74 research outputs found
Porcine Bioprosthetic Aortic Valve Endocarditis with Ring Abscess and Aortic Stenosis
Porcine bioprosthetic valve endocarditis is an infrequent but serious complication of valve replacement surgery. Ring (or annular) abscess is a frequent finding in mechanical valve endocarditis. In contrast, porcine valve endocarditis most often involves the cusps, and annular infection is uncommon. Porcine valvular dysfunction secondary to endocarditis usually takes the form of incompetence, whereas stenosis is less frequent. We report a case of a 76-year-old female who developed endocarditis wilh Staphylococcus epidermidis nine months after placement of a Carpenter-Edwards porcine aortic valve. Her initial presentation included complete heart block and moderate aortic stenosis. Transesophageal echocardiography aided the diagnosis by demonstrating large vegetations, while transthoracic echocardiography showed only slight thickening of the valve leaflets. At operation, there was a circumferential abscess around the sewing ring causing valve dehiscence and virtual discontinuity of the aorta from the left ventricle. Valve degeneration and organisms within the cusps were observed on microscopy. This case illustrates two infrequent complications of porcine aortic valve endocarditis, namely massive annular abscess with invasion of the conducting system and aortic stenosis. It also demonstrates the utility and limitations of transesophageal echocardiography in the diagnosis of this disorder
First-pass contrast bolus hemodynamics contain information on right ventricular function, remodeling, and lung resistance in pulmonary arterial hypertension patients
Coronary flow reserve correlates with right ventricular dysfunction and predicts right heart failure in patients with pulmonary arterial hypertension
Rationale and design of a phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT
Background - Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH.
Methods - ASA-STAT is a phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in 6 min at 6 months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups.
Screening and enrollment - We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin.
Conclusions - This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed
Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension
Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865)
Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension
Background—Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH.
Methods and Results—We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at 4 centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was 6-minute walk distance at 6 months. Sixty-five subjects had been randomized when the trial was terminated by the Data Safety and Monitoring Board after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6-minute walk distance, there was no significant difference in the 6-minute walk distance at 6 months between aspirin (n=32) and placebo (n=33; placebo-corrected difference −0.5 m, 95% confidence interval −28.4 to 27.4 m; P=0.97) or between simvastatin (n=32) and placebo (n=33; placebo-corrected difference −27.6 m, 95% confidence interval −59.6 to 4.3 m; P=0.09). There tended to be more major bleeding episodes with aspirin than with placebo (4 events versus 1 event, respectively; P=0.17).
Conclusions—Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications
Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom
Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531
Erythroid-Specific Transcriptional Changes in PBMCs from Pulmonary Hypertension Patients
Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression
Bronchiolitis Obliterans after Lung Transplantation: Are we making progress?
Overall Goals and Objectives:
1. Understand the risk factors for Bronchiolitis Obliterans Syndrome after lung transplantation
2. Be familiar with recent developments in the therapy of Bronchiolitis Obliterans Syndrome
3. Be aware of strategies for prevention
Recurrent Leukemia Cutis in Acute Myeloblastic Leukemia
We report the case of a 64-year-old female with acute myeloblastic leukemia (French-American- British classification: M2) who developed two specific cutaneous manifestations during her illness. She presented with extensive cellulitis involving the face, neck, and upper chest wall. While the cellulitis resolved with antibiotic therapy, a fungating ulcerated nodule remained on the lower lip which proved to be leukemic on biopsy. Concomitant blood and bone marrow findings were diagnostic of acute myeloblastic leukemia. The lip lesion cleared with a course of chemotherapy. An erythematous macular rash subsequently developed over the lower trunk which was thought to be an allergic reaction to the penicillin treatment. However biopsy results were consistent with leukemia cutis. A repeat bone marrow examination revealed excessive blasts. Our observations emphasize the various presentations of leukemia cutis and the need to biopsy any cutaneous lesion of unclear etiology in the setting of acute leukemia
- …