Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

AIM: Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. METHODS AND RESULTS: One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). CONCLUSION: Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling.

Symptom severity and quality of life in patients with atrial fibrillation: Psychological function outweighs clinical predictors.

BACKGROUND: The key drivers of symptom severity and health-related quality of life (hr-QOL) in patients with atrial fibrillation (AF) remain unclear. We aimed to determine the relative contribution to symptom severity and hr-QOL of clinical factors including left ventricular (LV) diastolic function and ventricular rate control during AF and of psychological functioning. METHODS: Seventy-eight consecutive patients with symptomatic AF and preserved LV systolic function underwent detailed evaluation of i) AF symptom severity and hr-QOL; ii) clinical factors including left ventricular (LV) diastolic function, AF burden, and ventricular rate during AF and iii) state and trait aspects of psychological functioning. RESULTS: Moderate-to-severe AF-related symptoms were reported by 64% of the study population whilst 36% reported no more than mild symptoms. Worse symptom severity was associated with a higher score on the Perceived Stress Scale (16.7 ±â€¯4.4 vs. 5.4 ±â€¯4.4, p < 0.0001) and higher prevalence of the Type D Personality (20/50 vs. 4/28, p = 0.012). In multivariable models, only a predisposition to subjectively appraise life situations as stressful (higher PSS score) and a personality with a higher degree of negative affectivity and social inhibition (higher TDPS score) were independent predictors of higher AF symptom severity and poorer hr-QOL. No clinical factors including AF burden, ventricular rates during AF or LV diastolic function were significant predictors of AF-specific symptoms or hr-QOL. CONCLUSION: In a tertiary AF population with preserved LV systolic function, only psychological functioning consistently predicts both AF-related symptoms and hr-QOL. LV diastolic function, AF burden, and ventricular rate during AF are not independent predictors.

Psychological Distress and Suicidal Ideation in Patients With Atrial Fibrillation: Prevalence and Response to Management Strategy.

Background An association between atrial fibrillation ( AF ), anxiety, and depression is recognized, but the spectrum of psychological distress remains unclear. We aimed to characterize the severity and predictors of distress associated with AF in a tertiary population and its response to AF management. Methods and Results Seventy-eight patients with symptomatic AF underwent evaluation, including of AF symptom severity, health-related quality of life, psychological distress, suicidal ideation, and specific personality traits. Twenty participants underwent AF ablation and 58 were managed medically, with repeat assessments at 4, 8, and 12 months. Severe distress (Hospital Anxiety and Depression Scale score, ≥15/42) was identified in 27 of 78 (35%). Independent predictors were a personality marked by vulnerability to stress (Perceived Stress Scale: R2, 0.54; ß=0.7±0.1; t=7.8; P<0.001) and 1 marked by negativity/social inhibition (Type D Personality Scale: R2, 0.47; ß=0.7±0.1; t=6.7; P<0.001). Suicidal ideation was reported by 16 of 78 (20%) and was predicted by personality traits (Perceived Stress Scale score: R2, 0.35; odds ratio, 1.22±0.06; P<0.001; Type D Personality Scale score: R2, 0.48; odds ratio, 1.43±0.14; P<0.001). Effective AF ablation (median AF burden 1% [0-1%] over 12 months) was associated with significant reductions in distress (Hospital Anxiety and Depression Scale score, 13.9±1.8 to 4.3±1.8; P<0.05) and prevalence of suicidal ideation (30-5%; P=0.02). Conclusions There was a high prevalence of severe psychological distress (35%) and of suicidal ideation (20%) in a tertiary AF population, with personality traits predicting both. Effective AF ablation was associated with significant improvements, suggesting AF itself may be a treatable causative factor of distress.

Progression of atrial remodeling in patients with high-burden atrial fibrillation: Implications for early ablative intervention.

BACKGROUND: Advanced atrial remodeling predicts poor clinical outcomes in human atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to define the magnitude and predictors of change in left atrial (LA) structural remodeling over 12 months of AF. METHODS: Thirty-eight patients with paroxysmal AF managed medically (group 1), 20 undergoing AF ablation (group 2), and 25 control patients with no AF history (group 3) prospectively underwent echocardiographic assessment of strain variables of LA reservoir function at baseline and at 4, 8, and 12 months. In addition, P-wave duration (Pmax,, Pmean) and dispersion (Pdis) were measured. AF burden was quantified by implanted recorders. Twenty patients undergoing ablation underwent electroanatomic mapping (mean 333 ± 40 points) for correlation with LA strain. RESULT: Group 1 demonstrated significant deterioration in total LA strain (26.3% ± 1.2% to 21.7% ± 1.2%, P < .05) and increases in Pmax (132 ± 3 ms to 138 ± 3 ms, P < .05) and Pdis (37 ± 2 ms to 42 ± 2 ms, P < .05). AF burden ≥10% was specifically associated with decline in strain and with P-wave prolongation. Conversely, group 2 manifest improvement in total LA strain (21.3% ± 1.7% to 28.6% ± 1.7%, P <.05) and reductions in Pmax (136 ± 4 ms to 119 ± 4 ms, P < .05) and Pdis (47 ± 3 ms to 32 ± 3 ms, P < .05). Change was not significant in group 3. LA mean voltage (r = 0.71, P = .0005), percent low voltage electrograms (r = -0.59, P = .006), percent complex electrograms (r = -0.68, P = .0009), and LA activation time (r = -0.69, P = .001) correlated with total strain as a measure of LA reservoir function. CONCLUSION: High-burden AF is associated with progressive LA structural remodeling. In contrast, AF ablation results in significant reverse remodeling. These data may have implications for timing of ablative intervention.