Arrhythmogenic response to isoproterenol testing vs. exercise testing in arrhythmogenic right ventricular cardiomyopathy patients.

Aims: To compare the arrhythmic response to isoproterenol and exercise testing in newly diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results: We studied isoproterenol [continuous infusion (45 µg/min) for 3 min] and exercise testing (workload increased by 30 W every 3 min) performed in consecutive newly diagnosed ARVC patients. Both tests were evaluated with regard to the incidence of (i) polymorphic premature ventricular contractions (PVCs) and couplet(s) or (ii) sustained or non-sustained ventricular tachycardia (VT) with left bundle branch block [excluding right ventricular outflow tract VT]; and compared to a control group referred for the evaluation of PVCs without structural heart disease. Thirty-seven ARVC patients (63.5% male, age 38 ± 16 years) were included. The maximal sinus rhythm heart rate achieved during isoproterenol testing was significantly lower compared to exercise testing (149 ± 17 bpm vs. 166 ± 19 bpm, P < 0.0001). However, the incidence of polymorphic ventricular arrhythmias was much higher during isoproterenol testing compared to exercise testing [33/37 (89.2%) vs. 16/37 (43.2%), P < 0.0001]. Interestingly, isoproterenol testing was arrhythmogenic in all 15 patients in whom baseline PVCs were reduced or suppressed during exercise testing. During both isoproterenol and exercise testing, control group presented a low incidence of ventricular arrhythmias compared to ARVC patients (8.1% vs. 89.2%, P < 0.0001 and 2.7% vs. 43.2%, P < 0.0001, respectively). Conclusions: The incidence of polymorphic ventricular arrhythmias is significantly higher during isoproterenol compared to exercise testing in newly diagnosed ARVC patients, suggesting its potential utility for the diagnosis.

Pulmonary vein triggers, focal sources, rotors and atrial cardiomyopathy: implications for the choice of the most effective ablation therapy.

Understanding of the pathophysiological mechanism(s) underlying atrial fibrillation (AF) is the foundation on which current ablation strategies are built. In the vast majority of patients with paroxysmal AF, the ablation procedure should target the pulmonary veins. In patients with nonparoxysmal AF, however, pulmonary vein isolation alone seems to be insufficient to prevent the arrhythmia. Several recent clinical trials have investigated the concept that rotors (re-entry based on a meandering central core from which spiral waves emanate) might be the mechanism responsible for sustaining AF. Ablation of these localized AF sources is an important step towards substrate-driven procedures in persistent AF. Hybrid AF ablation procedures, based on the integration of endocardial transcatheter and epicardial off-pump surgical techniques, have been introduced to overcome their mutual shortcomings. The long-term results are encouraging, especially in currently challenging settings such as nonparoxysmal AF and failed endocardial catheter ablation procedures.

Accuracy of the pacemaker-mediated tachycardia algorithm in Boston Scientific devices.

INTRODUCTION: The incidence of pacemaker-mediated tachycardia (PMT) varies as a function of patient characteristics, device programming and algorithm specificities. We investigated the efficacy of the Boston Scientific algorithm by reviewing PMT episodes in a large device population. METHODS: In this multicenter study, we included 328 patients implanted with a Boston Scientific device: 157 non-dependent patients with RYTHMIQ™ activated (RYTHMIQ group), 76 patients with permanent AV-conduction disorder (AV-block group) and 95 Cardiac Resynchronization Therapy patients (CRT group). For each patient, we reviewed the last 10 remote monitoring-transmitted EGMs diagnosed as PMT. RESULTS: We analyzed 784 PMT episodes across 118 patients. In the RYTHMIQ group, the diagnosis of PMT was correct in most episodes (80%) of which 69% was directly related to the prolongation of the AV-delay associated with the RYTHMIQ algorithm. The usual triggers for PMT were also observed (PVC 16%, PAC 9%). The remainder of the episodes (20%) in RYTHMIQ patients and most episodes of AV-block (66%) and CRT patients (74%) were incorrectly diagnosed as PMT during sinus tachycardia at the maximal tracking rate. The inappropriate intervention of the algorithm during exercise causes non-conducted P-waves, loss of CRT (sustained in six patients) and may have been pro-arrhythmogenic in one patient (induction of ventricular tachycardia). CONCLUSION: Algorithms to minimize ventricular pacing can occasionally have unintended consequences such as PMT. The PMT algorithm in Boston Scientific devices is associated with a high rate of incorrect PMT diagnosis during exercise resulting in inappropriate therapy with non-conducted P-waves, loss of CRT and limited risk of pro-arrhythmic events.

Surgical management of dysthyroid optic neuropathy: A systematic review.

OBJECTIVE: There is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). DATA SOURCES: MEDLINE, Cochrane Library, and clinicaltrials.gov REVIEW METHODS: A systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. RESULTS: Fifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. CONCLUSION: The results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.

[MEN for multiple endocrin neoplasms: When evokate MEN? Update 2022]. / Mise au point sur les néoplasies endocriniennes multiples.

Multiple endocrine neoplasia (MEN) are genetic predisposition syndromes to endocrine tumors including MEN1, MEN2 and exceptionally MEN4. MEN are transmitted in an autosomal dominant fashion with a high penetrance. Classically, there is no genotype/phenotype correlation for NEM1 whereas this is the case for NEM2. Patients with NEM1, linked to an inactivating mutation of the menin gene, may present with: primary hyperparathyroidism, pituitary adenoma, duodeno-pancreatic neuroendocrine tumors (NETs), bronchial tumors with an increased risk of thymoma, adrenal cortical tumors, an increased risk of breast cancer and characteristic skin involvement such as collagenomas, lentiginomas and an increased risk of skin cancer. These patients require at least annual follow-up. Screening of children is proposed from the age of 5 years. Patients with NEM2, linked to an activating mutation of the RET proto-oncogene, all present with medullary thyroid carcinoma (MTC) at a variable age depending on the genotype. Some patients present a pheochromocytoma (50 %) and hyperparathyroidism (20 %). Pediatric forms with aggressive CMT, ganglioneuromatosis and marfanoid syndrome exist (rare NEM2B). Some mutations are associated with a risk of aggressive CMT, justifying prophylactic thyroidectomy before 6 months of age. The age of genetic testing depends on the mutation subtype in the NEM2 parent. NEM4, related to a mutation in the CDKN1B gene, are rare, with a less well-known pathogenesis and their follow-up is not well codified.

Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

A 3D high resolution MRI method for the visualization of cardiac fibro-fatty infiltrations.

Modifications of the myocardial architecture can cause abnormal electrical activity of the heart. Fibro-fatty infiltrations have been implicated in various cardiac pathologies associated with arrhythmias and sudden cardiac death, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Here, we report the development of an MRI protocol to observe these modifications at 9.4 T. Two fixed ex vivo human hearts, one healthy and one ARVC, were imaged with an Iterative decomposition with echo asymmetry and least-square estimations (IDEAL) and a magnetization transfer (MT) 3D sequences. The resulting fat fraction and MT ratio (MTR) were analyzed and compared to histological analysis of the three regions ("ARVC triangle") primarily involved in ARVC structural remodeling. In the ARVC heart, high fat content was observed in the "ARVC triangle" and the superimposition of the MTR and fat fraction allowed the identification of fibrotic regions in areas without the presence of fat. The healthy heart exhibited twice less fat than the ARVC heart (31.9%, 28.7% and 1.3% of fat in the same regions, respectively). Localization of fat and fibrosis were confirmed by means of histology. This non-destructive approach allows the investigation of structural remodeling in human pathologies where fibrosis and/or fatty tissue infiltrations are expected to occur.

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory.

AIMS: As diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to 'glucose memory' by evaluating patients' HbA1c over previous years and their skin autofluorescence (SAF). METHODS: In 334 patients with T2D and HbA1c levels≤8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment]. RESULTS: Our patients were mostly men (58.4%) aged 63±10years, with a duration of diabetes of 13±10years and HbA1c=7.1±0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods -4±3 months (n=255), -16±4months (n=152), -30±4months (n=93) and -62±26 months (n=105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR=6.75, 95% CI: 1.90-23.90. Moreover, SAF values were higher in those with DR [2.95±0.67 arbitrary units (AU)] vs 2.65±0.65 AU with no DR (P<0.01) and were also associated with the oldest previous HbA1c values (P<0.01). CONCLUSION: Our study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5years prior to study admission and their SAF values, a marker of glucose memory.

S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study.

OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. DESIGN: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. METHODS: The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0; 3 = 1; 4 = 2), grade (Ki67 index 0-9% = 0; 10-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3), age (<50 years = 0; ≥50 years = 1), symptoms (no = 0; yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic. RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

[Chronic pheochromocytoma-induced myocardial injuries: What should we expect from modern and classical echocardiographic tools?] / Apport du 2D strain et des outils échocardiographiques classiques pour la recherche d'anomalies myocardiques induites par l'exposition chronique à un phéochromocytome.

INTRODUCTION: Pheochromocytoma is a rare disease, which may manifest as severe cardiac complications. Apart from these situations, the "chronic" cardiac impact is not clearly defined. A cardiac MRI study suggests that these patients are carrying areas of fibrosis and foci of left ventricular myocarditis. Since these abnormalities are usually associated with altered left ventricular longitudinal systolic strain, we hypothesize that this strain is altered in patients with a "chronic" pheochromocytoma. METHOD: This retrospective case-control study was performed using patients from the Bordeaux University Hospital database, included between 2008 and 2016. We compared the left ventricular global longitudinal strain (GLS), radial and circumferential systolic strain and classic echocardiographic parameters between patients with pheochromocytoma and controls matched for age, sex, body mass index and systolic blood pressure. RESULTS: The analysis included 47 patients and 47 correctly matched controls. There were no statistically significant differences between the 2 groups in terms of GLS (-20.7±2.4% vs. -20.2±2.7%, P=0.40), radial strain, left ventricular mass or diastolic function. Left ventricular ejection fraction and circumferential strain were significantly higher in patients than in controls, with a significantly lower telediastolic diameter. CONCLUSION: No significant changes in GLS were observed in our pheochromocytoma patients, compared with controls. Several hypotheses may explain these results. The presence of fibrosis foci and areas of left ventricular myocarditis being associated with a poor cardiological prognosis, a systematic cardiac MRI could be discussed in these patients, until further studies are performed.

Serum fructosamine predicts macrosomia in well-controlled hyperglycaemic pregnant women: An observational cross-sectional study.

AIM: While serum fructosamine may be a good marker of glucose control in pregnant women with diabetes, its relationship with macrosomia is still uncertain. METHODS: In 130 hyperglycaemic women with singleton pregnancies (117 gestational diabetes mellitus, 13 pregestational diabetes), serum fructosamine and HbA1c levels were measured at 25±7 weeks of gestation. Levels in mothers of infants with and without macrosomic newborns (birth weight>4000g and/or large-for-gestational-age birth weight>90th percentile) were compared using logistic regression analysis adjusted for macrosomia risk factors. RESULTS: These 130 pregnant women were 33±5 years old; their BMI before pregnancy was 27.7±6.9kg/m2, and they gained 7.5±5.1kg during the first 6 months of gestation. Glucose control was good according to HbA1c levels (5.3±0.3%; 34±2mmol/mol), yet 17/130 (13%) newborns had macrosomia: 3900±227g vs 3057±512g (P<0.001) in the others. These mothers were older and had higher parity, whereas their BMI scores before pregnancy and gestational weight gains did not differ. Fructosamine levels were also higher at 221±40µmol/L vs 192±22µmol/l (P<0.001), respectively, and remained significant even after adjusting for maternal age, BMI, parity, type of diabetes, antecedents of macrosomia and excessive gestational weight gain. By contrast, HbA1c did not differ between the two groups. In fact, nearly two-thirds (64.7%) of the mothers of macrosomic newborns had fructosamine levels>200µmol/l vs 31.9% of mothers with non-macrosomic newborns (P<0.05). CONCLUSION: High fructosamine levels are associated with macrosomia in the newborns of well-controlled hyperglycaemic pregnant women.

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

Expert opinions on adrenal complications in immunotherapy.

Primary adrenal insufficiency during immunotherapy is rare and does not warrant systematic screening during treatment. It should be suspected in case of typical clinical and biological presentation, but also in case of subclinical presentation with impaired general health status and/or hyponatremia. Diagnosis is based on low cortisol levels, measured at any time in case of emergency or else at 8 am, associated to elevated ACTH to rule out pituitary origin. Secondarily, anti-21-hydroxylase antibody assay may be performed, with screening for mineralocorticoid deficiency. Imaging is recommended, although not urgent, to screen for "adrenalitis" or adrenal atrophy and rule out differential diagnosis of adrenal metastasis. Primary adrenal insufficiency during immunotherapy is a medical emergency requiring hydrocortisone replacement adapted to the clinical and biological context. Management by an endocrinologist is essential, in order to adapt hydrocortisone and fludrocortisone replacement therapy and to educate both patient and oncologist in hydrocortisone dose adaptation. Current data suggest that treatment needs to be life-long, even after termination of immunotherapy. The present article does not deal with secondary adrenal insufficiency, which is included in the section on "Pituitary toxicity".

Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population.

CONTEXT: The recent recommendations of the European Endocrine Society states that the performance of computed tomography (CT) to characterize 'true' adrenal incidentalomas (AIs) remains debatable. OBJECTIVE: To determine relevant thresholds for usual CT parameters for the diagnosis of benign tumors using robust reference standard among a large series of 'true' AIs recruited in an endocrinological setting. DESIGN: Retrospective study of 253 AIs in 233 consecutive patients explored in a single university hospital: 183 adenomas, 33 pheochromocytomas, 23 adrenocortical carcinomas, 5 other malignant tumors and 9 other benign tumors. Reference standard was histopathology in 118 AIs, biological diagnosis of pheochromocytoma in 2 AIs and size stability after at least 1 year of follow-up in 133 AIs. METHODS: Sensitivity, specificity and positive and negative predictive values were estimated for various thresholds of size, unenhanced attenuation (UA), relative and absolute wash-out (RPW, APW) of contrast media. 197 scans were reviewed independently in a blinded fashion by two expert radiologists to assess inter-observer reproducibility of measurements. RESULTS: Criteria associated with a 100% positive predictive value for the diagnosis of benign AI were: a combination of size and UA: 30 mm and 20 HU or 40 mm and 15 HU, respectively; RPW >53%; and APW >78%. Non-adenomatous AIs with rapid contrast wash-out were exclusively benign pseudocysts and pheochromocytomas, suggesting that classical thresholds of 60% and 40% for APW and RPW, respectively, can be safely used for patients with normal metanephrine values. Inter-observer reproducibility of all parameters was excellent (intra-class correlation coefficients: 0.96-0.99). CONCLUSIONS: Our study, the largest conducted in AIs recruited in an endocrinological setting, suggests safe thresholds for quantitative CT parameters to avoid false diagnoses of benignity.

Cabergoline for Cushing's disease: a large retrospective multicenter study.

OBJECTIVE: The efficacy of cabergoline in Cushing's disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD. DESIGN: We conducted a retrospective multicenter study from thirteen French and Belgian university hospitals. METHODS: Sixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded. RESULTS: Twenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week, P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19-105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1-240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5-3.5). CONCLUSIONS: About 20-25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline.

The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans.

BACKGROUND: This study determined the histological features of the atrial myocardium connecting the coronary sinus and the left atrium in humans. METHODS AND RESULTS: Ten necropsied hearts were studied by performing serial longitudinal sections parallel to the long axis of the coronary sinus that extended its full length using a large microtome. In all specimens, the venous wall of the coronary sinus was surrounded by a cuff of striated muscle extending 40+/-8 mm from the ostium. Striated myocardial connections of varying number and morphology left this coronary muscle cuff and connected to the left atrium; they ranged from 1 to 2 fascicles to a widely intermingled continuum (thickness, 2.79+/-2 mm; width, 2.91+/-3.5 mm). These connections originated 8.8+/-5.7 mm from the coronary sinus ostium and inserted 18+/-11 mm distally into the left atrium. The insulating compartment in which the connections traversed between the left atrium and the coronary sinus was mostly formed of adipose tissue. The valve of Vieussens was found in 6 hearts at a mean distance of 3.4+/-3.2 mm from the distal extremity of the coronary sinus muscle cuff. CONCLUSIONS: In the human heart, a consistent but morphologically variable left atrial coronary sinus myocardial connection was found. This emphasizes the need for surgical dissection or catheter ablation in or around the coronary sinus to eliminate these connections.

Differential pacing for distinguishing block from persistent conduction through an ablation line.

BACKGROUND: Because complete linear conduction block is necessary to minimize the recurrence of reentrant tachycardias such as typical atrial flutter, we investigated a simple technique to recognize a persistent gap or complete linear block. METHODS AND RESULTS: We prospectively evaluated cavotricuspid isthmus conduction in 50 patients (age 63+/-8 years, 43 men) after radiofrequency ablation. The distal and proximal bipoles of a quadripolar catheter placed close to the ablation line were successively stimulated during recording from the ablation line. We hypothesized that because the initial and terminal components of local potentials reflected activation at the ipsilateral and contralateral borders of the ablation lesion, a change to a more proximal pacing site without moving the catheter would prolong the stimulus to the initial component timing, whereas the response of the terminal component would depend on the presence of block or persistent conduction. A shortening or no change in timing of the terminal component would indicate block, whereas lengthening would indicate persistent gap conduction. The results were compared with previously described criteria for isthmus block. Ninety-two sites were assessed: 17 before and 75 after the achievement of complete isthmus block. The timing of the initial component was delayed by 19+/-9 ms, and the terminal component was advanced by 13+/-8 ms after block and delayed by 12+/-9 ms in case of persisting conduction. The sensitivity, specificity, and positive and negative predictive values for linear block were 100%, 75%, 94%, and 100%, respectively. CONCLUSIONS: An accurate assessment of isthmus block or persistent isthmus conduction is possible with this technique of differential pacing.

High-density mapping of activation through an incomplete isthmus ablation line.

BACKGROUND: Activation mechanisms through gaps in ablation lines and resulting electrograms are poorly understood. METHODS AND RESULTS: Eight patients (all men; age, 59+/-9 years) were studied during a recurrence of typical atrial flutter (cycle length, 233+/-19 ms) after a previous catheter ablation in the cavotricuspid isthmus. High-density 3-dimensional mapping of the isthmus was performed with the Cordis-Biosense EP Navigation system, and local conduction velocity (CV) was estimated. Maps created with 96+/-19 points revealed 0.8+/-0.3-cm gaps of recovered conduction in the ablation line. A broad wave front entered the lateral isthmus with a CV of 1.8+/-0.7 m/s, halted on the lesion line, and penetrated slowly through the gap with a CV of 0.3+/-0.1 m/s. Activation then curved and returned antidromically to activate the downstream flank of the line with a CV of 1.1+/-0.7 m/s. This front fused downstream of the line with slow transverse activation (CV, 0.4+/-0.3 m/s) parallel to it. The ablation line was demarcated by an incomplete line of convergent double potentials with isoelectric intervals (from 123+/-34 to 62+/-16 ms); each potential corresponded to local activation upstream and downstream of the lesions, while the intervening delay was produced by slow conduction through the gap combined with the progressively longer curved pathway of downstream antidromic activation as a function of distance from the gap. CONCLUSIONS: High-density isthmus mapping during recurrent flutter indicates slow conduction through gaps of recovered conduction of varying dimensions in the ablation line followed by a curved front of activation antidromically activating its downstream flank, this detour producing wide double potentials on the line.