Trombosis del stent 10 años después de la intervención coronaria percutánea con stents nuevos frente a stents de la primera generación. Observaciones del metanálisis DECADE / Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation

Introducción y objetivos El metanálisis DECADE es un análisis de datos de pacientes individuales de ensayos de stents liberadores de fármacos (SLF) con un seguimiento de 10 años. El objetivo del estudio es analizar el riesgo de trombosis definitiva del stent (TS) hasta 10 años después de la intervención coronaria percutánea (ICP) en pacientes tratados con DES de primera y de nueva generación. Métodos Se agruparon los datos de pacientes individuales de cinco ensayos de SLF con un seguimiento de 10 años. El objetivo primario fue la TS hasta 10 años después de la ICP. Los pacientes se dividieron en 2 grupos según la generación de stent implantada (primera y nueva). El análisis de los datos de los participantes individuales se realizó mediante el enfoque de una etapa. Resultados Se incluyeron 9.700 pacientes, 6.866 en el grupo de SLF nuevos y 2.834 en el grupo de SLF de primera generación. A los 10 años, la TS se produjo en 69 de los 6.866 pacientes tratados con SLF de nueva generación y en 91 de los 2.834 pacientes tratados con la SLF de primera generación (1,0% frente a 3,5%, razón de tasas 0,32; IC95%, 0,23-0,45). La tasa de TS fue menor en el grupo de SLF de nueva generación en comparación con el grupo de SLF de primera, de 1-5 años (razón de tasas 0,14; IC95%, 0,08-0,26) y de 5-10 años (razón de tasas 0,23; IC95%, 0,08-0,61) después de la ICP. Conclusiones La incidencia de TS hasta 10 años después de la ICP con los SLF de nueva generación es del 1%. Los SLF de nueva generación se asocian a una menor incidencia de TS a 10 años comparados con los SLF de primera generación, especialmente después de 1 año de la ICP (AU)

Introduction and objectives The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. Methods Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. Results We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. Conclusions The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PC (AU)

Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion.

We aimed to identify factors influencing the sensitivity of perfusion imaging after an initial positive coronary computed tomography angiography (CCTA) using invasive coronary angiography (ICA) with conditional fractional flow reserve (FFR) as reference. Secondly we aimed to identify factors associated with revascularisation and to evaluate treatment outcome after ICA. We analysed 292 consecutive patients with suspected significant coronary artery disease (CAD) at CCTA, who underwent perfusion imaging with either cardiac magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS) followed by ICA with conditional FFR. Stratified analysis and uni- and multiple logistic regression analyses were performed to identify predictors of diagnostic agreement between perfusion scans and ICA and predictors of revascularisation. Myocardial ischemia evaluated with perfusion scans was present in 65/292 (22%) while 117/292 (40%) had obstructive CAD evaluated by ICA. Revascularisation rate was 90/292 (31%). The overall sensitivity for perfusion scans was 39% (30-48), specificity 89% (83-93), PPV 69% (57-80) and NPV 68% (62-74). Stratified analysis showed higher sensitivities in patients with multi-vessel disease at CCTA 49% (37-60) and typical chest pain 50% (37-60). Predictors of revascularisation were multi-vessel disease by CCTA (OR 3.51 [1.91-6.48]) and a positive perfusion scan (OR 4.69 [2.49-8.83]). The sensitivity for perfusion scans after CCTA was highest in patients with typical angina and multiple lesions at CCTA and predicted diagnostic agreement between perfusion scans and ICA. Abnormal perfusion and multi vessel disease at CCTA predicted revascularisation.

Diagnosing coronary artery disease after a positive coronary computed tomography angiography: the Dan-NICAD open label, parallel, head to head, randomized controlled diagnostic accuracy trial of cardiovascular magnetic resonance and myocardial perfusion scintigraphy.

Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA. Methods and results: Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively. Conclusion: Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.

Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation.

BACKGROUND: Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. AIM: To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment. METHODS: We conducted this population-based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. RESULTS: During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]. CONCLUSIONS: The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention.

Negative vascular remodelling after implantation of bioabsorbable magnesium alloy stents in porcine coronary arteries: a randomised comparison with bare-metal and sirolimus-eluting stents.

OBJECTIVE: We sought to assess vascular remodelling and neointima formation after implantation of bioabsorbable magnesium alloy stents (AMS). DESIGN: Randomised experimental study. INTERVENTIONS: AMS (n = 11), sirolimus-eluting stents (Cypher; n = 11) and bare-metal stents (BMS; n = 9) were randomly implanted in 31 porcine coronary arteries (n = 11 pigs). MAIN OUTCOME MEASURES: Neointima formation was measured by histomorphometry at 90 days. Vascular remodelling defined as change in external elastic membrane area from index intervention to follow-up was assessed by serial intravascular ultrasound (IVUS). RESULTS: By histomorphometry, lumen (median (quartiles); AMS: 1.75 mm2 (1.07-3.26), Cypher 2.52 mm2 (2.22-5.01), BMS 4.55 mm2 (3.2-7.44); p = 0.013) and external elastic membrane area (AMS: 5.56 mm2 (4.09-6.95), Cypher 7.95 mm2 (6.45-10.92), BMS 9.08 mm2 (7.85-11.63); p = 0.014) were smallest after AMS implantation. By IVUS, external elastic membrane area at follow-up was smallest (AMS: 7.5 (2.8) mm2, Cypher 9.1 (2.7) mm2, BMS 9.9 (3.1) mm2; p = 0.33) and change in external elastic membrane area from index intervention to follow-up (remodelling; AMS: -1.0 (3.1) mm2, Cypher 1.0 (0.8) mm2, BMS 0.9 (1.2) mm2; p = 0.30) was greatest in the AMS group. In a dichotomised IVUS assessment of vascular remodelling, six AMS stents were remodelled (negative remodelling: n = 5; positive remodelling: n = 1) at 90-day follow-up (AMS versus Cypher + BMS: p = 0.001). Neointima formation was smallest in the AMS group (p<0.05 for both histomorphometry and IVUS). CONCLUSION: Coronary implantation of absorbable magnesium stents, compared to two non-absorbable stents, was associated with the smallest lumen area at three-month follow-up because of negative vascular remodelling.

Time course of vascular remodeling, formation of neointima and formation of neoadventitia after angioplasty in a porcine model.

BACKGROUND: Vascular remodeling is the major cause of restenosis after coronary balloon angioplasty but the pathophysiology of this process is not known. OBJECTIVE: To examine the time courses of vascular remodeling, formation of neointima and adventitial changes after coronary angioplasty. DESIGN: An experimental study on pigs using coronary angiography, intravascular ultrasound (IVUS), and histology. METHODS: Deep vessel-wall injury was induced by conventional balloon angioplasty in the circumflex and right coronary arteries, and by retraction of a chain-encircled balloon in the left anterior descending artery. Angiography in all three arteries and IVUS measurements in circumflex and left anterior descending arteries were performed before and after angioplasty, and at follow-up on days 0, 1, 4, 7, 14, 28, and 56 (n = 5 in each group). Serial IVUS measurements were used to determine vascular remodeling. Formation of neointima and neoadventitia was measured by histomorphometry. RESULTS: Angiographically evident loss of lumen and ultrasonographically detectable constrictive remodeling occurred between day 7 and day 28. IVUS measurements showed that late loss of lumen (days 28 and 56) was correlated to vascular remodeling but not to the increase in wall area (neointima plus media). Histomorphometry revealed that neointima was present from day 7 and that amount of neointima increased up to day 28. Area of adventitia increased during the first 4 days and remained unchanged thereafter. Adventitial neovascularization by vasa vasorum was observed from day 4 onward. CONCLUSIONS: Formation of neoadventitia precedes late loss of lumen, constrictive remodeling, and formation of neointima. The time course of vascular remodeling coincides with growth of neointima rather than with changes in the adventitia.

Histopathologic validation of in-vivo angioscopic observation of coronary thrombus after angioplasty in a porcine model.

BACKGROUND: Coronary angioscopy has been reported to be superior to angiography and intravascular ultrasound for detecting intracoronary thrombus. However, in-vivo histopathologic validation of angioscopic detection of intracoronary thrombus had not been performed. OBJECTIVE: To perform histopathologic validation of in-vivo angioscopic detection of coronary thrombus. DESIGN: An experimental, blinded comparison of angioscopy and histopathology. METHODS: Coronary angioscopy was performed from 0 to 14 days after angioplasty in 39 porcine coronary arteries. When thrombus was detected by angioscopy, it was subclassified into white, mixed red-white, or red thrombus according to color. By histopathology the presence of thrombus was determined and subclassified into platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich thrombus. RESULTS: Angioscopy correctly classified 19 of 21 coronary thrombi (sensitivity 90%) but incorrectly classified nine of 18 arteries without formation of thrombus as having a thrombus (specificity 50%). Positive and negative predictive values were 68 and 82%, respectively. The angioscopic subclassification of thrombus into white, mixed red-white, or red thrombi was not correlated to the corresponding histopathologic morphology (platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich) of the observed thrombi (chi2 test: P = 0.5). CONCLUSIONS: Angioscopic detection of thrombus in vivo had high sensitivity and negative predictive value but low-to-moderate specificity and positive predictive value. Visual assessment of color of angioscopically detected thrombi seemed not to reflect histopathologic morphology of thrombus according to the definitions used in the present study.

Thrombus organization plays no major role in late neointimal formation after angioplasty in porcine coronary arteries.

Thrombus organization has been suggested to play a major role in late neointimal formation after coronary angioplasty. We sought to describe the time sequence of lesion formation after angioplasty in porcine coronary arteries and to quantify the relation between early thrombosis and late neointimal formation. Deep vessel wall injury was induced by conventional balloon angioplasty in the circumflex (CX) and right coronary (RCA) arteries and by retraction of a chain-encircled balloon in the left anterior descendent artery (LAD). Lesions were assessed by histomorphometry at days 0, 1, 4, 7, 14, 28, and 56 after angioplasty. A response-to-injury index (lesion area/injury length) was determined for each artery. Angioplasty led to rupture/removal of media. Thrombus was present at the exposed adventitia at days 0, 1, and 4. From day 7, neointima was observed on the luminal side of the arterial wall. All thrombus had disappeared at day 28, at which only neointima was observed. Histomorphometry revealed that lesion formation after angioplasty was a gradually increasing process from day 0 to day 28 with no further growth from day 28 to day 56. Maximal thrombus size (day 4, RCA: 0.07+/-0.04 mm, CX: 0.23+/-0.16 mm, LAD: 0.15+/-0.11 mm) was significantly smaller than late neointimal formation (day 28, RCA: 0.68+/-0.18 mm, CX: 0.63+/-0.23 mm, LAD: 0.71+/-0.18 mm) in all three arteries (p < .03). Lesion formation after angioplasty is a gradually increasing process for 4 weeks. Maximal thrombus size is about four times smaller than late neointimal formation. Thus, thrombus organization plays no major role in late neointimal formation.

[A young woman with metabolic acidosis and recently discovered IDDM without ketonuria. A rare autoimmune (?) combination of hypothyroidism, diabetes mellitus and distal renal tubular acidosis]. / Ung kvinde med metabolisk acidose og nyopdaget IDDM uden ketonuri. En sjaelden autoimmun? kombination af hypotyreose, diabetes mellitus og distal renal tubulaer acidose.

A case of a 29-year-old woman with a multiple autoimmune disorder is reported. She had a history of hypothyroidism since the age of 18. She was admitted to hospital due to hyperglycaemia. At admission she had hyperglycaemia, metabolic acidosis, but no urinary ketone bodies. Further laboratory studies revealed that the acidosis was due to distal renal tubular acidosis rather than diabetic ketoacidosis (although the patient had type 1 diabetes mellitus). Blood tests revealed antibodies to glutamic acid decarboxylase (GAD-65; associated with type 1 diabetes mellitus), thyroid and adrenal tissue, and gastric parietal cells. The patient had not developed pernicious anaemia or Addison's disease. The multiple positive antibody titres in this patient indicate that the diabetes, hypothyroidism and distal renal tubular acidosis are part of an autoimmune syndrome.

Remodeling rather than neointimal formation explains luminal narrowing after deep vessel wall injury: insights from a porcine coronary (re)stenosis model.

BACKGROUND: Oversized balloon dilatation of normal porcine coronary arteries usually heals without stenosis formation. METHODS AND RESULTS: With the purpose of developing a stenotic model and examining the mechanisms of luminal narrowing after angioplasty, we produced a circumferential deep vessel wall injury by inflating and withdrawing an oversized chain-encircled angioplasty balloon in the left anterior descending coronary artery (LAD) of 20 pigs. Three pigs died and did not complete the study. In 8 pigs (group 1), serial coronary arteriography was performed. The lumen diameter (mean+/-SD) before dilation was 3.4 +/- .4 mm; after dilation, 4.2 +/- 0.6 mm; and at follow-ups 2 and 4 weeks later, 1.6 +/- 0.4 mm (P<.0001). In 9 pigs (group 2) examined postmortem 3 weeks after dilatation, histology revealed that the injury was deep (out to adventitia) in all arteries and completely circumferential (360 degrees) in all but two arteries. Adventitia was markedly thickened as a result of neoadventitial formation. Injury correlated strongly with neointimal formation (middle LAD, r=.71, P=.00001, but neither injury nor neointima correlated with lumen size (r=.14, P=.46 and r=.34, P=.07, respectively); ie, neointimal formation did not explain late luminal narrowing. Lumen size, however, did correlate strongly with vessel size (r=.74, P=000005). The late loss in lumen diameter observed angiographically in group 1 substantially exceeded that caused by neointimal formation seen by histology in group 2. CONCLUSIONS: The chain-encircled angioplasty balloon produced a circumferential deep vessel wall injury that healed by luminal narrowing. In this porcine model, arterial remodeling was more important than neointimal formation in late luminal narrowing.