Multimodality Imaging for the Evaluation of an Undifferentiated Pleomorphic Sarcoma Presenting as Cardioembolic Stroke.

Background: Cancer and ischemic stroke are associated with significant morbidity and mortality. Hypercoagulability, disseminated intravascular coagulation, venous-to-arterial embolism, and non-bacterial thrombotic endocarditis are among recognized mechanisms. Emboli to the brain, or to other organs, are known to occur as a consequence of liberated thrombotic debris originating from the thrombogenic surface of intracardiac neoplastic entities. The most common primary malignancy of the heart is sarcoma; however, masses that occur in the heart are 20 to 40 times more likely as a consequence of metastasis from other sites. Case Report. A 67-year-old woman presented to the emergency room with two brief episodes of dizziness and diplopia for 2 minutes. She had a medical history of provoked upper extremity DVT after a fracture, hypothyroidism, hyperlipidemia, and soft tissue sarcoma. The sarcoma was initially diagnosed in, and subsequently resected from, the right triceps muscle. During posttreatment surveillance, a second lesion was discovered in the left upper pulmonary lobe, and this was also completely resected 9 months following initial diagnosis. We present a case of a woman with a tertiary (cardiac) site sarcoma that presented with embolic stroke. Conclusion: Our case highlights the benefits of multimodality imaging, heart-team approach with oncology support to define anatomy, thereby enable surgical treatment, of a complex intracardiac lesion.

Inflammation and atherosclerosis: Cardiovascular evaluation in patients with autoimmune diseases.

Evidence now indicates that inflammation contributes considerably to the initiation and progression of atherosclerosis and active inflammatory processes may trigger plaque rupture and enhance the risk of coronary thrombosis leading to a clinical ischemic event. Interest in characterizing inflammatory markers that predict clinical events have dominated clinical investigation. Such markers include C-reactive protein, Fibrinogen and a number of interleukins. Human macrophages avidly phagocytize cholesterol crystals. These cholesterol crystals induce a dose-dependent secretion of mature Interleukin 1-beta (IL-1ß) from human monocytes and macrophages (an NLRP3 inflammasome-mediated pathway). Since IL-1ß production leads to increased levels of IL-6 and C-reactive protein, this could be a mechanistic link between early deposition of cholesterol crystals within the vessel wall to the macrophage-monocyte interactions that initiate fatty streaks and promote local atherosclerotic progression. We have entered a time where a pure anti-inflammatory drug without significant effects on lipids or any other traditional cardiovascular risk factor decreased cardiovascular events. Patients with autoimmune diseases are at increase cardiovascular risk. In this review we describe the link between inflammation and atherosclerosis. Furthermore we explore the data regarding primary prevention, cardiac imaging for risk stratification and the implications of targeting inflammation in patients with autoimmune disease.

Comparison of treatment strategies for femoro-popliteal disease: A network meta-analysis.

OBJECTIVES: We sought to compare treatment strategies in a Bayesian network meta-analysis of randomized controlled trials. BACKGROUND: Peripheral artery disease (PAD) is a prevalent morbidity that is treated with various strategies. METHODS: We performed a MEDLINE search for randomized studies comparing at least 2 treatment strategies, including bypass surgery, percutaneous transluminal angioplasty (PTA) balloons, stents, covered stents, drug-eluting stents (DES), and drug-coated balloons (DCB), in patients with native femoro-popliteal disease. Mixed treatment comparison model generation was performed to directly and indirectly compare the strategies in terms of restenosis and target lesion revascularization (TLR) presented as odds ratios (OR, [95% credible intervals]). RESULTS: Twenty-nine studies with 4,820 patients were included in the present study. PTA was the largest group with 1,900 patients, followed by DCB (n = 1,343), bare metal stents (n = 941), covered stents (n = 304), DES (n = 236), and bypass (n = 92). Mean age was 68 ± 9 years, 64% were male, 37% diabetic, and 55% smokers. Mean lesion length was 77 ± 44 mm, and 39% were total occlusions. Bayesian hierarchical random-effects model demonstrated all treatments were significantly better than, or had a trend toward superiority over, PTA, with DCB ranking well in both restenosis (OR = 0.29, [0.17-0.47]) and TLR (OR = 0.31, [0.20-0.46]). Nonetheless, none of the therapies showed superiority in terms of survival or amputations. CONCLUSION: Treatment of femoro-popliteal disease has significantly evolved in recent years, with higher rates of patency and freedom from TLR. However, the utility of these treatment strategies in terms of reduction of amputations and overall survival remains in question.

Vascular access in critical limb ischemia.

Currently, percutaneous endovascular intervention is considered a first line of therapy for treating patients with critical limb ischemia. As the result of remarkable development of techniques and technologies, percutaneous endovascular intervention has led to rates of limb salvage comparable to those achieved with bypass surgery, with fewer complications, even in the presence of lower rates of long-term patency. Currently, interventionalists have a multiplicity of access routes including smaller arteries, with both antegrade and retrograde approaches. Therefore, the choice of the optimal access site has become an integral part of the success of the percutaneous intervention. By understanding the technical aspects, as well as the advantages and limitations of each approach, the interventionalists can improve clinical outcomes in patients with severe peripheral arterial disease. This article reviews the access routes in critical limb ischemia, their advantages and disadvantages, and the clinical outcomes of each.

Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium.

INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model. METHODS: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

Does the disparity in baseline characteristics of patients undergoing transcatheter aortic valve replacement with 23 mm vs. 26 mm valves impact clinical outcome?

OBJECTIVES: We sought to identify if baseline characteristic differences in patients who receive a 23 mm vs. 26 mm valve impact clinical outcomes. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is currently an approved therapy for patients with severe aortic stenosis who are considered inoperable or are at high risk. METHODS: We retrospectively examined baseline characteristics and outcomes of patients receiving a 23 mm (n = 132) vs. 26 mm valve (n = 81) via the transfemoral approach. RESULTS: Gender (P < 0.01), previous coronary artery bypass surgery (P < 0.01), history of atrial fibrillation (P = 0.04), and mean Society of Thoracic Surgeons (STS) score (P < 0.01) were significantly different between groups. There were no significant differences in the rates of minor/major vascular complications (2.2 vs. 3.7%, P = 0.68 and 13.0 vs. 12.3%, P = 0.89, respectively). Bleeding complications were also comparable (major bleed 2.3 vs. 1%, P >0.99, minor bleed 19.0 vs. 22.0%, P = 0.67 and life threatening bleed 7.0 vs. 5.0%, P = 0.77). In-hospital death (6.0 vs. 5.0%, P >0.99), 30-day all-cause death (7.6 vs. 6.2%, P = 0.69), and all-cause death at 1 year (17.4 vs. 25.9%, P = 0.13) were also similar between groups. Gender, valve size, previous coronary bypass surgery and atrial fibrillation were not independently associated with mortality; however, on multivariate analysis STS score was (HR 1.11; 95% CI 1.02-1.19; P = 0.01). CONCLUSION: Patients undergoing TAVR with 23 and 26 mm valves have similar clinical outcomes despite significant differences in baseline characteristics. © 2015 Wiley Periodicals, Inc.

The choice of arterial access for percutaneous coronary intervention and its impact on outcome: An expert opinion perspective.

The prevention of major bleeding during percutaneous coronary intervention is one of the most widely discussed and often controversial topics within interventional cardiology. The choice of arterial access should be considered a mechanism for bleeding avoidance, and various strategies have been proposed to prevent or lower major bleeding and vascular complications with varying levels of strength. Herein, we review the current literature on arterial access as a bleeding avoidance strategy during percutaneous coronary intervention and its impact on outcome and provide a consensus opinion based on the strength of the evidence supporting various techniques.

Oblique coronary artery prolongation approach in anomalous left coronary artery from the pulmonary artery in a low-birth-weight neonate.

A 19-day-old newborn girl weighing 1.9-kg was born with anomalous origin of the left coronary artery (LCA) from the pulmonary artery (PA). Because of the small anatomic structures and long distance between the anomalous origin of the LCA high within the left posterior sinus of the main PA, a simple transfer of the anomalous LCA to the aorta was deemed impossible. A coronary button was created with an oblique flap of tissue cut from the posterior pulmonary arterial wall. An oblique flap was created from the anterior aortic wall. The two flaps were used to create a tubular prolongation that connected the LCA to the aorta. This created a tension-free anastomosis with potential for growth. The aorta and PA were then patched with pericardium. A left coronary angiogram three years after surgery demonstrated a patent coronary tube.

Meta-analysis of direct and indirect comparison of ticagrelor and prasugrel effects on platelet reactivity.

Studies have linked on-treatment platelet reactivity (PR) to adverse clinical outcomes. Because new P2Y12 inhibitors (prasugrel and ticagrelor) have been predominantly tested against clopidogrel, data on pharmacodynamic comparisons between these 2 drugs are scarce. We compared ticagrelor with prasugrel in a network meta-analysis. PubMed, Cochrane, and EMBASE were searched for studies assessing PR in patients with coronary artery disease treated with ticagrelor or prasugrel. All studies using prasugrel and/or ticagrelor providing platelet function measurement data using VerifyNow P2Y12 reaction units (PRUs), platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein phosphorylation, or maximal platelet aggregation (MPA) by light transmission aggregometry were considered eligible. Mixed treatment comparison models directly compared ticagrelor and prasugrel and indirectly compared them using clopidogrel as a comparator with data presented as mean difference (95% confidence interval). Data were extracted from 29 studies, including 5,395 patients. Compared with clopidogrel 75 mg, both prasugrel 10 mg and ticagrelor 90 mg twice daily were associated with lower PRU (mean difference -117 [-134.1, -100.5] and -159.7 [-182.6, -136.6], respectively), a lower PRI (-24.2 [-28.2, -20.3] and -33.6 [-39.9, -27.6], respectively), and lower MPA (-11.8 [-17, -6.3] and -20.7 [-28.5, -12.8], respectively). Similar results were obtained with clopidogrel 150 mg. Ticagrelor 90 mg twice daily was associated with lower PRU (-42.5 [-62.9, -21.9]), lower PRI (-9.3 [-15.6, -3.5]), and lower MPA (-8.9 [-16.4, -1.2]) compared with prasugrel 10 mg. In conclusion, our meta-analysis suggests that ticagrelor achieved significantly lower on-treatment PR compared with prasugrel, with both being superior to clopidogrel standard or high dose.

Impact of blood transfusions on short- and long-term mortality in patients who underwent transcatheter aortic valve implantation.

Baseline anemia is associated with transfusions and increased risk of mortality in patients who underwent cardiac surgery and percutaneous coronary intervention. The impact of blood transfusions in anemic patients who underwent transcatheter aortic valve implantation (TAVI) remains unclear. All patients who underwent transfemoral TAVI at our institution were retrospectively included. We determined the effect of blood transfusions on short- and long-term mortality and its interaction with baseline hemoglobin levels and bleeding complications. Additionally, we evaluated baseline hemoglobin effect on mortality. A total of 332 patients were included. All patients (99%) except 2 (1%) met the definition for anemia. Of the 332 patients, 124 (37%) received a blood transfusion and 208 (63%) did not. Blood transfusions were associated with increased in-hospital (p <0.001), 30-day (p <0.001), and 1-year (28% vs 13%, p = 0.001) mortality; however, after a landmark analysis, the effect of blood transfusion on mortality was only seen within 30 days of the procedure (p = 0.001). The increased risk of mortality associated with blood transfusion was present after multivariate adjustment at 30 days (hazard ratio 3.59 [1.04 to 12.4]; p = 0.04). Major vascular complications were a correlate for short- and long-term death. In contrast, baseline hemoglobin level and bleeding complications were not independently associated with mortality. The p value for interaction was not significant between transfusion and hemoglobin level and for transfusion and bleeding complication and transfusion and major vascular complication. In conclusion, the presence of anemia in patients who underwent TAVI does not affect mortality. Transfusion is a correlate of all-cause mortality in this patient population and should be used with caution.

Safety of eptifibatide when added to bivalirudin during ST-segment elevation myocardial infarction.

BACKGROUND: Patients presenting with ST-segment elevation myocardial infarction (STEMI) represent a high-risk group for in-hospital adverse events and bleeding. The safety and outcomes of eptifibatide in addition to bivalirudin in this population have not been determined. METHODS: Over an 11-year period, we identified 1849 STEMI patients undergoing primary percutaneous coronary intervention (PCI), of which 1639 received bivalirudin monotherapy compared with 210 patients who received both bivalirudin and provisional eptifibatide. Safety of combination therapy was assessed by the occurrence of thrombolysis in myocardial infarction (TIMI) major bleeding. In-hospital event rates of death, Q-wave myocardial infarction (MI), and acute stent thrombosis were evaluated for efficacy. Multivariate analysis was used to adjust for significant differences between groups. RESULTS: Patients treated with bivalirudin plus eptifibatide, when compared with patients with bivalirudin monotherapy, had increased rates of cardiogenic shock (15.7% vs. 9.4%), aspiration thrombectomy (48.5% vs. 23.7%), pre-TIMI flow ≤1 (63.5% vs. 40%), and higher peak troponin I (93.65±92.7 vs. 49.16±81.59; all p <0.01). These, however, were not associated with differences in the primary end point after adjusting for significant baseline and procedural characteristics (OR: 1.63; 95% CI, 0.90-2.96, p=0.12). Importantly, TIMI major bleeding was not significantly different between groups (OR 1.78; 95% CI, 0.79-2.95, p=0.20). CONCLUSION: The addition of eptifibatide to bivalirudin during primary PCI reflects a high-risk STEMI population. This therapy results in similar in-hospital outcomes without an increase in major bleeding. Therefore, when required, combination therapy may be considered in this population.

Nonatherosclerotic obstructive vascular diseases of the mesenteric and renal arteries.

Nonatherosclerotic vascular diseases of the mesenteric and renal arteries are considered to occur less frequently than those caused by occlusive atherosclerotic disease. However, when present, they pose a significant diagnostic and therapeutic challenge. Such disorders include fibromuscular dysplasia, median arcuate ligament syndrome, the renal nutcracker syndrome, and some forms of acute and chronic mesenteric ischemia (embolic and thrombotic). This is a heterogeneous group of disorders with substantial differences in the pathogenesis and diagnostic approaches to these diseases. We provide an overview of the pathogenesis, clinical presentation, diagnosis, and current management of fibromuscular dysplasia, median arcuate ligament syndrome, and the renal nutcracker syndrome.

Carcinoid heart disease: current understanding and future directions.

Carcinoid tumors are rare and aggressive malignancies. A multitude of vasoactive agents are central to the systemic effects of these tumors. The additional burden of cardiac dysfunction heralds a steep decline in quality of life and survival. Unfortunately, by the time carcinoid syndrome surfaces clinically, the likelihood of cardiac involvement is 50%. Although medical therapies such as somatostatin analogues may provide some symptom relief, they offer no mortality benefit. On the other hand, referral to surgery following early detection has shown increased survival. The prompt recognition of this disease is therefore of the utmost importance.

Transradial percutaneous coronary intervention without on-site cardiac surgery for stable coronary disease and myocardial infarction: preliminary report and initial experience in 174 patients.

BACKGROUND: On-site cardiac surgery is not widely available in developing countries despite a high prevalence of coronary artery disease. OBJECTIVES: To analyze the safety, feasibility and cost-effectiveness of transradial percutaneous coronary intervention without on-site cardiac surgery in a community hospital in a developing country. METHODS: Of the 174 patients who underwent PCI for the first time in our center, we analyzed two groups: stable coronary disease and acute myocardial infarction. The primary endpoint was the rate of complications during the first 24 hours after PCI. We also analyzed the length of hospital stay and the rate of hospital readmission in the first week after PCI, and compared costs between the radial and femoral approaches. RESULTS: The study group comprised 131 patients with stable coronary disease and 43 with acute MI. Among the patients with stable coronary disease 8 (6.1%) had pulse loss, 12 (9.16%) had on-site hematoma, and 3 (2.29%) had bleeding at the site of the puncture. Among the patients with acute MI, 3 (6.98) had pulse loss and 5 (11.63%) had bleeding at the site of the puncture. There were no cases of atriovenous fistula or nerve damage. In the stable coronary disease group, 130 patients (99%) were discharged on the same day (2.4 +/- 2 hours). In the acute MI group, the length of stay was 6.6 +/- 2.5 days with at least 24 hours in the intensive care unit. There were no hospital readmissions in the first week after the procedure. The total cost, which includes equipment related to the specific approach and recovery room stay, was significantly lower with the radial approach compared to the femoral approach (US$ 500 saving per intervention). CONCLUSIONS: The transradial approach was safe and feasible in a community hospital in a developing country without on-site cardiac surgery backup. The radial artery approach is clearly more cost-effective than the femoral approach.

Therapeutic options in autoimmune myasthenia gravis.

Autoimmune myasthenia gravis (MG) is associated with circulating antibodies to AChR, modification of the synaptic cleft, and destruction of the postsynaptic neuromuscular membrane. The hallmark is fluctuating muscular weakness and fatigability of muscles on sustained repeated activity. Various drugs and invasive procedures have been used in the treatment of MG including acetylcholinesterase inhibitors, corticosteroids, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, etanercept, intravenous immunoglobulin, plasma exchange and thymectomy. We review the role of each of these drugs and invasive procedures in MG. Although current treatment is highly successful and mortality is almost nil, further trials are required to identify the most suitable treatments for different subgroups of MG patients. In addition, safer and more potent drugs are required as most current drugs have major side effects due to immunosuppression. Therefore, the goal of novel therapies should be increased specificity of the immune-directed agents.

Thyroid disease in Sjögren's syndrome.

From 1960 to 2007, an important number of patients with primary Sjögren's syndrome (pSS) along with thyroid disease diagnosed by laboratory data and clinical presentation were reported. The most common thyroid disorder found was autoimmune thyroiditis and the most common hormonal pattern was subclinical hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a common genetic or environmental factor predisposition with similar pathogenic mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid disease and autoimmune thyroiditis was nine times more frequent in pSS. Therefore, SS should be studied in patients with thyroid disease and vice versa. Antigens are shared by both thyroid and salivary glands, which could be responsible for the association between both diseases. Immunogenetic studies had suggested that both diseases have a common genetic predisposition. pSS and thyroid disease patients were mostly women with positive antithyroglobulin, antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is frequent in pSS patients and those prone to develop thyroid disorders are identified by thyroid-related autoantibodies or by rheumatoid factor and anti-Ro/SSA activity. Patients with pSS have an increased tendency to develop other autoimmune diseases. Hypothyroidism was the most common autoimmune disease developed in pSS patients during follow-up of 10.5 years. Lymphomas are also associated with SS and thyroiditis and a 67-fold increased risk for thyroid mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is suggested that immune mechanism deficiency is a causal factor for B cell lymphoma in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the shared pathogenesis mechanism in SS and autoimmune thyroid disease and to understand this fascinating autoimmune association.