Assessment of left atrial appendage function by transthoracic pulsed Doppler echocardiography: Comparing against transesophageal interrogation and predicting echocardiographic risk factors for stroke.

AIMS: Transesophageal echocardiographic (TEE) findings of left atrial appendage (LAA) thrombus, spontaneous echo contrast (SEC), and LAA dysfunction are established risk factors of cardioembolic stroke. The semi-invasive nature of TEE limits its utility as a routine risk stratification tool. We aim to correlate TEE and transthoracic echocardiography (TTE) pulsed Doppler measurements of LAA flow velocities and use TTE measurements to predict TEE findings. METHODS AND RESULTS: We prospectively measured pulsed Doppler LAA flow velocities in 103 consecutive patients on TEE and TTE. There was a strong correlation between TEE and TTE LAA emptying velocity (LAA E) (r = .88, P < .001) and a moderate correlation between LAA filling velocities (r = .50, P < .001). TTE LAA E predicted the presence of thrombus or SEC independent of atrial fibrillation (AF). To predict the presence of thrombus or SEC, the optimal TTE LAA E cutoff was ≤30 cm/s in all patients (75% sensitive, 90% specific) and ≤31 cm/s in AF patients (80% sensitive, 79% specific). To predict LAA dysfunction (TEE E ≤ 20 cm/s), the optimal TTE LAA E cutoff was ≤27 cm/s (100% sensitive, 89% specific in all patients and 100% sensitive, 74% specific in AF patients). CONCLUSIONS: TTE assessment of LAA function is feasible and correlates well with the more invasive TEE method. It predicts the presence of thrombus, SEC, and LAA dysfunction on TEE. TTE LAA assessment has incremental value in thromboembolic risk stratification and should be utilized more frequently.

Screening for Obstructive Sleep Apnea in the Assessment of Coronary Risk.

There is increasing awareness that health screening may prevent some acute coronary events. Yet, obstructive sleep apnea (OSA) is seldom screened for and its relation with coronary risk markers is not well established. Consecutive adults (n = 696) enrolled in a cardiovascular health screening program were approached to determine the feasibility of incorporating OSA screening. Screening included questionnaires and a home-based sleep study. High-sensitivity C-reactive protein was the primary coronary risk marker, and other laboratory- and exercise treadmill-based markers were also reported. Two thirds of the participants (66%) agreed to undergo OSA screening and most (78%) successfully completed the sleep study. The prevalence of OSA (apnea-hypopnea index ≥15/hour) was 38.0%. The Berlin Questionnaire (53%) and Epworth Sleepiness Scale (26%) had low sensitivity in identifying OSA. After full adjustment for age, gender, body mass index, hypertension, and diabetes mellitus, OSA remained an independent predictor of serum levels of high-sensitivity C-reactive protein (relative mean difference 1.29, 95% CI 1.03 to 1.62; p = 0.025), triglyceride (relative mean difference 1.15, 95% CI 1.03 to 1.28; p = 0.014), and exercise time (mean difference -26.4 seconds; 95% CI -51.6 to -1.2; p = 0.04). The INTERHEART Risk Score analysis suggested more participants with (31%) than without (14%, p <0.001) OSA will develop future cardiovascular events. In conclusion, based on the acceptance for OSA screening, high prevalence of OSA and independent associations between OSA and coronary risk markers, incorporation of sleep studies into cardiovascular health screening programs appears feasible.

Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography.

Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure-activity relationship study was carried out. Positron Emission Tomography (PET) using (18)F-L-1-(2'-deoxy-2'-FluoroArabinofuranosyl) Cytosine ((18)F-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = ∼1-12 nM) using the (18)F-L-FAC PET pharmacodynamic assay identified compounds demonstrating superior in vivo efficacy.

Immigrant status and disparities in health care delivery in patients with myocardial infarction.

BACKGROUND: We investigated the differences in socioeconomic status and quality health care between Singapore-born citizens and immigrants presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: In a prospective study, patients admitted with STEMI were recruited for a questionnaire survey. The recruited patients were categorized based on their immigration status into Singapore-born citizens (SBC), foreign-born citizens (FBC), permanent residents (PR) and non-residents (NR). RESULTS: Among the 374 recruited patients, 286 (76.5%) patients were categorized as SBC, and the remaining 88 (23.5%) as immigrants. Further breakdown of the immigrants revealed that 33 were FBC (median duration of living in Singapore, 53 years), 22 were PR (18 years), and 33 were NR (11 years). Significant differences in socioeconomic status among SBC, FBC, PR and NR were detected. NR were in the lowest, while PR in the highest, socioeconomic class based on occupation (p=0.003), education level (p<0.001), and average monthly household income (p=0.020). There were no disparities in the proportion of patients treated with primary PCI (SBC 88%, FBC 82%, PR 91%, NR 79%, p=0.555). Median door-to-balloon times were similar among the four groups (56, 52, 60, 56min, p=0.614). Compared with SBC, PR was associated with longer symptom-to-balloon times (median difference 54.1 min; 95% CI 9.0 to 99.2). CONCLUSION: There were major differences in the socioeconomic status among SBC, FBC, PR and NR who presented with STEMI. Although there were no major disparities in access to high quality health care to these patients with different immigration status, symptom-to-balloon time differed substantially among the different migrant classes.

Update on drug-eluting stents for prevention of restenosis.

Despite the success of coronary stent implantations in the last decade, in-stent restenosis due to neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury and mainly consists of proliferation of smooth muscle cells and deposition of extracellular matrix. Recently, local drug delivery has been advocated as a potential strategy to prevent in-stent restenosis. Unprecedented results have been obtained in early clinical studies on sirolimus-eluting and paclitaxel-eluting stents. Trials using various pharmaceutical coatings on different coronary stents are ongoing. More types of drug-eluting stents are expected on the market in the near future. Meanwhile, the evaluation of drug-eluting stents is entering the second phase in which the safety and efficacy in more complex lesion subsets and different clinical presentations are being investigated. Results including cost-benefit analyses are expected to have a tremendous impact on the practice of interventional cardiology in the next decade.