Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury. OBJECTIVES: This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA). METHODS: In a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events. RESULTS: Of the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51). CONCLUSIONS: In patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months.

Durability of Pulmonary Vein Isolation Using Pulsed-Field Ablation: Results From the Multicenter EU-PORIA Registry.

BACKGROUND: Pulsed-field ablation (PFA) is a novel nonthermal ablation technology with high procedural safety and efficiency for pulmonary vein isolation (PVI). Premarket data showed high PVI durability during mandatory remapping studies. Data on lesion durability in real-world patients with clinically indicated redo procedures are scarce. OBJECTIVES: This study sought to report PVI durability rates in patients undergoing a clinically indicated redo procedure after an index PVI using PFA. METHODS: Patients from 7 European centers undergoing an index PVI using PFA were included the EU-PORIA (European Real-world Outcomes With Pulsed Field Ablation in Patients With Symptomatic Atrial Fibrillation) registry. In patients with subsequent left atrial redo procedures due to arrhythmia recurrence, 3-dimensional electroanatomical maps were acquired. PVI durability was assessed on a per-vein and per-patient level, and sites of reconnections and predictors of lesion durability were identified. RESULTS: Of 1,184 patients (62% paroxysmal atrial fibrillation) undergoing an index PVI using PFA, 272 (23%) had an arrhythmia recurrence. Of these, 144 (53%) underwent a left atrial redo procedure a median of 7 (Q1-Q3: 5-10) months after the first ablation. Three-dimensional electroanatomical maps identified 404 of 567 pulmonary veins (71%) with durable isolation. In 54 patients (38%), all pulmonary veins were durably isolated. Prior operator experience with cryoballoon ablation was associated with a higher PVI durability compared to operators with only point-by-point radiofrequency experience (76% vs 60%; P < 0.001). Neither the operators' cumulative experience in atrial fibrillation ablation (≤5 vs >5 years) nor the size of the PFA device used (31 mm vs 35 mm) had an impact on subsequent lesion durability (both P > 0.50). CONCLUSIONS: In 144 patients with arrhythmia recurrence after PFA PVI, durable isolation was observed in 71% of the pulmonary veins during the redo procedure, and 38% of all patients showed durable isolation of all veins.

The Association of HIV-Specific Risk Factors with Cardiovascular Events in Addition to Traditional Risk Factors in People Living with HIV.

Traditional cardiovascular risk scores underestimate the incidence of cardiovascular diseases (CVD) in people living with HIV (PLH). This study compared the effect of HIV-specific cardiovascular risk factors (CRF) with traditional CRF at baseline for their association with incident CVD in PLH. The ongoing, prospective HIV HEART Aging (HIVH) study assesses CVD in PLH in the German Ruhr Area since 2004. PLH from the HIVH study with at least 5 years of follow-up were examined with the help of Cox proportional hazards models using inverse probability-of-censoring weights. The models were adjusted for age and sex. The obtained hazard ratios (HR) and 95% confidence limits (CL) assessed the strength of the associations between CRF and CVD. One thousand two hundred forty-three individuals (male 1,040, female 203; mean age of 43 ± 10 years) with 116 incident CVD events were analyzed. After adjusting for the traditional CRF, the HIV-specific CRF "a history of AIDS" and "higher age at diagnosis of HIV infection" (per 10 years) were associated with an increased CVD risk (HR 1.55, 95% CL: 1.05-2.28 and HR 1.55, 95% CL: 1.09-1.22, respectively). Higher CD4/CD8 ratio (per standard deviation), longer cumulative duration of antiretroviral therapies, and longer duration of HIV infection (per 10 years) showed indications for a decreased CVD risk (HR 0.75, 95% CL: 0.58-0.97, HR 0.71, 95% CL: 0.41-1.23, and HR 0.63, 95% CL: 0.44-0.90, respectively). Out of the traditional CRF, current smoking showed the strongest impact on CVD risk (HR 3.12, 95% CL: 2.06-4.74). In conclusion, HIV-specific factors, such as history of AIDS and CD4/CD8 ratio, were independently associated with an increased cardiovascular risk. Traditional CRF maintained a major effect on CVD. Clinical Trials Number (NCT04330287).

Predictors of Atrial Fibrillation in Patients with Embolic Stroke of Unknown Etiology and Implantable Loop Recorders-Further Insights of the TRACK AF Study on the Role of ECG and Echocardiography.

Aims-Electrocardiography (ECG) and echocardiographic left atrial (LA) parameters may be helpful to assess the risk of atrial fibrillation (AF) in embolic stroke of unknown etiology (ESUS) and could therefore guide intensity of ECG monitoring. Methods-1153 consecutive patients with ischemic stroke or transient ischemic attack (TIA) were analyzed. An internal loop recorder (ILR) was implanted in 104 consecutive patients with ESUS. Multiple morphologic P-wave parameters in baseline 12-channel ECG and echocardiographic LA parameters were measured and analyzed in patients with and without ILR-detected AF. Using logistic regression, we evaluated the predictive value of several ECG parameters and LA dimensions on the occurrence of AF. Results-In 20 of 104 (19%) patients, AF was diagnosed by ILR during a mean monitoring time of 575 (IQR 470-580) days. Patients with AF were significantly older (72 (67-75) vs. 60 (52-72) years; p = 0.001) and premature atrial contractions (PAC) were more frequently observed (40% vs. 2%; p < 0.001) during baseline ECG. All morphologic P-wave parameters did not show a significant difference between groups. There was a non-significant trend towards a larger LA volume index (31 (24-36) vs. 29 (25-37) mL/m2; p = 0.09) in AF patients. Conclusions-Age and PAC are independently associated with incident AF in ESUS and could be used as markers for selecting patients that may benefit from more extensive rhythm monitoring or ILR implantation. In our consecutive cohort of patients with ESUS, neither morphological P-wave parameters nor LA size were predictive of AF.

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

AIMS: Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. METHODS AND RESULTS: All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. CONCLUSION: The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Pearls and Pitfalls of Pulsed Field Ablation.

Pulsed field ablation (PFA) was recently rediscovered as an emerging treatment modality for the ablation of cardiac arrhythmias. Ultra-short high voltage pulses are leading to irreversible electroporation of cardiac cells subsequently resulting in cell death. Current literature of PFA for pulmonary vein isolation (PVI) consistently reported excellent acute and long-term efficacy along with a very low adverse event rate. The undeniable benefit of the novel ablation technique is that cardiac cells are more susceptible to electrical fields whereas surrounding structures such as the pulmonary veins, the phrenic nerve or the esophagus are not, or if at all, minimally affected, which results in a favorable safety profile that is expected to be superior to the current standard of care without compromising efficacy. Nevertheless, the exact mechanisms of electroporation are not yet entirely understood on a cellular basis and pulsed electrical field protocols of different manufactures are not comparable among one another and require their own validation for each indication. Importantly, randomized controlled trials and comparative data to current standard of care modalities, such as radiofrequency- or cryoballoon ablation, are still missing. This review focuses on the "pearls" and "pitfalls" of PFA, a technology that has the potential to become the future leading energy source for PVI and beyond.

Bronchial Safety After Pulsed Field Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Thermal left atrial ablation can cause bronchial damage. Pulsed field ablation (PFA) is a novel, nonthermal ablation modality for paroxysmal atrial fibrillation. We report on bronchial effects after pulmonary vein isolation using PFA for paroxysmal atrial fibrillation. METHODS: A computed tomography scan showing the respiratory tract adjacent to the left atrial was obtained. Oral anticoagulation was interrupted on procedure day. Peri-procedurally, patients received heparin with an activated clotting time goal of >350 seconds. All pulmonary veins were individually isolated with a 13F steerable sheath and a pentaspline PFA catheter using either a straight-tip or J-tip guide wire. The J-tip guide wire patients were added to test the hypothesis that the straight-tip guidewire was associated with bleeding complications. One day afterward, bronchoscopy was performed. Serial hemoglobin levels were measured during 30-day follow-up. RESULTS: In 2 series of 30 patients, PFA was performed, with all pulmonary veins acutely isolated. Clinical course was uneventful, no patient had chest discomfort, coughing, or hemoptysis. All patients underwent uncomplicated bronchoscopy, without thermal lesions or ulcers. In 12 out of 30 (40%) straight-tip guide wire patients, small amounts of old blood without active bleeding were seen in multiple segments. All hemoglobin levels remained clinically stable. At 30-day follow-up, all patients were asymptomatic. CONCLUSIONS: Pulmonary vein isolation using PFA for paroxysmal atrial fibrillation does not cause thermal lesions in the bronchial system. Use of a straight-tip, extrastiff guide wire for the over-the-wire PFA catheter can lead to asymptomatic bleeding in the bronchial system without clinical relevance at 30-day follow-up, opposite to use of a J-tip guide wire.

Cerebral safety after pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Pulsed field ablation (PFA) is a novel, nonthermal ablation modality that can ablate myocardial tissue with minimal effects on surrounding tissue. Preclinical data show an absence of cerebral emboli after extensive PFA. However, clinical data on silent cerebral lesions (SCLs) and/or silent cerebral events (SCEs) after PFA are lacking. OBJECTIVES: The purpose of this study was to investigate the occurrence of neurological deficits and SCL and/or SCE after PFA in paroxysmal atrial fibrillation (AF) using National Institutes of Health Stroke Scale (NIHSS) scores and magnetic resonance imaging (MRI). METHODS: In patients with symptomatic paroxysmal AF, pulmonary vein isolation (PVI) using PFA was performed. NIHSS scores were assessed before and 2 days and 30 days after PVI. One day after PVI, patients underwent cerebral 1.5-T MRI scanning using diffusion-weighted imaging and fluid-attenuated inversion recovery sequences to document the occurrence of SCL/SCE. RESULTS: PFA was performed in 30 patients (age 63 ± 10 years). No patient showed neurological deficits. All NIHSS scores showed the minimum value of 0. Cerebral MRI scans were normal in 29 of 30 patients (97%). In 1 patient (3%), a single 7-mm cerebellar lesion was observed. Forty days after the procedure, follow-up cerebral MRI scan showed complete regression of the lesion. CONCLUSION: In patients treated with PFA for symptomatic paroxysmal AF, the incidence of MRI-detected asymptomatic thromboembolic cerebral events or lesions was as low as 3%. No neurological deficits occurred in any of the patients.

First experience with pulsed field ablation as routine treatment for paroxysmal atrial fibrillation.

AIMS: Catheter ablation for atrial fibrillation (AF) using thermal energy can cause collateral damage. Pulsed field ablation (PFA) is a novel non-thermal energy source. Few small clinical studies have been published. We report on the first 'real-world' experience with pulmonary vein isolation (PVI) using PFA for paroxysmal AF (PAF). METHODS AND RESULTS: Pre- and post-ablation, phrenic nerve function was assessed. After high-density left atrial (LA) bipolar voltage mapping, all PVs were individually isolated using a 13 Fr steerable sheath and a pentaspline PFA over-the-wire catheter. After ablation, bipolar voltage mapping was repeated to assess lesion formation. In 30 PAF patients (mean 63 years; 53% female), uncomplicated PFA was performed, with all PVs acutely isolated. The median procedure time was 116 min. The median PFA catheter LA dwell time was 29 min. The median fluoroscopy time was 26 min. In one patient with roof-dependent flutter, a roof line was intentionally created. In two patients, unintentional bidirectional mitral isthmus block was created. There was no phrenic nerve or oesophageal damage. In one patient, pericardial drainage after cardiac tamponade was performed. In-hospital stay and 30-day follow-up were uneventful. After 90 days, 97% of patients were in sinus rhythm. CONCLUSION: PVI using PFA for PAF in a 'real-world' setting appears to be safe and feasible in this small patient cohort. Procedure times are homogeneous, and LA dwell time is short. Atrial ablation lines can easily be created. Unintentional ablation of atrial tissue can occur, accurate catheter alignment to the PV ostium and axis should be ensured.

The BIOMONITOR III Injectable Cardiac Monitor: Clinical Experience with a Novel Injectable Cardiac Monitor.

BACKGROUND: Injectable cardiac monitors (ICMs) are leadless subcutaneous devices for long-term monitoring of arrhythmias. The BIOTRONIK BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector, and simplified implantation technique. METHODS: R-wave amplitude was recorded immediately after implantation, the day after implantation, and after 3 months. Follow-up was scheduled after 3 months or after an event. All data from the ICM were retrieved. The anatomical position of the ICM was determined post-implantation and after 3 months. A patient questionnaire was conducted after 3 months. RESULTS: In 36 patients (mean age 67 ± 13 years; 40% male) an ICM was inserted. Six patients were not included in the final analysis. The median time from skin cut to wound closure was 6 [IQR 5-7] minutes. Mean R-wave amplitude increased over time (0.73 ± 32 mV vs. 0.78 ± 0.38 mV vs. 0.81 ± 0.39 mV; p = ns). Three months after implantation, the ICM was in an anatomically stable position. In 14 (47%) patients, true episodes were detected. False arrhythmia alerts were detected in 13 (43%) patients. The total number of false detections was low, and the patient satisfaction rate was high. CONCLUSION: Implantation of the novel BIOMONITOR III is fast and uncomplicated; its sensing characteristics are excellent and improve over time, and patient satisfaction is high.

[Pulsed field ablation : The ablation technique of the future?] / "Pulsed field ablation" : Die Ablationstechnik der Zukunft?

The ablation of cardiac arrhythmias is now standard therapy in invasive electrophysiology with a focus on atrial fibrillation due to its high prevalence. Thermal energy sources such as radiofrequency or cryoablation are the most commonly used techniques to date. Due to limitations in terms of effectiveness and safety because of possible indiscriminate tissue destruction, ablation using pulsed field ablation (PFA) can be a safe and effective alternative to thermal ablation techniques. This is a nonthermal form of energy that creates effective myocardial lesions by means of irreversible electroporation by generating short, high-energy electrical impulses. Preliminary data show high effectiveness with a low complication rate. Myocardial tissue shows a high specificity while sparing surrounding structures such as the esophagus, the phrenic nerve and surrounding vascular structures. Therefore, irreversible electroporation is a very promising technique and has the potential to become the perfect form of energy for many catheter ablations and especially for pulmonary vein isolation. In this article we provide an overview of the current status of PFA as well as an outlook on future fields of treatment.

One-year outcome and durability of pulmonary vein isolation after prospective use of ablation index for catheter ablation in patients with persistent atrial fibrillation.

BACKGROUND: Radiofrequency (RF) catheter ablation for persistent atrial fibrillation (peAF) is associated with less favorable outcomes than for paroxysmal AF (PAF). Recent studies have shown improved clinical outcomes with use of ablation index (AI) targets for pulmonary vein isolation (PVI) in PAF. AI is a novel ablation quality marker that incorporates contact force (CF), time, and power in a weighted formula. This is a single-arm registry to investigate the 1-year efficacy of AF ablation guided by the AI in patients with peAF, and further to evaluate pulmonary vein reconduction at repeat electrophysiology study in case of recurrent AF. METHODS: In total, 55 consecutive patients (69 ± 10 years, 55% male, median time since first AF diagnosis: 31 months (Q1-Q3: 10-70)) with peAF underwent AIguided PVI using a CF surround-flow catheter. AI targets were 600 for anterior and 450 for roof/posterior/inferior antral segments. Patients were monitored for atrial tachyarrhythmia recurrence using 5-day Holter-ECG recordings at 3, 6, and 12 months. RESULTS: The median procedure time was 173 min (Q1-Q3: 152-204). The median fluoroscopy time was 4 min (Q1-Q3: 3-6) and the median fluoroscopy dose was 2.64 Gy/cm2 (Q1-Q3: 1.04-3.99). The median ablation time was 57 min (Q1-Q3: 47-63). At 12 months, 42% of the patients were in sinus rhythm. AF recurrence was seen in 58% of patients. No major complications occurred. CONCLUSIONS: RF ablation using AI in peAF is a feasible and safe technique. At 1 year, AI-guided ablation was associated with AF recurrence in 58% of the patients.

Influence of ablation index on the incidence of cardiac tamponade complicating pulmonary vein isolation.

BACKGROUND: Cardiac tamponade (CT) complicating pulmonary vein isolation (PVI) for atrial fibrillation (AF) is a complication that can increase morbidity and mortality. Radiofrequency energy is a known cause of CT. Ablation Index (AI) is a novel ablation quality marker. We hypothesized that use of AI reduces the incidence of CT. METHODS: All AF procedures between 10/2014 and 06/2019 were included. Three ablation groups were defined: group A, RF ablation with non-contact force (CF) catheter; group B, RF ablation with CF catheter; and group C, RF ablation with CF catheter using AI. All episodes of CT were analyzed. RESULTS: In total, 1222 consecutive AF patients underwent PVI. Group A consisted of 100 (8%) procedures, while group B included 432 (35%) procedures and group C 690 (57%) procedures. The overall risk for CT in all patients was 2.1% (26/1222). The risk in group A was 2.9% (3/100), in group B 2.5% (11/432), and in group C 1.7% (12/690), including all 1222 patients in the analysis (p < 0.05). Univariate analysis identified no further specific predictors for CT. With the exception of one patient (1/26; 3.8%), who needed surgical treatment, all CT could be successfully drained. CONCLUSIONS: In a high-volume center, the use of AI decreased the risk of CT in patients undergoing RF ablation for AF by 32%.

Investigation of air pollution and noise on progression of thoracic aortic calcification: results of the Heinz Nixdorf Recall Study.

AIMS: Air pollution and noise are potential risk factors for subclinical atherosclerosis. Longitudinal analyses, especially on the interplay of these environmental factors, are scarce and inconsistent. Hence we investigated long-term traffic-related exposure to air pollution and noise with the development and progression of thoracic aortic calcification, a marker of subclinical atherosclerosis. METHODS: We used baseline (2000-2003) and follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4814 middle-aged adults. Residence-based air pollution (PM2.5 (aerodynamic diameter ≤ 2.5 µm), PM10, nitrogen dioxide and particle number), and noise was assessed with dispersion models. Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. The presence and extent of thoracic aortic calcification progression were analysed with multiple logistic and linear regression models, respectively, adjusting for age, sex, lifestyle variables, socioeconomic status and respective co-exposure. RESULTS: We observed no association in the full study sample (n = 3155, mean age 59.1 (±7.6) years, 52.8% women). While an interquartile range in particle number and night-time noise yielded odds ratios of 1.20 (1.03, 1.40) and 1.21 (1.00, 1.46) for binary thoracic aortic calcification progression, and 0.02 (-0.01, 0.05) and 0.04 (0.00, 0.07) higher growth rates of thoracic aortic calcification in participants with baseline thoracic aortic calcification less than 10, negative findings were observed in those with baseline thoracic aortic calcification of 10 or greater. Results were similar for other pollutants and daytime noise. CONCLUSION: Our study shows no overall associations. Subgroup analyses suggest independent associations of traffic-related air pollution and noise with the development and progression of subclinical atherosclerosis in participants with no or minor thoracic aortic calcification at baseline, in contrast to negative findings in those with advanced calcification.

B-type natriuretic peptides for the prediction of cardiovascular events and mortality in patients living with HIV: Results from the HIV-HEART study.

AIMS: B-type natriuretic peptide (BNP) has been suggested to improve risk prediction of cardiovascular (CV) events and mortality. We aimed to evaluate the value of BNP to predict the composite primary endpoint of CV events and mortality alongside traditional and HIV specific risk factors in a HIV-infected population. METHODS: In this prospective multicenter HIV-HEART study we followed 808 HIV-positive subjects in the German Ruhr area for a median follow up of 120 (IQR:113-129) months since 2004. Association of BNP with the composite primary endpoint was assessed using Cox regression adjusting for traditional cardiovascular and HIV specific risk factors. RESULTS: At baseline, median BNP was 10.3 (IQR 5.4-18.9) pg/ml. The composite endpoint occurred in 158 (19.6%) patients. Subjects with high BNP levels showed significantly increased frequencies of CV events and death (22% for BNP ≤5 pg/ml, 30% for BNP >5 up to ≤20 pg ml, 38% for BNP >20 up to ≤35 pg ml, 59% for BNP >35 up to ≤100 pg ml and 86% for BNP >100 pg/ml, p-value < 0.01). In the fully adjusted model that included traditional CV risks as well as HIV specific factors, after a log2 transformation, doubling of BNP was significantly associated with increased risk for the composite endpoint (HR:1.16 (95%CI 1.01-1.33); p = 0.031). Comparing BNP of <5 pg/ml to BNP > 100 pg/ml, HR in the fully adjusted model was 3.25 (95%CI 1.50-7.08; p < 0.001). CONCLUSIONS: Increased BNP is associated with significant excess of incident CV events and mortality in HIV-infected patients. BNP is a valuable marker to improve the prediction of CV events and mortality.

Association of progressive thoracic aortic calcification with future cardiovascular events and all-cause mortality: ability to improve risk prediction? Results of the Heinz Nixdorf Recall (HNR) study.

AIMS: Thoracic aortic calcification (TAC) is measured by computed tomography (CT). We investigated the association of TAC-progression with incident cardiovascular (CV) events and all-cause mortality in a population-based cohort and to determine its predictive value for these endpoints. METHODS AND RESULTS: In 3080 participants (45-74 years, 53.6% women), risk factors and TAC via CT were measured at baseline and at a second examination after 5.1 ± 0.3 years. Hard coronary, hard CV events as well as CV events including revascularization and all-cause mortality were recorded during a follow-up time of 7.8 ± 2.2 years after the second CT scan. Cox regression analysis determined the association of TAC-progression with observed endpoints. The predictive value of TAC-progression was assessed using Harrell's C index. We observed 81 hard coronary, 154 hard CV, 231 CV events including revascularization, and 266 deaths. In the crude analysis, event rates increased continuously with the level of TAC-change over 5 years for all endpoints. After adjustment, the significant association of TAC-progression with hard CV events [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57] and all-cause mortality (HR 1.34, 95% CI 1.14-1.58) persisted, per one standard deviation increase in TAC-progression (log(TAC + 1)). Regarding aortic segments separately, HRs were consistently higher for descending thoracic aorta. When adding TAC (baseline and progression) to the model containing classical risk factors and coronary artery calcification (CAC), Harrell's C indices did not increase for any of the observed endpoints. CONCLUSION: TAC-progression is associated with incident hard CV events and all-cause mortality but fails to improve event prediction over CAC.

Gut Microbiota in Human Immunodeficiency Virus-Infected Individuals Linked to Coronary Heart Disease.

Background: Human immunodeficiency virus (HIV) infection is an independent risk factor for coronary heart disease (CHD) and is associated with perturbation of the gut microbiota. Methods: We analyzed gut microbiota in 30 HIV-infected individuals with CHD (CHD+) and 30 without CHD (CHD-) of the HIV-HEART study group. Results: Gut microbiota linked to CHD was associated with lower α-diversity. Despite insignificant differences in ß-diversity, co-occurrence networks of bacterial genera clearly diverged between CHD+ and CHD- individuals. Multidimensional scaling separated HIV-infected individuals into 2 microbiome clusters, dominated by the genus Prevotella or Bacteroides. The relative abundance of 49 other genera was significantly different between both clusters. The Prevotella-rich cluster was largely composed of men who have sex with men (MSM) (97%), whereas the Bacteroides-rich cluster comprised both MSM (45%) and heterosexual individuals (55%). MSM of the Bacteroides-rich cluster were characterized by reduced α-diversity, advanced immunological HIV stage, longer antiretroviral therapy with more ART regimens, and longer use of protease inhibitors, compared with Prevotella-rich MSM. Conclusions: Community structures of gut microbiota rather than individual species might facilitate risk assessment of CHD in HIV-infected individuals. Sexual behavior appears to be an important factor affecting gut microbiota ß-diversity and should be considered in future studies.