Evidence map›Paper›PMID 31311300›Full record

ArticleCirculation2019

Insights Into the Pathogenesis of Catecholaminergic Polymorphic Ventricular Tachycardia From Engineered Human Heart Tissue.

Sung-Jin Park, Donghui Zhang, Yan Qi, Yifei Li, Keel Yong Lee, Vassilios J Bezzerides, Pengcheng Yang, Shutao Xia, Sean L Kim, Xujie Liu and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 141 citations in OpenAlex.

  1. Human cardiovascular organoids: Biomedical applications and ethical challenges.American heart journal plus : cardiology research and practice · 2026
    Review
  2. Article
  3. Article
  4. An RYR2-interacting fragment of MYBPC3 mitigates arrhythmia in human iPSC-CM and mouse models of CPVT.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  5. Article
  6. Review
  7. Characterization of cardiac disease-associated mutations in RyR2 CaAmerican journal of physiology. Cell physiology · 2026
    Article
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  9. Article
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  11. Review
  12. Article
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  19. Review
  20. Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024
    Review

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 5 countries.

Sung-Jin ParkDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Donghui ZhangState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China (D.Z., Y.Q., P.Y., S.X.).
Yan QiState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China (D.Z., Y.Q., P.Y., S.X.).
Yifei LiDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Keel Yong LeeDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Vassilios J BezzeridesDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Pengcheng YangState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China (D.Z., Y.Q., P.Y., S.X.).
Shutao XiaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China (D.Z., Y.Q., P.Y., S.X.).
Sean L KimDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Xujie LiuDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Fujian LuDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Francesco S PasqualiniDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Patrick H CampbellDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Judith GevaDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Amy E RobertsDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
Andre G KleberDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.G.K.).
Dominic J AbramsDepartment of Cardiology, Boston Children's Hospital, MA (D.Z., Y.L., V.J.B., X.L., F.L., J.G., A.E.R., D.J.A., W.T.P., K.K.P.).
William T PuHarvard Stem Cell Institute (W.T.P., K.K.P.), Harvard University, Cambridge, MA.
Kevin Kit ParkerDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences (S.-J.P., K.Y.L., S.L.K., F.S.P., P.H.C., K.K.P.), Harvard University, Cambridge, MA.
Boston Children's Hospital · USNorwegian Womens Public Health Association · NOHubei University · CNBeth Israel Deaconess Medical Center · USSt. John's University · US

Funding

Microenvironmental control of progenitors in organ dysfunction and repairU01HL100401 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI OLSON, ERIC N, SCHNEIDER, JAY W · 2009 to 2015
$8.3M
Multi-scale modeling of inherited pediatric cardiomyopathiesUH3HL141798 · NHLBI · HARVARD UNIVERSITY · PI PARKER, KEVIN KIT, PU, WILLIAM TSWENCHING · 2019 to 2021
$3.9M
Human Cardio-Pulmonary System on a ChipUH3TR000522 · NCATS · HARVARD MEDICAL SCHOOL · PI PARKER, KEVIN KIT · 2014 to 2016
$3.6M
Multi-scale modeling of inherited pediatric cardiomyopathiesUG3HL141798 · NHLBI · HARVARD UNIVERSITY · PI PARKER, KEVIN KIT, PU, WILLIAM TSWENCHING · 2017 to 2018
$2.6M
NCATS NIH HHS UH3 TR000522NHLBI NIH HHS U01 HL100401NHLBI NIH HHS UG3 HL141798NHLBI NIH HHS UH3 HL141798
6 · The paper itself

Abstract

backgroundModeling of human arrhythmias with induced pluripotent stem cell-derived cardiomyocytes has focused on single-cell phenotypes. However, arrhythmias are the emergent properties of cells assembled into tissues, and the impact of inherited arrhythmia mutations on tissue-level properties of human heart tissue has not been reported.

methodsHere, we report an optogenetically based, human engineered tissue model of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia caused by mutation of the cardiac ryanodine channel and triggered by exercise. We developed a human induced pluripotent stem cell-derived cardiomyocyte-based platform to study the tissue-level properties of engineered human myocardium. We investigated pathogenic mechanisms in CPVT by combining this novel platform with genome editing.

resultsIn our model, CPVT tissues were vulnerable to developing reentrant rhythms when stimulated by rapid pacing and catecholamine, recapitulating hallmark features of the disease. These conditions elevated diastolic Ca

conclusionsOur study illuminates the molecular and cellular pathogenesis of CPVT and reveals a critical role of calmodulin-dependent protein kinase II-dependent reentry in the tissue-scale mechanism of this disease. We anticipate that this approach will be useful for modeling other inherited and acquired cardiac arrhythmias.

Indexed as

Action PotentialsCells, CulturedHumansInduced Pluripotent Stem CellsMyocytes, CardiacOptogeneticsPolymorphic Catecholaminergic Ventricular TachycardiaTachycardia, VentricularTissue Engineeringarrhythmias, cardiacbiological engineeringCaMKIIcatecholaminergic polymorphic ventricular tachycardia disease modelsgene editingstem cells

Identifiers

PMID31311300
PMCPMC6750809
OpenAlexW2961188119

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.