Risk Stratification of Ischaemic Patients ICDs by CRP
Risk Stratification of Ischaemic Patients ICDs by CRP
Aims Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can be offered therapy with implantable cardioverter defibrillators (ICDs). Whether plasma biomarkers can help risk stratify for SCD and ventricular arrhythmias (VT/VF) is unclear.
Methods and results The primary objective of the CAMI-GUIDE study is to assess the predictive role of C-reactive protein for SCD or VT/VF in ischaemic patients with the ejection fraction <30% and ICDs. Secondary endpoints included all-cause mortality, hospitalizations, and death from heart failure. Additional analyses incorporated cystatin-C and NT-ProBNP in multi-marker approach for the prediction of adverse outcomes. A total of 300 patients were enrolled. All-cause mortality at 2 years was 22.6%, mortality from heart failure was 8.3%. Primary endpoint occurred in 17.3%. At a competing risk multivariable analysis adjusted for baseline variables, no significant difference in primary endpoint was found between patients with C-reactive protein ≤3 vs. >3 mg/L [heart rate (HR) 0.91 (0.50–1.64) P = 0.76], while C-reactive protein >3 mg/L was strongly associated with mortality due to heart failure [HR: 3.17 (1.54–6.54) P = 0.002]. NT-proBNP above median was significantly associated with the primary endpoint [adjusted HR: 1.46 (1.020–2.129) P = 0.042]. A risk function, including the three biomarkers, NYHA class and resting HR, allowed stratification of patient mortality risk from 5 to 50%.
Conclusion C-reactive protein >3 mg/L is not associated with SCD or fast VT/VF, however, is a strong predictor of HF mortality. Biomarkers combined with clinical markers allow an excellent risk stratification of mortality at 2 years.
Several clinical trials have shown that implantable cardioverter defibrillators (ICDs) are effective means for the prevention of sudden cardiac death (SCD) in both ischaemic and non-ischaemic patients. However, despite current evidence-based guidelines, ICDs still remain underused or misused, with implantation rates varying from country to country. Notably, patients with ischaemic heart disease and low left ventricular ejection fraction (LVEF) are exposed to an increased risk of SCD and although international guidelines were updated, years ago, to include this population into a Class IA indication for ICD implantation, criticisms still remain. In particular, whether or not all patients with a previous myocardial infarction (MI) and low LVEF should receive an ICD still remains an issue prompting debate and attempts are being made to better risk stratify these patients.
Although re-entry mechanisms have been considered the primary cause of ventricular arrhythmias in post-MI patients, recent findings support the hypothesis that acute ischaemia might also represent a prevalent mechanism of sudden death in post-MI, through different mechanisms, from increased release of cytokines, changes in metabolic and ions substrate to inhomogeneous conduction delays and blocks that may also, in turn, facilitate re-entry.
The hypothesis behind the study was that different mechanisms underlay the genesis of arrhythmias in these patients and that acute ischaemia may play a dominant role in the occurrence of SCD or in the most fast and life-threatening forms of ventricular arrhythmias [i.e. ventricular fibrillation (VF) or fast ventricular tachycardia (VT)], while re-entry could be mainly associated to slower arrhythmias. Recently, specific plasma biomarkers have been introduced for risk stratification of acute coronary events (e.g. inflammatory cytokines, biomarkers of plaque destabilization and rupture, biomarkers of myocardial stretch).
Therefore, the aim of the CAMI-GUIDE (C-reactive protein Assessment post Myocardial Infarction to GUIde DEfibrillator implantation) study was to prospectively test the hypothesis that plasma levels of the prototypic inflammatory biomarker C-reactive protein were associated with the risk of potentially fatal arrhythmias and SCD in a population of ischaemic patients with previous MI and LVEF <30% who received an ICD according to the inclusion criteria of the MADIT II study. Additionally, NT-proBNP and cystatin-C were also assessed in order to evaluate the potential additive benefit of a multi-marker approach for risk stratification.
Abstract and Introduction
Abstract
Aims Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can be offered therapy with implantable cardioverter defibrillators (ICDs). Whether plasma biomarkers can help risk stratify for SCD and ventricular arrhythmias (VT/VF) is unclear.
Methods and results The primary objective of the CAMI-GUIDE study is to assess the predictive role of C-reactive protein for SCD or VT/VF in ischaemic patients with the ejection fraction <30% and ICDs. Secondary endpoints included all-cause mortality, hospitalizations, and death from heart failure. Additional analyses incorporated cystatin-C and NT-ProBNP in multi-marker approach for the prediction of adverse outcomes. A total of 300 patients were enrolled. All-cause mortality at 2 years was 22.6%, mortality from heart failure was 8.3%. Primary endpoint occurred in 17.3%. At a competing risk multivariable analysis adjusted for baseline variables, no significant difference in primary endpoint was found between patients with C-reactive protein ≤3 vs. >3 mg/L [heart rate (HR) 0.91 (0.50–1.64) P = 0.76], while C-reactive protein >3 mg/L was strongly associated with mortality due to heart failure [HR: 3.17 (1.54–6.54) P = 0.002]. NT-proBNP above median was significantly associated with the primary endpoint [adjusted HR: 1.46 (1.020–2.129) P = 0.042]. A risk function, including the three biomarkers, NYHA class and resting HR, allowed stratification of patient mortality risk from 5 to 50%.
Conclusion C-reactive protein >3 mg/L is not associated with SCD or fast VT/VF, however, is a strong predictor of HF mortality. Biomarkers combined with clinical markers allow an excellent risk stratification of mortality at 2 years.
Introduction
Several clinical trials have shown that implantable cardioverter defibrillators (ICDs) are effective means for the prevention of sudden cardiac death (SCD) in both ischaemic and non-ischaemic patients. However, despite current evidence-based guidelines, ICDs still remain underused or misused, with implantation rates varying from country to country. Notably, patients with ischaemic heart disease and low left ventricular ejection fraction (LVEF) are exposed to an increased risk of SCD and although international guidelines were updated, years ago, to include this population into a Class IA indication for ICD implantation, criticisms still remain. In particular, whether or not all patients with a previous myocardial infarction (MI) and low LVEF should receive an ICD still remains an issue prompting debate and attempts are being made to better risk stratify these patients.
Although re-entry mechanisms have been considered the primary cause of ventricular arrhythmias in post-MI patients, recent findings support the hypothesis that acute ischaemia might also represent a prevalent mechanism of sudden death in post-MI, through different mechanisms, from increased release of cytokines, changes in metabolic and ions substrate to inhomogeneous conduction delays and blocks that may also, in turn, facilitate re-entry.
The hypothesis behind the study was that different mechanisms underlay the genesis of arrhythmias in these patients and that acute ischaemia may play a dominant role in the occurrence of SCD or in the most fast and life-threatening forms of ventricular arrhythmias [i.e. ventricular fibrillation (VF) or fast ventricular tachycardia (VT)], while re-entry could be mainly associated to slower arrhythmias. Recently, specific plasma biomarkers have been introduced for risk stratification of acute coronary events (e.g. inflammatory cytokines, biomarkers of plaque destabilization and rupture, biomarkers of myocardial stretch).
Therefore, the aim of the CAMI-GUIDE (C-reactive protein Assessment post Myocardial Infarction to GUIde DEfibrillator implantation) study was to prospectively test the hypothesis that plasma levels of the prototypic inflammatory biomarker C-reactive protein were associated with the risk of potentially fatal arrhythmias and SCD in a population of ischaemic patients with previous MI and LVEF <30% who received an ICD according to the inclusion criteria of the MADIT II study. Additionally, NT-proBNP and cystatin-C were also assessed in order to evaluate the potential additive benefit of a multi-marker approach for risk stratification.