Person:

Mahmood, Feroze-Ud-Den

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-(1\alpha), a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-(1\alpha). Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

Background-Patients with preeclampsia are at risk for cardiovascular disease. Changes in cardiac function are subtle in preeclampsia and are difficult to quantify with conventional imaging. Strain measurements using speckle-tracking echocardiography have been used to sensitively quantify abnormalities in other disease settings.Methods and Results-We evaluated the feasibility and sensitivity of strain imaging using speckle-tracking echocardiography in women with preeclampsia. Forty-seven women were enrolled in this pilot study and 39 were analyzed: 11 with preeclampsia, 17 without a hypertensive disorder, and 11 with nonproteinuric hypertension. Echocardiographic ejection fraction and global peak longitudinal, radial, and circumferential strain were measured. Longitudinal strain was significantly worsened in women with preeclampsia compared with women without a hypertensive disorder (P=0.0001). Similar results were observed for radial strain (P=0.006) and circumferential strain (P=0.03). Women with preeclampsia also had significantly worsened longitudinal (P=0.04), radial (P=0.01), and circumferential (P=0.002) strain compared with women with nonproteinuric hypertension. Women with preeclampsia did not have a significantly different ejection fraction compared with women without a hypertensive disorder (P=0.16) and women with nonproteinuric hypertension (P=0.44).Conclusions-Myocardial strain imaging using speckle tracking is more sensitive than left ventricular ejection fraction to detect differences in left ventricular systolic function in women with and without preeclampsia.

Background: Mitral valve (MV) annular dynamics have been well described in animal models of functional mitral regurgitation (FMR). Despite this little, if any, data exists regarding the dynamic MV annular geometry in humans with FMR. In the current study we hypothesized that three-dimensional (3D) echocardiography, in conjunction with commercially available software, could be used to quantify the dynamic changes in MV annular geometry associated with FMR. Methods: Intraoperative 3D transesophageal echocardiographic data obtained from 34 patients with FMR and 15 controls undergoing cardiac surgery were dynamically analyzed for differences in mitral annular geometry with TomTec© 4D MV Assessment 2.0 software. Results: In patients with FMR, the mean mitral annular area (14.6cm2 vs. 9.6cm2), circumference (14.1cm vs. 11.4 cm), anteroposterior (4.0cm vs. 3.0cm) and anterolateral-posteromedial (4.3cm vs. 3.6cm) diameters, tenting volume (6.2mm3 vs. 3.5mm3) and nonplanarity angle (154° ± 15 vs. 136° ± 11) were greater at all points during systole compared to controls (p<0.01). Vertical mitral annular displacement (5.8mm vs. 8.3mm) was reduced in FMR compared to controls (p<0.01). Conclusions: There are significant differences in dynamic mitral annular geometry between patients with and without FMR. We were able to analyze these changes in a clinically feasible fashion. Ready availability of this information has the potential to aid comprehensive quantification of mitral annular function and possibly assist in both clinical decision-making and annuloplasty ring selection.

Background: Proficiency in transthoracic echocardiography (TTE) requires an integration of cognitive knowledge and psychomotor skills. Whereas cognitive knowledge can be quantified, psychomotor skills are implied after repetitive task performance. We applied motion analyses to evaluate psychomotor skill acquisition during simulator-based TTE training.

Methods and Results: During the first month of their fellowship training, 16 cardiology fellows underwent a multimodal TTE training program for 4 weeks (8 sessions). The program consisted of online and live didactics as well as simulator training. Kinematic metrics (path length, time, probe accelerations) were obtained at the start and end of the course for 8 standard TTE views using a simulator. At the end of the course TTE image acquisition skills were tested on human models. After completion of the training program the trainees reported improved self-perceived comfort with TTE imaging. There was also an increase of 8.7% in post-test knowledge scores. There was a reduction in the number of probe accelerations [median decrease 49.5, 95% CI = 29-73, adjusted P < 0.01], total time [median decrease 10.6 s, 95% CI = 6.6-15.5, adjusted P < 0.01] and path length [median decrease 8.8 cm, 95% CI = 2.2-17.7, adjusted P < 0.01] from the start to the end of the course. During evaluation on human models, the trainees were able to obtain all the required TTE views without instructor assistance.

Conclusion: Simulator-derived motion analyses can be used to objectively quantify acquisition of psychomotor skills during TTE training. Such an approach could be used to assess readiness for clinical practice of TTE.