Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system

Objectives

To assess ventricular dysfunction and ventricular interaction after repair of Tetralogy of Fallot (ToF) employing echocardiography speckle-tracking and cardiac magnetic resonance imaging (CMR).

Background

Severe pulmonary regurgitation and right ventricular (RV) dysfunction are common after repair of ToF and may also affect the shape and function of the left ventricle (LV). Recent studies suggest that LV dysfunction may be of particular prognostic value.

Methods and results

Twenty-one consecutive adults with repaired ToF (15 male, mean age 38 ± 11 years, 7 with severe PR) underwent a comprehensive echocardiographic exam including speckle-tracking analysis, CMR and cardiopulmonary exercise testing. Twenty-one subjects without relevant heart disease served as controls. Echocardiographically measured RV diameters correlated with RV volumes obtained from CMR (r = 0.63; p = 0.006). In addition, a close correlation was found between RV and LV function on CMR (r = 0.74, p = 0.002), speckle-tracking LV and RV peak longitudinal 2D strain (r = 0.66, p = 0.003) and mitral and tricuspid annular plain systolic excursion (r = 0.71, p = 0.0003). While LV ejection fraction was normal in the majority of patients and not different from controls, LV longitudinal strain was significantly reduced in ToF patients (− 16.5 ± 3.3 vs. -20.5 ± 2.7%, p = 0.0001).

Conclusion

Left and right ventricular function both by CMR and speckle-tracking is interrelated in adults with repaired ToF. Despite normal LV ejection fraction, 2D longitudinal strain is significantly reduced in ToF patients, suggesting subclinical LV myocardial damage. Considering the potential prognostic value of LV dysfunction in ToF, this measurement may gain importance and should be included in future outcome studies.     

Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy

OBJECTIVES

This study evaluated oxidative stress in the failing ventricle in patients with dilated cardiomyopathy (DCM).

BACKGROUND

Oxidative stress appears to increase in the failing myocardium and may contribute to ventricular dysfunction in patients with DCM. Tumor necrosis factor-alpha (TNF-alpha), which is expressed in the failing heart, may stimulate oxidative stress.

METHODS

We measured plasma oxidized low density lipoprotein (oxLDL) by sandwich enzyme-linked immunosorbent assay using specific antibodies against oxLDL in the aortic root (AO) and the coronary sinus (CS) in control subjects (n = 8) and in 22 patients with DCM and mild congestive heart failure. We also measured the plasma levels of TNF-alpha and angiotensin II.

RESULTS

There was no difference in oxLDL between the AO and CS in control subjects. In contrast, plasma oxLDL was significantly higher in the CS than the AO in patients with DCM, suggesting that the transcardiac gradient of oxLDL reflects oxidative stress in the failing heart in these patients. Plasma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. Moreover, a significant negative correlation existed between the transcardiac gradient of oxLDL and left ventricular ejection fraction. The transcardiac gradient of plasma oxLDL was significantly lower in 6 patients who received carvedilol than in 16 patients who did not receive carvedilol.

CONCLUSIONS

These findings indicate that the transcardiac gradient of oxLDL may be a marker of oxidative stress in the heart and that left ventricular dysfunction may be partly due to the oxidative stress in patients with DCM. In addition, TNF-alpha may stimulate oxidative stress in the failing heart in patients with DCM.     

Variable effects of anti-diabetic drugs in animal models of myocardial ischemia and remodeling: A translational perspective for the cardiologist

Diabetes and heart failure are very prevalent, and affect each other's incidence and severity. Novel therapies to reduce post-myocardial infarction (MI) remodeling that progresses into heart failure are urgently needed, especially in diabetic patients. Clinical studies have suggested that some oral anti-diabetic agents like metformin exert cardiovascular protective effects in heart failure patients with diabetes, whereas other agents may be deleterious. In the current review, we provide an overview of the cardio-specific effects of oral anti-diabetic drugs in animal models of acute MI, post-MI remodeling, and heart failure. Metformin has consistently been shown to ameliorate cardiac remodeling after ischemia/reperfusion (I/R) injury, as well as in several models of heart failure. Sulfonylurea derivatives are controversial with respect to their direct effects on the cardiovascular system. Thiazolidinediones protect against myocardial I/R injury, but their effects on post-MI remodeling are less clear and clinical studies raised concerns about their cardiovascular safety. Glucagon-like peptide-1 analogs have potential beneficial effects on the cardiovascular system that require further confirmation, whereas the results with dipeptidyl peptidase-4 inhibitors are equivocal. Current clinical guidelines, in the absence of prospective clinical trials that evaluated if certain oral anti-diabetic agents are superior over others, only provide generic recommendations, and do not take into account interesting experimental and mechanistic data. The available experimental evidence indicates that some anti-diabetic agents should be preferred over others if cardio-protective effects are warranted. These experimental clues need to be confirmed by clinical trials.