Pascal Sbragia

Long-term follow-up of patients with short QT syndrome.

OBJECTIVES The aim of this study was to investigate the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (SQTS). BACKGROUND SQTS is a rare channelopathy characterized by an increased risk of sudden death. Data on the long-term outcome of SQTS patients are not available. METHODS Fifty-three patients from the European Short QT Registry (75% males; median age: 26 years) were followed up for 64 ± 27 months. RESULTS A familial or personal history of cardiac arrest was present in 89%. Sudden death was the clinical presentation in 32%. The average QTc was 314 ± 23 ms. A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1). Twenty-four patients received an implantable cardioverter defibrillator, and 12 patients received long-term prophylaxis with hydroquinidine (HQ), which was effective in preventing the induction of ventricular arrhythmias. Patients with a HERG mutation had shorter QTc at baseline and a greater QTc prolongation after treatment with HQ. During follow-up, 2 already symptomatic patients received appropriate implantable cardioverter defibrillator shocks and 1 had syncope. Nonsustained polymorphic ventricular tachycardia was recorded in 3 patients. The event rate was 4.9% per year in the patients without antiarrhythmic therapy. No arrhythmic events occurred in patients receiving HQ. CONCLUSIONS SQTS carries a high risk of sudden death in all age groups. Symptomatic patients have a high risk of recurrent arrhythmic events. HQ is effective in preventing ventricular tachyarrhythmia induction and arrhythmic events during long-term follow-up.

Short QT syndrome. Update on a recent entity.

The short QT syndrome, a recently discovered ion channel disorder, combines shortened repolarization, a predisposition to atrial and ventricular fibrillatory arrhythmias, and a risk of sudden death. Few cases have been reported, but the prevalence may be underestimated. This syndrome might account for some cases of unexplained ventricular fibrillation in patients with otherwise healthy hearts. Patients have abnormally short QT intervals and refractory periods, and atrial/ventricular fibrillation can be triggered during investigations. Gain-of-function mutations have been detected in three genes encoding potassium channels. Treatment is based on defibrillator implantation, sometimes as a preventive measure. Quinidine may be beneficial in certain cases.

Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention

Objective: To evaluate the effect of pre-procedural acute oral administration of trimetazidine (TMZ) on percutaneous coronary intervention (PCI)-induced myocardial injury. Design: Single-centre, prospective, randomised evaluation study. Setting: Patients with stable angina pectoris and single-vessel disease undergoing PCI. Patients: 582 patients were prospectively randomised. Patients who underwent more than one inflation during PCI were excluded, resulting in 266 patients randomly assigned to 2 groups. Interventions: Patients were randomly assigned to receive or not an acute loading dose of 60 mg of TMZ prior to intervention. Main outcome: The frequency and the increase in the level of cardiac troponin Ic (cTnI) after successful PCI. cTnI levels were measured before and 6, 12, 18 and 24 h after PCI. Results: 136 patients were assigned to the TMZ group and 130 to the control group. Although no statistically significant difference was observed in the frequency of cTnI increase between the two groups, post-procedural cTnI levels were significantly reduced in the TMZ group at all time points (6 h: mean (SD) 4.2 (0.8) vs 1.7 (0.2), p<0.001; 12 h: 5.5 (1.5) vs 2.3 (0.4), p<0.001; 18 h: 9 (2.3) vs 3 (0.5), p<0.001; and 24 h: 3.2 (1.2) vs 1 (0.5), p<0.001). Moreover, the total amount of cTnI released after PCI, as assessed by the area under the curve of serial measurement, was significantly reduced in the TMZ group (p<0.05). Conclusion: Pre-procedural acute oral TMZ administration significantly reduces PCI-induced myocardial infarction.

Differences in twelve-lead electrocardiogram between symptomatic and asymptomatic subjects with short QT interval

rom the *Department of Medicine, Päijät-Häme Central Hospital, Lahti, Finland, Institute of Clinical Medicine, epartment of Internal Medicine, University of Oulu, Oulu, Finland, 1st Department of Medicine, University Hospital annheim, University of Heidelberg, Mannheim, Germany, Department of Cardiology, Cardinal Massaia Hospital, Asti, taly, Federation of Cardiology, University Hospital Ranqueil, Toulouse, France, Division of Cardiology, Hospital Nord, arseille, France, **Hopital Cardiologique du Haut-Leveque, Bordeaux-Pessac, France, and Montreal Heart Institute, ontreal, Quebec, Canada.

Predictors of B-type natriuretic peptide and left atrial volume index in patients with preserved left ventricular systolic function: An echocardiographic-catheterization study

BACKGROUND B-type natriuretic peptide (BNP) and left atrial volume index (LAVi) are used as surrogate measures for global myocardial function and are recommended for the diagnosis of heart failure with normal ejection fraction. Little is known, however, about predictors in patients with preserved systolic function. AIMS To identify factors that influence the relation of BNP and left atrial size to invasively determined left ventricular end-diastolic pressure in stable patients with preserved left ventricular systolic function. METHODS Fifty-nine consecutive patients were included prospectively. Clinical, biological, Doppler echocardiographic and invasive variables were collected simultaneously. RESULTS BNP was predicted independently by left ventricular ejection fraction, diastolic function and age (p<0.05). LAVi was predicted independently by left ventricular mass index and invasive left ventricular end-diastolic pressure (p<0.01). BNP predicted increased left ventricular end-diastolic pressure greater than 16 mmHg (p=0.004); the optimal cut-off value was 33 pg/mL (area under the receiver-operating characteristic curve [AUC] 0.74 [0.6-0.84], p<0.001, sensitivity 72%, specificity 70%). LAVi predicted increased left ventricular end-diastolic pressure (p<0.001); the optimal cut-off value for LAVi was 26 mL/m(2) (AUC 0.87 [0.75-0.94], p<0.001; sensitivity 85%, specificity 80%). Unlike BNP (p=0.1), LAVi performed well in patients with abnormal relaxation at mitral filling (p<0.01). CONCLUSION BNP is influenced by age in stable patients with preserved systolic function and should be interpreted cautiously. LAVi is a powerful surrogate for invasively determined left ventricular end-diastolic pressure regardless of age and mitral filling.

Non-invasive coronary angiography for patients with acute atypical chest pain discharged after negative screening including maximal negative treadmill stress test. A prospective study

UNLABELLED Among patients admitted in the emergency department for acute atypical chest pain those with an acute coronary syndrome (ACS) who are mistakenly discharged home have high mortality. A recent retrospective study has demonstrated that multislice computed tomography (MSCT) coronary angiography could improve triage of these patients. We aimed to prospectively confirm these data on patients with a negative screening including maximal treadmill stress. PATIENTS 30 patients discharged from the emergency department after negative screening for an ACS were included. All patients underwent MSCT angiography of the coronary artery. Patients with coronary atheroma on MSCT had an invasive coronary angiography to confirm these findings. RESULTS Seven patients (23%) had obstructive coronary artery disease on MSCT. Invasive coronary angiography (ICA) confirmed the diagnosis in all patients. CONCLUSION In patients with no previously known coronary artery disease admitted to the emergency department with atypical acute chest pain and discharged after negative screening, including maximal treadmill stress test, MSCT coronary angiography is useful for the diagnosis of obstructive coronary artery disease.

PQ segment depression in patients with short QT syndrome: A novel marker for diagnosing short QT syndrome?

BACKGROUND Patients with short QT syndrome (SQTS) have an increased risk for atrial tachyarrhythmias, ventricular tachyarrhythmias, and/or sudden cardiac death. PQ segment depression (PQD) is related to atrial fibrillation and carries a poor prognosis in the setting of acute inferior myocardial infarction and is a well-defined electrocardiographic (ECG) marker of acute pericarditis. OBJECTIVE To evaluate the prevalence of PQD in SQTS and to analyze the association with atrial arrhythmias. METHODS Digitalized 12-lead ECGs of SQTS patients were evaluated for PQD in all leads and for QT intervals in leads II and V5. PQD was defined as ≥0.05 mV (0.5 mm) depression from the isoelectric line. RESULTS A total of 760 leads from 64 SQTS patients (mean age 36 ± 18 years; 48 [75%] men) were analyzed. PQD was seen in 265 (35%) leads from 52 (81%) patients and was more frequent in leads II, V3, aVF, V4, and I (n = 43 [67%], n = 30 [47%], n = 27 [42%], n = 25 [39%], and n = 25 [39%], respectively). Nine of 64 (14%) patients presented with atrial tachyarrhythmias, and all of them had PQD. CONCLUSION Fifty-two of 64 (81%) patients with SQTS reveal PQD. As PQD is rarely observed in healthy individuals, this ECG stigma may constitute a novel marker for SQTS in addition to a short QT interval.

Early and late outcomes of clopidogrel and Coumadin combination for patients on oral anticoagulants undergoing coronary stenting

BACKGROUND In patients under oral anticoagulant requiring percutaneous coronary intervention (PCI) with stent implantation, the optimal association between aspirin, clopidogrel and oral anticoagulant (OAC) remains cumberstome. Triple therapy and dual therapy using aspirin and OAC have been evaluated and are associated with a high frequency of major bleedings. The combination of clopidogrel and OAC has never been evaluated. OBJECTIVE We aimed to investigate the safety and efficacy of clopidogrel and OAC in patients requiring OAC undergoing PCI for acute coronary syndrome. METHODS A monocenter retrospective study was undertaken between 2000 and 2006 and included all patients undergoing PCI with stent implantation on OAC. On discharge dual therapy with clopidogrel and OAC was prescribed. The primary end-point was the frequency of major TIMI bleedings. Secondary end-points were major cardiovascular event (MACE). Results are reported as rate of events with 95% confidence intervals (CI). RESULTS Two hundreds and nine patients were followed for 71 +/- 22 months. The indication for oral anticoagulation was atrial fibrillation in 80% of patients, a valvular prothesis in 18% and a history of pulmonary embolism in 5%. The rate (95%CI) of major bleeding was 2.4% (0.9%-5.8%) 2.87% (1.17%-6.44%) and 3.8% (1.79%-7.68%) at 1 month, 12 months and 71 months respectively, which represent 8 events among which 2 were fatal. The MACE rate (95%CI) was low: 0% at one month, 3.8% (1.79%-7.68%) at 12 months and 24.4% (19.07%-30.65%) at 71 months of follow up. Only one stent thrombosis was recorded at the ninth month. The overall rate of death was 9.5% (6.28%-14.32%) among which 2.87% (1.17%-6.44%) were of cardiovascular origin. CONCLUSION The use of clopidogrel and OAC combination in patients on OAC undergoing coronary stenting is safe and efficient at the short-term. At the long-term, this combination is probably not safe, with a relatively high incidence of fatal stroke.

ECG repolarization syndrome abnormalities (J wave syndromes) and idiopathic ventricular fibrillation

Early repolarization (ER) pattern has been recognized for several decades and was interpreted as a variant of the normal electrocardiogram (ECG) as it was frequently observed in young healthy subjects or athletes. It is characterized by a J point elevation and ST-segment elevation inscribed as a QRS slurring or a notch of the S wave in the inferior leads or/and the lateral leads. The ER pattern has been the subject of increased interest since the report of its higher prevalence in subjects resuscitated from cardiac arrest related to idiopathic ventricular fibrillation (VF). Furthermore, population-based studies showed in healthy young adults that ER pattern was associated with an increased cardiovascular mortality and total mortality. A relationship between ER pattern and malignant arrhythmias is also supported by the experimental work of Antzelevitch et al. which provided the cellular and ionic basis for the J point elevation and its arrhythmogenic potential. The ER pattern may coexist with a number of cardiac or extracardiac conditions such as hypothermia. But this review will focus attention on the “isolated ER pattern” in healthy individuals. Antzelevitch and Yan proposed because of a number of similarities between the “ER syndrome” and the Brugada syndrome to group both syndromes under the heading of “J wave syndromes”. The management of ER syndrome (associated with idiopathic VF) is clearly the insertion of an implantable cardioverter defibrillator (ICD). The ER pattern associated with symptoms such as syncope or a familial history of sudden cardiac death requires a complete work-up. Caution should be raised not to generate anxiety in the subject with asymptomatic “isolated ER pattern” as the odds of developing malignant ventricular arrhythmias or to suffer sudden death in this case are extremely low.

Clinical Impact of Genetically Determined Platelet Reactivity

Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the rate of major adverse cardiac events following percutaneous coronary intervention. Clopidogrel is a prodrug which requires a two-step hepatic biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered clopidogrel metabolism is a major cause of high on-treatment platelet reactivity (HTPR), which translates into thrombotic events in stented patients. Studies demonstrated that HTPR could be overcome in poor metabolizers thanks to increased loading doses or maintenance doses of clopidogrel or with the use of more potent antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials with clinical endpoints remain necessary to determine the optimal antiplatelet therapy in patients carrying genetic polymorphism associated with HTPR and thrombotic events.