Browsing by Subject "right ventricular dysfunction"

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    Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study
    (Elsevier, 2018-02) Jimenez, David; Nieto, Rosa; Corres, Jesús; Fernández-Golfín, Covadonga; Barrios, Deisy; Morillo, Raquel; Quezada, Carlos Andres; Huisman, Menno; Yusen, Roger D.; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
    Background The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction. Methods We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75 mg in the first 24 h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter > 30 mm in the parasternal window; ii) RV diameter > left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure > 30 mm Hg. Persistence of RV dysfunction at 48 h and 7 days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7 days after randomization. Results Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48 h in 59% (95% confidence interval [CI], 33–82%) of the diclofenac group and in 76% (95% CI, 50–93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], − 17 percentage points; 95% CI, − 47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7 days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2–29%) of patient in the placebo group. Conclusions Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE.
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    Exercise Training Improves Cardiac and Skeletal Muscle Metabolism in Rats with Pulmonary Arterial Hypertension
    (Office of the Vice Chancellor for Research, 2013-04-05) Gaidoo, Richard G.; Crist, Jacob; Little, Nathaniel; Chingombe, Tsungai J.; Fisher, Amanda; Presson, Robert G.; Lahm, Tim; Petrache, Irina; Brown, Mary Beth
    In patients with pulmonary arterial hypertension (PAH), a shift from oxidative to glycolytic metabolism promotes right ventricular (RV) and skeletal muscle dysfunction that contributes to reduced exercise tolerance. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this glycolytic switch in PAH and improve exercise capacity. The purpose of this research is to investigate ExT in a rat model of PAH on markers of glycolytic and oxidative metabolism in RV and skeletal muscle. Male Sprague-Dawley rats received monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 13), or saline, for healthy controls (n=5). After 2 wks, with MCT-induced PAH established, 6 wks of treadmill (TM) ExT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=3). ExT runs progressed up to 60 min at mild relative intensity, 50% of maximal aerobic capacity (VO2max). VO2max was assessed at baseline, in pre-training and post-training TM testing via analysis of expired gases. Abundance of Glut-1, a marker of glycolytic metabolism, was evaluated in cryosections of RV and soleus with immunofluorescent (IF) staining and quantification. Data are presented as mean±SE. MCT-ExT rats maintained aerobic capacity over 6 wks better than sedentary counterparts (MCT-SED)(VO2max= -134±109 vs. -521±129 ml/kg/hr, p=0.04) and was not different than CON-ExT (-201±31 ml/kg/hr, p=0.82). A lower abundance of Glut-1 was observed in both RV and soleus myocytes of PAH-ExT rats (MPI= 10.9 ±0.9 for RV; 13.7±0.8 for soleus) compared to PAH-SED rats (15.7±2.4, p=0.05, for RV; 17.4±1.4, p=0.04, for soleus) and was similar to CON-ExT rats (13.0±2.2, p=0.33, for RV; 9.0±2.3, p=0.26, for soleus), indicative of a shift toward greater dependency on oxidative metabolism. Exercise training attenuates functional decline following MCT administration in rats. Preservation of aerobic capacity may be explained by promotion of more efficient RV and skeletal muscle mitochondrial substrate utilization.
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    High Rate Of Right Ventricular Dysfunction After Negative Computed Tomographic Pulmonary Angiography
    (American Thoracic Society, 2014-05) Kline, Jeffrey A.; Lahm, T; Russell, F
    Background: Prior work found that 20% of patients with persistent dyspnea have right ventricular (RV) dysfunction. Many patients with suspected pulmonary embolism (PE) who have a negative CTPA have persistent yet unexplained dyspnea. We hypothesized that a substantial proportion of these patients have unrecognized RV dysfunction. We sought to estimate this proportion and develop criteria to predict RV dysfunction on echocardiography after CTPA negative for PE. Methods: This was a four-center, prospective study of patients with ≥one symptom or sign and ≥one risk factor for PE, and CTPA scan performed. To assess potential predictors of RV dysfunction, we recorded 82 clinical predictors in real time. These included clinical findings, 12-lead electrocardiography (ECG), exhaled volumetric CO2/O2, plasma D-dimer and fibrinogen measurements. Patients underwent echocardiography within one week. Isolated RV dysfunction was defined as normal LV function with either moderate-severe RV hypokinesis, or estimated RV systolic pressure >35 mmHg. To assess if RV dysfunction led to symptoms that prompted reevaluation, we compared the frequency of repeat CTPA within 90 days. CTPA scans were interpreted by two independent radiologists. Predictors of RV dysfunction were assessed using a univariate (P<0.1)-multivariate (P<0.05) statistical approach. Results: 647 patients were enrolled; 120 with CPTA positive for PE were excluded, and 97 were excluded because of lack of persistent dyspnea. Of the 430 remaining patients, 184 underwent echocardiography, which demonstrated isolated RV dysfunction in 34% (95% CI: 30-41%). 27% of patients with isolated RV dysfunction had repeat CTPA within 90 days, a significantly higher rate than in patients without echocardiography (4%, P=0.03, Chi Square) or a normal echocardiogram (5%, P=0.02). No repeat CTPA scan showed PE. Of 82 candidate predictors of examined, univariate analysis found only 6 significant: active malignancy, normal CTPA, right bundle branch block on ECG, T-wave inversion in V1-V2 on ECG, history of COPD, and fibrinogen concentration. Of these six, multivariate logistic regression analysis found only normal CTPA as a significant predictor of isolated RV dysfunction. Conclusion: Patients with persistent dyspnea who have a normal CTPA performed for suspected PE have a high rate of unexplained isolated RV dysfunction on echocardiography. These patients are more likely to have persistent symptoms leading to unnecessary repeat CTPA in the short term. These findings form the starting point for a screening protocol to select patients with negative CTPA scanning for formal echocardiography and specialist referral to evaluate for pulmonary hypertension or other treatable causes of RV dysfunction.