P-wave duration as a marker of atrial remodeling in patients referred to ablation for atrial fibrillation: A new stratification tool emerging?

Ablation of atrial fibrillation is one of the most widely applied invasive procedures in cardiovascular medicine, and populations with atrial fibrillation continuously rise. Recurrence rates are, however, consistently high, even in patients without severe comorbidities. Robust stratification algorithms to distinguish patients suitable for ablation are generally lacking. This is a fact caused by the inability to incorporate evidence of atrial remodeling and fibrosis, e.g., atrial remodeling, in the decision pathways. Cardiac magnetic resonance is a powerful tool in identifying fibrosis; however, it is costly and not routinely used. Electrocardiography has been generally underutilized in clinical practice during pre-ablative screening. One of the characteristics of the electrocardiogram that can give us valuable data depicting the existence and the extent of atrial remodeling and fibrosis is the duration of the P-wave. Currently, many studies support the implementation of P-wave duration in the routine practice of patient evaluation as a surrogate marker of existing atrial remodeling, that in turn predicts recurrence after ablation of atrial fibrillation. Further research is guaranteed to establish this electrocardiographic characteristic in our stratification quiver.

Heart failure and atrial fibrillation: new concepts in pathophysiology, management, and future directions.

A bidirectional pathophysiological link connects heart failure and atrial fibrillation, creating a frequent and challenging comorbidity, which includes neurohormonal hyperactivation, fibrosis development, and electrophysiologic remodeling, while they share mutual risk factors. Management for these devastating comorbidities includes most of the established treatment measures for heart failure as well as rhythm or rate control and anticoagulation mostly for atrial fibrillation, which can be achieved with either pharmaceutical or non-pharmaceutical approaches. The current manuscript aims to review the existing literature regarding the underlying pathophysiology, to present the novel trends of treatment, and to predict the future perspective of these two linked diseases with the numerous unanswered questions.

Characteristics of Patients with Obstructive Sleep Apnea at High Risk for Cardiovascular Disease.

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 < 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 < 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.

Anticoagulation for atrial fibrillation in heart failure patients: balancing between Scylla and Charybdis.

The management of heart failure (HF) and atrial fibrillation (AF) in real-world practice remains a debating issue, while the number of HF patients with AF increase dramatically. While it is unclear if rhythm or rate control therapy is more beneficial and under which circumstances, anticoagulation therapy is the cornerstone of the AF-HF patients' approach. Vitamin-K antagonists were the gold-standard during the past, but currently their usage is limited in specific conditions. Non-vitamin K oral anticoagulants (NOACs) have gained ground during the last ten years and considered as gold-standard of a wide spectrum of HF phenotypes. The current manuscript aims to review the current literature regarding the indications and the optimal choice and usage of NOACs in HF patients with AF.

Impact of Sustained Cardiac Tachyarrhythmias Recorded in Coronary Intensive Care Unit on Short- and Long-Term Mortality and Duration of Hospitalization.

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.

Evaluation of Inflammatory Markers in a Large Sample of Obstructive Sleep Apnea Patients without Comorbidities.

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 < 5 served as controls. Demographics, PSG data, and levels of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and uric acid (UA) were measured and compared between groups. A significant difference was found between groups in hs-CRP, fibrinogen, and UA. All biomarkers were independently associated with OSA severity and gender (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 number NCT03070769.

Cardiac resynchronization therapy (CRT) device replacement considerations: upgrade or downgrade? A complex decision in the current clinical setting.

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.

Electrophysiological and Electroanatomical Mapping of the Right Atrium in Persistent Atrial Fibrillation: Relation to Collagen Turnover.

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.

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.

Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein.

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.

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.

Sinus rhythm restoration affects collagen turnover in patients with persistent atrial fibrillation.

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.

Echocardiographic demonstration of coronary artery to left ventricle fistulas: case report and review of the literature.

We describe the case of a 45-year-old female patient with coronary fistulas arising from both the left and right coronary artery system and emptying in the left ventricle. Only sporadically do coronary artery fistulas drain into the left ventricle. In our patient, the most likely explanation of the fistulous communications was a congenital cause. We review the literature on coronary cameral fistulas and discuss the etiology of the diagnostic findings. Small coronary artery fistulas are generally well-tolerated and should impose no significant restriction on daily routine and activities. Nevertheless, small fistulas may under certain conditions produce a "steal" phenomenon and shunt blood flow away from the myocardial capillary network, causing ischemia.

Atrial fibrillation: a progressive atrial myopathy or a distinct disease?

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.

Type 2 Kounis syndrome in an allergic woman: An uncommon presentation of acute coronary syndrome.

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. .

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.

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.