The Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target.

Elevated concentrations of free thyroid hormones are established cardiovascular risk factors, but the association of thyrotropin (TSH) levels to hard endpoints is less clear. This may, at least in part, ensue from the fact that TSH secretion depends not only on the supply with thyroid hormones but on multiple confounders including genetic traits, medication and allostatic load. Especially psychosocial stress is a still underappreciated factor that is able to adjust the set point of thyroid function. In order to improve our understanding of thyroid allostasis, we undertook a systematic meta-analysis of published studies on thyroid function in post-traumatic stress disorder (PTSD). Studies were identified via MEDLINE/PubMed search and available references, and eligible were reports that included TSH or free thyroid hormone measurements in subjects with and without PTSD. Additionally, we re-analyzed data from the NHANES 2007/2008 cohort for a potential correlation of allostatic load and thyroid homeostasis. The available evidence from 13 included studies and 3386 euthyroid subjects supports a strong association of both PTSD and allostatic load to markers of thyroid function. Therefore, psychosocial stress may contribute to cardiovascular risk via an increased set point of thyroid homeostasis, so that TSH concentrations may be increased for reasons other than subclinical hypothyroidism. This provides a strong perspective for a previously understudied psychoendocrine axis, and future studies should address this connection by incorporating indices of allostatic load, peripheral thyroid hormones and calculated parameters of thyroid homeostasis.

Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

INTRODUCTION: The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling. METHODS: We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control. These were compared with observed data points derived from clinical trials. RESULTS: A random mix of individual set points was reconstructed by simulative modelling with defined structural parameters. The pattern displayed by the cluster of hypothetical points resembled that observed in a natural control group. Moderate variation of the TSH-FT4 gradient over the functional range introduced further flexibility, implementing a scenario of adaptive set points. Such a scenario may be a realistic possibility for instance in treatment where relationships and equilibria between thyroid parameters are altered by various influences such as LT4 dose and conversion efficiency. CONCLUSIONS: We validated a physiologically based homeostatic model that permits simulative reconstruction of individual set points. This produced a pattern resembling the observed data under various conditions. Applied modelling, although still experimental at this stage, shows a potential to aid our physiological understanding of the interplay between TSH and thyroid hormones. It should eventually benefit personalised clinical decision making.

Impact of periprocedural anticoagulation strategy on the incidence of new-onset silent cerebral events after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCEs) have been observed on diffusion-weighted cerebral magnetic resonance imaging (MRI) in a substantial number of asymptomatic patients after atrial fibrillation (AF) ablation procedures. The purpose of this study was to investigate if periprocedural oral anticoagulation (OAC) management affects the incidence of new-onset SCE after radiofrequency catheter ablation (RFCA) of AF. METHODS AND RESULTS: One hundred ninety-two consecutive patients (64 ± 10.1 years, 38.5 % women) with symptomatic paroxysmal (n = 80, 41.7 %) or persistent AF undergoing RFCA of AF were prospectively enrolled. Periprocedural anticoagulation strategies were defined as uninterrupted use of novel oral anticoagulants (NOACs) (group I, n = 64), interrupted use of NOACs (group II, n = 42), continuation of vitamin K antagonist (VKA) with an international normalized ratio (INR) between 2.0 and 3.0 (group III, n = 43), and VKA discontinuation bridged with low molecular weight heparin (group IV, n = 43). Cerebral MRI was performed 1 to 2 days after RFCA for detection of new SCE. Overall, new SCEs were detected in 41 patients (21.4 %) after AF ablation. New SCEs were detected in 12.5 % in group I, 35.7 % in group II, 18.6 % in group III, and 23.3 % in group IV (p < 0.05). Multivariable logistic regression analysis revealed persistent AF and discontinuation of periprocedural OAC (group II and IV) to be independent predictors for the development of SCE. No relevant complications were identified. CONCLUSIONS: Periprocedural continuation of NOAC as well as continuation of VKA seems to be safe and significantly reduce the occurrence of SCE after AF ablation.

Association between left atrial low-voltage area, serum apoptosis, and fibrosis biomarkers and incidence of silent cerebral events after catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCE) have been identified on cerebral diffusion-weighted cerebral magnetic resonance imaging (DE-MRI) after catheter ablation (CA) of atrial fibrillation (AF). The purpose of this study was to investigate the impact of atrial remodeling on the incidence of SCE after AF CA. METHODS: Forty patients (67.8 ± 10 years, 47.5 % women) with symptomatic paroxysmal (n = 11, 27.5 %) or persistent AF undergoing AF CA were prospectively enrolled. LA fibrosis was estimated by intraprocedural bipolar voltage mapping in sinus rhythm. Apoptosis-stimulating fragment (Fas-Ligand) and amino terminal peptide from collagen III (PIIINP) concentrations were analyzed of LA and femoral vein blood. Cerebral DE-MRI was performed 1 to 2 days after CA of AF for detection of SCE. In nine patients (22.5 %), new SCE were detected on DE-MRI after AF CA. RESULTS: Patients with SCE had higher CHA2DS2-VASc score, larger left atrial diameter (LADmax), and higher surface area of left atrial low-voltage (24 ± 11.2 vs 3.5 ± 4.2 %, p < 0.0001). Concentrations of peripheral PIIINP (103.7 ± 25.9 vs 81.8 ± 16.7 pg/ml, p < 0.01) and Fas-Ligand (124.1 ± 22.4 vs 87.6 ± 19.4 pg/ml, p < 0.01) were significantly higher in patients with SCE and correlated to low-voltage surface area (p < 0.01). Multivariable logistic regression analysis revealed peripheral Fas-Ligand, LADmax, CHA2DS2-Vasc score, and LA low-voltage area proportion to be independent predictors for the development of SCE. CONCLUSIONS: LA remodeling, estimated by LADmax and LA low-voltage area, has significant relationship with the risk of SCE after AF ablation. Moreover, Fas-Ligand may act as an independent predictor for SCE in the context of AF CA.

Higher incidence of esophageal lesions after ablation of atrial fibrillation related to the use of esophageal temperature probes.

BACKGROUND: Endoscopically detected esophageal lesions (EDELs) have been identified in apparently asymptomatic patients after catheter ablation of atrial fibrillation (AF). The use of esophageal probes to monitor luminal esophageal temperature (LET) during catheter ablation to protect esophageal damage is currently controversial. OBJECTIVE: The purpose of this study was to investigate the impact of the use of esophageal temperature probes during AF catheter ablation on the incidence of EDELs. METHODS: Eighty consecutive patients (mean age 63.8 ± 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal (n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter ablation were prospectively enrolled. Posterior wall ablation was power limited (≤25 W). In the first 40 patients, LET was monitored continuously (group A), whereas no esophageal temperature probe was used in group B (n = 40 patients). Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency catheter ablation. RESULTS: Overall, 13 patients (16%) developed EDELs after AF ablation. The incidence of EDELs was significantly higher in group A than group B (30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher maximal LET during AF ablation than patients without EDEL (40.97 ± 0.92°C vs 40.14 ± 1.1°C, P = .02). Multivariable logistic regression analysis revealed the use of an esophageal temperature probe as the only independent predictor for the development of EDEL (odds ratio 16.7, P < .01). CONCLUSION: The use of esophageal temperature probes in the setting of AF catheter ablation per se appears to be a risk factor for the development of EDEL.

Reverse atrial remodeling in patients who maintain sinus rhythm after electrical cardioversion: evidence derived from the measurement of total atrial conduction time assessed by PA-TDI interval.

BACKGROUND: A key mechanism of atrial fibrillation (AF) is atrial remodeling. Total atrial conduction time non-invasively assessed via tissue Doppler imaging (PA-TDI interval) may reflect the degree of electrical and structural atrial remodeling. The purpose of this study was to determine whether the PA-TDI interval is an independent predictor of recurrent AF after successful electrical cardioversion (eCV) and if it suggests reverse atrial remodeling. METHODS: Fifty-one patients (mean ± SD 66 ± 10.6 years; 35 % women) with persistent AF and successful eCV were prospectively enrolled. The PA-TDI interval was measured 6 h and 90 days post-cardioversion. AF relapse was determined via 7-day Holter-ECG immediately after eCV and repeated after 90 days. RESULTS: Early recurrent AF (within 7 days) occurred in 21 patients (41.2 %), whereas after 90-day follow-up 26 patients (51 %) had AF recurrence. PA-TDI interval was longer in patients with AF recurrence within 90 days compared to patients who remained in sinus rhythm (SR) (149.1 ± 8.3 vs. 129.8 ± 10.9 ms, p < 0.0001). Optimal cut-off values for recurrent AF after 7 or 90 days from ROC analysis were 142 and 143 ms, respectively. Furthermore, the PA-TDI interval decreased significantly from baseline in those who remained in SR (129.8 ± 10.9 vs. 125.8 ± 10 ms, p < 0.0001), whereas the PA-TDI interval increased in patients who developed AF after 90 days (149.1 ± 8.3 vs. 152 ± 9 ms, p < 0.0001). CONCLUSIONS: The PA-TDI interval is an independent predictor of early and mid-term AF recurrence after eCV. Moreover, our data suggests reverse atrial remodeling in those patients who remained in stable SR.

Increased preoperative serum apoptosis marker fas ligand correlates with histopathology and new-onset of atrial fibrillation in patients after cardiac surgery.

BACKGROUND: We evaluated if preoperative serum apoptosis markers correlate with atrial histological remodeling and postoperative atrial fibrillation (POAF) after cardiac surgery. METHODS AND RESULTS: A total of 33 patients with sinus rhythm (SR) and without history of atrial fibrillation (AF) undergoing cardiac surgery were prospectively enrolled. Serum concentrations of Fas (apoptosis-stimulating fragment ligand) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured preoperatively. Right atrial appendage (RAA) tissue was obtained during surgery. Atrial apoptosis was assessed via TUNEL assay and degree of atrial fibrosis was categorized histologically by visual quantification. Continuous ECG-Monitoring was used to screen for POAF throughout 10 days after cardiac surgery. POAF occurred in 15 patients (45%). Atrial apoptosis was higher in patients with POAF as compared to those without (35.9 ± 9.8% vs 14.5 ± 7.5%; P < 0.0001) and correlated with the degree of atrial fibrosis (r = 0.69; P < 0.0001). In contrast to TRAIL (87.0 ± 8.2 pg/mL vs 83.3 ± 9.4 pg/mL; P = 0.77), preoperative Fas serum concentration was significantly higher in patients with POAF compared to patients in stable SR (91.3 ± 7.2 pg/mL vs 66.7 ± 3.0 pg/mL; P < 0.01). Serum Fas concentration correlated with the degree of atrial apoptosis (r = 0.63; P < 0.001) and the degree of atrial fibrosis (r = 0.39; P < 0.05). CONCLUSION: Preoperative evaluation of serum apoptosis marker Fas is useful to identify patients at risk for POAF undergoing cardiac surgery. Fas but not TRAIL correlates with the documented degree of atrial apoptosis and atrial fibrosis in RAA tissue. Further studies need to identify the prospective role of Fas in predicting POAF events.