In search for "healthy" landing zones for coronary stent placement: are the largest intrasegmental lumens adequate?

Background: Coronary lesions are supposed to be enclosed between proximal and distal reference segments (RSs), the sites with the largest lumens within the same vessel segment. Finding "healthy" landing zones has been fundamental for efficient stent implantation. Consequently, our study aimed to determine, using optical coherence tomography (OCT), to what degree RSs conform to this concept. Methods: Sixty-seven patients with a mean age of 63.5 years underwent culprit lesion stenting due to acute myocardial infarction (MI) (Group 1) or stable angina (Group 2). OCT was performed with commercially available equipment; all evaluations were made at RSs and minimal lumens. Results: Normal vessel wall was infrequent (~10%) at RSs. Acceptable external elastic 220°) occurred in 55% to 67% and in 28% to 31% of RSs, respectively. Tissue composition at RSs was similar in both study groups except for a greater accumulation of thin-cap fibroatheromas (TCFA) in acute MI (29% in Group 1 vs. 9% in Group 2, P=0.035). Flow deterioration after stenting was associated with TCFA clusters extending from culprit main bodies into proximal RSs (P=0.008). Conclusions: Optimal landing zones for stent placement should frequently be searched for beyond the culprit lesion segments although utilizing the largest intrasegmental lumens does not seem to cause immediate harm. However, TCFA at the landings should definitely be avoided.

Diffuse non-obstructive coronary artery disease: two clinical faces of the same disease-a case report.

Background: Coronary artery disease has a long preclinical phase before manifesting itself clinically due to diffuse non-obstructive disease, stenoses, or thrombosis. Case summary: We present a case of a middle-aged male complaining of atypical chest pain, then severe retrosternal pain, and, eventually, effort angina. We performed non-invasive testing, coronary angiography, intravascular imaging, and flow reserve tests, each as appropriate. Cardiovascular risk control, optimization of drug therapy, and percutaneous coronary intervention were considered trying to comply with the best clinical practice. Discussion: Diffuse non-obstructive coronary artery disease may present clinically in different ways. Exercise stress test might be sufficient to assess effort angina before a potential angiography. Flow reserve tests across the diseased vessel can distinguish between diffuse and focal pattern of the disease and assist in the adequate selection of therapy. Finally, intravascular imaging is invaluable for the assessment of the plaque risk features.

Correction: Complete Revascularization and Survival in STEMI.

[This corrects the article DOI: 10.5334/gh.1040.].

Complete Revascularization and Survival in STEMI.

Background: Complete revascularization (CR) of ST-elevation myocardial infarction patients with multivessel coronary artery disease (MVD) has proven better regarding combined endpoints than incomplete revascularization (IR) in recent randomized control trials with no impact on survival. Objective: To retrospectively evaluate the impact of complete CR during the index hospitalization on survival in STEMI patients with MVD. Methods and results: We included all patients with MVD who underwent successful primary percutaneous coronary intervention for STEMI during their index hospitalization at the University Medical Centre Ljubljana, Slovenia (from 1 January 2009 to 3 April 2011). Coronary angiograms were reviewed for non-culprit coronary arteries (>2 mm in diameter and ≥50% stenosis) treated with percutaneous coronary intervention. Rates of all-cause and cardiovascular death were compared between 235 patients who underwent CR (N = 70) or IR (N = 165). After a median follow-up of 7.0 years (interquartile range 6.0-8.2) the CR group had lower rates of all-cause death (15.7% vs 35.8%, log-rank p = 0.003) and cardiovascular death (12.9% vs 23.6%, log-rank p = 0.046). Multivariable analysis with adjustment for confounders showed no benefit of CR for all-cause death (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.31-1.18, p = 0.139) or cardiovascular death (HR 0.80, 95% CI 0.37-1.72, p = 0.560). Age, elevated serum creatinine at inclusion, diabetes and cardiogenic shock at presentation were predictors of death. Conclusions: Patients with STEMI and MVD who underwent CR showed lower all-cause and cardiovascular death during follow-up than those who underwent IR. However, after adjustment for confounders, the real determinates of survival were independent of the revascularization method.

Optical coherence tomography versus intravascular ultrasound for culprit lesion assessment in patients with acute myocardial infarction.

INTRODUCTION: In patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) the implanted stent may not fully cover the whole intravascular ultrasound (IVUS)-derived thin-cap fibroatheroma (TCFA) related to the culprit lesion (CL). AIM: Whether this phenomenon is more pronounced when optical coherence tomography (OCT) assessment of the CL is performed is not known. MATERIAL AND METHODS: Thus, we aimed to assess CLs in 40 patients with AMI treated with PCI, using VH (virtual histology)-IVUS and OCT before and after intervention. The results were blinded to the operator and PCI was done under angiography guidance. RESULTS: Uncovered lipid-rich plaques were identified in the stent reference segments of 23 (57.5%) patients: in 13 (32.5%) of them in the distal reference segment and in 19 (47.5%) of them in the proximal reference segment. In 9 of them (22.5%) lipid plaques were found in both reference segments. In 36 (90%) patients OCT confirmed lipid plaques identified as VH-derived TCFA by VH-IVUS in the reference segments of the stented segment. However, OCT confirmed that only in 2 (5%) patients were uncovered lipid plaques true TCFA as defined by histology. Comparing IVUS and OCT qualitative characteristics of the stented segments OCT detected more thrombus protrusions and proximal and distal stent edge dissections compared to IVUS (92.5 vs. 55%, p = 0.001; 20% vs. 7.5%, p = 0.03 and 25% vs. 5%, p < 0.001, respectively). CONCLUSIONS: Due to its superior resolution, OCT identifies TCFA more precisely. OCT more often shows remaining problems related to stent implantation than IVUS after angiographically guided PCI.

Robustness of Percutaneously Completed Coronary Revascularization in Stable Coronary Artery Disease: Obstructive Versus Occlusive Lesions.

Our study sought to assess long-term outcomes of percutaneously completed coronary revascularization (CCR) in patients with obstructive coronary artery disease (CAD) comprising chronic total occlusions (CTOs). Between 2010 and 2014, percutaneous coronary interventions (PCIs) of the CTOs were attempted in 213 patients: the CCR was achieved in 125 patients (group 1), while the PCI failed in 88 patients (group 2). They were matched against 252 patients (group 3) with the CCR obtained by the non-CTO PCIs. In the 5-year follow-up, more adverse cardiovascular (CV) events occurred in group 2 (29.5% vs 4.8% in group 1 vs 3.5% in group 3, P = .0001), mainly due to recurrent severe symptoms and additional revascularization of the CTOs; CV mortality did not seem to be significantly affected. Survival curves for the successful CTO and non-CTO PCIs appeared indistinguishable. Stent thromboses were infrequent in the CCR groups. In conclusion, long-term outcomes of the patients with the obstructive CAD containing the CTOs showed a favorable outcome if the CCR had been achieved percutaneously.

Acute myocardial infarction in a young athlete: Optical coherence tomographic features of the culprit lesion.

OBJECTIVES: We report on a young male athlete who suffered from acute myocardial infarction immediately after a vigorous training. METHODS: A comprehensive optical coherence tomographic investigation of the culprit coronary artery was performed after the combined mechanical and pharmacological thrombus removal. RESULTS AND CONCLUSION: The imaging discovered a tear at the junction of the non-obstructive, largely fibrotic plaque with the normal arterial wall. This exertion-related vessel damage resulted in a dynamic thrombosis that almost completely occluded the culprit artery. As the vessel obstruction was not considered flow-limiting, the stent implantation was not required and the patient was discharged on the double antiplatelet therapy and statin.

Platelet reactivity in comatose survivors of cardiac arrest undergoing percutaneous coronary intervention and hypothermia.

AIMS: To investigate the effects of clopidogrel and eptifibatide on platelet reactivity in patients resuscitated from cardiac arrest undergoing percutaneous coronary intervention (PCI) and hypothermia. METHODS AND RESULTS: VerifyNow® and Multiplate® aggregometry were used before, and 4, 12, 22 and 48 hours after 600 mg clopidogrel treatment in 28 post-cardiac arrest hypothermic patients and in 14 normothermic patients with acute coronary syndrome. Basal platelet reactivity after stimulation with iso-thrombin receptor-activating peptide (TRAP) and PAR4-activating peptide (BASE) was significantly lower in the post-cardiac arrest group and persisted up to 48 hours. The antiplatelet effect of clopidogrel measured by VerifyNow and expressed as % inhibition was significantly lower in the post-cardiac arrest group. It was close to zero with an increase to only around 10% after 48 hours. Post-cardiac arrest patients receiving eptifibatide showed profound platelet inhibition measured by both VerifyNow IIb/IIIa and Multiplate TRAP tests for at least 22 hours after administration. CONCLUSIONS: Post-resuscitation syndrome with ongoing hypothermia is associated with decreased platelet reactivity. Clopidogrel loading does not significantly affect platelet function during the first 48 hours. This is in contrast with eptifibatide which produces profound platelet inhibition, and may be used to bridge insufficient inhibition by clopidogrel.

Acute ischemic events are frequent after primary coronary stenting.

AIMS: The purpose of this study was to assess the incidence, predictors, and presentation of target vessel failure (TVF) after primary stenting for ST-segment elevation myocardial infarction (MI) as opposed to elective stenting. METHODS: A total of 8237 consecutive patients undergoing urgent or elective percutaneous coronary intervention (PCI) were enrolled in our database and followed for a median of 1234 days (interquartile range 782-1688 days). Any acute ischemic event attributed to the obstruction of the stented vessel was considered as TVF. Stent thrombosis was classified according to the Academic Research Consortium, whereas restenosis and new culprit lesion were defined as obstructions within or outside stent boundaries, respectively. Unstable clinical presentation required urgent hospital admission or caused unexplained sudden death. Multivariable analyses were performed with Cox proportional hazards regression models. RESULTS: TVF occurred in 4.2% of our population. A measurable proportion of patients had to be re-admitted to hospital: 1.6% because of stent thrombosis, 1.5% because of restenosis, and 0.3% because of new culprit lesion. Ten (0.1%) patients were found victims of sudden death. De-novo lesions showed less TVF [hazard ratio (HR) 0.22, 95% confidence interval (CI) 0.16-0.30, P < 0.0001]. Primary PCI was associated with increased risk of TVF (HR 1.83, 95% CI 1.43-2.36, P < 0.0001), stent thrombosis (HR 2.59, 95% CI 1.80-3.72, P < 0.0001), and MI (HR 2.16, 95% CI 1.61-2.91, P < 0.0001). The events appeared earlier after primary PCI with more than 50% within the first month; after the first year, further occurrences were similar in both groups. Finally, the use of everolimus-eluting stents suggested the best safety profile. CONCLUSION: The present study shows that acute ischemic events are frequent after primary PCI and occur earlier compared with elective PCI. Particular attention should be directed towards optimal stent selection and implantation technique.

Glycogen phosphorylase isoenzyme BB, creatine kinase isoenzyme MB and troponin I for monitoring patients with percutaneous coronary intervention - a pilot study.

AIM: The glycogen phosphorylase isoenzyme BB (GPBB), as an ischemic marker, has not yet been investigated after elective percutaneous coronary intervention (PCI). ose aim of the study was to monitor GPBB, creatine kinase myocardial isoform (CK-MB) mass) and troponin I (TnI) value after PCI in correlation with ischemic incidents. METHODS: Forty-two consecutive patients undergoing elective PCI were included in the study. Baseline blood samples and two more after the PCI (3 and 24 hours) were taken. The significance of cardiac markers in twenty-ththe stable patients with baseline values of CK-MB mass and TnI below the upper reference limit (URL) was evaluated based on ischemic incidents after PCI. RESULTS: TnI value was the only biomarker that was statistically significant at 3 and 24 hours after PCI in group of 23 stable patients. An overall comparisonthe biomarkers of 18 patients without and five patients with ischemic incidents displayed significant differences only for the baseline GPBB (p=0.019) and CK-MB mass 24 hours after PCI (p=0.034). Ischemic incidents were independently predictable only based on overall CK-MB mass measurements (OR=1.680, p=0.041) and particularly GPBB at baseline (OR=1.899, p=0.008) and CK-MB mass 24 hours after PCI (OR=2.111, p=0.022). CONCLUSIONS: Only significant increases in TnI were observed after elective PCI with ischemic incidents predicted using GPBB and CK-MB mass measurements.

Atherosclerotic burden in coronary and peripheral arteries in patients with first clinical manifestation of coronary artery disease.

The aim of our study was to assess the atherosclerotic burden in patients with the first symptoms of coronary artery disease (CAD). The study population consisted of 100 consecutive patients (new-onset severe angina or myocardial infarction) and 70 age and sex matched asymptomatic volunteers. Functional and morphologic atherosclerotic markers were sought in carotid, brachial and femoral arteries of all individuals by means of high-resolution ultrasonography, whereas coronary arteriography was performed in the CAD patients only. A total of 347 coronary lesions [230 (66%) obstructive] were discovered in the CAD patients as well as 105 peripheral plaques [26 (25%) obstructive]. The mean percentage diameter stenosis of the culprit coronary lesion was 83.8 ± 15.8%, the mean vessel score 1.7 (range 0-3), the mean stenosis score 19.8 (range 1.5-89.0), and the mean extent score 49.1% (range 10-65%). Endothelium-dependent vasodilation, as assessed by the brachial flow-mediated response (FMR), was reduced by 50% in the CAD patients (P < 0.001 vs. controls). Furthermore, endothelium-independent vasodilation was significantly impaired in all investigated peripheral arteries of the CAD patients (P < 0.05-0.001 vs. controls). Intima-media thickness (IMT) was increased in the carotid arteries of the CAD patients by 43%, in brachial arteries by 20% and in femoral arteries by 57% (P < 0.01-0.001 vs. controls). Decreased FMR or increased carotid IMT was found to be independent risk factors for the CAD, and they correlated with the coronary vessel and extent scores. In conclusion, the atherosclerotic process was quite advanced in coronary as well as peripheral arteries of our patients with the first clinical presentation of CAD.

Influence of age on the clinical outcomes of coronary revascularisation for the treatment of patients with multivessel de novo coronary artery lesions: sirolimus-eluting stent vs. coronary artery bypass surgery and bare metal stent, insight from the multicentre randomised Arterial Revascularisation Therapy Study Part I (ARTS-I) and Part II (ARTS-II).

AIMS: We sought to evaluate the prognostic impact of age on the procedural results and subsequent clinical outcomes in patients with multivessel disease (MVD) treated either by coronary artery bypass surgery (CABG) or by percutaneous coronary intervention (PCI) with or without drug eluting stents, based on data of the Arterial Revascularisation Therapies Study (ARTS) part I and part II. The potential influence of age in determining the most appropriate revascularisation strategy for patients with MVD is largely unknown. METHODS AND RESULTS: Three year clinical outcome of ARTS I patients randomised to PCI with bare metal stent (BMS) (n= 600) or CABG (n= 605), and matched patients treated by PCI with sirolimus-eluting stents (SES) in ARTS II (n= 607) were reviewed according to four age quartiles. Endpoints were measured in terms of major adverse cardiac and cerebrovascular events MACCE) during hospital stay and up to three years. The frequency of female, diabetes, hypertension, peripheral vascular disease, pulmonary disease, as well as lesion complexity increased with age. At three years, MACCE free survival was comparable between patients treated by CABG or SES PCI, regardless of age quartile. The incidence of MACCE was higher among ARTS I BMS treated patients in all but the second age quartile. This was primarily related to a higher need for repeat revascularisation among BMS treated patients. However, age, which emerged as a strong independent predictor of MACCE following CABG (p<0.005), was not predictive of adverse events following PCI. Conversely, diabetes was the strongest independent predictor of MACCE among PCI treated patients (p<0.02), but didn't affect three-year outcomes following CABG. CONCLUSIONS: Age seems to influence the CABG outcome in-hospital but not PCI. PCI-SES could offer lower immediate risk in patients with MVD and comparable long-term outcome as CABG especially in older patients. The worst outcome of PCI-BMS group is primarily related to the need for repeat revascularisation. Diabetes is the most important predictor of MACCE following PCI.

Optimisation of methods for quantifying plasma mRNA levels from genes responsible for coronary artery plaque development and destabilization.

AIM: To investigate the hypothesis that in patients with coronary atherosclerosis it is possible to measure plasma mRNA levels from genes responsible for plaque development and destabilization. METHODS: Methods for RNA isolation, mRNA transcription and quantitative PCR were evaluated and optimised, in order to achieve reliable mRNA quantification. RESULTS mRNA level was possible to quantify from plasma of patients with coronary atherosclerosis, as well as from healthy volunteers, from genes encoding cathepsin S, cathepsin B, CD40 molecule, monocyte chemotactic protein 1, death-associated protein kinase 1, matrix metallopeptidase 9, vascular cell adhesion molecule 1 and phosphoglycerate kinase 1 (reference gene). Analytical between-run imprecision of average threshold cycle, expressed as coefficient of variation was below 2%. EDTA blood samples should be centrifuged within one hour of venesection. It was not possible to quantify plasma mRNA level from genes encoding macrophage scavenger receptor 1, perilipin, tissue factor, phospholipase A2 group IIA, collagen type I alpha 2 and interleukin 1 alpha. CONCLUSION: Further plasma mRNA analysis is reasonable to access its potential usefulness in non-invasive in vivo monitoring of gene expression profile in vascular beds.

CTSS activation coexists with CD40 activation in human atheroma: evidence from plasma mRNA analysis.

OBJECTIVES: By the analysis of plasma mRNA levels, we tested the hypothesis that, in human atheroma, CTSS activation coexists with activation of CD40. DESIGN AND METHODS: mRNAs were isolated from plasma of patients with coronary atherosclerosis and quantified by real-time RT-PCR. RESULTS: CTSS mRNA levels correlated with CD40 mRNA levels, independently of observed traditional risk factors for atherosclerosis and pharmacological treatment. CONCLUSIONS: Our results suggest that CTSS mediated atherogenesis may be associated with a CD40 mediated inflammatory and immune response. Further invasive atheroma analysis is reasonable.

Increased DAPK1 but decreased CCL2 plasma levels of nucleic acids in patients with stable angina.

INTRODUCTION: We hypothesized that patients with stable angina have increased plasma levels of mRNA from genes responsible for atherosclerotic plaque development and destabilisation, i.e. from death-associated protein kinase (DAPK1) and monocyte chemotactic protein-1 (CCL2). MATERIALS AND METHODS: Nucleic acids were isolated from plasma of patients with stabile angina and healthy subjects as controls. mRNAs were transcribed to cDNAs, quantified by real-time PCR and standardized to the amount of a reference gene. Reagents for PCR quantification are declared to be mRNA specific, but in our test conditions DNA was found to interfere in both assays. RESULTSs: Patients had 5.1-times higher plasma level of DAPK1 nucleic acids (mRNA and DNA) than controls (P < 0.001) and the highest levels were associated with the presence of diabetes. However, plasma levels of CCL2 tended to be lower than in controls, and in statin-treated patients the decrement reached significance (-66.3%; P = 0.041). CONCLUSION: The estimated levels are explicable in terms of current knowledge. Further studies with specific assays for mRNA PCR quantification are reasonable to access whether this approach offers non-invasive in vive assessment and monitoring of gene expression profile in atherosclerotic vascular beds.

Increased plasma levels of CATS mRNA but not CATB mRNA in patients with coronary atherosclerosis.

BACKGROUND: We hypothesized that patients with coronary atherosclerosis have increased plasma levels of cathepsin S (CATS) and cathepsin B (CATB) mRNA, the genes that are involved in atherosclerotic plaque development and destabilization. METHODS: mRNAs were isolated from plasma of 67 patients with coronary atherosclerosis (29 with stable angina, 38 with acute coronary syndrome) and 33 healthy subjects as controls, transcribed to cDNA and quantified by real-time PCR. RESULTS: Plasma levels were successfully measured in all samples. Patients with coronary atherosclerosis had 2.75 times higher plasma levels of CATS mRNA than controls (median 6.10 vs. 2.22; p<0.001). No difference was observed in CATB mRNA levels (median 5.62 vs. 6.19; p=0.866). Patients on therapy with statins and aspirin tended to have higher plasma levels of CATS mRNA than patients without statins and aspirin (median 6.41 vs. 4.27; p=0.028). CONCLUSIONS: Further evaluation of plasma CATS mRNA levels in patients with coronary atherosclerosis is reasonable.

Late thrombosis of sirolimus-eluting stent: a multifactorial problem.

We report a case of a young patient in whom a sirolimus-eluting stent was implanted on the culprit left anterior descending coronary artery at primary percutaneous coronary intervention (PCI) for acute myocardial infarction. Nine months later she suffered from a reinfarction due to the late stent thrombosis despite a continuous antiplatelet therapy with aspirin and clopidogrel. A cluster of factors that might have contributed to the development of the stent thrombosis were identified: suboptimal PCI technique, complete stent fracture, and clopidogrel resistance. The obstructed stent was successfully reopened by repeat PCI, while the clopidogrel maintenance dosage was doubled to 150 mg daily for the following year. The further long-term clinical course was uneventful.