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Papers by Daniela Brady

Research paper thumbnail of Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact

Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact

The Annals of Thoracic Surgery

Research paper thumbnail of Fate of Tricuspid Valve Regurgitation after Pulmonary Endarterectomy in Chronic Thromboembolic Pulmonary Hypertension

The Journal of Heart and Lung Transplantation, 2021

Research paper thumbnail of PH Professional Network: Screening for Caregiver's Burden in Management of Scleroderma: Pulmonary Arterial Hypertension

Advances in Pulmonary Hypertension, 2017

Research paper thumbnail of Severe Postoperative Acute Kidney Injury Linked to Worse Two-Year Survival in Pulmonary Thromboendarterectomy Patients

The Journal of Heart and Lung Transplantation

Purpose: Baseline and periodic hemodynamic monitoring of pulmonary artery pressures using right h... more Purpose: Baseline and periodic hemodynamic monitoring of pulmonary artery pressures using right heart catheterization (RHC) is recommended for initiating and titrating pulmonary arterial hypertension (PAH) therapies as well as for prognostication. The CardioMEMS HF System is an ambulatory implantable hemodynamic monitor, previously only used in patients with left heart failure (HF). In this study, we describe the long-term safety and outcomes using the CardioMEMS device in PAH patients implanted as a part of an investigational pilot study. Methods: 23 PAH patients between the ages of 31-80 years, were implanted with CardioMEMS device as a part of an investigational pilot study (VITA contract HHSN268201400008C) between 08/2014-09/ 2018. 3 patients were lost to follow-up. Complete follow up data was available for 20 patients who were included in this analysis. Results: 85% of the PAH patients were female, with a median postimplant follow-up period of 58.5 months. The number of right heart catheterization (RHC) prior to the device implant was 4.37 per patient year, while only 1.99 RHC per patient year were done post implant. In long term follow up there were no significant device related adverse events and all devices remain functional. 8 patients did require RHC for recalibration of the device. 12 patients are still undergoing active monitoring. Of the remaining patients, 1 was enrolled in hospice, 4 patients died from progression of PAH, 1 patient died from malignancy; 1 from end-stage cirrhosis. There was a total of 13 HF hospitalizations between these 20 patients over 3 to 7 year follow-up based on the time of implant. Conclusion: The CardioMEMS device has previously been reported to reduce hospitalizations in patients with left sided heart failure. Based on our study, deployment of the device was safe in PAH patients with no long-term device related complications. It reduced the number of followup invasive RHC by more than 50%. Larger prospective studies are warranted before widespread use of the device for monitoring PA pressures in PAH patients.

Research paper thumbnail of PH Professional Network: Conference 2016 Recap: 25 Years of Progress

Advances in Pulmonary Hypertension, 2017

Research paper thumbnail of PH Professional Network: Dental Care in Children With Pulmonary Hypertension

Advances in Pulmonary Hypertension, 2016

Research paper thumbnail of 1123-177 Treatment for children with idiopathic pulmonary arterial hypertension: Long-term survival and outcomes

Journal of the American College of Cardiology, 2004

Methods: Human umbilical endothelial cells were cultured to confluence and stimulated with either... more Methods: Human umbilical endothelial cells were cultured to confluence and stimulated with either thrombin or histamine with or without inhibitors of protein kinases possibly involved in the regulation of eNOS activity. Phosphorylation of eNOS was analyzed with a phosphospecific eNOS(Ser1179) antibody by Western blotting. Results: Stimulation (using short term 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment) or inhibition (by GF 109203X) of protein kinase C had no effect on eNOS phosphorylation and neither did the Rho-dependent kinase inhibitorY27632, the calmodulin kinase inhibitor KN-62, the ERK-inhibitor PD98059 or the p38 inhibitor SB203580. Conversly, H89 which is an inhibitor of both protein kinase A (PKA) and the AMP-activated kinase (AMPK) strongly inhibited eNOS phosphorylation. Neither thrombin nor histamine caused a rise in endothelial cyclic-AMP and neither forskolin nor dibutyryl-cyclic-AMP affected eNOS phosphorylation contradicting the possible role of PKA in the activation pathway. On the other hand, thrombin and histamine caused phosphorylation of the AMPK downstream substances acetyl-CoA carboxylase and elongation factor-2. Conclusion: The G-protein activators thrombin and histamine stimulate eNOS phosphorylation on Ser1179 via an Akt-independent, AMPK-dependent pathway.

Research paper thumbnail of We've Come—and Are Going—a Long Way

Advances in Pulmonary Hypertension, 2012

Research paper thumbnail of Abstract 4380: Transition from IV Epoprostenol to Oral/Inhaled Targeted Pulmonary Arterial Hypertension Therapy in Pediatric Idiopathic Pulmonary Arterial Hypertension

Abstract 4380: Transition from IV Epoprostenol to Oral/Inhaled Targeted Pulmonary Arterial Hypertension Therapy in Pediatric Idiopathic Pulmonary Arterial Hypertension

Circulation, 2008

Introduction : Prior to the availability of oral/inhaled (inh) PAH drugs, i.e. 2001–2007, IV epop... more Introduction : Prior to the availability of oral/inhaled (inh) PAH drugs, i.e. 2001–2007, IV epoprostenol (EPO) was the only approved drug for pts un-responsive to calcium channel blockade (CCB). We report our experience transitioning selected pediatric IPAH pts from EPO (initiated prior to 2001) to oral/inh PAH drugs. Methods : We retrospectively reviewed all pediatric IPAH pts treated at Columbia Univ (1991–2008) who transitioned off EPO to oral/inh drugs. Pre-specified criteria for transition included: functional class (FC) I/II, mPAP<35mmHg, normal CO and age > 6 yrs at transition. Hemodynamic and exercise data were obtained at baseline (prior to EPO initiation), at peak EPO dose, and at least 2 mos after EPO discontinuation (d/c) on stable oral/inh drug doses. Data: m ± SD. Results : 13 IPAH pts (6 F) transitioned off EPO between 4/03–11/07 (max dose 100 ± 42ng/kg/min) to oral/inh drugs at 11.6 ± 3.6 yrs of age. Mean duration on EPO: 6.6 ± 3.4yrs (range 1.2–12yrs); f/u post EPO d/c: 10.4 ± 11.6 mos (range 2–42.8 mos). Treatment with EPO improved hemodynamics vs. baseline (p<0.05) with no significant changes in hemodynamics or exercise capacity off EPO. In addition, further improvement was reported in FC off EPO (p<0.002; n=13). Conclusions : In selected IPAH children who began EPO prior to the availability of oral/inh PAH drugs, transition to oral/inh PAH therapy appears safe with efficacy maintained. Whether early initiation of EPO improves long-term outcome vs. deferral of EPO until oral/inh therapy fails remains unknown; further studies with longer-term follow-up are warranted.

Research paper thumbnail of Pulmonary Arterial Hypertension Short and Long-Term Effects of Inhaled Iloprost Therapy in Children With

Pulmonary Arterial Hypertension Short and Long-Term Effects of Inhaled Iloprost Therapy in Children With

Research paper thumbnail of Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension

Pediatric Pulmonology, 2013

Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, t... more Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 AE 18 vs. 45 AE 20 mmHg, n ¼ 13, P ¼ 0.04, add-on; 52 AE 17 vs. 45 AE 19 mmHg, n ¼ 13, P ¼ 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4-44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 AE 452 ng/ml, mean time to peak plasma concentration was 3.2 AE 2.1 hours, and mean area under the curve plasma concentration was 6657 AE 4246 ngÁhour/ml. In conclusion, initial experience with ambrisentan in children suggests that treatment is safe with similar pharmacokinetics to those in adults and may improve PAH in some children. Pediatr Pulmonol. ß

Research paper thumbnail of Common Atrium and Pulmonary Vascular Disease

Pediatric Cardiology, 2011

This report describes a case series of six patients with congenital common atrium who developed p... more This report describes a case series of six patients with congenital common atrium who developed pulmonary vascular disease. Three developed early pulmonary vascular disease within their first year of life, while the others became symptomatic at ages 2, 5, and 17. Four of the six underwent surgical repair, and five of the six patients are being treated on targeted pulmonary hypertension therapy. Based on our observations, the clinical course of children with common atrium may differ from patients with a large atrial septal defect. Early monitoring and surgical correction, if necessary, may prevent the onset of severe pulmonary vascular disease.

Research paper thumbnail of Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

Journal of the American College of Cardiology, 2008

Objectives-This study investigated the short-and long-term outcome of children with pulmonary art... more Objectives-This study investigated the short-and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost.

Research paper thumbnail of Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact

Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact

The Annals of Thoracic Surgery

Research paper thumbnail of Fate of Tricuspid Valve Regurgitation after Pulmonary Endarterectomy in Chronic Thromboembolic Pulmonary Hypertension

The Journal of Heart and Lung Transplantation, 2021

Research paper thumbnail of PH Professional Network: Screening for Caregiver's Burden in Management of Scleroderma: Pulmonary Arterial Hypertension

Advances in Pulmonary Hypertension, 2017

Research paper thumbnail of Severe Postoperative Acute Kidney Injury Linked to Worse Two-Year Survival in Pulmonary Thromboendarterectomy Patients

The Journal of Heart and Lung Transplantation

Purpose: Baseline and periodic hemodynamic monitoring of pulmonary artery pressures using right h... more Purpose: Baseline and periodic hemodynamic monitoring of pulmonary artery pressures using right heart catheterization (RHC) is recommended for initiating and titrating pulmonary arterial hypertension (PAH) therapies as well as for prognostication. The CardioMEMS HF System is an ambulatory implantable hemodynamic monitor, previously only used in patients with left heart failure (HF). In this study, we describe the long-term safety and outcomes using the CardioMEMS device in PAH patients implanted as a part of an investigational pilot study. Methods: 23 PAH patients between the ages of 31-80 years, were implanted with CardioMEMS device as a part of an investigational pilot study (VITA contract HHSN268201400008C) between 08/2014-09/ 2018. 3 patients were lost to follow-up. Complete follow up data was available for 20 patients who were included in this analysis. Results: 85% of the PAH patients were female, with a median postimplant follow-up period of 58.5 months. The number of right heart catheterization (RHC) prior to the device implant was 4.37 per patient year, while only 1.99 RHC per patient year were done post implant. In long term follow up there were no significant device related adverse events and all devices remain functional. 8 patients did require RHC for recalibration of the device. 12 patients are still undergoing active monitoring. Of the remaining patients, 1 was enrolled in hospice, 4 patients died from progression of PAH, 1 patient died from malignancy; 1 from end-stage cirrhosis. There was a total of 13 HF hospitalizations between these 20 patients over 3 to 7 year follow-up based on the time of implant. Conclusion: The CardioMEMS device has previously been reported to reduce hospitalizations in patients with left sided heart failure. Based on our study, deployment of the device was safe in PAH patients with no long-term device related complications. It reduced the number of followup invasive RHC by more than 50%. Larger prospective studies are warranted before widespread use of the device for monitoring PA pressures in PAH patients.

Research paper thumbnail of PH Professional Network: Conference 2016 Recap: 25 Years of Progress

Advances in Pulmonary Hypertension, 2017

Research paper thumbnail of PH Professional Network: Dental Care in Children With Pulmonary Hypertension

Advances in Pulmonary Hypertension, 2016

Research paper thumbnail of 1123-177 Treatment for children with idiopathic pulmonary arterial hypertension: Long-term survival and outcomes

Journal of the American College of Cardiology, 2004

Methods: Human umbilical endothelial cells were cultured to confluence and stimulated with either... more Methods: Human umbilical endothelial cells were cultured to confluence and stimulated with either thrombin or histamine with or without inhibitors of protein kinases possibly involved in the regulation of eNOS activity. Phosphorylation of eNOS was analyzed with a phosphospecific eNOS(Ser1179) antibody by Western blotting. Results: Stimulation (using short term 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment) or inhibition (by GF 109203X) of protein kinase C had no effect on eNOS phosphorylation and neither did the Rho-dependent kinase inhibitorY27632, the calmodulin kinase inhibitor KN-62, the ERK-inhibitor PD98059 or the p38 inhibitor SB203580. Conversly, H89 which is an inhibitor of both protein kinase A (PKA) and the AMP-activated kinase (AMPK) strongly inhibited eNOS phosphorylation. Neither thrombin nor histamine caused a rise in endothelial cyclic-AMP and neither forskolin nor dibutyryl-cyclic-AMP affected eNOS phosphorylation contradicting the possible role of PKA in the activation pathway. On the other hand, thrombin and histamine caused phosphorylation of the AMPK downstream substances acetyl-CoA carboxylase and elongation factor-2. Conclusion: The G-protein activators thrombin and histamine stimulate eNOS phosphorylation on Ser1179 via an Akt-independent, AMPK-dependent pathway.

Research paper thumbnail of We've Come—and Are Going—a Long Way

Advances in Pulmonary Hypertension, 2012

Research paper thumbnail of Abstract 4380: Transition from IV Epoprostenol to Oral/Inhaled Targeted Pulmonary Arterial Hypertension Therapy in Pediatric Idiopathic Pulmonary Arterial Hypertension

Abstract 4380: Transition from IV Epoprostenol to Oral/Inhaled Targeted Pulmonary Arterial Hypertension Therapy in Pediatric Idiopathic Pulmonary Arterial Hypertension

Circulation, 2008

Introduction : Prior to the availability of oral/inhaled (inh) PAH drugs, i.e. 2001–2007, IV epop... more Introduction : Prior to the availability of oral/inhaled (inh) PAH drugs, i.e. 2001–2007, IV epoprostenol (EPO) was the only approved drug for pts un-responsive to calcium channel blockade (CCB). We report our experience transitioning selected pediatric IPAH pts from EPO (initiated prior to 2001) to oral/inh PAH drugs. Methods : We retrospectively reviewed all pediatric IPAH pts treated at Columbia Univ (1991–2008) who transitioned off EPO to oral/inh drugs. Pre-specified criteria for transition included: functional class (FC) I/II, mPAP<35mmHg, normal CO and age > 6 yrs at transition. Hemodynamic and exercise data were obtained at baseline (prior to EPO initiation), at peak EPO dose, and at least 2 mos after EPO discontinuation (d/c) on stable oral/inh drug doses. Data: m ± SD. Results : 13 IPAH pts (6 F) transitioned off EPO between 4/03–11/07 (max dose 100 ± 42ng/kg/min) to oral/inh drugs at 11.6 ± 3.6 yrs of age. Mean duration on EPO: 6.6 ± 3.4yrs (range 1.2–12yrs); f/u post EPO d/c: 10.4 ± 11.6 mos (range 2–42.8 mos). Treatment with EPO improved hemodynamics vs. baseline (p<0.05) with no significant changes in hemodynamics or exercise capacity off EPO. In addition, further improvement was reported in FC off EPO (p<0.002; n=13). Conclusions : In selected IPAH children who began EPO prior to the availability of oral/inh PAH drugs, transition to oral/inh PAH therapy appears safe with efficacy maintained. Whether early initiation of EPO improves long-term outcome vs. deferral of EPO until oral/inh therapy fails remains unknown; further studies with longer-term follow-up are warranted.

Research paper thumbnail of Pulmonary Arterial Hypertension Short and Long-Term Effects of Inhaled Iloprost Therapy in Children With

Pulmonary Arterial Hypertension Short and Long-Term Effects of Inhaled Iloprost Therapy in Children With

Research paper thumbnail of Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension

Pediatric Pulmonology, 2013

Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, t... more Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 AE 18 vs. 45 AE 20 mmHg, n ¼ 13, P ¼ 0.04, add-on; 52 AE 17 vs. 45 AE 19 mmHg, n ¼ 13, P ¼ 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4-44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 AE 452 ng/ml, mean time to peak plasma concentration was 3.2 AE 2.1 hours, and mean area under the curve plasma concentration was 6657 AE 4246 ngÁhour/ml. In conclusion, initial experience with ambrisentan in children suggests that treatment is safe with similar pharmacokinetics to those in adults and may improve PAH in some children. Pediatr Pulmonol. ß

Research paper thumbnail of Common Atrium and Pulmonary Vascular Disease

Pediatric Cardiology, 2011

This report describes a case series of six patients with congenital common atrium who developed p... more This report describes a case series of six patients with congenital common atrium who developed pulmonary vascular disease. Three developed early pulmonary vascular disease within their first year of life, while the others became symptomatic at ages 2, 5, and 17. Four of the six underwent surgical repair, and five of the six patients are being treated on targeted pulmonary hypertension therapy. Based on our observations, the clinical course of children with common atrium may differ from patients with a large atrial septal defect. Early monitoring and surgical correction, if necessary, may prevent the onset of severe pulmonary vascular disease.

Research paper thumbnail of Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

Journal of the American College of Cardiology, 2008

Objectives-This study investigated the short-and long-term outcome of children with pulmonary art... more Objectives-This study investigated the short-and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost.