P1810 Impact of pulmonary hypertension on survival in patients with degenerative aortic stenosis, prospective clinical trial

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
D Mercea ◽  
R Ianos ◽  
C Pop ◽  
D Pop ◽  
D Zdrenghea ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Survival Rate ◽  
Aortic Stenosis ◽  
Survival Data ◽  
Proportional Hazards ◽  
Negative Impact ◽  
Severe Aortic Stenosis ◽  
Cox Proportional Hazards ◽  
Logrank Test ◽  
Pulmonary Pressure

Abstract Introduction Aortic stenosis has become the most common degenerative valvular heart disease, due to aging of the population. It represents 43% of degenerative valvular disease. Methods We prospectively followed 196 patients with degenerative aortic stenosis, for a period of 6 years. Of these, 106 had mild aortic stenosis, 28 had moderate aortic stenosis and 62 patients had severe aortic stenosis. Of the 196 patients, 54 had mild pulmonary hypertension (PH), 22 had moderate PH and 7 had severe PH. The survival data were estimated by the Kaplan - Meier method and the logrank test. The Cox proportional- hazards regression was performed to assess the differences between the groups. Results During the follow-up period, of a total of 196 patients, 61 patients died. We studied if the presence of PH has an influence on survival in patients with aortic stenosis and we found out that the patients who had PH had reduced survival rates, compared with those who hadn"t. The survival rate at 5 years was lower in the group with mild PH compared with the group with normal pulmonary pressure ( p = 0.045, HR 1.84, 95%CI 1.01-3.36). In the group with mild PH, 20 patients (37.03%) died at 5 years, compared with 23 in the group without PH (20.35%). The survival rate at 5 years was also lower in the group with moderate PH compared with the group with normal pulmonary pressure ( p = 0.001, HR 5.82, 95% CI 3.02-11.22). At 5 years, 15 patients with moderate PH died ( 68.18% compared with 20.35 in the group without PH). Comparing the group with severe PH with the group with normal pulmonary pressure the results showed a reduced survival rate in those with severe pulmonary hypertension ( p = 0.139, HR 2.48, 95% CI 0.74-8.27). At 5 years, 3 patients with severe PH died (42.85% compared with 20.35 in the group without PH). Conclusion The presence of PH in patients with degenerative aortic stenosis has a negative impact on survival, highly statistically significant (p <0.001, HR 1.03, 95% CI, 1.02-1.04). Given these findings, perhaps an increased attention should be paid to the treatment of the patients with PH compared to those without PH.

scholarly journals Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

2021 ◽  
Vol 15 (3) ◽  
pp. 155798832110294
Author(s):  
Zhen-Chun Lv ◽  
Fei Li ◽  
Lan Wang ◽  
Qin-Hua Zhao ◽  
Gong-Su Gang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Proportional Hazards ◽  
Clinical Status ◽  
Disease Onset ◽  
Adenosine Diphosphate ◽  
Cox Proportional Hazards ◽  
Enzyme Linked Immunosorbent Assay ◽  
Increased Risk ◽  
Male Patients ◽  
Parp 1

There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan–Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all p < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all p < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all p < .005). Patients with PARP-1 levels <11.24 ng/mL or AIF levels <1.459 pg/mL had significantly better survival than those with higher PARP-1 or AIF levels ( p < .0001). Circulating levels of PARP-1 and AIF were independent predictors for PH onset and mortality, which indicated that parthanatos might be associated with the pathogenesis of PH.

scholarly journals First-phase ejection fraction by cardiovascular magnetic resonance predicts outcomes in aortic stenosis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Haotian Gu ◽  
Rong Bing ◽  
Calvin Chin ◽  
Lingyun Fang ◽  
Audrey C. White ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Ejection Fraction ◽  
Proportional Hazards ◽  
Function Analysis ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Cox Proportional Hazards

Abstract Background First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. Methods In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). Results Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89–0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. Conclusions EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure–function analysis.

Abstract 15388: Persistent Pulmonary Hypertension After Transcatheter Aortic Valve Implantation: Impact on Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Maria Drakopoulou ◽  
Konstantinos Stathogiannis ◽  
Konstantinos Toutouzas ◽  
George Latsios ◽  
Andreas Synetos ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Aortic Stenosis ◽  
Pulmonary Artery ◽  
Severe Aortic Stenosis ◽  
Systolic Pressure ◽  
Right Atrial ◽  
Pulmonary Artery Systolic Pressure ◽  
End Point ◽  
The Right ◽  
The Impact

Objective: Severe aortic stenosis leads to increased pulmonary arterial systolic pressure. A controversy still remains regarding the impact of persistent pulmonary hypertension (PHT) on prognosis of patients undergoing transcatheter aortic valve implantation (TAVI). We sought to investigate the impact of persistent PHT on 2-year all-cause mortality of patients with severe aortic stenosis following TAVI. Methods: Patients with severe and symptomatic aortic stenosis (effective orifice area [EOA]≤1 cm 2 ) who were scheduled for TAVI with a self-expanding valve at our institution were prospectively enrolled. Prospectively collected echocardiographic data before and after TAVI were retrospectively analyzed in all patients. Pulmonary artery systolic pressure was estimated as the sum of the right ventricular to the right atrial gradient during systole and the right atrial pressure. PHT following TAVI was classified as absent if <35 mmHg and persistent if ≥35 mmHg. Primary clinical end-point was 2-year all-cause mortality defined according to the criteria proposed by the Valve Academic Research Consortium-2. Results: Hundred and forty patients (mean age: 82±9 years) were included in the study. The primary clinical end point occurred in 17 patients (12%) during a median follow-up period of 2 years. Mean pulmonary artery systolic pressure was reduced in all patients following TAVI (45±9 versus 41±6 mmHg, p<0.01). Mortality rate was higher in patients with persistent PHT compared to patients with normal pulmonary artery systolic pressure following TAVI (26% versus 14 %, p<0.01). Patients that reached the primary clinical end point had a higher post procedural mean systolic pulmonary pressure (43±9 versus 39±6 mmHg, p=0.02). In multivariate regression analysis, persistence of PHT (OR: 2.51, 95% CI: 1.109-7.224, p=0.01) was an independent predictor of long-term mortality. Conclusions: The persistence of pulmonary hypertension after TAVI is associated with long term mortality. Identifying the population that will clearly benefit from TAVI is still need to be validated by larger trials.

scholarly journals 1388. Dose Discrimination for ASN100: Bridging from Rabbit Survival Data to Predicted Activity in Humans Using a Minimal Physiologically Based Pharmacokinetic (mPBPK) Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S426-S426
Author(s):  
Christopher M Rubino ◽  
Lukas Stulik ◽  
Harald Rouha ◽  
Zehra Visram ◽  
Adriana Badarau ◽  
...  
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Virulent Strain ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Simulated Patients ◽  
Research Support ◽  
Mpbpk Model

Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.

scholarly journals Social deprivation in Scottish populations with pulmonary hypertension secondary to connective tissue disease and chronic thromboembolic disease

2020 ◽  
Vol 6 (4) ◽  
pp. 00297-2019 ◽  
Author(s):  
Michael McGettrick ◽  
Paul McCaughey ◽  
Alexander MacLellan ◽  
Melanie Brewis ◽  
A. Colin Church ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Proportional Hazards ◽  
Social Deprivation ◽  
Population Distribution ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Cox Proportional Hazards ◽  
Functional Class ◽  
The Usa

Socioeconomic factors have been shown to have an adverse impact on survival in some respiratory diseases. Studies from the USA and China have suggested worse survival in idiopathic pulmonary arterial hypertension in low socioeconomic groups. We looked at the effect of deprivation on the outcomes in patients with connective tissue disease-associated pulmonary hypertension (CTDPH) and chronic thromboembolic pulmonary hypertension (CTEPH) in a retrospective observational study.Data were obtained from 232 patients with CTDPH and 263 with CTEPH who were under the care of the Scottish Pulmonary Vascular Unit, Glasgow, UK. We used Cox proportional hazards regression to assess for a relationship between deprivation and survival.We found no difference in survival across deprivation quintiles in the CTDPH (p=0.26) or CTEPH cohorts (p=0.18). We constructed multivariate models using enrolment time, age, sex and body mass index, with no significant change in findings. There was no difference between expected and observed population distribution of CTDPH (p=0.98) and CTEPH (p=0.36). Whilst there was no difference in presenting functional class in the CTDPH group, the CTEPH patients in more deprived quintiles presented in a worse functional class (p=0.032). There was no difference between quintiles of CTEPH patients who had distal or proximal disease (p=0.75), or who underwent surgery (p=0.5).Increased social deprivation is not associated with worse survival in patients with CTDPH and CTEPH managed in the Scottish National Health Service. Whilst there is no evidence of referral barriers in CTDPH, this may not be the case in CTEPH, as lower deprivation was associated with worse functional class at presentation.

Effect of HPV Status on Survival of Oropharynx Cancer with Distant Metastasis

2020 ◽  
Vol 163 (2) ◽  
pp. 372-374 ◽  
Author(s):  
Adam W. Kaplon ◽  
Thomas J. Galloway ◽  
Mihir K. Bhayani ◽  
Jeffrey C. Liu
Keyword(s):  
Distant Metastasis ◽  
Survival Data ◽  
Regression Models ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
National Cancer Database ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Hpv Status ◽  
Oropharynx Squamous Cell Carcinoma

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.

scholarly journals High SALM3 Expression in Tumor Cells and Fibroblasts Is Correlated with Poor Prognosis in Gastric Cancer Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Liu ◽  
Xiaoli Chen ◽  
Xi Chen ◽  
Xiaobing Yang ◽  
Qingjie Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Survival Data ◽  
Proportional Hazards ◽  
Synapse Formation ◽  
Tissue Microarrays ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.

Depressive Symptoms

2016 ◽  
Vol 39 (4) ◽  
pp. 539-552
Author(s):  
Muna H. Hammash ◽  
Terry A. Lennie ◽  
Timothy Crawford ◽  
Seongkum Heo ◽  
Misook L. Chung ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Survival Data ◽  
Proportional Hazards ◽  
Heart Association ◽  
Cox Proportional Hazards ◽  
Health Perceptions ◽  
Class Iii ◽  
Event Free Survival ◽  
Free Survival ◽  
The Relationship

Depressive symptoms and poor health perceptions are predictors of higher hospitalization and mortality rates (heart failure [HF]). However, the association between depressive symptoms and health perceptions as they affect event-free survival outcomes in patients with HF has not been studied. The purpose of this secondary analysis was to determine whether depressive symptoms mediate the relationship between health perceptions and event-free survival in patients with HF. A total of 458 HF patients (61.6 ± 12 years, 55% New York Heart Association Class III/IV) responded to one-item health perception question and completed the Patient Health Questionnaire–9. Event-free survival data were collected for up to 4 years. Multiple regression and Cox proportional hazards regression analysis showed that depressive symptoms mediated the relationship between health perceptions and event-free survival. Decreasing depressive symptoms is essential to improve event-free survival in patients with HF.

Natriuretic Peptide Levels Correlate with Pulmonary Pressures and Prospective Mortality in SCD: Use of This Biomarker To Identify Prevalence and Mortality of Pulmonary Hypertension in the MSH Cohort.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1-1
Author(s):  
Roberto Machado ◽  
Martin Steinberg ◽  
Duane Bonds ◽  
Samir Ballas ◽  
William Blackwelder ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cell Disease ◽  
Risk Of Death ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Pulmonary hypertension [PH-tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s] is a common complication of sickle cell disease associated with high mortality. Identification of biomarkers of PH and mortality could facilitate screening and risk stratification in this population. Validated biomarkers would provide methods for retrospective evaluation of the prevalence and prognosis of PH in large historical cohorts of patients such as the Multicenter Study of Hydroxyurea in Sickle Cell Anemia(MSH). Because brain natriuretic peptide(BNP) is released from the ventricles during pressure strain, we hypothesized that BNP levels would correlate with the severity of PH and prospective risk of death in patients with SCD. BNP was measured in 45 African-American control subjects and 230 patients with SCD. Median (interquartile range) BNP(pg/ml) was higher in patients with PH than patients without PH or controls[+PH: 206(81–701),-PH: 47(26–104), C: 29, P&lt;0.001]. BNP levels directly correlated with age (R=0.32, P&lt;0.001), creatinine (R=0.22, P&lt;0.001), LDH(R=0.31, P&lt;0.001), TRV (R=0.5, P&lt;0.001), pulmonary vascular resistance (R=0.5, P=0.001); and inversely with hemoglobin(R=0.41, P&lt;0.001), cardiac output(R=0.47, P= 0.003) and 6-minute walk distance(R=0.51, P=0.001). The area under the ROC for BNP and the diagnosis of pulmonary hypertension was 0.84 (P&lt;0.001). A cutoff value of 160 pg/ml (corresponding to the 75th percentile for the population) had 58% sensitivity and 98% specificity for the diagnosis of PH. Cox proportional hazards regression identified BNP as an independent predictor of mortality(RR 2.17,95% CI 1.2–3.8, P =0.001) with clear mortality break point at the 75th percentile(160 pg/ml). To independently explore the prevalence and associated risk of PH in patients with sickle cell disease, a BNP value of 160 pg/ml was used as an indicator of PH. BNP levels were then measured in plasma samples collected in 121 patients who were enrolled in the MSH patient’s follow-up study that started in 1996. These patients had received hydroxyurea or placebo for two years, had moderately severe disease based on study entry criteria, and had 9-years of comprehensive follow-up. An abnormal BNP level ≥160 pg/ml was present in 30% of patients in the MSH cohort. BNP levels correlated directly with age(R=0.35, P&lt;0.001) and creatinine (R=0.24, P&lt;0.001), and inversely with hemoglobin(R=−0.54, P&lt;0.001). There was no correlation between BNP and rate of painful episodes or acute chest syndrome, use of hydroxyurea or leukocyte count. A high BNP level in the MSH cohort was associated with mortality by logistic regression(OR 3.04,95% CI 1.2–7.6, P = 0.018) and Cox proportional hazards regression analysis(RR 2.87, P=0.017). The relationship remained significant for continuous log- transformed BNP values and after adjustment for other covariates. These studies confirm that PH is common, mechanistically linked to hemolytic anemia and the major risk factor for death in SCD. Provocatively, the MSH analysis suggests that rates of pain episodes in this small sample of seriously ill patients were unrelated to risk of death: this risk was largely determined by a high BNP level, which is probably explained by undiagnosed hemolysis-associated PH.

Sign in / Sign up

Export Citation Format

Share Document