Intraoperative management of a patient undergoing cardiac surgery requires continuous and independent interventions by multiple healthcare professionals, including surgeons, anesthesiologists, and perfusionists, among others. Although each clinician performs tasks based on their training and accepted techniques, guidelines, and protocols, an action by one member of the team can have immediate consequences for other team members. Aortic surgery adds a level of complexity, with the need for interventions such as single-lung ventilation, systemic cooling (and subsequent rewarming), and myocardial, cerebral, and visceral protection. Much has been made of the utility of the multidisciplinary team. This scientific statement is intended to approach the patient undergoing aortic surgery from 3 different viewpoints: that of the surgeon, the anesthesiologist, and the perfusionist. This scientific statement is not intended to provide an exhaustive summary of approaches to aortic surgery but rather to illustrate the specific concerns that each member of the team may have.
Chronic kidney disease is a global epidemic affecting ≈10% of adults worldwide. Women have a higher prevalence of chronic kidney disease than men yet are less likely to progress to kidney failure, to initiate dialysis, or to receive a kidney transplantation, underscoring the influence of biological sex on chronic kidney disease development, progression, treatment response, and outcomes. Women may also respond differently from men to pharmacological therapies, but they remain underrepresented in clinical trials, limiting the evidence base for sex-specific kidney care. Preclinical evidence implicates a role for estrogen receptor signaling in renal physiology and pathophysiology. Women with chronic kidney disease are at increased risk for adverse pregnancy outcomes and hypertensive disorders of pregnancy, and pregnancy complications can also increase future chronic kidney disease risk. Menopause and aging accelerate chronic kidney disease progression in women as a result of declining estradiol and shifts in kidney estrogen receptor profiles. Endocrine and metabolic disorders such as polycystic ovary syndrome increase susceptibility to chronic kidney disease. Family planning, prepregnancy counseling, and antenatal care are essential to support reproductive health in women with chronic kidney disease. Because chronic kidney disease and cardiovascular disease are tightly intertwined, chronic kidney disease is also a leading contributor to cardiovascular mortality in women. Advancing precision kidney medicine for women requires equitable access to kidney care, embedding assessment of reproductive health in chronic care, trial design with adequate power that includes both women and men, and mechanistic studies linking reproductive health to long-term cardiovascular disease and chronic kidney disease development and progression.
BACKGROUND: Variants in the ion channel gene KCNQ1 are the leading cause of congenital long QT syndrome (LQTS), a disorder characterized by QT prolongation and risk of fatal arrhythmias. The expanding use of genetic testing has led to the identification of numerous variants of uncertain significance, complicating clinical interpretation and risk stratification. Functional characterization of KCNQ1 variants is essential to define their role in long QT syndrome and advance precision medicine in cardiovascular care. METHODS: We generated a nearly comprehensive variant library of 13 403 protein-coding variants in KCNQ1 . Using 4 pooled assays followed by high-throughput sequencing, we characterized the variants’ effects on cell surface abundance and channel function in both the variant-only and heterozygous states. Case–control analyses and data from large-scale biobanks were used to assess the clinical impact of loss-of-function variants on QT prolongation and long QT syndrome. Heterozygous assay results were used to determine dominant-negative effects, which were also evaluated for association with arrhythmia risk. Protein structural clustering of distinct classes of deleterious variants was analyzed. RESULTS: Across the 4 assays, we generated 49 305 functional measurements of KCNQ1 variants. Of the 13 403 KCNQ1 studied variants, 1757 demonstrated strong pathogenic evidence, and 6660 showed moderate benign evidence. Loss-of-function variants were significantly associated with QT prolongation and long QT syndrome in case–control and biobank analyses. Deleterious variants clustered within distinct structural domains based on their functional classification. A majority of pathogenic variants exhibited dominant-negative effects; these variants were linked to a higher risk of arrhythmia diagnoses than were haploinsufficient variants. CONCLUSIONS: This comprehensive KCNQ1 functional atlas provides novel functional evidence for most KCNQ1 variants of uncertain significance. It also reveals mechanistic principles linking genetic variation to ion channel biology and arrhythmia susceptibility, advancing cardiovascular precision medicine.
Radiation-associated coronary artery disease (RACAD) is a distinct form of coronary artery disease with several specific biological and clinical aspects as well as key knowledge gaps. RACAD is prevalent in patients with cardiac exposure to radiotherapy. As radiotherapy is integral to the effective treatment of many thoracic malignancies, improved long-term survivorship is coupled with increased risk for RACAD. Ionizing radiation induces free radical generation and activation of proinflammatory cascades, leading to endothelial dysfunction and accelerated atherosclerosis. Risks for RACAD are determined both by radiotherapy, including the radiation dose and the proximity of coronary arteries to the radiotherapy field, and by patient-specific factors, such as younger age, higher baseline cardiovascular risk, and concurrent cardiotoxic systemic therapies. Importantly, radiotherapy delivery is highly individualized on the basis of tumor location and treatment strategy, resulting in heterogeneous coronary exposure to radiation and patient-to-patient variability. Clinical presentation may occur early, within 1 to 2 years, especially in patients with higher cardiac radiation doses (eg, lung or esophageal cancer), or after a latency period of 5 to 20 years with lower cardiac dose radiation exposure (eg, left-sided breast cancer). Patients generally present with symptoms similar to conventional coronary artery disease. However, RACAD symptoms may be underrecognized in cancer survivors due to overlapping treatment-related fatigue, pulmonary disease, or competing oncologic symptoms. Diagnosis and management generally follow standard coronary artery disease guidelines while incorporating cancer-specific considerations, such as planned oncologic surgeries, bleeding risk, postradiotherapy complications such as atretic internal mammary arteries, and cardiotoxic effects of systemic cancer therapies. Primary prevention of RACAD is critical, emphasizing advances in precision radiotherapy, including delivery techniques with improved coronary dosimetry, and cardiac shielding. Key knowledge gaps include understanding long-term outcomes with contemporary 3-dimensional conformal radiotherapy techniques, validated cancer-specific risk prediction models on the basis of coronary dosimetry, optimal surveillance protocols, targeted molecular pharmacotherapies, and risk analysis of percutaneous versus surgical management of RACAD. Prospective studies are needed to develop cancer- and dosimetry-specific risk calculators, validating cardioprotective interventions, and improving multidisciplinary cardio-oncology collaboration to optimize early detection of RACAD and timely intervention in the growing population of cancer survivors.
