Immunity and inflammation in cardiovascular disorders.

Recent studies have developed our understanding of the role of the immune system and inflammation in Cardiovascular Disease (CVD), opening new avenues for risk stratification and therapeutic intervention. However, gaps in our knowledge remain. To address this issue, BMC Cardiovascular Disorders has launched a Collection on "Immunity and Inflammation in Cardiovascular Disorders".

The long-term outcomes of cardiac implantable electronic devices implanted via the femoral route.

BACKGROUND: Conventional superior access for cardiac implantable electronic devices (CIEDs) is not always possible and femoral CIEDs (F-CIED) are an alternative option when leadless systems are not suitable. The long-term outcomes and extraction experiences with F-CIEDs, in particular complex F-CIED (ICD/CRT devices), remain poorly understood. METHODS: Patients referred for F-CIEDs implantation between 2002 and 2019 at two tertiary centers were included. Early complications were defined as ≤30 days following implant and late complications >30 days. RESULTS: Thirty-one patients (66% male; age 56 ± 20 years; 35% [11] patients with congenital heart disease) were implanted with F-CIEDs (10 ICD/CRT and 21 pacemakers). Early complications were observed in 6.5% of patients: two lead displacements. Late complications at 6.8 ± 4.4 years occurred in 29.0% of patients. This was higher with complex F-CIED compared to simple F-CIED (60.0% vs. 14.3%, p = .02). Late complications were predominantly generator site related (n = 8, 25.8%) including seven infections/erosions and one generator migration. Eight femoral generators and 14 leads (median duration in situ seven [range 6-11] years) were extracted without complication. CONCLUSIONS: Procedural success with F-CIEDs is high with clinically acceptable early complication rates. There is a notable risk of late complications, particularly involving the generator site of complex devices following repeat femoral procedures. Extraction of chronic F-CIED in experienced centers is feasible and safe.

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial.

BACKGROUND: Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. OBJECTIVE: The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. METHODS: Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. RESULTS: Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81-1.83; P = .41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57-1.88; P = .91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31-2.59) for CA and 2.32 (95% CI 2.13-2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746-£27,618) than for CA (mean £18,002; 95% CI £15,422-£20,581). CONCLUSION: In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04280042.

Biomarkers as predictors of recurrence of atrial fibrillation post ablation: an updated and expanded systematic review and meta-analysis.

BACKGROUND: A high proportion of patients undergoing catheter ablation (CA) for atrial fibrillation (AF) experience recurrence of arrhythmia. This meta-analysis aims to identify pre-ablation serum biomarker(s) associated with arrhythmia recurrence to improve patient selection before CA. METHODS: A systematic approach following PRISMA reporting guidelines was utilised in libraries (Pubmed/Medline, Embase, Web of Science, Scopus) and supplemented by scanning through bibliographies of articles. Biomarker levels were compared using a random-effects model and presented as odds ratio (OR). Heterogeneity was examined by meta-regression and subgroup analysis. RESULTS: In total, 73 studies were identified after inclusion and exclusion criteria were applied. Nine out of 22 biomarkers showed association with recurrence of AF after CA. High levels of N-Terminal-pro-B-type-Natriuretic Peptide [OR (95% CI), 3.11 (1.80-5.36)], B-type Natriuretic Peptide [BNP, 2.91 (1.74-4.88)], high-sensitivity C-Reactive Protein [2.04 (1.28-3.23)], Carboxy-terminal telopeptide of collagen type I [1.89 (1.16-3.08)] and Interleukin-6 [1.83 (1.18-2.84)] were strongly associated with identifying patients with AF recurrence. Meta-regression highlighted that AF type had a significant impact on BNP levels (heterogeneity R2 = 55%). Subgroup analysis showed that high BNP levels were more strongly associated with AF recurrence in paroxysmal AF (PAF) cohorts compared to the addition of non-PAF patients. Egger's test ruled out the presence of publication bias from small-study effects. CONCLUSION: Ranking biomarkers based on the strength of association with outcome provides each biomarker relative capacity to predict AF recurrence. This will provide randomised controlled trials, a guide to choosing a priori tool for identifying patients likely to revert to AF, which are required to substantiate these findings.

Novel aggregated multiposition noncontact mapping of atrial tachycardia in humans: From computational modeling to clinical validation.

BACKGROUND: A novel aggregated multiposition noncontact mapping (AMP-NCM) algorithm is proposed to diagnose cardiac arrhythmias. OBJECTIVE: The purpose of this study was to computationally determine an accuracy threshold and to compare the accuracy and clinical utility of AMP-NCM to gold standard contact mapping. METHODS: In a cellular automata model, the number of catheter positions and chamber coverage were varied to establish accuracy requirements for clinically relevant AMP-NCM. This guided the clinical study protocol. In a prospective cohort of patients with atrial tachycardia (AT), noncontact mapping (NCM) recordings from a single position (SP) and multiple positions were compared to contact mapping with a high-density multipolar catheter using morphology and timing differences of reconstructed signals. Identification of AT mechanisms and ablation targets using both AMP-NCM and contact mapping were randomly evaluated by 5 blinded reviewers. RESULTS: AMP-NCM accuracy was asymptotic at 60 catheter positions in computational modeling. Twenty patients (age 65 ± 12 years; 19 male) with 26 ATs (5 focal, 21 reentrant) were studied. Morphologic correlation of signals derived from AMP-NCM was significantly better than those from SP-NCM compared to contact signals (median 0.93 vs 0.76; P <.001). AMP-NCM generated maps more rapidly than contact mapping (3 ± 1 minutes vs 13 ± 6 minutes; P <.001) and correctly diagnosed AT mechanisms in 25 of 26 maps (96%). Overall, 80% of arrhythmia mechanisms were correctly identified using AMP-NCM by blinded reviewers. CONCLUSION: Once 60 catheter positions were achieved, AMP-NCM successfully diagnosed mechanisms of AT and identified treatment sites equal to gold standard contact mapping in 3 minutes of procedural time.

A comparison of non-invasive methods of measuring body composition in patients with heart failure: a report from SICA-HF.

BACKGROUND: Cachexia is common in patients with chronic heart failure and is associated with poor prognosis. How best to measure body composition is not clear. METHODS AND RESULTS: We characterized body composition in 120 patients with chronic heart failure: mean (SD) age 70 (10) years, left ventricular ejection fraction 44 (10) %, and median (Q1-Q3) N-terminal pro B-type natriuretic peptide 845 (355-1368) ng/L. We measured body composition using dual-energy X-ray absorptiometry (DEXA) and a multi-frequency bioelectrical impedance analysis (BIA) device (Tanita BIA MC-180MA). Mean (SD) fat mass (FM) was 27.2 (11.7) kg by BIA and 32.3 (12.2) kg by DEXA (mean difference -5.1 kg, 95% limits of agreement: -11.7, 1.5; 4% of values outside limit of agreement); mean (SD) lean mass (LM) was 56.6 (10.9) kg by BIA and 51.1 (9.9) kg by DEXA (mean difference 5.5 kg, 95% limits of agreement: -1.3, 12.3; 6% of values outside limit of agreement); and mean (SD) bone mass (BM) was 3.0 (0.5) kg by BIA and 2.8 (0.6) kg by DEXA (mean difference 0.2 kg, 95% limits of agreement: -0.5, 0.8; 5% of values outside limit of agreement). There was a close correlation between DEXA and BIA for both LM and FM (LM: r = 0.95, P < 0.001; FM: r = 0.96, P < 0.001) but less so for BM (r = 0.84, P < 0.001). Both DEXA and BIA body composition measurements correlated well with other measures of body size (body mass index, hip circumference, and waist circumference). CONCLUSIONS: There are differences in the measurements of FM, LM, and BM between the two techniques, which should not be used interchangeably.

Internationally validated score to predict the outcome of non-paroxysmal atrial fibrillation ablation: the 'FLAME score'.

BACKGROUND: The clinical effectiveness of ablating non-paroxysmal atrial fibrillation (non-PAF) relies on proper patient selection. We developed and validated a scoring system to predict non-PAF ablation outcomes. METHODS: Data on 416 non-PAF ablations were analysed using binary logistic regression at a London centre. Identified preprocedural variables, which independently predicted freedom from atrial tachyarrhythmia. Twenty-one possible predictive variables and a model with c-statistic 0.751-explained outcome variation in London at mean follow-up 12±3 months. An additive point score (range 0-9) was developed-the FLAME score: female=1; long-lasting persistent atrial fibrillation=1; left atrial diameter in mm: 40 to <45 = 1, 45 to <50 = 2, 50 to <55=3, ≥55 =4; mitral regurgitation (MR) mild to moderate=1; extreme comorbidity=2. Extreme comorbidities include severe MR, moderate mitral stenosis, mitral replacement, hypertrophic cardiomyopathy or congenital heart disease. RESULTS: The FLAME score was applied to data (882 non-PAF ablations) at a Californian centre, and predicted the outcome of both single (p<0.0001) and multiple (p<0.0001) procedures. For first ablation (follow-up 2.1 years (median, IQR 1.0-4.1)), FLAME score: 0-1 predicts 62% success, 2-4 44% and ≥5 29% (Ptrend <0.0001). After the final ablation (mean procedures: 1.4±0.6, follow-up 1.8 years (median, IQR 0.8-3.6)), FLAME score: 0-1 predicts 81% success, 2-4 65% and ≥5 44% (Ptrend <0.0001). CONCLUSIONS: FLAME score is easily calculated, derived in London, and predicted single and multiple procedural outcomes for non-PAF ablations in California. In patients with a high score, even multiple procedures are usually ineffective.

Individualized ablation strategy to treat persistent atrial fibrillation: Core-to-boundary approach guided by charge-density mapping.

BACKGROUND: Noncontact charge-density mapping allows rapid real-time global mapping of atrial fibrillation (AF), offering the opportunity for a personalized ablation strategy. OBJECTIVE: The purpose of this study was to compare the 2-year outcome of an individualized strategy consisting of pulmonary vein isolation (PVI) plus core-to-boundary ablation (targeting the conduction pattern core with an extension to the nearest nonconducting boundary) guided by charge-density mapping, with an empirical PVI plus posterior wall electrical isolation (PWI) strategy. METHODS: Forty patients (age 62 ± 12 years; 29 male) with persistent AF (10 ± 5 months) prospectively underwent charge-density mapping-guided PVI, followed by core-to-boundary stepwise ablation until termination of AF or depletion of identified cores. Freedom from AF/atrial tachycardia (AT) at 24 months was compared with a propensity score-matched control group of 80 patients with empirical PVI + PWI guided by conventional contact mapping. RESULTS: Acute AF termination occurred in 8 of 40 patients after charge-density mapping-guided PVI alone and in 21 of the remaining 32 patients after core-to-boundary ablation in the study cohort, compared with 8 of 80 (10%) in the control cohort (P <.001). On average, 2.2 ± 0.6 cores were ablated post-PVI before acute AF termination. At 24 months, freedom from AF/AT after a single procedure was 68% in the study group vs 46% in the control group (P = .043). CONCLUSION: An individualized ablation strategy consisting of PVI plus core-to-boundary ablation guided by noncontact charge-density mapping is a feasible and effective strategy for treating persistent AF, with a favorable 24-month outcome.

Diverse activation patterns during persistent atrial fibrillation by noncontact charge-density mapping of human atrium.

BACKGROUND: Global simultaneous recording of atrial activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for an individualized ablation strategy to treat persistent AF. The study aims to characterize left atrial endocardial activation patterns during AF using noncontact charge-density mapping. METHODS: Twenty-five patients with persistent AF were studied. Activation patterns were characterized into three subtypes: (i) focal with centrifugal activation (FCA); (ii) localized rotational activation (LRA); and (iii) localized irregular activation (LIA). Continuous activation patterns were analyzed and distributed in 18 defined regions in the left atrium. RESULTS: A total of 144 AF segments with 1068 activation patterns were analyzed. The most common pattern during AF was LIA (63%) which consists of four disparate features of activation: slow conduction (45%), pivoting (30%), collision (16%), and acceleration (7%). LRA was the second-most common pattern (20%). FCA accounted for 17% of all activations, arising frequently from the pulmonary veins (PVs)/ostia. A majority of patients (24/25; 96%) showed continuous and highly dynamic patterns of activation comprising multiple combinations of FCA, LRA, and LIA, transitioning from one to the other without a discernible order. Preferential conduction areas were typically seen in the mid-anterior (48%) and lower-posterior (40%) walls. CONCLUSION: Atrial fibrillation is characterized by heterogeneous activation patterns identified in PV-ostia and non-PV regions throughout the LA at varying locations between individuals. Clinical implications of individualized ablation strategies guided by charge-density mapping need to be determined.

Prescribing patterns to optimize heart rate: analysis of 1,000 consecutive outpatient appointments to a single heart failure clinic over a 6-month period.

OBJECTIVES: This study sought to characterize patients attending a community heart failure (HF) clinic and identified those who were eligible for optimization of beta-blockers (BB) or ivabradine. BACKGROUND: Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, those with higher resting heart rate have a worse prognosis. Reducing sinus rate to 50 to 60 beats/min might improve outcomes. METHODS: A total of 1,000 consecutively scheduled HF clinic follow-up appointments over a 6-month period were reviewed. Demographic, clinical, and echocardiographic data were collected for patients who attended (824 unique patients; 555 men). Mean age was 74 ± 11 years, median N-terminal pro-B-type natriuretic peptide levels were 1,002 ng/l (interquartile range: 367 to 2,151 ng/l), and the mean left ventricular ejection fraction (LVEF) was 44 ± 11%. A total of 202 (25%), 252 (31%), and 370 (45%) patients had LVEFs of ≤35%, 36% to 49%, and ≥50%, respectively. Of patients with LVEF ≤35%, 142 (70%) were in sinus rhythm. RESULTS: At 70 clinic visits, 58 patients with LVEFs of ≤35% were in sinus rhythm and had heart rates ≥70 beats/min. Of these, 13 patients had their BB dose increased, 20 were potentially eligible for, but did not have, BB uptitration, 15 were already taking target doses of BBs, and 10 patients were reported to be intolerant of higher doses. Thus, 25 patients were potentially eligible for ivabradine according to European Society of Cardiology guidelines; this number dropped to 14 when the United Kingdom National Institute for Health and Care Excellence guidelines were applied. CONCLUSIONS: Among patients with LVEFs of ≤35%, most are treated with BBs and have a heart rate at rest of <70 beats/min; 12% of these patients might be eligible for ivabradine.

Prognostic significance of ultrasound-assessed jugular vein distensibility in heart failure.

AIMS: Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically. METHODS AND RESULTS: Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p<0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p<0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93). CONCLUSIONS: Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome. CLINICAL TRIAL REGISTRATION: NCT01872299.

If home telemonitoring reduces mortality in heart failure, is this just due to better guideline-based treatment?

UNLABELLED: To investigate, in a 'real-world' setting, the impact of home telemonitoring (HTM) compared to usual care on achieved dose of guideline-recommended medication, hospitalisation rate and mortality in patients with heart failure (HF). METHODS: We retrospectively analyzed data on 333 patients with HF referred to a HTM service supported by a nurse-specialist (mean age 71±12 years, mean left ventricular ejection fraction (LVEF) 36 ± 11% and median N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) 2,972 ng/L (interquartile range (IQR): 1,447-7,801 ng/L)). Most patients (n = 278) accepted HTM (HTM-group) but 55 refused and received usual care (UC-group). In the HTM-group, weight, heart rate, blood pressure and symptom severity were measured daily. RESULTS: At referral, respectively 90%, 90%, 67% and 94% of patients with LVEF ≤40% (n = 229) were treated with ß-blockers (BB), angiotensin converting enzyme-inhibitors (ACE-I) or angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA) and diuretics, with rates similar between groups. After 6 months, prescription of BB (92% vs 83%), ACE-I/ARB (92% vs 90%) and MRA (68% vs 67%) did not differ significantly between groups. The proportions of patients who achieved ≥50% and ≥100% of target doses of BB, ACE-I/ARB and MRA were also similar in each group. However, during a median follow-up of 1094 days (IQR 767-1419) fewer patients who chose HTM died (33% vs 49%; P = 0.002). CONCLUSION: Patients who choose HTM have a better prognosis than those who do not but this does not appear to be mediated through greater prescription of key HF medications.