Abstract Background Short-term mortality has been studied thoroughly in patients undergoing primary percutaneous coronary intervention (PCI), whereas long-term cause of death in patients with ...ST-segment elevation myocardial infarction (STEMI) remains unknown. Objectives The goal of this study was to describe the association between time and cause of death in patients with STEMI undergoing primary PCI. Methods A centralized civil registration system, patient files, and public disease and death cause registries with an accurate record linkage were used to trace time and cause of death in 2,804 consecutive patients with STEMI (age 63 ± 13 years, 72% males) treated with primary PCI. Results Patients were followed up for a median of 4.7 years. During a total of 13,447 patient-years, 717 patients died. Main causes of death within the first 30 days were cardiogenic shock and anoxic brain injury after cardiac arrest. Age, culprit vessel size and flow, and the presence of heart failure and diabetes were independent predictors of mortality. After 30 days, the annual cardiac mortality rate was <1.5%. Causes of death beyond 30 days were noncardiac in 65% of cases (mainly malignancies and pulmonary diseases). The 30-day, 1-year, and 5-year all-cause (and cardiac) mortality rates were 7.9% (7.3%), 11.4% (8.4%), and 23.3% (13.8%), respectively. Conclusions Patients who survive the first month after an STEMI treated with primary PCI have an excellent prognosis, with a <1.5% annual risk of successive cardiac death. Noncardiac causes are responsible for the majority of later deaths in these patients.
The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is an independent predictor of cardiovascular disease and all-cause mortality in healthy ...subjects. The prognostic capability of suPAR, its temporal course, and its relation to plasma C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention (PCI) is unknown. Therefore, the plasma suPAR and CRP levels were measured in 296 consecutive patients with ST-segment elevation myocardial infarction admitted for primary PCI at baseline and every 6 to 8 hours thereafter until the cardiac biomarker levels had peaked. The end points were all-cause mortality and fatal or nonfatal recurrent myocardial infarction (MI). During a median follow-up period of 5.75 years, 69 deaths and 48 nonfatal and 14 fatal recurrent MIs occurred. All-cause mortality increased significantly from 8.1% to 41.5% across increasing quartiles of suPAR levels at the end of follow-up (log-rank p <0.0001). After adjustment for other independent prognostic factors, a highly significant increase was seen in all-cause mortality (hazard ratio 1.45, 95% confidence interval, 1.19 to 1.76; p <0.001) and recurrent MI (hazard ratio 1.53, 95% confidence interval 1.16 to 2.01; p <0.01) for each standard deviation increment of suPAR levels). In contrast to plasma CRP, the suPAR levels remained stable after primary PCI. Furthermore, CRP did not predict mortality or reinfarction after adjustment for age and gender (p = 0.34). In conclusion, suPAR is a stable plasma biomarker after ST-segment elevation myocardial infarction treated with primary PCI that predicts all-cause mortality and recurrent MI.
Abstract Background Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely ...introduced to lower-risk patients. Objectives The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. Methods Patients ≥70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. Results A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. Conclusions In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial NOTION; NCT01057173 )
Summary Background Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous ...coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. Methods TRILOGY ACS ( ClinicalTrials.gov number NCT00699998 ) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management without revascularisation were randomly assigned to clopidogrel or prasugrel. The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not. Findings 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 12·8% vs 480/4158 16·5%, adjusted hazard ratio HR 0·63, 95% CI 0·53–0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 10·7% vs 159/1561 14·9%, HR 0·77, 95% CI 0·61–0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 16·3% vs 238/2062 16·7%, HR 1·01, 0·84–1·20; p=0·94; pinteraction =0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort. Interpretation Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention. Funding Daiichi Sankyo, Eli Lilly.
Background In patients with severe aortic stenosis (AS), treatment with angiotensin-converting enzyme inhibitors has previously been considered contraindicated. However, there is a lack of clinical ...evidence to confirm these potential hemodynamic risks and benefits. Methods Forty-four patients with severe AS (aortic valve area <1 cm2 ) were randomized to treatment with trandolapril 22 mg daily/placebo (1:1). Right heart catheterization and echocardiography were performed at rest and during exercise at baseline and on day 3. Follow-up was performed before valve replacement or after a maximum of 8 weeks, when exercise echocardiography was repeated. Results Compared with placebo, systolic blood pressure and systemic arterial compliance significantly changed at day 3 (−14 ± 11 vs −5 ± 13 mm Hg, P = .02, and 0.08 ± 0.16 vs −0.05 ± 0.86 mL/m2 per mm Hg, P = .03, respectively). Changes in left ventricular end systolic volume (LVESV) was nonsignificant (−8 ± 9 vs −3 ± 11 mL, P = .17). At a median of 49 days of follow-up, changes in LVESV and N-terminal pro-brain natriuretic peptide were even lower revealing significant differences between the groups (−7.8 ± 2.6 vs −0.5 ± 2.5 mL, P = .04, and −19 ± 7 vs 0.8 ± 6 pmol/L, P = .04, respectively). No episodes of symptomatic hypotension were noted, and other hemodynamic parameters remained unchanged. Conclusion Angiotensin-converting enzyme inhibition in severe AS caused a decrease in LVESV and N-terminal pro-brain natriuretic peptide with other hemodynamic parameters preserved both at rest and during exercise implying hemodynamic improvement with left ventricular unloading.
Background The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been ...conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less prone to bias and is also modifiable. The purpose was to evaluate the impact of system delay on myocardial salvage index (MSI) and infarct size in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI). Methods In patients with ST-elevation myocardial infarction, MSI and final infarct size were assessed using cardiovascular magnetic resonance. Myocardial area at risk was measured within 1 to 7 days, and final infarct size was measured 90 ± 21 days after intervention. Patients were grouped according to system delay (0 to 120, 121 to 180, and >180 minutes). Results In 219 patients, shorter system delay was associated with a smaller infarct size (8% interquartile range 4-12%, 10% 6-16%, and 13% 8-17%; P < .001) and larger MSI (0.77 interquartile range 0.66-0.86, 0.72 0.59-0.80, and 0.68 0.64-0.72; P = .005) for a system delay of up to 120, 121 to 180, and >180 minutes, respectively. A short system delay as a continuous variable independently predicted a smaller infarct size ( r = 0.30, P < .001) and larger MSI ( r = −0.25, P < .001) in multivariable linear regression analyses. Finally, shorter system delay (0-120 minutes) was associated with improved function ( P = .019) and volumes of left ventricle ( P = .022). Conclusions A shorter system delay resulted in smaller infarct size, larger MSI, and improved LV function in patients treated with primary PCI. Thus, this study confirms that minimizing system delay is crucial for primary PCI-related benefits.
Objectives The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention. Background FX06, a naturally occurring ...peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury. Methods In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety. Results There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g interquartile range 0.0, 9.09 g vs. 4.20 g interquartile range 0.3, 9.93 g; p < 0.025). There were no significant differences in troponin I levels (at 48 h, −17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events. Conclusions In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury F.I.R.E.; NCT00326976 )
Previous studies have shown a poor correlation between angiographic assessment of stenosis grade (%) and its functional assessment by fractional flow reserve (FFR). This study aimed to investigate ...whether a more comprehensive evaluation of the coronary angiogram may contribute to a better identification of flow-limiting stenoses. Coronary angiograms of 1,350 patients (1,883 lesions) were retrospectively analyzed for stenosis grade (eyeballing, %) and matched with FFR values. Angiography-derived optimal cut-off values and intervals delineating the 90% sensitivity–90% specificity range were 50.8% 42.5–65.0% for the left main (LM), 62.2% 50.0–72.5% for the proximal (prox)/mid left anterior descending (LAD) artery, 66.3% 57.5–77.5% for the prox/mid right coronary artery (RCA), 70.5% 60.0–80.0% for the prox left circumflex/first obtuse marginal (LCX/OM1), and 71.4% 62.5–82.5% for the more distal segments. In patients with intermediate LAD lesions, 5 angiographic parameters were identified as independent predictors of flow limitation: (1) a 30–50% lesion prox to the lesion of interest, (2) lesion length >20 mm, (3) distal take-off of all diagonal branches ≥2 mm diameter, (4) “apical wrap” of LAD, and (5) collaterals to an occluded LCX/RCA. Based on these results, a risk score (P20-DAC2 ) for prediction of flow limitation in intermediate LAD lesions was derived. In conclusion, a comprehensive evaluation of the coronary angiogram–in which besides stenosis grade also other lesion/vessel characteristics are evaluated–can lead to a more accurate identification of functionally significant coronary stenoses.
Background Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among ...medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. Methods Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 39%) and men (n = 5,676 61%) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. Results Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. Conclusions Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.
The aims of this study were to assess the effectiveness of 2 automated electrocardiogram interpretation programs in patients with suspected acute coronary syndrome transported to hospital by ...ambulance in 1 rural region of Denmark with hospital discharge diagnosis used as the gold standard and to assess the effectiveness of cardiologists' triage decisions for these patients based on initial electrocardiogram. Twelve-lead electrocardiograms were recorded in ambulances using a LIFEPAK 12 monitor/defibrillator (Physio-Control, Inc., Redmond, Washington) and transmitted digitally to an attending cardiologist. If a diagnosis of ST elevation myocardial infarction was made, a patient was taken to a regional interventional center for primary percutaneous coronary intervention or to a local hospital. One thousand consecutive digital electrocardiograms and corresponding interpretations from LIFEPAK 12 were available, and these were subsequently interpreted by the University of Glasgow program. Electrocardiogram interpretations and cardiologists' decisions were compared to hospital discharge diagnoses. The sensitivity, specificity, and positive predictive values for a report of ST elevation myocardial infarction with respect to discharge diagnosis were 78%, 91%, and 81% for LIFEPAK 12 and 78%, 94%, and 87% for the Glasgow program. Corresponding data for attending cardiologists were 85%, 90%, and 81%. In conclusion, the Glasgow program had significantly higher specificity than the LIFEPAK 12 program (p = 0.02) and the cardiologists (p = 0.004). Triage decisions were effective, with good agreement between cardiologists' decisions and discharge diagnoses.
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