Journal: Circ Heart Fail

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Abstract

Reference Ranges for NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and Risk Factors for Higher NT-proBNP Concentrations in a Large General Population Cohort.

Welsh P, Campbell RT, Mooney L, Kimenai DM, ... McMurray JJV, Sattar N
Background
Demographic differences in expected NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration are not well established. We aimed to establish reference ranges for NT-proBNP and explore the determinants of moderately elevated NT-proBNP under the universal definition of heart failure criteria.
Methods
This is a cross-sectional study. NT-proBNP was measured in serum from 18 356 individuals without previous cardiovascular disease in the Generation Scotland Scottish Family Health Study. Age- and sex-stratified medians and 97.5th centiles were generated. Sex stratified risk factors for moderately elevated NT-proBNP (≥125 pg/mL) were investigated.
Results
In males, median (97.5th centile) NT-proBNP concentration at age <30 years was 21 (104) pg/mL, rising to 38 (195) pg/ml at 50 to 59 years, and 281 (6792) pg/mL at ≥80 years. In females, median NT-proBNP at age <30 years was 51 (196) pg/mL, 66 (299) pg/mL at 50 to 59 years, and 240 (2704) pg/mL at ≥80 years. At age <30 years, 9.8% of females and 1.4% of males had elevated NT-proBNP, rising to 76.5% and 81.0%, respectively, at age ≥80 years. After adjusting for risk factors, an NT-proBNP ≥125 pg/mL was more common in females than males (OR, 9.48 [95% CI, 5.60-16.1]). Older age and smoking were more strongly associated with elevated NT-proBNP in males than in females (Psex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (Psex interaction=0.007).
Conclusions
An NT-proBNP ≥125 pg/mL is common in females without classical cardiovascular risk factors as well as older people. If NT-proBNP becomes widely used for screening in the general population, interpretation of NT-proBNP levels will require that age and sex-specific thresholds are used to identify patients with potential pathophysiology.



Circ Heart Fail: 13 Sep 2022:101161CIRCHEARTFAILURE121009427; epub ahead of print
Welsh P, Campbell RT, Mooney L, Kimenai DM, ... McMurray JJV, Sattar N
Circ Heart Fail: 13 Sep 2022:101161CIRCHEARTFAILURE121009427; epub ahead of print | PMID: 36098049
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Abstract

Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction.

Billingsley HE, Del Buono MG, Canada JM, Kim Y, ... Abbate A, Carbone S
Background
Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF.
Methods
Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO2), circulatory power, oxygen uptake efficiency slope, O2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate.
Results
Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO2 (NSO, 1.62±0.53 L·min-1 versus SO, 1.27±0.44 L·min-1, P=0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P=0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P=0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO2 when adjusted for age, sex, adiposity, and HF severity.
Conclusions
In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.



Circ Heart Fail: 13 Sep 2022:101161CIRCHEARTFAILURE122009518; epub ahead of print
Billingsley HE, Del Buono MG, Canada JM, Kim Y, ... Abbate A, Carbone S
Circ Heart Fail: 13 Sep 2022:101161CIRCHEARTFAILURE122009518; epub ahead of print | PMID: 36098058
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Abstract

Demographic and Regional Trends of Hypertrophic Cardiomyopathy-Related Mortality in the United States, 1999 to 2019.

Minhas AMK, Wyand RA, Ariss RW, Nazir S, ... Alam M, Virani SS
Background
Hypertrophic cardiomyopathy (HCM)-related mortality has been decreasing within the United States; however, persistent disparities in demographic subsets may exist. In this study, we assessed nationwide trends in mortality related to HCM among people ≥15 years of age in the United States from 1999 to 2019.
Methods
Trends in mortality related to HCM were assessed through a cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research database. Age-adjusted mortality rates per 1 000 000 people and associated annual percent changes with 95% CIs were determined. Joinpoint regression was used to assess the trends in the overall, demographic (sex, race and ethnicity, age), and regional groups.
Results
Between 1999 and 2019, 39 200 HCM-related deaths occurred. In the overall population, age-adjusted mortality rate decreased from 11.2 in 1999 to 5.4 in 2019. Higher mortality rates were observed for males, Black patients, and patients ≥75 years of age. Large metropolitan counties experienced pronounced declines in age-adjusted mortality rate over the study period. In addition, California had the highest overall age-adjusted mortality rate.
Conclusions
Over the past 2 decades, HCM-related mortality has decreased overall in the United States. However, demographic and geographic disparities in HCM-related mortality have persisted over time and require further investigation.



Circ Heart Fail: 01 Sep 2022; 15:e009292
Minhas AMK, Wyand RA, Ariss RW, Nazir S, ... Alam M, Virani SS
Circ Heart Fail: 01 Sep 2022; 15:e009292 | PMID: 36126142
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Abstract

Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure and Preserved Ejection Fraction.

Zylla MM, Leiner J, Rahm AK, Hoffmann T, ... Frey N, Thomas D
Background
Coexistence of atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) is common, affecting morbidity and prognosis. This study evaluates outcome after cryoballoon ablation for AF in HFpEF compared with patients without heart failure.
Methods
A total of 102 AF patients with left ventricular ejection fraction ≥50% undergoing cryoballoon ablation were prospectively enrolled. Baseline evaluation included echocardiography, stress echocardiography, 6-minute walk test, biomarkers, and quality of life assessment (Short-Form-36). Procedural parameters and clinical, functional and echocardiographic end points at follow-up ≥12 months after AF ablation were compared between patients with and without HFpEF.
Results
Patients with HFpEF (n=24) were older (median, 74 years versus 65 years; P=0.001) more often female (83% versus 28%; P<0.001) and characterized by more pronounced AF-related symptoms (median European Heart Rhythm Association score 3 versus 2; P<0.001), higher left atrial pressures (median, 14 mm Hg versus 10 mm Hg; P=0.008), reduced left atrial-appendage velocity (median, 36 cm/s versus 59 cm/s; P<0.001), and reduced distance in the 6-minute walk test (median, 488 m versus 539 m; P<0.001). Patients with HFpEF more often experienced AF recurrence (57% versus 23%; P=0.003), repeat AF ablation (39% versus 14%; P=0.01) and AF-related rehospitalization (26% versus 7%; P=0.016). Heart failure symptoms and elevated cardiac biomarkers persisted, even in patients with HFpEF with successful rhythm control at follow-up. Echocardiographic follow-up showed progression of adverse left atrial remodeling and no relevant improvement in diastolic function in HFpEF. Quality of life improved in patients without HFpEF, whereas patients with HFpEF still exhibited a lower physical component summary score (median, 41.5 versus 53.4; P<0.004).
Conclusions
Patients with HFpEF constitute a distinct subgroup with elevated risk for AF recurrence after cryoballon ablation. Functional hallmarks of HFpEF persist, irrespective of rhythm status at follow-up. Future research is needed to optimize treatment strategies in patients with HFpEF.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT04317911.



Circ Heart Fail: 01 Sep 2022; 15:e009281
Zylla MM, Leiner J, Rahm AK, Hoffmann T, ... Frey N, Thomas D
Circ Heart Fail: 01 Sep 2022; 15:e009281 | PMID: 36126143
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Abstract

Proteomic Analysis of Effects of Spironolactone in Heart Failure With Preserved Ejection Fraction.

Javaheri A, Diab A, Zhao L, Qian C, ... Cappola TP, Chirinos JA
Background
The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed.
Methods
We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction. Mean percentage change from baseline was calculated for each protein. Additionally, we conducted pathway analysis of proteins altered by spironolactone.
Results
Spironolactone therapy was associated with proteome-wide significant changes in 7 proteins. Among these, CARD18 (caspase recruitment domain-containing protein 18), PKD2 (polycystin 2), and PSG2 (pregnancy-specific glycoprotein 2) were upregulated, whereas HGF (hepatic growth factor), PLTP (phospholipid transfer protein), IGF2R (insulin growth factor 2 receptor), and SWP70 (switch-associated protein 70) were downregulated. CARD18, a caspase-1 inhibitor, was the most upregulated protein by spironolactone (-0.5% with placebo versus +66.5% with spironolactone, P<0.0001). The top canonical pathways that were significantly associated with spironolactone were apelin signaling, stellate cell activation, glycoprotein 6 signaling, atherosclerosis signaling, liver X receptor activation, and farnesoid X receptor activation. Among the top pathways, collagens were a consistent theme that increased in patients receiving placebo but decreased in patients randomized to spironolactone.
Conclusions
Proteomic analysis in the TOPCAT trial revealed proteins and pathways altered by spironolactone, including the caspase inhibitor CARD18 and multiple pathways that involved collagens. In addition to effects on fibrosis, our studies suggest potential antiapoptotic effects of spironolactone in heart failure with preserved ejection fraction, a hypothesis that merits further exploration.



Circ Heart Fail: 01 Sep 2022; 15:e009693
Javaheri A, Diab A, Zhao L, Qian C, ... Cappola TP, Chirinos JA
Circ Heart Fail: 01 Sep 2022; 15:e009693 | PMID: 36126144
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Abstract

Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial.

Peikert A, Martinez FA, Vaduganathan M, Claggett BL, ... McMurray JJV, Solomon SD
Background: The prevalence of heart failure (HF) with mildly reduced or preserved ejection fraction (EF) markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.
Methods:
The DELIVER trial (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular EF >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years. We examined efficacy and safety outcomes by age categories (<55, 55-64, 65-74 and ≥75 years) and across age as a continuous measure.
Results:
Among 6,263 randomized patients (aged 40-99 years, mean age 71.7 ± 9.6 years), 338 (5.4%) were <55 years, 1,007 (16.1%) were 55-64 years, 2,326 (37.1%) were 65-74 years, and 2,592 (41.4%) were ≥75 years. Dapagliflozin reduced the risk of the primary composite outcome compared with placebo in all age categories (pinteraction=0.95) and across the age spectrum as a continuous function (pinteraction=0.76). Similar benefits were observed for the components of the primary outcome, with no significant interaction between randomized treatment and age category. Adverse events occurred more frequently with increasing age, but there were no significant differences in predefined safety outcomes between patients randomized to dapagliflozin and placebo across all age categories. Conclusions: In patients with HF and mildly reduced or preserved EF enrolled in DELIVER, Dapagliflozin reduced cardiovascular death or HF events across the spectrum of age, with a consistent safety profile, including among the traditionally under-treated older segment of patients ≥75 years. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT03619213.




Circ Heart Fail: 27 Aug 2022; epub ahead of print
Peikert A, Martinez FA, Vaduganathan M, Claggett BL, ... McMurray JJV, Solomon SD
Circ Heart Fail: 27 Aug 2022; epub ahead of print | PMID: 36029467
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Abstract

Association of Lifestyle With Incidence of Heart Failure According to Metabolic and Genetic Risk Status: A Population-Based Prospective Study.

Zhu Z, Li FR, Jia Y, Li Y, ... Qin LQ, Chen GC
Background
Whether lifestyle factors are similarly associated with risk of heart failure (HF) for individuals with different metabolic or genetic risk status remains unclear.
Methods
We included 464 483 participants from UK Biobank who were free of major cardiovascular disease or HF during baseline recruitment. Healthy lifestyle factors included avoidance of smoking, no obesity, regular physical activity, and healthy diet. Lifestyle was categorized as favorable (3 or 4 healthy lifestyle factors), intermediate (2 healthy lifestyle factors), and unfavorable (0 or 1 healthy lifestyle factor) lifestyles. Metabolic status was defined by the presence of hypertension, high total cholesterol, or diabetes at baseline. A weighted genetic risk score was created based on 12 single-nucleotide polymorphisms associated with HF.
Results
Compared with favorable lifestyle, the multivariable-adjusted hazard ratios of HF were 1.79 (95% CI, 1.68-1.90) and 2.90 (95% CI, 2.70-3.11) for intermediate lifestyle and unfavorable lifestyle, respectively (Ptrend <0.0001). This association was largely consistent regardless of the presence of any single metabolic risk factor or the number of metabolic risk factors (Pinteraction ≥0.21). The association was also similar across different genetic risk categories (Pinteraction=0.92). In a joint analysis, the hazard ratio of HF was 4.05 (95% CI, 3.43-4.77) comparing participants who had both higher genetic risk and an unfavorable lifestyle with those having lower genetic risk and a favorable lifestyle.
Conclusions
Combined lifestyle was associated with incident HF regardless of metabolic or genetic risk status, supporting the recommendation of healthy lifestyles for HF prevention across the entire population.



Circ Heart Fail: 17 Aug 2022:101161CIRCHEARTFAILURE122009592; epub ahead of print
Zhu Z, Li FR, Jia Y, Li Y, ... Qin LQ, Chen GC
Circ Heart Fail: 17 Aug 2022:101161CIRCHEARTFAILURE122009592; epub ahead of print | PMID: 35975661
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Abstract

Efficacy of Implantable Cardioverter Defibrillator in Nonischemic Systolic Heart Failure According to Sex: Extended Follow-Up Study of the DANISH Trial.

Butt JH, Yafasova A, Elming MB, Dixen U, ... Thune JJ, Køber L
Background
Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex.
Methods
In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality.
Results
Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47-0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46-0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42-0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40-1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69-1.06]; women, HR, 0.98 [95% CI, 0.64-1.50]; P for interaction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36-0.92]; women, HR, 0.68 [95% CI, 0.26-1.77]; P for interaction=0.76).
Conclusions
In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT00542945.



Circ Heart Fail: 09 Aug 2022:101161CIRCHEARTFAILURE122009669; epub ahead of print
Butt JH, Yafasova A, Elming MB, Dixen U, ... Thune JJ, Køber L
Circ Heart Fail: 09 Aug 2022:101161CIRCHEARTFAILURE122009669; epub ahead of print | PMID: 35942877
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Abstract

Temporal Trends of Heart Failure Hospitalizations in Cardiology Versus Noncardiology Wards According to Ejection Fraction: 16-Year Data From the SwedeHF Registry.

Canepa M, Kapelios CJ, Benson L, Savarese G, Lund LH
Background
Patients hospitalized for acute heart failure (AHF) may receive different care depending on type of ward. We describe temporal changes in triage of HF patients with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF) hospitalized for AHF to cardiology versus noncardiology wards in Sweden.
Methods
We analyzed temporal changes in ward type for AHF for HFrEF versus HFmrEF versus HFpEF between 2000 and 2016.
Results
Among 37 918 patients with AHF, 19 777 (52%) had HFrEF, 7712 (20%) had HFmrEF, and 10 429 (28%) had HFpEF. Overall, 19 646 (52%) were hospitalized in cardiology and 18 272 (48%) in noncardiology. The proportions hospitalized in noncardiology in 2000 to 2004 versus in 2013 to 2016 were for HFrEF: 45 versus 47%, for HFmrEF: 52 versus 56%, and for HFpEF: 46 versus 64%, respectively. The overall proportion of HFrEF in 2000 to 2004 versus in 2013 to 2016 decreased (60% versus 49%) especially in noncardiology (58% versus 41%), whereas the overall proportion of HFpEF increased (20% versus 30%) especially in noncardiology (21% versus 37%). The average age and prevalence of comorbidities also increased over time, with older patients with multiple comorbidities being more frequently admitted to noncardiology wards.
Conclusions
Over time, AHF hospitalization for HFpEF occurred increasingly in noncardiology, whereas for HFrEF and HFmrEF the proportions of patients treated in cardiology versus noncardiology were substantially unchanged over time. This may have implications for implementation of emerging HFpEF therapy.



Circ Heart Fail: 08 Aug 2022:101161CIRCHEARTFAILURE121009462; epub ahead of print
Canepa M, Kapelios CJ, Benson L, Savarese G, Lund LH
Circ Heart Fail: 08 Aug 2022:101161CIRCHEARTFAILURE121009462; epub ahead of print | PMID: 35938444
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Abstract

Current Approach to the Diagnosis of Sarcopenia in Heart Failure: A Narrative Review on the Role of Clinical and Imaging Assessments.

Mirzai S, Eck BL, Chen PH, Estep JD, Tang WHW
Sarcopenia has been established as a predictor of poor outcomes in various clinical settings. It is particularly prevalent in heart failure, a clinical syndrome that poses significant challenges to health care worldwide. Despite this, sarcopenia remains overlooked and undertreated in cardiology practice. Understanding the currently proposed diagnostic process is paramount for the early detection and treatment of sarcopenia to mitigate downstream adverse health outcomes.



Circ Heart Fail: 04 Aug 2022:101161CIRCHEARTFAILURE121009322; epub ahead of print
Mirzai S, Eck BL, Chen PH, Estep JD, Tang WHW
Circ Heart Fail: 04 Aug 2022:101161CIRCHEARTFAILURE121009322; epub ahead of print | PMID: 35924562
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Abstract

Sequential Interventions for Major Depression and Heart Failure Self-Care: A Randomized Clinical Trial.

Freedland KE, Skala JA, Carney RM, Steinmeyer BC, Rubin EH, Rich MW
Background
Major depression and inadequate self-care are common in patients with heart failure (HF). Little is known about how to intervene when both problems are present. This study examined the efficacy of a sequential approach to treating these problems.
Methods
Stepped Care for Depression in HF was a single-site, single-blind, randomized controlled trial of cognitive behavior therapy (CBT) versus usual care (UC) for major depression in patients with HF. The intensive phase of the CBT intervention lasted between 8 and 16 weeks, depending upon the rate of improvement in depression. All participants received a tailored HF self-care intervention that began 8 weeks after randomization. The intensive phase of the self-care intervention ended at 16 weeks post-randomization. The coprimary outcome measures were the Beck Depression Inventory (version 2) and the Maintenance scale of the Self-Care of HF Index (v6.2) at week 16.
Results
One hundred thirty-nine patients with HF and major depression were enrolled; 70 were randomized to UC and 69 to CBT. At week 16, the patients in the CBT arm scored 4.0 points ([95% CI, -7.3 to -0.8]; P=0.02) lower on the Beck Depression Inventory, version 2 than those in the usual care arm. Mean scores on the Self-Care of HF Index Maintenance scale were not significantly different between the groups ([95% CI, -6.5 to 1.5]; P=0.22).
Conclusions
CBT is more effective than usual care for major depression in patients with HF. However, initiating CBT before starting a tailored HF self-care intervention does not increase the benefit of the self-care intervention.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT02997865.



Circ Heart Fail: 01 Aug 2022; 15:e009422
Freedland KE, Skala JA, Carney RM, Steinmeyer BC, Rubin EH, Rich MW
Circ Heart Fail: 01 Aug 2022; 15:e009422 | PMID: 35973032
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Abstract

Trending Cardiac Biomarkers During Pregnancy in Women With Cardiovascular Disease.

Chang SA, Khakh P, Janzen M, Lee T, ... Rychel V, Grewal J
Background
Clinical utility of cardiac biomarker testing during pregnancy in women with preexisting cardiac disease is not well known. We studied the levels and temporal trends of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-cTnI (high-sensitivity cardiac troponin I) throughout pregnancy in women with preexisting cardiac disease and sought to assess the association between NT-proBNP and hs-cTnI and pregnancy outcomes.
Methods
Three hundred seven pregnant women with preexisting cardiac disease were prospectively recruited. Mixed-effects linear regression analysis was used to compare the NT-proBNP and hs-cTnI levels between time periods and subgroups. Logistic regression analysis adjusted for maternal age and CARPREG II (Cardiac Disease in Pregnancy) risk score assessed the association between NT-proBNP levels and adverse events.
Results
Geometric mean NT-proBNP (95% CI) was stable through pregnancy with a transient significant increase with labor and delivery (101.4 pg/mL [87.1-118.1], 90.2 pg/mL [78.5-103.6], 153.6 pg/mL [126.8-186.1], and 112.2 pg/mL [94.2-133.7] for first/second trimester, third trimester, labor/delivery and postpartum, respectively). We observed a statistically significant difference in the NT-proBNP between women with preserved versus decreased systemic ventricular function, structurally normal versus abnormal heart, modified World Health Organization class 1, 2 versus modified World Health Organization class 3, 4 and no congenital heart disease versus congenital heart disease. Compared to those without events, median (interquartile range) NT-proBNP levels were significantly higher in those who had heart failure (204 pg/mL [51-450] versus 55 pg/mL [31-97]; P=0.001) and preeclampsia (98 pg/mL [40-319] versus 55 pg/mL [31-99]; P=0.027). NT-proBNP, adjusted for age and CARPREG II risk score, was significantly associated with combined heart failure and preeclampsia (adjusted odds ratio, 2.14 [95% CI, 1.48-3.10] per log NT-proBNP increase; P<0.001). NT-proBNP <200 pg/mL had a specificity of 91% and negative predictive value of 95% in predicting combined heart failure and preeclampsia.
Conclusions
NT-proBNP remains steady over the course of pregnancy with a transient increase during labor and delivery with higher levels in subgroups of stable cardiac patients. NT-proBNP level of 200 pg/mL can be used in the diagnosis of heart failure/preeclampsia in the pregnant cardiac population.



Circ Heart Fail: 29 Jul 2022:101161CIRCHEARTFAILURE121009018; epub ahead of print
Chang SA, Khakh P, Janzen M, Lee T, ... Rychel V, Grewal J
Circ Heart Fail: 29 Jul 2022:101161CIRCHEARTFAILURE121009018; epub ahead of print | PMID: 35904022
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Abstract

Medical Therapy for Functional Mitral Regurgitation.

Milwidsky A, Mathai SV, Topilsky Y, Jorde UP
Functional mitral regurgitation (FMR) can be broadly categorized into 2 main groups: ventricular and atrial, which often coexist. The former is secondary to left ventricular remodeling usually in the setting of heart failure with reduced ejection fraction or less frequently due to ischemic papillary muscle remodeling. Atrial FMR develops due to atrial and annular dilatation related to atrial fibrillation/flutter or from increased atrial pressures in the setting of heart failure with preserved ejection fraction. Guideline-directed medical therapy is the first step and prevails as the mainstay in the treatment of FMR. In this review, we address the medical therapeutic options for FMR management and highlight a targeted approach for each FMR category. We further address important clinical and echocardiographic characteristics to aid in determining when medical therapy is expected to have a low yield and an appropriate window for effective interventional approaches exists.



Circ Heart Fail: 13 Jul 2022:101161CIRCHEARTFAILURE122009689; epub ahead of print
Milwidsky A, Mathai SV, Topilsky Y, Jorde UP
Circ Heart Fail: 13 Jul 2022:101161CIRCHEARTFAILURE122009689; epub ahead of print | PMID: 35862021
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Abstract

Transcutaneous Vagus Nerve Stimulation Ameliorates the Phenotype of Heart Failure With Preserved Ejection Fraction Through Its Anti-Inflammatory Effects.

Elkholey K, Niewiadomska M, Morris L, Whyte S, ... Humphrey MB, Stavrakis S
Background
A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction (HFpEF). Low-level transcutaneous vagus nerve stimulation (LLTS) suppresses inflammation in animals and humans, mediated by an α7nAchR (alpha7 nicotinic acetylcholine receptor)-dependent pathway. We examined the effects of LLTS on cardiac function, inflammation, and fibrosis in the presence of α7nAchR pharmacological blockade in a rat model of HFpEF.
Methods
Dahl salt-sensitive rats at 7 weeks of age were treated with high-salt diet for 6 weeks to induce HFpEF, followed by 4 weeks of (1) LLTS, (2) LLTS with the α7nAchR blocker methyllycaconitine, (3) sham, and (4) olmesartan. Blood pressure, cardiac function by echocardiography, heart rate variability, and serum cytokines were measured at 13 and 17 weeks of age. Cardiac fibrosis, inflammatory cell infiltration, and gene expression were determined at 17 weeks.
Results
LLTS attenuated the increase in blood pressure; improved cardiac function; decreased inflammatory cytokines, macrophage infiltration, and fibrosis; and improved survival compared with other groups. Methyllycaconitine attenuated these effects, whereas olmesartan did not improve cardiac function or fibrosis despite maintaining similar blood pressure as LLTS. Heart rate variability was similarly improved in the LLTS and LLTS plus methyllycaconitine groups but remained low in the other groups. LLTS reversed the dysregulated inflammatory signaling pathways in HFpEF hearts.
Conclusions
Neuromodulation with LLTS improved cardiac function in a rat model of HFpEF through its anti-inflammatory and antifibrotic effects. These results provide the basis for further clinical trials in humans.



Circ Heart Fail: 07 Jul 2022:101161CIRCHEARTFAILURE122009288; epub ahead of print
Elkholey K, Niewiadomska M, Morris L, Whyte S, ... Humphrey MB, Stavrakis S
Circ Heart Fail: 07 Jul 2022:101161CIRCHEARTFAILURE122009288; epub ahead of print | PMID: 35862007
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Abstract

Variation in Left Ventricular Assist Device Postdischarge Caregiver Requirements: Results From a Mixed-Methods Study With Equity Implications.

Knoepke CE, Siry-Bove B, Mayton C, Latimer A, ... Matlock DD, Khazanie P
Background
Left ventricular assist device (LVAD) evaluation includes a psychosocial assessment, conducted by social workers (SWs) on the advanced heart failure multidisciplinary team. Postdischarge caregiving plans are central to psychosocial evaluation. Caregiving\'s relationship with LVAD outcomes is mixed, and testing patients\' social resources may disadvantage those from historically undertreated groups. We describe variation in policies defining adequate caregiving plans post-LVAD implant and possible impacts on patients from marginalized groups.
Methods
This was a 2-phase sequential mixed-methods study: (1) phase 1, survey of US-based LVAD SWs, describing assessment structure and policies guiding candidacy outcomes; and (2) phase 2, individual interviews with SWs to further describe how caregiving plan adequacy impacts LVAD candidacy.
Results
Sixty-seven SWs returned surveys (rr=47%) from unique programs. Caregiving plan inadequacy (n=30) was the most common psychosocial dealbreaker. When asked what duration of caregiving is required, 23% indicated ≥3 months, 27% 4 to 12 weeks, and 30% <4 weeks. Two reported no duration requirement, 6 stated an indefinite 24/7 commitment was necessary. Across 22 interviews, SWs mirrored that caregiving plans were the most common psychosocial contraindication. How caregiving is operationalized varied. Participants voiced a tension between extended caregiving improving outcomes and the sense that some people of color, women, or low socioeconomic status patients struggle to meet stringent requirements.
Conclusions
Policies regarding adequate duration of 24/7 caregiving vary, but inadequate caregiving plans are the most common psychosocial contraindication. Participants worry about patients\' ability to meet restrictive requirements, particularly from historically undertreated groups. This highlights a need to operationalize quality caregiving, standardize assessment, and support medically appropriate patients with strained social resources.



Circ Heart Fail: 07 Jul 2022:101161CIRCHEARTFAILURE122009583; epub ahead of print
Knoepke CE, Siry-Bove B, Mayton C, Latimer A, ... Matlock DD, Khazanie P
Circ Heart Fail: 07 Jul 2022:101161CIRCHEARTFAILURE122009583; epub ahead of print | PMID: 35862012
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Impact:

This program is still in alpha version.