Impact of obstructive sleep apnea on cardiopulmonary performance, endothelial dysfunction, and pulmonary hypertension during exercise.

RATIONALE: OSA has been associated with reduced exercise capacity. Endothelial dysfunction and exercise-induced pulmonary hypertension (ePH) may be mediators of this impairment. We hypothesized that OSA severity would be associated with impaired exercise performance, endothelial dysfunction, and ePH. METHODS: Subjects with untreated OSA were recruited. Subjects underwent endothelial function, and cardiopulmonary exercise testing with an echocardiogram immediately before and following exercise. RESULTS: 22 subjects were recruited with mean age 56 ± 8 years, 74 % male, BMI 29 ± 3 kg/m2, and AHI 22 ± 12 events/hr. Peak V˙O2 did not differ from normal (99.7 ± 17.3 % predicted; p = 0.93). There was no significant association between OSA severity (as AHI, ODI) and exercise capacity, endothelial function, or pulmonary artery pressure. However, ODI, marker of RV diastolic dysfunction, and BMI together explained 59.3 % of the variability of exercise performance (p < 0.001) via our exploratory analyses. CONCLUSIONS: Exercise capacity was not impaired in this OSA cohort. Further work is needed to elucidate mechanisms linking sleep apnea, obesity, endothelial dysfunction and exercise impairment.

Predictive Factors for Progression of Mitral Regurgitation in Asymptomatic Patients With Mitral Valve Prolapse.

Risk factors predicting progression from low grade to severe mitral regurgitation (MR), which is a guideline criterion for surgical intervention, remain unknown. We hypothesized that abnormalities of cardiac structure and function may predict progression in MR severity. We followed 82 asymptomatic mitral valve prolapse (MVP) patients (65 ± 12 years, 51% men) with mild or moderate MR (36 mild, 46 moderate, mean LVEF: 62%), without significant co-morbidities. We examined clinical findings and 13 echo measurements. The primary end point was progression to severe MR. In a mean follow-up period of 4.5 ± 2.7 years, mortality and heart failure development were similar for mild and moderate MR. No mild MR patient progressed to severe, but 23 moderate MR patients (50.0%) progressed to severe with 9 patients (39.1%) who underwent surgery. No clinical variables were predictive for progression. Only mean mitral annulus diameter (apical 4 and 2 chamber) was predictive for progression to severe MR (hazards ratio 1.14, 95% confidence interval 1.03 to 1.26, p = 0.01). A cut-off annulus diameter of 39.6 mm had a good accuracy (area under the curve 0.78, sensitivity 100%, and specificity 63.8%) for progression to severe. In conclusion, over a 4.5-year period, 50% of asymptomatic MVP patients with moderate MR, but none with mild, progressed to severe MR. Only mitral annular dimension predicted progression of moderate to severe MR, and values >39.6 mm predicted progression accurately. Mitral annulus diameter may be of value in identifying asymptomatic MVP patients at risk of developing severe MR.

Acute right heart failure caused by tacrolimus after renal transplantation: Serial observation by speckle tracking and Doppler echocardiography.

Tacrolimus is an immunosuppressive agent well known to be capable of producing renal impairment. Acute renal failure with right heart failure caused by tacrolimus is rarely described. We report the findings of one such case in which tacrolimus caused acute renal failure with severe tricuspid regurgitation and right ventricular failure documented by echocardiography.

Tricuspid annular plane systolic excursion in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy.

BACKGROUND: Right ventricular function is impaired in chronic thromboembolic pulmonary hypertension (CTEPH). Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) have been shown to help assess right ventricular function in pulmonary hypertension. Our goal was to (1) assess TAPSE and RVFAC before and after PTE, and (2) assess correlation of these variables with right heart catheterization data and PVR. METHODS: We evaluated 67 consecutive patients with CTEPH for pulmonary thromboendarterectomy (PTE). Of these 67 patients, 48 were deemed surgical candidates. Preoperative right heart catheterization was performed within 1.3±1.2 days of the preoperative echocardiogram. All postoperative right heart catheterizations were performed on the first postoperative day. RESULTS: TAPSE dropped from 18±6 to 10±3 mm after PTE (P<.0001). RVFAC remained the same (25%±10% vs 30%±12%). Mean pulmonary artery (mPAP) pressure dropped from 45±12 to 28±6 mm Hg after PTE, and pulmonary vascular resistance (PVR) decreased from 757±406 to 306±147 dyne-s/cm5 (P<.0001 for both). Before PTE, TAPSE correlated inversely with PVR (r=-.57, P<.0001, TAPSE=-5.904×ln[PVR]+56.318). RVFAC did not correlate well with PVR or mean pulmonary artery pressure. After PTE, both TAPSE and RVFAC correlated poorly with PVR (r=-.12 and .01, respectively). CONCLUSION: In patients with CTEPH, TAPSE paradoxically decreased by 50% early after PTE. TAPSE correlated inversely with PVR prior to PTE, but this correlation was lost completely after PTE. Thus, despite the immediate and marked decrease in afterload postoperatively, TAPSE did not improve; thus, TAPSE cannot be used as an early marker for surgical success.

Right ventricular strain before and after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Right ventricular (RV) function is significantly impaired in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Two-dimensional speckle tracking RV strain and strain rate are novel methods to assess regional RV systolic function in CTEPH patients before and after pulmonary thromboendarterectomy (PTE). Our goal was to (1) assess baseline longitudinal strain and strain rate of the basal RV free wall in CTEPH and (2) measure early changes in RV strain and strain rate after PTE. METHODS: We performed echocardiography on 30 consecutive patients with CTEPH referred for PTE with adequate pre- and post-PTE strain imaging. Strain and strain rate were assessed 6.4 ± 4.5 days before and 9.1 ± 3.9 after PTE. RESULTS: Basal RV free wall strain and time to peak strain-but not basal RV strain rate and time to peak strain rate-changed significantly after PTE. Unexpectedly, basal RV strain became less negative, from -24.3% to -18.9% after PTE (P = 0.005). Time to peak strain decreased from 356 to 287 msec after PTE (P < 0.001). Preoperatively, RV strain correlated with pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP) but this relationship was not evident postoperatively. Furthermore, the change in RV strain did not correlate with the change in mPAP or PVR. CONCLUSIONS: In patients with CTEPH, RV basal strain paradoxically became less negative (i.e., relative systolic shortening decreased) following PTE. This change in RV strain could be due to intraoperative RV ischemia and/or postoperative stunning. Thus, RV basal strain cannot be used as a surrogate marker for surgical success early after PTE.

Long-term persistence of IgE anti-influenza A HIN1 virus antibodies in serum of children and adults following influenza A vaccination with subsequent H1N1 infection: a case study.

BACKGROUND AND METHODS: The role of immunoglobulin (Ig) E in immunity against influenza A H1N1 has not been studied. Total serum IgE and specific IgE and IgG anti-H1N1 virus responses were studied in children and adults (n = 2) who received influenza virus vaccination (Flumist(®) or Fluzone(®) ) in autumn 2008 and 2009, and then subsequently became infected with the H1N1 virus in spring 2009. Twelve months after infection, antibodies in their serum were compared with those in the serum of subjects who were either vaccinated but not infected (n = 4) or nonvaccinated and noninfected subjects (n = 2), using UniCAP total IgE fluoroenzyme immunoassay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and Western blotting. Band sizes for the influenza virus (58, 56, 40, 30, 25, and 17 kDa) and H1N1 viral proteins (58, 56, 25, and 17 kDa) were determined, using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Coomassie brilliant blue. RESULTS: We found that the serum of vaccinated and subsequently infected children and adults contained IgE and IgG antibodies to both H1N1 and influenza virus, with a strong IgE and IgG band intensity at 56 kDa. Interestingly, in subjects who were vaccinated but not infected, band intensity at 56 kDa was lowered by approximately two-fold. Serum of nonvaccinated and noninfected subjects had no detectable IgE or IgG antibodies to influenza virus or H1N1. CONCLUSION: This is the first description of IgE anti-influenza A H1N1 antibodies in human serum and the first demonstration of their long-term persistence. The decreased intensity of the 56 kDa band in vaccinated noninfected subjects compared with vaccinated infected subjects suggests augmented IgE and IgG antibody responses to influenza A H1N1.

Long term persistence of IgE anti-influenza virus antibodies in pediatric and adult serum post vaccination with influenza virus vaccine.

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, Parainfluenza virus, Varicella Zoster Virus), and the ability of IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Nevertheless, the presence and persistence of IgE anti-Influenza virus antibodies has not been studied. Total serum IgE and specific IgE and IgG anti-Influenza virus antibodies were studied in children (N = 3) (m/f 14-16 y/o) and adults (N = 3) (m/f, 41-49 y/o) 2-20 months after vaccination with Influenza virus (Flumist(®) or Fluzone(®)), as well as in non-vaccinated children (N = 2). (UniCAP total IgE Fluoroenzymeimmunoassay, ELISA, Immunoblot). We found that serum of vaccinated children and adults contained IgE and IgG anti-Influenza virus antibodies approaching two years post vaccination. Non-vaccinated children did not make either IgE or IgG anti-Influenza antibodies. Similar levels of IL-2, IFN-γ, IL-4, and IL-10 cytokines were detected in serum of vaccinated compared with non vaccinated subjects (p > 0.05), as well as between vaccinated adults compared with vaccinated children and non vaccinated subjects (p > 0.05). Vaccinated children and adults continue to produce IgE anti-Influenza virus antibodies long term post vaccination. The long term production of IgE anti-Influenza virus antibodies induced by vaccination may contribute to protective immunity against Influenza.