American journal of respiratory and critical care medicine, Jul 22, 2017
Prognostication is important when counselling patients and defining treatment strategies in pulmo... more Prognostication is important when counselling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). To determine the value of MRI metrics for prediction of mortality in PAH. Consecutive patients with PAH undergoing MRI were identified from the ASPIRE-Pulmonary-Hypertension-Registry. During the follow-up period of 42 (range 17-142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n=288, 115 deaths) and validation cohort (n=288, 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P<0.01); RV-end-systolic-volume-index adjusted for age and sex (RVESVI%pred) and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year: sensitivity 70 (95% CI 53-83), specificity 62 (95% CI 62-68), positive predictive value (PPV) 24 (95% CI 16-32) and negative predict...
In recent years there has been growing attention to the epistemology of clinical decision‐making,... more In recent years there has been growing attention to the epistemology of clinical decision‐making, but most studies have taken the individual physicians as the central object of analysis. In this paper we argue that knowing in current medical practice has an inherently social character and that imaging plays a mediating role in these practices. We have analyzed clinical decision‐making within a medical expert team involved in diagnosis and treatment of patients with pulmonary hypertension (PH), a rare disease requiring multidisciplinary team involvement in diagnosis and management. Within our field study, we conducted observations, interviews, video tasks, and a panel discussion. Decision‐making in the PH clinic involves combining evidence from heterogeneous sources into a cohesive framing of a patient, in which interpretations of the different sources can be made consistent with each other. Because pieces of evidence are generated by people with different expertise and interpretation and adjustments take place in interaction between different experts, we argue that this process is socially distributed. Multidisciplinary team meetings are an important place where information is shared, discussed, interpreted, and adjusted, allowing for a collective way of seeing and a shared language to be developed. We demonstrate this with an example of image processing in the PH service, an instance in which knowledge is distributed over multiple people who play a crucial role in generating an evaluation of right heart function. Finally, we argue that images fulfill a mediating role in distributed knowing in 3 ways: first, as enablers or tools in acquiring information ; second, as communication facilitators; and third, as pervasively framing the epistemic domain. With this study of clinical decision‐making in diagnosis and treatment of PH, we have shown that clinical decision‐making is highly social and mediated by technologies. The epistemol-ogy of clinical decision‐making needs to take social and technological mediation into account.
Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary a... more Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.
Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique wher... more Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for d...
Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary art... more Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH). All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases. 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (&amp;amp;amp;amp;amp;amp;lt;1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy. Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.
The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE)... more The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) features in patients with pulmonary hypertension. The prognostic significance of LGE in the clinical assessment of patients with pulmonary hypertension remains uncertain. Consecutive patients with suspected pulmonary hypertension seen at a specialist pulmonary hypertension referral center who underwent right heart catheterization and CMR with LGE imaging within 48 h were identified. Short-axis late-enhancement imaging was performed using a 3-dimensional gradient spoiled echocardiography sequence on a 1.5-T scanner. Three groups were identified: 1) no late enhancement of the myocardium; 2) late enhancement at the right ventricular insertion points (LGE-IP); and 3) late enhancement involving the right ventricular insertion points and the interventricular septum (LGE-S). Of 194 patients, 162 had pulmonary hypertension. LGE was identified in 135 of 162 (83%) patients with pulmonary hypertension, and 47 (29%) of patients demonstrated LGE-S. Patients with LGE-S had significantly higher right ventricular end-diastolic volume index (p = 0.013) and lower mixed venous oxygen saturation (p = 0.045) than patients with LGE-IP alone. The presence of LGE-S (p = 0.022), but not LGE-IP alone, right ventricular end-systolic volume (p = 0.045), right ventricular ejection fraction (p = 0.034), mixed venous oxygen saturation (p = 0.021), mean right atrial pressure (0.027), and male sex (p = 0.002) predicted mortality. At multivariate analysis, male sex was the only significant predictor of mortality independent of covariate predictors (p = 0.027). The presence of LGE at the right ventricular insertion points is suggestive of the presence of pulmonary hypertension. LGE may also be more extensive, involving the septum; however, after multivariable analysis including other factors associated with pulmonary hypertension, septal LGE was not associated with an increase in overall mortality.
Gerekçe: Bağ dokusu hastaliklariyla ilişkili pulmoner arteriyel hiper- tansiyon (BDH-PAH) tarihse... more Gerekçe: Bağ dokusu hastaliklariyla ilişkili pulmoner arteriyel hiper- tansiyon (BDH-PAH) tarihsel olarak kötü bir prognoza sahiptir; sis- temik skleroza bağli pulmoner arteriyel hipertansiyonu (SSc-PAH) olan hastalarin %45'inde sağkalim orani 1 yildir. Ancak, artik daha fazla tedavi olanaklari gündeme gelmektedir. Amaç: U.K. pulmoner hipertansiyon servisinde BDH-PAH tanisi al- miş bütün hastalarin sağkalimlarini ve özelliklerini araştirmak. Yöntem: Ocak 2001 ve Haziran 2006
The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of pat... more The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of patients with suspected pulmonary hypertension (PH). We hypothesized that in patients with SSc it may predict the presence or absence of PH. Details of all consecutive SSc patients undergoing MRI and right heart catheterization were collected prospectively. Subsequently, the VMI for all patients was calculated, and further baseline data were collected. Data for 40 patients, 28 of whom were diagnosed with PH at rest (PH(REST)), were analysed. VMI correlated strongly with mean pulmonary artery pressure (mPAP; r = 0.79). Using a VMI threshold of 0.56, positive predictive value (PPV) for PH(REST) was 88% and negative predictive value (NPV) was 100%. Using a threshold of 0.7, PPV was found to be 100% and NPV 53%. Echocardiographically obtained tricuspid gradient (TG) also demonstrated a strong correlation with mPAP. Two-year survival in patients with VMI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.7 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =0.7 was 91 and 43%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). VMI correlates well with mPAP in patients with SSc and may have a role in non-invasively excluding clinically significant PH in breathless SSc patients in whom echocardiographic screening has failed. Further study in larger groups of patients is justified.
ABSTRACT The incremental prognostic significance of late gadolinium enhanced (LGE) cardiovascular... more ABSTRACT The incremental prognostic significance of late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging in the clinical assessment of patients with pulmonary hypertension remains uncertain. We aimed to determine the prognostic value of LGE-CMR imaging in patients with pulmonary hypertension at 1-year follow-up.
After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), Europe... more After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data (&quot;potential safety signals&quot;) from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.
In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal dea... more In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.
American journal of respiratory and critical care medicine, Jul 22, 2017
Prognostication is important when counselling patients and defining treatment strategies in pulmo... more Prognostication is important when counselling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). To determine the value of MRI metrics for prediction of mortality in PAH. Consecutive patients with PAH undergoing MRI were identified from the ASPIRE-Pulmonary-Hypertension-Registry. During the follow-up period of 42 (range 17-142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n=288, 115 deaths) and validation cohort (n=288, 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P<0.01); RV-end-systolic-volume-index adjusted for age and sex (RVESVI%pred) and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year: sensitivity 70 (95% CI 53-83), specificity 62 (95% CI 62-68), positive predictive value (PPV) 24 (95% CI 16-32) and negative predict...
In recent years there has been growing attention to the epistemology of clinical decision‐making,... more In recent years there has been growing attention to the epistemology of clinical decision‐making, but most studies have taken the individual physicians as the central object of analysis. In this paper we argue that knowing in current medical practice has an inherently social character and that imaging plays a mediating role in these practices. We have analyzed clinical decision‐making within a medical expert team involved in diagnosis and treatment of patients with pulmonary hypertension (PH), a rare disease requiring multidisciplinary team involvement in diagnosis and management. Within our field study, we conducted observations, interviews, video tasks, and a panel discussion. Decision‐making in the PH clinic involves combining evidence from heterogeneous sources into a cohesive framing of a patient, in which interpretations of the different sources can be made consistent with each other. Because pieces of evidence are generated by people with different expertise and interpretation and adjustments take place in interaction between different experts, we argue that this process is socially distributed. Multidisciplinary team meetings are an important place where information is shared, discussed, interpreted, and adjusted, allowing for a collective way of seeing and a shared language to be developed. We demonstrate this with an example of image processing in the PH service, an instance in which knowledge is distributed over multiple people who play a crucial role in generating an evaluation of right heart function. Finally, we argue that images fulfill a mediating role in distributed knowing in 3 ways: first, as enablers or tools in acquiring information ; second, as communication facilitators; and third, as pervasively framing the epistemic domain. With this study of clinical decision‐making in diagnosis and treatment of PH, we have shown that clinical decision‐making is highly social and mediated by technologies. The epistemol-ogy of clinical decision‐making needs to take social and technological mediation into account.
Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary a... more Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.
Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique wher... more Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for d...
Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary art... more Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH). All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases. 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (&amp;amp;amp;amp;amp;amp;lt;1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy. Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.
The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE)... more The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) features in patients with pulmonary hypertension. The prognostic significance of LGE in the clinical assessment of patients with pulmonary hypertension remains uncertain. Consecutive patients with suspected pulmonary hypertension seen at a specialist pulmonary hypertension referral center who underwent right heart catheterization and CMR with LGE imaging within 48 h were identified. Short-axis late-enhancement imaging was performed using a 3-dimensional gradient spoiled echocardiography sequence on a 1.5-T scanner. Three groups were identified: 1) no late enhancement of the myocardium; 2) late enhancement at the right ventricular insertion points (LGE-IP); and 3) late enhancement involving the right ventricular insertion points and the interventricular septum (LGE-S). Of 194 patients, 162 had pulmonary hypertension. LGE was identified in 135 of 162 (83%) patients with pulmonary hypertension, and 47 (29%) of patients demonstrated LGE-S. Patients with LGE-S had significantly higher right ventricular end-diastolic volume index (p = 0.013) and lower mixed venous oxygen saturation (p = 0.045) than patients with LGE-IP alone. The presence of LGE-S (p = 0.022), but not LGE-IP alone, right ventricular end-systolic volume (p = 0.045), right ventricular ejection fraction (p = 0.034), mixed venous oxygen saturation (p = 0.021), mean right atrial pressure (0.027), and male sex (p = 0.002) predicted mortality. At multivariate analysis, male sex was the only significant predictor of mortality independent of covariate predictors (p = 0.027). The presence of LGE at the right ventricular insertion points is suggestive of the presence of pulmonary hypertension. LGE may also be more extensive, involving the septum; however, after multivariable analysis including other factors associated with pulmonary hypertension, septal LGE was not associated with an increase in overall mortality.
Gerekçe: Bağ dokusu hastaliklariyla ilişkili pulmoner arteriyel hiper- tansiyon (BDH-PAH) tarihse... more Gerekçe: Bağ dokusu hastaliklariyla ilişkili pulmoner arteriyel hiper- tansiyon (BDH-PAH) tarihsel olarak kötü bir prognoza sahiptir; sis- temik skleroza bağli pulmoner arteriyel hipertansiyonu (SSc-PAH) olan hastalarin %45'inde sağkalim orani 1 yildir. Ancak, artik daha fazla tedavi olanaklari gündeme gelmektedir. Amaç: U.K. pulmoner hipertansiyon servisinde BDH-PAH tanisi al- miş bütün hastalarin sağkalimlarini ve özelliklerini araştirmak. Yöntem: Ocak 2001 ve Haziran 2006
The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of pat... more The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of patients with suspected pulmonary hypertension (PH). We hypothesized that in patients with SSc it may predict the presence or absence of PH. Details of all consecutive SSc patients undergoing MRI and right heart catheterization were collected prospectively. Subsequently, the VMI for all patients was calculated, and further baseline data were collected. Data for 40 patients, 28 of whom were diagnosed with PH at rest (PH(REST)), were analysed. VMI correlated strongly with mean pulmonary artery pressure (mPAP; r = 0.79). Using a VMI threshold of 0.56, positive predictive value (PPV) for PH(REST) was 88% and negative predictive value (NPV) was 100%. Using a threshold of 0.7, PPV was found to be 100% and NPV 53%. Echocardiographically obtained tricuspid gradient (TG) also demonstrated a strong correlation with mPAP. Two-year survival in patients with VMI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.7 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =0.7 was 91 and 43%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). VMI correlates well with mPAP in patients with SSc and may have a role in non-invasively excluding clinically significant PH in breathless SSc patients in whom echocardiographic screening has failed. Further study in larger groups of patients is justified.
ABSTRACT The incremental prognostic significance of late gadolinium enhanced (LGE) cardiovascular... more ABSTRACT The incremental prognostic significance of late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging in the clinical assessment of patients with pulmonary hypertension remains uncertain. We aimed to determine the prognostic value of LGE-CMR imaging in patients with pulmonary hypertension at 1-year follow-up.
After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), Europe... more After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data (&quot;potential safety signals&quot;) from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.
In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal dea... more In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.
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