{"doi":"10.1371/journal.pone.0246768","title":"Assessment of dynamic cardiac repolarization and contractility in patients with hypertrophic cardiomyopathy","abstract":"AIMS: Arrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy. METHODS: All participants had a cardiac implantable device capable of atrial pacing. Cases had clinical diagnosis of hypertrophic cardiomyopathy, controls were age-matched. Continuous electrocardiogram and blood pressure were recorded during and immediately after 30 second pacing trains delivered at increasing rates. RESULTS: Nine hypertrophic cardiomyopathy patients and 10 controls were enrolled (47% female, median 55 years), with similar baseline QRS duration, QT interval and blood pressure. Median septal thickness in hypertrophic cardiomyopathy patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak sub-aortic velocity >50mmHg. Ventricular ectopy occurred during or immediately after pacing trains in 4/9 hypertrophic cardiomyopathy patients and 0/10 controls (P = 0.03). During delivery of steady rate pacing across a range of cycle lengths, the QT-RR relationship was not statistically different between HCM and control groups; no differences were seen in subgroup analysis of patients with or without intact AV node conduction. Similarly, there was no difference between groups in the QT interval of the first post-pause recovery beat after pacing trains. No statistically significant differences were seen in surrogate measures for cardiac contractility. CONCLUSION: Rapid pacing trains triggered ventricular ectopy in hypertrophic cardiomyopathy patients, but not controls. This finding aligns with pre-clinical descriptions of excessive cardiomyocyte calcium loading during rapid pacing, increased post-pause sarcoplasmic reticulum calcium release, and subsequent calcium-triggered activity. Normal contractility at all diastolic intervals argues against clinical significance of altered length-dependent myofilament activation.","journal":"PLoS ONE","year":2021,"id":223176,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.cjsxksn4k"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":378518,"name":"Lucy Y. Lei","orcid":"0000-0002-4036-7697","position":1,"is_corresponding":false},{"id":420940,"name":"Sachin Y. Paranjape","orcid":"0000-0002-4597-9705","position":2,"is_corresponding":false},{"id":314113,"name":"Daniel J. Blackwell","orcid":"0000-0001-6619-1792","position":3,"is_corresponding":false},{"id":825136,"name":"Robert L. Abraham","orcid":null,"position":4,"is_corresponding":false},{"id":378519,"name":"Derek S. Chew","orcid":"0000-0003-3539-7485","position":5,"is_corresponding":false},{"id":378520,"name":"Satish R. Raj","orcid":"0000-0002-5890-3785","position":6,"is_corresponding":false},{"id":236808,"name":"Björn C. Knollmann","orcid":"0000-0003-4956-9735","position":7,"is_corresponding":false},{"id":824664,"name":"Andrew E. Radbill","orcid":"0000-0003-2360-3552","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-18T23:54:11.061295Z","pmid":"33571287","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}