Atrial fibrillation in the setting of cardiac amyloidosis - A review of the literature.

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA2DS2-VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients.

Cardioneuroablation for neurally-mediated syncope: Initial experience.

Cardioneuroablation is an emerging alternative therapeutic modality for young patients with severe neurally-mediated syncope. We present two images of cardioneuroablation performed in young patients who suffered from recurrent neurally-mediated syncope with asystole and functional atrioventricular block. The patients remain syncope-free during follow-ups.

Radiofrequency versus cryoballoon catheter ablation in patients with persistent atrial fibrillation: A randomized trial.

INTRODUCTION: Patients with persistent atrial fibrillation (AF) represent a challenging population for rhythm control therapies. Catheter ablation (CA) with pulmonary vein isolation (PVI) is an effective treatment option for the reduction of the arrhythmic burden. Data regarding the comparability between radiofrequency (RF) and cryoballoon ablation (CRYO) in persistent AF are limited. METHODS: This is a prospective, randomized, single-center study designed to compare the efficacy in terms of rhythm control between RF and CRYO in persistent AF. Eligible participants were randomized 2:1 in two arms: RF and CRYO. The primary endpoint of the study was arrhythmia relapse in the early postprocedural period (first 3 months) and in the middle term follow-up (3 months to 12 months). Secondary endpoints included procedure duration, fluoroscopy time, and complications. RESULTS: A total of 199 patients participated in the study (133 patients in the RF arm, 66 in the CRYO arm). No statistically significant difference occurred between the two groups regarding the primary endpoint (recurrences ≤3 months: 35.5% RF vs. 37.9% CRYO, p .755, recurrences >3 months: 26.3% RF vs. 27.3% CRYO, p .999). From the secondary endpoints, CRYO was a procedure of significantly shorter duration (75.15 ± 17.21 in CRYO vs. 136.6 ± 43.33 in RF group, p < .05). CONCLUSION: CRYO and RF ablation appear to be equally effective for rhythm control in patients with persistent AF. CRYO ablation is advantageous in terms of procedure duration.

Electrocardiographic Features of Immune Checkpoint Inhibitor-Associated Myocarditis.

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events including myocarditis, whilst improving cancer-related outcomes. There is thus a clinical need to identify electrocardiographic manifestations of ICI-related myocarditis to guide clinical management. PubMed was searched for clinical studies and case reports describing electrocardiographic changes in patients with ICI-related myocarditis. A total of 6 clinical studies and 79 case reports were included. This revealed a range of presentations for patients on ICIs, including supraventricular arrhythmias, ventricular arrhythmias and heart block, and new changes of ST-T segment unrelated to coronary artery disease, ST-segment elevation or depression and T-wave abnormalities. Several patients showed low voltages in multiple leads and new onset Q-wave development. Patients with ICI-related myocarditis may develop new arrhythmia and ST-T changes, and infrequently low voltages in multiple leads.

Soluble suppression of tumorigenicity 2 (sST2) for predicting disease severity or mortality outcomes in cardiovascular diseases: A systematic review and meta-analysis.

OBJECTIVES: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes. METHODS: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality. RESULTS: A total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta-analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I 2: 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99-1.27, P = 0.07; I 2: 88%). In chronic heart failure, sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I 2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27-2.12, P < 0.001; I 2: 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 ± 0.46 ng/ml; P = 0.001; I 2: 98%). Finally, in stable coronary artery disease, sST2 levels were higher in non-survivors than survivors (MD: 3.0 ± 1.1 ng/ml; P = 0.005; I 2: 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04-1.68, P < 0.05; I 2: 57%). CONCLUSIONS: sST2 significantly predicts disease severity and mortality in cardiovascular disease and is a good predictor of mortality in patients with stable coronary artery disease and chronic heart failure.

Contrast-induced early repolarization pattern and ventricular fibrillation.

Malignant arrhythmias during coronary angiography consist a complication of the procedure. Clinicians should be aware that intracoronary infusion of contrast medium can lead to physiological changes that lower the ventricular fibrillation threshold.

A novel variant of RyR2 gene in a family misdiagnosed as congenital long QT syndrome: The importance of genetic testing.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) and Long-QT syndrome (LQTS) are two distinct entities with similar clinical presentation and management but different clinical course. In this study, we present two family members presented with aborted sudden cardiac death (SCD) that was attributed to CPVT. The CPVT may be underrecognized in SCD victims and a diagnosis of "atypical LQTS" may warrant consideration of CPVT and analysis of RyR2 if the standard cardiac channel gene screen for LQTS is negative. Although the management of both channelopathies is quite common the clinical outcomes are different, with CPVT displaying a more malignant clinical course.

Atrial fibrillation in Brugada syndrome: Current perspectives.

The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS.

Predictors of Adverse Outcomes in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy: A Meta-Analysis of Observational Studies.

Arrhythmogenic cardiomyopathy (AC) is a hereditary disorder characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle. Our study aimed to systematically evaluate the impact of significant demographic, clinical, electrocardiographic, and echocardiographic factors in arrhythmic events in AC patients. MEDLINE and Cochrane library databases were manually searched without year or language restriction or any other limits until July 31, 2017. A pooled odds ratio with 95% confidence intervals was calculated for each of the risk factors. Our search retrieved 26 studies (n = 2680 patients, mean age: 37.9 years old, males: 51.9%) which were included in the quantitative synthesis. The most reliable predicting factors/parameters are the following: (1) male gender, (2) presyncope, (3) left ventricular dysfunction, (4) T-wave inversions in inferior leads, (5) proband status, (6) late potentials, (7) syncope, (8) inducibility at electrophysiological study, (9) right ventricular dysfunction, (10) epsilon waves, and (11) premature ventricular contractions greater than 1000/24 h. On the contrary, family history of sudden cardiac death, palpitations, premature ventricular contractions greater than 500/24 h, and T-wave inversions in right precordial leads fail to determine the outcome in this meta-analysis. In conclusion, multiple risk factors have been associated with arrhythmic events in AC patients. However, larger studies are needed to discriminate those patients who will benefit from implantable cardioverter defibrillators.

Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform.

The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.

Higher Dispersion Measures of Conduction and Repolarization in Type 1 Compared to Non-type 1 Brugada Syndrome Patients: An Electrocardiographic Study From a Single Center.

Background: Brugada syndrome (BrS) is a cardiac ion channelopathy that predisposes affected individuals to sudden cardiac death (SCD). Type 1 BrS is thought to take a more malignant clinical course than non-type 1 BrS. We hypothesized that the degrees of abnormal repolarization and conduction are greater in type 1 subjects and these differences can be detected by electrocardiography (ECG). Methods: Electrocardiographic data from spontaneous type 1 and non-type 1 BrS patients were analyzed. ECG parameters were measured from leads V1 to V3. Values were expressed as median [lower quartile-upper quartile] and compared using Kruskal-Wallis ANOVA. Results: Compared to non-type 1 BrS patients (n = 29), patients with spontaneous type 1 patterns (n = 22) showed similar (P > 0.05) heart rate (73 [64-77] vs. 68 [62-80] bpm), QRS duration (136 [124-161] vs. 127 [117-144] ms), uncorrected QT (418 [393-443] vs. 402 [386-424] ms) and corrected QT intervals (457 [414-474] vs. 430 [417-457] ms), JTpeak intervals (174 [144-183] vs. 174 [150-188] ms), Tpeak- Tend intervals (101 [93-120] vs. 99 [90-105] ms), Tpeak- Tend/QT ratios (0.25 [0.23-0.27] vs. 0.24 [0.22-0.27]), Tpeak- Tend/QRS (0.77 [0.62-0.87] vs. 0.77 [0.69-0.86]), Tpeak- Tend/(QRS × QT) (0.00074 [0.00034-0.00096] vs. 0.00073 [0.00048-0.00012] ms-1), index of Cardiac Electrophysiological Balance (iCEB, QT/QRS, marker of wavelength: 3.14 [2.56-3.35] vs. 3.21 [2.85-3.46]) and corrected iCEB (QTc/QRS: 3.25 [2.91-3.73] vs. 3.49 [2.99-3.78]). Higher QRS dispersion was seen in type 1 subjects (QRSd: 34 [24-66] vs. 24 [12-34] ms) but QT dispersion (QTd: 48 [39-71] vs. 43 [22-94] ms), QTc dispersion (QTcd: 52 [41-79] vs. 46 [23-104] ms), JTpeak dispersion (44 [23-62] vs. 45 [30-62] ms), Tpeak- Tend dispersion (28 [15-34] vs. 29 [22-53] ms) or Tpeak- Tend/QT dispersion (0.06 [0.03-0.08] vs. 0.08 [0.04-0.12]) did not differ between the two groups. Type 1 subjects showed higher (QRSd × Tpeak- Tend)/QRS (25 [19-44] vs. 19 [9-30] ms) but similar iCEB dispersion (0.83 [0.49-1.14] vs. 0.61 [0.34-0.92]) and iCEBc dispersion (0.93 [0.51-1.15] vs. 0.65 [0.39-0.96]). Conclusion: Higher levels of dispersion in conduction and repolarization are found in type 1 than non-type 1 BrS patients, potentially explaining the higher incidence of ventricular arrhythmias in the former group.

Predictive Value of T peak - T end Indices for Adverse Outcomes in Acquired QT Prolongation: A Meta-Analysis.

Background: Acquired QT interval prolongation has been linked with malignant ventricular arrhythmias, such as torsade de pointes, in turn predisposing to sudden cardiac death. Increased dispersion of repolarization has been identified as a pro-arrhythmic factor and can be observed as longer Tpeak - Tend interval and higher Tpeak - Tend/QT ratio on the electrocardiogram. However, the values of these repolarization indices for predicting adverse outcomes in this context have not been systematically evaluated. Method: PubMed, Embase and Cochrane Library databases were searched until 14th February 2018, identifying 232 studies. Results: Five studies on acquired QT prolongation met the inclusion criteria and 308 subjects with drug-induced LQTS patients (mean age: 66 ± 18 years old; 46% male) were included in this meta-analysis. Tpeak - Tend intervals were longer [mean difference [MD]: 76 ms, standard error [SE]: 26 ms, P = 0.003; I2 = 98%] and Tpeak - Tend/QT ratios were higher (MD: 0.14, SE: 0.03, P = 0.000; I2 = 29%) in patients with torsade de pointes compared to those without these events. Conclusion: Tpeak - Tend interval and Tpeak - Tend/QT ratio were higher in patients with acquired QT prolongation suffering from torsade de pointes compared to those who did not. These repolarization indices may provide additional predictive value for identifying high-risk individuals.

Steroids prevent early recurrence of atrial fibrillation following catheter ablation: a systematic review and meta-analysis.

Previous studies have reported that steroids may reduce the risk of atrial fibrillation (AF) recurrence after catheter ablation, but data regarding this issue have been controversial. Therefore, we conducted a meta-analysis of randomized clinical trials (RCTs) and observational studies to ascertain the association of steroids and AF recurrence after ablation. PubMed, Embase, and Cochrane online databases were searched from inception to December 2017. The primary outcome of the meta-analysis was short-term or long-term AF recurrence following a single ablation procedure with or without the use of steroids. Both fixed- and random-effects models were used to calculate the overall effect estimates. Eight studies (four RCTs and four observational studies), with a total 992 patients, were included in the present study. Our meta-analysis shows that steroid use was associated with reduced AF occurrence at 3 months (odd ratio (OR) = 0.53, 95% confidence interval (CI) = 0.31-0.90, P=0.02) and 12-14 months (OR = 0.67, 95% CI = 0.47-0.95, P=0.02) after radiofrequency (RF) catheter ablation (RFCA). No clear benefit was observed for AF recurrence at 2-3 days, 1 or 24 months of follow-up. Steroid use was associated with decreased risk of early AF recurrence 3 and 12-14 months after ablation. No clear relationship was observed for 2-3 days, 1 and 24 months of follow-up and further data are needed to clarify these results.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in clinical practice.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited myocardial disease characterized by fibro-fatty replacement of the right ventricular myocardium, and associated with paroxysmal ventricular arrhythmias and sudden cardiac death (SCD). It is currently the second most common cause of SCD after hypertrophic cardiomyopathy in young people <35 years of age, causing up to 20% of deaths in this patient population. This condition has a male preponderance and is more commonly found in individuals of Italian and Greek descent. To date, there is no single diagnostic test for ARVC/D and the diagnosis is made based on clinical, electrocardiographic, and radiological findings according to the Revised 2010 Task Force Criteria. In this review, we will discuss the mainstay treatment which includes pharmacotherapy, implantable cardioverter-defibrillator insertion for abortion of sudden cardiac death, and in the advanced stages of the disease cardiac transplantation.

Prognostic value of soluble ST2 postaortic valve replacement: a meta-analysis.

OBJECTIVES: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family and a modulator of hypertrophic and fibrotic responses. Its prognostic value for patients undergoing aortic valve replacement (AVR) has been examined in prospective studies but to date, there has been no systematic evaluation or meta-analysis on this issue. METHODS: PubMed and Embase were searched until 1 October 2017 for studies that evaluated the relationship between sST2 levels and mortality after AVR. RESULTS: A total of 18 and 37 entries were retrieved from both databases, from which four studies were included in the final meta-analysis. In a total of 1154 subjects (50% male, mean age 80±10 years old, mean follow-up 14 months), elevated sST2 levels were significantly associated with a 44% increase in the risk of all-cause mortality (HR 1.44, 95% CI 1.30 to 1.60, p<0.0001; I2: 44%). CONCLUSIONS: sST2 significantly predicts all-cause mortality in patients who have undergone AVR, but this conclusion is limited by the small number of patients. Larger prospective studies are required to better elucidate its value for risk stratification in this patient population.

Cancer antigen-125 and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Cancer antigen-125 (Ca-125) is traditionally recognised as a tumour marker and its role in cardiovascular diseases has been studied only in recent years. Whether Ca-125 is elevated in patients with atrial fibrillation (AF) and its levels predict the risk of AF remains controversial. Therefore, we conducted a systematic review and meta-analysis of the association between Ca-125 levels and AF. METHODS: PubMed and EMBASE databases were searched until 1 June 2017 for studies that evaluated the association between Ca-125 and AF. Inclusion criteria included studies that compare Ca-125 in patients with and without AF, or those reporting HRs/ORs for risk of AF stratified by Ca-125 levels. RESULTS: A total of 39 entries were retrieved from the databases, of which 10 studies were included in the final meta-analysis. Ca-125 was significantly higher in patients with AF compared with those in sinus rhythm (mean difference=16 U/mL, 95% CI 2 to 30 U/mL, P<0.05; I2: 98%). Ca-125 significantly increased the risk of AF (HR: 1.39, 95% CI 1.06 to 1.82, P<0.05; I2: 84%). CONCLUSION: Ca-125 was significantly higher in patients with AF than in those in sinus rhythm, and high Ca-125 is predictive of AF occurrence. However, the high heterogeneity observed means there is an uncertainty in the relationship between Ca-125 and AF, which needs to be confirmed by larger prospective studies.

Frailty and Clinical Outcomes in Advanced Heart Failure Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review and Meta-analysis.

BACKGROUND: Frailty has been identified as a risk factor for adverse clinical outcomes after cardiac intervention or surgery. However, whether it increases the risk of adverse outcomes in patients undergoing left ventricular assist device (LVAD) therapy has been controversial. Therefore, we conducted a systematic review and meta-analysis of the frailty measures and clinical outcomes of length of stay and mortality in this setting. METHODS: PubMed and Embase were searched until September 11, 2017, for studies evaluating the association between frailty and clinical outcomes in advanced heart failure patients undergoing LVAD implantation. RESULTS: A total of 46 and 79 entries were retrieved from our search strategy. A total of 13 studies involving 3435 patients were included in the final meta-analysis (mean age: 57.7 ± 15.3 years; 79% male, follow-up duration was 13 ± 14 months). Compared to nonfrail patients (n = 2721), frail patients (n = 579) had significantly longer time-to-extubation (n = 3; mean difference: 45 ± 6 hours; I2: 0%) and hospital length of stay (n = 4; mean difference: 2.9 ± 1.2 days; P = .001; I2: 21%). Frailty was not a predictor of inpatient or short-term mortality [n = 3; hazard ratio (HR): 1.22, 95% confidence interval (CI): 0.66-2.26; P > .05; I2: 0%] but predicted long-term mortality (n = 7; HR: 1.44, 95% CI: 1.15-1.80; P = .001; I2: 0%). CONCLUSIONS: Frailty leads to significantly longer time to extubation, hospital length of stay, and long-term mortality in advanced heart failure patients who have undergone LVAD implantation. Older patients being considered for LVAD implantation should therefore be assessed for frailty status. The risk and benefit of the procedure should be explained to the patient, emphasizing that frailty increases the likelihood of adverse clinical outcomes.

Adenosine-guided radiofrequency catheter ablation of atrial fibrillation: A meta-analysis of randomized control trials.

BACKGROUND: The prognostic significance of adenosine-mediated dormant pulmonary vein conduction, and whether such dormant conduction should be eliminated, remains controversial. We sought to perform a meta-analysis of data from eligible studies to delineate the prognostic impact of adenosine-guided radiofrequency catheter ablation of atrial fibrillation. METHODS: A systematic literature search was performed using online databases in order to identify relevant studies from January 2004 to September 2016. Ten studies [six observational and four randomized control trials (RCTs)] were included in the analysis. RESULTS: Five studies (two observational and three RCTs) compared the efficacy of adenosine-mediated elimination of dormant conduction versus no adenosine test. Overall, the adenosine-guided ablation strategy displayed better long-term outcomes as compared with no adenosine testing (RR 1.08, 95% CI 1.01-1.14, p=0.02; Heterogeneity: I2=42%, p: 0.14). The meta-analysis of only RCTs failed to show any differences between the two strategies (RR 1.03, 95% CI 0.96-1.11, p=0.37; Heterogeneity: I2 0%, p: 0.41). Eight studies (five observational and three RCTs) addressed the efficacy of adenosine-induced dormant conduction and additional ablation versus no dormant conduction during adenosine challenge. Overall, a trend towards a better outcome in those without dormant conduction during drug challenge was noted (RR 0.89, 95% CI 0.77-1.03, p=0.11; Heterogeneity: I2 65% p: 0.006). The pooled analysis of RCTs failed to show any differences between the two arms (RR 0.90, 95% CI 0.62-1.30, p= 0.57; Heterogeneity: I2 88%, p: 0.0002). CONCLUSIONS: Adenosine-guided radiofrequency catheter ablation of atrial fibrillation does not provide additional benefit in terms of freedom of arrhythmia recurrence.