The Association of Echocardiographic Peak Systolic Strain Rate with Cardiovascular Outcomes in Haemodialysis Patients.

BACKGROUND/AIMS: Echocardiographic abnormalities of systolic function can be detected earlier with advancing echocardiographic technologies. Given the high prevalence of left ventricular hypertrophy in dialysis patients, we hypothesised that one such marker of strain, peak systolic strain rate (SR) would demonstrate association with cardiovascular outcome in a haemodialysis cohort. METHODS: Recruited prevalent haemodialysis patients underwent standard transthoracic echocardiography as part of a detailed cardiovascular assessment on a non-dialysis day during a short inter-dialytic midweek break. Patients were followed up to mortality and cardiovascular end points. Multivariate Cox proportional hazard models were built to determine the association of above versus below median SR in a model adjusted for confounding factors. RESULTS: 183 patients were enrolled and followed up for a median 925 days. Median age was 64.9 years, prevalence of LVH 55%, and median SR -0.86 (-1.00 to -0.72). An SR greater than -0.86 S-1 (less negative) had a hazard ratio (HR) of 2.32 (1.36 to 3.95) in association with all-cause mortality after adjustment for EF, age, smoking history, MI, previous transplant, albumin and systolic blood pressure. For cardiovascular mortality, the HR was 2.343 (0.99 to 5.553) p =0.046. The only echocardiographic parameter independently associated with MACE was above median E/e (HR 2.09 [1.03 to 4.24], p=0.04). No echocardiographic parameter was associated with heart failure episodes. CONCLUSION: SR demonstrates association with outcome in this population and highlights the consideration that such sub-clinical cardiac changes should be routinely sought when referring haemodialysis patients for cardiac assessments.

Non-recruitment to and selection bias in studies using echocardiography in haemodialysis patients.

BACKGROUND: It is unknown whether patients recruited to renal cardiac imaging studies are fully representative of the investigated population and whether there are differences in characteristics and survival between participants and non-participants (excluded or declined consent). Subjects and Methods Four hundred thirty-five maintenance haemodialysis patients were screened in an observational, prospective study. Baseline demographics, laboratory results, social deprivation scores and survival data were collected from patient records. All patients were followed-up until death, renal transplantation or 16 November 2015. RESULTS: Forty-four patients were excluded (16 language barrier, 10 mental incapacity, 9 severe co-morbid illness and 9 because of immobility), 172 patients declined consent (84% due to reluctance to attend for an extra visit) and 219 patients were recruited. Excluded patients had a lower mean haemoglobin (10.2 g/dL vs 10.7 g/dL), phosphate (4.15 mg/dL vs 4.74 mg/dL), albumin (3.6 g/dL vs 3.8 g/dL) and higher C-reactive protein (3.2 mg/dL vs 1.6 mg/dL) compared with recruited patients. No difference was identified between groups for Charleston comorbidity index (P = 0.115) or social deprivation scores. After a median follow-up of 29.7 (25th-75th percentile, 21.1-34.3) months, there were 141 deaths. In a multivariable Cox regression model adjusting for BMI, age, Charleston comorbidity index, haemoglobin, albumin, smoking status and diabetes mellitus, patients who declined consent had an adjusted HR of 1.70, 95% CI 1.10-2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75-2.25, for all-cause mortality compared with recruited patients. CONCLUSIONS: Patients recruited to the study had longer survival compared with non-participants. Research studies should document phenotypes of non-participants to aid interpretation and generalizability of results.

Novel Approach to Cardiovascular Outcome Prediction in Haemodialysis Patients.

BACKGROUND: Cardiovascular mortality is high in haemodialysis (HD) patients. Arterial stiffness and global longitudinal strain (GLS) are important non-atheromatous cardiovascular risk predictors. No study has encompassed both parameters in a combined model for prediction of outcomes in HD patients. This is important because left ventricular (LV) dysfunction can result from fibrotic remodelling secondary to increased arterial stiffness. METHODS: Two hundred and nineteen HD patients had pulse wave velocity (PWV) and echocardiography (including GLS) assessments. Patients were followed-up until death, transplantation or November 16, 2015, whichever happened first. Pearson's correlation coefficient was used to determine factors associated with PWV and GLS. A multivariable Cox regression model investigated factors associated with all-cause, cardiac death and events. RESULTS: One hundred and ninety eight HD patients had full datasets (median age 64.2, 68.7% males) with a mean LV ejection fraction (LVEF) of 61.7 ± 10.1% and GLS -13.5 ± 3.3%; 51% had LV hypertrophy. Forty eight deaths (15 cardiac) and 44 major cardiac events occurred during a median follow-up of 27.6 (25th-75th percentile, 17.3-32.7) months. In separate survival models, PWV and GLS were independently associated with all-cause mortality; however, in a combined model, LV mass indexed to height2.7 (LVMI/HT2.7; adjusted hazard ratio (HR) 1.02, 95% CI 1.00-1.04) and PWV (adjusted HR 1.23, 95% CI 1.03-1.47) were significant. PWV was neither associated with cardiac death nor associated with related cardiac events. However, GLS was associated with cardiac death (adjusted HR 1.24, 95% CI 1.00-1.54) and cardiac events (adjusted HR 1.13, 95% CI 1.03-1.25). CONCLUSIONS: PWV and LVMI/HT2.7 were superior to GLS in prediction of all-cause mortality. However, GLS was associated with cardiac death and events even when accounting for LVEF and LVMI/HT2.7.

Echocardiography in hemodialysis patients: uses and challenges.

Patients with end-stage renal disease undergoing hemodialysis have high rates of morbidity and mortality. Cardiovascular disease accounts for almost half of this mortality, with the single most common cause being sudden cardiac death. Early detection of abnormalities in cardiac structure and function may be important to allow timely and appropriate cardiac interventions. Echocardiography is noninvasive cardiac imaging that is widely available and provides invaluable information on cardiac morphology and function. However, it has limitations. Echocardiography is operator dependent, and image quality can vary depending on the operator's experience and the patient's acoustic window. Hemodialysis patients undergo regular hemodynamic changes that also may affect echocardiographic findings. An understanding of the prognostic significance and interpretation of echocardiographic results in this setting is important for patient care. There are some emerging techniques in echocardiographic imaging that can provide more detailed and accurate information compared with conventional 2-dimensional echocardiography. Use of these novel tools may further our understanding of the pathophysiology of cardiac disease in patients with end-stage renal disease undergoing hemodialysis.

Validated Model for Prediction of Adverse Cardiac Outcome in Patients With Fabry Disease.

BACKGROUND: The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear. OBJECTIVES: The objective of this study was to develop, internally validate, and evaluate the performance of, a prognostic model, including contemporary deep phenotyping, which can be used to generate individual risk estimates for adverse cardiac outcome in patients with Fabry disease. METHODS: This longitudinal prospective cohort study consisted of 200 consecutive patients with Fabry disease undergoing clinical cardiac magnetic resonance. Median follow-up was 4.5 years (IQR: 2.7-6.3 years). Prognostic models were developed using Cox proportional hazards modeling. Outcome was a composite of adverse cardiac events. Model performance was evaluated. A risk calculator, which provides 5-year estimated risk of adverse cardiac outcome for individual patients, including men and women, was generated. RESULTS: The highest performing, internally validated, parsimonious multivariable model included age, native myocardial T1 dispersion (SD of per voxel myocardial T1 relaxation times), and indexed left ventricular mass. Median optimism-adjusted c-statistic across 5 imputed model development data sets was 0.77 (95% CI: 0.70-0.84). Model calibration was excellent across the full risk profile. CONCLUSIONS: This study developed and internally validated a risk prediction model that accurately predicts 5-year risk of adverse cardiac outcome for individual patients with Fabry disease, including men and women, which could easily be integrated into clinical care. External validation is warranted.

Non-attendance to the paediatric clinics in a Malaysian tertiary hospital: a sizeable problem and identification of an efficacious intervention.

AIM: To determine the rate, causes and risk factors of non-attendance to the paediatric clinic in a tertiary hospital in Malaysia and to determine the efficacy of one telephone call to confirm a new appointment. METHODS: For all non-attending patients, during a 2-month period, a pro forma was filled up based on patients' records. During a phone call, additional questions were asked, and a new appointment was offered. RESULTS: Of 1563 patients who had an appointment, 497 (31.8%) were non-attendees. Weather conditions, the sub-specialty and timing (morning or afternoon) had a significant effect on non-attendance. Forgetfulness was the main cause. Only 160 patients could be successfully contacted. Among the contactable patients, 55 already had an appointment, and 10 had reasons not to get a new appointment. Of the 95 remaining patients, 73 (76.8%) attended the new appointment. CONCLUSION: The non-attendance rate was high. One telephone call had a reasonable efficacy for the contactable patients, but because a high number of patients were not contactable, overall effectiveness was poor.

Thymic carcinoma with extrinsic occlusion of the left anterior descending artery: a distinctive case of myocardial infarction in a young woman.

BACKGROUND: Thymic epithelial tumour (TET) is the most common tumour affecting the anterior mediastinum in adults. The cardiac extension is often limited to the pericardium, and intracardiac extension is rare. We present a unique case of encasement and displacement of the left anterior descending coronary artery by the large mediastinal tumour leading to myocardial ischemia. CASE PRESENTATION: Our patient is a 28-year-old lady with stage 4 TET. She presented with acute chest pain associated with 12-lead ECG changes and a significant rise in serial troponin I. Multimodality cardiac imaging revealed encasement and displacement of the left anterior descending coronary artery by the large mediastinal tumour. CT-FFR demonstrates evidence of ischemia which would account for her acute presentation. Following detailed MDT discussions between cardiologists, oncologists and cardiothoracic surgeons, the decision was made to treat this lady with palliative chemotherapy. Given the extent of the tumour invasion and failure of the initial therapy, her prognosis and the outcome were poor. CONCLUSIONS: TET could cause atrial compression, myocardial infiltration, and invasion of the pulmonary and caval veins; however, to the best of our knowledge, this is the first case reported of coronary artery displacement and encasement by TET.

Infective Endocarditis in Patients With Intestinal Failure: Experience From a National Referral Center.

BACKGROUND: Infective endocarditis (IE) is a recognized complication of central line-associated bloodstream infection (CLABSI). Central venous access devices (CVADs) are essential for the delivery of long-term parenteral nutrition (PN), yet there are no published data as to the prevalence, characteristics and outcomes of IE in this population. METHODS: A prospectively maintained database of patients with intestinal failure (IF) types 2 and 3, managed by a national intestinal failure center between January 2010 and December 2018, was analyzed retrospectively and relevant factors extracted from case records. RESULTS: A total of 745 patients with IF and CVADs in situ on admission, or placed during their stay, were admitted over the duration of this study, 640 with type 2 IF and 105 with type 3 IF. Two hundred eighty-two echocardiograms were performed to investigate potential IE associated with a CLABSI event. Four cases of IE were identified in the entire cohort of 782,666 catheter days (IE incidence rate: 0.005 per 1000 catheter days and 187 per 100,000 person-years for the entire cohort; 0.048 per 1000 inpatient catheter days for acute type 2 IF, 0.0026 per 1000 outpatient catheter days [ie, 99 per 100,000 person-years for outpatients with type 3 IF]). CONCLUSION: IE is rare in the type 3 IF population and a rare consequence of CLABSI in inpatient acute type 2 IF. However, mortality and morbidity are high. Routine echocardiography may not be warranted for investigation of CLABSI unless there is a high risk of IE or a virulent organism is involved.

Relationship of dysglycemia to acute myocardial infarct size and cardiovascular outcome as determined by cardiovascular magnetic resonance.

BACKGROUND: Improved outcomes for normoglycemic patients suffering acute myocardial infarction (AMI) over the last decade have not been matched by similar improvements in mortality for diabetic patients despite similar levels of baseline risk and appropriate medical therapy. Two of the major determinants of poor outcome following AMI are infarct size and left ventricular (LV) dysfunction. METHODS: Ninety-three patients with first AMI were studied. 22 patients had diabetes mellitus (DM) based on prior history or admission blood glucose ≥ 11.1 mmol/l. 13 patients had dysglycemia (admission blood glucose ≥ 7.8 mmol/l but < 11.1 mmol/l) and 58 patients had normoglycemia (admission blood glucose < 7.8 mmol/l). Patients underwent cardiac magnetic resonance (CMR) imaging at index presentation and median follow-up of 11 months. Cine imaging assessed LV function and late gadolinium contrast-enhanced imaging was used to quantify infarct size. Clinical outcome data were collected at 18 months median follow-up. RESULTS: Patients with dysglycemia and DM had larger infarct sizes by CMR than normoglycemic patients; at baseline percentage LV scar (mean (SD)) was 23.0% (10.9), 25.6% (12.9) and 15.8% (10.3) respectively (p = 0.001), and at 11 months percentage LV scar was 17.6% (8.9), 19.1% (9.6) and 12.4% (7.8) (p = 0.017). Patients with dysglycemia and DM also had lower event-free survival at 18 months (p = 0.005). CONCLUSIONS: Patients with dysglycemia or diabetes mellitus sustain larger infarct sizes than normoglycemic patients, as determined by CMR. This may, in part, account for their adverse prognosis following AMI.

The role of neurohormonal blockers in the primary prevention of acute-, early-, and late-onset anthracycline-induced cardiotoxicity.

BACKGROUND: Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1-156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. SHORT CONCLUSION: Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.

A case report: multiple right ventricular diverticula with constrictive pericarditis and right heart failure.

BACKGROUND: Right ventricular diverticula (RVD) are very rare congenital anomalies and their association with constrictive pericarditis is even rarer. So far, only one case has been published in literature. CASE SUMMARY: We report a case of multiple congenital RVD with constrictive pericarditis and right heart failure which was incidentally identified on surveillance computed tomography (CT) for abdominal lymphangioma. Interval CT, echocardiography, and cardiac magnetic resonance imaging (CMR) studies were performed and reviewed. Computed tomography abdomen showed hepatic congestion with features of portal hypertension, increasing size of the RVD on review of serial CTs, and eccentric foci of pericardial calcification. Echocardiography performed for breathlessness demonstrated supranormal early diastolic tissue velocities with average of 19.8 cms-1 and a septal bounce phenomenon on m-mode imaging suggesting constrictive physiology, which triggered a CMR referral. Cardiac magnetic resonance imaging HASTE and right ventricular (RV) outflow tract imaging showed four outpouchings along RV free wall, the largest measuring 4.5 × 2 cm with a sizeable neck. These outpouchings displayed a trabecular network and/or were contractile aiding the diagnosis of diverticula as opposed to aneurysms. Right ventricular function was moderately compromised, whereas left ventricular function was preserved. DISCUSSION: Right ventricular diverticula can be associated with, and potentially be causative of, pericardial thickening and calcification eventually leading to constrictive pericarditis and heart failure.

Measurement of left ventricular dimensions with contrast-enhanced three-dimensional cine imaging facilitated by k-t SENSE.

AIM: To compare three-dimensional (3D) k-t sensitivity encoded (k-t SENSE) cine cardiovascular magnetic resonance (CMR), before and after contrast administration, against standard 2D imaging for the assessment of left ventricular volumes and mass. METHOD: Twenty-six subjects (14 volunteers, 12 patients) underwent multiple breathhold 2D balanced turbo-field echo cine CMR in addition to k-t SENSE accelerated 3D imaging (acceleration factor 5; 5x k-t SENSE), performed before and after administration of a high-relaxivity gadolinium-based contrast agent (Gadobutrolum). k-t acceleration factors of 7 and 10 were also assessed in six volunteers. Left ventricular end diastolic volume (EDV), end systolic volume (ESV), mass, and ejection fraction (EF) were calculated for each method. RESULTS: There was at least moderate agreement between the EDV, ESV, mass and EF calculated by 2D and 3D 5x k-t SENSE methods before contrast (concordance coefficients 0.92, 0.95, 0.97, 0.92, respectively). Agreement improved following contrast (concordance coefficients 0.97, 0.99, 0.98, 0.93, respectively). The 3D method underestimated all parameters compared to 2D (mean bias pre-contrast 6.1 ml, 0.6 ml, 3.5 g, 2.0% respectively). 3D image quality scores were significantly poorer than 2D, showing a non-significant trend to improvement following contrast administration. Parameters derived with k-t acceleration factors of 7 and 10 showed poorer agreement with 2D values. CONCLUSION: Left ventricular volumes and mass are reliably assessed using 3D 5x k-t SENSE accelerated CMR. Contrast administration further improves agreement between 5x k-t SENSE and 2D-derived measurements. k-t acceleration factors greater than 5, though feasible, produce poorer agreement with 2D values.

Speckle tracking determination of mitral tissue annular displacement: comparison with strain and ejection fraction, and association with outcomes in haemodialysis patients.

Abnormal Global longitudinal strain (GLS) and reduced left ventricular ejection fraction (LVEF) are established poor prognostic risk factors in haemodialysis patients. Tissue motion annular displacement of mitral valve annulus (TMAD), determined by speckle tracking echocardiography (STE), can be performed rapidly and is an indicator of systolic dysfunction, but has been less well explored. This study aims to compare TMAD with GLS and LVEF and its association with outcomes in haemodialysis patients. 198 haemodialysis patients (median age 64.2 years, 69 % men) had 2D echocardiography, with STE determined GLS and TMAD. Bland-Altman analysis and linear regression assessed relationship between GLS, LVEF and TMAD. Cox regression analysis investigated association of TMAD with mortality and cardiac events. TMAD had low inter- and intra-observer variability with small biases and narrow limits of agreement (LOA) (bias of -0.01 ± 1.32 (95 % LOA was -2.60 to 2.58) and -0.07 ± 1.27 (95 % LOA -2.55 to 2.41) respectively). There was a moderate negative correlation between GLS and LVEF (r = -0.383, p < 0.001) and a weak positive correlation between TMAD and LVEF (r = 0.248, p < 0.001). There was strong negative correlation of TMAD with GLS (r = -0.614, p < 0.001). In a multivariable Cox regression analysis, TMAD was not associated with mortality (HR 1.04, 95 % CI 0.91-1.19), cardiac death (HR 1.03, 95 % CI 0.80-1.32) or cardiac events (HR 0.91, 95 % CI 0.80-1.02). TMAD is a quick and reproducible alternative to GLS which may be very useful in cardiovascular risk assessment, but does not have the same prognostic value in HD patients as GLS.

Three-Dimensional Imaging of a Central Venous Dialysis Catheter Related Infected Thrombus.

Three-dimensional (3D) echocardiography is becoming widely available and with novel applications. We report an interesting case of a 68-year-old lady with a central venous thrombosis coincident with both a dialysis catheter infection and a recent pacemaker insertion. Two-dimensional transesophageal echocardiography was unable to delineate whether the thrombosis was involved with the pacemaker wire or due to the tunneled catheter infection. The use of 3D echocardiography was able to produce distinct images aiding diagnosis. This circumvented the need for invasive investigations and inappropriate, high-risk removal of the pacing wire. This case highlights the emerging application of 3D echocardiography in routine nephrology practice.

Cardiac imaging in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) carry a high cardiovascular risk. In this patient group, cardiac structure and function are frequently abnormal and 74% of patients with CKD stage 5 have left ventricular hypertrophy (LVH) at the initiation of renal replacement therapy. Cardiac changes, such as LVH and impaired left ventricular systolic function, have been associated with an unfavourable prognosis. Despite the prevalence of underlying cardiac abnormalities, symptoms may not manifest in many patients. Fortunately, a range of available and emerging cardiac imaging tools may assist with diagnosing and stratifying the risk and severity of heart disease in patients with CKD. Moreover, many of these techniques provide a better understanding of the pathophysiology of cardiac abnormalities in patients with renal disease. Knowledge of the currently available cardiac imaging modalities might help nephrologists to choose the most appropriate investigative tool based on individual patient circumstances. This Review describes established and emerging cardiac imaging modalities in this context, and compares their use in CKD patients with their use in the general population.

The association of ECG and echocardiographic abnormalities with sudden cardiac death in a dialysis patient cohort.

BACKGROUND: Cardiovascular mortality is greater in dialysis patients than the general population. More specifically, sudden cardiac death (SCD) accounts for 26% of dialysis patient deaths. However, SCD risk assessment tools used in the general population are not adequate for dialysis patients indicating that the hierarchy of pathopysiological factors appears to be different. The aim of this study was to use simple bedside tests to determine parameters independently predictive of cardiovascular mortality and SCD in dialysis patients. METHOD AND RESULTS: This was a sub-study of the Chronic Renal Insufficient Standards Implementations Study, a longitudinal cohort study of outcomes in CKD. ECG and echocardiographic abnormalities were assessed in a cross-section of prevalent dialysis patients. Patients were followed up until death or transplantation. Forward stepwise Cox regression then determined factors independently associated with all-cause, cardiovascular and SCD mortality. 323 patients were included (age 61.5 ± 14.6 years, 113 deaths, 66 cardiovascular deaths, 18 SCD). A number of factors were independently associated with all-cause mortality. These were age, time on dialysis, smoking, the difference between QRS and T-wave axes, resting heart rate, and pulmonary artery pressure (PAP) >35 mmHg. The only parameters predictive of SCD were elevated PAP (HR = 5.99, p = 0.05) and mitral regurgitation (HR = 6.71, p = 0.01). CONCLUSION: That PAP is associated with SCD in dialysis patients demonstrates that the pathophysiological mechanism is likely to be different in these patients compared to the general population. Because of this, a population specific approach to risk stratification is advisable.

Incidental extra-cardiac findings on clinical CMR.

AIMS: Cardiac magnetic resonance (CMR) imaging benefits from a large field of view, but consequently captures incidental extra-cardiac findings (IEFs). There is a relative paucity of data for CMR in this regard. Our objectives were to assess the frequency and significance of IEFs reported from clinically indicated CMR scans, and additionally to ascertain if reporting rates differed between radiologist and cardiologist in a 'real-world' setting. METHODS AND RESULTS: A total of 714 patients were included for the study. All patients were referred to a single tertiary cardiac unit for clinically indicated scans. The clinical reports were retrospectively reviewed for reported IEF, and classified as 'minor', or 'major' depending on the need of further investigation or clinical correlation. A total of 180 IEFs were reported in 154 (21.6%) patients. Ninety IEFs were considered minor, and 90 major. Of the latter, eight (1.1%) were considered highly significant. Two hundred scans were reported by a consultant radiologist, and 514 by cardiologists. There was no significant difference in the rates of IEF reporting between the two specialties (P = 0.38). CONCLUSION: IEFs are common, requiring further investigation in a substantial minority. The incidence of highly significant findings in this study was low (∼1%), and similar to the reported incidence in the computed tomography literature. No significant difference was found between the reporting rates of IEFs between different specialties.

Effects of angiotensin receptor blockade on atrial electrical remodelling and the 'second factor' in a goat burst-paced model of atrial fibrillation.

Atrial fibrillation (AF) is self-perpetuating, via mechanisms of acute electrical remodelling and 'second factors' acting over a longer time course. Renin-angiotensin system (RAS) blockade may inhibit AF self-perpetuation. We evaluated the effects of RAS blockade with candesartan in a burst-paced goat model of lone AF in which both mechanisms are known to operate. Bioactivity of oral candesartan was demonstrated in 10 goats by inhibition of the pressor effect of angiotensin II. The effects of candesartan on electrical remodelling were assessed in 12 placebo and 12 candesartan-treated goats in a 28-day burst pacing protocol. To assess the effects of candesartan on second factors (structural remodelling), 16 goats underwent further 28-day periods of burst pacing (two periods in 16 goats, three periods in eight goats) each separated by periods of sinus rhythm sufficient for electrical remodelling to reverse. There was a progressive rise in angiotensin levels in both groups. Candesartan (0.5 mg/kg/day) achieved a 76% blunting of the pressor effect of angiotensin II and had no effect on electrical remodelling; the half time for fall of atrial effective refractory period (AERP) was 22.3 ± 4.9 h (placebo) and 22.0 ± 3.2 h (candesartan) (p = ns). Candesartan had no effect on AF stability, which progressively increased over successive 28-day periods (ANOVA p < 0.05). Candesartan had no effect on atrial electrical remodelling or the operation of 'second factors' in a goat model of lone AF. These findings suggest that any benefits of RAS blockade in patients with AF are unlikely to be due to direct effects on atrial remodelling.

Sildenafil as treatment for Human Immunodeficiency Virus-related pulmonary hypertension in a child.

Human Immunodeficiency Virus (HIV)-related pulmonary hypertension is a relatively rare disease that can affect HIV sufferers. This is almost always associated with a poor outcome and death. An 18 month-old girl, probably the youngest on record, was diagnosed to have pulmonary hypertension (PHT) and retrospectively found to have HIV infection. Sildenafil was used to control her PHT and she remains alive even after 2 years.