Race, hypertensive disorders of pregnancy and outcomes in peripartum cardiomyopathy.

BACKGROUND: Black women with peripartum cardiomyopathy (PPCM) have a higher prevalence of hypertensive disorders of pregnancy (HDP) and worse clinical outcomes compared with non-Black women. We examined the impact of HDP on myocardial recovery in Black women with PPCM. METHODS: A total of 100 women were enrolled into the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months post-partum (PP). Women were followed for 12 months postpartum and outcomes including persistent cardiomyopathy (LVEF ≤35%), left ventricular assist device, (LVAD), cardiac transplantation, or death were examined in subsets based on race and the presence of HDP. RESULTS: Black women with HDP were more likely to present earlier compared to Black women without HDP (days PP HDP: 34 ± 21 vs 54 ± 27 days, P = .03). There was no difference in LVEF at study entry for Black women based on HDP, but better recovery with HDP at 6 (HDP: 52 ± 11% vs no HDP: 40 ± 14%, P = .03) and 12-months (HDP:53 ± 10% vs no HDP:40 ± 16%, P = .02). At 12-months, Black women overall had a lower LVEF than non-Black women (P < .001), driven by less recovery in Black women without HDP compared to non-Black women (P < .001). In contrast, Black women with HDP had a similar LVEF at 12 months compared to non-Black women (P = .56). CONCLUSIONS: In women with PPCM, poorer outcomes evident in Black women were driven by women without a history of HDP. In Black women, a history of HDP was associated with earlier presentation and recovery which was comparable to non-Black women.

Guidance Directed Care of Spontaneous Coronary Artery Dissection: A Healthcare System-Based Experience.

Introduction: Data on treatment of spontaneous coronary artery dissection (SCAD) has evolved with guidance from national societies beginning around 2018. Given emerging guidance and relatively uncommon presentation of SCAD, we hypothesized that a specialized SCAD clinic would improve guidance-based care. Methods: We utilized a system-wide electronic medical record search to identify individuals with SCAD diagnosis from 2018 to 2023. All diagnostic angiograms were reviewed to verify diagnosis. We analyzed frequency of guidance-based care since 2018 system-wide. We also compared guidance-based care for individuals with index visits to the SCAD outpatient clinic as compared to non-SCAD clinic providers from initiation of specialty clinic in 2021. Results: Differences were observed in pregnancy and contraception discussions (88 % vs 0 %, p < 0.001) among pre-menopausal individuals in SCAD clinic compared to non-SCAD clinics. Safety of hormone replacement therapy (HRT) in menopausal women was addressed more by SCAD clinic providers (85 % vs 7 %, p < 0.001). There was more fibromuscular dysplasia (FMD) screening in SCAD clinic (100 % vs 30 %, p < 0.001). Among individuals with migraines, there was more discussion of triggering medications (triptans) in SCAD clinic (80 % vs 14 %, p = 0.008). In individuals prescribed statins not by primary prevention guidelines and without atherosclerosis, there was a trend toward more discussion of statin use in SCAD clinic follow up vs non-SCAD clinic providers (63 % vs 17 %, p = 0.06). Conclusions: Individuals with follow up in SCAD clinic compared to non-SCAD clinics were more likely to have future pregnancy and contraception counseling, discussion of HRT safety, and FMD screening following index outpatient visit. Future quality improvement initiatives will target these aspects of guidance-based care among non-SCAD clinic providers with integration into cardiology fellow training.

Sex-based utilization of guideline recommended statin therapy and cardiovascular disease outcomes: Data from a multisite healthcare network primary prevention cohort.

Background: In the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) vs. men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Sex-Based Utilization of Guideline Recommended Statin Therapy and Cardiovascular Disease Outcomes: A Primary Prevention Healthcare Network Registry.

Background: In the US, women have similar cardiovascular death rates than men. Less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013-2019. Guideline-directed statin intensity (GDSI) at index and follow-up visits were compared among sexes across ASCVD risk groups, defined by pooled-cohort equation. Cox regression hazard ratios (HR) [95% CI] were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1% women and 19.5% men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-ups was lower compared to high-risk men (2-years: 27.7 vs 32.0%, and 5-years: 47.2 vs 55.2%, p<0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA amongst both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) versus men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to be initiated on GDSI compared with high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Updates in Cardiovascular Disease Prevention, Diagnosis, and Treatment in Women.

Cardiovascular disease (CVD) is the leading cause of death for American women. CVD is preventable although risk reduction goals are not achieved for women compared with men. Considering a woman's cardiometabolic profile for prevention counseling and prescribing may help. Coronary artery calcium scores provide additional risk assessment and reproductive and menopause histories identify risk enhancers. Diagnosis of CVD is often delayed, and treatment is less optimal for women compared with men. Differences in presentation and underlying CVD etiology (Including spontaneous coronary artery dissection and microvascular disease) may partially account for these disparities. Improvements in CVD imaging to better diagnose these etiologies may benefit women's care.

Immune Markers, Blood Pressure Severity, and Cardiac Remodeling 1 to 2 Years After Hypertensive Disorders of Pregnancy.

Background Cardiovascular dysfunction and hypertension can persist postpartum following hypertensive disorders of pregnancy (HDPs). This study hypothesized that activin A, proinflammatory markers and concentric remodeling by echo would be higher 1-2 years postpartum following HDP with persistent hypertension compared to HDP with normalized blood pressure (BP). We further hypothesized correlations between biomarkers with BP and echocardiographic indices. Methods and Results This study enrolled participants with HDPs but no prepregnancy hypertension followed 1 to 2 years after delivery. Activin A and inflammatory cytokines, BP, and echocardiograms were obtained. Biomarker concentrations and echocardiographic parameters were compared between HDP with and without persistent hypertension. Individuals with persistent hypertension at a mean of 1.6 years postpartum had significantly higher activin A concentrations (median[interquartile range 25-75] 230.6 [196.0-260.9] versus 175.3 pg/mL [164.3-188.4]; P<0.01), more concentric left ventricular concentric remodeling (relative wall thickness >0.42, 48% versus 7%; P<0.01), and worse peak left atrial strain (33.4% versus 39.3%; P<0.05) as compared with those whose BP normalized. Higher activin A and interleukin-6 concentrations correlated with higher systolic (activin A: r=0.43, P=0.01) and diastolic BP (activin A: r=0.58, P<0.01; interleukin-6: r=0.36; P<0.05), as well as greater left ventricular thickness (activin A and interventricular septal thickness: r=0.41, interleukin-6 and interventricular septal thickness: r=0.36; both P<0.05). Conclusions Individuals with HDPs and persistent hypertension had significantly higher activin A and greater concentric remodeling compared with those with HDPs and normalized BP at 1 to 2 years postpartum. Activin A was positively correlated with both BP and echocardiographic indices (left ventricular thickness), suggesting overlapping processes between persistent hypertension and cardiac remodeling.

Association of activin A and postpartum blood pressure in peripartum cardiomyopathy.

BACKGROUND: Activin A has been implicated in the pathogenesis of patients with chronic hypertension and heart failure as well as patients with hypertensive disorders of pregnancy (HDP). Whether activin A correlates with blood pressure in patients with peripartum cardiomyopathy (PPCM) and HDP history has not previously been explored. METHODS AND RESULTS: 82 women with PPCM w/ and w/out HDP or hypertension history were selected for analysis from the Investigations in Pregnancy Associated Cardiomyopathy (IPAC) study. Serum biomarkers and blood pressure were assessed at the time of enrollment (median postpartum day 24). Levels of both sFlt-1 (SBP: r 0.47, p = 0.008; DBP: r 0.57, p < 0.001) and activin A (SBP: r 0.59, p < 0.001;DBP: r 0.68, p < 0.001) were noted to significantly correlate with blood pressure in patients with a history of HDP who went on to develop PPCM, but not in patients with chronic hypertension or no hypertensive history. The strongest correlation was between activin A levels and postpartum diastolic blood pressure for the subset with preeclampsia (DBP: r0.82, p < 0.001). This remained significant in multivariable linear regression analysis (DBP: ß = 0.011, p = 0.015). CONCLUSION: In patients with PPCM, activin A and sFlt-1 levels had direct correlations with both systolic (SBP) and diastolic blood pressures (DBP), but only in participants with history of HDP. This correlation was more evident for activin A and strongest with a history of preeclampsia. Our findings suggest that activin A may play an important role in blood pressure modulation in women with HDP who subsequently develop PPCM.

Characteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes.

BACKGROUND: Adverse pregnancy outcomes (APOs), hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are associated with ischemic heart disease in later life. OBJECTIVES: The authors aimed to study the features of premature myocardial infarction (MI) among women with and without prior APOs. METHODS: We performed a retrospective analysis of women with premature MI (<65 years of age) referred for left heart catheterization matched with a database of abstracted pregnancy data. We compared MI characteristics and epicardial coronary anatomy between women with and without APOs during their index pregnancy and evaluated time from delivery to MI. RESULTS: Of 391 women with premature MI and associated coronary angiography (age: 49 ± 8 years), 154 (39%) had a prior APO (hypertensive disorders of pregnancy n = 78, preeclampsia n = 35, gestational diabetes mellitus n = 28, and preterm birth n = 48). Women with APO history had a higher prevalence of diabetes (33% vs 16% without APO; P = 0.001) and presented earlier with MI following delivery (19.6 [IQR: 14.3-23.5] years vs those without APO 21.5 [IQR: 17.0-25.4] years; P = 0.012), driven by preeclampsia (17.1 [IQR: 12.7-22.4] years, P = 0.010). Women with and without APOs had similar MI features including rates of ST-segment elevation MI, obstructive and multi-vessel coronary artery disease, percutaneous coronary intervention, and shock. CONCLUSIONS: Among women with premature MIs, 39% had a history of an APO. Women with APO history presented sooner after pregnancy but had similar MI characteristics vs those without APOs. Pregnancy history may identify women who warrant early, aggressive cardiovascular disease prevention.

Proinflammatory TH17 cytokine activation, disease severity and outcomes in peripartum cardiomyopathy.

BACKGROUND: Immune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM). METHODS AND RESULTS: 98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-α and IL-22 were associated with poorer event-free survival. Higher TNF-α levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up. CONCLUSION: Proinflammatory cytokines IL-22 and TNF-α were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.

Breastfeeding, Cellular Immune Activation, and Myocardial Recovery in Peripartum Cardiomyopathy.

The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women.

Atrial arrhythmias are associated with increased mortality in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a deadly vascular disease, characterized by increased pulmonary arterial pressures and right heart failure. Considering prior non-US studies of atrial arrhythmias in PAH, this retrospective, regional multi-center US study sought to define more completely the risk factors and impact of paroxysmal and non-paroxysmal forms of atrial fibrillation and flutter (AF/AFL) on mortality in this disease. We identified patients seen between 2010 and 2014 at UPMC (Pittsburgh) hospitals with hemodynamic and clinical criteria for PAH or chronic thromboembolic pulmonary hypertension (CTEPH) and determined those meeting electrocardiographic criteria for AF/AFL. We used Cox proportional hazards regression with time-varying covariates to analyze the association between AF/AFL occurrence and survival with adjustments for potential cofounders and hemodynamic severity. Of 297 patients with PAH/CTEPH, 79 (26.5%) suffered from AF/AFL at some point. AF/AFL was first identified after PAH diagnosis in 42 (53.2%), identified prior to PAH diagnosis in 27 (34.2%), and had unclear timing in the remainder. AF/AFL patients were older, more often male, had lower left ventricular ejection fractions, and greater left atrial volume indices and right atrial areas than patients without AF/AFL. AF/AFL (whether diagnosed before or after PAH) was associated with a 3.81-fold increase in the hazard of death (95% CI 2.64-5.52, p < 0.001). This finding was consistent with multivariable adjustment of hemodynamic, cardiac structural, and heart rate indices as well as in sensitivity analyses of patients with paroxysmal versus non-paroxysmal arrhythmias. In these PAH/CTEPH patients, presence of AF/AFL significantly increased mortality risk. Mortality remained elevated in the absence of a high burden of uncontrolled or persistent arrhythmias, thus suggesting additional etiologies beyond rapid heart rate as an explanation. Future studies are warranted to confirm this observation and interrogate whether other therapies beyond rate and rhythm control are necessary to mitigate this risk.

Evidence for a Soft Nuclear Equation-of-State from Kaon Production in Heavy-Ion Collisions.

The production of pions and kaons has been measured in 197Au+197Au collisions at beam energies from 0.6 to 1.5A GeV with the kaon spectrometer at SIS/GSI. The K+ meson multiplicity per nucleon is enhanced in Au+Au collisions by factors up to 6 relative to C+C reactions, whereas the corresponding pion ratio is reduced. The ratio of the K+ meson excitation functions for Au+Au and C+C collisions increases with decreasing beam energy. This behavior is expected for a soft nuclear equation-of-state.

Superspreading driven by Marangoni flow.

The spontaneous spreading (called superspreading) of aqueous trisiloxane ethoxylate surfactant solutions on hydrophobic solid surfaces is a fascinating phenomenon with several practical applications. For example, the ability of trisiloxane ethoxylate surfactants to enhance the spreading of spray solutions on waxy weed leaf surfaces, such as velvetleaf (Abutilion theophrasti), makes them excellent wetting agents for herbicide applications. The superspreading ability of silicone surfactants has been known for decades, but its mechanism is still not well understood. In this paper, we suggest that the spreading of trisiloxane ethoxylates is controlled by a surface tension gradient, which forms when a drop of surfactant solution is placed on a solid surface. The proposed model suggests that, as the spreading front stretches, the surface tension increases (the surfactant concentration becomes lower) at the front relative to the top of the droplet, thereby establishing a dynamic surface tension gradient. The driving force for spreading is due to the Marangoni effect, and our experiments showed that the higher the gradient, the faster the spreading. A simple model describing the phenomenon of superspreading is presented. We also suggest that the superspreading behavior of trisiloxane ethoxylates is a consequence of the molecular configuration at the air/water surface (i.e. small and compact hydrophobic part), as shown by molecular dynamics modeling. We also found that the aggregates and vesicles formed in trisiloxane solutions do not initiate the spreading process and therefore these structures are not a requirement for the superspreading process.

Flow characteristics of the SAPIEN aortic valve: the importance of recognizing in-stent flow acceleration for the echocardiographic assessment of valve function.

BACKGROUND: The percutaneously implanted Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA) consists of cusps mounted within a stent. The individual impact of the stent and cusps on transvalvular flow and its implications for the echocardiographic assessment of valve function have not been previously reported. METHODS: The study group consisted of 40 patients who underwent successful implantation with the SAPIEN valve. Pulsed Doppler was recorded with sample volumes immediately proximal to the stent (prestent), within the stent but proximal to the cusps (in-stent precusp), and distal to the cusps (in-stent postcusp). The Doppler velocity index and effective orifice area were calculated using both prestent and in-stent precusp velocities to represent "subvalvular" flow and continuous-wave recordings of the left ventricular outflow tract and aortic valve to represent postvalvular flow. RESULTS: In all patients, there was flow acceleration at two levels: in-stent precusp and in-stent postcusp. The mean in-stent precusp peak velocities were significantly higher than the prestent values (1.5 ± 0.2 vs 1.0 ± 0.2 m/sec, P < .0001). Effective orifice area and Doppler velocity index calculated using the prestent versus in-stent precusp velocities were also significantly different (1.79 ± 0.34 vs 2.54 ± 0.46 cm(2), P < .0001, and 0.48 ± 0.12 vs 0.73 ± 0.13, P < .0001, respectively). CONCLUSIONS: The SAPIEN valve demonstrates flow acceleration at two levels, representing contributions of both the stent and valve cusps to the total valve gradient. Failure to recognize this phenomenon may result in inappropriate selection of the in-stent precusp pulsed Doppler spectrum to represent "subvalvular" flow, thereby overestimating the effective orifice area and Doppler velocity index.

Alteration in subendocardial and subepicardial myocardial strain in patients with aortic valve stenosis: an early marker of left ventricular dysfunction?

BACKGROUND: It has been suggested that myocardial systolic impairment may not be accurately detected by the evaluation of endocardial excursion alone. The aim of this study was to test the hypothesis that changes in left ventricular (LV) subendocardial and subepicardial strain are sensitive markers of severity of aortic stenosis (AS) and LV function in patients with AS. METHODS: Transthoracic echocardiography was performed in 73 consecutive patients with AS who had preserved systolic function and in 20 controls. Longitudinal strain, subendocardial radial strain, subepicardial radial strain, and transmural radial strain were measured using LV apical and short-axis images. RESULTS: The 73 patients enrolled in this study were classified according to AS severity: mild (n = 10), moderate (n = 15), or severe (n = 48). Although transmural and subepicardial radial strain showed similar values in all groups, subendocardial radial strain and longitudinal strain could differentiate mild or moderate AS from severe AS. Only the ratio of subendocardial to subepicardial radial strain (the bilayer ratio) decreased significantly as the severity of AS increased. Bilayer ratio showed weak correlations with LV ejection fraction (r = 0.37) and E/E' ratio (r = -0.33) and moderate correlations with LV mass (r = -0.55) and aortic valve area (r = 0.71). Moreover, bilayer ratio was independently associated with AS severity (P = .001). In 21 patients who underwent aortic valve replacement, subendocardial radial strain and bilayer ratio increased 7 days after surgery, whereas other echocardiographic parameters of LV function showed no improvement. CONCLUSIONS: Bilayer ratio can reliably differentiate patients with varying degrees of AS severity and is a sensitive marker of LV function. These findings suggest that the evaluation of subendocardial and subepicardial radial strain might be a novel method for assessing LV mechanics in patients with AS.

Accurate measurement of mitral annular area by using single and biplane linear measurements: comparison of conventional methods with the three-dimensional planimetric method.

AIMS: The planimetry method using three-dimensional (3D) echocardiography is useful for providing an accurate mitral annulus area (MAA) value. However, this method is relatively unavailable. Therefore, we evaluated the accuracy of conventional methods for MAA measurement compared with that of 3D planimetry. METHODS AND RESULTS: Two-dimensional (2D) and 3D transoesophageal echocardiography (TEE) were performed in 70 patients. The mitral annulus diameter (MAD) was measured using four standard TEE imaging planes: four-chamber (4Ch), two-chamber (2Ch), anterior-posterior (LAX), and commissure-commissure (CC). MAA was calculated using a single diameter based on that of a circle and using two diameters based on that of an ellipse. MAA measurements using the single 4Ch MAD method (r = 0.84, P < 0.001), and two anatomically orthogonal MAD method in 4Ch/2Ch (r = 0.93, P < 0.001) and LAX/CC (r = 0.97, P < 0.001) planes correlated with 3D planimetric MAA measurements. Further analysis with Bland-Altman plots revealed that the LAX/CC MAD measurement exhibited the closest limits of agreement with the 3D planimetric MAA measurement. Notably, in patients showing an elliptical annulus shape, only LAX/CC MAD, but not 4Ch or 4Ch/2Ch MAD, provided results comparable with those of 3D planimetric MAA measurements. However, in patients with a circular annulus shape, reliable MAA measurements can be achieved using either single 4Ch MAD or any biplane MAD. CONCLUSION: Conventional LAX/CC MAD can be recommended for MAA measurements in a diverse patient population. This method is applicable as an alternative to the 3D planimetric method, regardless of the mitral annulus shape.