Crispin H. Davies

Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans: implications for SERCA2a as a therapeutic target in heart failure

Objective: To verify whether a deficiency in the cardiac sarcoplasmic reticulum pump SERCA2a causes cardiac dysfunction in humans. Design: Cardiac performance was measured in a serendipitous human model of primary SERCA2a deficiency, Darier’s disease, an autosomal dominant skin disorder caused by mutations inactivating one copy of the ATP2A2 gene, which encodes SERCA2a. Methods: Systolic and diastolic function and contractility were assessed by echocardiography at rest and during exercise in patients with Darier’s disease with known mutations. Fourteen patients with Darier’s disease were compared with 14 normal controls and six patients with dilated cardiomyopathy with stable heart failure. Results: Resting systolic and diastolic function was normal in patients with Darier’s disease and in controls. The increase in systolic function during exercise was not different between patients with Darier’s disease and normal controls; neither was there a difference in contractility. As expected, patients with dilated cardiomyopathy had impaired diastolic and systolic function with depressed contractility at rest and during exercise. Conclusion: Contrary to expectations, heterozygous disruption of SERCA2a is not associated with the impairment of cardiac performance in humans. Attempts to increase SERCA2a levels in heart failure, although showing promise in rodent studies, may not be addressing a critical causal pathway in humans.

Quantification of flow volume with a new digital three-dimensional color Doppler flow approach: an in vitro study.

The quantification of flow stroke volume is important for evaluation of patients with cardiac dysfunction and cardiovascular disease. Three‐dimensional digital color Doppler flow imaging allows the acquisition of flow data in an orientation approximately parallel to flow and analysis of the Doppler flow velocities perpendicular to flow (cross‐sectional flow calculation). This in vitro study assessed the applicability of this method for quantifying cardiac output in a funnel‐shaped tube model similar to mitral inflow or the left ventricular outflow tract.

Will a handheld ultrasound scanner be applicable for screening for heart abnormalities in newborns and children

BACKGROUND There is significant interest in opportunities to provide echocardiography services for detection of congenital heart disease with portable, or even handheld, devices in remote areas or third world countries where conventional ultrasound systems may not be available. We tested a handheld system (HHS) (SonoHeart, SonoSite Inc, Bothell, Wash) equipped with a broadband, 7- to 4-MHz, miniaturized, curved, linear-array transducer and implemented with an improved directional Doppler flow map. METHODS All echocardiography scanning was performed in the neonatal nursery, pediatric intensive care department, or pediatric echocardiography laboratory of our institution. We reviewed limited echocardiography view sequences sequentially obtained by the same expert examiner (D.J.S.) in 50 infants and children (age: 1 day to 6 years), with preoperative or postoperative forms of congenital heart disease. Each patient was studied twice, once with a conventional full-feature system (FFS) and then a limited scan with the HHS using similar frequency transducers. The cardiologist (D.J.S.) and blinded research laboratory reviewers (X.L., G.K.M., R.A.R.) read the FFS and HHS image sequences for diagnosis and for grading the quality of the anatomic and flow feature images. The studies were performed and reviewed with the examiner and reviewers blinded to patient diagnosis. RESULTS The major diagnoses (eg, patent ductus arteriosus, atrio-ventricular (AV) canal, peripheral pulmonary valve stenosis, aortic coarctation, atrial septal defect, ventricular septal defect, preoperative or postoperative tetralogy of Fallot, and mitral regurgitation) were made by both readers, who were unaware of each others diagnosis results. Furthermore, the average composite HHS cardiac anatomic feature score on a scale of 0 (not visualized) to 3 (visualized precisely) from the parasternal long-axis and 4- or 5-chamber view for cardiac anatomy were 2.67 +/- 0.49 (SD) and 2.50 +/- 0.55, respectively, versus 2.73 +/- 0.45 and 2.55 +/- 0.54 for the FFS. The mean flow feature score, comprising all views, was 2.67 +/- 0.45 (HHS) versus 2.72 +/- 0.48 (FFS). The P values for all above comparisons were >.05. Image quality of the FFS anatomic structures were, thus, not statistically different from the HHS. Although the color cosmetic was different for the HHS directional (nonvelocity) map, only 9% of 150 total findings (including structural abnormalities and flow features, none of which were critical) were missed, whereas the other 91% regurgitant, shunt, stenosis flow features or heart structure were imaged adequately by the HHS in this population. CONCLUSIONS Implementing high-frequency transducers and programs optimized for tissue and flow imaging on the HHS should provide images of sufficient quality for targeted echocardiography examinations to determine the presence, absence, or status of congenital heart disease in newborns and young children.

Strain rate imaging: an in vitro "validation" study using a physiologic balloon model mimicking the left ventricle.

Background: Strain rate imaging (SRI) can be implemented from digital ultrasound loops of tissue Doppler imaging (TDI) data and is performed as an autocorrelation solution of the distance between intramyocardial targets. As such, it should have better resolution along longer distances of wall segments that are imaged at the length of individual ultrasound scan lines. Methods: We used a new left ventricular double‐balloon phantom with a tissue‐mimicking gel between the walls. Mounted in a water bath and connected to a pulsatile flow pump at four‐stroke volume (30–50 ml/beat), the high frame rate, digital, multiple two‐dimensional/tissue/TDI loops of balloon wall motion were recorded using a GE VingMed system FiVe (3.5 MHz phased array transducer), with the model scanned longitudinally from the apex. The strain rate (SR) values were measured at the apex and the lateral wall using an offline measurement program, and mean SR values for every 100 msec were calculated by averaging three determinations at each point. The excursions of the apex and lateral wall also were measured directly by high speed digital video imaging, and consecutive velocity profiles were calculated every 100 msec. A total of 40 data points for four‐stroke volumes were analyzed. Results: While our balloon model had enough gel targets between the walls to produce a good mimic of myocardial speckle with walls that thickened and thinned, samples immediately across the apex and apex SR values (Hz) varied substantially. In contrast, systematic signals could be obtained from lines imaged >15° from the true apex and crossing a longer length of myocardium. At the lateral wall, there was a close correlation between the video velocities and SR values, as well as a close overlap of the phasic patterns. Conclusions: SRI produces more reliable data from wall segments parallel to scan lines.

Detection and significance of subclinical mitral regurgitation by colour Doppler techniques

Two papers in this issue demonstrate clinical consequences from the presence of clinically silent mitral regurgitation in paediatric and adolescent populations. Both are potentially important as the development of progressive doxorubicin cardiomyopathy1 and the presence of rheumatic carditis2 have long term implications. A parallel example, which highlights some of the problems inherent in attempting to derive clinical conclusions from the presence of mild regurgitation in an adult population, exists in the recent “phen/fen” controversy.3 Attempting to extract useful prognostic information from the presence of clinically silent, Doppler detected, mitral regurgitation through morphologically normal valves is not new—its negative impact on the prognosis of acute infarction has been recognised for over a decade.4 However, a fundamental prerequisite in attempting to utilise this type of information is an appreciation of the factors which underlie the presence of the colour flow signal. The appearance of mitral regurgitation is dependent upon the mechanical substrate for regurgitation itself, the fluid dynamics of the resultant flow disturbance, and lastly, processing using a colour flow mapping algorithm to produce an image. In particular, we need to question the reproducibility of findings obtained by different examiners and between different echo system implementations of colour flow mapping before we can feel comfortable about extrapolating these findings into clinical practice. In some very mild cases of rheumatic carditis and subtle forms of the “phen/fen” effect, leaflet damage not apparent on two dimensional echo is the intuitive mechanism of subclinical regurgitation. However, in the majority of cases, the valve is merely responding …

Reconstructive three-dimensional tissue Doppler imaging for quantifying left ventricular myocardial infarction area after coronary artery occlusion: an in vivo chronic animal study

目的通过活体动物实验探讨三维重建组织多普勒超声成像测量心肌梗死面积的方法和可行性.方法用三维重建组织多普勒显像的方法,对8只开胸的心尖部心肌梗死和室壁瘤的活体羊模型在4种不同的血流状态下进行心肌梗死面积的测量.结果重建三维超声组织多普勒成像测量的活体羊心内膜梗死的面积与尸检标本测量的面积密切相关(r=0.90, Y=0.83X+1.33,s=0.92 cm2,P<0.000 1).结论重建三维组织多普勒成像提供了一系列动态空间组织多普勒数据确定室壁异常运动区,并能定量测量心肌梗死面积,在缺血性心脏疾病中,有助于非侵入性心脏功能的估测.