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The optimal timing of valve replacement surgery in chronic severe aortic regurgitation (AR) has remained a major clinical problem in the management of these patients. Although the onset of symptoms is the generally accepted indication for aortic valve replacement (AVR), the unpredictable development of pre-symptomatic left ventricular (LV) dysfunction as a result of prolonged volume overload has resulted in numerous reports attempting to formulate a risk profile for these patients. Although aortic root and LV cineangiography have been the "gold standard" for defining the severity of AR and its effect on LV performance, serial follow-up by these means is impractical. More recently numerous non-invasive measures of LV size (echocardiogram) and function both at rest and on exercise (echocardiogram and equilibrium radionuclide angiocardiography., ERNA) have been serially utilised~ In these endeavours, the thinking has been clouded by a tendency to equate these two measures and failing to appreciate that apparent preoperative LV dysfunction (particularly on exercise) may be rapidly reversible by AVR and the consequent changes in LV loading conditions. This study was a prospective, sequential evaluation of left ventricular function using both non-invasive and invasive techniques in symptomatic and asymptomatic patients with isolated chronic, severe (4+) AR at cardiac catheterisation. The aims of the study were to (I) Identify differences in the clinical, echocardiographic, resting and exercise haemodynamic and I radionuclide measures of left ventricular function in symptomatic and asymptomatic patients with chronic severe A.R. with particular reference to the incidence of presymptomatic development of left ventricular dysfunction. (II) Critically evaluate the role of exercise stress (both isotonic and isometric) in the assessment of patients with chronic severe A.R. (III) Evaluate the influence of time (sequential studies) on the haemodynamic burden in asymptomatic patients. (IV) Study the impact of successful aortic valve replacement on the reversibility of abnormal pre-operative LV function in an attempt to predict which patients would benefit from this therapeutic intervention and whether operation for symptoms alone is the correct clinical practice.

<p>Aortic stenosis is the most common valvular disease in the adult population. A significant aortic stenosis is a serious condition, and if a symptomatic patient is not operated on, it may in most cases cause death. We have examined how many aortic stenoses that were diagnosed during one year, and a follow-up of the patients was also performed. We found 77 patients with significant aortic stenosis with a mean age of 76±13 years. At the time of follow-up 30 (39%) patients, aged between 29-85 years, had been surgically treated with implantation of a valve prosthesis within 2-23 months after the initial examination. At this initial examination 14 of the 30 patients who later underwent surgery had no symptoms. A coronary bypass operation was also performed on seven patients. Postoperative complications were observed in six patients, but none of them was fatal. At the initial examinations there were 26 (34%) patients with a significant aortic stenosis and symptoms who were not treated surgically. The main reason why these patients were not operated was high age, unwillingness, or severe left ventricular dysfunction. This study indicates the importance of repeated clinical and echocardiograpic examinations in patients with aortic stenosis. Almost half of the patients, that later underwent surgery, had no symptoms at the initial examination, but later developed symptoms which made surgery necessary. In one third of the patients no surgery was performed in spite of clinical symptoms.</p>

Conventional echocardiographic parameters are currently used in determining the timing for surgery in patients with mitral regurgitation. Since brain natriuretic peptide (BNP) rises in response to ventricular muscle stretch, and is to detect early heart failure, we hypothesized that BNP would be activated in patients with regurgitant valvular heart disease and concomitant left ventricular dilatation. Aim/Objectives: We therefore studied the pattern of changes in NT-pro BNP in patients with chronic severe rheumatic mitral regurgitation who were undergoing mitral valve replacement and compared this with the newer modality of tissue Doppler imaging (TDI). Setting: Patients submitted to surgery were prospectively evaluated over 8 months at Inkosi Albert Luthuli Central Hospital, Department of Cardiology. Controls were obtained from the outpatients' follow-up clinic. Methods: Simultaneous quantification of the severity of mitral regurgitation (MR), left ventricular (LV) end systolic volume (ESV), left atrial (LA) volume and Doppler filling ratios (mitral (E)/annulus (Ea)) were performed at baseline in all patients and was repeated at 1-week and at the six-week follow-up visit in surgical patients. Results: Both groups were similar for age and gender and echo-Doppler parameters in all patients preoperatively except LA size (p< 0.01) and volume (p<0.004) which were more elevated in the surgical group. Mean NT-pro BNP levels were markedly elevated preoperatively (262 pmolll) in all surgical cases compared to controls (57 pmol/l; p=0.0001). NT-pro BNP levels increased further at one week post surgery (395 pmol/l) and subsided at the six week follow-up visit (94 pmol/I). These changes were accompanied by significant reduction in LA (p= 0.003) and LV chamber dimensions (EDD = 0.004) with an increase in the ejection fraction from 42% at one week to 52 % at six weeks. Four patients had abnormally elevated NT-pro BNP levels (>53pmol/l) at the 6-week follow-up visit. A ROC curve was constructed for all variables to separate surgical cases from controls. The area under the curve was highest for NT-pro BNP (sensitivity= 96%, specificity 45 %). Conclusion: 1. There was a significant difference in the left atrial chamber size and volume, as well as Em/Ea (TDI) and NT-proBNP levels preoperatively between the two groups. The lack of a significant difference in the LV parameters between surgical and control groups suggest an almost total reliance on symptoms in deciding the timing of surgery which was reflected by markedly elevated NT-pro BNP in all surgical patients. 2. Postoperatively, there was a significant reduction in LA and LV dimensions. 3. The high false positivity rate for NT-pro BNP suggests that the test is most likely reflecting early LV decompensation in the less symptomatic control patients who rightly need surgery. 4. Tissue Doppler indices had similar sensitivity but low specificity compared to NT-proBNP. 5. Serial estimations of NT-pro BNP may prove useful in selecting patients for surgery. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2007.

Aortic stenosis is a life-threatening valvular heart disease. At the onset of symptoms, a patient’s prognosis becomes poor and the risk of death rapidly increases. Aortic valve replacement surgery remains the gold standard in treatment for aortic stenosis. However, in the total population of patients with severe aortic stenosis, about one third are deemed inoperable due to their high surgical risk. In recent years, the development of transcatheter aortic valve implantation (TAVI), a non-invasive heart valve replacement procedure brought hope for the elderly, high-risk and inoperable aortic stenosis patient population pool. A literature review was performed to examine the safety, efficacy and effectiveness evidence for transcatheter aortic valve treatment option. The results showed that TAVI is a safe treatment option, however the effectiveness for the whole patient population is unknown. The adoption of this alternative treatment option is certainly coupled with multiple dimension of impact from a public health perspective. It remains inconclusive whether TAVI is an effective treatment option to be adopted. / published_or_final_version / Public Health / Master / Master of Public Health

Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics. The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated. Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I). In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation. Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases. In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis. Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).

The purpose of this scientific work was to evaluate safety and efficacy of treatment of atrial fibrillation using monopolar radiofrequency ablation electrodes in patients who undergo mitral valve surgical correction using incisions of atrial septum (trans-septal and superior septal approaches). More than 80% of the patients are free of atrial fibrillation one year after the operation and 76% of these patients do not use anti-arrhythmic drugs. During the final visit of follow-up it was recorded that 71.5% of the patients remained free of atrial fibrillation and flutter. The maze procedure increases duration of cardiopulmonary by-pas for 16 ± 3 min, only. The baseline and surgical correction data in groups of patients of trans-septal and superior septal approaches did not differ. The method of mitral valve correction (implantation of mitral valve prosthesis or plasty of the valve) had no statistically significant influence on the results of atrial fibrillation treatment. The factors influencing the efficacy of the treatment include higher class of heart failure and larger longitudinal measurement of the left atrium found on echoscopy using M-mode. Combined therapy of secondary atrial tachycardia and atypical atrial flutter (by means of anti-arrhythmic drugs, trans-oesophageal stimulation and per-catheter ablation) enables to improve the results of maze procedure. The superior septal approach should be used in complicated operations as using this incision it is more convenient... [to full text] / Šio mokslinio darbo tikslas buvo įvertinti efektyvumą bei saugumą gydant prieširdžių virpėjimą, naudojant elektrofiziologinius RD abliacijos unipolinius elektrodinius kateterius pacientams, kuriems mitralinio vožtuvo ydą koreguojančios operacijos atliekamos per prieširdžių pertvaros(tarprieširdinės ir viršutinio pertvaros) pjūvius. Atlikus šią operaciją – po 1 metų >80% pacientų neturi prieširdžių virpėjimo/plazdėjimo, iš jų 76% nevartoja antiaritminių vaistų. Galutinio sekimo metu fiksuota, kad išliko 71,5% pacientų be prieširdžių virpėjimo ir plazdėjimo. Labirinto procedūra prailgina tik 16 ± 3 min dirbtinės kraujotakos laiką. Išeities ir operacinių parametrų atžvilgiu tarprieširdinės ir viršutinio pertvaros pjūvių grupės nesiskyrė. Mitralinio vožtuvo ydos korekcijos pobūdis – protezavimas ar plastika - statistiškai patikimai neturėjo PV gydymo rezultams. Gydymo efektyvumui įtakos turi: didesnė širdies nepakankamumo funkcinė klasė ir kairiojo prieširdžio išilginis dydis nustatytas echoskopiškai M - režimu. Pooperacinių antrinių prieširdinių tachikardijų ir atipinių prieširdžių plazdėjimo kombinuota (taikant antiaritminius vaistus, perstemplinę stimuliaciją ir perkateterinę radiodažnuminę abliacija) terapija leidžia pagerinti labirinto procedūros rezultatus. Viršutinis pertvaros pjūvis naudotinas sudėtingose operacijose, taip galima lengviau apžiūrėti mitralinį vožtuvą ir koreguoti mitralinę ydą.