Demosthenes G. Katritsis

Catheter ablation of atrial fibrillation in patients with diabetes mellitus: a systematic review and meta-analysis.

AIMS Diabetes mellitus (DM) and atrial fibrillation (AF) share pathophysiological links, as supported by the high prevalence of AF within DM patients. Catheter ablation of AF (AFCA) is an established therapeutic option for rhythm control in drug resistant symptomatic patients. Its efficacy and safety among patients with DM is based on small populations, and long-term outcome is unknown. The present systematic review and meta-analysis aims to assess safety and long-term outcome of AFCA in DM patients, focusing on predictors of recurrence. METHODS AND RESULTS A systematic review was conducted in MEDLINE/PubMed and Cochrane Library. Randomized controlled trials, clinical trials, and observational studies including patients with DM undergoing AFCA were screened and included if matching inclusion and exclusion criteria. Fifteen studies were included, adding up to 1464 patients. Mean follow-up was 27 (20-33) months. Overall complication rate was 3.5 (1.5-5.0)%. Efficacy in maintaining sinus rhythm at follow-up end was 66 (58-73)%. Meta-regression analysis revealed that advanced age (P < 0.001), higher body mass index (P < 0.001), and higher basal glycated haemoglobin level (P < 0.001) related to higher incidence of arrhythmic recurrences. Performing AFCA lead to a reduction of patients requiring treatment with antiarrhythmic drugs (AADs) from 55 (46-74)% at baseline to 29 (17-41)% (P < 0.001) at follow-up end. CONCLUSIONS Catheter ablation of AF safety and efficacy in DM patients is similar to general population, especially when performed in younger patients with satisfactory glycemic control. Catheter ablation of AF reduces the amount of patients requiring AADs, an additional benefit in this population commonly exposed to adverse effects of AF pharmacological treatments.

Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease : A meta-analysis

Background—Percutaneous coronary intervention (PCI) has been shown to improve symptoms compared with conservative medical treatment in patients with stable coronary artery disease (CAD); however, there is limited evidence on the effect of PCI on the risk of death, myocardial infarction, and subsequent revascularization. Therefore, we performed a meta-analysis of 11 randomized trials comparing PCI to conservative treatment in patients with stable CAD. Methods and Results—A total of 2950 patients were included in the meta-analysis (1476 received PCI, and 1474 received conservative treatment). There was no significant difference between the 2 treatment strategies with regard to mortality, cardiac death or myocardial infarction, nonfatal myocardial infarction, CABG, or PCI during follow-up. By random effects, the risk ratios (95% CIs) for the PCI versus conservative treatment arms were 0.94 (0.72 to 1.24), 1.17 (0.88 to 1.57), 1.28 (0.94 to 1.75), 1.03 (0.80 to 1.33), and 1.23 (0.80 to 1.90) for these 5 outcomes, respectively. A possible survival benefit was seen for PCI only in trials of patients who had a relatively recent myocardial infarction (risk ratio 0.40, 95% CI 0.17 to 0.95). Except for PCI during follow-up, there was no significant between-study heterogeneity for any outcome. Conclusions—In patients with chronic stable CAD, in the absence of a recent myocardial infarction, PCI does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.

Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium.

The aim of the study was to investigate whether a combination of mesenchymal stem cells (MSCs) capable of differentiating into cardiac myocytes and endothelial progenitors (EPCs) that mainly promote neoangiogenesis might be able to facilitate tissue repair in myocardial scars. Previous studies have shown that intracoronary transplantation of autologous bone marrow stem cells results in improvement of contractility in infracted areas of human myocardium. Eleven patients with an anteroseptal myocardial infarction (MI) underwent transcoronary transplantation of bone marrow‐derived MSCs and EPCs to the infarcted area through the left anterior descending artery. Eleven age‐ and sex‐matched patients served as controls. Wall motion score index was significantly lower at follow‐up in the transplantation (P = 0.04) but not in the control group. On stress echocardiography, there was improvement of myocardial contractility in one or more previously nonviable myocardial segments in 5 out of 11 patients (all with recent infarctions) and in none of the controls (P = 0.01). Restoration of uptake of Tc99m sestamibi in one or more previously nonviable myocardial scars was seen in 6 out of 11 patients subjected to transplantation and in none of the controls (P = 0.02). Cell transplantation was an independent predictor of improvement of nonviable tissue. Intracoronary transplantation of MSCs and EPCs is feasible, safe, and may contribute to regional regeneration of myocardial tissue early or late following MI.

Prognostic Value of Fractional Flow Reserve: Linking Physiologic Severity to Clinical Outcomes

BACKGROUND Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Mortality risk conferred by small elevations of creatine Kinase-MB isoenzyme after percutaneous coronary intervention

OBJECTIVES The aim of this study was to assess whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk. BACKGROUND Several studies have evaluated the relationship of CK-MB levels after PCI with the subsequent risk of death. While there is consensus that elevations exceeding 5 times the upper limit of normal increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations. METHODS We performed a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23230 subjects who underwent PCI. Data were combined with random effects models. RESULTS Mean follow-up was 6 to 34 months per study. By random effects, 19% (95% confidence interval [CI], 16% to 23%) had one- to five-fold CK-MB elevations, while only 6% (95% CI, 5% to 9%) had >5-fold elevations. Compared with subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2 to 1.8, no between-study heterogeneity) with one- to three-fold CK-MB elevations, 1.8 (95% CI, 1.4 to 2.4, no between-study heterogeneity) with three- to five-fold CK-MB elevations, and 3.1 (95% CI, 2.3 to 4.2, borderline between-study heterogeneity) with over five-fold CK-MB elevations (p < 0.001 for all). CONCLUSIONS Any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death.

Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions.

OBJECTIVES We sought to evaluate the impact of intravenous antagonists of the platelet IIb/IIIa receptor on the survival of patients undergoing percutaneous coronary interventions (PCIs). BACKGROUND Several trials have shown that intravenous antagonists of the platelet glycoprotein (GP) IIb/IIIa receptor reduce the incidence of myocardial infarction (MI) and composite cardiac outcomes (death, MI, or revascularization) in patients undergoing PCI. However, individual studies have not had adequate power to examine differences in mortality. METHODS We performed a meta-analysis of 19 randomized, placebo-controlled trials (20 comparisons, n = 20,137). Death was the primary outcome. Secondary outcomes included MI, composite cardiac outcomes, and major bleeding. RESULTS Mortality was significantly reduced at 30 days (risk ratio [RR] 0.69 [95% confidence interval [CI] 0.53 to 0.90]), at six months (RR 0.79 [95% CI 0.64 to 0.97]), and including longer follow-up (RR 0.79 [95% CI 0.66 to 0.94]), with no significant between-study heterogeneity. The relative risk reduction was largely similar in trials of patients with or without acute myocardial infarction (AMI), in trials continuing or discontinuing heparin after the procedure, and in trials using stents or another PCI as the intended primary procedure. Myocardial infarction and composite outcomes were significantly reduced (p < 0.001 for all) at 30 days and six months. Major bleeding was significantly increased only in trials where heparin infusion was continued after the procedure (RR 1.70 [95% CI 1.36 to 2.14]), although there was no excess bleeding when heparin was discontinued (RR 1.02 [95% CI 0.85 to 1.24]). CONCLUSIONS In patients undergoing PCI, GP IIb/IIIa receptor antagonists confer a significant and sustained decrease (20% to 30%) in the risk of death.

Autonomic Denervation Added to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation : A Randomized Clinical Trial

OBJECTIVES The aim of this study was to investigate whether the combination of conventional pulmonary vein isolation (PVI) by circumferential antral ablation with ganglionated plexi (GP) modification in a single ablation procedure, yields higher success rates than PVI or GP ablation alone, in patients with paroxysmal atrial fibrillation (PAF). BACKGROUND Conventional PVI transects the major left atrial GP, and it is possible that autonomic denervation by inadvertent GP ablation plays a central role in the efficacy of PVI. METHODS A total of 242 patients with symptomatic PAF were recruited and randomized as follows: 1) circumferential PVI (n = 78); 2) anatomic ablation of the main left atrial GP (n = 82); or 3) circumferential PVI followed by anatomic ablation of the main left atrial GP (n = 82). The primary endpoint was freedom from atrial fibrillation (AF) or other sustained atrial tachycardia (AT), verified by monthly visits, ambulatory electrocardiographic monitoring, and implantable loop recorders, during a 2-year follow-up period. RESULTS Freedom from AF or AT was achieved in 44 (56%), 39 (48%), and 61 (74%) patients in the PVI, GP, and PVI+GP groups, respectively (p = 0.004 by log-rank test). PVI+GP ablation strategy compared with PVI alone yielded a hazard ratio of 0.53 (95% confidence interval: 0.31 to 0.91; p = 0.022) for recurrence of AF or AT. Fluoroscopy duration was 16 ± 3 min, 20 ± 5 min, and 23 ± 5 min for PVI, GP, and PVI+GP groups, respectively (p < 0.001). Post-ablation atrial flutter did not differ between groups: 5.1% in PVI, 4.9% in GP, and 6.1% in PVI+GP. No serious adverse procedure-related events were encountered. CONCLUSIONS Addition of GP ablation to PVI confers a significantly higher success rate compared with either PVI or GP alone in patients with PAF.

Selective ganglionated plexi ablation for paroxysmal atrial fibrillation.

BACKGROUND Selective ganglionated plexi (GP) ablation guided by high-frequency stimulation has been proposed for the treatment of paroxysmal atrial fibrillation (AF), but the efficacy of the method is not established. OBJECTIVE This study sought to compare selective ablation of GP identified by high-frequency stimulation with extensive regional ablation targeting the anatomic areas of GP in patients with paroxysmal AF. METHODS Eighty patients with paroxysmal AF (age 53 +/- 9 years) were randomized to undergo selective GP ablation or regional left atrial ablation at the anatomic sites of GP. For selective GP ablation (n = 40), ablation targets were the sites where vagal reflexes were evoked by high-frequency stimulation. Vagal reflexes were defined as prolongation of the R-R interval by >50% and a concomitant decrease in blood pressure (>20 mm Hg) during AF. The end point of the procedure was failure to reproduce vagal reflexes with repeated high-frequency stimulation. For anatomic ablation, lesions were delivered at the sites of GP clustering. RESULTS At 13.1 +/- 1.9 months, 42.5% of patients with selective GP and 77.5% of patients with anatomic ablation were free of symptomatic paroxysmal AF (PAF) (P = .02). Parasympathetic denervation was more prominent in patients with anatomic than selective GP ablation, and in patients free of AF compared to these with AF recurrence immediately after ablation, but this trend was abolished at 6 months. CONCLUSION Selective GP ablation directed by high-frequency stimulation does not eliminate paroxysmal AF in the majority of patients. An anatomic approach for regional ablation at the sites of GP confers better results.

Optimal timing of coronary angiography and potential intervention in non-ST-elevation acute coronary syndromes

AIMS An invasive approach is superior to medical management for the treatment of patients with acute coronary syndromes without ST-segment elevation (NSTE-ACS), but the optimal timing of coronary angiography and subsequent intervention, if indicated, has not been settled. METHODS AND RESULTS We conducted a meta-analysis of randomized trials addressing the optimal timing (early vs. delayed) of coronary angiography in NSTE-ACS. Four trials with 4013 patients were eligible (ABOARD, ELISA, ISAR-COOL, TIMACS), and data for longer follow-up periods than those published became available for this meta-analysis by the ELISA and ISAR-COOL investigators. The median time from admission or randomization to coronary angiography ranged from 1.16 to 14 h in the early and 20.8-86 h in the delayed strategy group. No statistically significant difference of risk of death [random effects risk ratio (RR) 0.85, 95% confidence interval (CI) 0.64-1.11] or myocardial infarction (MI) (RR 0.94, 95% CI 0.61-1.45) was detected between the two strategies. Early intervention significantly reduced the risk for recurrent ischaemia (RR 0.59, 95% CI 0.38-0.92, P = 0.02) and the duration of hospital stay (by 28%, 95% CI 22-35%, P < 0.001). Furthermore, decreased major bleeding events (RR 0.78, 95% CI 0.57-1.07, P = 0.13), and less major events (death, MI, or stroke) (RR 0.91, 95% CI 0.82-1.01, P = 0.09) were observed with the early strategy but these differences were not nominally significant. CONCLUSION Early coronary angiography and potential intervention reduces the risk of recurrent ischaemia, and shortens hospital stay in patients with NSTE-ACS.

Rapid pulmonary vein isolation combined with autonomic ganglia modification: A randomized study

BACKGROUND Evidence indicates that the combination of left atrial ganglionated plexi (GP) ablation and pulmonary vein (PV) isolation is beneficial for treatment of paroxysmal atrial fibrillation (AF). OBJECTIVE The purpose of this study was to compare GP and PV ablation with PV isolation alone for treatment of paroxysmal AF. METHODS Sixty-seven patients with paroxysmal AF were randomized to either PV isolation using a circular catheter suitable for both mapping and ablation (PV group) or anatomic GP modification followed by PV isolation (GP+PV group). Patients were seen at monthly visits, and 48-hour ambulatory ECG recordings were obtained every 3 months for a predefined follow-up period of 12 months. Primary endpoint was freedom from AF or other sustained atrial arrhythmia recurrence 3 to 12 months postablation after one or two procedures, without antiarrhythmic medications. RESULTS Recurrence of arrhythmia was documented in 18 (54.5%) patients in the PV group 4.7 ± 1.0 months after ablation, and repeat PV isolation was performed in 7 (21.2%) of these patients 5.1 ± 1.1 months after the first procedure. Recurrence of arrhythmia was documented in 9 (26.5%) patients in the GP+PV group 5.0 ± 1.3 months after ablation, and repeat ablation was performed in 6 (17.6%) of these patients 4.3 ± 0.5 months after the first procedure. At the end of follow-up, 20 (60.6%) patients in the PV group and 29 (85.3%) patients in the GP+PV group remained arrhythmia-free (log rank test, P = .019). CONCLUSION Addition of anatomic GP modification to PV isolation confers significantly better outcomes than PV isolation alone during a follow-up period of 12 months.