Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

박재형,Margaret M. Park,Samar Farha,Jacqueline Sharp,Erika Lundgrin,Suzy Comhair,Wai Hong Tang,Serpil C. Erzurum,James D. Thomas 한국심초음파학회 2015 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.23 No.2

Background: New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics byassessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, theprognostic significance of impaired GLSRV is unclear in these patients. Methods: Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI,Siemens Medical System, Mountain View, CA, USA). Results: GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular planesystolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonaryvascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followuptime (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heartfailure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p =0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were alsosignificant predictors of death. Impaired GLSRV (≥ -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001)and increased mortality (HR = 8.842, p = 0.005). Conclusion: GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RVsystolic function. Lower GLSRV (≥ -15.5%) was significantly associated with presence of adverse clinical events and deaths inPAH patients.

Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial

Easterhoff, David,Moody, M. Anthony,Fera, Daniela,Cheng, Hao,Ackerman, Margaret,Wiehe, Kevin,Saunders, Kevin O.,Pollara, Justin,Vandergrift, Nathan,Parks, Rob,Kim, Jerome,Michael, Nelson L.,O’Connell, Public Library of Science 2017 PLoS pathogens Vol.13 No.2

<▼1><P>The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1-uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell V<SUB>H</SUB> mutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports. While post-boost plasma did not have bnAb activity, the vaccine boosts expanded a pool of envelope CD4 binding site (bs)-reactive memory B cells with long third heavy chain complementarity determining regions (HCDR3) whose germline precursors and affinity matured B cell clonal lineage members neutralized the HIV-1 CRF01 AE tier 2 (difficult to neutralize) primary isolate, CNE8. Electron microscopy of two of these antibodies bound with near-native gp140 trimers showed that they recognized an open conformation of the Env trimer. Although late boosting of RV144 vaccinees expanded a novel pool of neutralizing B cell clonal lineages, we hypothesize that boosts with stably closed trimers would be necessary to elicit antibodies with greater breadth of tier 2 HIV-1 strains.</P><P><B>Trial Registration:</B> ClinicalTrials.gov NCT01435135</P></▼1><▼2><P><B>Author summary</B></P><P>Developing a successful HIV-1 vaccine remains a high global health priority. Several HIV-1 vaccine trials have been performed with only the RV144 vaccine trial showing vaccine efficacy, albeit modest. No broadly neutralizing antibody activity was identified in RV144 and inducing sterilizing immunity against a complex pathogen like HIV-1 remains a major challenge. Here we characterize the B cell responses after RV144 vaccine-recipients received two additional boosts severals years after the conclusion of the RV144 vaccine trial. Delayed and repetitive boosting of RV144 vaccine-recipients was capable of increasing somatic hypermutation of the Env-reactive antibodies and expanding subdominant pools of neutralizing B cell clonal lineages. These data are pertinent to HIV-1 vaccine-regimen design.</P></▼2>

Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension

박재형,Kenya Kusunose,Deborah H. Kwon,Margaret M. Park,James D. Thomas,Richard A. Grimm,Brian P. Griffin,Thomas H. Marwick,Zoran B. Popović 대한심장학회 2016 Korean Circulation Journal Vol.46 No.2

Background and Objectives Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. Subjects and Methods Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45±13 years old). RVLS were analyzed with velocity vector imaging. Results Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLSglobal, -17±5 vs. -12±3%, p<0.01) and RV free wall (RVLSFW, -19±5 vs. -14±4%, p<0.01 to NYHA class I/II). Baseline RVLSglobal and RVLSFW showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<0.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54±13 to 46±16 mmHg, p=0.03) and PVR (11±5 to 6±2 wood units, p<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12±5 to -16±5%, p<0.01) and RVLSFW (-14±5 to -18±5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p<0.01) and RVLSFW (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p<0.01). Conclusion RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS.

Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension

박재형,Kenya Kusunose,Deborah H. Kwon,Margaret M. Park,Serpil C. Erzurum,James D. Thomas,Richard A. Grimm,Brian P. Griffin,Thomas H. Marwick,Zoran B. Popović 대한심장학회 2015 Korean Circulation Journal Vol.45 No.5

Background and Objectives: Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. Subjects and Methods: Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45±13 years old). RVLS were analyzed with velocity vector imaging. Results: Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLSglobal, -17±5 vs. -12±3%, p<0.01) and RV free wall (RVLSFW, -19±5 vs. -14±4%, p<0.01 to NYHA class I/II). Baseline RVLSglobal and RVLSFW showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<0.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54±13 to 46±16 mmHg, p=0.03) and PVR (11±5 to 6±2 wood units, p<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12±5 to -16±5%, p<0.01) and RVLSFW (-14±5 to -18±5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p<0.01) and RVLSFW (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p<0.01). Conclusion: RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS