Individuals with type 2 diabetes mellitus have a high residual risk of cardiovascular disease (CVD) despite maximal statin therapy and lifestyle interventions. In addition, adults with diabetes frequently exhibit the pattern of elevated triglycerides, small dense LDL, and reduced levels of high density lipoprotein cholesterol (HDL), also known as diabetic dyslipidemia. The role of combination therapy with an additional agent such as niacin, ezetimibe, fenofibrate, and n-3 fatty acids have been extensively studied with disappointing results. Review of key trials assessing benefit of combination therapy to reduce CVD risk from dyslipidemia is performed. While combination therapy frequently results in an improvement in lipid profile, to date, no consistent improvement in clinical outcomes has been observed. Therefore, current guidelines do not recommend combination therapy in individuals with diabetes, highlighting the role of intensifying statin therapy and lifestyle interventions. The recently released The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE IT) demonstrated a small but significant improvement in clinical endpoints with addition of ezetimibe to statins in high-risk patients. Although this trial was not specifically targeted towards patients with diabetes, the results may influence the future role of a combination therapy in such a population.

Individuals with type 2 diabetes mellitus have a high residual risk of cardiovascular disease (CVD) despite maximal statin therapy and lifestyle interventions. In addition, adults with diabetes frequently exhibit the pattern of elevated triglycerides, small dense LDL, and reduced levels of high density lipoprotein cholesterol (HDL), also known as diabetic dyslipidemia. The role of combination therapy with an additional agent such as niacin, ezetimibe, fenofibrate, and n-3 fatty acids have been extensively studied with disappointing results. Review of key trials assessing benefit of combination therapy to reduce CVD risk from dyslipidemia is performed. While combination therapy frequently results in an improvement in lipid profile, to date, no consistent improvement in clinical outcomes has been observed. Therefore, current guidelines do not recommend combination therapy in individuals with diabetes, highlighting the role of intensifying statin therapy and lifestyle interventions. The recently released The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE IT) demonstrated a small but significant improvement in clinical endpoints with addition of ezetimibe to statins in high-risk patients. Although this trial was not specifically targeted towards patients with diabetes, the results may influence the future role of a combination therapy in such a population.

BACKGROUND AND PURPOSE: Thromboembolism in paroxysmal atrial fibrillation (AF) has often been attributed to occult AF. We hypothesized that the surface ECG may not always reflect left atrial appendage (LAA) mechanical function. METHODS: Transesophageal echocardiographic images from 201 consecutive patients undergoing transesophageal echocardiography by a single operator were reviewed. LAA pulse wave Doppler phenotype, ECG rhythm, and mitral valve motion for rhythm of the body of the left atrium and the electronic medical record were reviewed by 3 blinded, independent observers. RESULTS: Of 201 patients (63.4+/-15 years; 61% men) undergoing transesophageal echocardiography, 15 (7.5%) demonstrated LA-LAA discordance including 7 (3.5%) with a sinus rhythm ECG/mitral valve motion and an AF LAA pulse wave Doppler phenotype. Of 24 patients with a clinical history of AF but sinus rhythm ECG, 25% demonstrated a discordant AF LAA pulse wave Doppler phenotype. Compared with concordant AF, the AF discordant group had greater CHA2DS2-VASc (CHADS2, vascular disease, age, sex category; P=0.008) and lower LAA ejection velocity (P=0.02). CONCLUSIONS: A quarter of patients with paroxysmal AF demonstrate a prothrombotic AF LAA pulse wave Doppler phenotype, despite concurrent sinus rhythm ECG. These findings provide a novel explanation for ongoing thromboembolism in the paroxysmal AF population, despite apparent ECG maintenance of sinus rhythm.

BACKGROUND: Psoriasis patients have a high prevalence of cardiovascular events and are thought to have a relative risk increase of 25% as compared to the general population. However, a causal relationship between psoriasis and cardiovascular disease has not been established. We sought to perform a systematic review of existing data regarding the presence of endothelial dysfunction and subclinical atherosclerosis in patients with plaque psoriasis. METHODS: A systematic literature search was performed, using Medline database and Ovid SP for relevant literature up to November 2012. Twelve studies met inclusion criteria from an initial search result of 529 articles. RESULTS: Among the twelve studies meeting inclusion criteria, two (17%) reported increased mean coronary artery calcification (CAC) in psoriatic patients. Six studies (50%) showed carotid intima-media thickness [CIMT] increase in psoriasis. Five studies (42%) examined flow mediated dilation [FMD], of which three showed decreased FMD in psoriasis patients. One study (8%) each demonstrated a decreased coronary flow reserve and increased arterial stiffness as assessed by pulse wave velocity. CONCLUSIONS: Patients with psoriasis have an increased burden of subclinical atherosclerosis and endothelial dysfunction. Patients with greater severity and/or disease duration should be targeted for primary screening for cardiovascular disease risk reduction.

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

Patients with diabetes mellitus are at particularly high risk for cardiovascular disease. Although global risk factor scoring systems, such as the Framingham Risk Score, are well established for screening asymptomatic adults, they are not as predictive in diabetics. Therefore, there has been considerable interest in new screening tests to establish cardiovascular risk in diabetics. Coronary artery calcium assessment, both baseline levels and progression, have been shown to be additive to risk factor scoring systems and are independently predictive of cardiovascular mortality in diabetics. Current American Heart Association/American College of Cardiology Foundation guidelines recommend coronary calcium scoring for asymptomatic diabetics. Myocardial perfusion studies are recommended for patients with a coronary calcium score >400 but the level of evidence is poor. The data for other screening tests is limited. Further research is required into assessing what would be an appropriate follow-up duration for serial coronary calcium scanning.

BACKGROUND: Mitral valve (MV) annular dynamics have been well described in animal models of functional mitral regurgitation (FMR). Despite this, little if any data exist regarding the dynamic MV annular geometry in humans with FMR. In the current study we hypothesized that 3-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 operations were dynamically analyzed for differences in mitral annular geometry with TomTec 4D MV Assessment 2.0 software (TomTec Imaging Systems GmbH, Munich, Germany). RESULTS: In patients with FMR, the mean mitral annular area (14.6 cm(2) versus 9.6 cm(2)), circumference (14.1 cm versus 11.4 cm), anteroposterior (4.0 cm versus 3.0 cm) and anterolateral-posteromedial (4.3 cm versus 3.6 cm) diameters, tenting volume (6.2 mm(3) versus 3.5 mm(3)) and nonplanarity angle (NPA) (154 degrees +/- 15 versus 136 degrees +/- 11) were greater at all points during systole compared with controls (p < 0.01). Vertical mitral annular displacement (5.8 mm versus 8.3 mm) was reduced in FMR compared with controls (p < 0.01). CONCLUSIONS: There are significant differences in dynamic mitral annular geometry between patients with FMR and those without. 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.

The impact of aortic valve replacement (AVR) on the dynamic geometry and motion of the mitral annulus remains unknown. We analyzed the effects of AVR on the dynamic geometry and motion of the mitral annulus. We used 3-dimensional transesophageal echocardiography to analyze 39 consecutive patients undergoing elective surgical AVR for aortic stenosis. Intraoperative 3-dimensional transesophageal echocardiography was performed immediately before and after AVR. Volumetric data sets were analyzed using a software package capable of dynamically tracking the mitral annulus and leaflets during the entire systolic ejection phase. After AVR, there were significant decreases (p <0.01) in annular dimensions such as anteroposterior (3.5 +/- 0.1 vs 3.2 +/- 0.1 cm), anterolateral-posteromedial (3.7 +/- 0.1 vs 3.5 +/- 0.1 cm), and commissural diameters (3.7 +/- 0.1 vs 3.3 +/- 0.1 cm), as well as annular circumference (12.0 +/- 0.30 vs 11.1 +/- 0.2 cm) and 3-dimensional mitral annular area (mean 10.9 +/- 0.6 vs 9.3 +/- 0.3 cm(3)). Vertical mitral annular displacement was also reduced (6.2 +/- 3.1 vs 4.3 +/- 2.2 mm). Mitral annular nonplanarity angle (154 +/- 1.5 degrees vs 161 +/- 1.6 degrees ) and aorto-mitral angle (133 +/- 3.3 degrees vs 142 +/- 2.0 degrees ) were both increased after AVR, suggesting reduced nonplanar shape of the mitral annulus and reduced aorto-mitral flexion. In conclusion, these data demonstrate that mitral annular size is reduced immediately after AVR and that the dynamic motion of the mitral annulus is restricted. These findings may have important clinical implications for patients undergoing AVR with concurrent mitral regurgitation.

BACKGROUND: Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates>45/1000 live births. METHODS: Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD. Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days. RESULTS: Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95% confidence interval: 1.09-3.79] by intention-to-treat analysis. Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89-3.23). By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26-24.72 (group 3 versus 1)]. CONCLUSION: When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

BACKGROUND AND AIM OF THE STUDY: Intraoperative real-time three-dimensional transesophageal echocardiography (RT-3D TEE) was used to examine the geometric changes that occur in the mitral annulus immediately after aortic valve replacement (AVR). METHODS: A total of 35 patients undergoing elective surgical AVR under cardiopulmonary bypass was enrolled in the study. Intraoperative RT-3D TEE was used prospectively to acquire volumetric echocardiographic datasets immediately before and after AVR. The 3D echocardiographic data were analyzed offline using TomTec Mitral Valve Assessment software to assess changes in specific mitral annular geometric parameters. RESULTS: Datasets were successfully acquired and analyzed for all patients. A significant reduction was noted in the mitral annular area (-16.3%, p < 0.001), circumference (-8.9%, p < 0.001) and the anteroposterior (-6.3%, p = 0.019) and anterolateral-posteromedial (-10.5%, p < 0.001) diameters. A greater reduction was noted in the anterior annulus length compared to the posterior annulus length (10.5% versus 6.2%, p < 0.05) after AVR. No significant change was seen in the non-planarity angle, coaptation depth, and closure line length. During the period of data acquisition before and after AVR, no significant change was noted in the central venous pressure or left ventricular end-diastolic diameter. CONCLUSION: The mitral annulus undergoes significant geometric changes immediately after AVR. Notably, a 16.3% reduction was observed in the mitral annular area. The anterior annulus underwent a greater reduction in length compared to the posterior annulus, which suggested the existence of a mechanical compression by the prosthetic valve.

BACKGROUND: Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates>45/1000 live births. METHODS: Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD. Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days. RESULTS: Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95% confidence interval: 1.09-3.79] by intention-to-treat analysis. Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89-3.23). By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26-24.72 (group 3 versus 1)]. CONCLUSION: When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

A 3-dimensional echocardiographic view of the mitral valve, called the "en face" or "surgical view," presents a view of the mitral valve similar to that seen by the surgeon from a left atrial perspective. Although the anatomical landmarks of this view are well defined, no comprehensive echocardiographic definition has been presented. After reviewing the literature, we provide a definition of the left atrial and left ventricular en face views of the mitral valve. Techniques used to acquire this view are also discussed.