Sendaway capillary NT-proBNP in pulmonary hypertension.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing. METHODS: Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata. RESULTS: 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was -7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP. CONCLUSIONS: Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling.

Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

BACKGROUND: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. METHODS: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. RESULTS: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. CONCLUSIONS: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Clinical-radiological-pathological correlation in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary arterial pressure >20 mmHg. Current guidelines describe five groups of PH with shared pathophysiological and clinical features. In this paper, the first of a series covering all five PH classification groups, the clinical, radiological and pathological features of pulmonary arterial hypertension (PAH) will be reviewed. PAH may develop in the presence of associated medical conditions or a family history, following exposure to certain medications or drugs, or may be idiopathic in nature. Although all forms of PAH share common histopathological features, the presence of certain pulmonary arterial abnormalities, such as plexiform lesions, and extent of co-existing pulmonary venous involvement differs between the different subgroups. Radiological investigations are key to diagnosing the correct form of PH and a systematic approach to interpretation, especially of computed tomography, is essential.

BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing?

Despite the advent of new therapies and improved outcomes in patients with pulmonary arterial hypertension (PAH), it remains a life-shortening disease and the time to diagnosis remains unchanged. Strategies to improve outcomes are therefore currently focused on earlier diagnosis and a treatment approach aimed at moving patients with PAH into a category of low-risk of 1-year mortality. B-type natriuretic peptide (BNP; or brain natriuretic peptide) and N-terminal prohormone of BNP (NT-proBNP) are released from cardiac myocytes in response to mechanical load and wall stress. Elevated levels of BNP and NT-proBNP are incorporated into several PAH risk stratification tools and screening algorithms to aid diagnosis of systemic sclerosis. We have undertaken a systematic review of the literature with respect to the use of BNP and NT-proBNP in PAH and the use of these biomarkers in the diagnosis and risk stratification of PAH, their relation to pulmonary haemodynamics and the potential for point-of-care testing to improve diagnosis and prognosis.

Pathophysiology and Diagnosis of Pulmonary Hypertension Due to Left Heart Disease.

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common type of pulmonary hypertension, although an accurate prevalence is challenging. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. In recent years a new and distinct phenotype of "combined post-capillary and pre-capillary PH," based on diastolic pulmonary gradient and pulmonary vascular resistance, has been recognized. The roles of right ventricular dysfunction and pulmonary vascular compliance in PH-LHD have also been elucidated recently and they appear to have significant clinical implications. Echocardiography continues to play a seminal role in diagnosis of PH-LHD and heart failure with preserved LV ejection fraction, as it can identify valve disease and help to distinguish PH-LHD from pre-capillary PH. Right, and occasionally left heart catheterization, remains the gold-standard for diagnosis and phenotyping of PH-LHD, although Cardiac Magnetic Resonance Imaging is emerging as a useful alternative tool in non-invasive diagnostic and prognostic assessment of PH-LHD. In this review, the latest evidence for more recent advances will be discussed, including the role of fluid challenge and exercise during cardiac catheterization to unravel occult post-capillary and the role of vasoreactivity testing. The use of many or all of these diagnostic techniques will undoubtedly provide key information about sub-groups of patients with PH-LHD that might benefit from medical therapy previously considered to be only suitable for pulmonary arterial hypertension.