Aging-Related Immune Cell Phenotypes and Mortality in the Framingham Heart Study.

Background: The global increase in human life expectancy is evident. The total number of individuals aged 60 or above is anticipated to reach 2 billion by 2050. Aging, an inherently complex process, manifests prominently in the changes observed in the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their significance, the connections between various ARIPs and mortality have not been thoroughly investigated. We prospectively investigated 16 different ARIPs using flow cytometry, namely, CD4/CD8 ratio, Granzyme B + CD8/Granyzme B + CD4, TN/TM = Tn / (Teff + Tem + Tcm) for TN/TM CD4 + and TN/TM CD8 + ratios, Th17/CD4 + Treg, Tc17/CD8 + Treg, Th17, Tc17, CD4 + Temra, CD8 + Temra, CD4 + CD25 + FoxP3+ (CD4 + Treg), CD8 + CD25 + FoxP3+ (CD8 + Treg) CD4 + CD27-, CD4 + CD28-CD27-, CD8 + CD27-, CD8 + CD28-CD27- and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001). Results: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the survival rate was 65% during 19 years of follow-up. For the model adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR:0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively) and higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3+) were associated with higher all-cause mortality (HR = 1.17, [1.03-1.32]). Higher IL-6 levels were associated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively).

Early and late post-operative arrhythmias after surgical myectomy: 45 years of follow-up.

AIMS: The aims of this study are to investigate the incidence and determinants of post-operative atrial arrhythmias, conduction disorders and mortality in hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing transaortic myectomy. METHODS AND RESULTS: This retrospective single-center study was conducted in 249 patients (median age 54 years [40-64], 42% female) undergoing transaortic myectomy. Post-operative atrial fibrillation (AF) was reported in 84 patients (33.7%), including 56 patients (22.5%) with de novo AF. Older age (HR = 1.027 (1.003-1.052), p = 0.029) and hypercholesterolemia (HR = 2.296 (1.091-4.832) p = 0.029) were independent predictors for de novo post-operative AF. Late post-operative AF and atrial flutter (AFL) occurred in 18.9% and 6.8% of the patients, respectively. De novo early post-operative AF increased the risk of late post-operative AF (HR = 3.138 (1.450-6.789), p = 0.004). Patients with a right bundle branch block had a higher risk of early-postoperative pacemaker implantation (p = 0.003, HR = 9.771 (2.195-43.505)). Higher age at time of surgery (HR = 1.053 (1.026-1.081), p < 0.001) was a predictor for late mortality (n = 47, 18.9%). CONCLUSION: Early and late post-operative AF, AFL and other SVTs are common sequelae after myectomy and are associated with older age at surgery, history of AF and early post-operative AF. Early post-operative arrhythmias are not transient and periodic rhythm monitoring is therefore essential to initiate therapy as soon as possible.

The Genetic Puzzle of Familial Atrial Fibrillation.

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia. In Europe, AF is expected to reach a prevalence of 18 million by 2060. This estimate will increase hospitalization for AF to 4 million and 120 million outpatient visits. Besides being an independent risk factor for mortality, AF is also associated with an increased risk of morbidities. Although there are many well-defined risk factors for developing AF, no identifiable risk factors or cardiac pathology is seen in up to 30% of the cases. The heritability of AF has been investigated in depth since the first report of familial atrial fibrillation (FAF) in 1936. Despite the limited value of animal models, the advances in molecular genetics enabled identification of many common and rare variants related to FAF. The importance of AF heritability originates from the high prevalence of lone AF and the lack of clear understanding of the underlying pathophysiology. A better understanding of FAF will facilitate early identification of people at high risk of developing FAF and subsequent development of more effective management options. In this review, we reviewed FAF epidemiological studies, identified common and rare variants, and discussed their clinical implications and contributions to developing new personalized therapeutic strategies.

Ventricular Dysrhythmias During Long-Term Follow-Up in Patients With Inherited Cardiac Arrhythmia.

Reports on development of frequent ventricular premature complexes (fVPC), (non)sustained ventricular tachycardias ([n]sVT), or ventricular fibrillation (VF) and their interrelationship in patients with different inherited cardiac arrhythmia (ICA) have sofar not been reported. The aim of this study is therefore to examine incidences and recurrences rates of sVT and VF ("malignant ventricular tachyarrhythmias, VTA") in addition to the incidence of fVPC and nsVT ("ventricular dysrhythmias, VDR") in patients with various ICA during long-term follow up. Patients (N = 167, 88 male, age 45 ± 15 years) with ICA including definite/borderline arrhythmogenic right ventricular cardiomyopathy (ARVC, N = 47), Brugada syndrome (BrS, N = 71), catecholaminergic polymorphic ventricular tachycardia (CPVT, N = 7), long QT syndrome (LQTS, N = 41) or short QT syndrome (SQTS, N = 1) who had frequent 24-hour Holter monitoring during a follow-up period of 4.6 ± 4.4 years. During the initial screening visit, 15 patients had a history of malignant VTA. fVPC and nsVT was observed in respectively 19% (OHCA/VF/sVT: N = 9) and 13% (OHCA/VF/sVT: N = 4) of all patients. Compared with the ARVC group, patients with BrS and LQTS had less frequent fVPC and nsVT (fVPC: odds ratio [OR] 0.20, 95% confidence interval [CI] 0.08 to 0.49, p <0.000 and OR 0.09, 95% CI 0.02 to 0.33, p <0.000; nsVT:OR 0.17, 95% CI 0.06 to 0.50, p = 0.001 and OR 0.09, 95% CI 0.02 to 0.46, p = 0.003). The recurrence rate of malignant VTA was 33%. In conclusion, variety of VDR and malignant VTA were found during long-term follow-up in patients with ICA. During nearly a 5 years follow-up period, the recurrence rate of malignant VTA was considerable. fVPC, nsVT, and malignant VTA were most often found in patients with an ARVC.

A Rare Case of the Digenic Inheritance of Long QT Syndrome Type 2 and Type 6.

We report a 37-year-old woman with an out-of-hospital cardiac arrest caused by ventricular fibrillation due to digenic inheritance of long QT syndrome type 2 (KCNH2 gene) and type 6 (KCNE2 gene). During hospitalization, prolonged QTc intervals and frequent episodes of ventricular tachyarrhythmias manifested. Genetic testing identified a mutation of the KCNH2 gene and an unclassified variant, most likely pathogenic, of the KCNE2 gene. This digenic inheritance is extremely rare.

QRS Vector Magnitude as Predictor of Ventricular Arrhythmia in Patients With Brugada Syndrome.

Risk stratification is the most challenging part in management of patients with Brugada syndrome (BrS). Conduction delay in the right ventricular outflow tract (RVOT) is the major mechanism underlying ventricular tachyarrhythmia (VTA) in BrS. However, QRS duration was not useful in stratifying high-risk patients in large registries. Reconstructing the traditional 12-lead electrocardiogram into QRS vector magnitude can be used to quantify depolarization dispersion and identify high-risk BrS patients. The aim of the study is to test the significance of the QRSvm as a predictor for VTA in patients with BrS. In this retrospective cohort, we included 136 patients (47 ± 15 years, 66% male) who visited outpatient clinic for cardiogenetic screening. All medical records were examined, all 12- lead electrocardiograms were reconstructed into QRSvm using Kors' quasiorthogonal method and were assessed for the presence of electrocardiographic signs indicative of RVOT conduction delay including R wave sign, deep SI, SII >SIII pattern, and Tzou criteria. QRSvm was significantly lower in patients who either presented with VTA or developed VTA during follow-up (1.24 ± 0.35 vs 1.78 ± 0.42 mV, p < 0.001). Positive RVOT conduction delay signs occurred more frequently in symptomatic patients (20% vs 7%, p < 0.001).The area under receiver operator characteristic curve for QRSvm was 0.85 (95% confidence interval [CI] 0.77 to 0.92). Using QRSvm cutoff of 1.55 mV, sensitivity and specificity were 89% and 71%, respectively. Multivariate regression analysis showed that QRSvm and RVOT signs are independent predictors for VTA in BrS patients (QRS vector magnitude: odds ratio 3.68, 95% CI 2.4 to 6.2, p = 0.001; RVOT: odds ratio 2.6, 95% CI 1.4 to 4.9, p = 0.001). In conclusion, not only electrocardiographic signs indicative of RVOT conduction delay but also QRSvm can be used as a predictor for VTA events in BrS patients.

Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.

BACKGROUND: Brugada syndrome (BrS) is an autosomal dominant disease responsible for sudden cardiac death in young individuals without structural anomalies. The most critical part in the management of this channelopathy is identification of high-risk patients, especially asymptomatic subjects. Prior studies have shown that conduction delay in the right ventricular outflow tract (RVOT) is the main mechanism for developing ventricular tachyarrhythmia (VTA) in BrS patients. The aim of this study was to investigate the significance of electrocardiographic RVOT conduction delay parameters as predictors for development of VTA in patients with BrS. METHODS AND RESULTS: We retrospectively analyzed electrocardiograms obtained from 147 BrS patients (43 ± 15 years, 65% men) and assessed the following electrocardiographic parameters: (1) Tzou criteria (V1R > 0.15 mV, V6S > 0.15 mV, and V6S:R > 0.2), (2) prominent S wave in lead I, lead II, and lead III, (3) SII > SIII, and (4) prominent Q wave in lead III as possible predictors of VTA occurrences during follow-up. Prominent SI, SII, SIII, SII > SIII, QIII, and +ve Tzou criteria occurred more frequently in patients who either presented with VTA or developed VTA during the follow-up of 56 (IQR: 40-76) months. SII > SIII has the highest area under the curve for prediction of VTA (AUC: 0.84, sensitivity: 80%, specificity: 89%). Multivariable regression analysis showed that prominent S waves in lead I, SII > SIII and +ve Tzou criteria are independent predictors for VTA in BrS patients. CONCLUSION: Prominent S in lead I, SII > SIII and +ve Tzou criteria can be used as effective signs for predicting VTA in patients with BrS.

Impact of Supraventricular Tachyarrhythmia in Patients With Inherited Cardiac Arrhythmia.

Supraventricular tachyarrhythmia (SVT), especially atrial fibrillation (AF), has been observed in patients with inherited cardiac arrhythmia (ICA). Data on the time course of SVT and the occurrence of SVT other than AF is limited. In this study, we examined the prevalence, co-existence, and the time course of different types of SVT in patients with various ICAs. In this retrospective study, we selected 393 patients (median 49 years, range 17 to 87, 57% male) from a cohort of patients visiting the outpatient clinic for cardiogenetic screening of ICA. Patients' medical records were examined for the occurrence of AF and other SVT. AF/SVT was found in 49 patients (12%, 31 male, 42 ± 17 years). Patients presenting with only AF (n = 12, 3%) were older than patients presenting with only SVT (n = 28, 7%), respectively 52 ± 18 versus 37 ± 14, p = 0.007. Nineteen patients (5%) had multiple episodes of either AF (n = 7, 2%) or SVT (n = 12, 3%). Alternating episodes of AF and SVT occurred in 9 patients (2%). Intervals between second and third AF episodes were significantly shorter than between first and second episodes (p = 0.02). An implantable cardioverter defibrillator (ICD) was implanted in 158 patients (40.2%) and 26 patients (16%) had inappropriate ICD shocks (SVT 25, AF 1), particularly those with multiple SVT episodes (p = 0.003). In patients with a variety of ICAs, episodes of AF/SVT occurred in 12%. In patients with multiple AF episodes, intervals between consecutive episodes became significantly shorter over time. AF/SVT episodes are associated with inappropriate ICD shocks and aggressive therapy of AF/SVT is therefore justified.

Usefulness of the R-Wave Sign as a Predictor for Ventricular Tachyarrhythmia in Patients With Brugada Syndrome.

Brugada syndrome (BrS) is an autosomal dominant channelopathy which is responsible for a large number of sudden cardiac deaths in young subjects without structural abnormalities. The most challenging step in management of patients with BrS is identifying who is at risk for developing malignant ventricular tachyarrhythmia (VTA). In patients with BrS, conduction delay in the right ventricular outflow tract (RVOT) causes a prominent R wave in lead aVR. This electrocardiographic parameter can be useful to detect these high-risk patients. The goal of this study was to test the significance of R-wave elevation in lead aVR as a predictor for VTA in patients with BrS. In this retrospective study, we included 132 patients with BrS (47 ± 15 years, 65% men) who visited the outpatient clinic for cardiogenetic screening. Patients' medical records were examined for the presence of a positive R-wave sign in lead aVR and VTA. A positive R-wave sign in lead aVR was observed in 41 patients (31%). This sign was more frequently observed in patients who experienced VTA (n = 24) before the initial diagnosis, during electrophysiological studies, or during follow-up (p <0.001). The positive R-wave sign occurred more frequently in symptomatic patients with a history of an out of hospital cardiac arrest, VTA, or syncope than asymptomatic patients (60% vs 26%; p = 0.002). During the follow-up period, this sign was more frequently detected in patients who developed either de novo (50%) or recurrent VTA (80%) (p = 0.017). Multivariable regression analysis showed that R-wave sign is an independent predictor for VTA development (odds ratio 4.8, 95% confidence interval 1.79 to 13.27). The presence of a positive R-wave sign in lead aVR is associated with the development of VTA. In conclusion, positive R-wave sign in lead aVR can be used to identify patients with BrS at risk for malignant VTA.