Thyroid Hormone and Cardiac Disease: From Basic Concepts to Clinical Application

Nature's models of regeneration provide substantial evidence that a natural healing process may exist in the heart. Analogies existing between the damaged myocardium and the developing heart strongly indicate that regulatory factors which drive embryonic heart development may also control aspects of heart regeneration. In this context, thyroid hormone (TH) which is critical in heart maturation during development appears to have a reparative role in adult life. Thus, changes in TH -thyroid hormone receptor (TR) homeostasis are shown to govern the return of the damaged myocardium to the fetal phenotype. Accordingly, thyroid hormone treatment preferentially rebuilds the injured myocardium by reactivating developmental gene programming. Clinical data provide further support to this experimental evidence and changes in TH levels and in particular a reduction of biologically active triiodothyronine (T3) in plasma after myocardial infarction or during evolution of heart failure, are strongly correlated with patients morbidity and mortality. The potential of TH to regenerate a diseased heart has now been testing in patients with acute myocardial infarction in a phase II, randomized, double blind, placebo-controlled study (the THiRST study)

Is Atherosclerosis Amenable to Anti-Inflammatory Compounds?

The hypothesis of an inflammatory component in the pathogenesis of atherosclerosis has been under investigation for a long time but the data have not been conclusive. No clinical trial of anti-inflammatory, anti-oxidant, or anti-bacterial agents has ever proven efficacious. However, the recent announcement and publication of the CANTOS trial has raised expectations. This pivotal trial showed for the first time that anti-inflammatory therapy targeting the interleukin-1β innate immunity pathway with subcutaneous injections of canakinumab every 3 months conferred significantly, albeit modestly (15%), lower rate of the composite end-point of nonfatal MI, nonfatal stroke and cardiovascular (CV) death than placebo, independent of lipid-level lowering, in patients with prior myocardial infarction (MI). An unexpected corollary of this investigation revealed significant concomitant reduction in lung cancer mortality. Despite the initial enthusiasm about the trial results, sceptics point to that fact that CV mortality was not affected, while the incidence of fatal infections was much higher with the drug compared with placebo, and the cost of this therapy remains currently prohibitive for wider use. Ongoing and future trials with similar or more convenient and less expensive anti-inflammatory agents may provide more data whether such results are reproducible and/or supportive or evidential of the inflammatory hypothesis of atherosclerosis. Rhythmos 2017; 12(4):63-68

2:1 and Mobitz Type II Atrioventricular Block: A Common Fallible Diagnosis

A patient with Wenckebach phenomenon followed by runs of 2:1 atrioventricular (AV) block, labeled as Mobitz type II AV block by the referring physician, was referred for permanent pacemaker implantation. Apropos with this case and similar publications with this fallible diagnosis, the correct diagnosis of second degree AV block is revisited. It is pointed out that an ECG diagnosis of 2:1 AV block is by no means synonymous to Mobitz type II AV block, as two successive PR intervals are required to make a distinction between Mobitz type I and type II, which is never the case with a constant 2:1 AV block recording. On the other hand, the correct diagnosis can only be made by association. When longer ECG recordings are available and at least two consecutive PR intervals are seen, as in the present case, and one can discern a definite pattern of Mobitz type I (with progressive PR prolongation) or type II block (with stable PR intervals), then one can conclude that the 2:1 AV block is a consequence of one of the two types. Rhythmos 2018;13(2): 35-37

Cardiac Resynchronization Via Left Ventricular Anterior Wall Pacing

A case of cardiac resynchronization is presented with paced-QRS narrowing effected via a left ventricular (LV) lead placed at an anterior cardiac vein after failed implantation at the lateral wall due to phrenic nerve stimulation. Data are presented indicating that an anterior LV pacing site selection may not be that bad after all, particularly when biventricular pacing from this position produces a QRS that is narrower than the baseline native QRS. Rhythmos 2018;13(1):10-11.

Cell-Type-Dependent Thyroid Hormone Effects on Glioma Tumor Cell Lines

Purpose. The present study investigated the potential effects of long-term T3 treatment on glioma tumor cell lines. Thyroid hormone action on cell growth, differentiation and survival during development may be of therapeutic relevance Methods and Results 1321N1 cell line, an astrocytoma grade II, and U87MG, a glioblastoma grade IV, were exposed for 2 and 4 days in medium deprived of T3 and in medium containing 1 nM T3. T3 promoted re-differentiation in both cell lines. However, T3 increased cell proliferation in 1321N1 (2 days) which declined thereafter (4 days) while in U87MG resulted in suppression of cell proliferation. At the molecular level, a 2.9 fold increase in the expression of TRα1 receptor was observed in U87MG versus 1321N1, P < 0.05. TRβ1 receptor was undetectable. These changes corresponded to a distinct pattern of T3-induced kinase signaling activation; T3 had no effect on ERK activation in both cell lines but significantly increased phospho-Akt levels in 1321N1. Conclusion. In conclusion, T3 can re-differentiate glioma tumor cells, whereas its effect on cell proliferation appears to be dependent on the type of tumor cell line with aggressive tumors being more sensitive to T3. TRα1 receptor may, at least in part, be implicated in this response

Echocardiographic Datasets Showing Development of Cardiac Remodelling in Rats at Different Time-points after Acute Myocardial Infarction

K E Y W O R D S: myocardial infarction heart failure cardiac remodelling echocardiography rat A B S T R A C T The simulation of the time course of development of heart failure after an acute myocardial infarction requires large, open-access datasets. In this report, we present large echocardiographic datasets of cardiac function in rats after myocardial infarction at two different time points (2 and 13 weeks). We present measurements that show the deterioration of global left ventricular (LV) function, regional function, development of LV dilation, reactive hypertrophy and changes in LV geometry. We present in addition measurements showing the degree of cardiac injury assessed by the area and weight of the scar tissue. These data represent the progressive nature of cardiac remodelling and could be used to build computational models to predict the development of heart function deterioration based on the extent of myocardial injury and the development of LV remodelling. Creative Commons BY-NC-SA 4.

The Emerging Role of TR α

Thyroid hormone (TH) is critical for adapting living organisms to environmental stress. Plasma circulating tri-iodothyronine (T3) levels drop in most disease states and are associated with increased oxidative stress. In this context, T3 levels in plasma appear to be an independent determinant for the recovery of cardiac function after myocardial infarction in patients. Thyroid hormone receptor α1 (TRα1) seems to be crucial in this response; TRα1 accumulates to cell nucleus upon activation of stress induced growth kinase signaling. Furthermore, overexpression of nuclear TRα1 in cardiomyocytes can result in pathological or physiological growth (dual action) in absence or presence of its ligand, respectively. Accordingly, inactivation of TRα1 receptor prevents reactive hypertrophy after myocardial infarction and results in heart failure with increased phospholamban (PLB) expression and marked activation of p38MAPK. In line with this evidence, TH is shown to limit ischemia/reperfusion injury and convert pathologic to physiologic growth after myocardial infarction via TRα1 receptor. TRα1 receptor may prove to be a novel pharmacological target for cardiac repair/regeneration therapies