Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment
Abstract
:1. The Health Challenge of Arrhythmias in Ischemic Heart Disease
2. Current Management: Much to Be Desired from Pharmacotherapy
3. The Unique Nature and Central Role of the Border Zone
4. Origin and Maintenance of VT–Mechanistic Insights Obtained In Vivo
4.1. The Conceptual Framework
4.2. Triggers and Arrhythmia Initiation
4.3. Arrhythmia Substrates for Progression and Sustenance/Maintenance
5. Cellular Remodelling in the BZ Underlying In Vivo Arrhythmogenesis
5.1. Animal Models for Post-MI Remodelling
5.2. Myocyte Electrical Remodelling in the BZ–Role in Re-Entry and Triggered Activity
5.3. Role of Autonomic Inputs in the BZ for Arrhythmogenesis
6. Emerging Concepts and Future Research Directions for Post-MI Arrhythmia Management
6.1. Systemic Small Molecule Therapy or Local BZ Targeted Therapy
6.2. Understanding the Complexity of the Arrhythmia Sites
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Species | MI Stage | Disease Model | Regions | Preparation | Observations |
---|---|---|---|---|---|---|
Tsujii et al., 2003 [148] | Rat | Acute (2 h) | LAD ligation | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | Ca2+ waves in BZ, uniform synchronous CaT in remote. |
Takahashi et al., 2004 [149] | Dog | Acute (3–4 h) | Ligation side branch of LCX (ex vivo) | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | ↓ APD90, ↓ CV, ↓ APA, ↓ diastolic potential in BZ vs. remote. |
Baba et al., 2005 [99] | Dog | Intermediate (5 d) | LAD ligation | central vs. outer reentry path (cBZ vs. oBZ) | single myocytes LV (whole-cell patch-clamp) | ↓ INa, ↓ ICaL, ↓ Ito in cBZ and oBZ. |
Cabo et al., 2006 [150] | Dog | Intermediate (5 d) | LAD ligation | different regions of reentry path within BZ (epi): central vs. outer reentry path (cBZ vs. oBZ) | single myocytes and tissue LV (electrogram) | ↓ CV longitudinal and transverse vs. normal hearts, ↓ longitudinal CV in cBZ vs. oBZ myocytes, transverse CV unchanged in cBZ vs. oBZ myocytes. ↑ Cx43 laterisation in cBZ vs. oBZ myocytes |
Hund T et al., 2008 [151] | Dog | Intermediate (5 d) | LAD ligation (2h) + reperfusion In silico model | BZ (epi) vs. remote (epi) | in silico | ↓ CaT amplitude, ↓ Vmax in BZ vs. remote with hyperactive CaMKII ↑ P-CaMKII in BZ vs. remote ↑ P-CaMKII at intercalated disk in BZ vs. control |
Chou et al., 2007 [152] | Rabbit | Intermediate (7 d) | LCX ligation | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | ↑ extrasystoles in BZ, steeper ADP restitution in BZ, ↑ pacing-induced Ca2+ alternans in BZ vs. remote |
Mills et al., 2006 [153] | Rat | Intermediate (7 d) | LAD ligation | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | APD90 = in BZ vs. remote, ↓ CV in BZ vs. remote. |
Pop et al., 2012 [154] | Pig | Chronic (4 w) | Balloon occlusion in LAD or LCX (90 min) + reperfusion | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | ↓ APD90 in BZ vs. remote |
Pinali et al., 2017 [155] | Pig | Chronic (4 w) | Microbead embolisation in LAD side branch | BZ vs. remote | tissue LV sampling | Cav1.2 =, BIN1 =, ↓JP2 in BZ vs. remote ↓ TT in BZ and remote vs. control, ↑ cell capacitance in BZ and remote vs. control. |
Dun et al., 2004 [156] | Dog | Intermediate (14 d), Chronic (8 w) | LAD ligation | BZ (epi) vs. remote (epi) | single myocytes LV (whole-cell patch-clamp) | 14d: ↓ ICaL in BZ vs. remote, ↑ ISO effect in remote (presence of regional heterogeneity in adrenergic response); ↓ Ito in BZ vs. remote 8w: ↓ ICaL in BZ and remote, no ISO effect in BZ and remote (absence of regional heterogeneity in adrenergic response); Ito = in BZ vs. remote cell capacitance = in BZ vs. remote |
Dries and Amoni et al., 2020 [89] | Pig | Chronic (6 w) | Copper-coated stent in LAD | BZ (mid) vs. remote (mid) | single myocytes LV (whole-cell patch-clamp) | ↑ DADs and spontaneous AP in BZ vs. remote, ↑ BVR in BZ vs. remote (with adrenergic signalling). Gene expression ↑ NPPA in BZ vs. remote. ↑ cell width, = cell length, = TTs in BZ vs. remote. |
Kim et al., 2002 [157] | Sheep | Chronic (8 w) | LAD ligation | BZ (endo) vs. remote (endo) | single myocytes LV (whole-cell patch-clamp) | ↓ ICaL, ↓ CaT amplitude, ↑ CaT relaxation time, ↓ contraction in BZ vs. remote. ↓ SERCA in BZ vs. remote. ↑ cell length, ↑ cell width, ↑ cell capacitance in BZ vs. remote. |
Shimkunas et al., 2013 [158] | Sheep | Chronic (17 w) | LCX ligation | BZ (epi) vs. remote (epi) | tissue LV (force measurements) | ↓ force development in BZ vs. remote |
Wong et al. 1982 [139] | Cat | Chronic (2–7 months) | Ligation side branches of LAD and LCX | BZ (endo) vs. remote (endo) | tissue LV (microelectrode) | ↓ APD90, ↓ RMP (depolarised), ↓ Vmax in BZ vs. remote |
Kimura et al. 1986 [159] | Cat | Chronic (2–6 months) | Ligation side branches of LAD and LCX | BZ (endo) vs. remote (endo) | tissue LV (ion-sensitive microelectrodes) | ↓ [K+], ↑ [Na+] in BZ vs. remote |
Pinto et al. 1997 [160] | Cat | Chronic (>2 months) | Ligation side branches of LAD | BZ (endo) vs. remote (endo) | single myocytes LV (whole-cell patch-clamp) | ↓ ICaL in BZ and remote vs. control, ↓ APD in BZ, ↑ ADP in remote ↑ cell capacitance in remote vs. BZ/control |
Kimura et al. 1988 [161] | Cat | Chronic (>2 months) | Ligation side branches of LAD and LCX | BZ (endo) vs. remote (endo) | tissue LV (microelectrode) | RMP =, APA =, APD90 =, APD50 = in BZ vs. remote |
Weigand et al., 2016 [162] | Rat | Chronic (6 w) | LAD ligation | BZ (epi) vs. remote (epi) | whole heart (in vivo LV mapping) | ↓ MAPA, ↑ heterogeneity of repolarisation, ↓ Vmax, MAPD = in BZ vs. remote |
Walker et al., 2007 [163] | Rabbit | Chronic (8 w) | LCX ligation | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | ↓ CV in BZ vs. remote |
Dangman et al. 1982 [164] | Human | Chronic (end-stage HF) | - | BZ (endo) vs. remote (endo) | tissue LV (microelectrode) | ADP50 =, ADP100 =, Vmax =, RMP =, APA = in BZ vs. remote |
Heygi et al., 2018 [88] | Pig | Chronic (5 months) | Microbead embolisation in LAD side branch | BZ vs. remote | single myocytes LV (whole-cell patch-clamp) | ↓APD95 in BZ, ↑ APD95 in remote, CaT amplitude/relaxation =, INa =, ↓ ICaL, ↓IK1, IKr =, INCX =, IKs =, ↑ DAD/AP frequency in BZ vs. remote ↓ cell shortening in BZ/remote vs. control, = cell shortening in BZ vs. remote |
Loennechen et al., 2002 [165] | Rat | Chronic (56 d) | LAD ligation | Remote vs. sham, Remote vs. BZ | single myocytes LV | ↑ diastolic and systolic [Ca2+] in remote MI vs. sham; = diastolic and systolic [Ca2+] in remote vs. BZ ↑ cell length, ↑ cell width in remote vs. sham; = cell length, = cell width in remote vs. BZ cell shortening = in remote vs. BZ |
Kilic et al., 2006 [166] | Sheep | Chronic (8 w) | LAD ligation | BZ vs. remote | whole heart (in vivo LV echo) | ↓ SERCA, ↓ PLB in peri-infarct vs. remote (correlated with regional strain on echo) |
Tomek et al., 2019 [167] | Rat | Chronic (8 w) | Antero-apical cryo-infarction | BZ (epi) vs. remote (epi) | tissue LV (optical mapping) | ↑ alternans at longer cycle length in BZ vs. remote at baseline; ↓ alternans at longer cycle length in BZ vs. remote during adrenergic signalling |
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Amoni, M.; Dries, E.; Ingelaere, S.; Vermoortele, D.; Roderick, H.L.; Claus, P.; Willems, R.; Sipido, K.R. Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment. Cells 2021, 10, 2629. https://doi.org/10.3390/cells10102629
Amoni M, Dries E, Ingelaere S, Vermoortele D, Roderick HL, Claus P, Willems R, Sipido KR. Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment. Cells. 2021; 10(10):2629. https://doi.org/10.3390/cells10102629
Chicago/Turabian StyleAmoni, Matthew, Eef Dries, Sebastian Ingelaere, Dylan Vermoortele, H. Llewelyn Roderick, Piet Claus, Rik Willems, and Karin R. Sipido. 2021. "Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment" Cells 10, no. 10: 2629. https://doi.org/10.3390/cells10102629
APA StyleAmoni, M., Dries, E., Ingelaere, S., Vermoortele, D., Roderick, H. L., Claus, P., Willems, R., & Sipido, K. R. (2021). Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment. Cells, 10(10), 2629. https://doi.org/10.3390/cells10102629