Spontaneous Coronary Artery Dissection: A Review of Epidemiology, Pathophysiology and Principles of Management.

Spontaneous coronary artery dissection (SCAD) is a sudden rupture of coronary artery wall leading to false lumen and intramural hematoma formation. It commonly occurs in young and middle-aged women lacking typical cardiovascular risk factors. Fibromuscular dysplasia and pregnancy are strongly associated with SCAD. To date, the "inside-out" and "outside-in" are the 2 proposed hypothesis for the pathogenesis of SCAD. Coronary angiography is the gold standard and first line diagnostic test. Three types of SCAD have been described according to coronary angiogram. Intracoronary imaging modalities are reserved for patients with ambiguous diagnosis or to guide percutaneous coronary intervention view the increased risk of secondary iatrogenic dissection. The management of SCAD includes conservative approach, coronary revascularization strategies accounting for percutaneous coronary intervention and coronary artery bypass graft, and long-term follow-up. The overall prognosis of patients with SCAD is favorable marked by a spontaneous healing in a large proportion of cases.

Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome.

Background: The discovery of novel biomarkers that improve current cardiovascular risk prediction models of acute coronary syndrome (ACS) is needed for the identification of very high-risk patients and therapeutic decision-making. Autophagy is a highly conserved catabolic mechanism for intracellular degradation of cellular components through lysosomes. The autophagy process helps maintain cardiac homeostasis and dysregulated autophagy has been described in cardiovascular conditions. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) is a key regulator of autophagy with a potential role in cardiac stress. Objectives: The aims of the present study were to assess whether changes in circulating Rubicon levels are associated with ACS and to evaluate the added value of Rubicon to a clinical predictive risk model. Methods and results: The study population included ACS patients (n = 100) and control subjects (n = 99) at high to very high cardiovascular risk but without known coronary event. Plasma Rubicon levels were measured in the whole study population by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses established that Rubicon levels were inversely associated with ACS. A receiver operating characteristic curve analysis demonstrated that the addition of Rubicon improved the predictive performance of the model with an increased area under the curve from 0.868 to 0.896 (p = 0.038). Conclusions: Plasma levels of the autophagy regulator Rubicon are associated with ACS and provide added value to classical risk markers for ACS.

Incidence, management, and prognosis of post-ischaemic ventricular septal defect: Insights from a 12-year tertiary centre experience.

Background: Among mechanical complications of acute myocardial infarction, ventricular septal defect (VSD) is uncommon but still serious. The evolution of emergency coronary revascularisation paradoxically decreased our knowledge of this disease, making it even rarer. Aim: To describe ischaemic VSD incidence, management, and associated in-hospital and 1-year outcomes over a 12-years period. Methods: A retrospective single-centre register of patients managed for ischaemic VSD between January 2009 and December 2020. Results: Ninety-seven patients were included representing 8 patients/ years and an incidence of 0.44% of ACS managed. The majority of the patients were 73-years-old males (n = 54, 56%) with STEMI presentation (n = 75, 79%) and already presented with Q necrosis on ECG (n = 70, 74%). Forty-nine (51%) patients underwent PCI, 60 (62%) inotrope/vasopressors infusion, and 70 (72%) acute mechanical circulatory support (IABP 62%, ECMO 13%, and Impella® 3%). VSD surgical repair was performed for 44 patients (45%) and 1 patient was transplanted. In-hospital mortality was 71%, and 86% at 1 year, without significant improvement over the decade. Surgery appears to be a protective factor [0.51 (0.28-0.94) p = 0.003], whereas age [1.06 (1.03-1.09), p < 0.001] and lactate [1.16 (1.09-1.23), p < 0.001] were linked to higher 1-year mortality. None of the patients that were managed medically survived 1 year. Conclusion: Post-ischaemic VSD is a rare but serious complication still associated with high mortality. Corrective surgery is associated with better survival, however, timing, patient selection, and a place for mechanical circulatory support need to be defined.

Evaluation of Mitral and Aortic Valvular Disease and Left Ventricular Dysfunction in a Lebanese Population: Retrospective Single-Center Experience.

BACKGROUND Recently, new therapeutic approaches have revolutionized the management of left ventricular dysfunction (LVD) and valvular heart disease (VHD), which are a growing public health problem. In parallel, there are no available epidemiological data about LVD and VHD in developing countries, especially in the Mediterranean area. This retrospective study was conducted at a single center and aimed to evaluate the associations between mitral and aortic valvular disease and left ventricle systolic and diastolic dysfunction in the Lebanese population. MATERIAL AND METHODS A retrospective study was conducted of 4520 consecutive patients aged >18 years who were referred to the Cardiovascular Department of Notre Dame de Secours-University Hospital in Jbeil-Lebanon for transthoracic echocardiography between December 2016 and December 2019. The study population was divided into different groups based on types of LVD and VHD. Left ventricle systolic dysfunction was defined as a left ventricle ejection fraction (EF) ≤40%. Statistical analysis was carried out using SPSS software version 20. RESULTS VHD and systolic dysfunction were more common in men, whereas diastolic dysfunction was more common in women. Being older than age 65 years and smoking were significantly associated with heart failure with preserved EF, whereas female sex was a significant preventive factor against heart failure with reduced EF. Systemic hypertension was correlated with mitral stenosis and tricuspid regurgitation, whereas diabetes mellitus was associated with tricuspid regurgitation (TR). Smoking and older age also appeared to be associated with aortic stenosis. CONCLUSIONS Mitral valve disease (regurgitation and stenosis) was significantly correlated with systolic dysfunction, whereas aortic and mitral regurgitation were associated with diastolic dysfunction. Better monitoring of cardiovascular disease risk factors may lead to a reduced burden of LVD and VHD.

Incidental discovery of right ventricular lipoma in a young female associated with ventricular hyperexcitability: An imaging multimodality approach.

BACKGROUND: Cardiac lipomas are rare benign tumors commonly found in the right atrium or left ventricle. Patients are usually asymptomatic, and clinical presentation depends on location and adjacent structures impairment. Right ventricle lipomas are scarce in the literature. Moreover, the previous published cases were reported in over 18-year-old patients. CASE SUMMARY: We report a giant right ventricle lipoma discovered incidentally in a 17-year-old female while performing preoperative work-up. The diagnosis was confirmed by histopathological examination, and a conservative approach was performed. CONCLUSION: Multimodal cardiac imaging and histopathological examination are required for a definitive diagnosis. The therapeutic approach depends on clinical presentation.

Long-term Prognostic Impact of Physical Activity in Patients With Stable Coronary Heart Disease.

Stable coronary heart disease (CHD) patients are advised to practice regular physical activity (PA). However, data on very long-term prognosis impact of regular exercise remain scarce. We aimed to evaluate the impact of physical activity level on mortality at long term in stable CHD patients. We analyzed 822 patients with stable CHD. They answered questionnaires on medical history, underwent a standardized clinical examination, and provided a fasting blood sample. PA was evaluated by the MOSPA questionnaire. Three tertiles of patients were individualized according to PA level: 0.0-9 Metabolic Equivalent of Task (METs) hour per week (n = 267); 10-39.9 METs hour per week (n = 279); and ≥40 METs hour per week (n = 276). After a median follow-up of 14.6 years, 324 patients had died. In a multivariate analysis adjusted for age, dyslipidemia, smoking status, diabetes, high blood pressure, waist circumference, left ventricular ejection fraction, Gensini score, heart rate, ankle-brachial index and duration of disease, physical activity was significantly and independently associated with all-cause mortality. Compared to the lowest PA tertile, both the median and the highest PA tertiles, were associated to a reduction of all-cause mortality risk with hazard ratios at 0.79 (95%confidence interval [0.61:1.03], P = 0.08) and 0.71 ([0.53:0.96], P = 0.025) respectively; P for trend = 0.02. Adjusted hazard ratios for an increase of 10 METs hour per week was 0.95 [0.92 to 0.98], (P <0.002). In conclusion, our study demonstrates an independent association between PA and long term vital prognosis with a 5% total mortality decrease for an increase of 10 METs hour per week.

Coronary angiography in the setting of acute infective endocarditis requiring surgical treatment.

BACKGROUND: International guidelines recommend that preoperative coronary angiography is performed on patients at risk of coronary disease who have infective endocarditis requiring surgical treatment. However, the risks of contrast-induced nephropathy or vegetation embolization in case of aortic endocarditis should be considered. AIMS: To assess the safety, therapeutic implications and prognostic impact of coronary angiography in patients requiring surgical treatment for active infective endocarditis. METHODS: This retrospective monocentric study was conducted in patients referred to a tertiary care centre for active endocarditis management with a theoretical indication for surgery between January 2013 and February 2017. RESULTS: One hundred and ninety-three patients were included; 73.1% were men, the mean age was 61.9±16.3 years and the median EuroSCORE II was 5.8%. One hundred and nineteen patients (61.7%) had aortic endocarditis, which was associated with aortic vegetation in 74 cases (38.3%). Invasive coronary angiography was performed in 142 patients (73.6%) - 130 (91.6%) by radial approach - and 14 patients were evaluated by coronary multislice computed tomography (one patient had exploration with both techniques). Acute renal failure after coronary angiography was observed in 15 patients (10.6%), two patients (1.4%) presented a stroke within 24h after coronary angiography, but none had aortic endocarditis. Among the 178 patients (92.2%) who underwent surgery, 35 (19.7%) had significant coronary lesion(s) and 25 (14.0%) underwent an associated coronary artery bypass graft. CONCLUSIONS: Preoperative coronary angiography in patients affected by infective endocarditis provides relevant information in a significant proportion of patients and can be performed safely.

In-hospital outcomes and 5-year mortality following an acute myocardial infarction in patients with a history of cancer: Results from the French registry on Acute ST-elevation or non-ST-elevation myocardial infarction (FAST-MI) 2005 cohort.

BACKGROUND: Cancer and acute myocardial infarction (AMI) have important prognostic consequences. Treatment of some cancers may affect coronary artery disease, myocardial function and/or AMI management. Whether the early and long-term mortality of patients with AMI differ according to their history of cancer remains questionable. AIMS: To determine in-hospital outcomes and 5-year mortality following AMI according to patient history of cancer. METHODS: The FAST-MI registry is a nationwide French survey collecting data on characteristics, management and outcomes of 3670 consecutive patients admitted for AMI during October 2005. RESULTS: Overall, 246/3664 patients (6.7%) admitted for an AMI (47.6% with ST-segment elevation myocardial infarction [STEMI]; 52.4% with non-STEMI [NSTEMI]) had a history of cancer. In-hospital mortality was not significantly different for patients with versus without a history of cancer, overall (adjusted odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0.68-1.94; P=0.61) and in patients with STEMI (adjusted OR: 1.37, 95% CI: 0.69-2.71; P=0.37) or NSTEMI (adjusted OR: 0.97, 95% CI: 0.41-2.28; P=0.95). All-cause mortality at 5 years was higher among patients with a history of cancer (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.08-1.69; P=0.008), whereas 5-year cardiovascular mortality did not differ (adjusted HR: 1.17, 95% CI: 0.89-1.53; P=0.25), regardless of whether the patients had STEMI or NSTEMI. Similar results were found in populations matched on a propensity score including baseline characteristics and early management. CONCLUSION: A history of cancer, per se, does not appear to be a risk factor for increased in-hospital mortality or long-term cardiovascular mortality in patients admitted for AMI.

Effects of remote ischemic conditioning on kidney injury in at-risk patients undergoing elective coronary angiography (PREPARE study): a multicenter, randomized clinical trial.

The ability of remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN) following percutaneous coronary angiography in at-risk patients is controversial. No evidence exists regarding potential RIPC positive effects on renal function and clinical outcomes in the long-term. The PREPARE study was a randomized, prospective, multicenter, and double-blinded trial. A total of 222 patients scheduled for coronary angiography and/or percutaneous transluminal coronary angioplasty with an estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2, or eGFR between 40 and 60 mL/min/1.73 m2 and two further risk factors were allocated to RIPC or control groups. Preventive measures were applied to all patients, including continuous intravenous saline infusion, withdrawal of nephrotoxic drugs, and limited volume of contrast medium. The primary endpoint, namely incidence of CIN, was 3.8% in the control group and 5.1% in the RIPC group (p = 0.74). The secondary endpoints, i.e., changes in serum creatinine and eGFR levels from baseline to 48 hours and from baseline to 12 months following contrast medium exposure, did not differ between both groups. The incidences of all major clinical events at 12 months were similar in both groups. In this population at risk of CIN, preventive strategies were associated with low CIN incidence. RIPC impacted neither the CIN incidence nor both the renal function and clinical outcomes at 1-year follow-up.

Re-endothelialisation after Synergy stent and Absorb bioresorbable vascular scaffold implantation in acute myocardial infarction: COVER-AMI study.

BACKGROUND/AIMS: Drug eluting stent (DES) decrease the risk of restenosis by reducing the neointimal response. However, DES may impair strut coverage, and this has been associated with late stent/scaffold thrombosis. Bioresorbable vascular scaffold (BVS) may overcome the risk of stent/scaffold thrombosis when completely resorbed. The purpose of this randomised trial was to compare the arterial healing response in the short term, as a surrogate for safety and efficacy, between the metallic everolimus-eluting stent (Synergy; Boston Scientific, Marlborough, MA, USA) and the everolimus BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) in the particular setting of acute myocardial infarction (AMI). This pilot study sought to compare the neointimal response of metallic everolimus DES (Synergy) with polymeric everolimus BVS (Absorb) by optical coherence tomography (OCT) 3 months after an AMI. METHODS: COVER-AMI was a single-centre, single-blind, non-inferiority, randomised controlled trial. Patients with ST segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention were randomly allocated (1:1) to treatment with the Synergy DES or Absorb BVS. The primary endpoint was the 3-month neointimal response assessed as the percentage of uncovered struts, neointimal thickness, in-stent/scaffold area obstruction, and pattern of neointima. The main secondary endpoint included the device-oriented composite endpoint according to the Academic Research Consortium definition. RESULTS: Twenty patients without clinical and/or angiographic complications (Synergy (n = 10) or BVS (n = 10); mean age 59.0 years; 20% female) were enrolled in our centre. The stent diameter was higher in the Synergy group (3.7 ± 0.4 mm vs 3.4 ± 0.4 mm in the BVS group, p = 0.01). At 3 months, no significant differences in angiographic lumen loss were observed between the everolimus DES and everolimus BVS (0.04 mm (IQR 0.00-0.07) vs 0.11 mm (IQR 0.04-0.31), p = 0.165). OCT analysis of 420 cross-sections showed that the total neointimal area and in-stent obstruction were lower in the Synergy group, while OCT analysis at the strut level (n = 3942 struts) showed that the rate of uncovered struts was lower in the BVS group. CONCLUSIONS: Stenting of culprit lesions in the setting of STEMI resulted in a nearly complete arterial healing for both the Synergy and the BVS devices. Lower neointimal thickness and in-stent obstruction but a higher rate of uncovered struts were observed in the Synergy group. These findings provide the basis for further exploration in clinically oriented outcome trials.

Common p2y13 polymorphisms are associated with plasma inhibitory factor 1 and lipoprotein(a) concentrations, heart rate and body fat mass: The GENES study.

BACKGROUND: The P2Y13 purinergic receptor regulates hepatic high-density lipoprotein uptake and biliary sterol secretion; it acts downstream of the membrane ecto-F1-adenosine triphosphatase, which generates extracellular adenosine diphosphate that selectively activates P2Y13, resulting in high-density lipoprotein endocytosis. Previous studies have shown that the serum concentration of the F1-adenosine triphosphatase inhibitor inhibitory factor 1 is negatively associated with cardiovascular risk. AIM: To evaluate whether p2y13 genetic variants affect cardiovascular risk. METHODS: Direct sequencing of the p2y13 coding and flanking regions was performed in a subcohort of 168 men aged 45-74 years with stable coronary artery disease and 173 control subjects from the GENES study. The two most frequent mutations, rs3732757 and rs1466684, were genotyped in 767 patients with coronary artery disease and 789 control subjects, and their association with cardiovascular risk markers was analysed. RESULTS: Carriers of the rs3732757 261T and rs1466684 557G alleles represented 9% and 27.5% of the entire population, respectively. The allele frequencies were identical in patients with coronary artery disease and control subjects. The presence of 261T was associated with higher concentrations of plasma lipoprotein A-I and inhibitory factor 1, increased fat mass and a lower heart rate. Moreover, the proportion of patients with coronary artery disease with a pejorative systolic ankle-brachial index was lower in carriers of the 261T allele. In both populations, the 557G allele was associated with increased concentrations of lipoprotein(a), and an allele dose effect was observed. CONCLUSIONS: Two frequent p2y13 variants are associated with specific bioclinical markers of cardiovascular risk. Although neither one of these variants appears to be related to the development of atherosclerotic disease, they may modulate the risk of additional cardiovascular complications.

Long-term outcomes of rotational atherectomy of underexpanded stents. A single center experience.

OBJECTIVES: To analyze the procedural and long-term outcomes of the use of rotational atherectomy (RA) in underexpanded stents in our cohort and to provide an overview of currently available data on this technique. BACKGROUND: Stent underexpansion (SU) has been related to stent thrombosis and restenosis. RA has been used to treat undilatable SU as a bail-out strategy with encouraging results. METHODS: This is an observational, single-center study. We included patients who underwent stentablation between 2013 and 2017. Baseline demographics, procedural results, in-hospital major adverse cardiac events (MACE), and long-term follow-up MACE were retrospectively collected. RESULTS: A total of 11 patients (90.9% males, mean age 65.4 ± 18.6) were included in this study. Median left ventricle ejection fraction was 53.5% [46.2-55]. Median calculated Syntax score was 16 [9-31] and 45.5% of patients were admitted for acute coronary syndrome. Radial approach was used in 63.6% of cases. Most patients only required one burr (45% used a 1.5 mm diameter burr) during the intervention. Procedural success was achieved in 90.9% of the cases. Acute lumen gain was 42.7% [30.7-61.49]. There were no in-hospital deaths or MACE. At a median follow-up of 26 months, only one patient (9.1%) suffered MACE in the context of acute coronary syndrome, and two patients (18.2%) required non-target lesion revascularization. No deaths were reported. CONCLUSIONS: RA of under expanded stents is a feasible option with a high rate of procedural success. At long-term follow-up, all of them were alive and 90.9% of patients remained free from MACE.

Absolute iron deficiency without anaemia in patients with chronic systolic heart failure is associated with poorer functional capacity.

BACKGROUND: Functional status is one of the main concerns in the management of heart failure (HF). Recently, the FAIR-HF and CONFIRM-HF trials showed that correcting anaemia using intravenous iron supplementation improved functional variables in patients with absolute or relative iron deficiency. Relative iron deficiency is supposed to be a marker of HF severity, as ferritin concentration increases with advanced stages of HF, but little is known about the impact of absolute iron deficiency (AID). AIMS: To study the impact of AID on functional variables and survival in patients with chronic systolic HF. METHODS: One hundred and thirty-eight non-anaemic patients with chronic systolic HF were included retrospectively. Patients were divided into two groups according to iron status: the AID group, defined by a ferritin concentration<100µg/L and the non-AID group, defined by a ferritin concentration≥100µg/L. Functional, morphological and biological variables were collected, and survival was assessed. RESULTS: Patients in the AID group had a poorer 6-minute walking test (342 vs. 387m; P=0.03) and poorer peak exercise oxygen consumption (13.8 vs. 16.0mL/min/kg; P=0.01). By multivariable analysis, ferritin<100µg/L was associated with impaired capacity of effort, assessed by peak exercise oxygen consumption. By multivariable analysis, there was no difference in total mortality between groups, with a mean follow-up of 5.1±1.1 years. CONCLUSIONS: The poorer functional evaluations in iron-deficient patients previously reported are not caused by the merging of two different populations (i.e. patients with absolute or relative iron deficiency). Our study has confirmed that non-anaemic HF patients with AID have poorer peak oxygen consumption. However, AID has no impact on the survival of these patients.

Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study.

BACKGROUND: Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. METHOD: Serum IF1 levels were measured in 577 male participants with stable CAD (age 45-74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. RESULTS: IF1 levels were positively correlated with HDL-C (r s = 0.40; P < 0.001) and negatively with triglycerides (r s = -0.21, P < 0.001) and CAD severity documented by the Gensini score (r s = -0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38-0.89 and 0.50 (0.28-0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02). CONCLUSIONS: We investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy.

The medical history of adults with complex congenital heart disease affects their social development and professional activity.

BACKGROUND: In recent decades, advances in surgery and therapeutic catheterization have steadily increased the life expectancy and prevalence of adults with congenital heart disease (CHD). AIMS: We assessed medical and psychosocial variables of adults with CHD, according to the disease complexity. METHODS: We included, from a single-centre observational cohort study, 135 consecutive adults with CHD (median age of 40 years, interquartile range: 28.0-51.0) followed in our cardiology unit, who answered a questionnaire assessing daily activity and psychosocial functioning. Disease complexity was classified according to the Bethesda conference. RESULTS: Cardiac malformation complexity was simple in 61 (45.2%), moderate in 50 (37.0%) and complex in 24 (17.8%) patients. Cardiac surgery had been performed in 86.5% of moderate and complex patients. Complications (such as heart failure, arrhythmia and pulmonary hypertension) were mainly observed in the complex group (P=0.003). Physical activity was lower in the complex group (no activity in 58.8%, but sport previously contraindicated in 50% of these; P=0.03). Education level tended to be lower in the complex and moderate groups than in the simple group (respectively, 31.2% and 33.3% vs. 45.7% had passed the Baccalaureate; P=0.47). The pass rate was lower in patients with complications (P=0.037) or more than one cardiac surgery (P=0.03). In the complex group, 56.3% of patients were unemployed (P=0.048). CONCLUSIONS: Complexity of heart disease and medical history affect education level and employment of adults with CHD. Academic education of children with a complex defect and career counselling are important to prevent unemployment among adults with CHD.

Targeting high-density lipoproteins: update on a promising therapy.

Numerous epidemiological studies have demonstrated the atheroprotective roles of high density lipoproteins (HDL), so that HDL is established as an independent negative risk factor. The protective effect of HDL against atherosclerosis is mainly attributed to their capacity to bring peripheral excess cholesterol back to the liver for further elimination into the bile. In addition, HDL can exert other protective functions on the vascular wall, through their anti-inflammatory, antioxidant, antithrombotic and cytoprotective properties. HDL-targeted therapy is thus an innovative approach against cardiovascular risk and atherosclerosis. These pleiotropic atheroprotective properties of HDL have led experts to believe that "HDL-related therapies" represent the most promising next step in fighting against atherosclerosis. However, because of the heterogeneity of HDL functions, targeting HDL is not a simple task and HDL therapies that lower cardiovascular risk are NOT yet available. In this paper, an overview is presented about the therapeutic strategies currently under consideration to raise HDL levels and/or functions. Recently, clinical trials of drugs targeting HDL-C levels have disappointingly failed, suggesting that HDL functions through specific mechanisms should be targeted rather than increasing per se HDL levels.

Prognostic usefulness of clinical and subclinical peripheral arterial disease in men with stable coronary heart disease.

The prognostic value of symptomatic peripheral arterial disease (PAD) in patients with coronary heart disease (CHD) is well documented, but few reports differentiating between symptomatic and asymptomatic forms of PAD are available. We investigated the respective prognostic effect of clinical and subclinical PAD on long-term all-cause mortality in patients with stable CHD. We analyzed 710 patients with stable CHD referred for hospitalization for CHD evaluation and management. As a part of the study, they completed questionnaires on medical history, underwent a standardized clinical examination, including ankle-brachial index (ABI) measurement, and provided a fasting blood sample. Three groups of patients were individualized: no PAD (no history of PAD and ABI >0.9 but ≤1.4); subclinical PAD (no history of PAD but abnormal ABI [i.e., ≤0.9 or >1.4); and clinical PAD (history of claudication, peripheral arterial surgery, or amputation due to PAD). Clinical and subclinical PAD was present in 83 (11.7%) and 181 (25.5%) patients, respectively. After a median follow-up of 7.2 years, 130 patients died. On multivariate analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking, left ventricular ejection fraction, CHD duration, heart rate, history of stroke or transient ischemic attack, and coronary revascularization, previous clinical PAD (hazard ratio 2.11, 95% confidence interval 1.28 to 3.47) and subclinical PAD (hazard ratio 1.65, 95% confidence interval 1.11 to 2.44) were significantly associated with increased all-cause mortality. In conclusion, our study has demonstrated that the detection of subclinical PAD by ABI in patients with stable CHD provides additional information for long-term mortality risk evaluation.

A simple nomogram for early prediction of myocardial reperfusion after pre-hospital thrombolysis.

AIMS: To discriminate early ST-segment elevation myocardial infarction (STEMI) presenters at a high probability of successful pre-hospital thrombolysis (PHT) using a simple nomogram based on independent predictors of complete ST resolution. METHODS AND RESULTS: OPTIMAL was an observational, prospective study undertaken at 79 medical centres in France in patients with STEMI undergoing pre-hospital thrombolysis (PHT) within six hours of symptom onset and coronary angiography within six hours of thrombolysis. The baseline and pre-coronary angiography ECGs of 800 patients were analysed. The main outcome measure was ST segment resolution ≥ 70%. ST resolution was associated with a significant reduction in mortality (1.8% vs. 4.3%; p=0.05). After multivariable logistic regression analysis, five independent predictors of successful myocardial reperfusion were identified: ≤ 1 h between pain onset and thrombolysis (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.18-2.62); body mass index (BMI) <30 kg/m2 (OR 1.74, CI 1.12-2.72); current/previous smoking (OR 1.71, CI 1.21-2.43); non-anterior infarct territory (OR 1.75, CI 1.27-2.41); and maximum amplitude of ST elevation <3 mm (OR 1.83, CI 1.32-2.54). The C-statistic of the model was 0.71 (95% CI 0.67-0.74). Using these five independent factors, a simple nomogram was developed to assess the probability of ST resolution after PHT. This nomogram allows discrimination of probabilities ranging from 13 to 72%. CONCLUSIONS: This simple nomogram can predict the probability of successful myocardial reperfusion after thrombolysis. This may be useful in the triage of STEMI presenters.

Usefulness of initial glucose level to improve acute coronary syndrome diagnosis in the emergency department.

INTRODUCTION: The aim of the study was to analyse the incremental usefulness of high blood glucose level for non-ST elevation acute coronary syndrome (ACS) diagnosis in patients admitted to the emergency department (ED) for chest pain and suspected ACS. METHODS: A post hoc analysis of a prospective, observational study of 11 months duration was carried out. Initial glucose levels were analysed in 672 consecutive patients admitted to the ED with chest pain and suspected non-ST elevation ACS. A cut-off glucose level (>140 mg/dl) for high glucose level diagnosis was defined. Based on hospital diagnostic test results, patients were classified as having non-ST elevation ACS by two independent physicians. The association and performance of high glucose level for ACS diagnosis were studied by univariate and multivariate analysis and receiver operator characteristic (ROC) curves. RESULTS: Out of the 672 eligible patients who were recruited, 181 (26.9%) had a confirmed non-ST elevation ACS. The independent factors associated with a diagnosis of ACS were age, previous coronary artery disease, hyperlipidaemia, smoking status and glucose level >140 mg/dl (OR 1.98 95% CI 1.14 to 3.45). In addition to a predictive model that included the usual diagnostic tools for non-ST elevation ACS management, a glucose level >140 mg/dl added significant incremental information (p=0.03). However, the addition of blood glucose level >140 mg/dl to the conventional diagnostic tool resulted in small increases in the ability to classify ACS, as measured by the c-statistic (0.82, 95% CI 0.79 to 0.85). CONCLUSION: An initial serum glucose level >140 mg/dl is associated with non-ST elevation ACS in patients admitted to an ED for chest pain but added moderately to conventional tools used for ACS diagnosis. CLINICAL TRIAL NUMBER: NCT00714298.

Variations in duration and composition of the excitable gap around the tricuspid annulus during typical atrial flutter.

BACKGROUND: Differences in the duration of the excitable gap along the reentry circuit during typical atrial flutter are poorly known. AIM: To prospectively evaluate and compare the duration and composition of the excitable gap during typical counterclockwise atrial flutter in different parts of the circuit all around the tricuspid annulus. METHODS: The excitable gap was determined by introducing a premature stimulus at various sites around the tricuspid annulus during typical counterclockwise atrial flutter in 34 patients. Excitable gap was calculated as the difference between the longest resetting coupling interval and the effective atrial refractory period. RESULTS: The duration of the excitable gap, the effective atrial refractory period and the resetting coupling interval differed significantly along the tricuspid annulus. Duration of excitable gap was significantly longer at the low lateral right atrium (79±22 ms) than at the cavotricuspid isthmus (66±23 ms; P=0.002). The effective atrial refractory period was significantly longer at the cavotricuspid isthmus (160±26 ms) than at the high lateral right atrium (149±29 ms; P=0.004). Other locations, such as coronary sinus ostium, right atrial septum and atrial roof displayed intermediate values. CONCLUSION: The duration of the excitable gap differed significantly along the tricuspid annulus, with a larger excitable gap at the lateral right atrium and a shorter excitable gap at the cavotricuspid isthmus, because of longer refractory periods at the isthmus.