Identification of pathogenic gene mutations in LMNA and MYBPC3 that alter RNA splicing.

Genetic variants that cause haploinsufficiency account for many autosomal dominant (AD) disorders. Gene-based diagnosis classifies variants that alter canonical splice signals as pathogenic, but due to imperfect understanding of RNA splice signals other variants that may create or eliminate splice sites are often clinically classified as variants of unknown significance (VUS). To improve recognition of pathogenic splice-altering variants in AD disorders, we used computational tools to prioritize VUS and developed a cell-based minigene splicing assay to confirm aberrant splicing. Using this two-step procedure we evaluated all rare variants in two AD cardiomyopathy genes, lamin A/C (LMNA) and myosin binding protein C (MYBPC3). We demonstrate that 13 LMNA and 35 MYBPC3 variants identified in cardiomyopathy patients alter RNA splicing, representing a 50% increase in the numbers of established damaging splice variants in these genes. Over half of these variants are annotated as VUS by clinical diagnostic laboratories. Familial analyses of one variant, a synonymous LMNA VUS, demonstrated segregation with cardiomyopathy affection status and altered cardiac LMNA splicing. Application of this strategy should improve diagnostic accuracy and variant classification in other haploinsufficient AD disorders.

Partial Brain Tissue Oxygen Levels Predict Arrhythmia and Prognosis in Patients With Brain Injury.

The objective of this study was to examine the clinical determinants of incidence and prognosis of arrhythmias in the setting of acute brain injury. Acute brain injury is known to cause electrocardiographic abnormalities and cardiac arrhythmias. The relation between partial brain tissue oxygen (PBTO) and intracranial pressure (ICP) with arrhythmia incidence and prognosis remains unknown. Consecutive patients with acute brain injury and intracranial bleed admitted to the neurosurgical intensive care unit were enrolled in the study. Baseline characteristics [demographics, medical history, etiology of brain injury, Glasgow Coma Scale (GCS) score, blood pressure, and respiratory rate] were documented. Patient's telemetry recordings were reviewed for daily mean heart rates and arrhythmias. If arrhythmia was noted, PBTO levels at the beginning of arrhythmia, ICP, brain tissue temperature, and outcomes were recorded. A total of 106 subjects (53% men, age 39 ± 18 years, 65 traumatic and 41 nontraumatic brain injuries) were studied. Overall, 62% of subjects developed a total of 241 arrhythmia episodes. Ventricular arrhythmias were associated with significantly higher daily mean heart rates, low PBTO levels, and low GCS scores, whereas atrial arrhythmias were associated with lower daily mean heart rates, normal PBTO levels, and higher GCS and ICP. Three or more episodes of arrhythmia predicted worse outcomes, including mortality (P = 0.001). In patients with acute brain injury, poor PBTO levels are associated with higher incidence of ventricular tachyarrhythmias. In contrast, atrial tachyarrhythmias occur in patients with normal PBTO levels and higher ICP. Incidence of ventricular arrhythmia in those with poor PBTO is associated with increased mortality.

The prevention of contrast-induced nephropathy.

OBJECTIVE: Contrast-induced nephropathy (CIN) is a complication which may develop after exposure to iodinated contrast media. The resulting acute kidney injury (AKI) is associated with an increase in both short- and long-term morbidity and mortality, increased hospital length of stay, and greater health care costs. The pathophysiological mechanism associated with the development of CIN remains unknown. This narrative review summarizes the pathophysiology, risk factors, and current evidence for the prevention of CIN. DATA SOURCES: A MEDLINE literature search (2004-May 2014) was performed using search terms contrast-induced nephropathy and prevention. Additional references were identified from literature citations, review articles, and meta-analyses. STUDY SELECTION AND DATA EXTRACTION: Abstracts of English-language human clinical trials that examined therapies for the prevention of CIN were evaluated. Studies that did not investigate a preventative intervention for CIN were excluded. Emphasis was placed on recent publications. DATA SYNTHESIS: A multitude of therapies focused on the prevention of CIN have been investigated. Unfortunately, many of these studies have produced negative and/or inconsistent results. There is a paucity of adequately designed clinical studies evaluating strategies for the prevention of CIN. However, the best data supports use of preprocedural hydration with isotonic solution as the standard of care for prophylaxis. CONCLUSION: Given the poor prognosis associated with CIN, there is need for improved methods to prevent it. At present, the best tools to protect patients from unnecessary risk for CIN are careful assessment of renal function, judicious use of procedures that utilize contrast media, and adequate hydration with isotonic solution.

Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine.

INTRODUCTION: Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy. OBJECTIVE: The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue (EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT. METHODS: Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat. RESULTS: Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in the vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3. CONCLUSION: These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D-deficient population might be helpful in reducing inflammation and cardiovascular risk.

Fenofibric acid for hyperlipidemia.

INTRODUCTION: 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) are the mainstay of therapy for hyperlipidemia, as per the current National Cholesterol Education Program (NCEP) recommendation. However, the role of other agents, such as the fibrates, is continually being debated in the context of incremental risk reduction, especially in the setting of mixed dyslipidemia. Results from the ACCORD Trial have further added to the confusion. Fibrates also have a role to play in familial hyperlipidemias and in hypertriglyceridemia. Fenofibric acid is one of the newly approved forms of fenofibrate with enhanced bioavailability and was recently approved by the Food and Drug Administation (FDA) for the treatment of various types of hyperlipidemia, in conjunction with statins. AREAS COVERED: This article reviews the role of fenofibric acid in the context of results from recent randomized trials on fenofibrate, including the ACCORD Trial. It discusses the current status of fenofibric acid in the management of dyslipidemia, especially in combination with statins, and also addresses the comparative efficacy and safety profile of this new molecule against other agents in its class. EXPERT OPINION: Fenofibric acid in combination with low- to moderate-dose statins is an effective and safe option in the treatment of mixed dyslipidemia, although the long-term effects on cardiovascular risk reduction need to be explored further.

Development and validation of a risk calculator for prediction of cardiac risk after surgery.

BACKGROUND: Perioperative myocardial infarction or cardiac arrest is associated with significant morbidity and mortality. The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool; however, it has several limitations, one of which is its relatively low discriminative ability. The objective of the present study was to develop and validate a predictive cardiac risk calculator. METHODS AND RESULTS: Patients who underwent surgery were identified from the American College of Surgeons' 2007 National Surgical Quality Improvement Program database, a multicenter (>250 hospitals) prospective database. Of the 211 410 patients, 1371 (0.65%) developed perioperative myocardial infarction or cardiac arrest. On multivariate logistic regression analysis, 5 predictors of perioperative myocardial infarction or cardiac arrest were identified: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists' class, and increasing age. The risk model based on the 2007 data set was subsequently validated on the 2008 data set (n=257 385). The model performance was very similar between the 2007 and 2008 data sets, with C statistics (also known as area under the receiver operating characteristic curve) of 0.884 and 0.874, respectively. Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic (0.747). The risk model was used to develop an interactive risk calculator. CONCLUSIONS: The cardiac risk calculator provides a risk estimate of perioperative myocardial infarction or cardiac arrest and is anticipated to simplify the informed consent process. Its predictive performance surpasses that of the Revised Cardiac Risk Index.

Outcomes after carotid artery stenting and endarterectomy in the Medicare population.

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for stroke prevention. The value of this therapy relative to CEA remains uncertain. METHODS: In 10 958 Medicare patients aged 66 years or older between 2004 and 2006, we analyzed in-hospital, 1-year stroke, myocardial infarction, and death rate outcomes and the effects of potential confounding variables. RESULTS: CAS patients (87% were asymptomatic) had a higher baseline risk profile, including having a higher percentage of coronary and peripheral arterial disease, heart failure, and renal failure. In-hospital stroke rate (1.9% CAS versus 1.4% CEA; P=0.14) and mortality (CAS 0.9% versus 0.6% CEA; P=0.20) were similar. By 1 year, CAS patients had similar stroke rates (5.3% CAS versus 4.1% CEA; P=0.12) but higher all-cause mortality rates (9.9% CAS versus 6.1% CEA; P<0.001). Using Cox multivariable models, there was a similar stroke risk (hazard ratio, 1.28; 95% CI, 0.90-1.79) but CAS patients had a significantly higher mortality (HR, 1.32; 95% CI, 1.02-1.71). Sensitivity analyses suggested that unmeasured confounders could be responsible for the mortality difference. In multivariable analysis, stroke risk was highest in the patients symptomatic at the time of revascularization. CONCLUSIONS: CAS patients had a similar stroke risk but an increased mortality rate at 1 year compared with CEA patients, possibly related to the higher baseline risk profile in the CAS patient group.

Evaluating optimal lipid levels in patients with mixed dyslipidemia following short- and long-term treatment with fenofibric acid and statin combination therapy: a post hoc analysis.

OBJECTIVE: To evaluate the achievement of individual and combined lipid and lipoprotein/biomarker targets as specified by treatment guidelines with the combination of fenofibric acid and statin therapy in patients with mixed dyslipidemia. METHODS: Data for the post hoc analyses were derived from three 12-week controlled studies and a 52-week extension study. Patients were treated with fenofibric acid 135 mg; low-, moderate-, or high-dose statin (rosuvastatin 10, 20, or 40 mg; atorvastatin 20, 40, or 80 mg; or simvastatin 20, 40, or 80 mg); or fenofibric acid + low- or moderate-dose statin in the controlled studies; and with fenofibric acid + moderate-dose statin in the extension study. Achievement of risk-stratified low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (ApoB) targets; and optimal levels of ApoB <90 mg/dL, HDL-C >40/50 mg/dL in men/women, triglycerides (TG) < 150 mg/dL, and high-sensitivity C-reactive protein <2 mg/L were assessed. RESULTS: In the controlled studies, significantly lower percentage of high-risk patients treated with fenofibric acid + moderate-dose statin, and significantly higher percentage of high-risk patients treated with fenofibric acid + low-dose statin, compared with corresponding-dose statin monotherapies, achieved their LDL-C (51.3% vs. 72.9%, p < 0.001) and non-HDL-C targets (53% vs. 38%, p = 0.02), respectively. Among all patients, optimal levels of ApoB, HDL-C, TG, and the combined target of LDL-C + non-HDL-C + ApoB + HDL-C + TG were achieved by higher percentage of patients treated with fenofibric acid + low- and moderate-dose statin versus corresponding dose-statin monotherapies (p ≤ 0.04 for all comparisons). In the extension study, significantly (p < 0.001 for all comparisons) higher percentage of patients had achieved individual and combined targets at final visit, compared with baseline. CONCLUSIONS: In patients with mixed dyslipidemia, short-term treatment with the combination of fenofibric acid and low- or moderate-dose statin resulted in comparable or more patients achieving individual targets of non-HDL-C, ApoB, HDL-C, and TG, and combined targets for these parameters and LDL-C, compared with corresponding-dose statin monotherapy. In the long-term study, the proportion meeting these targets was significant, compared with baseline. Limitations include the post hoc nature of the analysis, and the fact that all patients had mixed dyslipidemia and majority were white, which limits generalization to other populations.

Impact of statin use on heart failure mortality.

BACKGROUND: There is conflicting data regarding the mortality benefit of statins in patients with heart failure. The objectives of our study were to determine whether statin therapy is associated with decreased all-cause mortality and to assess the effect of incremental duration of therapy. METHODS: We studied 10,510 consecutive patients from the Veterans Affairs health system with a diagnosis of heart failure from January 2002 through December 2006. Mean follow-up was 2.66 years. Statin use and duration of therapy were identified. Veterans were classified into four groups based on duration of statin use during the study period (none, 1-25%, 26-75% and >75% use of statins). Logistic regression was performed to identify the association between incident statin use and all-cause mortality following a diagnosis of heart failure. The Kaplan-Meier method was employed to assess for differences in survival time between the four statin use classifications. RESULTS: Statin use was significantly associated with decreased all-cause mortality following a diagnosis of heart failure after controlling for age, gender, concurrent medications and comorbid diagnoses [χ(3)(2) (N = 10,510) = 1077.82, p < 0.001]. The benefit was seen within a relatively short duration (within 1 year) after starting statins, and in patients with <25% use of statins, there was no mortality benefit. CONCLUSION: Veterans who were not exposed to statin therapy at any time during the study period were 1.56 times more likely to suffer all-cause mortality.

Clinical utility of valsartan in treatment of children and adolescents with high blood pressure.

The incidence of hypertension in the pediatric population has been increasing secondary to lifestyle changes in children and adolescents. Recent studies have enhanced our understanding of the treatment of pediatric hypertension. Angiotensin-converting enzyme inhibitors have traditionally been the most commonly used class of medication in children with hypertension. This is partly due to the important role of the renin angiotensin aldosterone system pathway in the mediation of pediatric hypertension. Angiotensin receptor blockers provide a reasonable alternative to angiotensin-converting enzyme inhibitors. The need for better tolerated antihypertensives had led to development of many new antihypertensives. Valsartan is a relatively novel angiotensin receptor blocker that has been shown to be effective in the treatment of pediatric hypertension. Two recent trials have demonstrated the efficacy of valsartan monotherapy in the pediatric population aged 1-16 years. Once-daily oral preparations of valsartan achieve adequate blood pressure control in the pediatric population. Lack of generic formulations is an important disadvantage. Plasma levels are predictable and clearance is primarily by the liver. Valsartan should be prescribed cautiously for sexually active adolescent females due to concern about angiotensin receptor blocker fetopathy. Otherwise, the drug has infrequent side effects. In summary, valsartan is a new and useful alternative to conventional antihypertensive therapy in pediatric population.

Fibrate therapy in the management of dyslipidemias, alone and in combination with statins: role of delayed-release fenofibric acid.

IMPORTANCE OF THE FIELD: Optimization of lipid management is a crucial aspect in the treatment of cardiovascular disease. Currently, HMG-CO reductase inhibitors (statins) are a mainstay of therapy. While this class of drugs has proven efficacy at lowering low-density lipoprotein cholesterol (LDL-C), their effects on other important lipid parameters, such as high-density lipoprotein cholesterol (HDL-C) and triglycerides, are less robust. AREAS COVERED IN THIS REVIEW: The current paper will address the significance of these secondary targets and review currently available therapies, including a new formulation of delayed-release fenofibric acid. A comprehensive MEDLINE search (1966 to September 2009) was performed. WHAT THE READER WILL GAIN: The reader will gain a comprehensive review of the importance of secondary cholesterol targets, as well as the effectiveness of currently available therapies to address non-LDL-C. The role of the newly released fenofibric acid will also be addressed, as well as its potential use in combination therapy with a statin. TAKE HOME MESSAGE: Adequate treatment of lipid parameters beyond LDL-C is an essential component in the treatment of dyslipidemia. The fibrate class of drugs has proven efficacy in improving secondary targets; however, concerns regarding severe myopathy and rhabdomyolysis have limited their combination with statins. Recently, a new fibrate derivative, fenofibric acid, has become available. Studies to date reflect a positive safety and tolerability profile when combined with statins. This may offer a new tool to address the important secondary cholesterol targets that are becoming increasingly recognized as important contributors to cardiovascular outcomes.

Impact of moderate to severe renal impairment on mortality and appropriate shocks in patients with implantable cardioverter defibrillators.

Background. Due to underrepresentation of patients with chronic kidney disease (CKD) in large Implantable-Cardioverter Defibrillator (ICD) clinical trials, the impact of ICD remains uncertain in this population. Methods. Consecutive patients who received ICD at Creighton university medical center between years 2000-2004 were included in a retrospective cohort after excluding those on maintenance dialysis. Based on baseline Glomerular filtration rate (GFR), patients were classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30-59 mL/min; and mild or no CKD: GFR ≥ 60 mL/min. The impact of GFR on appropriate shocks and survival was assessed using Kaplan-Meier method and Generalized Linear Models (GLM) with log-link function. Results. There were 509 patients with a mean follow-up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated GFR: 2 fold higher risk with GFR between 30-59 mL/min and 5 fold higher risk with GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate shock(s); appropriate shock-free survival was lower in patients with severe CKD (GFR < 30) compared to mild or no CKD group (2.8 versus 4.2 yrs). Conclusion. Even moderate renal dysfunction increases all cause mortality in CKD patients with ICD. Severe but not moderate CKD is an independent predictor for time to first appropriate shock.

C-Reactive Protein and The Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

There is increasing evidence linking C-reactive protein (CRP) and atrial fibrillation (AF). Despite the abundance of literature, confusion exists regarding this association because of inconsistent results. MEDLINE and Cochrane Controlled Trials Register databases were carefully searched through July, 2009 combining the following terms "C-reactive protein" and "atrial fibrillation". Reference lists of selected articles and reviews were also screened to identify additional relevant studies. Of the 129 studies initially identified, 8 studies with 7507 subjects (719 with AF) were included in the meta-analysis. Analysis yielded a relative risk of 1.63 (1.43, 1.86) for occurrence of AF when CRP level was above a cut off of 3-3.5 mg/l. When 3 studies with data on a higher cut off of 4.5-5.0 mg/l were analyzed separately, the relative risk was 4.03 (3.1, 5.25). Our study suggests that elevated CRP is associated with increased risk for AF. The risk appears incremental with higher CRP levels conferring proportionately increased risk. There is an urgent need for further large scale, well designed prospective studies to assess the relationship between CRP and AF.

Thrombectomy reduces the systemic complications in device-related right atrial septic thrombosis.

BACKGROUND: Septic thrombosis of the right atrium is an unusual complication associated with the use of indwelling devices. The optimal management of this condition is unclear. Our experience with a patient with hemodialysis catheter-related septic thrombosis of the right atrium illustrates the difficulties associated with this condition. OBJECTIVES: To determine the effects of surgical thrombectomy compared with nonsurgical treatment with antibiotics (with or without anticoagulation) on mortality rates and complications in patients with device-related septic thrombosis of the right atrium. METHODS: A retrospective analysis of all reported cases of device-related right heart septic thrombosis in which therapy and outcome were reported was conducted using a PubMed search in the English-language literature (1985 to 2006). RESULTS: Forty cases of device-related right atrial septic thromboses were reported in the literature during the chosen time period. The treatments administered were none (12.5%), antibiotics (12.5%), antibiotics and anticoagulation (20%), and thrombectomy (55%). The mean clot size was significantly larger in patients who underwent thrombectomy. All untreated patients died. Excluding the untreated patients from the analysis, systemic complications were significantly lower in the thrombectomy group than in the groups receiving nonsurgical therapies. Using multivariate modelling with survival as the primary outcome, age, sex, clot size, clot location, microbial organism or type of treatment were not predictive of the outcome. CONCLUSION: Device-related right atrial septic thrombosis is associated with significant mortality and is uniformly fatal if untreated. Surgical thrombectomy is associated with less frequent systemic complications. A well-designed prospective, randomized trial is needed to determine the optimal treatment of this condition.

Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study.

BACKGROUND: Patients with mixed dyslipidemia often require combination therapy to effectively control lipid abnormalities. This study compared the effects of combination therapy with ABT-335 (a new formulation of fenofibric acid) and simvastatin to ABT-335 and simvastatin monotherapies on lipid and nonlipid parameters in patients with mixed dyslipidemia. METHODS: This was a phase 3, multicenter, randomized, double-blind, active-controlled study. A total of 657 patients with mixed dyslipidemia (low-density lipoprotein cholesterol [LDL-C] > or =130 mg/dL, triglycerides [TGs] > or =150 mg/dL, and high-density lipoprotein cholesterol [HDL-C]<40 mg/dL [men] or <50 mg/dL [women]) were randomized to 12 weeks of treatment with ABT-335 + simvastatin (20 or 40 mg) combination therapy, ABT-335 monotherapy (135 mg), or simvastatin monotherapy (20, 40, or 80 mg). RESULTS: Combination therapy resulted in significantly greater increases in HDL-C and decreases in TGs compared to the corresponding simvastatin monotherapy dose (P < .001) and decreases in LDL-C compared to ABT-335 monotherapy (P < .001). HDL-C increased 17.8% versus 7.2% and TGs decreased -37.4% versus -14.2% (ABT-335 + simvastatin 20 vs simvastatin 20); LDL-C decreased -24.0% versus -4.0% (ABT-335 + simvastatin 20 vs ABT-335). HDL-C increased 18.9% versus 8.5% and TGs decreased -42.7% versus -22.4% (ABT-335 + simvastatin 40 vs simvastatin 40); LDL-C decreased -25.3% versus -4.0% (ABT-335 + simvastatin 40 vs ABT-335). Twelve-week treatment with combination therapy was generally well tolerated with a safety profile consistent with ABT-335 and simvastatin monotherapies. No cases of rhabdomyolysis were reported. CONCLUSION: For patients with mixed dyslipidemia, combination therapy provided more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies.

Peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare, idiopathic, life-threatening disease of late pregnancy and early puerperium, occurring in patients with previously healthy hearts. Risk factors include multiparity, age>30 years, African American race, multiple pregnancies, obesity, hypertension, and toxemia. Signs and symptoms of PPCM resemble systolic heart failure, and it is diagnosed by exclusion. An echocardiogram typically reveals an ejection fraction of <45% and/or fractional shortening of <30%, along with a left ventricular end-diastolic dimension>2.7 cm/m2 of body surface area. Early diagnosis and treatment are important for a successful outcome. Management is similar to other forms of systolic heart failure. Patients with PPCM are at high risk of thromboembolism, and therefore anticoagulation therapy should be considered. The prognosis is variable, ranging from complete recovery, to worsening heart failure requiring cardiac transplantation, or death. Future pregnancies are often discouraged because of the high mortality rate and risk of recurrence.

Ventricular metastasis without atrial or caval involvement: a rare presentation.

Right ventricular metastases from renal cell carcinoma without inferior vena cava (IVC) or right atrium involvement are rare. We discuss a 44-year-old male who presented with a left thigh mass, which was resected and the pathology revealed an epithelial sarcoma or a possible metastasis from another organ. His preradiotherapy cardiac evaluation showed mass in the right and left ventricles, which was confirmed by transesophagial echocardiogram. Computed tomography revealed a right renal mass in addition to the ventricular masses without any involvement of IVC or the atria. The patient underwent right radical nephrectomy without complications and systemic chemotherapy with interleukin-1 for metastatic renal cell carcinoma. He is doing well and follow-up echocardiogram showed significant reduction in the size of the cardiac metastases, even without surgical resection of these tumors. Thus, our article presents this unique case of asymptomatic ventricular metastases of renal cell carcinoma without any atrial or caval involvement and provides a new insight into the management of this syndrome.

Long-term safety and efficacy of fenofibric acid in combination with statin therapy for the treatment of patients with mixed dyslipidemia.

BACKGROUND: Co-administration of a fibrate and statin is an effective treatment option for patients with multiple lipid abnormalities, yet adequate long-term safety and efficacy data are lacking. OBJECTIVE: To evaluate the long-term safety and efficacy of fenofibric acid combined with statins in adults with mixed dyslipidemia. METHODS: Three large, 12-week, phase three, double-blind, randomized, controlled trials evaluated fenofibric acid 135 mg combined with a low- or moderate-dose statin compared to fenofibric acid or statin monotherapy, and a subsequent 52-week open-label extension study evaluated fenofibric acid 135 mg combined with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg). This prespecified analysis integrated results from these studies to assess the long-term safety and efficacy of combination therapy. RESULTS: Across the controlled studies and the extension study, 2201 patients received at least one dose of fenofibric acid + statin for a median duration of 364 days. The most common adverse events were headache, upper respiratory tract infection, nasopharyngitis, and back pain, with the incidence of all adverse events being similar across all combination therapy treatment groups. Rhabdomyolysis or treatment-related death was not reported in any group. Combination therapy resulted in sustained improvements in multiple lipid parameters, including triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. CONCLUSION: Long-term fenofibric acid + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in multiple lipid parameters in adults with mixed dyslipidemia.

Circadian, daily, and seasonal distributions of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

This study investigated the circadian, daily, and seasonal distributions of ventricular arrhythmias in patients with new implantable cardioverter-defibrillator placement at Creighton University Medical Center from January 2000 to December 2004. The incidence and distribution of ventricular tachyarrhythmias as recorded by implantable cardioverter-defibrillators were analyzed with respect to season, month, day of the week, and average daily temperature. Data from 154 consecutive patients (mean age 67 +/- 14 years; 78% men, 71% with ischemic heart disease [IHD], mean left ventricular ejection fraction 34 +/- 15%) were analyzed. During a mean follow-up of 35 +/- 19 months, a total of 1,055 episodes of spontaneously terminated ventricular tachycardia (VT) and 612 episodes of VT or ventricular fibrillation with appropriate device therapy occurred. Distributions in the incidence of VT and VT or ventricular fibrillation receiving appropriate therapy were similar in patients with IHD and non-IHD. Spontaneously terminated VT and appropriately treated VT or ventricular fibrillation episodes occurred with the greatest incidence in the winter months and the lowest incidence in summer, spring, and fall. A linear regression between the number of episodes and the average daily temperature showed a greater likelihood of the 2 events occurring on cooler days, irrespective of the cause of cardiac disease. A weekly distribution was also observed, with the greatest proportion of episodes occurring on Fridays and the lowest on Saturdays and Sundays. A bimodal circadian distribution was present, with the greatest peak occurring from 8 a.m. to 1 p.m. and a smaller peak occurring from 5 p.m. to 10 p.m. In conclusion, the occurrence of ventricular tachyarrhythmias appears to follow circadian, daily, and seasonal distributions that are similar in patients with IHD and non-IHD. The incidence inversely correlates with average daily temperatures.