New electrocardiographic criteria to differentiate acute pericarditis and myocardial infarction

Objective Transmural myocardial ischemia induces changes in QRS complex and QT interval duration but, theoretically, these changes might not occur in acute pericarditis provided that the injury is not transmural. This study aims to assess whether QRS and QT duration permit distinguishing acute pericarditis and acute transmural myocardial ischemia. Methods Clinical records and 12-lead electrocardiogram (ECG) at ×2 magnification were analyzed in 79 patients with acute pericarditis and in 71 with acute ST-segment elevation myocardial infarction (STEMI). Results ECG leads with maximal ST-segment elevation showed longer QRS complex and shorter QT interval than leads with isoelectric ST segment in patients with STEMI (QRS: 85.9 ± 13.6 ms vs 81.3 ± 10.4 ms, P = .01; QT: 364.4 ± 38.6 vs 370.9 ± 37.0 ms, P = .04), but not in patients with pericarditis (QRS: 81.5 ± 12.5 ms vs 81.0 ± 7.9 ms, P = .69; QT: 347.9 ± 32.4 vs 347.3 ± 35.1 ms, P = .83). QT interval dispersion among the 12-ECG leads was greater in STEMI than in patients with pericarditis (69.8 ± 20.8 ms vs 50.6 ± 20.2 ms, P <.001). The diagnostic yield of classical ECG criteria (PR deviation and J point level in lead aVR and the number of leads with ST-segment elevation, ST-segment depression, and PR-segment depression) increased significantly (P = .012) when the QRS and QT changes were added to the diagnostic algorithm. Conclusions Patients with acute STEMI, but not those with acute pericarditis, show prolongation of QRS complex and shortening of QT interval in ECG leads with ST-segment elevation. These new findings may improve the differential diagnostic yield of the classical ECG criteria

Exploring the Electrophysiologic and Hemodynamic Effects of Cardiac Resynchronization Therapy: From Bench to Bedside and Vice Versa

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with prolonged QRS duration. In patients with left bundle branch block the altered left ventricular electrical activation results in dyssynchronous, inefficient contraction of the left ventricle. CRT aims to reverse these changes and to improve cardiac function. This article explores the electrophysiologic and hemodynamic changes that occur during CRT in patient and animal studies. It also addresses how novel techniques, such as multipoint and endocardial pacing, can further improve the electromechanical response.</p

Exploring the Electrophysiologic and Hemodynamic Effects of Cardiac Resynchronization Therapy: From Bench to Bedside and Vice Versa

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with prolonged QRS duration. In patients with left bundle branch block the altered left ventricular electrical activation results in dyssynchronous, inefficient contraction of the left ventricle. CRT aims to reverse these changes and to improve cardiac function. This article explores the electrophysiologic and hemodynamic changes that occur during CRT in patient and animal studies. It also addresses how novel techniques, such as multipoint and endocardial pacing, can further improve the electromechanical response

Percutaneous microembolization of the left coronary artery to model ischemic heart disease in rats

Small animal models of myocardial infarction are used for a wide variety of research purposes, but common techniques for generating such models require thoracic surgeries that increase mortality risk and damage important structures, such as the pericardial sac. Here, we describe a technique for modeling myocardial infarction in rats by selective coronary microembolization, which has hitherto been described only in large animals. This technique selectively catheterizes the left coronary artery using a custom-made catheter that is introduced and precisely placed under fluoroscopic guidance. Microspheres are then injected through the catheter to cause embolization. This process creates multiple simultaneous micro-infarcts that resemble those from clinical embolization after a percutaneous coronary intervention. As this technique does not require thoracic surgery, a low attrition rate was expected and once it was optimized, this technique had a low mortality rate of just 14% during experimental application. This technique creates infarcts that appear small but are associated with transient ECG changes and a persistently lower ejection fraction after embolization. Microspheres are retained in the myocardial tissue and are visible by epifluorescent microscopy after histological staining and recognizable as a distinct speckle pattern in ultrasound images

Electrophysiological changes in heart failure and their implications for arrhythmogenesis

Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors. Diet and ventricular wall stretch are discussed as modulating factors. Finally, emphasis is placed on the hitherto poorly studied aspects of right ventricular failure. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic intervention

Transmural dispersion of refractoriness and conduction velocity is associated with heterogeneously reduced connexin43 in a rabbit model of heart failure

BACKGROUND Heterogeneity of repolarization and conduction is a potential source of arrhythmogenesis. In heart failure (HF), intercellular coupling is reduced and heterogeneities may become evident because of reduced intercellular coupling. OBJECTIVE This study sought to investigate connexin43 (Cx43) expression, conduction velocity (CV), refractoriness and inducibility of arrhythmias at multiple sites of the left ventricle during HF. METHODS HF was induced by pressure-volume overload in rabbits. Epcardial and intramural mapping was performed in isolated perfused hearts following programmed stimulation. Myocytes were enzymatically dissociated and studied using D-4-ANEPPS fluorescence. Western blotting and immunohistochemistry was performed to quantify heterogeneity of Cx43 expression. RESULTS Cx43 was heterogeneously reduced in the midmyocardial, but not in the sub epicardium layer of the left ventricular free watt in HF compared to control rabbits. In HF, subepicardial and midmyocardial refractory periods (RPs) were increased compared to control rabbits (148 +/- 3 ms and 143 +/- 3 versus 131 2 and 129 +/- 2 ms, respectively, both P <0.001). Also, transmural dispersion of RPs was Larger in HF (30 +/- 4 ms) than in control rabbits (24 +/- 3 ms, P <0.05). Intrinsic dispersion of action potential duration in isolated myocytes was similar in HF and control rabbits. Transmural CV was heterogeneous, although the mean CV was not different between groups. Arrhythmias were more easily inducible in HF, especially from midmyocardium. CONCLUSION In HF, midmyocardial Cx43 expression is heterogeneously reduced. This is associated with increased transmural dispersion in refractoriness and conduction, and with increased arrhythmia inducibilit

Cardiac activation-repolarization patterns and ion channel expression mapping in intact isolated normal human hearts

BACKGROUND: The repolarization pattern of the human heart is unknown. OBJECTIVE: The purpose of this study was to perform a multisite analysis of the activation-repolarization patterns and mRNA expression patterns of ion channel subunits in isolated human hearts. METHODS: Hearts from 3 donors without reported cardiac disease were Langendorff perfused with the patient's own blood. A standard ECG was obtained before explantation. Up to 92 unipolar electrograms from 24 transmural needles were obtained during right atrial pacing. Local activation and repolarization times and activation-recovery intervals (ARI) were measured. The mRNA levels of subunits of the channels carrying the transient outward current and slow and rapid components of the delayed rectifier current were determined by quantitative reverse transcriptase polymerase chain reaction at up to 63 sites. RESULTS: The repolarization gradients in the 3 hearts were different and occurred along all axes without midmural late repolarization. A negative activation-repolarization relationship occurred along the epicardium, but this relationship was positive in the whole hearts. Coefficients of variation of mRNA levels (40%-80%) and of the Kv7.1 protein (alpha-subunit slow delayed rectifier channel) were larger than those of ARIs (7%-17%). The regional mRNA expression patterns were similar in the 3 hearts, unlike the ARI profiles. The expression level of individual mRNAs and of Kv7.1 did not correlate with local ARIs at the same sites. CONCLUSION: In the normal human heart, repolarization gradients encompass all axes, without late midmural repolarization. Last activated areas do not repolarize first as previously assumed. Gradients of mRNAs of single ion channel subunits and of ARIs do not correlate

Larger cell size in rabbits with heart failure increases myocardial conduction velocity and QRS duration

BACKGROUND: Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations. METHODS AND RESULTS: HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P <0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P <0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P <0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P <0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer. CONCLUSIONS: Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duratio