Nikolaos Fragakis

Comparison of Effectiveness of Ranolazine Plus Amiodarone Versus Amiodarone Alone for Conversion of Recent-Onset Atrial Fibrillation

Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (<48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p <0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF.

Improving cardiac resynchronization therapy response with multipoint left ventricular pacing: Twelve-month follow-up study

BACKGROUND Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. OBJECTIVE The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. METHODS Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure-volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. RESULTS Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders (P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median -25%, interquartile range [IQR] [-39% to -20%] vs median -18%, IQR [-25% to -2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [-1% to 8%], P <.001). CONCLUSION Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

Ablation Therapy of Type I Atrial Flutter May Eradicate Paroxysmal Atrial Fibrillation

In patients with paroxysms of atrial fibrillation preceded by episodes of atrial flutter on Holter monitoring, eradication of the flutter circuit may also abolish the episodes of atrial fibrillation. At electrophysiology study, these patients are identified by documentation of simultaneous flutter of the right atrium and fibrillation of the left atrium.

Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation

AIMS Amiodarone is used commonly for pharmacological cardioversion of atrial fibrillation (AF), but it is limited by moderate efficacy and delayed action. Ranolazine and amiodarone are markedly synergistic in suppressing experimental AF in vitro, yet the clinical efficacy of ranolazine combined with amiodarone for AF conversion has only undergone minimal investigation. This prospective, single-blinded, randomized study compared the safety and efficacy of ranolazine added to amiodarone vs. amiodarone alone for conversion of recent-onset AF. METHODS AND RESULTS We enroled 121 patients (64 ± 10 years, 45% male) with recent-onset (<48 h duration) AF who were eligible for pharmacological cardioversion. Patients received either 24 h amiodarone infusion (loading dose 5 mg/kg followed by maintenance dose of 50 mg/h; n = 60), or amiodarone infusion at the same dosage plus a single oral dose of ranolazine 1500 mg (n = 61). Patients in the amiodarone plus ranolazine group compared with the amiodarone-only group showed significantly higher conversion rates at 24 h (87 vs. 70%, respectively; P = 0.024) and at 12 h (52 vs. 32%; P = 0.021), and shorter time to conversion (10.2 ± 3.3 vs. 13.3 ± 4.1 h; P = 0.001). Subgroup analysis identified higher 24 h conversion in patients with left atrial (LA) diameter >46 mm who received the combination treatment vs. amiodarone alone (81 vs. 54%; P = 0.02), whereas the efficacy of the two interventions did not differ among patients with LA diameter ≤46 mm (P = 0.77). There was modest QT prolongation in both the groups, no serious adverse reactions, and no pro-arrhythmic events. CONCLUSION Addition of ranolazine to amiodarone was safe and well tolerated in this study, and it demonstrated efficacy superior to amiodarone alone for conversion of recent-onset AF. These findings may have clinical implications by offering a simple therapeutic manoeuvre to enhance amiodarones effectiveness for conversion of AF.

Trimetazidine Administration Minimizes Myocardial Damage and Improves Left Ventricular Function after Percutaneous Coronary Intervention

Background and objectiveThe aim of this study was to evaluate whether the administration of trimetazidine, a piperazine derivative, to patients before and after percutaneous coronary intervention (PCI) minimizes the PCI-induced myocardial damage and improves left ventricular function 1 and 3 months after the procedure.MethodsFifty-two patients hospitalized for acute coronary syndromes (ACS) were included in this study. Patients were randomized into two groups: group A (trimetazidine group; n = 27) and group B (placebo group; n = 25). All patients received conventional antianginal therapy. In addition, group A patients received oral trimetazidine 20mg every 8 hours, starting 15 days before PCI and continuing for 3 months after the procedure. For each patient, serum troponin I and creatinine kinase (CK)-MB levels were measured before PCI, then at 6, 24, and 48 hours after the procedure; a 2D cardiac echocardiogram was performed before PCI and at 1 and 3 months after the procedure.ResultsTwenty-four hours after PCI, troponin I levels were >1 ng/mL in 7 of 27 patients (26%) of group A and 11 of 25 patients (44%) in group B. Fourty-eight hours after revascularization troponin levels remained elevated in 15% of patients in group A and in 32% of patients in group B. Twenty-two percent of patients in group A had CK-MB levels >5 ng/mL, 24 hours after PCI, compared with 40% of patients in group B; four patients of group A had high CK-MB levels prior to PCI procedure.Echocardiographic measurements before revascularization revealed that 11 of 27 patients (40%) in group A had an ejection fraction <50% versus 8 of 24 patients (33%) in group B. The number of patients with an ejection fraction <50% was significantly reduced in group A compared with group B at 1 and 3 months after PCI, i.e. 11 % versus 16% (p = 0.046) at 1 month and 4% versus 16% (p = 0.017) at 3 months.A significant improvement in regional wall motion was noted after treatment with trimetazidine compared with placebo. One month after PCI, inferior left ventricular (LV) wall hypokinesia had improved in 4 of 6 trimetazidine recipients and in 4 of 14 placebo recipients (p = 0.014, group A vs group B). After 3 months inferior wall hypokinesia improved in four patients in group A versus six patients in group (p = 0.05). Similarly, anterior LV wall motion improved in 3 of 11 patients in group A and in 1 of 6 patients in group B at 1 month. After 3 months anterior wall hypokinesia had improved in eight patients in group A and in two patients in group B (p = 0.04, group A vs group B).ConclusionThe metabolic agent trimetazidine appears to minimize myocardial reperfusion injury during PCI and improves global and regional wall motion at 1 and 3 months after PCI. This study was limited by small patient numbers and further studies are necessary to evaluate exact mechanisms of action and clinical implications of using trimetazidine in conjunction with PCI.

Clinical Improvement and Successful Pregnancy in a Preeclamptic Patient With Antiphospholipid Syndrome Treated With Pravastatin

The clinical hallmarks of the antiphospholipid syndrome (APS) are thrombosis and adverse obstetric outcomes. Women with APS have a higher incidence of preeclampsia.1 Currently, treatment of APS focuses on anticoagulation therapy, treatment mostly given empirically and often ineffective. Similarly, treatment for preeclampsia remains symptomatic and also ineffective. Studies in animal models support the hypothesis that pravastatin may be an effective therapy to prevent pregnancy complications in APS and in preeclampsia.2–5 Here, we describe a patient, with a previous history of preeclampsia, thrombosis, and APS, presenting with preeclampsia at 23 weeks’ gestation in her second pregnancy that was treated with pravastatin, which resulted in marked clinical improvement and successful pregnancy outcome. A 30-year-old woman with no previous medical history had a first pregnancy complicated with early preeclampsia with bilateral notching (22 weeks and 0 days) and hypertension and edema at 24 weeks, leading to a still birth at week 26. She developed deep vein thrombosis 2 days postpartum. Based on her history of deep vein thrombosis, early preeclampsia, and twice positive lupus anticoagulant, with an interval of 3 months between the tests, the patient was diagnosed with APS. The patient received therapeutic doses of low-molecular-weight heparin for 3 months and prophylactic doses while trying to conceive again. Her blood pressure and proteinuria remained normal. Ten months later, she got pregnant and was started on intermediate doses of enoxaparin (0.6 OD) and aspirin (100 mg OD). Blood pressure …

Anticoagulation and antiplatelet therapy in implantation of electrophysiological devices

The growing implantations of electrophysiological devices in the context of increasing rates of chronic antithrombotic therapy in cardiovascular disease patients underscore the importance of an effective periprocedural prophylactic strategy for prevention of bleeding complications. In this review, we provide a concise overview of the data regarding anticoagulation and antiplatelet therapy in arrhythmia device surgery. Also, we critically discuss risk factors and procedural parameters that are potentially associated with haemorrhagic untoward events in this setting. Of note, current evidence suggests that heparin bridging therapy in patients on chronic anticoagulation and dual-antiplatelet therapy are associated with increased risk of pocket haematoma formation. Continuation of oral anticoagulation and short-term interruption of clopidogrel with aspirin maintenance in eligible patients, respectively, represent promising strategies with an acceptable safety profile. Besides the perioperative management of antithrombotic therapy, some extra supportive measures may also reduce the incidence of haematomas. High-risk cases should be better treated by experienced operators in high-volume centres. More randomized studies are needed to elucidate the exact role of particular antithrombotic therapy protocols. Finally, the recently accumulated data on this subject should be incorporated into the professional guidelines regarding arrhythmia device therapy.

Clinical and angiographic characteristics of patients with coronary artery ectasia

BACKGROUND The relationship of the extent of coronary artery ectasia (CAE) with coronary blood flow in the major epicardial arteries has not been adequately assessed. This study aimed at investigating the association of the topographical extent of CAE with coronary flow velocity and clinical characteristics in patients with isolated CAE and in patients with coexisting obstructive coronary artery disease (CAD). METHODS We reviewed 3764 consecutive coronary angiograms performed at Athens Euroclinic and identified patients with CAE according to standard criteria. The topographical extent of ectasia was considered, and coronary flow velocity was determined using the TIMI frame count (TFC). The severity of CAD was assessed using the modified Gensini index and the number of diseased vessels. Clinical data were correlated with TFC and CAD severity analysis. RESULTS Ectatic lesions were identified in 119 patients. The mean TFC correlated positively with the topographical extent of CAE (rs=0.733, p<0.001). Stepwise multiple linear regression revealed that the topographical extent of CAE and the maximum diameter of the ectatic segment in the corresponding artery are independent predictors of TFC in LAD and RCA. Using multivariate analysis, a history of myocardial infarction was independently associated with CAE extent, and CAD severity. CONCLUSIONS The extent of ectasia in the coronary vasculature is correlated with coronary flow velocity and associated with clinical presentation independent of coexisting significant coronary stenoses.

Epidemiological characteristics, management and early outcomes of acute coronary syndromes in Greece: The PHAETHON study.

INTRODUCTION In view of recent therapeutic breakthroughs in acute coronary syndromes (ACS) and essential demographic and socioeconomic changes in Greece, we conducted the prospective, multi-center, nationwide PHAETHON study (An Epidemiological Cohort Study of Acute Coronary Syndromes in the Greek Population) that aimed to recruit a representative cohort of ACS patients and examine current management practices and patient prognosis. METHODS The PHAETHON study was conducted from May 2012 to February 2014. We enrolled 800 consecutive ACS patients from 37 hospitals with a proportional representation of all types of hospitals and geographical areas. Patients were followed for a median period of 189 days. Outcome was assessed with a composite endpoint of death, myocardial infarction, stroke, urgent revascularization and urgent hospitalization for cardiovascular causes. RESULTS The mean age of patients was 62.7 years (78% males). The majority of patients (n=411, 51%) presented with ST-elevation myocardial infarction (STEMI), whereas 389 patients presented with NSTEMI (n=303, 38%) or UA (n=86, 11%). Overall, 58.8% of the patients had hypertension, 26.5% were diabetic, 52.5% had dyslipidemia, 71.1% had a smoking history (current or past), 25.8% had a family history of coronary artery disease (CAD) and 24.1% had a prior history of CAD. In STEMI patients, 44.5% of patients were treated with thrombolysis, 38.9% underwent a coronary angiogram (34.1% were treated with primary percutaneous coronary intervention) and 16.5% did not receive urgent treatment. The pain-to-door time was 169 minutes. During hospitalization, 301 (38%) patients presented one or more complications, and 13 died (1.6%). During follow-up, 99 (12.6%) patients experienced the composite endpoint, and 21 died (2.7%). CONCLUSIONS The PHAETHON study provided valuable insights into the epidemiology, management and outcome of ACS patients in Greece. Management of ACS resembles the management observed in other European countries. However, several issues still to be addressed by public authorities for the timely and proper management of ACS.

Surgical ablation for atrial fibrillation

This paper reviews the history of surgical procedures developed for eradication of atrial fibrillation (AF) during cardiac surgery for structural heart disease, and in patients with AF without other indication for cardiac surgery. Current evidence indicates that, despite their proven efficacy, the Cox-Maze procedure and its modifications require cardiopulmonary bypass and cannot be easily justified in the case of AF without other indication for cardiac surgery. In patients undergoing cardiac surgery for mitral valve disease, concomitant ablation techniques using modifications of the Maze and alternative energy sources appear to be safe and effective in treating AF, especially in non-rheumatic disease. Minimally invasive epicardial ablation has been recently developed and can be performed on a beating heart through small access incision ports. Various techniques combining pulmonary vein isolation, ganglionated plexi ablation, and left atrial lines have been tried. Initial results are promising but further clinical experience is required to establish ideal lesion sets, appropriate energy sources, and the benefit-risk ratio of such an approach in patients without other indication for cardiac surgery. The role of surgical ablation in the current management of AF is under investigation.