Journal: Circ Heart Fail

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Abstract

Temporal Trends and Clinical Trial Characteristics Associated With the Inclusion of Women in Heart Failure Trial Steering Committees: A Systematic Review.

Eliya Y, Whitelaw S, Thabane L, Voors AA, Douglas PS, Van Spall HGC
Background
Trial steering committees (TSCs) steer the conduct of randomized controlled trials (RCTs). We examined the gender composition of TSCs in impactful heart failure RCTs and explored whether trial leadership by a woman was independently associated with the inclusion of women in TSCs.
Methods
We systematically searched MEDLINE, EMBASE, and CINAHL for heart failure RCTs published in journals with impact factor ≥10 between January 2000 and May 2019. We used the Jonckheere-Terpstra test to assess temporal trends and multivariable logistic regression to explore trial characteristics associated with TSC inclusion of women.
Results
Of 403 RCTs that met inclusion criteria, 127 (31.5%) reported having a TSC but 20 of these (15.7%) did not identify members. Among 107 TSCs that listed members, 56 (52.3%) included women and 6 of these (10.7%) restricted women members to the RCT leaders. Of 1213 TSC members, 11.1% (95% CI, 9.4%-13.0%) were women, with no change in temporal trends (P=0.55). Women had greater odds of TSC inclusion in RCTs led by women (adjusted odds ratio, 2.48 [95% CI, 1.05-8.72], P=0.042); this association was nonsignificant when analysis excluded TSCs that restricted women to the RCT leaders (adjusted odds ratio 1.46 [95% CI, 0.43-4.91], P=0.36).
Conclusions
Women were included in 52.3% of TSCs and represented 11.1% of TSC members in 107 heart failure RCTs, with no change in trends since 2000. RCTs led by women had higher adjusted odds of including women in TSCs, partly due to the self-inclusion of RCT leaders in TSCs.



Circ Heart Fail: 19 Jul 2021:CIRCHEARTFAILURE120008064; epub ahead of print
Eliya Y, Whitelaw S, Thabane L, Voors AA, Douglas PS, Van Spall HGC
Circ Heart Fail: 19 Jul 2021:CIRCHEARTFAILURE120008064; epub ahead of print | PMID: 34281362
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Abstract

Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post-Left Ventricular Assist Device Aortic Incompetence.

Shad R, Kaiser AD, Kong S, Fong R, ... Marsden AL, Hiesinger W
Background
Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem.
Methods
Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients\' aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver.
Results
The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, -0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, -0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15-0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, -0.009 to 0.001; P=0.17).
Conclusions
Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.



Circ Heart Fail: 29 Jun 2021; 14:e008034
Shad R, Kaiser AD, Kong S, Fong R, ... Marsden AL, Hiesinger W
Circ Heart Fail: 29 Jun 2021; 14:e008034 | PMID: 34139862
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Abstract

Multiparametric Implantable Cardioverter-Defibrillator Algorithm for Heart Failure Risk Stratification and Management: An Analysis in Clinical Practice.

Calò L, Bianchi V, Ferraioli D, Santini L, ... D\'Onofrio A, Full list of participant centers and investigators
Background
The HeartLogic algorithm combines multiple implantable cardioverter-defibrillator sensors to identify patients at risk of heart failure (HF) events. We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events.
Methods
The HeartLogic feature was activated in 366 implantable cardioverter-defibrillator and cardiac resynchronization therapy implantable cardioverter-defibrillator patients at 22 centers. The median follow-up was 11 months [25th-75th percentile: 6-16]. The HeartLogic algorithm calculates a daily HF index and identifies periods IN alert state on the basis of a configurable threshold.
Results
The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients. The time IN alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations, and 8 patients died of HF during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (hazard ratio, 24.53 [95% CI, 8.55-70.38], P<0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with less HF events (hazard ratio, 0.37 [95% CI, 0.14-0.99], P=0.047). No differences in event rates were observed between in-office and remote alert management.
Conclusions
This multiparametric algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required to effectively manage HeartLogic alerts.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02275637.



Circ Heart Fail: 29 Jun 2021:CIRCHEARTFAILURE120008134; epub ahead of print
Calò L, Bianchi V, Ferraioli D, Santini L, ... D'Onofrio A, Full list of participant centers and investigators
Circ Heart Fail: 29 Jun 2021:CIRCHEARTFAILURE120008134; epub ahead of print | PMID: 34190592
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Abstract

Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit.

Logantha SJRJ, Cai XJ, Yanni J, Jones CB, ... Boyett MR, Hart G
Background
Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs.
Methods
Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used.
Results
Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected.
Conclusions
Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients.



Circ Heart Fail: 29 Jun 2021; 14:e007505
Logantha SJRJ, Cai XJ, Yanni J, Jones CB, ... Boyett MR, Hart G
Circ Heart Fail: 29 Jun 2021; 14:e007505 | PMID: 34190577
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Abstract

Characteristics and Outcomes of Women Developing Heart Failure After Early Stage Breast Cancer Chemotherapy: A Population-Based Matched Cohort Study.

Abdel-Qadir H, Tai F, Croxford R, Austin PC, ... Lee DS, Thavendiranathan P
Background
The prognosis of heart failure (HF) after early stage breast cancer (EBC) treatment with anthracyclines or trastuzumab is not well-characterized.
Methods
Using administrative databases, women diagnosed with HF after receiving anthracyclines or trastuzumab for EBC in Ontario during 2007 to 2017 (the EBC-HF cohort) were categorized by cardiotoxic exposure (anthracycline alone, trastuzumab alone, sequential therapy with both agents) and matched on age with ≤3 cancer-free HF controls to compare baseline characteristics. To study prognosis after HF onset, we conducted a second match on age plus important HF prognostic factors. The cumulative incidence function was used to describe risk of hospitalization or emergency department visits (hospital presentations) for HF and cardiovascular death.
Results
A total of 804 women with EBC developed HF after anthracyclines (n=312), trastuzumab (n=112), or sequential therapy (n=380); they had significantly fewer comorbidities than 2411 age-matched HF controls. After the second match, the anthracycline-HF cohort had a similar 5-year incidence of HF hospital presentations (16.5% [95% CI, 12.0%-21.7%]) as controls (17.1% [95% CI, 14.4%-20.1%]); the 5-year incidence was lower than matched controls for the trastuzumab-HF (9.7% [95% CI, 4.7%-16.9%]; controls 16.4% [95% CI, 12.1%-21.3%]; P=0.03) and sequential-HF cohorts (2.7% [95% CI, 1.4%-4.8%]; controls 10.8% [95% CI, 8.9%-13.0%]; P<0.001). At 5 years, the incidence of cardiovascular death was 2.9% (95% CI, 1.2%-5.9%) in the anthracycline-HF cohort vs. 9.5% (95% CI, 6.9%-12.6%) in controls, and 1.7% (0.6%-3.7%) for women developing HF after trastuzumab vs. 4.3% (95% CI, 3.1-5.8%) for controls.
Conclusions
Women developing HF after cardiotoxic EBC chemotherapy have fewer comorbidities than cancer-free women with HF; trastuzumab-treated women who develop HF have better prognosis than matched HF controls.



Circ Heart Fail: 29 Jun 2021; 14:e008110
Abdel-Qadir H, Tai F, Croxford R, Austin PC, ... Lee DS, Thavendiranathan P
Circ Heart Fail: 29 Jun 2021; 14:e008110 | PMID: 34187164
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Abstract

Comprehensive Proteomics Profiling Reveals Circulating Biomarkers of Hypertrophic Cardiomyopathy.

Shimada YJ, Raita Y, Liang LW, Maurer MS, ... Fifer MA, Reilly MP
Background
Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development of HCM. The objectives were to determine plasma protein biomarkers of HCM and to reveal molecular pathways differentially regulated in HCM.
Methods
We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma proteomics profiling of 1681 proteins. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (ie, the training set). We tested the discriminative ability in independent samples from the other institution (ie, the test set). As an exploratory analysis, we executed pathway analysis of significantly dysregulated proteins. Pathways with false discovery rate <0.05 were declared positive.
Results
The study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83-0.94) in the test set. Pathway analysis revealed that the Ras-MAPK (mitogen-activated protein kinase) pathway, along with its upstream and downstream pathways, was upregulated in HCM. Pathways involved in inflammation and fibrosis-for example, the TGF (transforming growth factor)-β pathway-were also upregulated.
Conclusions
This study serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, revealing circulating biomarkers and exhibiting both novel (eg, Ras-MAPK) and known (eg, TGF-β) pathways differentially regulated in HCM.



Circ Heart Fail: 29 Jun 2021; 14:e007849
Shimada YJ, Raita Y, Liang LW, Maurer MS, ... Fifer MA, Reilly MP
Circ Heart Fail: 29 Jun 2021; 14:e007849 | PMID: 34192899
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Abstract

Liberation From Venoarterial Extracorporeal Membrane Oxygenation: A Review.

Brahmbhatt DH, Daly AL, Luk AC, Fan E, Billia F
Venoarterial extracorporeal membrane oxygenation may be used for circulatory support in cardiogenic shock as a bridge to recovery, a bridge to a ventricular assist device (VAD), or a bridge to transplant. While the determination of potential exit strategies is essential before cannulation, the final determination of a patient\'s options may change, in part, through their in-hospital clinical course. We propose that liberation from venoarterial extracorporeal membrane oxygenation should be conceptualized as a process of discovery in the assessment of a patient\'s underlying clinical status and a key driver of further clinical decision-making. A trial of liberation from support should be considered when the goals of the weaning trial are well-defined and, ideally, in the absence of potentially confounding clinical factors. In this review, we will discuss readiness to wean criteria from venoarterial extracorporeal membrane oxygenation, as well as specific clinical, biochemical, and echocardiographic parameters that may prove useful in determining weaning timing and revealing the patient\'s underlying hemodynamic status and prognosis. The role of various cannula configurations, support devices, and pharmacological adjuncts will also be discussed. Finally, we highlight current gaps in evidence and suggest areas of future research.



Circ Heart Fail: 29 Jun 2021; 14:e007679
Brahmbhatt DH, Daly AL, Luk AC, Fan E, Billia F
Circ Heart Fail: 29 Jun 2021; 14:e007679 | PMID: 34247519
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Abstract

Ex Vivo Assessment of Different Oral Anticoagulant Regimens on Pump Thrombosis in a HeartWare Ventricular Assist Device.

Rao SD, Connor DE, Shehab S, Kerr NP, ... Jansz P, Hayward CS
Background
In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents.
Methods
A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity.
Results
Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127-134.5); in vitro aspirin, 124 (114.5-137); and patients on dabigatran, 131 (130.5-135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5-143.5); in vitro low-dose apixaban, 141 (138.5-142); and patients on apixaban, 140 (138-142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137-150) versus 133.5 (128.5-140) minutes, P=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points.
Conclusions
In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.



Circ Heart Fail: 29 Jun 2021; 14:e007231
Rao SD, Connor DE, Shehab S, Kerr NP, ... Jansz P, Hayward CS
Circ Heart Fail: 29 Jun 2021; 14:e007231 | PMID: 34210157
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Abstract

Avoidable Hospitalization for Heart Failure Among a Cohort of 18- to 64-Year-Old Italian Citizens and Immigrants: Results From the Italian Network for Longitudinal Metropolitan Studies.

Dalla Zuanna T, Cacciani L, Barbieri G, Batzella E, ... Marino C, Canova C
Background
Heart failure (HF) represents a severe public health burden. In Europe, differences in hospitalizations for HF have been found between immigrants and native individuals, with inconsistent results. Immigrants face many barriers in their access to health services, and their needs may be poorly met. We aimed to compare the rates of avoidable hospitalization for HF among immigrants and native individuals in Italy.
Methods
All 18- to 64-year-old residents of Turin, Venice, Reggio Emilia, Modena, Bologna, and Rome between January 1, 2001 and December 31, 2013 were included in this multicenter open-cohort study. Immigrants from high migratory pressure countries (divided by area of origin) were compared with Italian citizens. Age-, sex-, and calendar year-adjusted hospitalization rate ratios and the 95% CIs of avoidable hospitalization for HF by citizenship were estimated using negative binomial regression models. The hospitalization rate ratios were summarized using a random effects meta-analysis. Additionally, we tested the contribution of socioeconomic status to these disparities.
Results
Of the 4 470 702 subjects included, 15.8% were immigrants from high migratory pressure countries. Overall, immigrants showed a nonsignificant increased risk of avoidable hospitalization for HF (hospitalization rate ratio, 1.26 [95% CI, 0.97-1.68]). Risks were higher for immigrants from Sub-Saharan Africa and for males from Northern Africa and Central-Eastern Europe than for their Italian citizen counterparts. Risks were attenuated adjusting for socioeconomic status, although they remained consistent with nonadjusted results.
Conclusions
Adult immigrants from different geographic macroareas had higher risks of avoidable hospitalization for HF than Italian citizens. Possible explanations might be higher risk factors among immigrants and reduced access to primary health care services.



Circ Heart Fail: 29 Jun 2021; 14:e008022
Dalla Zuanna T, Cacciani L, Barbieri G, Batzella E, ... Marino C, Canova C
Circ Heart Fail: 29 Jun 2021; 14:e008022 | PMID: 34235937
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Abstract

ERBB4 and Multiple MicroRNAs That Target ERBB4 Participate in Pregnancy-Related Cardiomyopathy.

Feyen E, Ricke-Hoch M, Van Fraeyenhove J, Vermeulen Z, ... Hilfiker-Kleiner D, De Keulenaer GW
Background
Peripartum cardiomyopathy (PPCM) is a life-threatening disease in women without previously known cardiovascular disease. It is characterized by a sudden onset of heart failure before or after delivery. Previous studies revealed that the generation of a 16-kDa PRL (prolactin) metabolite, the subsequent upregulation of miR-146a, and the downregulation of the target gene Erbb4 is a common driving factor of PPCM.
Methods
miRNA profiling was performed in plasma of PPCM patients (n=33) and postpartum-matched healthy CTRLs (controls; n=36). Elevated miRNAs in PPCM plasma, potentially targeting ERBB4 (erythroblastic leukemia viral oncogene homolog 4), were overexpressed in cardiomyocytes using lentiviral vectors. Next, cardiac function, cardiac morphology, and PPCM phenotype were investigated after recurrent pregnancies of HZ (heterozygous) cardiomyocyte-specific Erbb4 mice (Erbb4F/+ αMHC-Cre+, n=9) with their age-matched nonpregnant CTRLs (n=9-10).
Results
Here, we identify 9 additional highly conserved miRNAs (miR-199a-5p and miR-199a-3p, miR-145a-5p, miR-130a-3p, miR-135a-5p, miR-221-3p, miR-222-3p, miR-23a-3p, and miR19b-3p) that target tyrosine kinase receptor ERBB4 and are over 4-fold upregulated in plasma of PPCM patients at the time of diagnosis. We confirmed that miR-146a, miR-199a-5p, miR-221-3p, miR-222-3p, miR-23a-3p, miR-130a-5p, and miR-135-3p overexpression decreases ERBB4 expression in cardiomyocytes (-29% to -50%; P<0.05). In addition, we demonstrate that genetic cardiomyocyte-specific downregulation of Erbb4 during pregnancy suffices to induce a variant of PPCM in mice, characterized by left ventricular dilatation (postpartum second delivery: left ventricular internal diameter in diastole, +19±7% versus HZ-CTRL; P<0.05), increased atrial natriuretic peptide (ANP) levels (4-fold increase versus HZ-CTRL mice, P<0.001), decreased VEGF (vascular endothelial growth factor) and VE-cadherin levels (-33±17%, P=0.07; -27±20%, P<0.05 versus HZ-CTRL), and histologically enlarged cardiomyocytes (+20±21%, versus HZ-CTRL, P<0.05) but without signs of myocardial apoptosis and inflammation.
Conclusions
ERBB4 is essential to protect the maternal heart from peripartum stress. Downregulation of ERBB4 in cardiomyocytes induced by multiple miRNAs in the peripartum period may be crucial in PPCM pathophysiology. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00998556.



Circ Heart Fail: 29 Jun 2021; 14:e006898
Feyen E, Ricke-Hoch M, Van Fraeyenhove J, Vermeulen Z, ... Hilfiker-Kleiner D, De Keulenaer GW
Circ Heart Fail: 29 Jun 2021; 14:e006898 | PMID: 34247489
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Abstract

Exception Status Listing in the New Adult Heart Allocation System: A New Solution to an Old Problem?

Topkara VK, Clerkin KJ, Fried JA, Griffin J, ... Sayer G, Uriel N
Background
One of the goals of the revised 6-tiered US adult heart allocation policy was to improve risk stratification of patients to lower exception status utilization for transplant listing. We sought to define the characteristics and outcomes of waitlisted patients using exception status and to examine region- and center-level differences in utilization of exception status in the new heart allocation system.
Methods
This retrospective cohort analysis of the United Network for Organ Sharing database included adult waitlisted patients for heart transplant between October 18, 2018, and June 30, 2020, in the United States, stratified by use of exception status versus standard criteria.
Results
Out of 6351 patients, 1907 (30.0%) were waitlisted under exception status. Patients using exception status were more likely to have a nonischemic cause of heart failure, blood type O, United Network for Organ Sharing status 2 at listing and were less likely to have a durable left ventricular assist device at listing. Exception status utilization varied significantly between and within United Network for Organ Sharing regions. Listing by exception criteria was associated with a significantly higher incidence of heart transplantation compared with listing by standard criteria (hazard ratio, 1.25 [1.15-1.38], P<0.001), without increased risk of death or delisting for worsening clinical status (hazard ratio, 0.83 [0.65-1.05], P=0.12) after multivariable adjustment.
Conclusions
The status tiers of the new heart allocation system may not fully capture medical urgency and complexity of waitlisted patients as assessed by transplant physicians and review committees and may limit the ability to develop a heart allocation score.



Circ Heart Fail: 30 May 2021; 14:e007916
Topkara VK, Clerkin KJ, Fried JA, Griffin J, ... Sayer G, Uriel N
Circ Heart Fail: 30 May 2021; 14:e007916 | PMID: 34044577
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Abstract

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

Murphy SP, Prescott MF, Maisel AS, Butler J, ... Solomon SD, Januzzi JL
Background
Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain.
Methods
In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index.
Results
Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures.
Conclusions
Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.



Circ Heart Fail: 30 May 2021; 14:e008410
Murphy SP, Prescott MF, Maisel AS, Butler J, ... Solomon SD, Januzzi JL
Circ Heart Fail: 30 May 2021; 14:e008410 | PMID: 33998243
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Abstract

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

Yang JH, Choi KH, Ko YG, Ahn CM, ... Choi SH, Gwon HC
Background
In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.
Methods
The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality.
Results
In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89-3.94], P<0.001), body mass index <25 kg/m2 (OR, 1.52 [95% CI, 1.08-2.16], P=0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44-3.23], P<0.001), vasoactive-inotrope score >80 (OR, 3.55 [95% CI, 2.54-4.95], P<0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88-5.95], P<0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16-4.63], P<0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07-2.24], P=0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25-2.76], P=0.002) were independent predictors for in-hospital mortality.
Conclusions
The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.



Circ Heart Fail: 30 May 2021; 14:e008141
Yang JH, Choi KH, Ko YG, Ahn CM, ... Choi SH, Gwon HC
Circ Heart Fail: 30 May 2021; 14:e008141 | PMID: 34129366
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Abstract

Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial.

Ferreira JP, Lamiral Z, McMurray JJV, Swedberg K, ... Pitt B, Zannad F
Background
Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms).
Methods
The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used.
Results
The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.50-0.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes.
Conclusions
Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.



Circ Heart Fail: 30 May 2021; 14:e008075
Ferreira JP, Lamiral Z, McMurray JJV, Swedberg K, ... Pitt B, Zannad F
Circ Heart Fail: 30 May 2021; 14:e008075 | PMID: 34129365
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Impact:
Abstract

Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure.

Caravaca Pérez P, Nuche J, Morán Fernández L, Lora D, ... Arribas Ynsaurriaga F, Delgado JF
Background
Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization.
Methods
Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0-9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST.
Results
Median UNa after FST in the 65 patients included was 113 (97-122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P=0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P<0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months.
Conclusions
Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.



Circ Heart Fail: 30 May 2021; 14:e008166
Caravaca Pérez P, Nuche J, Morán Fernández L, Lora D, ... Arribas Ynsaurriaga F, Delgado JF
Circ Heart Fail: 30 May 2021; 14:e008166 | PMID: 34129364
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Impact:
Abstract

Remote Hemodynamic Monitoring Equally Reduces Heart Failure Hospitalizations in Women and Men in Clinical Practice: A Sex-Specific Analysis of the CardioMEMS Post-Approval Study.

DeFilippis EM, Henderson J, Axsom KM, Costanzo MR, ... Brett ME, Givertz MM
Background
Response to pharmacological and device-based therapy for heart failure (HF) may vary by sex. We examined sex differences in response to ambulatory hemodynamic monitoring in clinical practice using the CardioMEMS PAS (Post-Approval Study).
Methods
The CardioMEMS PAS was a prospective, single-arm, multicenter, open-label study of 1200 adults with New York Heart Association class III HF and at least 1 HF hospitalization (HFH) within 12 months who underwent pulmonary artery pressure sensor implantation between 2014 and 2017. Changes in pulmonary artery pressure over time were stratified by ejection fraction <40% and sex. Clinical outcomes including HFH rate at 12 months, 1-year mortality, and quality of life were examined in women and men.
Results
Four hundred fifty-two women (38% of total) enrolled in the PAS were less likely to be White (78% versus 86%) and more likely to have nonischemic cardiomyopathy (44% versus 34%) and had significantly higher SBP (132 versus 124 mm Hg), mean ejection fraction (44% versus 36%), and pulmonary vascular resistance (3.2 versus 2.6 WU) than men (P<0.001 for all). There were similar reductions in pulmonary artery pressure from baseline to 12 months in both men and women for the whole cohort and for subgroups with HF with reduced ejection fraction and HF with preserved ejection fraction. Both sexes experienced significant decreases in HFH over 12 months (men: HR, 0.46 [95% CI, 0.40-0.52]; women: HR, 0.39 [95% CI, 0.33-0.46]). In adjusted models, there were no significant differences in change in HFH between men and women (interaction P=0.13) or all-cause mortality at 1 year (adjusted HR, 1.25 [95% CI, 0.88-1.77]).
Conclusions
Women and men enrolled in the CardioMEMS PAS had similar reductions from baseline in pulmonary artery pressure over 1 year and experienced similar reductions in HFH. Hemodynamic monitoring provides similar benefit with regard to HF events in both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02279888.



Circ Heart Fail: 30 May 2021; 14:e007892
DeFilippis EM, Henderson J, Axsom KM, Costanzo MR, ... Brett ME, Givertz MM
Circ Heart Fail: 30 May 2021; 14:e007892 | PMID: 34129363
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Impact:
Abstract

Cardiolipin Remodeling Defects Impair Mitochondrial Architecture and Function in a Murine Model of Barth Syndrome Cardiomyopathy.

Zhu S, Chen Z, Zhu M, Shen Y, ... Kunfu O, Fang X
Background
Cardiomyopathy is a major clinical feature in Barth syndrome (BTHS), an X-linked mitochondrial lipid disorder caused by mutations in Tafazzin (TAZ), encoding a mitochondrial acyltransferase required for cardiolipin remodeling. Despite recent description of a mouse model of BTHS cardiomyopathy, an in-depth analysis of specific lipid abnormalities and mitochondrial form and function in an in vivo BTHS cardiomyopathy model is lacking.
Methods
We performed in-depth assessment of cardiac function, cardiolipin species profiles, and mitochondrial structure and function in our newly generated Taz cardiomyocyte-specific knockout mice and Cre-negative control mice (n≥3 per group).
Results
Taz cardiomyocyte-specific knockout mice recapitulate typical features of BTHS and mitochondrial cardiomyopathy. Fewer than 5% of cardiomyocyte-specific knockout mice exhibited lethality before 2 months of age, with significantly enlarged hearts. More than 80% of cardiomyocyte-specific knockout displayed ventricular dilation at 16 weeks of age and survived until 50 weeks of age. Full parameter analysis of cardiac cardiolipin profiles demonstrated lower total cardiolipin concentration, abnormal cardiolipin fatty acyl composition, and elevated monolysocardiolipin to cardiolipin ratios in Taz cardiomyocyte-specific knockout, relative to controls. Mitochondrial contact site and cristae organizing system and F1F0-ATP synthase complexes, required for cristae morphogenesis, were abnormal, resulting in onion-shaped mitochondria. Organization of high molecular weight respiratory chain supercomplexes was also impaired. In keeping with observed mitochondrial abnormalities, seahorse experiments demonstrated impaired mitochondrial respiration capacity.
Conclusions
Our mouse model mirrors multiple physiological and biochemical aspects of BTHS cardiomyopathy. Our results give important insights into the underlying cause of BTHS cardiomyopathy and provide a framework for testing therapeutic approaches to BTHS cardiomyopathy, or other mitochondrial-related cardiomyopathies.



Circ Heart Fail: 30 May 2021; 14:e008289
Zhu S, Chen Z, Zhu M, Shen Y, ... Kunfu O, Fang X
Circ Heart Fail: 30 May 2021; 14:e008289 | PMID: 34129362
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Impact:
Abstract

Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis.

Yuzefpolskaya M, Bohn B, Javaid A, Mondellini GM, ... Colombo PC, Demmer RT
Background
Trimethylamine N-oxide (TMAO)-a gut-derived metabolite-is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis.
Methods
We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity.
Results
ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] µM, respectively; all P<0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity.
Conclusions
TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.



Circ Heart Fail: 30 May 2021; 14:e007909
Yuzefpolskaya M, Bohn B, Javaid A, Mondellini GM, ... Colombo PC, Demmer RT
Circ Heart Fail: 30 May 2021; 14:e007909 | PMID: 34129361
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Impact:
Abstract

Clinical Outcomes Associated With Acute Mechanical Circulatory Support Utilization in Heart Failure Related Cardiogenic Shock.

Hernandez-Montfort J, Sinha SS, Thayer KL, Whitehead EH, ... Burkhoff D, Kapur NK
Background
Cardiogenic shock occurring in the setting of advanced heart failure (HF-CS) is increasingly common. However, recent studies have focused almost exclusively on acute myocardial infarction-related CS. We sought to define clinical, hemodynamic, metabolic, and treatment parameters associated with clinical outcomes among patients with HF-CS, using data from the Cardiogenic Shock Working Group registry.
Methods
Patients with HF-CS were identified from the multicenter Cardiogenic Shock Working Group registry and divided into 3 outcome categories assessed at hospital discharge: mortality, heart replacement therapy (HRT: durable ventricular assist device or orthotopic heart transplant), or native heart survival. Clinical characteristics, hemodynamic, laboratory parameters, drug therapies, acute mechanical circulatory support device (AMCS) utilization, and Society of Cardiovascular Angiography and Intervention stages were compared across the 3 outcome cohorts.
Results
Of the 712 patients with HF-CS identified, 180 (25.3%) died during their index admission, 277 (38.9%) underwent HRT (durable ventricular assist device or orthotopic heart transplant), and 255 (35.8%) experienced native heart survival without HRT. Patients who died had the highest right atrial pressure and heart rate and the lowest mean arterial pressure of the 3 outcome groups (P<0.01 for all). Biventricular and isolated left ventricular congestion were common among patients who died or underwent HRT, respectively. Lactate, blood urea nitrogen, serum creatinine, and aspartate aminotransferase were highest in patients with HF-CS experiencing in-hospital death. Intraaortic balloon pump was the most commonly used AMCS device in the overall cohort and among patients receiving HRT. Patients receiving >1 AMCS device had the highest in-hospital mortality rate irrespective of the number of vasoactive drugs used. Mortality increased with deteriorating Society of Cardiovascular Angiography and Intervention stages (stage B: 0%, stage C: 10.7%, stage D: 29.4%, stage E: 54.5%, 1-way ANOVA=<0.001).
Conclusions
Patients with HF-CS experiencing in-hospital mortality had a high prevalence of biventricular congestion and markers of end-organ hypoperfusion. Substantial heterogeneity exists with use of AMCS in HF-CS with intraaortic balloon pump being the most common device used and high rates of in-hospital mortality after exposure to >1 AMCS device.



Circ Heart Fail: 29 Apr 2021; 14:e007924
Hernandez-Montfort J, Sinha SS, Thayer KL, Whitehead EH, ... Burkhoff D, Kapur NK
Circ Heart Fail: 29 Apr 2021; 14:e007924 | PMID: 33905259
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Impact:
Abstract

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages.

Shah P, Psotka M, Taleb I, Alharethi R, ... Kfoury AG, Drakos SG
Background
Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD.
Methods
The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders.
Results
Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively.
Conclusions
Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.



Circ Heart Fail: 29 Apr 2021; 14:e007991
Shah P, Psotka M, Taleb I, Alharethi R, ... Kfoury AG, Drakos SG
Circ Heart Fail: 29 Apr 2021; 14:e007991 | PMID: 33947201
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Impact:
Abstract

Current Limitations of Invasive Exercise Hemodynamics for the Diagnosis of Heart Failure With Preserved Ejection Fraction.

Baratto C, Caravita S, Soranna D, Faini A, ... Parati G, Vachiéry JL
Background
Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWPexp) ≥25 mm Hg; (2) PAWPexp/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistanceavg >3 WU, PAWPavg ≥20 mm Hg.
Methods
Fifty-seven patients with unexplained dyspnea (70% women, 70±9 years) underwent exercise cardiac catheterization. The difference between end-expiratory and averaged hemodynamic values, as well as the concordance among the 3 hemodynamic definitions of HFpEF, were assessed.
Results
End-expiratory hemodynamics measurements were higher than values averaged across the respiratory cycle. During exercise, a larger proportion of patients exceeded the threshold of 25 mm Hg for PAWPexp rather than for PAWPavg (70% versus 53%, P<0.01). The concordance of 3/3 HFpEF exercise hemodynamic criteria was recorded in 70% of patients. PAWPexp/cardiac output slope identified HFpEF more frequently than the other 2 criteria (81% versus 64% to 69%), incorporating over 97% of abnormal responses to the latter. Patients with 3/3 positive criteria had worse clinical, gas-exchange, and hemodynamic profiles.
Conclusions
Respiratory pressure swings impact on the exercise hemodynamic definitions of HFpEF that provide discordant results in 30% of patients. Equivocal diagnoses of HFpEF might be limited by adopting the most sensitive and inclusive criterion alone (ie, PAWPexp/cardiac output slope).



Circ Heart Fail: 29 Apr 2021; 14:e007555
Baratto C, Caravita S, Soranna D, Faini A, ... Parati G, Vachiéry JL
Circ Heart Fail: 29 Apr 2021; 14:e007555 | PMID: 33951935
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Impact:
Abstract

Bridging With Extracorporeal Membrane Oxygenation Under the New Heart Allocation System: A United Network for Organ Sharing Database Analysis.

Nordan T, Critsinelis AC, Mahrokhian SH, Kapur NK, ... Couper GS, Kawabori M
Background
The effect of the new donor heart allocation system on survival following bridging to transplantation with venous-arterial extracorporeal membrane oxygenation remains unknown. The new allocation system places extracorporeal membrane oxygenation-supported candidates at the highest status.
Methods
The United Network for Organ Sharing database was queried for adults bridged to single-organ heart transplantation with extracorporeal membrane oxygenation from October 2006 to February 2020. Association between implementation of the new system and recipient survival was analyzed using Kaplan-Meier estimates, Cox proportional hazards models, and propensity score matching.
Results
Of 364 recipients included, 173 and 191 were transplanted under new and old systems, respectively. Compared with the old system, waitlist time was halved under the new system (5 versus 10 days, P<0.01); recipients also demonstrated lower rates of prior cardiac surgery (32.9% versus 44.5%, P=0.03) and preoperative ventilation (30.6% versus 42.4%, P=0.02). Unadjusted 180-day survival was 90.2% (95% CI, 84.7%-94.2%) and 69.6% (95% CI, 62.6%-76.1%) under the new and old systems, respectively. Cox proportional hazards analysis demonstrated listing and transplantation under the new system to be an independent predictor of post-transplant survival (adjusted hazard ratio, 0.34 [95% CI 0.20-0.59]). Propensity score matching demonstrated a similar trend (hazard ratio, 0.36 [95% CI, 0.19-0.66]). Candidates listed under the new system were significantly less likely to experience waitlist mortality or deterioration (subhazard ratio, 0.38 [95% CI, 0.25-0.58]) and more likely to survive to transplant (subhazard ratio, 4.29 [95% CI, 3.32-5.54]).
Conclusions
Recipients transplanted following extracorporeal membrane oxygenation bridging to transplantation under the new system achieve greater 180-day survival compared with the old and demonstrate less preoperative comorbidity. Waitlist outcomes have also improved significantly under the new allocation system.



Circ Heart Fail: 29 Apr 2021; 14:e007966
Nordan T, Critsinelis AC, Mahrokhian SH, Kapur NK, ... Couper GS, Kawabori M
Circ Heart Fail: 29 Apr 2021; 14:e007966 | PMID: 33951934
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Impact:
Abstract

Estimated Health Care Utilization and Expenditures in Individuals With Heart Failure From the Medical Expenditure Panel Survey.

Klein S, Jiang S, Morey JR, Pai A, ... Lala A, Ferket BS
Background
Heart failure (HF) constitutes a growing burden for public health and the US health care system. While the prevalence of HF is increasing, differences in health care utilization and expenditures within various sociodemographic groups remain poorly defined.
Methods
We used the Medical Expenditure Panel Survey to assess annual health care utilization and expenditures from 2012 to 2017. Health care utilization was based on the annual frequency of various health care encounters. Annual total and out-of-pocket expenditures were evaluated for hospital inpatient stays, emergency room visits, outpatient visits, office-based medical provider visits, prescribed medicines, dental visits, home health aid visits, and other medical expenses. We performed univariable and multivariable regression analysis based on patient characteristics including sociodemographic and comorbidity variables.
Results
Our results showed that total health care expenditures among patients with HF were $21 177 (95% CI, $18 819-$24 736) per year as compared with $5652 (95% CI, $5469-$5837) in those without HF (P<0.001). Total expenditures within the population with HF were primarily being driven by expenditures associated with inpatient hospitalizations. Increasing number of comorbid conditions was associated with significant increases in total health care expenditures. Older age, female sex, earlier study years, number of comorbidities, higher level of education, and increasing family income brackets independently raised out-of-pocket expenditures.
Conclusions
Our findings of increased health care utilization and expenditures based on sex, age, increasing number of comorbidities, wealthier income status, and increased education attainment level may be used for efforts aimed at better distributing health care resources to improve health outcomes in HF.



Circ Heart Fail: 29 Apr 2021; 14:e007763
Klein S, Jiang S, Morey JR, Pai A, ... Lala A, Ferket BS
Circ Heart Fail: 29 Apr 2021; 14:e007763 | PMID: 33980040
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Impact:
Abstract

Intersection of Heart Failure and Pregnancy: Beyond Peripartum Cardiomyopathy.

DeFilippis EM, Haythe JH, Walsh MN, Kittleson MM
Heart failure (HF) is a leading cause of morbidity and mortality in pregnant women in the United States. Although peripartum cardiomyopathy is the most common diagnosis for pregnant women with HF, women with preexisting cardiomyopathies and systolic dysfunction are also at risk as the hemodynamic demands of pregnancy can lead to decompensation, arrhythmia, and rarely death. The differential diagnosis of HF in pregnancy is broad and includes Takotsubo or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, such as familial cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or left ventricular noncompaction. This review will explore the implications of pregnancy in women with preexisting cardiomyopathies and de novo HF, risk assessment and preconception planning, decisions about contraception, the safety of HF medications and implantable cardioverter-defibrillators during pregnancy, pregnancy in women with left ventricular assist devices and following heart transplantation.



Circ Heart Fail: 29 Apr 2021; 14:e008223
DeFilippis EM, Haythe JH, Walsh MN, Kittleson MM
Circ Heart Fail: 29 Apr 2021; 14:e008223 | PMID: 33980039
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Impact:
Abstract

Randomized Placebo-Controlled Trial of Ferric Carboxymaltose in Heart Failure With Iron Deficiency: Rationale and Design.

Mentz RJ, Ambrosy AP, Ezekowitz JA, Lewis GD, ... Hernandez AF, HEART-FID Trial Investigators
Background
Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early and sustained improvement in patient-reported outcomes and functional capacity in patients with HF with reduced ejection fraction with ID, yet morbidity and mortality data are limited.
Methods
The objective of the HEART-FID trial (Ferric Carboxymaltose in Heart Failure With Iron Deficiency) is to assess efficacy and safety of ferric carboxymaltose compared with placebo as treatment for symptomatic HF with reduced ejection fraction with ID. HEART-FID is a multicenter, randomized, double-blind, placebo-controlled trial enrolling ≈3014 patients at ≈300 international centers. Eligible patients are aged ≥18 years in stable chronic HF with New York Heart Association functional class II to IV symptoms, ejection fraction ≤40%, ID (ferritin <100 ng/mL or ferritin 100-300 ng/mL with a transferrin saturation <20%), and documented HF hospitalization or elevated N-terminal pro-brain natriuretic peptide. Consented patients are assigned to ferric carboxymaltose or placebo at baseline, with repeated visits/assessments every 6 months for additional study drug based on hemoglobin and iron indices for the trial duration. The primary end point is a hierarchical composite of death and HF hospitalization at 12 months and change from baseline to 6 months in the 6-minute walk test distance.
Conclusions
The HEART-FID trial will inform clinical practice by clarifying the role of long-term treatment with intravenous ferric carboxymaltose, added to usual care, in ambulatory patients with symptomatic HF with reduced ejection fraction with ID. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.



Circ Heart Fail: 29 Apr 2021; 14:e008100
Mentz RJ, Ambrosy AP, Ezekowitz JA, Lewis GD, ... Hernandez AF, HEART-FID Trial Investigators
Circ Heart Fail: 29 Apr 2021; 14:e008100 | PMID: 34003690
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Impact:
Abstract

Association of Health Insurance Payer Type and Outcomes After Durable Left Ventricular Assist Device Implantation: An Analysis of the STS-INTERMACS Registry.

Khatana SAM, Hanff TC, Nathan AS, Dayoub EJ, ... Giri J, Groeneveld PW
Background
Due to the high cost of left ventricular assist device (LVAD) therapy, payer type may be an important factor in determining eligibility. How payer type influences outcomes after LVAD implantation is unclear. We, therefore, aimed to study the association of health insurance payer type with outcomes after durable LVAD implantation.
Methods
Using STS-INTERMACS (Society of Thoracic Surgeons-Interagency Registry for Mechanically Assisted Circulatory Support), we studied nonelderly adults receiving a durable LVAD from 2016 to 2018 and compared all-cause mortality and postindex hospitalization adverse event episode rate by payer type. Multivariable Fine-Gray and generalized linear models were used to compare the outcomes.
Results
Of the 3251 patients included, 26.0% had Medicaid, 24.9% had Medicare alone, and 49.1% had commercial insurance. Compared with commercially insured patients, mortality did not differ for patients with Medicaid (subdistribution hazard ratio, 1.00 [95% CI, 0.75-1.34], P=0.99) or Medicare (subdistribution hazard ratio, 1.09 [95% CI, 0.84-1.41], P=0.52). Medicaid was associated with a significantly lower adjusted incidence rate (incidence rate ratio, 0.88 [95% CI, 0.78-0.99], P=0.041), and Medicare was associated with a significantly higher adjusted incidence rate (incidence rate ratio, 1.16 [95% CI, 1.03-1.30], P=0.011) of adverse event episodes compared with commercially insured patients.
Conclusions
All-cause mortality after durable LVAD implantation did not differ significantly by payer type. Payer type was associated with the rate of adverse events, with Medicaid associated with a significantly lower rate, and Medicare with a significantly higher rate of adverse event episodes compared with commercially insured patients.



Circ Heart Fail: 29 Apr 2021; 14:e008277
Khatana SAM, Hanff TC, Nathan AS, Dayoub EJ, ... Giri J, Groeneveld PW
Circ Heart Fail: 29 Apr 2021; 14:e008277 | PMID: 33993721
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Impact:

This program is still in alpha version.