Clinical Trial: Thrombus and Inflammation Study in Sudden Cardiac DEath

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Thrombus and Inflammation in Sudden Cardiac DEath

Brief Summary: Sudden death is a natural death occurring within one hour after the onset of symptoms. It remains a major public health problem and accounts for 5 to 10 % of the annual total mortality ie about 300.000 in the United States. Despite community-based interventions, overall survival remains below 5%. Better understanding of the mechanisms causing sudden death could allow early identification of high risk subjects and implementation of specific prevention strategies. The cause of more than 90% of sudden deaths is cardiac with ventricular fibrillation or fast ventricular tachycardia complicating an underlying heart disease. Coronary heart disease and its consequences account for at least 80% of sudden cardiac deaths. Several risk factors associated with sudden death and not with myocardial infarction have been identified in population-based studies. However, the relationship between the occurrence of a coronary artery occlusion and the onset of arrhythmia is unclear. In particular, coronary artery occlusion can be rapidly followed by chest pain, which acts as a signal and allows identification of patients for emergency reperfusion. However, in some cases, the coronary artery occlusion is followed by a sudden onset of arrhythmia and sudden death. Recent data suggest that acute coronary occlusion is caused by plaque erosion or rupture and is followed by an intense local inflammation and rapid thrombus formation. Our hypothesis is that the speed of thrombus formation and coronary occlusion determines the clinical symptoms. Slow and progressive thrombus formation is likely to induce myocardial pre-conditioning thereby reducing the occurrence of ventricular arrhythmia. In contrast, rapid thrombus formation followed by acute coronary artery occlusion and ischemia is more likely to trigger fatal ventricular arrhythmia. During angioplasty procedures, coronary artery thrombus are aspirated, providing the opportunity for pathological studies. The aim of the TIDE study (Thrombus and

Detailed Summary: Sudden death is a natural death occurring within one hour after the onset of symptoms. It remains a major public health problem and accounts for 5 to 10 % of the annual total mortality ie about 40 000 deaths in France and 300.000 in the United States.(1) Despite community-based interventions, overall survival remains below 5%. (2) Better understanding of the mechanisms causing sudden death could allow early identification of high risk subjects and implementation of specific prevention strategies. (3)The cause of more than 90% of sudden deaths is cardiac with ventricular fibrillation or fast ventricular tachycardia complicating an underlying heart disease. (4) Coronary heart disease and its consequences account for at least 80% of sudden cardiac deaths and hypertrophic and dilated cardiomyopathies account for another 10 to 15% of cardiac causes.(4,5) Several risk factors associated with sudden death and not with myocardial infarction have been identified in population-based studies.(6-10) However, the relationship between the occurrence of a coronary artery occlusion and the onset of arrhythmia is unclear.The Framingham study reported that sudden death occurred without prior manifestations of coronary heart disease in more than 50% of men and 65% of women. (11) Data from 10 countries from WHO MONICA PROJECT show that sudden deaths are more frequent than non sudden coronary deaths until age 60. (figure). In a study on the value of immediate coronary angiography and angioplasty in survivors of SCD, a recent coronary artery occlusion was found in over 50% of patients and unstable coronary artery lesions in 20% (12). In two series based on autopsies, the rate of coronary artery lesions in non-survivors of SCD was over 80% (13-15). In a study based on autopsies of non-survivors of SCD, fresh thrombus was found in a majority of cases. (2)Furthermore, noninflammatory plaque erosion was found as an underlying cause to thrombus formation in 40% of cases (14). In this case, th
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Age of thrombus collected at the site of acute coronary occlusion. [ Time Frame: one day ]

Original Primary Outcome: Age of thrombus collected at the site of acute coronary occlusion. [ Time Frame: 36 months ]

Current Secondary Outcome: Local and systemic inflammation and endothelial cell apoptosis in patients with sudden death due to acute coronary occlusion, acute myocardial infarction and stable angina treated with coronary angioplasty. [ Time Frame: one day ]

Original Secondary Outcome: Local and systemic inflammation and endothelial cell apoptosis in patients with sudden death due to acute coronary occlusion, acute myocardial infarction and stable angina treated with coronary angioplasty. [ Time Frame: 36 months ]

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: July 31, 2008
Date Started: August 2008
Date Completion:
Last Updated: December 15, 2015
Last Verified: December 2015