Transapical Mitral Valve Replacement: 1-Year Results of the Real-World Tendyne European Experience Registry.

BACKGROUND: Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort. OBJECTIVES: The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry. METHODS: All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year. RESULTS: Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year. CONCLUSIONS: This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335).

Prognostic benefits of early vascular surgical intervention in patients with major peripheral vascular complications following transcatheter aortic valve implantation.

OBJECTIVES: This study aimed to analyze the incidence, surgical management of major vascular complications, and outcomes in patients undergoing transfemoral (TF) transcatheter aortic valve replacement (TAVR) at our center after strict selection of the access route, carefully considering all known major predictors. METHODS: Data of 494 consecutive patients with pre-interventional multi-slice computed tomography (CT) of the aorta who had undergone TF TAVR from 2009 to 2019 were analyzed. RESULTS: In total, 23/494 (4.7%) patients had major vascular and access-related complications of peripheral vessels and/or infrarenal aorta. These included hematomas that met the Valve Academic Research Consortium 3-criteria of major vascular complications (7/494, 1.4%), arterial dissections (3/494, 0.6%), pseudoaneurysm (6/494, 1.2%), thrombus of the external iliac artery leading to acute limb ischemia (1/494, 0.2%), fistula (1/494, 0.2%), and perforation (5/494, 1.0%). In total, 17/23 (73.9%) major vascular complications required immediate endovascular and/or open surgery. In 16/17 (94%) cases, only 1 surgical procedure was performed. The long-term survival of patients with and without major vascular complications of the peripheral vessels was determined after 2 years. CONCLUSIONS: Early vascular surgery intervention reversed the mortality disadvantage in patients with major complications of the peripheral vessels after TAVR. This underscores the importance of immediate vascular surgery stand-by as an indispensable requirement.

Do Glucagonlike Peptide-1 Receptor Agonist and Sodium-glucose Co-transporter 2 Inhibitor Prescriptions in Germany Reflect Recommendations for Type 2 Diabetes with Cardiovascular Disease of the ADA/EASD Consensus Report?

OBJECTIVES: To analyze whether prescription use of GLP-1RA and SGLT2i in individuals with type 2 diabetes with cardiovascular disease (CVD) has increased after the ADA/EASD consensus guidelines (2018) in a German Real-World setting and which clinical characteristics are associated with prescription use of these drugs. METHODS: The Disease Analyzer database (IQVIA) comprises a representative panel of 1,373 general practitioners, diabetologists, and cardiologists throughout Germany (01/2015-12/2020: 12.6 million patients). Newly diagnosed type 2 diabetes (n=45,531) was identified by ICD-10 codes (E11). Matching (1:1) on practice specialty, sex, age, and year of diabetes diagnosis was performed for CVD. Logistic regression models were fitted to obtain adjusted odds ratios (OR) for characteristics associated with prescription use (median follow-up: 1.9 years). RESULTS: Overall, 35% of patients (n=16,006) were treated with glucose-lowering drugs during the first year after type 2 diabetes diagnosis (HbA1c≥7.0%: 80%). GLP-1RA (2.4%) and SGLT2i (8.5%) were rarely prescribed. After the consensus, use of GLP-1RA and SGLT2i increased, however, almost independently of pre-existing CVD (12/2019-11/2020 vs. 12/2017-11/2018: yes, no): GLP-1RA: from 5.7 to 9.2%, 5.2 to 7.6%; SGLT2i: from 13.9 to 20.4%, 12.1 to 16.6%. Among cardiovascular risk factors, the largest OR for GLP-1RA was for obesity (4.5; 95%CI: 3.2-6.3). CVD was moderately related with SGLT2i (1.45; 1.32-1.60) and GLP-1RA (1.35; 1.08-1.69) prescriptions. A weak association was observed between SGLT2i and heart failure (1.18; 95%CI: 1.05-1.32). CONCLUSION: National prescription use of GLP-1RA and SGLT2i did not come close to the recommendation in subjects with CVD issued by the 2018 ADA/EASD consensus.

Acute oesophageal safety of high-power short duration with 50 W for atrial fibrillation ablation.

AIMS: Pulmonary vein isolation (PVI) using radiofrequency (RF) ablation is an effective treatment option for patients with atrial fibrillation (AF). This study aims to investigate the safety of high-power short duration (HPSD) with emphasis on oesophageal lesions after PVI. METHODS AND RESULTS: Consecutive patients undergoing AF ablation with HPSD (50 W; ablation index (AI)-guided; target AI 350 for posterior wall ablation, AI 450 for anterior wall ablation) using the ThermoCool SmartTouch SF catheter were included. Patients underwent post-ablation oesophageal endoscopy to detect and categorize thermal oesophageal injury (EDEL). Occurrence and risk factors of oesophageal lesions and perforating complications were analysed. A total of 1033 patients underwent AF ablation with HPSD. Of them, 953 patients (67.6 ± 9.6 years; 58% male; 43% paroxysmal AF; 68% first PVI) underwent post-procedural oesophageal endoscopy and were included in further analyses. Median procedure time was 82.8 ± 24.4 min with ablation times of 16.1 ± 9.2 min. Thermal oesophageal injury was detected in 58 patients (6%) (n = 29 Category 1 erosion, n = 29 Category 2 ulcerous). One patient developed oesophageal perforation (redo, 4th AF ablation). No patient died. Using multivariable regression models, increased total ablation time [odds ratio (OR) 1.029, P = 0.010] and history of stroke (OR 2.619, P = 0.033) were associated with increased incidence of EDEL after AF ablation, whereas increased body mass index was protective (OR 0.980, P = 0.022). CONCLUSION: Thermal oesophageal lesions occur in 6% of HPSD AF ablations. The risk for development of perforating complications seems to be low. Incidence of atrio-oesophageal fistula (0.1%) is comparable to other reported series about RF ablation approaches.

Incidence of acute thermal esophageal injury after atrial fibrillation ablation guided by prespecified ablation index.

INTRODUCTION: Ablation index (AI), a novel parameter defining energy application at single ablation lesions, calculated by integration of ablation time, energy, catheter stability, and contact force, has been documented to be associated with effective lesions and higher ablation efficacy. Using a prespecified target AI in addition to acute lesion efficacy may affect local collateral damage like esophageal thermal injury when used for guiding radiofrequency (RF) ablation at the posterior left atrial (LA) wall. METHODS AND RESULTS: Consecutive patients undergoing first AF ablations using AI were included. Ablation energy was reduced to 25 W when ablating at posterior LA wall. Two different individually defined AI target values were used (300 and 350 for posterior wall ablation). Esophageal endoscopy (EE) was performed 1 to 3 days after ablation procedure to document and categorize endoscopically detected esophageal thermal lesion (EDEL). Two-hundred and eleven consecutive patients with postprocedural EE were included. Incidence of EDEL was 14% (29 of 211 patients; mild category 1 lesions in 22 of 29 patients (76%) and severe category 2 lesions (ulcers > 5 mm) in 7 of 29 patients (24% of EDEL group, 3% of total group). Ablation time at posterior LA wall (9.5 vs 9.0 minutes [P = .67]) was comparable in patients with and without EDEL. CONCLUSION: LA posterior wall RF ablation adopting AI ≤350 was associated with 14% esophageal thermal injury including 3% of severe esophageal thermal ulcers. This incidence is comparable to historic control groups with non AI-guided AF ablation.

Transfemoral versus transapical transcatheter aortic valve implantation: a single-centre experience.

OBJECTIVES: Transapical transcatheter aortic valve implantation (TAVI) is associated with increased mortality as compared to the transfemoral (TF) access. Possible mechanisms include different patient risk profiles as well as an intrinsic injury caused by the access route itself. METHODS: All consecutive patients scheduled for TAVI between January 2009 and June 2016 at a single centre were evaluated. A comparison of 30-day mortality and morbidity rates for patients undergoing TF or transapical (TA) TAVI was performed according to the criteria of the Valve Academic Research Consortium 2. RESULTS: During the investigated period, 1130 patients (TF: n = 619, TA: n = 511) were scheduled for TAVI. TA patients had a higher operative risk profile (logistic EuroSCORE: 24% vs 17%; P < 0.001). Unadjusted 30-day mortality rate was higher in TA than in TF patients, albeit this difference was not significant [TA: 6.7%, TF: 4.8%; odds ratio (OR) 1.3 (0.8-2.3); P = 0.216]. The multivariate logistic regression analysis revealed the logistic EuroSCORE and institutional experience, but not the access mode as independent predictors of 30-day mortality. Major access-site complications occurred with a similar frequency in both groups [TA: 9.4%; TF: 9.2%; OR 1.02 (0.68-1.53); P = 0.915]. Unadjusted long-term mortality rate was higher after TA TAVI. After adjustment, the Cox regression analysis revealed similar long-term mortality rates after TF and TA TAVI [hazard ratio 1.1 (0.88-1.36)]. CONCLUSIONS: The increased mortality of patients undergoing TA TAVI is associated with the patient risk profile and the institutional experience but not with the access mode itself.

Progression From Esophageal Thermal Asymptomatic Lesion to Perforation Complicating Atrial Fibrillation Ablation: A Single-Center Registry.

BACKGROUND: Up to 40% of patients demonstrate endoscopically detected asymptomatic esophageal lesions (EDEL) after atrial fibrillation ablation. METHODS AND RESULTS: Patients undergoing first atrial fibrillation ablation and postinterventional esophageal endoscopy were included in the study. Occurrence of esophageal perforating complications during follow-up was related to documented EDEL (category 1: erythema/erosion; category 2: ulcer). In total, 1802 patients underwent first atrial fibrillation ablation procedure between January 2013 and August 2016 at our institution. Out of this group, 832 patients (506 male patients, 61%; 64.0±10.0 years) with symptomatic paroxysmal (n=345; 42%) or persistent atrial fibrillation underwent postprocedural esophageal endoscopy. Patients were ablated using single-tip ablation with conventional or surround flow irrigation and circular ablation catheters with open irrigation (nMARQ). In 295 of 832 patients (35%), a temperature probe was used. EDEL occurred in 150 patients (18%; n=98 category 1 EDEL, n=52 category 2 EDEL). In 5 of 832 patients (0.6%), an esophageal perforation (n=3) or an esophagopericardial or atrioesophageal fistula (n=2) occurred 15 to 28 days (19±6 days) after ablation. Two patients (1 atrioesophageal fistula and 1 esophagopericardial fistula) died. Esophageal perforation occurred only in patients with category 2 lesions (absolute risk, 9.6%). In a logistic regression analysis, ulcers were identified to be a significant predictor for esophageal perforating complications. CONCLUSIONS: Postablation endoscopy seems to identify patients at high risk of esophageal perforating complications only occurring in patients with category 2 EDEL. One out of 10 postablation esophageal ulcers progressed to perforation, and no patient without esophageal thermal ulcers showed the occurrence of perforating esophageal complications.

Declining radiation dose of coronary computed tomography angiography: German cardiac CT registry experience 2009-2014.

BACKGROUND: Coronary computed tomography angiography (CTA) is increasingly used as a test to rule out coronary artery disease (CAD) in patients with a low to intermediate pre-test probability of the disease. We used the database of the German CT registry, collected between 2009 and 2014 in a broad patient population, to analyze contemporary radiation dose associated with coronary CTA in clinical practice. PATIENTS AND METHODS: The prospective observational registry included a total of 7061 patients ≥18 years, referred to 12 participating centers for a clinically indicated cardiac CT examination. All centers were cardiology units well experienced in CTA and used multi-slice CT scanners with at least 64 rows. Coronary CTA was performed in a subset of 5001 patients, 59.6 ± 11.8 years, body mass index (BMI) 26.9 ± 4.5 kg/m2, 38% females. Three time periods with approximately equal numbers of patients were created (01/09-03/10, 04/10-03/11, 04/11-07/14). The dose-length product of all examinations and derived effective dose in mSv (conversion factor k = 0.014) as well as the influence of patient characteristics on dose were compared for the three time periods. RESULTS: BMI and proportion of female patients remained stable over time, and mean heart rate decreased from 60.3 ± 9.0 to 58.5 ± 9.3 bpm from the first to the last time period (p < 0.001). Overall, the mean effective dose of coronary CTA was 3.6 mSv (Q1 1.8 mSv, Q3 7.4 mSv). Within the three time periods, it declined from 5.6 (2.7, 8.6) mSv during the first to 4.8 (2.1, 8.2) mSv during the second and 2.5 (1.3, 4.6) mSv during the last time period (p < 0.001). Paralleling the decline in radiation dose over time, the proportion of prospectively ECG-triggered examinations increased (68, 79, 83%; p < 0.001), and the proportion of examinations with retrospective gating and no tube current modulation decreased (5.3, 4.0, 1.6%; p < 0.001). Tube current (mAs) and voltage (kV) both decreased over time. In multivariable analysis, besides earlier time period, further independent predictors of an increased radiation dose were older age, higher heart rate, and higher BMI as well as the technical factors higher mAs, higher kV, and retrospective gating. At three sites, CT scanners with improved technology were installed during the last time period. CONCLUSIONS: In current clinical practice among German cardiology units with specific expertise in cross-sectional cardiovascular imaging, overall radiation dose of coronary CTA was comparably low. Over time, a decline in radiation dose was demonstrated, probably due to a combination of improvements in data acquisition protocols and patient preparation as well as installation of new CT scanners with advanced technology.

Repetitive atrial activation during ongoing atrial fibrillation-comparison using different mapping algorithms: preliminary findings.

PURPOSE: Targeting repetitive sources identified during atrial fibrillation (focal impulse and rotor modulation, FIRM) has been used as an ablation strategy using specific mapping tools. Aim of this study was to evaluate FIRM mapped rotors with a new multipolar mapping algorithm. METHODS: Patients with persistent atrial fibrillation undergoing FIRM ablation were included. Mapping of left atrial rotors was performed with a 64-pole basket catheter in conjunction with a specialized phase mapping algorithm. Subsequently, raw signals were analyzed by a novel mapping system (CARTOFINDER™). Comparison of FIRM identified sources with areas of repetitive activation analyzed by CARTOFINDER™ was performed. RESULTS: Nine patients were included (5 redo procedures; male n = 6; 66.5 ± 8.6 years) and 28 left atrial rotors were compared with the findings of the novel mapping system. CARTOFINDER™ identified repetitive activation patterns in 6 mapping sequences at remote sites (2 rotational patterns, 4 linear activation patterns). CONCLUSIONS: In this comparative preliminary study, two different mapping technologies to detect repetitive atrial activation during ongoing AF were used. Whereas rotational activation was documented using FIRM mapping no corresponding repetitive activation patterns near sites of FIRM-mapped rotor cores were identified using the novel mapping technology even though using the same electrogram characteristics and mapping basket position.

Omission of predilation in balloon-expandable transcatheter aortic valve implantation: retrospective analysis in a large-volume centre.

AIMS: We aimed to evaluate the effect of omitting predilation on feasibility, procedural results and safety in balloon-expandable TAVI. METHODS AND RESULTS: We performed an analysis of all 680 patients scheduled for a balloon-expandable TAVI prosthesis between January 2011 and August 2016. Patients treated with or without predilation were compared. Procedure times decreased from 85.6±42.9 to 56.7±26.1 minutes (p<0.001), fluoroscopy times from 9.5±5.7 to 6.2±3.9 minutes (p<0.001) and contrast volume from 131.9±60.8 to 85.4±37.4 ml (p<0.001) without predilation. Intraprocedural CPR was significantly more frequent in the predilation group (5.3% vs. 1.4%, p=0.01). Stroke rate was low at 1.5% and with no detectable difference. Applying VARC-2 definitions, the combined endpoints device success (88.3% vs. 92.4%, p=0.07) and clinical efficacy (88.7% vs. 92.4%, p=0.11) were comparable with or without prior valvuloplasty, while early safety was less frequent with predilation (85.2% vs. 90.2%, p=0.04). At 30 days, all-cause mortality and cardiovascular mortality were 6.8% with predilation vs. 2.9% without predilation (p=0.03) and 5.3% vs. 1.4% (p=0.01). CONCLUSIONS: TAVI without prior valvuloplasty is feasible without apparent adverse impact in patients receiving a balloon-expandable TAVI prosthesis. The omission of predilation is associated with shorter procedure time, less radiation exposure and lower rates of intraprocedural resuscitation.

Impact of surround flow catheter tip irrigation in contact force ablation on the incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation: a prospective comparative study.

AIMS: Aim of this study was to evaluate the impact of a recently introduced contact force ablation catheter with modified irrigation technology compared with a conventionally irrigated ablation catheter on the incidence of endoscopically detected oesophageal lesions (EDEL). METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent atrial fibrillation (AF) who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter with conventional irrigation (Group 1; n = 50) or with a recently introduced intensified 'surround flow' irrigation technology (Group 2; n = 50). Assessment of EDEL was performed by oesophagogastroduodenoscopy in all patients after ablation. A total of 100 patients (mean age 63.6 ± 12.1 years; men 58%) with paroxysmal (n = 41; 41%) or persistent AF were included. Groups 1 and 2 patients were comparable in regard to baseline characteristics and procedural parameters, especially ablation time at posterior left atrial wall. Overall, 13 patients (13%) developed EDEL after AF ablation (8 oesophageal ulcerations, 5 erythema). The incidence of EDEL including oesophageal ulcerations was higher in Group 2 compared with Group 1 patients without statistical significance (18 vs. 8%, P = 0.23). One pericardial tamponade and one access site bleeding occurred in Group 2. No further adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of an improved ablation catheter irrigation technology (surround flow) in conjunction with contact force measurement was associated with a higher but not statistically significant probability of oesophageal thermal lesions. Further studies including larger patient cohorts are needed.

Incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation using an oesophageal temperature probe with insulated thermocouples: a comparative controlled study.

AIMS: Oesophageal probes to monitor luminal oesophageal temperature (LET) during atrial fibrillation (AF) catheter ablation have been proposed, but their effects remain unclear. Aim of this study is to evaluate the effects of an oesophageal temperature probe with insulated thermocouples. METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent AF who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter. An intraluminal oesophageal temperature probe was used in Group 1. In Group 2, patients were ablated without LET monitoring. Assessment of asymptomatic endoscopically detected oesophageal lesions (EDEL) was performed by oesophagogastroduodenoscopy (EGD) in all patients. Eighty patients (mean age 63.7 ± 10.7 years; men 56%) with symptomatic, drug-refractory paroxysmal (n = 28; 35%) or persistent AF were included. Group 1 and Group 2 patients (n = 40 in each group) were comparable in regard to baseline characteristics, but RF duration on the posterior wall was significantly shorter in Group 1 patients. Overall, seven patients (8.8%) developed EDEL (four ulcerations, three erythema). The incidence of EDEL in Group 1 and Group 2 patients was comparable (7.5 vs. 10%, P = 1.0). No major adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of oesophageal temperature probes with insulated thermocouples seems to be feasible in patients undergoing AF RF catheter ablation. The incidence of post-procedural EDEL when using a cut-off of 39°C is comparable to the incidence of EDEL without using a temperature probe.

Hemodynamic Improvement at Three Months after MitraClip® Treatment in End-Stage Heart Failure Patients with Functional Mitral Regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is common in patients with advanced heart failure and impaired left ventricular function. The study aim was to examine functional and hemodynamic effects at three months after MitraClip® implantation in high-risk surgical patients with FMR. METHODS: A group of 93 patients was rejected for surgical treatment by heart-team decisions due to an inacceptable risk for conventional mitral valve surgery. Between October 2011 and May 2015, 89 of these patients (96%) were treated successfully with MitraClip implantation. A subsequent complete follow up was performed over three months in 32 patients with FMR, including pro-brain natriuretic peptide (pro-BNP) measurements, six-minute walk test, echocardiography, and right heart catheterization. RESULTS: The patients (mean age 73 ± 7 years) presented with a mean left ventricular ejection fraction (LVEF) of 32 ± 13%, and mitral regurgitation (MR) grade ≥3 in 30 of 32 cases (93%). All patients suffered from severe FMR and were highly symptomatic (NYHA functional class III or IV). The mean logistic EuroSCORE was 33%. MitraClip implantation resulted in a significant clinical improvement and reverse cardiac remodelling with a decrease in LV end-diastolic and LV endsystolic diameters, while LVEF was unchanged. In addition, a statistically relevant reduction of systolic, diastolic and mean pulmonary artery pressures (PAPsystolic -7.2 mmHg, p = 0.011; PAPdiastolic -4.5 mmHg, p = 0.003; and PAPmean -5.3 mmHg, p = 0.007) were measured, while the cardiac index (+0.3 l/min/m2, p <0.001) and cardiac output (+0.5 l/min, p <0.001) were increased significantly. The 30-day mortality was 8.6% (n = 8). CONCLUSIONS: Among the study population, MitraClip implantation led to clinical improvement, reverse cardiac remodeling, and a sustained hemodynamic benefit during the three-month follow up period.

The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics.

BACKGROUND: Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disease incidence remains uncertain. METHODS: A nested case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random subcohort (n=778) and primary cases of myocardial infarction (MI, n=276) and ischemic stroke (n=151). Pre-diagnostic FOXP3+ Treg and total CD3+ T-lymphocyte (tTL) frequencies in blood were measured by epigenetic-based, quantitative real-time PCR-assisted cell counting. RESULTS: Multivariate, Prentice-weighted Cox regression analyses revealed that lower Treg/tTL ratios were not associated with the risk of either MI (lowest vs. highest sex-specific quartile; hazard ratio: 0.72, 95% confidence interval: 0.46 to 1.13; Ptrend=0.51) or stroke (HR: 0.90, 95% CI: 0.51 to 1.60; Ptrend=0.78). There were no correlations of Treg/tTL ratios with C-reactive protein, HbA1c, and various lipid parameters. CONCLUSIONS: Among middle-aged adults from the general population, imbalances in the relative frequency of Tregs within the total T cell compartment do not confer an increased risk of MI or stroke.

Treg-Mediated Immune Tolerance and the Risk of Solid Cancers: Findings From EPIC-Heidelberg.

BACKGROUND: Laboratory-based, mechanistic, and prognosis studies suggest that a shift from antitumor immunity towards tumor-immune tolerance plays a major role in carcinogenesis. However, prospective epidemiological studies on the consequences of differing immune tolerance levels prior to clinical manifestation are missing. METHODS: A case-cohort study embedded in EPIC-Heidelberg was conducted comprising incident cases of breast (n = 399), colorectal (n = 185), lung (n = 149), and prostate (n = 378) cancer, which occurred during 6.6 years of follow-up, and a subcohort (n = 807). Foxp3+ regulatory T-lymphocytes and CD3+ T-lymphocytes were measured by quantitative polymerase chain reaction-based DNA methylation analysis in prediagnostic leukocyte samples. Hazard ratios (HRs) for associations of cancer risk with the ratio of both parameters, the "cellular ratio of immune tolerance" (ImmunoCRIT), were estimated using Cox regression models. All statistical tests were two-sided. RESULTS: ImmunoCRIT values were positively associated with the risk of lung (highest vs lowest tertile, HR = 1.98, 95% confidence interval = 1.06 to 3.69, P trend = .0263) and colorectal cancer (HR = 1.59, 95% CI = 0.99 to 2.54, P trend = .0069) after multivariable adjustment, but not with prostate cancer risk. Regarding breast cancer significant heterogeneity by estrogen receptor (ER) status was observed (P heterogeneity = .02), and the ImmunoCRIT was associated with the risk of ER-negative breast cancer (HR = 3.34, 95% CI = 1.52 to 7.35, P trend ≤ .001), but not ER-positive breast cancer. CONCLUSION: The present study indicates that increased peripheral immune tolerance may be an independent risk factor for lung, colorectal, and ER-negative breast cancer, whereas its role on the development of prostate and ER-positive breast tumors remains uncertain.

Association between left atrial low-voltage area, serum apoptosis, and fibrosis biomarkers and incidence of silent cerebral events after catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCE) have been identified on cerebral diffusion-weighted cerebral magnetic resonance imaging (DE-MRI) after catheter ablation (CA) of atrial fibrillation (AF). The purpose of this study was to investigate the impact of atrial remodeling on the incidence of SCE after AF CA. METHODS: Forty patients (67.8 ± 10 years, 47.5 % women) with symptomatic paroxysmal (n = 11, 27.5 %) or persistent AF undergoing AF CA were prospectively enrolled. LA fibrosis was estimated by intraprocedural bipolar voltage mapping in sinus rhythm. Apoptosis-stimulating fragment (Fas-Ligand) and amino terminal peptide from collagen III (PIIINP) concentrations were analyzed of LA and femoral vein blood. Cerebral DE-MRI was performed 1 to 2 days after CA of AF for detection of SCE. In nine patients (22.5 %), new SCE were detected on DE-MRI after AF CA. RESULTS: Patients with SCE had higher CHA2DS2-VASc score, larger left atrial diameter (LADmax), and higher surface area of left atrial low-voltage (24 ± 11.2 vs 3.5 ± 4.2 %, p < 0.0001). Concentrations of peripheral PIIINP (103.7 ± 25.9 vs 81.8 ± 16.7 pg/ml, p < 0.01) and Fas-Ligand (124.1 ± 22.4 vs 87.6 ± 19.4 pg/ml, p < 0.01) were significantly higher in patients with SCE and correlated to low-voltage surface area (p < 0.01). Multivariable logistic regression analysis revealed peripheral Fas-Ligand, LADmax, CHA2DS2-Vasc score, and LA low-voltage area proportion to be independent predictors for the development of SCE. CONCLUSIONS: LA remodeling, estimated by LADmax and LA low-voltage area, has significant relationship with the risk of SCE after AF ablation. Moreover, Fas-Ligand may act as an independent predictor for SCE in the context of AF CA.

Recurrence of paroxysmal atrial fibrillation after cryoisolation of the pulmonary veins. Is a "redo" procedure using the cryoballoon useful?

BACKGROUND: Pulmonary vein (PV) isolation with the cryoballoon technique is an effective and safe method to treat patients with paroxysmal atrial fibrillation (AF). However, the optimal treatment strategy for patients with recurrences after this ablation is unclear. AIMS: The aim of this single centre study was to evaluate the efficacy and safety of a "redo" procedure using the cryoballoon in this patient cohort. The secondary study objectives were to determine the rate of reconduction for individual PVs of the patients undergoing "redo" ablation and potential predictors of persistent PV isolation (PVI). METHODS: Between April 2006 and September 2009, all patients with paroxysmal AF recurrences after cryoballoon ablation a "redo" ablation with the cryoballoon was offered. PV conduction was determined and cryoapplications were performed in all reconnected PVs. Every 3 months, 7-day Holter ECG, symptom-driven transtelephonic ECG recordings, and questionnaires were collected for 12 months. RESULTS: Forty-seven patients underwent "redo" cryoballoon ablation. In all these patients, at least one PV with reconduction was found. Recurrent conduction was documented in 63 % of the left superior PV, 56 % of the left inferior PV, 43 % of the right superior PV, and 56 % of the right inferior PV. In 28 of the 47 patients (60 %), no AF recurrence was detectable during the 12-month follow-up (after 3 months blanking period). Rate of severe complications was low and not significantly different from that of the initial ablations. CONCLUSION: "Redo" ablation using cryoballoon technology may be an effective and safe method to treat patients with recurrence of paroxysmal AF after cryoballoon PVI.