Long-term outcomes of domiciliary intravenous iloprost in idiopathic and connective tissue disease-associated pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: There are few published data on the efficacy of i.v. iloprost in pulmonary arterial hypertension (PAH). We present long-term outcomes in PAH patients receiving i.v. iloprost in a large UK referral centre. METHODS: Eighty patients with idiopathic PAH (iPAH, n = 46) or PAH associated with connective tissue disease (CTD-PAH, n = 34) were identified as receiving domiciliary i.v. iloprost between January 1999 and April 2015. Baseline characteristics, doses achieved, functional class at follow-up and survival data were retrieved from hospital databases. RESULTS: Median maximum dose achieved was 4.6 ng/kg/min in the iPAH group and 5.0 ng/kg/min in CTD-PAH patients. Exercise capacity significantly improved in the first 6 months of therapy in IPAH patients. Overall 1-, 3- and 5-year survival was 78%, 64% and 52% in iPAH (P = 0.002) and 64%, 26% and 21% in CTD-PAH. Independent predictors of survival were age and exercise capacity. CONCLUSION: We report improved survival to that previously reported in iPAH patients treated with domiciliary i.v. iloprost. This may be in part related to higher administered doses. Patients with CTD-PAH had poorer survival, reinforcing the need for early transplantation referral in suitable patients.

Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes.

BACKGROUND: Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. METHODS: Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. RESULTS: Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P < .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP = 0.61 sPAP + 2 mm Hg). The relationship in SSc-PAH was similar: mPAP = 0.58 sPAP + 2 mm Hg (P value for difference with IPAH = 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. CONCLUSIONS: The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

Pulmonary arterial hypertension associated with congenital heart disease: Comparison of clinical and anatomic-pathophysiologic classification.

BACKGROUND: Between 5% and 10% of patients with congenital heart disease (CHD) develop pulmonary arterial hypertension (PAH-CHD). Patients can be classified using either a clinical or anatomic-pathophysiologic system. No study has previously utilized both systems in a large cohort of patients. METHODS: Two hundred forty consecutive PAH-CHD patients diagnosed at a pulmonary hypertension referral center during 1995 to 2014 were identified from our unit database. Baseline characteristics, treatment and survival data were retrieved and survival analyses was performed. RESULTS: Both systems identified clear differences in baseline characteristics between subgroups. The anatomic-pathophysiologic system identified patients with post-tricuspid defects as having superior survival from point of referral to those with pre-tricuspid or complex defects (p < 0.05). Survival from point of referral was, however, not significantly different when patients were grouped using the clinical classification, although survival in all 4 groups was superior to that of 175 patients with idiopathic pulmonary arterial hypertension. Older age and higher creatinine, lower transfer factor of the lung for DLCO percent predicted and FEV1 percent predicted were independent adverse prognostic factors. CONCLUSION: Both PAH-CHD classification systems identified groups of patients distinct in terms of baseline characteristics. In our cohort, however, only the anatomic-pathophysiologic classification identified significantly different survival from point of referral. The presence of adverse prognostic markers may be useful in identifying patients requiring more aggressive pulmonary vascular therapy.

Pulmonary hypertension in patients with heart failure and preserved ejection fraction: differential diagnosis and management.

The most common cause of pulmonary hypertension (PH) due to left heart disease (LHD) was previously rheumatic mitral valve disease. However, with the disappearance of rheumatic fever and an aging population, nonvalvular LHD is now the most common cause of group 2 PH in the developed world. In this review, we examine the challenge of investigating patients who have PH and heart failure with preserved ejection fraction (HF-pEF), where differentiating between pulmonary arterial hypertension (PAH) and PH-LHD can be difficult, and also discuss the entity of combined precapillary and postcapillary PH. Given the proven efficacy of targeted therapy for the treatment of PAH, there is increasing interest in whether these treatments may benefit selected patients with PH associated with HF-pEF, and we review current trial data.

High prevalence of undetected heart failure in long-term care residents: findings from the Heart Failure in Care Homes (HFinCH) study.

AIMS: Diagnosis of heart failure in older people in long-term care is challenging because of co-morbidities, cognitive deficit, polypharmacy, immobility, and poor access to services. This study aimed to ascertain heart failure prevalence and clinical management in this population. METHODS AND RESULTS: A total of 405 residents, aged 65-100 years, in 33 UK care facilities were prospectively enrolled between April 2009 and June 2010. The presence of heart failure was determined using European Society of Cardiology guidelines, modified where necessary for immobility. Evaluation of symptoms and signs, functional capacity, and quality of life, portable on-site echocardiography, and medical record review were completed in 399 cases. The point prevalence of heart failure was 22.8% [n = 91, 95% confidence interval (CI) 18.8-27.2%]; of these, 62.7% (n = 57, 95% CI 59.6-66.5%) had heart failure with preserved ejection fraction and 37.3% had left ventricular systolic dysfunction (n = 34, 95% CI 34.8-40.5%). A total of 76% (n = 61) of previous diagnoses of heart failure were not confirmed, and up to 90% (n = 82) of study cases were new. No symptoms or signs were reliable predictors of heart failure. CONCLUSION: Heart failure was diagnosed in almost a quarter of residents: the prevalence was substantially higher than in other populations. The majority of heart failure cases were undiagnosed, while three-quarters of previously recorded cases were misdiagnosed. Common symptoms and signs appear to have little clinical utility in this population. Early, accurate differential diagnosis is key to the effective management of heart failure; this may be failing in long-term care facilities.

Utility of biomarkers in the differential diagnosis of heart failure in older people: findings from the heart failure in care homes (HFinCH) diagnostic accuracy study.

BACKGROUND: The performance of biomarkers for heart failure (HF) in older residents in long-term care is poorly understood and has not differentiated between left ventricular systolic dysfunction (LVSD) and HF with preserved ejection fraction (HFpEF). METHODS: This is the first diagnostic accuracy study in this population to assess the differential diagnostic performance and acceptability of a range of biomarkers against a clinical diagnosis using portable echocardiography. A total of 405 residents, aged 65-100 years (mean 84.2), in 33 UK long-term care facilities were enrolled between April 2009 and June 2010. RESULTS: For undifferentiated HF, BNP or NT-proBNP were adequate rule-out tests but would miss one in three cases (BNP: sensitivity 67%, NPV 86%, cut-off 115 pg/ml; NT-proBNP: sensitivity 62%, NPV 87%, cut-off 760 pg/ml). Using higher test cut-offs, both biomarkers were more adequate tests of LVSD, but would still miss one in four cases (BNP: sensitivity 76%, NPV 97%, cut-off 145 pg/ml; NT-proBNP: sensitivity 73%, NPV 97%, cut-off 1000 pg/ml). At these thresholds one third of subjects would test positive and require an echocardiogram. Applying a stricter 'rule out' threshold (sensitivity 90%), only one in 10 cases would be missed, but two thirds of subjects would require further investigation. Biomarkers were less useful for HFpEF (BNP: sensitivity 63%, specificity 61%, cut-off 110 pg/ml; NT-proBNP: sensitivity 68%, specificity 56%, cut-off 477 pg/ml). Novel biomarkers (Copeptin, MR-proADM, and MR-proANP) and common signs and symptoms had little diagnostic utility. CONCLUSIONS: No test, individually or in combination, adequately balanced case finding and rule-out for heart failure in this population; currently, in-situ echocardiography provides the only adequate diagnostic assessment. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN19781227.

Prolonged time between donor brain death and organ retrieval results in an increased risk of mortality in cardiac transplant recipients.

In cardiac transplantation longer ischemic times relate to poorer outcomes. However, brain death also promotes donor organ injury. The aim of this study was to ascertain if there was an association between longer time periods between donor brain death and organ retrieval with recipient mortality. This retrospective single centre study included 157 cardiac transplants performed between February 1999 and 2009. The time between the second brain stem death test and the cross-clamp time at organ retrieval was noted in hours. This was compared with survival time in years. Cox regression analysis was performed. The following variables were included: donor and recipient sex, age and cytomegalovirus status; donor smoking history; ischemic time and number of rejection episodes. Of the 157 transplants, 37 recipients have died. The mean follow-up was 4.1 years. The mean time between brain stem death test and cross-clamp time was 13.2±3.96 hours. Considering the above variables, the most significant finding is: increased time between brain stem death test and organ retrieval cross-clamp time, predicted a greater recipient mortality [hazard ratio (HR)=1.15; 95% confidence interval (CI)=1.06-1.24; P<0.001]. Longer delays between donor brain death and cross-clamp time are associated with a higher-risk of mortality in cardiac transplant recipients.