Eleftherios M. Kallergis

Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and potential upstream therapies

Diabetes mellitus (DM) represents one of the most important risk factors for atrial fibrillation (AF) while AF is a strong and independent marker of overall mortality and cardiovascular morbidity in diabetic patients. Autonomic, electrical, electromechanical, and structural remodeling, including oxidative stress, connexin remodeling and glycemic fluctuations seem to be implicated in AF pathophysiology in the setting of DM. The present review highlights the association between DM and AF, provides a comprehensive overview of the responsible pathophysiological mechanisms and briefly discusses potential upstream therapies for DM-related atrial remodeling.

Extracellular Matrix Alterations in Patients With Paroxysmal and Persistent Atrial Fibrillation Biochemical Assessment of Collagen Type-I Turnover

OBJECTIVES We investigated whether the serum markers of collagen turnover differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in humans. BACKGROUND Structural alterations and fibrosis have been implicated in the generation and perpetuation of AF. METHODS Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation in 70 patients with AF and 20 healthy control subjects in SR. RESULTS C-terminal propeptide of collagen type-I and CITP were significantly higher in AF patients than in control subjects (91 +/- 27 ng/ml vs. 67 +/- 11 ng/ml, p < 0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25 +/- 0.08 ng/ml, p < 0.001, respectively). Persistent AF patients had higher levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p < 0.001), but not CITP, compared with those with paroxysmal AF. Patients with persistent AF had lower levels of matrix metalloproteinase-1 but increased levels of tissue inhibitor of matrix metalloproteinases-1 compared with patients with paroxysmal AF (11.90 +/- 4.79 ng/ml vs. 14.98 +/- 6.28 ng/ml, p = 0.03 and 155 +/- 45 ng/ml vs. 130 +/- 38 ng/ml, p < 0.001, respectively). Tissue inhibitor of matrix metalloproteinases-1 levels were significantly lower in control subjects compared with those in both paroxysmal and persistent AF patients (102 +/- 15 ng/ml vs. 130 +/- 38 ng/ml vs. 155 +/- 45 ng/ml, respectively, p < 0.001). CONCLUSIONS Serum markers of collagen type-I turnover differed significantly between patients with AF and SR. Furthermore, these markers also differed significantly between paroxysmal and persistent AF patients, suggesting that the intensity of the extracellular synthesis and degradation of collagen type-I may be related to the burden or type of AF.

Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

Long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.

Effects of Amiodarone and Diltiazem on Persistent Atrial Fibrillation Conversion and Recurrence Rates: A Randomized Controlled Study

AbstractPurpose: To assess the effects of amiodarone and diltiazem on atrial fibrillation (AF) induced atrial electrical remodeling and their clinical implications. Methods: Persistent AF patients were randomly assigned to three treatment groups over a period from 6 weeks before to 6 weeks after internal cardioversion: group A (35 patients, oral diltiazem), group B (34 patients, oral amiodarone) and group C (37 patients, no antiarrhythmic drugs). Several electrophysiological parameters were assessed 5 min and 24 h after cardioversion. Results: Compared with controls, group B patients had significantly higher conversion rates (83% vs. 100%, p = 0.041) and a higher probability to maintain sinus rhythm (p = 0.037). Patients of group B had longer fibrillatory cycle length intervals than patients of group A and C (180 ± 18 ms vs. 161 ± 17 ms vs. 164 ± 19 ms, p = 0.001) and longer atrial effective refractory periods (211 ± 22 ms vs. 198 ± 16 ms vs. 194 ± 17 ms, p = 0.003) as assessed 5 min after conversion. Post-conversion density of supraventricular ectopics was significantly lower in group B compared to groups A and C (p = 0.001). Conclusions: Oral amiodarone increases conversion rates, prolongs fibrillatory cycle length and atrial effective refractory period and preserves sinus rhythm after cardioversion in persistent AF patients by suppressing the atrial ectopics that trigger AF.

Serum Markers of Collagen Turnover Predict Future Shocks in Implantable Cardioverter-Defibrillator Recipients With Dilated Cardiomyopathy on Optimal Treatment

OBJECTIVES We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy (NIDC) who had received an implantable cardioverter-defibrillator (ICD) for primary prevention. BACKGROUND Extracellular matrix alterations in NIDC might provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent sudden cardiac death (SCD). METHODS Serum C-terminal propeptide of collagen type-I, C-terminal telopeptide of collagen type-I, matrix metalloproteinase (MMP)-1, and tissue inhibitor of MMP-1 were measured as markers of collagen synthesis and degradation in 70 patients with mild to moderate symptomatic heart failure due to NIDC with left ventricular ejection fraction <35%, who received an ICD for primary prevention of SCD. Patients were evaluated for any appropriate ICD delivered therapy, whether shock or antitachycardia pacing, during a 1-year follow-up period. RESULTS Appropriate device therapies were delivered in 14 of the 70 patients during the follow-up period, with antitachycardia pacing in 2, antitachycardia pacing with shocks in 4, and shocks in 8. Pre-implantation serum concentrations of C-terminal telopeptide of collagen type-I levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (0.46 +/- 0.19 ng/ml vs. 0.19 +/- 0.07 ng/ml, p < 0.001, respectively). The same was true for baseline MMP-1 and tissue inhibitor of MMP-1 (27.7 +/- 1.6 ng/ml vs. 24.1 +/- 2.5 ng/ml, p < 0.001, and 89 +/- 14 ng/ml vs. 58 +/- 18 ng/ml, p = 0.008, respectively). CONCLUSIONS If the maximum benefit is to be achieved from ICD therapy in NIDC patients for the primary prevention of SCD, a more precise risk stratification is required. As extracellular matrix alterations affect the arrhythmogenic substrate in NIDC, we observed that serum markers of collagen turnover could predict arrhythmic events in ICD recipients.

Sleep patterns in patients with acute coronary syndromes

BACKGROUND Little is known about sleep quality in patients with acute coronary syndromes (ACS) admitted to the coronary care unit (CCU). The aim of this study was to assess nocturnal sleep in these patients, away from the CCU environment, and to evaluate potential connections with the disease process. METHODS Twenty-two patients with first ever ACS, who were not on sedation or inotropes, underwent a full-night polysomnography (PSG) in our sleep disorders unit within 3 days of the ACS and follow-up PSGs 1 and 6 months later. RESULTS PSG parameters showed a progressive improvement over the study period. There was a statistically significant increase in total sleep time (TST), sleep efficiency, slow wave sleep (SWS), and rapid eye movement (REM) sleep, while arousal index, wake after sleep onset (WASO) and sleep latency decreased. Six months after the acute event, sleep architecture was within the normal range. CONCLUSIONS Patients with ACS have marked alterations in sleep macro- and micro-architecture, which have a negative influence on sleep quality. The changes tend to disappear over time, suggesting a relationship with the acute phase of the underlying disease.

Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links.

Obesity is a worldwide health problem with epidemic proportions that has been associated with atrial fibrillation (AF). Even though the underlying pathophysiological mechanisms have not been completely elucidated, several experimental and clinical studies implicate obesity in the initiation and perpetuation of AF. Of note, hypertension, diabetes mellitus, metabolic syndrome, coronary artery disease, and obstructive sleep apnea, represent clinical correlates between obesity and AF. In addition, ventricular adaptation, diastolic dysfunction, and epicardial adipose tissue appear to be implicated in atrial electrical and structural remodeling, thereby promoting the arrhythmia in obese subjects. The present article provides a concise overview of the association between obesity and AF, and highlights the underlying pathophysiological mechanisms.

Extracellular matrix alterations in the atria: insights into the mechanisms and perpetuation of atrial fibrillation

Atrial fibrillation is the most common arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Atrial fibrosis, a detrimental process that causes imbalance in extracellular matrix deposition and degradation, has been implicated as a substrate for atrial fibrillation, but the precise mechanisms of structural remodelling and the relationship between atrial fibrosis and atrial fibrillation are not completely understood. A large number of experimental and clinical studies have shed light on the mechanisms of atrial fibrosis at the molecular and cellular level, including interactions between matrix metalloproteinases and their endogenous tissue inhibitors, and profibrotic signals through specific molecules and mediators such as angiotensin II, transforming growth factor-β1, connective tissue growth factor, and platelet-derived growth factor. This review focuses on the mechanisms of atrial fibrosis and highlights the relationship between atrial fibrosis and atrial fibrillation.

Sleep Disordered Breathing in Patients with Acute Coronary Syndromes

STUDY OBJECTIVES Although the prevalence of obstructive sleep apnea/hypopnea syndrome (OSAHS) is high in patients with acute coronary syndromes (ACS), there is little knowledge about the persistence of OSAHS in ACS patients after the acute event. We aimed to assess the prevalence and time course of OSAHS in patients with ACS during and after the acute cardiac event. METHODS Fifty-two patients with first-ever ACS, underwent attended overnight polysomnography (PSG) in our sleep center on the third day after the acute event. In patients with an apnea hypopnea index (AHI) > 10/h, we performed a follow up PSG 1 and 6 months later. RESULTS Twenty-eight patients (54%) had an AHI > 10/h. There was a significant decrease in AHI 1 month after the acute event (13.9 vs. 19.7, p = 0.001), confirming the diagnosis of OSAHS in 22 of 28 patients (79%). At 6-month follow-up, the AHI had decreased further (7.5 vs. 19.7, p < 0.05), and at that time only 6 of the 28 patients (21%) were diagnosed as having OSAHS. Twelve of the 16 current smokers stopped smoking after the acute event. CONCLUSIONS We have demonstrated a high prevalence of OSAHS in ACS patients, which did not persist 6 months later, indicating that, to some degree, OSAHS may be transient and related with the acute phase of the underlying disease or the reduction in the deleterious smoking habit.

C-reactive protein evolution in obstructive sleep apnoea patients under CPAP therapy

Eur J Clin Invest 2010; 40 (11): 968–975