High-Risk Congenital Heart Disease in Pregnancy.

High-risk congenital heart disease (CHD) in pregnancy presents a complex clinical challenge. With improved medical care and increased survival rates, a growing population of adults with complex CHD are surviving to adulthood, including women of reproductive age. This chapter focuses on risk stratification and management of pregnant women with high-risk CHD, emphasizing the importance of considering both anatomical and physiological complexity. Maternal physiological changes, such as blood volume increase, cardiac output changes, and alterations in vascular resistance, can significantly impact high-risk CHD patients. Management of high-risk CHD in pregnancy necessitates a multidisciplinary approach and individualized care.

Female-specific risk factors of parity and menopause age and risk of carotid plaque: the multi-ethnic study of atherosclerosis.

BACKGROUND: Female-specific factors of grand multiparity (≥5 births) and early menopause age are associated with an increased risk of cardiovascular disease (CVD). However, mechanisms are incompletely understood. Carotid plaque is a marker of subclinical atherosclerosis and associated with increased CVD risk. We evaluated the association of female-specific factors with plaque burden. METHODS: We included 2,313 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, free of clinical CVD, whose parity and menopause age were ascertained by questionnaires and carotid plaque measured by ultrasound at baseline and 10 years later. Parity was categorized as nulliparity (reference), 1-2, 3-4 and ≥5 live births. Menopause age was categorized as <45, 45-49, 50-54 (reference) and ≥55 years. Multivariable regression was performed to evaluate the association of parity and menopause age with carotid plaque presence (yes/no) and extent [carotid plaque score (CPS)]. RESULTS: The mean age was 64±9 years; 52.3% had prevalent carotid plaque at baseline. Compared to nulliparity, grand multiparity was significantly associated with prevalent carotid plaque after adjustment for CVD risk factors (prevalence ratio 1.17 (95% CI 1.03-1.35)) and progression of CPS over 10 years [percent difference 13% (95% CI 3-23)]. There was not any significant association of menopause age with carotid plaque presence or progression in fully-adjusted models. CONCLUSION: In a multiethnic cohort, grand multiparity was independently associated with carotid plaque presence and progression. Early menopause, a known risk factor for CVD, was not captured by carotid plaque in this study. These findings may have implications for refining CVD risk assessment in women.

Neuroimaging Correlates of Post-Traumatic Stress Disorder in Traumatic Brain Injury: A Systematic Review of the Literature.

Neuroimaging is widely utilized in studying traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). The risk for PTSD is greater after TBI than after non-TBI trauma, and PTSD is associated with worse outcomes after TBI. Studying the neuroimaging correlates of TBI-related PTSD may provide insights into the etiology of both conditions and help identify those TBI patients most at risk of developing persistent symptoms. The objectives of this systematic review were to examine the current literature on neuroimaging in TBI-related PTSD, summarize key findings, and highlight strengths and limitations to guide future research. A Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) compliant literature search was conducted in PubMed (MEDLINE®), PsycINFO, Embase, and Scopus databases prior to January 2022. The database query yielded 4486 articles, which were narrowed based on specified inclusion criteria to a final cohort of 16 studies, composed of 854 participants with TBI. There was no consensus regarding neuroimaging correlates of TBI-related PTSD among the included articles. A small number of studies suggest that TBI-related PTSD is associated with white matter tract changes, particularly in frontotemporal regions, as well as changes in whole-brain networks of resting-state connectivity. Future studies hoping to identify reliable neuroimaging correlates of TBI-related PTSD would benefit from ensuring consistent case definition, preferably with clinician-diagnosed TBI and PTSD, selection of comparable control groups, and attention to imaging timing post-injury. Prospective studies are needed and should aim to further differentiate predisposing factors from sequelae of TBI-related PTSD.

Mobile Cardiac Telemetry Use to Predict Adverse Pregnancy Outcomes in Patients With Congenital Heart Disease.

Background: Patients with congenital heart disease (CHD) have a higher incidence of arrhythmias during pregnancy, yet the utility of mobile cardiac telemetry (MCT) to predict adverse outcomes is unknown. Objectives: The purpose of this study is to determine whether arrhythmias on screening MCT correlate with adverse pregnancy outcomes. Methods: Patients with CHD prospectively enrolled in the Standardized Outcomes in Reproductive Cardiovascular Care initiative underwent 24-hour MCT (within 18 months prior to pregnancy). Positive findings on MCT were defined as episodes of bradyarrhythmia, symptomatic atrioventricular block, ectopic atrial or ventricular activity, and supraventricular or ventricular tachycardia. Clinically significant arrhythmia events (CSAEs) were those requiring medical or device intervention or an emergency room visit. Clinical events during the antepartum, intrapartum, and postpartum periods were compared using Fisher's exact test. Analyses were performed using Stata version 16. Results: In 141 pregnancies in 118 patients with CHD, MCT detected positive findings in 17%. Adverse cardiac outcomes occurred in 11% of pregnancies, of which CSAE occurred in 3.5%. Positive MCT was significantly associated with subsequent CSAE (21% vs 0%, P < 0.001) and cumulative adverse maternal cardiac outcomes (33% vs 7%, P = 0.001) but did not correlate with obstetric (46% vs 41%, P = 0.660) or neonatal outcomes (33% vs 31%, P = 0.810). Of the patients with CSAE, 75% had ≥moderate CHD complexity. Conclusions: Patients with CHD had a high rate of positive MCT findings. This was associated with CSAE and adverse maternal cardiac outcomes. Patients with ≥moderate CHD complexity may benefit from screening MCT to improve preconceptual counseling and planning.

Association between parity and markers of inflammation: The multi-ethnic study of atherosclerosis.

Introduction: Multiparity has been associated with increased risk of cardiovascular disease (CVD). Inflammation may be a mechanism linking parity to CVD. We investigated the association between parity and later-life markers of inflammation. Methods: We studied 3,454 female MESA participants aged 45-84, free of CVD, who had data on parity and inflammatory markers. Parity was categorized as 0 (reference), 1-2, 3-4, or ≥5. Linear regression was used to evaluate the association between parity and natural log-transformed levels of fibrinogen, D-dimer, GlycA, high sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). Results: Mean age was 62 ± 10 years. The proportion of women with nulliparity, 1-2, 3-4, and ≥5 live births were 18, 39, 29, and 14%, respectively. There was no association between parity and fibrinogen. Women with grand multiparity (≥5 live births) had 28, 10, and 18% higher levels of hsCRP, IL-6 and D-dimer, respectively, compared to nulliparous women, after adjustment for demographic factors. After additional adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher hsCRP and women with 1-2 live births had higher GlycA. Conclusion: In this diverse cohort of middle-to-older aged women, we found that higher parity was associated with some inflammatory markers; however, these associations were largely attenuated after adjustment for CVD risk factors. There was no clear dose-response relationship between parity and these inflammatory markers. Future studies are needed to evaluate how inflammation may influence the link between parity and CVD and whether healthy lifestyle/pharmacotherapies targeting inflammation can reduce CVD risk among multiparous women. Clinical trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Parity History and Later Life Sex Hormone Levels in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Multiparity is a risk factor for cardiovascular disease (CVD). A more androgenic sex hormone profile, with a higher testosterone (T)/estradiol (E2) ratio, is associated with worse CVD outcomes in women and might be one mechanism linking multiparity to increased CVD risk. We investigated the relationship between parity and sex hormones at mid-to-older age. METHODS: We performed a cross-sectional analysis of 2979 women with data on parity and endogenous sex hormone levels from the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort. Parity and gravidity (our exposures) were categorized as 0 (reference), 1-2, 3-4, or ≥ 5. Our outcome measures were T, E2, sex hormone binding globulin, dehydroepiandrosterone, and T/E2 ratio. Progressively adjusted linear regression was used to evaluate the association of parity/gravidity with sex hormones. RESULTS: In multivariable adjusted models, there were no significant associations of parity with E2, dehydroepiandrosterone, and sex hormone binding globulin. Compared with nulliparity, after adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher T, but this was not significant for grand multiparity (≥ 5 live births). However, grand multigravidity (≥ 5 pregnancies) was associated with 10% (95% confidence interval [CI], 1%-20%) higher T and 14% (95% CI, 1%-29%) higher T/E2, compared with null gravidity. Grand multiparity was associated with an 18% (95% CI, 4%-34%) higher T/E2 ratio compared with nulliparity, after adjustment for CVD risk factors. CONCLUSIONS: In this multiethnic cohort, women with grand multigravidity and grand multiparity had higher T/E2 levels, reflecting a more androgenic sex hormone profile. Longitudinal studies on sex hormones' influence on the relationship between multiparity and CVD are warranted.

Behavioral and Emotional Dyscontrol Following Traumatic Brain Injury: A Systematic Review of Neuroimaging and Electrophysiological Correlates.

BACKGROUND: Behavioral and emotional dyscontrol commonly occur following traumatic brain injury (TBI). Neuroimaging and electrophysiological correlates of dyscontrol have not been systematically summarized in the literature to date. OBJECTIVE: To complete a systematic review of the literature examining neuroimaging and electrophysiological findings related to behavioral and emotional dyscontrol due to TBI. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted in PubMed (MEDLINE), PsycINFO, EMBASE, and Scopus databases prior to May 2019. The database query yielded 4392 unique articles. These articles were narrowed based on specific inclusion criteria (e.g., clear TBI definition, statistical analysis of the relationship between neuroimaging and dyscontrol). RESULTS: A final cohort of 24 articles resulted, comprising findings from 1552 patients with TBI. Studies included civilian (n = 12), military (n = 10), and sport (n = 2) samples with significant variation in the severity of TBI incorporated. Global and region-based structural imaging was more frequently used to study dyscontrol than functional imaging or diffusion tensor imaging. The prefrontal cortex was the most common neuroanatomical region associated with behavioral and emotional dyscontrol, followed by other frontal and temporal lobe findings. CONCLUSIONS: Frontal and temporal lesions are most strongly implicated in the development of postinjury dyscontrol symptoms although they are also the most frequently investigated regions of the brain for these symptom categories. Future studies can make valuable contributions to the field by (1) emphasizing consistent definitions of behavioral and emotional dyscontrol, (2) assessing premorbid dyscontrol symptoms in subjects, (3) utilizing functional or structural connectivity-based imaging techniques, or (4) restricting analyses to more focused brain regions.

The Association Between Multiparity and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

Background: Multiparity is a risk factor for cardiovascular disease (CVD). However, the mechanisms of this relationship are unknown. Adipokines may predispose multiparous women to certain cardiometabolic complications that can increase their risk of future CVD. Materials and Methods: We studied 973 female participants of the Multi-Ethnic Study of Atherosclerosis free of CVD, who had complete data on parity and adipokines measured at Examination 2 or 3 (randomly assigned). Parity was categorized as nulliparity, 1-2, 3-4, and ≥5 live births. Multivariable linear regression was used to evaluate the association of parity with leptin, resistin, and adiponectin levels. Results: The women had mean age of 65 ± 9 years. After adjustment for age, race/ethnicity, study site, education, menopause status, smoking, physical activity, use of hormone therapy, and waist circumference, a history of grand multiparity (≥5 live births) was associated with 11% higher resistin levels (95% confidence interval [CI] 0-23) and 3-4 live births was associated with 23% higher leptin levels (95% CI 7-42), compared with nulliparity. After adjustment for computed tomography-measured visceral fat, the association of 3-4 live births with leptin remained significant. There were no significant associations of parity with adipokines after further adjustment for additional CVD risk factors. Multigravidity (but not parity) was inversely associated with adiponectin levels. Conclusions: In a multiethnic cohort of women, greater parity was associated with resistin and leptin; however, this association was attenuated after accounting for CVD risk factors. Dysregulation of adipokines could contribute to the excess CVD risk associated with multiparity. Further studies are needed to determine whether adipokines independently mediate the relationship between multiparity and CVD. Clinical trials registration: The MESA cohort is registered at NCT00005487.

Cognitive impairment in adult CHD survivors: A pilot study.

The most common comorbidities in children with congenital heart disease (CHD) are neurodevelopmental impairments, particularly in areas of executive function, memory and attention. Limited studies have demonstrated similar impairments in CHD adults although no studies have screened specifically for mild cognitive impairment and dementia. Methods We performed a prospective cross-sectional study of CHD patients, ages 30-65 years, who were coming for clinic visits. We administered the Mini-Mental State Exam (MMSE), and scores were compared with population norms adjusted by age and education level. Results A total of 125 patients were recruited (55% male). The median age was 40 years (range 30-65). More than a half (80%) had some college education or advanced degrees. Adjusting for age and education, CHD participants scored significantly lower than the general population (median 1 point lower, p<0.001) on the MMSE. The greatest impairments occurred in recall and orientation. Five percent of the total cohort met the general threshold for mild cognitive impairment (MMSE < 24). Clinical factors associated with this degree of cognitive impairment were duration of cyanosis (p=0.005) and decreased systemic ventricular function (p=0.003). Conclusions Our pilot study showed that, when adjusted for age and education level, CHD adults had significantly lower MMSE scores than the general population, with 5% meeting criteria for mild cognitive impairment. These findings suggest that subtle and early cognitive changes are present in the adult CHD population. Further studies are needed to investigate those changes that might influence long-term outcomes in the adult CHD population.

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial.

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibition. Here we report for the first time interim results of our ongoing phase I clinical trial (NCT02544880) in patients with recurrent HNSCC to evaluate the safety of and immunological effects of combining Tadalafil with the antitumor vaccine composed of Mucin1 (MUC1) and polyICLC. The combined treatment of Tadalafil and MUC1/polyICLC vaccine was well-tolerated with no serious adverse events or treatment limiting toxicities. Immunologically, this trial also confirms the positive immunomodulation of Tadalafil in patients with recurrent HNSCC and suggests an adjuvant effect of the anti-tumor vaccine MUC1/polyICLC. Additionally, image cytometry analysis of scanned tumors indicates that the PDE5 inhibitor Tadalafil in conjunction with the MUC1/polyICLC vaccine effectively reduces the number of PDL1+macrophages present at the tumor edge, and increases the number of activated tumor infiltrating T cells, suggesting reversion of immune exclusion. However, this analysis shows also that CD163 negative cells within the tumor upregulate PDL1 after treatment, suggesting the instauration of additional mechanisms of immune evasion. In summary, our data confirm the safety and immunologic potential of PDE5 inhibition in HNSCC but also point to PDL1 as additional mechanism of tumor evasion. This supports the rationale for combining checkpoint and PDE5 inhibitors for the treatment of human malignancies.

A Broken Heart: Takotsubo Cardiomyopathy.

This case illustrates the unusual presentation of Takotsubo cardiomyopathy in an elderly male patient with characteristic chest pain and dyspnea associated with electrocardiographic changes of biphasic T wave inversions and QT-interval prolongation on anterior segment, mimicking acute coronary syndrome. Takotsubo cardiomyopathy is a transient systolic dysfunction of the apical and/or mid and anterior segments of left ventricle most frequently seen in post- menopausal women, up to 80 to 100% of cases. Often there is a history of a recent (within the previous two months) episode of severe emotional or physical stress associated with the event.

Cardiac computed tomography angiography in a Puerto Rico population with chest pain: initial experience at HIMA-San Pablo Bayamón.

Cardiac computed tomography angiography (CCTA) is an efficient tool for the assessment of patients with chest pain and intermediate probability for coronary artery disease (CAD). Based on high negative predictive value results of CCTA, we decide to evaluate our performance at HIMA San Pablo Bayamón. For our study, 59 patients were selected based on history of chest pain having an intermediate CAD probability. Only 53 were accessible to interviewing and questioning. As exclusion criteria, patients had to be over 19 years old, without a permanent pacemaker, persistent intractable cardiac arrhythmias, history of contrast allergy, significant active COPD and having a creatinine below 1.5 mg/dl. The study was performed with the Toshiba Aquilion 64 CT scanner. We searched retrospectively for the occurrence of major adverse cardiovascular events (MACE) in this study such as unstable angina, myocardial infarction, revascularization, and death. Statistical evaluation was performed separately and as MACE. Patients were classified in three categories: normal, no significant and significant findings based on CCTA results. Statistical calculation of these results demonstrated no events in the normal category, 10% in the nonsignificant and 25% in the significant category. Our review of the efficacy of CCTA in patients in our setting in HIMA San Pablo Bayamón demonstrates an impressive negative predictive value of the test excluding significant cardiac events or MACE, which concurs with the recent literature about CCTA. The safety, ease of realization and short duration of the procedure makes this test an excellent technique to assess clinical prognosis.