Transgender Women Exhibit a Distinct Stress Echocardiography Profile Compared to Age-Matched Cisgender Counterparts: The Mayo Clinic Women's Heart Clinic Experience.

BACKGROUND: Stress echocardiography (SE) is an important modality in cardiovascular risk stratification and obstructive coronary artery disease (CAD) assessment. Binary sex-based parameters are classically used for interpretation of these studies, even among transgender women (TGW). CAD is a leading cause of morbidity and mortality in this population. Yet, it remains unclear whether TGW exhibit a distinct stress testing profile from their cisgender counterparts. METHODS: Using a matched case-control study design, we compared the echocardiographic stress testing profiles of TGW (n=43) with those of matched cisgender men (CGM, n=84) and cisgender women (CGW, n=86) at a single center. Relevant data, including demographics, comorbidities, and cardiac testing data were manually extracted from the patients' charts. RESULTS: The prevalence of hypertension and dyslipidemia was similar between TGW and CGW and lower than that of CGM (p= .003 and .009, respectively). The majority of comorbidities and lab values were similar. On average, TGW had higher heart rates than CGM (p=.002) and had lower blood pressures than CGM and CGW (p<.05). The TGW's double product and metabolic equivalents were similar to those among CGW and lower than those of CGM (p=.016, p=.018, respectively). On echocardiography, the left ventricular end-diastolic and end-systolic diameters among TGW were similar to those of CGW but lower than CGM's (p=.023, p=.018, respectively). Measures of systolic and diastolic function, except for the exercise mitral valve E:e' ratio which was lower in TGW than CGW (p=.029), were largely similar among the three groups. There was no difference in the wall motion score index, and therefore, no difference in the percentage of positive SE tests. CONCLUSION: Our study shows, for the first time, that TGW have a SE profile that is distinct from that of their cisgender counterparts. Larger, multicenter, prospective studies are warranted to further characterize the SE profile of TGW.

Trends in the Prevalence of Infiltrative Cardiomyopathy Among Patients With in-Hospital Cardiac Arrest.

Sarcoidosis, amyloidosis, hemochromatosis and scleroderma are the most forms of infiltrative/nonischemic cardiomyopathy (NICM) associated with sudden cardiac death. In patients who undergo in-hospital cardiac arrest, a high index of suspicion is required to rule out NICM as an underlying contributor. We aimed to analyze the prevalence of NICM among patients with in-hospital cardiac arrest and identify factors associated with increased mortality. We analyzed data from the National Inpatient Sample, and identified patients who were hospitalized across 10 years from 2010 to 2019 with a diagnosis of cardiac arrest and NICM. The total number of patients with in-hospital cardiac arrest was 19,34,260. The total number with NICM was 14,803 (0.77%). Mean age was 63 years. Overall prevalence of NICM across the years ranged between 0.75% to 0.9%, with a significant temporal increase (P < 0.01). Incidence of in-hospital mortality ranged between 61% to 76% for females and 30% to 38% for males. The following comorbidities were more prevalent in patients with NICM than those without: heart failure, chronic obstructive pulmonary disease (COPD), chronic kidney disease, anemia, malignancy, coagulopathy, ventricular tachycardia, acute kidney injury and stroke. The following factors were independent predictors of in-hospital mortality-age, female gender, Hispanic race, history of COPD and presence of malignancy (P = 0.042). The prevalence of infiltrative cardiomyopathy in patients with in-hospital cardiac arrest is increasing. Females, older patients and Hispanic population are at an increased risk of mortality. Sex and race-based disparities in the prevalence of NICM in patients with in-hospital cardiac arrest is an area of further research.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Assessment of Cardiac Risk in Women with Autoimmune Disease.

PURPOSE OF REVIEW: The purpose of our review was to evaluate current standards in clinical practice in determining overall cardiac risk in female patients with chronic rheumatologic diseases. We hoped to not only summarize known cardiac manifestations of various chronic rheumatologic diseases but also determine the effectiveness of new risk scores in determining cardiac risk in this patient population. RECENT FINDINGS: Chronic rheumatologic diseases have been associated with various cardiac manifestations for some time, with initial studies involving risk of coronary artery disease (CAD) in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, recent studies have shown numerous other cardiac manifestations associated with these and other chronic rheumatologic diseases. Risk scores have been used for several decades to help determine overall cardiac risk in the general population, but these risk scores have notoriously underestimated the risk of cardiac disease in woman and in patients with chronic rheumatologic diseases. These diseases, often with a female predominance, can impact long-term mortality and have devastating consequences if not monitored and treated appropriately. Thus, new risk scores have been developed over the last several years to help improve detection and awareness of cardiac disease in these patients. Novel modified risk scores have found some success at improving the detection of cardiac disease in patients with chronic rheumatologic diseases. Further studies looking at these risk scores need to determine the accuracy of these scores and where they fall short. With the advent of advanced imaging technologies, future risk scores may involve certain imaging-based markers to help guide accurate risk determination.

A case of a large leiomyomatous uterus with multiple arteriovenous malformations and subsequent high cardiac output state with severe four chamber cardiac enlargement.

Uterine arteriovenous malformations (AVMs) are rare and potentially life-threatening. They can be congenital or acquired. Uterine artery embolization or hysterectomy are considered mainstays of management. AVMs can be associated with leiomyomas, and patients may require both procedures. We present a case of a 42-year-old woman with a massively enlarged leiomyomatous uterus supplied and drained by multiple large AVMs, leading to high cardiac output state with severe four chamber cardiac dilation. Management required a multidisciplinary team of interventional radiology, gynecologic oncology surgery, vascular surgery, cardiac anesthesiology, cardiology, and urology and a 2-day interventional approach of preoperative arterial embolization followed by hysterectomy.

Characteristics of Transgender Women Referred to Women's Heart Clinic.

INTRODUCTION: Transgender women have been reported to have a high burden of cardiovascular disease (CVD) and risk factors based largely on surveys. Our aim was to describe the prevalence of CVD and associated comorbidities among a cohort of older transgender women referred to cardiology as part of their gender-affirming care. METHODS: This was a retrospective, cross-sectional study of transgender women at a single institution from 2017 to 2019. RESULTS: Fifty-two consecutive patients were included. The most common reasons for referral were cardiac risk factor management (45%) and pre-operative cardiac risk stratification prior to gender-affirming surgery (35%). The mean age was 57 ± 10 years, 87% were white, and 92% had insurance coverage. Forty-eight patients (92%) were taking gender-affirming hormone therapy; 5 had undergone breast augmentation, 4 had undergone orchiectomy, and 2 had undergone vaginoplasty. The most common comorbidities were depression and/or anxiety (63%), obesity (58%), and hyperlipidemia (54%). Excluding aldosterone antagonists, 46% were on cardiac medications; changes were recommended for 25% of patients: new prescriptions in 9, dose adjustments in 5, and discontinuations in 4. According to the pooled cohort equation, the 10-year risk of atherosclerotic CVD was 9.4 ± 7.7% when the study population was calculated as male and 5.2 ± 5.1% when calculated as female (p <0.001). For patients who completed exercise testing, the functional aerobic capacity was fair (77.6 ± 21.4%) when calculated as male and average (99.5 ± 27.5%) as female (p < .0001); there was inconsistency in sex used for calculating the result on the formal report. CONCLUSIONS: Older transgender women may have an underestimated prevalence of CVD and its risk factors. More research is needed to identify cardiovascular health profiles, improve practice consistency, and establish normative values for transgender patients.

Elevated Prosthetic Valve Gradients: What to Consider When Determining an Etiology.

DOPPLER echocardiography is a useful noninvasive tool for the assessment of cardiac hemodynamics. However, it is subject to limitations that can have important clinical implications, especially in the setting of valve prosthesis. Elevation in mean transvalvular gradient is a finding that has a variety of etiologies. One such etiology is the pressure-recovery (PR) phenomenon, a consequence of stream convergence and energy conversion across a narrowing, which is an artifact of Doppler echocardiographic calculations of valvular flow. The elevated gradient measured with Doppler echocardiography as a result of PR is not present on cardiac catheterization and does not represent true problematic valve hemodynamics. PR should be suspected with an elevated gradient on Doppler echocardiography with normal leaflet motion, especially in the setting of a small proximal aorta. Understanding and awareness of PR are important because PR can lead to overestimation of disease severity in the clinical setting.

Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication.

OBJECTIVE: Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at the time of SSc diagnosis and incidence of VHD during follow-up compared to non-SSc subjects. METHODS: Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age and sex to non-SSc subjects. RESULTS: The study included 78 incident SSc cases and 156 non-SSc comparators (56 yrs [± 15.7], 91% female). A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs 0%; P = 0.004) was identified. During follow-up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI 10.7-29.9) in patients with SSc compared with 2.3% (95% CI 0.7-7.0) in non-SSc subjects (HR 4.23, 95% CI 2.03-8.83). Coronary artery disease was the only significant risk factor for VHD. CONCLUSION: Patients with SSc have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in patients with SSc, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis.

OBJECTIVE: To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). METHODS: In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. RESULTS: The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). CONCLUSION: Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.

Systemic Sclerosis Portends Increased Risk of Conduction and Rhythm Abnormalities at Diagnosis and During Disease Course: A US Population-Based Cohort.

Objectives: To study the incidence, risk factors and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis (SSc) vs. non-SSc comparators. Methods: An incident cohort of patients with SSc (1980-2016) from Olmsted County, MN was compared to age- and sex-matched non-SSc subjects (1:2). Electrocardiograms (ECGs), Holter ECGs, and need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: 78 incident SSc cases and 156 comparators were identified (mean age 56 y, 91% female). The prevalence of any conduction disorder prior to SSc diagnosis compared to non-SSc subjects was 15% vs. 7% (p=0.06), and any rhythm disorder was 18% vs. 13% (p=0.33). During a median follow-up of 10.5 years in patients with SSc and 13.0 years in non-SSc comparators, conduction disorders developed in 25 patients with SSc with cumulative incidence of 20.5% (95% CI: 12.4-34.1%) vs. 28 non-SSc patients with cumulative incidence of 10.4% (95% CI: 6.2-17.4%) (HR: 2.57; 95% CI: 1.48-4.45), while rhythm disorders developed in 27 patients with SSc with cumulative incidence of 27.3% (95% CI: 17.9-41.6%) vs. 43 non-SSc patients with cumulative incidence of 18.0% (95% CI: 12.3-26.4%) (HR: 1.62; 95% CI: 1.00-2.64). Age, pulmonary hypertension and smoking were identified as risk factors. Conclusion: Patients with SSc have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to non-SSc patients. These findings warrant increased vigilance and screening for ECG abnormalities in SSc patients with pulmonary hypertension.

A Tale of Two Valves: Bioprosthetic Aortic Valve Obstruction in Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome.

Patients with systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLAS) are at risk for cardiac manifestations, specifically valvular heart disease requiring valve replacement. Bioprosthetic valve endocarditis is an important cause of valve failure, and it is important to keep a wide differential, especially in patients with preexisting SLE and APLAS. In this E-challenge, 2 cases of bioprosthetic aortic valve endocarditis are presented; 1 case describes infective bacterial endocarditis on an aortic prosthesis and the second describes a patient with SLE and APLAS who developed bioprosthetic valve obstruction secondary to vegetations, consistent with nonbacterial endocarditis and thrombus. Etiologies for bioprosthetic valve obstruction and evaluation by echocardiography are explored. The comparison between these 2 cases specifically highlights the importance of keeping a wide differential in endocarditis, prosthetic valve vegetations, and bioprosthetic valve obstruction.

Cardiovascular Risk Factors and Atherosclerotic Cardiovascular Events Among Incident Cases of Systemic Sclerosis: Results From a Population-Based Cohort (1980-2016).

OBJECTIVE: To characterize cardiovascular (CV) risk factors and outcomes among incident cases of systemic sclerosis (SSc) in a population-based cohort. METHODS: Medical records of patients with SSc diagnosed in Olmsted County, Minnesota, between January 1, 1980, and December 31, 2016, were reviewed to identify 78 incident SSc cases. The comparators were 156 sex- and age-matched individuals from the same population. Data for SSc characteristics, traditional CV risk factors, and CV events were collected. Cumulative incidence was adjusted for the competing risk for death. RESULTS: During a median follow-up of 9.8 (SSc) and 9.2 years (non-SSc), 21 patients with SSc and 17 patients without SSc developed CV events, corresponding to 10-year cumulative incidence of 24.4% and 15.2%, respectively. The risk for incident CV disease was increased by 2-fold (hazard ratio, 2.38; 95% CI, 1.28-4.43) in patients with SSc vs comparators, predominately due to coronary artery disease (hazard ratio, 2.35; 95% CI, 1.17-4.71). Mean body mass index and prevalence of diabetes mellitus were lower in SSc vs non-SSc. There was no significant difference in smoking, hypertension, or hyperlipidemia. Observed CV events were increased compared with CV events predicted by the Framingham Risk Score and American College of Cardiology/American Heart Association score with standardized incident ratios of 4.16 (95% CI, 2.16-7.99) and 5.69 (95% CI, 2.71-11.94), respectively. CONCLUSION: Patients with SSc are at >2-fold increased risk for experiencing a CV event compared with persons without SSc. Framingham Risk Score and American College of Cardiology/American Heart Association score dramatically underestimate CV risk in SSc.

Antiphospholipid syndrome and the relationship between laboratory assay positivity and prevalence of non-bacterial thrombotic endocarditis: A retrospective cohort study.

BACKGROUND: Nonbacterial thrombotic endocarditis (NBTE) is a potential complication of antiphospholipid syndrome (APS) manifesting as noninfectious lesions on one or more cardiac valves. There are limited tools to inform clinicians regarding which APS patients would benefit most from echocardiographic screening for this complication. OBJECTIVES: We tested the hypothesis that the risk of both prevalent and incident NBTE is directly related to the number of positive laboratory assays for APS. PATIENTS/METHODS: In this single-center, retrospective, cohort study design, consecutive patients with confirmed APS seen at Mayo Clinic Rochester, MN (1/1/1993-6/26/2016), were identified by searching a centralized electronic database. Demographic data, clinical presentation, echocardiographic features, laboratory findings, and survival data were scrutinized. RESULTS: During the study period, 611 patients met the diagnostic criteria for APS and 386 (63%) underwent echocardiography. Of these, 58 (15%) were found to have NBTE. NBTE was more common in those with double (19.4%) and triple-positive laboratory criteria (27.0%) compared with single-positive disease (5.7%, P < .001). Survival free of NBTE diagnosis was significantly shorter in those patients with >1 positive laboratory assay (P < .01). Cox proportional hazard analysis suggests that patients with APS are more likely to be diagnosed with NBTE if they have >1 positive laboratory assay (relative risk 20.1; 95% confidence interval 1.3-316.6; P < .03). CONCLUSION: Antiphospholipid syndrome carries a high prevalence of NBTE (15%). This prevalence is particularly high for patients with either double- or triple-positive laboratory criteria.

Mitral Valve Prolapse Patients with Less than Moderate Mitral Regurgitation Exhibit Early Cardiac Chamber Remodeling.

BACKGROUND: Mild physiologic mitral regurgitation (MR) is common in normal individuals. Patients with primary MR due to mitral valve prolapse (MVP) may also exhibit less than moderate MR. We sought to determine whether MVP patients with less than moderate MR displayed early cardiac chamber remodeling or factors related to early remodeling and whether early remodeling predicted MR progression. METHODS: Consecutive MVP patients with less than moderate MR by proximal isovelocity surface area-derived effective regurgitant orifice < 20 mm2 and regurgitant volume < 30 mL, were matched for age and sex with non-MVP patients (controls) having less than moderate MR. Patients with moderate or greater dysfunctional left- or right-sided valves and left ventricular ejection fraction < 50% were excluded. We evaluated left ventricle (LV) and left atrium (LA) remodeling parameters (LV end-diastolic and end-systolic indexed diameters, LA volume-index, and LV mass-index) as well as determinants of remodeling. The last available transthoracic echocardiography was reviewed to identify progression to moderate-severe MR or more. RESULTS: A total of 253 MVP patients with less than moderate MR were matched to 344 controls (P for age and sex, ≥.18) with less than moderate MR. Patients with MVP (mean effective regurgitant orifice and regurgitant volume, 12 ± 4 mm2 and 18 ± 6 mL, respectively) had more premature ventricular contractions (PVCs), larger LV and LA remodeling parameters, and more mild-to-moderate MR (all P < .0001). Multivariate linear regression models showed that larger LV remodeling parameters were independently associated with MVP and female sex but not MR severity (all P < .0001). The LA volume index was independently associated with MVP, age, and E/e' (all P < .0001). The LV mass index was associated with MVP, age, and hypertension (all P ≤ .002). Presence of PVCs was associated with LV end-systolic diameter ≥ 40 mm and indexed ≥ 22 mm2 (P = .005). Among 323 (54%) patients having subsequent transthoracic echocardiography, 17 patients (all MVP) progressed to moderate-severe MR or more at a median of 4.3 (interquartile range, 1.7-6.4) years. Isolated posterior leaflet prolapse was the single factor associated with MR progression (adjusted hazard ratio, 2.70; 95% CI, 0.99-7.34; P = .048) after adjustment for MR severity. At a median of 5.9 (interquartile range, 4.6-7.2) years of follow-up, female sex and MVP (vs controls) were protective factors for mortality. CONCLUSIONS: Patients with less than moderate MR due to MVP exhibit early LV and LA remodeling, which does not predict MR progression or mortality. Left ventricle remodeling is associated with MVP, female sex, and presence of PVCs. Early chamber remodeling associated with MVP may be the phenotypical expression of a genetically mediated process and is at least partially related to PVCs.