Jose Dizon

Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction The INFUSE-AMI Randomized Trial

CONTEXT Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. OBJECTIVE To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. DESIGN, SETTING, AND PATIENTS Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. INTERVENTIONS A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. MAIN OUTCOME MEASURES Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). RESULTS Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). CONCLUSION In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00976521.

Predictors and Clinical Outcomes of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement: The PARTNER (Placement of AoRtic TraNscathetER Valves) Trial and Registry

OBJECTIVES The purpose of this study was to identify predictors and clinical implications of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND Cardiac conduction disturbances requiring PPM are a frequent complication of TAVR. However, limited data is available regarding this complication after TAVR with a balloon-expandable valve. METHODS The study included patients without prior pacemaker who underwent TAVR in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and investigated predictors and clinical effect of new PPM. RESULTS Of 2,559 TAVR patients, 586 were excluded due to pre-existing PPM. A new PPM was required in 173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to 1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI: 0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77, 95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean duration of post-procedure hospitalization (7.3 ± 2.7 days vs. 6.2 ± 2.8 days, p = 0.001). At 1 year, new PPM was associated with significantly higher repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between groups in LV ejection fraction at 1 year. CONCLUSIONS PPM was required in 8.8% of patients without prior PPM who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. In addition to pre-existing right bundle branch block, the prosthesis to LV outflow tract diameter ratio and the LV end-diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM was associated with a longer duration of hospitalization and higher rates of repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

Prospective, Randomized, Multicenter Evaluation of a Polyethylene Terephthalate Micronet Mesh-Covered Stent (MGuard) in ST-Segment Elevation Myocardial Infarction The MASTER Trial

OBJECTIVES This study sought to evaluate the potential utility of a novel polyethylene terephthalate micronet mesh-covered stent (MGuard) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). BACKGROUND Suboptimal myocardial reperfusion after PCI in STEMI is common and results in increased infarct size and mortality. The MGuard is a novel thin-strut metal stent with a polyethylene terephthalate micronet covering designed to trap and exclude thrombus and friable atheromatous debris to prevent distal embolization. METHODS A total of 433 patients with STEMI presenting within 12 h of symptom onset undergoing PCI were randomized at 50 sites in 9 countries to the MGuard (n = 217) or commercially available bare metal or drug-eluting stents (n = 216). The primary endpoint was the rate of complete (≥70%) ST-segment resolution measured 60 to 90 min post-procedure. RESULTS Baseline characteristics were well matched between the groups. The primary endpoint of post-procedure complete ST-segment resolution was significantly improved in patients randomized to the MGuard stent compared with control patients (57.8% vs. 44.7%; difference: 13.2%; 95% confidence interval: 3.1% to 23.3%; p = 0.008). By core laboratory analysis, the MGuard stent compared with control stents also resulted in superior rates of Thrombolysis In Myocardial Infarction 3 flow (91.7% vs. 82.9%, p = 0.006) with comparable rates of myocardial blush grade 2 or 3 (83.9% vs. 84.7%, p = 0.81). Mortality (0% vs. 1.9%, p = 0.06) and major adverse cardiac events (1.8% vs. 2.3%, p = 0.75) at 30 days were not significantly different between patients randomized to the MGuard stent and control stent, respectively. CONCLUSIONS Among patients with acute STEMI undergoing emergent PCI, the MGuard micronet mesh-covered stent compared with conventional metal stents resulted in superior rates of epicardial coronary flow and complete ST-segment resolution. A larger randomized trial is warranted to determine whether these benefits result in reduced infarct size and/or improved clinical outcomes. (Safety and Efficacy Study of MGuard Stent After a Heart Attack [MASTER]; NCT01368471).

Clinical implications of new-onset left bundle branch block after transcatheter aortic valve replacement: analysis of the PARTNER experience

AIMS Cardiac conduction disturbances, including a left bundle branch block (LBBB), occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events. This analysis examines the incidence and implications of new onset, persistent LBBB in patients undergoing TAVR with a balloon-expandable valve. METHODS AND RESULTS Patients undergoing TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) trial and continued access registries with baseline and discharge/7-day electrocardiograms were included. Prior permanent pacemaker implantation (PPI) and baseline intraventricular conduction abnormalities were exclusion criteria. Predictors of new LBBB were identified and outcomes compared between patients with and without new LBBB. New LBBB occurred in 121 of 1151 (10.5%) patients and persisted in more than half at 6 months to 1 year. The only predictor of new LBBB was prior coronary artery bypass grafting. New LBBB was not associated with significant differences in 1-year mortality, cardiovascular mortality, repeat hospitalization, stroke, or myocardial infarction. However, it was associated with increased PPI during hospitalization (8.3 vs 2.8%, P = 0.005) and from discharge to 1 year (4.7 vs. 1.5%, P = 0.01). The ejection fraction failed to improve after TAVR in patients with new LBBB and remained lower at 6 months to 1 year (52.8 vs. 58.1%, P < 0.001). CONCLUSION Persistent, new-onset LBBB occurred in 10.5% of patients without intraventricular baseline conduction who underwent TAVR in the PARTNER experience. New LBBB was not associated with death, repeat hospitalization, stroke, or myocardial infarction at 1 year, but was associated with a higher rate of PPI and failure of left ventricular ejection fraction to improve.

Chronic pacing and adverse outcomes after transcatheter aortic valve implantation

Objective Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes. Methods and results Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Δ=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Δ=4.1 prior vs 7.4% no PPM for baseline LVEF 35–50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%). Conclusions In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings. Trial registration number (ClinicalTrials.gov NCT00530894).

Intralesional Abciximab and Thrombus Aspiration in Patients With Large Anterior Myocardial Infarction One-Year Results From the INFUSE-AMI Trial

Background—Whether intralesional abciximab administration and thrombus aspiration confer clinical benefits to patients undergoing primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction is controversial. Methods and Results—A total of 452 patients with ST-segment–elevation myocardial infarction caused by proximal or mid left anterior descending artery occlusion undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation were randomized in a 2×2 factorial design to bolus abciximab delivered locally at the infarct lesion site versus no abciximab and to manual thrombus aspiration versus no aspiration. Treatment with intralesional abciximab, thrombus aspiration, or both therapies compared with no active therapy before stent implantation resulted in lower 1-year rates of death (4.5% versus 10.4%; P=0.03), severe heart failure (4.2% versus 10.3%; P=0.02), and stent thrombosis (0.9% versus 3.8%; P=0.046). Between 30 days and 1 year of follow-up, treatment with intralesional abciximab compared with no abciximab was associated with a lower rate of death (1.4% versus 4.9%; P=0.04) and composite major adverse ischemic events (3.3% versus 7.8%; P=0.04), with nonsignificantly different overall 1-year rates of mortality, composite ischemic events, and heart failure–related events. Thrombus aspiration compared with no aspiration was associated with lower rates of new-onset severe heart failure between 30 days and 1 year (0.9% versus 4.5%; P=0.02) and of rehospitalization for heart failure from randomization to 1 year (0.9% versus 5.4%; P=0.0008), with nonsignificantly different rates of mortality. Conclusions—Intralesional abciximab and thrombus aspiration may have long-term benefits in patients with anterior ST-segment–elevation myocardial infarction presenting early after symptom onset and undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00976521.

Mechanisms of Atrial Tachyarrhythmias Following Surgical Atrial Fibrillation Ablation

Introduction: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown.

Metabolic inhibition in the perfused rat heart: evidence for glycolytic requirement for normal sodium homeostasis.

Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control of the ATP-sensitive K+ channel. Recent data suggest that the control of intracellular sodium (Nai) may also rely on glycolytically derived ATP; however, the degree of this dependence is unclear. To examine this question, isolated, perfused rat hearts were exposed to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 μmol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy phosphate levels were monitored using triple-quantum-filtered (TQF)23Na and31P magnetic resonance spectroscopy, respectively. The effects of ion exchange mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na spectral amplitudes, increased by ∼220% relative to baseline after 45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai increased by ∼200% during rapid pacing but did not increase in unpaced hearts or when the Na+/H+exchange blocker ethylisopropylamiloride (EIPA, 10 μmol/l) was used. Neither EIPA nor a low-Ca2+perfusate (50 μmol/l) could prevent the rise in Nai during perfusion with IAA. Myocardial function and high-energy phosphate stores were preserved during inhibition of glycolysis with IAA and continued oxidative metabolism. These results suggest that glycolysis is required for normal Na+ homeostasis in the perfused rat heart, possibly because of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived ATP.Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control of the ATP-sensitive K+ channel. Recent data suggest that the control of intracellular sodium (Nai) may also rely on glycolytically derived ATP; however, the degree of this dependence is unclear. To examine this question, isolated, perfused rat hearts were exposed to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 mumol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy phosphate levels were monitored using triple-quantum-filtered (TQF) 23Na and 31P magnetic resonance spectroscopy, respectively. The effects of ion exchange mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na spectral amplitudes, increased by approximately 220% relative to baseline after 45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai increased by approximately 200% during rapid pacing but did not increase in unpaced hearts or when the Na+/H+ exchange blocker ethylisopropylamiloride (EIPA, 10 mumol/l) was used. Neither EIPA nor a low-Ca2+ perfusate (50 mumol/l) could prevent the rise in Nai during perfusion with IAA. Myocardial function and high-energy phosphate stores were preserved during inhibition of glycolysis with IAA and continued oxidative metabolism. These results suggest that glycolysis is required for normal Na+ homeostasis in the perfused rat heart, possibly because of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived ATP.

Relationship between myocardial reperfusion, infarct size, and mortality: the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction) trial.

OBJECTIVES This study sought to compare infarct size (IS) measured by magnetic resonance imaging in patients with successful (myocardial blush grade [MBG] 2/3) versus unsuccessful (MBG 0/1) microcirculatory reperfusion in the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction) trial. BACKGROUND Successful microcirculatory reperfusion, defined angiographically by MBG 2 or 3, is associated with improved outcomes in patients with ST-segment elevation myocardial infarction. The precise mechanism underlying this association is not well defined. METHODS The INFUSE-AMI trial randomized 452 patients with anterior ST-segment elevation myocardial infarction to intracoronary bolus abciximab delivered locally at the infarct lesion versus no abciximab, and to manual thrombus aspiration versus no aspiration. The primary endpoint was IS (percentage of left ventricular mass) at 30 days. RESULTS MBG 2/3 was achieved in 367 patients (81.4%). IS was significantly lower in patients with MBG 2/3 than in those with MBG 0/1 (median: 16.7% [interquartile range (IQR): 7.0 to 22.7] vs. 19.5% [IQR: 11.1 to 29.2]; p = 0.002). Intracoronary abciximab further reduced IS in patients with MBG 2/3 (median: 14.4% [IQR: 5.4 to 20.9] vs. 17.4% [IQR: 10.5 to 23.8]; p = 0.01). MBG 2/3 was associated with ∼30% reduction in infarct mass (p = 0.002) and ∼90% reduction in microvascular obstruction on day 5. Ejection fraction was higher with MBG 2/3 at 30 days: median: 50.3% (IQR: 43.8 to 57.8) versus 46.9% (IQR: 37.5 to 54.0); p = 0.004. At 30 days, the rate of death was significantly lower (1.7% vs. 8.3%; p = 0.0008) in the MBG 2/3 group. CONCLUSIONS MBG 2/3 occurs in 80% of ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention and is associated with smaller infarct size, less microvascular obstruction, improved ejection fraction, and significantly lower 30-day mortality. (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction [INFUSE-AMI]; NCT00976521).

Effects of the Ventricular Activation Sequence on the JT Interval

In a retrospective and prospective analysis of electrocardiograms, we noted that the JT interval is not independent of the ventricular depolarization pattern, but is paradoxically shorter for wider QRS morphologies. Such an affect on the JT interval must be accounted for if it is to be used as an accurate means of following the duration of ventricular repolarization for clinical purposes, such as guidance of drug administration.