II. UNAMUNO EN EUROPA EXCITATOR HISPANIAE
2.2. Unamuno: excitator en Alemania y en Austria
Left Ventricular function was assessed by trans-thoracic echocardiography. (TTE) As described in the introduction, TTE has become a key part of the diagnostic and follow up process for patients with heart failure.
Its ease of use and widespread availability has meant that it is a routine examination for patients with heart failure. Using ultrasonic waves generated via a piezoelectric crystal, it is able to offer the ability to image the heart in real time. It does not involve radiation, nor invasive testing and is safe. It has been previously been demonstrated to be reproducible and enables the visualisation of intra-cardiac structures such as valves and chambers.
All echocardiography for this thesis was carried out by accredited trained professionals working in the Derek Gibson echocardiography laboratory at the Royal Brompton Hospital, London. All images were acquired either on Vivid 7 (General Electric, Andover,
Massachusetts, US) or on iE33 (Phillips, Amsterdam, The Netherlands) with a multi-
frequency transducer. The echocardiographer was blinded to the results of the other end point measures.
As per the American Society of Echocardiography guidelines, all LVEF measurements were calculated using the Biplane Simpson’s technique.(202) This measured LVEF using a standardised format in the four chamber view and two chamber view. The accuracy of the measurement of LVEF is enhanced by choosing two planes which are perpendicular to each other. The measurement of LVEF via this technique is the suggested gold standard, however it is also recognised that there may be a reproducibility error with repeated measurement of such views.(203) Additionally, the echocardiographer also measured and recorded the left ventricular end systolic and end diastolic diameters. These were measured at rest, from the
cross sectional M- Mode recordings of the LV minor axis using the left parasternal long-axis view with the cursor at the tips of the mitral valve leaflets. The LV dimensions were taken at end-diastole and at end systole. The left atrial diameter was measured from the M-Mode recording from the left parasternal view at the level of the aortic valve.
During the routine echocardiographic study, co existent valvular disease was assessed. If mitral regurgitation was present, its severity was documented by using the colour Doppler of the regurgitant jet width at the level of the mitral valve. The regurgitant fraction was
quantified using the recommendations from the American Society of Echocardiography for the assessment of valvular regurgitation.(204) Peak pulmonary artery pressure (PAP) was also recorded where possible. The technique was reliant on the patient having a degree of tricuspid regurgitation.
3.2 Six Minute Walk Test
The symptoms of heart failure are usually more severe on exertion. Symptoms such as shortness of breath and fatigue may not be prominent at rest or on minimal exertion but may be more apparent on mild – moderate exertion.
Exercise testing for patients with heart failure has been described over the past four decades. One option is to establish the patient’s maximal oxygen (MvO2) consumption via treadmill or ergonometric bicycle testing. Though it is a reproducible and reliable measure which is predictive of prognosis and the need for cardiac transplantation; it requires the use of trained personnel and complex equipment.
An alternative method which tests the patient’s sub-maximal exercise tolerance in a standardised format is a six minute walk test. This was initially described in patients with respiratory disease; however two subsequent studies then described its application in patients with heart failure.(205-207) It was shown to be reproducible and reliable.(207)
It is also a prognostic marker in heart failure cohorts, and for patients undergoing
implantation of cardiac resynchronisation therapy (CRT).(208-210) The 6 minute walk test has also been demonstrated to be able to predict long term mortality following CRT
implantation.(211) The data from Brugada’s group indicates a pre CRT implantation six minute walking distance of 225m predicts long term mortality.
Within this thesis where used, the 6 MWT was performed according to one of its initial descriptions in patients with heart failure.(207) It was administered by two experienced observers familiar with the protocol. No encouragement was given to the patient during the 6 minutes. A walking track of twenty metres was marked out and the patients walked
continuously from the start to the finish during the test period. Patients completed the course at their own pace. All tests were performed at least 2 hours after the administration of heart failure medication.
3.3 B-Type Natriuretic Peptide (BNP)
Previously described within the introduction, natriuretic peptides are released in response to myocardial stress. BNP is released by myocytes in response to raised ventricular filling pressures and volume overload. It should be noted that though BNP is specific for excluding heart failure, it has a limited sensitivity. BNP carries prognostic information for all aetiologies of heart failure and has been shown to be associated with adverse outcomes in patients
undergoing CRT implantation.(212-214)
All BNP results quoted within this thesis, were collected and then subsequently analysed by the Department of Biochemistry, Royal Brompton Hospital, Royal Brompton & Harefield NHS Foundation Trust. A standardised assay was used for all samples. (Alere Triage BNP Assay, Alere Corporation, San Diego, California, US) All samples were processed on the same immunoassay system. (Beckman-Coulter Incorporated, Brea, California, US). The normal reference range for serum BNP for the duration of the studies performed within this thesis was <4 pmol/Litre.
3.4 Statistics
Statistical analysis was performed using SPSS version 19.0 for Microsoft Windows.
variables were analysed with the appropriate statistical test depending on the statistical relationship under investigation. More complex statistics were performed under the supervision of a senior statistician. A p value <0.05 was deemed to be of statistical significance for all analyses.