Daniela Lina

Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis

Background— It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. Methods and Results— Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm2 versus 4.2±2.1 mm2; P=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P=0.01). Conclusions— CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.

Strong association of the APOA5-1131T>C gene variant and early-onset acute myocardial infarction

BACKGROUND Epidemiological studies support the role for a strong genetic component in the occurrence of early-onset myocardial infarction (MI), although the specific genetic variants responsible for familial clustering remain largely unknown. METHODS The Italian study of early-onset MI is a nationwide case-control study involving 1864 case patients <45 years old who were hospitalized for a first MI, and age/sex/place of origin-matched controls (n = 1864). We investigated the association between early-onset MI, lipid levels and 20 single nucleotide polymorphisms (SNPs) in the candidate genes ADIPOQ, APOA5, ALOX5AP, CYBA, IL6, LPL, PECAM1, PLA2G2A and PLA2G7, chosen because of previously reported associations with Coronary Heart Disease (CHD) or with CHD risk factors. RESULTS Of all the SNPs investigated, APOA5-1131T>C [(rs662799), minor allele frequency 0.084 (95% confidence interval (CI) 0.07-0.09)] alone showed a statistically significant association with risk of early-onset MI (p = 6.7 × 10(-5)), after Bonferroni correction, with a per C allele odds ratio of 1.44 (95% CI 1.23-1.69). In controls, APOA5-1131T>C was significantly associated with raised plasma triglyceride levels (p = 0.001), compared with non-carriers, the per C allele increase being 11.4% (95% CI 4-19%), equivalent to 0.15 mmol/L (95% CI 0.11-0.20 mmol/L). In cases, the association with early MI risk remained statistically significant after adjustment for triglycerides (p = 0.006). CONCLUSIONS The APOA5-1131C allele, associated with higher fasting triglyceride levels, strongly affects the risk for early-onset MI, even after adjusting for triglycerides. This raises the possibility that APOA5-1131T>C may affect the risk of early MI over and above effects mediated by triglycerides.

64-slice computed tomography coronary angiography: diagnostic accuracy in the real world

PurposeThis study was done to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis in the real clinical world.Materials and methodFrom the CTCA database of our institution, we enrolled 145 patients (92 men, 52 women, mean age 63.4 ± 10.2 years) with suspected coronary artery disease. All patients presented with atypical or typical chest pain and underwent CTCA and conventional coronary angiography (CA). For the CTCA scan (Sensation 64, Siemens, Germany), we administered an IV bolus of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). The CTCA and CA reports used to evaluate diagnostic accuracy adopted ≥50% and ≥70%, respectively, as thresholds for significant stenosis.ResultEleven patients were excluded from the analysis because of the nondiagnostic quality of CTCA. The prevalence of disease demonstrated at CA was 63% (84/134). Sensitivity, specificity and positive and negative predictive values for CTCA on a per-segment, per-vessel, and per-patient basis were 75.6%, 85.1%, 97.6%; 86.9%, 81.8%, 58.0%; 48.2%, 68.1%, 79.6%; and 95.7%, 92.3%, 93.5%, respectively. Only two out of 134 eligible patients were false negative. Heart rate did not significantly influence diagnostic accuracy, whereas the absence or minimal presence of coronary calcification improved diagnostic accuracy. The positive and negative likelihood ratios at the per-patient level were 2.32 and 0.041, respectively.ConclusionCTCA in the real clinical world shows a diagnostic performance lower than reported in previous validation studies. The excellent negative predictive value and negative likelihood ratio make CTCA a noninvasive gold standard for exclusion of significant coronary artery disease.RiassuntoObiettivoValutare l’accuratezza diagnostica dell’angiografia coronarica non invasiva con tomografia computerizzata (CT-CA) a 64 strati nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥50%) basando la valutazione sulla refertazione clinica.Materiali e metodiDal database della CT-CA sono stati arruolati nello studio 145 pazienti (92 maschi, 52 femmine, età media 63,4±10,2 anni) con sospetta malattia coronarica. I pazienti si presentavano con dolore toracico atipico o angina pectoris stabile e hanno poi eseguito CT-CA e coronarografia convenzionale (CAG). Per la scansione CT-CA (Sensation 64, Siemens, Germania) sono stati iniettati endovena 100 ml di mezzo di contrasto. (Iomeprol 400 mgI/ml, Bracco, Italia). I referti della CT-CA e della CAG sono utilizzati per la valutazione dell’accuratezza diagnostica utilizzano la definizione di stenosi ≥50% per la CT-CA e ≥70% per la CAG.RisultatiUndici pazienti sono stati esclusi dall’analisi per CT-CA di qualità insufficiente. La prevalenza di malattia dimostrata alla CAG era del 63% (84/134). Sensibilità, specificità, valore predittivo positivo e negativo della CT-CA nella determinazione delle stenosi significative utilizzando un’analisi per segmento, per vaso e per paziente sono risultate del 75,6%, 85,1%, 97,6%; 86,9%, 81,8%, 58,0%; 48,2%, 68,1%, 79,6%; e 95,7%, 92,3%, 93,5%, rispettivamente. Solo due pazienti su 134 eleggibili per lo studio sono risultati falsi negativi. La frequenza cardiaca non ha mostrato influenzare significativamente l’accuratezza diagnostica, mentre la presenza di scarse o assenti calcificazioni coronariche ha determinato un incremento dei valori di accuratezza diagnostica. I likelihood ratio positivo e negativo nell’analisi per paziente sono risultati 2,32 e 0,041, rispettivamente.ConclusioniLa CT-CA nel mondo reale mostra una performance diagnostica inferiore rispetto agli studi di validazione pubblicati in letteratura. I valori ottimali di valore predittivo negativo e likelihood ratio negativo collocano la CT-CA tra le metodiche non invasive gold standard per l’esclusione di malattia coronarica critica.

Evaluation of coronary atherosclerosis by multislice computed tomography in patients with acute myocardial infarction and without significant coronary artery stenosis: a comparative study with quantitative coronary angiography.

Background—It is known that 9% to 31% of women and 4% to 14% of men with acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at angiography. These patients represent a diagnostic and therapeutic challenge. Multislice computed tomography (CT) can noninvasively identify the presence of coronary plaques even in the absence of significant coronary artery stenosis. This study evaluated the role of 64-slice CT, in comparison with coronary angiography, in detecting and characterizing coronary atherosclerosis in patients with acute myocardial infarction without significant coronary artery stenosis. Methods and Results—Thirty consecutive patients with acute myocardial infarction but without significant coronary stenosis at coronary angiography underwent 64-slice CT. All coronary segments were quantitatively analyzed by means of coronary angiography (CA-QCA) and 64-slice CT (CT-QCA). Forty-seven (10.4%) of the 450 coronary segments were not evaluable by CT. The mean proximal reference diameters at CT-QCA and CA-QCA were, respectively, 2.88±0.75 mm and 2.65±0.9 mm; the overall correlation between CT-QCA and CA-QCA for quantification of reference diameter was rs=0.77; P<0.001. The mean percent stenosis was 14.4±8.0% at CT-QCA and 4.0±11.0% at CA-QCA and the correlation was rs=0.11; P=0.03. Overall CT-QCA showed the presence of 50 plaques, of which only 11 were detected by CA-QCA. CT-QCA identified 25 plaques in infarct-related coronary arteries. Positive remodeling was present in 38 of the 50 plaques (76%), with a higher prevalence in the coronary plaques not visualized by CA-QCA (82.1% versus 54.5%). Conclusions—CT-QCA correlates well with CA-QCA in terms of coronary reference diameter analysis, but not stenosis quantification. Multislice CT can detect coronary atherosclerotic plaques in segments of nonstenotic coronary arteries that are underestimated by CA and may have an incremental diagnostic value for the diagnosis of acute myocardial infarction in patients without significant coronary stenosis at CA.

Familial aggregation of early-onset myocardial infarction

BACKGROUND An inherited predisposition is an important factor in the etiology of myocardial infarction (MI) at a young age. However, the extent of the risk for early-onset MI in relatives of young patients is still unclear, due to the paucity of family history data. Hence familial aggregation of early-onset MI was investigated in a cohort of relatives of Italian patients who had survived MI who occurred at the age of 45 or earlier. METHODS In the framework of a case-control study, lifetime data and early-onset MI status for 11,696 relatives of cases and 8897 relatives of controls were collected using a standardized questionnaire. RESULTS Occurrence of early-onset MI in females was very uncommon (Kaplan-Meier risk=0.6%, 95% confidence interval (CI): 0.38-0.82%, for female case relatives), and significantly lower than that for male case relatives (5.0%, 95% CI: 4.41-5.56%). The hazard ratio (HR) for case relatives was approximately 3-fold greater than that for control aunts (taken as reference category). Risk for early-onset MI to siblings (HR=1.7, 95% CI: 1.33-2.18) was significantly different from that to parents (HR=0.9, 95% CI: 0.71-1.16). The familial risk ratio λ(R) was 2.6 (95% CI: 2.30-2.89) for case relatives, using control parents as reference population for early-onset MI risk estimates (i.e. 37 per 100,000 in fathers and 7 per 100,000 in mothers). CONCLUSION We evaluated the risk of early-onset MI by category of relatives, obtaining evidence for familial aggregation of the disease in this Italian sample and providing figures for genetic counselling and planning genetic epidemiological studies.

Protein Kinase C ε Expression in Platelets from Patients with Acute Myocardial Infarction

Objective Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C ε (PKCε) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKCε in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKCε with a pathophysiological role in the disease. Methods and Results We therefore studied platelet PKCε expression from 24 patients with myocardial infarction, 24 patients with stable coronary artery disease and 24 healthy subjects. Indeed, platelets from myocardial infarction patients expressed PKCε with a significant frequency as compared to both stable coronary artery disease and healthy subjects. PKCε returned negative during patient follow-up. The forced expression of PKCε in normal donor platelets significantly increased their response to adenosine diphosphate-induced activation and adhesion to subendothelial collagen. Conclusions Our data suggest that platelet generations produced before the acute event retain PKCε-mRNA that is not down-regulated during terminal megakaryocyte differentiation. Results are discussed in the perspective of peri-infarctual megakaryocytopoiesis as a critical component of myocardial infarction pathophysiology.

Antiplatelet therapy in acute coronary syndromes

Introduction: Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved. Areas covered: We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development). Expert opinion: This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of ‘personalised medicine’.

Response to the Letter by Opolski et al Regarding Article, “Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis”

We thank Opolski et al for their comments and appreciate their interest in our study.1 They raise several points, which we address below. As the authors note, coronary atherosclerosis is a common finding also in asymptomatic patients; indeed, we think that, in the special setting of patients with acute myocardial infarction proven by cardiac magnetic resonance imaging and without significant coronary stenosis, coronary atherosclerosis is often underestimated because of an apparently normal coronary angiogram. As a consequence, the diagnosis may be challenged, and patients may not receive an adequate secondary prevention therapy. The mechanisms of myocardial infarction in this setting are certainly multiple and are not related exclusively to atherosclerosis, but we think that the different distributions of …

Patients with non-ST segment elevation acute coronary syndromes managed without coronary revascularization: A population needing treatment improvement

NSTE-ACS patients are a heterogeneous population, with different clinical features and prognosis. A large proportion of them is medically managed, without any revascularization. In the EYSHOT and FAST-MI registries such patients were 40% and 35%, respectively. These patients are at higher risk of adverse cardiovascular events and have a worse prognosis compared with those receiving revascularization. Medically managed NSTE-ACS patients consist of different subgroups: those not undergoing coronary angiography, those without significant coronary artery disease, and those with coronary stenoses not referred to revascularization. Patients with NSTE-ACS for whom a conservative strategy without coronary angiogram is planned must be very carefully selected. In patients with comorbidities, frailty, or advanced age, a careful balance between benefits and risks is needed to choice the management strategy (perform or not coronary angiography and/or revascularization), as evidence-based medicine data are lacking in the setting of frailty and comorbidities. In this decisional process, it should be also taken into consideration the role of coronary anatomy in risk stratification and treatment guidance. NSTE-ACS patients managed without revascularization less frequently receive guideline-recommended pharmacological treatment. Dual antiplatelet therapy (DAPT) is recommended for 12months also in medically managed patients, after careful balancing of ischemic and bleeding risk. In these patients it is mandatory to optimize pharmacological treatment, including antiplatelet therapy, to improve outcome. In NSTE-ACS medically managed, the proportion of patients discharged with DAPT should be increased in comparison with current practice, and the use of ticagrelor in place of clopidogrel should be considered in selected patients.

I pazienti con sindrome coronarica acuta senza sopraslivellamento persistente del tratto ST non sottoposti a rivascolarizzazione coronarica: una popolazione sottotrattata

: Non-ST-elevation acute coronary syndromes (NSTE-ACS) represent one of the most common clinical presentations of ischemic heart disease. Patients with NSTE-ACS are a heterogeneous population, with different clinical features and prognosis. A significant proportion of this population is medically managed, without any revascularization. In the Italian EYESHOT and French FAST-MI registries, patients managed with a conservative strategy were 40% and 35%, respectively. NSTE-ACS patients not undergoing coronary revascularization are at higher risk of adverse cardiovascular events and have a worse prognosis, including short- and long-term mortality, compared with those receiving revascularization. Patients with NSTE-ACS medically managed consist of three different subgroups: those not undergoing coronary angiography, those receiving coronary angiography and without significant coronary artery disease, and those with significant coronary artery disease at angiography but not receiving revascularization. Patients presenting with NSTE-ACS for whom a conservative strategy without coronary angiography is planned should be selected very carefully and coronary angiography should not be denied because of the lack of on-site cath-lab facilities. In addition, advanced age alone, in the absence of severe comorbidities or frailty, should not be considered as a reason for denying coronary angiography and, in general, optimal treatment. Given that evidence-based data are lacking, a careful balance between benefits and risks is needed in the decision to perform or not coronary angiography and/or revascularization in patients with important comorbidities, or frailty, or advanced age. In this decisional process, it should be also taken into consideration the role of coronary anatomy in risk stratification and treatment guidance.NSTE-ACS patients managed without revascularization less frequently receive guideline-recommended pharmacological treatment. Dual antiplatelet therapy is recommended for 12 months also in medically managed patients, after careful balance of ischemic and bleeding risk. Indeed, in this group of patients it is mandatory to optimize pharmacological treatment, including antiplatelet therapy, in order to improve clinical outcome. In NSTE-ACS not undergoing revascularization, the proportion of patients discharged with dual antiplatelet therapy should be increased in comparison to current clinical practice, and the use of ticagrelor instead of clopidogrel should be considered in selected patients.