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Background: The left and right ventricles of the human heart differ in embryology, shape, thickness, and function. Ventricular dyssynchrony often occurs in cases of heart failure. Our objectives were to assess whether differences in contractile properties exist between the left and right ventricles and to evaluate signs of left/right ventricular mechanical synchrony in isolated healthy and diseased human myocardium., Methods: Myocardial left and right ventricular trabeculae were dissected from nonfailing and end-stage failing human hearts. Baseline contractile force and contraction/relaxation kinetics of the left ventricle were compared to those of the right ventricle in the nonfailing group (n=41) and in the failing group (n=29). Correlation analysis was performed to assess the mechanical synchrony between left and right ventricular myocardium isolated from the same heart, in nonfailing (n=41) and failing hearts (n=29)., Results: The failing right ventricular myocardium showed significantly higher developed force (Fdev; P =0.001; d=0.98), prolonged time to peak ( P <0.001; d=1.14), and higher rate of force development ( P =0.002; d=0.89) and force decline ( P =0.003; d=0.82) compared to corresponding left ventricular myocardium. In healthy myocardium, a strong positive relationship was present between the left and right ventricles in time to peak (r=0.58, P <0.001) and maximal kinetic rate of contraction (r=0.63, P <0.001). These coefficients were much weaker, often nearly absent, in failing myocardium., Conclusions: At the level of isolated cardiac trabeculae, contractile performance, specifically of contractile kinetics, is correlated in the nonfailing myocardium between the left and right ventricles' but this correlation is significantly weaker, or even absent, in end-stage heart failure, suggesting an interventricular mechanical dyssynchrony.

Background Because body mass index (BMI) is generally used clinically to define obesity and to estimate body adiposity, BMI likely is positively correlated with epicardial adipose tissue (EAT) level. Based on echocardiography, previous outcomes on this matter have varied from almost absent to rather strong correlations between BMI and EAT. The purpose of our study was to unambiguously examine EAT content and determine if correlations exist between EAT content and BMI, cause of heart failure, or contractile force. Methods and Results We qualitatively scored 150 human hearts ex vivo on EAT distribution. From each heart, multiple photographs of the heart were taken, and both atrial and ventricular adipose tissue levels were semiquantitatively scored. Main findings include a generally higher EAT content on nonfailing hearts compared with end-stage failing hearts (atrial adipose tissue level 5.70±0.13 vs. 5.00±0.12, P <0.001; ventricular adipose tissue level 5.14±0.16 vs. 4.57±0.12, P =0.0048). The results also suggest that EAT quantity is not strongly correlated with BMI in nonfailing (atrial adipose tissue level r =0.069, ventricular adipose tissue level r =0.14) or failing (atrial adipose tissue level r =-0.022, ventricular adipose tissue level r =0.051) hearts. Atrial EAT is closely correlated with ventricular EAT in both nonfailing ( r =0.92, P <0.001) and failing ( r =0.87, P <0.001) hearts. Conclusions EAT volume appears to be inversely proportional to severity of or length of time with heart failure based on our findings. Based on a lack of correlation with BMI, it is incorrect to assume high EAT volume given high body fat percentage.

The relationship between hypothyroidism and the occurrence and progression of heart failure (HF) has had increased interest over the past years. The low T3 syndrome, a reduced T3 in the presence of normal thyroid stimulating hormone (TSH), and free T4 concentration, is a strong predictor of all-cause mortality in HF patients. Still, the impact of hypothyroidism on the contractile properties of failing human myocardium is unknown. Our study aimed to investigate that impact using ex-vivo assessment of force and kinetics of contraction/relaxation in left ventricular intact human myocardial muscle preparations. Trabeculae were dissected from non-failing (NF; n = 9), failing with no hypothyroidism (FNH; n = 9), and failing with hypothyroidism (FH; n = 9) hearts. Isolated muscle preparations were transferred into a custom-made setup where baseline conditions as well as the three main physiological modulators that regulate the contractile strength, length-dependent and frequency-dependent activation, as well as β-adrenergic stimulation, were assessed under near-physiological conditions. Hypothyroidism did not show any additional significant impact on the contractile properties different from the recognized alterations usually detected in such parameters in any end-stage failing heart without thyroid dysfunction. Clinical information for FH patients in our study revealed they were all receiving levothyroxine. Absence of any difference between failing hearts with or without hypothyroidism, may possibly be due to the profound effects of the advanced stage of heart failure that concealed any changes between the groups. Still, we cannot exclude the possibility of differences that may have been present at earlier stages. The effects of THs supplementation such as levothyroxine on contractile force and kinetic parameters of failing human myocardium require further investigation to explore its full potential in improving cardiovascular performance and cardiovascular outcomes of HF associated with hypothyroidism., Competing Interests: The authors have declared that no competing interests exist.

Background: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium., Methods and Results: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the β-adrenergic response to isoproterenol was depressed in both pathologies., Conclusions: Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)