16-year follow-up of the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial: primary percutaneous coronary intervention vs. fibrinolysis in ST-segment elevation myocardial infarction.

AIMS: The DANish Acute Myocardial Infarction 2 (DANAMI-2) trial found that interhospital transport to primary percutaneous coronary intervention (pPCI) was superior to fibrinolysis at the local hospital in patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The present study investigates the 16-year cardiovascular outcomes. METHODS AND RESULTS: We randomized 1572 STEMI patients to pPCI or fibrinolysis at 24 referral hospitals and 5 invasive centres in Denmark. Patients randomized to pPCI at referral hospitals were immediately transported to the nearest invasive centre. The main endpoint of the current study was a composite of death or rehospitalization for myocardial infarction (MI). Outcome information beyond 3 years was obtained through Danish health registries. After 16 years, pPCI-treated patients had a sustained lower rate of composite endpoint compared to patients treated with fibrinolysis in the overall cohort [58.7% vs. 62.3%; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76-0.98], and among patients transported for pPCI (58.7% vs. 64.1%; HR 0.82, 95% CI 0.71-0.96). No difference in all-cause mortality was found, but cardiac mortality was reduced by an absolute of 4.4% in favour of pPCI (18.3% vs. 22.7%; HR 0.78, 95% CI 0.63-0.98). pPCI postponed a main event with 12.3 months in average compared to fibrinolysis (95% CI 5.0-19.5). CONCLUSION: The benefit of pPCI over fibrinolysis was maintained at 16-year follow-up. pPCI reduced the composite endpoint of death or rehospitalization for MI, reduced cardiac mortality, and delayed average time to a main event by approximately 1 year.

Aortic valve and left ventricular outflow tract calcium volume and distribution in transcatheter aortic valve replacement: Influence on the risk of significant paravalvular regurgitation.

OBJECTIVES: We sought to determine the impact of aortic root calcium on the risk of significant paravalvular regurgitation (sPAR) in transcatheter aortic valve replacement (TAVR). METHODS: In 302 consecutive patients from 3 centers, aortic root calcium was quantified volumetrically on pre-TAVR multidetector computed tomography (MDCT) in three regions: 1) the aortic valve region, 2) the overall left ventricular outflow tract (LVOT) and 3) the upper LVOT. Transcathether heart valve (THV) oversizing was calculated as (THV nominal area/MDCT annular area-1) × 100. The study endpoint sPAR was a composite of post-dilatation (PD) and PAR > mild. RESULTS: sPAR occurred in 15% (46/302) of patients. Upper LVOT calcium volume was more predictive of sPAR than overall LVOT calcium volume, with an area under the receiver operating curve (AUC) (95% confidence interval [CI]) of 0.80 (0.67-0.89) vs. 0.60 (0.51-0.70); p = 0.0001. The optimal cut-off calcium volume thresholds determined from receiver operating curves were 21 mm3 and 30 mm3 for upper LVOT and overall LVOT calcium, respectively. Upper LVOT calcium ≥ 21 mm3, but not overall LVOT calcium ≥ 30 mm3, independently predicted sPAR, odds ratio (95%CI): 9.5 (4.1-22.3) vs 1.6 (0.6-2.7). Upper LVOT calcium was more predictive of sPAR in patients with THV oversizing ≥ 13% compared to patients with THV oversizing <13%, AUC (95% CI): 0.83 (0.72-0.93) vs. 0.67 (0.51-0.74); p < 0.0001. CONCLUSIONS: Upper LVOT calcium predicts more-than-mild paravalvular regurgitation following TAVR or the need for postdilatation. Upper LVOT calcium is most predictive of paravalvular regurgitation in the event of THV oversizing ≥ 13%.

Transcatheter Aortic Valve Thrombosis: Incidence, Predisposing Factors, and Clinical Implications.

BACKGROUND: There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR. METHODS: Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis. RESULTS: MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT. CONCLUSIONS: Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications.

Stroke Related to Transcatheter Heart Valve Thrombosis.

Non-obstructive transcatheter heart valve (THV) thrombosis as a potential mechanism after stroke after transapical transcatheter aortic valve replacement (TAVR) is demonstrated by the present case report. By performing cardiac computed tomography (CT) in addition to standard transthoracic echocardiography (TTE) follow up after TAVR, it has been shown recently that non-obstructive THV thrombosis may be more common than previously anticipated. However, the clinical implications of non-obstructive THV thrombosis remain unclear. In the present patient, post-TAVR TTE and transeophageal echocardiography demonstrated normal THV function, and showed no evidence of THV thrombosis. In contrast, cardiac CT revealed findings consistent with THV thrombosis. The patient subsequently developed acute ischemic stroke that was treated with thrombolysis. Follow up cardiac CT and echocardiography demonstrated complete THV thrombus resolution.

The impact of calcium volume and distribution in aortic root injury related to balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: A detailed assessment of calcium within the aortic root may provide important additional information regarding the risk of aortic root injury during transcatheter heart valve replacement (TAVR). OBJECTIVE: We sought to delineate the effect of calcium volume and distribution on aortic root injury during TAVR. METHODS: Thirty-three patients experiencing aortic root injury during TAVR with a balloon-expandable valve were compared with a control group of 153 consecutive TAVR patients without aortic root injury (as assessed by post-TAVR multidetector CT). Using commercial software to analyze contrast-enhanced pre-TAVR CT scans, calcium volume was determined in 3 regions: (1) the overall left ventricular outflow tract (LVOT), extending 10 mm down from the aortic annulus plane; (2) the upper LVOT, extending 2 mm down from the annulus plane; and (3) the aortic valve region. RESULTS: Calcium volumes in the upper LVOT (median, 29 vs 0 mm(3); P < .0001) and overall LVOT (median, 74 vs 3 mm(3); P = .0001) were higher in patients who experienced aortic root injury compared with the control group. Calcium in the aortic valve region did not differ between groups. Upper LVOT calcium volume was more predictive of aortic root injury than overall LVOT calcium volume (area under receiver operating curve [AUC], 0.78; 95% confidence interval, 0.69-0.86 vs AUC, 0.71; 95% confidence interval, 0.62-0.82; P = .010). Upper LVOT calcium below the noncoronary cusp was significantly more predictive of aortic root injury compared to calcium underneath the right coronary cusp or the left coronary cusp (AUC, 0.81 vs 0.68 vs 0.64). Prosthesis oversizing >20% (likelihood ratio test, P = .028) and redilatation (likelihood ratio test, P = .015) improved prediction of aortic root injury by upper LVOT calcium volume. CONCLUSION: Calcification of the LVOT, especially in the upper LVOT, located below the noncoronary cusp and extending from the annular region, is predictive of aortic root injury during TAVR with a balloon-expandable valve.

Early aortic transcatheter heart valve thrombosis: diagnostic value of contrast-enhanced multidetector computed tomography.

BACKGROUND: Early stent valve thrombosis after transcatheter aortic valve implantation (TAVI) is a rare complication, which is diagnosed based on the appearance of clinical symptoms of heart failure and echocardiographic findings. After TAVI, transthoracic echocardiography is performed to assess transcatheter heart valve (THV) function. However, preliminary reports indicate the potential additive clinical value of multidetector computed tomography (MDCT) for the diagnosis of THV thrombosis. We sought to determine the value of MDCT for the diagnosis of THV thrombosis and the frequency of this complication after balloon-expandable TAVI. METHODS AND RESULTS: MDCT was performed in 140 patients within 1 to 3 months after TAVI with the Edwards Sapien XT THV to assess the presence of THV thrombosis and THV stent geometry. Post-TAVI MDCT identified THV thrombosis in 5 patients (4%). Of note, 4 of these patients were asymptomatic and had a normal transthoracic echocardiographic examination without signs of thrombus formation or flow obstruction. In patients with THV thrombosis, a left ventricular ejection fraction of <35% was present in 3 (60%), whereas 2 (40%) did not receive standard post-TAVI dual-antiplatelet therapy. Neither THV underexpansion nor THV noncircularity was detected in patients with THV thrombosis. CONCLUSIONS: Post-TAVI MDCT is a valuable tool for the diagnosis of THV thrombosis, and this complication seems to be more common than previously anticipated. Larger studies are required to identify specific risk factors of THV thrombosis.

Does atrial pacing lead to atrial fibrillation in patients with sick sinus syndrome? Insights from the DANPACE trial.

AIMS: Paroxysmal atrial fibrillation (AF) is common in patients with sick-sinus syndrome (SSS) and pacemakers leading to morbidity and an increased risk of stroke or death. Previous studies indicate that atrial pacing may precipitate AF. We investigated the relation between atrial pacing and the occurrence of AF during long-term follow-up among patients with SSS, no prior AF, and dual-chamber pacemakers (DDDRs). METHODS AND RESULTS: We analysed data from 396 patients who received DDDR pacemakers in the DANPACE trial. The percentage of atrial pacing (%AP) was compared with the number of mode-switch (MS) episodes collected by the pacemaker at each follow-up as an indicator of AF. Mean follow-up was 4.2 ± 2.4 years. The mean proportion of atrial and ventricular pacing was 59 ± 31 and 65 ± 33%, respectively. Approximately 72% developed AF as indicated by MS episodes at some point during follow-up. Unadjusted regression analysis indicated a relation between %AP and AF (P = 0.04), but after adjustment for possible confounders (sex, age, hypertension, diabetes, myocardial infarction, PQ interval, and left atrial diameter) there was no significant relationship (P = 0.37). CONCLUSION: Atrial fibrillation is very common among patients with SSS. No association between %AP and development of AF was found in patients with SSS. Future trials may randomize patients to different levels of AP exposure.

Three-dimensional multidetector computed tomography versus conventional 2-dimensional transesophageal echocardiography for annular sizing in transcatheter aortic valve replacement: Influence on postprocedural paravalvular aortic regurgitation.

OBJECTIVES: In transcatheter aortic valve replacement (TAVR), the influence of aortic annular assessment with either multidetector computed tomography (MDCT) or conventional transesophageal echocardiography (TEE) on the incidence of postprocedural paravalvular aortic regurgitation (PAR) was evaluated. BACKGROUND: PAR remains a major limitation in TAVR. Appropriate selection of transcatheter heart valve (THV) size is crucial to prevent PAR. METHODS: Outcomes following TAVR with a balloon-expandable THV were compared in two retrospective cohorts identified according to whether THV size selection was based on TEE (study group 1, n = 80) or MDCT (study group 2, n = 58). RESULTS: The two study groups were comparable with regard to baseline clinical, risk score, and echocardiographic characteristics. The incidence of moderate/severe PAR was lower in study group 2 than in group 1, 8.6% versus 28.8% (P < 0.01). The difference between the THV nominal diameter and MDCT annular diameter was predictive of moderate/severe PAR (AUC 0.84; 95% CI: 0.72-0.92). Neither age, gender, body mass index, annular eccentricity index, aortic valve calcification nor the difference between the THV diameter and the TEE annular diameter predicted postprocedural PAR. Increased THV oversizing relative to the MDCT mean annular diameter was associated with reduced severity of PAR. No difference in perprocedural complications between two study groups was observed. CONCLUSION: MDCT-based annular sizing in TAVR significantly reduces postprocedural PAR, and THV oversizing appears pivotal in this aspect. Further delineation of the optimal degree of THV oversizing is needed.

Left ventricular global systolic longitudinal deformation and prognosis 1 year after femoral and apical transcatheter aortic valve implantation.

BACKGROUND: Aortic valve replacement is the recommended therapy for patients with severe aortic stenosis who have symptoms or decreased left ventricular (LV) function. Transcatheter aortic valve implantation (TAVI) is a treatment alternative in surgically high-risk or inoperable patients with severe aortic stenosis. The objective of this study was to analyze LV function assessed by global LV longitudinal systolic strain (GLS) and relation to prognosis in patients with severe aortic stenosis treated with femoral or apical TAVI. METHODS: Two-dimensional echocardiography was performed before and 1 year after TAVI. Ejection fraction (EF) was retrospectively measured using the biplane Simpson's method, and GLS was obtained as an average of 16 segments in the three standard apical views by speckle-tracking. GE Vivid 7 and Vivid 9 machines were used for echocardiography, and speckle-tracking analysis was performed using EchoPAC PC '08 version 7.0.1. RESULTS: The total population consisted of 100 TAVI patients. Eighty-one patients survived to 1-year follow-up, with a mean age of 81 ± 7 years (range, 64-93 years) and a mean European System for Cardiac Operative Risk Evaluation score of 9.6 ± 2.7. Nineteen patients died before 1-year follow-up (12 women), with a mean age of 82 ± 7 years (range, 66-92 years) and a mean European System for Cardiac Operative Risk Evaluation score of 10.5 ± 2.8. No differences were found between the 19 patients who died before follow-up and the 81 patients who survived to 1-year follow-up. GLS was increased significantly 1 year after TAVI. In 34 patients with EFs > 50%, GLS increased from -15.3 ± 3.4 to -17.1 ± 3.6 (P = .04). In these patients, the mean EF increased numerically from 57.9 ± 5.3% to 60 ± 7.7% (P = .19). In 74 patients with EFs ≤ 50%, mean GLS and EF improved significantly from -10 ± 2.8 to -13.8 ± 3.8 (P < .0001) and 39 ± 9.4% to 52 ± 12.5% (P < .0001), respectively. The 1-year gain in EF was the same after femoral TAVI (9.7 ± 10.1%) and after apical TAVI (8 ± 10.8%) (P = .52). Furthermore, GLS did not differ significantly after femoral and apical TAVI (-3.8 ± 3.3 and -2.6 ± 3.7, respectively, P = .21). There was no difference in causes of death according to approach. In the total population (n = 100), 35 deaths occurred, 19 before 1-year follow-up and 16 afterward. The median follow-up time was 30 months. Twenty-five patients (71%) died from cardiac causes. Overall 1-year mortality was 19%, and overall 2-year mortality was 28%. In the patients who died, the median survival time in the apical group was 28.5 ± 15.4 months, compared with 31.6 ± 19 months in the femoral group (P = .47). There was no impact on prognosis according to high (≥47.5%) versus low (<47.5%) baseline EF or high (≥11.95%) versus low (<11.95%) baseline GLS. However, the magnitude of changes in GLS seemed to have a prognostic impact. CONCLUSIONS: LV EF and longitudinal systolic deformation were improved in TAVI independent of technical approach using the Edwards SAPIEN valve prosthesis during 1-year follow-up. The mortality rate was comparable between technical approaches and independent of baseline LV function. However, patients with the greatest improvement in LV systolic longitudinal deformation after TAVI had a lower mortality rate.

A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis: the STACCATO trial.

AIMS: In a prospective randomised trial we aimed to compare transapical transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve replacement (SAVR) in operable elderly patients. METHODS AND RESULTS: The study was designed as a randomised controlled trial of a-TAVI (Edwards SAPIEN heart valve system; Edwards Lifesciences, Irvine, CA, USA) vs. SAVR. Operable patients with isolated aortic valve stenosis and an age ≥75 years were included. The primary endpoint was the composite of all-cause mortality, cerebral stroke and/or renal failure requiring haemodialysis at 30 days. After advice from the Data Safety Monitoring Board, the study was prematurely terminated after the inclusion of 70 patients because of an excess of events in the a-TAVI group. The primary endpoint was met in five a-TAVI patients (two deaths, two strokes, and one case of renal failure requiring dialysis) vs. one stroke in the SAVR group (p=0.07). In the a-TAVI group, one patient was converted to SAVR because of an abnormally positioned heart, and four patients were re-operated with open heart surgery because of annulus rupture (n=1), severe paravalvular leakage (n=2), and blockage of the left coronary artery (n=1). In the SAVR group, one patient was converted to TAVI because of a large intra-thoracic goitre. CONCLUSIONS: Given the limitations of a small prematurely terminated study, our results suggest that a-TAVI in its present form may be associated with complications and device success rates in low-risk patients similar or even inferior to those found in high-risk patients with aortic valve stenosis. This will probably change in the near future with improved catheter based devices and better pre-procedural assessment.

Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site.

AIMS: Previous studies indicate that ventricular pacing may precipitate heart failure (HF). We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome (SSS) randomized to AAIR or DDDR pacing. Furthermore, we investigated effects of percentage of ventricular pacing (%VP) and pacing site in the ventricle. METHODS AND RESULTS: We analysed data from 1415 patients randomized to AAIR (n = 707) or DDDR pacing (n = 708). Ventricular pacing leads were recorded as located in either an apical or a non-apical position. The %VP and HF hospitalizations were recorded during follow-up. Patients were classified with new HF, if in New York Heart Association (NYHA) functional class IV or if presence of ≥2 of: oedema; dyspnoea; NYHA functional class III. Mean follow-up was 5.4 ± 2.4 years. Heart failure hospitalizations did not differ between groups. In the AAIR group, 170 of the 707 (26%) patients developed HF vs. 169 of the 708 (26%) patients in the DDDR group, hazard rate ratio (HR) 1.00, 95% confidence interval (CI) 0.79-1.22, P = 0.87. In DDDR patients, 146 of the 512 patients (29%) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients (17%) with the leads in a non-apical position, HR 0.67, CI 0.45-1.00, P = 0.05. After adjustments this difference was non-significant. The incidence of HF was not associated with %VP (P = 0.57). CONCLUSION: In patients with SSS, HF was not associated with pacing mode, %VP, or ventricular lead localization. This suggests that DDDR pacing is safe in patients with SSS without precipitating HF.

Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing.

AIMS: In the recently published DANPACE trial, incidence of atrial fibrillation (AF) was significantly higher with single-lead atrial (AAIR) pacing than with dual-chamber (DDDR) pacing. The present analysis aimed to evaluate the importance of baseline PQ-interval and percentage of ventricular pacing (VP) on AF. METHODS AND RESULTS: We analysed data on AF during follow-up in 1415 patients included in the DANPACE trial. In a subgroup of 650 patients with DDDR pacemaker, we studied whether %VP, baseline PQ-interval, and programmed atrio-ventricular interval (AVI) was associated with AF burden measured as time in mode-switch (MS) detected by the pacemaker. In the entire DANPACE study population, the incidence of AF was significantly higher in patients with baseline PQ-interval >180 ms (P< 0.001). Among 650 patients with DDDR pacemaker, telemetry data were available for 1.337 ± 786 days, %VP was 66 ± 33%, AF was detected at planned follow-up in 160 patients (24.6%), MS occurred in 422 patients (64.9%), and AF burden was marginally higher with baseline PQ-interval >180 ms (P= 0.028). No significant association was detected between %VP and %MS (Spearman's ρ 0.056, P= 0.154). %MS was not different between minimal-paced programmed AVI ≤ 100 and >100 ms (median value), respectively (P= 0.60). CONCLUSIONS: The present study indicates that a longer baseline PQ-interval is associated with an increased risk of AF in patients with sick sinus syndrome. Atrial fibrillation burden is not associated with the percentage of VP or the length of the programmed AVI.

Are elderly patients at increased risk of complications following pacemaker implantation? A meta-analysis of randomized trials.

BACKGROUND: Patients over the age of 75 represent more than half the recipients of permanent pacemakers. It is not known if they have a different risk of complications than younger patients. METHODS: Patient-level data were pooled from the CTOPP, UKPACE, and Danish pacing trials. These three randomized trials of pacing mode systematically captured early and late complications following pacemaker insertion. Early postimplant complications included lead dislodgement or loss of capture, cardiac perforation, pneumothorax, hematoma, infection, and death. Lead fracture was considered a late complication. RESULTS: A total of 4,814 patients were included in this analysis, with an average follow-up of 5.1 years. The average age was 76 years and 43% were female. Any early complication occurred in 5.1% of patients ≥75 years of age compared to 3.4% of patients aged <75 years (P = 0.006). This was driven by an increased risk of pneumothorax (1.6% vs 0.8%, P = 0.07) and both atrial and ventricular lead dislodgement/loss of capture (2.0% vs 1.1%, P = 0.07). Early complications were higher in patients receiving atrial-based pacemakers in both age groups (<75 years: 4.6% vs 2.4%; ≥75 years: 6.6% vs 3.7%); however, the relative risk was not influenced by age group. Older patients had a lower risk of lead fracture (3.6% vs 2.7%, P = 0.08). CONCLUSION: Elderly patients (≥75 years of age) are at increased risk of early postimplant complications but are at lower risk for lead fracture.

Primary percutaneous coronary intervention as a national reperfusion strategy in patients with ST-segment elevation myocardial infarction.

BACKGROUND: In Denmark, primary percutaneous coronary intervention (PPCI) was chosen as a national reperfusion strategy for patients with ST-segment elevation myocardial infarction in 2003. This study describes the temporal implementation of PPCI in Western Denmark, the gradual introduction of field triage for PPCI (patients rerouted from the scene of the event directly to the invasive center), and the associated outcome. METHODS AND RESULTS: The study population comprised 9514 patients treated with PPCI from 1999 to 2009 with symptom duration ≤12 hours and either a delay from the emergency medical service (EMS) call to PPCI (healthcare system delay) of ≤6 hours or as self-presenters. The median follow-up time was 3.7 years. The number of patients treated with PPCI increased from 190 in 1999 to 1212 in 2009. Among patients transported by the EMS from the scene of the event, the proportion who were field triaged directly to a PCI center increased from 33% (34/103) to 72% (616/851, P<0.001). Patients who were field triaged had lower long-term mortality, with adjusted hazard ratios (95% CI) of 1.26 (1.12-1.43) among patients transported by the EMS to a local hospital and then transferred, 1.28 (1.10-1.49) among patients self-presenting at a local hospital and then transferred, and 1.37 (1.18-1.58) among patients self-presenting at a PCI center. CONCLUSIONS: A reperfusion strategy with PPCI only for patients with ST-segment elevation myocardial infarction was successfully implemented in Western Denmark, and the majority of patients transported by the EMS are now triaged directly to the PPCI centers. This strategy is associated with lower mortality.

System delay and timing of intervention in acute myocardial infarction (from the Danish Acute Myocardial Infarction-2 [DANAMI-2] trial).

The interval from the first alert of the healthcare system to the initiation of reperfusion therapy (system delay) is associated with mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI). The importance of system delay in patients treated with fibrinolysis versus pPCI has not been assessed. We obtained data on system delay from the Danish Acute Myocardial Infarction-2 study, which randomized 1,572 patients to fibrinolysis or pPCI. The study end points were 30-day and 8-year mortality. The short system delays were associated with reduced absolute mortality in both the fibrinolysis group (<1 hour, 5.6%; 1 to 2 hours, 6.9%; 2 to 3 hours, 9.5%; and >3 hours, 11.5%; test for trend, p = 0.08) and pPCI group (<1 hour, not assessed; 1 to 2 hours, 2.6%; 2 to 3 hours, 7.5%; >3 hours, 7.7%; test for trend, p = 0.02). The lowest 30-day mortality was obtained with pPCI and a system delay of 1 to 2 hours (vs fibrinolysis within <1 hour, adjusted hazard ratio 0.33; 95% confidence interval 0.10 to 1.10; p = 0.07; vs fibrinolysis within 1 to 2 hours, adjusted hazard ratio 0.37; 95% confidence interval 0.14 to 0.95; p = 0.04). pPCI and system delay >3 hours was associated with a similar 30-day and 8-year mortality as fibrinolysis within 1 to 2 hours. In conclusion, short system delays are associated with reduced mortality in patients with ST-segment elevation myocardial infarction treated with fibrinolysis as well as pPCI. pPCI performed with a system delay of <2 hours is associated with lower mortality than fibrinolysis performed with a faster or similar system delay.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design.

BACKGROUND: Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. METHODS: The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. DISCUSSION: patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Association between ST segment Resolution following Fibrinolytic therapy or Intracoronary stenting, and Reinfarction in the same myocardial region in the DANAMI-2 study population.

BACKGROUND: ST-segment resolution has long been used as one of several clinical markers of response to reperfusion therapy. With the use of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) database, this case-control study tests the hypothesis that incomplete ST-segment resolution (<70%) will be predictive of the risk of reinfarction in the same myocardial region regardless of the reperfusion therapy employed. METHODS AND RESULTS: One hundred forty-nine (9.5%) patients with clinical reinfarction were matched to patients with no documented reinfarction ("no reinfarction"). With the use of the initial DANAMI-2 and reinfarction electrocardiograms, 80 patients were found to have reinfarction in the same myocardial region ("reinfarction"). "Reinfarction" and their matched "no-reinfarction" patients were included (n=160), and prereperfusion and postreperfusion ST segments were measured manually. Of all "reinfarction" patients, 66% (53 of 80) had incomplete ST-segment resolution [P=.13; odds ratio (OR)=1.69]. Stratified by the reperfusion strategy employed, this corresponded to 67% (35 of 52) being treated with fibrinolytics (P=.45; OR=1.33), suggesting that these patients were equally likely to reinfarct in the same myocardial region regardless of the degree of ST-segment resolution. In the primary percutaneous coronary intervention (pPCI) arm, 64% (18 of 28) of patients with reinfarction in the same myocardial region had incomplete ST-segment resolution (P=.10; OR=6.0). In the pPCI arm, the trend was that patients with incomplete ST-segment resolution were more likely to reinfarct in the same myocardial region than those with complete ST-segment resolution, but these findings did not reach statistical significance. No statistically significant difference was found in the association of reinfarction in the same myocardial region and ST-segment resolution between the two treatment arms (P=.11). CONCLUSION: The results from this study suggest that, although fibrinolytic-treated patients are more likely to reinfarct in the same myocardial region than pPCI-treated patients, there is no clear statistically significant association between ST-segment resolution and reinfarction in the same myocardial region. Trends in the data suggest that fibrinolytic-treated patients are equally likely to reinfarct in the same myocardial region regardless of the degree of ST-segment resolution. However, the trend in the pPCI population is such that incomplete ST-segment resolution is associated with a higher likelihood of reinfarction in the same myocardial region.

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome.

AIMS: In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR). METHODS AND RESULTS: We randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n = 707) or DDDR (n = 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6%) died during follow-up vs. 193 patients (27.3%) in the DDDR group, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.88-1.29, P = 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4%) in the AAIR group vs. 163 patients (23.0%) in the DDDR group, HR 1.27, 95% CI 1.03-1.56, P = 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1%) in the AAIR group vs. 84 (11.9%) in the DDDR group (HR 1.99, 95% CI 1.53-2.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups. CONCLUSION: In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158.

Primary angioplasty versus fibrinolysis in acute myocardial infarction: long-term follow-up in the Danish acute myocardial infarction 2 trial.

BACKGROUND: The Danish Acute Myocardial Infarction 2 (DANAMI-2) study found that primary angioplasty (primary percutaneous coronary intervention [pPCI]) compared with fibrinolysis reduced 30-day adverse events in patients with ST-segment elevation myocardial infarction. The present study investigated whether the benefit of pPCI was maintained at a long-term follow-up. METHODS AND RESULTS: We randomly assigned 1572 patients with ST-segment elevation myocardial infarction-1129 patients at referral hospitals and 443 patients at invasive hospitals-to pPCI or fibrinolysis. Median time from randomization to arrival in the catheterization laboratory for patients admitted to referral hospitals was 67 minutes, with 96% of patients arriving in the catheterization laboratory within 120 minutes. The primary study end point was a composite of death or reinfarction. Median follow-up time was 7.8 years. For the primary end point, 8-year cumulative incidence (1-Kaplan-Meier) was 34.8% in the pPCI group and 41.3% in the fibrinolysis group (hazard ratio, 0.78; 95% confidence interval, 0.66 to 0.92). Reinfarction rates were reduced in the pPCI group (11.7% versus 18.5%; hazard ratio, 0.60; 95% confidence interval, 0.46 to 0.77). Among patients randomized at referral hospitals, pPCI reduced reinfarction (13% versus 18.5%; hazard ratio, 0.66; 95% confidence interval, 0.49 to 0.89) and mortality (26.7% versus 33.3%; hazard ratio, 0.78; 95% confidence interval, 0.63 to 0.97). CONCLUSIONS: The benefit of pPCI over fibrinolysis was maintained at a long-term follow-up. pPCI reduced the risk of reinfarction in the overall cohort and reduced reinfarction and mortality among patients randomized at referral hospitals. This result reinforces that pPCI should be offered to ST-segment elevation myocardial infarction patients when interhospital transport to an invasive hospital can be completed within 120 minutes.