Göran Olivecrona

Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction

BACKGROUND The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. METHODS We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. RESULTS No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. CONCLUSIONS Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.).

Outcomes 1 Year after Thrombus Aspiration for Myocardial Infarction

BACKGROUND Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration. METHODS We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial. RESULTS No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients (191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6% (202 of 3623) in the PCI-only group (hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P=0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively (hazard ratio, 0.97; 95% CI, 0.73 to 1.28; P=0.81), and stent thrombosis in 0.7% and 0.9%, respectively (hazard ratio, 0.84; 95% CI, 0.50 to 1.40; P=0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively (hazard ratio, 0.94; 95% CI, 0.80 to 1.11; P=0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI. CONCLUSIONS Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year. (Funded by the Swedish Research Council and others; TASTE ClinicalTrials.gov number, NCT01093404.).

A Pilot Study of Rapid Cooling by Cold Saline and Endovascular Cooling Before Reperfusion in Patients With ST-Elevation Myocardial Infarction

Background—Experimental studies have shown that induction of hypothermia before reperfusion of acute coronary occlusion reduces infarct size. Previous clinical studies, however, have not been able to show this effect, which is believed to be mainly because therapeutic temperature was not reached before reperfusion in the majority of the patients. We aimed to evaluate the safety and feasibility of rapidly induced hypothermia by infusion of cold saline and endovascular cooling catheter before reperfusion in patients with acute myocardial infarction. Methods and Results—Twenty patients with acute myocardial infarction scheduled to undergo primary percutaneous coronary intervention were enrolled in this prospective, randomized study. After 4±2 days, myocardium at risk and infarct size were assessed by cardiac magnetic resonance using T2-weighted imaging and late gadolinium enhancement imaging, respectively. A core body temperature of <35°C (34.7±0.3°C) was achieved before reperfusion without significant delay in door-to-balloon time (43±7 minutes versus 40±6 minutes, hypothermia versus control, P=0.12). Despite similar duration of ischemia (174±51 minutes versus 174±62 minutes, hypothermia versus control, P=1.00), infarct size normalized to myocardium at risk was reduced by 38% in the hypothermia group compared with the control group (29.8±12.6% versus 48.0±21.6%, P=0.041). This was supported by a significant decrease in both peak and cumulative release of Troponin T in the hypothermia group (P=0.01 and P=0.03, respectively). Conclusions—The protocol demonstrates the ability to reach a core body temperature of <35°C before reperfusion in all patients without delaying primary percutaneous coronary intervention and that combination hypothermia as an adjunct therapy in acute myocardial infarction may reduce infarct size at 3 days as measured by MRI. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00417638.

Cardiac arrest in the catheterisation laboratory: a 5-year experience of using mechanical chest compressions to facilitate PCI during prolonged resuscitation efforts.

PURPOSE Lengthy resuscitations in the catheterisation laboratory carry extremely high rates of mortality because it is essentially impossible to perform effective chest compressions during percutaneous coronary intervention (PCI). The purpose of this study was to evaluate the use of a mechanical chest compression device, LUCAS, in the catheterisation laboratory, in patients who suffered circulatory arrest requiring prolonged resuscitation. MATERIALS AND METHODS The study population was comprised of patients who arrived alive to the catheterisation laboratory and then required mechanical chest compression at some time during the angiogram, PCI or pericardiocentesis between 2004 and 2008 at the Lund University Hospital. This is a retrospective registry analysis. RESULTS During the study period, a total of 3058 patients were treated with PCI for ST-elevation myocardial infarction (STEMI) of whom 118 were in cardiogenic shock and 81 required defibrillations. LUCAS was used in 43 patients (33 STEMI, 7 non-ST-elevation myocardial infarction (NSTEMI), 2 elective PCIs and 1 patient with tamponade). Five patients had tamponade due to myocardial rupture prior to PCI that was revealed at the start of the PCI, and all five died. Of the remaining 38 patients, 1 patient underwent a successful pericardiocentesis and 36 were treated with PCI. Eleven of these patients were discharged alive in good neurological condition. CONCLUSION The use of mechanical chest compressions in the catheterisation laboratory allows for continued PCI or pericardiocentesis despite ongoing cardiac or circulatory arrest with artificially sustained circulation. It is unlikely that few, if any, of the patients would have survived without the use of mechanical chest compressions in the catheterisation laboratory.

Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial). A multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish angiography and angioplasty registry (SCAAR) platform. Study design and rationale.

BACKGROUND In ST-elevation myocardial infarction (STEMI), distal embolization of thrombus material often precludes restoration of normal coronary artery flow. Small-scaled studies have demonstrated that intracoronary thrombus aspiration improves flow and myocardial perfusion, but only one larger randomized single-center study has suggested a survival benefit. Thrombus aspiration is widely used in clinical practice and is recommended by international guidelines despite limited evidence. METHODS/DESIGN The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia is a multicenter, prospective, randomized, controlled, clinical open-label trial based on the Swedish angiography and angioplasty registry (SCAAR) platform with blinded evaluation of end points. A total of 5,000 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) will randomly be assigned either to conventional PCI or to thrombus aspiration followed by PCI. SCAAR will be used as the platform for randomization, allowing a broad population of all-comers in the registry network to be enrolled. All follow-up will also be done in SCAAR and other national registries. The primary end point is time to all-cause death at 30 days. DISCUSSION The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial is the largest trial to date to evaluate the effect of thrombus aspiration on death following PCI in patients with STEMI. We propose the term randomized clinical registry trial to describe the novel entity of using an online national registry as platform for case records, randomization, and follow-up.

ADP Acting on P2Y13 Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells

Red blood cells may regulate tissue circulation and O2 delivery by releasing the vasodilator ATP in response to hypoxia. When released extracellularly, ATP is rapidly degraded to ADP in the circulation by ectonucleotidases. In this study, we show that ADP acting on P2Y13 receptors on red blood cells serves as a negative feedback pathway for the inhibition of ATP release. mRNA of the ADP receptor P2Y13 was highly expressed in human red blood cells and reticulocytes. The stable ADP analogue 2-MeSADP decreased ATP release from red blood cells by inhibition of cAMP. The P2Y12 and P2Y13 receptor antagonist AR-C67085 (30 &mgr;mol/L), but not the P2Y1 blocker MRS2179, inhibited the effects of 2-MeSADP. At doses where AR-C67085 only blocks P2Y12 (100 nmol/L), it had no effect. AR-C67085 and the nucleotidase apyrase increased cAMP per se, indicating a constant cAMP inhibitory effect of endogenous extracellular ADP. 2-MeSADP reduced plasma ATP concentrations in an in vivo pig model. Our results indicate that the ATP degradation product ADP inhibits ATP release by acting on the red blood cell P2Y13 receptor. This negative feedback system could be important in the control of plasma ATP levels and tissue circulation.

Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

BackgroundThe aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model.MethodsPigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4°C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI.ResultsPre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 ± 8%) compared to post-reperfusion hypothermia (80 ± 6%, p < 0.05) and by 39% compared to normothermia (75 ± 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 ± 5%; p < 0.05), compared to normothermia: (30.2 ± 5%).ConclusionRapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.

Transapical Versus Transfemoral Aortic Valve Implantation: A Comparison of Survival and Safety

BACKGROUND Transcatheter aortic valve implantation (TAVI) is a therapeutic option for high-risk patients with aortic stenosis. Procedural mortality remains high in comparison with conventional aortic valve replacement (AVR) because patients determined for TAVI are commonly denied conventional surgery. We aimed to evaluate access-related complications between the transfemoral (TF) and the transapical (TA) approach and to compare survival between TAVI and conventional AVR in propensity-score-matched patients. METHODS Between January 2008 and November 2009, 40 patients underwent TAVI (TF, n=10; TA, n=30) with the Edwards Sapien bioprosthesis (Edwards Lifesciences, Irvine, CA). Survival and postoperative complications were evaluated between the TF and the TA approach. A comparison of survival was made between the TAVI patients and propensity-score-matched patients undergoing conventional AVR. RESULTS Successful implantation rate was 92.5% (37 of 40). Thirty-day mortality was 5.0% (2 of 40), and the overall in-hospital mortality was 10.0% (4 of 40). Survival after TAVI was 77% at both 6 months and 1 year. Major vascular complications occurred in 3 of 10 patients (all in the TF group), and 3 of 40 patients (7.5%) suffered cerebrovascular events. A comparison of survival between TAVI and propensity score-matched conventional AVR patients showed no significant difference in either the TA group (p=0.73) or the TF group (p=0.59). CONCLUSIONS The vascular complications occurring when using the TF approach were probably related to a combination of a wide introducer sheath and heavily calcified femoral arteries in a high-risk population. No serious complications were encountered when using the TA approach. After propensity-score matching, survival with both the TA and TF approaches is similar to that after AVR.

Mild hypothermia reduces acute mortality and improves hemodynamic outcome in a cardiogenic shock pig model.

INTRODUCTION Cardiogenic shock is the main cause of death in patients hospitalized due to an acute myocardial infarction. Mild hypothermia reduces metabolism and could offer protective effects for this condition. The aim of our study was to investigate if mild therapeutic hypothermia would improve outcome and hemodynamic parameters in an ischemic cardiogenic shock pig model. METHODS Twenty-five pigs (40-50 kg) were anesthetized and a normothermic temperature of 38 degrees C was established utilising an endovascular cooling catheter in a closed-chest model. A Swan-Ganz catheter was placed in the pulmonary artery. Hemodynamic parameters were continuously monitored and blood gases were sampled every 30 min. Ischemia was induced by inflation of a PCI balloon in proximal LAD for 40 min. Sixteen pigs that have fulfilled predefined shock criteria were randomized to hypothermia (n=8), or normothermia (n=8). Hypothermia (33 degrees C) was induced after onset of reperfusion by using an endovascular temperature modulating catheter and was maintained until termination of the experiment. RESULTS The pigs in the hypothermia group were cooled to <34 degrees C in approximately 45 min. 5/8 pigs in the normothermia group died while all pigs in the hypothermia group survived (p<0.01). Stroke volume and blood pressure were significantly higher in the hypothermia group (p<0.05), whereas heart rate was significantly lower in the hypothermia group (p=0.01). Cardiac output did not differ among the groups (p=0.13). Blood gas analysis revealed higher mixed venous oxygen saturation, pH, and base excess in the hypothermia group indicating less development of metabolic acidosis (p<0.05). CONCLUSIONS In this pig model, mild therapeutic hypothermia reduces acute mortality in cardiogenic shock, improves hemodynamic parameters and reduces metabolic acidosis. These findings suggest a possible clinical benefit of therapeutic hypothermia for patients with acute cardiogenic shock.

Procedural Volume and Outcomes With Radial or Femoral Access for Coronary Angiography and Intervention

OBJECTIVES The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach. BACKGROUND RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021), which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non-coronary artery bypass graft major bleeding. METHODS In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables. RESULTS In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate- (HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p = 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p = 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p = 0.98). CONCLUSIONS Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273).