Brief Review: Racial and Ethnic Disparities in Cardiovascular Care with a Focus on Congenital Heart Disease and Precision Medicine.

PURPOSE OF REVIEW: This is a brief review about racial and ethnic disparities in healthcare with focused attention to less frequently covered areas in the literature such as adult congenital heart disease, artificial intelligence, and precision medicine. Although diverse racial and ethnic populations such as Black and Hispanic groups are at an increased risk for CHD and have worse related outcomes, they are woefully underrepresented in large clinical trials. Additionally, although artificial intelligence and its application to precision medicine are touted as a means to individualize cardiovascular treatment and eliminate racial and ethnic bias, serious concerns exist about insufficient and inadequate available information from diverse racial and ethnic groups to facilitate accurate care. This review discusses relevant data to the aforementioned topics and the associated nuances. RECENT FINDINGS: Recent studies have shown that racial and ethnic minorities have increased morbidity and mortality related to congenital heart disease. Artificial intelligence, one of the chief methods used in precision medicine, can exacerbate racial and ethnic bias especially if inappropriate algorithms are utilized from populations that lack racial and ethnic diversity. Dedicated resources are needed to engage diverse populations to facilitate participation in clinical and population-based studies to eliminate racial and ethnic healthcare disparities in adult congenital disease and the utilization of artificial intelligence to improve health outcomes in all populations.

Incidence of Right Ventricular Dysfunction in an Echocardiographic Referral Cohort.

Introduction: Incidence rates (IRs) of RV dysfunction (RVD) are unknown. We examined the rates, risk factors, and heart failure (HF) hospitalization hazard associated with incident RVD in patients referred for Transthoracic Echocardiogram (TTE). Methods: In this retrospective cohort study, we extracted tricuspid regurgitant velocity (TRV) and tricuspid annular systolic plane excursion (TAPSE) from TTEs at Vanderbilt (2010-2023). We followed patients from their earliest TTE with normal RV function (TAPSE≥17mm) and a reported TRV. The primary outcome was new RVD (TAPSE<17mm), and the secondary outcome was HF hospitalization after second TTE. Poisson regression and multivariable cox models estimated IRs and hazard ratios, adjusted for demographics, comorbidities, and TTE measures. Results: Among 45,753 patients (63 years [IQR 50-72], 45% Male, 13% Black) meeting inclusion criteria, 13,735 (30.1%) underwent a follow up TTE and 4,198 (9.2%) developed RVD. The IR of RVD in the full cohort was 3.2/100 person/years (95%CI 3.1-3.3) and 8.2 (95%CI 8.0-8.5) in the repeat TTE cohort. IRs increased with rising RVSP. Risk factors for incident RVD were most prominently HF (HR 1.88; 95%CI 1.75-2.03), left-sided valvular disease (HR 1.68; 95%CI 1.53-1.85), and other cardiovascular comorbidities. Baseline RVSP >35 mmHg associated with TAPSE decline over time. Incident RVD increased hazard of HF hospitalization (HR 2.02; 95%CI 1.85-2.21). Hazard of HF hospitalization increased when TAPSE declined by ≥5mm. Conclusions: RVD incidence is substantial among patients referred for TTE. Clinical monitoring is warranted if RVSP >35mmHg. Cardiovascular comorbidities drive RVD in this population. Incident RVD associates with increased hazard of HF hospitalization.

Incidence of Pulmonary Hypertension in the Echocardiography Referral Population.

RATIONALE: Incidence rates for pulmonary hypertension using diagnostic data in patients with cardiopulmonary disease are not known. OBJECTIVES: To determine incidence rates of, risk factors for, and mortality hazard associated with pulmonary hypertension among patients referred for transthoracic echocardiography Methods: Retrospective cohort study using data from the Veterans Health Administration (1999-2020) and Vanderbilt University Medical Center (1994-2020). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35mmHg with prevalent cases excluded. Heart failure and chronic obstructive pulmonary disease were the primary exposures of interest. The primary outcome was incident pulmonary hypertension. Secondarily, we examined mortality rate following incident diagnosis. MEASUREMENTS AND MAIN RESULTS: We identified 245,067 VA patients (94% male, 20% Black) and 117,526 Vanderbilt patients (46% male, 11% Black) without pulmonary hypertension, of whom 38,882 VA patients and 8,061 Vanderbilt patients developed pulmonary hypertension. Only 18-19% of patients with echo-based pulmonary hypertension also had a diagnostic code. Hazard of pulmonary hypertension was 4-fold higher in patients with heart failure and chronic obstructive pulmonary disease compared to patients without either. Mortality rates increased from pulmonary artery systolic pressure of 35mmHg to 45mmHg then plateaued. Independent risk factors for incident pulmonary hypertension included older age, male sex, black race, and cardiometabolic comorbidities. CONCLUSIONS: Pulmonary hypertension incidence rates estimated by diagnostic data are higher than code-based rates. Heart failure and chronic obstructive pulmonary disease strongly associate with incident pulmonary hypertension. Pulmonary artery systolic pressure >45mmHg at diagnosis is associated with high mortality. New pulmonary hypertension on echocardiography is an important prognostic sign.

Clinical features do not identify risk of progression from isolated postcapillary pulmonary hypertension to combined pre- and postcapillary pulmonary hypertension.

Pulmonary hypertension is a common sequelae of left heart failure and may present as isolated postcapillary pulmonary hypertension (Ipc-PH) or combined pre- and postcapillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not yet been described. We extracted clinical data from patients who underwent right heart catheterizations (RHC) on two separate occasions. Ipc-PH was defined as mean pulmonary pressure >20 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance (PVR) < 3 WU. Progression to Cpc-PH required an increase in PVR to ≥3 WU. We performed a retrospective cohort study with repeated assessments comparing subjects that progressed to Cpc-PH to subjects that remained with Ipc-PH. Of 153 patients with Ipc-PH at baseline who underwent a repeat RHC after a median of 0.7 years (IQR 0.2, 2.1), 33% (50/153) had developed Cpc-PH. In univariate analysis comparing the two groups at baseline, body mass index (BMI) and right atrial pressure were lower, while the prevalence of moderate or worse mitral regurgitation (MR) was higher among those who progressed. In age- and sex-adjusted multivariable analysis, only BMI (OR 0.94, 95% CI 0.90-0.99, p = 0.017, C = 0.655) and moderate or worse MR (OR 3.00, 95% CI 1.37-6.60, p = 0.006, C = 0.654) predicted progression, but with poor discriminatory power. This study suggests that clinical features alone cannot distinguish patients at risk for development of Cpc-PH and support the need for molecular and genetic studies to identify biomarkers of progression.

Cardiometabolic Risk Factors Associated With Right Ventricular Function and Compensation in Patients Referred for Echocardiography.

Background Pulmonary hypertension and right ventricular (RV) dysfunction are drivers of adverse outcomes; however, modifiable risk factors for RV dysfunction are not well described. We investigated the association between clinical markers of metabolic syndrome and echocardiographic RV function in a large referral population. Methods and Results Using electronic health record data, we performed a retrospective cohort study of patients aged ≥18 years referred for transthoracic echocardiography between 2010 and 2020 with RV systolic pressure (RVSP) or tricuspid annular plane systolic excursion (TAPSE) values. Pulmonary hypertension was defined by RVSP >33 mm Hg and RV dysfunction by TAPSE ≤1.8 cm. Our sample included 37 203 patients of whom 19 495 (52%) were women, 29 752 (83%) were White, with a median age of 63 years (interquartile range, 51-73). Median (interquartile range) RVSP was 30.0 mm Hg (24.0-38.7), and median TAPSE was 2.1 cm (1.7-2.4). Within our sample, 40% had recorded RVSP >33 mm Hg, and 32% with TAPSE <1.8 cm. Increase in RVSP from normal (<33 mm Hg) to mildly elevated (33-39 mm Hg) or elevated (>39 mm Hg) was associated with lower low-density lipoprotein and high-density lipoprotein, and higher hemoglobin A1c and body mass index (P<0.001). A decrease in TAPSE between groups of TAPSE >1.8 cm, TAPSE 1.5-1.8 cm, and TAPSE <1.5 cm was associated with increased triglyceride:high-density lipoprotein ratio and hemoglobin A1c, and decreased body mass index, low-density lipoprotein, high-density lipoprotein, and systolic blood pressure (P<0.001). Most associations between cardiometabolic predictors and RVSP and TAPSE were nonlinear with clear inflection points associated with higher pulmonary pressure and lower RV function. Conclusions Clinical measures of cardiometabolic function were highly associated with echocardiographic measures of right ventricular function and pressure.

Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Outcomes in Patients With Heart Failure Using Cocaine.

Cocaine is an established cardiovascular toxin, but the impact of cocaine use on clinical outcomes in heart failure (HF) remains unknown. Although nonselective ß-blocker use in cocaine users with HF and reduced ejection fraction (HFrEF) appears to be safely tolerated, selective ß-blockers have not been evaluated. This study aimed to assess whether cocaine use is associated with worse clinical outcomes in patients with HF and evaluate the safety of ß-blocker prescription upon discharge in cocaine users with HFrEF. This was a single-center retrospective cohort study of patients with incident HF hospitalization at a safety-net hospital. Primary outcomes included all-cause mortality and readmissions, including HF. Cocaine users were compared with nonusers matched by age, gender, and year of index admission. In cocaine users with HFrEF, outcomes were compared according to ß-blocker prescription at discharge. From 2001 to 2019, 738 cocaine users were identified and compared with 738 matched nonusers. Cocaine use was associated with increased mortality (adjusted hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.00 to 1.48) and 90-day readmission (all-cause: adjusted HR 1.49; 95% CI 1.20 to 1.85; HF: adjusted HR 1.49; 95% CI 1.10 to 2.01), persisting at 1 year. In cocaine users who were prescribed metoprolol, carvedilol, or no ß-blocker at discharge, the rates of 1-year mortality and 30-day readmission were similar. In conclusion, cocaine use is associated with increased all-cause mortality, HF readmission, and all-cause readmission. Both nonselective and selective ß-blocker may be safe in managing patients with HFrEF and cocaine use.

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

BACKGROUND: Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH. METHODS: The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL RESULTS: Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09). CONCLUSIONS: Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

A pilot study assessing the spiritual, emotional, physical/environmental, and physiological needs of mechanically ventilated surgical intensive care unit patients via eye tracking devices, head nodding, and communication boards.

BACKGROUND: Mechanically ventilated patients in the intensive care unit (ICU) are unable to communicate verbally. We sought to evaluate their needs via a communication board (CB) and a novel eye tracking device (ETD) that verbalizes selections made by gazing. METHODS: This was a pilot prospective study conducted in a tertiary care surgical ICU. Continuously mechanically ventilated adult surgical ICU patients with a Richmond Agitation-Sedation Scale score of -1 to +1, without cognitive impairment, were eligible. We asked patients four yes-or-no questions to assess basic needs regarding presence of pain, need for endotracheal suction, satisfactory room temperature, and position comfort. Patients were then asked if there was anything else that they wanted to communicate. All responses were confirmed by head nodding. RESULTS: The median accuracy of the CB (100% (IQR 100%-100%)) for basic needs communication (yes/no questions) was comparable with that of the ETD (100% (IQR 68.8%-100%); p=0.14) in the 12 enrolled patients. Notably, 83% of patients desired to communicate additional information, ranging from spiritual (eg, desire for prayer/chaplain), emotional (eg, frustration, desire for comfort), physical/environmental (eg, television), to physiological (eg, thirst/hunger) needs. DISCUSSION: The majority of patients desired to communicate something other than basic needs. Unless specifically assessed via an assistive communication device (eg, CB or ETD), some of these other needs would have been difficult to discern. LEVEL OF EVIDENCE: IV therapeutic care/management.

Incidence of pulmonary embolism in patients with isolated calf deep vein thrombosis.

BACKGROUND: The severity of pulmonary embolism (PE) after isolated calf deep vein thrombosis (C-DVT) is controversial, which leads to inconsistent clinical decision making when treating C-DVT. This systematic review assessed PE frequency and severity in patients with C-DVT. METHODS: Database searches were completed using MEDLINE and Scopus along with cross-referencing. Two independent reviewers used using rigorous inclusion and exclusion criteria to screen the papers. Data concerning PE and C-DVT characteristics as well as methods of detection were abstracted. Studies reporting combined outcomes for patients with proximal and C-DVT, those with concurrent PE at diagnosis, and retrospective studies not allowing the determination of C-DVT and PE as separate events were excluded. RESULTS: Of 586 papers that were screened, 21 met inclusion criteria, which included eight randomized clinical trials and 13 prospective cohort studies. There was data heterogeneity among patients, methods of diagnosis, and follow-up. PE diagnosis was often based on ventilation/perfusion scanning, where more recent studies used computed tomography angiography. The PE is usually overestimated because it includes concurrent events. The incidence of PE from isolated C-DVT in our review was 0% to 6.2%. No fatal PEs were reported. No data were found on PE severity and patient outcomes regarding this complication. CONCLUSIONS: Reported adverse outcomes of PE from C-DVT are infrequent, and clinical severity is unclear. Further studies are necessary to determine the actual risk associated with PE after C-DVT to establish proper treatment.

Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes.

Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities - a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy.

A pilot study of eye-tracking devices in intensive care.

BACKGROUND: Eye-tracking devices have been suggested as a means of improving communication and psychosocial status among patients in the intensive care unit (ICU). This study was undertaken to explore the psychosocial impact and communication effects of eye-tracking devices in the ICU. METHODS: A convenience sample of patients in the medical ICU, surgical ICU, and neurosciences critical care unit were enrolled prospectively. Patients participated in 5 guided sessions of 45 minutes each with the eye-tracking computer. After completion of the sessions, the Psychosocial Impact of Assistive Devices Scale (PIADS) was used to evaluate the device from the patient's perspective. RESULTS: All patients who participated in the study were able to communicate basic needs to nursing staff and family. Delirium as assessed by the Confusion Assessment Method for the Intensive Care Unit was present in 4 patients at recruitment and none after training. The device's overall psychosocial impact ranged from neutral (-0.29) to strongly positive (2.76). Compared with the absence of intervention (0 = no change), patients exposed to eye-tracking computers demonstrated a positive mean overall impact score (PIADS = 1.30; P = .004). This finding was present in mean scores for each PIADS domain: competence = 1.26, adaptability = 1.60, and self-esteem = 1.02 (all P < .01). CONCLUSION: There is a population of patients in the ICU whose psychosocial status, delirium, and communication ability may be enhanced by eye-tracking devices. These 3 outcomes are intertwined with ICU patient outcomes and indirectly suggest that eye-tracking devices might improve outcomes. A more in-depth exploration of the population to be targeted, the device's limitations, and the benefits of eye-tracking devices in the ICU is warranted.