Prediction of coronary atherosclerotic disease with liver transaminase level.

BACKGROUND/AIMS: Recent studies have shown that liver transaminases are associated with components of the metabolic syndrome including central obesity, type 2 diabetes, dyslipidaemia and high blood pressure, but their direct influence on coronary atherosclerosis has not been investigated before. We conducted this study to evaluate the predictive value of liver transaminases for angiography-documented coronary atherosclerosis in patients with coronary heart disease. METHODS: Six hundred and thirty consecutive patients with suspicious coronary artery disease (CAD) who were candidates for coronary angiography were enrolled. In addition to coronary angiography, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, C-reactive protein (CRP) level and assessment of the traits of the metabolic syndrome were performed in all patients. RESULTS: ALT and ALT/AST ratios were significantly correlated with angiographic atherosclerosis score in women (r=0.17 and 0.24 respectively). Logistic regression analysis showed that the ALT/AST ratio in women could predict severe CAD [odds ratio (OR) 3.93, 95% confidence interval (CI) 1.76-8.76]. After adjustment for components of the metabolic syndrome and CRP concentration, the OR remained significant (4.00 [1.76-9.14]). Although significant in univariate analysis, neither ALT (OR 0.98, 95% CI 0.77-1.15) nor AST (OR 0.99, 95% CI 0.72-1.22) could predict severe CAD in men. CONCLUSION: An elevated ALT/AST ratio in women predicts coronary atherosclerosis independently of the metabolic syndrome and serum CRP concentration, and should warrant further diagnostic and therapeutic interventions.     

Coronary artery disease in adults with tetralogy of Fallot

Background: There are limited data about outcomes of coronary artery disease (CAD) in adults with repaired tetralogy of Fallot (TOF). The purpose of this study was to describe the prevalence and treatment of CAD in adults with TOF, and the impact of CAD on long‐term survival.
Methods: Retrospective review of MACHD database for adults with repaired TOF who underwent aortic root/selective coronary angiogram, 1990‐2017. Patients were categorized into three groups: (1) No CAD defined as normal coronary angiogram; (2) Mild CAD defined as ≤50% stenosis in all vessels; and, (3) Significant CAD defined as >50% stenosis in any vessel.
Results: We identified 105 (23%) of 465 TOF patients that had angiograms; mean age 47 ± 12 years. The prevalence of mild CAD and significant CAD was 19% (20 pa‐ tients) and 15% (16 patients), respectively. Of these 16 patient with significant CAD, 9 (56%), 3 (19%), and 4 (24%) patients received guideline directed medical therapy, percutaneous coronary intervention, and coronary artery bypass grafting, respec‐ tively. Significant CAD was an independent risk factor for mortality (HR: 2.03, 95% CI 1.64‐4.22, P = .022) after adjustment for differences in age, and prevalence of atrial fibrillation and renal dysfunction.
Conclusions: Based on a review of a selected cohort of 105 TOF patients, the preva‐ lence of mild CAD and significant CAD was 19% and 15%, respectively. Significant CAD was an independent risk factor for mortality. There is need for more research to determine optimal noninvasive diagnostic strategies and optimal patient selections and methods for revascularization.     

Enhanced efficacy of pH-sensitive nystatin liposomes against Cryptococcus neoformans in murine model

OBJECTIVES: To evaluate the efficacy of pH-sensitive liposomes of nystatin against Cryptococcus neoformans infection in a murine model. METHODS: In the present study, we investigated the antifungal activity of nystatin entrapped in pH-sensitive liposomes in a murine model. Mice infected with C. neoformans were treated with nystatin in neutral egg phosphatidylcholine (egg-PC) liposomes, as well as pH-sensitive nystatin liposomes. The anticryptococcal efficacy of liposomal formulations of nystatin was assessed by continued survival and colony-forming units (cfu) in liver and brain of the treated mice. RESULTS: pH-sensitive liposomes of nystatin showed better efficacy compared with its free or egg-PC liposome form against C. neoformans infection in BALB/c mice. Mice treated with pH-sensitive nystatin liposomes showed 80% survival with less fungal burden in liver and brain of treated mice. However, there was only 40% survival in the group of animals treated with egg-PC liposome-intercalated nystatin, whereas its free form had poor efficacy with 20% survival. CONCLUSIONS: The enhanced anticryptococcal efficacy of the pH-sensitive nystatin liposomes can be attributed to the pH-dependent release of the drug in the low pH environment of lysosomes. The destabilization of the pH-sensitive liposomes in the acidic environment of macrophages results in the site-specific targeting of nystatin that improves its intracellular antifungal activity.     

Combined use of 1C and III agents for highly symptomatic, refractory atrial fibrillation

Background Despite advances in non-pharmacologic therapy for atrial fibrillation (AF), some patients remain highly refractory.Objective We report our experience with the unique combined use of 1C and III agents in patients with highly refractory paroxysmal atrial fibrillation.Materials and methods Six patients with symptomatic AF (three persistent) were selected after failing multiple antiarrhythmic medications and radiofrequency ablation. They were started on flecainide or propafenone and sotalol or dofetilide during three days of inpatient monitoring. No patient had coronary artery disease. All patients had loop recorder follow-up and ECG recordings during clinic visits for a mean follow-up of 9 ± 11 months.Results After therapy, all patients had complete, sustained control of their symptoms with no evidence of AF or proarrhythmia on monitoring. One patient had recurrence of AF after stopping sotalol and was started back on the drug with complete control.Conclusions Combined therapy with a 1C and III agent may be an effective alternative for the treatment of selective, highly refractory AF. Careful patient selection and hospitalization for initiation is necessary to minimize potential proarrhythmic effects. As this is a short-term therapy, further study is needed to assess the extent of efficacy in a larger number of patients.     

Evaluation and treatment strategies in patients at high risk of sudden death post myocardial infarction

Over 50 percent of deaths in patients who survive an acute myocardial infarction are due to fatal ventricular tachyarrhythmias. Patients who survive an episode of sustained ventricular arrhythmia are at highest risk of recurrent cardiac arrest. Electrophysiologic studies have been found to be useful in guiding therapy and reducing mortality in these patients and in patients with syncope due to arrhythmic etiology. Evaluation and treatment of nonsustained ventricular tachycardia post infarction remains somewhat controversial. A recently published trial (MADIT), however, showed improved survival with an implanted defibrillator in patients with coronary disease and asymptomatic nonsustained ventricular tachycardia. Asymptomatic patients post infarction at high risk include those who have significant left ventricular dysfunction, late potentials, high-grade ventricular ectopy, and abnormal heart rate variability. These tests individually, however, have a low positive predictive accuracy. This, combined with the fact that antiarrhythmic drugs are frequently not effective and can be proarrhythmic, leaves the best treatment for these patients uncertain. It is known, however, that beta-adrenoreceptor blocking agents do reduce mortality after an acute myocardial infarction. Early studies have shown mixed results relating to sudden death and total mortality with amiodarone. To date, no other antiarrhythmic drug has shown benefit, while several have been shown to be harmful. Recent studies have also shown some beneficial effects of angiotensin-converting enzyme inhibitors, carvedilol, a third-generation beta-blocking agent with vasodilator properties, and the angiotensin II receptor antagonist losartan. However, their precise role in reducing sudden death needs to be defined further.     

Echocardiographic assessment of the right ventricle in the current era: Application in clinical practice

The right ventricle has unique structural and functional characteristics. It is now well recognized that the so‐called forgotten ventricle is a key player in cardiovascular physiology. Furthermore, there is accumulating evidence that demonstrates right ventricular dysfunction as an important marker of morbidity and mortality in several commonly encountered clinical situations such as heart failure, pulmonary hypertension, pulmonary embolism, right ventricular myocardial infarction, and adult congenital heart disease. In contrast to the left ventricle, echocardiographic assessment of right ventricular function is more challenging as volume estimations are not possible without the use of three‐dimensional (3D) echocardiography. Guidelines on chamber quantification provide a standardized approach to assessment of the right ventricle. The technique and limitations of each of the parameters for RV size and function need to be fully understood. In this era of multimodality imaging, echocardiography continues to remain a useful tool for the initial assessment and follow‐up of patients with right heart pathology. Several novel approaches such as 3D and strain imaging of the right ventricle have expanded the usefulness of this indispensable modality.     

Biventricular pacing and QT interval prolongation

Introduction: The purpose of this study was to examine BiV pacing-dependent changes in QT interval and the related potential for proarrhythmia. Biventricular (BiV) pacing has emerged as a promising therapy for patients with advanced congestive heart failure (CHF) and bundle branch block (BBB).
Methods and Results: One hundred and seventy-six consecutive patients (123 men and 53 women; mean age 67 ± 16 years) with ischemic (n = 128) or nonischemic (n = 48) cardiomyopathy in New York Heart Association Class II (8%) or III (92%) CHF (ejection fraction 24 ± 9%) underwent atrial synchronous BiV pacing. The QRS, QT, and JT intervals were measured at 30 minutes after initiation of BiV pacing, at 24 hours, and at 1 month postimplant. QT interval was defined as the time interval between the initial deflection of the QRS complex and the point at which the T wave crossed the isoelectric line. At baseline, the average QRS duration was 178 ± 10 ms, attributable to left BBB (n = 158) or intraventricular conduction delay (n = 18). BiV pacing resulted in a small but statistically significant reduction in QRS duration (148 ± 9 ms during BiV pacing vs 178 ± 10 ms at baseline [P < 0.0001]), yet the QT increased to 470 ± 34 ms with BiV pacing versus 445 ± 32 ms at baseline [P < 0.0001]). The JTc interval during BiV pacing was significantly shorter than during LV pacing (290 ± 9 ms vs 320 ± 20 ms, P < 0.0001). During a mean follow-up of 24 ± 6 months, one patient developed recurrent torsade de pointes. That was eliminated once left ventricular pacing was discontinued.
Conclusion: Biventricular pacing prolongs QT interval. However, the occurrence of torsade de pointes is uncommon.