Editor's Choice- Reperfusion cardiac arrhythmias and their relation to reperfusion-induced cell death.

Reperfusion does not only salvage ischaemic myocardium but can also cause additional cell death which is called lethal reperfusion injury. The time of reperfusion is often accompanied by ventricular arrhythmias, i.e. reperfusion arrhythmias. While both conditions are seen as separate processes, recent research has shown that reperfusion arrhythmias are related to larger infarct size. The pathophysiology of fatal reperfusion injury revolves around intracellular calcium overload and reactive oxidative species inducing apoptosis by opening of the mitochondrial protein transition pore. The pathophysiological basis for reperfusion arrhythmias is the same intracellular calcium overload as that causing fatal reperfusion injury. Therefore both conditions should not be seen as separate entities but as one and the same process resulting in two different visible effects. Reperfusion arrhythmias could therefore be seen as a potential marker for fatal reperfusion injury.

Bursts of reperfusion arrhythmias occur independently of area at risk size and are the first marker of reperfusion injury.

BACKGROUND: The presence of reperfusion ventricular arrhythmias (VA) has been shown to correlate with larger infarct size (IS). However it is unclear whether the initial area at risk (AAR), also a determining factor for IS, is responsible for this correlation. We hypothesized that IS would be significantly larger in the presence of VA, while AAR would not differ. METHODS: 68 STEMI patients from the MAST study with 24-hour, continuous, 12­lead Holter monitoring initiated prior to primary percutaneous coronary intervention (PCI) resulting in TIMI 3 flow post PCI were included. VA bursts were identified against subject-specific background VA rates using a previously validated statistical outlier method. IS, and infarct endocardial surface area (ESA) were obtained using CMR at mean 4.9 days after admission. Holter and CMR results were determined in core laboratories blinded to all other data. RESULTS: VA bursts were present in 69% (45/65) of patients. No significant differences were found for demographic characteristics, comorbidities, infarct location, number of diseased coronary vessels, or duration of ischemia between groups with and without VA burst. IS was significantly smaller in the group without VA bursts (median 9.3% vs 17.0%; p = 0.025). Infarct ESA did not significantly differ between the population with and without VA burst; median 24.3% vs 20.0%; p = 0.15. CONCLUSION: VA bursts are a marker for larger IS independent of AAR, assessed by surrogate markers. These findings support the hypothesis that VA bursts are a marker of reperfusion damage occurring downstream at myocellular level.

Reperfusion ventricular arrhythmia bursts identify larger infarct size in spite of optimal epicardial and microvascular reperfusion using cardiac magnetic resonance imaging.

AIMS: Ventricular arrhythmia (VA) bursts following recanalisation in acute ST-elevation myocardial infarction (STEMI) are related to larger infarct size (IS). Inadequate microvascular reperfusion, as determined by microvascular obstruction (MVO) using cardiac magnetic resonance imaging (CMR), is also known to be associated with larger IS. This study aimed to test the hypothesis that VA bursts identify larger infarct size in spite of optimal microvascular reperfusion. METHODS: All 65 STEMI patients from the Maastricht ST elevation (MAST) study with brisk epicardial flow (TIMI 3), complete ST recovery post-percutaneous coronary intervention and early CMR were included. Using 24-hour Holter registrations from the time of admission, VA bursts were identified against subject-specific Holter background VA rates using a statistical outlier method. MVO and final IS were determined using delayed enhancement CMR. RESULTS: MVO was present in 37/65 (57%) of patients. IS was significantly smaller in the group without MVO (median 9.4% vs. 20.5%; p < 0.001). IS in the group with MVO did not differ depending on VA burst ( n = 28/37; median 20.8% vs. 19.7%; p = 0.64). However, in the group without MVO, VA burst was associated with significantly larger IS ( n = 17/28; median 10.5% vs. 4.1%; p = 0.037). In multivariable analyses, VA burst as well as anterior infarct location remained independent predictors of larger infarct size. CONCLUSION: In the presence of suboptimal reperfusion with MVO by CMR, VA burst does not further define MI size. However, with optimal TIMI 3 reperfusion and optimal microvascular perfusion (i.e. no MVO), VA burst is associated with larger IS, indicating that VA burst is a marker of additional cell death.

Ventricular arrhythmia burst is an independent indicator of larger infarct size even in optimal reperfusion in STEMI.

OBJECTIVE: We hypothesized that ventricular arrhythmia (VA) bursts during reperfusion phase are a marker of larger infarct size despite optimal epicardial and microvascular perfusion. METHODS: 126 STEMI patients were studied with 24h continuous, 12-lead Holter monitoring. Myocardial blush grade (MBG) was determined and VA bursts were identified against subject-specific background VA rates in core laboratories. Delayed-enhancement cardiovascular magnetic resonance imaging was used to determine infarct size. RESULTS: In the group with MBG 3 no significant differences were found for baseline characteristics between burst versus no burst (102 vs. 24). In those with optimal epicardial and microvascular reperfusion (TIMI 3, stable ST-recovery, and MBG 3), VA burst was associated with larger infarct size (N=102/126; median 11.0 vs. 5.1%; p=0.004). CONCLUSION: In the event of MBG 3, VA bursts were associated with significantly larger infarct size even if optimal epicardial and microvascular reperfusion was present.

Prospective evaluation of where reperfusion ventricular arrhythmia "bursts" fit into optimal reperfusion in STEMI.

BACKGROUND: Early reperfusion of ischemic myocytes is essential for optimal salvage in acute myocardial infarction. VA (ventricular arrhythmia) bursts after recanalization of the culprit vessel have been found to be related to larger infarct size (IS), using SPECT. OBJECTIVE: The hypothesis was tested that this finding could be confirmed in an independent cohort using a more accurate technique, i.e. delayed-enhancement cardiovascular magnetic resonance imaging (DE-CMR). METHODS: All 196 patients from the PREPARE and MAST studies who had 24-hour, continuous, 12-lead Holter, started before primary percutaneous coronary intervention resulting in brisk TIMI (thrombolysis in myocardial infarction) 3 flow and stable ST-recovery were included. VA bursts were identified against subject-specific background VA rates using a previously published statistical outlier method. IS was assessed using DE-CMR. Angiography, Holter and DE-CMR results were assessed in core laboratories, blinded to all other data. RESULTS: VA bursts were present in 154/196 (79%) of patients. Baseline characteristics between the groups with and without bursts were similar. VA burst was associated with significantly larger infarct size in the population as a whole (median 11.3% vs 5.3%; p=0.001) and also when divided in non-anterior (median 9.9% vs 4.9%; p=0.003) and anterior myocardial infarction (median 21.4% vs 12.0%; p=0.48), the latter not reaching statistical significance due to the small subset of patients. CONCLUSION: Beyond the classical markers of "optimal" reperfusion such as TIMI 3 flow and stable ST-segment recovery, VA bursts occurring during the reperfusion phase are an early electrobiomarker of larger IS. CLINICAL TRIAL REGISTRATION: PREPARE: ISRCTN71104460 http://www.controlled-trials.com/ISRCTN71104460.

Electrocardiographic prediction of lateral involvement in acute non-anterior wall myocardial infarction.

PURPOSE: Recent research has established that a tall R-wave in V1 indicates lateral wall involvement in non-anterior wall myocardial infarction (MI). The objective of this study was to assess the value of the admission electrocardiogram (ECG) to predict R-waves and consequently lateral wall damage in the late phase of non-anterior MI. METHODS: ECGs of 69 patients were analyzed. ST-segment changes in representative leads for lateral wall infarction such as V1, V2, V6 and I were correlated with the extent of QRS-wave changes in V1 and V6. RESULTS: ST-segment elevation in V6 showed correlations with R/S ratio in V1 (r=0.802, B=0.440, P=<0.001) and with the depth of Q-waves in V6 (r=0.671, B=0.441, P=0.007). This correlation was higher in a small subgroup where the left circumflex branch (Cx) was the culprit vessel (r=0.888, B=1.469 and P=0.018). ST-segment depression in lead I correlated with the height of R and the surface of R in V1 (height times width of R) (r=0.542, B=-0.150, P=0.005 and r=0.538, B=-0.153, P=0.005 respectively), especially in the subgroup without proximal occlusions of RCA (r=0.711 and r=0.699). ST-segment depression in lead I also predicted Q-waves in V6 (r=0.538, B=0.114, P=0.006). ST-segment changes in V2 showed no significant correlation with either R- or Q-wave measurements. CONCLUSIONS: ST-segment elevation in V6 in the acute phase of non-anterior MI predicts lateral involvement as expressed by the R/S ratio in V1 in the post reperfusion phase. A subgroup with Cx occlusion showed especially strong correlations, although the size of the group was small. In lead I ST-segment depression is correlated to height and surface of R in V1 and Q-waves in V6.

The predictive value of an ECG-estimated Acute Ischemia Index for prognosis of myocardial salvage and infarct healing 3months following inferior ST-elevated myocardial infarction.

BACKGROUND AND PURPOSE: Identification of prognostic markers can be used to stratify patients in the acute phase of ST-elevated myocardial infarction (STEMI) according to their potential to retain viable myocardium after reperfusion. The percentage of the myocardial area at risk (MaR) that is ischemic at admission, defined as the Acute Ischemia Index, is potentially salvageable. The percentage of the MaR viable at 3months post-reperfusion, by salvage and healing, was defined as the Chronic Salvage Index. A positive relationship between the Acute Ischemia Index and the Chronic Salvage Index was hypothesized. METHODS: Both indices were assessed by using the ECG indices Aldrich ST and Selvester QRS scores estimating the ischemic and infarcted myocardium. The study population comprised inferior STEMI patients. (N=59). RESULTS: A correlation of 0.253 (P=0.053) was found. CONCLUSIONS: These results are relevant and suggest evidence of a trend in the association between these indices.

Evaluation of the electrocardiogram in identifying and quantifying lateral involvement in nonanterior wall infarction using cardiovascular magnetic resonance imaging.

PURPOSE: The objective of this study was to assess the involvement and extent of lateral wall myocardial infarction (MI) in patients with a first nonanterior wall MI, as reflected by changes in precordial leads. Delayed enhancement cardiac magnetic resonance imaging was used as a gold standard to localize and quantify myocardial scar tissue. METHODS: Electrocardiogram and cardiac magnetic resonance were studied in 56 patients. Areas involved were related to QRS changes in precordial leads. RESULTS: Significant correlations were found between lateral wall involvement and R waves in V(1) and V(6) (P = 0.009-0.022). For patients with circumflex branch occlusions, the MI size of the apical and lateral segments correlated strongly with the characteristics of R waves in V(1) and V(2) (P = 0.001-0.034). CONCLUSIONS: Tall and broad R waves in V(1) reflect lateral wall MI, especially in circumflex occlusions.

The relationship between initial ST-segment deviation and final QRS complex changes related to the posterolateral wall in acute inferior myocardial infarction.

OBJECTIVES: The aim of this study was to assess the relationship between initial ST-segment deviation and final QRS complex changes related to the posterolateral left ventricular wall in patients with acute inferior myocardial infarction receiving reperfusion therapy. The secondary aim was to determine if this relationship is stronger for patients who present early in the ischemia/infarction process in comparison with patients who present late. METHODS: The ST-segment depression in the leads V(1), V2, and -V6 were measured in the electrocardiograph (ECG) just before initiation of myocardial reperfusion. These leads were chosen because they represent the posterolateral wall in the Selvester score. In addition, the Anderson-Wilkins acuteness score was calculated in the admission ECG. Selvester criteria related to the posterolateral wall were identified in the ECG performed before hospital discharge to assess final infarct size. RESULTS: Fifty-six patients were included in this study. No significant relationship was found between the sum of initial ST-segment depression in the leads V(1), V(2), and -V(6), and final infarct size in the posterolateral left ventricular wall for the total study population (r = 0.19, P = .16). Patients were subgrouped by Anderson-Wilkins acuteness score of less than 3 vs 3 or more. In those with a low acuteness score, the amount of ST-segment depression had no relationship with final infarct size (r = -0.16, P = .41). However, the correlation was statistically significant for those with a high acuteness score (r = 0.42, P = .04). CONCLUSION: The initial ST-segment depression in leads V(1), V(2), and -V(6) can predict ECG-estimated amount of infarction in the posterolateral left ventricular wall in patients with acute inferior myocardial infarction receiving reperfusion therapy, but only in those who present early in the ischemia/infarction process.