The Electrophysiology of Atrial Fibrillation: From Basic Mechanisms to Catheter Ablation.

The electrophysiology of atrial fibrillation (AF) has always been a deep mystery in understanding this complex arrhythmia. The pathophysiological mechanisms of AF are complex and often remain unclear despite extensive research. Therefore, the implementation of basic science knowledge to clinical practice is challenging. After more than 20 years, pulmonary vein isolation (PVI) remains the cornerstone ablation strategy for maintaining the sinus rhythm (SR). However, there is no doubt that, in many cases, especially in persistent and long-standing persistent AF, PVI is not enough, and eventually, the restoration of SR occurs after additional intervention in the rest of the atrial myocardium. Substrate mapping is a modern challenge as it can reveal focal sources or rotational activities that may be responsible for maintaining AF. Whether these areas are actually the cause of the AF maintenance is unknown. If this really happens, then the targeted ablation may be the solution; otherwise, more rough techniques such as atrial compartmentalization may prove to be more effective. In this article, we attempt a broad review of the known pathophysiological mechanisms of AF, and we present the recent efforts of advanced technology initially to reveal the electrical impulse during AF and then to intervene effectively with ablation.

Incidence, electrophysiological characteristics, and long-term follow-up of perimitral atrial flutter in patients with previously confirmed mitral isthmus block.

INTRODUCTION: After mitral isthmus (ΜΙ) catheter ablation, perimitral atrial flutter (PMF) circuits can be maintained due to the preservation of residual myocardial connections, even if conventional pacing criteria for complete MI block are apparently met (MI pseudo-block). We aimed to study the incidence, the electrophysiological characteristics, and the long-term outcome of these patients. METHODS: Seventy-two consecutive patients (mean age 62.4 ± 10.2, 62.5% male) underwent MI ablation, either as part of an atrial fibrillation (AF) ablation strategy (n = 35), or to treat clinical reentrant atrial tachycardia (AT) (n = 32), or to treat AT that occurred during ablation for AF (n = 5). Ιn all patients, the electrophysiological characteristics of PMF circuits were studied by high-density mapping. RESULTS: Mitral isthmus block was successfully achieved in 69/72 patients (95.6%). Five patients developed PMF after confirming MI block. In these patients, high-density mapping during the PMF showed a breakthrough in MI with extremely low impulse conduction velocity (CV). In contrast, in usual PMF circuits that occurred after AF ablation, the lowest CV of the reentrant circuit was of significantly higher value (0.07 ± 0.02 m/s vs 0.25 ± 0.07 m/s, respectively; P < .001). Patients presented with clinical AT had better prognosis in maintaining sinus rhythm after MI ablation compared with patients presented with AF. CONCLUSION: Perimitral atrial flutter with MI pseudo-block may be present after MI ablation and has specific electrophysiological features characterized by remarkably slow CV in the MI. Thus, even after MI block is achieved, a more detailed mapping in the boundaries of the ablation line or reinduction attempts may be needed to exclude residual conduction.

Ventricular ectopy from the non-coronary cusp: Pathophysiological and anatomical considerations.

Non-coronary cusp (NCC) is a rare site for ventricular arrhythmias because it does not come into direct contact with the ventricular myocardium. Instead, the NCC comes in contact with the membranous septum near the His region. We describe a case of a young man with a ventricular ectopy who was successfully ablated in the NCC. In our case the much greater prematurity in the NCC than in the His region suggests that the arrhythmic site of origin is not in the peri-His area but most likely a myocardial extension adjoining the aortic root.

Impact of early vs late postoperative radioiodine remnant ablation on final outcome in patients with low-risk well-differentiated thyroid cancer.

OBJECTIVE: Postoperative radioiodine remnant ablation (RRA) represents an adjunctive therapeutic modality in patients with differentiated thyroid cancer (DTC). The impact of late vs early RRA on the outcome of DTC is currently unclear. The aim of the study was to evaluate the outcome of patients with DTC according to RRA timing. DESIGN RETROSPECTIVE STUDY PATIENTS: A total of 107 TNM stage 1 DTC patients were divided into two groups. In group A (n = 50), RRA was administered in less than 4·7 months median 3·0 (range 0·8-4·7), while in group B (n = 57) in more than 4·7 months median 6 (4·8-30·3) after thyroidectomy. Remission was achieved when stimulated serum Tg levels were undetectable, in the absence of local recurrence or cervical lymph node metastases on the neck ultrasound. RESULTS: All patients underwent near-total thyroidectomy. The mean age at diagnosis was 49·3 years (range: 18-79 years). There were no statistically significant differences in the histological subtype, the TNM stage, the dose of radioiodine and the time of follow-up, between the two groups. After the RRA treatment, 44 group A patients (88%) were in remission and 6 (12%) in persistence; while in group B, 52 (91·2%) were in remission, 1 (1·8%) in persistence and 4 (7%) in recurrence. At their latest follow-up median 87·3 (23·3-251·6 months), all patients were in remission, either as a result of further iodine radioiodine therapy (in 11 patients) or watchful monitoring. CONCLUSIONS: The timing of RRA seems to have no effect on the long-term outcome of the disease. Therefore, urgency for radioiodine ablation in patients with low-risk thyroid cancer is not recommended.

Health status of Greek thyroid cancer patients after radioiodine administration compared to a demographically matched general population sample.

The impact of radioiodine-131 ((131)I) treatment on thyroid cancer patients' quality of life is controversial. We conducted a cross-sectional study of 60 patients aged 18-73 years old who had recently underwent near total thyroidectomy due to papillary thyroid cancer and were scheduled for (131)I treatment. On admission to our department, prior to (131)I administration patients underwent clinical and laboratory investigation including routine clinical biochemistry, thyroid stimulating hormone (TSH) and thyroglobulin (Tg) measurements. Health-related quality of life (HRQoL) was estimated by the SF-36 Health Survey a generic instrument which consisted from eight scales (four for physical and four for mental health). After (131)I administration patients were discharged and approximately 6 months later they were re-evaluated. Our results showed that HRQoL in thyroid cancer patients receiving (131)I treatment is independent of age/gender and thyroid cancer-related variables. All SF-36 scales significantly improved six months after administration (P<0.05). Compared to Greek general population, before (131)I administration all scales were significantly lower (P<0.05). Six months post (131)I administration, scales were significantly lower for physical functioning (P=0.02), physical role (P=0.01), social functioning (P=0.03) and emotional role limitations (P=0.04), whereas the remaining SF-36 scales were comparable to the general population. In conclusion, hypothyroidism and anxiety for the outcome of their disease before (131)I treatment exert a negative impact on thyroid cancer patients. Quality of life improvement post (131)I is mainly attributed to the resumption of euthyroidism and familiarization with treatment and followup procedures rather than (131)I treatment itself. There was no significant difference between patients receiving lower (2220-3700MBq) and higher (3700-7400MBq) dosage.

Glucose homeostasis in patients with acromegaly treated with surgery or somatostatin analogues.

OBJECTIVE: Long-acting somatostatin analogues (SSA) are widely used for the treatment of acromegaly; however, they also alter ß-cell function by inhibiting insulin secretion. In this study, we assess the effect of SSA on glucose homeostasis in patients with acromegaly treated with SSAs, compared to patients treated with surgery. DESIGN: We studied four groups of patients with acromegaly: at the time of diagnosis (group I, n = 53), after successful transsphenoidal surgery (TSS, group II, n = 30) and under successful SSA treatment (group III, n = 20); 22 patients were studied only before treatment, 19 only post-treatment, while 31 patients (group IV) were studied before and after the treatment. MEASUREMENTS: Patients underwent an oral glucose tolerance test. Insulin sensitivity and ß-cell insulin secretion were estimated using appropriate mathematical models. RESULTS: Control of acromegaly with either TSS or SSA improved insulin sensitivity as evident by significantly lower fasting and postglucose insulin levels and HOMA-IR. In addition, patients of group III compared to patients of group II demonstrated significantly lower HOMA-ß% (52·5 ± 10·9 vs 189·6 ± 86·7, P < 0·05) and lower first and second phase insulin release (443 ± 83·5 vs 1077 ± 140·8, P < 0·05 and 150 ± 18·2 vs 285 ± 33·3, P < 0·05), respectively. Also, lower fasting glucose levels and a lower prevalence of diabetes were noted in group II compared to group III (5·1 ± 0·2 vs 6·2 ± 0·2 mm, P < 0·05, and 13·3%vs 40%, P < 0·0031, respectively). CONCLUSIONS; Control of acromegaly with SSA seems to exhibit a negative effect on pancreatic ß-cell function. Whether this has long-term clinical implications remains to be established. Nevertheless, careful monitoring of glucose metabolism in patients under SSA is beneficial for their optimal management.

The effect of body mass index on the diagnosis of GH deficiency in patients at risk due to a pituitary insult.

OBJECTIVES: Diminished GH response to stimulation has been demonstrated in obesity, leading to erroneous diagnosis of GH deficiency. The aim of this study was to evaluate the influence of body mass index (BMI) on GH responsiveness in patients at risk for pituitary function deficits. METHODS: A total of 59 healthy subjects and 75 patients with a pituitary insult underwent insulin tolerance test or pyridostigmine+GHRH test in order to assess GH secretory reserve. Normal subjects and patients were classified as normal weight (BMI <24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >30 kg/m(2)). RESULTS: All normal individuals with BMI <24.9 kg/m(2) demonstrated adequate GH responses, while three of the 21 overweight (14.3%) and nine of the 28 obese subjects (32.1%) did not respond to GH stimulation. Among patients, four of 14 (28.6%) with BMI <24.9 kg/m(2), 18 of 22 (81.8%) who were overweight, and 28 of 39 (71.7%) who were obese did not respond to GH stimulation. Of the 46 nonresponder patients with increased BMI, nine (19.6%) had normal insulin-like growth factor 1 (IGF1) values and no other pituitary hormone deficits, raising questions about the accuracy of somatotroph function assessment, while all nonresponders with BMI <24.9 kg/m(2) had low IGF1 values and panhypopituitarism. CONCLUSIONS: Our results indicate that BMI >25 kg/m(2) has a negative effect on GH response not only in normal healthy subjects but also in patients at risk for pituitary function deficit as well. Parameters such as IGF1 levels and anterior pituitary deficits should be taken into account to accurately assess GH status in these patients.

Atrioventricular re-entrant and ventricular tachycardias of left origin: a rare combination.

The simultaneous occurrence of atrial and ventricular tachycardias, or junctional and ventricular tachycardias, has been reported previously. We report on a patient presenting with syncope and demonstrating, simultaneously, atrioventricular re-entrant tachycardia and ventricular tachycardia of left origin. A left lateral concealed pathway was responsible for the former arrhythmia, while the latter arrhythmia was located in the anterolateral wall of the left ventricle. This is a rare type of double tachycardia and stresses the need for a thorough investigation of patients who have concealed accessory pathways and a previous history of atrioventricular re-entrant tachycardia, when they present with syncope.

Iodine 131 treatment for differentiated thyroid carcinoma in patients with end stage renal failure: dosimetric, radiation safety, and practical considerations.

BACKGROUND: Iodine 131 ablation following total thyroidectomy is considered an indispensable element of successful treatment of differentiated thyroid carcinoma (Dtc). because of the essential role of the kidneys in iodine clearance, (131)I therapy of Dtc in patients with end stage renal disease, particularly those maintained on haemodialysis, present a number of special features: the (131)I activity needs to be modified, the haemodialysis sessions need to be adjusted at the time of (131)I therapy, and there are radiation safety considerations during dialysis. there is considerable controversy over these crucial questions in the reports published so far in the literature, which concern a total of fourteen patients. OBJECTIVE: the aim of our study was to present our experience on (131)I treatment of 5 Dtc patients with end stage renal disease. DESIGN: the data of 5 Dtc patients with end stage renal disease, treated with (131)I, were retrospectively analysed; four cases were treated for remnant ablation and one for locoregional progression. In order to allow for prolonged plasma clearance of (131)I, we used a lower activity of radioiodine, reduced to roughly 40-50% of the empirically calculated activity used for normal individuals; dialysis sessions were performed immediately before and at 48 hours after (131)I administration. All patients had (131)I retention measurements performed post dialysis; in two of them some additional measurements such as iodine clearances were also performed. RESULTS: None of the patients experienced any short-term side effects, while they all had undetectable thyroglobulin levels on the first post therapy evaluation off thyroxine. (131)I elimination in the first haemodialysis was about 60%. staff incidental exposure and (131)I contamination were insignificant. CONCLUSIONS: On the basis of our experience, an empiric activity of 40-50% of that used for normal individuals appears to be effective as well as safe. these encouraging findings are discussed in relation with other reports in the literature.

Torsades de pointes as a cause of sudden death in a patient with aortic stenosis and atrial fibrillation.

The occurrence of sudden cardiac death during Holter monitoring in patients with aortic stenosis has been reported previously. In the majority of the reported cases, the cause of death was a malignant ventricular tachyarrhythmia. The presence of a strong association between frequency and complexity of ventricular arrhythmias and sudden death in patients with aortic stenosis has been proposed. We report the case of a 77-year-old woman with aortic stenosis and atrial fibrillation who had an episode of torsades de pointes that degenerated into ventricular fibrillation during Holter monitoring. A short-long-short sequence, but not increased ventricular ectopics, precipitated torsades de pointes and sudden death in this case which is strongly indicative of triggered activity as the underlying mechanism of the lethal arrhythmia.

Electroanatomical mapping and ablation of upper loop reentry atrial flutter.

Upper loop reentry is a rare type of non isthmus-dependent atrial flutter with a reentry circuit around the superior vena cava. We present a case of atrial flutter of this type in a 75-year-old man with concomitant sick sinus syndrome. The diagnostic approach used three-dimensional electroanatomical mapping with the upgraded ENSITE 3000 system. This is the first case to be described where, apart from non-contact mapping, the circuit was also tracked in detail with three-dimensional contact mapping. The reentry circuit followed a clockwise course around the superior vena cava and passed through a conduction gap in the crista terminalis. Radiofrequency ablation of this region successfully eliminated the tachycardia.

Increased plasma plasminogen activator inhibitor-1 levels: a possible marker of hypertensive target organ damage.

High plasma plasminogen-activator inhibitor-1 (PAI-1) concentrations have been reported in coronary artery disease and stroke. We therefore, prospectively studied the association of PAI-1 with early target organ damage in patients with arterial hypertension has not been clearly established. We therefore investigated 136 subjects, 64 males and 72 females, mean age 50.0 +/- 12.3 years, with newly diagnosed essential hypertension who were free of cardiovascular events and were not receiving any antihypertensive medication. Plasma PAI-1 levels were measured by an ELISA method (STAGO). The study population was divided into two groups, group A with PAI-1 levels below 40 ng/mL and group B with more than 40 ng/mL. The left ventricular mass was calculated according to the formula of Devereux and was normalized by the individual's body surface area (LVM/BSA). Carotid intima-media thickness (IMT) was determined by ultrasonography. Microalbuminuria was assessed by an immunoturbidimetric method (SERA-PAK). Group A consisted of 89 individuals with hypertension (65.4%), 41 males and 48 females and group B of 47 individuals with hypertension (34.6%), 21 males and 26 females. Individuals in group B exhibited significantly higher LVM/BSA than individuals in group A (155.9 +/- 23.1 g/m2 vs. 129.7 +/- 32.2g/m2, respectively, p = 0.004) and increased IMT (0.97 +/- 0.20mm vs. 0.87 +/- 0.21 mm, respectively, p < 0.001). Microalbumin excretion rate was greater in group B than group A (70.9 +/- 84.4 mg/24 hrs vs. 20.9 +/- 45.1 mg/24 hrs, respectively, p = 0.002). In conclusion, elevated PAI-1 levels are associated with target organ damage in subjects with newly diagnosed arterial hypertension. Thus, it can be postulated that this fibrinolytic inhibitor may characterize hypertensives in the early stages of the atherothrombotic process.