Plasma ACE2 Activity Predicts Mortality in Aortic Stenosis and Is Associated With Severe Myocardial Fibrosis.

OBJECTIVES: This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality. BACKGROUND: ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease. METHODS: Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement. RESULTS: The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m2 vs. 48 ml/m2; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027). CONCLUSIONS: In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.

Right ventricular global longitudinal strain is an independent predictor of right ventricular function: a multimodality study of cardiac magnetic resonance imaging, real time three-dimensional echocardiography and speckle tracking echocardiography.

OBJECTIVES: Accurate assessment of right ventricular (RV) systolic function is important, as it is an established predictor of mortality in cardiac and respiratory diseases. We aimed to compare speckle tracking-derived longitudinal deformation measurements with traditional two-dimensional (2D) echocardiographic parameters, as well as real time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR)-derived RV volumes and ejection fraction (EF). METHOD: Subjects referred for CMR also underwent echocardiography. On both RT3DE and CMR, we measured RV volumes and EF. On 2D echocardiography, we analyzed RV fractional area change, RV internal diastolic diameter, tricuspid annular plane systolic excursion, tricuspid annular tissue Doppler-derived velocity, myocardial performance index, and RV global longitudinal strain (RV GLS). RESULTS: Sixty subjects were recruited (mean age = 45 ± 10 years; 60% male). RV GLS (R = -0.69, P < 0.001) and RT3DE RVEF (R = 0.56, P < 0.001) correlated well with CMR RVEF. RT3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes also correlated with CMR RV volumes: RVEDV, R = 0.74, P < 0.001 and RVESV, R = 0.84, P < 0.001. In addition, RV GLS best predicted the presence of RV dysfunction, defined as RVEF <48% on CMR (hazard ratio = 7.0 [1.5-31.7], P < 0.01). On receiver operator characteristic analysis, a RV GLS of -20% was the most sensitive and specific predictor of RV dysfunction (AUC 0.8 [0.57-1.0], P < 0.02). CONCLUSION: RVEF and volumes estimated on RT3DE were closely correlated with CMR measurements. When compared to more traditional markers of RV systolic function and RT3DE, RVGLS produced the highest correlation with CMR RVEF and was a good predictor of RV dysfunction. RV GLS should be considered a complementary modality to RT3DE and CMR in the assessment of RV systolic function.

Cardiorenal anemia syndrome as a prognosticator for death in heart failure.

Anemia and chronic kidney disease are common in patients with heart failure (HF) and are associated with adverse outcomes. We analyzed the effect of cardiorenal anemia (CRA) syndrome, defined as anemia (hemoglobin <130 g/L for men, <120 g/L for women) and stage 3 or greater chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m(2)), in outpatients with HF. Consecutive patients with HF were prospectively enrolled from 2000 to 2005 (n = 748). The baseline clinical characteristics, pathology test results, and medication use were compared between those with and without CRA syndrome. The primary end point was all-cause mortality. The mean follow-up was 2.5 ± 1.6 years, with a left ventricular ejection fraction <45% present in 70% of patients. Angiotensin-converting enzyme inhibitors, ß blockers, and spironolactone were used in 87%, 67%, and 37%, respectively. CRA syndrome was present in 224 patients (30%). These patients had greater all-cause mortality (51% vs 26%, p <0.001), older age (mean 77 ± 8 vs 67 ± 14 years, p <0.001), and greater rates of diabetes mellitus (35% vs 23%, p <0.001) and ischemic heart disease (50% vs 35%, p <0.001). The independent predictors of mortality were CRA syndrome (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p <0.001), left ventricular systolic dysfunction per grade (hazard ratio 1.5, 95% confidence interval 1.3 to 1.8, p <0.001), the absence of a ß blocker (hazard ratio 1.6, 95% confidence interval 1.1 to 2.2, p = 0.005), New York Heart Association class per class (hazard ratio 1.5, 95% confidence interval 1.2 to 1.9, p <0.01), and age per decade (hazard ratio 1.6, 95% confidence interval 1.4 to 2.0, p <0.001). In conclusion, CRA syndrome was common in patients with HF and was an independent predictor of all-cause mortality. Consideration should be given to identifying CRA syndrome and modifying reversible factors.

Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control.

BACKGROUND: The prognostic benefits of beta-blockers (BB) in patients with systolic heart failure (SHF) are known but despite this, in patients with diabetes they are underutilized. The aim of this study was to assess the effect of beta-blockers (BB) on glycaemic control in patients with Type 2 Diabetes (T2DM) and systolic heart failure (SHF) stratified to beta-1 selective (Bisoprolol) vs. nonselective BB (Carvedilol). METHODS: This observational, cohort study was conducted in patients with T2DM and SHF attending an Australian tertiary teaching hospital's heart failure services. The primary endpoint was glycaemic control measured by glycosylated haemoglobin (HbA1c) at initiation and top dose of BB. Secondary endpoints included microalbuminuria, changes in lipid profile and estimated glomerular filtration rate (eGFR). RESULTS: 125 patients were assessed. Both groups were well matched for gender, NYHA class and use of guideline validated heart failure and diabetic medications. The mean treatment duration was 1.9 ± 1.1 years with carvedilol and 1.4 ± 1.0 years with bisoprolol (p = ns). The carvedilol group achieved a reduction in HbA1c (7.8 ± 0.21% to 7.3 ± 0.17%, p = 0.02) whereas the bisoprolol group showed no change in HbA1c (7.0 ± 0.20% to 6.9 ± 0.23%, p = 0.92). There was no significant difference in the change in HbA1c from baseline to peak BB dose in the carvedilol group compared to the bisoprolol group. There was a similar deterioration in eGFR, but no significant changes in lipid profile or microalbuminuria in both groups (p = ns). CONCLUSION: BB use did not worsen glycaemic control, lipid profile or albuminuria status in subjects with SHF and T2DM. Carvedilol significantly improved glycemic control in subjects with SHF and T2DM and this improvement was non significantly better than that obtained with bisoprolol. BB's should not be withheld from patients with T2DM and SHF.

Pericardial tamponade: a life threatening complication of laparoscopic gastro-oesophageal surgery.

Laparoscopic surgical procedures involving the gastro-oesophageal region are commonly performed for the management of morbid obesity and refractory gastro-oesophageal reflux disease (GORD). In general, laparoscopic procedures are associated with lower morbidity and mortality in comparison with open techniques. This report highlights cases of potentially life threatening, late onset pericardial tamponade, occurring in the absence of infection or trauma, complicating laparoscopic gastro-oesophageal surgery. Possible mechanisms, clinical manifestations, diagnostic investigations and management of pericardial tamponade are reviewed.

Validation of rapid automated tissue synchronization imaging for the assessment of cardiac dyssynchrony in sinus and non-sinus rhythm.

AIMS: Cardiac resynchronization therapy is showing benefits for an increasing number of indications but fails to predict response in up to 20-30% of subjects. Echocardiographically assessed dyssynchrony has been proposed as a potential stratifier but current methods are time-consuming and suffer poor reproducibility, thus limiting their clinical utility. This study compared the accuracy, time efficiency, and reproducibility of automated tissue synchronization imaging (Auto TSI) vs. established manual tissue velocity imaging (TVI) techniques for the assessment of intra-ventricular dyssynchrony in sinus and non-sinus rhythm. METHODS AND RESULTS: Fifty consecutive stable systolic heart failure patients on optimal guideline-based medical therapy underwent intra-ventricular dyssynchrony assessment [time to peak velocity (Ts), septal to lateral delay (SLD), and dyssynchrony index (DI)] with TVI and Auto TSI techniques, enabling the assessment of agreement, time efficiency, and reproducibility. Statistical analyses included Pearson's correlation, Bland-Altman's statistics, and coefficient of reproducibility. There was excellent agreement between Auto TSI and TVI for the measurement of Ts [r=0.92, P<0.001, limits of agreement (LOA): -27.3 to 56.5 ms], SLD (r=0.94, P<0.001, LOA: -41 to 49 ms), and DI (r=0.89, P<0.001, LOA: -12.2 to 12.6 ms) which persisted irrespective of cardiac rhythm [Ts: sinus (n=32) r=0.93, P<0.001; non-sinus (n=18) r=0.91, P<0.001]. Automated TSI was more time efficient (3±1 vs. 14±2 min, P<0.001) and demonstrated superior reproducibility: intra-observer (5.5 vs. 9.6%) and inter-observer variability (9.5 vs. 13.4%). CONCLUSION: Automated TSI enables rapid, reproducible intra-ventricular dyssynchrony assessment and overcomes some of the limitations of conventional techniques in sinus and non-sinus rhythm.

Thrombus entrapped in a patent foramen ovale: a potential source of pulmonary and systemic embolism.

Patent foramen ovale (PFO) occurs in up to 30% of the population, making it the most common site for intra-cardiac shunting. The passage of thrombus across a PFO is typically transient, thus is rarely proven. We describe a rare case of a 79-year-old man with thrombus entrapped across a PFO providing a source for ongoing pulmonary and systemic thromboembolism, despite systemic anticoagulation. There is a paucity of literature to guide primary management of this condition. Management options include surgical thrombectomy with PFO closure, thrombolysis and systemic anticoagulation. The role of percutaneous PFO closure devices for secondary prevention of thromboembolic complications is currently under investigation.