Percutaneous debulking of tricuspid valve infective endocarditis vegetations using a large bore manual aspiration device - AlphaVac.

Most infectious endocarditis patients can be managed medically. However, non-responders to antibiotics and ongoing sequelae such as septic emboli, may require mechanical interventions. AngioVac (Angiodynamics, Latham, NY, USA) is a percutaneous aspiration device used for removal of thrombi, emboli, masses, and vegetations. Main drawbacks are the requirement for a perfusionist, two large-bore accesses, and meticulous de-airing. These drawbacks make the procedure more time-consuming and possibly increase the risk of complications. AlphaVac (Angiodynamics) omits the motor element, thereby overcoming several of the limitations. In the current report, we describe two cases of percutaneous aspiration of tricuspid valve vegetations using AlphaVac. Learning objective: To consider manual percutaneous aspiration of infective valvular vegetations using the AlphaVac cannula in case of insufficient response to antibiotics or for prevention of emboli.

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.

BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per µL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 µL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. FINDINGS: Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). INTERPRETATION: The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. FUNDING: US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.

Elevation of cardiovascular risk by non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used medications. NSAIDs profoundly modify prostaglandin homeostasis through inhibition of the enzyme, cyclooxygenase (COX), especially COX-2. COX-2 inhibition is associated with adverse cardiovascular outcomes as demonstrated by recent trials using this type of drug. This review explores the latest available data, including recent, randomized, clinical trials, controversies, and pathophysiology of the adverse effects of COX-inhibition.

Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging.

The process of vascular aging encompasses alterations in the function of endothelial (ECs) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species generation, inflammatory signaling and migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein B-containing low-density lipoproteins resulting in activation of ECs and recruitment of monocytes. Activated ECs secrete 'chemokines' that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a proinflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and nonvascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 exerts antioxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability.

Systematic review of interventions to repair ascending aortic pseudoaneurysms.

BACKGROUND: The safety and efficacy of endovascular therapies for ascending aortic pseudoaneurysms (AAPs) are still controversial. METHODS: We report an endovascular correction of an AAP in a high-risk surgical patient and present the results of a literature review focusing on AAP treatment strategies. A multilingual search of AAP therapy was performed with limiting dates of January 1980 to May 2014. The studies were classified by intervention. RESULTS: A 79-year-old male with a 9 × 10 × 7 cm AAP in the anterior mediastinum was considered too high risk for surgery. An endovascular closure with a 12 mm Amplatzer septal occluder device (St. Jude Medical) was performed, and computed tomography angiography at 3-month follow-up exhibited a thrombosed AAP with minimal residual shunt. In our literature search, we identified 355 cases of AAPs, mostly case reports (91.5%) and a few patient series (8.5%). Surgical correction accounted for 73.8% of the cases, 5% of the patients were conservatively treated or considered too critically ill for any intervention, and 21.2% were treated with endovascular techniques. The most commonly reported endovascular techniques were stent grafts (9.8%) and septal occluder devices (9.8%). CONCLUSION: Although endovascular closure of AAPs with off-label devices is a reliable option for controlling the expansion and symptoms in high-risk surgical patients, solid data on survival are lacking. Efforts to promote discussion within the heart team to expand the application of endovascular techniques can provide groundbreaking evidence to support the use of endovascular techniques as guideline therapy when facing these complicated cases.

Acute profound thrombocytopenia secondary to local abciximab infusion.

Glycoprotein (GP) IIb/IIIa receptor antagonists are powerful antiplatelet agents that are typically used in percutaneous coronary intervention. All three GP IIb/IIIa agents currently approved for use in the United States cause thrombocytopenia as a rare side effect. Abciximab is unique to the class in that it is a modified monoclonal antibody to the GP IIb/IIIa receptor, a property that can lead to increased platelet destruction. Presented herein is a patient who received a local infusion of abciximab for a lower-extremity thrombus and within 2 hours developed an acute profound thrombocytopenia that likely caused a large retroperitoneal hematoma. This case demonstrates the importance of checking platelet count within 2 to 4 hours after local (in addition to systemic) abciximab administration. Additionally, this report outlines how other causes of acute precipitous platelet drops, such as heparin-induced thrombocytopenia and pseudothrombocytopenia, can be rapidly excluded and allow for the prompt initiation of optimal therapy to minimize bleeding.

Aging, atherosclerosis, and IGF-1.

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1-induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging.

Evaluating traditional prognostic measures in patients undergoing hypothermia after cardiac arrest.

BACKGROUND: Therapeutic hypothermia is one of the few interventions that improve mortality and neurologic outcomes in patients who have experienced cardiac arrest. There is a lack of validated tools to predict survival in patients who have undergone hypothermia after cardiac arrest (HACA). METHODS: A retrospective analysis was performed of all patients who underwent HACA at Aurora St. Luke's Medical Center (ASLMC) since the protocol was implemented in September 2008. Initial rhythm, whether percutaneous coronary intervention (PCI) was performed, lactate levels, duration of resuscitation, and APACHE II scores were compared for survivors and non-survivors, and a logit binary regression model was constructed. RESULTS: A total of 143 patients were identified and had data abstracted. APACHE-II, duration of resuscitation, and initial rhythm were all strongly correlated with survival. Initial serum lactate levels were higher in non-survivors than survivors (p=0.005), though the trend of lactate change at next draw was not predictive. Quantitative TnI was not significantly different between arms. CONCLUSION: Lactate levels show promise as a biomarker for survival in HACA patients resuscitation length, presence of PCI, and APACHE-II scores can provide good prognostic information, even in the early hours following a resuscitation event.

C-reactive protein is an independent predictor for carotid artery intima-media thickness progression in asymptomatic younger adults (from the Bogalusa Heart Study).

BACKGROUND: Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study. METHODS: The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years. RESULTS: Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 µm/y, common carotid artery = 0.0 ± 51 µm/y, carotid bulb = 8.8 ± 103 µm/y, and internal carotid artery = 18.9 ± 81 µm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors. CONCLUSION: In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.

IGF-1, oxidative stress and atheroprotection.

Atherosclerosis is a chronic inflammatory disease in which early endothelial dysfunction and subintimal modified lipoprotein deposition progress to complex, advanced lesions that are predisposed to erosion, rupture and thrombosis. Oxidative stress plays a crucial role not only in initial lesion formation but also in lesion progression and destabilization. Although most growth factors are thought to promote vascular smooth muscle cell proliferation and migration, thereby increasing neointima, recent animal studies indicate that insulin-like growth factor (IGF)-1 exerts both pleiotropic anti-oxidant effects and anti-inflammatory effects, which together reduce atherosclerotic burden. This review discusses the effects of IGF-1 in models of vascular injury and atherosclerosis, emphasizing the relationship between oxidative stress and potential atheroprotective actions of IGF-1.

Neurohormonal factors in the development of catabolic/anabolic imbalance and cachexia.

Mechanisms that lead to cachexia are still poorly understood. The neurohormonal changes that occur in severe disease states may cause an imbalance between protein synthesis and degradation at the cellular level, followed by muscle wasting. Here, we review actions of angiotensin II, TNF-alpha, corticosteroids, insulin-like growth factor-I (IGF-I), and the IGF binding proteins, factors that may each contribute to the metabolic imbalance. The complex endocrine, autocrine and intracellular interactions between these factors will be described with examples from patient, rat and cell culture studies. Moreover, some of the data supporting that each of these hormones may directly affect cellular protein degradation mechanisms will be reviewed. Knowledge on these regulatory mechanisms will facilitate the development of new pharmaceutical strategies to treat cachexia.