I'm searching PubMed for the main FHOD3 papers so I can pull exact abstract quotes.

I'm caching the key FHOD3 papers with the repo's fetcher so I can quote their abstracts word for word.

I'm reading the cached abstracts for the mechanism and model papers now. Next I'll check the ontology terms, then write the report.

Hypertrophic Cardiomyopathy 28 (CMH28; FHOD3-related HCM): research report

Target: cardiomyopathy, familial hypertrophic, 28, MONDO:0030317 Prepared: 2026-10-08 for the kb/disorders/Hypertrophic_Cardiomyopathy_28.yaml entry

How the evidence was gathered. I fetched 17 PubMed records into references_cache/ with just fetch-reference. Every quotation below was copied from those cache files or from an existing structured record. A few points come only from web search and are marked [unverified lead]; check them before citing.

Housekeeping: this run added 17 new references_cache/PMID_*.md files. They are untracked in the worktree. One of them, PMID_30442289.md (the Pinto & Reckman JACC editorial), came back with no quotable text. Remove it unless a retry with --force returns an abstract.

1. Disease information

Overview. CMH28 is autosomal dominant hypertrophic cardiomyopathy caused by heterozygous variants in FHOD3. FHOD3 is a formin, a protein that assembles actin filaments, and it organises the sarcomere in heart muscle. FHOD3 is not itself a sarcomere protein; it is one of the main "non-sarcomeric" HCM genes. The disease typically appears in adulthood, penetrance is incomplete, and expression is variable. Most patients have asymmetric septal hypertrophy, and some also have left ventricular hypertrabeculation or noncompaction.

The gene was established by Ochoa et al. 2018, which studied 3,189 HCM probands:

"FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases." (PMID:30442288)

Identifiers

Synonyms: CMH28; FHOD3-related hypertrophic cardiomyopathy; familial hypertrophic cardiomyopathy 28.

Data provenance. The knowledge comes from aggregated disease-level resources (OMIM, ClinGen) and from cohort and family studies. No EHR data were used.

2. Etiology

Primary cause. The cause is a heterozygous germline FHOD3 variant. The variants are mostly non-truncating: missense, in-frame indels, splice-site changes and exon deletions.

ClinGen. FHOD3 is classified Definitive for HCM: - Expert panel paper: "Five genes recently reported to cause HCM were curated: RPS6KB1 and RBM20 (limited), KLHL24 and MT-TI (moderate), and FHOD3 (definitive)." (PMID:39971408) - ClinGen record row: FHOD3 | HGNC:26178 | hypertrophic cardiomyopathy | MONDO:0005045 | AD | Definitive (CGGV:assertion_c31027fe-8143-4022-8bbb-867eb1692c51-2023-09-29T160000.000Z)

Curation caveat: that ClinGen assertion is filed against MONDO:0005045 (HCM in general), not MONDO:0030317. Under the repo's gene-validity rules it is an other_disease case. Record it in gene_disease_validity only if the entry carries a MONDO:0005045 exactMatch mapping, which would be wrong for a numbered subtype. Otherwise cite it as ordinary evidence, or explain in notes.

Review context (PMID:34526680):

"variants in several additional genes (ACTN2, ALPK3, CSRP3, FHOD3, FLNC, JPH2, KLHL24, PLN and TRIM63), encoding non-sarcomeric proteins with diverse functions, have been shown to be disease-causing in a small number of patients."

Genetic risk and modifier factors

• Intermediate-effect allele p.Arg637Gln (PMID:38160043). This variant was enriched in HCM: "284 of 9668 probands; 2.94%" against "0.58%" in gnomAD controls, an OR of about 5.2. In heterozygotes it "can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%." Homozygotes are more severe (see Section 9). This makes p.Arg637Gln a RISK_FACTOR or SUSCEPTIBILITY allele, not a simple Mendelian one.
• Intermediate-effect variants in general (PMID:40879562). FHOD3 is among the five non-sarcomeric genes included. Across genes, "IEVs are present in 6.1% of HCM cases and account for 4.8% of HCM genetic burden. IEVs also influence disease severity and outcomes, particularly when combined with monogenic disease-causing variants."
• Common variants (PMID:23255317). A GWAS found "an intronic FHOD3 variant (rs516514) associated with HCM (odds ratio, 2.45…)". It also found that the missense variant FHOD3-V1151I (rs2303510) gave "an even stronger association with HCM (P=1.76×10(-9))". These are susceptibility or modifier variants, not CMH28-causing alleles.
• Possible cosegregating modifiers in one family (PMID:31742804). "RNF207 (p.Q268P), CCM2 (p. E233K) and SGCZ (p.Q134X) may be related to the clinical heterogeneity of the family." This is weak evidence from a single family.

Environmental, protective and gene-environment factors. None is documented specifically for CMH28. A large HCM GWAS (PMID:33495597, not fetched) links diastolic blood pressure mainly to sarcomere-negative HCM. That makes hypertension a plausible but unestablished modifier for FHOD3 carriers. No protective factors are reported.

3. Phenotypes

The main quantitative source is the Ochoa 2018 cohort of 70 carriers of (likely) pathogenic variants (PMID:30442288):

"Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up."

Mortality in the Chinese cohort (PMID:33586461):

"the FHOD3 candidate variant experienced significantly more risk of cardiovascular death and all-cause death (adjusted hazard ratio [HR], 3.71 …"

Severity and progression: variable, ranging from asymptomatic to heart failure. The Ochoa cohort's event rates are "similar to those reported in unselected cohorts" (PMID:30442288).

Quality of life: no CMH28-specific data (EQ-5D, SF-36 or similar) were found.

4. Genetic and molecular information

Gene: FHOD3 (formin homology 2 domain containing 3), chromosome 18q12.2 (gene table), hgnc:26178.

Structure and isoforms. The domains are GBD, DID, coiled-coil, FH1, FH2 and DAD. The heart-enriched long isoform (FHOD3L) includes exon 12. That exon encodes the region that binds cMyBP-C (cardiac myosin-binding protein C) and targets FHOD3 to the sarcomere C-zone (PMID:29686099; PMID:38051749 introduction).

Variant spectrum and clustering (PMID:30442288):

"One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects"

Burden test (PMID:30442288). Candidate variants were found in 2.32% of HCM probands, against 0.65% of disease controls and 0.76% in gnomAD. Cosegregation in 17 families gave a combined LOD score of 7.92.

Somatic or germline: germline.

Functional consequence. The functional consequence is unresolved, and this is the key open question for curation: - Pathogenic HCM variants "seem to be restricted to non-truncating variants (missense, splice-site, and in-frame deletions/insertions variants)" and cluster in the DID domain, exon 12 and the coiled-coil (PMID:38051749 introduction, a background statement). - This pattern argues against simple haploinsufficiency. It is consistent with dominant-negative or altered-regulation (DID/DAD autoinhibition) mechanisms, but that is an inference. - Recommendation: leave functional_impact_category unset, or explain in notes why it is not set, rather than asserting GAIN_OF_FUNCTION or LOSS_OF_FUNCTION.

Other phenotypes reported with FHOD3. LVNC (PMID:35205353). FHOD3 variants have also been reported in dilated cardiomyopathy (PMID:24088304, Arimura 2013; not fetched), but the DCM association "remains as yet unproven" (PMID:38051749 introduction).

Epigenetics and chromosomal abnormalities: nothing reported. RBM20 and PTBP1 regulate alternative splicing of FHOD3 (PMID:30468920, not fetched). This is relevant to isoform balance but has not been linked to CMH28.

5. Environmental information

There are no known environmental, lifestyle or infectious causes. General HCM lifestyle advice applies (Section 13). Leave environmental: empty, or add a "Left deliberately uncited." waiver only if an exposure is listed.

6. Mechanism and pathophysiology

Ordered causal chain

1. Heterozygous germline FHOD3 variant, most often non-truncating and clustered in the DID or coiled-coil region (aa 622–655, exons 15–16), leads to an altered FHOD3 protein. Demonstrated genetically: PMID:30442288, PMID:32335906. Inferred: how a coiled-coil or DID change alters protein function has not been shown biochemically for patient alleles.
2. Normal role of FHOD3L: it nucleates and, critically, elongates actin filaments, and it is recruited to the sarcomere C-zone by cMyBP-C. Its elongation activity is needed for sarcomere formation and contraction. Demonstrated in vitro: PMID:40663059 ("FHOD3L's elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes"); PMID:19706596; PMID:29686099.
3. A disturbed FHOD3 function results in defective thin-filament (actin) organisation and impaired sarcomere and myofibril maintenance in cardiomyocytes. Demonstrated for loss of FHOD3 (knockdown or knockout), not for patient alleles: "RNA interference-mediated depletion of Fhod3 results in a marked reduction in filamentous actin and disruption of the sarcomeric structure" (PMID:19706596). In FHOD3-/- human embryonic stem cell–derived cardiomyocytes, "marked sarcomere disorganization and degradation, impaired calcium handling and compromised mitochondrial function, ultimately leading to reduced contractility" (PMID:41540467).
4. Branch A (mislocalisation, dominant effect): wrongly placed FHOD3 is harmful. In cMyBP-C-null mice, "Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized" (PMID:29686099). This is a mouse model and inferred to apply to CMH28.
5. Branch B (deficiency): loss of FHOD3 activates CaMKII. "FHOD3 deficiency triggered the phosphorylation of CaMKII (Thr286), a key regulator of cardiac hypertrophy and remodeling" (PMID:41540467). This is a knockout model; patient variants are mostly non-truncating.
6. Sarcomere dysfunction and stress signalling lead to a maladaptive hypertrophic response of cardiomyocytes, with fetal gene reactivation. Model evidence: in adult Fhod3-deleted mice, phenylephrine "induced expression of fetal cardiac genes that was more pronounced … suggesting that Fhod3 modulates hypertrophic changes in the adult heart" (PMID:29158260). The step from this to human septal hypertrophy is inferred.
7. Cardiomyocyte hypertrophy results in left ventricular and asymmetric septal hypertrophy (82%). Disturbed myocardial development or maintenance may account for hypertrabeculation or LVNC (16%). Clinical: PMID:30442288. Link to trabeculation: Fhod3-/- embryos show aborted "chamber formation and myocardial development with trabeculation" (PMID:23213483). This is a developmental knockout; the link to adult hypertrabeculation is inferred.
8. Downstream, myocardial fibrosis, systolic dysfunction (14% LVEF <50%), arrhythmia and thromboembolism lead to heart failure and cardiovascular or sudden death (about 1%/yr). Sources: PMID:30442288; PMID:35205353; PMID:33586461.

Suggested ontology terms

All of these are in the repo caches.

• GO biological process: GO:0045214 sarcomere organization; GO:0055003 cardiac myofibril assembly; GO:0030239 myofibril assembly; GO:0030041 actin filament polymerization; GO:0045010 actin nucleation; GO:0003300 cardiac muscle hypertrophy; GO:0014898 cardiac muscle hypertrophy in response to stress; GO:0060048 cardiac muscle contraction; GO:0055117 regulation of cardiac muscle contraction; GO:0048738 cardiac muscle tissue development.
• GO cellular component: GO:0030017 sarcomere; GO:0031672 A band (the C-zone sits within it); GO:0005884 actin filament; GO:0030016 myofibril.
• Cell types: CL:0000746 cardiac muscle cell; CL:0002131 regular ventricular cardiac myocyte; CL:0002548 fibroblast of cardiac tissue (for the fibrosis node).

Scale tags: steps 1–2 are MOLECULAR, 3 is CELLULAR, 4–5 are TISSUE, and 6 is ORGANISM.

Molecular profiling. The only omics data are bulk transcriptomics of FHOD3-KO human cardiomyocytes, which showed "significant downregulation of sarcomere-related genes and calcium-handling genes" (PMID:41540467). FHOD3 expression "is increased in the setting of HCM" in myectomy tissue (PMID:23255317). No single-cell, spatial, proteomic or metabolomic data specific to CMH28 were found.

Reproducibility caveat. PMID_23213483.md caches the full-text body without a separate abstract block. Quotes from its "Here we show…" introduction paragraph are the authors' own results, so record quote_role: PRIMARY_RESULT.

7. Anatomical structures affected

• Organ: heart (UBERON:0000948). Cardiovascular system only; there are no reported extracardiac features.
• Sites: interventricular septum (UBERON:0002094; asymmetric septal hypertrophy), heart left ventricle (UBERON:0002084), myocardium (UBERON:0002349), cardiac muscle tissue (UBERON:0001133).
• Cells: ventricular cardiomyocytes. FHOD3L is "predominantly expressed in striated muscle" (PMID:40663059).
• Subcellular: sarcomere C-zone in the A band, and actin thin filaments. Fhod3 also localises near the M-line (PMID:22509354).
• Lateralisation: asymmetric, septum-predominant hypertrophy.

8. Temporal development

• Onset: mainly adult. Carriers "were diagnosed after age 30 years (mean 46.1 ± 18.7 years)" (PMID:30442288). The Balkan founder variant shows "a wide range of ages at onset of the disease (4-63 years)" (PMID:38051749). Homozygous p.Arg637Gln gives "an early presentation" (PMID:38160043).
• Course: chronic and lifelong, insidious, and slowly progressive. "Events were rare before age 30 years" (PMID:30442288).
• Stages: the generic HCM progression applies (preclinical carrier → hypertrophy → possible systolic dysfunction or heart failure). No CMH28-specific staging exists.
• Remission: none.
• Window for intervention: before age 30, when cascade screening of relatives can identify carriers before events.

9. Inheritance and population

• Inheritance: autosomal dominant (ClinGen AD Definitive). Incomplete penetrance is noted repeatedly (PMID:38051749). Expressivity is variable.
• Biallelic dosage effect: homozygous p.Arg637Gln causes more severe disease. "Seven homozygous carriers of p.Arg637Gln in FHOD3 were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype." (PMID:38160043) This suggests semidominant behaviour for that allele. Do not encode it as recessive inheritance.
• Frequency within HCM: about 1–2% of HCM cases (PMID:30442288). Background HCM prevalence is "∼1 in 500" (PMID:39971408). That implies a CMH28 prevalence of roughly 1–4 per 100,000. This is derived, not measured; do not record it as a sourced rate_per_100000.
• Founder effects: Balkan c.1646+2T>C (PMID:38051749). The Iberian cohorts carry p.Arg637Gln at 2.94% of probands (PMID:38160043).
• Sex ratio: "two-thirds (66%) were males" (PMID:30442288).
• Ancestry: cohorts from Spain/UK, China (3.3% of HCM vs 1.6% of controls; PMID:33586461), the Balkans and Russia.
• Not reported: consanguinity, anticipation and germline mosaicism.

10. Diagnostics

• Imaging: echocardiography and cardiac MRI showing LV wall thickness ≥15 mm, which is the standard HCM criterion (PMID:38051749 introduction). CMR also assesses hypertrabeculation or LVNC and fibrosis (late gadolinium enhancement).
• ECG and Holter: for AF, NSVT and T-wave abnormalities (NCIT:C38053 Electrocardiography).
• Genetic testing: a multigene HCM panel that includes FHOD3. "The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels." (PMID:30442288)
• CNV analysis is required: "This study highlights the importance of performing CNV analysis systematically in NGS genetic testing panels for HCM" (PMID:32335906).
• Exome or genome sequencing is useful for panel-negative cases (PMID:31742804; PMID:33586461).
• Variant interpretation: pay attention to intermediate-effect alleles such as p.Arg637Gln. "Evaluation of IEVs should be considered when HCM genetic testing is performed." (PMID:40879562)
• Not applicable: karyotype, FISH, mtDNA testing and repeat-expansion testing.
• Biomarkers: none specific to CMH28. Generic HCM markers are NT-proBNP and high-sensitivity troponin. A troponin I GWAS hit near FHOD3 (PMID:33961016) is not established as diagnostic.
• Differential diagnosis:
• sarcomeric HCM (MYH7, MYBPC3 and others)
• other non-sarcomeric HCM (ALPK3, FLNC, TRIM63, CSRP3)
• phenocopies: Fabry disease, PRKAG2, Danon disease, transthyretin amyloidosis, RASopathies
• isolated LVNC
• hypertensive heart disease
• athlete's heart
• Screening: cascade genetic and clinical screening of first-degree relatives. No newborn screening exists.

11. Outcome and prognosis

• Mortality: annual cardiovascular death incidence of 1% (PMID:30442288). In a Chinese cohort, FHOD3 candidate variants were "an independent risk for cardiovascular death and all-cause death in HCM" (PMID:33586461). In contrast, the Balkan founder carriers had "No adverse cardiac events" (PMID:38051749). The literature conflicts here, so record both.
• Prognostic modifiers: an intermediate-effect variant added to a monogenic variant gives a more aggressive course. Major adverse cardiac event–free survival at 70 years was 93.3% vs 69.3% (PMID:40879562; this is a pooled finding across genes). Homozygosity for p.Arg637Gln also worsens prognosis (PMID:38160043).
• Complications: heart failure, systolic dysfunction, arrhythmia, thromboembolism (LVNC) and sudden death.
• Not found: CMH28-specific survival curves and quality-of-life data.

12. Treatment

No FHOD3-specific therapy exists, so management follows HCM guidelines. Suggested bindings, all in the repo caches:

Caveat on myosin inhibitors. Their trials enrolled obstructive HCM regardless of genotype. There are no FHOD3-stratified efficacy data.

Experimental. The only FHOD3-specific therapeutic signal is in vitro. In FHOD3-KO human cardiomyocytes, "Treatment with the myosin activator Omecamtiv mecarbil (OM) partially restored contractility without affecting calcium handling" (PMID:41540467). This is IN_VITRO evidence, based on a loss-of-function model and not on patient alleles. It is a hypothesis, not a treatment. I found no CMH28 trials, gene therapy or RNA-based programmes.

Pharmacogenomics: mavacamten dosing depends on CYP2C19 genotype (generic, not FHOD3-specific) [unverified lead; source it before use].

13. Prevention

• Primary: none is possible. Genetic counselling covers the 50% transmission risk, and preimplantation or prenatal testing is possible when a pathogenic variant is known. Incomplete penetrance complicates counselling.
• Secondary: cascade genotyping of relatives followed by serial echocardiography and ECG of carriers.
• Tertiary: sudden-death risk stratification and ICD; anticoagulation for AF or LVNC thrombus; managing hypertension as a possible modifier (inferred).
• Not applicable: immunisation and public-health or environmental measures.

14. Other species and natural disease

• Naturally occurring FHOD3 cardiomyopathy: none found in OMIA during this search. Feline and canine HCM are mainly MYBPC3-associated.
• Orthologues: mouse Fhod3, rat Fhod3, and Drosophila fhos. "its fly homolog fhos is required for normal adult heart systolic contraction" (PMID:23255317).
• Zebrafish: fhod3 paralogues are involved in skeletal myofibril stability (PMID:41416849, not fetched).
• Not verified: NCBI Gene IDs for the orthologues.

15. Model organisms and systems

Limitations. Every in vivo model is a knockout or overexpression model. No knock-in of a patient allele exists, for example a coiled-coil missense variant, p.Arg637Gln, or the exon 15–16 deletion. A complete knockout is embryonic lethal, while the human disease is heterozygous, non-truncating and adult-onset.

This is a good candidate for a HUMAN_MODEL_MISMATCH discussion: the models remove or overexpress FHOD3, whereas patients carry heterozygous non-truncating alleles. The proposed experiment is a patient-allele knock-in in mice or iPSC-derived cardiomyocytes.

Model divergence typing for modeled_mechanisms: - BOUNDARY_OMISSION — no patient allele is modelled. - PROXY_QUANTITY — knockout loss stands in for altered function of a variant protein. - SPECIES_MISMATCH — mouse and rat models.

Curation notes for the entry

1. Fill in the stub fields. The existing draft has a one-line description and a single phenotype. The evidence above supports roughly 6–7 pathophysiology nodes, about 10 phenotypes with frequencies, 3–5 genetic rows and the treatments in Section 12.
2. Do not write functional_impact_category for the causal alleles, because the mechanism is unresolved. Record that reasoning in notes.
3. Model p.Arg637Gln as a separate genetic row with relationship_type: RISK_FACTOR, plus a homozygous-severity note.
4. ClinGen: the Definitive tier is against MONDO:0005045, so use it as evidence rather than as a gene_disease_validity assertion for this entry (see Section 2).
5. Unverified leads: the AF, NSVT and dyspnoea frequencies come only from the OMIM/MalaCards text. They need an exact quotable source before they go into the entry. A GeneReviews chapter specific to FHOD3 is unlikely; run just check-genereviews to confirm.

Sources (all PMIDs cached in references_cache/ unless marked)

• PMID:30442288 Ochoa 2018 JACC
• PMID:39971408 Hespe 2025 JACC (ClinGen)
• CGGV:assertion_c31027fe-… (ClinGen FHOD3/HCM Definitive)
• PMID:34526680 Walsh 2022 Nat Rev Cardiol
• PMID:38160043 Piqueras-Flores 2024 J Med Genet
• PMID:40879562 García Hernández 2025 Circulation
• PMID:32335906 Ochoa 2020 Clin Genet
• PMID:38051749 Vodnjov 2023 PLoS One
• PMID:33586461 Wu 2021 JAHA
• PMID:31742804 Huang 2020 J Gene Med
• PMID:35205353 Myasnikov 2022 Genes
• PMID:23255317 Wooten 2013 Circ Cardiovasc Genet
• PMID:19706596 Taniguchi 2009 JBC
• PMID:23213483 Kan-o 2012 Biol Open
• PMID:22509354 Kan-o 2012 PLoS One
• PMID:29158260 Ushijima 2018 JBC
• PMID:29686099 Matsuyama 2018 PNAS
• PMID:40663059 Valencia 2025 eLife
• PMID:41540467 Wei 2026 Stem Cell Res Ther
• Not fetched: PMID:24088304, PMID:30468920, PMID:33495597, PMID:33961016, PMID:41416849
• Web: PubMed 30442288, MalaCards CMH28, DrugMap DISIHJ7B, Gene Table ref 30442288, Mayo Clinic Wooten 2013, UCL Discovery

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

• PMID:29158260: "induced expression of fetal cardiac genes that was more pronounced … suggesting that Fhod3 modulates hypertrophic changes in the adult heart"
• closest text in source: "In addition to these age-related changes, systemic stimulation with the α1-adrenergic receptor agonist phenylephrine, which induces sustained hypertension and hypertrophy development, induced expression of fetal cardiac genes that was more pronounced in adult Fhod3-deleted mice than in the control mice, suggesting that Fhod3 modulates hypertrophic changes in the adult heart"

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• MONDO:0005045 (5 mentions) - the report calls it "HCM in general"; MONDO calls it hypertrophic cardiomyopathy
• NCIT:C15986 (5 mentions) - the report calls it "Verapamil", "Disopyramide (obstructive HCM)", "Cardiac myosin inhibitors", "Antiarrhythmic (AF)"; NCIT calls it Pharmacotherapy

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

• UBERON:0000948 (1 mention) - the report calls it "Organ: heart"; UBERON calls it heart**, and lists "branchial heart" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• NCIT:C15986 - called "Verapamil", "Disopyramide (obstructive HCM)", "Cardiac myosin inhibitors", "Antiarrhythmic (AF)"