Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

Influence of subacute starvation on cardiac response to isoproterenol in rats.

Several studies have reported that the heart is severely affected by chronic malnutrition. However, the influence of these alterations on cardiac function remains unclear. The aim of this study was to evaluate the effects of subacute starvation on the heart chronotropic response to a beta-adrenergic agonist (isoproterenol). Twelve rats were fed rat chow ad libitum or a 50%-restricted diet for 17 days. The rats were killed, the right atrium was isolated and incubated, and in vitro spontaneous cardiac contractions and frequency were registered. Cumulative doses of isoproterenol were added to the solution until maximal cardiac frequency was achieved. A deficit of 25% in the weight gain was observed in study rats compared with controls (92.6 +/- 10.2 vs. 113.8 +/- 19.2 g, p less than 0.05). Mean daily food intake was 4.8 +/- 0.1 and 9.8 +/- 0.5 g/day for semistarved and control rats, respectively. The in vitro cardiac frequency of the semistarved rats was similar to that of controls (290 +/- 15 and 305 +/- 23 beats/min, respectively, NS). However, when isoproterenol was added to the solution, maximal cardiac frequency of the semistarved rats (435 +/- 51 beats/min) was lower than that of control rats (508 +/- 34 beats/min, p less than 0.005). These findings suggest that subacute starvation may alter the cardiac response to beta-adrenergic agonists.     

颈内动脉接近完全闭塞时的处理

目的由于卒中风险随着狭窄严重程度的增加而升高，因此认为颈内动脉（ICA）接近闭塞患者的卒中风险很高。在现有的随机试验中，还没有专门针对这种情况进行探讨，因此其处理尚存在争汶。方法：对相关文献进行系统评价。结果：对ICA接近闭塞患者的处理还存在争议：一些学者支持进行干预，而另一些学者则认为存在风险或没有益处而反对进行干预。在ICA接近闭塞的有症状患者中进行一项比较外科治疗与最佳内科治疗的多中心前瞻性随机试验似乎非常困难，因为这类研究需要大量的患者。尽管如此，基于目前的证据，似乎很难拒绝手术治疗。结论：由于目前对ICA接近闭塞患者的最佳处理方案仍存在着争议，因此需要前瞻性观察性研究以证实其在有症状和无症状人群中的患病率以及相关的卒中风险。基于目前的证据，大多数医疗中心选择手术治疗，但它相对干内科治疗的特粱尚右待证章．     

Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months     

Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

The use of myocardial perfusion (82)Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. METHODS: A sex-independent normal database and criteria for abnormality for rest-stress (82)Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age +/- SD, 63.3 +/- 13.3 y; 145 males: mean age +/- SD, 63.9 +/- 12.8 y) who underwent a rest-adenosine stress (82)Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. RESULTS: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis > or =50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (> or =50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (< or =50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). CONCLUSION: The quantitative (82)Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.