Thyroid (Dys)Function in Heart Failure: Is it a Potential Target for Medical Treatment?

Alessandro Pingitore, Giorgio IervasiInstitute of Clinical Physiology, CNR, Pisa, ItalyIntroductionCurrently, there is little doubt that activation of the neuroendocrine (NE) system is predominately responsible for the progressive decline of heart function in heart failure (HF). This is due to the complex action of neurotransmitters, hormonal factors, and/or immunological pathways. Evidence that supports this point of view is the clear prognostic benefit and the reduction of HF progression by using NE-guided therapeutic approaches (SOLVD investigators 1992; Eichhorn and Bristow 1996; Packer et al 1996; Opie 2004; Solomon et al 2004). However, the fact that HF represents one of the major causes of morbidity and mortality in Western countries also suggests that the current portfolio of NE antagonists fails to completely explain and possibly counteract disease progression (Guyatt and Deveraux 2004). In this context, interest in the relationship between thyroid hormones (THs) and HF is increasingly gaining prominence. The chief reason for the latter is the emerging novel actions of THs on the cardiovascular system and, more specifically, the role of TH as a prognostic biomarker of cardiac disease as well as the potential benefit of TH administration in patients with HF

Thyroid hormone and heart failure: from myocardialprotection to systemic regulation

Heart failure (HF) is an intriguing model of chronic disease. It starts as an organ disorder developing, in its progression, into a systemic disease in which the dysfunction of other organs plays a relevant clinical and prognostic impact. Furthermore, continuous activation of systemic pathways plays a role in disease progression, switching their effect from protective to harmful. In this combination of organ dysfunction and systemic derangement, thyroid hormone (TH) have an important regulative impact from cardiovascular to systemic level and from molecular/cellular processes to clinical setting. Whether it is accepted to include TH and thyroid stimulating hormone assessment in the clinical HF course, the next challenge will be to ascertain the benefit of TH replacement therapy in HF patients, taking into consideration the type of hormone to administer, dosage and treatment schedule

Sweat Rate Monitoring During Maximal Exercise in Healthy Soccer Players: A Close Relationship with Anaerobic Threshold

Purpose: Sweating is a homeostatic phenomenon regulated by both thermal and non-thermal factors during exercise. There are no evidences whether anaerobic metabolism induced during isotonic maximal exercise can modify sweating rate. Aim of the study was to investigate the relationship between sweating and the anaerobic threshold (AT). Methods: The sweat rate in thirteen soccer players was measured by a sensor providing a continuous monitoring of sweating, whereas the anaerobic threshold was assessed with ergospirometry during maximal isotonic stress test. During stress test, cardio respiratory, metabolic and galvanic skin response (GSR) were also monitored. Results: At AT, stroke volume, heart rate and systolic blood pressure significantly increased (p<0.001), as well as GSR (p=0.04). Sweat rate abruptly increased at AT compared with rest (p<0.001). AT-to-rest changes in sweating rate were associated with concomitant changes in VO2 max (r=0.82, p<0.001), heart rate (r=0.73, p=0.04) and GSR (r=0.79, p=0.001). Conclusion: We suggest that aerobic-to-anaerobic switch is associated with a sudden increase in sweating likely induced by sympathetic activation. Considering the role of hydration in preserving the health status and optimizing the physical performance, we believe that this finding may have relevant practical implication in particular in soccer, which is characterized by an alternation of aerobic and anaerobic phases

Low-T3 Syndrome

Background— Clinical and experimental data have suggested a potential negative impact of low-T3 state on the prognosis of cardiac diseases. The aim of the present prospective study was to assess the role of thyroid hormones in the prognosis of patient population with heart disease. Methods and Results— A total of 573 consecutive cardiac patients underwent thyroid function profile evaluation. They were divided in two subgroups: group I, 173 patients with low T3, ie, with free T3 (fT3) <3.1 pmol/L, and group II, 400 patients with normal fT3 (≥3.1 pmol/L). We considered cumulative and cardiac death events. During the 1-year follow-up, there were 25 cumulative deaths in group I and 12 in group II (14.4% versus 3%, P <0.0001); cardiac deaths were 13 in group I and 6 in group II (7.5% versus 1.5%, P =0.0006). According to the Cox model, fT3 was the most important predictor of cumulative death (hazard ratio [HR] 3.582, P <0.0001), followed by dyslipidemia (HR 2.955, P =0.023), age (HR 1.051, P <0.005), and left ventricular ejection fraction (HR 1.037, P =0.006). At the logistic multivariate analysis, fT3 was the highest independent predictor of death (HR 0.395, P =0.003). A prevalence of low fT3 levels was found in patients with NYHA class III-IV illness compared with patients with NYHA class I-II (χ 2 5.65, P =0.019). Conclusions— Low-T3 syndrome is a strong predictor of death in cardiac patients and might be directly implicated in the poor prognosis of cardiac patients

Different substrates of non-sustained ventricular tachycardia in post-infarction patients with and without left ventricular dilatation

Background: We investigated the relationship between nonsustained ventricular tachycardia (NSVT) and left ventricular (LV) dilatation, function, remodeling, and scar tissue extent in patients with previous myocardial infarction (MI). Methods and Results: Eighty-two patients (ages 64610 years) with first previous MI were referred for 24-hour electrocardiogram recording and cine and delayed enhancement (DE) cardiac magnetic resonance (CMR). LVvolumes, ejection fraction, systolic wall thickening, sphericity index, and core and peri-infarctual areas of scar tissue by CMR were evaluated. LV dilatation was observed in 39 patients. Episodes of NSVT were recorded in 32 patients: 23 with LV dilatation and 9 without. In the entire population, NSVTwas related to ejection fraction, LV volumes, LV mass, and sphericity index; end-systolic volume (P5.001) resulted in the only independent predictor at multivariate analysis. In patients without LV dilatation, the occurrence of NSVTwas only positively related with percentage of contracting segments with DE (P5.008). Conversely, in patients with LV dilatation, increase in LV mass (P5.020) and end-systolic volume (P5.038) were independent predictors of NSVT. Conclusions: Necrotic and viable myocardium coexistence within the same wall segments predicted occurrence of NSVT in patients without LV dilatation, whereas LV mass and end-systolic volume were predictors of NSVT in those with LV dilatation. (J Cardiac Fail 2010;16:61e68

Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy

Background: Cardiovascular Magnetic resonance (CMR) with the late gadolinium enhancement (LGE) technique allows the detection of myocardial fibrosis in Hypertrophic cardiomyopathy (HCM). The aim of this study was to compare different methods of automatic quantification of LGE in HCM patients. Methods: Forty HCM patients (mean age 48 y, 30 males) and 20 normal subjects (mean age 38 y, 16 males) underwent CMR, and we compared 3 methods of quantification of LGE: 1) in the SD2 method a region of interest (ROI) was placed within the normal myocardium and enhanced myocardium was considered as having signal intensity&gt;2 SD above the mean of ROI; 2) in the SD6 method enhanced myocardium was defined with a cut-off of 6 SD above mean of ROI; 3) in the RC method a ROI was placed in the background of image, a Rayleigh curve was created using the SD of that ROI and used as ideal curve of distribution of signal intensity of a perfectly nulled myocardium. The maximal signal intensity found in the Rayleigh curve was used as cut-off for enhanced myocardium. Parametric images depicting non enhanced and enhanced myocardium was created using each method. Three investigators assigned a score to each method by the comparison of the original LGE image to the respective parametric map generated. Results: Patients with HCM had lower concordance between the measured curve of distribution of signal intensity and the Rayleigh curve than controls (63.7 ± 12.3 % vs 92.2 ± 2.3%, p &lt; 0.0001)

Mind-body relationships in elite apnea divers during breath holding: a study of autonomic responses to acute hypoxemia

The mental control of ventilation with all associated phenomena, from relaxation to modulation of emotions, from cardiovascular to metabolic adaptations, constitutes a psychophysiological condition characterizing voluntary breath-holding (BH). BH induces several autonomic responses, involving both autonomic cardiovascular and cutaneous pathways, whose characterization is the main aim of this study. Electrocardiogram and skin conductance (SC) recordings were collected from 14 elite divers during three conditions: free breathing (FB), normoxic phase of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features describing signal dynamics between the three experimental conditions: from heart rate variability (HRV) features (in time and frequency-domains and by using nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main result of the study rises by applying a Factor Analysis to the subset of features significantly changed in the two BH phases. Indeed, the Factor Analysis allowed to uncover the structure of latent factors which modeled the autonomic response: a factor describing the autonomic balance (AB), one the information increase rate (IIR), and a latter the central nervous system driver (CNSD). The BH did not disrupt the FB factorial structure, and only few features moved among factors. Factor Analysis indicates that during BH (1) only the SC described the emotional output, (2) the sympathetic tone on heart did not change, (3) the dynamics of interbeats intervals showed an increase of long-range correlation that anticipates the HPBH, followed by a drop to a random behavior. In conclusion, data show that the autonomic control on heart rate and SC are differentially modulated during BH, which could be related to a more pronounced effect on emotional control induced by the mental training to BH

Early Hypertension Is Associated With Reduced Regional Cardiac Function, Insulin Resistance, Epicardial, and Visceral Fat

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47±1 years; body mass index: 28.4±0.6 kg . m −2 ; mean±SEM) included 13 with normal blood pressure (BP: 113±5/67±2 mm Hg), 13 with prehypertension (BP: 130±1/76±2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150±2/94±2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from −17.0±0.5% in normal blood pressure to −15.2±0.7% in prehypertension to −13.6±0.8% in those newly diagnosed with essential hypertension; P =0.004). Reduced circumferential strain was significantly associated with raised BP independent of age ( r =0.41; P =0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function