{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:06:57Z","timestamp":1790194017770,"version":"4.1.0"},"reference-count":8,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by obliterative pulmonary vascular remodelling. Pathogenic variants in KCNK3 represent a recognized cause of heritable PAH (hPAH). Loss-of-function mutations lead to membrane depolarization, increased calcium influx, and enhanced pulmonary vasoconstriction. Calcium channel blockers (CCBs) are recommended for patients demonstrating a positive acute vasoreactivity test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case summary<\/jats:title>\n                    <jats:p>A 50-year-old man carrying a pathogenic KCNK3 (E34K) mutation was referred to a tertiary PAH centre during familial screening after two of his children were diagnosed with PAH and were non-responders to acute vasoreactivity testing. He was mildly symptomatic, World Health Organization functional class (WHO-FC) II, with preserved exercise capacity, 6-min walk distance (6MWD) of 580\u2005m, and normal NT-proBNP levels. Echocardiography showed mild right ventricular dilatation with preserved systolic function. Right heart catheterization (RHC) confirmed mild pre-capillary pulmonary hypertension with a positive acute vasoreactivity testing response. Considering the mild haemodynamic impairment, the underlying KCNK3 mutation, and prior clinical improvement during amlodipine therapy for systemic hypertension, high-dose amlodipine was initiated. At 6-month follow-up, the patient improved to WHO-FC I, with increased 6MWD and haemodynamic improvement on repeat RHC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This case describes a favourable clinical and haemodynamic response to CCB therapy in KCNK3-associated PAH. It highlights phenotypic variability within familial KCNK3-related disease and indicates that longitudinal data may help identify patients who could benefit from targeted therapies despite borderline haemodynamic profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcr\/ytag679","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:46:30Z","timestamp":1789213590000},"source":"Crossref","is-referenced-by-count":0,"title":["An unexpected therapeutic overlap: long-term control of KCNK3-associated pulmonary arterial hypertension during treatment of systemic hypertension\u2014a case report"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3678-6830","authenticated-orcid":false,"given":"Leonardo","family":"Carli","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies, Division of Cardiology, University of Siena , Via Mario Bracci 16, Siena 53100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1046-6677","authenticated-orcid":false,"given":"Michele","family":"di Leo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna , Via Massarenti 9, Bologna 40138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3005-8994","authenticated-orcid":false,"given":"Federico","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna , Via Massarenti 9, Bologna 40138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1922-2930","authenticated-orcid":false,"given":"Chiara","family":"Barozzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna , Via Massarenti 9, Bologna 40138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9611-6021","authenticated-orcid":false,"given":"Fabio","family":"Dardi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Via Massarenti 9, Bologna 40138 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026092315512887600_ytag679-B1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa1211097","article-title":"A novel channelopathy in pulmonary arterial hypertension","volume":"369","author":"Ma","year":"2013","journal-title":"N Engl J Med"},{"key":"2026092315512887600_ytag679-B2","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/CIRCULATIONAHA.115.020951","article-title":"Potassium channel subfamily K member 3 (KCNK3) contributes to the development of pulmonary arterial hypertension","volume":"133","author":"Antigny","year":"2016","journal-title":"Circulation"},{"key":"2026092315512887600_ytag679-B3","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur Heart J"},{"key":"2026092315512887600_ytag679-B4","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01324-2024","article-title":"Definition, classification and diagnosis of pulmonary hypertension","volume":"64","author":"Kovacs","year":"2024","journal-title":"Eur Respir J"},{"key":"2026092315512887600_ytag679-B5","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1161\/CIRCULATIONAHA.105.601930","article-title":"Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension","volume":"113","author":"Elliott","year":"2006","journal-title":"Circulation"},{"key":"2026092315512887600_ytag679-B6","doi-asserted-by":"crossref","DOI":"10.1136\/openhrt-2025-003591","article-title":"Phenotyping of patients with mild pulmonary hypertension","volume":"12","author":"Dardi","year":"2025","journal-title":"Open Heart"},{"key":"2026092315512887600_ytag679-B7","article-title":"Acute pulmonary vasoreactivity: a simple test revisited in the contemporary era \u2212 a narrative review","volume":"62","author":"Grignola","year":"2026","journal-title":"IJC Heart Vasc"},{"key":"2026092315512887600_ytag679-B8","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1161\/CIRCRESAHA.119.314793","article-title":"Characterization of Kcnk3-mutated rat, a novel model of pulmonary hypertension","volume":"125","author":"Lambert","year":"2019","journal-title":"Circ Res"}],"container-title":["European Heart Journal - 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