Prospective Use of Microvolt T-Wave Alternans Testing to Guide Primary Prevention Implantable Cardioverter Defibrillator Therapy.

BACKGROUND: We hypothesized that a negative microvolt T-wave alternans (MTWA) test would identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillator (ICD) therapy in a prospective cohort. METHODS AND RESULTS: Data were pooled from 8 centers where MTWA testing was performed specifically for the purpose of guiding primary prevention ICD implantation. Cohorts were included if the ratio of ICDs implanted in patients who were MTWA "non-negative" to patients who were MTWA negative was >2:1, indicating that MTWA testing had a significant impact on the decision to implant an ICD. The pooled cohort included 651 patients: 371 MTWA non-negative and 280 MTWA negative. Among non-negative patients, 62% underwent ICD implantation whereas only 13% of MTWA-negative patients received an ICD (P<0.01). Despite a substantially lower prevalence of ICDs, long-term survival (6.9 years) was significantly better among MTWA-negative patients (68.2% non-negative vs. 87.1% negative, P=0.026). CONCLUSIONS: MTWA-negative patients had significantly better survival than MTWA non-negative patients, the majority of whom had ICDs. Despite a very low prevalence of ICDs, long-term survival among patients with left ventricular ejection fraction ≤40% and a negative MTWA test was better than in the ICD arm of any study to date that has demonstrated a benefit of ICDs. This provides further evidence that MTWA-negative patients are unlikely to benefit from primary prevention ICD therapy.

Demonstration of the Protective Effect of Vinpocetine in Diabetic Cardiomyopathy.

Background: Diabetic cardiomyopathy (DCM) poses a significant risk for heart failure in individuals with diabetes, yet its underlying mechanisms remain incompletely understood. Elevated blood sugar levels initiate harmful processes, including apoptosis, collagen accumulation, and fibrosis in the heart. Vinpocetine, a derivative of Vinca minor L., has demonstrated diverse pharmacological effects, including vasodilation, anti-inflammatory properties, and enhanced cellular metabolism. This study aims to investigate Vinpocetine's protective and remodeling effects in diabetic cardiomyopathy by evaluating biochemical and histopathological parameters. Methods: Twenty-one adult male Wistar rats were induced with diabetes using streptozocin and divided into Diabetes and Diabetes + Vinpocetine groups. Histopathological analyses, TGF-ß1 immunoexpression, and measurements of plasma markers (TGF-ß, pro-BNP, Troponin T) were performed. Biochemical analyses included HIF-1 alpha and neuregulin-1ß quantification and evaluation of lipid peroxidation. Results: Vinpocetine significantly reduced cardiac muscle thickness, TGF-ß1 expression, and plasma in diabetic rats. HIF-1 alpha and neuregulin-1ß levels increased with Vinpocetine treatment. Histopathological observations confirmed reduced fibrosis and structural abnormalities in Vinpocetine-treated hearts. Conclusions: This study provides comprehensive evidence supporting the protective effects of Vinpocetine against diabetic cardiomyopathy. Vinpocetine treatment improved cardiac morphology, immunohistochemistry, and modulation of biochemical markers, suggesting its potential as a therapeutic intervention to attenuate the negative impact of diabetes on heart function.

[Assessment of coronary artery calcium scoring]. / Kalsiyum skorunun koroner arterlerdeki segmenter dagilimi

OBJECTIVES: Calcium accumulation in the coronary arteries is a known indicator of atherosclerosis. The purpose of this study was to demonstrate the effect of patients' demographic characteristics on calcium scoring and the topographic accumulation of calcium in the coronary arteries. STUDY DESIGN: Two-hundred ninety-nine patients were included in the study (192 male, 107 female; mean age 59.08±10.7; range 19 to 84 years). All patients with total calcium scores of 1 Hounsfield unit or more underwent 16-slice multi-detector computed tomography with calcium scoring evaluation. Their coronary trees were divided into 14 different segments, and the number of lesions in each segment was calculated separately. RESULTS: When the coronary arteries were examined for calcium accumulation by segment, the proximal segment of the LAD (left anterior descending coronary artery) had the most calcium accumulation. Total calcium scores were higher in patients with high total and LDL cholesterol values than in normolipidemic patients. Total calcium scores were higher for patients with hypertension than for patients without hypertension. Calcium scores of smokers and non-smokers were not significantly different. Diabetic patients had higher calcium scores than patients without diabetes. No significant difference was identified between patients with and without a positive family history of coronary artery disease. Total calcium scores were higher for older patients and for patients with hyperlipidemia. CONCLUSION: Segmental analysis of calcium scoring demonstrates that calcium accumulation is mostly seen in the proximal LAD. Coronary artery calcification is increased by hypertension, age and hyperlipidemia.

[The microvolt T-wave alternans test]. / Mikrovolt T-dalgasi degisim testi.

Several clinical parameters and noninvasive tests have been developed to identify patients under the risk for sudden cardiac death (SCD). The microvolt T-wave alternans (MTWA) test is a noninvasive diagnostic method based on the measurement of subtle (microvolt) beat-to-beat alternation of the T-wave on the surface electrocardiogram and used for risk stratification of patients under the risk for SCD. Studies in the last decade have shown that the MTWA test is an effective method to distinguish patients with a high risk for arrhythmogenic mortality among patients suffering ischemic or nonischemic cardiomyopathies or with a history of myocardial infarction, with a high negative predictive value. This review revisits the MTWA test in the light of the most recent clinical studies.

Incidence of atrial fibrillation post-cavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence.

INTRODUCTION: Atrial fibrillation and atrial flutter often coexist. The long-term occurrence of atrial fibrillation in patients presenting with atrial flutter alone is unknown. We report the long-term follow-up in patients who underwent cavotricuspid isthmus ablation for treatment of lone atrial flutter. METHODS AND RESULTS: Between January 1997 and June 2002, 632 patients underwent cavotricuspid isthmus ablation for the treatment of typical atrial flutter at the Cleveland Clinic Foundation. Three hundred sixty-three patients were included in this study and followed for a mean duration of 39 +/- 11 months. The mean duration of atrial flutter symptoms was 12 +/- 5 months. Mean left-atrial size and left-ventricular ejection fraction were 4.2 +/- 0.8 cm and 47 +/- 13%, respectively. After a mean follow-up time of 39 +/- 11 months, 13% (48 of 363) of the patients remained in sinus rhythm. Five percent (18 of 363) of patients experienced recurrence of atrial flutter only. Sixty-eight percent (246 of 363) experienced the onset of atrial fibrillation and 14% (51 of 363) experienced recurrence of atrial flutter and the new onset of atrial fibrillation. Overall, 82% (297 of 363) of the patients experienced new onset of drug refractory atrial fibrillation. Left-atrial size was a predictor of atrial fibrillation recurrence post-atrial flutter ablation. CONCLUSION: At long-term follow-up, approximately 82% of patients post-cavotricuspid isthmus ablation for atrial flutter developed drug refractory atrial fibrillation. This finding suggests that elimination of atrial flutter might delay, but does not prevent, atrial fibrillation. Evidence suggests both arrhythmias may share common triggers and such patients may derive a better long-term benefit from anatomical ablative treatment of atrial fibrillation as well.

Randomized study comparing combined pulmonary vein-left atrial junction disconnection and cavotricuspid isthmus ablation versus pulmonary vein-left atrial junction disconnection alone in patients presenting with typical atrial flutter and atrial fibrillation.

BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist in the same patient. Recently it has been demonstrated that the triggers for both AF and AFL may originate in the pulmonary veins (PVs). We hypothesized that in patients with both AF and typical AFL, pulmonary vein-left atrial junction (PV-LAJ) disconnection may eliminate both arrhythmias. METHODS AND RESULTS: Consecutive patients with documented symptomatic AF and typical AFL were randomly assigned to have PV-LAJ disconnection combined with cavotricuspid isthmus (CTI) ablation (group 1, n=49) or PV-LAJ disconnection alone (group 2, n=59). Within the first 8 weeks after ablation, 32 of the group 2 patients had typical AFL documented, whereas none was seen in group 1. Twenty of these 32 converted to sinus rhythm after initiating antiarrhythmic drugs (AADs). Twelve were cardioverted, and AADs were started. After 8 weeks, all AADS were stopped, and only 3 patients continued to have recurrent sustained typical AFL that was eliminated by CTI ablation. Beyond 8 weeks of follow-up, 7 patients in group 1 and 6 patients in group 2 (14% and 11%, respectively) continued to have AF. Ten of these 13 patients underwent a repeat PV-LAJ disconnection procedure and were cured. The remaining 3 remained in normal sinus rhythm while taking AADs. CONCLUSIONS: In patients with both AFL and AF, PV-LAJ disconnection alone may be sufficient to control both arrhythmias. CTI block reduced early postablation recurrence of arrhythmias, which in the majority of patients reflects a short-term clinical problem.

Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described. METHODS AND RESULTS: PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (> or =70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P=0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans. CONCLUSIONS: V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.

Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function.

OBJECTIVES: We aimed to determine the safety and efficacy of pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients with impaired left ventricular (LV) systolic function. BACKGROUND: To date, PVI has been performed primarily in patients with normal LV function. Yet, many AF patients have impaired LV systolic function. The outcomes of PVI in patients with impaired LV systolic function are unknown. METHODS: We included 377 consecutive patients undergoing PVI between December 2000 and January 2003. Ninety-four patients had impaired LV function (ejection fraction [EF] <40%), and they comprised the study group. The control group was the remaining 283 patients who had a normal EF. End points included AF recurrence and changes in EF and quality of life (QoL). RESULTS: Mean EF was 36% in our study group, compared with 54% in controls. After initial PVI, 73% of patients with impaired EF and 87% of patients with normal EF were free of AF recurrence at 14 +/- 6 months (p = 0.03). In the study group, there was a nonsignificant increase in EF of 4.6% and significant improvement in QoL. Complication rates were low and included a 1% risk of pulmonary vein stenosis. CONCLUSIONS: Although the AF recurrence rate after initial PVI in impaired EF patients was higher than in normal EF subjects, nearly three-fourths of patients with impaired EF remained AF-free. Although our sample size was nonrandomized, our results suggest PVI may be a feasible therapeutic option in AF patients with impaired EF. Randomized studies with more patients and longer follow-up are warranted.

Pulmonary vein antrum isolation for treatment of atrial fibrillation in patients with valvular heart disease or prior open heart surgery.

OBJECTIVES: The goal of this study was to assess the safety and efficacy of pulmonary vein antrum isolation in patients with moderate valvular heart disease or open-heart surgery and atrial fibrillation (AF). BACKGROUND: Valvular heart disease and open-heart surgery are commonly associated with AF and increase the risk of adverse events in AF patients. METHODS: A total of 391 consecutive patients who had pulmonary vein antrum isolation performed between December 2000 and December 2002 were screened. A total of 142 of these patients had clinically significant valvular disease or prior cardiac surgery. End points included AF recurrence and pulmonary vein antrum isolation complication rates. RESULTS: Patients with valvular heart disease or prior open-heart surgery were older, had larger left atria and a more advanced New York Heart Association class. They did not differ significantly with respect to gender, but had a longer history of AF. Procedure times were similar between patients with and without valvular heart disease or prior open-heart surgery. After 18 +/- 7 months in the lone AF patients, 11 +/- 5 months in patients with valvular heart disease, and 10 +/- 5 months in patients with prior open heart surgery, there was a trend toward lower recurrence of AF in patients with lone AF who enjoyed a 98% overall cure rate after up to 2 pulmonary vein antrum isolations versus 93% among patients with valvular heart disease (P = .04) and prior open heart surgery (P = .07). Complication rates were comparable between groups. CONCLUSIONS: Pulmonary vein antrum isolation is safe and effective in patients with moderate valvular heart disease and the patients who developed AF after open-heart surgery. These results have implications for our understanding of the pathophysiology of AF in patients with moderate valvular heart disease or past cardiac surgery and should be considered when discussing treatment options in these patients.

Comparison of intracoronary versus intravenous administration of tirofiban in primary percutaneous coronary intervention.

OBJECTIVE: The purpose of this study was to compare the intravenous bolus dose of tirofiban with intracoronary bolus dose in primary percutaneous coronary intervention (PCI) with regard to in hospital and six months clinical outcomes and peak cardiac enzyme levels. METHODS: We retrospectively examined 84 ST elevation myocardial infarction (STEMI) patients who underwent primary PCI from March 2006 to February 2007. All patients received the systemic bolus dose of tirofiban 10 mcg/kg either via intracoronary (IC) or intravenous (IV) route, followed by a 36 hours of IV infusion at 0.15 mcg/kg/min. Thirty six patients in IC group were compared with 48 patients in IV group in terms of peak cardiac enzyme levels, in-hospital and six months major adverse cardiac events (MACE) rates (death, myocardial infarction and repeat revascularization). Fisher's exact test, Yates Chi-square, unpaired Student's t-test and Mann-Whitney U test were used for statistical analysis. RESULTS: There was no difference in cardiovascular risk profile or cardiac history between two groups. At six months the incidence of MACE was 6.25% in IV group and 11.1% in IC group (p=0.45). Peak cardiac phosphokinase (CPK) levels between IV and IC groups were also statistically non significant (2657+/-2181 U/L in IV group and 2529+/-1929 U/L in IC group) (p=0.92). CONCLUSION: Intracoronary bolus application of tirofiban was not associated with reduction in MACE rates compared to intravenous administration in patients with STEMI who underwent primary PCI. Future prospective trials with higher bolus doses of IC tirofiban should addressed to clarify this issue.

Response to pharmacological challenge of dissociated pulmonary vein rhythm.

UNLABELLED: Dissociated pulmonary vein rhythm. INTRODUCTION: Characterization of the electrophysiologic behavior of the pulmonary vein (PV) triggers initiating atrial fibrillation (AF) is still lacking. We conducted the current study to evaluate the behavior of the dissociated PV rhythm (PVD) observed after electrical disconnection from the left atrium of the PV responsible for initiation of AF. METHODS AND RESULTS: Four hundred and seven consecutive patients (102 women; mean age 55+/-11 years) presented for ablation of symptomatic AF to our laboratory. After isolation, sustained dissociated rhythm (>10 minutes) was documented in 2.1% (34 of 1,568 PVs) of the PVs (initiating AF prior to isolation). Adenosine (18 mg IV bolus), verapamil (10 mg IV bolus), phenylephrine (200 mcg bolus followed by infusion at 100 mcg/hour), and isoproterenol (infusion rate of 15 mcg/hour) were administered in these patients. The cycle length of the PV rhythm before and after the administration of drugs was measured. Adenosine prolonged the sinus node (SN) cycle length (from 750+/-105 to 1,900+/-200 ms; P<0.05) and suppressed the PVD. Isoproterenol shortened both the SN (from 750+/-105 to 420+/-150 ms; P<0.05) and the PVD (from 2,225+/-300 to 800+/-190 ms; P<0.05) cycle length. A similar response to adenosine and isoproterenol of the PV firing was observed prior to isolating the arrhythmogenic PV. Phenylephrine prolonged the cycle length of both the SN (from 740+/-115 to 960+/-90 ms; P<0.05) and the PV rhythm (from 2,200+/-300 to 2,355+/-280 ms; P=0.87). Verapamil did not cause a significant change either in the SN or in the PVD cycle length. CONCLUSION: Our data suggest that the PVD within isolated PV responsible for initiating AF exhibits a response to pharmacologic agents similar to the SN cells.

Embolic events and char formation during pulmonary vein isolation in patients with atrial fibrillation: impact of different anticoagulation regimens and importance of intracardiac echo imaging.

UNLABELLED: Thromboembolic events are important complications of pulmonary vein isolation (PVI) procedures, occurring in up to 2.8% of patients. In this study, we report the incidence of char formation and embolic events with different anticoagulation protocols prospectively changed to reduce such complication. METHODS: A total of 785 patients (mean age: 54 years, 83.5% male) underwent catheter-based PVI for treatment of drug refractory, symptomatic atrial fibrillation (AF). PVI was performed utilizing different strategies including radiofrequency (RF) using temperature control energy delivery and RF using intracardiac echocardiography (ICE)-guided power titration. Patients were divided based on the anticoagulation protocol into three groups: in group 1 (194 patients), activation coagulation time (ACT) was maintained between 250 and 300 seconds; in group 2 (180 patients), ACT was maintained between 300 and 350 seconds plus the IV infusion of eptifibatide (135 microg/kg bolus + 0.5 microg/kg/min); and in group 3 (411 patients), ACT was maintained between 350 and 400 seconds. RESULTS: Char formation was detected in 69 patients of group 1, 5 of group 2, and 8 of group 3. An embolic event was observed in 7 patients of group 1, 3 of group 2, and 2 of group 3 (P = 0.01; group 1 vs group 3). Higher degree of anticoagulation with heparin was associated with a reduced incidence of embolic events even after removing the patients undergoing ICE-guided ablation (P = 0.04). CONCLUSION: More aggressive anticoagulation with heparin reduced periprocedural embolic events. The use of platelet inhibition does not have incremental beneficial effect. None of the anticoagulation protocol abolished char formation.

Impact of age on the outcome of pulmonary vein isolation for atrial fibrillation using circular mapping technique and cooled-tip ablation catheter:.

INTRODUCTION: A retrospective analysis was performed to define the impact of age on the outcomes and complications in patients undergoing pulmonary vein isolation (PVI). PVI is an evolving technique for the management of atrial fibrillation (AF). The impact of age on the risks, outcomes, and complications of PVI has not been well defined. METHODS AND RESULTS: A total of 323 patients (259 men and 64 women; age 18-79 years) underwent PVI for treatment of drug-refractory symptomatic AF. An ostial isolation of the pulmonary veins was done using a cooled-tip ablation catheter guided by circular mapping. The patients were divided into three groups based on age (group I: <50 years, group II: 51-60 years, group III: >60 years) and the results were compared. There were 106 patients in group I, 114 patients in group II, and 103 patients in group III (mean age 41.3 +/- 7.8 years, 55.4 +/- 2.75 years, and 66.6 +/- 4.18 years, respectively) who underwent PVI for paroxysmal (53.8%), persistent (10.8%), or permanent (35.3%) AF. Baseline characteristics were similar except for a higher prevalence of hypertension and/or structural heart disease in groups II and III (58% and 63% vs 33% in group I, respectively). The procedural variables were similar in all age groups. The overall risk of complications was similar in the three groups, except that the risk of stroke was significantly higher in patients >60 years of age (3% vs 0%; P < 0.05). The recurrence rates of AF were similar in the three age groups (15.1%, 16.7%, and 18.4%, respectively; P > 0.05). The risk of severe pulmonary vein stenosis (1.8%, 2.6%, and 0.9%, respectively) was low and did not vary with age. CONCLUSION: PVI is a safe and effective treatment for patients with drug-refractory symptomatic AF, and its benefits extend to all age groups. The risk of procedural complications, especially thromboembolic events, appears to be higher in the elderly age group. This observation needs to be considered while assessing potential candidates for the procedure.