Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

BACKGROUND: Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). METHODS: Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. RESULTS: The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. CONCLUSION: We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

Technical success and long-term outcomes after anomalous right coronary artery stenting with cardiac computed tomography angiography correlation.

INTRODUCTION: Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. METHODS: Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. RESULTS: All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. CONCLUSIONS: Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

Endovascular Repair of Bilateral Internal Mammary Artery Aneurysms in a Patient with Marfan Syndrome-A Case Report.

Marfan syndrome (MFS) is an autosomal dominant condition that is caused by abnormal synthesis of connective tissue. The syndrome classically affects the ocular, musculoskeletal, and cardiovascular systems. The most common cardiovascular manifestations include mitral valve prolapse/regurgitation and aortic aneurysms at high risk of rupture and dissection. However, internal mammary artery (IMA) true aneurysms are rarely reported. In this case report, we describe a 43-year-old male patient with MFS and three previous thoracotomies referred for endovascular repair of bilateral IMA true aneurysms. To the best of our knowledge, there are no cases of endovascular treatment of bilateral IMA true aneurysms reported in the literature.

Nonhemostatic adverse effects of anticoagulants and antiplatelet agents.

The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.

Renal artery dissection following marathon running.

A 38-year-old, previously healthy man presented with flank pain after competing in a marathon. Initial laboratory tests and urinalysis were essentially normal. Both contrast enhanced-computed tomography and magnetic resonance angiography showed an infarcted region of the left lower kidney without renal artery dissection. Thromboembolism was suspected, but further testing was negative. The diagnosis of renal artery dissection was established by angiogram, showing dissection of the segmental branch. The patient remained normotensive, maintained normal renal function, and had resolution of pain symptoms prior to discharge. On the basis of our experience and review of the literature, renal artery dissection occurs in otherwise healthy men and often goes undiagnosed. The management strategy tends to be conservative unless the patient develops progressive decline in renal function or worsening hypertension, with an excellent prognosis. This case also shows the importance of discussing the pros and cons of extreme physical exertion with all patients.

Percutaneous coronary intervention in patients with acute coronary syndrome: focus on bivalirudin.

Previously, indirect thrombin inhibitors such as unfractionated heparin or low-molecular-weight heparin were used as a standard anticoagulation during percutaneous coronary intervention to prevent procedural thrombotic complications but at a risk of hemorrhagic complications. More recently, bivalirudin, a member of the direct thrombin inhibitor class, has been shown to have 1) predictable pharmacokinetics, 2) ability to inhibit free- and clot-bound thrombin, 3) no properties of platelet activation, 4) avoidance of heparin-induced thrombocytopenia, and 5) a significant reduction of bleeding without a reduction in thrombotic or ischemic endpoints compared to heparin and glycoprotein IIbIIIa inhibitors when used in patients presenting with acute coronary syndrome who are planned for an invasive treatment strategy.

Steroid induced atrial fibrillation.

A 72-year-old female presented with an acute flaure of Crohn's disease and received intravenous methylprednisolone. The following morning ECG showed atrial fibrillation with a rapid ventricular response of 111 bts/min, which spontaneously resolved within 7 hours. The underlying arrhythmogenenic mechanism is unknown.

Predictors of clinical outcome in patients with heparin-induced thrombocytopenia treated with direct thrombin inhibition.

We aimed to identify predictors of poor outcome in patients with heparin-induced thrombocytopenia, a serious immune-mediated reaction to heparin. All patients were treated with direct thrombin inhibition therapy, as part of two prospective studies. We performed a risk factor analysis of adverse outcomes (defined as death, amputation, new thrombosis, or their composite within a 37-day study period) in 809 patients from two reported prospective studies of the direct thrombin inhibitor argatroban in clinically diagnosed heparin-induced thrombocytopenia. We initially identified from among 14 baseline variables the significant predictors of poor outcome in the first study (304 patients), and then tested our resultant hypothesis in the second, independent study (505 patients), using multivariate analysis. Seven significant predictors were identified in the first study; three were confirmed in the second study. The strongest relationship occurred between the baseline platelet count and the composite of death, amputation, or new thrombosis (P = 0.0001), with the most severely thrombocytopenic patients being at greatest risk. The other significant associations were between renal impairment and death (odds ratio = 2.13, 95% confidence interval = 1.23-3.66, P = 0.007), and between cardiovascular surgery (particularly peripheral vascular surgery) and amputation (odds ratio = 3.39, 95% confidence interval = 1.65-6.95, P = 0.0009). In conclusion, in patients with clinically diagnosed heparin-induced thrombocytopenia, the severity of the baseline thrombocytopenia is the best predictor of death, amputation or thrombotic progression. The identification of higher risk subgroups for poor outcomes, such as patients with more severe thrombocytopenia or a history of renal impairment or peripheral vascular surgery, could allow more targeted therapy.

Long-term clinical outcomes of real-world experience using sirolimus-eluting stents in saphenous vein graft disease.

OBJECTIVE: To evaluate the long-term clinical outcomes of patients undergoing percutaneous coronary intervention for saphenous vein graft (SVG) disease. Specifically, we compared clinical endpoints of patients who received sirolimus-eluting stents (SES) versus bare-metal stents (BMS) for SVG disease. BACKGROUND: A recent small randomized-controlled trial (RCT) reported increased mortality with the use of SES in SVG disease. METHODS: We retrospectively identified patients who underwent SES placement for a SVG lesion(s) at our institutions over a 4-year period. The procedural and medical records were reviewed to identify predetermined clinical outcomes. RESULTS: 318 patients who underwent SES placement for a SVG lesion were identified. 7 patients were lost to follow-up. 141/311 patients (45%) received SES, while 170/311 (55%) received BMS. At a mean follow-up of 34 months, there was a reduction in target lesion revascularization (TLR) (7% vs. 14%, P = 0.07) without an increased risk of mortality (6% vs. 12%, P = 0.06) in patients who received SES compared to patients who received BMS. When compared to the recent RCT's SES patients at long-term follow-up, our SES patients had significantly less mortality; rates of myocardial infarction, TLR, target vessel revascularization, and major adverse cardiac events; and were more likely to be taking dual antiplatelet and statin medications. CONCLUSION: Our results support that SES used in SVG lesions result in a reduction in TLR without an increased risk of mortality, and therefore may be an equally safe and feasible technique for revascularization with excellent long-term clinical outcomes. These patients may benefit from prolonged dual antiplatelet and statin medication regimens.

Femoral angiogram prior to arteriotomy closure device does not reduce vascular complications in patients undergoing cardiac catheterization.

OBJECTIVES: To compare the efficacy of achieving hemostasis without vascular access site complications (VCs) in patients who did not undergo femoral angiogram (FA) prior to arteriotomy closure device (ACD) placement. BACKGROUND: Following coronary angiogram/percutaneous coronary intervention (CA/PCI), VCs increase morbidity and mortality. Previous studies in which an FA was highly recommended but not mandatory suggest that a predictor of VC is ACD use. METHODS: We retrospectively identified consecutive patients who underwent CA/PCI and attempted ACD deployment at our institution over a three-year period. These patients' medical and procedural records, angiogram films, and subsequent hospitalization records were reviewed to identify predetermined clinical outcomes. RESULTS: One thousand four hundred and twenty-two patients underwent CA/PCI from the transfemoral approach with ACD deployment. Seven hundred and eight (49.8%) patients did not undergo FA prior to ACD deployment. The use of ACD without FA guidance was not associated with an increased rate of combined measured clinical end-point; immediate ACD failure; retroperitoneal bleed; TIMI minor bleed; infectious complications; need for surgical intervention; or mortality (5.3 vs. 4.9; 2.7% vs. 2.2%; 1.4% vs. 0.9%; 0.5% vs. 0.4%; 0% vs. 0%; 0.1% vs. 0.1%; 0% vs. 0%, respectively, P = NS). CONCLUSION: We found no evidence that performing an FA prior to ACD placement as recommended by the manufacturer had any influence on the clinical success rate of ACD placement or rates of VCs. Therefore, ACD use without FA guidance in patients undergoing CA/PCI is an equally safe and effective method in successfully obtaining hemostasis without an increased risk of VCs.

Argatroban therapy for heparin-induced thrombocytopenia in acutely ill patients.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. To evaluate clinical outcomes and effects of argatroban therapy in acutely ill HIT patients. Retrospective analysis. Hospital in-patient. Acutely ill patients with clinically diagnosed HIT from previous multicenter, historically controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times 1.5 to 3 times baseline, or historical control therapy (ie, no direct thrombin inhibition). We identified 488 patients who received argatroban (N = 390; mean dose of 1.9 microg/kg/min for a mean 6 days) or historical control therapy (N = 98) for HIT. The primary all-cause composite endpoint of death, amputation, or new thrombosis within 37 days occurred in 133 (34.1%) argatroban-treated patients and 38 (38.8%) controls (P = .41). Argatroban, versus control, significantly reduced the primary thrombosis-related composite endpoint of death because of thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis (17.7% vs 30.6%, P = .007). Significant reductions also occurred in new thrombosis and death because of thrombosis. Major bleeding was similar between groups (7.7% vs 8.2%; P = .84). Adverse outcomes were more likely to occur in patients who were initially diagnosed with HIT and thrombosis, had undergone cardiac surgery, were not white, or had more severe thrombocytopenia. In acutely ill HIT patients, argatroban, versus historical control, provides effective antithrombotic therapy without increasing major bleeding. Patients with more severe thrombocytopenia or HIT-related thrombosis on HIT diagnosis have a poorer prognosis, emphasizing the importance of prompt recognition/ treatment of HIT in acutely ill patients.

Utility of BNP in differentiating constrictive pericarditis from restrictive cardiomyopathy in patients with renal insufficiency.

BACKGROUND: Differentiating between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCMP) is difficult because of similar clinical and hemodynamic presentation. Brain natriuretic peptide (BNP) has been reported a useful noninvasive biomarker to differentiate CP from RCMP; however, its utility in patients with renal insufficiency has not been evaluated. METHODS AND RESULTS: Consecutive patients with suspected CP or RCMP were enrolled. All but 7 patients underwent transseptal catheterization. BNP, renal function, and comorbid conditions were recorded at the time of the procedure. Renal function was estimated using the Cockcroft-Gault formula. Descriptive statistics, Student t-test, and Mann-Whitney U test were performed; P < .05 was significant. Twenty-two patients had hemodynamically or surgically proven CP or RC. In patients with CP, 9 had at least Stage II kidney disease (GFR <90 mL/min, mean 58) and 8 had normal or Stage I kidney disease (GFR >90 mL/min, mean 118). BNP was higher in patients with CP and renal insufficiency versus those with CP and normal renal function (433 versus 116 pg/mL; P = .016). BNP in patients with CP and normal renal function was lower than in patients with RC (116 versus 728 pg/mL; P = .005). CONCLUSION: BNP has reduced clinical utility in renal insufficiency to differentiate CP from RCMP.

Direct thrombin inhibition during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are undergoing percutaneous coronary intervention (PCI) are at particular risk of thrombosis due to the prothrombotic nature of HIT and the endovascular disruption from PCI. Patients require aggressive anticoagulation during PCI, and alternative, nonheparin anticoagulation is recommended over heparin in patients with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs). Multicenter, prospective studies have demonstrated that argatroban and lepirudin each reduce thrombosis in HIT and that argatroban and bivalirudin each provide adequate anticoagulation during PCI in patients with or at risk of HIT. We review current therapeutic practices with direct thrombin inhibitors in patients with or at risk of HIT during PCI, including individuals requiring periprocedural anticoagulation, and the factors influencing the choice of DTI in this setting.

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

Transitioning from argatroban to warfarin therapy in patients with heparin-induced thrombocytopenia.

Argatroban, a direct thrombin inhibitor used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT), is routinely monitored using the activated partial thromboplastin time (aPTT) yet also prolongs the international normalized ratio (INR). Peritransitional INRs, aPTTs, anticoagulant dosing patterns, and outcomes were evaluated in 165 HIT patients who were transitioned, without guidelines, from argatroban to warfarin therapy. Argatroban (median doses: 1.5-2.0 mcg/kg/min) and warfarin (median dose: 5 mg initially with 3.8 mg/day thereafter) overlapped a median 4 days. Median (5-95th percentile) aPTTs (in seconds) and INRs, respectively, were 59.8 (38.8-82.9) and 3.2 (1.7-7.0) during argatroban monotherapy, 68.6 (44.5-104) and 5.3 (2.4-16) maximally during cotherapy, 59.9 (38.7-92.2) and 4.0 (2.2-11.6) immediately before argatroban cessation during cotherapy, and 36.0 (25.6-60.2) and 2.3 (1.3-7.3) within a median 10-12 hours after argatroban cessation. Major bleeding occurred in 1 (0.6%) patient pretransitionally and no patient during or after cotherapy. Eighteen (10.9%) patients experienced 19 peritransitional adverse outcomes (one death, two amputations, 16 new thromboses); these patients had more severe HIT than event-free patients (median baseline platelet count, 39 vs. 83 x 10(9)/L). Of 108 patients with post-transitional INR data, 43 achieved a therapeutic INR (prospectively defined as 1.9-3.5), 34 were subtherapeutic, and 31 were supratherapeutic, with no across-group trend in new thrombosis. Hence in the absence of guidelines, physicians transfer patients from argatroban to warfarin therapy with acceptably low complication rates in HIT, without systematically over- or under-dosing warfarin. Furthermore, INRs greater than 5 commonly occur in HIT patients during argatroban monotherapy and argatroban/warfarin cotherapy, without major bleeding.

Thiazolidinediones do not reduce target vessel revascularization in diabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: Animal studies have suggested that thiazolidinediones (TZDs) have antirestenotic properties. However, human data are lacking. The goal of this single-center study was to assess the target vessel revascularization (TVR) rate following percutaneous coronary intervention (PCI) among diabetic patients according to TZD use. METHODS: A total of 325 consecutive diabetic patients who underwent PCI between January 2000 and December 2001 were included in the analysis. Among them, 82 patients were on TZD and 243 patients were on other hypoglycemic regimens. All patients were treated with stents and platelet glycoprotein IIb/IIIa inhibitors at the time of intervention. TVR and death/myocardial infarction/TVR were assessed at 1 year. RESULTS: TZD patients were more likely to be younger, male and have hyperlipidemia. TVR occurred in 36.6% of TZD patients compared with 23.9% of non-TZD patients (p=0.04). One-year death, myocardial infarction and TVR occurred in 41.1% of TZD patients compared with 30.8% of non-TZD patients (p=0.04). CONCLUSION: In this retrospective analysis, TZD therapy did not decrease the need for repeat revascularization following PCI. Prospective randomized studies are warranted.

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.