Non-invasive assessment of the cardiac effects of Chironex fleckeri and Carukia barnesi venoms in mice, using pulse wave doppler.

Both Chironex fleckeri venom (CFV) and Carukia barnesi venoms (CBV) are known to cause significant cardiac morbidity and mortality. Many animal studies have demonstrated cardiac dysfunction with these venoms. This study specifically examines the systolic and diastolic cardiac functions using non-invasive pulse wave doppler. Mitral and aortic doppler sonograms of anaesthetised mice were obtained utilising a 10 MHz doppler probe. These continuous sonograms were analysed to ascertain changes in cardiac function before and after the parenteral administration of the test venoms. We found that CFV administration causes rapid cardiac dysfunction without a change in heart rate. Analysis of the resulting sonograms shows both systolic and diastolic dysfunction which together is suggestive of a progressively poorly compliant, contracted left ventricle. Additionally, the rapidity of cardiac dysfunction suggests a direct effect of CFV on myocardial cells. In contrast CBV showed a moderate immediate inotropic and chronotropic effect that was sustained until precipitous cardiac decompensation. This is consistent with the hypotheses of a toxin induced stress cardiomyopathy from sustained catecholaminergic activity.

Osteoprotegerin and Myocardial Fibrosis in Patients with Aortic Stenosis.

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).

Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular magnetic resonance.

BACKGROUND: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. METHODS: A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). RESULTS: Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). CONCLUSION: There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.

Effects of myocardial ischaemia on left ventricular untwist and filling pressure.

OBJECTIVE: To link ischaemia, left ventricular (LV) untwisting and changes in filling pressure during dobutamine stress echocardiography (DSE). DESIGN: Cross-sectional study at rest and at peak dobutamine stress. SETTING: Academic medical centre. PATIENTS: Patients who had undergone routine DSE between January and September 2009. METHODS: Routine DSE was combined with measurement of transmitral pulsed-wave Doppler, myocardial tissue Doppler and speckle-tracking echocardiography at baseline and peak dose in 110 patients (51 women, 62±12 years). Untwisting rates (proto-diastolic and during isovolumic relaxation time (IVRT)) were measured by speckle tracking. Raised filling pressure was defined as E/e'>15. DSE studies were classified into normal, ischaemic or scar responses, independent of E/e'. MAIN OUTCOMES: Echocardiographic outcomes. RESULTS: Patients were categorised in three groups: group 1 (n=44), normal resting and peak E/e'; group 2 (n=33), normal resting E/e' but raised peak E/e'; group 3 (n=33), abnormal resting E/e'. Risk factors and resting ejection fraction were similar in each group. Proto-diastolic untwisting rate was an independent predictor of raised filling pressure at peak stress (r(2)=0.3, p=0.03). An abnormal filling response during DSE was independently predicted by resting untwisting rate (UTR)-IVRT (p=0.003), and resting E/a (p=0.0001) (model pseudo-r(2)=0.76). Proto-diastolic UTR was lower in the ischaemic and scar groups at peak. CONCLUSION: Patients with abnormal filling pressure response have an impaired LV untwisting rate during isovolumic relaxation. This phenomenon supports the role of impaired LV suction as the mediator of the effect of myocardial ischaemia during DSE on filling pressure response to stress.