Echocardiographic Evaluation of Cardiac Dyssynchrony in Patients with Congestive Heart Failure

The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure（CHF）. A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization（CRT） and presented with low ejection fraction（EF） and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio（FT/RR）, left ventricular pre-ejection delay（PED）, interventricular mechanical delay（IVMD）, longitudinal opposing wall delay（LOWD） and radial septal to posterior wall delay（RSPWD）. Response to CRT was defined as a ≥15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group（P〈0.01）. In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter（LVESd）, LV end-diastolic volume（LVEDV） and LV end-systolic volume（LVESV）（P〈0.01）, but positively with the LVEF（P〈0.01）. Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV（P〈0.01）, but negatively with the LVEF（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. Speckle tracking radial dyssynchrony ≥130 ms was predictive of an EF response in patients in QRS-1 group（78% sensitivity, 83% specificity）, those in QRS-2 group（83% sensitivity, 77% specificity） and in QRS-3 group（89% sensitivity, 79% specificity）. In conclusion, echocardiography is a convenient and sensitive method for evaluating cardiac dyssynchrony in patients with CHF.

Signaling Pathways Involved in Cardiac Hypertrophy

Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy （normal growth） and physiological hypertrophy （growth induced by conditioning）, and maladaptive hypertrophy, physical including pathologic or reactive hypertrophy （growth induced by pathologic stimuli） and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response, including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt （PI3Ks/Akt）, G protein-coupled receptors, small G proteins, MAPK, PKCs, Gp130/STAT3, Na＋/H＋ exchanger, peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.