Genetic testing for long QT syndrome in the West of Scotland
Nisar H, Ramsay R, Longmuir M, Constantinou P, Coats C, McGowan R and Myles RC
West of Scotland Inherited Cardiac Conditions Service, Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, Scotland
Introduction: Inherited Long QT syndrome (iLQTS) carries a risk of arrhythmic sudden cardiac death (SCD) and accurate diagnosis is important to allow preventative therapy. Clinical assessment is complicated as (i) QTc prolongation may be acquired and (ii) QTc ranges in iLQTS patients overlap with the normal population. Use of a clinical risk score (Schwartz score, SS1) >3.5 is recommended prior to genetic testing.2 We audited SS of patients undergoing genetic testing for suspected iLQTS in the West of Scotland (WoS).
Methods: Caldicott Guardian approval for the audit was granted by NHS GGC. Genetic test samples sent for diagnostic LQTS testing from the WoS between 2013 and 2021 were included. Demographic data were summarised. Test rates were expressed per 1000 population using publicly available estimates of population by health board. In a subgroup of patients from GGC (n = 81), health records were reviewed to determine SS. Receiver operating curves were used for sensitivity analysis.
Results: LQTS testing results from 508 patients were included (62% female, mean age 38 years). Test rates per 100,000 population ranged from 7 (D&G) to 26 (GGC). Ninety-two tests (18%) were positive, 34 (7%) identified a VUS and 382 (75%) were negative. There were no significant differences in results by age or gender. VUS result was more frequent with NGS versus Sanger sequencing (20/209 vs. 14/299, p < 0.05). Of positive tests, 63% were KCNQ1 (LQT1), 21% KCNH2 (LQT2) and 16% SCN5A (LQT3). For the subgroup of 81 patients, 32 (40%) were positive, 17 (20%) VUS and 32 (40%) negative. There were no differences between the groups in age, gender split and QTc at presentation, max. QTc, symptomatic status, history of ventricular arrhythmias or family history of SCD. Exercise tolerance tests (ETTs) were performed in 24/81 (33%). Mean SS was 2.9 ± 1.2 and was significantly higher for the positive group (3.6 ± 0.9) than negative (2.6 ± 1.2) or VUS (2.4 ± 1.3, p < 0.01, Figure 1). AUC for SS to predict a positive result was 0.73.
Conclusion: These data support the use of SS during clinical phenotyping for LQTS, and suggest that SS could improve yield without missing affected cases. ETT use was low and increased use of this may further improve clinical phenotyping. Our data suggest variation in testing rates which may reflect the visibility of regional ICC services.
References
1. Schwartz and Crotti. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation. 2011;124(20):2181–2184.
2. Wilde et al. EHRA / HRS / APHRS / LAHRS Expert Consensus Statement on the state of genetic testing for cardiac diseases. Europace 2022; 0:1–61.
Oxygen uptake efficiency slope from submaximal cardiopulmonary exercise: A valuable substitute for peak VO2?
Rudd AE, Khan H, Gamble D, Stephen P, Horgan G, Dawson A, Frenneaux MP and Dawson DK
Cardiovascular Research Facility, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZD, UK
Introduction: Cardiopulmonary exercise testing (CPEX) provides valuable diagnostic and prognostic cardiopulmonary function data. However, in the clinical setting, a maximal test is not always achievable. The Oxygen Efficiency Uptake Slope (OUES) has been proposed as a possible submaximal measure of cardiopulmonary function as it remains relatively stable during the final quartile of the exercise test. This study explored the validity of OUES as a surrogate marker for cardiopulmonary function in the event of a submaximal test.
Methods: Four groups of subjects [128 healthy controls (73 M), 44 asymptomatic hypertensive (HT) patients (26 M), 67 adult cardiac congenital heart disease (ACHD) patients (44 M) and 35 heart failure with preserved ejection fraction (HFpEF) (10 M) patients] were recruited after informed consent. All subjects underwent clinical assessment, resting ECG, blood pressure and spirometry prior to a treadmill CPEX to volitional exhaustion and a respiratory exchange ratio (RER) of at least 1.1 using the same testing protocol. Peak VO2 (ml/min) was recorded from the last 5 s of the maximal test (RER = 1.1) and OUES was calculated from complete (RER = 1.1) and truncated (RER = 0.9) gas exchange data. The linear relationships between absolute peak VO2 and OUES from complete and truncated gas exchange data were assessed using Pearson's correlation coefficient. Subsequently, the two correlations obtained in each patient group were compared. Statistical significance was set at p < 0.01.
Results: Mean and 95% confidence intervals of the peak VO2 for males and females in each decile of life examined in the 4 subject groups are shown in the figure. Peak VO2 values achieved in each of the patient groups were significantly lower when matched for age and sex compared to healthy participants (HT p = 0.006, ACHD patients p < 0.001 and HFpEF patients p < 0.001).
In all four groups, there was a good correlation between absolute peak VO2 and the OUES at RER 1.1 (healthy volunteers r = 0.910, p < 0.001, HT r = 0.899, p < 0.001, ACHD r = 0.816, p < 0.001 and HFpEF r = 0.846, p < 0.001). Correlations were inferior for absolute peak VO2 and OUES at RER 0.9 (healthy volunteers r = 0.74, p < 0.001, HT r = 0.780, p < 0.001, ACHD r = 0.651, p < 0.001 and HFpEF r = 0.817, p < 0.001). Correlations between absolute peak VO2 versus OUES at RER of 1.1 and 0.9 were significantly different only for healthy controls (p = 0.001, Z-score = −4.649), but not for HT (p = 0.05, Z-score = −1.909), ACHD (p = 0.04, Z-score = −2.080) or HFpEF (p = 0.7, Z-score = −0.377) patients.
Conclusion: Our data support the use of submaximal OUES at an RER of 0.9 as a surrogate marker for absolute peak VO2 obtained at an RER of 1.1, especially in patients, in whom it can often be difficult to achieve maximal exercise.
Long-term outcomes of aortic valve replacement with bioprosthetic and mechanical valves
Santhia Seeva Balan1, Patrick Eves1, Jeevan Francis1 and Vipin Zamvar2
1University of Edinburgh, UK
2Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Scotland
Introduction: Global incidence of aortic stenosis and regurgitation are the first and third most occurring valvular heart disease respectively. With 5-year mortality rates without treatment as high as 67%, it is, therefore, essential to provide medical treatment for this debilitating condition. Generally, patients are offered surgical aortic valve replacement (AVR) or trans-aortic valve implantation (TAVI) with either bioprosthetic valves (BV) or mechanical valves (MV). While there are guidelines in place to dictate valve choice, continual research evaluating the long-term outcomes associated with AVR using BVs and MVs are vital to have a greater understanding of how valve selection affects a patient [10,11]. This study, therefore, aims to contribute to this research by analysing the long-term outcomes, including mortality and morbidity associated with each type of valve.
Methods: A total of 288 patients had undergone AVR at the Royal Infirmary of Edinburgh (RIE) from January 2011 to December 2015 and were followed up for 11 years. Of the 288 patients, 229 (79.5%) patients had BVs and the remaining 59 (20.5%) patients had MVs with mean ages of 73.0 ± 9.5 and 54.9 ± 11.5 years respectively. Baseline and post-operative findings were documented prospectively. The outcomes of the AVR were generally categorised into early and late mortality, early and late complications, and MAPE-related events. Continuous and categorical data were evaluated using Student’s t-test and chi-square test with odds ratio, respectively. Patient survival was determined using Kaplan–Meier analysis and a log-rank test was performed to determine the significance of the results obtained. The results were reported as survival mean probability ± standard error. To account for confounding variables affecting survival, a multivariate cox proportional hazards model was used to analyse the association between measured variables and mortality. Variables with a p-value of 0.20 or less were included in the model using a stepwise selection process. The results obtained were presented as a hazard ratio (HR) with a 95% confidence interval (CI).
Results: The 1-, 5- and 11-year actuarial survival for patients who had BVs and MVs were 93% ± 1.69%, 74.3% ± 3.04%, 44.9% ± 4.47% and 100%, 97.8% ± 2.15%, 82.8% ± 7.3% respectively. Additionally, it was found that patients aged more than 70 years old with BVs were associated with 13.9 (95% CI: 3.30–58.4, p = 0.0003) times greater odds of mortality. Likewise, it was also determined that BVs were associated with greater odds of late all-cause mortality (OR: 6.0, 95% CI: 2.3–15.7, p = 0.0002) and late valve-related mortality (OR: 19.5, 95% CI: 1.2–324.6, p = 0.0379). Confounding variables found to affect survival included (a) patients more than 70 years old (HR: 20.71, 95% CI: 0.18–0.51, p < 0.0001), (b) Poor left ventricular ejection fraction before surgery (HR: 6.57, 95% CI: 1.54–28.04, p = 0.0110), (c) Carotid occlusion before surgery (HR: 12.54, 95% CI: 2.86 – 55.07, p = 0.0008), (d) Pre-existing hypertension (HR: 1.54, 95% CI: 1.01–2.38, p = 0.0495), (e) Choice of bioprosthetic valve (HR: 4.56, 95% CI: 1.84–11.27, p = 0.0010), (f) Major bleeding as a complication of AVR (HR: 2.51, 95% CI: 1.18–5.31, p = 0.0161) and (g) Heart failure as a complication of AVR (HR: 1.80, 95% CI: 1.14–2.82, p = 0.011). Data analysis of late complications also showed that BVs were associated with greater cardiac-related complications (OR: 2.1.95% CI: 1.2–3.8, p = 0.0108) and heart failure (OR: 3.2, 95% CI: 1.1–9.2, p = 0.0338). However, the incidence of MAPE-related complications was found to be similar between the two groups.
Conclusion: Overall, BVs had more significant mortality rates than MVs. The odds of developing cardiac-related complications and heart failure were also greater in patients with BVs. However, no significant difference in the incidence of MAPE-related events was found between the two groups. Nevertheless, this study cannot be used to compare the outcomes between the two valves as surgeons generally prefer to use BVs in older patients with more extensive comorbidities and/or if they have a life expectancy of less than 15 years. However, the findings from this study could serve to inform patients undergoing AVR about potential long-term outcomes and prognosis associated with each type of valve.
Presentation and outcomes in patients with acute myocardial injury and type 2 myocardial infarction with prior coronary artery disease
Caelan Taggart, Anton Gard, Anda Bularga, Ryan Wereski, Bertil Lindahl, Andrew R. Chapman Kai Eggers and Nicholas L. Mills
The Chancellors Building, Edinburgh, Scotland
Purpose: To determine if there are similarities between patients with type 2 myocardial infarction or acute myocardial injury who have underlying coronary artery disease.
Background: Acute myocardial injury and type 2 myocardial infarction typically occur in the setting of a concurrent illness and do not result from atherosclerotic plaque rupture and thrombosis. Separating acute myocardial injury and type 2 myocardial infarction is challenging in practice as this relies on the assessment of ischaemia. Indeed, some have challenged whether this distinction is important, as to date no study has demonstrated differences in clinical outcomes between these groups, both of which have a high rate of all-cause death, and significant future cardiovascular risk at five years.
Methods: We conducted a secondary analysis of a multi-centre randomised controlled trial of 48,282 consecutive patients with suspected acute coronary syndrome. Patients with an adjudicated diagnosis of acute myocardial injury and type 2 myocardial infarction were stratified according to previous coronary artery disease defined as prior coronary revascularisation, myocardial infarction, or angina. Cardiovascular death or myocardial infarction adjusted for the competing risk of non-cardiovascular death and all-cause death at one year was compared.
Results: There were 9115 patients with cardiac troponin concentrations above the 99th centile in whom a diagnosis of acute myocardial injury and type 2 myocardial infarction was made in 1676 (18%) and 1121 (12%) patients, respectively. In the total population of 2797 patients with type 2 myocardial infarction or acute myocardial injury, those with coronary disease were older than those without coronary disease (mean [standard deviation] age 78 [11] vs. 73 [16] years) and were more likely to be female than male (55% vs. 45%). Coronary disease was previously identified in 40% (454/1121) and 30% (509/1167) of those with type 2 myocardial infarction and acute myocardial injury. Cardiovascular death or myocardial infarction at one year occurred more frequently in those patients known to have coronary artery disease than those without for type 2 myocardial infarction (20% [91/454] vs. 10% [69/667]; log-rank p < 0.001) and acute myocardial injury (23% [115/509]) vs. 14% [158/11.67]; log-rank p < 0.001) respectively (Figure 1). Similarly, all-cause death at one year was higher in patients with coronary disease in both type 2 myocardial infarction (40% [115/509] vs. 30% [135/454]; log-rank p < 0.001) and acute myocardial injury (31% [357/1167] vs. 18% [123/667]; log-rank p < 0.001), respectively (Figure 2).
Conclusion: Coronary artery disease is recognised in around one-third of patients with acute myocardial injury and type 2 myocardial infarction and is associated with a higher rate of cardiovascular events or death. The risk doubled in those with coronary artery disease and was similar whether the index diagnosis was myocardial injury or infarction.
Post-COVID-19 syndromes involve peripheral vasoconstriction, impaired endothelium-independent vasodilation and Rho kinase activation: A novel target for therapy
Robert A. Sykes*1,2, Karla B. Neves*1, Rhéure Alves-Lopes1, Ilaria Caputo3, Nigel B. Jamieson4, Anna Kamdar1, Assya Legrini4, Holly Leslie4, Alasdair McIntosh5, Alex McConnachie5, Andrew Morrow1,2, Richard Macfarlane1, Kenneth Mangion1,7, John McAbney6, Augusto C. Montezano1,8, Rhian Touyz1,8, Colin Wood4 and Colin Berry1,2,7
1British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK
*Joint lead authors.
Background: The aetiology of symptoms persisting beyond acute SARS-CoV-2 infection is unclear, and systemic vascular dysfunction is implicated.
Methods: Convalescent hospitalised patients with COVID-19 infection and risk-factor matched controls underwent deep clinical phenotyping using blood biomarkers, cardiorenal magnetic resonance imaging, pulmonary and coronary CT angiography, and gluteal subcutaneous biopsy. Small resistance arteries were isolated and examined using histopathology, wire myography, and spatial transcriptomics (Nanostring technology). Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction (U46619 and endothelin-1, ET-1) in the presence or absence of a RhoA/Rho kinase inhibitor (fasudil) were investigated. Rho-kinase activity in cultured vascular smooth muscle cells (VSMC) before and after incubation with SARS-CoV-2 recombinant S1 protein (rS1p) was assessed by ELISA.
Results: Twenty-seven patients (mean age 57 years, 13 (48%) female) post-COVID-19 and ten controls were included. Endothelium-independent vasorelaxation was impaired compared with controls (p = 0.02), and U46619-induced vasoconstriction was increased (p = 0.01). RhoA/Rho-kinase inhibition ameliorated vascular dysfunction (p = 0.02). U46619-induced calcium influx in VSMC following incubation with SARS-CoV-2 rS1p (p = 0.02) and VSMC Rho-kinase activity was greater compared with controls (p = 0.02). Histopathology demonstrated increased aniline blue in COVID-19 arterioles (69.7% [95%CI: 67.8, 71.7]) vs. controls (64.9% [95%CI: 59.4, 70.3]) (p = 0.02). Gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication was upregulated.
Conclusion: Post-COVID-19 syndromes with persisting symptoms and impairments in cardio-respiratory function at three months are associated with peripheral vascular dysfunction, despite resolution of systemic inflammation. Vascular mechanisms involve impaired endothelium-independent vasodilation, increased vasoconstriction, and Rho-kinase activation, representing a target for therapy and clinical trials in post-COVID-19 syndromes.
A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: Results of two phase I studies
J. Osmanska, K. Brooksbank, KF. Docherty, S. Robertson, K. Wetherall, A. Mcconnachie, J. Hu, RS. Gardner, AL. Clark, IP Squire, PR. Kalra, P. Muntendam, JV. Mcmurray, MC. Petrie, RT. Campbell
University of Glasgow, Scotland
Background: Worsening heart failure (HF) is the most common cardiovascular indication for hospital admission. Intravenous (IV) loop diuretics constitute the primary treatment for the majority of these admissions. Subcutaneous (SC) furosemide has potential advantages over IV furosemide such as preventing hospitalisations, facilitating early discharge in those who are admitted and in palliative care. A novel, small-volume, non-irritant, furosemide formulation has been designed for SC administration using a small patch infusor pump placed on patient's abdomen (Figure 1).
Methods: A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 ml (infused over 5 h) was investigated in two phase 1 studies. The first study was a pharmacokinetic/pharmacodynamic (PK/PD) study comparing SC infusion of the novel formulation with the same dose (80 mg) of standard furosemide administered by IV bolus in 18 ambulatory patients with HF. The primary endpoint was absolute bioavailability of novel SC furosemide. Secondary endpoints were other PK parameters, PD parameters (urine volume and sodium collected over 24 h) and infusion site reaction. The second study investigated the same novel SC furosemide formulation infused over 5 h by a small patch pump placed on the abdominal wall in 20 patients hospitalised with HF. The primary outcome measures were adverse events, infusion site pain, device failure and PK measurements.
Results: SC infusion resulted in complete bioavailability (112%) when compared to IV bolus of standard furosemide. The plasma-concentration time curve showed the expected and desired profiles and differences. IV bolus resulted in a high peak plasma concentration (Cmax) of furosemide followed by elimination while the 5 h SC infusion provided rapid achievement of therapeutic levels which were maintained over approximately 5 h at steady state (Figure 2). At 8 h, there was no difference between the median urine output achieved with SC versus IV furosemide (2850 ml [IQR: 2150–3380 ml] vs. 2390 ml [IQR: 1790–2850]) but over 24 h median urine output was greater with SC versus IV furosemide (3540 ml [IQR: 2910–4220 ml] vs. 3060 ml [IQR: 2520–3760 ml]). SC infusion resulted in a more tempered diuretic response. Administration of SC furosemide by the small patch pump in the second study resulted in plasma furosemide concentrations and urine output that were comparable to those observed in the first study. One of 20 pumps detached before the end of the infusion which was attributed to profuse sweating that interfered with adhesion. 14 of 20 patients rated acceptability as ‘excellent’. SC infusion was well-tolerated in both studies with no adverse events attributable to the treatment.
Conclusion: Subcutaneous infusion over 5 h of a novel furosemide formulation (30 mg/ml) resulted in complete bioavailability and similar efficacy in terms of diuresis and natriuresis when compared to IV bolus administration of the standard furosemide injection. Administration via a small patch pump placed on the abdominal wall was feasible and well tolerated.
Cumulative incidence plot of cardiovascular death or MI (myocardial infarction) at one year in patents with acute myocardial injury and type 2 MI stratified by the presence of coronary disease (CAD).
Cumulative incidence plot of all-cause death at one year in patients with acute myocardial injury and type 2MI |(myocardial infarction) stratified by the presence of coronary disease (CAD).
Appropriateness of pre-operative transthoracic echocardiograms referrals in non-cardiac surgery in Greater Glasgow and Clyde (South Sector)
Sophie Vennard, Stephen Dobbin, Faheem Ahmad and Sabrina Nordin
Cardiology Department, Queen Elizabeth University Hospital, Govan Road, Glasgow G51 4TF, Scotland
Background: The COVID-19 pandemic has put the echocardiography service across the United Kingdom under further significant strain. Pre-operative echocardiography requests for non-cardiac surgery place a notable burden on the service in Greater Glasgow and Clyde (GGC) South Sector. These requests often demand urgent slots, limiting the flexibility of the service, demanding immediate resource use and increasing patient waiting times. Pre-operative echocardiography is currently recommended for selected patients prior to intermediate to high-risk surgical procedures1. The British Society of Echocardiography guidelines emphasised on symptomatic patients or if there are clinical features or signs of severe structural heart disease 2.
Methods: This is a multicentre retrospective analysis reviewing the suitability of pre-operative echocardiography requests in GGC between October 2020 and April 2022. Patients were identified based on transthoracic echocardiogram requests. Data on clinical information were obtained from the clinical portal. A criterion for vetting requests was developed based on recognised international guidelines.(12,3)
Results: One hundred transthoracic echocardiogram referrals were reviewed. Only three of these patients were undergoing high-risk surgery. Using the revised vetting criteria, 18% of these requests would have been accepted and 82% rejected. 55% of the echocardiography requests ‘accepted’ and 13% of those ‘rejected’ had significant abnormalities identified on the report. Of the rejected scans with significant abnormalities, none had severe valve disease or severe left ventricular dysfunction. Only one procedure did not go ahead based on echocardiogram findings alone. Applying the vetting criteria prospectively leads to a projected 82% reduction in pre-operative scans in 2022 (figure 1), leading to at least an annual cost-saving of £14,784. These figures are likely underestimated as it is likely not all pre-operative requests are included during this analysis.
Conclusion: Our findings suggest that the majority of pre-operative echocardiography requests for non-cardiac surgery currently are unnecessary. Implementation of our proposed vetting system could lead to fewer pre-operative scans and prioritising the use of transthoracic echocardiogram in higher-risk pre-operative patients.
Abdominal patch infusor device designed to administer SC furosemide.
References
1. Kristiansen et al. (2014) ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). European Heart Journal. 35 (35): 2383–2431.
2. British Society of Echocardiography (2022). Clinical indications for echocardiography. Retrieved from: https://www.bsecho.org.
3. Fleisher et al. (2014). ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Journal of the American College of Cardiology. 64 (22): e77–e137.
High prevalence of asymptomatic left ventricular diastolic dysfunction and its detection among South Asian patients with type 2 diabetes mellitus compared with White Europeans
CCE. Lee1, S. Poongothai2, P. Ananth2, S. Jebarani2, U. Bhalraam1, C. Victor1, R. Venkatesan2, V. Prathiba2, RM. Anjana2, CNA. Palmer1, AD. Struthers1, JS. Singh1, IR. Mordi1, V. Mohan2 and CC. Lang1
1Division of Molecular & Clinical Medicine, School of Medicine, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.
2Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai, India.
Background: Heart failure (HF) is an important manifestation of Type 2 Diabetes (T2D). The development of HF in T2D may be preceded by Stage B HF. Asymptomatic left ventricular impairment, especially left ventricular diastolic dysfunction (LVDD), is a defining early feature of Stage B HF. Detection of Stage B HF is crucial as it provides an opportune target for intervention with cardio-protective therapy to prevent the development of symptomatic HF in T2D. The risk of T2DM is higher in South Asian populations resulting in increased risk of macrovascular and microvascular complications. The prevalence of Stage B HF in South Asian patients with T2DM is not known.
Purpose: (i) To compare the prevalence of Stage B HF in South Asians in India compared with White Europeans in Scotland; (ii) To test the role of NT-proBNP in identifying Stage B HF
Methods: This study involved the comparison between two independently conducted, cross-sectional studies. The patients were asymptomatic patients with T2DM with no prior history of cardiovascular disease from Chennai, India (n = 246) and Tayside, Scotland (n = 246). All patients underwent transthoracic echocardiogram (echo) examination to detect the presence of structural and functional echo features of Stage B HF: left atrial enlargement (LAE), left ventricular hypertrophy (LVH), LVDD and LV systolic dysfunction (LVSD). Receiver operating curves (ROC) were used to determine the predictive ability of NT-proBNP to predict LAE/LVDD/LVD/LVSD.
Results: The prevalence of Stage B HF was high in South Asian patients with T2DM (median age of 55 [49, 62] with a high prevalence of LVDD (5% had LVH, 7.3% had LAE, 70% had LVDD and 0% had LVSD (Figure 1B). 10% of the South Asian patients had at least 2 factors contributing to Stage B HF and these patients had higher NT-proBNP titres (703.4 [500.0, 949.2] vs 423.7 [35.0, 754.2], p < 0.001). ROC curves show that NT-proBNP can predict these participants with 2 or more echo features: Figure 2B: (AUC: 0.7043 (0.6159, 0.7928) p < 0.05). The prevalence of Stage B HF among White Europeans (median age of 67[61, 72].) was lower compared with South Asian patients: 15% had LVH, 13% had LAE, 19% had LVDD and 2% had LVSD (Figure 1A). 8% of White Europeans had at least 2 factors contributing to Stage B HF and these had higher NT-proBNP titres. (368.9 [154.6, 1087.8] vs. 186.8 [79.7, 411.5], p = 0.02). ROC curves show that NT-proBNP can predict participants with 2 or more factors. Figure 2A: (AUC: 0.6399 (0.5122, 0.7676) p < 0.05).
Conclusion: Our study has shown that South Asian patients with T2DM have a high prevalence of Stage B HF compared with White Europeans and that the predominant Stage B HF feature is LVDD.
We also found that NTproBNP could potentially be used to detect Stage B HF and help identify at-risk patients for cardio-protective therapy such as SGLT2 inhibitor therapy which has been shown to prevent the development of future HF events.
Plasma furosemide concentration in PK/PD study.
Projected number of pre-operative echocardiograms required in 2022 (vetting vs. non-vetting), leading to a reduction in the number of scans from 220 to 40 (82%).
Clinical characteristics and outcomes of community patients with suspected heart failure referred through an NT-proBNP pathway
Mon Myat Oo1, Justin Chiong Wei2, Tony Shang Yun Yap3, Lim Ren Jye3, Carrie Martin2, Ellie Dow2, Heather Kerr2, Benjamin Szwejkowski2, Chim C. Lang1 and Ify Mordi1
1Division of Molecular and Clinical Medicine, University of Dundee, United Kingdom of Great Britain and Northern Ireland
2Ninewells Hospital, Dundee, United Kingdom of Great Britain and Northern Ireland
3Ninewells Medical School, Dundee, United Kingdom of Great Britain and Northern Ireland
Background: NT-proBNP is recommended as a screening tool for suspected heart failure in the community. We have developed this service in Tayside over the past 5 years. Patients with suspected heart failure have an NT-proBNP performed by their primary care practitioner, and those with an elevated NT-proBNP are added to the echocardiography waiting list and referred for cardiology assessment.
Purpose: The purpose of this study was to report the clinical characteristics and outcomes of patients in Tayside referred through pro-BNP pathway.
Methods: Patients who were referred through NT-proBNP referral pathway from April 2018 to August 2020 were studied. Clinical characteristics and outcomes were obtained from electronic health records. The primary outcome was time to all-cause mortality or cardiovascular-related hospitalisation. Caldicott approval was obtained.
Results: A total of 1268 patients were screened with NT-proBNP. The mean age of the cohort was 72+/−12 years. The cohort was predominantly female (59%) with a mean BMI of 31+/−7 kg/m2 was noted in the overall study population. Six hundred fifty-six patients (51.7%) were noted to have NT-proBNP >125 pg/ml (Table). Patients with NT-proBNP >125 pg/ml were older and more likely to be female, with a lower BMI but higher prevalence of other comorbidities such as hypertension, cerebrovascular disease, atrial fibrillation, and ischaemic heart disease.
In those individuals with NT-proBNP >125 pg/ml, 473 patients (72.1%) had preserved LV systolic function (left ventricular ejection fraction ≥50%). Patients with reduced ejection fraction had a higher mean NT-proBNP (3864 ± 5403 vs. 1166 ± 1612, p-value < 0.001). HFpEF patients had a higher prevalence of comorbidities such as obesity (44.6% vs. 30.6%, p-value = 0.001) and hypertension (63.4% vs. 45.9%, p < 0.001). A severe valvular lesion was noted in 10 patients among those with preserved LV systolic function.
Over 26 ± 9 months follow-up duration, patients with NT-proBNP <125 pg/ml were at lower risk of death or CV hospitalisation, with only 41 occurrences (6.7%) of the primary outcome over 42 months of follow-up. Only 1 person had a cardiovascular death and only 1 had a heart failure hospitalisation. In contrast, 129 patients (19.7%) with NT-proBNP>125 pg/ml had an incidence of the primary outcome, a difference that was statistically significant (p < 0.001). Outcomes in HFpEF patients were similar to those with HFrEF and significantly worse than those with NT-proBNP <125 ng/ml after adjustment for age and sex (HFpEF hazard ratio 2.16, 95% CI 1.43–3.27, HFpEF hazard ratio 2.68, 95% CI 1.68–4.27, both p < 0.001 compared to NT-proBNP <125 ng/ml) (Figure).
Conclusions: Since introducing our NT-proBNP pathway we have been able to exclude heart failure in over half of all referrals, reducing the requirement for echocardiography. Patients with a low NT-proBNP are extremely unlikely to have a subsequent cardiovascular event. The prevalence of heart failure with preserved ejection fraction was substantial. This cohort of patients represents a substantial unmet need with poor outcomes and should be considered in future design of heart failure services.
Clinical characteristics.
BNP < 125(n = 612)
BNP > 125(n = 656)
P-value
Age (years)
66 +/− 12
78 +/− 9
.000
Female gender (%)
352 (57.5%)
400 (61.0%)
.210
BMI (kg/m2)
33 +/− 7
30 +/− 6
.040
NT-proBNP (pg/mL)
62 +/− 32
1919 +/− 3385
.0000012
Smoking (current)
93 (15.2%)
45 (6.9%)
.00003
Obesity (%)
341 (55.7%)
267 (40.7%)
.0000008
T2DM (%)
117 (19.1%)
126 (19.2%)
.968
Hypertension (%)
261 (42.6%)
384 (58.5%)
.000002
Dyslipidaemia (%)
65 (10.6%)
76 (11.6%)
.585
CVA
23 (3.8%)
94 (14.3%)
.000004
PVD
21 (3.4%)
16 (2.4%)
.294
AF
18 (2.9%)
226 (34.5%)
.000004
Ischaemic heart Disease (%)
61 (10.0%)
128 (19.5%)
.000003
Primary outcome Incidence (%)
41 (6.7%)
129 (19.7%)
.000008
All-cause mortality
23 (3.8%)
91 (13.9%)
.00000009
Cardiac death
1 (4.3%)
22 (24.2%)
.034
Cardiac-related hospitalization
20 (3.3%)
57 (8.7%)
.0004
Heart failure-related hospitalization
1 (15.0%)
19 (33.3%)
.013
Distribution of cardiac target organ damage in (A) Scottish and (B) South Asian populations.
Receiver of operating characteristic curve showing NT-proBNP's predictive ability for 2 or more cTODs in (A) Scottish and (B) South Asian populations.
