Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Optimal Method for Assessing Right Ventricular to Pulmonary Arterial Coupling in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

BACKGROUND: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21-24 mmHg). METHODS: The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks. DISCUSSION: The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04797286.

Reference Values for Indexed Echocardiographic Chamber Sizes in Older Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics. METHODS AND RESULTS: A total of 3032 individuals underwent comprehensive 2-dimensional echocardiography at Exam 6 in MESA (Multi-Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height1.6, height2.7) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height2.7 was associated with the least variability across sex categories. CONCLUSIONS: In this diverse cohort of community-dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.

Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.

BACKGROUND: Obesity and insulin resistance are prevalent in heart failure with preserved ejection fraction (HFpEF) and are associated with adverse cardiovascular outcomes. Measuring insulin resistance is difficult outside of research settings, and its correlation to parameters of myocardial dysfunction and functional status is unknown. METHODS: A total of 92 HFpEF patients with New York Heart Association class II to IV symptoms underwent clinical assessment, 2D echocardiography, and 6-min walk (6 MW) test. Insulin resistance was defined by estimated glucose disposal rate (eGDR) using the formula: eGDR = 19.02 - [0.22 × body mass index (BMI), kg/m2] - (3.26 × hypertension, presence) - (0.61 × glycated hemoglobin, %). Lower eGDR indicates increased insulin resistance (unfavorable). Myocardial structure and function were assessed by left ventricular (LV) mass, average E/e' ratio, right ventricular systolic pressure, left atrial volume, LV ejection fraction, LV longitudinal strain (LVLS), and tricuspid annular plane systolic excursion. Associations between eGDR and adverse myocardial function were evaluated in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression. RESULTS: Mean age (SD) was 65 (11) years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m2, glycated hemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg-1 min-1. Increased insulin resistance was associated with worse LVLS in a graded fashion [mean (SD) -13.8 % (4.9 %), -14.4 % (5.8 %), -17.5 % (4.4 %) for first, second, and third eGDR tertiles, respectively, p = 0.047]. This association persisted after multivariable adjustment, p = 0.040. There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable adjusted analysis. CONCLUSION: Our findings may inform treatment strategies focused on the use of tools to estimate insulin resistance and selection of insulin sensitizing drugs which may improve cardiac function and exercise capacity.

Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients.

BACKGROUND: Detecting right heart failure post left ventricular assist device (LVAD) is challenging. Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. METHODS: Thirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial coupling (ratio of Ees/Ea). RESULTS: LVAD patients had lower RV Ees (0.20 ± 0.08 vs 0.30 ± 0.15 mm Hg/ml, p = 0.01) and lower RV Ees/Ea (0.37 ± 0.14 vs 1.20 ± 0.54, p < 0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r = 0.68, p = 0.004) as well as the LVAD cohort itself (r = 0.78, p = 0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p = 0.048), driven by an inability to augment RV Ees (0.22 ± 0.11 vs 0.19 ± 0.02 mm Hg/ml, p = 0.95) to accommodate higher RV Ea (0.82 ± 0.38 vs 0.39 ± 0.08 mm Hg/ml, p = 0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients ((area under the curve) AUC = 0.80); during the ramp study, change in PAPi also correlated with change in RV Ees/Ea (r = 0.58, p = 0.04). CONCLUSIONS: LVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD left ventricular unloading, which reduces septal contractility.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Background: Echocardiographic (2DE) thresholds indicating disease or impaired functional status compared to normal physiologic aging in individuals ≥ 65 years are not clearly defined. In the present study, we sought to establish standard values for 2DE parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. Methods: In this cross-sectional study of 3032 individuals who underwent 2DE at Exam 6 in the Multi-Ethnic Study of Atherosclerosis (MESA), 608 participants fulfilled our inclusion criteria, with normative values defined as the mean value ± 1.96 standard deviations and compared across sex and race/ethnicity. Functional status measures included NT-proBNP, 6-minute walk distance [6MWD], and Kansas City Cardiomyopathy Questionnaire [KCCQ]. Prognostic performance using MESA cutoffs was compared to established guideline cutoffs using time-to-event analysis. Results: Participants meeting our inclusion criteria (69.5 ± 7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6MWD, and higher (better) KCCQ summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, while Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. Conclusions: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function across sexes and races/ethnicities, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement.

Derangements in the innate and adaptive immune responses observed in systemic inflammatory syndromes contributes to unique elevated atherosclerotic risk and incident cardiovascular disease. Novel multimodality imaging techniques may improve diagnostic precision for the screening and monitoring of disease activity. The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes. We review the common cardiovascular manifestations of immune-mediated systemic inflammatory diseases and address the clinical and investigational role of advanced multimodality cardiac imaging.

Acute cardiovascular complications of immune-mediated systemic inflammatory diseases.

Immune-mediated systemic inflammatory conditions (IMIDs) are associated with an increased risk of atherosclerosis and adverse cardiovascular (CV) events secondary to pathogenic inflammation and derangements in the innate and adaptive immune responses inherent to the underlying rheumatic diseases. As the intersection of cardio-rheumatology continues to expand, a multi-disciplinary approach must be considered to optimize clinical outcomes and long-term survival. This review will highlight acute cardiac manifestations of systemic inflammatory diseases and propose a clinically relevant framework for diagnosis, management, and the role of integrated multimodality imaging.

Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize RV myocyte contractile depression in HFrEF-PH, identify those components reflected by clinical RV indices, and uncover underlying biophysical mechanisms. METHODS: Resting, calcium-, and load-dependent mechanics were prospectively studied in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 patients with HFrEF-PH undergoing cardiac transplantation and 9 organ donor controls. RESULTS: Unsupervised machine learning using myocyte mechanical data with the highest variance yielded 2 HFrEF-PH subgroups that in turn mapped to patients with decompensated or compensated clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in decompensated clinical RV function, whereas surprisingly, many other major myocyte contractile measures including peak power and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick filament defects, myofibrillar structure was assessed by x-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in decompensated clinical RV function, but not compensated clinical RV function, as compared with controls. This corresponded to reduced myosin ATP turnover in decompensated clinical RV function myocytes, indicating less myosin in a crossbridge-ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Last, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human heart failure. CONCLUSIONS: Although there are many RV myocyte contractile deficits in HFrEF-PH, commonly used clinical indices only detect reduced isometric calcium-stimulated force, which is related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.

Characteristics of Right Ventricular to Pulmonary Arterial Coupling and Association With Functional Status Among Older Aged Adults from the Multi-Ethnic Study of Atherosclerosis.

Although the echocardiographic:derived ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) is an important prognostic tool in heart failure (HF), the relation with 6-minute walk distance (6MWD) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is less established. We sought to establish the normative values of TAPSE:PASP among older adults without cardiovascular disease (CVD) and evaluate the relation with NT-proBNP and 6MWD. Among 1,542 participants of the Multi-Ethnic Study of Atherosclerosis-HF ancillary study, the cross-sectional association of TAPSE:PASP with the outcomes of 6MWD and NT-proBNP was analyzed using multivariable linear regression, with progressive adjustment for sociodemographic and CVD risk factors. Our cohort had a mean age (SD) of 73 ± 8 years, 55% women, and a mean TAPSE:PASP ratio of 0.68 ± 0.16. In the unadjusted analysis, increasing tertiles of TAPSE:PASP were associated with younger age, less diabetes, higher estimated glomerular filtration rate, and less antihypertensive medication use. The TAPSE:PASP ratio significantly correlated with both 6MWD and NT-proBNP in the fully adjusted models. A 1-unit increment in TAPSE:PASP was associated with an adjusted 9.9% (4.8% to 15.2%) higher 6MWD, whereas a 1-unit increment in TAPSE:PASP was associated with an adjusted 38.0% (16.0% to 54.2%) lower NT-proBNP. There was a significant gender interaction of the association of TAPSE:PASP ratio and 6MWD, with stronger association seen in women. Among multiethnic older adults free of clinical CVD, the TAPSE:PASP ratio decreased with age, especially in women and was associated with decreased 6MWD and increasing NT-proBNP, the markers of subclinical HF.

Validation of an administrative algorithm for transgender and gender diverse persons against self-report data in electronic health records.

OBJECTIVE: To adapt and validate an algorithm to ascertain transgender and gender diverse (TGD) patients within electronic health record (EHR) data. METHODS: Using a previously unvalidated algorithm of identifying TGD persons within administrative claims data in a multistep, hierarchical process, we validated this algorithm in an EHR data set with self-reported gender identity. RESULTS: Within an EHR data set of 52 746 adults with self-reported gender identity (gold standard) a previously unvalidated algorithm to identify TGD persons via TGD-related diagnosis and procedure codes, and gender-affirming hormone therapy prescription data had a sensitivity of 87.3% (95% confidence interval [CI] 86.4-88.2), specificity of 98.7% (95% CI 98.6-98.8), positive predictive value (PPV) of 88.7% (95% CI 87.9-89.4), and negative predictive value (NPV) of 98.5% (95% CI 98.4-98.6). The area under the curve (AUC) was 0.930 (95% CI 0.925-0.935). Steps to further categorize patients as presumably TGD men versus women based on prescription data performed well: sensitivity of 97.6%, specificity of 92.7%, PPV of 93.2%, and NPV of 97.4%. The AUC was 0.95 (95% CI 0.94-0.96). CONCLUSIONS: In the absence of self-reported gender identity data, an algorithm to identify TGD patients in administrative data using TGD-related diagnosis and procedure codes, and gender-affirming hormone prescriptions performs well.

Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure with Pulmonary Hypertension.

Rationale: Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in heart failure patients with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. Objective: To determine components of myocyte contractile depression in HFrEF-PH, identify those reflected by clinical RV indices, and elucidate their underlying biophysical mechanisms. Methods and Results: Resting, calcium- and load-dependent mechanics were measured in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 HFrEF-PH patients undergoing cardiac transplantation and 9 organ-donor controls. Unsupervised machine learning using myocyte mechanical data with the highest variance yielded two HFrEF-PH subgroups that in turn mapped to patients with depressed (RVd) or compensated (RVc) clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in RVd, while surprisingly, many other major myocyte contractile measures including peak power, maximum unloaded shortening velocity, and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick-filament defects, myofibrillar structure was assessed by X-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in RVd but not RVc, as compared to controls. This corresponded to reduced myosin ATP turnover in RVd myocytes, indicating less myosin in a cross-bridge ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Lastly, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human HF. Conclusions: While there are multiple RV myocyte contractile deficits In HFrEF-PH, clinical indices primarily detect reduced isometric calcium-stimulated force related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.

Pregnancy Considerations in the Multidisciplinary Care of Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a vasoconstrictive disease of the distal pulmonary vasculature resulting in adverse right heart remodeling. Pregnancy in PAH patients is associated with high maternal morbidity and mortality as well as neonatal and fetal complications. Pregnancy-associated changes in the cardiovascular, pulmonary, hormonal, and thrombotic systems challenge the complex PAH physiology. Due to the high risks, patients with PAH are currently counseled against pregnancy based on international consensus guidelines, but there are promising signs of improving outcomes, particularly for patients with mild disease. For patients who become pregnant, multidisciplinary care at a PAH specialist center is needed for peripartum monitoring, medication management, delivery, postpartum care, and complication management. Patients with PAH also require disease-specific counseling on contraception and breastfeeding. In this review, we detail the considerations for reproductive planning, pregnancy, and delivery for the multidisciplinary care of a patient with PAH.

Risk Stratification of Patients with Pulmonary Arterial Hypertension: The Role of Echocardiography.

Background: Given the morbidity and mortality associated with pulmonary arterial hypertension (PAH), risk stratification approaches that guide therapeutic management have been previously employed. However, most patients remain in the intermediate-risk category despite initial therapy. Herein, we sought to determine whether echocardiographic parameters could improve the risk stratification of intermediate-risk patients. Methods: Prevalent PAH patients previously enrolled in observational studies at 3 pulmonary hypertension centers were included in this study. A validated PAH risk stratification approach was used to stratify patients into low-, intermediate-, and high-risk groups. Right ventricular echocardiographic parameters were used to further stratify intermediate-risk patients into intermediate-low- and intermediate-high-risk groups based on transplant-free survival. Results: From a total of 146 patients included in our study, 38 patients died over a median follow-up of 2.5 years. Patients with intermediate-/high-risk had worse echocardiographic parameters. Tricuspid annular plane systolic excursion (TAPSE) and the degree of tricuspid regurgitation (TR) were highly associated with survival (p < 0.01, p = 0.04, respectively) and were subsequently used to further stratify intermediate-risk patients. Among intermediate-risk patients, survival was worse for patients with TAPSE < 19 mm compared to those with TAPSE ≥ 19 mm (estimated one-year survival 74% vs. 96%, p < 0.01) and for patients with moderate/severe TR compared to those with no/trace/mild TR (estimated one-year survival 70% vs. 93%, p < 0.01). Furthermore, among intermediate-risk patients, those with both TAPSE < 19 mm and moderate/severe TR had an estimated one-year survival (56%) similar to that of high-risk patients (56%), and those with both TAPSE ≥ 19 mm and no/trace/mild TR had an estimated one-year survival (97%) similar to that of low-risk patients (95%). Conclusions: Echocardiography, a routinely performed, non-invasive imaging modality, plays a pivotal role in discriminating distinct survival phenotypes among prevalent intermediate-risk PAH patients using TAPSE and degree of TR. This can potentially help guide subsequent therapy.

Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

BACKGROUND: The ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) is a validated index of right ventricular-pulmonary arterial (RV-PA) coupling with prognostic value. We determined the predictive value of TAPSE/PASP ratio and adverse clinical outcomes in hospitalized patients with COVID-19. METHODS: Two hundred and twenty-nine consecutive hospitalized racially/ethnically diverse adults (≥18 years of age) admitted with COVID-19 between March and June 2020 with clinically indicated transthoracic echocardiograms (TTE) that included adequate tricuspid regurgitation (TR) velocities for calculation of PASP were studied. The exposure of interest was impaired RV-PA coupling as assessed by TAPSE/PASP ratio. The primary outcome was in-hospital mortality. Secondary endpoints comprised of ICU admission, incident acute respiratory distress syndrome (ARDS), and systolic heart failure. RESULTS: One hundred and seventy-six patients had both technically adequate TAPSE measurements and measurable TR velocities for analysis. After adjustment for age, sex, BMI, race/ethnicity, diabetes mellitus, and smoking status, log(TAPSE/PASP) had a significantly inverse association with ICU admission (p = 0.015) and death (p = 0.038). ROC analysis showed the optimal cutoff for TAPSE/PASP for death was 0.51 mm mmHg-1 (AUC = 0.68). Unsupervised machine learning identified two groups of echocardiographic function. Of all echocardiographic measures included, TAPSE/PASP ratio was the most significant in predicting in-hospital mortality, further supporting its significance in this cohort. CONCLUSION: Impaired RV-PA coupling, assessed noninvasively via the TAPSE/PASP ratio, was predictive of need for ICU level care and in-hospital mortality in hospitalized patients with COVID-19 suggesting utility of TAPSE/PASP in identification of poor clinical outcomes in this population both by traditional statistical and unsupervised machine learning based methods.