Browsing by Subject "Cardiology"

Now showing 1 - 17 of 17
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    Access to diagnostic tests and essential medicines for cardiovascular diseases and diabetes care: cost, availability and affordability in the west region of Cameroon
    (Public Library of Science, 2014) Jingi, Ahmadou M; Noubiap, Jean Jacques N; Onana, Arnold Ewane; Nansseu, Jobert Richie N; Wang, Binhuan; Kingue, Samuel; Kengne, André Pascal
    Objective: To assess the availability and affordability of medicines and routine tests for cardiovascular disease (CVD) and diabetes in the West region of Cameroon, a low-income setting. METHODS: A survey was conducted on the availability and cost of twelve routine tests and twenty medicines for CVD and diabetes in eight health districts (four urban and four rural) covering over 60% of the population of the region (1.8 million). We analyzed the percentage of tests and medicines available, the median price against the international reference price (median price ratio) for the medicines, and affordability in terms of the number of days' wages it would cost the lowest-paid unskilled government worker for initial investigation tests and procurement for one month of treatment. RESULTS: The availability of tests varied between 10% for the ECG to 100% for the fasting blood sugar. The average cost for the initial investigation using the minimum tests cost 29.76 days' wages. The availability of medicines varied from 36.4% to 59.1% in urban and from 9.1% to 50% in rural settings. Only metformin and benzathine-benzylpenicilline had a median price ratio of ≤1.5, with statins being largely unaffordable (at least 30.51 days' wages). One month of combination treatment for coronary heart disease costs at least 40.87 days' wages. CONCLUSION: The investigation and management of patients with medium-to-high cardiovascular risk remains largely unavailable and unaffordable in this setting. An effective non-communicable disease program should lay emphasis on primary prevention, and improve affordable access to essential medicines in public outlets.
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    An analysis of defibrillation and cardiac resynchronization therapy strategies in patients with failing systemic right ventricles
    (2007) Michael, Kevin A; Morgan, John M
    The expanding application of cardiac resynchronization (CRT) and implantable cardioverter-defibrillator therapy (lCD) to include patients with congenital heart disease requires careful evaluation of selection criteria and unconventional adaptive strategies to ensure clinical efficacy. A single centre prospective analysis of adults post atrial redirection surgery (Mustard operation) for dextro-transposition of the great arteries (d-TGA) presenting with systemic right ventricular (sRV) dysfunction and at risk of sudden cardiac death (SCD). All patients ( mean age 25 years, range 18-35) with varying functional disability{New York Heart Association (NYHA) II-III} receiving ICDs ± concomitant CRT were evaluated. Total follow-up period was 24 months. A patient individualized approach was used for device implantation. Endocardial, epicardial and transthoracic defibrillation strategies were examined in 5 consecutive cases. A hybridized form of CRT was employed in two patients. Only one patient demonstrated response to therapy while the other deteriorated during biventricular pacing (BVP). This prompted a novel approach to CRT using noncontact mapping (NCM) and acute intra-arterial blood pressure response to guide endocardialsRV lead placement in a single patient. The ejection fraction increased from 23 -33% within 1week post procedure and clinical improvement was sustained after 6-months follow-up. Application of CRT II CD therapy to patients with sRV dysfunction requires individualized and adaptive strategies to overcome anatomical constraints. This study represents a chronological and evolutionary account of these measures.
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    The clinical, electrocardiographic and echocardiographic features and long-term outcome of patients with Tachycardia-induced cardiomyopathy
    (2010) Chin, Ashley; Okreglicki, A M
    Tachycardia-induced cardiomyopathy (TIC) is a reversible cause of LV systolic dysfunction that can complicate any supraventricular or ventricular tachyarrhythmia. This study is the first to compare features of pure and impure TIC. We found that impure TIC may develop more quickly than pure TIC, as impure TIC patients have a shorter duration and more severe symptoms at presentation, which suggests that underlying structural heart disease is a risk factor in the pathogenesis of TIC.
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    Cyclic stretch-mediated release of vascular endothelial growth factor by vascular smooth muscle cells : a role in improved vascular graft patency
    (1999) Smith, James Douglas; Zilla, Peter
    In the light of studies which show the upregulation of VEGF in contractile cells subjected to cyclic stretch and the profound effects which cyclic stretch has been shown to have on the release of other cytokines by SMC, this study investigates the role which cyclic stretch might play in VEGF expression by SMC in a compliant environment. Furthermore, following observations of receptor phosphorylation in response to cyclic stretch in vascular cells, the effect of cyclic strain on the KDR-mediated endothelial response to locally-released VEGF was also investigated. Low passage number bovine aortic SMC and EC were plated on collagen-coated elastomer plates and subjected to 10% repetitive strain at 1 Hz. The mRNA expression of VEGF in SMC and the phosphorylation of KDR on EC were determined by northern blotting and western blotting respectively. The biological activity on EC and levels of VEGF secreted into the medium by SMC under cyclic stretch were investigated using a migration assay and ELISA respectively. Cyclic stretch was found to cause a 3.3 (±1.5 p < 0.005) fold increase in VEGF mRNA levels over unstretched controls at 4 hours. This biomechanically-induced expression was found to drop slightly by 24 hours and to be approximately equivalent to expression induced by the cytokine bFGF over the same time course. These results correlated with an increase in VEGF levels in media from stretched SMC capable of inducing migration of EC by 1.6 fold although additional EC chemotactic factors appear to be released by stretch. Furthermore, although the levels of KDR remained constant under cyclic stretch, average KDR phosphorylation was found to increase weakly over time due to cyclic stretch. These results show that cyclic stretch affects the VEGF communication between SMC and EC at both the level of VEGF expression by SMC and at the level of VEGF recognition by the KDR receptor on EC. It is possible that through the nitric oxide (NO) pathway, VEGF release may alleviate abnormally high levels of cyclic strain. It is hoped that a better understanding of the role of VEGF communication between stretched SMC and EC will enable the design of a graft in which the level of compliance encourages SMC to maintain a functional endothelium. Following this it is hoped that the low levels of SMC and pericytes invading the graft, pacified by endothelial cell mediation, will not result in intimal hyperplasia but rather play a role in microvessel maintenance and more complete healing.
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    Heart failure care in low-and middle-income countries: a systematic review and meta-analysis
    (Public Library of Science, 2014) Callender, Thomas; Woodward, Mark; Roth, Gregory; Farzadfar, Farshad; Lemarie, Jean-Christophe; Gicquel, Stéphanie; Atherton, John; Rahimzadeh, Shadi; Ghaziani, Mehdi; Shaikh, Maaz
    In a systematic review and meta-analysis, Kazem Rahimi and colleagues examine the burden of heart failure in low- and middle-income countries. Please see later in the article for the Editors' Summary
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    Neurohormonal and inflammatory markers in valvular heart disease
    (2004) Gerber, Ivor Leslie; Stewart Ralph; Sack, Michael N
    Chronic valvular heart disease is characterised by compensatory mechanisms that result in a long asymptomatic phase associated with variable disease progression. After the development of symptoms or left ventricular dysfunction, mortality is high without surgical intervention. Currently there is no known medical therapy that influences disease progression or clinical outcome. While the development of symptoms or left ventricular dysfunction are the cardinal indications for valve surgery, routine echocardiography may not detect early left ventricular dysfunction and the development of early symptoms may not be appreciated. Numerous studies demonstrate that increased natriuretic peptide plasma levels, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and amino-terminal BNP (N-BNP) reflect left ventricular dysfunction, correlate with symptoms of cardiac failure and are independent prognostic markers for clinical outcomes in diverse cardiac conditions, but very few studies address natriuretic peptides in patients with valvular heart disease. The aims of this thesis are firstly, to determine the clinical utility of measuring natriuretic peptide plasma levels in patients with valvular heart disease, and secondly, to provide supportive biochemical evidence to established histological evidence that aortic stenosis is an inflammatory disease. One hundred and sixty three patients with chronic valvular heart disease, including aortic stenosis (n=74), aortic regurgitation (n=40) and mitral regurgitation (n=49) underwent independent assessment of symptoms, transthoracic echocardiography and measurement of plasma levels of ANP, BNP and N-BNP. Natriuretic peptide levels were significantly higher in symptomatic compared with asymptomatic patients after adjustment for echocardiographic measures of disease severity and left ventricular function. Of 29 asymptomatic patients with aortic stenosis followed for a mean of 18 months, patients with an N-BNF level above the normal range or with a greater increase in N-BNP/year were at increased risk of symptomatic deterioration. In 33 patients with aortic stenosis who underwent aortic valve replacement, N-BNP levels decreased and symptoms consistently improved by 6 months postoperatively in patients with a preoperative N-BNP level above the normal range, but N-BNP levels did not decrease and symptoms less reliably improved in patients with a preoperative N-BNP level within normal limits. In contrast to the established theory that aortic stenosis is a degenerative process not amenable to medical therapy, recent histological studies suggest that aortic stenosis may be an inflammatory disease with similarities to coronary atherosclerosis. To further address this issue, high sensitivity C-reactive protein (CRP) was measured in 20 patients with non-rheumatic aortic stenosis, 19 patients with non-rheumatic aortic regurgitation and 31 healthy controls, as well as 6 months after valve replacement in aortic stenosis. CRP was significantly increased in aortic stenosis, but not aortic regurgitation compared with controls and decreased after valve replacement in aortic stenosis. These observations are consistent with histological evidence that the aortic valve is the site of active inflammation. In conclusion, measurement of plasma natriuretic peptide levels complement clinical and echocardiographic evaluation of patients with valvular heart disease and may assist with the timing of valve surgery. Novel evidence that aortic stenosis may be an inflammatory disease is presented and suggests further studies are required to determine whether agents with anti-inflammatory actions may have a role in delaying disease progression. Following on the studies presented in this thesis, a large multicentre study has commenced in New Zealand to confirm these findings that has the potential to change clinical practice.
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    Prevalence, characteristics and additional stroke risk stratification: an analysis of the Atrial Fibrillation cohort within the REMEDY study
    (2017) Cupido, Blanche J; Mayosi, Bongani M; Zühlke, Liesl J
    Background: Atrial fibrillation (AF) is the most common arrhythmia and may be complicated by embolic stroke. It is also associated with a significant risk of heart failure and mortality. The burden of rheumatic heart disease remains great in the developing world. The prevalence of AF in those with rheumatic heart disease is in the order of 20% with a resultant 17-fold increased risk of embolic stroke. Over time, many other risk factors for stroke in the AF population have been described. Stroke risk stratification tools such as the CHADS₂ (Congestive heart failure, hypertension, age of 75 or older, diabetes mellitus or stroke/TIA) and CHA₂DS₂VASc (with the addition of a second age category, female gender, and peripheral artery disease) scores have been developed. These are used to assess the need for anticoagulation and have been well validated. These scores have traditionally excluded those patients with valvular AF. Valvular AF has not been studied extensively in the contemporary era. Oral anticoagulation had previously been advised in all patients with valvular AF. Little is known however about outcomes for stroke and mortality in this cohort of patients. Furthermore, the utilization of the CHADS₂ and CHA₂DS₂VASc scores may provide incremental benefit in prognostication and resultantly, both more diligent prescription of anticoagulation and improved outcomes. Objectives: The objectives of this study were as follows - 1. To determine the prevalence of AF in the Global Rheumatic Heart Disease Registry (the REMEDY study) and in the Groote Schuur Hospital (GSH) cohort. 2. To assess the demographic, social and clinical characteristics of patients with AF in the REMEDY study and in the GSH cohort. 3. To assess the frequency of CHADS₂ and CHA₂DS₂VASc risk factors in the GSH cohort and to calculate a CHADS₂ and CHA₂DS₂VASc score on each of the patients with AF. 4. To establish whether CHADS₂ and CHA₂DS₂VASc scores further increase the risk of stroke and death in this cohort of patients with valvular AF. Methods: This is a substudy of the Global Rheumatic Heart Disease Registry (the REMEDY study). We assessed those with AF from the entire cohort for prevalence and outcome data. Patients with ECG or Holter proven AF from the GSH cohort were further risk stratified using the CHADS₂ and CHA₂DS₂Vasc scores. Clinical data was obtained from folder reviews and telephonic interviews. The CHADS₂ and CHA₂DS₂Vasc scores for each patient in the GSH cohort were calculated. Patients were followed up for 2 years and information pertaining to death and stroke were obtained from folder reviews. These were then correlated with the CHADS₂ and CHA₂DS₂Vasc scores. Results: A total of 2624 REMEDY patients were analysed. Of these, 22% in the total cohort (586 of 2684 patients) and 38.2% in the GSH cohort (187 of 489 patients) had AF. These patients were older (35 years vs. 25 years, p<0.0001), more likely to be female (73.1% vs. 65.6%, p=0.001) and more frequently had a history of congestive heart disease (41.0% vs. 33.3%, p=0.001) when compared to those in sinus rhythm. They also had significantly more strokes (13.8% vs. 5%, p<0.0001) and a poorer NYHA class (NYHA III& IV 30.8% vs. 25.2%, p=0.002). The cohort with AF had more severely impaired left ventricular (LV) function compared to those in sinus rhythm (Ejection fraction (EF) 57% vs. 61%. P<0.0001). The presence of a larger left atrial (LA) size, spontaneous echo contrast and LA thrombus was much greater in the AF cohort. Of those patients in AF, only 68% had received a prescription for warfarin. The GSH cohort was risk stratified using the CHADS₂ and CHA₂DS₂VASc scores. Twenty-three percent of patients had a CHADS₂ score of 0 and 27.7% of 1. When the same cohort was scored using the CHA₂DS₂VASc score, only 5.4% had a score of 0; this difference was mainly driven by the additional category of female gender. The patients in our cohort were young (median age 28 years) and had few comorbidities. Despite this, patients with AF did significantly worse than those in sinus rhythm, with a stroke rate of 4.6% and a mortality rate of 13.1% observed at 2 years (compared to a 1.5% stroke rate and 5.5% mortality rate for those in sinus rhythm). The presence of any additional comorbidities significantly reduced survival in both the short and long term. Greater CHA₂DS₂VASc score categories (CHA₂DS₂VASc 1 and CHA₂DS₂VASc 2 or more) conferred an incrementally higher risk of death. Conclusion: In a contemporary cohort of patients with rheumatic heart disease, AF is common with a prevalence of 22-39%. These patients were older and exhibited features of more advanced disease both clinically and on echo, compared to their sinus rhythm counterparts. The mortality and stroke rates in the AF group were high despite the relatively young age of this cohort. Mortality and stroke increased significantly and incrementally with each greater CHA₂DS₂VASc score category. Given the differences in chronicity between RHD in the developed world (i.e., disease of older people) and RHD in developing countries (i.e., disease of the young), these results cannot be extrapolated to those living in the first world.
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    The prevalence, determinants, natural history and impact of atrial fibrillation and atrial flutter in patients with tuberculosis pericarditis - insights from the IMPI trial
    (2016) Chishala, Chishala; Pandie, Shaheen; Gumedze, Freedom; Mayosi, Bongani M
    Tuberculosis is the most common cause of pericarditis in Africa. The dual human immunodeficiency virus (HIV)-tuberculosis epidemics are major contributors to the burden of extra-pulmonary tuberculosis, including tuberculous pericarditis. Mortality rates remain unacceptably high. Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. It is associated with increased cardiovascular mortality and morbidity, as well as complications related to thromboembolic disease and haemodynamic instability. Similarly, atrial flutter (AFL) is a common macro-reentry arrhythmia, often associated with AF and its complications. While there is a recognized association between atrial fibrillation and / or atrial flutter (AF/AFL) and tuberculous pericarditis, there are limited data regarding the prevalence, determinants, natural history, and outcomes of AF/AFL in tuberculous pericarditis. Hypothesis: In patients with tuberculous pericarditis, AF/AFL is common, and when compared to tuberculous pericarditis patients that are in sinus rhythm, is associated with increased morbidity and mortality. Aims In participants with tuberculous pericarditis enrolled into the Investigation of the Management of Pericarditis (IMPI) trial, we intend to: 1. Estimate the prevalence of AF/AFL 2. Describe the natural history of AF/AFL 3. Identify clinical, biochemical and, echocardiographic predictors of AF/AFL 4. Determine the clinical impact of AF/AFL.
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    Profile, Presentation and Outcomes of Prosthetic Valve Endocarditis in a South African Tertiary Hospital: Insights From the Groote Schuur Hospital Infective Endocarditis Registry
    (2022) Mkoko, Philasande; Ntsekhe, Mpiko
    Background Prosthetic valve infective endocarditis (PVE) is associated with high morbidity and mortality. The prevalence of PVE in local retrospective studies ranges between 13% and 16%. However, the clinical patient profile and outcomes remains unknown. Methods We performed a prospective observational study of patients presenting or referred to Groote Schuur Hospital with definitive or probably infective endocarditis based on the 2015 European Society of Cardiology (ESC) infective endocarditis diagnostic criteria. Consenting adult patients who met inclusion criteria were enrolled into the Groote Schuur Hospital Infective Endocarditis Registry which was approved by the University of Cape Town Human Research Ethics. The current study is an analysis of the cohort of patients who were enrolled between 01/01/2017 to 31/12/2019. The primary objective of this study was to define the clinical profile and outcomes of patients with PVE. The secondary objective aimed to compare the clinical profile and outcomes of PVE patients with those of native valve endocarditis patients (NVE). Results During the study period a total of 135 patients received a diagnosis of possible and definitive infective endocarditis (IE). Of these, 18 patients had PVE and 117 patients NVE. Therefore, PVE accounted for 13.3% of the overall IE cohort. PVE patients had mean (Standard Deviation) age of 39.1 (14.6) years, 56.6% were male. PVE occurred within one year of valve surgery in 50% and the Duke's modified diagnostic criteria for definitive IE was met in 94.4% of the PVE cohort. Prosthetic valves in the aortic position were affected in isolation or in combination with prostheses in the mitral area in 66.7%. Further, tissue prosthetic valves were affected in 61.1% of the PVE cases. 55.6% of the PVE cases were health care associated. On transthoracic echocardiography, vegetations (61.1%), prosthetic valve regurgitation (44.4%) and abscess (22.2%) were discovered. Staphylococcus species and streptococcus species accounted for 38.8% and 22.2% of PVE cases, respectively. 27.8% cases were blood culture negative. Valve surgery was performed in 38.7% of the PVE patients. 55.6% of the PVE patients demised during the index hospitalisation. The secondary analysis indicated that the PVE patients were sicker, with a higher frequency of septic shock and heart block than the NVE patients, 22.2% vs 7% p= 0.02 and 27.8% vs 12% p =0.04 respectively. In addition, in hospital mortality was higher in PVE patients than NVE patients, 55.6% vs 31.6% p=0.04. Conclusion PVE is relatively uncommon in resource-limited settings and is associated with a high in hospital mortality. Staphylococcus and streptococcus species are the leading microbiological causes of PVE. The selected PVE patients that receive surgical treatment for endocarditis demonstrate better in-hospital survival than those who do not receive surgical treatment. This finding not only reaffirms the importance of surgery as treatment option for IE but further demonstrate the importance of the Heart team in selecting appropriate surgical candidates.
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    The protective role of tumour necrosis factor alpha in the heart
    (2002) Meiring, James Justus; Sack, Michael N
    The pleiotropic cytokine tumour necrosis factor alpha (TNFα) is produced by the heart in response to the ischaemic preconditioning (PC) stimulus. We hypothesised that this endogenously produced peptide may play a role in activating the ischaemic PC mediated tolerance towards a subsequent ischaemic insult in muscle cells. To test this and to delineate the downstream signalling cascades mediating this programme we developed classic PC protocols in adherent mature murine C2C12 myotubes and in human cardiac derived Girardi cell lines. The C2C12 myotubes were preconditioned using either one hour of simulated ischaemia (SI) or the PC-mimetic adenosine (0.1 mM) or TNFα (0.5 ng/ml) followed by one hour of reoxygenation followed by an eight hour SI insult. Cell viability was assessed by measuring lactate dehydrogenase (LOH) release. Simulated ischaemia (SI), PC, adenosine and TNFα activated the PC programme and increased cell viability by 40±3%, 28±5% and 36±4% respectively compared to the SI controls (p<0.005 in all experiments, n≥4 x 6 well plates in all groups). Cell viability was also evaluated by the measurement of propidium iodide uptake on flow cytometry. Preconditioning and TNFα enhanced cell viability with a reduction in propidium iodide uptake by 28% and 41 % respectively versus the ischaemic controls. To evaluate whether TNFα activation of the nuclear regulatory protein nuclear factor kappa B (NFₖ B) mediates this myocyte protection, the NFₖ B antagonists diethyldithiocarbamate (DDTC 10mM) or sodium salicylate (SA 100μM) were co-administered with TNFα. The myocyte protective effect of TNF a was significantly decrease with both antagonists, although not completely inhibited/blocked (DDTC - attenuated cell viability by 62 ±6% and SA by 45 ±5% compared to the TNFα preconditioned cells (p <0.05 vs SI controls and p<0.05 vs TNFα PC, with either antagonists). To confirm these data, TNFα was used as a PC-mimetic in the isolated Langendorff perfused rat heart (Langendorff) preparation. Infarct size was used as the end point. In parallel with cell culture studies, TNFα again conferred preconditioning induced cardioprotection with partial abrogation of these effects with the pharmacological antagonists of NFₖ B. Thus, TNFα administration mimics the cytoprotective effects of ischaemic PC in cardiac, skeletal myocytes and in the isolated perfused rat heart. Moreover, these data support the role of TNFα production as an endogenous paracrine / autocrine signalling peptide which promotes myocyte cellular survival, in part, through activation of NFₖ B.
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    Repeated full dose thrombolysis in patients hospitalised with myocardial infarction : safety and efficacy
    (2001) Kettles, David Ian; Commerford, P
    The treatment and outcome myocardial infarction has been revolutionised by the demonstration that thrombolytic grugs can open the infarct-related arterty, salvage ischaemic myocardium, preserve left ventricular function and save lives. However, thrombolytic drugs are not uniformly effective in securing or maintaining patency of the infarct-related artery.
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    Role of the SAFE pathway and the mitochondria in HDL cholesterol (and its constituent sphingosine-1-phosphate) induced cardioprotection
    (2011) Hacking, Damian; Lecour, Sandrine
    High density lipoprotein cholesterol (HDL) and its component sphingosine-1-phosphate (S1P) protect against myocardial infarction. Recently, the SAFE (survivor activating factor enhancement) pathway, involving tumour necrosis factor (TNF) and the transcription factor signal transducer and activator of transcription 3 (STAT-3), has been identified as a key signalling pathway in cardioprotection, although the end effector remains unclear.
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    Studies in cardiomyopathy: looking beyond the familiar
    (2016) Ntusi, Ntobeko A B; Mayosi, Bongani M
    Background: Little is known about the mechanisms, clinical characteristics, natural history and outcomes of cardiomyopathy amongst Africans. Familial aggregation of cardiomyopathy has not been studied systematically in an African setting. Further, it is not clear whether the various phenotypic expressions of cardiomyopathy represent disparate clinical entities, or whether they are merely different forms of the same disease manifested differently in different circumstances. Methods: Two cohorts of patients with cardiomyopathy were utilised for this study: (1) patients with cardiomyopathy seen at the specialist cardiomyopathy clinic at Groote Schuur Hospital, Cape Town between February 1, 1996 and December 31, 2009; and (2) a group of hypertrophic cardiomyopathy (HCM) patients and first degree relatives seen in a specialist cardiogenetic clinic at Tygerberg Hospital, who underwent cardiovascular magnetic resonance (CMR) imaging at Groote Schuur Hospital.
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    Studies of effusive constrictive pericarditis
    (2011) Ntsekhe, Mpiko
    Tuberculous (TB) pericarditis is associated with a mortality rate of 17-40% despite treatment with anti-tuberculosis drugs. The complications of TB pericarditis that confer mortality and morbidity are pericardial tamponade, effusive constrictive pericarditis, and constrictive pericarditis. Whilst the diagnosis and treatment of pericardial tamponade and constriction are well established, there is a paucity of evidence on the frequency and significance of tuberculous effusive constrictive pericarditis. The primary purpose of this work was to determine the prevalence, predictors, fractal (geometric) structure, biomarker signature, and outcome of effusive constrictive TB pericarditis.
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    Targeting heart rate as a novel therapeutic approach in acute heart failure
    (2018) Imamdin, Aqeela; Lecour, Sandrine; Azibani, Feriel; Sliwa, Karen; McCarthy, Joy
    Background and hypothesis: Standard pharmacological treatment for heart failure improves cardiac remodelling and survival in the setting of chronic heart failure, but is suboptimal in cases of acute heart failure (AHF). Peripartum cardiomyopathy (PPCM), de-novo hypotension (often due to haemorrhagic shock), and Takotsubo cardiomyopathy (TC) are conditions which have acute onset of heart failure, and often present with high mortality rates. In patients treated for these pathologies, a variation in the heart rate is observed and could potentially be used as a target to improve the treatment of AHF. We therefore questioned whether the use of a sinoatrial node inhibitor (ivabradine) to modulate heart rate may improve outcomes in AHF. Objectives and methods: Our objectives were 3-fold: (1) to explore the effect of a standard treatment strategy on heart rate in a South African cohort of PPCM patients after 6 and 12 months follow-up. (2) To explore the effect of ivabradine, a sinoatrial node inhibitor in an established signal transducer and activator of transcription 3 (STAT3) knockout mouse model of PPCM (with 3 consecutive pregnancies). Mice were fed ivabradine for 30 days (10mg/kg/day in drinking water), following the 3rd weaning. Trans-thoracic echocardiograms (TTE) were done at the end of the 3rd weaning, and after 30 days of treatment with ivabradine. Hearts were harvested after the second TTE for histology staining and messenger ribonucleic acid (mRNA) quantitation of transcripts involved in heart failure. (3) To explore the role of the sinoatrial node inhibitor in an ex-vivo model of de-novo AHF due to hypotension, and a newly developed ex-vivo model of TC. In the AHF model, hearts were stabilised before administering Ivabradine (3μM) in a buffer containing high free fatty-acids at a low pressure (to mimic hypotension/ haemorrhage shock conditions). A pressure- sensing balloon in the left ventricle measured heart rate, diastolic and systolic pressure, left ventricular developed pressure, rate pressure products and functional recovery. In the TC model, hearts were stabilised, then given a buffer with high free fatty-acid content and 10 times a physiological dose of adrenaline to mimic the adrenergic response seen in TC. Thereafter, hearts were restored to stabilisation pressure and substrate for recovery. Results: (1) Clinical outcomes indicated that patients on maximum standard therapy improved symptomatically and on the New York Heart Association scale. However, heart rates of PPCM patients remained elevated after 6 months of treatment. (2) In PPCM mice, a treatment with ivabradine was associated with reduced fibrotic infiltration in cardiac tissue and with a decrease in levels of atrial natriuretic peptide and Fibronectin mRNAs. (3) Both hypotensive AHF and TC models showed a tendency toward better cardiac function with ivabradine at the end of the acute phases. This advantage was lost after withdrawal of ivabradine during recovery. Conclusion: In South African women with PPCM treated with standard therapy, heart rate remains elevated, therefore suggesting that these women may benefit from the use of ivabradine as an additional therapy, particularly in patients who may be intolerant to β-blockers. The long-term use of ivabradine in the setting of cardiac dysfunction appears to have beneficial effects on remodelling, as treatment with ivabradine in our mouse PPCM model showed reduced cardiac fibrosis. The ex-vivo models of hypotensive AHF and TC both showed benefit in reducing heart rate during the acute phases, and hold the potential of being an intervention therapy to improve the outcome in patients who are brought to hospital while still in the acute phase.
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    Technology in cardiology
    (Health and Medical Publishing Group, 2003) Okreglicki, Andrzej
    Clinical technology and cardiology have a synergistic relationship with regard to investigation and intervention. Echocardiography complements clinical cardiology, but does not replace competent history taking and clinical examination. Cardiac catheterisation and angiography still remain the ‘gold standard’ for most complex cardiac conditions. Digital radiology systems allow image manipulation, measurement, instant replay and easy storage with less radiation. Magnetic resonance imaging is the investigation of choice for aortic dissection and certain cardiomyopathies. Conventional intra cardiac contact arrhythmia mapping is adequate for the majority of arrhythmias that can be ablated. 3D mapping systems are useful in abnormal hearts or after surgery. Most percutaneous cardiac intervention can be done using PTCA balloons and stents. Complex lesions occasionally may require other expensive techniques that are generally not needed; such as atherectomy and intravascular ultrasound. Arrhythmia devices (pacemakers and ICDs) need careful follow-up with monitoring and interrogation, as adjustments after implantation may be necessary. Great ca re must be taken with computer-generated interpretation of investigations (e.g. ECG), as reliance on this could potentially be dangerous. Cardiac technology and information management have important associated ethical issues.