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Background and Objectives: To evaluate the influence of obstructive sleep apnea (OSA)-related symptoms on prevalent cardiovascular disease (CVD) in a large clinical population of patients. Materials and Methods: A total of 2127 patients (mean age 55 years, 24% women) underwent diagnostic polysomnography and were evaluated using the Epworth sleepiness scale (ESS), the Athens Insomnia Scale (AIS), and the Beck Depression Inventory (BDI). We investigated the predictive value of OSA-associated symptoms for prevalent cardiovascular disease, after adjustment for relevant confounding factors including age, obesity, and co-morbidities. Results: Patients with OSA and CVD were older and had a higher Body Mass Index (BMI), the percentage of obese patients was also higher (83% vs. 70%, p &lt, 0001). They also had greater neck, waist, and hip circumferences and a higher waist-to-hip ratio. Excessive daytime sleepiness (ESS ≥ 10) [odds ratio (95% CI) 1.112 (0.708–1.748), p = 0.64], insomnia symptoms (AIS ≥ 6) [odds ratio (95% CI) 0.748 (0.473–1.184), p = 0.21], frequent awakenings [odds ratio (95% CI) 1.599 (1.019–2.508), p = 0.06], and nocturia [odds ratio (95% CI) 1.359 (0.919–2.009), p = 0.124] were not associated with CVD after adjustment for the previous confounders. On the other hand, depressive symptoms (BDI ≥ 10) independently predicted prevalent CVD [odds ratio (95% CI) 1.476 (1.154–1.887), p = 0.002]. Further analysis in subgroups stratified by age, BMI, and gender demonstrated that depressive symptoms predicted prevalent CVD but only in the subgroup of younger (age group &lt, 60 years), obese (BMI group ≥ 30), and male (OR = 1.959, 95% CI = 1.209–3.175, p = 0.006) OSA patients. Conclusions: OSA patients with CVD were more likely to complain of less typical OSA symptoms and depressive symptoms compared to patients without CVD in this large clinical patient cohort, supportingthecomplexity and heterogeneityof OSA.

Background: Studies conducted in coronary intensive care units (CICUs) have demonstrated that tachyarrhythmias are associated with increased mortality after acute coronary syndromes (ACSs). However, the data for tachyarrhythmias occurred in CICUs due to a variety of cardiovascular disorders are limited. Methods: We conducted a single-center prospective observational study, which included consecutive CICU patients (January 1, 2014 to May 31, 2018). We recorded the ventricular arrhythmias (VAs), supraventricular tachycardias (SVTs), and days of CICU hospitalization. The patients were followed up for 6 months after CICU discharge. Results: A total of 943 patients (age: 66.37 ±15.4 years; 673 males [71.4%]) were included. Patients with tachyarrhythmias had higher in-CICU mortality (8.0% vs 4.1%, P = .029, odds ratio [OR]: 2.04, 95% confidence interval [CI]: 1.08-3.86) and higher 6-month all-cause mortality (12.8% vs 6.1%, P = .002, OR: 2.27, 95% CI: 1.35-3.83) than those who did not develop tachyarrhythmias. Ventricular arrhythmias was significantly associated with higher all-cause mortality than no tachyarrhythmia (15.4% vs 6.1%; P = .001) or SVTs (15.4% vs 7.0%; P = .001). The mean duration of hospitalization for the patients with tachyarrhythmias was 3.89 ± 4.90 days, while for the patients without was 2.79 ± 3.31 days ( P < .001). Patients without ACS had higher short- and long-term mortality compared to patients with ACS (9.2% vs 2.9%, P < .001 and 12.9% vs 4.9%, P < .001). Conclusions: Tachyarrhythmias were associated with prolonged CICU hospitalization, while non-ACS cardiovascular disorders and the occurrence of VAs were associated with increased short- and long-term mortality.

Systemic inflammation is important in obstructive sleep apnea (OSA) pathophysiology and its comorbidity. We aimed to assess the levels of inflammatory biomarkers in a large sample of OSA patients and to investigate any correlation between these biomarkers with clinical and polysomnographic (PSG) parameters. This was a cross-sectional study in which 2983 patients who had undergone a polysomnography for OSA diagnosis were recruited. Patients with known comorbidities were excluded. Included patients (n=1053) were grouped according to apnea-hypopnea index (AHI) as mild, moderate, and severe. Patients with AHI p<0.05). Females had increased levels of hs-CRP, fibrinogen, and ESR (p<0.001) compared to men. In contrast, UA levels were higher in men (p<0.001). Our results suggest that inflammatory markers significantly increase in patients with OSA without known comorbidities and correlate with OSA severity. These findings may have important implications regarding OSA diagnosis, monitoring, treatment, and prognosis. This trial is registered with ClinicalTrials.gov numberNCT03070769.

There are limited data about the management of patients presenting for elective generator replacements in the setting of previously implanted cardiac resynchronization therapy (CRT) devices that are nearing end-of-life. The individual patient's clinical status and concomitant morbidities may evolve so that considerations may include not only replacement of the pulse generator, but also potentially changing the type of device [e.g. downgrading CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) or ICD or upgrading of CRT-P to CRT-D]. Moreover, the clinical evidence for CRT-D/CRT-P implantation may change over time, with ongoing research and availability of new trial data. In this review we discuss the ethical, clinical and financial implications related to CRT generator replacements and the need for additional clinical trials to better understand which patients should undergo CRT device downgrading or upgrading at the time of battery depletion.

Scientific data about the effects of positive airway pressure (PAP) treatment on blood pressure (BP) control are continuously increasing; however, they are controversial. We aimed to determine the long-term effects of compliance with PAP therapy on BP in both hypertensive and normotensive patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). One thousand one hundred sixty eight consecutive patients with newly diagnosed OSAHS, who had been recommended PAP therapy, were followed up for a minimum of 2 years. Patients with previous cardiovascular disease were excluded. BP was measured at baseline and after 2 years of PAP treatment. In addition, the correlation between the changes in BP with different levels of PAP compliance was assessed. At the end of the follow-up period, in the hypertensive group of patients (n=586), a significant decrease was shown in systolic (-11.2 mm Hg, P0.001) and diastolic BP (-4.2 mm Hg, P0.001). Furthermore, in the patients without hypertension (n=528), a significant decrease was noted both in systolic and diastolic BP (-3.6, P0.001 and -2.4, P0.001, respectively). A correlation between the magnitude of change in systolic and diastolic BP and hours of use of PAP (r=0.14, P=0.002 and r=0.1, P=0.025, respectively) was observed in all patients. Long-term use of PAP treatment, as well as increased hours of PAP in patients with OSAHS use showed significant reductions in BP not only in patients with hypertension, but also in normotensive patients. Therefore a significant potential reduction in cardiovascular mortality and morbidity should be expected in these patients.

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.

Background Atrial fibrillation (AF) is associated with abnormal atrial substrate. We investigated whether patients with persistent lone AF and patients with persistent AF and nonischemic dilated cardiomyopathy (NIDCM) exhibit any differences in electrophysiological and electroanatomical properties of right atrium (RA) and collagen turnover. We also investigated the relationship between mean RA bipolar voltage and collagen turnover. Methods Ten patients with a history of persistent lone AF and eight patients with a history of persistent AF and NIDCM were studied. Sinus node recovery times (SNRTs) and effective refractory periods (ERPs) at 600 ms, 500 ms, and 400 ms from the high (HLRA) and low (LLRA) lateral RA, proximal coronary sinus (pCS), and right atrial appendage (RAA) were evaluated, and RA electroanatomic mapping was created. Serum N-terminal propeptide of collagen type I (PINP), cross-linked C-terminal telopeptide of collagen type I (CTx), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinases (TIMP-1) were measured as markers of collagen synthesis and degradation. Results No differences were found in SNRTs, ERPs from the HLRA, LLRA at 600 ms, pCS and RAA, mean RA bipolar voltage, serum PINP, CTx, MMP-1, and TIMP-1 between the two groups. In persistent lone AF, serum levels of TIMP-1 were related with mean HLRA and HPRA bipolar voltage. Conclusions Persistent AF patients with or without NIDCM, demonstrate similar changes in electrophysiological and electroanatomical properties of the RA, as well as similar structural changes. Moreover, serum markers of collagen synthesis are correlated with bipolar voltage in specific regions of RA in persistent lone AF.

The presentation of atrial fibrillation (AF) varies remarkably, from totally asymptomatic to symptomatic patients, while the same individual may present symptomatic and asymptomatic episodes. We aimed to identify electrocardiographic differences between symptomatic and asymptomatic episodes and to find parameters related to the appearance of symptoms.Thirty consecutive patients (age 66.9±10years) with paroxysmal AF received an implantable loop recorder. Three types of episodes were defined: asymptomatic (ASx), symptomatic (Sx), and mixed asymptomatic-symptomatic (AS-Sx). The heart rate (HR) and heart rate variability (HRV) were recorded during the first 2min of each ASx or Sx episode, and during the first 2min of both the symptomatic and asymptomatic periods in AS-Sx.Eighty-two episodes from twenty-five patients were evaluated. Mean HR was 142.48±25.84bpm for Sx and 95.71±19.29bpm for ASx (p0.001). Mean HRV was 92.62±42.29ms for Sx and 150.06±49.68ms for ASx (p0.001). In AS-Sx, mean HR was 102.91±24.54bpm for the asymptomatic and 141.88±23.43bpm for the symptomatic period (p0.001). Mean HRV was 173.55±61.30ms for the asymptomatic and 87.33±30.65ms for the symptomatic period (p=0.003). There were no significant correlations between patients' characteristics and the clinical presentation of the arrhythmia.The ASx were characterized by a lower HR and higher HRV compared to Sx. In As-Sx, the asymptomatic period was characterized by a lower HR and higher HRV compared to the symptomatic. These findings suggest a possible contribution of variations in the autonomic nervous system activity to the perception of the arrhythmia.

Eur J Clin Invest 2010; 40 (11): 968–975 Abstract Background C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. Methods Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. Results A significant reduction in CRP levels was observed after CPAP therapy (0·74 ± 0·62 mg dL−1 vs. 0·31 ± 0·29 mg dL−1, P

ObjectivesWe 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.BackgroundExtracellular matrix alterations in NIDC might provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent sudden cardiac death (SCD).MethodsSerum 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

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.

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 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.

It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process.

Atrial fibrillation (AF) is associated with abnormal atrial substrate. We investigated whether patients with persistent lone AF and patients with persistent AF and nonischemic dilated cardiomyopathy (NIDCM) exhibit any differences in electrophysiological and electroanatomical properties of right atrium (RA) and collagen turnover. We also investigated the relationship between mean RA bipolar voltage and collagen turnover.Ten patients with a history of persistent lone AF and eight patients with a history of persistent AF and NIDCM were studied. Sinus node recovery times (SNRTs) and effective refractory periods (ERPs) at 600 ms, 500 ms, and 400 ms from the high (HLRA) and low (LLRA) lateral RA, proximal coronary sinus (pCS), and right atrial appendage (RAA) were evaluated, and RA electroanatomic mapping was created. Serum N-terminal propeptide of collagen type I (PINP), cross-linked C-terminal telopeptide of collagen type I (CTx), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinases (TIMP-1) were measured as markers of collagen synthesis and degradation.No differences were found in SNRTs, ERPs from the HLRA, LLRA at 600 ms, pCS and RAA, mean RA bipolar voltage, serum PINP, CTx, MMP-1, and TIMP-1 between the two groups. In persistent lone AF, serum levels of TIMP-1 were related with mean HLRA and HPRA bipolar voltage.Persistent AF patients with or without NIDCM, demonstrate similar changes in electrophysiological and electroanatomical properties of the RA, as well as similar structural changes. Moreover, serum markers of collagen synthesis are correlated with bipolar voltage in specific regions of RA in persistent lone AF.

Although inhaled beta2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled beta2-agonist in humans.Prospective study.Tertiary referral center.Six patients with bronchial asthma and 12 patients with mild COPD.All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose).Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective beta2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 +/- 19.5 ms at baseline to 78.8 +/- 18.4 ms (p0.001), and the WCL decreased from 354.4 +/- 44.2 to 336.6 +/- 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 +/- 12.8 beats/min at baseline to 93.1 +/- 16 beats/min, p0.001) and shortened the SNRT (from 1,073.5 +/- 178.7 to 925.2 +/- 204.9 ms, p = 0.001).Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.

Aim Changes in ventricular refractoriness and repolarization after successful electrical cardioversion to sinus rhythm in persistent atrial fibrillation (AF) patients were studied. Methods and results In 33 AF patients with controlled ventricular response, right ventricular ERP (VERP) at three basic cycle lengths (600, 500, 400 ms), as well as monophasic action potential duration (MAPd90) at a drive cycle length of 500 ms, were measured just before, 20 min and 24 h after cardioversion. VERP at 600 ms changed from 241 ± 19 ms to 249 ± 21 ms to 253 ± 24 ms ( P < 0.001), VERP at 500 ms changed from 234 ± 19 ms to 242 ± 22 ms to 246 ± 23 ms ( P < 0.001) and VERP at 400 ms changed from 224 ± 20 ms to 232 ± 23 ms to 236 ± 24 ms ( P < 0.001). MAPd90 changed from 247 ± 16 ms preconversion to 252 ± 17 ms 20 min postconversion to 253 ± 19 ms after 24 h ( P < 0.05). Change in refractoriness at 500 ms was well correlated with change of mean RR interval before and 20 min after conversion ( R = 0.616, P < 0.001). There was no correlation between RR variability and VERP before cardioversion. Conclusion Restoration of sinus rhythm in persistent AF patients is followed by significant effects on ventricular refractoriness and repolarization related to cycle length change. No AF related ventricular electrophysiological alterations were found.

Purpose: To assess the effects of amiodarone and diltiazem on atrial fibrillation (AF) induced atrial electrical remodeling and their clinical implications.

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.

Obstructive sleep apnea syndrome (OSAS) is a common medical condition, associated with atherosclerosis and cardiovascular disease (CVD). The underlying pathophysiologic mechanisms of this association have not been completely understood and may be multifactorial in origin. A number of studies suggest that inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS. A range of circulating inflammatory molecules has been identified and measured, with a view to assess inflammation and predict vascular damage risk, such as plasma cytokines, adhesion molecules, and C-reactive protein (CRP). CRP is a relevant marker worthy of further study, because not only is elevated in patients with OSAS, but also is rapidly becoming a risk factor for cardiac disease. Furthermore, in selected OSAS patients, aggressive treatment of the disorder may lead to retarding or even improvement of CVD progression. However, still there is a debate on the true correlation between CRP and OSAS, as well as the clinical effect of any reduction after OSAS treatment. Further research is required to define those OSAS patients who will have a considerable reduction with treatment, as well as to understand the significance of the interaction between cardiovascular risk factor and CRP reduction in patients with OSAS.

Aims Collagen turnover and atrial fibrosis have been implicated in the generation and perpetuation of atrial fibrillation (AF). We evaluated the importance of serum markers of collagen turnover in predicting the outcome of electrical cardioversion (CV) of persistent AF and the relationship between AF and fibrosis. Methods and results Serum C-terminal pro-peptide of collagen type-I (CICP) and C-terminal telopeptide of collagen type-I (CITP) were measured in 164 patients with AF before and 2 months after CV. All the patients were successfully cardioverted to sinus rhythm (SR) although in 38 of them AF recurred. Baseline CICP levels were comparable in patients in SR 60 days after CV and in those who experienced a relapse of AF (85.08 ± 16.99 vs. 87.55 ± 10.43 ng/mL, respectively, P = ns). Baseline CITP levels were significantly higher in patients with AF recurrence compared with those who remained in SR (0.48 ± 0.16 vs. 0.32 ± 0.17 ng/mL, respectively, P < 0.0001). In the 126 patients who maintained the SR, CICP levels were significantly lower at the end of the study as compared with the baseline (63.74 ± 15.92 vs. 85.08 ± 16.99 ng/mL P = 0.003), while there was a mild increase in plasma CITP levels (0.36 ± 0.21 vs. 0.32 ± 0.17 ng/mL, respectively, P = 0.03). Conclusion Atrial fibrillation can result in alterations in atrial structure and architecture that make the atrial myocardium more susceptible to the maintenance of the arrhythmia. Sinus rhythm restoration could affect the fibrotic process occurring or exacerbating during AF course.

Sinus Node Remodeling and Atrial Fibrillation. Introduction: The objective of this study was to investigate the temporal changes in sinus node function in postcardioversion chronic atrial fibrillation (AF) patients and their possible relation with the recurrence rates of AF. Methods and Results: In 37 chronic AF patients, internally cardioverted to sinus rhythm, corrected sinus node recovery time (CSNRT), and the pattern of corrected return cycle lengths were assessed 5 to 20 minutes and 24 hours after conversion. The last 20 consecutive patients also were evaluated after autonomic blockade. Twenty subjects with normal atrial structure and no history of AF served as the control group. Patients were followed-up for 1 month for recurrence, and the density of supraventricular ectopic beats per hour was obtained during the first 24 hours after conversion. Fifteen patients (40.5%) relapsed during follow-up. CSNRT values at 600 msec (371 ± 182 msec) and 500 ms (445 ± 338 msec) were significantly higher than those of control subjects (278 ± 157 msec, P = 0.050, and 279 ± 130 msec, P = 0.037, respectively). Significant temporal changes in CSNRT also were observed during the first 24 hours after conversion (600 msec: 308 ± 120 msec, P = 0.034; 500 msec: 340 ± 208 msec, P = 0.017). No significant interaction and temporal effects were observed with regard to corrected return cycle length pattern. Similar data regarding CSNRT and corrected return cycle length pattern were obtained after autonomic blockade. Patients with abnormal CSNRT after cardioversion had higher recurrence rates (50%) than those with normal function (37%; P = NS). Patients who relapsed had a higher density of supraventricular ectopic beats per hour (159 ± 120) compared with those who did not (35 ± 37; P = 0.001). Conclusion: Depressed sinus node function is observed after conversion of chronic AF. Recovery from this abnormality and its independence from autonomic function suggest that AF remodels the sinus node. Our data do not support a causative role of sinus node function in AF recurrence, but they do indicate such a role for the density of atrial ectopic beats.

Acute coronary syndromes secondary to allergy-induced coronary vasospasm are known as “Kounis syndrome.” The main pathophysiological mechanism of coronary spasm in Kounis syndrome is the release of inflammatory mediators during a hypersensitivity reaction triggered by food, insect bites, or drugs. Here, we report a case of an acute coronary syndrome secondary to allergic reaction following levofloxacin administration in a 68-year-old female without a prior history of coronary artery disease. Our patient's coronary angiography revealed moderate lesions in the coronary vasculature and she was diagnosed as having a type II variant Kounis syndrome. Type II variant includes patients in whom the acute release of inflammatory mediators due to mast cell degranulation such as histamine, serotonin, and leukotrienes can induce either coronary artery spasm with normal cardiac enzymes and troponins or plaque erosion or rupture manifesting as acute myocardial infarction. According to our knowledge, this is the first case report of Kounis syndrome attributed to levofloxacin administration.

Atrial fibrillation is a complex arrhythmia with multiple possible mechanisms. A lot of experimental and clinical studies have shed light on the pathophysiological mechanisms of arrhythmia, especially on molecular basis. Electrical, contractile and structural remodeling, calcium handling abnormalities, autonomic imbalance and genetic factors seem to play a crucial role in atrial fibrillation initiation and maintenance. However, the exact pathophysiological mechanisms of atrial fibrillation are not completely understood and whether atrial fibrillation is an unclassified cardiomyopathy or a distinct disease still remains to be answered. This review highlights proarrhythmic and pathophysiological mechanisms of atrial fibrillation and approaches the molecular basis underlying atrial fibrillation susceptibility.

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.

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.

Patients with atrial fibrillation (AF) frequently present with symptoms suggestive of myocardial isch- aemia, even in the absence of significant CAD, that seem to be attributable to abnormalities of myocardial perfusion and perfusion reserve. According to the results of recent human and previous experimen- tal studies the increase in coronary artery blood flow during AF is smaller, while the coronary vascular resistance during the arrhythmia does not decrease as much as we would expect, suggesting a mismatch between coronary blood flow and myocardial metabolic demand. AF itself diminishes coronary flow reserve, especially in the subendocardial layer, partly as a result of the increase in the myocardial com- ponent of coronary vascular resistance, and it is possible that irregular ventricular rhythm may play an important role. The mismatch of coronary blood flow and myocardial metabolic demand, especially in view of the severe reduction in coronary flow reserve, may have deleterious consequences that are not limited to patients with CAD.

C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6 months after the start of effective CPAP treatment.The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period.C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79 ± 0.65 mg/dL versus 0.70 ± 0.52 mg/dL (p0.05) after 3 months and 0.30 ± 0.33 mg/dL (p0.001) after 6 months of CPAP therapy]. When patients were divided into males and females, the above evolution pattern was changed. At the third month time point, the CRP values showed a statistically significant decrease only in males (from 0.74 ± 0.53 mg/dL to 0.61 ± 0.5 mg/dL, p0.01) while females showed only minimal and insignificant changes (from 0.87 ± 0.79 mg/dL to 0.83 ± 0.51 mg/dL, p0.05). After 6 months' treatment, CRP decreased significantly in both genders (males from 0.74 ± 0.53 mg/dL to 0.28 ± 0.32 mg/dL, p0.001 and females from 0.87 ± 0.79 mg/dL to 0.34 ± 0.36 mg/dL, p0.001).Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6 months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP's protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.

Because humoral alterations have been implicated in the generation and perpetuation of atrial fibrillation (AF), we aimed to elucidate possible abnormalities in atrial endocrine function in the setting of lone AF. Levels of plasma apelin and amino terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) were measured in 40 patients with persistent AF, before and 1 month after electrical cardioversion, and in 15 controls in sinus rhythm (SR). All patients were successfully cardioverted to SR, although in 9 of them AF recurred. Baseline apelin levels were lower and NT-pro-BNP levels higher in patients with AF compared to controls (380 +/- 186 vs 700 +/- 151 pg/ml, p0.001, and 615 +/- 611 vs 50 +/- 28 pg/ml, p0.001, respectively). Maintenance of SR resulted in an increase of apelin and a decrease of NT-pro-BNP levels during the postcardioversion follow-up period compared to baseline (497 +/- 170 vs 368 +/- 178 pg/ml, p0.001, and 206 +/- 106 vs 398 +/- 269 pg/ml, p0.001 respectively). Patients who developed AF recurrence by the end of the follow-up period had similar values of apelin and NT-pro-BNP on final and initial evaluations (444 +/- 142 vs 422 +/- 217 pg/ml, p = 0.62, and 1,328 +/- 714 vs 1,362 +/- 862 pg/ml, p = 0.74, respectively). Stepwise logistic regression analysis showed that left atrial diameter (b =-0.49, p = 0.05), and baseline NT-pro-BNP (b = 0.006, p = 0.022), but not apelin, were independent predictors for AF recurrence. In conclusion, this study suggests that endocrine heart function, as judged from apelin and NT-pro-BNP levels, is reversibly modified in the setting of lone AF. This could influence systemic hemodynamics and pharmacologic measures designed to treat this arrhythmia.

AIMS: To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with new-onset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. METHODS AND RESULTS: Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10-85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS. CONCLUSION: This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.

We investigated whether the serum markers of collagen turnover differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in humans.Structural alterations and fibrosis have been implicated in the generation and perpetuation of AF.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.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, p0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25 +/- 0.08 ng/ml, p0.001, respectively). Persistent AF patients had higher levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p0.001), 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, p0.001, 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, p0.001).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.

Several studies suggest the clinical efficacy of carvedilol in reducing atrial and ventricular arrhythmias in patients with left ventricular dysfunction (LVD) due to congestive heart failure (CHF) or following myocardial infarction. However, the mechanisms supporting its antiarrhythmic efficacy have been derived from experimental studies. In this prospective, placebo-controlled trial we examined the electrophysiological effects of a high oral dose of carvedilol in patients with CHF and LVD due to non-ischemic dilated cardiomyopathy.Thirty-one patients with stable CHF underwent electrophysiological study and were randomly assigned to treatment with carvedilol or placebo. After 2 months of treatment the study was repeated.Carvedilol prolonged almost all conduction times. In the same group atrial and ventricular effective refractory periods were significantly prolonged, while the parameters of repolarization remained virtually unchanged. The prolongation of refractoriness was most pronounced in the atrium. The change in ventricular refractoriness was correlated with ejection fraction (r = 0.94, p0.01) suggesting that patients with more preserved left ventricular function responded to treatment with greater prolongation.Even after a short period of administration carvedilol has marked and diffused electrophysiological effects that would be beneficial for patients with CHF and may contribute to the positive outcome of clinical trials.

Although recent studies suggest that inflammation is involved in the pathogenesis of atrial fibrillation (AF), it remains controversial whether it is a consequence or a cause of the arrhythmia.Prospective study.Tertiary referral centre.In 52 patients with persistent AF lasting3 months, high-sensitivity C-reactive protein (hs-CRP) was measured before and after electrical cardioversion.All patients were successfully cardioverted to sinus rhythm (SR), but the recurrence rate was 23% at 1 month. Baseline hs-CRP was higher in patients with AF recurrence than in those who remained in SR (0.5 (SD 0.18) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p0.001). Similarly, arrhythmia recurrence was associated with greater left atrial diameters (45.4 (SD 3.3) mm vs 40.7 (SD 3.1) mm, respectively, p0.001). However, logistic regression analysis showed that hs-CRP was the only independent predictor for AF recurrence (p0.001). Additionally, patients who were in SR on final evaluation had significantly lower hs-CRP levels than at baseline (0.10 (SD 0.06) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p0.001), while those who experienced AF recurrence had similar values on final and on initial evaluation (0.56 (SD 0.24) mg/dl vs 0.50 (SD 0.18) mg/dl, respectively, p = 0.42).High levels of hs-CRP are associated with an increased risk of AF recurrence after cardioversion. The restoration and maintenance of SR result in a gradual decrease of hs-CRP while AF recurrence has a different effect, suggesting that inflammation is a consequence, rather than a cause, of AF.

Although the maintenance of sinus rhythm would be the ideal scenario for patients with atrial fibrillation (AF), recent randomised trials have questioned the value of this approach. A careful interpretation of their results showed the limited efficacy of currently available antiarrhythmic drugs in maintaining sinus rhythm, as well as their potentially serious side effects. Therefore, it is imperative to develop safer and more effective drugs for AF. Based on our improved understanding of the pathophysiology of AF and the mechanism of action of antiarrhythmic drugs, significant efforts are being made to develop new antiarrhythmic agents that would prevent electrophysiological remodelling, would be selective for the atria and, therefore, would not prolong ventricular repolarisation, thus lacking any proarrhythmic effect.

Patients with atrioventricular nodal reentrant tachycardia (AVNRT) could serve as a clinical model to study the effects of mechanical stretch in the electrical properties of atrial myocardium. We studied 14 patients with AVNRT. Peak, mean and minimal atrial pressures, atrial refractoriness (ERP) in the right atrial appendage and high right atrial lateral wall and monophasic action potential duration at 90% of repolarisation (MAPd90) in the right atrial appendage were assessed during atrial pacing at 500 and 400 ms and after 2 min of pacing at the tachycardia cycle length. Measurements were repeated from the same positions after ventricular pacing at the same cycle lengths and after 2 min of tachycardia. Susceptibility to atrial fibrillation (AF) was assessed by noting whether AF was induced during ERP evaluation. Atrial pressure showed a statistically significant increase during ventricular pacing compared to baseline. This increase remained substantially unchanged when the tachycardia was induced. A significant reduction in atrial ERP and MAPd90 was also observed during ventricular pacing at all cycle lengths compared to atrial pacing. Two minutes of spontaneous tachycardia were enough to change the atrial ERP and MAPd90 to values significantly lower than those during atrial pacing at the cycle length of tachycardia. During the ERP evaluation AF was induced more often during the tachycardia (28%) than during ventricular (14%) and atrial pacing (0%). In AVNRT patients, ventricular pacing and reentrant tachycardia significantly increase right atrial pressures and subsequently shorten ERP and MAPd90, leading to an enhanced propensity for AF.

Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs).Prospective study.Tertiary referral center.Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria.Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit.During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events.To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.

To assess the effects of amiodarone and diltiazem on atrial fibrillation (AF) induced atrial electrical remodeling and their clinical implications.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.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).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.

Purpose A significant new cardiac marker in the prognosis of ischemic cardiomyopathy N-terminal pro brain natriuretic peptide (NT-proBNP) has recently been reported. Given the high incidence of sudden death in patients with congestive heart failure we examined the value of NT-proBNP in predicting the occurrence of malignant arrhythmias in patients with implantable cardioverter-defibrillators. Methods Baseline plasma concentrations of NT-proBNP were measured using ELISA in 25 patients (mean age 66±8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction ≤35%. In all patients an internal cardioverter-defibrillator had been implanted for primary prevention of sudden death according to MADIT I criteria. Results The implantable cardiac defibrillators were interrogated at 1-year follow-up to identify the type of arrhythmias patients had developed. NT-proBNP concentrations were significantly higher in patients who developed sustained monomorphic ventricular tachycardia (SVT) or ventricular fibrillation (VF) compared with those having only episodes of non-sustained ventricular tachycardia (NSVT), (1024 ± 462 vs. 675 ± 320 pmol/L). By regression analysis, NT-proBNP was found to be a powerful predictor of sustained monomorphic ventricular tachycardia (R=0.423, p=0.035). Conclusion Increased circulating levels of NT-proBNP predict the appearance of sustained ventricular tachycardia and may serve as an additional criterion defining patients at high risk for sudden cardiac death.