Rates of Reproductive Counseling and Contraception Use in Patients with Heart Failure at a Tertiary Care Center.

BACKGROUND: Increasing numbers of women of childbearing age have cardiac disease, including heart failure (HF). In these women, pregnancy can cause significant morbidity and mortality. Contraceptive use and pregnancy counseling in women with HF is an essential part of their medical care. Here, we assess contraceptive use and pregnancy counseling of patients with HF at a single tertiary care center. METHODS AND RESULTS: This was a retrospective, single-center cohort study of female patients with HF with reduced ejection fraction, left ventricular assist devices (LVADs), and heart transplants who were seen in the adult advanced HF outpatient clinics. Patients were identified in the electronic health care record system, and records were reviewed to assess for documentation of contraception and pregnancy counseling. We identified 156 women of childbearing age (aged >18 to <45), seen in the HF clinics between 2018 and 2023. Patients were subdivided by their most recent diagnosis and therapy: HF with reduced ejection fraction (83 [53.2%]), LVAD (18 [11.5%]), and heart transplant (55 [35.3%]). Contraception was documented for 74% of women with HF, 56% of women with LVAD, and 85% of women with heart transplants. Pregnancy counseling was documented for 18.00% of women with HF, 0.06% of women with LVAD, and 29.00% of women with heart transplants. CONCLUSIONS: In our study, many women with HF, LVAD, or transplant have documented contraceptive therapy; however, pregnancy counseling seems to be limited. This vital aspect of medical care should be available for all patients given potential pregnancy-associated risks.

Prenatal Low-Dose Aspirin Use Associated with Reduced Incidence of Postpartum Hypertension among Women with Preeclampsia.

OBJECTIVE: Postpartum hypertension (PP-HTN), defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90, on two occasions at least 4 hours apart after delivery occurs in up to 50% of preeclamptic pregnancies, and is associated with adverse maternal outcomes. Excessive production of antiangiogenic factors (i.e., soluble fms-like tyrosine kinase 1 [sFLT1]) and reduced levels of proangiogenic factors (i.e., placental growth factor [PlGF]) are associated with preeclamptic pregnancies. The aim of this study was to identify clinical risk factors and/or serum biomarkers associated with PP-HTN in preeclampsia. STUDY DESIGN: Preeclamptic women (n = 82, aged ≥18 years) were prospectively enrolled in an observational study. Serial blood pressures were obtained through the labor course and until 48 hours postpartum, and serum was obtained within 24 hours postpartum. Statistical analysis was performed by using Student's two-tailed t-test and Fisher's exact test. RESULTS: Baseline comorbidities and antihypertensive use were similar among those who developed PP-HTN and those who did not. Among preeclamptic patients, 33% developed PP-HTN; these had significantly more severe preeclampsia features versus no PP-HTN (96 vs. 78%, p = 0.05). PP-HTN was associated with higher re-hospitalization rates (26 vs. 6%, p = 0.01). Among those taking low-dose aspirin (ASA) for preeclampsia prophylaxis (n = 12), PP-HTN was significantly less frequent versus those not taking low-dose ASA (0 vs. 22%, p = 0.007). Low-dose ASA use was associated with significantly lower peripartum sFLT1 levels (4,650 ± 2,335 vs. 7,870 ± 6,282 pg/mL, p = 0.03) and sFLT1/PlGF ratio (397 ± 196 vs. 1,527 ± 2,668, p = 0.03). CONCLUSION: One-third of women with preeclampsia develop PP-HTN; these patients have more severe preeclampsia and have higher re-hospitalization rates. Prenatal low-dose ASA use was associated with significantly lower incidence of PP-HTN, reduced levels of antiangiogenic factors, and lower 6-week re-hospitalization rates. These findings, if replicated, may have clinical implications on the use of low-dose ASA during pregnancy to reduce incidence of postpartum HTN. KEY POINTS: · Postpartum hypertension is common in preeclampsia.. · Prenatal aspirin may reduce postpartum hypertension.. · Prenatal aspirin may reduce sFLT1 levels..

Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

The role of chronic suppressive antibiotics therapy in superficial drive line infection relapse of left ventricular assist devices: A retrospective cohort from a tertiary care center.

INTRODUCTION: Drive line infections (DLIs) are common complications of left ventricular assist devices (LVADs). Data on use of suppression antibiotic therapy are limited. METHODS: We performed a retrospective review of 451 patients who underwent LVAD placement from January 2009 to May 2015. First superficial DLIs were included for analysis. We examined factors associated with the use of chronic suppressive antibiotics (CSAs) therapy. Cox proportional hazards models were performed to identify factors associated with DLI relapse with the same organism as the initial DLI. RESULTS: A total of 69 patients developed a superficial DLI within a median of 195 (interquartile range [IQR] 98-348) days of LVAD insertion. The median age was 57 years, 87% were males, and 74% were White. Gram positive bacteria caused 61% of infections, with Staphylococcus aureus being the most common (35%). Forty-three (62%) patients received suppressive antibiotic therapy. Relapse DLI occurred in 29 (42%) patients. Independent risk factors for relapse infection in multivariable analysis were sepsis (aHR 5.94 [CI 1.42-24.92]), and MRSA DLI (aHR 4.19 [CI 1.37-12.79]). There was no difference in the proportion of patients with relapse among those who were treated with antibiotic suppression therapy versus not (44% vs. 38%, p = 0.64), although relapse occurred at a later time in those who received suppression (185 vs. 69 days, p < 0.01). CONCLUSION: CSA therapy was associated with delayed time to DLI relapse but no significant difference in the proportion of patients with relapse. A prospective study is needed to examine the effect of suppression on relapse rates.

Peripartum Cardiomyopathy: Progress in Understanding the Etiology, Management, and Prognosis.

Occurring in approximately 1 in 1000 live births in the United States, peripartum cardiomyopathy (PPCM) is characterized by left ventricular ejection fraction reduced to less than 45% near the end of pregnancy or within the first 5 months after delivery. Although the cause of PPCM remains unclear, increasing evidence supports a complex interaction of genetic and environmental factors contributing to angiogenic imbalance, which may lead to myocardial dysfunction in a susceptible woman. This article reviews the progress that has been made regarding understanding of the cause, management, and natural history of PPCM.

Socioeconomic and partner status in chronic heart failure: Relationship to exercise capacity, quality of life, and clinical outcomes.

BACKGROUND: Prognosis in patients with heart failure (HF) is commonly assessed based on clinical characteristics. The association between partner status and socioeconomic status (SES) and outcomes in chronic HF requires further study. METHODS: We performed a post hoc analysis of HF-ACTION, which randomized 2,331 HF patients with ejection fraction ≤35% to usual care ± aerobic exercise training. We examined baseline quality of life and functional capacity and outcomes (all-cause mortality/hospitalization) by partner status and SES using adjusted Cox models and explored an interaction with exercise training. Outcomes were examined based on partner status, education level, annual income, and employment. RESULTS: Having a partner, education beyond high school, an income >$25,000, and being employed were associated with better baseline functional capacity and quality of life. Over a median follow-up of 2.5 years, higher education, higher income, being employed, and having a partner were associated with lower all-cause mortality/hospitalization. After multivariable adjustment, lower mortality was seen associated with having a partner (hazard ratio 0.91, 95% CI 0.81-1.03, P=.15) and more than a high school education (hazard ratio 0.91, CI 0.80-1.02, P=.12), although these associations were not statistically significant. There was no interaction between any of these variables and exercise training on outcomes (all P>.5). CONCLUSIONS: Having a partner and higher SES were associated with greater functional capacity and quality of life at baseline but were not independent predictors of long-term clinical outcomes in patients with chronic HF. These findings provide information that may be considered as potential variables impacting outcomes.

Plasmapheresis in severe methemoglobinemia following occupational exposure.

Ferrous iron can be converted to ferric iron by oxidative stress which results in the formation of methemoglobin. Consequently, the oxygen dissociation curve is shifted to the left, which leads to tissue hypoxia and ultimately may cause death. Acquired methemoglobinemia can be due to a host of offending agents and chemicals including nitrites, local anesthetics, aniline and antimalarial drugs. There are several approaches to the management of methemoglobinemia. The first step is to stop the offending agent and initiate supportive measures. Methylene blue can be used successfully provided the patient has no evidence of glucose 6 phosphate deficiency. Hyperbaric oxygen and intravenous ascorbic acid are other treatment options. We present a case of unusually severe methemoglobinemia (82% methemoglobin) secondary to occupational exposure that failed to respond to several lines of management including methylene blue, red cell exchange, intravenous ascorbic acid, and hyperbaric oxygen. However, the patient responded swiftly to plasmapheresis started upon suspicion of concomitant thrombotic thrombocytopenic purpura, and he subsequently recovered completely. Thus, plasmapheresis may have a role in severe methemoglonbinemia unresponsive to standard treatment options.

Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways.

Wnt signaling has recently emerged as an important regulator of cardiac progenitor cell proliferation and differentiation, but the exact mechanisms by which Wnt signaling modulates these effects are not known. Understanding these mechanisms is essential for advancing our knowledge of cardiac progenitor cell biology and applying this knowledge to enhance cardiac therapy. Here, we explored the effects of Sfrp2, a canonical Wnt inhibitor, in adult cardiac progenitor cell (CPC) differentiation and investigated the molecular mechanisms involved. Our data show that Sfrp2 treatment can promote differentiation of CPCs after ischemia-reperfusion injury. Treatment of CPCs with Sfrp2 inhibited CPC proliferation and primed them for cardiac differentiation. Sfrp2 binding to Wnt6 and inhibition of Wnt6 canonical pathway was essential for the inhibition of CPC proliferation. This inhibition of Wnt6 canonical signaling by Sfrp2 was important for activation of the non-canonical Wnt/Planar Cell Polarity (PCP) pathway through JNK, which in turn induced expression of cardiac transcription factors and CPC differentiation. Taken together, these results demonstrate a novel role of Sfrp2 and Wnt6 in regulating the dynamic process of CPC proliferation and differentiation, as well as providing new insights into the mechanisms of Wnt signaling in cardiac differentiation.

Preconception Counseling in a Patient With a Mechanical Aortic Valve and Recent Ischemic Stroke.

A 31-year-old woman with a mechanical aortic valve for congenital aortic stenosis presented to the cardiology clinic for preconception counseling. After experiencing an acute stroke 4 weeks prior, she was subsequently discovered to have prosthetic valve thrombosis requiring replacement of the aortic valve. We discuss her clinical course and preconception considerations.

Toll-like receptors and human disease: lessons from single nucleotide polymorphisms.

Toll-like receptors (TLRs), a large group of proteins which recognize various pathogen-associated molecular patterns, are critical for the normal function of the innate immune system. Following their discovery many single nucleotide polymorphisms within TLRs and components of their signaling machinery have been discovered and subsequently implicated in a wide range of human diseases including atherosclerosis, sepsis, asthma, and immunodeficiency. This review discusses the effect of genetic variation on TLR function and how they may precipitate disease.

Cardiovascular symptom phenotypes of post-acute sequelae of SARS-CoV-2.

BACKGROUND: Acute COVID-19 infection has been shown to have significant effects on the cardiovascular system. Post-acute sequelae of SARS-CoV-2 (PASC) are being identified in patients; however, the cardiovascular effects are yet to be well-defined. The Post-COVID Cardiology Clinic at Washington University evaluates and treats patients with ongoing cardiovascular PASC. OBJECTIVES: This investigation aims to describe the phenotypes of cardiovascular symptoms of PASC in patients presenting to the Post-COVID Cardiology Clinic, including their demographics, symptoms, and the clinical phenotypes observed. METHODS: This was a retrospective analysis of symptoms, clinical findings, and test results from the first 100 consecutive adult patients who presented to the Post-COVID Cardiology Clinic at Washington University in St. Louis, between September 2020 to May 2021 with cardiovascular symptoms following COVID-19 infection. RESULTS: The population (n = 100) had a mean age of 46.3 years and was 81% female. Most patients had mild acute illness, with only 23% of patients requiring hospitalization during acute COVID-19 infection. The most commonly reported PASC symptoms were chest pain (66%), palpitations (59%), and dyspnea on exertion (56%). Of those presenting with these symptoms, 74/98 patients (75.5%) were found to have a significant blood pressure elevation, considerable sinus tachycardia burden, reduced global longitudinal strain, increased indexed left-ventricular end-diastolic volume (LVEDVi) by echocardiogram, and/or cMRI findings consistent with possible active or healing myocarditis. CONCLUSIONS: Our findings highlight clinical phenotypes of the cardiovascular manifestations of PASC. Further studies are needed to evaluate the pathophysiology, treatment options and long-term outcomes for these patients.

Angiotensin II Type 1 Receptor Antibody-mediated Rejection Following Orthotopic Heart Transplant: A Single-center Experience.

BACKGROUND: Antibody-mediated rejection (AMR) following orthotopic heart transplant (OHT) causes significant morbidity and mortality. There are limited data on antibodies to the angiotensin II type 1 receptor antibody (AT1R-Ab) causing rejection following OHT. METHODS: This is a retrospective, single-center study that presents our 2-y experience with a series of 11 patients with evidence of nonspecific graft dysfunction and pathologic levels of AT1R-Ab. The clinical outcomes and treatments were compared to a group of 10 patients, also with evidence of nonspecific graft dysfunction, but who had nonsignificant AT1R-Ab titers. RESULTS: The mean age of the AT1R-Ab cohort was 52% and 73% were bridged to transplant with an left ventricular assist device. The average left ventricular ejection fraction at presentation was 45%, and most were not on an angiotensin receptor blocker (ARB). Endomyocardial biopsies in those with elevated AT1R-Ab levels frequently showed reactive endothelium/endocardium without C4d or intravascular CD68 staining. Ten patients (91%) were started on an ARB. Other therapies included plasmapheresis and IVIg (64%), with 4 patients also receiving rituximab. Most patients had symptom improvement, but minimal change in graft function at an average 6 mo of follow-up. CONCLUSIONS: The role of AT1R-Ab-mediated rejection in OHT recipients remains poorly understood. More than half of patients at our center who presented with graft dysfunction in the absence of acute cellular rejection or AMR were found to have elevated AT1R-Ab titers. Empiric AMR treatment in conjunction with ARB therapy may improve patient outcomes. Future studies are needed to better define the optimal treatment modalities for ATR1-Ab-mediated AMR.

COVID-19 in orthotopic heart transplant recipients and association with donor specific antibodies.

De novo donor-specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection and worse clinical outcomes after orthotopic heart transplant (OHT). No study has reported the production of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in an OHT population. In this retrospective study, we described coronavirus disease 2019 (COVID-19) incidence and clinical course in a large, contemporary OHT cohort. We showed that the case-fatality rate has significantly decreased since the early days of the pandemic, although remains higher than that of the general population. In addition, we found that 10% of OHT recipients developed de novo DSAs or experienced an increase in pre-existing DSAs after COVID-19, with the majority occurring in unvaccinated patients (15% vs 2%). Further studies are necessary to substantiate our findings in an external cohort.

Pulmonary Arterial Hypertension in Pregnancy.

Pulmonary arterial hypertension is a rare disease that predominantly affects women. The pathophysiology of the disease is complex, with both genetic and hormonal influences. Pregnancy causes significant physiologic changes that may not be well tolerated with underlying pulmonary arterial hypertension, in particular leading to volume overload and increased pulmonary pressures. A multidisciplinary approach and careful monitoring are essential for appropriate management of pulmonary arterial hypertension during pregnancy. Nonetheless, outcomes are still poor, and pregnancy is considered a contraindication in patients with pulmonary arterial hypertension.

Acute myocarditis after a second dose of the mRNA COVID-19 vaccine: a report of two cases.

We report two cases of myocarditis, in two young and previously healthy individuals, temporally related to the second dose of the mRNA-COVID-19 vaccine. Both patients developed acute chest pain, changes on electrocardiogram (ECG), and elevated serum troponin within two days of receiving their second dose. Cardiac magnetic resonance (CMR) findings were consistent with acute myocarditis.

The Spectrum of Pregnancy-Associated Heart Failure Phenotypes: An Echocardiographic Study.

Compare echocardiographic phenotypes of women presenting with peripartum heart failure. A retrospective case-control study of pregnant women (n = 86) presenting with PP-HF symptoms (i.e., dyspnea, PND, orthopnea) and objective examination and laboratory findings (lung congestion, elevated JVP and/or HJR, elevated brain natriuretic peptide [BNP] and pulmonary edema on chest X-ray). Three distinct phenotypes based on echocardiographically-defined LVEF were identified: (a) PP-HF with preserved ejection fraction (PP HFpEF, LVEF: > 50%); (b) PP-HF with midrange ejection fraction (PP HFmrEF, LVEF: 40-50%); c) PP-HF with reduced ejection fraction (PP HFrEF, LVEF: < 40%); these were compared with 17 pregnant subjects without PP-HF symptoms/findings. Most patients were African American (n = 63; 73%), with low prevalence of hypertension (n = 15, 17%) or diabetes mellitus (n = 5, 5%); pre-eclampsia was highly prevalent (n = 52, 60%). Echocardiographically-defined phenotypes (HFpEF, n = 37; HFmrEF, n = 18; HFrEF, n = 31) showed progressively worse abnormalities in LV remodeling (LV enlargement, LV hypertrophy), LV diastolic function, and right ventricular function; the three PP-HF groups had comparable abnormalities in increased left atrial size and estimated peak tricuspid valve regurgitation velocity. Compared to controls, all three groups had significantly increased filling pressures, LV mass index and left atrial volume index. Peripartum women presenting with the clinical syndrome of heart failure exhibit a spectrum of echocardiographic phenotypes. Significant abnormalities in LV structure, diastolic function, LA size, peak TR velocity and RV function were identified in women with preserved and mid-range EFs, suggesting pregnancy-related cardiac pathophysiologic derangements.

A Cardio-Obstetric Approach to Management of the Complex Pregnant Cardiac Patient.

A 23-year-old female presented at 28.5 weeks gestation with symptomatic heart failure due to severe mitral stenosis and severe pulmonary arterial hypertension. After multidisciplinary planning, she underwent caesarean delivery with mitral valve replacement 48 h postpartum. Cardio-obstetric teams provide expert coordinated care for complex cardiovascular disease in pregnancy. (Level of Difficulty: Beginner.).

Rate pressure product and the components of heart rate and systolic blood pressure in hospitalized heart failure patients with preserved ejection fraction: Insights from ASCEND-HF.

BACKGROUND: Heart rate and systolic blood pressure (SBP) are prognostic markers in heart failure (HF) with reduced ejection fraction (HFrEF). Their combination in rate pressure product (RPP) as well as their role in heart failure with preserved ejection fraction (HFpEF) remains unclear. HYPOTHESIS: RPP and its components are associated with HFpEF outcomes. METHODS: We performed an analysis of Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF; http://www.clinicaltrials.gov NCT00475852), which studied 7141 patients with acute HF. HFpEF was defined as left ventricular ejection fraction ≥40%. Outcomes were assessed by baseline heart rate, SBP, and RPP, as well as the change of these variables using adjusted Cox models. RESULTS: After multivariable adjustment, in-hospital change but not baseline heart rate, SBP, and RPP were associated with 30-day mortality/HF hospitalization (hazard ratio [HR]: 1.17 per 5-bpm heart rate, HR: 1.20 per 10-mm Hg SBP, and HR: 1.02 per 100 bpm × mm Hg RPP; all P < 0.05). Baseline SBP was associated with 180-day mortality (HR: 0.88 per 10-mm Hg, P = 0.028). Though change in RPP was associated with 30-day mortality/HF hospitalization, the RPP baseline variable did not provide additional associative information with regard to outcomes when compared with assessment of baseline heart rate and SBP variables alone. CONCLUSIONS: An increase in heart rate and SBP from baseline to discharge was associated with increased 30-day mortality/HF hospitalization in HFpEF patients with acute exacerbation. These findings suggest value in monitoring the trend of vital signs during HFpEF hospitalization.