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.
Summary Background Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. ...We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. Methods We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov , number NCT01960933. Findings From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). Interpretation In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. Funding Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.
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.
Nodal upstaging after surgical intervention for non-small cell lung cancer (NSCLC) occurs when unsuspected lymph node metastases are found during the final evaluation of surgical specimens. Recent ...data from The Society of Thoracic Surgery (STS) database demonstrated significantly lower nodal upstaging after thoracoscopic (VATS) lobectomy than after thoracotomy. STS data, however, may be biased from voluntary reporting, and survival was not investigated. We used a complete national registry to compare nodal upstaging and survival after lobectomy by VATS or thoracotomy.
The Danish Lung Cancer Registry was used to identify patients who underwent lobectomy for clinical stage I NSCLC from 2007 to 2011. Patient demographics, comorbidity, preoperative staging, surgical approach, number of lymph nodes harvested, final pathology, and survival were evaluated. Nodal upstaging was identified by comparing cT N M with pT N M.
Lobectomy for clinical stage I NSCLC was performed in 1,513 patients: 717 (47%) by VATS and 796 (53%) by thoracotomy. Nodal upstaging occurred in 281 patients (18.6%) and was significantly higher after thoracotomy for N1 upstaging (13.1% vs 8.1%; p<0.001) and N2 upstaging (11.5% vs 3.8%; p<0.001). Overall unadjusted survival was significantly higher after VATS, but after adjusting for differences in sex, age, comorbidity, and pT N M by Cox regression analysis, we found no difference between VATS and thoracotomy (hazard ratio, 0.98; 95% confidence interval, 0.80 to 1.22, p=0.88).
National data confirm that nodal upstaging was lower after VATS than after open lobectomy for clinical stage I NSCLC. Multivariate survival analysis, however, showed no difference in survival, indicating that differences in nodal upstaging result from patient selection for reasons not captured in our registry.
Abstract Objectives The goal of this study was to compare the diagnostic accuracy of the coronary artery calcium score (CACS), coronary computed tomography angiography (CTA), single-photon emission ...computed tomography (SPECT), and a combination of these tools in the diagnosis of obstructive coronary artery disease (CAD) in patients with chronic kidney disease referred for cardiac evaluation before kidney transplantation. Background The optimal method for the detection of obstructive CAD in potential kidney transplant patients has not yet been identified. Previous studies have found that established noninvasive stress tests have low diagnostic accuracy, while the diagnostic performance of coronary CTA remains unknown. Methods We prospectively studied 138 patients referred for pre-transplant cardiac evaluation (mean age 54 years; age range 22 to 72 years; 68% male; 43% treated with dialysis). All patients underwent CACS, coronary CTA, SPECT, and invasive coronary angiography. The results of the noninvasive tests were merged into integrated hybrid imaging results: Hybrid (CACS/SPECT) and Hybrid (coronary CTA/SPECT). Results The overall prevalence of obstructive CAD (≥50% reduction in luminal diameter) according to quantitative invasive coronary angiography was 22%. Two-thirds of the patients with obstructive CAD had a stenosis located in a proximal coronary segment. In a patient-level model, the sensitivity and specificity, respectively, for diagnosing obstructive CAD were as follows: CACS (threshold of 400), 67% and 77%; coronary CTA, 93% and 63%; SPECT, 53% and 82%; Hybrid (CACS/SPECT), 33% and 97%; and Hybrid (coronary CTA/SPECT), 67% and 86%. The sensitivity for diagnosing obstructive CAD in a proximal segment was 70% for CACS (threshold 400), 100% for coronary CTA, 60% for SPECT, 40% for Hybrid (CACS/SPECT), and 75% for Hybrid (coronary CTA/SPECT). Conclusions Coronary CTA is a reliable test with high sensitivity and a high negative predictive value for diagnosing obstructive CAD before kidney transplantation. A noninvasive approach with use of either coronary CTA or a combination of coronary CTA and SPECT to rule out obstructive CAD seems recommendable in kidney transplant candidates. (ACToR-Study: Angiographic CT of Renal Transplantation Candidate–Study; NCT01344434 )
Aims Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and ...prognostic significance of possible FH in patients with myocardial infarction (MI). Methods and results By individual-level linkage of data from the Eastern Danish Heart Registry and national administrative registries, a study population of patients referred for coronary angiography due to MI was selected. The study population was divided into “unlikely FH” and “possible FH” based on the Dutch Lipid Clinic Network criteria, which included a plasma low-density lipoprotein cholesterol (LDL-C) and age for onset of cardiac disease. A score of ≥3 points was used as the cutpoint between the 2 groups. Among the study population of 13,174 MI patients, 1,281 (9.7%) had possible FH. These patients were younger (59.1 vs 65.7 years, P ≤ .0001), had similar levels of comorbidities, and were treated more aggressively with cholesterol-lowering drugs compared with patients with unlikely FH. During a median of 3.3 years of follow-up, the unadjusted and adjusted event rates of recurrent MI were higher in patients with possible FH compared with unlikely FH (16% vs 11%, adjusted hazard ratio 1.28, 95% CI 1.09-1.51, P = .003.). Differences in adjusted all-cause mortality were not statistically significant (17% vs 23%, adjusted hazard ratio 0.89 0.74-1.04, P = .1). Conclusion We found that MI patients with possible FH have higher risk of recurrent MI but similar risk of mortality compared with unlikely FH patients. Further studies on secondary prevention are warranted.
Abstract Background and Purpose One third of patients treated with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction develop a secondary increase in ...electrocardiographic ST segment (ST peak) during reperfusion. The purpose was to determine the clinical importance of ST peak during primary PCI. Methods A total of 363 patients with ST-elevation myocardial infarction were stratified to no ST peak or ST peak. Final infarct size and ejection fraction (EF) were assessed by cardiovascular magnetic resonance. Results Patients with ST peak had a larger infarct size (14% vs 10%; P = .003) and lower EF (53% vs 57%; P = .022). Rates of cardiac mortality (8% vs 3%; P = .047) and cardiac events (cardiac mortality and admission for heart failure; 19% vs 10%; P = .018) were higher among patients with ST peak, but not all-cause mortality (8% vs 5%; P = .46). In a multivariable Cox regression analysis, ST peak remained significantly associated with cardiac events (adjusted hazard ratio, 2.03 1.08-3.82). Conclusion ST peak during primary PCI is related to larger final infarct size, a reduced EF, and adverse cardiac clinical outcome.
Background Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined. Study ...Design The MSC-HF trial is a phase 2, single-center, double-blind, randomized, placebo-controlled trial of intramyocardial delivery of autologous bone-marrow derived mesenchymal stromal cells (MSCs) in patients with chronic ischemic heart failure. A total of 60 patients will be randomized in a 2:1 pattern to receive intramyocardial injections of either MSCs or placebo. Patients will be followed up for 12 months. Methods Bone marrow will be obtained by aspiration from the iliac crest. Mesenchymal stromal cells will be isolated, and culture will be expanded for 6 to 8 weeks. A total of 12 to 15 MSC or placebo injections will be placed in an ischemic viable region of the myocardium using the electromechanical NOGA-XP system (Biologics Delivery Systems Group, Johnson & Johnson, Irwindale, CA). Endpoints The primary endpoint is change in left ventricle end-systolic volume, measured by magnetic resonance imaging (MRI) or computed tomography (CT) at 6-month follow-up. Secondary endpoints are left ventricle ejection fraction, ventricular volumes, wall thickness, and systolic wall thickening measured by MRI or CT in addition to measurement of myocardial scar tissue by MRI. Other secondary endpoints are safety of treatment, clinical symptoms and functional capacity, weekly angina attacks, use of short-term nitroglycerine, and quality of life. Conclusion A randomized, double-blind, placebo-controlled, clinical trial of intramyocardial delivery of MSCs in patients with ischemic heart failure has been set up to confirm the positive findings in open-labeled clinical trials.
We aimed to assess the risk factors and outcome of ventricular fibrillation (VF) before and during primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial ...infarction. From 1999 to 2012, we consecutively enrolled 5,373 patients with ST-segment elevation myocardial infarction. In total, 410 of the patients had VF before and 88 had VF during PPCI. During a mean follow-up of 4.2 years, 1,196 subjects died. A logistic regression model identified younger age, anterior infarct, Killip class >I at admission, and a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I to be significantly associated with VF before PPCI, whereas inferior infarct, a preprocedural Thrombolysis In Myocardial Infarction flow grade of 0 to I, and Killip class >I at admission were significantly associated with VF during PPCI. All-cause mortality was evaluated using the Cox regression model. Compared with the patients without VF, those with VF before or during PPCI had a significantly increased 30-day mortality, with an adjusted hazard ratio = 3.40 (95% confidence interval 1.70 to 6.70) and 4.20 (95% confidence interval 1.30 to 13.30), respectively. Importantly, there was no tendency of 30-day mortality difference between VF before and during PPCI (p = 0.170). In patients with VF before or during PPCI who survived for at least 30 days, there was no increase in the long-term mortality. In conclusion, our data suggest that 30-day mortality is the same for patients with VF before PPCI compared with VF during PPCI, and the occurrence of VF before or during PPCI was associated with increased 30-day mortality but not with long-term mortality.
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.
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