Effects of Verapamil and Pinacidil on Extracellular K+, pH, and the Incidence of Ventricular Fibrillation during 60 Minutes of Ischemia.

Ca++-channel antagonist verapamil and ATP-sensitive K+-channel opener pinacidil are known to decrease the rise in extracellular K+ ([K+]e) level and pH (pHe) that occurs during reversible acute myocardial ischemia and to lessen the accompanying activation delay. Verapamil is also known to decrease the incidence of ventricular tachycardia (VT)/fibrillation (VF) during acute myocardial ischemia; however, the effects of ATP-sensitive K+-channel opener on the incidence of VT/VF are controversial. We studied, in an in vivo pig model, the effects of verapamil and pinacidil on the changes in [K+]e level and pHe, local activation, and the incidence of VT/VF during 60 minutes of ischemia. Thirty-one pigs were divided into 2 groups: a verapamil group (9 control pigs and 8 verapamil-treated pigs) and pinacidil group (5 control pigs and 9 pinacidil-treated pigs). In the verapamil group, VF developed in 1 of the 9 control pigs, whereas no VF developed in 8 verapamil-treated pigs. In the pinacidil group, VF developed in 3 of the 5 control pigs and all 9 pinacidil-treated pigs. Under verapamil treatment (versus the control condition), onset of the second rise in [K+]e level was delayed, and the maximum rise in [K+]e level was decreased. Under pinacidil treatment (versus the control condition), time to the onset of VT/VF was shorter than that under the control condition, and VT/VF developed at lower [K+]e level and higher pHe. In conclusion, VF may develop at a lesser [K+]e rise and pHe fall in the presence of pinacidil during acute myocardial ischemia.

Effects of Propranolol and Verapamil on Changes in TQ and ST Segment Potentials During Graded Coronary Flow Reduction in a Porcine Myocardial Ischemia Model.

Acute myocardial ischemia causes TQ depression and ST elevation. However, the effects of cardioprotective drugs such as ß-blockers and Ca++-antagonists on the extent of TQ depression, ST elevation, and myocardial ischemic injury are not fully understood.We created a carotid-coronary shunt in 30 pigs, and extracellular K+ ([K+]e), TQ, and ST segments were recorded simultaneously with K+-selective plunge electrodes placed in the left anterior descending artery (LAD) distribution during graded LAD flow reduction before and after administration of propranolol or verapamil. Unipolar DC-coupled electrograms were recorded from the reference pole of the K+-selective plunge electrodes. The microvolt readings from the K+-selective electrodes were converted to [K+]e and then to the changes in potassium equilibrium potential (ΔEK). The shunted LAD flow was reduced in a stepwise fashion at 5-minute intervals.segment depression at the similar ΔEK was not affected by propranolol or verapamil. However, ST segment elevation was reduced by propranolol but exacerbated by verapamil at the similar ΔEK.TQ-ST changes recorded by AC coupled ECG are not a reliable index of ischemia and therefore cannot be used to evaluate the effects of drugs that might affect the electrophysiologic properties of ischemic myocardium.

Initial and Secondary ST-T Alternans During Acute Myocardial Ischemia in the In-Situ Pig Heart.

The factors responsible for the ST-T wave alternans (STTA) and associated arrhythmias during acute ischemia have not been clarified.In acutely ischemic porcine myocardium, we recorded transmural unipolar and bipolar electrocardiograms and mid-myocardial extracellular K(+) ([K(+)]e) from the center of the ischemic zone during 8-minute episodes of ischemia. Two different STTAs occurred. The initial STTA, which occurred at 4 minutes 15 seconds ± 12 seconds of ischemia during sinus rhythm, was most prominent in the subendocardium, independent of [K(+)]e and activation block, and heart rate dependent. It occurred in 13/19 (68%) occlusions at heart rates ≤ 100 bpm and in 22/23 (96%) at > 100 bpm. The second STTA was more obvious and greatest in the subepicardium. It began in the later phase of ischemia and was also heart rate dependent (5/19 [26%] occlusions at heart rates ≤ 100 bpm and 10/23 [44%] at > 100 bpm). This STTA was consistently associated with 2:1 change in the bipolar electrogram morphology, possibly due to 2:1 conduction block. Ventricular fibrillation (VF) occurred only at > 100 bpm.The initial STTA may be independent of conduction abnormalities and represent primary repolarization alternans. The second STTA may be secondary to and indicative of 2:1 activation block or marked alternans of the action potential amplitude/duration. The associated VF most likely reflects the underlying conduction abnormality.

Stress-induced ST elevation with or without concomitant ST depression is predictive of presence, location and amount of myocardial ischemia assessed by myocardial perfusion SPECT, whereas isolated stress-induced ST depression is not.

BACKGROUND: Evaluation of stress-induced ST deviations constitutes a central part when interpreting the findings from an exercise test. The aim of this analysis was to assess the pathophysiologic correlate of stress-induced ST elevation and ST depression with regard to presence, amount and location of myocardial ischemia as assessed by myocardial perfusion SPECT (MPS) in patients with suspected coronary artery disease. METHODS AND RESULTS: 226 patients who had undergone bicycle stress test in conjunction with MPS were included. Of these, 198 were consecutive patients while 28 patients were included on the basis of having stress-induced ST elevation mentioned in their clinical report. The amount and location of ST changes were related to MPS findings. Summed stress scores (SSS) from MPS images were used to measure the amount of stress-induced ischemia. The positive predictive values for detecting stress-induced ischemia were 28% for the consecutive patients with ST depression and 75% for patients with ST elevation. The maximum and sum of stress-induced ST elevations correlated with SSS (r(2)=0.58, p<0.001 and r(2)=0.73, p<0.001), whereas the maximum and sum of significant ST depressions did not (r(2)=0.022, p=0.08 and r(2)=0.024, p=0.10). The location of ST elevation corresponded to the location of ischemia by MPS (kappa=1.0), whereas the location of ST depression did not (kappa=0.20). CONCLUSIONS: Stress-induced ST elevation, with or without concomitant ST depression, is predictive of the presence, amount and location of myocardial ischemia assessed by MPS, whereas stress-induced ST depression without concomitant ST elevation is not.

Prominent R wave in ECG lead V1 predicts improvement of left ventricular ejection fraction after cardiac resynchronization therapy in patients with or without left bundle branch block.

BACKGROUND: QRS morphology on postprocedural ECG indicating posterolateral left ventricular pacing may be predictive of response to cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess whether a positive vector in V1 and/or negative vector in lead I on the first postprocedural ECG, suggesting posterolateral capture from CRT, correlates with improvement in left ventricular ejection fraction (LVEF). METHODS: A retrospective chart review was conducted on all patients who underwent CRT implantation at our institution between April 2008 and December 2011. Biventricular (BiV) paced QRS morphology was defined as R/S ≥1 in V1 and/or R/S ≤ 1 in lead I. The primary outcome was improvement of LVEF ≥7.5%. The χ(2) and t tests were used for analysis. RESULTS: Of 68 patients, 49 (72%) met our BiV paced QRS morphology criteria. Thirty-four of these 49 patients (69%) had improvement in LVEF. Of the 19 patients who did not meet our criteria, 17 (89%) did not have an improvement in LVEF (sensitivity 94%, specificity 53%, χ(2) = 19.04, P < .0001). The average LVEF improvement in patients who met our BiV paced QRS morphology criteria was significantly greater than in those who did not (14.27% vs 2.63%, P = .0001). Preprocedural left bundle branch block was not a predictor of echocardiographic response. CONCLUSION: Our results highlight the importance of periprocedural ECG analysis to optimize response to CRT. Moreover, patients without left bundle branch block still benefited from CRT if they met our BiV paced morphology criteria. This suggests that postprocedural left ventricular activation as reflected on the ECG may supersede the baseline conduction delay.

Common pitfalls in the interpretation of electrocardiograms from patients with acute coronary syndromes with narrow QRS: a consensus report.

Acute coronary syndromes (ACS) with narrow QRS are divided into 2 groups: ST-elevation ACS that requires emergency percutaneous coronary intervention, and non-ST elevation ACS. The classification of ACS into these 2 groups is not always straightforward. In this document, we discuss several electrocardiogram patterns of acute ischemia that are often misinterpreted. We suggest that any new recommendations or guidelines from the Scientific Societies should acknowledge these aspects of electrocardiogram interpretation by including appropriate diagnostic criteria that should prove helpful for the optimal management of patients with ACS.

Should electrocardiogram criteria for the diagnosis of left bundle-branch block be revised?

In this study, we consider the proposition that the criteria for the electrocardiographic (ECG) diagnosis of left bundle-branch block (LBBB) be revised, a proposition born from analysis of results of cardiac resynchronization therapy trials. The various ECG definitions for LBBB (or lack thereof) used in these trials are reviewed as are the results of the analysis of ECGs from patients with left ventricular conduction disturbances by Grant and Dodge (Am J Med. 1956;20:834-852) and the criteria for the ECG diagnosis of LBBB recommended by the World Health Organization and the International Society and Federation for Cardiology in 1985. These criteria stress that the QRS complex be notched or slurred, that the initial portion of the QRS complex (the "septal Q waves") be absent, and that the QRS duration be at least 120 milliseconds in duration. This is in contrast to the recent suggestion that the QRS complex has a minimum duration of 130 to 140 milliseconds. We conclude that the criteria for the ECG diagnosis of LBBB should be standardized to that recommended by the World Health Organization and International Society and Federation for Cardiology with retention of the minimum duration of 120 milliseconds and that the QRS prolongation should be not be gradual. However, we also conclude that in patients with LBBB being considered for cardiac resynchronization therapy, the duration of the QRS complex should be at least 130 milliseconds.

Repolarization heterogeneity and rate dependency in a canine rapid pacing model of heart failure.

BACKGROUND: Repolarization heterogeneity and rate dependency have long been established as factors contributing to arrhythmogenic risk. However, there are conflicting observations regarding the nature and extent of ventricular repolarization heterogeneity that complicate understanding of arrhythmogenic mechanisms. To explore these disparate findings, we studied ventricular repolarization heterogeneity and rate dependency in a canine, rapid pacing model of heart failure. METHODS AND RESULTS: We studied ventricular repolarization heterogeneity and rate dependency in 10 canine hearts (5 normal and 5 after 1 month of rapid pacing at 240 beats per minute) by analyzing 64 body surface electrocardiograms, 64 epicardial, and 190 intramural plunge electrograms. We estimated mean ventricular depolarization and repolarization times from R- and T-wave peaks of the root-mean-square electrocardiogram (body surface) and local depolarization and repolarization times using activation-recovery interval (ARI) methods from recordings obtained during a range of fixed rate pacing. In addition, we estimated local epicardial and transmural gradients of ARIs to assess cardiac locations of greatest spatial repolarization heterogeneity. We compared changes in repolarization at different rates between normal and heart failure hearts. Findings documented prolongation of repolarization, repolarization rate dependency, and increased repolarization gradients in the heart failure hearts compared with control as observed from body surface, epicardial, and transmural measurements. Maximum local epicardial and intramural ARI gradients were comparable both in heart failure and control hearts. Intramural ARI distributions tended to be more irregular in the heart failure hearts compared with the systematic epicardium to endocardium ARI increase observed in control animals. CONCLUSIONS: This study documented prolongation of repolarization, increase in both epicardial and transmural repolarization gradients, and irregularity of transmural distribution in a rapid pacing canine model of heart failure compared with control animals. The findings support previously published results of increased repolarization heterogeneity and repolarization prolongation observed in rapid pacing models of heart failure. New findings are the irregularity of transmural heterogeneity and the ability of noninvasive root-mean-square electrocardiogram R-T intervals to estimate mean ventricular repolarization duration in the setting of rapid pacing models of heart failure. These findings suggest increased arrhythmogenic risk in this model and potentially in patients with heart failure.

Report of the third International Society for Holter and Noninvasive Electrocardiology working group on improved electrocardiographic criteria for acute and chronic ischemic heart disease--Lund, Sweden: June 2010.

The third meeting of the International Society for Holter and Noninvasive Electrocardiology working group was convened in Lund, Sweden, in June 2010 to consider the key clinical challenge of developing electrocardiographic (ECG) criteria for identification of the global subendocardial ischemia that results from subtotal occlusion of either the left main coronary artery or its equivalent. The participants considered the specific abnormalities typical of global subendocardial ischemia on the presenting ECG and outlined further studies to establish the optimal quantitative ECG criteria. Subgroups on Electrocardiology, Myocardial Imaging, and Coronary Intervention met separately to establish priorities on their topic and then joined together in a final session of the entire working group. The principles for a retrospective and then a prospective study were identified, and a writing group was formed.