Assessment of myocardial mechanics in chronic rheumatic mitral regurgitation

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, for the degree of Doctor of Philosophy Johannesburg 2016Chronic rheumatic mitral regurgitation (CRMR) is a commonly encountered lesion in the developing world, yet it remains an understudied disease in comparison to degenerative MR. There are several unresolved issues in CRMR ranging from limited data on the current demographic and clinical profile of the contemporary patient with CRMR, to the evaluation of this lesion with sophisticated techniques utilising strain (Ɛ), magnetic resonance imaging (MRI) and biomarkers. Furthermore, the role of medical therapy has been mainly restricted to studies pertaining to degenerative MR. Thus, in this thesis the aim was to address some of the aforementioned deficiencies in the field of CRMR. In the process of studying the atrioventricular functional parameters in CRMR, we established age and vendor-specific (Philips QLAB 9) normative data for left atrial (LA) functional and volumetric parameters in a normal black population. Eighty four subjects with CRMR were studied at Chris Hani Baragwanath Hospital (CHBAH) and compared with a prior landmark study by Marcus et al conducted at this institution. Mean age was 44.0±15.3 years, compared to 19 years in the study by Marcus et al. Acute rheumatic fever (ARF) was rare compared to the previous study. Hypertension and human immunodeficiency virus (HIV) were present in 52% and 26% respectively. Echocardiography showed leaflet thickening and calcification, restricted motion and sub-valvular disease, as opposed to pliable leaflets with predominant prolapse and chordal rupture in the study by Marcus et al. One hundred and twenty normal black subjects from 18 and 70 years of age were studied. Maximum LA volume indexed (LAVi) was 19.7±5.9 mL/m2. LA pump function increased with age (r=0.2, p=0.02), and the conduit function decreased with age (r=-0.3, p< 0.001). LA Ɛ in the reservoir phase was 39.0±8.3%. LA Ɛ in the reservoir phase declined with age (p<0.001). Two studies were conducted using speckle tracking in 77 patients with CRMR. The first study found that 86% had decreased LA peak reservoir Ɛ and 58% had depressed left ventricular (LV) peak systolic Ɛ. In the second study, right ventricle (RV) peak systolic Ɛ was lower in the MR group compared to controls (-16.8±4.5% vs -19.2±3.4%, p=0.003). LV peak systolic Ɛ was an independent predictor of RV peak systolic Ɛ (r=0.46, p<0.004). CRMR is a disease characterised by eccentric jets due to distorted leaflet architecture. Thus, the echocardiographic proximal isovelocity surface area (PISA) method, to assess MR severity, is suboptimal. In CRMR there may be involvement of the LV by the rheumatic process especially in the postero basal region. To study these issues, 22 patients without comorbidities underwent MRI. On comparison of MR severity assessment by echocardiography (using an integrated approach) and MRI, there was concordance between the two techniques in all but seven patients. Six patients were reclassified as severe MR after MRI and one patient was re-categorised as moderate MR. Only four patients had fibrosis on late gadolinium enhancement. No particular regional involvement was noted. We also studied markers of collagen degradation and synthesis in CRMR and their relation with MRI parameters. Matrix metalloproteinase-1 was increased compared to controls (log MMP-1 3.5±0.68 vs 2.7±0.9, p=0.02), implying increased collagen degradation rather than synthesis in CRMR. This supports the paucity of fibrosis found on MRI. Effects of combination medical therapy in heart failure (HF) secondary to severe CRMR in 31 patients was studied. On optimal therapy no HF-related admissions or deaths were noted. There was improvement in LA peak systolic strain. LV and RV functional indices remained unchanged on maximal therapy. In conclusion, the contemporary CRMR patients are older, have comorbidities and less ARF. Upper limits of maximum LAVi are lower in the black population compared to Caucasians, and age needs to be considered when interpreting abnormalities of LA function. LA dysfunction was noted with or without involvement of the LV, therefore perhaps in CRMR, LA dysfunction precedes LV dysfunction. RV peak systolic Ɛ was useful for assessment of subclinical RV dysfunction in CRMR, therefore quantitative measurement of RV systolic function should not rely solely on conventional indices. Cardiac MRI was a useful adjunctive tool for MR severity assessment in 32% of CRMR patients when echocardiography alone was insufficient. CRMR is characterised by predominant collagen degradation and is associated with low prevalence of fibrosis. Finally, there may be a role for combination anti-remodelling therapy in HF secondary to MR. Finally, we have provided normal reference ranges for LA volume and strain parameters that would serve as platform for future studies in this population. Our findings pertaining to imaging, biomarkers and role of combination anti-remodelling therapy in CRMR may aid in the clinical assessment and management of patients with CRMR, and serve as a base for further research in these fields.MT201

Role of Medical Therapy in Chronic Mitral Regurgitation

Mitral regurgitation is one of the most commonly encountered valvular heart diseases in both the developing and the developed world. From various studies, it is known that chronic mitral regurgitation is associated with progressive left ventricular dysfunction, and eventually death if left untreated. This disease has a long silent period before symptoms manifest. During this latent period, left ventricular function progressively deteriorates and results in poor outcomes for patients even if surgery is performed. A few studies have evaluated the role of medical therapy in patients with chronic mitral regurgitation. This chapter will provide an overview of the use of medical therapy in chronic mitral regurgitation

Right-Sided Infective Endocarditis Secondary to Intravenous Drug Abuse

Right-sided infective endocarditis is due to intravenous drug abuse. Right-sided infective endocarditis is rare. It comprises 5–10% of infective endocarditis cases. Traditionally, it has been reported more commonly in patients with medical devices such as pacemakers and defibrillators and dialysis catheters. Recently, there has been increase in right-sided infective endocarditis related to intravenous drug abuse. Right-sided infective endocarditis related to drug abuse mostly affects the tricuspid valve and rarely the pulmonary valve. Although, most uncomplicated cases do well with medical treatment, it is associated with considerable morbidity and mortality due to recurrent infection. Surgery for right-sided infective endocarditis is uncommon especially in resource limited setting. Few current studies have explored surgical options in this group of patients. This chapter will review current literature related to right-sided infective endocarditis due to intravenous drug abuse

Overview of cardiovascular manifestations of COVID-19 and echocardiographic features

COVID-19 or SARS-CoV-2, a novel coronavirus, has rapidly spread across the globe, resulting in millions of infections and thousands of deaths. In this short review we describe the pathophysiology, clinical and echocardiographic manifestations of the virus, with specific reference to the cardiovascular system. We conclude with a case summary reflective of the most common cardiovascular presentation in severely ill patients

Human Immunodeficiency Virus Associated Large Artery Disease

Advances in human immunodeficiency virus (HIV) therapy with highly active antiretroviral agents has increased the longevity of patients afflicted with this disease. HIV vasculopathy is a unique disease entity presenting as aneurysms, dissections and vascular occlusion amongst others due to HIV related vasculitis. A few studies have investigated the pathogenesis of HIV related vasculopathy. This chapter provides a brief overview of aortic aneurysms in general. Further, the current understanding of the pathogenic mechanisms underlying HIV vasculopathy with an emphasis on inflammatory mediators, histology, clinical presentation and imaging are discussed. Finally, a summary regarding management of HIV associated large vessel disease is presented

Coronary artery disease prevalence amongst patients undergoing valve replacement surgery: A South African perspective

Background: The prevalence of coronary artery disease (CAD) amongst patients presented for valve surgery has important implications for routine angiography. Information on the frequency of CAD in predominantly black patients presented for valve surgery in South Africa has not been published.Methods: A retrospective, descriptive study of 116 patients presented for valve surgery that underwent coronary angiography between 2010 and 2011 was performed. CAD was defined as stenosis of 70% or greater in one or more epicardial vessels or ≥50% in the left main coronary artery, as defined by quantitative coronary angiography.Results: Median age was 57.4 (IQR 43 - 67) years (56.9% females). Black patients represented 66.4%, whites 19.8%, and, coloured and Indian patients 13.8%. Hypertension and smoking were the most common cardiovascular risk factors (26.7% and 16.4% respectively). Diabetes mellitus, dyslipidaemia, chronic kidney disease and prior CAD occurred collectively in 15.5% of study subjects. HIV prevalence was 12%, half of whom were on antiretroviral therapy. An isolated valve lesion occurred in 69% of patients, with the remainder having 2 or more lesions. The most common valve lesion was aortic stenosis (43.1%), followed by mitral stenosis (36.2%), aortic regurgitation (29.3%), mitral regurgitation (25.9%) and tricuspid regurgitation (19%). The predominant aetiology was rheumatic heart disease (58.6%), followed by degenerative valve disease (24.1%). CAD was documented in 10 patients (8.6%), of whom 8 had single vessel disease and 2 had double vessel disease.Conclusion: The low prevalence of CAD found in younger, asymptomatic black patients without cardiovascular risk factors referred for valve surgery, raises the question of whether routine pre-operative coronary angiography in this sub-group is appropriate

Tricuspid valve endocarditis associated with intravenous nyoape use: A report of 3 cases

We report three cases of tricuspid valve infective endocarditis associated with intravenous nyoape use. Nyoape is a variable drug combination of an antiretroviral (efavirenz or ritonavir), heroin, metamphetamines and cannabis. Its use is becoming increasingly common among poor communities in South Africa. All our patients were young HIV-positive men from disadvantaged backgrounds. They all presented with tricuspid regurgitation and septic pulmonary emboli. They were treated with prolonged intravenous antibiotic courses, and one required referral for surgery