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Background Activation of fibroblast growth factor receptor (FGFR)-dependent signalling by FGF23 may contribute to the complex pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD, but its ability to treat and reverse established LVH is unknown. Methods CKD was induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function was determined by urine and blood analyses. Left ventricular (LV) structure and function were determined by echocardiography, histopathology, staining for myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression profiles by real-time PCR. Results Two weeks after inducing CKD by 5/6 nephrectomy, rats manifested higher (mean ± SEM) systolic blood pressure (208 ± 4 versus 139 ± 3 mmHg; P < 0.01), serum FGF23 levels (1023 ± 225 versus 199 ± 9 pg/mL; P < 0.01) and LV mass (292 ± 9 versus 220 ± 3 mg; P < 0.01) when compared with sham-operated animals. Thereafter, 3 weeks of treatment with PD173074 compared with vehicle did not significantly change blood pressure, kidney function or metabolic parameters, but significantly reduced LV mass (230 ± 14 versus 341 ± 33 mg; P < 0.01), myocardial fibrosis (2.5 ± 0.7 versus 5.4 ± 0.95% staining/field; P < 0.01) and cardiac expression of genes associated with pathological LVH, while significantly increasing ejection fraction (18 versus 2.5% post-treatment increase; P < 0.05). Conclusions FGFR blockade improved cardiac structure and function in 5/6 nephrectomy rats with previously established LVH. These data support FGFR activation as a potentially modifiable, blood pressure-independent molecular mechanism of LVH in CKD. [ABSTRACT FROM PUBLISHER]

Background: To overcome flow and electrocardiogram-trigger artifacts in cardiovascular magnetic resonance (CMR), we have implemented a cardiac and respiratory self-gated cine ultra-short echo time (UTE) sequence. We have assessed its performance in healthy mice by comparing the results with those obtained with a self-gated cine fast low angle shot (FLASH) sequence and with echocardiography. Methods: 2D self-gated cine UTE (TE/TR = 314 μs/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 5 min 5 sec) and self-gated cine FLASH (TE/TR = 3 ms/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 4 min 49 sec) images were acquired at 9.4 T. Volume of the left and right ventricular (LV, RV) myocardium as well as the end-diastolic and - systolic volume was segmented manually in MR images and myocardial mass, stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were determined. Statistical differences were analyzed by using Student t test and Bland-Altman analyses. Results: Self-gated cine UTE provided high quality images with high contrast-to-noise ratio (CNR) also for the RV myocardium (CNRblood-myocardium = 25.5 ± 7.8). Compared to cine FLASH, susceptibility, motion, and flow artifacts were considerably reduced due to the short TE of 314 μs. The aortic valve was clearly discernible over the entire cardiac cycle. Myocardial mass, SV, EF and CO determined by self-gated UTE were identical to the values measured with selfgated FLASH and showed good agreement to the results obtained by echocardiography. Conclusions: Self-gated UTE allows for robust measurement of cardiac parameters of diagnostic interest. Image quality is superior to self-gated FLASH, rendering the method a powerful alternative for the assessment of cardiac function at high magnetic fields. [ABSTRACT FROM AUTHOR]

Doppler-echocardiographic assessment of cardiovascular structure and function in murine models has developed into one of the most commonly used non-invasive techniques during the last decades. Recent technical improvements even expanded the possibilities. In this review, we summarize the current options to assess global left ventricular (LV) function in mice using echocardiographic techniques. In detail, standard techniques as structural and functional assessment of the cardiovascular phenotype using one-dimensional M-mode echocardiography, two-dimensional B-mode echocardiography and spectral Doppler signals from mitral inflow respective aortal outflow are presented. Further pros and contras of recently implemented techniques as three-dimensional echocardiography and strain and strain rate measurements are discussed. Deduced measures of LV function as the myocardial performance index according to Tei, estimation of the mean velocity of circumferential fibre shortening, LV wall stress and different algorithms to estimate the LV mass are described in detail. Last but not least, specific features and limitations of murine echocardiography are presented. Future perspectives in respect to new examination techniques like targeted molecular imaging with advanced ultrasound contrast bubbles or improvement of equipment like new generation matrix transducers for murine echocardiography are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2. Patients with ADPKD have an increased incidence of cardiac valve abnormalities and left ventricular hypertrophy. Systematic analyses of cardiovascular involvement have so far been performed only on genetically unclassified patients or on ADPKD1 patients, but not on genetically defined ADPKD2 patients. Even existing Pkd1 or Pkd2 mouse models were not thoroughly analyzed in this respect. Therefore, the aim of this project was the noninvasive functional cardiovascular characterization of a mouse model for ADPKD2. Methods: Pkd2+/LacZ mice and wildtype controls were classified into 8 groups with respect to gender, age and genotype. In addition, two subgroups of female mice were analyzed for cardiac function before and during advanced pregnancy. Doppler-echocardiographic as well as histological studies were performed. Results: Doppler-echocardiography did not reveal significant cardiovascular changes. Heart rate and left ventricular (LV) length, LV mass, LV enddiastolic and LV endsystolic diameters did not differ significantly among the various groups when comparing wildtype and knockout mice. There were no significant differences except for a tendency towards higher maximal early and late flow velocities over the mitral valve in old wildtype mice. Conclusions: Non-invasive phenotyping using ultrasound did not reveal significant cardiovascular difference between adult Pkd2+/LacZ and WT mice. Due to the lack of an obvious renal phenotype in heterozygous mice, it is likely that in conventional ADPKD knock out mouse models severe cardiac problems appear too late to be identified during the reduced lifespan of the animals. [Copyright &y& Elsevier]

Abstract: Objective: In the past years, Doppler echocardiography has evolved into a commonly used technique. More recent sophisticated advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to small animal models, particularly in rabbits but even in mice. Recently, parameters obtained by Tissue Doppler Imaging (TDI) have been shown to be more independent of pre- and afterload than classic hemodynamic Doppler measurements. Exploration of animal models may require anaesthesia but there is only very little information on the effect of anaesthesia on echocardiographic parameters in rabbits. Methods: We therefore performed Doppler-echocardiographic examinations of 20 wild-type New Zealand White rabbits in awake state and under light ketamine–xylazine anaesthesia. Special focus was put on the evaluation of global and regional left ventricular systolic and diastolic function using TDI and the myocardial performance index (Tei-index). Results: Doppler-echocardiographic measurements including TDI in rabbits were feasible to assess cardiac morphology and function within a short examination time. There were some distinct changes of functional parameters during anaesthesia. Exemplary for systolic function, fractional shortening, cardiac output and systolic TDI velocity of the lateral wall decreased distinctly. Global left ventricular function measured by the Tei-index deteriorated. Conclusions: Doppler echocardiography and TDI can be performed easily, quickly and safely in the rabbit. Anaesthesia with the cardiodepressive ketamine–xylazine shows some distinct Doppler-echocardiographically measurable negative effects on cardiac function. Thus, echocardiography with less cardiodepressive anaesthetic regimes or even without anaesthesia after training of the animals should be considered as alternatives whenever possible. [Copyright &y& Elsevier]

Assessment of replenishment kinetics (RK) following ultrasound-induced destruction of contrast microbubbles allows quantification of myocardial blood flow reserve (MBFR) applying the model , with parameter β describing mean flow velocity and parameter A representing blood volume. However, few data on the variability and reproducibility of RK in a clinical setting are available. Therefore, we examined 30 patients in a rest—adenosine protocol in one center. Off-line quantification of real-time perfusion imaging (RTPI) and triggered replenishment imaging (TRI) was performed at two sites and compared with coronary angiography and flow reserve measurements. Parameter A was found to be robust in all investigated segments (coefficient of variation (CV) < 7.2%± 5.1). Variability was lowest for parameter β using TRI in apical segments (CV 6.5%± 5.2, P < 0.01). Highest CV was found with RTPI in lateral segments (CV β: 39.8%± 40.6). Concerning day-to-day reproducibility both methods revealed similar results within range of heterogeneity of myocardial blood flow. Both sites obtained significantly lower MBFR in patients with flow-limiting CAD, compared to subjects without (P < 0.01). Correlation of both sites showed close relationship (y = 0.88x + 0.45, r = 0.83, P < 0.0001), without systematic bias. TRI significantly reduces variability of RK in quantitative MCE. Assessment of MBFR allows investigator-independent evaluation of CAD. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prognostic value of tissue Doppler imaging (TDI) in patients with chronic congestive heart failure (CHF) has not been compared against conventional measures of systolic, diastolic and overall left ventricular LV performance. The aim of this study was to assess the prognostic value of TDI-derived parameters in patients with CHF. Methods: One hundred thirty-two subjects with chronic CHF [due to ischemic (n=82) or dilated (n=50) cardiomyopathy, 101 males, mean age 57±11 years] underwent conventional two-dimensional/Doppler echocardiography and assessment of the Tei-index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic, early and late diastolic mitral annular velocities (S′, E′ and A′) were derived from pulsed TDI. A cardiac event (cardiac death, urgent cardiac transplantation or hospitalization due to decompensated CHF) was defined as the combined study endpoint. Results: The patients were followed for a mean of 224±123 days. Thirty-one patients suffered an event (cardiac death, n=5; urgent cardiac transplantation, n=2; hospitalization due to CHF, n=24). In patients with event, ejection fraction was lower (25±10 vs. 32±9%), mitral deceleration time was shorter (138±58 vs. 193±72 ms), and the peak mitral E/E′-ratio (16.1±6.6 vs. 10.6±5.0) was significantly elevated as compared to patients free of events (p&#60;0.001 for all comparisons). In those patients, the Tei-index was elevated (1.09±0.39 vs. 0.86±0.26, p&#60;0.01), and a restrictive mitral filling pattern was more frequent (51.6 vs. 17.5%, p&#60;0.001). Stepwise multivariate analysis identified the mitral E/E′-ratio (p&#60;0.001) and the Tei-index (p=0.019) as the only independent predictors of a combined event. E/E′-ratio was the best predictor of hospitalization due to CHF also. In patients with mitral E/E′-ratio>12.5 or Tei-index>0.90, outcome was poor. Conclusions: In subjects with chronic CHF, the mitral E/E′-ratio is a stronger predictor of future cardiac events than conventional parameters of systolic, diastolic or overall LV performance. The E/E′-ratio may be a useful addition in the routine follow-up of such patients. [Copyright &y& Elsevier]

Multiple statistics show that heart diseases are one of the main causes of mortality in our highly developed societies today. These diseases lead to a change of the physiology of the heart, which gives useful information about characteristic and severity of the defect. A fast and reliable diagnosis is the base for successful therapy. As a first step towards recognition of such heart remodeling processes, this work proposes a fully automatic processing pipeline for regional classification of the left ventricular wall in ultrasound images of small animals. The pipeline is based on state-of-the-art methods from computer vision and pattern classification. The myocardial wall is segmented and its motion is estimated. A feature extraction using the segmented data is realized to automatically classify the image regions into normal and abnormal myocardial tissue. The performance of the proposed pipeline is evaluated and a comparison of common classification algorithms on ultrasound data of living mice before and after artificially induced myocardial infarction is given. It is shown that the results of this work, reaching a maximum accuracy of 91.46%, are an encouraging base for further investigation. [ABSTRACT FROM AUTHOR]

Background: Because of the scarcity of donor hearts, surgical alternatives to heart transplantation, such as partial left ventriculectomy (PLV), were introduced for treatment of advanced heart failure. Here, we report our experience with this procedure performed in combination with mitral valve repair. Methods: Twelve patients with dilated cardiomyopathy (DCM), New York Heart Association (NYHA) class exceeding III on maximal medical therapy, cardiac index of 2.5 liter/min/m2 or less, VO2max of 14 ml/kg/min or less, left ventricular end-diastolic diameter (LVEDD) of 7.0 cm or more, and grade II or greater mitral incompetence, were selected for PLV and mitral valve reconstruction (MVR). Echocardiography, hemodynamics, spiroergometry, and clinical assessment were performed before and 1 year after the operation. Results: One-year survival was 83.3%. All 10 surviving patients were free from failure of the procedure 1 year post-operatively. From pre-operatively to 1 year post-operatively, NYHA functional class improved from 3.3 ± 0.3 to 1.9 ± 0.2 (p < 0.001), cardiac index increased from 2.0 ± 0.2 liter/min/m2 to 2.9 ± 0.2 liter/min/m2 (p < 0.001), stroke volume index from 25.9 ± 4.8 ml/m2 to 40.3 ± 7.3 ml/m2 (p = 0.008), and VO2max from 10.9 ± 2.4 ml/kg/min to 16.0 ± 3.6 ml/kg/min (p = 0.016), whereas LVEDD decreased from 8.4 ± 0.6 cm to 6.6 ± 0.3 cm (p < 0.001), left ventricular end-systolic diameter from 6.8 ± 0.8 cm to 5.3 ± 0.5 cm (p < 0.001), and mitral incompetence from 2.4 ± 0.6 to 0.9 ± 0.6 (p < 0.001). Pulmonary pressures and fractional shortening did not change significantly (p > 0.05). Four patients received an implantable cardioverter/defibrillator as a result of their pathologic electrophysiologic examination. Conclusions: In carefully selected patients, PLV combined with MVR achieves short-term results comparable to that after heart transplantation. However, long-term results and multicenter evaluation will be needed to define its place in the treatment of advanced heart failure. [Copyright &y& Elsevier]