Unipolar Electrogram Amplitude Research Articles

The electrophysiological substrate of biopsy-proven cardiac amyloidosis

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p<0.001); the unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis

Characteristics and Clinical Value of Electroanatomic Voltage Mapping in Cardiac Amyloidosis

BackgroundCardiac amyloidoses (CAs) are an increasingly recognised group of infiltrative cardiomyopathies associated with high risk of adverse cardiac events. We sought to characterise the characteristics and clinical value of right ventricular (RV) electroanatomic voltage mapping (EVM) in CA. MethodsFifteen consecutive patients undergoing endomyocardial biopsy (EMB) for suspected CA (median age 75 years, 1st-3rd quartiles 64-78 years], 67% male) were enrolled in an observational prospective study. Each patient underwent RV high-density EVM using a multipolar catheter and EMB. The primary outcome was death or heart failure hospitalisation at 1-year follow-up. We recorded electrographic features at EMB sampling sites and electroanatomic data in the overall RV, and explored their correlations with histopathologic findings and primary outcomes events. ResultsA final EMB-proven diagnosis of immunoglobulin light chain or transthyretin CA was formulated in 6 and 9 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.55 ± 0.44 mV and 5.14 ± 1.50 mV, respectively, in the overall RV, with lower values in AL CA patients. We found a significant inverse correlation between both bipolar and unipolar electrogram amplitude and amyloid burden according to EMB (P = 0.001 and P = 0.025, respectively). At 1-year follow-up, 7 patients (47%) experienced a primary outcome event; the extent of bipolar dense scar area at RV EVM was an independent predictor of primary outcome events at multivariable analysis (odds ratio 2.40; P = 0.037). ConclusionsIn CA, electrogram amplitudes are around the lower limit of normal yet disproportionately low compared with the increased wall thickness. Out data suggest that RV electrogram amplitude may be a quantitative marker of amyloid burden, and that RV EVM may have prognostic value.

Electroanatomical features of biopsy-proven cardiac amyloidosis

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of heart failure, thromboembolic events, arrhythmias, and sudden death. Endomyocardial biopsy may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose to provide a first description of electroanatomical characteristics of amyloid cardiomyopathy, and relate them to endomyocardial biopsy findings. Methods we enrolled ten consecutive patients (median age, 68 [63-77]; male, 50%) in an observational, retrospective study. All of them had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, all patients underwent right ventricular high-density electroanatomical mapping (EAM) using a multipolar catheter (Advisor HD Grid, Abbott), and EAM-guided endomyocardial biopsy (EMB). We recorded electrogram features at EMB sampling site, and explored their correlation with histological findings with mixed effect models. Results The clinical, electroanatomical, and histological features of enrolled patients according to the EMB-proven type of CA (AL, n=6; ATTR, n=4) are resumed in Table. Electrogram amplitudes in both the bipolar and the unipolar configuration were generally normal both in the overall right ventricle, and at EMB sites. We found a significant correlation between both unipolar and bipolar electrogram amplitude and the percentage of both amyloid tissue (p<0.01 and p=0.016, respectively) and fibrous tissue (both p<0.01) at EMB (Figure). We observed the strongest linear association (i.e., highest R2) between unipolar electrogram amplitude and amyloid tissue, as well as between bipolar electrogram amplitude and fibrous tissue. On the other hand, electrogram duration and the number of electrogram peaks were unrelated to histological findings. The unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). Conclusion CA is associated with normal electrogram amplitudes using ahigh density mapping catheter and conventional voltage cutoffs. Nevertheless, unipolar electrogram amplitude is strongly related to the extent of amyloid infiltration, and unipolar voltage<9.1 mV is 100% specific for >15% amyloid tissue deposition.

PO-02-213 ELECTROANATOMICAL ASPECTS OF BIOPSY-PROVEN CARDIAC AMYLOIDOSIS

Cardiac amyloidoses (CA) are a common and increasingly recognized group of infiltrative cardiomyopathies associated with high risk of heart failure, thromboembolic events, arrhythmias, and sudden death. Endomyocardial biopsy may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in selected cases. To describe electroanatomical characteristics of amyloid cardiomyopathy, and relate them to endomyocardial biopsy findings. We included ten consecutive patients (median age, 68 [63-77]; male, 50%) in an observational, retrospective study. All of them had a clinical diagnosis of CA, but a diagnosis of CA type was uncertain based on non-invasive findings. Therefore, all patients underwent right ventricular high-density electroanatomical mapping (EAM) using a multipolar catheter (Advisor HD Grid, Abbott), and EAM-guided endomyocardial biopsy (EMB). We recorded electrogram features at EMB sampling site, and assessed their correlation with histological findings with mixed effect models. The clinical, electroanatomical, and histological features of enrolled patients according to the EMB-proven type of CA (AL, n=6; ATTR, n=4) are resumed in Table. Electrogram amplitudes in both the bipolar and the unipolar configurations were largely preserved in the overall right ventricle, and at EMB sites. There were highly significant correlations among electrogram amplitudes in both the unipolar and bipolar configurations, and the extent of amyloid and fibrous tissue substitution at EMB (all p<0.01, Figure). We observed the strongest linear associations (i.e., highest R2) between unipolar electrogram amplitude and the percentage of amyloid tissue, as well as between bipolar electrogram amplitude and the percentage of fibrous tissue. On the other hand, electrogram duration and the number of electrogram peaks were unrelated to histological findings. The unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). CA is associated with preserved electrogram amplitudes at high-density electroanatomical mapping with conventional voltage cutoffs. Nevertheless, unipolar electrogram amplitude is strongly related to the extent of amyloid infiltration, and unipolar voltage<9.1 mV is 100% specific for >15% amyloid tissue deposition.

Abstract 9628: Association of Electrogram Features and Critical Reentrant Ventricular Tachycardia Sites with Nonischemic Scar on Late Gadolinium Enhanced Cardiac Magnetic Resonance

Introductions: The association of local electrogram features with nonischemic scar morphology and distribution on electroanatomic maps (EAM) has not been investigated. We aimed to quantitatively assess the association of nonischemic scar on late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) with local electrograms and critical sites in patients with nonischemic cardiomyopathy (NICM). Methods: LGE-CMR was performed in 19 patients with NICM. Scar characteristics were classified by scar transmurality and intramural scar types (endocardial, mid-wall, epicardial, patchy, transmural) on LGE-CMR short-axis planes (Figure, upper panel). EAM points were registered to the corresponding LGE-CMR images. Multivariable regression analysis clustered by patient was performed to assess the association of myocardium thickness, scar transmurality and intramural scar types, with electrogram bipolar/unipolar amplitude, duration and deflections. LGE-CMR characteristics of critical ventricular tachycardia (VT) sites were also investigated. Results: In pooled analyses, higher scar transmurality was significantly associated with lower bipolar (Figure, lower panel)and unipolar electrogram amplitude, longer duration and more deflections (P&lt;0.0001). Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P&lt;0.0001) and patchy scar (vs. endocardial, mid-wall, epicardial scar, P&lt;0.05). Most of the critical sites (16 sites; 89%) were located in scar with &gt;25% scar transmurality. Myocardial wall thickness, scar transmurality and intramural scar types were independently associated with electrogram features on multivariable regression analyses. Conclusions: Electrogram features on endocardial EAM are associated with scar morphology and distribution on LGE-CMR in NICM. This result may optimize procedural strategies including the decision to obtain epicardial access.

New Unipolar Electrogram Criteria to Identify Irreversibility of Nonischemic Left Ventricular Cardiomyopathy

This study sought to assess the value of left ventricular (LV) endocardial unipolar electroanatomical mapping (EAM) in identifying irreversibility of LV systolic dysfunction in patients with left ventricular nonischemic cardiomyopathy (LVCM). Identifying irreversibility of LVCM would be helpful but cannot be reliably accomplished by bipolar EAM or cardiac magnetic resonance identification of macroscopic scar. Detailed endocardial LV EAM was performed in 3 groups: 1) 24 patients with irreversible LVCM (I-LVCM) but with no or minimal macroscopic scar (<15% LV surface) evidenced on bipolar voltage EAM and/or cardiac magnetic resonance; 2) 14 patients with reversible ventricular premature depolarization-mediated LVCM (R-LVCM); and 3) 17 patients with structurally normal hearts. LV endocardial unipolar electrogram amplitude and area of unipolar amplitude abnormality were defined after excluding macroscopic scar. Unipolar amplitude differed in the 3 groups: median of 7.6 (interquartile range [IQR]: 5.5 to 9.7) mV in I-LVCM group, 13.2 (IQR: 10.4 to 16.2) mV in R-LVCM group, and 16.3 (IQR: 13.6 to 19.8) mV in structurally normal hearts group (p < 0.001). Areas of unipolar abnormality represented a large proportion of total LV surface in I-LVCM, 64.7% (IQR: 47.5% to 75.9%) compared with R-LVCM, 5.2% (IQR: 0.0% to 19.1%) and structurally normal hearts, 0.1% (IQR: 0.0% to 0.9%), groups (p < 0.001). A unipolar abnormality area cutoff of 32% of total LV surface was 96% sensitive and 100% specific in identifying irreversible cardiomyopathy among patients with LV dysfunction (I-LVCM and R-LVCM), p < 0.001. Detailed unipolar voltage mapping can identify irreversible myocardial dysfunction consistent with fibrosis, even in the absence of bipolar EAM or cardiac magnetic resonance abnormalities, and may serve as valuable prognostic tool in patients presenting with LVCM to facilitate clinical decision making.

Relation of High‐Pass Filtered Unipolar Electrograms to Bipolar Electrograms during Ventricular Mapping

A filtered bipolar electrogram (EG) amplitude <1.5 mV is a robust indicator of relatively dense scar, but is influenced by the wavefront direction. Unipolar recordings are not subject to directional influence. We hypothesized that high-pass filtered unipolar EGs would provide similar information to bipolar EGs, without potential errors related to wavefront direction. Simultaneous bipolar filtered at 30-500 Hz and unipolar (high-pass filtered at 30 Hz) signals were recorded during ventricular voltage maps in 24 patients (group A). In five subsequent patients, low voltage surface areas were compared in electroanatomic maps (group B). Of 2,789 mapping points in group A, filtered unipolar EG amplitude correlated well with bipolar EG amplitude. Agreement of filtered unipolar recordings in classifying sites as >1.5 mV or <1.5 mV with bipolar EG amplitude was 83%. Discordance was due to unipolar > bipolar amplitude at 83% of the discordant sites, consistent with possible reduction of bipolar amplitude due to direction dependence. Discordance was more frequent during epicardial than endocardial mapping. Double potentials were more frequently observed in bipolar than in unipolar recordings (3.2% vs 1.8%, P < 0.0001). In group B, the mean low-voltage surface area (<1.5 mV) was 70.1 ± 48.9 cm(2) for bipolar and 61.3 ± 52.2 cm(2) for filtered unipolar EG maps. Direction dependent effects on bipolar EG amplitude may influence the identification of substrate for arrhythmias. High-pass filtered unipolar EGs might be a reasonable alternative to bipolar recordings for creation of voltage maps.

Ablation lesion size correlates with pacing threshold: a physiological basis for use of pacing to assess ablation lesions.

The virtual electrode model predicts that pacing stimulus strength should reflect proximity of the pacing electrode to excitable myocardium, allowing pacing threshold to assess radiofrequency (RF) ablation lesions and unexcitable scar. The purpose of this study is to correlate RF lesion size with pacing threshold and electrogram (EG) amplitude change at the ablation site. In four swine (32-58 kg, 20 ventricular RF lesions were created using a 4-mm tip electrode catheters under fluoroscopic and electroanatomic guidance. Unipolar pacing threshold and bipolar and unipolar EG amplitude were measured before and after ablation and compared with lesion size measured in the fixed, serially sectioned tissue. Lesion diameter ranged from 6.4 to 19 mm and volume ranged from 29 to 1920 mm3. Ablation increased the pacing threshold by 320%, from 0.9 +/- 0.3 to 3.6 +/- 2.6 mA, P < 0.001. The change in pacing threshold correlated with lesion volume R = 0.88, P < 0.001). Linear regression predicts that lesion volume (mm3) = 160 X rise in pacing threshold + 13. Ablation reduced peak to peak bipolar EG amplitude by 56%, from 2.5 +/- 2.0 mV to 1.1 +/- 0.6 mV (P = 0.005). Unipolar EG amplitude diminished by only 22% from 4.0 +/- 1.6 to 3.2 +/- 0.9 mV postablation (P = 0.005). The correlations of lesion volume with change in either bipolar R = 0.14, P = 0.6) or unipolar R = 0.18, P = 0.6) EG amplitude were poor. Pacing threshold correlates with RF ablation lesion size, consistent with the virtual electrode model. In normal myocardium, change in pacing threshold is likely to be a better marker of lesion size than electrogram amplitude.

Myocardial viability assessment by endocardial electroanatomic mapping: comparison with metabolic imaging and functional recovery after coronary revascularization

OBJECTIVESThe objective of this study was to compare electroanatomic mapping for the assessment of myocardial viability with nuclear metabolic imaging using positron emission computed tomography (PET) and with data on functional recovery after successful myocardial revascularization.BACKGROUNDAnimal experiments and first clinical studies suggested that electroanatomic endocardial mapping identifies the presence and absence of myocardial viability.METHODSForty-six patients with prior (≥2 weeks) myocardial infarction underwent fluorine-18 fluorodeoxyglucose (FDG) PET and Tc-99m sestamibi single-photon emission computed tomography (SPECT) before mapping and percutaneous coronary revascularization. The left ventricular endocardium was mapped and divided into 12 regions, which were assigned to corresponding nuclear regions. Functional recovery using the centerline method was assessed in 25 patients with a follow-up angiography.RESULTSRegional unipolar electrogram amplitude was 11.0 mV ± 3.6 mV in regions with normal perfusion, 9.0 mV ± 2.8 mV in regions with reduced perfusion and preserved FDG-uptake and 6.5 mV ± 2.6 mV in scar regions (p < 0.001 for all comparisons). At a threshold amplitude of 7.5 mV, the sensitivity and specificity for detecting viable (by PET/SPECT) myocardium were 77% and 75%, respectively. In infarct areas with electrogram amplitudes >7.5 mV, improvement of regional wall motion (RWM) from −2.4 SD/chord ± 1.0 SD/chord to −1.5 SD/chord ± 1.1 SD/chord (p < 0.01) was observed, whereas, in infarct areas with amplitudes <7.5 mV, RWM remained unchanged at follow-up (−2.3 SD/chord ± 0.7 SD/chord to −2.4 SD/chord ± 0.7 SD/chord).CONCLUSIONSThese data suggest that the regional unipolar electrogram amplitude is a marker for myocardial viability and that electroanatomic mapping can be used for viability assessment in the catheterization laboratory.

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction

OBJECTIVESThis study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping.BACKGROUNDThe degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue.METHODSElectromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data.RESULTSFrom the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 ± 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 ± 0.7 mV, 1.4 ± 0.7 mV, 0.8 ± 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups.CONCLUSIONSThe degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.

Effects of coupling heterogeneity on fractionated electrograms in a model of nonuniformly anisotropic ventricular myocardium

To further understand the relation between heterogeneously infarcted myocardium and fractionated electrograms, a computer model was used to test the hypothesis that the way electrogram metrics change with electrode location relates to statistical properties of the underlying myocardium. A sheet of Beeler-Reuter elements was coupled with cytoplasmic resistance to form cells. Junctional resistance values were assigned using a recursive randomization to produce a fractal pattern, simulating damage from disrupted blood supply. The pattern's correlation dimension, D, was a statistical measure of heterogeneity. Unipolar electrogram's amplitude, duration, number of inflections, peak frequency, bandwidth, and the rate of change of metrics with height were calculated. Analysis of variance indicated ( P < .0001) that peak-to-peak amplitude and bandwidth decreased at a slower rate when height was increased above heterogeneous tissue as compared with homogeneous tissue. These findings could be useful during clinical mapping procedures as statistical estimates of tissue structure.

The effect of left ventricular intracavitary volume on the unipolar electrogram.

In order to examine the effects of ventricular distention on the unipolar electrogram (UEG), an isolated rabbit heart modified Langendorff preparation was utilized. Left ventricular (LV) volume was adjusted using ionically permeable (PB = 9 hearts) or ionically impermeable balloons (IB = 4 hearts). LV UEGs, LV end-diastolic pressure (EDP), and LV minor axis dimension (MAD), as measured by ultrasonic transducers, were recorded. Three hundred twenty-five electrograms were digitized and analyzed with custom-designed software. In the PB group, a significant inverse linear relationship was found between UEG amplitude and changes in MAD (P < 0.0001). For each animal, this relationship had an R value > 0.8 and a P value < 0.0001. There was also a significant inverse linear relationship between UEG slope and changes in MAD (P < 0.01). UEG amplitude and slope also exhibited a significant inverse relationship to changes in LV EDP, which were best described by a third order polynomial function. In the IB group, no significant relationship was found between either UEG amplitude or slope and MAD or EDP. In this study, intracavitary volume exerted a profound and significant influence on UEG amplitude and slope. This effect was due to increases in conductive intraventricular volume and not to myocardial stretch.