Coronary angiography in patients with kidney dysfunction and myocardial injury: A retrospective cohort study on management of myocardial injury in hospitalized patients with kidney disease.

BACKGROUND: Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction. METHODS: Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression. RESULTS: A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60-0.68], 0.38 [0.34-0.42], 0.18 [0.14-0.22], and 0.35 [0.30-0.40] in patients with eGFR 31-45 ml/min/1.73 m2, eGFR 15-30 ml/min/1.73 m2 for eGFR<15 ml/min/1.73 m2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were -7.8 [-7.0; -8.7] and -9.1 [-8.4; -9.9] for eGFR 46-60 ml/min/1.73 m2; -7.0 [-5.7;-8-3] and -8.0 [-6.6; -9.5] for eGFR 31-45 ml/min/1.73 m2; -5.4 [-3.0; -7.2] and -5.2 [-2.2; -8.3] for eGFR 15-30 ml/min/1.73 m2; -8.8 [-3.1; -13.7] and -5.4 [3.1; -13.4] for eGFR<15 ml/min/1.73 m2; and -4.9 [-0.1; -9.7] and -4.2 [1.5; -9.2] for chronic dialysis, respectively. CONCLUSION: Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization.

The association between self-reported health status and adverse events: a comparison among coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI).

PURPOSE: While several studies have investigated clinical outcomes following coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI), studies investigating self-reported health and the association with adverse outcomes are limited. Thus, the aim was to investigate differences in health-related quality of life (HRQoL), anxiety and depression at discharge and the association with a composite endpoint of the first event of acute cardiac readmission, revascularisation or 1-year mortality among patients undergoing CABG vs. PCI. METHODS: Data from the national cohort study, DenHeart, were used, including measures of HRQoL; EuroQoL-5D-5L (EQ-5D Index Score and VAS) and HeartQoL (Global, Physical and Emotional), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and register-based follow-up. A total of 7000 patients were included (CABG n = 652, PCI n = 6348) (median age 65, 75% men). Cox Proportional Hazard models were performed among a propensity-matched population of responders (n = 520). RESULTS: HRQoL was significantly better among patients undergoing PCI vs. CABG, but with no differences in time to readmission or revascularisation. HRQoL, anxiety and depression were significantly associated with the risk of the composite endpoint among the PCI group (Hazard Ratio, HR (95% confidence intervals, CI) [EQ-5D index score 3.07 (1.67-5.67), EQ-5D VAS 0.97 (0.96-0.99), HeartQol Global 0.61 (0.38-0.95), HeartQol Emotional 0.56 (0.39-0.80), HADS-D ≥ 8 3.12 (1.61-6.01), HADS-A ≥ 8 2.08 (1.14-3.80)]. CONCLUSION: Patients undergoing PCI reported better HRQoL at discharge compared with patients undergoing CABG, whereas readmission rates were similar. Self-reported health was associated with the risk of adverse events among patients undergoing PCI, but not among patients undergoing CABG. CLINICAL TRIAL REGISTRATION: NCT01926145.

Ultrasound-assisted thrombolysis for acute intermediate-high-risk pulmonary embolism.

INTRODUCTION: Eustachian tube dysfunction (ETD) may result in hearing loss, chronic otitis and cholesteatoma. With advances in treatment options, the identification of patients with obstructive ETD is becoming increasingly important. The objective of this study was to validate a Danish translation of the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). METHODS: All participants underwent tympanometry, otomicroscopy and completed the ETDQ-7. We included 34 ears from patients with obstructive ETD who had abnormal tympanometry curves but no history of cholesteatoma or adhesive otitis. As a control group, 48 otherwise healthy ears with a normal tympanometry curve were included from patients with known sensorineural hearing loss or normal hearing. RESULTS: A Cronbach's alpha of 0.77 indicated a good internal consistency reliability of the questionnaire. The mean ETDQ-7 score in the obstructive ETD group was 31 versus 13.5 in the control group (p = 0.00). A receiver operating characteristics analysis produced an area under the curve of 94%, showing excellent discriminatory abilities between the groups. CONCLUSIONS: The ETDQ-7 has previously been validated in English, German, Dutch and Portuguese, demonstrating good clinical relevance. The Danish translation of the ETDQ-7 has produced similar results and may be valuable in diagnosing obstructive ETD and in monitoring the effect of balloon dilation of the Eustachian tube. FUNDING: none. The study was approved by the Danish Data Protection Agency (VD-2018-33, I-Suite 6229).

Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine.

BACKGROUND: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management. METHODS: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded. RESULTS: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02). CONCLUSIONS: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II).

BACKGROUND: Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients. METHODS AND RESULTS: WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases. CONCLUSIONS: Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.

Pre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population.

BACKGROUND: ATLANTIC was a randomized study comparing pre- and in-hospital treatment with a ticagrelor loading dose (LD) in ongoing ST-segment elevation myocardial infarction (STEMI). We sought to compare patient characteristics and clinical outcomes in France with other countries participating in ATLANTIC. METHODS: The population comprised 1862 patients, 660 (35.4%) from France and 1202 from 12 other countries. The main endpoints were reperfusion (≥70% ST-segment elevation resolution) and TIMI flow grade 3 before (co-primary endpoints) and after percutaneous coronary intervention (PCI). Other endpoints included a composite ischaemic endpoint (death/myocardial infarction/stroke/urgent revascularization/definite stent thrombosis) and bleeding events at 30days. RESULTS: In France, median times from first LD to angiography and between first and second LDs were 49 and 35min, respectively, and were similar to other countries. French patients were younger (mean 58.7 vs 61.9years, p<0.0001) and characterized by a higher rate of radial access (89.9% vs 54.8%, p<0.0001), more frequent use of pre-hospital glycoprotein (GP) IIb/IIIa inhibitors (14.1% vs 3.1%, p<0.0001) and intravenous enoxaparin (57.3% vs 10.1%, p<0.0001). In France, as in other countries, the co-primary endpoints did not differ between the two randomization groups. The composite ischaemic endpoint was numerically lower in France (3.3% vs 5.1%, p=0.07), with a lower mortality (1.4% vs 3.3%, p=0.01). PLATO major bleeding was numerically less frequent in France (1.8% vs 3.2%, p=0.07). CONCLUSIONS: The French population appears to have better outcomes than the rest of the study population, and seems related to differences in demographics and management characteristics. TRIAL REGISTRY: ClinicalTrials.gov (NCT01347580).

P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study.

PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double-blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration.

Effect of Pre-Hospital Ticagrelor During the First 24 h After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H²4 Analysis.

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study. BACKGROUND: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. RESULTS: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).

Prehospital ticagrelor in ST-segment elevation myocardial infarction.

BACKGROUND: The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. METHODS: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. RESULTS: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used. CONCLUSIONS: Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.).

Prevention of contrast-induced nephropathy with N-acetylcysteine or sodium bicarbonate in patients with ST-segment-myocardial infarction: a prospective, randomized, open-labeled trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a serious condition in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. We compared the risk of acute CIN and the influence of preventive strategies in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: A total of 720 patients were randomized in the Prevention of Contrast-induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (CINSTEMI) trial. Patients were randomly assigned in a 1:1:1:1 ratio to receive hydration with sodium chloride together with 1 of 4 prophylactic regimes (1) N-acetylcysteine (NAC), (2) sodium bicarbonate (NaHCO3) infusion, (3) NAC in combination with NaHCO3, or (4) hydration with sodium chloride infusion alone. Patients in cardiogenic shock were excluded. Acute CIN was defined as an increase in serum creatinine concentration >25% from the baseline value within a 3-day period. Overall, CIN occurred in 141 (21.9%) patients. The prevention treatment with NAC, NaHCO3, or the combined NAC and NaHCO3 did not reduce the rate of CIN significantly compared with hydration with intravenous sodium chloride infusion alone (20.1% versus 20.1% versus 20.8% versus 26.5%; P=NS). However, an increase in serum creatinine >25% from the baseline value to 30 day was significantly lower in patients treated with combined NAC and NaHCO3 (18.7% versus 19.1% versus 9.2% versus 21.3%; P=0.033). CONCLUSIONS: Treatment with NAC or NaHCO3 did not reduce the rate of acute CIN significantly. Combined treatment with NAC and NaHCO3 may reduce the risk of renal dysfunction after 30 days. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01160627.

Similar five-year outcome with paclitaxel- and sirolimus-eluting coronary stents.

OBJECTIVE: Millions of patients were treated with the sirolimus-eluting Cypher™ and the paclitaxel-eluting Taxus™ coronary stents with potential late-occurring increase in event rates. Therefore, the long-term outcome follow-up is of major clinical interest. DESIGN: In total, 2.098 unselected patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI, stable or unstable angina pectoris were randomized to receive Cypher™ (n = 1.065) or Taxus™ (n = 1.033) stents and were followed for 5 years. RESULTS: The primary end-point; the composite of cardiac death, myocardial infarction and target vessel revascularization (major adverse cardiac event, MACE), occurred in 467 patients (22.3%); Cypher™ n = 222 (20.8%), Taxus™ n = 245 (23.7%), ns. Definite and probable stent thrombosis occurred in 107 patients (5.1%); Cypher™ n = 51 (4.8%), Taxus™ n = 56 (5.4%), ns. No statistically significant differences were found in the elements of the primary end-point or in other secondary end-points between the two stent groups. After one year, the annual rates of stent thrombosis and MACE remained constant. CONCLUSIONS: During 5-year follow-up, the Cypher™ and the Taxus™ coronary stents had similar clinical outcome with no signs of increasing rates of adverse events over time.

Long-term outcome following percutaneous coronary intervention with drug-eluting stents compared with bare-metal stents in saphenous vein graft lesions: from Western Denmark Heart Registry.

OBJECTIVES: We used the Western Denmark Heart Registry to assess one-year and long-term all-cause mortality and stent failure following Percutaneous Coronary Intervention (PCI) with drug-eluting stents (DES) or bare-metal stents (BMS). BACKGROUND: The use of DES compared with BMS during PCI has reduced the risk of restenosis in native coronary artery lesions. In saphenous vein grafts (SVG) the outcome after DES compared with BMS is insufficiently described. METHODS: From January 1, 2002 to December 31, 2010 all patients with PCI of SVG lesions were identified among 3.0 million inhabitants. Stent failure was defined as clinically driven target lesion revascularization, graft occlusion without intervention, or stent thrombosis. RESULTS: The study cohort consisted of 529 patients with 755 SVG lesions (348 DES patients with 510 lesions and 181 BMS patients with 245 lesions). Mean age did not differ between patients with DES-treated lesions compared to patients with BMS-treated lesions (67.5 ± 9.1 years vs. 67.6 ± 9.3 years; P = 0.85). The median follow-up time was 3.0 years (25th-75th percentile: 1.4-5.1 years). One-year (n = 27 (8.2%) vs. n = 12 (6.7%), log rank P = 0.60) and 3-year cumulative mortality (n = 31 (18.8%) vs. n = 59 (21.8%), log rank P = 0.64) did not differ significantly between DES- and BMS-treated patients. One-year cumulative stent failure was seen in 39 (6.6%) DES-treated lesions vs. 24 (10.8%) BMS-treated lesions (P = 0.088), and 3-year cumulative stent failure in 48 (15.4%) vs. 34 (18.8%) lesions (P = 0.25), respectively. CONCLUSION: In SVG lesions, DES showed no long-term benefit compared to BMS in rates of all-cause mortality or stent failure.

Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study.

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

BACKGROUND: Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. METHODS: 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. FINDINGS: 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). INTERPRETATION: Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. FUNDING: Fondation Leducq.

Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial.

OBJECTIVES: The purpose of this study was to evaluate the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The use of distal filter protection during primary PCI increases procedure complexity and may influence lesion treatment and stent implantation. METHODS: The STEMI patients were assigned to distal protection (DP) (n = 312) or conventional treatment (CT) (n = 314). Clinical follow-up was performed after 1, 6, and 15 months, and angiographic follow-up after 8 months. All target lesion revascularizations (TLRs) were clinically driven. We report the pre-specified end points of stent thrombosis according to the criteria of the Academic Research Consortium, TLR, and reinfarction after 15 months. RESULTS: The total number of stent thrombosis was 11 in the DP group and 4 in the CT group (p = 0.06). The rate of definite stent thrombosis was significantly increased in the DP group as compared with the CT group, with 9 cases versus 1 (p = 0.01). Clinically driven TLRs (31 patients vs. 18 patients, p = 0.05) and clinically driven target vessel revascularizations (37 patients vs. 22 patients, p = 0.04) were more frequent in the DP group. CONCLUSIONS: In primary PCI for STEMI, the routine use of DP increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization during 15 months of follow-up. (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction Trial [DEDICATION]; NCT00192868).

Recruitable collateral blood flow index predicts coronary instent restenosis after percutaneous coronary intervention.

AIMS: Collateral flow may influence long-term results after percutaneous coronary intervention (PCI) because of haemodynamic forces compete with the antegrade flow through the dilated lesion. The aim of the study was to assess the influence of recruitable collateral blood flow on restenosis in patients undergoing PCI with bare metal stents and using optimal antithrombotic treatment. METHODS AND RESULTS: In 95 patients, 95 de novo lesions were treated with PCI and a bare metal stent. Fractional flow reserve (FFR) at maximum hyperaemia induced by intravenous adenosine was determined. The pressure-derived collateral flow index (CFI) was determined as (P(w)-P(cvp))/(P(a)-P(cvp)), where P(w) represents coronary wedge pressure, P(cvp) central venous pressure, and P(a) mean aortic blood pressure. Both were measured during transient coronary occlusion by a balloon inflation of 30 s. Pre-interventional FFR (0.65 +/- 0.20) correlated inversely with the CFI (0.18 +/- 0.11), r =- 0.356, P < 0.001. After 9 months, binary angiographic restenosis (>/=50% diameter stenosis) was seen in 29.1%. Compared to patients with poorly developed collaterals (CFI < 0.25), patients with well-developed collaterals (CFI >/= 0.25) had a lower pre-interventional FFR (0.50 +/- 0.14 vs. 0.72 +/- 0.18, P < 0.001), a higher CFI (0.33 +/- 0.08 vs. 0.13 +/- 0.07, P < 0.001), and a higher binary restenosis rate (54.2% vs. 19.4, P = 0.003). CFI*100 was an independent predictor of restenosis after 9 months (odds ratio 1.07, 95% CI 1.02-1.12, P = 0.016). CONCLUSION: Recruitable collateral blood flow measured during balloon inflation predicts angiographic instent restenosis in PCI patients treated with bare metal stents.

Outcome of unprotected left main percutaneous coronary intervention in surgical low-risk, surgical high-risk, and acute myocardial infarction patients.

AIM: Percutaneous coronary intervention (PCI) of left main (LM) coronary artery stenosis may become an alternative to the standard therapy, coronary artery bypass graft surgery (CABG). The purpose of the present study was to describe the outcome after LM PCI in three cohorts of patients: patients with low surgical risk, patients with high surgical risk or patients considered inoperable, and patients with acute ST elevation MI. METHODS AND RESULTS: 104 consecutive patients who had LM PCI at the Department of Cardiology, Skejby University hospital between 1999 and 2004 were investigated. The patients were divided into three groups according to PCI indication and operability: surgical low risk patients and suitable lesions for PCI (n=27), poor CABG candidates (age > 80 years, severe comorbidity or inoperability) (n=50), and patients presenting with AMI (n=27). In the three groups mean ages+/-SD were: 60+/-14, 76+/-9, and 68+/-12 years, respectively. At thirty days follow-up the cumulative incidence of major adverse cardiac events (MACE); cardiac death, MI, or target lesion revascularization (95% CI) were 4 (1-24)%, 16 (8-30)%, and 41 (25-61)%, respectively. At 6 months the cumulative incidence of MACE were 4 (1-24)%, 27 (17-43)%, and 41 (25-62)%. CONCLUSIONS: PCI of LM coronary artery stenosis can be performed with good outcome in patients with low surgical risk and with acceptable outcome in surgical high risk patients or patients considered inoperable. Patients with AMI and culprit lesion in the LM have a high mortality in the acute phase, but mid-term prognosis is good if the patient is successfully treated with PCI. This follow-up study underlines the importance of risk stratification in the heterogeneous group of patients undergoing LM PCI.

Randomized comparison of deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents.

AIMS: To compare deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents in a randomized multicenter trial in five Danish interventional centres. METHODS AND RESULTS: Patients with planned stenting of at least one stenotic lesion in a native coronary artery were included in the study. There were 494 (664) patients (treated lesions) in the BxSonic(R), 499 (657) in the Express(R) and 500 (658) in the Flexmaster(R) groups. The groups were well matched with regard to age, sex, diabetes, smoking, hypercholesterolemia, hypertension, indication for PCI and coronary artery lesion complexity. The study stents were implanted with or without predilatation according to ordinary -clinical practice.Rates of successful stent implantation and in-hospital stent thrombosis, re-intervention, non-fatal myocardial infarction or death. The BxSonic(R), Express(R) and Flexmaster(R) stents were successfully implanted in 92,2%, 89,3% and 91,6% of all lesions (ns). There were no in-hospital deaths and the rates of in-hospital complications were similar in the three stent groups. CONCLUSION: We found similar deliverability and in-hospital complication rates of the BxSonic(R), Express(R) and Flexmaster(R) stents.

Cholesterol reduction following health screening in general practice.

OBJECTIVES: To evaluate changes in plasma cholesterol following health screening and health discussions in general practice. DESIGN: Randomised prospective population-based study conducted over a period of 5 years. SETTING: Primary care, all general practitioners (GPs) in a well-defined area. SUBJECTS: A random sample of inhabitants aged 30-49 years in January 1991, registered with a local GP was invited to participate. The participants (1507 persons, or 75.4% of the 2000 invited) were randomly allocated to two intervention groups and a control group. MAIN OUTCOME MEASURES: Plasma cholesterol, percentage of subjects with plasma cholesterol higher than 7 mmol/l. RESULTS: After 5 years of intervention, plasma cholesterol in the whole population was significantly lower in the intervention groups compared to the control group. The decrease was most pronounced (0.5 mmol/l) in subjects at high cardiovascular risk. The percentage of high-risk individuals with a cholesterol level higher than 7 mmol/l was significantly lower in the intervention groups compared to the control group (9.8% vs 6.2%, p = 0.04), corresponding to a 37% reduction. CONCLUSIONS: The study shows that the health checks had a measurable impact on plasma cholesterol levels, the most pronounced effect is seen among individuals at high cardiovascular risk.