Achieving bi-directional conduction block during catheter ablation is not enough to prevent recurrence of cavo-tricuspid isthmus dependant atrial flutter: Role of subclinical conduction.

BACKGROUND: Achieving bi-directional conduction block, as assessed by differential pacing and change in activation along tricuspid annulus (TA), across the cavo-tricuspid isthmus (CTI), is considered a satisfactory end point during catheter ablation of atrial flutter (AFL). AIM: To assess role of subclinical conduction by observing polarity reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, in predicting recurrence of CTI dependant AFL after ablation in patients with bidirectional conduction block. METHOD AND RESULTS: Of 683 patients undergoing ablation of CTI dependent AFL, 73 (10.6%) patients underwent redo flutter ablation and were evaluated further. The mean age was 60.8 years and 51% were males. Evidence of bidirectional block by differential pacing and change is activation along multipolar catheter and reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, during the 1st and subsequent procedure, were studied. 60% patients had confirmed bidirectional block of which 71% had lack of voltage reversal, at the end of 1st procedure. All patients with bidirectional block with lack of reversal of bipolar signals, after the first procedure had recurrence of AFL whereas only 3/11 (27%) people with bidirectional block and with absence of subclinical conduction had recurrence of AFL. CONCLUSION: Achieving bidirectional conduction block is not sufficient to prevent recurrence of AFL after CTI ablation. Reversal of local bipolar signals, from RS to QR pattern along with achieving bidirectional conduction delay would reduce recurrence of AFL, post ablation.

Safety and Long-Term Success of Persistent Atrial Fibrillation Ablation Using THERMOCOOL SMARTTOUCH® Catheter: Real-World Experience.

BACKGROUND: To investigate the real-world clinical experience of persistent atrial fibrillation (persAF) ablation using the THERMOCOOL SMARTTOUCH® catheter with contact force (CF)-sensing ability in a prospective, multicenter registry. METHODS: Patients with persAF (excluding long-standing persAF) undergoing ablation were enrolled. Primary adverse events (AEs), 12-month success, quality of life (QoL), and correlation of success with CF were assessed. RESULTS: Overall, 150 patients with persAF (age 61.6 ± 9.4 years; 76.0% male; 90.7% Caucasian; left ventricular ejection fraction 56.9% ± 10.3%; left atrial diameter 41.5 ± 7.9 mm) underwent catheter insertion (safety cohort); 142 met eligibility criteria and were ablated (evaluable cohort). Confirmation of entrance block for all targeted pulmonary veins was achieved in 99.3% of patients. The primary AE rate was 4.0% (6/150), and 12-month success was 63.1% (95% confidence interval: 54.2%-71.4%). A non-significant trend towards higher success was observed in patients with isoproterenol/adenosine challenge vs. those without (73.1% vs. 60.2%, respectively; P=0.065). Investigators stayed within their pre-selected CF working range (catheter-tissue contact stability) 79.7% ± 12.7% of the time. When investigators stayed within the CF range ≥80% vs. <80% of the time, ablation success was 69.2% vs. 58.5%, respectively (P=0.285). QoL improved significantly at 6 months and was sustained through the 12-month follow-up (P<0.0001). CONCLUSIONS: Symptom control in a real-world setting of persAF ablation using the THERMOCOOL SMARTTOUCH® catheter was 63.1%, with significant improvements in QoL, and trended non-significantly towards increased success in patients receiving isoproterenol/adenosine challenge and when investigators stayed within their pre-selected CF range ≥80% of the time.

Safety and long-term effectiveness of paroxysmal atrial fibrillation ablation with a contact force-sensing catheter: real-world experience from a prospective, multicentre observational cohort registry.

Aims: Real-time contact force (CF)-sensing radiofrequency ablation catheter for treatment of paroxysmal atrial fibrillation (PAF) allows optimization of electrode-tissue contact, which correlates with long-term success. This prospective, multicentre observational registry assessed the real-world clinical effectiveness of a CF-sensing catheter for ablation of drug-refractory PAF. Methods and results: Patients were followed-up at 3, 6, and 12 months after ablation. Outcome measures included isolation of targeted pulmonary veins (PVs) confirmed by entrance block (acute success), patient-reported freedom from symptomatic atrial fibrillation (AF) at 12 months (long-term effectiveness), Atrial Fibrillation Effect on Quality-of-life scores at 6 and 12 months, and incidence of predefined procedural complications. The registry enrolled 261 PAF patients (mean age 58.8 ± 11.3 years; 70.7% men; 91.7% Caucasian). Acute PV isolation was reported in 98.8% of patients [95% confidence interval (CI): 96.4-99.7%], and 12-month success for freedom from symptomatic AF was 75.7% (95% CI: 69.7-80.7%). Average CF for the evaluable cohort was 16.4 ± 3.9 g. There was a significant correlation between long-term effectiveness and stability of CF use [percentage of time CF was within investigator-selected working range; odds ratio (95% Wald CI), 1.0 (1.00-1.1); P = 0.030]. Average CF did not correlate with 12-month success. Clinically meaningful quality of life (QoL) improvements were observed at 6 and 12 months. Primary adverse events occurred in 2.7% patients. Conclusion: This observational registry showed that PAF ablation with a CF-sensing catheter had high acute success rates, favourable 12-month outcomes, and a good safety profile. Patients' QoL improved significantly. Long-term effectiveness significantly correlated with stable CF with adequate catheter-tissue contact (NCT01677052).

Outcomes in Patients With Congenital Heart Disease Receiving the Subcutaneous Implantable-Cardioverter Defibrillator: Results From a Pooled Analysis From the IDE Study and the EFFORTLESS S-ICD Registry.

OBJECTIVES: This study was conceived to determine the safety and efficacy of the subcutaneous implantable cardioverter-defibrillator (S-ICD) in patients with congenital heart disease (CHD). BACKGROUND: The S-ICD is a treatment option for patients with CHD in which a transvenous device is contraindicated due to anatomic considerations. However, efficacy in this group has not been determined. METHODS: A pooled analysis of 865 patients in the EFFORTLESS (Evaluation of Factors Affecting the Clinical Outcome and Cost-Effectiveness) registry (an international observational database) and a U.S. Investigational Device Exemption study were reviewed. RESULTS: Nineteen CHD patients versus 846 non-CHD patients with a median follow-up of 567 days and 639 days, respectively, were included. There were no deaths and no appropriate shocks for ventricular tachycardia/ventricular fibrillation in the CHD cohort, versus 26 deaths (3.1%, p = 0.42) and 111 appropriate shocks in 59 patients (7.1%) in the non-CHD cohort (p = 0.23). There were similar complication rates for the CHD versus non-CHD groups (10.5 vs. 9.6% [p = 0.89]), with inappropriate shocks for T-wave oversensing as the only complication in the CHD group (n = 2). The rate of inappropriate shocks was similar for both groups (10.5% vs. 10.9% [p = 0.96]). Successful defibrillation testing at 80J was comparable for the CHD versus non-CHD groups (100% vs. 98.5%). CONCLUSIONS: The overall analysis of the CHD cohort from the pooled data of the Investigational Device Exemption study and the EFFORTLESS registry shows that the S-ICD is a safe option in CHD patients deemed to be at high risk for sudden cardiac death who do not have pacing indications. Further research to accurately define sudden cardiac death risk in the diverse anatomic substrates of CHD patients is warranted.

Importance of superior vena cava isolation in successful ablation of persistent atrial fibrillation in patient with partial anomalous pulmonary vein.

Ectopic foci arising from pulmonary veins (PVs) are the predominant sources for the initiation and maintenance of atrial fibrillation (AF) in a vast majority of cases. However, ectopic foci also exist in the non-PV areas like superior vena cava (SVC) in 10-20% of the cases. We report the significance of SVC isolation in a patient with persistent AF and anomalous pulmonary venous connection of the right superior pulmonary vein into the SVC.

Laser Doppler assessment of dermal circulatory changes in people with coronary artery disease.

BACKGROUND: Dermal microcirculation provides an easily accessible vasculature bed which can be used to assess endothelial mediated vasodilatation. We studied and compared microcirculatory changes in response to acetylcholine iontophoresis (ACh), local heating of the skin and reactive hyperaemia in patients with coronary artery disease (CAD). METHODS AND RESULTS: Forty eight patients with CAD were studied and compared with 25 age and sex matched control subjects. Vasodilatory changes in the dermal microcirculation were assessed in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia using a laser Doppler flowmeter (LDF). RESULTS: Body mass index (BMI) and systolic BP were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured as absolute in agreement with our previous publish results) in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia, in healthy controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was significantly higher in patients with CAD, 14.1±4.0 vs 10.9±1.7s; p=0.001. There was a small but significant positive correlation between the perfusion change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On ROC curve analysis, perfusion changes with heating had higher sensitivity and specificity in discriminating patients with CAD from the healthy controls with an area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of 77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41% sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88% sensitivity and 60% specificity). CONCLUSION: Vasodilatation in the dermal microcirculation measured by the three techniques is attenuated in patients with coronary artery disease. Local heating of the skin is a better discriminator of patients with CAD than ACh iontophoresis and reactive hyperaemia.

Carotid intima-media thickness as a surrogate marker of cardiovascular disease in diabetes.

BACKGROUND: Diabetes mellitus is associated with a high risk of cardiovascular disease. Carotid intima-media thickness (CIMT) is increasingly used as a surrogate marker for atherosclerosis. Its use relies on its ability to predict future clinical cardiovascular end points. METHODS: This review examines the evidence linking CIMT as a surrogate marker of vascular complications in people with type 1 and type 2 diabetes. We have also reviewed the various treatment strategies which have been shown to influence CIMT. CONCLUSIONS: CIMT measurement is an effective, noninvasive tool which can assist in identifying people with diabetes who are at higher risk of developing microvascular and macrovascular complications. It may also help to evaluate the effectiveness of various treatment strategies used to treat people with diabetes.

The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease.

Endothelium plays a crucial role in the maintenance of vascular tone and structure. Endothelial dysfunction is known to precede overt coronary artery disease. A number of cardiovascular risk factors, as well as metabolic diseases and systemic or local inflammation cause endothelial dysfunction. Nitric oxide (NO) is one of the major endothelium derived vaso-active substances whose role is of prime importance in maintaining endothelial homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in human circulation. Elevated levels of ADMA inhibit NO synthesis and therefore impair endothelial function and thus promote atherosclerosis. ADMA levels are increased in people with hypercholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure. A number of studies have reported ADMA as a novel risk marker of cardiovascular disease. Increased levels of ADMA have been shown to be the strongest risk predictor, beyond traditional risk factors, of cardiovascular events and all-cause and cardiovascular mortality in people with coronary artery disease. Interventions such as treatment with L-arginine have been shown to improve endothelium-mediated vasodilatation in people with high ADMA levels. However the clinical utility of modifying circulating ADMA levels remains uncertain.

Comparative reproducibility of dermal microvascular blood flow changes in response to acetylcholine iontophoresis, hyperthermia and reactive hyperaemia.

Laser Doppler fluxmetry (LDF) can non-invasively measure skin microvascular changes in response to acetylcholine (ACh), local heating of the skin and reactive hyperaemia following arterial occlusion. Various studies have used microvascular changes in response to these stimuli, especially ACh iontophoresis and local heating, as a surrogate marker of endothelial function. There are few data in the literature regarding the comparative reproducibility of microvascular perfusion changes induced by the three stimuli. The aim of this study was to systematically assess and compare the reproducibility of skin microcirculatory function in response to each of these challenges. Ten healthy non-smoking subjects (seven males) median age 36 years (range 23-46), with no history of hypertension, diabetes, coronary artery disease or any connective tissue disorder, were studied. Changes in skin microcirculation in response to ACh iontophoresis, local heating of the skin and post-occlusive reactive hyperaemia, on two separate days (median 31, range 11-42 days), were assessed in all subjects. We measured three parameters: the change in perfusion from baseline perfusion (peak minus baseline perfusion), the relative percentage change in perfusion from baseline (peak--baseline)/baseline x 100 (%) and also the time-to-peak perfusion. The reproducibility of the change in perfusion had coefficients of variation (CV) of 9.3% for local skin heating, 19.4% for reactive hyperaemia and 25.5% for ACh iontophoresis. The relative percentage change in perfusion from baseline was more variable with CVs ranging from 23% to 39%. The coefficient of variation of time-to-peak perfusion was 7.0% for heating, 15.1% for reactive hyperaemia and 10.4% for ACh iontophoresis. We have shown that microcirculatory changes measured by the change in perfusion from baseline and time-to-peak perfusion in response to ACh, post-occlusive reactive hyperaemia and local skin heating had good reproducibility when carried out in a controlled environment with a standardized protocol. Relative change in perfusion had relatively poor reproducibility. The change in perfusion and time-to-peak perfusion for local skin heating were the most reproducible overall.

A study of endothelial function and circulating asymmetric dimethylarginine levels in people with Type 1 diabetes without macrovascular disease or microalbuminuria.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endothelial nitric oxide synthase (eNOS) that is associated with endothelial dysfunction, and is a risk marker for cardiovascular disease, a significant problem in Type 1 diabetes. The aim of the present study was to measure circulating ADMA, and define its association with endothelial dysfunction and endothelial markers in people with Type 1 diabetes with low likelihood of macrovascular disease. METHODS: Sixty-one young people with Type 1 diabetes without macrovascular disease or nephropathy and 62 healthy volunteers underwent brachial artery flow-mediated dilatation (FMD) and assay of plasma ADMA and adhesion molecules. RESULTS: Age, gender, BMI, lipid profile and renal function were similar in the two groups. People with Type 1 diabetes had impaired FMD compared to healthy controls (5.0 +/- 0.4 vs 8.9 +/- 0.4%; p < 0.001). Plasma ADMA levels were significantly lower in the people with diabetes compared to healthy controls (0.52 +/- 0.12 vs 0.66 +/- 0.20 micromol/l, p < 0.001). Plasma ICAM-1, E-selectin and PAI-1 levels were significantly higher in people with diabetes compared to healthy controls (median 201 (IQR 172-226) vs 180 (156-216) microg/l, p = 0.027; 44.2 (32.6-60.9) vs. 33.1 (22.4-51.0) microg/l; p = 0.003 and 70.8 (33.3-85.5) vs 46.3 (23.9-76.8) microg/l, p = 0.035). Plasma ADMA and VCAM-1 levels were positively correlated (r = 0.37, p = 0.003) in people with diabetes. There was no correlation between the plasma ADMA and FMD. CONCLUSION: ADMA levels are not associated with endothelial dysfunction in young adults with Type 1 diabetes without microalbuminuria or known macrovascular disease. This suggests that the impaired endothelial function in these individuals is not a result of eNOS inhibition by ADMA.

Predicting the development of macrovascular disease in people with type 1 diabetes: A 9-year follow-up study.

The aim of the article was to use prospectively collected data on people with type 1 diabetes to assess which routinely collected clinical measures predict the development of macrovascular disease in people with type 1 diabetes. Data have been collected in a structured format at an annual review since 1985. For this study, all people with type 1 diabetes in the database in both 1992 and 2001 were ascertained. Data were extracted for a diagnosis of coronary artery disease, stroke, and peripheral vascular disease (macrovascular complications). Presence of other microvascular complications was also ascertained. Forty-one of 404 (10.1%) people had macrovascular disease at the index visit in 1992 and 61 others developed macrovascular complications during follow-up. People who developed macrovascular complications were older (48 +/- 12 versus 36 +/- 11 [SD] years; P = 0.000), had longer duration of diabetes (28 +/- 12 versus 18 +/- 11 years; P = 0.000), higher BMI (26.7 +/- 4.6 versus 25.4 +/- 3.6 kg/m2; P = 0.041), higher base line serum cholesterol (5.9 +/- 1.7 versus 5.2 +/- 1.1 mmol/L, P = 0.007), higher median base line triglyceride levels (1.5 [IQ range 0.9-2.6] versus 1.1 [0.8-1.7] mmol/L; P = 0.002), higher systolic BP (145 +/- 21 versus 129 +/- 20 mmHg; P = 0.000), and higher serum creatinine (102 +/- 57 versus 86 +/- 17 micromol/L; P = 0.038) than those who did not. We found no significant difference in the base line glycated hemoglobin in the two groups. The multivariate model showed that age, duration of diabetes, systolic BP, and serum cholesterol and creatinine levels predicted the development of macrovascular complications, which were also associated with the later development of microalbuminuria. Macrovascular complications developed in 16.8% of people with type 1 diabetes over a 9-year follow-up, and were predicted by potentially modifiable factors including higher BP, BMI, and serum triglyceride and cholesterol levels.