Citations

Abstract Aims Significant secondary tricuspid regurgitation (STR) is associated with worse morbidity and mortality. To-date, evidence on isolated tricuspid valve surgery in STR remains controversial with uncertainty regarding management strategies. We aimed to investigate sex differences in the association of isolated tricuspid valve surgical repair/replacement (TVR) with outcomes of mortality and heart failure (HF) hospitalizations in STR. Methods and results Patients with severe STR without significant aortic valve or organic mitral valve disease, congenital heart disease, pacemakers, previous valve intervention, malignancy, or end-stage kidney/liver disease were identified. Isolated TVR was studied as a time-dependent covariate in association with mortality and HF hospitalizations. Among 2,857 patients (median age 76 years; 62% women), 143 underwent isolated TVR (58% repair; 42% replacement; 64% with low TRI-SCORE risk category) at median 56 days. Over median 1.6 (IQR 0.2-5.2) years, 1,771 patients died and 1,259 had HF hospitalization. When adjusting to age, comorbidities, left/right ventricular function, pulmonary hypertension, hemoglobin level, and dyspnea, isolated TVR was associated with lower mortality in females (HR 0.54 95% CI 0.35-0.83) but not males (HR 1.29 95% CI 0.90-1.83), p-interaction<0.01; this remained the case when restricting to groups with normal left/right ventricular function. Isolated TVR was associated with HF hospitalization without interaction with sex (HR 0.68 95% CI 0.46-0.998), p-interaction=0.51. Conclusion Isolated TVR for STR was associated with decreased HF hospitalizations in both females and males but improved survival only in females. Future studies are needed to understand differences in the natural history of TR between sexes and stratify outcomes after TR intervention by sex.

Abstract Background Lipomatous atrial septal hypertrophy (LASH) is generally viewed as a benign anatomical finding. Although extracardiac fat depots have been linked to adverse cardiometabolic outcomes, the prognostic implications of LASH have not been well defined. Purpose To evaluate whether LASH thickness is independently associated with long-term all-cause mortality. Methods We reviewed adult patients who underwent diagnostic transesophageal echocardiography at our Clinic sites from 2010–2017. LASH was identified by a dumbbell-shaped interatrial septum with maximal thickening ≥5 mm in the bicaval midesophageal view. All-cause mortality through January 1, 2024, served as the primary endpoint. Septal thickness was evaluated using restricted cubic splines and Cox proportional hazards models adjusted for age, sex, body mass index, Charlson Comorbidity Index, and left ventricular ejection fraction. Results Among 1,397 patients (mean age 69±12 years; 60% male), median LASH thickness was 14.2±4.4 mm. LASH severity was classified as mild (<15 mm; n=763), moderate (15-20 mm; n=522), or severe (>20 mm; n=112). During 7.5±4.0 years of follow-up, 586 deaths (42%) occurred. Mortality was higher with increasing septal thickness (37%, 46%, and 56%; p < 0.001). Each 1-mm increase in LASH-thickness was associated with higher adjusted mortality (adjusted-hazard-ratio 1.03; 95%-confidence-interval 1.01-1.05). Spline modeling suggested a risk increase beginning near 16 mm; thickness >16 mm carried a 26% higher mortality risk (adjusted-hazard-ratio 1.26; 95%-confidence-interval 1.06-1.50). Conclusions LASH was associated with long-term mortality independent of BMI and other clinical factors. Septal fat accumulation may provide a useful, noninvasive marker that complements broader cardiac risk assessment.Risk for all-cause mortality across LASHFor image description, please refer to the figure legend and surrounding text.

A 44-year-old recent heart transplant recipient supported by VA-ECMO presented to the operating room (OR) for left ventricular (LV) vent removal. She had a history of double-inlet LV with right atrioventricular valve atresia and transposition of great arteries, status post fenestrated Fontan complicated by end-stage heart failure. Three days ago, she underwent a fourth sternotomy and orthotopic heart transplant complicated by coagulopathy and severe bi-ventricular dysfunction necessitating initiation of central VA-ECMO. Due to massive blood product transfusion and ventricular dilatation, an apical LV vent was inserted. Postoperatively the arterial line waveform remained non-pulsatile. The patient was brought to the OR for mediastinal debridement and removal of the LV vent for the purpose of assessing ventricular function and improving arterial pulsatility. Pulse pressure remained negligible at an ECMO flow of 4.5 L/min. Transeosphageal echocardiography (TEE) demonstrated extensive thrombosis of the aortic root, particularly involving the right and non-coronary sinuses (Fig 1a). The aortic valve (AV) did not open. Patency of the left main coronary ostium was evident by color Doppler (Fig 1b) although no right coronary artery (RCA) flow could be visualized. The tip of LV vent was seen tenting the anterior leaflet of mitral valve (MV) causing significant regurgitation. (Fig. 2a-d) After vent removal, LV contraction gradually increased and the AV began to open. This progressively dislodged thrombus from the aortic root. At the conclusion of imaging, there was a highly mobile, bi-lobed thrombus attached to the sinotubular junction (Fig 1c-d). Right ventricular (RV) function remained severely reduced. Moderate mitral regurgitation persisted, arising from A2 leaflet prolapse. This patient subsequently underwent transcatheter thrombectomy and aspiration of the aortic root with cerebral protection device. Coronary angiogram confirmed proximal RCA occlusion (Fig. 3). Attempts to remove RCA thrombus were only partially successful. She eventually required a second heart transplant due to RV infarction. Discussion: This case illustrates a TEE-detected complication of excessive LV venting during VA-ECMO support, namely aortic root thrombosis associated with lack of AV opening. TEE also demonstrated the associated complications of RCA occlusion and iatrogenic mitral valve injury. Unfortunately, these complications were not detected soon enough to avoid RV infarction.

AbstractBackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types.ConclusionsCNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

AbstractBackgroundPostoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement.MethodsA multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations.ResultsConsensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management.ConclusionSalivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.