONS: The ORBIT II coronary OAS trial met both the primary safety and efficacy endpoints by significant margins. Preparation of severely calcified plaque with the OAS not only helped facilitate stent delivery, but improved both acute and 30-day clinical outcomes compared with the outcomes of historic control subjects in this difficult-to-treat patient population. (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions [ORBIT II]; NCT01092416).

Troponin I levels in patients with preeclampsia.

INTRODUCTION: Preeclampsia involves a diffuse inflammatory state and elevated levels of troponins in patients with preeclampsia have been anecdotally reported. It is, however, unknown whether it is attributable to the preeclampsia. OBJECTIVE: We sought to determine the troponin I levels at the time of delivery in pregnant women with and without preeclampsia. METHODS: Plasma samples were obtained at the time of delivery and serum troponin I was measured by ELISA method. RESULTS: Thirty-nine women were included (20 with preeclampsia and 19 without). Mean troponin I level was 0.008 ng/mL in patients with preeclampsia and 0.01 ng/mL in controls (P =.59). The highest troponin I level was 0.04 ng/mL for both patients with and without preeclampsia. CONCLUSIONS: Preeclampsia was not associated with a rise in troponin I levels in our study. Patients with preeclampsia and elevated troponin levels should have further cardiac investigations.

Presence of asymmetric dimethylarginine gradients across high-grade lesions in patients with coronary artery disease.

BACKGROUND: Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is a systemic marker of endothelial dysfunction. Although experimental evidence indicates that asymmetric dimethylarginine may play an important role in atherogenesis, local asymmetric dimethylarginine levels have not been measured in vivo. OBJECTIVES: We sought to determine whether: (i) asymmetric dimethylarginine is elevated locally at sites of coronary lesions, (ii) systemic asymmetric dimethylarginine concentrations correlate with local levels, and (iii) percutaneous coronary intervention produces immediate local asymmetric dimethylarginine elevation. METHODS: In patients undergoing percutaneous coronary intervention (n=15), blood samples were obtained from a peripheral venous site, the coronary ostium proximal to the lesion and the coronary vessel distal to the lesion, before percutaneous coronary intervention. Samples were also obtained distal to the coronary lesion immediately after percutaneous coronary intervention and from the peripheral venous line 24 h after percutaneous coronary intervention. RESULTS: Asymmetric dimethylarginine gradients were present across the coronary bed: local asymmetric dimethylarginine (micromol/l) was significantly higher distal to coronary lesions compared with proximally (2.39+/-1.27 vs. 1.52+/-0.68, P=0.005), and to systemic venous levels (2.39+/-1.27 vs. 1.17+/-0.72, P=0.001). Local asymmetric dimethylarginine did not increase immediately after percutaneous coronary intervention (1.88+/-0.89 vs. 2.39+/-1.27, P=0.11). Peripheral venous percutaneous coronary intervention levels 24 h after percutaneous coronary intervention were similar to baseline values (1.17+/-1.2 vs. 1.17+/-0.72, P=0.98). CONCLUSION: Asymmetric dimethylarginine gradients exist across coronary lesions, suggesting asymmetric dimethylarginine release at the plaque site. Local asymmetric dimethylarginine accumulation may contribute to the endothelial dysfunction associated with high-grade coronary lesions. Peripheral asymmetric dimethylarginine is a marker of generalized endothelial dysfunction, but our findings highlight its limitation in detecting focal injury.

The influence of low (81 mg) versus high (325 mg) doses of ASA on the incidence of sirolimus-eluting stent thrombosis.

BACKGROUND: Conflicting opinion exists regarding the optimal dose of acetyl salicylic acid (ASA) to be given after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). We sought to evaluate the influence of ASA dose on the incidence of unexplained subacute and late stent thrombosis in the era of DES. METHODS: We performed a retrospective analysis of the incidence of subacute and late stent thrombosis in our patient population over a 2-year period. The analysis was limited to patients being discharged and maintained on a daily ASA dose of either 81 mg or 325 mg and having received at least 1 sirolimus-eluting stent. RESULTS: During the study period, 1,093 patients (1,807 separate PCI procedures) met the inclusion criteria. The incidence of unexplained subacute and late stent thrombosis was 1.1% in the study population (12 out of 1,093 patients). When considering the total number of individual procedures performed on the study population during the study period (1,807 procedures), the incidence of unexplained subacute or late stent thrombosis was 0.7%. Six were subacute and 6 were late thrombosis. No significant difference was observed in the incidence of stent thrombosis between the 2 ASA dose groups. Seven patients had stent thrombosis in the 81 mg group (1.2% of 583 patients), while 5 had thrombosis in the 325 mg group (1% of 510 patients); p = 0.727. CONCLUSION: In conclusion, we found no significant difference in the incidence of unexplained subacute or late stent thrombosis with the use of an 81 mg versus 325 mg dose of aspirin post-PCI with sirolimus-eluting stents.

Alcohol septal ablation after failed surgical myectomy.

We describe the case of a successful alcohol septal ablation in a patient with persistent gradient and severe symptoms postsurgical myectomy. The alcohol ablation of the thickened septum abolished the left ventricular outflow gradient and the systolic anterior motion (SAM) of the mitral valve. Although the surgical literature advocates for mitral valve replacement in patients who continue to have SAM with significant outflow obstruction postmyectomy, targeted alcohol septal ablation of the remaining septum appears to be an attractive alternative.

Invasive assessment of mitral regurgitation: comparison of hemodynamic parameters.

OBJECTIVES: We sought to analyze several new hemodynamic characteristics which address the interplay of left atrial (LA) and left ventricular (LV) pressures, as well as to re-analyze several other V wave characteristics employed in the determination of mitral regurgitation (MR) severity in order to determine which, if any, had adequate correlation with grade of MR for clinical utility. BACKGROUND: Invasive assessment of mitral regurgitation includes analysis of intracardiac pressures and LV angiography. The V wave, when obtained from the pulmonary capillary wedge position (PCWP), and its various characteristics are believed to be of limited value for prediction of MR severity. METHOD: We analyzed the transeptal pressure tracings of patients with various degrees of MR. Several relationships from the simultaneous pressure-time curves of the LA and LV were defined. Biplane left ventricular angiography was used to grade MR. Correlation between each parameter and MR grade was determined by calculating a Pearson correlation coefficient. RESULTS: The ratio of the area under the V wave to the LV systolic area (V(a)/LV(a)) best correlates with the degree of MR with a Pearson correlation coefficient of 0.60. The V(a)/LV(a) was significantly lower in patients with 0-1+ MR compared to > or =2+ MR (0.14 vs. 0.23 p = 0.002). CONCLUSIONS: Invasive hemodynamic assessment of MR severity could be enhanced by calculating our new ratio, V(a)/LV(a), due to its ability to account for LV work that is lost to the LA with a proportional decrease in forward or useful LV work with progressively increasing severity of MR.

Clinical experience with rotational atherectomy in patients with severe left ventricular dysfunction.

OBJECTIVE: To evaluate the safety and efficacy of rotational atherectomy (RA) in patients with severe left ventricular (LV) dysfunction. BACKGROUND: RA, using a rotating diamond-crystal burr, is most commonly used to open lesions with severe calcification or diffuse disease that may prove difficult to cross or dilate. However, RA generates microparticular debris that may attenuate the coronary microcirculation, inducing transient myocardial stunning and LV dysfunction. In fact, the manufacturer does not support RA use in patients with severe LV dysfunction. METHODS: We retrospectively identified patients with a LV ejection fraction < 30% who underwent RA in our institution over a 4-year period. The medical records were reviewed and risk factors for cardiac disease were recorded. The procedural reports and subsequent hospitalization records were reviewed to identify predetermined positive and negative outcomes. RESULTS: Twenty-three patients (17 males) who underwent RA with severe LV dysfunction (mean LVEF 21.3%) were identified. The majority of these patients had multivessel coronary artery disease, hypertension, hyperlipidemia and/or tobacco use. Also, a substantial subset had diabetes, renal insufficiency and or in-stent restenosis. RA was 100% successful in opening the lesions without any in-hospital procedure-related mortality. Three patients experienced periprocedural myocardial infarctions. One patient died from malignancy during hospitalization. There were no major adverse cardiac events at 30 days. CONCLUSION: The transient effect of RA on ventricular function did not adversely affect short-term outcomes in our study population. These results suggest that RA, when performed by experienced operators, is safe and feasible in patients with severe LV dysfunction.

Coronary artery perforation during percutaneous coronary intervention: incidence and outcomes in the new interventional era.

BACKGROUND: Coronary artery perforation (CP) is a serious complication of percutaneous coronary intervention (PCI). We sought to define the incidence and outcome of CP given the advance in interventional techniques, devices and use of glycoprotein inhibitors (GP IIb/IIIa). METHODS: We retrospectively reviewed the records of patients who underwent PCI at our institution over a four-year period. The incidence of CP was derived from patient records and then confirmed by reviewing the angiogram. Perforations were classified as Type 1, 2, or 3, as previously defined. RESULTS: A total of 4,886 patients underwent PCI. Atherectomy devices were used in 329 patients and GP IIb/IIIa in 2,200 patients. Twenty-five CP were identified (0.5% incidence). Six were Type 1 (24%), 10 were Type 2 (40%), and 9 were Type 3 (36%). 13/25 (52%) of the CP were Type C Lesions, and 12/25 (48%) occurred in calcified vessels. All Type 1 perforations were caused by coronary wires and 4/6 CP occurred with the use of hydrophilic and extra stiff wires. Type 2 perforations were caused by coronary wires in 8/10 CP, and by stent deployment in 2/10. Two patients with Type 2 CP sustained a non-ST-elevation myocardial infarction. Type 3 perforations were caused by stent placement in 4/9 CP, 2/9 by atherectomy devices, and 3/9 by coronary wires. Four patients with Type 3 CP underwent pericardial drainage, 5 patients had a myocardial infarction and 2 patients died. CONCLUSION: Type 1 and 2 perforations are predominately caused by hydrophilic and stiff wires and do not require pericardial drainage or surgical intervention. Type 3 perforations are more often associated with stent and device use. A majority of Type 3 perforations can be initially managed by percutaneous methods.

Antiplatelet therapy in anticoagulated patients requiring coronary intervention.

OBJECTIVE: To define the optimal antiplatelet regime in patients requiring long-term anticoagulation who undergo percutaneous coronary intervention. BACKGROUND: Antiplatelet therapy following coronary intervention consists of a regime of aspirin and clopidogrel for the prevention of subacute stent thrombosis. The optimal antiplatelet therapy post-coronary intervention in patients on ongoing anticoagulation therapy remains to be defined. Addition of aspirin and clopidogrel to patients already on warfarin increases the risk of bleeding, while withholding antiplatelet therapy increases the risk of stent thrombosis. Discontinuation of warfarin in turn increases the risk of thromboembolism. METHODS: We performed a systematic review and synthesis of the English language literature examining the risk of subacute thrombosis with various antiplatelet regimens and the risk for thromboembolism with and without warfarin. The risk of bleeding complications with various drug combinations were reviewed. CONCLUSIONS: There are no data from randomized trials to clarify the optimum treatment in these patients; and the feasibility of such studies may be questionable. Hence, treatment decisions continue to be made on an individualized basis and should include assimilation of information on key factors, including the risk of bleeding and the risk of thromboembolism.

The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy.

OBJECTIVES: We sought to determine the usefulness of brain natriuretic peptide (BNP) measurements to differentiate constrictive pericarditis (CP) from restrictive cardiomyopathy (RCMP). BACKGROUND: The differentiation of CP from RCMP may be clinically difficult and often requires hemodynamic assessment. No laboratory marker has been shown to differentiate the two conditions. METHODS: We measured BNP levels in 11 patients suspected of having either CP or RCMP. All patients had hemodynamic assessment the day of BNP measurements. RESULTS: Six patients had CP and five patients had RCMP based on established hemodynamic criteria. Both CP and RCMP patients had similar elevation in intracardiac pressures. Despite similar pressures, the mean plasma BNP levels were significantly higher in RCMP compared to CP (825.8 +/- 172.2 pg/ml vs. 128.0 +/- 52.7 pg/ml, p < 0.001, respectively). CONCLUSIONS: The BNP levels are significantly elevated in RCMP compared to CP patients; BNP may prove to be a useful noninvasive marker for the differentiation of the two conditions.

Use of intravenous abciximab as adjunctive therapy for carotid angioplasty and stent placement.

The benefit of intravenous abciximab as an adjunctive to percutaneous coronary intervention has been demonstrated in large-scale randomized studies. The role of intravenous abciximab is being defined in carotid angioplasty and stent placement as the procedure is gaining popularity for the treatment of high-grade carotid stenosis in patients considered high-risk for carotid endarterectomy. This paper summarizes the pathophysiological basis and the available data for the use of abciximab as an adjunct to carotid artery stenting.

Cardiovascular manifestations of acute intracranial lesions: pathophysiology, manifestations, and treatment.

The objective of this article was to review the effects of acute intracranial lesions on myocardial function. The authors reviewed scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through January 2002. Pertinent literature was referenced, including clinical and laboratory investigations, to demonstrate the effects of acute intracranial lesions on the cardiovascular system. The literature was reviewed to summarize the mechanisms of cardiac damage and clinical manifestations and treatment of cardiovascular dysfunction caused by acute intracranial lesions. Myocardial damage and rhythm disturbances were shown to occur with acute intracranial neurological disease. The subgroup of patients used in this study formed a substantial pool of cardiac donors for cardiac transplantation. The pathophysiology of myocardial dysfunction and the optimal management continues to be a source of debate. In this article, the authors will review the anatomy, the available evidence of the pathophysiology, and the management of this complex group of patients. They will also discuss areas that need to be further investigated. Cardiovascular effects of acute intracranial lesions are common and contribute to increased morbidity and mortality.