Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

Fetal Arrhythmia Leading to a Diagnosis of Congenital Long QT Syndrome Type II.

We describe the case of an asymptomatic young pregnant woman with a diagnosis of congenital long QT syndrome type II in the context of in utero fetal 2:1 heart block and ventricular tachycardia. The presentation, clinical considerations, and management of the mother and baby in the antepartum and postpartum periods are discussed.

Heart transplantation: advances in expanding the donor pool and xenotransplantation.

Approximately 65 million adults globally have heart failure, and the prevalence is expected to increase substantially with ageing populations. Despite advances in pharmacological and device therapy of heart failure, long-term morbidity and mortality remain high. Many patients progress to advanced heart failure and develop persistently severe symptoms. Heart transplantation remains the gold-standard therapy to improve the quality of life, functional status and survival of these patients. However, there is a large imbalance between the supply of organs and the demand for heart transplants. Therefore, expanding the donor pool is essential to reduce mortality while on the waiting list and improve clinical outcomes in this patient population. A shift has occurred to consider the use of organs from donors with hepatitis C virus, HIV or SARS-CoV-2 infection. Other advances in this field have also expanded the donor pool, including opt-out donation policies, organ donation after circulatory death and xenotransplantation. We provide a comprehensive overview of these various novel strategies, provide objective data on their safety and efficacy, and discuss some of the unresolved issues and controversies of each approach.

Racial Differences in Atrial Fibrillation Management Between White Patients and Black Patients in Transthyretin Cardiac Amyloid.

Black patients have higher rates of stroke than White patients. Paradoxically, atrial fibrillation (AF) affects twice as many White patients compared with Black patients. Transthyretin cardiac amyloidosis (ATTR-CA) is associated with both AF and strokes. We hypothesized that although Black patients with ATTR-CA have a lower incidence of AF, when diagnosed with AF, they have increased thromboembolic events. Patients with ATTR-CA (n = 558) at 3 international centers were retrospectively identified. We compared baseline characteristics, presence of AF, outcomes of thromboembolism (stroke, transient ischemic attack, and peripheral embolism), major bleed, and mortality by race. Of all patients, 367 of 488 White patients (75%) were diagnosed with AF compared with 39 of 70 Black patients (56%) (p = 0.001). Black patients with AF had a hazard ratio of 5.78 (95% confidence interval 2.30 to 14.50) for time to first thromboembolic event compared with White patients. There were no racial differences in major bleeding. Black patients with AF more often lacked anticoagulation (p = 0.038) and had higher incidence of labile international normalized ratio (p <0.001). In conclusion, these data suggest that although Black patients with ATTR-CA have lower incidence of AF, they have increased thromboembolic events compared with White patients. These findings may be related to treatment discrepancies, time in therapeutic range for warfarin, and disparities in healthcare.

Systemic embolism in amyloid transthyretin cardiomyopathy.

AIMS: Although systemic embolism is a potential complication in transthyretin amyloid cardiomyopathy (ATTR-CM), data about its incidence and prevalence are scarce. We studied the incidence, prevalence and factors associated with embolic events in ATTR-CM. Additionally, we evaluated embolic events according to the type of oral anticoagulation (OAC) and the performance of the CHA2 DS2 -VASc score in this setting. METHODS AND RESULTS: Clinical characteristics, history of atrial fibrillation (AF) and embolic events were retrospectively collected from ATTR-CM patients evaluated at four international amyloid centres. Overall, 1191 ATTR-CM patients (87% men, median age 77.1 years [interquartile range-IQR 71.4-82], 83% ATTRwt) were studied. A total of 162 (13.6%) have had an embolic event before initial evaluation. Over a median follow-up of 19.9 months (IQR 9.9-35.5), 41 additional patients (3.44%) had an embolic event. Incidence rate (per 100 patient-years) was 0 among patients in sinus rhythm with OAC, 1.3 in sinus rhythm without OAC, 1.7 in AF with OAC, and 4.8 in AF without OAC. CHA2 DS2 -VASc did not predict embolic events in patients in sinus rhythm whereas in patients with AF without OAC, only those with a score ≥4 had embolic events. There was no difference in the incidence rate of embolism between patients with AF treated with vitamin K antagonists (VKAs) (n = 322) and those treated with direct oral anticoagulants (DOACs) (n = 239) (p = 0.66). CONCLUSIONS: Embolic events were a frequent complication in ATTR-CM. OAC reduced the risk of systemic embolism. Embolic rates did not differ with VKAs and DOACs. The CHA2 DS2 -VASc score did not correlate well with clinical outcome in ATTR-CM and should not be used to assess thromboembolic risk in this population.

Risk factor management of atrial fibrillation using mHealth: The Atrial Fibrillation - Helping Address Care with Remote Technology (AF-HEART) Pilot Study.

Background: Personalized treatment of atrial fibrillation (AF) risk factors using mHealth and telehealth may improve patient outcomes. Objective: The purpose of this study was to assess the feasibility of the Atrial Fibrillation Helping Address Care with Remote Technology (AF-HEART) intervention on the following patient outcomes: (1) heart rhythm tracking; (2) weight, alcohol, blood pressure (BP), and sleep apnea reduction; (3) AF symptom reduction; and (4) quality-of-life (QOL) improvement. Methods: A total of 20 patients with AF undergoing antiarrhythmic therapy, cardioversion, and/or catheter ablation were enrolled and followed for 6 months. The AF-HEART intervention included remote heart rhythm, weight, and BP tracking; televisits with a dietician focusing on AF risk factors; and referrals for sleep apnea and hypertension treatment. Results: Patients transmitted a median of 181 rhythm recordings during the 6-month follow-up period. Patients lost an average of 3.5 kilograms at 6 months (P = .005). Patients had improved SF-12 scores (P = .01), AFSS score (P = .01), EQ-5D score (P = .006), and AFEQT Global Score (P = .03). There was significant correlation between weight loss and decrease in symptom severity (r = -0.45, P = .05), and between % weight loss and decrease in symptom severity (r = -0.49, P = .03). Conclusion: This study described the feasibility of the AF-HEART intervention for (1) consistent remote tracking of heart rhythm, weight, and BP; (2) achievement of weight loss; (3) reduction of symptoms; and (4) improvement in QOL. Expansion to a larger randomized study is planned.

Anticoagulation with warfarin compared to novel oral anticoagulants for atrial fibrillation in adults with transthyretin cardiac amyloidosis: comparison of thromboembolic events and major bleeding.

BACKGROUND: Atrial fibrillation (AF) is common in patients with transthyretin cardiac amyloidosis (ATTR-CA). The optimal strategy to prevent strokes in patients with ATTR-CA and AF is unknown. OBJECTIVES: To compare outcomes in patients with ATTR-CA and AF treated with warfarin versus novel oral anticoagulants (NOACs). METHODS: This study was a retrospective analysis of patients with ATTR-CA stratified by presence or absence of AF and anticoagulation therapy. The primary outcome included a time to event analysis for the combined outcomes of stroke, transient ischaemic attack (TIA), major bleed, or death. RESULTS: Of 290 patients, 217 patients (74.8%) had AF. Of those with AF (n = 217), 78 (35.9%) patients received warfarin compared with 116 (53.5%) patients who received NOACs. There were 17 thrombotic events, all in those diagnosed with AF compared with none in the patients without AF (p = .01). Over a mean follow-up of 2.4 years (range 0.1-12) there was no difference in primary outcome between those with AF treated with warfarin compared with NOACs (p = .35). CONCLUSION: Patient with ATTR-CA and AF are at increased risk for stroke compared to patients with ATTR-CA and without AF. Thrombotic events and major bleeds did not differ between those who received warfarin and NOACs.

Early recognition of multiple sclerosis using natural language processing of the electronic health record.

BACKGROUND: Diagnostic accuracy might be improved by algorithms that searched patients' clinical notes in the electronic health record (EHR) for signs and symptoms of diseases such as multiple sclerosis (MS). The focus this study was to determine if patients with MS could be identified from their clinical notes prior to the initial recognition by their healthcare providers. METHODS: An MS-enriched cohort of patients with well-established MS (n = 165) and controls (n = 545), was generated from the adult outpatient clinic. A random sample cohort was generated from randomly selected patients (n = 2289) from the same adult outpatient clinic, some of whom had MS (n = 16). Patients' notes were extracted from the data warehouse and signs and symptoms mapped to UMLS terms using MedLEE. Approximately 1000 MS-related terms occurred significantly more frequently in MS patients' notes than controls'. Synonymous terms were manually clustered into 50 buckets and used as classification features. Patients were classified as MS or not using Naïve Bayes classification. RESULTS: Classification of patients known to have MS using notes of the MS-enriched cohort entered after the initial ICD9[MS] code yielded an ROC AUC, sensitivity, and specificity of 0.90 [0.87-0.93], 0.75[0.66-0.82], and 0.91 [0.87-0.93], respectively. Similar classification accuracy was achieved using the notes from the random sample cohort. Classification of patients not yet known to have MS using notes of the MS-enriched cohort entered before the initial ICD9[MS] documentation identified 40% [23-59%] as having MS. Manual review of the EHR of 45 patients of the random sample cohort classified as having MS but lacking an ICD9[MS] code identified four who might have unrecognized MS. CONCLUSIONS: Diagnostic accuracy might be improved by mining patients' clinical notes for signs and symptoms of specific diseases using NLP. Using this approach, we identified patients with MS early in the course of their disease which could potentially shorten the time to diagnosis. This approach could also be applied to other diseases often missed by primary care providers such as cancer. Whether implementing computerized diagnostic support ultimately shortens the time from earliest symptoms to formal recognition of the disease remains to be seen.

Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes. METHODS AND MATERIALS: Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance. RESULTS: Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically. CONCLUSIONS: Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

Survey of patient and physician influences and decision-making regarding CT utilization for minor head injury.

OBJECTIVE: Assess factors that influence both the patient and the physician in the setting of minor head injury in adults and the decision-making process around CT utilization. METHODS: This is a convenience sample survey study of adult minor head injury patients (GCS 15) and their physicians regarding factors influencing the decision to use CT to evaluate for intra-cranial haemorrhage. Once a head CT was ordered and before the results were known, both the patient and physician were given a one-page survey asking questions about their concern for injury and rationale for CT use. CT results and surveys were then recorded in a centralized database and analyzed. RESULTS: 584 subjects were enrolled over the 27-month study period. The rate of any intra-cranial haemorrhage was 3.3%. Both the physicians (6% pre-test estimate) and the patients (22% pre-test estimate) over-estimated risk for haemorrhage. Clinical decision rules were not met in 46% of cases where CT was used. Physicians listed an average of 5 factors from a list of 9 that influenced their decision to order CT. Patients listed an average of 1.7 factors influencing their decision to present to the Emergency Department for evaluation. Many patients felt cost (45%) and low risk stratification (34%) should weigh heavily in the decision to use CT. If asked to limit CT utilization, physicians were able to identify a group with less than 2% risk of injury. CONCLUSIONS: Patients with low risk of intra-cranial injury continue to be evaluated by CT. Physician decision-making around the use of CT to evaluate minor head injury is multi-factorial. Shared decision-making between the patient and the physician in a low risk minor head injury encounter shows promise as a method to reduce CT utilization in this low risk cohort.