Specific recommendations (or lack thereof) for older patients with cardiovascular disease in the current European Society of Cardiology guidelines : From the Dutch Working Group of Geriatric Cardiology of the Netherlands Society of Cardiology (NVVC) and Special Interest Group Geriatric Cardiology of the Netherlands Society for Clinical Geriatrics (NVKG).

Due to population ageing, the number of older and frail patients with cardiovascular disease is increasing. In the current guidelines of the European Society of Cardiology specific recommendations for this older population are missing or scarce, probably due to limited evidence concerning diagnosis and treatment of cardiovascular disease in older patients. Moreover, recommendations on shared decision making, palliative care and advanced care planning are also essential in these guidelines. In this article we evaluate the current European of Society of Cardiology guidelines (2013-2020) to determine whether specific recommendations for older patients have been included.

The nurse-coordinated cardiac care bridge transitional care programme: a randomised clinical trial.

BACKGROUND: after hospitalisation for cardiac disease, older patients are at high risk of readmission and death. OBJECTIVE: the cardiac care bridge (CCB) transitional care programme evaluated the impact of combining case management, disease management and home-based cardiac rehabilitation (CR) on hospital readmission and mortality. DESIGN: single-blind, randomised clinical trial. SETTING: the trial was conducted in six hospitals in the Netherlands between June 2017 and March 2020. Community-based nurses and physical therapists continued care post-discharge. SUBJECTS: cardiac patients ≥ 70 years were eligible if they were at high risk of functional loss or if they had had an unplanned hospital admission in the previous 6 months. METHODS: the intervention group received a comprehensive geriatric assessment-based integrated care plan, a face-to-face handover with the community nurse before discharge and follow-up home visits. The community nurse collaborated with a pharmacist and participants received home-based CR from a physical therapist. The primary composite outcome was first all-cause unplanned readmission or mortality at 6 months. RESULTS: in total, 306 participants were included. Mean age was 82.4 (standard deviation 6.3), 58% had heart failure and 92% were acutely hospitalised. 67% of the intervention key-elements were delivered. The composite outcome incidence was 54.2% (83/153) in the intervention group and 47.7% (73/153) in the control group (risk differences 6.5% [95% confidence intervals, CI -4.7 to 18%], risk ratios 1.14 [95% CI 0.91-1.42], P = 0.253). The study was discontinued prematurely due to implementation activities in usual care. CONCLUSION: in high-risk older cardiac patients, the CCB programme did not reduce hospital readmission or mortality within 6 months. TRIAL REGISTRATION: Netherlands Trial Register 6,316, https://www.trialregister.nl/trial/6169.

Managing older patients with heart failure calls for a holistic approach.

AIMS: This study aims to assess the presence of geriatric domain impairments in an older heart failure (HF) outpatient population and to relate these domain impairments with 1 year mortality risk in comparison with a geriatric outpatient population without HF. METHODS AND RESULTS: Data were used from two different prospective cohort studies: 241 outpatients with HF (mean age 78 ± 9 years, 48% female) and 686 geriatric outpatients (mean age 80 ± 7 years, 55% female). We similarly assessed the following geriatric domains in both cohorts: physical function, nutritional status, polypharmacy, cognitive function, and activities in daily living. Cox proportional hazards analyses were used to relate individual domains to 1 year mortality risk in both populations and to compare 1 year mortality risk between both populations. Of the patients with HF, 34% had impairments in ≥3 domains, compared with 38% in geriatric patients. One-year mortality rates were 13% and 8%, respectively, in the HF and geriatric populations; age-adjusted and sex-adjusted hazard ratio (95% confidence interval) for patients with HF compared with geriatric patients was 1.7 (1.3-2.6). The individual geriatric domains were similarly associated with 1 year mortality risk in both populations. Compared with zero to two impaired domains, age-adjusted and sex-adjusted mortality risk (hazard ratio, 95% confidence interval) for three, four, or five impaired domains ranged from 1.6 (0.6-4.2) to 6.5 (2.1-20.1) in the HF population and from 1.4 (0.7-2.9) to 7.9 (2.9-21.3) in the geriatric population. CONCLUSIONS: In parallel with geriatric patients, patients with HF often have multiple geriatric domain impairments that adversely affect their prognosis. This similarity together with the findings that patients with HF have a higher 1 year mortality risk than a general geriatric population supports the integration of a multi-domain geriatric assessment in outpatient HF care.

The relevance of a multidomain geriatric assessment in older patients with heart failure.

AIMS: Physical frailty screening is more commonly performed at outpatient heart failure (HF) clinics. However, this does not incorporate other common geriatric domains. This study assesses whether a multidomain geriatric assessment, in comparison with HF severity or physical frailty, is associated with short-term adverse outcomes. METHODS AND RESULTS: This is a prospective cohort study of 197 patients with HF (mean age 78, 44% female) attending outpatient HF clinics. HF severity was assessed with New York Heart Association class (I-II versus III-IV) and N-terminal pro b-type natriuretic peptide levels. Physical frailty was assessed with the Fried frailty criteria (not frail, pre-frail, and frail). The following geriatric domains were assessed: physical function, nutrition, polypharmacy, cognition, and dependency in activities of daily living. Logistic regression analyses adjusted for age, sex, diabetes and kidney function assessed 3 month risk of adverse health outcomes (emergency department visits, hospital admissions, and/or death) according to HF severity, physical frailty, and number of affected domains. Number (%) of patients with HF with no, 1, 2, and ≥3 domains affected were 36 (18%), 61 (31%), 58 (29%), and 42 (21%). Seventy-four adverse outcomes were experienced in 50 patients at follow-up. Severity of HF and physical frailty were not significantly associated with an increased risk of adverse health outcomes. However, increasing number of affected domains were significantly associated with an increased risk of adverse outcomes. Compared with no domains affected, odds ratios (95% confidence interval) for 1, 2, and ≥3 domains were 1.8 (0.5-6.5), 4.5 (1.3-15.4), and 7.2 (2.0-26.3) (P-trend <0.01). Further adjustment for HF severity and frailty status slightly attenuated the effect estimates (P-trend 0.02). CONCLUSIONS: Having limitations in multiple domains appears more strongly associated with short-term adverse outcomes than HF severity and physical frailty. This may illustrate the potential added value of a multidomain geriatric assessment in the evaluation and treatment of patients with HF with respect to relevant short-term health outcomes.

Long-term outcome of second-generation everolimus-eluting stents and Endeavor zotarolimus-eluting stents in a prospective registry of ST-elevation myocardial infarction patients.

AIMS: The optimal drug-eluting stent (DES) in ST-elevation myocardial infarction (STEMI) patients remains unclear. We sought to compare the long-term performance of everolimus-eluting stents (EES) and Endeavor zotarolimus-eluting stents (E-ZES) in STEMI. METHODS AND RESULTS: The current analysis of a prospective registry included consecutive patients treated with EES or E-ZES for STEMI. Adjustment for measured confounders was done using Cox regression. In total, 931 patients met the inclusion criteria (412 EES and 519 E-ZES). Baseline characteristics were balanced, apart from a lower rate of renal insufficiency in EES. Median follow-up duration was 2.4 years (IQR 1.6-3.1). Mortality outcomes were similar. Up to three-year follow-up, the composite endpoint of cardiac death, target vessel-related myocardial infarction and target lesion revascularisation (TLR) was lower in EES; 9.7% vs. 13.7% in E-ZES (HR 0.64, 95% CI: 0.42-0.99), primarily driven by reduced TLR rates; 3.4% in EES vs. 7.3% in E-ZES (HR 0.46, 95% CI: 0.23-0.92). Definite stent thrombosis rates were low and similar between groups (1.1% in EES vs. 1.9% in E-ZES, p=0.190). CONCLUSIONS: Use of EES led to lower rates of the composite endpoint, driven by reduced TLR. This suggests that EES are more efficacious than Endeavor ZES in STEMI. Definite ST rates were low, and the strategy of second-generation DES implantation and the administration of upfront GP IIb/IIIa inhibitors appear to be safe in STEMI.

Cardiovascular mortality and heart failure risk score for patients after ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention (Data from the Leiden MISSION! Infarct Registry).

The risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as the primary end point. Primary percutaneous coronary intervention in patients with STEMI has improved the outcome significantly and might have changed the relative contribution of different risk factors. Our patient population included 1,484 consecutive patients admitted with STEMI who had undergone primary percutaneous coronary intervention. The clinical, angiographic, and echocardiographic data obtained during hospitalization were used to derive a risk score for the prediction of short-term (30-day) and long-term (1- and 4-year) cardiovascular mortality and hospitalization for heart failure. During a median follow-up of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age ≥70 years, Killip class ≥2, diabetes, left anterior descending coronary artery as the culprit vessel, 3-vessel disease, peak cardiac troponin T level ≥3.5 µg/L, left ventricular ejection fraction ≤40%, and heart rate at discharge ≥70 beats/min as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed using the areas under the receiver operating characteristic curves was good (0.84, 0.83, and 0.81 at 30 days and 1 and 4 years, respectively), and the patients could be allocated to low-, intermediate-, or high-risk categories with an event rate of 1%, 6%, and 24%, respectively. In conclusion, the current risk model demonstrates for the first time that 8 parameters readily available during the hospitalization of patients with STEMI treated with primary percutaneous coronary intervention can accurately stratify patients at long-term follow-up (≤4 years after the index infarction) into low-, intermediate-, and high-risk categories.

Five-year clinical follow-up from the MISSION! Intervention Study: sirolimus-eluting stent versus bare metal stent implantation in patients with ST-segment elevation myocardial infarction, a randomised controlled trial.

AIMS: To evaluate the clinical outcomes of sirolimus-eluting stent (SES) versus bare metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) at long-term follow-up. METHODS AND RESULTS: After five years, 310 STEMI patients randomly assigned to implantation of either SES or BMS, were compared. Survival rates were comparable between groups (SES 94.3% vs. BMS 92.8%, p=0.57), as were the rates of reinfarction (10.6% vs. 13.7%, p=0.40), freedom of death/re-MI (84.4% vs. 79.8%, p=0.29) and target vessel failure (14.9% vs. 21.7%, p=0.11). Likewise, rates of overall stent thrombosis (ST) (5.4% vs. 2.7%, p=0.28) and very late ST (4.1% vs. 0.7%, p=0.07) did not significantly differ between the SES- and BMS-group. In 184 patients with IVUS data, definite and definite/probable VLST was more common in those with late stent malapposition versus those without late stent malapposition (4.3% and 6.6% vs. no events [p=0.018 and p=0.004], respectively). The cumulative incidences of target vessel and target lesion revascularisation (TVR and TLR) were not significantly lower in the SES-group (11.2% vs. 17.9%, p=0.09 and 7.2% vs. 12.9%, p=0.08), as was the rate of clinically driven TLR (6.6% vs. 9.5%, p=0.30). CONCLUSIONS: SES implantation was neither associated with increased rates of major adverse cardiac events, nor with a reduction in re-intervention, compared to implantation of a BMS in patients with STEMI after five years. However, a trend of more very late stent thrombosis was observed after SES implantation (ISRCTN62825862).

Asymmetric dimethylarginine (ADMA) levels display a morning peak in patients with acute myocardial infarction.

High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00-11:59 h. The absolute ADMA levels peak was between 06:00-07:59 h with a median (interquartile range) peak value of 1.01 (0.84-1.21) µmol/L for the n=9 patients vs. 0.75 (0.61-0.89) µmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p=0.003 for between groups comparison). The amplitude (95% 0.08 µmol/L (0.004-0.16) with p=0.042 for statistic model significance. In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.

The 5352 A allele of the pro-inflammatory caspase-1 gene predicts late-acquired stent malapposition in STEMI patients treated with sirolimus stents.

Late-acquired stent malapposition (LASM) is a common finding after sirolimus-eluting stent (SES) implantation and may be the cause for late stent thrombosis. Inflammation may play a pivotal role in LASM just as it plays in stent restenosis. We have therefore investigated seven polymorphisms involved in inflammatory processes, related in previous reports to restenosis, on the risk of LASM in SES patients. Patients with ST-elevation myocardial infarction who underwent SES implantation and had intravascular ultrasonography (IVUS) data available for both immediate post-intervention and 9-month follow-up were included in the present study. In total, 104 patients from the MISSION! Intervention Study were genotyped for the caspase-1 5352 G/A, eotaxin 1382 A/G, CD14 260 A/G, colony stimulating factor 2 1943 C/T, IL10 -1117 C/T, IL10 4251 C/T, and the tumor necrosis factor alpha 1211 C/T polymorphisms. LASM occurred in 26/104 (25%) of patients. We found a significantly higher risk for LASM in patients carrying the caspase-1 (CASP1) 5352 A allele (RR = 2.32; 95% CI 1.22-4.42). In addition, mean neointimal growth was significantly lower in patients carrying this LASM risk allele (1.6 vs. 4.1%, p = 0.014). The other six polymorphisms related to inflammation were not significantly related to the risk of LASM. In conclusion, carriers of the 5352 A allele in the caspase-1 gene are at increased risk of developing LASM after SES implantation. If this is confirmed in larger studies, then screening for this polymorphism in patients undergoing percutaneous coronary interventions could eventually help cardiologists to better select between commercially available stents.

Three-year outcome of sirolimus-eluting versus bare-metal stents for the treatment of ST-segment elevation myocardial infarction (from the MISSION! Intervention Study).

To compare the long-term efficacy and safety of sirolimus-eluting stents (SES) to those of bare-metal stents (BMS) for ST-segment elevation myocardial infarction, outcomes were assessed in 310 patients (mean age age 59 +/- 11 years, 78% men) included in the randomized MISSION! Intervention Study: A Prospective Randomised Controlled Trial to Evaluate the Efficacy of Drug-Eluting Stents Versus Bare-Metal Stents for the Treatment of Acute Myocardial Infarction after a median follow-up period of 38 months. All patients were treated with aspirin (lifelong) and clopidogrel for 1 year after stent implantation. Except for a significant difference between reference vessel diameters (SES 2.76 mm vs BMS 2.92 mm, p = 0.02), there were no significant differences in baseline and angiographic characteristics between the treatment groups (158 SES, 152 BMS). A significant difference between SES and BMS patients for all revascularization end points was found after the first year of follow-up. However, at 3 years of follow-up, although there was still a trend toward better clinical outcomes in SES-treated patients, differences were no longer significant (death 4.4% vs 6.6%, p = 0.41; target vessel-related myocardial infarction 2.5% vs 4.6%, p = 0.32; target vessel revascularization 8.9% vs 15.8%, p = 0.06), target lesion revascularization 6.3% vs 12.5%, p = 0.06; and target vessel failure 12.0% vs 19.7%, p = 0.06). Three cases of very late (definite) stent thrombosis were observed in the SES group (1.9%) versus none in the BMS group (p = 0.14). In conclusion, the significant SES benefit (compared to BMS) in patients with ST-segment elevation myocardial infarctions at 1-year follow-up in terms of target vessel revascularizations decreased to some extent because of more similar target vessel revascularization rates during the 2 subsequent years. Rates of death and nonfatal recurrent MI remained comparable.

Structured care for patients after acute myocardial infarction: sudden cardiac death prevention--data from the Leiden MISSION! AMI study.

AIMS: To assess the number of patients in daily clinical practice that meets criteria for implantation of an implantable cardioverter defibrillator (ICD) following acute myocardial infarction (AMI) when treated according to an aggressive treatment protocol. METHODS AND RESULTS: Patients were treated according to the MISSION! protocol. The protocol encompasses pre-hospital, in-hospital, and outpatient clinical framework for the acute and chronic treatment of AMI patients and the decision making regarding primary prevention of sudden cardiac death (SCD). A total of 676 consecutive AMI patients (78% male, mean age 59 +/- 12 years) treated according to the MISSION! protocol were included in this analysis. Left ventricular ejection fraction at 3 months was 54 +/- 10%. Only 39 (6%) patients met criteria for implantation of an ICD <1 year post-MI. These patients suffered more extensive infarctions as indicated by higher peak troponin T values (mean 14.5 +/- 8.3 vs. 6.5 +/- 14.7 microg/L; P < 0.001) and had more left anterior descending artery related infarctions (79 vs. 46%; P < 0.001). Cumulative first appropriate therapy rate was 15% at 3 years follow-up. No SCD was observed in the study population. CONCLUSION: Aggressive treatment of AMI patients and close monitoring after the index event according to a standardized protocol, results in only a small number of patients becoming candidate for prophylactic ICD implantation. An easy-to-use protocol combining aggressive reperfusion, optimal medication, and a risk stratification algorithm tailored to fit within routine practice may help to maintain ICD implantation rates within manageable proportions.

In-ambulance abciximab administration in STEMI patients prior to primary PCI is associated with smaller infarct size, improved LV function and lower incidence of heart failure: results from the Leiden MISSION! acute myocardial infarction treatment optimization program.

OBJECTIVES: Our aim was to evaluate the effects of early abciximab administration in the ambulance on immediate, short, and long term outcomes. BACKGROUND: Early abciximab administration before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is recommended in practice guidelines. However, optimal timing of administration remains indistinct. METHODS: Within a fixed protocol for PPCI, December 2006 was the cut-off point for this prospective study. A total of 179 consecutive patients with STEMI were enrolled, 90 patients received abciximab bolus in the hospital (in-hospital group), and 89 patients received abciximab bolus in the ambulance (in-ambulance group). RESULTS: The two groups were comparable for baseline and angiographic characteristics. The in-ambulance group received abciximab within the golden period (median 63 min). The infarct related artery (IRA) patency at onset of the PCI was four times higher in the in-ambulance group compared to in-hospital group (odds ratio = 4.9, 95% CI 2.4-10.1). Enzymatic infarct size was smaller in the in-ambulance group (cumulative 48-h CK release 8011 vs. 11267 U/L, P = 0.004). This was associated with higher left ventricular ejection fraction (LVEF) at 90 days post-PPCI measured by myocardial scintigraphy (59% vs. 54%, P = 0.01), and lower incidence of heart failure through a median of 210 days of clinical follow-up (3% vs.11%, P = 0.04). CONCLUSION: Early abciximab administration in the ambulance significantly improves early reperfusion in STEMI patients treated with PPCI. Moreover this is associated with a smaller infarct size, improved LV function and a lower risk of heart failure on clinical follow-up.

Myocardial infarction occurs with a similar 24 h pattern in the 4G/5G versions of plasminogen activator inhibitor-1.

PAI-1 expression is regulated by a 4G/5G promoter polymorphism. The 4G allele is associated with greater circadian variation of PAI-1 levels. We hypothesized that the 24 h variation of cardiac risk is more pronounced among persons with the 4G4G genotype than among ones with 4G5G and 5G5G genotypes. We assessed the time of onset of symptoms in 623 consecutive patients with acute myocardial infarction (AMI) enrolled in the MISSION! Study between February 1, 2004, and October 29, 2006. All of the patients were genotyped for the PAI-1 4G/5G polymorphism. We quantified the amplitude of the 24 h variation of AMI with a generalized linear model with Poisson distribution. A morning peak, between 06:00-11:59 h (n = 197; 32% of all cases), in the onset of symptoms of AMI was observed. The group composed of patients with the 4G4G genotype did not have a more pronounced morning peak than the groups composed of other genotypes; the 24 h variation was 38% (95% confidence interval 12-70%) in the group of 4G4G patients and 34% (14-58%) and 56% (20-100%) in the 4G5G and 5G5G groups of patients, respectively. Our findings show that 24 h variation of cardiac risk is not more pronounced among the 4G4G genotype of PAI-1.

Usefulness of peak troponin-T to predict infarct size and long-term outcome in patients with first acute myocardial infarction after primary percutaneous coronary intervention.

In acute myocardial infarction cardiac troponin-T (cTnT) is the preferred biomarker to detect myocardial necrosis. Our aim was to investigate the prognostic value of peak plasma cTnT in patients with ST-elevation myocardial infarction treated by primary percutaneous coronary intervention (PCI). Patients were eligible if ST-elevation myocardial infarction symptoms started <9 hours before the primary PCI. During the first 48 hours after primary PCI, cTnT and creatine kinase were measured repeatedly. Main outcome measures were left ventricular ejection fraction assessed by myocardial scintigraphy at 90 days, and clinical outcomes through 1-year follow-up after primary PCI in a dedicated outpatient clinic; 168 consecutive patients (79% men) with first ST-elevation myocardial infarction were studied. Mean age +/- SD was 59 +/- 12 years. Peak cTnT values were reached within 24 hours after primary PCI in all patients. The enzymatic infarct size, measured by cumulative 48-hours creatine kinase release, correlated positively with peak cTnT (r = 0.73, p <0.001). Left ventricular ejection fraction at 3 months was negatively correlated with peak cTnT (r = -0.52, p <0.001). A peak plasma cTnT > or = 6.5 microg/L predicted a left ventricular ejection fraction < or = 40% at follow-up with 86% sensitivity and 74% specificity. Multivariable Cox regression analysis identified peak cTnT as an independent predictor of major adverse cardiac events (hazard ratio 1.07, 95% confidence limits 1.01 to 1.12) and heart failure (hazard ratio 1.12, 95% confidence limits 1.05 to 1.20) during follow-up. In conclusion, peak cTnT after primary PCI for ST-elevation myocardial infarction offers a good estimation of infarct size and is a prognostic indicator in patients with first acute myocardial infarction.

Post-intervention IVUS is not predictive for very late in-stent thrombosis in drug-eluting stents.

OBJECTIVES: Stent thrombosis is a life-threatening complication associated with sudden death and acute myocardial infarction. Histopathologic studies have linked the occurrence of very late stent thrombosis in drug-eluting stents (DES) with delayed endothealisation and stent malapposition. Our aim was to investigate if late stent malapposition in DES could be predicted by immediate postintervention intra-vascular ultrasonography (IVUS). METHODS AND RESULTS: From our MISSION! database of 184 consecutive patients with ST-elevation myocardial infarction (STEMI) who had immediate post-intervention and nine-month follow-up IVUS examinations we prospectively identified three patients with very late (> 365 days) and definite (with angiographic evidence) in-stent thrombosis in DES. Patients had completed the twelve-month clopidogrel-aspirin dual treatment period, two of them were under aspirin therapy while the third patient had aspirin temporarily discontinued before planned surgery. When assessed by serial documentary (immediate post-intervention and nine-month) IVUS, all three patients demonstrated stent malapposition at nine months: in two cases the malapposition was acquired (immediate post-intervention IVUS showed a well apposed stent) and one case presented persistent malapposition (the stent was found malapposed both at immediate post-intervention and nine-month follow-up IVUS). CONCLUSIONS: Immediate post-intervention IVUS showing no malapposition does not guarantee an uneventful course after DES implantation.

CCL3 (MIP-1 alpha) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events.

As chemokines are considered instrumental in thrombotic plaque rupture and erosion as well as in ischemia-reperfusion injury processes, we aimed to identify previously unknown chemokines associated with acute coronary syndromes. Plasma of 44 patients with acute myocardial infarction (AMI) and 22 controls were profiled for a panel of chemokines by multiplex analysis. Levels of CCL3 were prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI mouse model was used to assess the relationship between differentially expressed chemokines and myocardial ischemia. CCL3 levels were significantly elevated in AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors attenuated this association. In support of a direct association with cardiac ischemia CCL3 levels were also seen to be elevated in patients with UAP at baseline and significantly down-regulated after 180 days (P<0.001). Importantly, baseline upper quartile levels were strongly correlated with future acute coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell homing towards the ischemic area. CCL3 levels are elevated during ACS and released upon ischemia. Since CCL3 specifically predicts future cardiovascular events, it may serve as a predictive biomarker.

Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.

OBJECTIVES: Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients. METHODS: A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months. RESULTS: In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p < 0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p < 0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different. CONCLUSIONS: Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients.

Stent malapposition after sirolimus-eluting and bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: acute and 9-month intravascular ultrasound results of the MISSION! intervention study.

OBJECTIVES: Acute and late stent malapposition (SM) after bare-metal stents (BMS) and sirolimus-eluting stents (SES) in ST-segment elevation myocardial infarction patients were studied. BACKGROUND: Stent thrombosis may be caused by SM after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients. METHODS: Post-procedure and follow-up intravascular ultrasound data were available in 184 out of 310 patients (60%; 104 SES, 80 BMS) included in the MISSION! Intervention Study. To determine the contribution of remodeling and changes in plaque burden to the change in lumen cross-sectional area (CSA) at SM sites, the change in lumen CSA (follow-up minus post-lumen CSA) was related to the change in external elastic membrane CSA (remodeling) and change in plaque and media CSA (plaque burden). RESULTS: Acute SM was found in 38.5% SES patients and 33.8% BMS patients (p = 0.51), late SM in 37.5% SES patients and 12.5% BMS patients (p < 0.001). Acquired SM was found in 25.0% SES patients and 5.0% BMS patients (p < 0.001). Predictors of acute SM were reference diameter (SES: odds ratio [OR] 3.49, 95% confidence interval [CI] 1.29 to 9.43; BMS: OR 28.8, 95% CI 4.25 to 94.5) and balloon pressure (BMS: OR 0.74, 95% CI 0.58 to 0.94). Predictors of late SM were diabetes mellitus (SES: OR 0.16, 95% CI 0.02 to 1.35), reference diameter (BMS: OR 19.2, 95% CI 2.64 to 139.7), and maximum balloon pressure (BMS: OR 0.74, 95% CI 0.55 to 1.00). Change in lumen CSA was related to change in external elastic membrane CSA (R = 0.73, 95% CI 0.62 to 0.84) after SES implantation and to change in plaque and media CSA (R = -0.62, 95% CI -0.77 to -0.46) after BMS implantation. After SES implantation, acquired SM was caused by positive remodeling in 84% and plaque reduction in 16% of patients. CONCLUSIONS: Acute SM was common after SES and BMS stent implantation in ST-segment elevation myocardial infarction patients. After SES implantation, late acquired SM is common and generally caused by positive remodeling.

Left ventricular dyssynchrony acutely after myocardial infarction predicts left ventricular remodeling.

OBJECTIVES: We sought to identify predictors of left ventricular (LV) remodeling after acute myocardial infarction. BACKGROUND: Left ventricular remodeling after myocardial infarction is associated with an adverse long-term prognosis. Early identification of patients prone to LV remodeling is needed to optimize therapeutic management. METHODS: A total of 178 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 h of intervention, 2-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), wall motion score index, left atrial dimension, E/E' ratio, and severity of mitral regurgitation. Left ventricular dyssynchrony was determined using speckle-tracking radial strain analysis. At 6-month follow-up, LV volumes, LVEF, and severity of mitral regurgitation were reassessed. RESULTS: Patients showing LV remodeling at 6-month follow-up (20%) had comparable baseline characteristics to patients without LV remodeling (80%), except for higher peak troponin T levels (p < 0.001), peak creatine phosphokinase levels (p < 0.001), wall motion score index (p < 0.05), E/E' ratio (p < 0.05), and a larger extent of LV dyssynchrony (p < 0.001). Multivariable analysis demonstrated that LV dyssynchrony was superior in predicting LV remodeling. Receiver-operating characteristic curve analysis demonstrated that a cutoff value of 130 ms for LV dyssynchrony yields a sensitivity of 82% and a specificity of 95% to predict LV remodeling at 6-month follow-up. CONCLUSIONS: Left ventricular dyssynchrony immediately after acute myocardial infarction predicts LV remodeling at 6-month follow-up.

Does left ventricular dyssynchrony immediately after acute myocardial infarction result in left ventricular dilatation?

BACKGROUND: Reverse remodeling of the left ventricle (LV) is one of the advantageous mechanisms of cardiac resynchronization therapy (CRT). Substantial LV dyssynchrony seems mandatory for echocardiographic response to CRT. Conversely, LV dyssynchrony early after acute myocardial infarction may result in LV dilatation during follow-up. OBJECTIVE: The purpose of this study was to evaluate the relation between LV dyssynchrony early after acute myocardial infarction and the occurrence of long-term LV dilatation. METHODS: A total of 124 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 hours of intervention, two-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), and wall motion score index (WMSI). LV dyssynchrony was quantified using color-coded tissue Doppler imaging (TDI). At 6-month follow-up, LV volumes and LVEF were reassessed. RESULTS: Patients with substantial LV dyssynchrony (> or =65 ms) at baseline (18%) had comparable baseline characteristics to patients without substantial LV dyssynchrony (82%), except for a higher prevalence of multivessel coronary artery disease (P = .019), higher WMSI (P = .042), and higher peak levels of creatine phosphokinase (P = .021). During 6 months of follow-up, 91% of the patients with substantial LV dyssynchrony at baseline developed LV remodeling, compared with 2% in the patients without substantial LV dyssynchrony. LV dyssynchrony at baseline was strongly related to the extent of long-term LV dilatation at 6 months of follow-up. CONCLUSION: Most patients with substantial LV dyssynchrony immediately after acute myocardial infarction develop LV dilatation during 6 months of follow-up.