Predictors of recurrence after durable pulmonary vein isolation for paroxysmal atrial fibrillation.

AIMS: Catheter ablation of paroxysmal atrial fibrillation (AF) reduces AF recurrence, AF burden, and improves quality of life. Data on clinical and procedural predictors of arrhythmia recurrence are scarce and are flawed by the high rate of pulmonary vein reconnection evidenced during repeat procedures after pulmonary vein isolation (PVI). In this study, we identified clinical and procedural predictors for AF recurrence 1 year after CLOSE-guided PVI, as this strategy has been associated with an increased PVI durability. METHODS AND RESULTS: Patients with paroxysmal AF, who received CLOSE-guided PVI and who participated in a prospective trial in our centre, were included in this study. Uni- and multivariate models were plotted to find clinical and procedural predictors for AF recurrence within 1 year. Three hundred twenty-five patients with a mean age of 63 years (CHA2DS2VASc 1 [1-3], left atrium diameter 41 ± 6 mm) were included. About 60.9% were male individuals. After 1 year, AF recurrence occurred in 10.5% of patients. In a binary logistic regression analysis, the diagnosis-to-ablation time (DAT) was found to be the strongest predictor of AF recurrence (P = 0.011). Diagnosis-to-ablation time ≥1 year was associated with a nearly two-fold increased risk for developing AF recurrence. CONCLUSION: The DAT is the most important predictor of arrhythmia recurrence in low-risk patients treated with durable pulmonary vein isolation for paroxysmal AF. Whether reducing the DAT could improve long-term outcomes should be investigated in another trial.

Effectiveness of Adjunctive Analgesics in Head and Neck Cancer Patients Receiving Curative (Chemo-) Radiotherapy: A Systematic Review.

OBJECTIVE: Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy. DESIGN: Systematic review. INTERVENTIONS: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy." OUTCOME MEASURES: Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc. RESULTS: Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy. CONCLUSIONS: More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain.

Evaluation of higher power delivery during RF pulmonary vein isolation using optimized and contiguous lesions.

AIMS: "CLOSE"-guided pulmonary vein isolation (PVI) is based on contiguous (≤6 mm) and optimized radiofrequency (RF) ablation lesions (ablation index [AI] ≥ 400 posteriorly and ≥ 550 anteriorly]. However, the optimal RF power to reach the desired AI is unknown. Therefore we evaluated the efficiency of an ablation strategy using higher power (40 W) during a first "CLOSE"-guided PVI. METHODS: Eighty consecutive patients undergoing "CLOSE"-guided PVI for symptomatic paroxysmal atrial fibrillation were ablated with 40 W (group A). Results were compared with 105 consecutive patients enrolled in the "CLOSE to CURE"-study and were ablated using the same protocol with 35 W (group B). RESULTS: In group A, ablation was associated with shorter ablation procedure time (91 vs 111 minutes; P < .001), shorter fluoroscopy time (5 vs 11 minutes; P < .001), shorter PVI time (48 vs 64 minutes; P < .001), shorter RF time (20 vs 28 minutes; P < .001), lower RF time per application (22 vs 29 seconds; P < .001), less RF applications (52 vs 58; P < .001), and less catheter dislocations (1 vs 2; P = .002). The impedance drop (12 vs 13 Ω; P = .192), first-pass isolation rate (99% vs 93%; P = .141) and acute reconnection rate (6% vs 4%; P > .733) were similar in both groups (groups A and B, respectively). No complications occurred. In group A, a gastroscopy-performed in five patients with esophageal temperature rise more than 42°C-did not reveal any esophageal lesion. Postprocedural recurrence of atrial tachyarrhythmia at 1 year was not significantly different between both groups. CONCLUSIONS: Using the "CLOSE"-protocol, increased power increases the efficiency of PVI without compromising patients' safety.

Quality of blood samples collected at home does not affect clinical decision making for the administration of systemic cancer treatment.

The aim of this exploratory clinical study was to evaluate whether the preanalytical quality of blood samples subjected to delayed centrifugation and transport - as a result of home-sampling - is affected in a way it alters the clinical decision-making for patients under systemic cancer therapy. This evaluation is part of a comprehensive investigation of the opportunities for oncological home-hospitalization. Forty-nine patients with cancer donated two additional blood samples during their ambulatory hospital visit. Fifteen blood analytes were compared between routine blood samples and samples that were subjected to transport and delayed centrifugation in order to mimic a locally implemented model for oncological home-hospitalisation. Deviations were analysed by means of Deming regression. For those analytes showing statistically significant intercepts and/or slopes, the mean deviations were compared to the desirable analytical bias; and the intra-individual differences were compared with the limits for clinical decision-making. Statistically significant intercepts and/or slopes were observed for haematocrit (HCT), mean cellular volume (MCV), platelets count (PLT) and C-reactive protein (CRP). Differences exceeding the allowable margins of desirable analytical bias were observed for HCT and MCV. Risk of different clinical decision-making couldn't be observed for any of the analytes showing statistically significant differences. These results demonstrate that home-collection of blood samples, transported at room temperature and centrifuged within a mean time of five hours after sampling, has no effect on clinical decision-making with regards to systemic cancer therapy. However, attention should be paid to the potential occurrence of haemolysis during the preanalytical phase, which can negatively influence haemolysis-dependent variables.

Identification of repetitive atrial activation patterns in persistent atrial fibrillation by direct contact high-density electrogram mapping.

INTRODUCTION: Recent studies have characterized drivers in persistent atrial fibrillation using automated algorithm detection with panoramic endocardial mapping by means of basket catheters. We aimed to identify repetitive atrial activation patterns (RAAPs) during ongoing atrial fibrillation (AF) based upon automated annotation of unipolar electrograms (EGMs) recorded with a high-density regional endocardial contact mapping catheter. METHODS: In 14 persistent AF patients, high-resolution EGMs were recorded for 30 seconds at sequential PentaRay (Biosense Inc) positions covering the entire biatrial surface. All recordings were reviewed off-line with dedicated software allowing automated annotation of the local activation time of the unipolar fibrillatory EGMs (CARTOFINDER; Biosense Inc). RAAPs were defined as a consistent activation pattern (for ≥3 consecutive beats) of either focal activity with centrifugal spread (RAAPfocal ) or rotational activity across the PentaRay splines spanning the AF cycle length (RAAProtational ). RESULTS: A total of 498 PentaRay recordings were analyzed (35.6 ± 7.6 per patient). The number of PentaRay recordings displaying RAAP was 9.8 ± 3.1 per patient (range = 3-15), of which 2.4 ± 2.4 RAAProtational (range = 0-7), and 7.4 ± 4.4 RAAPfocal (range = 1-13). 77% of RAAPs portrayed focal firing. The median number of repetitions per 30 second recording was 11 (range = 3-225) per recording. RAAPs were observed both in the right atrium (RA) (35%) and left atrium (LA) (65%), with the majority being near the left PVs/appendage (35% of all RAAPs) and the superior vena cava/right appendage (23% of all RAAPs). CONCLUSION: High-resolution, sequential endocardial EGM-based mapping allows identification of RAAPs in persistent AF. In our series, focal firing was the most frequently observed pattern.

Subjective, but not objective, cognitive complaints impact long-term quality of life in cancer patients.

OBJECTIVES: Cognitive complaints, of objective or subjective nature, may negatively impact cancer patients' quality of life (QoL). Further, the early detection of cognitive alterations may lead to an improved QoL. However, the content of such screening is yet unclear. This paper presents long-term QoL data of cancer patients treated with curative intent and its relation with objective and subjective cognitive complaints, and patient-reported outcome measures (PROMs). METHODS: QoL data, measured by the EORTC QLQ C-30, were obtained at baseline, 6 (T1), 12 (T2), and 24 months (T3) after treatment start, and compared between patients with and without objective and subjective cognitive complaints. The predictive value of PROMs was also examined. RESULTS: QoL data at baseline was collected in 125 patients. Response rates at T1, T2, and T3 were 84.7%, 81.5%, and 83.1%, respectively. Eighty-nine patients returned their QoL questionnaires at all times. Baseline subjective cognitive complaints had a stronger association with worse scores on patients' overall QoL and QoL subscale scores than objective cognitive complaints. An exploratory analysis into the value of PROMs in predicting long-term QoL at T3 revealed a significant effect for the Hospital Anxiety and Depression Scale-Depression and FACIT Fatigue scale. CONCLUSIONS: Self-perceived cognitive alterations are negatively associated with patients' overall QoL. As these troubles may already be present at baseline, oncology nurses should screen for the early signs of subjective cognitive complaints by use of PROMs, in order to refer the patient to proper intervention programs which may lead to an improved long-term QoL and faster reintegration into society.

Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment.

INTRODUCTION: Recent research in the field of cancer-related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors. METHODS: Patients (≥18 years) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated with a baseline neuropsychological assessment including Patient-Reported Outcome Measures (PROMs). PROMs entailed distress, anxiety and depression, fatigue, and cognitive complaints. The neuropsychological assessment comprised several cognitive domains such as premorbid IQ, attention, processing speed, flexibility, verbal and visual episodic memory, and verbal fluency. RESULTS: Cross-sectional data of 125 patients were collected. Patients had a mean age of 60.9 years (range: 30.0-85.0) and comprised primarily females (65.6%). Patients presented with cancer of following sites: breast (44.0%), digestive (28.8%), urological (11.2%), gynecologic (8.0%), hematologic malignancy (4.8%), and lung (3.2%). Patients presented with a premorbid IQ of 105.3 (range: 79.0-124.0). In 29.6% of patients, a CRCI was detected. Binary logistic regression analyses showed that a lower premorbid IQ (ß = -.084, P < .01) and a higher level of fatigue (ß = -.054, P < .05) predicted baseline CRCI. Premorbid IQ also predicted performance on individual cognitive domains. Some domains were also influenced by age, gender, having a breast cancer diagnosis, and an active treatment for hypertension. CONCLUSION: Premorbid IQ and fatigue are important predictors of baseline CRCI. Therefore, we advise researchers to implement a short IQ test when conducting clinical trials on CRCI.

The distress thermometer predicts subjective, but not objective, cognitive complaints six months after treatment initiation in cancer patients.

OBJECTIVES: Research has indicated that cancer-related cognitive impairments (CRCI) may be influenced by psychosocial factors such as distress, worry and fatigue. Therefore, we aimed to validate the distress thermometer (DT) as a screening tool to detect CRCI six months post-treatment-initiation in a group of general cancer patients. METHODS: Patients (≥18 years, n = 125) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated at baseline (T0) and six months post-treatment-initiation (T1) for CRCI by a neuropsychological assessment, including patient-reported outcome measures (PROMs). Assessed cognitive domains included premorbid intelligence, attention, processing speed, flexibility, verbal and visual episodic memory and verbal fluency. PROMs entailed distress (DT, cut-off ≥4, range 0-10), anxiety and depression, fatigue (FACIT-fatigue scale) and subjective cognitive complaints. RESULTS: At T0, 60.4% of patients showed a DT score of ≥4, whereas 50% met this criterion at T1. According to the definition of the International Cognition and Cancer Task Force, 25.5% and 28.3% of patients presented with a CRCI at T0 and T1, respectively. When evaluating the DT as a screening tool for CRCI at T1, data showed an inverse relationship between the DT and CRCI. ROC-curve analysis revealed an AUC <0.5. ROC-curve analyses evaluating the DT and FACIT-fatigue scale as screening tools for subjective cognitive complaints showed an AUC ± SE of, respectively, 0.642 ± 0.067 and 0.794 ± 0.057. CONCLUSIONS: The DT at T0 cannot be used to screen for objective CRCI at T1, but both the DT and FACIT-fatigue scale at T0 showed potential as screening tools for subjective cognitive complaints at T1.

G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy.

BACKGROUND: Evidence-based guidelines concerning the older head and neck cancer (HNCA) patient are lacking. Accurate patient selection for optimal care management is therefore challenging. We examined if geriatric assessment is indicative of long-term health-related quality of life (HRQOL) and overall survival in this unique population. METHODS: All HNCA patients, aged ≥65 years, eligible for curative radio(chemo)therapy were evaluated with the Geriatric-8 (G-8) questionnaire and a comprehensive geriatric assessment (CGA). Euroqol-5 dimensions (EQ-5D) and survival were collected until 36 months post treatment start. Repeated measures ANOVA was applied to analyse HRQOL evolution in 'fit' and 'vulnerable' patients, defined by G-8. Kaplan-Meier curves and cox proportional hazard analysis were established for determination of the prognostic value of geriatric assessments. Quality-adjusted survival was calculated in both patient subgroups. RESULTS: One hundred patients were recruited. Seventy-two percent of patients were considered vulnerable according to CGA (≥2 abnormal tests). Fit patients maintained a relatively acceptable long-term HRQOL, whilst vulnerable patients showed significantly lower median health states. The difference remained apparent at 36 months. Vulnerability, as classified by G-8 or CGA, came forward as independent predictor for lower EQ-5D index scores. After consideration of confounders, a significantly lower survival was observed in patients defined vulnerable according to G-8, compared to fit patients. A similar trend was seen based on CGA. Calculation of quality-adjusted survival showed significantly less remaining life months in perfect health in vulnerable patients, compared to fit ones. CONCLUSIONS: G-8 is indicative of quality-adjusted survival, and should be considered at time of treatment decisions for the older HNCA patient.

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

BACKGROUND: Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. METHODS: Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. RESULTS: A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. CONCLUSION: Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research.

Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment.

OBJECTIVE: We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in-depth cognitive evaluation within a comprehensive geriatric assessment (CGA). METHODS: Patients aged 70 years or older with a histologically confirmed diagnosis of cancer were evaluated with a full CGA, including CDT and Folstein Mini Mental State Examination (MMSE) as gold standard. Validation of the Freund CDT was defined in terms of diagnostic accuracy of the test through receiver operating characteristics (ROC)-analysis. To accept the Freund CDT as a screening tool, we estimated that the area under the ROC curve (AUC) had to differ significantly from 0.70 with an AUC of at least 0.85. RESULTS: Two hundred elderly cancer patients with a mean age of 79.0 years were included. Four patients were excluded from the analyses because of invalid results. Potential cognitive impairment (MMSE ≤23) was observed in 27.0% of patients. Based on of the AUC ± SE, the Freund CDT showed excellent diagnostic performance (0.95 ± 0.17). Furthermore, it provided excellent sensitivity (94.3%) and high specificity (87.4%). CONCLUSIONS: Our results indicate that the Freund CDT can be used as an initial screening tool to detect elderly cancer patients in need of a more in-depth cognitive assessment within CGA, instead of the MMSE.

Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial.

BACKGROUND: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. METHODS: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. RESULTS: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs -5%) and n-6 GLA (42% vs -20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs -1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. CONCLUSIONS: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01596933.

Impact of Catheter Ablation on Arrhythmia Burden in Patients With Shock-Resistant Persistent Atrial Fibrillation.

BACKGROUND: Persistent shock-resistant atrial fibrillation (AF) is a challenging entity, with modest results from catheter ablation according to conventional survival analysis. OBJECTIVES: The aim of this study was to determine the effect of catheter ablation on atrial tachyarrhythmia (ATA) burden in persistent AF patients undergoing first-time ablation with the use of an implantable cardiac monitor (ICM). METHODS: Patients with drug-resistant ongoing persistent AF and at least 1 previous failed cardioversion were implanted with an ICM 2 months before the procedure. All patients underwent pulmonary vein isolation with or without additional substrate ablation depending on the presence of self-terminating AF on ICM and left atrium size. Median AF burden before and after ablation, off antiarrhythmic medication, was determined from ICM recordings after review by 2 independent investigators. RESULTS: Sixty patients were recruited (mean age 66 ± 9 years, 70% male). Mean left atrial diameter was 48 ± 6 mm and median CHA2DS2VASc score was 2. Ten patients (17%) unexpectedly demonstrated self-terminating AF before ablation. The median burden of ATA before ablation was 100% (95% CI: 19.6%-100%), decreasing to 0% (95% CI: 0%-95.8%) after ablation during the post-blanking follow-up period (median reduction 100%; 95% CI: 4%-100%; P < 0.001). Twenty-seven patients (45%) experienced recurrent ATA during 12-month follow-up. In these patients, median burden before ablation was 100% (95% CI: 26.9%-100%), decreasing to 11.4% (95% CI: 0.35%-99.7%) after ablation (P < 0.001). Quality of life improved significantly from baseline, driven by lack of recurrence. CONCLUSIONS: Patient-tailored catheter ablation results in a significant reduction in ATA burden (off antiarrhythmic medication) in shock-resistant persistent AF patients using ICMs implanted 2-months pre-procedure. These data suggest that conventional arrhythmia-free survival analysis does not capture the true impact of catheter ablation in this challenging cohort.

Very High-Power Ablation for Contiguous Pulmonary Vein Isolation: Results From the Randomized POWER PLUS Trial.

BACKGROUND: Very high-power, short-duration (90-W/4-second) ablation for pulmonary vein isolation (PVI) may reduce procedural times. However, shorter applications with higher power may impact lesion quality. OBJECTIVES: In this multicenter, randomized controlled trial, the authors compared procedural efficiency, efficacy, and safety of PVI using 90-W/4-second ablation to 35/50-W ablation. METHODS: Patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI were randomized to pulmonary vein encirclement with contiguous applications using very high-power, short-duration applications (90 W over 4 seconds) or 35/50-W applications (titrated up to ablation index >550 anteriorly and >400 posteriorly). Prospective endpoints were procedural efficiency (procedure time and first-pass isolation), safety (including esophageal endoscopic evaluation), and 6-month effectiveness using repetitive Holter monitoring. RESULTS: A total of 180 patients were randomized, 90 to the 90-W group (mean age: 64.2 ± 8.9 years) and 90 to the 35/50-W group (mean age: 62.3 ± 10.8 years). Procedural time was shorter in the 90-W group vs the 35/50-W group (70 [IQR: 60-80] minutes vs 75 [IQR: 65-88.3] minutes; P = 0.009). A nonsignificant trend towards lower rates of first-pass isolation was seen in the 90-W group (83.9% vs 90%; P = 0.0852). No major complications were observed in both groups with esophageal injury occurring in 1 patient per group. At 6 months, 17% of patients in the 90-W group vs 15% in the 35/50-W group experienced recurrent arrhythmia (P = 0.681). CONCLUSIONS: Contiguous ablation using very high-power, short-duration applications results in a significant but modest reduction in procedure time with similar safety and 6-month efficacy vs a conventional approach. A hybrid approach combining both ablation modalities might be the most optimal strategy. (POWER PLUS [Very High Power Ablation in Patients With Atrial Fibrillation Schedule for a First Pulmonary Vein Isolation]; NCT04784013).

Vein of Marshall Ethanol Infusion as First Step for Mitral Isthmus Linear Ablation.

OBJECTIVES: In this study, the authors sought to investigate the added value of vein of Marshall ethanol infusion (VOMEt) as first step in facilitating radiofrequency (RF)-guided mitral isthmus (MI) block. BACKGROUND: Achieving MI block with the use of RF ablation is challenging. METHODS: Seventy patients planned for MI ablation were randomized 1:1 to VOMEt as a first step preceding RF (endocardial and epicardial, VOMFIRST group) vs RF ablation as a first step preceding VOMEt (RFFIRST group). The study end point was incidence of MI block after RF ablation and after the 2 steps. RESULTS: In VOMFIRST, VOMEt was successful in 30/35 patients (86%) resulting in a low-voltage area of 12 ± 7.4 cm2 and MI block in 2/35 patients (6%). VOMFIRST, compared with RFFIRST, was associated with higher incidence of MI block after endocardial (46% vs 11%; P < 0.001) and epicardial ablation (94% vs 43%; P < 0.001), with fewer endocardial applications (4 vs 11 vs 4; P < 0.001) and similar epicardial applications (7 vs 8; P = 0.68). Incidence of MI block after the 2 steps was 94% vs 63% (P = 0.001) in VOMFIRST vs RFFIRST, respectively. Additional touch-up RF ablation in both groups resulted in final MI block in all but 1 patient (99%). CONCLUSIONS: VOMEt as a first step in RF-guided MI line ablation significantly reduced the number of RF applications needed to achieve MI block, even if the sequence of the ablation steps did not affect the final incidence of block. (Evaluation of Vein of Marshall Ethanol Infusion During Left Atrial Linear Ablation in Patients With Persistent Atrial Fibrillation [MARSHALINE]; NCT04124328).

Trends in diagnosis, referral, red flag onset, patient profiles and natural outcome of de novo cardiac amyloidosis and their multidisciplinary implications.

BACKGROUND: Cardiac amyloidosis (CA) is often overlooked or misdiagnosed. Effects of growing disease awareness, diagnostic ameliorations and novel treatment options on CA diagnosis and management are scarcely reported. OBJECTIVE: To report trends in diagnosis, referral routes, clinical presentation, early onset diagnostic red flags and outcome in de novo CA subjects. METHODS: An unselected cohort of 139 de novo CA patients over an 8-year period in a tertiary referral hospital was recruited. RESULTS: Transthyretin (ATTR, 82%, n = 114) was the most common CA form; Light-chain (AL, 15%, n = 21) and secondary (AA, 3%, n = 4) are less prevalent. Increased awareness over time led to a marked ATTR diagnostic surge, steep non-invasive diagnostic approach increment and increased nuclear medicine and external cardiologist referrals (all p < 0.001). A total of 41% (n = 57/139) of patients were referred by non-cardiology specialist disciplines. Specific referral to rule out CA (24-36%) and diagnostic time lag from symptom onset (9 ± 12 to 8 ± 14 months), however, did not improve (all p > 0.050). Multiple early red flag events preceded CA diagnose several years in ATTR: Left ventricular hypertrophy (LVH, 60%, 4.9 ± 4.3 y), heart failure (54%, 2.5 ± 3.5 y), atrial fibrillation (47%, 5.9 ± 6.7 y), bilateral carpal tunnel syndrome (43%, 9.5 ± 5.7 y) and spinal stenosis (40%, 7.4 ± 6.5 y). LVH ≥ 12 mm was absent in 11% ATTR (n = 13/114) and 5% AL (n = 1/21) patients. Hypertension was common in both ATTR (n = 70/114, 62%) and AL (n = 10/21, 48%). 56% (n = 78/139) of CA presented with heart failure. Cumulative 1 and 5-year mortality of 10%/66%, 40%/52% and 75%/75% for ATTR, AL, and AA, respectively, remains high. CONCLUSIONS: Although CA diagnostic uptake and referral improve, specialist-specific disease and diagnostic red flag ignorance result in non-timely diagnosis and unfavourable outcome.

How Close Are We toward an Optimal Balance in Safety and Efficacy in Catheter Ablation of Atrial Fibrillation? Lessons from the CLOSE Protocol.

Catheter ablation for atrial fibrillation (AF) is a common treatment strategy in patients with drug-resistant, symptomatic AF. In patients with paroxysmal and short-standing persistent AF, pulmonary vein isolation (PVI) is often enough to prevent recurrence of atrial tachyarrhythmia (ATA). Point-by-point encircling of the PVs with radiofrequency (RF) applications, together with cryoballoon ablation, have been the mainstay strategies for the last 10 to 20 years. Each of these strategies, however, suffers from the delicate balance between preventing PV reconnection, on the one hand (toward more energy), and preventing (mainly esophageal) complications (toward less energy), on the other. The CLOSE protocol was developed as an RF ablation strategy that would result in the safe creation of durable isolation leading to improved outcomes. Basically, the aim of the protocol is to enclose the pulmonary veins with stable, contiguous (intertag distance, ITD ≤ 6 mm) and optimized lesions (35 Watts, W, RF applications up to ablation index targets of ≥400 and ≥550 at the posterior and anterior wall). In this review, we describe the background of the CLOSE protocol and the studies from the St Jan Bruges research group on procedural performance, efficacy, and safety of the CLOSE protocol in (a) single-center prospective PILOT study (CLOSE-PILOT), (b) a single-center prospective study with continuous rhythm monitoring (CLOSE to CURE), (c) a database of systematic esophageal endoscopic studies, (d) a multicenter prospective study (VISTAX), and (e) the CLOSE database (comprising > 400 patients). We also discuss the results of the randomized POWER-AF study comparing conventional CLOSE to high power CLOSE (up to 50 W). Finally, we discuss the performance, safety, and efficacy of the CLOSE protocol in light of the emerging changes in the field of catheter ablation being ultra-short high-power ablation and electroporation.

A randomised wait-list controlled trial to evaluate Emotional Freedom Techniques for self-reported cancer-related cognitive impairment in cancer survivors (EMOTICON).

BACKGROUND: Cancer-related cognitive impairment (CRCI) is a prevalent source of comprised quality of life in cancer survivors. This study evaluated the efficacy of Emotional Freedom Techniques (EFT) on self-reported CRCI (sr-CRCI). METHODS: In this prospective multicentre randomised wait-list controlled study (ClinicalTrials.gov Identifier: NCT02771028), eligible cancer survivors had completed curative treatment, were 18 years or older and screened positive for sr-CRCI with ≥ 43 on the Cognitive Failures Questionnaire (CFQ). Participants were randomised to the immediate treatment group (ITG) or wait-list control (WLC) group, based on age (< or ≥ 65 years), gender, treatment (chemotherapy or not), and centre. The ITG started to apply EFT after inclusion and performed this for 16 weeks. The WLC group could only start the application of EFT after 8 weeks of waiting. Evaluations took place at baseline (T0), 8 weeks (T1) and 16 weeks (T2). The primary outcome was the proportion of patients with sr-CRCI according to the CFQ score. FINDINGS: Between October 2016 and March 2020, 121 patients were recruited with CFQ ≥ 43 indicating sr-CRCI. At T1, the number of patients scoring positive on the CFQ was significantly reduced in the ITG compared to the WLC group (40.8% vs. 87.3% respectively; p<0.01). For the WLC group, a reduction in CFQ scores was observed at T2, comparable to the effect of the ITG at T1. Linear mixed model analyses indicated a statistically significant reduction in the CFQ score, distress, depressive symptoms, fatigue and also an improvement in quality of life. INTERPRETATION: This study provides evidence for the application of EFT for sr-CRCI in cancer survivors and suggests that EFT may be useful for other symptoms in cancer survivors.

Prospective Randomized Evaluation of High Power During CLOSE-Guided Pulmonary Vein Isolation: The POWER-AF Study.

BACKGROUND: CLOSE-guided atrial fibrillation (AF) ablation is based on contiguous (intertag distance ≤6 mm), optimized (Ablation Index >550 anteriorly and >400 posteriorly) point-by-point radiofrequency lesions. The optimal radiofrequency power remains unknown. METHODS: The POWER-AF study is a prospective, randomized controlled monocentric study including patients with paroxysmal AF, planned for first CLOSE-guided pulmonary vein isolation using a contact force radiofrequency catheter (Thermocool SmartTouch, Biosense Webster, Inc, Irvine, CA). A total of 100 patients were randomized into 2 groups (1:1). The control group received AF ablation using the standard CLOSE protocol (35 W), whereas in the experimental group, pulmonary vein isolation was performed using high power (45 W). Endoscopic evaluation was performed in patients with intraesophageal temperature rise >38.5 °C. RESULTS: The resulting sample size was 96 (48+48) patients. In the high power group, shorter procedure time (80 versus 102 minutes, P<0.001), shorter total radiofrequency application time (16 versus 26 minutes, P<0.001), and radiofrequency time per application (26 versus 37 s anteriorly, P<0.001 and 13 versus 17 s posteriorly, P<0.001) were observed. Endoscopic evaluation (performed in 19/48 versus 25/48 patients respectively, P=0.31) showed an ulcerative perforation in a high power group patient (treated by endoscopic stenting and normalization after ≈4 months) and a superficial ulcerative lesion in a control group patient (conservative treatment). Both occurred following excessive Ablation Index applications (up to 460 and 480, respectively) with excessive contact force (30 g on average, with peaks up to 50 g). Six-months AF recurrence was not significantly different (10% in high power versus 8% in control, P=0.74). CONCLUSIONS: This randomized controlled study shows that a 45 W radiofrequency power CLOSE protocol in patients with paroxysmal AF significantly increases the global procedural efficiency with similar midterm efficacy. However, our study showed a narrower safety margin and a limited increased efficiency at the posterior wall using high power. This advocates against the use of high power in the region neighboring the esophagus.

D-dimer blood concentrations to exclude left atrial thrombus in patients with atrial fibrillation.

OBJECTIVE: Left atrial (LA) thrombus is routinely excluded by transoesophageal echocardiography (TOE) before cardioversion for non-valvular atrial fibrillation (AF). In the D-dimer blood concentrations to exclude LA thrombus in patients with AF study, two D-dimer cut-offs were compared to exclude LA thrombus prior to cardioversion. One was fixed to 500 ng/mL (DD500), based on clinical practice where such values are commonly accepted to exclude a thrombus. The other cut-off was adjusted to 10 times the patient's age (DDAge), based on the cut-off used to exclude pulmonary embolism. METHODS: 142 consecutive patients with non-valvular AF aged 69.7±11.4 years (52% with paroxysmal AF) referred for precardioversion TOE to exclude LA thrombus were prospectively enrolled. D-dimers were measured at the time of TOE by an ELISA test. RESULTS: LA thrombus was excluded with TOE in 129 (91%) and confirmed in 13 (9%) patients. D-dimers were significantly lower in patients without LA thrombus (729±611 vs 2376±1081 ng/L; p<0.05). DDAge indicated absence of LA thrombus with higher specificity than DD500 (66.4% vs 50.4%; p<0.05). Both cut-offs were able to identify all 13 patients with LA thrombus (false negative 0%). Patients with D-dimers