Avaliação comparativa dos efeitos do anlodipino e da pimobendana na insuficiência valvar crônica de mitral em cães

A insuficiência valvar crônica de mitral (IVCM) é a principal cardiopatia de cães, correspondendo a 75-85% dos casos de cardiopatias. É causada pela degeneração mixomatosa da valva mitral (endocardiose de mitral) sendo, então, uma doença degenerativa adquirida e que pode ocasionar a insuficiência cardíaca congestiva (ICC). Pode acometer qualquer raça de cão, mas é mais frequentemente observada nas raças de pequeno porte, dentre as quais, Poodle miniatura, Spitz Alemão, Dachshund, Yorkshire Terrier, Chihuahua e Cavalier King Charles Spaniel. Na endocardiose de mitral, o volume sanguíneo regurgitado causa sobrecarga do lado esquerdo do coração, devido ao aumento das pressões atrial e ventricular esquerdas, seguida de dilatação e hipertrofia dessas cavidades cardíacas. A elevação da pressão ventricular esquerda pode causar hipertensão pulmonar, congestão e, em estágios avançados, edema pulmonar. A doença pode evoluir assintomática, enquanto que naqueles casos que evoluem para insuficiência cardíaca congestiva (ICC) os sintomas mais usuais são: tosse, intolerância ao exercício, dispneia e síncope. Em 2009 o colégio americano de medicina interna veterinária (American College of Veterinary Internal Medicine -ACVIM) elaborou diretrizes para o tratamento da IVCM, tendo por base a classificação funcional adaptada do American College of Cardiology. Neste trabalho foram utilizados os fármacos anlodipino e pimobendana em associação a outros usualmente indicados no tratamento da ICC em cães, segundo consenso de 2009, indicados no tratamento da ICC em cães. Dois grupos (A e B) de cães, cada um constituído por 10 pacientes com IVCM em estágio C, foram tratados com furosemida e maleato de enalapril, sendo que os animais do grupo A receberão pimobendana e os do grupo B, anlodipino. Os animais foram avaliados em diferentes momentos (T0, T30, T60) observando-se as alterações nos exames ecodopplercardiográfico e eletrocardiográfico, bem como de pressão arterial sistólica

Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure

Background - Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. Methods and Results - Thirty medically treated ambulatory hypertensive patients (19 women, age 62 +/- 6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A 250m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31 +/- 5 kg/m(2)) with reduced treadmill exercise capacity (6.7 +/- 2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133 +/- 17/80 +/- 7mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57 +/- 0.46 s(-1) versus 6-months: -1.91 +/- 0.36 s(-1), P < 0.01), peak systolic strain (-20.3 &PLUSMN; 5.0% versus -26.9 &PLUSMN; 4.3%, P < 0.001), and CVIB (7.4 +/- 1.7dB versus 8.6 +/- 1.7 dB, P = 0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P = 0.05, P = 0.02, and P = 0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P = 0.04) and a trend to reduced left atrial area (P = 0.09). Conclusions - Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Response of B-type natriuretic pepticle to exercise in hypertensive patients with suspected diastolic heart failure: Correlation with cardiac function, hemodynamics, and workload

Background Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Methods Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (So) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Results Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 57 to 74 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise So, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Conclusions Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.

Echocardiographic parameters in 14 healthy English Bull Terriers

Objective To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. Design Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. Procedure All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. Results These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the maximising method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific normal left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. Conclusion These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used.

Population-based detection of systolic and diastolic dysfunction with amino-terminal pro-B-type natriuretic peptide

Background There is limited information regarding the clinical utility of amino-terminal pro-B-type natriuretic pepticle (NT-proBNP) for the detection of left ventricular (LV) dysfunction in the community. We evaluated predictors of circulating NT-proBNP levels and determined the utility of NT-proBNP to detect systolic and diastolic LV dysfunction in older adults. Methods. A population-based sample of 1229 older adults (mean age 69.4 years, 50.1% women) underwent echocardiographic assessment of cardiac structure and function and measurement of circulating NT-proBNP levels. Results Predictors of NT-proBNP included age, female sex, body mass index, and cardiorenal parameters (diastolic dysfunction [DID] severity; LV mass and left atrial volume; right ventricular overload; decreasing ejection fraction [EF] and creatinine clearance). The performance of NT-proBNP to detect any degree of LV dysfunction, including mild DID, was poor (area under the curve 0.56-0.66). In contrast, the performance of NT-proBNP for the detection of EF 0.90 regardless of age and sex; history of hypertension, diabetes, coronary artery disease; or body mass category. The ability of NT-proBNP to detect EF

Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Associates of an elevated natriuretic peptide level in stable heart failure patients:implications for targeted management

BACKGROUND: Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population.

METHODS: In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured.

RESULTS: Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates.

CONCLUSION: Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes

In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?

AIMS: Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.

METHODS AND RESULTS: This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.

CONCLUSION: These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.

Oclusão percutânea do apêndice auricular esquerdo e estrutura auricular: efeito na função mecânica e endócrina auricular

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Intervenção Cardiovascular.

Cardiac magnetic resonance imaging in the diagnosis and determination of outcome of pulmonary hypertension

Pulmonary hypertension (PH) is a rare but serious condition that causes progressive right ventricular (RV) failure and death. PH may be idiopathic, associated with underlying connective-tissue disease or hypoxic lung disease, and is also increasingly being observed in the setting of heart failure with preserved ejection fraction (HFpEF). The management of PH has been revolutionised by the recent development of new disease-targeted therapies which are beneficial in pulmonary arterial hypertension (PAH), but can be potentially harmful in PH due to left heart disease, so accurate diagnosis and classification of patients is essential. These PAH therapies improve exercise capacity and pulmonary haemodynamics, but their overall effect on the right ventricle remains unclear. Current practice in the UK is to assess treatment response with 6-minute walk test and NYHA functional class, neither of which truly reflects RV function. Cardiac magnetic resonance (CMR) imaging has been established as the gold standard for the evaluation of right ventricular structure and function, but it also allows a non-invasive and accurate study of the left heart. The aims of this thesis were to investigate the use of CMR in the diagnosis of PH, in the assessment of treatment response, and in predicting survival in idiopathic and connective-tissue disease associated PAH. In Chapter 3, a left atrial volume (LAV) threshold of 43 ml/m2 measured with CMR was able to distinguish idiopathic PAH from PH due to HFpEF (sensitivity 97%, specificity 100%). In Chapter 4, disease-targeted PAH therapy resulted in significant improvements in RV and left ventricular ejection fraction (p<0.001 and p=0.0007, respectively), RV stroke volume index (p<0.0001), and left ventricular end-diastolic volume index (p=0.0015). These corresponded to observed improvements in functional class and exercise capacity, although correlation coefficients between Δ 6MWD and Δ RVEF or Δ LVEDV were low. Finally, in Chapter 5, one-year and three-year survival was worse in CTD-PAH (75% and 53%) than in IPAH (83% and 74%), despite similar baseline clinical characteristics, lung function, pulmonary haemodynamics and treatment. Baseline right ventricular stroke volume index was an independent predictor of survival in both conditions. The presence of LV systolic dysfunction was of prognostic significance in CTD-PAH but not IPAH, and a higher LAV was observed in CTD-PAH suggesting a potential contribution from LV diastolic dysfunction in this group.

Heart dimensions may influence the occurrence of the heart rate deflection point in highly trained cyclists

To determine whether the heart rate (HR) response to exercise in 21 highly trained cyclists (mean (SD) age 25 (3) years) was related to their heart dimensions. Methods—Before performing an incremental exercise test involving a ramp protocol with workload increases of 25 W/min, each subject underwent echocardiographic evaluation of the following variables: left ventricular end diastolic internal diameter (LVIDd), left ventricular posterior wall thickness at end diastole (LVPWTd), interventricular septal wall thickness at end diastole (IVSTd), left ventricular mass index (LVMI), left atrial dimension (LAD), longitudinal left atrial (LLAD) and right atrial (LRAD) dimensions, and the ratio of early to late (E/A) diastolic flow velocity. Results—The HR response showed a de- flection point (HRd) at about 85% V~ O2MAX in 66.7% of subjects (D group; n = 14) and was linear in 33.3% (NoD group; n = 7). Several echocardiographic variables (LVMI, LAD, LLAD, LRAD) indicative of heart dimensions were similar in each group. However, mean LPWTd (p<0.01) and IVSTd (p<0.05) values were signifi- cantly higher in the D group. Finally, no significant diVerence between groups was found with respect to the E/A. The HR response is curvilinear during incremental exercise in a considerable number of highly trained endurance athletes—that is, top level cyclists. The departure of HR increase from linearity may predominantly occur in athletes with thicker heart walls.

Accidental closure of the left upper pulmonary vein with an Amplatzer atrial septal defect occluder

We report the clinical outcome of a 46-year-old man referred for percutaneous closure of an atrial septal defect under transthoracic echocardiographic and fluoroscopic guidance, whose upper left pulmonary vein was erroneously obliterated using an Amplatzer atrial septal defect occluder. Various medical conditions have been associated with pulmonary vein stenosis including dyspnea on exertion or at rest, cough, and hemoptysis. However, there were no short- or long-term symptoms in this patient.

Disparate activation of the coronary sinus and inferior left atrium during atrial tachycardia after persistent atrial fibrillation ablation: prevalence, pitfalls, and impact on mapping

Persistent atrial fibrillation (AF) ablation may lead to partial disconnection of the coronary sinus (CS). As a result, disparate activation sequences of the local CS versus contiguous left atrium (LA) may be observed during atrial tachycardia (AT). We aimed to evaluate the prevalence of this phenomenon and its impact on activation mapping.

Electroanatomic reconstruction of the left atrium, pulmonary veins, and esophagus compared with the "true anatomy" on multislice computed tomography in patients undergoing catheter ablation of atrial fibrillation

BACKGROUND: Current concepts of catheter ablation for atrial fibrillation (AF) commonly use three-dimensional (3D) reconstructions of the left atrium (LA) for orientation, catheter navigation, and ablation line placement. OBJECTIVES: The purpose of this study was to compare the 3D electroanatomic reconstruction (Carto) of the LA, pulmonary veins (PVs), and esophagus with the true anatomy displayed on multislice computed tomography (CT). METHODS: In this prospective study, 100 patients undergoing AF catheter ablation underwent contrast-enhanced spiral CT scan with barium swallow and subsequent multiplanar and 3D reconstructions. Using Carto, circumferential plus linear LA lesions were placed. The esophagus was tagged and integrated into the Carto map. RESULTS: Compared with the true anatomy on CT, the electroanatomic reconstruction accurately displayed the true distance between the lower PVs; the distances between left upper PV, left lower PV, right lower PV, and center of the esophagus; the longitudinal diameter of the encircling line around the funnel of the left PVs; and the length of the mitral isthmus line. Only the distances between the upper PVs, the distance between the right upper PV and esophagus, and the diameter of the right encircling line were significantly shorter on the electroanatomic reconstructions. Furthermore, electroanatomic tagging of the esophagus reliably visualized the true anatomic relationship to the LA. On multiple tagging and repeated CT scans, the LA and esophagus showed a stable anatomic relationship, without relevant sideward shifting of the esophagus. CONCLUSION: Electroanatomic reconstruction can display with high accuracy the true 3D anatomy of the LA and PVs in most of the regions of interest for AF catheter ablation. In addition, Carto was able to visualize the true anatomic relationship between the esophagus and LA. Both structures showed a stable anatomic relationship on Carto and CT without relevant sideward shifting of the esophagus.