Esther Jorge

Effects of Open-Irrigated Radiofrequency Ablation Catheter Design on Lesion Formation and Complications: In Vitro Comparison of 6 Different Devices

Open‐irrigated radiofrequency ablation catheters with slight differences in tip architecture are widely used, although limited comparative data are available. The purpose of this study was to compare the lesion size and potential complications produced by commercially available open‐irrigated catheters in an in vitro porcine heart model.

Changes in QRS duration and R-wave amplitude in electrocardiogram leads with ST segment elevation differentiate epicardial and transmural myocardial injury

BACKGROUND Acute transmural ischemia increases QRS duration and R-wave amplitude owing to depressed intramyocardial activation. Theoretically, when myocardial injury is confined to the epicardium, the intramyocardial activation is preserved without affecting QRS duration. OBJECTIVE The purpose of this study was to distinguish epicardial from transmural myocardial injury based on the analysis of the QRS complex in leads with ST segment elevation. METHODS Electrophysiological effects of epicardial injury induced by topical application (n = 7) or intrapericardial injection (n = 10) of potassium were assessed in pigs in local electrograms recorded with needles in the left ventricle and in the peripheral 12-lead electrocardiogram (ECG), respectively, and were compared with transmural injury induced by acute left anterior descending (LAD) occlusion in the same pig. RESULTS Epicardial application of 50 mM potassium induced ST segment elevation in epicardial (0.2 ± 0.06 to 0.5 ± 0.09 mV; P <.05) but not in midmyocardial local electrograms (0.1 ± 0.07 to -0.1 ± 0.09 mV). Local midmyocardial activation times were not affected by epicardial applied potassium (182 ± 5.9 vs. 183 ± 5.8 ms) but increased significantly during acute LAD occlusion (246 ± 20.9 ms; P <.01). Intrapericardial injected potassium induced ST segment elevation on average in nine of 12 ECG leads but did not change QRS duration and R-wave amplitude. Acute LAD occlusion induced ST segment elevation (five of 12 leads) associated with increased QRS duration (69 ± 1.2 to 89 ± 3.6 ms; P <.001) and R-wave amplitude (0.1 ± 0.01 to 0.7 ± 0.09 mV; P <.001) in the ECG. CONCLUSION Transmural but not epicardial myocardial injury delays intramural local activation and is associated with QRS prolongation and enlarged R-wave amplitude in leads with ST segment elevation. This differential ECG pattern may help to distinguish acute pericarditis (epicardial injury) from acute transmural ischemia in clinical practice.

Mechanism and diagnostic potential of reciprocal ECG changes induced by acute coronary artery occlusion in pigs

BACKGROUND Reciprocal ST-segment depression simulating additional subendocardial ischemia is commonly observed in ST-segment elevation myocardial infarction. OBJECTIVE To study the mechanism and characterization of the whole reciprocal electrocardiogram (ECG) patterns induced by acute coronary artery occlusion at different locations in the absence of additional subendocardial ischemia in pigs. METHODS Conventional 12-lead ECG and/or local extracellular epicardial, mid-myocardial, and endocardial electrograms were recorded during the acute occlusion of right coronary (RC) and left anterior descending (LAD) coronary arteries in the in situ (n = 9) or in the isolated perfused (n = 5) pig hearts. RESULTS Mid-RC occlusion induced reciprocal ST-segment depression (-0.43 ± 0.14 mV; P<.01) and S-wave deepening (-0.74 ± 0.23 mV; P<.01) in anterior ECG leads. Mid-LAD occlusion induced reciprocal S-wave deepening (-0.43 ± 0.37 mV; P = .02) but not ST-segment depression in inferior leads. Proximal LAD induced reciprocal ST-segment depression (-0.21 ± 0.20 mV; P = .03) and S-wave deepening (-0.56 ± 0.58 mV; P = .04) in inferior leads. Reciprocal QRS widening was observed only during proximal LAD occlusion. Local extracellular recordings did not show significant reciprocal QRS and ST-segment changes. CONCLUSIONS In the absence of additional subendocardial ischemia, acute coronary artery occlusion induces reciprocal ST-segment and S-wave changes in the 12-lead ECG that allow better differentiation between proximal and mid-LAD occlusion. Reciprocal ECG changes depend on conventional lead system design and not on the transmission of injury currents from the ischemic border zone to distant normal myocardium.

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 patients 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.

Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance

Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.

Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance

Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz-1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 Ω·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5-10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 Ω·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemia.

Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction.

Aims Disruptions in cardiac ion channels have shown to influence the impaired cardiac contraction in heart failure. We sought to determine the altered gene expression profile of this category in dilated cardiomyopathy (DCM) patients and relate the altered gene expression with the clinical signs present in our patients, such as ventricular dysfunction and sustained monomorphic ventricular tachycardia (SMVT). Methods and Results Left ventricular (LV) tissue samples were used in RNA-sequencing technique to elucidate the transcriptomic changes of 13 DCM patients compared to controls (n = 10). We analyzed the differential gene expression of cardiac ion channels, and we found a total of 34 altered genes. We found that the calcium channel CACNG8 mRNA and protein levels were down-regulated and highly and inversely related with LV ejection fraction (LVEF) (r = –0.78, P<0.01). Furthermore, the potassium channels KCNN3 and KCNJ2 mRNA and protein levels were up-regulated and showed also a significant and inverse correlation with LVEF (r = –0.61, P<0.05; r = –0.60, P<0.05) in patients with SMVT. Conclusion A broad set of deregulated genes have been identified by RNA-sequencing technique. The relationship of CACNG8, KCNN3 and KCNJ2 with LVEF, and the up-regulation of KCNN3 and KCNJ2 in all patients with SMVT, irrespective of CACNG8 expression, suggest a significant role for these three ion flux related genes in the LV dysfunction present in this cardiomyopathy and an important relationship between KCNN3 and KCNJ2 up-regulation and the presence of SMVT.

Endocardial infarct scar recognition by myocardial electrical impedance is not influenced by changes in cardiac activation sequence

BACKGROUND Measurement of myocardial electrical impedance can allow recognition of infarct scar and is theoretically not influenced by changes in cardiac activation sequence, but this is not known. OBJECTIVES The objectives of this study were to evaluate the ability of endocardial electrical impedance measurements to recognize areas of infarct scar and to assess the stability of the impedance data under changes in cardiac activation sequence. METHODS One-month-old myocardial infarction confirmed by cardiac magnetic resonance imaging was induced in 5 pigs submitted to coronary artery catheter balloon occlusion. Electroanatomic data and local electrical impedance (magnitude, phase angle, and amplitude of the systolic-diastolic impedance curve) were recorded at multiple endocardial sites in sinus rhythm and during right ventricular pacing. By merging the cardiac magnetic resonance and electroanatomic data, we classified each impedance measurement site either as healthy (bipolar amplitude ≥1.5 mV and maximum pixel intensity <40%) or scar (bipolar amplitude <1.5 mV and maximum pixel intensity ≥40%). RESULTS A total of 137 endocardial sites were studied. Compared to healthy tissue, areas of infarct scar showed 37.4% reduction in impedance magnitude (P < .001) and 21.5% decrease in phase angle (P < .001). The best predictive ability to detect infarct scar was achieved by the combination of the 4 impedance parameters (area under the receiver operating characteristic curve 0.96; 95% confidence interval 0.92-1.00). In contrast to voltage mapping, right ventricular pacing did not significantly modify the impedance data. CONCLUSION Endocardial catheter measurement of electrical impedance can identify infarct scar regions, and in contrast to voltage mapping, the impedance data are not affected by changes in cardiac activation sequence.

ST-segment deviation behavior during acute myocardial ischemia in opposite ventricular regions: Observations in the intact and perfused heart

BACKGROUND Acute myocardial ischemia in opposite regions may attenuate ST-segment changes, but whether this effect is expressed differently in extracardiac compared to direct intramyocardial recordings is not well known. OBJECTIVE The purpose of this study was to characterize ST-segment changes induced by opposite ischemic regions in intact and isolated perfused pig hearts. METHODS Left anterior descending (LAD) and right coronary arteries (RCA) were occluded in 7 closed chest pigs and in 5 isolated pig hearts. ST-segment changes were analyzed in 12-lead ECG and in local extracellular electrograms. RESULTS Isolated LAD or RCA occlusion induced maximal ST-segment elevation in leads V4 (0.84 ± 0.30 mV, P = .003) and III (0.16 ± 0.11 mV, P = .04), respectively. RCA occlusion also induced reciprocal ST-segment depression maximal in lead V4 (-0.40 ± 0.16 mV, P = .005). Simultaneous LAD and RCA occlusion reduced ST-segment elevation by about 60% and blunted reciprocal ST-segment changes. Reperfusion of 1 of the 2 occluded arteries induced immediate regional reversion of ST-segment elevation with concurrent beat-to-beat re-elevation in the opposite ischemic region and reappearance of reciprocal ST-segment changes. In the isolated heart, single LAD or RCA ligature induced regional transmural ST-segment elevation that was maximal in endocardial electrograms with no appreciable reciprocal ST-segment depression. Simultaneous LAD and RCA ligature reduced ST-segment elevation by about 30% with no appreciable re-elevation after 1-vessel selective reperfusion. CONCLUSION Acute myocardial ischemia in opposite ventricular regions attenuated ST-segment elevation and blunted reciprocal depression in conventional ECG leads but not in direct local myocardial electrograms.

Myocardial contractility assessed by dynamic electrical impedance measurements during dobutamine stress

In this study, the electrical impedance of myocardial tissue is measured dynamically during the cardial cycle. The multisine-based approach used to perform electrical impedance spectroscopy (EIS) measurements allows acquiring complete spectral impedance information of the tissue dynamics during contraction. Measurements are performed in situ in the left ventricule of swines during contractility stress tests induced by dobutamine infusion. Additionally, the ECG and the left ventricular (LV) pressure are also acquired synchronously to the impedance signals. The calculated impedance magnitude exhibits a periodic behavior during tissue contraction. The amplitude (peak-to-peak) of this signal is quantified and the compared to the maximum first derivative of the LV pressure (dP/dtmax) that is used as an indicator of contractility variations. The results show a linear correlation between impedance amplitude and dP/dtmax during dobutamine-increased contractility. The present work demonstrates how fast EIS measurements during heart contraction can represent a feasible method to assess changes in myocardial contractility.