Eur Heart Research Articles

PS-P03-4: LOW LEVELS OF HYPERTENSION AWARENESS AND HIGH PROPORTIONS OF UNCONTROLLED BLOOD PRESSURE IN THE UNITED KINGDOM AND IRELAND

Objective: Globally, it is estimated that 10.4 million people die each year due to raised blood pressure (BP). Unfortunately, at least 40% of those with high BP globally are unaware of their condition. In the most recent UK and Ireland community-based data, 66.5% of people were unaware of their high BP(1). The UK and Ireland have taken part in the global May Measurement Month (MMM) campaign, in a bid to increase awareness of BP and to evidence the proportion of those in the community with undiagnosed high BP. The aim of this study was to investigate the large and combined 2017, 2018 and 2019 MMM dataset, to evidence the proportion of people with raised BP, undiagnosed hypertension and levels of hypertension not treated to target in the UK and Ireland. Design and method: As part of the MMM protocol, community-based opportunistic BP screening sites were set up across the UK and Ireland in places of worship, supermarkets, pharmacies, GP surgeries, workplaces, gyms and other public spaces in 2017, 2018 and 2019. A questionnaire recording medical history, lifestyle and demographics was used to collate participant information. BP was measured three times and the average of 2nd and 3rd readings used for analyses. Multiple imputations were performed to impute the mean BP, where data were missing. The term Hypertension was used for those with systolic BP >/ = 140 or diastolic BP >/ = 90 mmHg, or the participant was on BP medication. Controlled BP was considered as < 140 and < 90 mmHg. Results: Data on 22,910 individuals were analysed as part of the combined MMM dataset. Mean age of participants was 52 ± 18 years, with 60% reporting as female gender. See Table 1 below for the proportion of those considered hypertensive, levels of awareness and the proportion of hypertensives treated to target. Conclusion: In the largest community-based BP dataset to date in the UK and Ireland, our data highlight the concerning levels of people with high BP unaware of their condition and poor levels of controlled BP in hypertensive patients. Better community based and primary care screening initiatives are required to improve awareness and early identification of those at high risk of cardiovascular disease. REFERENCES: (1) McDonnell BJ, Rees E, Cockcroft JR, et al. May Measurement Month 2019: an analysis of blood pressure screening results from the UK and the Republic of Ireland. Eur Heart J Suppl. 2021 May;23 Suppl_B. 147–150.

1021 VASODILATOR CHALLENGE TEST WITH ISOSORBIDE DINITRATE DURING RIGHT HEART CATHETERIZATION: ANY ROLE IN POST-CAPILLARY PULMONARY HYPERTENSION PHENOTYPING?

Abstract Background and aims Despite recent advances in the diagnosis and treatment of pulmonary arterial hypertension (PAH), pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF-PH) still represents a diagnostic and therapeutic dilemma. Among HFpEF-PH patients, discriminating between isolated post-capillary (IpcPH) from combined post-/pre-capillary (CpcPH) PH, and especially a better understanding of the latter, is still challenging. Such a distinction can have an important therapeutic impact, as new evidence suggests that therapy with PDE5i might be beneficial in specific CpcPH patients [Humbert M, Kovacs G, Hoeper M et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022]. Our study sought to comprehensively assess and explore the role of Isosorbide Dinitrate (ISDN) testing in HFpEF-PH phenotyping. Methods From November 2019, all patients referred to our service to investigate PH and elevated pulmonary artery wedge pressures (PAWP) at rest or after fluid challenge at the time of the right heart catheterization, had a vasodilator test with a slow IV bolus of ISDN (with a specific protocol). Clinical, echocardiographic and hemodynamic data were collected. Results 38 patients (25 CpcPH, 13 IpcPH) were included in the analysis. Baseline characteristics are shown in table 1. Based on ISDN response, patients were stratified into three groups (Table 2). Group 1 showed a lack of significant pressures reduction after ISDN (“vasodilator negative Cpc-PH”). Group 2 displayed a significant reduction of PAWP < 15 mmHg, but persistent PH and high Pulmonary Vascular Resistance (PVR) (“vasodilator positive Cpc-PH”). Group 3 were patients whose pulmonary pressures normalized after ISDN (Ipc-PH). Conclusions albeit on a small group of patients, our preliminary results warrant further studies on the potential role of ISDN in better phenotyping HFpEF-PH and identify subgroups of patients who might benefit from PH specific therapies (“vasodilator positive Cpc-PH”) after treatment of the underling left heart disease.

The potential of blood pressure telemonitoring: experience in the UK and Japan.

Hypertension is the most important and modifiable risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide, and a growing issue as the global population with hypertension increases (estimated to be 626 million women and 652 million men in 2019, almost double the number in 1990). In addition, global control rates for hypertension remain poor: 23% for women and 18% for men in 2019 (Lancet. 2021:957). Measures to reduce the number of poorly controlled hypertensive patients are urgently needed. Remarkable advances in healthcare technology have changed healthcare delivery dramatically in the last decade with out-of-office blood pressure (BP) telemonitoring being widely used in clinical research (Hypertension. 2020:1368). We have demonstrated the efficacy of BP telemonitoring and digital intervention for the management of hypertension in the Telemonitoring And Self-Management IN the control of Hypertension (TASMINH) trials (Lancet. 2010:163, JAMA. 2014:799, Lancet. 2018:949), the Home and Online Management and Evaluation of Blood Pressure (HOME BP) trial (BMJ. 2021:m4858), and the HERB Digital Hypertension 1(HERB-DH1) pivotal trial (Eur Heart J. 2021:4111). A recent meta-analysis found that home BP telemonitoring improved office systolic BP (SBP) by 3.99 mmHg and home BP telemonitoring plus additional support (e.g., counselling and medications management) also showed a reduction of office SBP by 2.44 mmHg versus home BP telemonitoring alone (J Hum Hypertens. 2017:427). This evidence suggests that BP telemonitoring is an optimal tool for reducing BP levels and that combining BP telemonitoring and co-interventions would be the most effective approach for the management of hypertension. There are additional benefits from BP telemonitoring system in clinical practice, including assessment of accurate and reliable out-of-office BP data, and ease of BP measurement and recording by patients without the need for manual systems. Furthermore, such systems can reduce nonadherence of antihypertensive medications and clinical inertia, both of which contribute to a treatment-resistant hypertension (J Hypertens. 2017:2346, J Hypertens. 2021:1238). In practical terms, telemonitoring also facilitates optimal BP management for patients living in geographically remote or poorly medically resourced areas (Hypertension. 2021:1927). In this session, through discussion of the evidence base and clinical experience in the UK and Japan, we will examine the prospects of BP telemonitoring systems for the future management of hypertension. We will examine how BP telemonitoring systems are used and affect BP control in both clinical trials and subsequent implementation. In addition, by comparing such work in the UK and Japan, we will assess the potential of BP telemonitoring systems as a solution to the inadequate BP control status worldwide.

Natural history of ‘silent’ atrial fibrillation from subclinical to asymptomatic: State of the art and need for research

In the last 30 years clinical research in the atrial fibrillation (AF) field has seen a great advance both in terms of productivity and heterogeneity of areas that developed significant new knowledge and evidence. Indeed, it is very easy to verify how in the last 3 decades the number of articles regarding AF registered in MEDLINE has increased exponentially overtime. This large amount of evidence led to significant changes in the guidelines, with an improvement of the overall quality of recommendations and an increase in the high-quality recommendations (despite being still generally low) [ [1] Boriani G. Vitolo M. Lane D.A. Potpara T.S. Lip G.Y. Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology. Eur J Intern Med. 2021; 86: 1-11https://doi.org/10.1016/j.ejim.2021.01.006 Google Scholar , [2] Barnett A.S. Lewis W.R. Field M.E. Fonarow G.C. Gersh B.J. Page R.L. et al. Quality of evidence underlying the American Heart Association/American College of Cardiology/Heart Rhythm Society Guidelines on the management of atrial fibrillation. JAMA Cardiol. 2017; 2: 319https://doi.org/10.1001/jamacardio.2016.4936 Google Scholar ]. Several areas about AF clinical management are now largely assessed and established, as the need for oral anticoagulant (OAC) prescription, the preference of the non-vitamin K antagonist oral anticoagulants over vitamin k antagonist ones, as well as the assessment of thromboembolic and bleeding risks [ [3] Imberti J.F. Mei D.A. Vitolo M. Bonini N. Proietti M. Potpara T. et al. Comparing atrial fibrillation guidelines: focus on stroke prevention, bleeding risk assessment and oral anticoagulant recommendations. Eur J Intern Med. 2022; 101: 1-7https://doi.org/10.1016/j.ejim.2022.04.023 Google Scholar , [4] Hindricks G. Potpara T. Dagres N. Arbelo E. Bax J.J. Blomström-Lundqvist C. et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021; 42: 373-498https://doi.org/10.1093/eurheartj/ehaa612 Google Scholar ]. Also, the need for implementation of integrated care, emerged as the main AF management strategy in the last guidelines, is now largely assessed and evidence based [ 4 Hindricks G. Potpara T. Dagres N. Arbelo E. Bax J.J. Blomström-Lundqvist C. et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021; 42: 373-498https://doi.org/10.1093/eurheartj/ehaa612 Google Scholar , 5 Romiti G.F. Pastori D. Rivera-Caravaca J.M. Ding W.Y. Gue Y.X. Menichelli D. et al. Adherence to the “atrial fibrillation better care” pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost. 2022; 122: 406-414https://doi.org/10.1055/a-1515-9630 Google Scholar , 6 Romiti G.F. Proietti M. Vitolo M. Bonini N. Fawzy A.M. Ding W.Y. et al. Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry. BMC Med. 2022; 20: 326https://doi.org/10.1186/s12916-022-02526-7 Google Scholar ].

Collapsed Woman With a D-Shaped Left Ventricle on Echocardiogram

A 45-year-old woman presented to the emergency department with unwitnessed out-of-hospital cardiac arrest with asystole rhythm. After intubation, transesophageal echocardiography was performed to search for possible etiologies of cardiac arrest. It showed a D-shaped left ventricle at the midventricular level in the transgastric short-axis view (Figure A and Video, available at http://www.annemergmed.com). After the return of spontaneous circulation, transesophageal echocardiography revealed the resolution of the D-shaped left ventricle (Figure B). Dilated right ventricle because of cardiac arrest. The right ventricle to left ventricle ratio was described as an echocardiographic sign suggesting pulmonary embolism with high specificity in previous studies.1Fields J.M. Davis J. Girson L. et al.Transthoracic echocardiography for diagnosing pulmonary embolism: a systematic review and meta-analysis.J Am Soc Echocardiogr. 2017; 30: 714-723.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar In our case, right ventricle dilation with septal flattening was also observed during resuscitation, which returned to normal size after the return of spontaneous circulation. In Aagaard's porcine studies,2Aagaard R. Caap P. Hansson N.C. et al.Detection of pulmonary embolism during cardiac arrest—ultrasonographic findings should be interpreted with caution.Crit Care Med. 2017; 45: e695-e702Crossref PubMed Scopus (27) Google Scholar,3Aagaard R. Granfeldt A. Bøtker M.T. et al.The right ventricle is dilated during resuscitation from cardiac arrest caused by hypovolemia: a porcine ultrasound study.Crit Care Med. 2017; 45: e963-e970Crossref PubMed Scopus (32) Google Scholar the right ventricle size showed no correlation with the causes of arrest. The right ventricle dilation might be inherent to cardiac arrest. Our case supported Aagaard’s studies; therefore, the dilated right ventricle noted on the echocardiography during resuscitation must be interpreted cautiously. Other differential diagnoses should be considered if the dilated right ventricle resolves after the return of spontaneous circulation. In patients with cardiac arrest, thrombus visualized in the proximal pulmonary arteries or right heart might be a more specific sign to diagnose pulmonary embolism and guide further treatment, such as thrombolytic therapy.4Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1340) Google Scholar Gastric ulcer perforation was diagnosed following the return of spontaneous circulation by computed tomography. Gastrorrhaphy and drainage of intra-abdominal abscess were done; however, the patient died the next day because of a profound septic shock. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ODMwZGY4ZmNmZjg3MWZkNjRiYzVkNTgyMjQ1YTNhNyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcwOTg5Mzc1fQ.GE5j2RbdtAaHLdnx_AuVeAXfSftnIEpj1OAn9NZU9Stpu06w5LMVtZlgBhaB1tMFs6TOjMwr5LfsP17MhOD7AgBQr4O2BAy1vl0OVBHuhL5TuNK8RFAIVShVmQL_BYFiB4Py1xh8kiU5JsL9kuInpRDAEX4P1ANaxTL9CyTD4X3O9sFEHJLh6LgERT2fq6XjhXu3qODqLCmCDR5S7EOiP8HuU5Mt_PONO5bLGStTYYHOK1vIP7OlT_nLlacBrdeUxJqIHmLdtMZCEkZLFAPedhLGI0Tok-ncrbC-qlUnk1JI2PIYwPtgdKEJrxh6SHIK4D0haEmqAqE7Fbj6EggPDw Download .mp4 (2.92 MB) Help with .mp4 files VideoThe transesophageal echocardiography showing a D-shaped left ventricle at the midventricular level in the transgastric short-axis view during resuscitation, which turned back to a normal shape after the return of spontaneous circulation was achieved.

Endothelial-Targeted CD39 Ameliorates Pulmonary Hypertension in a Murine Model of Endothelial Toxin Administration

Background: Endothelial toxicity (by toxins, viral and bacterial sepsis) and associated inflammation can lead to acute and chronic vasculopathy leading to cardiac compromise. CD39 helps to maintain the endogenous antithrombotic profile of the endothelium. CD39 is an endothelial cell membrane-anchored enzyme that hydrolyses ATP and ADP to AMP. Subsequently, another enzyme CD73 further hydrolyses AMP to adenosine. The consequence of this important pathway is that pro-inflammatory (ATP) and pro-thrombotic (platelet aggregation amplifier, ADP) are converted to adenosine, which is anti-inflammatory, vasodilatory, and anti-thrombotic. CD39 enzyme activity drives this pathway. We have published before that CD39 is anti-thrombotic/anti-inflammatory (N Engl J Med. 2012;367(24):2322-2333; J Clin Invest. 2004;113(10):1440-1446) and also protects from ischaemia-reperfusion injury in heart and kidney (Eur Heart J. 2018;39(2):111-116; Am J Transplant. 2010;10(12):2586-2595) As a human disease correlate, CD39 activity and adenosine signalling is disrupted in human pulmonary hypertension (J Am Heart Assoc. 2020;9:e017404). Moreover, CD39-null mice are predisposed towards the development of experimental pulmonary hypertension after hypoxic injury (Am J Physiol Heart Circ Physiol 311: H286-H298, 2016). In this work, we demonstrate that the administration of a single dose of an endothelial cell toxin (monocrotaline pyrrole) leads to the development of vasculopathy and pulmonary hypertension as characterised by cardiac echo and right ventricular pressure studies. Single administration of endothelial (Vascular cell adhesion molecule, VCAM-1)-targeted soluble CD39 (Anti-VCAM-CD39) ameliorates pulmonary hypertension. Hypothesis: Targeted delivery of CD39 to the pulmonary endothelium will relieve pulmonary hypertension. Methods: 'Anti-VCAM-CD39' is novel therapeutic that contains a scFv recognising VCAM-1 fused to human soluble CD39. It is expressed as a single polypeptide from insect or mammalian cells and affinity purified using a FLAG-affinity tag. Prior work has demonstrated that Anti-VCAM-CD39 administration intravenously leads to dose-dependent prolongation of murine tail bleeding time only at doses above 1mg/kg. We have developed a murine model of pulmonary hypertension by a single administration of monocrotaline pyrrole (MCTP, 8mg/kg). Development of pulmonary hypertension was verified by cardiac echo showing abnormal (decreased) pulmonary acceleration time (PAT): pulmonary ejection (PET) ratio (an accepted parameter of pulmonary hypertension and increased heart weight ratio (heart weight/body weight x100). Pulmonary hypertension was also confirmed by right ventricular systolic pressure (RVSP) measurement. Cardiac echo was done with the Vevo2100 small animal high-frequency ultrasound machine and the 55Mhz MS550s transducer. RVSP was quantified in anaesthetised mice using a Millar pressure catheter (1.4Fr) inserted into the RV, via the right external jugular vein. Results:Development of pulmonary hypertension with single dose of MCTP 8mg/kg shows features of: 1. Increased endothelial VCAM-1 expression (mRNA expression, not shown) 2. Decreased PAT/PET ratios consistent with pulmonary hypertension (Table 1) with typical cardiac echo appearance (Fig. 1) 3. Increased cardiac weight:body weight ratio at D21 (vehicle 0.45±0.05; MCTP 0.6±0.1, p<0.05) 4. Leads to fibrin deposition (Carstairs stain, not shown). Anti-VCAM-CD39 ameliorates pulmonary hypertension, quantitated with cardiac echo and RVSP: 1.Single administration of Anti-VCAM-CD39 at doses of 0.4mg/kg and 1.0mg/kg at 72 h post MCTP improved (increased) PAT/PET ratio at D10 compared with saline control (Fig. 2). 2. Single administration of Anti-VCAM-CD39 at 1.0mg/kg reduced right ventricular systolic pressure (RVSP mmHg) at D10 consistent with amelioration of pulmonary hypertension. (Fig. 3). Effect of lower dose of Anti-VCAM-CD39 at 0.4mg/kg is awaited. Conclusion: 1. MCTP administration cause endothelial activation, VCAM-1 expression and vascular remodelling leading to a model of pulmonary hypertension with right ventricular pressure overload. 2. Single administration of Anti-VCAM-CD39 at doses 0.4mg/kg and 1.0mg/kg (below the threshold prolonging tail-bleeding time) leads to amelioration of pulmonary hypertension suggesting a novel new treatment for this condition. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

EP News: Pediatric and Congenital Electrophysiology.

Jorda et al (Eur Heart J 2022;43:3041, PMID 35766180) validated the ARVCrisk.com prediction model in an observational, retrospective, longitudinal study in an external multicenter cohort and compared its performance to current guideline recommendations for implantable cardioverter-defibrillator (ICD) use on the basis of decision curve analysis. (The ARVCrisk.com calculator is an online algorithm published in 2019 that intends to predict the occurrence of sustained ventricular arrhythmias [including sudden cardiac death or arrest] within 5 years of arrhythmogenic right ventricular cardiomyopathy diagnosis in patients aged 14 years.) The validation cohort included 429 patients (mean age 43 years), of whom 103 (24%) experienced sustained ventricular tachycardia during a median follow-up of 5 years.

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

A SENSE OF IMPENDING DOOM: MASSIVE AORTIC ABDOMINAL ANEURYSM PRESENTING AS SUBACUTE BACK PAIN

A SENSE OF IMPENDING DOOM: MASSIVE AORTIC ABDOMINAL ANEURYSM PRESENTING AS SUBACUTE BACK PAIN

TUBERCULOUS TAMPONADE WITH A TWIST: A CASE OF TB AND COVID-19

TUBERCULOUS TAMPONADE WITH A TWIST: A CASE OF TB AND COVID-19

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

BEFORE OUR EYES: A CLOT-IN-TRANSIT LEADING TO CARDIAC ARREST AND RETURN OF SPONTANEOUS CIRCULATION WITH SYSTEMIC THROMBOLYSIS

BEFORE OUR EYES: A CLOT-IN-TRANSIT LEADING TO CARDIAC ARREST AND RETURN OF SPONTANEOUS CIRCULATION WITH SYSTEMIC THROMBOLYSIS

MIMICKER OF MYOCARDIAL INFARCTION (MI): PHENYLEPHRINE-ASSOCIATED CORONARY VASOSPASM

MIMICKER OF MYOCARDIAL INFARCTION (MI): PHENYLEPHRINE-ASSOCIATED CORONARY VASOSPASM

SQUAMOUS CELL CARCINOMA OF THE LUNG LEADING TO MALIGNANT CARDIAC TAMPONADE DUE TO LARGE CARDIAC METASTASES

SQUAMOUS CELL CARCINOMA OF THE LUNG LEADING TO MALIGNANT CARDIAC TAMPONADE DUE TO LARGE CARDIAC METASTASES

VENTRICULAR FIBRILLATION AS PRESENTATION FOR TAKOTSUBO CARDIOMYOPATHY

VENTRICULAR FIBRILLATION AS PRESENTATION FOR TAKOTSUBO CARDIOMYOPATHY

PURULENT PERICARDITIS AND PURULENT PERICARDIAL EFFUSION DUE TO METHICILLIN-SENSITIVE STAPHYLOCOCCUS AUREUS (MSSA) IN A PATIENT TAKING SARILUMAB AND STEROIDS

PURULENT PERICARDITIS AND PURULENT PERICARDIAL EFFUSION DUE TO METHICILLIN-SENSITIVE STAPHYLOCOCCUS AUREUS (MSSA) IN A PATIENT TAKING SARILUMAB AND STEROIDS

Cardiovascular prevention in old age-Cardiovascular prevention of ageing?

Cardiovascular prevention is also particularly successful in old people in terms of preventing major cardiovascular events. The concept of prevention of geriatric diseases can, however, be expanded taking the insights of geroscience into consideration, so that slowing the ageing process per se can be set as anew goal: ageing is the pertinent basis of nearly all chronic diseases in adulthood, aline of argument for which the cardiovascular system can serve as aprototype. Consequently, treating ageing can help prevent the typical chronic diseases in old people, i.e. multimorbidity and frailty. According to the current guidelines of the European Society of Cardiology (ESC, Eur Heart J 42:3227-3337, 2021) and the German Society for Cardiology (DGK, https://leitlinien.dgk.org/files/03_pocket_leitlinien_praevention_aktualisiert.pdf ) cardiovascular prevention incorporates age-stratified and individually adapted measures and treatment targets in the domains lifestyle (physical activity, body weight, nutrition), psychosocial factors, cardiovascular risk factors (smoking, blood lipids, blood pressure, diabetes), antithrombotic treatment and disease-specific interventions. From abiogerontological perspective, in the midterm these measures could be supplemented by measures and medicinal treatment strategies to slow the biological ageing process, e.g. with senolytics and metformin. Initial clinical studies using senolytics have already been reported.

EP News: Clinical

Lambiase et al (Eur Heart J 2022;43:2037, PMID 35090007) evaluated 5-year outcomes of EFFORTLESS registry patients with early generation subcutaneous implantable cardioverter-defibrillator (S-ICD) devices. Overall, 984 of 994 enrolled patients (28% female; mean age 48 ± 17 years; ejection fraction 43% ± 18%) underwent S-ICD implantation. The median follow-up was 5.1 years. All-cause mortality was 9.3% at 5 years; 703 patients remained in follow-up on study completion, 171 withdrew including 87 (8.8%) with device explanted, and 65 (6.6%) lost to follow-up.

May Measurement Month: beyond boosting hypertension awareness

May Measurement Month: beyond boosting hypertension awareness

Designing a longitudinal clinical trial based on a composite endpoint: Sample size, monitoring, and adaptation.

Longitudinal clinical trials are often designed to compare treatments on the basis of multiple outcomes. For example in the case of cardiac trials, the outcomes of interest include mortality as well as cardiac events and hospitalization. For a COVID-19 trial, the outcomes of interest include mortality, time on ventilator, and time in hospital. Earlier work by these authors proposed a non-parametric test based on a composite of multiple endpoints referred to as the Finkelstein-Schoenfeld (FS) test (Finkelstein and Schoenfeld. Stat Med. 1999;18(11):1341-1354.). More recently, an estimate of the treatment comparison based on multiple endpoints (related to the FS test) was proposed (Pocock et al. Eur Heart J. 2011;33(2):176-182.). This estimate, which summarized the ratio of the number of patients who fared better vs worse on the experimental arm was coined the win ratio. The aim of this article is to provide guidance in the design of a trial that will use the FS test or the win ratio. The issues that will be considered are the sample size, sequential monitoring, and adaptive designs.