Atrial flutter

Summary

Atrial flutter (MONDO:0005310) is a disease with 72 GWAS associations across 12 studies and 171 clinical trials. Top therapeutic interventions include amiodarone, diltiazem, and apixaban. A subtype of atrial tachycardia — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 72
• ClinVar variants: 1
• Clinical trials: 171

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial flutter
Mondo ID	MONDO:0005310
EFO	EFO:0003911
MeSH	D001282
ICD-11	1034471684
NCIT	C51224
SNOMED CT	5370000
UMLS	C0004239
MedGen	13955
Anatomy (UBERON)	UBERON:0002081
Is cancer (heuristic)	no

Also known as: atrial flutter · atrial flutter (disease)

Data availability: 1 ClinVar variant · 72 GWAS associations (12 studies) · 1 HPO phenotype.

Disease family

This is a subtype of atrial tachycardia. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › atrial tachycardia › atrial flutter

Subtypes (1): idiopathic neonatal atrial flutter

Genetics & variants

GWAS landscape

72 GWAS associations across 12 studies. Top hits map to 18 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr4:111704080	4e-208		G	0.34
rs13143308	7e-207	LINC01438	T	0.32
rs6843082	2e-75	LINC01438	?
rs2359171	1e-43	ZFHX3	T	0.17
chr1:154824750	2e-28		A	0.12
rs651386	4e-28	GORAB - PRRX1	A	0.1
rs11588763	8e-26	KCNN3	C	0.11
rs34219605	7e-25	KNOP1P1 - RN7SL38P	A	0.14
chr1:203030685	8e-25		T	0.1
chr6:118635079	2e-24		C	0.1
rs59430691	3e-24	ATXN1	G	0.14
rs542777476	7e-24	RNU6-1148P - WNT8A	C	0.12
chr10:73647891	9e-24		?	0.14
chr10:73647532	1e-23		?	0.13
chr10:73655919	3e-23		?	0.13
chr10:73647154	7e-23		?	0.14
rs2738413	1e-22	SYNE2, ESR2	A	0.09
rs12122060	2e-22	LINC01681	T	0.14
chr10:73767950	3e-22		?	0.13
chr4:111712236	6e-22		C	0.46
chr10:73799319	7e-22		?	0.13
rs4074536	2e-21	CASQ2	T	0.1
rs1906596	3e-21	LINC01438	?
rs871298	5e-21	PPFIA4	C	0.09
chr10:105319707	1e-20		G	0.11
rs9481816	3e-20	CEP85L	T	0.11
rs10883886	7e-19	NEURL1	T	0.1
rs3807989	6e-18	CAV1	A	0.08
chr4:111699831	8e-18		C	0.23
chr2:178678490	1e-17		?	0.11

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475973	Verma A	2024	23,153	417,764	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651130	Liu TY	2025	4,968	208,597	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90475972	Verma A	2024	3,470	116,761	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480169	Verma A	2024	3,470	116,761	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475971	Verma A	2024	1,322	57,945	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651185	Liu TY	2025	657	208,597	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90727112	Kim HI	2026	642	43,384	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90726644	Kim HI	2026	639	43,387	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90726911	Kim HI	2026	631	43,395	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90832959	Kim HI	2026	631	43,395	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	37
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	13

Functional consequences

Consequence	Count
unknown	24
intron_variant	16
intergenic_variant	6
non_coding_transcript_exon_variant	2
missense_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr4:111704080				0.226			4e-208	Tier 4: intronic/intergenic
rs13143308	4	110793263	T>A,C,G	0.257	intron_variant	LINC01438	7e-207	Tier 4: intronic/intergenic
rs6843082	4	110796911	G>A,T	0.05	non_coding_transcript_exon_variant	LINC01438	2e-75	Tier 4: intronic/intergenic
rs2359171	16	73019123	T>A	0.184	intron_variant	ZFHX3	1e-43	Tier 4: intronic/intergenic
chr1:154824750				0.258			2e-28	Tier 4: intronic/intergenic
rs651386	1	170622169	A>C,G,T	0.434	intron_variant	GORAB - PRRX1	4e-28	Tier 4: intronic/intergenic
rs11588763	1	154841108	C>G,T	0.238	intron_variant	KCNN3	8e-26	Tier 4: intronic/intergenic
rs34219605	12	24607522	A>G	0.149	intergenic_variant	KNOP1P1 - RN7SL38P	7e-25	Tier 4: intronic/intergenic
chr1:203030685				0.454			8e-25	Tier 4: intronic/intergenic
chr6:118635079				0.499			2e-24	Tier 4: intronic/intergenic
rs59430691	6	16414322	G>A	0.14	intron_variant	ATXN1	3e-24	Tier 4: intronic/intergenic
rs542777476	5	138070554	C>G,T	0.169	intergenic_variant	RNU6-1148P - WNT8A	7e-24	Tier 4: intronic/intergenic
chr10:73647891							9e-24	Tier 4: intronic/intergenic
chr10:73647532							1e-23	Tier 4: intronic/intergenic
chr10:73655919							3e-23	Tier 4: intronic/intergenic
chr10:73647154							7e-23	Tier 4: intronic/intergenic
rs2738413	14	64213242	A>G	0.487	intron_variant	SYNE2, ESR2	1e-22	Tier 4: intronic/intergenic
rs12122060	1	170224718	T>A	0.095	intron_variant	LINC01681	2e-22	Tier 4: intronic/intergenic
chr10:73767950							3e-22	Tier 4: intronic/intergenic
chr4:111712236				0.232			6e-22	Tier 4: intronic/intergenic
chr10:73799319							7e-22	Tier 4: intronic/intergenic
rs4074536	1	115768346	T>C	0.294	missense_variant	CASQ2	2e-21	Tier 1: coding
rs1906596	4	110791080	C>A,G,T	0.05	intron_variant	LINC01438	3e-21	Tier 4: intronic/intergenic
rs871298	1	203070474	C>G,T	0.465	intron_variant	PPFIA4	5e-21	Tier 4: intronic/intergenic
chr10:105319707				0.187			1e-20	Tier 4: intronic/intergenic
rs9481816	6	118491240	T>C	0.227	intron_variant	CEP85L	3e-20	Tier 4: intronic/intergenic
rs10883886	10	103578237	T>C	0.196	intron_variant	NEURL1	7e-19	Tier 4: intronic/intergenic
rs3807989	7	116546187	A>G	0.41	intron_variant	CAV1	6e-18	Tier 4: intronic/intergenic
chr4:111699831				0.31			8e-18	Tier 4: intronic/intergenic
chr2:178678490							1e-17	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
617741	NM_000257.4(MYH7):c.5190G>T (p.Met1730Ile)	LOC126861897	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

1 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dofetilide	Approved (phase 4)
Amiodarone	Phase 3 (in late-stage trials)
Apixaban	Phase 3 (in late-stage trials)
Ascorbic Acid	Phase 3 (in late-stage trials)
Dronedarone	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Betrixaban, Celivarone, Onabotulinumtoxina, Vanoxerine, Vernakalant.

Clinical trials & evidence

Clinical trials

Clinical trials: 171.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	122
PHASE4	19
PHASE3	18
PHASE2	8
PHASE2/PHASE3	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03129490	PHASE4	ACTIVE_NOT_RECRUITING	The Danish Non-vitamin K Antagonist Oral Anticoagulation Study in Patients With Atrial Fibrillation
NCT04436978	PHASE4	RECRUITING	What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?
NCT07571447	PHASE4	NOT_YET_RECRUITING	Cardiologist-Administered Midazolam vs. Anaesthesiologist-Assisted Propofol Sedation For Transoesophageal Echocardiography-Guided Cardioversion of Atrial Fibrillation
NCT00196170	PHASE4	UNKNOWN	Randomized Study of Radiofrequency- vs. Cryo-Ablation for Typical Isthmus-Dependent Atrial Flutter
NCT00213408	PHASE4	TERMINATED	Catheter Ablation as the First Line Therapy for Typical Atrial Flutter
NCT00232232	PHASE4	COMPLETED	Use of Fish Oils to Prevent Atrial Mechanical Stunning and Atrial Remodeling Due to Atrial Arrhythmia
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00318565	PHASE4	COMPLETED	Catheter Evaluation for Endocardial Ablation in Patients With Typical Atrial Flutter
NCT00326001	PHASE4	COMPLETED	Isthmus Ablation With Gold Electrode for Treatment of Atrial Flutter (AURUM 8)
NCT00491010	PHASE4	UNKNOWN	Maximum Targeted Ablation of Atrial Flutter
NCT00559988	PHASE4	TERMINATED	Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk
NCT01596959	PHASE4	COMPLETED	The Contact-CTI Study: Use of Tissue Contact Data to Guide Atrial Flutter Ablation
NCT01818583	PHASE4	COMPLETED	Potassium Infusion for Conversion of Atrial Fibrillation/-Flutter
NCT01976507	PHASE4	COMPLETED	Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism
NCT02025465	PHASE4	UNKNOWN	Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control
NCT04126486	PHASE4	COMPLETED	A Study to Determine if Identification of Undiagnosed Atrial Fibrillation in People at Least 70 Years of Age Reduces the Risk of Stroke
NCT04141553	PHASE4	UNKNOWN	Bolus vs IVP (Intravenous Push) Diltiazem for Atrial Fibrillation or Flutter
NCT04187196	PHASE4	COMPLETED	Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion
NCT05391893	PHASE4	COMPLETED	Effect of Oral and Intravenous Diltiazem Protocol for Emergency Department Atrial Fibrillation
NCT00113178	PHASE3	COMPLETED	Safety and Efficacy of the CryoCor™ Cardiac Cryoablation System for the Treatment of Atrial Flutter
NCT00115791	PHASE3	COMPLETED	Study to Determine the Response and Effectiveness of RSD1235 in Subjects With Atrial Fibrillation or Atrial Flutter
NCT00125320	PHASE3	COMPLETED	Response to RSD1235 Compared to Placebo in Subjects With Atrial Arrhythmia After Heart Surgery
NCT00126022	PHASE3	COMPLETED	Intravenous Tedisamil in the Rapid Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm in Female Subjects
NCT00126061	PHASE3	COMPLETED	Intravenous Tedisamil in the Rapid Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm in Male Subjects
NCT00126074	PHASE3	COMPLETED	Intravenous Tedisamil in the Rapid Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm in Female Subjects
NCT00174785	PHASE3	COMPLETED	A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation
NCT00180336	PHASE2/PHASE3	COMPLETED	Safety and Efficacy Study of RENEWAL 4 AVT
NCT00233441	PHASE2/PHASE3	COMPLETED	Placebo Controlled Double-blind Dose Ranging Study of the Efficacy and Safety of SSR149744C 50, 100, 200 or 300 mg OD With Amiodarone as Calibrator for the Maintenance of Sinus Rhythm in Patients With Recent Atrial Fibrillation/Flutter
NCT00259376	PHASE3	COMPLETED	American-Australian-African Trial With Dronedarone in Patients With Atrial Fibrillation or Atrial Flutter for the Maintenance of Sinus Rhythm
NCT00259428	PHASE3	COMPLETED	EURopean Trial In Atrial Fibrillation(AF) or Flutter (AFL) Patients Receiving Dronedarone for the maIntenance of Sinus Rhythm (EURIDIS)
NCT00412984	PHASE3	COMPLETED	Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation
NCT00476112	PHASE2/PHASE3	COMPLETED	A Phase II/III Tolerance and Efficacy Study of RSD1235 in Patients With Atrial Flutter
NCT00691470	PHASE2/PHASE3	UNKNOWN	Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation
NCT00736294	PHASE3	TERMINATED	Prevention of Atrial Fibrillation by Inhibition Conversion Enzyme (ICE) After Radiofrequency Ablation of Atrial Flutter
NCT00839657	PHASE3	COMPLETED	Clarification of Optimal Anticoagulation Through Genetics
NCT00953212	PHASE3	COMPLETED	Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery
NCT02065388	PHASE3	COMPLETED	Pharmacogenetic Dosing of Warfarin
NCT02088489	PHASE3	COMPLETED	Thermocool SF Catheter Versus Thermocool Catheter in Isthmus-dependent Atrial Flutter Ablation
NCT02426710	PHASE3	COMPLETED	Intracardiac Echocardiography in Atrial Flutter Ablation
NCT03153150	PHASE3	COMPLETED	Start or STop Anticoagulants Randomised Trial (SoSTART)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMIODARONE	4	6
DILTIAZEM	4	6
APIXABAN	4	3
DABIGATRAN ETEXILATE	4	3
DRONEDARONE	4	3
EDOXABAN	4	2
METOPROLOL	4	2
VERNAKALANT HYDROCHLORIDE	4	2
WARFARIN	4	2
ACENOCOUMAROL	4	1
ASCORBIC ACID	4	1
BETRIXABAN	4	1
COLCHICINE	4	1
DEXTROSE	4	1
FISH OIL	4	1
MANNITOL	4	1
METHOHEXITAL	4	1
PHENINDIONE	4	1
POTASSIUM CHLORIDE	4	1
RAMIPRIL	4	1
RIVAROXABAN	4	1
SORBITOL	4	1
TEDISAMIL SESQUIFUMARATE	3	3
CELIVARONE	3	2
TECARFARIN	3	2
VANOXERINE	3	2
DABIGATRAN	3	1
AZD1305	2	1
CHEMBL4303203	0	2
CHEMBL4643136	0	2