Endorsed by: association for European Paediatric and Congenital Cardiology (AEPC), Endocardial unipolar voltage mapping to detect epicardial ventricular tachycardia substrate in patients with nonischemic left ventricular cardiomyopathy, Characteristics of intramural scar in patients with nonischemic cardiomyopathy and relation to intramural ventricular arrhythmias, Contrast-enhanced MRI-derived scar patterns and associated ventricular tachycardias in nonischemic cardiomyopathy: implications for the ablation strategy, New unipolar electrogram criteria to identify irreversibility of nonischemic left ventricular cardiomyopathy, Effect of epicardial fat on electroanatomical mapping and epicardial catheter ablation, Integration of cardiac magnetic resonance imaging with three-dimensional electroanatomic mapping to guide left ventricular catheter manipulation: feasibility in a porcine model of healed myocardial infarction, Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation, Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy, Epicardial substrate mapping for ventricular tachycardia ablation in patients with non-ischaemic cardiomyopathy: a new algorithm to differentiate between scar and viable myocardium developed by simultaneous integration of computed tomography and contrast-enhanced magnetic resonance imaging, Isolated septal substrate for ventricular tachycardia in nonischemic dilated cardiomyopathy: incidence, characterization, and implications, Idiopathic dilated cardiomyopathy: analysis of 152 necropsy patients, Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy, Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy, Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy, Histological validation of cardiac magnetic resonance analysis of regional and diffuse interstitial myocardial fibrosis, Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance, Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy, Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy, Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing, Head-to-head comparison of contrast-enhanced magnetic resonance imaging and electroanatomical voltage mapping to assess post-infarct scar characteristics in patients with ventricular tachycardias: real-time image integration and reversed registration, Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction, Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality, Use of electrogram characteristics during sinus rhythm to delineate the endocardial scar in a porcine model of healed myocardial infarction, Impact of nonischemic scar features on local ventricular electrograms and scar-related ventricular tachycardia circuits in patients with nonischemic cardiomyopathy, Spread of activation in the left ventricular wall of the dog. Pattern and architecture of fibrosis in a random selection of TB were reviewed by a co-author (C.B.) Corresponding author. of his, which branches to form Purkinje Nazarian S, Bluemke DA, Lardo AC, Zviman MM, Watkins SP, Dickfeld TL, Meininger GR, Roguin A, Calkins H, Tomaselli GF, Weiss RG, Berger RD, Lima JA, Halperin HR. Voltages and histological parameters of TB with normal and abnormal amounts of fibrosis are given in Table 2. Wrobleski D, Houghtaling C, Josephson ME, Ruskin JN, Reddy VY. the heart valves. To date, LGE-CMR to detect and determine scar size has only been histologically validated in an ex vivo animal model for post-infarct scar.25 Current LGE-CMR methods to detect fibrosis require either bright areas with dense fibrosis or normal reference myocardium. Electroanatomical voltage mapping (EAVM) is an important diagnostic tool for fibrosis identification and risk stratification in non-ischaemic cardiomyopathy (NICM); currently, distinct cut-offs are applied. Five underwent combined endo-epicardial mapping (Supplementary material online, Table S1). Our data demonstrated such a linear relationship. membrane, there is a small layer of loose connective tissue and The basal-anterior and basal-septal segments were most frequently affected, followed by mid-anterior and apical-anteroseptal involvement. This layer contains fibroelastic connective tissue, blood vessels, lymphatics and adipose tissue. The myocardium is the largest of the three layers, and contains to assess inter-observer agreement (Supplementary material online, methods). Accordingly, any cut-off to delineate fibrosis performed poorly. The fibrosis architecture is most often patchy or diffuse and a combination of more than one architecture occurs frequently. In all TB, a linear relationship between amount of viable myocardium and UV generated was observed. Not only the WT, but also the amount of fibrosis, affects the amount of viable myocardium present and thus influences both UV and BV. Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, Luu TM, Di CMF, Reynolds HG, Stevenson WG, Kwong RY. Our study is the first to specifically describe the fibrosis pattern and architecture in patients with NICM and sustained MVT. Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. layer in this photograph? Histological and voltage parameters of all biopsies, and biopsies subdivided based on location of voltage data (endocardial and epicardial) and on quantity of fibrosis [normal (<21%) and abnormal (>21%)]. These specific characteristics of fibrosis are likely to impact its accurate delineation by current LGE-CMR methods. (B) Viable myocardium and corresponding voltages. around the atria via gap junctions between the muscle fibres. Patchy and diffuse architectures dominate whereas compact fibrosis is rare. Cultured dissociated primary dorsal root ganglion neurons from adult horses enable study of axonal transport. sac that encloses the heart. Transmural biopsies with signs of acute or old ablation lesions were excluded. In this patient population, neither BV nor UV is restricted by a field of view. This study has taken an important step in this regard, providing an equation for detection of fibrosis based on UV and/or BV and WT. On histological analysis, all NICM hearts showed pathological amounts of fibrosis. (C) Custom software used to calculate the amount of fibrosis. To what extend is socioeconomic status associated with not taking up and dropout from cardiac rehabilitation: a population-based follow-up study. To date, the only histological validation of electroanatomical voltage mapping (EAVM) for scar detection arises from animal infarct models.12 Infarct scars, with a transmural pattern and compact fibrosis interspersed with viable myocardial bundles, may be substantially different from NICM scars.4,13 Animal models mimicking NICM scar patterns are lacking. Transmural biopsies were systematically assessed on the following parameters: The fibrotic involvement of the seven LV segments was macroscopically assessed in the stained TB to determine the location of fibrosis. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ, Kolh P, Lip GYH, Agewall S, Baron-Esquivias G, Boriani G, Budts W, Bueno H, Capodanno D, Carerj S, Crespo-Leiro MG, Czerny M, Deaton C, Dobrev D, Erol C, Galderisi M, Gorenek B, Kriebel T, Lambiase P, Lancellotti P, Lane DA, Lang I, Manolis AJ, Morais J, Moreno J, Piepoli MF, Rutten FH, Sredniawa B, Zamorano JL, Zannad F, Cardiology ES. This diagram shows that the simple squamous epithelium of the Department of Cardiology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Published on behalf of the European Society of Cardiology. For every millimetre increase in ex vivo WT the UV increased by 0.28mV (P=0.010). In 457 (90%) TB, a combination of two or three architectures was observed. Additionally, the amount of fibrosis affects UV and BV. de Leeuw N, Ruiter DJ, Balk AH, de Jonge N, Galama JMD, Melchers WJG. Seven patients died and one patient was successfully transplanted a median of 25 (IQR 6217) days after EAVM. A 1 mm2 increase in amount of viable myocardium resulted in a 0.06mV (P=0.001) increase in endocardial BV. I, Comparison of echocardiographic and necropsy measurements of ventricular wall thicknesses in patients with and without disproportionate septal thickening. Additionally, BV is less sensitive to the activity of viable myocardium occurring at distances remote from the catheter tip than UV, leading to the concept of a limited field of view.7,16. Depolarization of the sinoatrial node cells allows for conduction of the electrical impulse through the conduction tracts within the wall of the right atrium: Anterior tract (Bachmann bundle): extends to left atrium, Depolarization also facilitates atrial contraction, Receives impulses from the sinoatrial nodal tracts, in order to propagate electrical cardiac impulse and facilitate ventricular contraction, Located in the right atrium, in the space between the ostium of the coronary sinus, septal leaflet of the tricuspid valve and tendon of Todaro (Koch triangle) (Koch triangle), Located in the membranous septum that separates the right atrium from the left ventricle, Relays electrical impulses to the left and right bundle branches of the ventricular (muscular) septum. Sustained ventricular tachycardia (VT) in patients with non-ischaemic cardiomyopathy (NICM) is often due to myocardial re-entry and occasionally to triggered activity both associated with the presence of fibrosis.1,2 Animal models and human data in end-stage heart failure suggest that the degree of arrhythmogeneity depends on amount and architecture of fibrosis with highest propensity for intermediate degrees and patchy architecture.35 However, histological data from patients with NICM and sustained monomorphic VT (MVT) is lacking. Red: scar core. All patients were treated according to our standard clinical protocol and provided informed consent for mapping and ablation. (A) Endocardial and epicardial bipolar voltage maps, colour-coded according to bar in an anteriorposterior view. Excitation of the SA node sets of a wave of depolarisation which is found in the wall of the superior vena cava. We demonstrate a linear relationship between the amount of viable myocardium and both the UV and BV amplitudes (Take home figure). In total, 160 (32%) TB had normal amounts of fibrosis if matched for age. Eight patients with NICM and VT underwent EAVM prior to death or heart transplantation. Soejima K, Stevenson WG, Sapp JL, Selwyn AP, Couper G, Epstein LM. Of importance, only 3% of TB showed compact fibrosis with the density of ischaemic scars, and this fibrosis was never transmural. Heart serves as a pump that drives 2 parallel vascular circuits: Blood is ejected from the left ventricle through the aortic valve during systole at a normal pressure of 120 mmHg, Blood travels through the ascending aorta, aortic arch and descending aorta; it then progresses through peripheral arteries, arterioles and eventually the systemic capillary beds, before entering the venous return, Systemic venous blood returns to the right atrium from the superior and inferior vena cava at a pressure of < 5 mmHg, Spontaneous contraction of the right atrium moves deoxygenated blood through the tricuspid valve to the right ventricle, Ventricular contraction (systole) moves blood from the ventricle through the pulmonic valve to the pulmonary artery at a normal pressure of 25 mmHg, Blood travels through the arteries and arterioles of the lung before reaching the alveolar capillaries, Newly oxygenated blood returns to the left atrium via 4 pulmonic veins at a normal pressure of approximately 10 mmHg, Left atrial contraction moves blood through the mitral valve into the left ventricle, The cardiac conduction system allows for coordinated atrioventricular contraction via the conduction of electrical impulses by specialized myocardial cells (, Pacemaker of the heart located near the sinotubular junction, where the superior vena cava meets the right atrium. This study is the first to provide detailed histological data on fibrosis in NICM patients with sustained MVT and to couple EAVM data with the true gold standard for fibrosis identificationhistology. autonomic nervous system that speed up and slow down the heart rate. is the inner layer.The space between the two layers Continuous variables were compared using (multivariable) linear regression analysis in a model that allowed for intragroup correlation. (D) Example of four slices with electroanatomical voltage mapping points and ablation locations projected. A 1 mm2 increase in viable myocardium resulted in a 0.09mV (P=0.002) increase in endocardial UV (Figure 3B) and a 0.08mV (P=0.016) increase in epicardial UV. Unverferth DV, Baker PB, Swift SE, Chaffee R, Fetters JK, Uretsky BF, Thompson ME, Leier CV. Firstly, a single BV or UV cut-off to detect fibrosis, as currently applied in practice, cannot be valid considering the range of observed WT. endocardium (tunica intima). system. Whilst we have described the fibrosis present in NICM patients with VT, the specific fibrosis needed to sustain VT has not been identified. All patients and/or next of kin provided informed consent for post-mortem analysis. de Bakker JM, van Capelle FJ, Janse MJ, Wilde AA, Coronel R, Becker AE, Dingemans KP, van Hemel NM, Hauer RN. Smaller electrodes are likely to reduce far field contamination and may be beneficial for areas with sub-endocardial involvement but would be potentially less helpful in areas with a mid-wall pattern of fibrosis. (C) Integration of voltage maps with 3D anatomical mesh (grey). Renal disease, COPD, and diabetes mellitus. Statistical analysis was performed using IBM SPSS version 23 (SPSS Inc., Chicago, IL, USA) or STATA Statistical Software (StataCorp, College Station, TX, USA), version 14. Transmural biopsies with a width of 5mm (7m thick) were taken from left ventricular (LV) sites corresponding to non-ablation EAVM sites and stained with Picrosirius Red (Figure 1D) (Supplementary material online, methods). fluid. (A) Equations to predict amount of fibrosis when wall thickness (mm) and voltages (mV) are known. myocardium (tunica media) The AV node lies in the interatrial septum. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Search for other works by this author on: LKEBDivision of Image Processing, Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands, Department of Anatomy and Embryology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, The Netherlands, Department of Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands, Department of Clinical and Experimental Cardiology, Academic Medical Centre, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. McCrohon JA, Moon JC, Prasad SK, McKenna WJ, Lorenz CH, Coats AJ, Pennell DJ. Both BV and UV mapping are sensitive not only to the amount of fibrosis but also to myocardial WT. Electroanatomical bipolar voltage (BV) and unipolar voltage (UV) mapping is considered an invasive reference method to detect fibrosis.6 Different endocardial BV and UV cut-off values for detecting fibrosis have been proposed.79 It has been suggested that the presence of a viable sub-endocardial layer overlying fibrosis may prevent its detection by BV mapping using the currently uniformly applied BV cut-off of 1.5 mV.8,9 Unipolar voltage mapping is considered to have a larger field of view and thus superior in detecting mid-wall and sub-epicardial fibrosis.911 However, neither the currently used cut-off values for detecting fibrosis in NICM, nor the field of view of UV or BV have been validated. Despite high quantity, less well-delineated fibrosis (Insert 1) was only identified as core scar when using the 23SD method; as borderzone when using the MaxSI or modified Full-Width Half Maximum (FWHM) method. discs at the end of each muscle cell. Impulses are sent from the AV node into the AV bundle, or bundle Next the atrioventricular node (AV) starts impulse generation The endocardium lines the atria and ventricles and covers The fibrous pericardium Of interest, the same linear relationship was observed between BV and WT: for every millimetre increase in ex vivo WT the BV increased by 0.23mV (P=0.009). Hence The 1.5mV and 8.27mV mark indicate clinically applied cut-off values. connective tissue of the tunica intima The amount of fibrosis in each biopsy was assessed, with a median of 6.5% (IQR 4.99.3) fibrosis. Claire A Glashan, Alexander F A Androulakis, Qian Tao, Ross N Glashan, Lambertus J Wisse, Micaela Ebert, Marco C de Ruiter, Berend J van Meer, Charlotte Brouwer, Olaf M Dekkers, Daniel A Pijnappels, Jacques M T de Bakker, Marta de Riva, Sebastiaan R D Piers, Katja Zeppenfeld, Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischaemic cardiomyopathy and ventricular tachycardia, European Heart Journal, Volume 39, Issue 31, 14 August 2018, Pages 28672875, https://doi.org/10.1093/eurheartj/ehy168. High-density EAVM was performed during sinus rhythm or right ventricular pacing using a 3.5mm irrigated-tip catheter (1mm ring electrode, 2mm inter-electrode spacing; NaviStar Thermocool, Biosense Webster Inc., CA, USA) and the CARTO system (Figure 1A) (Supplementary material online, methods).7,11,14,15. The AV node is also supplied by nerve fibres from the It has previously been suggested that BV is limited by a field of view.7,16 To test the impact of fibrosis remote from the endocardial surface, the relationship between amount of viable myocardium within TB and the endocardial voltages generated was analysed within a sub-selection of TB which had a normal amount of fibrosis in the 4mm sub-endocardium (Figure 3C). Predictability of Metabolic Syndrome Diagnosed by Body Mass Index for Cardiovascular Risk in Older Patients Treated with Levothyroxine. Integration of the ex vivo 3D meshes with the in vivo mapping data was accurate based on good agreement between macroscopically or histologically identified ablation lesion and ablation sites on EAVM (Figure 1D). Kawara T, Derksen R, de Groot JR, Coronel R, Tasseron S, Linnenbank AC, Hauer RN, Kirkels H, Janse MJ, de Bakker JM. From each heart, four LV TB were taken from the anterior, lateral, inferior, and septal walls. The amount of fibrosis can be calculated, if WT and voltages are known. Histology [title] heart [TIAB] free full text[sb], UpToDate: Biomarkers of Myocardial Injury Other Than Troponin [Accessed 15 January 2021], UpToDate: Natriuretic Peptide Measurement in Heart Failure [Accessed 15 January 2021], Allen: Moss & Adams' Heart Disease in Infants, Children, and Adolescents, 8th Edition, 2012, Buja: Cardiovascular Pathology, 4th Edition, 2015, Specialized muscle cells, namely cardiomyocytes, allow for synchronized contractions to facilitate the pumping of blood throughout the body, Heart wall consists of 3 layers: endocardium, myocardium and epicardium, Variation in the relative thickness of each of these layers exists between ventricles and atria, and between left and right sided chambers, Myocardium is primarily composed of cardiac myocytes: specialized striated muscle cells organized in fascicles and bands. This facilitates the pumping action of the heart. Control tissue for histology was obtained from seven age-matched hearts [five male, median age 65 (IQR 5967) years]. Accurate integration confirmation by visual inspection of projection of ablation locations over pathology ablation lesions. Fibrosis architecture was rarely compact, but typically patchy and/or diffuse. The presence and extent of particularly mid-wall fibrosis has been associated with inducible VT23 and with mortality and (aborted) sudden cardiac death in a recent cohort of 472 NICM patients.24. blood at high pressure round the body through the blood vessels. The area of viable myocardium was used as a surrogate for the volume of viable myocardium at that location (Supplementary material online, methods and Figure S2). A further 30% showed a sub-endocardial pattern and a transmural pattern was seen in 28%. Morita N, Mandel WJ, Kobayashi Y, Karagueuzian HS. (B) Voltages (mV) generated when ex vivo wall thickness (mm) and % fibrosis are known. Stained 5-mm wide biopsy corresponding to non-ablation site A. Collagen stains red and myocardium yellow. Desjardins B, Yokokawa M, Good E, Crawford T, Latchamsetty R, Jongnarangsin K, Ghanbari H, Oral H, Pelosi FJr, Chugh A, Morady F, Bogun F. Piers SR, Tao Q, van Huls van Taxis CF, Schalij MJ, van der Geest RJ, Zeppenfeld K. Campos B, Jauregui ME, Park KM, Mountantonakis SE, Gerstenfeld EP, Haqqani H, Garcia FC, Hutchinson MD, Callans DJ, Dixit S, Lin D, Riley MP, Tzou W, Cooper JM, Bala R, Zado ES, Marchlinski FE. Wijnmaalen AP, van der Geest RJ, van Huls van Taxis CF, Siebelink HM, Kroft LJ, Bax JJ, Reiber JH, Schalij MJ, Zeppenfeld K. Schmidt A, Azevedo CF, Cheng A, Gupta SN, Bluemke DA, Foo TK, Gerstenblith G, Weiss RG, Marban E, Tomaselli GF, Lima JA, Wu KC. Non-ischaemic cardiomyopathy patients who underwent detailed EAVM and ablation for MVT and either died or received heart transplantation after the procedure were included (Supplementary material online, methods). The fibrosis pattern is highly variable and not restricted to the mid-wall and sub-epicardium. We welcome suggestions or questions about using the website. In end-stage heart failure patients a variable degree of interstitial fibrosis was seen at sites of induced focal, non-sustained, polymorphic VTs.20, Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) is the imaging reference method for the non-invasive detection of regional fibrosis in NICM.21 A study including 63 unselected patients with dilated cardiomyopathy reported no LGE in the majority of patients (59%), sub-endocardial LGE in 13% (attributed to ischaemia), and mid-wall or sub-epicardial LGE in 28% typically involving the basal and mid-LV22. the apex of the heart contracts first, followed by the papillary The comparison of in vivo LGE-CMR data from one patient obtained 133days before mapping and ablation illustrates the variation in scar size dependent on the applied LGE-CMR method and supports the limitation of LGE-CMR to accurately identify and delineate diffuse fibrosis (Figure 5 and Supplementary material online, methods).23,2628. (C) Transmural biopsies with <21% in the 4mm sub-endocardial rim (n=79): unipolar voltage and bipolar voltage against viable myocardium within the entire biopsy. This study reported ex vivo WT. In total, 507 TB [56 (IQR 3496) TB per patient] were taken; 277 corresponding to endocardial non-ablation EAVM sites (endocardial TB) and 230 corresponding to epicardial non-ablation EAVM sites (epicardial TB) (Supplementary material online, Table S2). Tel: +31715262020, Fax: +31715266809, Email: Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia, Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low-voltage scars, Cardiac fibrosis as a determinant of ventricular tachyarrhythmias, Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis, 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). The histological substrate has been described, and the relationship between the amount of fibrosis as well as wall thickness and both bipolar and unipolar voltages demonstrated. and the intercalated A clinical review, Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction, Extracellular volume fraction by T1 mapping predicts omprovement of left ventricular ejection fraction after catheter ablation in patients with non-ischemic cardiomyopathy and atrial fibrillation, Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy. The Author(s) 2018. Three-dimensional meshes were created from 5mm thick slices of the fixed heart, imported into CARTO, and merged with EAVM data (Figure 1B and C) (Supplementary material online, methods).9. You also need to know about Purkinje fibres, which lie in the endocardium. The amount of viable myocardium showed a linear association with both UV and BV. Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O'Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK. Unipolar voltage mapping overestimated and BV mapping underestimated involvement as derived from histology (Supplementary material online, Table S2). Importantly, for relatively large distances between 1020mm, the relationship between WT and amplitude is near linear (Supplementary material online, Figure S5), which is in line with the linear relationship we found between BV and UV within the clinically relevant range of WT in our cohort. Yellow: scar borderzone according to different methods (Supplementary material online, methods). The cut-off values for UV and BV proposed in the literature vary in their absolute value and in the population in which they were derived. tunica adventitia layer of the heart (mesothelium) In all patients, TB were taken from seven locations: the anterior-septal, lateral and inferior wall at the mid, and basal level and the apex. First, impulses are generated by the sinoatrial node (SA), system, the heart has three layers, as shown in the diagram In NICM, biopsies without abnormal fibrosis unipolar voltage (UV) and bipolar voltage (BV) showed a linear association with wall thickness (WT). According to the dominant site of fibrosis throughout the myocardium, five patterns were defined by visual assessment: minimal interstitial fibrosis (not restricted to one area of the biopsy), sub-endocardial, mid-wall, sub-epicardial, and transmural fibrosis (Figure 2A). A 1 mm2 increase in the amount of viable myocardium beyond the 4mm sub-endocardial rim resulted in a UV increase of 0.09mV (P=0.012) and BV increase of 0.05mV (P=0.046). Patchy: areas of replacement fibrosis, surrounded by confluent viable myocardium. Reddy VY, Malchano ZJ, Holmvang G, Schmidt EJ, d'Avila A, Houghtaling C, Chan RC, Ruskin JN. Compact: dense areas of fibrosis, spanning the full width of the TB devoid of any viable myocardium. Clinical evaluation of cardiac structure and function is multifaceted and may include: Common myocardial heart specimens include: Interventionalist uses a bioptome via an endovascular procedure, to sample endocardium and myocardium from the right ventricular septum, Most common indication for endomyocardial biopsy is in the setting of transplant rejection monitoring, In the appropriate clinical context, biopsies may also be used for the evaluation of heart disease, especially if there is concern for myocarditis, amyloidosis, hemochromatosis, drug toxicity or storage disorders, Surgeon enters the left ventricle, either through the aortic valve (after aortotomy) or through the apical ventricular wall (ventriculotomy), Endocardium and myocardium are shaved for evaluation of septal abnormalities seen on echocardiogram, Most common indication / etiology is hypertrophic cardiomyopathy but in the right demographic ruling out amyloidosis or storage disease is prudent, Apical core resection: full thickness ventricular wall excision, allowing for placement of a ventricular assist device, Atriotomy: normally excised for access to the heart chambers in a valve replacement procedure, Atrial appendage: often excised prophylactically or incidentally during surgical procedures, Serologic markers of acute coronary syndrome (, Normal proteins that are present in myocardium which are released into systemic circulation in response to myocyte injury, May remain elevated for up to 10 - 14 days post insult, Enzyme that is present in both cardiac and skeletal muscle, Elevations begin 4 - 6 hours post insult and resolve within 36 - 48 hours, Isoenzyme CK-MB is proportionally greater in cardiac muscle but is present in larger absolute quantities in skeletal muscle, Formerly the preferred test of choice but has now been replaced by troponin; CK-MB is less specific for cardiac injury than troponin, Heme complexed protein that is present in wide range of cell types and is released in response to damage, Low specificity makes this an antiquated test that should rarely be employed, Brain natriuretic peptide (BNP, proBNP, NT proBNP), Protein (and cleavage products) is initially found in the brain but is present in ventricular myocytes, Released in response to increased ventricular pressure; elevated BNP is highly sensitive but not very specific for heart failure, Released in response to dilation of atria due to increased volumes, Endocardium: thin, shiny, translucent layer without fibrotic (tan-white) thickening, Myocardium: uniform tan-brown to red striated tissue with firm but pliable texture, No areas of gray-brown mottling and no areas of dense fibrosis, Epicardium: thin, shiny and translucent without fibrosis; epicardial fat may be present, Evaluation of the surgical or autopsy specimen should be conducted with a systematic approach (.