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Background-Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH. Methods and Results-Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak V O 2 from baseline, the primary end point, was greater in the sildenafil group (1.8Ϯ0.7 mL · kg Ϫ1 · min

BACKGROUND The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS Data of 617 adult patients (75% males, mean age of 53±12 years, mean BMI of 25±4 and mean ejection fraction of 19±9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard model for end Stage liver disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anticoagulation. RESULTS Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25 and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathological values decreased significantly except ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS In this large, single-center retrospective study, we demonstrate dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome following OHT. Therefore, preoperative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.

Background Continuous-flow left ventricular assist devices (LVAD) are increasingly used for patients with end-stage heart failure (HF). We analyzed the effects of ventricular decompression by continuous- versus pulsatile-flow LVADs on myocardial structure and function in this population. Methods and Results Sixty-one patients who underwent LVAD implantation as bridge-to-transplant were analyzed (pulsatile-flow LVAD: Group P, n=31; continuous-flow LVAD: Group C, n=30). Serial echocardiograms, serum levels of brain natriuretic peptide (BNP) and extracellular matrix biomarkers (ECM) were compared between the groups. Myocardial BNP and ECM gene expression were evaluated in a subset of 18 patients. Postoperative left ventricular (LV) ejection fraction was greater (33.2±12.6 vs. 17.6±8.8%, p<0.0001) and the mitral E/E′ was lower (9.9±2.6 vs. 13.2±3.8, p=0.0002) in Group P versus Group C. Postoperative serum levels of BNP, metalloproteinases (MMP)-9 and tissue inhibitor of MMP (TIMP)-4 were significantly lower in Group P compared to Group C (BNP: 552.6±340.6 vs. 965.4±805.7 pg/mL, p<0.01; MMP9: 309.0±220.2 vs. 475.2±336.9 ng/dL, p<0.05; TIMP4: 1490.9±622.4 vs. 2014.3±452.4 ng/dL, p<0.001). Myocardial gene expression of ECM markers and BNP decreased in both groups; however, expression of TIMP-4 decreased only in Group P (p=0.024). Conclusions Mechanical unloading of the failing myocardium using pulsatile devices is more effective as indicated by echocardiographic parameters of systolic and diastolic LV function as well as dynamics of BNP and ECM markers. Therefore, specific effects of pulsatile mechanical unloading on the failing myocardium may have important implications for device selection especially for the purpose of bridge-to-recovery in patients with advanced HF.

BACKGROUND Neurologic complications (NCs) are the major adverse events after left ventricular assist device (LVAD) surgery. Pre-operative and post-operative factors associated with NCs in patients with LVADs were investigated. METHODS We reviewed 307 consecutive patients undergoing LVAD surgery (167 HeartMate I and 140 HeartMate II devices) at Columbia University Medical Center between November 2000 and December 2010. Clinical characteristics and hemodynamic and laboratory indexes were analyzed. NC was defined according to the Interagency Registry for Mechanically Assisted Circulatory Support definition of neurologic dysfunction, including transient ischemic attack (TIA) and ischemic or hemorrhagic cerebrovascular accident (CVA). RESULTS NCs developed in 43 patients (14.0%) at 91.8 ± 116.3 days post-operatively. The frequency of NC development was similar in HeartMate I and II patients. Patients with NC showed a higher frequency of pre-LVAD CVA history (27.9% vs 15.5%, p = 0.046), lower pre-operative sodium (129.0 ± 7.0 vs 132.1 ± 8.1 mg/dl, p = 0.018) and albumin concentrations (3.5 ± 0.7 vs 3.7 ± 0.6 mg/dl, p = 0.049), lower post-operative hematocrit (34.9% ± 5.1% vs 37.8% ± 6.1%, p = 0.0034), sodium (131.6 ± 7.7 vs 134.4 ± 6.4 mg/dl, p = 0.010) and albumin concentrations (3.7 ± 0.5 vs 3.9 ± 0.5 mg/dl, p = 0.0016), and higher frequency of post-operative infection (39.5% vs 19.3%, p = 0.003) than those without NC. Multiple regression analysis revealed that CVA history (odds ratio, 2.37, 95% confidence interval, 1.24 –5.29; p = 0.011) and post-operative infection (odds ratio, 2.99, 95% confidence interval, 1.16 –10.49; p = 0.011) were highly associated with NC development. The combination of CVA history, pre-operative and post-operative sodium and albumin, and post-operative hematocrit and infection could discriminate patients developing NCs with a probability of 76.6%. CONCLUSIONS Previous stroke, persistent malnutrition and inflammation, severity of heart failure, and post-LVAD infections are key factors associated with development of NCs after LVAD implantation.

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Background: This study aimed to estimate the prevalence and to identify some risk factors of adult asthma in male leather tannery workers in Karachi, Pakistan.

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