Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial.

OBJECTIVES This study was conducted to determine if an additional procedural endpoint of unexcitability (UE) to pacing along the ablation line reduces recurrence of atrial fibrillation (AF) or atrial tachycardia (AT) after radiofrequency catheter ablation. BACKGROUND AF/AT recurrence is common after pulmonary vein isolation (PVI). METHODS We included 102 patients from 2 centers (age 63 ± 10 years; 33 women; left atrium 38 ± 7 mm; left ventricular ejection fraction 61 ± 6%) with symptomatic paroxysmal AF. A 3-dimensional mapping system and circumferential mapping catheter were used in all patients for PVI. In group 1 (n = 50), the procedural endpoint was bidirectional block across the ablation line. In group 2 (n = 52), additional UE to bipolar pacing at an output of 10 mA and 2-ms pulse width was required. The primary endpoint was freedom from any AF/AT (>30 s) after discontinuation of antiarrhythmic drugs. RESULTS Procedural endpoints were successfully achieved in all patients. Procedure duration was significantly longer in group 2 (185 ± 58 min vs. 139 ± 57 min; p < 0.001); however, fluoroscopy times were not different (23 ± 9 min vs. 23 ± 9 min; p = 0.49). After a follow-up of 12 months in all patients, 26 patients (52%) in group 1 versus 43 (82.7%) in group 2 were free from any AF/AT (p = 0.001) after a single procedure. No major complications occurred. CONCLUSIONS The use of pacing to ensure UE along the PVI line markedly improved near-term single-procedure success, compared with demonstration of bidirectional block alone. This additional endpoint significantly improved patient outcomes after PVI. (Unexcitability Along the Ablation as an Endpoint for Atrial Fibrillation Ablation; NCT01724437).

Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study

BACKGROUND The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. METHODS AND RESULTS The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality. CONCLUSIONS We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies

The association between subclinical thyroid dysfunction and cardiovascular outcomes has been recently clarified with the publication of three individual participant data (IPD) analyses from the Thyroid Studies Collaboration. We identified original cohort studies with a systematic review and pooled individual data from over 70'000 participants to obtain a more precise estimate of the risks of cardiovascular outcomes associated with subclinical thyroid dysfunction. Subclinical hypothyroidism and subclinical hyperthyroidism, defined as normal thyroxine (FT4) levels with increased or decreased Thyroid-Stimulating Hormones (TSH or thyrotropin) respectively, are associated with increased risk of cardiovascular outcomes compared to euthyroid state, particularly in those with a more pronounced thyroid dysfunction. Specifically, subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD) events, CHD mortality and heart failure (HF) events in individuals with higher TSH levels, particularly in those with TSH levels ≥10.0 mIU/L. Conversely, subclinical hyperthyroidism is associated with an increased risk of total mortality, CHD mortality, HF and atrial fibrillation, particularly in those with suppressed TSH levels <0.10 mIU/L. Pending ongoing randomized controlled trials, these observational findings allow identifying potential TSH thresholds for thyroid medication initiation based on risk of clinical outcomes, although clinical decision based solely on observational data need caution. The impact of thyroid replacement among the elderly with subclinical hypothyroidism is currently studied in a multicenter international randomized controlled trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial, TRUST trial).

Anticoagulation in primary care - a cross sectional study in 14 heterogeneous countries

Background: New oral anticoagulants (NOACs) are predicted to become the new standard treatment for stroke prevention in patients with atrial fibrillation, and may replace vitamin K antagonists (VKAs). NOACs are prescribed less than expected, even though they do not require international normalised ratio (INR) monitoring. In this study we assessed methods for INR monitoring after the introduction of NOACs a in heterogeneous sample of countries. Methods: We asked representatives of the Vasco da Gama Movement, a network of junior and future gen- eral practitioners (GPs) in Europe, and WONCA, the World Organization of Family Doctors, to describe the way INR is monitored in their respective countries. Results: Representatives of 14 countries responded. In most countries, the INR is monitored by GPs; in some countries, these patients are treated by other specialists or in specialised anticoagulation centres. In only a few countries, anticoagulated patients monitor the INR themselves. Conclusion: Our study showed several strategies for managing anticoagulation in different countries. In most countries, the INR is monitored by GPs. These consultations offer opportunities to address other is- sues, such as blood pressure control or medication adherence. These factors may be considered when de- ciding to switch patients from VKAs to NOACs.

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

PURPOSE In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODS We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. RESULTS In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

Impact of cardiac computed tomography of the interatrial septum before pulmonary vein isolation

BACKGROUND Multidetector computed tomography (MDCT) may be useful to identify patients with patent foramen ovale (PFO). The aim of this study was to analyze whether a MDCT performed before pulmonary vein isolation reliably detects a PFO that may be used for access to the left atrium. METHODS AND RESULTS In 79 consecutive patients, who were referred for catheter ablation of symptomatic paroxysmal or persistent atrial fibrillation (AF), the presence of a PFO was explored by MDCT and transesophageal echocardiography (TEE). TEE was considered as the gold standard, and quality of TEE was good in all patients. In 16 patients (20.3%), MDCT could not be used for analysis because of artifacts, mainly because of AF. On TEE, a PFO was found in 15 (23.8%) of the 63 patients with usable MDCT. MDCT detected six PFO of which four were present on TEE. This corresponded to a sensitivity of 26.7%, a specificity of 95.8%, a negative predictive value of 80.7%, and a positive predictive value of 66.7%. The receiver operating characteristics curve of MDCT for the detection of PFO was 0.613 (95% confidence interval 0.493-0.732). CONCLUSIONS MDCT may detect a PFO before pulmonary isolation. However, presence of AF may lead to artifacts on MDCT impeding a meaningful analysis. Furthermore, in this study sensitivity and positive predictive value of MDCT were low and therefore MDCT was not a reliable screening tool for detection of PFO.

Patient self-management of oral anticoagulation with vitamin k antagonists in everyday practice: efficacy and safety in a nationwide long-term prospective cohort study.

Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2-12.8 years). Median age at the time of training was 54.2 years (range 18.2-85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1-1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6-3.7; p<0.001), patients>50 years of age (2.0; 1.6-2.6; p<0.001), and men (1.6; 1.2-2.1; p = 0.036). The rate of thromboembolic events was 0.4 (0.2-0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9-1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

Long-term outcome of elderly patients with severe aortic stenosis as a function of treatment modality

OBJECTIVE To assess long-term clinical outcomes of consecutive high-risk patients with severe aortic stenosis according to treatment allocation to transcatheter aortic valve implantation (TAVI), surgical aortic valve replacement (SAVR) or medical treatment (MT). METHODS Patients with severe aortic stenosis were consecutively enrolled into a prospective single centre registry. RESULTS Among 442 patients (median age 83 years, median STS-score 4.7) allocated to MT (n=78), SAVR (n=107), or TAVI (n=257) all-cause mortality amounted to 81%, 37% and 43% after a median duration of follow-up of 3.9 years (p<0.001). Rates of major adverse cerebro-cardiovascular events were lower in patients undergoing SAVR or TAVI as compared with MT (SAVR vs MT: HR 0.31, 95% CI 0.21 to 0.46) (TAVI vs MT: HR 0.34, 95% CI 0.25 to 0.46), with no significant difference between SAVR and TAVI (HR 0.88, 95% CI 0.62 to 1.25). Whereas SAVR (HR 0.39, 95% CI 0.24 to 0.61), TAVI (HR 0.37, 95% CI 0.26 to 0.52), and female gender (HR 0.72, 95% CI 0.53 to 0.99) were associated with improved survival, body mass index ≤20 kg/m(2) (HR 1.60, 95% CI 1.04 to 2.47), diabetes (HR 1.48, 95% CI 1.03 to 2.12), peripheral vascular disease (HR 2.01, 95% CI 1.44 to 2.81), atrial fibrillation (HR 1.74, 95% CI 1.28 to 2.37) and pulmonary hypertension (HR 1.43, 95% CI 1.03 to 2.00) were identified as independent predictors of mortality. CONCLUSIONS Among high-risk patients with severe aortic stenosis, long-term clinical outcome through 5 years was comparable between patients allocated to SAVR or TAVI. In contrast, patients with MT had a dismal prognosis.

Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis

BACKGROUND Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. METHODS AND RESULTS Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. CONCLUSIONS The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism.

Patent foramen ovale and closure technique with the amplatzer occluder.

Proof that percutaneous closure of the patent foramen ovale (PFO) is superior to medical treatment is still incomplete. Paradoxical embolism is a rare event occurring over decades rather than years. None of the 4 randomized trials published carried enough patients or was followed up for long enough to reach superiority endpoints. All data, however, point to a benefit of PFO closure. Free wall erosion (exceedingly rare) and triggering of atrial fibrillation (in about 1% of patients) are the only noteworthy complications. They are outweighed by the supposedly prevented events of paradoxical embolisms, such as stroke, transient ischemic attacks, myocardial infarctions, or other systemic embolisms. Medical treatment with perhaps the exception of lifelong oral anticoagulation provides less protection. During a 10-year follow-up of a comparative study the annual mortality was significantly lower in the patients with PFO closure (0.4%) than in those with medical treatment (1.1%, P < 0.03). PFO closure can be accomplished in less than 1 hour with immediate resumption of physical activity. It represents thus a kind of mechanical vaccination.

Closure of patent foramen ovale for secondary prevention of cerebrovascular events

Stroke is the most debilitating cardiovascular event. It has a variety of causes that may be present simultaneously. In young or otherwise healthy people a patent foramen ovale (PFO) is increasingly searched for. In stroke of the elderly atherosclerosis and atrial fibrillation are in the foreground but the PFO should not be ignored. The risk of a PFO related stroke over time is controversial and so is its prevention by PFO closure. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. We review the rationale for PFO closure for secondary prevention of embolic events.

Antioxidant supplementation attenuates oxidative stress in patients undergoing coronary artery bypass graft surgery.

Ischemia-reperfusion has been reported to be associated with augmented oxidative stress in the course of surgery, which might be causally involved in the onset of atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. We hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty acids (n-3 PUFAs) might lower the incidence of AF following coronary artery bypass graft (CABG) surgery. In the present study, by monitoring oxidative stress in the course of CABG surgery, we analyzed the efficacy of vitamins (ascorbic acid and α-tocopherol) and/or n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid). Subjects (n = 75) were divided into 4 subgroups: control, vitamins, n-3 PUFAs, and a combination of vitamins and n-3 PUFAs. Fluorescent techniques were used to measure the antioxidative capacity, i.e. ability to inhibit oxidation. Total peroxides, endogenous peroxidase activity, and antibodies against oxidized LDL (oLAb) were used as serum oxidative stress biomarkers. Post-operative increase in oxidative stress was associated with the consumption of antioxidants and a simultaneous onset of AF. This was confirmed through an increased peroxide level and a decreased oLAb titer in control and n-3 PUFAs groups, indicating the binding of antibodies to oxidative modified epitopes. In both subgroups that were supplemented with vitamins, total peroxides decreased, and the maintenance of a constant IgG antibody titer was facilitated. However, treatment with vitamins or n-3 PUFAs was inefficient with respect to AF onset and its duration. We conclude that the administration of vitamins attenuates post-operative oxidative stress in the course of CABG surgery.

Stroke Prevention - Medical and Lifestyle Measures.

Background: According to the World Health Organization, stroke is the 'incoming epidemic of the 21st century'. In light of recent data suggesting that 85% of all strokes may be preventable, strategies for prevention are moving to the forefront in stroke management. Summary: This review discusses the risk factors and provides evidence on the effective medical interventions and lifestyle modifications for optimal stroke prevention. Key Messages: Stroke risk can be substantially reduced using the medical measures that have been proven in many randomized trials, in combination with effective lifestyle modifications. The global modification of health and lifestyle is more beneficial than the treatment of individual risk factors. Clinical Implications: Hypertension is the most important modifiable risk factor for stroke. Efficacious reduction of blood pressure is essential for stroke prevention, even more so than the choice of antihypertensive drugs. Indications for the use of antihypertensive drugs depend on blood pressure values and vascular risk profile; thus, treatment should be initiated earlier in patients with diabetes mellitus or in those with a high vascular risk profile. Treatment of dyslipidemia with statins, anticoagulation therapy in atrial fibrillation, and carotid endarterectomy in symptomatic high-grade carotid stenosis are also effective for stroke prevention. Lifestyle factors that have been proven to reduce stroke risk include reducing salt, eliminating smoking, performing regular physical activity, and maintaining a normal body weight. © 2015 S. Karger AG, Basel.

Paroxysmale supraventrikuläre Tachykardien – Mechanismen, Diagnostik und Therapie

Supraventrikuläre Tachykardien sind definitionsgemäß Tachykardien, die ihren Ursprungsort oberhalb der His-Bündel-Bifurkation haben. Der Ausdruck supraventrikulär ist aber ungenau und historisch bedingt. Die häufigsten supraventrikulären Tachykardien im eigentlichen Sinn umfassen die AV-Knoten-Reentry-Tachykardie und die AV-Reentry-Tachykardie, wobei die letztere die Ventrikel als integraler Bestandteil der kreisenden Erregung braucht und somit also nicht rein supraventrikulär ist. Die häufigste supraventrikuläre Tachykardie überhaupt ist aber die Sinustachykardie, die in der Regel physiologisch ist, gefolgt von Vorhofflimmern und Vorhofflattern. Da Vorhofflimmern und Vorhofflattern in dieser Ausgabe der Therapeutischen Umschau gesondert besprochen werden, liegt der Fokus dieser Übersichtsarbeit in der Diskussion von Mechanismen, Diagnostik und Therapie der AV-Knoten-Reentry-Tachykardie, der AV-Reentry-Tachykardie via akzessorische Leitungsbahn und am Rande auch der fokalen atrialen Tachykardie.

Pulmonary Vein Isolation Versus Defragmentation: The CHASE-AF Clinical Trial

BACKGROUND Long-term success rates using ablation for persistent atrial fibrillation (AF) are disappointing and usually do not exceed 60%. OBJECTIVES This study sought to compare arrhythmia-free survival between pulmonary vein isolation (PVI) and a stepwise approach (full defrag) consisting of PVI, ablation of complex fractionated electrograms, and additional linear ablation lines in the setting of atrial tachycardias (AT) in patients with persistent AF after PVI. METHODS From November 2010 to February 2013, 205 patients (151 men; 61.7 ± 10.2 years of age) underwent de novo ablation for persistent AF. Subsequently, patients were prospectively randomized to either PVI alone (n = 78) or full defrag (n = 75), with 52 patients not randomized due to AF termination with the original PVI. The primary endpoint was recurrence of any AT after a blanking period of 3 months. RESULTS During the entire study, 241 ablations were performed (mean: 1.59 in the PVI-alone group, 1.55 in the full-defrag group). With the stepwise approach, termination of AF occurred in 45 (60%) patients. However, arrhythmia-free survival did not differ whether patients underwent single or multiple procedures (p = 0.468). Procedure duration, fluoroscopy time, and radiofrequency duration were significantly longer in the full-defrag group (all p < 0.001). CONCLUSIONS A stepwise approach aimed at AF termination does not seem to provide additional benefit over PVI alone in patients with persistent AF, but it is associated with significantly longer procedural and fluoroscopic duration as well as radiofrequency application time. (The Randomized Catheter Ablation of Persist End Atrial Fibrillation Study [CHASE-AF]; NCT01580124).