ABSTRACT
Background: Prior studies have established the impact of sex differences on pulmonary arterial hypertension (PAH). However, it remains unclear whether these sex differences extend to other hemodynamic subtypes of pulmonary hypertension (PH). Methods: We examined sex differences in PH and hemodynamic PH subtypes in a hospital-based cohort of individuals who underwent right heart catheterization between 2005-2016. We utilized multivariable linear regression to assess the association of sex with hemodynamic indices of RV function [PA pulsatility index (PAPi), RV stroke work index (RVSWI), and right atrial: pulmonary capillary wedge pressure ratio (RA:PCWP)]. We then used Cox regression models to examine the association between sex and clinical outcomes among those with PH. Results: Among 5208 individuals with PH (mean age 64 years, 39% women), there was no significant sex difference in prevalence of PH overall. However, when stratified by PH subtype, 31% of women vs 22% of men had pre-capillary (P<0.001), 39% vs 51% had post-capillary (P=0.03), and 30% vs 27% had mixed PH (P=0.08). Female sex was associated with better RV function by hemodynamic indices, including higher PAPi and RVSWI, and lower RA:PCWP ratio (P<0.001 for all). Over 7.3 years of follow-up, female sex was associated with a lower risk of heart failure hospitalization (HR 0.83, CI 95% CI 0.74- 0.91, p value <0.001). Conclusions: Across a broad hospital-based sample, more women had pre-capillary and more men had post-capillary PH. Compared with men, women with PH had better hemodynamic indices of RV function and a lower risk of HF hospitalization. CLINICAL PERSPECTIVE: What Is New? Although sex differences have been explored in pulmonary arterial hypertension, sex differences across pulmonary hypertension (PH) in broader samples inclusive of all hemodynamic subtypes remain less well definedWe delineate sex differences in hemodynamic subtypes of PH and associated right ventricular function in a large, heterogenous, hospital-based sample of individuals who underwent right heart catheterizationSex has a significant impact on prevalence of PH across hemodynamic subtypes as well as associated RV function What Are the Clinical Implications? Understanding sex differences across different PH hemodynamic subtypes is paramount to refining risk stratification between men and womenFurther elucidating sex differences in associated RV function and clinical outcomes may aid in developing sex-specific therapies or management strategies to improve clinical outcomes.
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Increased left atrial volume and decreased left atrial function have long been associated with atrial fibrillation. The availability of large-scale cardiac magnetic resonance imaging data paired with genetic data provides a unique opportunity to assess the genetic contributions to left atrial structure and function, and understand their relationship with risk for atrial fibrillation. Here, we use deep learning and surface reconstruction models to measure left atrial minimum volume, maximum volume, stroke volume, and emptying fraction in 40,558 UK Biobank participants. In a genome-wide association study of 35,049 participants without pre-existing cardiovascular disease, we identify 20 common genetic loci associated with left atrial structure and function. We find that polygenic contributions to increased left atrial volume are associated with atrial fibrillation and its downstream consequences, including stroke. Through Mendelian randomization, we find evidence supporting a causal role for left atrial enlargement and dysfunction on atrial fibrillation risk.
Subject(s)
Atrial Fibrillation , Deep Learning , Genome-Wide Association Study , Heart Atria , Humans , Atrial Fibrillation/physiopathology , Atrial Fibrillation/genetics , Atrial Fibrillation/diagnostic imaging , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Heart Atria/pathology , Male , Female , Middle Aged , Aged , Magnetic Resonance Imaging , Mendelian Randomization Analysis , Risk Factors , Atrial Function, Left/physiology , Stroke Volume , Stroke , United Kingdom/epidemiology , Genetic Loci , Genetic Predisposition to DiseaseABSTRACT
We present the case of a term newborn with trisomy 21 who presented to the paediatric emergency department with periumbilical flare and green-brown discharge from a clamped umbilical cord, initially suspected to be omphalitis. However, it was noticed later, that when the infant strained or cried, a thick, bubbling and offensive green-brown discharge came out of the clamped umbilical cord with umbilical flatus. An ultrasound abdomen and umbilical cord confirmed the presence of a persistent omphalomesenteric duct (POMD). He was then transferred to the paediatric surgical unit. There, he underwent a laparotomy and surgical resection of the POMD and was discharged home 2 days later.
Subject(s)
Down Syndrome , Vitelline Duct , Humans , Down Syndrome/complications , Infant, Newborn , Vitelline Duct/abnormalities , Vitelline Duct/diagnostic imaging , Male , Umbilical Cord/abnormalities , Umbilical Cord/diagnostic imaging , Umbilical Cord/pathology , Laparotomy/methodsABSTRACT
BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. METHODS: Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mmâ Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mmâ Hg·L-1·min-1). RESULTS: Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). CONCLUSIONS: Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.
Subject(s)
Dyspnea , Exercise Test , Heart Failure , Obesity , Stroke Volume , Humans , Female , Heart Failure/physiopathology , Heart Failure/diagnosis , Male , Middle Aged , Stroke Volume/physiology , Dyspnea/physiopathology , Obesity/physiopathology , Obesity/complications , Obesity/epidemiology , Obesity/diagnosis , Aged , Echocardiography , Adult , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Pulmonary Wedge Pressure/physiology , Ventricular Function, Left/physiology , Biomarkers/blood , PrevalenceABSTRACT
BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mmâ Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.
Subject(s)
Coronary Circulation , Pre-Eclampsia , Vascular Endothelial Growth Factor Receptor-1 , Vascular Resistance , Humans , Female , Pre-Eclampsia/physiopathology , Pre-Eclampsia/blood , Pregnancy , Adult , Vascular Resistance/physiology , Coronary Circulation/physiology , Vascular Endothelial Growth Factor Receptor-1/blood , Microcirculation/physiology , Positron-Emission Tomography/methods , Placenta Growth Factor/blood , Postpartum Period , Severity of Illness Index , Fractional Flow Reserve, Myocardial/physiology , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Microvessels/physiopathology , Microvessels/diagnostic imagingABSTRACT
Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating pro- and anti-angiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. Methods: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography (PET) within 4 weeks of delivery. A control group of pre-menopausal, non-postpartum women was also included. Myocardial flow reserve (MFR), myocardial blood flow (MBF), and coronary vascular resistance (CVR) were compared across groups. Soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) were measured at imaging. Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean 16.0 days postpartum), 5 with normotensive pregnancy (mean 14.4 days postpartum), and 13 non-postpartum female controls. Preeclampsia was associated with lower MFR (ß=-0.67 [95% CI -1.21 to -0.13]; P=0.016), lower stress MBF (ß=-0.68 [95% CI, -1.07 to -0.29] mL/min/g; P=0.001), and higher stress CVR (ß=+12.4 [95% CI 6.0 to 18.7] mmHg/mL/min/g; P=0.001) vs. non-postpartum controls. MFR and CVR after normotensive pregnancy were intermediate between preeclamptic and non-postpartum groups. Following preeclampsia, MFR was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest MBF (r=0.71; P<0.001), independent of hemodynamics. Conclusions: In this exploratory study, we observed reduced coronary microvascular function in the early postpartum period following severe preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves the coronary microcirculation. Further research is needed to establish interventions to mitigate risk of preeclampsia-associated cardiovascular disease.
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Acute lung injury (ALI) is a life-threatening condition with limited treatment options. The pathogenesis of ALI involves macrophage-mediated disruption and subsequent repair of the alveolar barriers, which ultimately results in lung damage and regeneration, highlighting the pivotal role of macrophage polarization in ALI. Although exosomes derived from mesenchymal stromal cells have been established as influential modulators of macrophage polarization, the specific role of exosomal microRNAs (miRNAs) remains underexplored. This study aimed to elucidate the role of specific exosomal miRNAs in driving macrophage polarization, thereby providing a reference for developing novel therapeutic interventions for ALI. We found that miR-7704 is the most abundant and efficacious miRNA for promoting the switch to the M2 phenotype in macrophages. Mechanistically, we determined that miR-7704 stimulates M2 polarization by inhibiting the MyD88/STAT1 signaling pathway. Notably, intra-tracheal delivery of miR-7704 alone in a lipopolysaccharide-induced murine ALI model significantly drove M2 polarization in lung macrophages and remarkably restored pulmonary function, thus increasing survival. Our findings highlight miR-7704 as a valuable tool for treating ALI by driving the beneficial M2 polarization of macrophages. Our findings pave the way for deeper exploration into the therapeutic potential of exosomal miRNAs in inflammatory lung diseases.
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BACKGROUND: Whether systemic oxygen levels (SaO2) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown. METHODS: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension. RESULTS: Among 253 patients (mean ± SD, age 63 ± 14 years, 55% female, arterial O2 [PaO2] 87 ± 14 mmHg, SaO2 96% ± 4%, resting pulmonary capillary wedge pressure [PCWP] 18 ± 4mmHg, and pulmonary vascular resistance [PVR] 2.7 ± 1.2 Wood units), there was no exercise PCWP threshold, measured up to 49 mmHg, above which hypoxemia was consistently observed. Exercise PaO2 was not correlated with exercise PCWP (rhoâ¯=â¯0.04; Pâ¯=â¯0.51) but did relate to exercise PVR (rhoâ¯=â¯-0.46; P < 0.001). Exercise PaO2 and SaO2 levels distinguished left-heart-predominant dysfunction from pulmonary-vascular-predominant dysfunction with an area under the curve of 0.89 and 0.89, respectively. CONCLUSION: Systemic O2 levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction.
Subject(s)
Heart Failure , Oxygen , Humans , Female , Middle Aged , Aged , Male , Physical Exertion , Hemodynamics , Pulmonary Wedge Pressure , Dyspnea/diagnosis , Hypoxia , Exercise Test , Stroke VolumeABSTRACT
AIMS: To leverage deep learning on the resting 12-lead electrocardiogram (ECG) to estimate peak oxygen consumption (VËO2peak) without cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: V Ë O 2 peak estimation models were developed in 1891 individuals undergoing CPET at Massachusetts General Hospital (age 45 ± 19 years, 38% female) and validated in a separate test set (MGH Test, n = 448) and external sample (BWH Test, n = 1076). Three penalized linear models were compared: (i) age, sex, and body mass index ('Basic'), (ii) Basic plus standard ECG measurements ('Basic + ECG Parameters'), and (iii) basic plus 320 deep learning-derived ECG variables instead of ECG measurements ('Deep ECG-VËO2'). Associations between estimated VËO2peak and incident disease were assessed using proportional hazards models within 84 718 primary care patients without CPET. Inference ECGs preceded CPET by 7 days (median, interquartile range 27-0 days). Among models, Deep ECG-VËO2 was most accurate in MGH Test [r = 0.845, 95% confidence interval (CI) 0.817-0.870; mean absolute error (MAE) 5.84, 95% CI 5.39-6.29] and BWH Test (r = 0.552, 95% CI 0.509-0.592, MAE 6.49, 95% CI 6.21-6.67). Deep ECG-VËO2 also outperformed the Wasserman, Jones, and FRIEND reference equations (P < 0.01 for comparisons of correlation). Performance was higher in BWH Test when individuals with heart failure (HF) were excluded (r = 0.628, 95% CI 0.567-0.682; MAE 5.97, 95% CI 5.57-6.37). Deep ECG-VËO2 estimated VËO2peak <14 mL/kg/min was associated with increased risks of incident atrial fibrillation [hazard ratio 1.36 (95% CI 1.21-1.54)], myocardial infarction [1.21 (1.02-1.45)], HF [1.67 (1.49-1.88)], and death [1.84 (1.68-2.03)]. CONCLUSION: Deep learning-enabled analysis of the resting 12-lead ECG can estimate exercise capacity (VËO2peak) at scale to enable efficient cardiovascular risk stratification.
Researchers here present data describing a method of estimating exercise capacity from the resting electrocardiogram. Electrocardiogram estimation of exercise capacity was accurate and was found to predict the onset of the wide range of cardiovascular diseases including heart attacks, heart failure, arrhythmia, and death.This approach offers the ability to estimate exercise capacity without dedicated exercise testing and may enable efficient risk stratification of cardiac patients at scale.
Subject(s)
Electrocardiography , Heart Failure , Humans , Female , Adult , Middle Aged , Male , Prognosis , Exercise Test/methods , Oxygen ConsumptionABSTRACT
Importance: The gold standard for outcome adjudication in clinical trials is medical record review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication of medical records by natural language processing (NLP) may offer a more resource-efficient alternative but this approach has not been validated in a multicenter setting. Objective: To externally validate the Community Care Cohort Project (C3PO) NLP model for heart failure (HF) hospitalization adjudication, which was previously developed and tested within one health care system, compared to gold-standard CEC adjudication in a multicenter clinical trial. Design, Setting, and Participants: This was a retrospective analysis of the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial, which compared 2 influenza vaccines in 5260 participants with cardiovascular disease at 157 sites in the US and Canada between September 2016 and January 2019. Analysis was performed from November 2022 to October 2023. Exposures: Individual sites submitted medical records for each hospitalization. The central INVESTED CEC and the C3PO NLP model independently adjudicated whether the cause of hospitalization was HF using the prepared hospitalization dossier. The C3PO NLP model was fine-tuned (C3PO + INVESTED) and a de novo NLP model was trained using half the INVESTED hospitalizations. Main Outcomes and Measures: Concordance between the C3PO NLP model HF adjudication and the gold-standard INVESTED CEC adjudication was measured by raw agreement, κ, sensitivity, and specificity. The fine-tuned and de novo INVESTED NLP models were evaluated in an internal validation cohort not used for training. Results: Among 4060 hospitalizations in 1973 patients (mean [SD] age, 66.4 [13.2] years; 514 [27.4%] female and 1432 [72.6%] male]), 1074 hospitalizations (26%) were adjudicated as HF by the CEC. There was good agreement between the C3PO NLP and CEC HF adjudications (raw agreement, 87% [95% CI, 86-88]; κ, 0.69 [95% CI, 0.66-0.72]). C3PO NLP model sensitivity was 94% (95% CI, 92-95) and specificity was 84% (95% CI, 83-85). The fine-tuned C3PO and de novo NLP models demonstrated agreement of 93% (95% CI, 92-94) and κ of 0.82 (95% CI, 0.77-0.86) and 0.83 (95% CI, 0.79-0.87), respectively, vs the CEC. CEC reviewer interrater reproducibility was 94% (95% CI, 93-95; κ, 0.85 [95% CI, 0.80-0.89]). Conclusions and Relevance: The C3PO NLP model developed within 1 health care system identified HF events with good agreement relative to the gold-standard CEC in an external multicenter clinical trial. Fine-tuning the model improved agreement and approximated human reproducibility. Further study is needed to determine whether NLP will improve the efficiency of future multicenter clinical trials by identifying clinical events at scale.
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BACKGROUND: Infertility has been shown to be associated with a greater risk of incident heart failure with preserved ejection fraction. We studied the association of infertility with subclinical markers of heart failure with preserved ejection fraction, including echocardiographic signs of cardiac remodeling and cardiac biomarkers. METHODS AND RESULTS: A history of infertility was ascertained in 2002 women enrolled in the Framingham Heart Study. We examined the association of infertility with echocardiographic measures and cardiac biomarkers with multivariable-adjusted linear regression models. Among 2002 women (mean age 40.84 ± 9.71 years), 285 (14%) reported a history of infertility. Infertility was associated with a greater E/e' ratio (ßâ¯=â¯0.120, standard error 0.057, Pâ¯=â¯.04), even after adjustment for common confounders. Infertility was not associated with other echocardiographic measures or cardiac biomarkers. CONCLUSIONS: Infertility was associated with a greater E/e' ratio, a marker of diastolic dysfunction that may signal earlier subclinical cardiac remodeling in women with infertility.
Subject(s)
Heart Failure , Infertility , Humans , Female , Adult , Middle Aged , Heart Failure/diagnosis , Heart Failure/epidemiology , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Biomarkers , Longitudinal StudiesABSTRACT
The proportion of patients with new-onset heart failure who have preserved rather than reduced left ventricular ejection fraction (HFpEF and HFrEF) has been increasing over recent decades. In fact, HFpEF now outweighs HFrEF as the predominant heart failure subtype and likely remains underdiagnosed in the community. This is due in part to an aging population and a rise in other risk factors for HFpEF, including obesity and associated cardiometabolic disease. Whereas the diagnosis of HFrEF is relatively straightforward, the diagnosis of HFpEF is often more challenging because there can be other causes for symptoms, including dyspnea and fatigue, and cardinal physical examination findings of elevated jugular venous pressure or pulmonary congestion may not be evident at rest. In 2022, the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America published a comprehensive guideline on heart failure that included recommendations for the management of HFpEF. The use of diuretics for the management of congestion remained the only class 1 (strong) recommendation. New recommendations included broader use of sodium-glucose cotransporter-2 inhibitors (SGLT2i, class 2a), and angiotensin receptor-neprilysin inhibitors (class 2b). In 2023, the American College of Cardiology published an expert consensus decision pathway for the management of HFpEF that suggests treatment strategies based on sex assigned at birth, ejection fraction, clinical evidence of congestion, and candidacy for SGLT2i therapy. Here, 2 experts, a cardiologist and a geriatrician, discuss their approach to the diagnosis and management of HFpEF and how they would apply guidelines to an individual patient.
Subject(s)
Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Teaching Rounds , Infant, Newborn , Humans , Aged , Heart Failure/diagnosis , Heart Failure/drug therapy , Stroke Volume , Ventricular Function, Left , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
BACKGROUND: Deep learning interpretation of echocardiographic images may facilitate automated assessment of cardiac structure and function. OBJECTIVES: We developed a deep learning model to interpret echocardiograms and examined the association of deep learning-derived echocardiographic measures with incident outcomes. METHODS: We trained and validated a 3-dimensional convolutional neural network model for echocardiographic view classification and quantification of left atrial dimension, left ventricular wall thickness, chamber diameter, and ejection fraction. The training sample comprised 64,028 echocardiograms (n = 27,135) from a retrospective multi-institutional ambulatory cardiology electronic health record sample. Validation was performed in a separate longitudinal primary care sample and an external health care system data set. Cox models evaluated the association of model-derived left heart measures with incident outcomes. RESULTS: Deep learning discriminated echocardiographic views (area under the receiver operating curve >0.97 for parasternal long axis, apical 4-chamber, and apical 2-chamber views vs human expert annotation) and quantified standard left heart measures (R2 range = 0.53 to 0.91 vs study report values). Model performance was similar in 2 external validation samples. Model-derived left heart measures predicted incident heart failure, atrial fibrillation, myocardial infarction, and death. A 1-SD lower model-left ventricular ejection fraction was associated with 43% greater risk of heart failure (HR: 1.43; 95% CI: 1.23-1.66) and 17% greater risk of death (HR: 1.17; 95% CI: 1.06-1.30). Similar results were observed for other model-derived left heart measures. CONCLUSIONS: Deep learning echocardiographic interpretation accurately quantified standard measures of left heart structure and function, which in turn were associated with future clinical outcomes. Deep learning may enable automated echocardiogram interpretation and disease prediction at scale.
Subject(s)
Atrial Fibrillation , Deep Learning , Heart Failure , Humans , Stroke Volume , Ventricular Function, Left , Retrospective StudiesABSTRACT
Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Heart Failure , Male , Adult , Female , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , American Heart Association , Risk Assessment , Kidney , Risk FactorsABSTRACT
Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.
Subject(s)
Heart Failure , Humans , Stroke Volume , Dyspnea , Exercise Test , Eicosanoids , Exercise ToleranceABSTRACT
A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.
Subject(s)
Cardiovascular Diseases , Metabolic Syndrome , Renal Insufficiency, Chronic , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/therapy , American Heart Association , Risk Factors , Kidney , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapyABSTRACT
Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.
Subject(s)
Cardiovascular Diseases , Cardiovascular System , Metabolic Syndrome , United States/epidemiology , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/therapy , American Heart Association , Risk Factors , KidneyABSTRACT
BACKGROUND: Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear. METHODS: We examined patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction (pulmonary artery pulsatility index, right atrial pressure:pulmonary capillary wedge pressure ratio, RV stroke work index). Cox models were used to examine the association of RV function measures with clinical outcomes. RESULTS: Among 8285 patients (mean age, 63 years; 40% women), higher body mass index was associated with worse indices of RV dysfunction, including lower pulmonary artery pulsatility index (ß, -0.23; SE, 0.01; P<0.001), higher right atrium:pulmonary capillary wedge pressure ratio (ß, 0.25; SE, 0.01; P<0.001), and lower RV stroke work index (ß, -0.05; SE, 0.01; P<0.001). Over median of 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure hospitalization events. RV dysfunction was associated with a greater risk of mortality (eg, pulmonary artery pulsatility index:hazard ratio, 1.11 per 1-SD increase [95% CI, 1.04-1.18]), with similar associations with risk of heart failure hospitalization. Body mass index modified the effect of RV dysfunction on all-cause mortality (Pinteraction≤0.005 for PAPi and RA:PCWP ratio), such that the effect of RV dysfunction was more pronounced at higher body mass index. CONCLUSIONS: Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and heart failure hospitalization, this association was especially pronounced among individuals with higher body mass index.