High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa.

Background: High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). Objectives: To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. Methods: We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. Results: A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p<0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p<0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p<0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2 /FiO2 ) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p<0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Conclusion: Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome. Study synopsis: What the study adds. This study adds to the body of evidence demonstrating the utility of high-flow nasal oxygen (HFNO) in avoiding invasive mechanical ventilation (IMV) in patients with severe COVID-19 hypoxaemic respiratory failure, and shows that this utility remained consistent across different waves of the COVID-19 pandemic.Implications of the study. In resource-constrained settings, HFNO is a feasible non-invasive alternative to IMV and can be employed with favourable and consistent outcomes outside traditional critical care wards. It also confirms that the degree of gas exchange abnormality, and not pre-existing patient-related factors, circulating wave variant or provider experience, is the main predictor of HFNO failure.

Clinical and cardiovascular magnetic resonance profile of cardiomyopathy patients from South Africa: Pilot of the IMHOTEP study.

BACKGROUND: Cardiomyopathy is an important cause of heart failure, however, there is notable lack of data on causes and manifestations of cardiomyopathy in Africa. AIMS: The African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) aims to address the knowledge gap on etiology, treatment, and outcomes of cardiomyopathy in sub-Saharan Africa. METHODS AND RESULTS: We conducted a single-center pilot study to delineate the clinical and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy in South African patients. Assessment of the first 99 adult incident cases [mean age 36.8 ± 12.5 years; females 53.5%] enrolled in IMHOTEP showed that dilated cardiomyopathy (n = 77) was commonest, followed by hypertrophic (n = 13), restrictive (n = 5) and arrhythmogenic (n = 4) cardiomyopathies. A broad range of etiologies were encountered with secondary causes identified in 42% of patients. Onset of symptoms in the peripartum period was observed in 47% of women, and peripartum cardiomyopathy was diagnosed in 32.1% of women recruited. In addition to electrocardiography and echocardiography, CMR was performed in 67 cases and contributed diagnostically in a third of cases. Acute inflammation was rarely observed [2%] on CMR, however, late gadolinium enhancement (LGE) was noted in 92% of cases. CONCLUSION: We report a diverse spectrum of causes of cardiomyopathy in the South African population, with secondary, potentially treatable, etiologies in a significant proportion of cases. CMR was useful in delineating specific phenotypes and etiologies, influencing clinical care. A higher-than-expected burden of LGE was observed in this young patient cohort - the implications of which are yet to be determined.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Prognostic value of NT-proBNP for myocardial recovery in peripartum cardiomyopathy (PPCM).

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. METHODS: Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). RESULTS: This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2-1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05-0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04-0.89], p = 0.035) at follow-up. CONCLUSIONS: We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

Myocardial Fibrosis Among Antiretroviral Therapy-Treated Persons With Human Immunodeficiency Virus in South Africa.

BACKGROUND: Heart failure is a prominent cardiovascular disease (CVD) manifestation in sub-Sarahan Africa. Myocardial fibrosis is a central feature of heart failure that we aimed to characterize among persons with human immunodeficiency virus (PWH) in South Africa. METHODS: Cardiovascular magnetic resonance (CMR) imaging was performed among PWH with viral suppression and uninfected controls, both free of known CVD. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured. Comparisons by human immunodeficiency virus (HIV) status were made using linear and logistic regression, adjusted for age, sex, and hypertension. RESULTS: One hundred thirty-four PWH and 95 uninfected persons completed CMR imaging; age was 50 and 49 years, with 63% and 67% female, respectively. Compared with controls, PWH had greater myocardial fibrosis by extracellular volume fraction ([ECV] absolute difference, 1.2%; 95% confidence interval [CI], 0.1-2.3). In subgroup analyses, the effect of HIV status on ECV was more prominent among women. Women (vs controls) were also more likely to have elevated NT-proBNP levels (>125 pg/mL; odds ratio, 2.4; 95% CI, 1.0-6.0). Among all PWH, an elevated NT-proBNP level was associated with higher ECV (3.4% higher; 95% CI, 1.3-5.5). CONCLUSIONS: Human immunodeficiency virus disease may contribute to myocardial fibrosis, with an effect more prominent among women. Research is needed to understand heart failure risk among PWH within sub-Saharan Africa.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Clinical management of COVID-19: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has presented clinicians with an enormous challenge in managing a respiratory virus that is not only capable of causing severe pneumonia and acute respiratory distress syndrome, but also multisystem disease. The extraordinary pace of clinical research, and particularly the surge in adaptive trials of new and repurposed treatments, have provided rapid answers to questions of whether such treatments work, and has resulted in corticosteroids taking centre stage in the management of hospitalised patients requiring oxygen support. Some treatment modalities, such as the role of anticoagulation to prevent and treat potential thromboembolic complications, remain controversial, as does the use of high-level oxygen support, outside of an intensive care unit setting. In this paper, we describe the clinical management of COVID-19 patients admitted to Groote Schuur Hospital, a major tertiary level hospital at the epicentre of South Africa's SARS-CoV-2 epidemic during its first 4 months.

2020 Heart Failure Society of South Africa perspective on the 2016 European Society of Cardiology Chronic Heart Failure Guidelines.

Heart failure with a reduced ejection fraction (HFrEF) is a condition frequently encountered by healthcare professionals and, in order to achieve the best outcomes for patients, needs to be managed optimally. This guideline document is based on the European Society of Cardiology Guidelines for the treatment of acute and chronic heart failure published in 2016, and summarises what is considered the best current management of patients with the condition. It provides information on the definition, diagnosis and epidemiology of HFrEF in the African context. The best evidence-based treatments for HFrEF are discussed, including established therapies (beta-blockers, ACE-i/ARBs, mineralocorticoid receptor antagonists (MRAs), diuretics) that form the cornerstone of heart failure management as well as therapies that have only recently entered clinical use (angiotensin receptor-neprilysin inhibitor (ARNI), sodium/glucose cotransporter-2 (SGLT2) inhibitors). Guidance is offered in terms of more invasive therapies (revascularisation, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) by implantation of a biventricular pacemaker with (CRT-D) or without (CRT-P) an ICD, left ventricular assist device (LVAD) use and heart transplantation) in order to ensure efficient use of these expensive treatment modalities in a resource-limited environment. Furthermore, additional therapies (digoxin, hydralazine and nitrates, ivabradine, iron supplementation) are discussed and advice is provided on general preventive strategies (vaccinations). Sections to discuss conditions that are particularly prevalent in sub-Saharan Africa (HIV-associated cardiomyopathy (CMO), peripartum CMO, rheumatic heart disease, atrial fibrillation) have been added to further improve clinical care for these commonly encountered disease processes. You are encouraged to read the complete 2016 ESC Heart Failure guideline: Ponikowski P, Voors AA, Anker SD, et al.; on behalf of the European Society of Cardiology. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016,37:2129-2200.

Research on COVID-19 in South Africa: Guiding principles for informed consent.

Research is imperative in addressing the COVID-19 epidemic, both in the short and long term. Informed consent is a key pillar of research and should be central to the conduct of COVID-19 research. Yet a range of factors, including physical distancing requirements, risk of exposure and infection to research staff, and multiple pressures on the healthcare environment, have added layers of challenges to the consent process in COVID-19 patients. Internationally, the recognition that consent for COVID-19 research may be imperfect has led to a range of suggestions to ensure that research remains ethical. Drawing on these guidelines, we propose a consent process for COVID-19 research in the South African context that combines individual consent with delayed and proxy consent for individuals who may be temporarily incapacitated, combined with key principles that should be considered in the design of a consent process for COVID-19 research.

Research on COVID-19 in South Africa: Guiding principles for informed consent

Research is imperative in addressing the COVID-19 epidemic, both in the short and long term. Informed consent is a key pillar of research and should be central to the conduct of COVID-19 research. Yet a range of factors, including physical distancing requirements, risk of exposure and infection to research staff, and multiple pressures on the healthcare environment, have added layers of challenges to the consent process in COVID-19 patients. Internationally, the recognition that consent for COVID-19 research may be imperfect has led to a range of suggestions to ensure that research remains ethical. Drawing on these guidelines, we propose a consent process for COVID-19 research in the South African context that combines individual consent with delayed and proxy consent for individuals who may be temporarily incapacitated, combined with key principles that should be considered in the design of a consent process for COVID-19 research

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa

The COVID-19 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves

Heart failure in sub-Saharan Africa: A clinical approach.

Despite medical advances, heart failure (HF) remains a global health problem and sub-Saharan Africa (SSA) is no exception, with decompensated HF being the most common primary diagnosis for patients admitted to hospital with heart disease. In SSA the in-hospital mortality rate of decompensated HF is up to 8.3%. HF is a clinical syndrome that is caused by a diverse group of aetiologies, each requiring unique management strategies, highlighting the need for diagnostic certainty and a broad understanding of the complex pathophysiology of this condition. While there are a number of advanced medical, device and surgical interventions being tailored for HF internationally, the fundamental basic principles of HF management, such as patient education, effective management of congestion and initiation of disease-modifying medical therapies, remain a challenge on our continent. This review addresses both the epidemiology of HF in SSA and principles of management that focus specifically on symptom relief, prevention of hospitalisation and improving survival in this population.

Dyspnoea: Pathophysiology and a clinical approach.

Dyspnoea, also known as shortness of breath or breathlessness, is a subjective awareness of the sensation of uncomfortable breathing. It may be of physiological, pathological or social origin. The pathophysiology of dyspnoea is complex, and involves the activation of several pathways that lead to increased work of breathing, stimulation of the receptors of the upper or lower airway, lung parenchyma, or chest wall, and excessive stimulation of the respiratory centre by central and peripheral chemoreceptors. Activation of these pathways is relayed to the central nervous system via respiratory muscle and vagal afferents, which are consequently interpreted by the individual in the context of the affective state, attention, and prior experience, resulting in the awareness of breathing. The clinical evaluation and approach to the management of dyspnoea are directed by the clinical presentation and underlying cause. The causes of dyspnoea are manifold, and include a spectrum of disorders, from benign to serious and life-threatening entities. The pathophysiology, aetiology, clinical presentation and management of dyspnoea are reviewed.

An approach to the diagnosis and management of valvular heart disease.

Valvular heart disease poses a common yet difficult problem in everyday clinical practice. A thorough clinical evaluation with basic common investigations such as an electrocardiogram (ECG) and a chest radiograph (CXR) remains the cornerstone of diagnosis. Echocardiography and more invasive testing, if needed, are usually performed at specialist level to confirm the diagnosis, assess severity and assist in definitive decision-making.The causes and clinical, ECG and CXR features of the common valve lesions are described. Patients with symptomatic valve lesions should be referred for specialist assessment. In most cases, medical therapy serves as a bridge to definitive mechanical or surgical therapy.