Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin.

OBJECTIVE: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS. PATIENTS AND METHODS: One-hundred- seventeen successfully treated first STEMI (age 63.8±12.5 yrs, 70% men) and 64 AS (age 80.3±6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up. RESULTS: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7±2.1 vs. 11.3±1.7, p=ns). GLS cut-off ≤12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS ≤12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (χ2 6.691 vs. 1.364, p=0.010). CONCLUSIONS: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

Reduced performance of Troponin T for acute coronary syndromes diagnosis in the elderly and very elderly patients: a retrospective study of 2688 patients.

STUDY OBJECTIVE: We evaluated the performance of Troponin T (cTnT) for acute coronary syndrome (ACS) diagnosis in elder compared to younger patients. MATERIALS AND METHODS: We retrospectively evaluated 2688 patients admitted to our Emergency Department for suspected ACS. All patients received ECG, serum creatinine determination, and serial cTnT samplings. Patients were considered positive for cTnT if they had a cTnT above our reference standard (>0.03 microg/L) in any determination obtained within 6 hours from admission. ACS diagnosis, either acute myocardial infarction or unstable angina, was based on reviewed data and discharge diagnosis hospital. Patients were divided in three groups according to age: <65-years-old, elders > or =65 and <80 years, and very elders > or =80 years. CTnT diagnostic accuracy for ACS was compared in these three groups in patients <65 years. RESULTS: Two thousands six and hundred eighty-eight patients (35.3% female) were enrolled in this study. 1087 patients (40.4%) were <65 years old, while 1205 patients (44.8%) were >or =65 and <80 years, and 396 patients (14.8%) were > or =80 years. The overall sensitivity of cTnT for ACS diagnosis was 0.57 (CI 95% 0.54-0.60) with a specificity of 0.71 (CI 95% 0.69-0.73). In older cohorts cTnT showed a reduced performance for ACS diagnosis. Area under the receiver operating characteristic curve of abnormal cTnT for ACS was 0.70 (0.66-0.73) in <65 years, 0.61 (95% CI 0.60-0.66) in > or =65 and <80 years, and 0.59 (0.53-0.65) in > or =80 years. CONCLUSION: Compared to younger patients cTnT showed a reduced performance for ACS diagnosis in elders > or =65 and <80 years; cTnT performance was further reduced in patients > or =80 years.

Coronary plaque instability assessed by positron emission tomography and optical coherence tomography.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) are caused often by destabilization of non-flow limiting inflamed coronary artery plaques. 18F-fluorodeoxyglucose (FDG) uptake with positron emission tomography/computed tomography (PET/CT) reveals plaque inflammation, while intracoronary optical coherence tomography (OCT) reliably identifies morphological features of coronary instability, such as plaque rupture or erosion. We aimed to prospectively compare these two innovative biotechnologies in the characterization of coronary artery inflammation, which has never been attempted before. METHODS: OCT and FDG PET/CT were performed in 18 patients with single vessel coronary artery disease, treated by percutaneous coronary intervention (PCI) with stent implantation, divided into 2 groups: NSTEMI/UA (n = 10) and stable angina (n = 8) patients. RESULTS: Plaque rupture/erosion recurred more frequently [100% vs 25%, p = 0.001] and FDG uptake was greater [TBR median 1.50 vs 0.87, p = 0.004] in NSTEMI/UA than stable angina patients. FDG uptake resulted greater in patients with than without plaque rupture/erosion [1.2 (0.86-1.96) vs 0.87 (0.66-1.07), p = 0.013]. Among NSTEMI/UA patients, no significant difference in FDG uptake was found between ruptured and eroded plaques. The highest FDG uptake values were found in ruptured plaques, belonging to patients with NSTEMI/UA. OCT and PET/CT agreed in 72% of patients [p = 0.018]: 100% of patients with plaque rupture/erosion and increased FDG uptake had NSTEMI/UA. CONCLUSION: For the first time, we demonstrated that the correspondence between increased FDG uptake with PET/CT and morphology of coronary plaque instability at OCT is high.

Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S): a randomized pilot clinical trial.

BACKGROUND: Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. METHODS: To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. DISCUSSION: Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. TRIAL REGISTRATION: EudraCT No. 2016-004746-28. No. NCT02701140.  TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. TRIAL SPONSOR: Fondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Sirolimus, Tacrolimus and Zotarolimus eluting stents to treat bifurcated lesions: a 7-month clinical outcome comparison.

AIM: Drug eluting stents (DES) have been shown to reduce restenosis compared with bare metal stents in bifurcated lesions. The aim of this study was to evaluate the long-term clinical outcomes of patients with bifurcated lesions treated by 3 different DES. METHODS: Consecutive patients with symptomatic coronary artery disease on one bifurcated lesion with SB>2.25 mm (on visual estimation) undergoing at the Department of Cardiology of the Catholic University of Rome, Italy were screened. Patients treated with Sirolimus-eluting stent (Cypher Select; SES Group), Tacrolimus-eluting stent (Taxus-Libertè; TA Group) and Zotarolimus-eluting stent (Endeavor Driver; ZOT Group) were enrolled in the study. Clinical and angiographic characteristics of all patients were prospectively recorded. Major adverse clinical events (MACE), including death, acute myocardial infarction (MI) or target lesion revascularization (TVR) by either percutaneous coronary intervention (PCI) or coronary surgery were recorded during the follow-up. Incidence of definite or probable stent thrombosis was calculated according to the ARC criteria. RESULTS: Two hundred and forty-one consecutive patients were enrolled (89 Group CY, 98 Group TA and 54 Group EN). Length of follow-up was 235+/-60 days. Baseline clinical and angiographic characteristic were similar across the groups. The adopted technique for stent implantation was provisional stenting (73.4%), T-stenting technique (7%), crush (7%) and V-stenting (2.6%). The rate of patients finally treated with two stents was similar among groups. The cumulative rate of MACE (9% SES, 12% TA, 11% ZOT: P=0.7) and of TVR (2% SES, 9% TA, 7% ZOT) was similar among groups. No definite stent thrombosis was observed during follow-up, while 1 probable stent thrombosis was observed in TA group. CONCLUSION: The clinical outcome of bifurcated lesions using DES and mainly a technique of single stent implantation is good. In the present observational study, clinical adverse events did not differ in patients with bifurcated lesions treated by Cypher, Taxus or Endeavor stent implantation.

Filter no reflow during percutaneous coronary interventions using the Filterwire distal protection device.

BACKGROUND: Distal protection devices are increasingly used to prevent embolization during percutaneous coronary interventions (PCI) in saphenous vein grafts (SVG) and native coronary arteries (NV). During interventions with the Filterwire device we have observed reduced flow that is reversible following removal of the filter (filter no reflow, FNR), which might be erroneously interpreted as true no reflow and might be associated with reduced capture efficiency of the basket. METHODS: We analyzed the incidence of FNR in 58 patients (60 lesions) at high risk of embolization undergoing PCI of either a SVG or a NV using the Filterwire (Boston Scientific, Natick, MA). Qualitative and quantitative angiographic analysis was performed, and the volume of collected debris was estimated using a photographic technique. RESULTS: In our population, about 1/3 of the cases showed FNR, which was associated with angiographically visible filling defects within the basket, indicating macroembolism. However some patients (especially those undergoing vein graft interventions) showed filling defects without FNR, and some others FNR without filling defects. Thus we tried to understand the predictors of FNR: FNR was associated with higher amount of collected debris (36.97 +/- 42.98 mm(3) vs. 11.31 +/- 18.47 mm(3), p = 0.005), was neither prevented by abciximab, nor predicted by high thrombotic burden, increasing stent volume or need for predilatation. When patient with and without angiographically evident macroembolisation were separately analyzed, a linear correlation of FNR with the quantity of debris was only apparent in the macroembolization group. CONCLUSIONS: Interventionalists should be aware of the "Filter No Reflow", a common but reversible angiographic complication when the Filterwire device is used. Reduced flow seen during these procedures should be treated conservatively. Mechanical obstruction of the filter, but also other mechanisms (pharmacologically active debris? platelet aggregates?) play a role in this phenomenon.

A method for coronary bifurcation centerline reconstruction from angiographic images based on focalization optimization.

A method for the reconstruction of a vessel centerline from angiographic images is outlined in this work. A typical coronary artery segment with bifurcations was emulated with a 3D printed static phantom and several angiograms were acquired at various angular positions on the C-Arm. The effectiveness of the reconstruction turned out to be largely influenced by the intrinsic parameters of the angiographic system, particularly the homogeneous coordinates system scaling factor λ. Therefore, recourse was made to a heuristic optimization method to estimate the optimal value of λ for each view. We measured the reliability of the reconstruction method by varying the fitness function of the optimization step and measuring the distances of 8 test points in comparison to the corresponding points identified in the µCT centerline. Preliminary results showed that, with an adequate number of views, the adoption of the optimal fitness function allowed the median distance error to be decreased below the acceptance threshold of 10%. As expected, the reliability of the method is improved by increasing the number of processed views.

4G/5G promoter PAI-1 gene polymorphism is associated with plasmatic PAI-1 activity in Italians: a model of gene-environment interaction.

The PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in Northern and Central Europe populations, but no data are available on the association between this polymorphism and PAI-1 levels in Southern Europe countries (such as Italy) where the incidence of ischemic disorders is lower. This study shows that among populations with different incidence of atherothrombotic disorders the 4G/5G PAI-1 gene promoter polymorphism has the same importance in the regulation of plasma PAI-1 activity. Moreover, we have analysed some gene-environmental interactions: the correlation between PAI-1 and cholesterol in non dyslipidemic subjects and the correlation between PAI-1 activity and tryglicerides in dyslipidemic subjects differed according to the 4G/5G genotype class. Thus, our findings suggest that, among subjects with or without metabolic disorders such as dyslipidemia, completely different gene-environment interactions may occur.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

Prognostic role of heart rate variability in patients with a recent acute myocardial infarction.

A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).

Reversible left anterior descending artery spasm, prolonged cardiac arrest and left main thrombosis during a PTCA attempt of the circumflex artery.

The authors report a case of percutaneous transluminal coronary angioplasty of the circumflex artery complicated by occlusion of the non-diseased left anterior descending artery by spasm. During advanced cardiac life support, required for the subsequent cardiac arrest, intra-coronary nitrates and calcium antagonists were administered. After 45 minutes, the spasm resolved, but N probably as a result of prolonged blood stasis N a thrombus appeared in the left main artery. While attempting to stent the left main, the thrombus was mechanically dislodged, leaving the epicardial coronary tree free, with a good flow.

Increased mortality after coronary stenting in patients treated with clopidogrel without loading dose. Evidence from a meta-analysis.

AIM: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its hematologic safety, but its efficacy in comparison to ticlopidine is debated. We thus systematically reviewed randomized trials comparing clopidogrel vs ticlopidine after coronary stenting. METHODS: Medline (1/1986-10/2003), BioMed Central, Central, Current Contents, LILACS and mRCT were searched. Fixed-effect relative risks (RR [95% CI]) were computed, and the primary end-point was death. Heterogeneity tests and subgroup analyses were performed according to loading vs non-loading clopidogrel scheme. RESULTS: Five trials were retrieved (2 962 patients, average follow-up 7.4 months). In 3 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (p for heterogeneity=0.12) showed a non-significant trend toward increased mortality in patients treated with clopidogrel (38/1 649 [2.3%]) vs ticlopidine (22/1 313 [1.7%], RR=1.64 [0.94-2.86], p=0.080). After stratification, clopidogrel with loading was associated with non-significantly lower mortality rates than ticlopidine (9/959 [0.9%] vs 13/798 [1.6%], RR=0.68 [0.29-1.63], p=0.39). Instead, clopidogrel without any loading yielded a highly significantly 3-fold increased risk of death than ticlopidine (29/690 [4.2%] vs 9/515 [1.7%], RR=2.9 [1.45-6.1], p=0.0029). Similar results were obtained for the rate of death or non-fatal myocardial infarction. CONCLUSION: This meta-analysis suggests that clopidogrel treatment including a loading regimen is equivalent or may even be superior to ticlopidine after coronary stenting. However, current evidence shows conversely that clopidogrel therapy in the absence of a loading dose is associated with a significantly higher risk of death or myocardial infarction.

Radial artery intima-media ratio predicts presence of coronary thin-cap fibroatheroma: a frequency domain-optical coherence tomography study.

BACKGROUND: Peripheral arterial disease is a risk factor for cardiac mortality but pathophysiologic mechanisms linking atherosclerosis of peripheral arteries with coronary events in the single patient have not been established. METHOD AND RESULTS: We evaluated by frequency-domain optical coherence tomography (FD-OCT) the possible association between culprit coronary plaque characteristics and proximal radial artery features in a cohort of 51 patients symptomatic coronary artery disease undergoing coronary procedures by transradial route. FD-OCT coronary artery analysis included assessment of TCFA and thrombus. FD-OCT radial artery analysis included intimal thickness index (ITI: intimal area/medial area), intima-media ratio (IMR: the maximum intimal thickness/medial thickness), and percentage of luminal narrowing [%LN: (intimal area+medial area)/external elastic membrane area × 100]. Coronary TCFA and thrombus were detected in 19 (37%) and 7 (14%) patients, respectively. TCFA was significantly associated with higher values of radial artery ITI (0.35 vs. 0.26, p=0.02) and IMR (0.45 vs. 0.32, p=0.03), but not with %LN. In contrast, coronary thrombus was only associated with higher %LN (26.7 vs. 22.8, p=0.02). Multivariate logistic regression analysis identified proximal radial artery IMR (OR 16.3, 95% CI 1.1 to 245.1) as an independent predictor of TCFA. CONCLUSIONS: In patients with symptomatic coronary atherosclerosis, vessel wall modifications at the level of the proximal radial artery are associated with adverse coronary features like TCFA and thrombus.

EuroSCORE as predictor of in-hospital mortality after percutaneous coronary intervention.

OBJECTIVE: To date, no common risk stratification system is available to predict the risk of surgical or percutaneous myocardial revascularisation in patients with coronary artery disease (CAD). Thus, we sought to assess the European System for Cardiac Operative Risk Evaluation (EuroSCORE) validity to predict in-hospital mortality after percutaneous coronary intervention (PCI). DESIGN, SETTING AND PARTICIPANTS: EuroSCORE was prospectively and systematically assessed in 1173 consecutive patients undergoing PCI in a high-volume single centre between April 2005 and October 2006. MAIN OUTCOME MEASURE: The receiver-operating characteristics (ROC) curve was used to describe performance and accuracy of the EuroSCORE risk model for the prediction of in-hospital mortality after PCI. RESULTS: The EuroSCORE model demonstrated an overall relation between EuroSCORE rank and the incidence of in-hospital mortality, showing consistency in predicting patient risk across many subgroups and levels of global risk. At multivariable logistic regression analysis the EuroSCORE value was an independent in-hospital mortality predictor (p = 0.002) together with left main disease (p = 0.005), procedural urgency (p = 0.001), ACC/AHA C type lesion (p = 0.02) and PCI failure (p = 0.01). The area under the ROC curve for the EuroSCORE system was 0.91 (95% CI 0.86 to 0.97), indicating a good ability of the model to discriminate patients at risk of dying during the index hospitalisation. CONCLUSION: The EuroSCORE risk model, already extensively validated for the prediction of early mortality following open-heart surgery, can also be efficiently utilised in the setting of PCI. The introduction of the EuroSCORE assessment in patients with documented CAD may help to improve the revascularisation strategy decision-making process.