{
  "abstract": "Cystic fibrosis (CF) has undergone a remarkable transformation from a fatal childhood disease to a chronic adult condition, with a median predicted survival now exceeding 50 years following the introduction of highly effective CFTR modulator therapy (HEMT). This demographic shift has unmasked cardiovascular complications that were previously unrecognized due to premature mortality. In a multinational propensity-matched cohort, CF conferred a 65% higher risk of major adverse cardiac events (MACEs), including myocardial infarction, heart failure, and atrial fibrillation, versus matched controls (Frost et al., HR 1.65). In a separate Canadian population-based cohort, cardiovascular disease occurred at 2.9 times the rate of the general population and at least 20 years earlier (Arya et al., RR 2.9). Cardiac involvement extends beyond the traditional paradigm of cor pulmonale. CFTR is expressed in cardiomyocytes, vascular endothelium, and smooth muscle, where its dysfunction disrupts ion homeostasis, impairs nitric oxide-dependent vasodilation, and promotes oxidative stress. Clinically, these mechanisms manifest as biventricular dysfunction detectable by strain echocardiography and cardiac MRI even when ejection fraction is preserved, diffuse myocardial fibrosis, endothelial dysfunction and accelerated arterial stiffness from childhood, increased arrhythmia susceptibility, and, in a single-center cohort, an unexpectedly high prevalence of pericardial calcification (18%) on chest CT that awaits independent replication. Paradoxically, while HEMT has dramatically improved pulmonary outcomes, it introduces new cardiovascular considerations including hypertension, dyslipidemia, and obesity, and cross-sectional data in modulator-treated cohorts show persistent cardiac abnormalities, though whether these predate treatment or would differ without it is unknown. This review synthesizes the genetic, molecular, and clinical dimensions of cardiovascular disease in CF; distinguishes direct CFTR-mediated cardiac effects from indirect consequences of chronic lung disease; examines vascular, electrophysiological, valvular, and pericardial manifestations; and discusses management implications including CFTR modulator therapy, exercise, nutritional paradigm shifts, and transplantation considerations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA",
    "Department of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA",
    "Department of Internal Medicine, University of Arkansas for Medical Sciences, Fayetteville, AR 72703, USA",
    "Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA",
    "Department of Internal Medicine, Yale New-Haven Health System, New Haven, CT 06510, USA",
    "Department of Internal Medicine, Unity Health, Searcy, AR 72143, USA",
    "Green Lane Cardiovascular Service, Te Toka Tumai Auckland City Hospital, Auckland 1023, New Zealand"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Keshav Garg",
      "orcid": "0000-0003-1995-1626"
    },
    {
      "affs": [
        1
      ],
      "name": "Ankit Agrawal"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmad Mustafa",
      "orcid": "0009-0000-7907-7569"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohab Elnashar",
      "orcid": "0009-0006-2033-5424"
    },
    {
      "affs": [
        2
      ],
      "name": "Gunner Gilbert"
    },
    {
      "affs": [
        3
      ],
      "name": "Akiva Rosenzveig",
      "orcid": "0000-0001-6757-8841"
    },
    {
      "affs": [
        0
      ],
      "name": "Arnav Lakkimsetti"
    },
    {
      "affs": [
        4
      ],
      "name": "Elio Haroun",
      "orcid": "0000-0001-6230-0031"
    },
    {
      "affs": [
        5
      ],
      "name": "Aro Daniela Arockiam"
    },
    {
      "affs": [
        3
      ],
      "name": "Karim Hoyek",
      "orcid": "0009-0002-8486-8466"
    },
    {
      "affs": [
        3
      ],
      "name": "Clement Tan",
      "orcid": "0009-0000-4837-2637"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Tom Kai Ming Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8drgbb3009hd4.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15207988",
  "fulltext_url": "https://europepmc.org/articles/PMC13705640",
  "id": "8drgbb3009hd4",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://www.mdpi.com/2077-0383/15/20/7988",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Cystic Fibrosis Research Advances"
    ]
  ],
  "openalex": "W7221934416",
  "pdf_url": "https://europepmc.org/articles/PMC13705640?pdf=render",
  "pmcid": "PMC13705640",
  "pmid": "42941501",
  "published": "2026-10-15",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/8drgbb3009hd4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "10.3390/jcm15207988",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/20/7988"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42941501",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42941501"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Cystic Fibrosis Research Advances",
      "subfield": "general"
    }
  ],
  "title": "Cardiovascular Manifestations of Cystic Fibrosis",
  "title_text": "Cardiovascular Manifestations of Cystic Fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/8drgbb3009hd4",
  "venue": "Journal of Clinical Medicine",
  "versions": []
}