Clinical features and outcome of lupus myocarditis in the Western Cape, South Africa.

BACKGROUND: African American ethnicity is independently associated with lupus myocarditis compared with other ethnic groups. In the mixed racial population of the Western Cape, South Africa, no data exists on the clinical features/outcome of lupus myocarditis. OBJECTIVES: The objective of this study was to give a comprehensive description of the clinical features and outcome of acute lupus myocarditis in a mixed racial population. METHODS: Clinical records (between 2008 and 2014) of adult systemic lupus erythematosus (SLE) patients at a tertiary referral centre were retrospectively screened for a clinical and echocardiographic diagnosis of lupus myocarditis. Clinical features, laboratory results, management and outcome were described. Echocardiographic images stored in a digital archive were reanalysed including global and regional left ventricular function. A poor outcome was defined as lupus myocarditis related mortality or final left ventricular ejection fraction (LVEF) <40%. RESULTS: Twenty-eight of 457 lupus patients (6.1%) met inclusion criteria: 92.9% were female and 89.3% were of mixed racial origin. Fifty-three per cent of patients presented within three months after being diagnosed with SLE. Seventy-five per cent had severely active disease (SLE disease activity index ≥ 12) and 67.9% of patients had concomitant lupus nephritis. Laboratory results included: lymphopenia (69%) and an increased aRNP (61.5%). Treatment included corticosteroids (96%) and cyclophosphamide (75%); 14% of patients required additional immunosuppression including rituximab. Diastolic dysfunction and regional wall motion abnormalities occurred in > 90% of patients. LVEF improved from 35% to 47% (p = 0.023) and wall motion score from 1.88 to 1.5 (p = 0.017) following treatment. Overall mortality was high (12/28): five patients (17.9%) died due to lupus myocarditis (bimodal pattern). Patients who died of lupus myocarditis had a longer duration of SLE (p = 0.045) and a lower absolute lymphocyte count (p = 0.041) at diagnosis. LVEF at diagnosis was lower in patients who died of lupus myocarditis (p = 0.099) and in those with a persistent LVEF < 40% (n = 5; p = 0.046). CONCLUSIONS: This is the largest reported series on lupus myocarditis. The mixed racial population had a similar prevalence, but higher mortality compared with other ethnic groups (internationally published literature). Patients typically presented with high SLE disease activity and the majority had concomitant lupus nephritis. Lymphopenia and low LVEF at presentation were of prognostic significance, associated with lupus myocarditis related mortality or a persistent LVEF < 40%.

Novel role of cardiovascular MRI to contextualise tuberculous pericardial inflammation and oedema as predictors of constrictive pericarditis.

Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome have reached epidemic proportions, particularly affecting vulnerable populations in low- and middle-income countries of sub-Saharan Africa. TB pericarditis is the commonest cardiac manifestation of TB and is the leading cause of constrictive pericarditis, a reversible (by surgical pericardiectomy) cause of diastolic heart failure in endemic areas. Unpacking the complex mechanisms underpinning constrictive haemodynamics in TB pericarditis has proven challenging, leaving various basic and clinical research questions unanswered. Subsequently, risk stratification strategies for constrictive outcomes have remained unsatisfactory. Unique pericardial tissue characteristics, as identified on cardiovascular magnetic resonance imaging, enable us to stage and quantify pericardial inflammation and may assist in identifying patients at higher risk of tissue remodelling and pericardial constriction, as well as predict the degree of disease reversibility, tailor medical therapy, and determine the ideal timing for surgical pericardiectomy.

TYPICAL VALUES OF DOSIMETRIC DATA FOR CARDIAC FLUOROSCOPY-GUIDED PROCEDURES IN A SOUTH AFRICAN TEACHING HOSPITAL.

Currently there are limited diagnostic reference level (DRL) data for South African (SA) public sector cardiac fluoroscopy-guided procedures (FGPs). A 4-y retrospective study of dosimetric data on 6265 patients determined typical values (50th percentile) of dosimetric data for the seven most frequent cardiac FGPs at a SA teaching hospital. Kerma-area-product (KAP), reference point air Kerma (Ka,r) and fluoroscopy time (FT) were, respectively, calculated for coronary angiography (CA) (n = 1935; 61Gy.cm2, 624 mGy, 5 min); CA with left ventriculography (n = 1687; 85Gy.cm2, 840 mGy, 3.9 min), valve screening (n = 129; 6Gy.cm2, 164 mGy, 2.3 min), percutaneous coronary intervention (n = 1922; 145Gy.cm2, 1569 mGy, 11.9 min), pacemaker implantation (n = 432; 9Gy.cm2, 100 mGy, 6.5 min), pericardial tap (n = 115; 1.9Gy.cm2, 18 mGy, 1.5 min) and transcatheter aortic valve implantation (n = 45; 65Gy.cm2, 658 mGy, 14.1 min). This work presents the largest SA public sector cardiac FGP dosimetric data to date and provides a key resource for future work in this domain.

Autonomous auscultation of the human heart employing a precordial electro-phonocardiogram and ensemble empirical mode decomposition.

The research presented in this paper serves to provide a tool to autonomously screen for cardiovascular disease in the rural areas of Africa. With this tool, cardiovascular disease can potentially be detected in its initial stages, which is essential for effective treatment. The autonomous auscultation system proposed here utilizes recorded heart sounds and electrocardiogram signals to automatically distinguish between normal and abnormal heart conditions. Patients that are identified as abnormal by the system can then be referred to a specialist consultant, which will save a lot of unnecessary referrals. In this study, heart sound and electrocardiogram signals were recorded with the prototype precordial electro-phonocardiogram device, as part of a clinical study to screen patients for cardiovascular disease. These volunteers consisted of 28 patients with a diagnosed cardiovascular disease and, for control purposes, 34 persons diagnosed with healthy hearts. The proposed system employs wavelets to first denoise the recorded signals, which is then followed by segmentation of heart sounds. Frequency spectrum information was extracted as diagnostic features from the heart sounds by means of ensemble empirical mode decomposition and auto regressive modelling. The respective features were then classified with an ensemble artificial neural network. The performance of the autonomous auscultation system used in concert with the precordial electro-phonocardiogram prototype showed a sensitivity of 82% and a specificity of 88%. These results demonstrate the potential benefit of the precordial electro-phonocardiogram device and the developed autonomous auscultation software as a screening tool in a rural healthcare environment where large numbers of patients are often cared for by a small number of inexperienced medical personnel.

Evaluating the time interval from diagnosis to fibrinolysis at centres in the drainage area of Tygerberg Hospital, Cape Town, South Africa.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is one of the main contributors to morbidity and mortality in South Africa (SA). Timeous intervention by means of percutaneous coronary intervention (PCI) or fibrinolysis can significantly improve the outcome of STEMI. OBJECTIVES: To determine the median time interval between diagnosis and fibrinolysis in patients presenting to centres within the drainage area of Tygerberg Hospital, Cape Town, SA, and compare it with the European Society of Cardiology (ESC) recommendation of 10 minutes. METHODS: A retrospective medical record review of patients presenting to the abovementioned centres between 1 March 2017 and 28 February 2018 was performed. The primary presenting centre, time between diagnosis and fibrinolysis and discharge medication were recorded, in addition to other relevant demographic information. RESULTS: A total of 492 patients were identified, of whom 447 were included in the study. Three hundred and eighteen patients received fibrinolysis, of whom 18 (5.7%) were treated within 10 minutes of diagnosis. The median time interval between diagnosis and fibrinolysis was 67 (interquartile range (IQR) 32.5 -122.5) minutes. CONCLUSIONS: Most patients received fibrinolysis >10 minutes after diagnosis, which indicates suboptimal therapy when compared with the ESC guidelines. Future studies should investigate the factors prolonging this therapeutic delay.

Autonomous detection of heart sound abnormalities using an auscultation jacket.

This paper presents a study using an auscultation jacket with embedded electronic stethoscopes, and a software classification system capable of differentiating between normal and certain auscultatory abnormalities. The aim of the study is to demonstrate the potential of such a system for semi-automated diagnosis for underserved locations, for instance in rural areas or in developing countries where patients far outnumber the available medical personnel. Using an "auscultation jacket", synchronous data was recorded at multiple chest locations on 31 healthy volunteers and 21 patients with heart pathologies. Electrocardiograms (ECGs) were also recorded simultaneously with phonocardiographic data. Features related to heart pathologies were extracted from the signals and used as input to a feed-forward artificial neural network. The system is able to classify between normal and certain abnormal heart sounds with a sensitivity of 84% and a specificity of 86%. Though the number of training and testing samples presented are limited, the system performed well in differentiating between normal and abnormal heart sounds in the given database of available recordings. The results of this study demonstrate the potential of such a system to be used as a fast and cost-effective screening tool for heart pathologies.

Prominent inter-scallop separations of the posterior leaflet of the mitral valve: an important cause of 'pathological' mitral regurgitation.

The 2012 World Heart Federation (WHF) criteria for echocardiographic diagnosis of rheumatic heart disease (RHD) identify that the finding of 'pathological' mitral regurgitation (MR) in a screened individual increases the likelihood of detecting underlying RHD. Cases of isolated "pathological MR are thus identified as 'borderline RHD'. A large-scale echocardiographic screening program (Echo in Africa) in South Africa has identified that inter-scallop separations of the posterior mitral valve leaflet (PMVL) can give rise to 'pathological' MR. The authors propose that this finding when associated with isolated 'pathological' MR is unrelated to the rheumatic disease process. In this case report, we present two examples of 'pathological' MR related to inter-scallop separation from the Echo in Africa image database. We provide additional screening tips to accurately identify this entity.

Screening for rheumatic heart disease: is a paradigm shift required?

This focused review presents a critical appraisal of the World Heart Federation criteria for the echocardiographic diagnosis of rheumatic heart disease (RHD) and its performance in African RHD screening programmes. It identifies various logistical and methodological problems that negatively influence the current guideline's performance. The authors explore novel RHD screening methodology that could address some of these shortcomings and if proven to be of merit, would require a paradigm shift in the approach to the echocardiographic diagnosis of subclinical RHD.

An approach to the patient with suspected pericardial disease.

Diseases of the pericardium commonly manifest in one of three ways: acute pericarditis, pericardial effusion and constrictive pericarditis. In the developed world, the most common cause of acute pericarditis is viral or idiopathic disease, while in the developing world tuberculous aetiology, particularly in sub-Saharan Africa, is commonplace owing to the high prevalence of HIV. This article provides an approach to the diagnosis, investigation and management of these patients.

Identification of a calcium dependent atrial secretory binding protein as calmodulin.

OBJECTIVE: The role of calcium in the regulation of atrial natriuretic factor (ANF) secretion has focused attention on calcium binding proteins as regulatory components of the secretory machinery for ANF. Two members of the annexin family of calcium binding proteins have emerged as candidates for this role. The aim of this paper is to report the isolation, purification, and identification of another calcium dependent atrial secretory granule binding protein. METHODS: A 20 kDa calcium binding protein was isolated from rat cardiac tissue by affinity chromatography and purified by ion exchange high pressure liquid chromatography followed by reverse phase high pressure liquid chromatography. Identification of the protein was based on its electrophoretic mobility, chromatographic properties, amino acid composition, and ability to stimulate the activity of calmodulin dependent phosphodiesterase. RESULTS: Analysis of this protein and its interaction with atrial secretory granules revealed that it was identical to calmodulin and that the calcium dependent interaction with atrial secretory granules takes place at physiological calcium concentrations. CONCLUSIONS: The study identifies calmodulin as a calcium dependent atrial secretory binding protein. The interaction of calmodulin with atrial secretory granules at physiological calcium concentrations suggest a possible role for calmodulin in the regulation of ANF release from the secretory granules.

Identification and immunolocalisation of annexins V and VI, the major cardiac annexins, in rat heart.

OBJECTIVE: The heart contains proteins of the annexin family, a unique group of calcium binding proteins. This study was aimed at identifying the major cardiac annexins and determining their distribution in the rat heart. METHODS: Annexins were isolated by affinity chromatography and purified by ion exchange high pressure liquid chromatography. Identification of isolated proteins by immunoblotting was confirmed by partial amino acid sequence determination. Antisera raised against the isolated proteins were used for immunohistochemistry by the avidin-biotin-peroxidase technique. RESULTS: Two annexins were isolated and purified. Amino acid sequencing confirmed their identities as annexin V and VI. Immunohistochemistry showed that both annexins were present in cardiac myocytes and non-myocytes, but a distinct pattern of distribution was seen for each annexin. Annexin V immunoreactivity was enhanced in the atria compared with the ventricles, whereas annexin VI was more uniformly distributed. In individual cardiac myocytes annexin V was distributed throughout the cell by contrast with annexin VI, which localised to the sarcolemma. Intercalated discs displayed immunoreactivity for both annexins, most prominently for annexin VI. The most striking immunoreactivity for annexin V occurred in vascular endothelial cells, both in the microcirculation and in the major coronary vessels. Immunoreactivity for annexin VI in vascular structures was localised to the nuclei of endothelial and smooth muscle cells. CONCLUSIONS: Annexins V and VI are the major cardiac annexins. The localisation of these annexins to different components of cardiac myocytes will serve to direct the search for their functions in the heart. The striking immunoreactivity for annexins, particularly annexin V, in the coronary vessels indicates that the functions of cardiac annexins include a role in the coronary circulatory system.

Annexins V and VI: major calcium-dependent atrial secretory granule-binding proteins.

Atrial natriuretic peptide is stored by atrial myocytes in secretory granules, known as atrial specific granules, and is released from these granules by exocytosis. We have isolated a group of atrial proteins by affinity chromatography that bind to atrial specific granules in a calcium-dependent manner. The two major proteins isolated (32.5 kd and 67 kd) are calcium-binding proteins and have been identified as annexins V and VI by immunoblotting with specific antisera. The calcium dependence of their binding to atrial specific granules has been characterized in vitro and indicates that this interaction takes place at micromolar levels of calcium. In addition, the group of proteins isolated includes another calcium-binding protein of 20 kd, as well as GTP-binding proteins of 22 to 26 kd. Membrane interactions during exocytosis are presumably mediated by the interaction of specific proteins with the granule membrane. The properties of the proteins described here, and their ability to bind to atrial specific granules in a calcium-dependent manner, make them likely candidates in the search for regulatory proteins mediating atrial natriuretic peptide secretion.

Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study.

BACKGROUND: The last 50 years have seen major changes in the epidemiology of infective endocarditis (IE). AIM: To evaluate local patient characteristics, risk factors, clinical sequelae, microbiology, morbidity and mortality in patients with definite IE. DESIGN: Prospective observational study. METHODS: Over a three-year period, patients referred with probable IE were prospectively enrolled. All received a standardized diagnostic evaluation. Epidemiological data were documented; underlying risk factors for IE were sought. Initial evaluation and follow-up (to 6 months) included the documentation of vascular or immunological phenomena, morbidity and mortality. RESULTS: Of 92 patients referred with probable IE, 47 had definite IE. These patients had a mean age of 37.7 years with a male predominance (1.6:1). Rheumatic heart disease was present in 36 (76.6%). Eight had prosthetic valves. Three had congenital heart disease, mitral valve prolapse or multiple central intravascular catheters, respectively. All denied the use of intravenous recreational drugs and only one tested seropositive for HIV. Renal involvement (59.6%) and clubbing (29.8%) were commonly observed. The 6-month mortality rate was 35.6%, while 44.7% needed valvular replacement. An aetiological diagnosis was made in 21, with viridans streptococci the most common isolate. DISCUSSION: Infective endocarditis in the Western Cape of South Africa is a disease of younger adults, with a male predominance. Rheumatic heart disease is the major predisposing factor. Degenerative heart disease and intravenous drug abuse are not important risk factors. Our data do not support the notion that HIV infection is an independent risk factor for IE. Local mortality rates are much higher than recent international figures, as is the proportion of 'culture-negative' IE.

Cytokine production in patients with tuberculous pericarditis.

SETTING: An academic hospital in the Western Cape, South Africa. OBJECTIVE: To evaluate cytokine production (interferon-gamma [IFN-gamma], interleukin-1 [IL-1], interleukin-2 [IL-2], interleukin-6 [IL-6], interleukin-10 [IL-10], interleukin-4 [IL-4] and tumour necrosis factor-alpha [TNF-alpha]) in patients with tuberculous pericarditis. DESIGN: Subpopulation of a consecutive prospective case series. PATIENTS: Thirty patients presenting with pericardial effusions due to tuberculosis (n = 19), malignancy (n = 6) and non-tuberculous infections (n = 5), and five control subjects who had undergone open heart surgery. RESULTS: The concentration of IFN-gamma was significantly higher in tuberculous pericardial effusions than in the other diagnostic classes (P < 0.0005). The concentration of TNF-alpha was similar in both infective and tuberculous effusions, but was significantly higher than that of malignant effusions. IL-1 and IL-2 were undetectable in malignant effusions, but elevated in both infective and tuberculous pericardial effusions. The levels of IL-1 and IL-2 were furthermore significantly higher in pericardial effusions due to infective compared to tuberculous causes. The concentration of IL-6, while elevated in all diagnostic classes, was significantly higher in the malignant group. Elevated levels of IL-10 and undetectable levels of IL-4 were observed in all three diagnostic groups. CONCLUSION: These findings suggest that tuberculous pericardial effusions arise due to a hypersensitivity reaction that is orchestrated by the TH-1 lymphocytes.

The second messenger system(s) mediating the secretion of atrial natriuretic peptide (ANP) from the isolated rat heart during rapid cardiac pacing.

This study demonstrates that rapid cardiac pacing elevates Atrial Natriuretic Peptide (ANP) levels, independently from atrial stretch. The second messenger system mediating this response was examined. The phosphoinositide system, generally regarded to be important in mediating ANP release, was shown to play only a modulating role during rapid cardiac pacing. The main mediator would appear to be calcium, and a non-calmodulin dependent, calcium mediated system controlling ANP release during rapid cardiac pacing is suggested.

Clinical experience with pericardiocentesis and extended drainage in a population with a high prevalence of HIV.

BACKGROUND: The data presented were generated in a prospective study on the immunopathogenesis and management of tuberculous (TB) pericarditis at Tygerberg Hospital in Cape Town. We report our experience with 2D echocardiographically guided pericardiocentesis in 170 consecutive patients who presented to us with large pericardial effusions since 1995. METHODS: All patients referred to our department with echocardiographically confirmed large pericardial effusions underwent a clinical assessment followed by pericardiocentesis and drainage by an indwelling pigtail catheter. The appearance and amount of drained effusion were noted and fluid was sent for diagnostic assessment. The pigtail catheter was kept in place and fluid was aspirated once daily until the aspirate was less than 100 ml, at which stage the catheter was removed. RESULTS: A chest wall puncture site was chosen in 165 of the 170 patients (97%), while the subcostal approach was only used in five patients. Echocardiographic signs of tamponade were seen in 88% of cases. In the majority of patients (68.2%) a diagnosis of TB could be established and of these 46.6% were HIV positive. TB could not be proven in only three HIV-positive patients (1.8% of all patients). Neither hospital stay nor complications were increased in the HIV-positive group when compared with the HIV-negative group and no patient developed intrapericardial sepsis. No death could be attributed with certainty to the procedure. One patient developed non-fatal tamponade within 24 hours after the tap and in another patient a left ventricular thrombus was noted on echo after 16 days. Twenty-four patients underwent a pericardial window procedure according to protocol for diagnostic purposes. In another four patients a window was performed for therapeutic reasons. The most common minor complication was local pain at the site of catheter insertion. Repeat drainage was necessary in only six (3.5%) cases. CONCLUSIONS: 2D echocardiographically directed pericardiocentesis with extended catheter drainage has an excellent profile in terms of simplicity, safety and efficacy, even in a population with a very high prevalence of HIV.

Cardiac sarcoidosis: Case-studies and a brief review of the literature.

Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy.

Application of Laser Doppler Vibrometery for human heart auscultation.

In this study the potential of a Laser Doppler Vibrometer (LDV) was tested as a non-contact sensor for the classification of heart sounds. Of the twenty participants recorded using the LDV, five presented with Aortic Stenosis (AS), three were healthy and twelve presented with other pathologies. The recorded heart sounds were denoised and segmented using a combination of the Electrocardiogram (ECG) data and the complexity of the signal. Frequency domain features were extracted from the segmented heart sound cycles and used to train a K-nearest neighbor classifier. Due to the small number of participants, the classifier could not be trained to differentiate between normal and abnormal participants, but could successfully distinguish between participants who presented with AS and those who did not. A sensitivity of 80 % and a specificity of 100 % were achieved a test dataset.