Topic: Heart Failure

Abstract

Targeting Cyclic Guanosine Monophosphate to Treat Heart Failure: JACC Review Topic of the Week.

Emdin M, Aimo A, Castiglione V, Vergaro G, ... Metra M, Senni M

The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)-GMP-phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF. Other strategies to increase tissue cyclic guanosine monophosphate have been attempted, such as PDE-3 or PDE-5 inhibition (with negative or neutral results), NO-independent soluble guanylate cyclase (sGC) activation, or enhancement of sGC sensitivity to endogenous NO. Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Oct 2020; 76:1795-1807
Emdin M, Aimo A, Castiglione V, Vergaro G, ... Metra M, Senni M
J Am Coll Cardiol: 12 Oct 2020; 76:1795-1807 | PMID: 33032741
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Abstract

A Unique Population of Regulatory T Cells in Heart Potentiates Cardiac Protection from Myocardial Infarction.

Xia N, Lu Y, Gu M, Li N, ... Yang X, Cheng X

Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in parenchymal tissues and maintaining local homeostasis. However, the existence, unique phenotype and function of so-called tissue Tregs in the heart remain unclear.In mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury (I/R injury) or cardiac cryoinjury, the dynamic accumulation of Tregs in the injured myocardium was monitored. The bulk RNA-sequencing was performed to analyze the transcriptomic characteristics of Tregs from the injured myocardium after MI or I/R injury. Photoconversion, parabiosis, single-cell TCR sequencing and adoptive transfer were applied to determine the source of heart Tregs. The involvement of the interleukin (IL)-33/ST2 axis and secreted acidic cysteine rich glycoprotein (Sparc), a molecule upregulated in heart Tregs, was further evaluated in functional assays.We showed that Tregs were highly enriched in the myocardium of MI, I/R injury and cryoinjury mice. Transcriptomic data revealed that Tregs isolated from the injured hearts had plenty of differentially expressed transcripts compared to their lymphoid counterparts including heart draining lymphoid nodes, with a phenotype of promoting infarct repair, indicating a unique characteristic. The heart Tregs were accumulated mainly due to recruitment from circulating Treg pool, while local proliferation also contributed to their expansion. Moreover, a remarkable case of repeatedly detected TCR of heart Tregs, more than that of spleen Tregs, suggests a model of clonal expansion. Besides, HeliosNrp-1 phenotype proved the mainly thymic origin of heart Tregs, with a small contribution of phenotypic conversion of conventional CD4 T cells (Tconvs), proved by the analysis of TCR repertoires and Tconvs adoptive transfer experiments. Notably, the IL-33/ST2 axis was essential for sustaining heart Treg populations. Finally, we demonstrated that Sparc, which was highly expressed by heart Tregs, acted as a critical factor to protect the heart against MI by increasing collagen content and boosting maturation in the infarct zone.We identified and characterized a phenotypically and functionally unique population of heart Tregs, which may lay the foundation to harness Tregs for cardioprotection in MI and other cardiac diseases.



Circulation: 27 Sep 2020; epub ahead of print
Xia N, Lu Y, Gu M, Li N, ... Yang X, Cheng X
Circulation: 27 Sep 2020; epub ahead of print | PMID: 32985264
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Abstract

Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients with Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial.

Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, ... McGuire DK,

In patients with type 2 diabetes mellitus (T2DM), sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes.VERTIS CV, a double-blind, placebo-controlled trial, randomized patients with T2DM and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF/CV death, overall and stratified by prespecified characteristics. Cox proportional hazard modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF/CV death events.8246 patients were randomized to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pre-trial ejection fraction (EF) available, including n=959 with EF≤45%. Ertugliflozin did not significantly reduce first HHF/CV death (HR, 0.88; 95% CI, 0.75, 1.03). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70; 95% CI, 0.54, 0.90; =0.006). Prior HF did not modify this effect (HF: HR, 0.63; 95% CI, 0.44, 0.90; no HF: HR, 0.79; 95% CI, 0.54, 1.15;interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF≤45% vs preserved EF>45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF≤45% (HR, 0.48; 95% CI, 0.30, 0.76) versus EF>45% (HR, 0.86; 95% CI, 0.58, 1.29). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in three populations with baseline eGFR<60mL/min/1.73m, albuminuria, and diuretic use (eachinteraction<0.05). Ertugliflozin reduced total events of HHF (RR, 0.70; 95% CI, 0.56, 0.87) and total HHF/CV death (RR, 0.83; 95% CI, 0.72, 0.96).In patients with T2DM with or without baseline HF, ertugliflozin reduced risk for first and total HHF and total HHF/CV death, adding further support for the use of SGLT2 inhibitors in primary and secondary prevention of HHF.URL: https://clinicaltrials.gov Unique Identifier: NCT01986881.



Circulation: 06 Oct 2020; epub ahead of print
Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, ... McGuire DK,
Circulation: 06 Oct 2020; epub ahead of print | PMID: 33026243
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Abstract

Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure with Preserved Ejection Fraction: Results from the PROMIS-HFpEF Study.

Sanders-van Wijk S, Tromp J, Beussink-Nelson L, Hage C, ... Lam CSP, Shah SJ

A systemic pro-inflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.In 228 HFpEF patients from the multicenter PROMIS-HFpEF study, 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component (PC) analysis to summarize 47 proteins knownto be involved in inflammation. In an inductive approach, we performed unbiased weighted co-expression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without HF.Comorbidity burden was associated with abnormal cardiac structure/function and with PCs/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e\' ratio, and tricuspid regurgitation (TR) velocity; and worse right ventricular function (tricuspid annular plane systolic excursion [TAPSE] and right ventricular. [RV] free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19-35%), E/e\' ratio (18-29%), TR velocity (27-41%), and tricuspid annular plane systolic excursion (13%) (P<0.05 for all) but not RV free wall strain. TNF-R1, UPAR, IGFBP-7 and GDF-15 were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort.Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and RV dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.



Circulation: 08 Oct 2020; epub ahead of print
Sanders-van Wijk S, Tromp J, Beussink-Nelson L, Hage C, ... Lam CSP, Shah SJ
Circulation: 08 Oct 2020; epub ahead of print | PMID: 33034202
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Abstract

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Results of DAPA-HF.

Jhund PS, Solomon SD, Docherty KF, Heerspink HJL, ... Sjöstrand M, McMurray JJV

Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization.HFrEF patients with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (CV death or worsening HF) according to eGFR category at baseline (<60 and ≥60 ml/min/1.73m) as well as using eGFR at baseline as a continuous measure. Secondary cardiovascular outcomes and a pre-specified composite renal outcome (≥ 50% sustained decline eGFR, end stage renal disease (ESRD) or renal death) were also examined, along with decline in eGFR over time.Of 4742 with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% confidence interval (CI)) for the primary endpoint in patients with CKD was 0.71 (0.59, 0.86) vs. 0.77 (0.64, 0.93) in those with an eGFR ≥60 ml/min/1.73m (interaction p=0.54). The composite renal outcome was not reduced by dapagliflozin (HR=0.71, 95% CI 0.44, 1.16; p=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.41, -0.78) vs. placebo -2.87 (-3.19, -2.55) ml/min/1.73m per year (p<0.001). This was observed in those with and without type 2 diabetes (p for interaction=0.92)Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes.https://clinicaltrials.gov Unique Identifier: NCT03036124.



Circulation: 11 Oct 2020; epub ahead of print
Jhund PS, Solomon SD, Docherty KF, Heerspink HJL, ... Sjöstrand M, McMurray JJV
Circulation: 11 Oct 2020; epub ahead of print | PMID: 33040613
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Abstract

Redox-Resistant SERCA Attenuates Oxidant-Stimulated Mitochondrial Calcium and Apoptosis in Cardiac Myocytes and Pressure Overload-Induced Myocardial Failure in Mice.

Goodman JB, Qin F, Morgan R, Chambers JM, ... Cohen RA, Colucci WS

Sarco(endo)plasmic reticulum calcium ATPase (SERCA) is regulated by oxidative post-translational modifications at cysteine 674 (C674). Since sarcoplasmic reticulum (SR) calcium has been shown to play a critical role in mediating mitochondrial dysfunction in response to reactive oxygen species (ROS), we hypothesized that SERCA oxidation at C674 would modulate the effects of ROS on mitochondrial calcium and mitochondria-dependent apoptosis in cardiac myocytes.Adult rat ventricular myocytes (ARVM) expressing wild-type (WT) SERCA2b or a redox-insensitive mutant in which C674 is replaced by serine (C674S) were exposed to HO (100 M). Free mitochondrial calcium concentration was measured in ARVM using a genetically-targeted fluorescent probe and SR calcium content was assessed by measuring caffeine-stimulated release. Mice with heterozygous knock-in of the SERCA C674S mutation (SKI) were subjected to chronic ascending aortic constriction (AAC).In ARVM expressing WT SERCA, HO caused a 25% increase in mitochondrial calcium concentration that was associated with a 50% decrease in SR calcium content, both of which were prevented by the ryanodine receptor inhibitor tetracaine. In cells expressing the C674S mutant, basal SR calcium content was decreased by 31% and the HO-stimulated rise in mitochondrial calcium concentration was attenuated by 40%. In WT cells, HO caused cytochrome c release and apoptosis, both of which were prevented in C674S-expressing cells. In myocytes from SKI mice, basal SERCA activity and SR calcium content were decreased. To test the effect of C674 oxidation on apoptosis , SKI mice were subjected to chronic AAC. In WT mice, AAC caused myocyte apoptosis, LV dilation and systolic failure - all of which were inhibited in SKI mice.Redox activation of SERCA C674 regulates basal SR calcium content thereby mediating the pathologic ROS-stimulated rise in mitochondrial calcium required for myocyte apoptosis and myocardial failure.



Circulation: 19 Oct 2020; epub ahead of print
Goodman JB, Qin F, Morgan R, Chambers JM, ... Cohen RA, Colucci WS
Circulation: 19 Oct 2020; epub ahead of print | PMID: 33076678
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Abstract

Effect of Empagliflozin on the Clinical Stability of Patients with Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial.

Packer M, Anker SD, Butler J, Filippatos GS, ... Zannad F,

Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure.We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints.Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001.In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy.URL: https://clinicaltrials.gov Unique Identifier: NCT03057977.



Circulation: 20 Oct 2020; epub ahead of print
Packer M, Anker SD, Butler J, Filippatos GS, ... Zannad F,
Circulation: 20 Oct 2020; epub ahead of print | PMID: 33081531
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Abstract

Heart Failure and Atrial Fibrillation Modify the Associations of Nocturnal Blood Pressure Dipping Pattern With Mortality in Hemodialysis Patients.

Mayer CC, Schmaderer C, Loutradis C, Matschkal J, ... Wassertheurer S, Sarafidis PA

Heart failure (HF), hypertension, and abnormal nocturnal blood pressure dipping are highly prevalent in hemodialysis patients. Atrial fibrillation (AF) and HF might be important mediators for the association of abnormal dipping patterns with worse prognosis. Thus, the aim of this study is to investigate the association of dipping with mortality in hemodialysis patients and to assess the influence of AF and HF. In total, 525 hemodialysis patients underwent 24-hour ambulatory blood pressure monitoring. All-cause and cardiovascular mortality served as end points. Patients were categorized according to their systolic dipping pattern (dipper, nondipper, and reverse dipper). Cox regression analysis was performed to determine the association between dipping pattern and study end points with dipping as reference. Subgroup analysis was performed for patients with and without AF or HF. In total, 185 patients with AF or HF and 340 patients without AF or HF were included. During a median follow-up of 37.8 months, 177 patients died; 81 from cardiovascular causes. Nondipping and reverse dipping were significantly associated with all-cause mortality in the whole cohort (nondipper: hazard ratio, 1.95 [1.22-3.14]; =0.006; reverse dipper: hazard ratio, 2.31 [1.42-3.76]; <0.001) and in patients without AF or HF (nondipper: hazard ratio, 2.78 [1.16-6.66]; =0.02; reverse dipper: hazard ratio, 4.48 [1.87-10.71]; <0.001) but not in patients with AF or HF. For cardiovascular mortality, associations were again significant in patients without AF or HF and in the whole cohort. The observed associations remained significant after adjustment for possible confounders. This study provides well-powered evidence for the association between abnormal dipping patterns and mortality in hemodialysis patients and suggests that HF or AF modifies this association.



Hypertension: 29 Sep 2020; 76:1231-1239
Mayer CC, Schmaderer C, Loutradis C, Matschkal J, ... Wassertheurer S, Sarafidis PA
Hypertension: 29 Sep 2020; 76:1231-1239 | PMID: 32862707
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Abstract

Heart Failure in Women With Hypertensive Disorders of Pregnancy: Insights From the Cardiovascular Disease in Norway Project.

Honigberg MC, Riise HKR, Daltveit AK, Tell GS, ... Natarajan P, Rich-Edwards JW

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84-2.35], =0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50-2.68, <0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.



Hypertension: 30 Oct 2020; 76:1506-1513
Honigberg MC, Riise HKR, Daltveit AK, Tell GS, ... Natarajan P, Rich-Edwards JW
Hypertension: 30 Oct 2020; 76:1506-1513 | PMID: 32829667
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Abstract

Clinical and Proteomic Correlates of Plasma ACE2 (Angiotensin-Converting Enzyme 2) in Human Heart Failure.

Chirinos JA, Cohen JB, Zhao L, Hanff T, ... Gordon DA, Cappola T

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.



Hypertension: 27 Sep 2020:HYPERTENSIONAHA12015829; epub ahead of print
Chirinos JA, Cohen JB, Zhao L, Hanff T, ... Gordon DA, Cappola T
Hypertension: 27 Sep 2020:HYPERTENSIONAHA12015829; epub ahead of print | PMID: 32981365
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Abstract

Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure.

Wilcox CS, Testani JM, Pitt B

Diuretic resistance implies a failure to increase fluid and sodium (Na) output sufficiently to relieve volume overload, edema, or congestion, despite escalating doses of a loop diuretic to a ceiling level (80 mg of furosemide once or twice daily or greater in those with reduced glomerular filtration rate or heart failure). It is a major cause of recurrent hospitalizations in patients with chronic heart failure and predicts death but is difficult to diagnose unequivocally. Pharmacokinetic mechanisms include the low and variable bioavailability of furosemide and the short duration of all loop diuretics that provides time for the kidneys to restore diuretic-induced Na losses between doses. Pathophysiological mechanisms of diuretic resistance include an inappropriately high daily salt intake that exceeds the acute diuretic-induced salt loss, hyponatremia or hypokalemic, hypochloremic metabolic alkalosis, and reflex activation of the renal nerves. Nephron mechanisms include tubular tolerance that can develop even during the time that the renal tubules are exposed to a single dose of diuretic, or enhanced reabsorption in the proximal tubule that limits delivery to the loop, or an adaptive increase in reabsorption in the downstream distal tubule and collecting ducts that offsets ongoing blockade of Na reabsorption in the loop of Henle. These provide rationales for novel strategies including the concurrent use of diuretics that block these nephron segments and even sequential nephron blockade with multiple diuretics and aquaretics combined in severely diuretic-resistant patients with heart failure.



Hypertension: 29 Sep 2020; 76:1045-1054
Wilcox CS, Testani JM, Pitt B
Hypertension: 29 Sep 2020; 76:1045-1054 | PMID: 32829662
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Abstract

Gut Microbiota Profile Identifies Transition From Compensated Cardiac Hypertrophy to Heart Failure in Hypertensive Rats.

Gutiérrez-Calabrés E, Ortega-Hernández A, Modrego J, Gómez-Gordo R, ... González P, Gómez-Garre D

Microcirculatory alterations displayed by patients with heart failure (HF) induce structural and functional intestinal changes that may affect normal gut microbial community. At the same time, gut microbiota can influence pathological mechanisms implicated in HF progression. However, it is unknown whether gut microbiota dysbiosis can precede the development of cardiac alterations in HF or it is only a mere consequence. Our aim was to investigate the potential relationship between gut microbiota composition and HF development by comparing spontaneously hypertensive heart failure and spontaneously hypertensive rat models. Gut microbiota from spontaneously hypertensive heart failure, spontaneously hypertensive rat, and normotensive Wistar Kyoto rats at 9 and 19 months of age was analyzed by sequencing the 16S ribosomal RNA gene, and KEGG metabolic pathways associated to 16S profiles were predicted. Beta diversity, / ratio, taxonomic abundances, and potential metabolic functions of gut microbiota were significantly different in spontaneously hypertensive heart failure with respect to spontaneously hypertensive rat before (9 months) and after (19 months) cardiac differences were presented. Nine-month-old spontaneously hypertensive heart failure showed a significant increase in the generacompared with both Wistar Kyoto and spontaneously hypertensive rat, while , , , , andwere diminished. Of them, , , andwere associated to changes in cardiac structure and function. Our results demonstrate an association between specific changes in gut microbiota and the development of HF in a hypertensive model of HF and further support the intervention to restore gut microbiota as an innovative therapeutic strategy for preventing HF.



Hypertension: 30 Oct 2020; 76:1545-1554
Gutiérrez-Calabrés E, Ortega-Hernández A, Modrego J, Gómez-Gordo R, ... González P, Gómez-Garre D
Hypertension: 30 Oct 2020; 76:1545-1554 | PMID: 32921194
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Abstract

Home monitoring with technology-supported management in chronic heart failure: a randomised trial.

Rahimi K, Nazarzadeh M, Pinho-Gomes AC, Woodward M, ... Cleland J,
Objectives
We aimed to investigate whether digital home monitoring with centralised specialist support for remote management of heart failure (HF) is more effective in improving medical therapy and patients\' quality of life than digital home monitoring alone.
Methods
In a two-armed partially blinded parallel randomised controlled trial, seven sites in the UK recruited a total of 202 high-risk patients with HF (71.3 years SD 11.1; left ventricular ejection fraction 32.9% SD 15.4). Participants in both study arms were given a tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. Participants randomised to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of guideline-recommended medical therapy for chronic HF and major comorbidities, measured as a composite opportunity score (total number of recommended treatment given divided by the total number of opportunities the treatment should have been given, with a score 1 indicating 100% adherence to recommendations). Co-primary outcome was change in physical score of Minnesota Living with Heart Failure questionnaire.
Results
101 patients were randomised to \'enhanced self-management\' and 101 to \'supported medical management\'. At the end of follow-up, the opportunity score was 0.54 (95% CI 0.46 to 0.62) in the control arm and 0.61 (95% CI 0.52 to 0.70) in the intervention arm (p=0.25). Physical well-being of participants also did not differ significantly between the groups (17.4 (12.4) mean (SD) for control arm vs 16.5 (12.1) in treatment arm; p for change=0.84).
Conclusions
Central provision of tailored specialist management in a multi-morbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based treatment nor health-related quality of life.
Trial registration number
ISRCTN86212709.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1573-1578
Rahimi K, Nazarzadeh M, Pinho-Gomes AC, Woodward M, ... Cleland J,
Heart: 29 Sep 2020; 106:1573-1578 | PMID: 32580977
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Abstract

Characteristics and outcomes of patients with suspected heart failure referred in line with National Institute for Health and Care Excellence guidance.

Zheng A, Cowan E, Mach L, Adam RD, ... Flett A, Morton G
Objective
To describe the population, heart failure (HF) diagnosis rate, and 1-year hospitalisation and mortality of patients with suspected HF and elevated N-terminal pro B-type natriuretic peptide (NTproBNP) investigated according to UK National Institute for Health and Care Excellence (NICE) guidelines.
Methods
NICE recommends patients with suspected HF, based on clinical presentation and elevated NTproBNP, are referred for specialist assessment and echocardiography. Patients should be seen within 2 weeks when NTproBNP is >2000 pg/mL (2-week pathway: 2WP) or within 6 weeks when NTproBNP is 400-2000 pg/mL (6-week pathway: 6WP). This is a retrospective, multicentre, observational study of consecutive patients with suspected HF referred from primary care between 2014 and 2016 to dedicated secondary care HF clinics based on the NICE 2WP and 6WP. Data were obtained from hospital records and episode statistics. Mortality and hospitalisation rates were calculated 1 year from NTproBNP measurement.
Results
1271 patients (median age 80; IQR 73-85) were assessed, 680 (53%) of whom were female. 667 (53%) were referred on the 2WP and 604 (47%) on the 6WP. 698 (55%) were diagnosed with HF (369 HF with reduced ejection fraction) and 566 (45%) as not HF (NHF). 1-year mortality was 10% (n=129) and hospitalisation was 33% (n=413). Patients on the 2WP had higher mortality and hospitalisation rates than those on the 6WP, 14% vs 6% (p<0.001) and 38% vs 27% (p<0.001), respectively. All-cause mortality (11% vs 9%; p=0.306) and hospitalisation rates (35% vs 29%; p=0.128) did not differ between HF and NHF patients, respectively.
Conclusions
Outcomes using the NICE approach of short waiting time targets for specialist assessment of patients with suspected HF and raised NTproBNP are not known. The model identifies an elderly population a high proportion of whom have HF. Irrespective of diagnosis, patients have high rates of adverse outcomes. These contemporary real-world data provide a platform for discussions with patients and shaping HF services.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2020; 106:1579-1585
Zheng A, Cowan E, Mach L, Adam RD, ... Flett A, Morton G
Heart: 29 Sep 2020; 106:1579-1585 | PMID: 32690621
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Impact:
Abstract

Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation.

Bhatia HS, Nishimura M, Dickson S, Adler E, Greenberg B, Thomas IC
Objective
Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes.
Methods
We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months.
Results
Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E\' ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group.
Conclusions
METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Oct 2020; epub ahead of print
Bhatia HS, Nishimura M, Dickson S, Adler E, Greenberg B, Thomas IC
Heart: 04 Oct 2020; epub ahead of print | PMID: 33020227
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Abstract

Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

Davidson MT, Grimsrud PA, Lai L, Draper JA, ... Kelly DP, Muoio DM
Rationale
Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse.
Objective
This study sought to explore the premise that mitochondrial Kac contributes to heart failure by disrupting oxidative metabolism.
Methods and results
A DKO (dual knockout) mouse line with deficiencies in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)-enzymes that oppose Kac by buffering the acetyl group pool and catalyzing lysine deacetylation, respectively-was developed to model extreme mitochondrial Kac in cardiac muscle, as confirmed by quantitative acetyl-proteomics. The resulting impact on mitochondrial bioenergetics was evaluated using a respiratory diagnostics platform that permits comprehensive assessment of mitochondrial function and energy transduction. Susceptibility of DKO mice to heart failure was investigated using transaortic constriction as a model of cardiac pressure overload. The mitochondrial acetyl-lysine landscape of DKO hearts was elevated well beyond that observed in response to pressure overload or Sirt3 deficiency alone. Relative changes in the abundance of specific acetylated lysine peptides measured in DKO versus Sirt3 KO hearts were strongly correlated. A proteomics comparison across multiple settings of hyperacetylation revealed ≈86% overlap between the populations of Kac peptides affected by the DKO manipulation as compared with experimental heart failure. Despite the severity of cardiac Kac in DKO mice relative to other conditions, deep phenotyping of mitochondrial function revealed a surprisingly normal bioenergetics profile. Thus, of the >120 mitochondrial energy fluxes evaluated, including substrate-specific dehydrogenase activities, respiratory responses, redox charge, mitochondrial membrane potential, and electron leak, we found minimal evidence of oxidative insufficiencies. Similarly, DKO hearts were not more vulnerable to dysfunction caused by transaortic constriction-induced pressure overload.
Conclusions
The findings challenge the premise that hyperacetylation per se threatens metabolic resilience in the myocardium by causing broad-ranging disruption to mitochondrial oxidative machinery.



Circ Res: 24 Sep 2020; 127:1094-1108
Davidson MT, Grimsrud PA, Lai L, Draper JA, ... Kelly DP, Muoio DM
Circ Res: 24 Sep 2020; 127:1094-1108 | PMID: 32660330
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Abstract

Comparison of incidence rates and risk factors of heart failure between two male cohorts born 30 years apart.

Ergatoudes C, Hansson PO, Svärdsudd K, Rosengren A, ... Pivodic A, Fu M
Objective
To compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF).
Methods
Two population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963-1994 and 1993-2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF.
Results
Eighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913.
Conclusions
Men born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2020; 106:1672-1678
Ergatoudes C, Hansson PO, Svärdsudd K, Rosengren A, ... Pivodic A, Fu M
Heart: 30 Oct 2020; 106:1672-1678 | PMID: 32114518
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Impact:
Abstract

Dietary Carbohydrates Restriction Inhibits The Development Of Cardiac Hypertrophy And Heart Failure.

Nakamura M, Odanovic N, Nakada Y, Dohi S, ... Abdellatif M, Sadoshima J
Aims
A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how a LC diet impacts on cardiac pathology during hemodynamic stress remains elusive. This study evaluated the effects of a LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodeling.
Methods and results
Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, hemodynamic, histological and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3β, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3β cardiac-specific knockout mice. β-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signaling.
Conclusions
Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
Translational perspective
Hemodynamic stress, such as hypertension, induces pathological cardiac hypertrophy, leading to heart failure. There is growing evidence that modulating components of diet affects cardiac function in humans, although the causality and underlying mechanisms are poorly understood. Our study demonstrates that strict restriction of dietary carbohydrates supplemented with either fat or proteins during acute hemodynamic stress attenuates the development and progression of cardiac hypertrophy and heart failure by activating distinct anti-hypertrophic and cardioprotective signaling mechanisms. The study suggests that it would be useful to investigate the therapeutic benefit of carbohydrate restriction in patients with hypertension and cardiac hypertrophy in clinical studies.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: [email protected]

Cardiovasc Res: 17 Oct 2020; epub ahead of print
Nakamura M, Odanovic N, Nakada Y, Dohi S, ... Abdellatif M, Sadoshima J
Cardiovasc Res: 17 Oct 2020; epub ahead of print | PMID: 33070172
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Impact:
Abstract

Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial.

Udelson JE, Lewis GD, Shah SJ, Zile MR, ... Profy AT, Konstam MA
Importance
Heart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency.
Objective
To evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF.
Design, setting, and participants
CAPACITY HFpEF was a randomized, double-blind, placebo-controlled, phase 2 trial. Fifty-nine sites enrolled 196 patients with heart failure and an ejection fraction of at least 40%, impaired peak rate of oxygen consumption (peak V̇o2), and at least 2 conditions associated with nitric oxide deficiency (diabetes, hypertension, obesity, or advanced age). The trial randomized patients to 1 of 3 praliciguat dose groups or a placebo group, but was refocused early to a comparison of the 40-mg praliciguat dose vs placebo. Participants were enrolled from November 15, 2017, to April 30, 2019, with final follow-up on August 19, 2019.
Interventions
Patients were randomized to receive 12 weeks of treatment with 40 mg of praliciguat daily (n = 91) or placebo (n = 90).
Main outcomes and measures
The primary efficacy end point was the change from baseline in peak V̇o2 in patients who completed at least 8 weeks of assigned dosing. Secondary end points included the change from baseline in 6-minute walk test distance and in ventilatory efficiency (ventilation/carbon dioxide production slope). The primary adverse event end point was the incidence of treatment-emergent adverse events (TEAEs).
Results
Among 181 patients (mean [SD] age, 70 [9] years; 75 [41%] women), 155 (86%) completed the trial. In the placebo (n = 78) and praliciguat (n = 65) groups, changes in peak V̇o2 were 0.04 mL/kg/min (95% CI, -0.49 to 0.56) and -0.26 mL/kg/min (95% CI, -0.83 to 0.31), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -0.30 mL/kg/min ([95% CI, -0.95 to 0.35]; P = .37). None of the 3 prespecified secondary end points were statistically significant. In the placebo and praliciguat groups, changes in 6-minute walk test distance were 58.1 m (95% CI, 26.1-90.1) and 41.4 m (95% CI, 8.2-74.5), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -16.7 m (95% CI, -47.4 to 13.9). In the placebo and praliciguat groups, the placebo-adjusted least-squares between-group difference in mean change in ventilation/carbon dioxide production slope was -0.3 (95% CI, -1.6 to 1.0). There were more dizziness (9.9% vs 1.1%), hypotension (8.8% vs 0%), and headache (11% vs 6.7%) TEAEs with praliciguat compared with placebo. The frequency of serious TEAEs was similar between the groups (10% in the praliciguat group and 11% in the placebo group).
Conclusions and relevance
Among patients with HFpEF, the soluble guanylate cyclase stimulator praliciguat, compared with placebo, did not significantly improve peak V̇o2 from baseline to week 12. These findings do not support the use of praliciguat in patients with HFpEF.
Trial registration
ClinicalTrials.gov Identifier: NCT03254485.



JAMA: 19 Oct 2020; 324:1522-1531
Udelson JE, Lewis GD, Shah SJ, Zile MR, ... Profy AT, Konstam MA
JAMA: 19 Oct 2020; 324:1522-1531 | PMID: 33079154
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Impact:
Abstract

Evaluation and treatment of premature ventricular contractions in heart failure with reduced ejection fraction.

Mulder BA, Rienstra M, Blaauw Y

Premature ventricular complexes (PVCs) are often observed in patients presenting with heart failure with a reduced ejection fraction (HFrEF). PVCs may in some patients be considered to be the cause of heart failure, while in others it may be the consequence of heart failure. PVCs are important prognostic markers in HFrEF. The uncertainty whether PVCs are the cause or effect in HFrEF impacts clinical decision making. In this review, we discuss the complexity of the cause-effect relationship between PVCs and HFrEF. We demonstrate a workflow with the use of a trial period of amiodarone that may discover whether the reduced LVEF is reversible, the symptoms are due to PVCs and whether biventricular pacing can be increased by the reduction of PVCs. The use of non-invasive and invasive (high-density) mapping techniques may help to improve accuracy and efficacy in the treatment of PVC, which will be demonstrated. With these results in mind, we conclude this review highlighting the future directions for PVC research and treatment.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 18 Oct 2020; epub ahead of print
Mulder BA, Rienstra M, Blaauw Y
Heart: 18 Oct 2020; epub ahead of print | PMID: 33077503
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Impact:
Abstract

Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial.

Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, ... Butler J,
Importance
Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life.
Objective
To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ).
Design, setting, and participants
Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019.
Interventions
Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1.
Main outcomes and measures
The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks.
Results
Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively.
Conclusions and relevance
Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ.
Trial registration
ClinicalTrials.gov Identifier: NCT03547583.



JAMA: 19 Oct 2020; 324:1512-1521
Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, ... Butler J,
JAMA: 19 Oct 2020; 324:1512-1521 | PMID: 33079152
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Impact:
Abstract

Income level and outcomes in patients with heart failure with universal health coverage.

Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
Objective
We aimed to investigate the influence of income level on guideline-directed medical therapy (GDMT) prescription rates and prognosis of patients with heart failure (HF) following implementation of a nationwide health insurance programme.
Methods
A total of 633 098 hospitalised patients with HF from 1996 to 2013 were identified from Taiwan National Health Insurance Research Database. Participants were classified into low-income, median-income and high-income groups. GDMT utilisation, in-hospital mortality and postdischarge HF readmission, and mortality rates were compared.
Results
The low-income group had a higher comorbidity burden and was less likely to receive GDMT than the other two groups. The in-hospital mortality rate in the low-income group (5.07%) was higher than in the median-income (2.47%) and high-income (2.51%) groups. Compared with the high-income group, the low-income group had a significantly higher risk of postdischarge HF readmission (adjusted HR (aHR): 1.29, 95% CI 1.27 to 1.31), all-cause mortality (aHR: 1.98, 95% CI 1.95 to 2.02) and composite HF readmission/all-cause mortality (aHR: 1.54, 95% CI 1.52 to 1.56). These results were generally consistent among the population after propensity matching (low vs high: HR=2.08 for mortality and 1.36 for HF readmission; median vs high: HR=1.23 for mortality and 1.12 for HF readmission; all p<0.001) and after inverse probability of treatment weighting (low-income vs high-income group: HR: 2.19 for mortality and 1.16 for HF readmission; median-income vs high-income group: HR: 1.53 for mortality and 1.09 for HF readmission; all p<0.001). Lower utilisation of GDMT and poorer prognosis in lower-income hospitalised patients with HF appeared to mitigate over time.
Conclusions
Low-income patients with HF had nearly a twofold increase in the risk of in-hospital mortality and postdischarge events compared with the high-income group, partly due to lower GDMT utilisation. The differences between postdischarge HF outcomes among various income groups appeared to mitigate over time following the implementation of nationwide universal health coverage.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Oct 2020; epub ahead of print
Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
Heart: 19 Oct 2020; epub ahead of print | PMID: 33082175
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Impact:
Abstract

Adaptive immune disorders in hypertension and heart failure: focusing on T-cell subset activation and clinical implications.

Rai A, Narisawa M, Li P, Piao L, ... Yang G, Cheng XW

: Hypertension is a growing health concern worldwide. Established hypertension is a causative factor of heart failure, which is characterized by increased vascular resistance and intractable uncontrolled blood pressure. Hypertension and heart failure have multiple causes and complex pathophysiology but cellular immunity is thought to contribute to the development of both. Recent studies showed that T cells play critical roles in hypertension and heart failure in humans and animals, with various stimuli leading to the formation of effector T cells that infiltrate the cardiovascular wall. Monocytes/macrophages also accumulate in the cardiovascular wall. Various cytokines (e.g. interleukin-6, interleukin-17, interleukin-10, tumor necrosis factor-α, and interferon-γ) released from immune cells of various subtypes promote vascular senescence and elastic laminal degradation as well as cardiac fibrosis and/or hypertrophy, leading to cardiovascular structural alterations and dysfunction. Recent laboratory evidence has defined a link between inflammation and the immune system in initiation and progression of hypertension and heart failure. Moreover, cross-talk among natural killer cells, adaptive immune cells (T cells and B cells), and innate immune cells (i.e. monocytes, macrophages, neutrophils, and dendritic cells) contributes to end-cardiovasculature damage and dysfunction in hypertension and heart failure. Clinical and experimental studies on the diagnostic potential of T-cell subsets revealed that blood regulatory T cells, CD4 cells, CD8 T cells, and the ratio of CD4 to CD8 T cells show promise as biomarkers of hypertension and heart failure. Therapeutic interventions to suppress activation of these cells may prove beneficial in reducing end-organ damage and preventing consequences of cardiovascular failure, including hypertension of heart failure.



J Hypertens: 29 Sep 2020; 38:1878-1889
Rai A, Narisawa M, Li P, Piao L, ... Yang G, Cheng XW
J Hypertens: 29 Sep 2020; 38:1878-1889 | PMID: 32890260
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Impact:
Abstract

A Novel Neuromodulation Approach to Improve LV Contractility in Heart Failure: A First-in-Human Proof-of-Concept Study.

Reddy V, Petrů J, Málek F, Stylos L, Goedeke S, Neužil P

- Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery.- Fifteen (15) subjects admitted for defibrillator implantation and ejection fraction ≤ 35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomical rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20Hz, 4ms pulse width, and ≤ 20mA. Changes in maximum positive dP/dt (dP/dt) indicated changes in ventricular contractility.- Of 15 enrolled subjects, five were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dt increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dt), mean arterial pressure, systolic pressure, diastolic pressure and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure.- In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.



Circ Arrhythm Electrophysiol: 28 Sep 2020; epub ahead of print
Reddy V, Petrů J, Málek F, Stylos L, Goedeke S, Neužil P
Circ Arrhythm Electrophysiol: 28 Sep 2020; epub ahead of print | PMID: 32991220
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Impact:
Abstract

Glymphatic failure as a final common pathway to dementia.

Nedergaard M, Goldman SA

Sleep is evolutionarily conserved across all species, and impaired sleep is a common trait of the diseased brain. Sleep quality decreases as we age, and disruption of the regular sleep architecture is a frequent antecedent to the onset of dementia in neurodegenerative diseases. The glymphatic system, which clears the brain of protein waste products, is mostly active during sleep. Yet the glymphatic system degrades with age, suggesting a causal relationship between sleep disturbance and symptomatic progression in the neurodegenerative dementias. The ties that bind sleep, aging, glymphatic clearance, and protein aggregation have shed new light on the pathogenesis of a broad range of neurodegenerative diseases, for which glymphatic failure may constitute a therapeutically targetable final common pathway.

Copyright © 2020, American Association for the Advancement of Science.

Science: 01 Oct 2020; 370:50-56
Nedergaard M, Goldman SA
Science: 01 Oct 2020; 370:50-56 | PMID: 33004510
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Impact:
Abstract

Dyspnea, Acute Respiratory Failure, Psychological Trauma, and Post-ICU Mental Health: A caution and a call for research.

Worsham CM, Banzett RB, Schwartzstein R

Dyspnea is an uncomfortable sensation with the potential to cause psychological trauma. Patients presenting with acute respiratory failure, particularly when tidal volume is restricted during mechanical ventilation, may experience the most distressing form of dyspnea known as air hunger. Air hunger activates brain pathways known to be involved in post-traumatic stress disorder (PTSD), anxiety, and depression. These conditions are considered part of the post-intensive care syndrome. These sequelae may be even more prevalent among patients with acute respiratory distress syndrome (ARDS). Low tidal volume, a mainstay of modern therapy for ARDS is difficult to avoid and is likely to cause air hunger despite sedation. Adjunctive neuromuscular blockade does not prevent or relieve air hunger, but it does prevent the patient from communicating discomfort to caregivers. Consequently, paralysis may also contribute to the development of PTSD. Although research has identified post-ARDS PTSD as a cause for concern and investigators have taken steps to quantify the burden of disease, there is little information to guide mechanical ventilation strategies designed to reduce its occurrence. We suggest such efforts will be more successful if they are directed at the known mechanisms of air hunger. Investigation of the anti-dyspnea effects of sedative and analgesic drugs commonly used in the ICU and their impact on post-ARDS PTSD symptoms is a logical next step. While in practice we often accept negative consequences of life-saving therapies as unavoidable, we must understand the negative sequalae of our therapies and work to minimize them under our primary directive to \"first, do no harm\" to our patients.

Copyright © 2020. Published by Elsevier Inc.

Chest: 30 Sep 2020; epub ahead of print
Worsham CM, Banzett RB, Schwartzstein R
Chest: 30 Sep 2020; epub ahead of print | PMID: 33011205
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Impact:
Abstract

Behavioral nudges reduce failure to appear for court.

Fishbane A, Ouss A, Shah AK

Each year, millions of Americans fail to appear in court for low-level offenses, and warrants are then issued for their arrest. In two field studies in New York City, we make critical information salient by redesigning the summons form and providing text message reminders. These interventions reduce failures to appear by 13-21% and lead to 30,000 fewer arrest warrants over a 3-year period. In lab experiments, we find that while criminal justice professionals see failures to appear as relatively unintentional, laypeople believe they are more intentional. These lay beliefs reduce support for policies that make court information salient and increase support for punishment. Our findings suggest that criminal justice policies can be made more effective and humane by anticipating human error in unintentional offenses.

Copyright © 2020, American Association for the Advancement of Science.

Science: 07 Oct 2020; epub ahead of print
Fishbane A, Ouss A, Shah AK
Science: 07 Oct 2020; epub ahead of print | PMID: 33033154
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Impact:
Abstract

Pressure-Support Ventilation vs T-Piece During Spontaneous Breathing Trials Before Extubation Among Patients at High Risk of Extubation Failure: A Post-Hoc Analysis of a Clinical Trial.

Thille AW, Coudroy R, Nay MA, Gacouin A, ... Frat JP,
Background
Spontaneous breathing trial (SBT) using a T-piece remains the most frequently performed trial before extubation in ICUs.
Research question
We aimed at determining whether initial SBT using pressure-support ventilation (PSV) could increase successful extubation rates among patients at high risk of extubation failure.
Study design and methods
Post hoc analysis of a multicenter trial focusing on reintubation in patients at high-risk of extubation failure. The initial SBT was performed using PSV or T-piece according to the physician/center decision. The primary outcome was the proportion of patients successfully extubated 72 hours after initial SBT, that is, extubated after initial SBT and not reintubated within the following 72 hours.
Results
Among the 641 patients included in the original study, initial SBT was performed using PSV (7.0 cm HO in median without positive end-expiratory pressure) in 243 patients (38%) and using a T-piece in 398 patients (62%). The proportion of patients successfully extubated 72 hours after initial SBT was 67% (162/243) using PSV and 56% (223/398) using T-piece (absolute difference 10.6%; 95% CI, 2.8 to 28.1; P = .0076). The proportion of patients extubated after initial SBT was 77% (186/283) using PSV and 63% (249/398) using T-piece (P = .0002), whereas reintubation rates within the following 72 hours did not significantly differ (13% vs 10%, respectively; P = .4259). Performing an initial SBT using PSV was independently associated with successful extubation (adjusted OR, 1.60; 95% CI, 1.30 to 2.18; P = .0061).
Interpretation
In patients at high risk of extubation failure in the ICU, performing an initial SBT using PSV may hasten extubation without an increased risk of reintubation.

Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 29 Sep 2020; 158:1446-1455
Thille AW, Coudroy R, Nay MA, Gacouin A, ... Frat JP,
Chest: 29 Sep 2020; 158:1446-1455 | PMID: 32439503
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Impact:
Abstract

A Previously Healthy 37-Year-Old Man With Acute Hypoxic Respiratory Failure and Fevers.

Axell-House DB, Harris DA
Case presentation
A previously healthy 37-year-old man initially presented to a hospital near his home with persistent cough after failing outpatient azithromycin for empiric treatment of pneumonia. He was newly employed as a bulldozer operator burying trash in a landfill in Virginia, which he continued throughout his illness. He owned two healthy dogs, had never traveled outside the state, and denied a history of cigarette smoking, alcohol, and substance use. His WBC count was 13.4 × 10/L (11% eosinophils). CT scan of the chest showed ground glass opacities. Subsequent bronchoscopy with BAL of the right middle lobe showed eosinophilic predominance (46%); transbronchial biopsy of right lower lobe was performed. Infectious and autoimmune work up that was negative included blood, urine, and BAL cultures, BAL Pneumocystis pneumonia direct immunofluorescence assay, urine legionella antigen, serum HIV antibody, antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and angiotensin converting enzyme. After improvement in hypoxia with inpatient corticosteroid therapy, he was discharged home with a two week course of prednisone for a presumptive diagnosis of acute eosinophilic pneumonia. He subsequently experienced worsening fever and difficulty breathing; six weeks after his symptoms began, he was admitted to our hospital.

Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 29 Sep 2020; 158:e169-e174
Axell-House DB, Harris DA
Chest: 29 Sep 2020; 158:e169-e174 | PMID: 33036114
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Impact:
Abstract

Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure.

Meran L, Massie I, Campinoti S, Weston AE, ... De Coppi P, Li VSW

Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy.



Nat Med: 29 Sep 2020; 26:1593-1601
Meran L, Massie I, Campinoti S, Weston AE, ... De Coppi P, Li VSW
Nat Med: 29 Sep 2020; 26:1593-1601 | PMID: 32895569
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Impact:
Abstract

Sudden cardiac arrest with shockable rhythm in patients with heart failure.

Woolcott OO, Reinier K, Uy-Evanado A, Nichols GA, ... Jui J, Chugh SS
Background
Patients with shockable sudden cardiac arrest (SCA; ventricular fibrillation/tachycardia) have significantly better resuscitation outcomes than do those with nonshockable rhythm (pulseless electrical activity/asystole). Heart failure (HF) increases the risk of SCA, but presenting rhythms have not been previously evaluated.
Objective
We hypothesized that based on unique characteristics, HFpEF (HF with preserved ejection fraction; left ventricular ejection fraction [LVEF] ≥50%), bHFpEF (HF with borderline preserved ejection fraction; LVEF >40% and <50%), and HFrEF (HF with reduced ejection fraction; LVEF ≤40%) manifest differences in presenting rhythm during SCA.
Methods
Consecutive cases of SCA with HF (age ≥18 years) were ascertained in the Oregon Sudden Unexpected Death Study (2002-2019). LVEF was obtained from echocardiograms performed before and unrelated to the SCA event. Presenting rhythms were identified from first responder reports. Logistic regression was used to evaluate the independent association of presenting rhythm with HF subtype.
Results
Of 648 subjects with HF and SCA (median age 72 years; interquartile range 62-81 years), 274 had HFrEF (23.4% female), 92 had bHFpEF (35.9% female), and 282 had HFpEF (42.5% female). The rates of shockable rhythms were 44.5% (n = 122), 48.9% (n = 45), and 27.0% (n = 76) for HFrEF, bHFpEF, and HFpEF, respectively (P < .001). Compared with HFpEF, the adjusted odds ratios for shockable rhythm were 1.86 (95% confidence interval 1.27-2.74; P = .002) in HFrEF and 2.26 (95% CI 1.35-3.77; P = .002) in bHFpEF. The rates of survival to hospital discharge were 10.6% (n = 29) in HFrEF, 22.8% (n = 21) in bHFpEF, and 9.9% (n = 28) in HFpEF (P = .003).
Conclusion
The rates of shockable rhythm during SCA depend on the HF clinical subtype. Patients with bHFpEF had the highest likelihood of shockable rhythm, correlating with the highest rates of survival.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Sep 2020; 17:1672-1678
Woolcott OO, Reinier K, Uy-Evanado A, Nichols GA, ... Jui J, Chugh SS
Heart Rhythm: 29 Sep 2020; 17:1672-1678 | PMID: 32504821
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Impact:
Abstract

Catheter Ablation for Atrial Fibrillation in Patients with Concurrent Heart Failure.

Arora S, Jaswaney R, Jani C, Zuzek Z, ... Viles-Gonzalez J, Deshmukh A

Due to limited real-world data, the aim of this study was to explore the impact of catheter ablation (CA) for atrial fibrillation (AF) in heart failure (HF). This retrospective cohort study identified 119,694 patients with AF and HF from the Nationwide Readmissions Database (NRD) from 2016-2017. Propensity-matching was generated using demographics, comorbidities, hospital and other characteristics through multivariate logistic regression. Greedy\'s propensity score match (1:15) algorithm was used to create matched data. The primary endpoint was a composite of HF readmission and mortality at one year. Secondary outcomes include HF readmission, mortality, AF readmission, and any-cause readmission at one year. Of the 119,694 patients, 63,299 had heart failure with reduced ejection fraction (HFrEF), and 56,395 had heart failure with preserved ejection fraction (HFpEF). In the overall HFrEF cohort, the primary outcome was similar (HR, 95% CI, p-value) (1.01, 0.91-1.13, 0.811). AF readmission (0.41, 0.33-0.49, <0.001) and any readmission (0.87, 0.82-0.93, <0.001) were reduced with CA. In the propensity-matched HFrEF cohort, results were unchanged (primary outcome- 1.10, 0.95-1.27, 0.189; AF readmission- 0.46, 0.36-0.59, <0.001; any readmission- 0.89, 0.82-0.98, 0.015). In the overall HFpEF cohort, the primary outcome was similar (0.90, 0.78-1.04, 0.154). AF readmission was reduced with CA (0.54, 0.44-0.65, <0.001). In the propensity-matched HFpEF cohort, results were unchanged (primary outcome 1.10, 0.92-1.31, 0.289; AF readmission 0.44, 0.33-0.57, <0.001). CA did not reduce mortality and HF readmission at one year irrespective of the type of HF, but significantly reduce readmission due to AF.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 27 Sep 2020; epub ahead of print
Arora S, Jaswaney R, Jani C, Zuzek Z, ... Viles-Gonzalez J, Deshmukh A
Am J Cardiol: 27 Sep 2020; epub ahead of print | PMID: 33002464
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Impact:
Abstract

PROVIDE-HF primary results: Patient-reported outcomes inVestigation following initiation of drug therapy with Entresto (Sacubitril/valsartan) in heart failure.

Mentz RJ, Xu H, O\'Brien EC, Thomas L, ... Duffy CI, Hernandez AF
Background
In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) vs. enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice.
Methods
PROVIDE-HF was a prospective study within a national research network (PCORnet) of HFrEF outpatients recently initiated on sacubitril/valsartan vs. controls with recent ACE-I/ARB initiation/dose change. The primary endpoint was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12weeks. Other endpoints included responder analyses: ≥5-point and≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting.
Results
Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and NT-proBNP 1083pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference+4.76; P=.027) and were more likely to have a≥5-point and≥20-point response (all P<.05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI: -0.89, 9.99; P=.101) and likelihood of ≥5-point increase (OR 1.55; 95% CI: 0.84, 2.86; P=.16); ≥20-pt increase remained statistically significant (OR 3.79; 95% CI: 1.47, 9.73; P=.006).
Conclusions
In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent ACE-I/ARB initiation/dose change, the between-group difference in the primary endpoint, mean KCCQ change at 12weeks, was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-pt improvement in KCCQ at 12weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 23 Sep 2020; epub ahead of print
Mentz RJ, Xu H, O'Brien EC, Thomas L, ... Duffy CI, Hernandez AF
Am Heart J: 23 Sep 2020; epub ahead of print | PMID: 32980364
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Impact:
Abstract

Relation of Body Mass Index to Outcomes in Patients With Heart Failure Implanted With Left Ventricular Assist Devices.

Galand V, Flécher E, Lelong B, Chabanne C, ... Leclercq C, Martins RP

We aimed at characterizing the impact of low and high body mass index (BMI) on outcomes after left-ventricular assist device (LVAD) surgery and define the predictors of mortality in patients with abnormal BMI (low/high). This study was conducted in 19 centers from 2006 to 2016. Patients were divided based on their baseline BMI into 3 groups of BMI: low (BMI ≤18.5 kg/m²); normal (BMI = 18.5 to 24.99 kg/m²) and high (BMI ≥25 kg/m²) (including overweight (BMI = 25 to 29.99 kg/m²), and obesity (BMI ≥30 Kg/m²)). Among 652 patients, 29 (4.4%), 279 (42.8%) and 344 (52.8%) had a low-, normal-, and high BMI, respectively. Patients with high BMI were significantly more likely men, with more co-morbidities and more history of ventricular/supra-ventricular arrhythmias before LVAD implantation. Patients with abnormal BMI had significantly lower survival than those with normal BMI. Notably, those with low BMI experienced the worst survival whereas overweight or obese patients had similar survival. Four predictors of mortality for LVAD candidates with abnormal BMI were defined: total bilirubin ≥16 µmol/L before LVAD, hypertension, destination therapy, and cardiac surgery with LVAD. Depending on the number of predictor per patients, those with abnormal BMI may be divided in 3 groups of 1-year mortality risk, i.e., low (0 to 1 predictor: 29% and 31%), intermediate (2 to 3 predictors, 51% and 52%, respectively), and high (4 predictors: 83%). In conclusion, LVAD recipients with abnormal BMI experience lower survival, especially underweight patients. Four predictors of mortality have been identified for LVAD population with abnormal BMI, differentiating those a low-, intermediate-, and high risks of death.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2020; 133:81-88
Galand V, Flécher E, Lelong B, Chabanne C, ... Leclercq C, Martins RP
Am J Cardiol: 14 Oct 2020; 133:81-88 | PMID: 32861423
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Impact:
Abstract

Utility of 6-Minute Walk Test to Predict Response to Cardiac Resynchronization Therapy in Patients With Mild Heart Failure.

Rosero SZ, Hernandez N, Goldenberg I, McNitt S, ... Solomon SD, Kutyifa V

Clinical studies of heart failure (HF) generally utilize the 6-minute walk test (6MWT) for functional capacity (FC) assessment. However, data on the impact of cardiac resynchronization therapy (CRT) on 6MWT and its role to predict long-term outcomes in mild HF patients with CRT are lacking. We studied 1,381 subjects with mild HF enrolled in Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy with 6MWT data at baseline and 1 year. We assessed the effects of CRT-D on percent change in 6MWT at 1 year by left bundle branch block (LBBB) status, identified independent predictors of 6MWT at 1 year, and evaluated the association between changes in 6MWT and risk for HF or death. Treatment with CRT-D versus implantable cardiac defibrillator (ICD) was not associated with a significant improvement in 6MWT at 1-year in LBBB subjects (2.2 % vs 0.0%, p = 0.428, but it was associated with a deterioration in 6MWT in non-LBBB subjects (4.1% vs 0.0%, p = 0.308). Multivariate analysis showed that each 5% reduction in 6MWT was independently associated with a corresponding 3% increase in the risk of subsequent HF or death (p = 0.014). In conclusion, our findings suggest that 6MWT has limited utility to identify CRT response in mild HF subjects with LBBB. However, 6MWT showed a signal toward deterioration in mild HF subjects with non-LBBB, and this was predictive of subsequent increased risk of HF or death.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 30 Sep 2020; 132:79-86
Rosero SZ, Hernandez N, Goldenberg I, McNitt S, ... Solomon SD, Kutyifa V
Am J Cardiol: 30 Sep 2020; 132:79-86 | PMID: 32819680
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Impact:
Abstract

Diagnostic Usefulness of Histological Examination of the Left Ventricular \"Core\" Excised to Insert a Left Ventricular Assist Device in Patients with Severe Heart Failure.

Roberts WC, Everett BP, Won VS, Kondapalli N

The left ventricular assist device (LVAD) has proven to be beneficial for patients with severe heart failure poorly responsive to anti heart failure medicine. To examine both grossly and histologically the portion of left ventricular (LV) free wall excised (\"the left ventricular core\") to insert a LVAD in 337 patients with severe heart failure from a variety of causes. We collected together all photographs of LV \"cores\" and the histologic sections prepared from them and reexamined both. Despite the fact that these LV cores usually weighed >100 times the quantity of myocardium available to examine compared to that available by biotome inserted via a transvenous catheter, the number in which histologic study allowed an unequivocal diagnosis was limited. Examination of the clinical records usually was required to establish the definitive diagnosis. Although the presence of a scarred myocardial wall usually suggested ischemic cardiomyopathy (IC), the scarring may not have involved the LV apex resulting in a non-scarred portion of myocardium simulating idiopathic dilated cardiomyopathy (IDC). Moreover, about 10% of the patients with IDC have myocardial scars thus simulating IC. Involvement of the LV core by amyloid, sarcoid, myocarditis, and acute infarction, of course, allowed a specific anatomic diagnosis. Despite the presence of ample tissue to secure a definitive diagnosis, the combination of clinical input and morphologic assessment was required to arrive at a definite diagnosis in most patients.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 30 Sep 2020; epub ahead of print
Roberts WC, Everett BP, Won VS, Kondapalli N
Am J Cardiol: 30 Sep 2020; epub ahead of print | PMID: 33011180
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Impact:
Abstract

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 x 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (met-HeFT).

Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Objectives
The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 x 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT).
Methods
Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4years.
Results
As of May 2020, 296 patients have been randomized at 20 centers in Denmark.
Conclusion
The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of two commonly prescribed drugs with limited randomized data in patients with HFrEF.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 07 Oct 2020; epub ahead of print
Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Am Heart J: 07 Oct 2020; epub ahead of print | PMID: 33039340
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Impact:
Abstract

In-hospital outcomes after bariatric surgery in patients with heart failure.

Blumer V, Greene SJ, Ortiz M, Kittipibul V, ... Mentz RJ, Vest AR

Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 25 Sep 2020; epub ahead of print
Blumer V, Greene SJ, Ortiz M, Kittipibul V, ... Mentz RJ, Vest AR
Am Heart J: 25 Sep 2020; epub ahead of print | PMID: 32991845
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Impact:
Abstract

Relation of Peripheral Venous Pressure to Central Venous Pressure in Patients with Heart Failure, Heart Transplant, and Left Ventricular Assist Device.

Vlismas PP, Wiesenfeld E, Oh KT, Murthy S, ... Jorde UP, Sims DB

Peripheral venous pressure (PVP) monitoring is a non-invasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r=0.93, p < 0.00001). High correlation was also noted when broken down by HF (r=0.93, p < 0.00001), HTx (r=0.93, p < 0.00001), and LVAD groups (r=0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, non-invasive estimate of volume status in these patient populations.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 11 Oct 2020; epub ahead of print
Vlismas PP, Wiesenfeld E, Oh KT, Murthy S, ... Jorde UP, Sims DB
Am J Cardiol: 11 Oct 2020; epub ahead of print | PMID: 33058805
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Impact:
Abstract

Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients with COVID-19.

Goerlich E, Gilotra NA, Minhas AS, Bavaro N, Hays AG, Cingolani OH
Background
COVID-19 has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain (LS) on speckle-tracking echocardiography (STE) in hospitalized COVID-19 patients and subsequently aimed to identify characteristics of affected patients. We hypothesized that COVID-19 patients with reduced basal LV strain would demonstrate elevated cardiac biomarkers.
Methods
81 consecutive COVID-19 patients underwent STE. Those with poor quality STE (n=2) or known LV ejection fraction<50% (n=4) were excluded. Patients with absolute value basal LS<13.9% (2SD below normal) were designated as cases (n=39); those with basal LS≥13.9% as controls (n=36). Demographics and clinical variables were compared.
Results
Of 75 included patients (mean age 62±14 years, 41% women), 52% had reduced basal strain. Cases had higher BMI (median[IQR]) (34.1[26.5-37.9]kg/m vs. 26.9[24.8-30.0]kg/m, p=0.009), and greater proportions of Black (74% vs. 36%, p=0.0009), hypertensive (79% vs. 56%, p=0.026) and diabetic patients (44% vs. 19%, p=0.025) compared to controls. Troponin and NT-proBNP levels trended higher in cases but were not significantly different.
Conclusions and relevance
Reduced basal LV strain is common in COVID-19 patients. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 25 Sep 2020; epub ahead of print
Goerlich E, Gilotra NA, Minhas AS, Bavaro N, Hays AG, Cingolani OH
J Card Fail: 25 Sep 2020; epub ahead of print | PMID: 32991982
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Impact:
Abstract

Left Atrial Strain in Evaluation of Heart Failure with Preserved Ejection Fraction.

Ye Z, Miranda WR, Yeung DF, Kane GC, Oh JK
Background
Patients with heart failure with preserved ejection fraction (HFpEF) may have elevated left ventricular filling pressure with exercise (LVFP-ex), despite normal LVFP at rest. The aim of this study was to assess the diagnostic value of resting left atrial strain (LAS) in detecting elevated LVFP-ex in patients with dyspnea evaluated on exercise stress echocardiography.
Methods
Two-dimensional speckle-tracking analysis for LAS was performed in 669 consecutive patients (mean age, 64 ± 14 years; 53% men) who underwent treadmill echocardiographic evaluation and had left ventricular ejection fractions ≥ 50%. Assessment of LVFP at rest LVFP-ex was based on the 2016 American Society of Echocardiography guidelines for diastolic function assessment. An E/e\' ratio ≥ 15 after exercise is considered to indicate elevated LVFP-ex. A continuous diagnostic score of HFpEF was calculated on the basis of the European Society of Cardiology HFA-PEFF diagnostic algorithm.
Results
LAS was lowest in patients with elevated LVFP at rest (n = 81) and lower in those with normal resting filling pressure who developed elevated LVFP-ex (n = 108) compared with those who maintained normal LVFP-ex (29.0 ± 5.2% vs 33.1 ± 5.0% vs 39.3 ± 4.8%, P < .001). Lower LAS was associated with worse exercise capacity as assessed by metabolic equivalents, exercise time, and functional aerobic capacity (multivariate-adjusted P values all < .05). In patients with normal or indeterminate LVFP at rest (n = 587), LAS and preexercise HFA-PEFF score demonstrated areas under the curve of 0.82 and 0.7, respectively, for elevated LVFP-ex. There were 28% higher odds of developing elevated LVFP-ex per 1% decrease in LAS (odds ratio, 0.78; 95% CI, 0.74-0.82). Among patients with intermediate scores (n = 461), 123 developed elevations in LVFP-ex and were classified as having HFpEF per the diagnostic algorithm. The addition of LAS improved the diagnostic value of HFA-PEFF score for HFpEF (area under the curve increased from 0.71 to 0.80, P = .01).
Conclusions
LAS has potential to identify patients with intermediate scores for HFpEF who may develop elevated LVFP-ex only and is therefore a promising alternative to aid in diagnosis when exercise testing is not feasible.

Copyright © 2020. Published by Elsevier Inc.

J Am Soc Echocardiogr: 23 Sep 2020; epub ahead of print
Ye Z, Miranda WR, Yeung DF, Kane GC, Oh JK
J Am Soc Echocardiogr: 23 Sep 2020; epub ahead of print | PMID: 32981787
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Impact:
Abstract

Healthcare Utilization and Cost in Patients with Atrial Fibrillation and Heart Failure Undergoing Catheter Ablation.

Field ME, Gold MR, Rahman M, Goldstein L, ... Piccini JP, Friedman DJ
Background
Catheter ablation is an effective treatment for patients with atrial fibrillation (AF) and heart failure (HF). However, little is known how healthcare utilization and cost change after ablation in this population. We sought to determine healthcare utilization and cost patterns among patients with AF and HF undergoing ablation.
Methods
Using a large US administrative database, we identified (n=1,568) treated with ablation with a primary and secondary diagnosis of AF and HF, respectively, were evaluated 1-year pre- and post-ablation for outcomes including inpatient admissions (AF or HF), emergency department (ED) visits, cardioversions, length of stay (LOS), and cost. A secondary analysis was extended to 3-years post-ablation.
Results
Reductions were observed in AF-related admissions (64%), LOS (65%), cardioversions (52%), ED visits (51%, all values, p<0.0001), and HF-related admissions (22%, p=0.01). There was a 40% reduction in inpatient admission cost ($4,165 pre-ablation to $2,510 post-ablation, p<0.0001). In a sensitivity analysis excluding repeat-ablation patients, greater reduction in overall AF management cost was observed compared to the full cohort (-43% vs -2%). Comparing 1-year pre- to 3-years post-ablation, both total mean AF-management cost ($850 per-patient per-month 1-year pre- to $546 3-years post-ablation, p<0.0001) and AF-related healthcare utilization was reduced.
Conclusions
Catheter ablation in patients with AF and HF resulted in significant reductions in healthcare utilization and cost through 3-years of follow-up. This reduction was observed regardless of whether repeat ablation was performed, reflecting positive impact of ablation on longer-term cost reduction. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 05 Oct 2020; epub ahead of print
Field ME, Gold MR, Rahman M, Goldstein L, ... Piccini JP, Friedman DJ
J Cardiovasc Electrophysiol: 05 Oct 2020; epub ahead of print | PMID: 33022815
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Impact:
Abstract

Evaluation of the right heart using cardiovascular magnetic resonance imaging in patients with cardiac devices.

Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Background
Patients with cardiac implantable electronic devices (CIED) necessitate comprehensive cardiovascular magnetic resonance (CMR) examinations. The aim of this study was to provide data on CMR image quality and feasibility of functional assessment of the right heart in patients with CIED depending on the device type and imaging sequence used.
Methods
120 CIED carriers (Insertable cardiac monitoring system, n = 13; implantable loop-recorder, n = 22; pacemaker, n = 30; implantable cardioverter-defibrillator (ICD), n = 43; and cardiac resynchronization therapy defibrillator (CRT-D), n = 12) underwent clinically indicated CMR imaging using a 1.5 T. CMR protocols consisted of cine imaging and myocardial tissue characterization including T1-and T2-weighted blackblood imaging and late gadolinium enhancement (LGE) imaging. Image quality was evaluated with regard to device-related imaging artifacts per right-ventricular (RV) segment.
Results
RV segmental evaluability was influenced by the device type and CMR imaging sequence: Cine steady-state-free-precision (SSFP) imaging was found to be non-diagnostic in patients with ICD/CRT-D and implantable loop recorders; a significant improvement of image quality was achieved when using cine turbo-field-echo (TFE) sequences with a further improvement on post-contrast TFE imaging. LGE scans were artifact-free in at least 91% of RV segments with best results in patients with a pacemaker or an insertable cardiac monitoring system.
Conclusions
In patients with CIED, artifact-free CMR imaging of the right ventricle was performed in the majority of patients and resulted in highly reproducible evaluability of RV functional parameters. This finding is of particular importance for the diagnosis and follow-up of right-ventricular diseases.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Sep 2020; 316:266-271
Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Int J Cardiol: 30 Sep 2020; 316:266-271 | PMID: 32389768
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Impact:
Abstract

Revascularisation therapies improve the outcomes of ischemic stroke patients with atrial fibrillation and heart failure.

Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Background
Atrial fibrillation (AF) and heart failure (HF) carry a poor prognosis in acute ischaemic stroke (AIS). The impact of revascularisation therapies on outcomes in these patients is not fully understood.
Method
National Inpatient Sample (NIS) AIS admissions (January 2004-September 2015) were included (n = 4,597,428). Logistic regressions analysed the relationship between exposures (neither AF nor HF-reference, AF-only, HF-only, AF + HF) and outcomes (in-hospital mortality, length-of-stay >median and moderate-to-severe disability on discharge), stratifying by receipt of intravenous thrombolysis (IVT) or endovascular thrombectomy (ET).
Results
69.2% patients had neither AF nor HF, 16.5% had AF-only, 7.5% had HF-only and 6.7% had AF + HF. 5.04% and 0.72% patients underwent IVT and/or ET, respectively. AF-only and HF-only were each associated with 75-85% increase in the odds of in-hospital mortality. AF + HF was associated with greater than two-fold increase in mortality. Patients with AF-only, HF-only or AF + HF undergoing IVT had better or at least similar in-hospital outcomes compared to their counterparts not undergoing IVT, except for prolonged hospitalisation. Patients undergoing ET with AF-only, HF-only or AF + HF had better (in-hospital mortality, discharge disability, all-cause bleeding) or at least similar (length-of-stay) outcomes to their counterparts not undergoing ET. Compared to AIS patients without AF, AF patients had approximately 50% and more than two-fold increases in the likelihood of receiving IVT or ET, respectively.
Conclusions
We confirmed the combined and individual impact of co-existing AF or HF on important patient-related outcomes. Revascularisation therapies improve these outcomes significantly in patients with these comorbidities.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 02 Oct 2020; epub ahead of print
Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Int J Cardiol: 02 Oct 2020; epub ahead of print | PMID: 33022289
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Abstract

Omecamtiv Mecarbil in Chronic Heart Failure with Reduced Ejection Fraction, GALACTIC-HF: Baseline Characteristics and Comparison with Contemporary Clinical Trials.

Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Kurtz CE,
Aims
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials.
Methods and results
Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT-proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC-HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m (n = 528), and treated with sacubitril-valsartan at baseline (n = 1594).
Conclusions
GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 26 Sep 2020; epub ahead of print
Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Kurtz CE,
Eur J Heart Fail: 26 Sep 2020; epub ahead of print | PMID: 32985088
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Abstract

Prognostic value of multiple cardiac magnetic resonance imaging parameters in patients with idiopathic dilated cardiomyopathy.

Fu H, Wen L, Xu H, Liu H, ... Yang Z, Guo Y
Purpose
Our study aimed to comprehensively explore efficient prognostic indicators in idiopathic dilated cardiomyopathy (IDCM) patients with reduced left ventricular ejection fraction (LVEF<40%).
Background
Prognostic value of cardiac magnetic resonance(CMR) parameters for IDCM have been inconsistent.
Methods
126 IDCM patients with reduced LVEF (<40%) were retrospectively enrolled. Cardiac function parameters, myocardial strain indices and myocardial fibrosis were evaluated. Laboratory data also were analyzed. The endpoint was a combination of major adverse cardiac events (MACEs), including cardiac death, heart transplantation, and rehospitalization. Prognostic value was evaluated by the Kaplan-Meier method and Cox regression.
Results
During a median follow-up of 31 months, 44 patients experienced MACEs, including 9 deaths, 1 heart transplantation, and 34 rehospitalizations due to heart failure. Univariate and multivariate Cox analyses showed that cardiac function and myocardial strain indexes were not associated with the prognosis of IDCM (all p > 0.05). NT-proBNP (HR 1.5, 95%CI: 1.053 to 2.137), Late‑gadolinium enhancement(LGE) mass (HR 1.022, 95%CI: 1.005 to 1.038), and LGE mass/left ventricle mass were significant predictors (HR 1.027, 95%CI: 1.007 to 1.046) for MACEs, all p < 0.05. Besides, poorest prognosis was observed in IDCM patients with positive LGE combined with NT-proBNP (log-rank = 27.261, p ≤ 0.001).
Conclusion
NT-proBNP and extent of LGE were reliable predictors in IDCM patients with reduced LVEF. Additionally, presence of LGE combined with NT-proBNP showed the strongest prognostic value in IDCM with reduced LVEF. Myocardial strain parameters seemed to have no prognostic value in IDCM patients with reduced LVEF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 Oct 2020; epub ahead of print
Fu H, Wen L, Xu H, Liu H, ... Yang Z, Guo Y
Int J Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33038407
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Impact:
Abstract

Systolic dysfunction of the subpulmonary left ventricle is associated with the severity of heart failure in patients with a systemic right ventricle.

Surkova E, Segura T, Dimopouosl K, Bispo D, ... Gatzoulis MA, Li W
Background
The study aimed to assess the relation between echocardiographic parameters of subpulmonary left ventricular (LV) size and function, and the severity of heart failure in patients with a systemic right ventricle (SRV).
Methods and results
A total of 157 patients (89 post Mustard/Senning operations, 68 with congenitally corrected transposition of great arteries [ccTGA]) were included. The size and function of the SRV and subpulmonary LV were assessed on the most recent echocardiographic exam. Clinical data were collected from the electronic records. The majority (133, 84.7%) were in NYHA functional class 1-2. Median BNP concentration was 79.5[38.3-173.3] ng/l, and 100 (63.7%) patients were receiving heart failure therapy. Both LV and SRV fractional area change (FAC) differed significantly between patients with NYHA class 1-2 vs 3-4 (48[41.5-52.8]% vs 34[28.6-38.6]%, p < 0.0001 and 29.5[23-35]% vs 22[20-27]%, p < 0.0001, respectively), but LV FAC had a higher discriminative power for functional class >2 than SRV FAC (AUC 0.90, p < 0.0001 vs 0.79; p < 0.0001, respectively). A LV FAC cut-off value <39.2% had the highest accuracy in identifying patients with NYHA class 3-4 (sensitivity 83% and specificity 88%). In multivariable logistic regression analysis, LV FAC and SRV FAC independently associated to NYHA class 3-4 (OR 0.80 [95%CI 0.72-0.88], p < 0.0001 and OR 0.85 [95%CI 0.76-0.96], p = 0.007, respectively).
Conclusions
Subpulmonary LV systolic dysfunction is associated with NYHA functional class 3-4 in patients with ccTGA or after Mustard or Senning operation. Careful evaluation of the subpulmonary LV should be a part of the routine assessment of patients with a SRV.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 24 Sep 2020; epub ahead of print
Surkova E, Segura T, Dimopouosl K, Bispo D, ... Gatzoulis MA, Li W
Int J Cardiol: 24 Sep 2020; epub ahead of print | PMID: 32987051
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Impact:
Abstract

Sex Disparities in the Management and Outcomes of Cardiogenic Shock Complicating Acute Myocardial Infarction in the Young.

Vallabhajosyula S, Ya\'Qoub L, Singh M, Bell MR, ... Holmes DR, Barsness GW
Background
There are limited data on how sex influences the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in young adults.
Methods
A retrospective cohort of AMI-CS admissions aged 18 to 55 years, during 2000 to 2017, was identified using the National Inpatient Sample. Use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support and noncardiac interventions was identified. Outcomes of interest included in-hospital mortality, use of cardiac interventions, hospitalization costs, and length of stay.
Results
A total 90 648 AMI-CS admissions ≤55 years of age were included, of which 26% were women. Higher rates of CS were noted in men (2.2% in 2000 to 4.8% in 2017) compared with women (2.6% in 2000 to 4.0% in 2017; <0.001). Compared with men, women with AMI-CS were more frequently of Black race, from a lower socioeconomic status, with higher comorbidity, and admitted to rural and small hospitals (all <0.001). Women had lower rates of ST-segment elevation presentation (73.0% versus 78.7%), acute noncardiac organ failure, cardiac arrest (34.3% versus 35.7%), and received less-frequent coronary angiography (78.3% versus 81.4%), early coronary angiography (49.2% versus 54.1%), percutaneous coronary intervention (59.2% versus 64.0%), and mechanical circulatory support (50.3% versus 59.2%; all <0.001). Female sex was an independent predictor of in-hospital mortality (23.0% versus 21.7%; adjusted odds ratio, 1.11 [95% CI, 1.07-1.16]; <0.001). Women had lower hospitalization costs ($156 372±$198 452 versus $167 669±$208 577; <0.001) but comparable lengths of stay compared with men.
Conclusions
In young AMI-CS admissions, women are treated less aggressively and experience higher in-hospital mortality than men.



Circ Heart Fail: 28 Sep 2020:CIRCHEARTFAILURE120007154; epub ahead of print
Vallabhajosyula S, Ya'Qoub L, Singh M, Bell MR, ... Holmes DR, Barsness GW
Circ Heart Fail: 28 Sep 2020:CIRCHEARTFAILURE120007154; epub ahead of print | PMID: 32988218
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Impact:
Abstract

Multidisciplinary Cardiac Rehabilitation and Long-Term Prognosis in Patients With Heart Failure.

Kamiya K, Sato Y, Takahashi T, Tsuchihashi-Makaya M, ... Makita S, Isobe M
Background
Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction.
Methods
This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants.
Results
Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65-0.92) for composite outcome, 0.67 (95% CI, 0.51-0.87) for all-cause mortality, and 0.82 (95% CI, 0.67-0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients.
Conclusions
Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.



Circ Heart Fail: 27 Sep 2020:CIRCHEARTFAILURE119006798; epub ahead of print
Kamiya K, Sato Y, Takahashi T, Tsuchihashi-Makaya M, ... Makita S, Isobe M
Circ Heart Fail: 27 Sep 2020:CIRCHEARTFAILURE119006798; epub ahead of print | PMID: 32986957
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Abstract

Predicting the Risk of Right Ventricular Failure in Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review.

Frankfurter C, Molinero M, Vishram-Nielsen JKK, Foroutan F, ... Orchanian-Cheff A, Alba AC
Background
Right ventricular failure (RVF) is a cause of major morbidity and mortality after left ventricular assist device (LVAD) implantation. It is, therefore, integral to identify patients who may benefit from biventricular support early post-LVAD implantation. Our objective was to explore the performance of risk prediction models for RVF in adult patients undergoing LVAD implantation.
Methods
A systematic search was performed on Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until August 2019 for all relevant studies. Performance was assessed by discrimination (via C statistic) and calibration if reported. Study quality was assessed using the Prediction Model Risk of Bias Assessment Tool criteria.
Results
After reviewing 3878 citations, 25 studies were included, featuring 20 distinctly derived models. Five models were derived from large multicenter cohorts: the European Registry for Patients With Mechanical Circulatory Support, Interagency Registry for Mechanically Assisted Circulatory Support, Kormos, Pittsburgh Bayesian, and Mechanical Circulatory Support Research Network RVF models. Seventeen studies (68%) were conducted in cohorts implanted with continuous-flow LVADs exclusively. The definition of RVF as an outcome was heterogenous among models. Seven derived models (28%) were validated in at least 2 cohorts, reporting limited discrimination (C-statistic range, 0.53-0.65). Calibration was reported in only 3 studies and was variable.
Conclusions
Existing RVF prediction models exhibit heterogeneous derivation and validation methodologies, varying definitions of RVF, and are mostly derived from single centers. Validation studies of these prediction models demonstrate poor-to-modest discrimination. Newer models are derived in cohorts implanted with continuous-flow LVADs exclusively and exhibit modest discrimination. Derivation of enhanced discriminatory models and their validations in multicenter cohorts is needed.



Circ Heart Fail: 27 Sep 2020:CIRCHEARTFAILURE120006994; epub ahead of print
Frankfurter C, Molinero M, Vishram-Nielsen JKK, Foroutan F, ... Orchanian-Cheff A, Alba AC
Circ Heart Fail: 27 Sep 2020:CIRCHEARTFAILURE120006994; epub ahead of print | PMID: 32981331
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Impact:
Abstract

The role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and Cardio-Oncology Council of the European Society of Cardiology.

Pudil R, Mueller C, Čelutkienė J, Henriksen PA, ... de Boer RA, Lyon AR

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research are discussed.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 01 Oct 2020; epub ahead of print
Pudil R, Mueller C, Čelutkienė J, Henriksen PA, ... de Boer RA, Lyon AR
Eur J Heart Fail: 01 Oct 2020; epub ahead of print | PMID: 33006257
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Impact:
Abstract

Prognostic value of cardio-pulmonary exercise testing in cardiac amyloidosis.

Nicol M, Deney A, Lairez O, Vergaro G, ... Arnulf B, Logeart D
Background
In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis.
Purpose
We sought to study how the cardio-pulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA).
Methods
We carried out a multicenter study including patients with light chain (AL) or transthyretin (TTR) CA. All patients underwent exhaustive examination including CPET and follow-up. The primary prognostic endpoint was the occurrence of death or heart failure (HF) hospitalization.
Results
We included 150 patients: 91 AL and 59 TTR CA. Median age, systolic blood pressure, NT-proBNP and cardiac troponin T were 70 [64-78] years old, 121 [IQR 109-139] mmHg, 2809 [IQR 1218-4638] ng/L and 64 [IQR 33-120] ng/L respectively. NYHA classes were I- II in 64%. Median peak VO and circulatory power were low at 13.0 mL/kg/min [10.0-16.9] and 1729 mmHg.mL min [1318-2614] respectively. The VE/VCO slope was increased to 37 [IQR 33-45]. Seventy-seven patients (51%) had chronotropic insufficiency. After a median follow-up of 20 months, there were 37 deaths and 44 HF hospitalizations. Multivariate Cox analysis shows that peak VO  ≤ 13 mL/kg/min (HR 2.7; CI95% 1.6-4.8), circulatory power ≤ 1800 mmHg.mL.min (HR 2.4; CI95% 1.2-4.6) and NT-proBNP ≥1800 ng/L (HR 2.2; CI95% 1.1-4.3) were associated with the primary outcome. There was no event in patients with both peak VO2 > 13 mL/kg/min and NTproBNP <1800 ng/L, while the association of VO2 ≤ 13 mL/kg/min and NTproBNP ≥1800 ng/L identified a very high-risk subgroup.
Conclusion
In CA, CPET helps to assess functional capacity, circulatory and chronotropic responses and helps to assess the prognosis of patients along with cardiac biomarkers.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 01 Oct 2020; epub ahead of print
Nicol M, Deney A, Lairez O, Vergaro G, ... Arnulf B, Logeart D
Eur J Heart Fail: 01 Oct 2020; epub ahead of print | PMID: 33006180
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Impact:
Abstract

Standardized Definitions for Evaluation of Heart Failure Therapies: Scientific Expert Panel from the Heart Failure Collaboratory and Academic Research Consortium (HF-ARC).

Abraham WT, Psotka MA, Fiuzat M, Filippatos G, ... Anker SD, O\'Connor CM

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation. CONDENSED ABSTRACT: The Heart Failure Collaboratory and Academic Research Consortium multi-stakeholder partnership convened to establish expert consensus definitions and key concepts for heart failure clinical trials including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. With uniform definitions, heart failure interventions can be better standardized, evaluated, and compared between trials and patient populations, and the quality of generated evidence may be strengthened.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 04 Oct 2020; epub ahead of print
Abraham WT, Psotka MA, Fiuzat M, Filippatos G, ... Anker SD, O'Connor CM
Eur J Heart Fail: 04 Oct 2020; epub ahead of print | PMID: 33017862
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Impact:
Abstract

ACE inhibitor/angiotensin II receptor blocker treatment and hemodynamic factors are associated with increased cardiac mRNA expression of ACE2 in patients with cardiovascular disease.

Lebek S, Tafelmeier M, Messmann R, Provaznik Z, ... Arzt M, Wagner S
Aims
The coronavirus disease 2019 (Covid-19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either ACE inhibitors or angiotensin 1-receptor blockers (ACEi/ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic.
Methods and results
We have measured ACE2 mRNA expression using real-time qPCR in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB versus 19 patients that were not ACEi/ARB-treated. We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent from potential confounding comorbidities. Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end-stage heart failure that were treated with ACEi/ARB. On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression.
Conclusion
Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery heart disease and in patients with end-stage heart failure. Further trials are needed to test whether this association is deleterious for patients with COVID-19, or possibly protective. Nevertheless, hemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 04 Oct 2020; epub ahead of print
Lebek S, Tafelmeier M, Messmann R, Provaznik Z, ... Arzt M, Wagner S
Eur J Heart Fail: 04 Oct 2020; epub ahead of print | PMID: 33017071
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Impact:
Abstract

Blood carbon dioxide tension and risk in pulmonary arterial hypertension.

Harbaum L, Fuge J, Kamp JC, Hennigs JK, ... Hoeper MM, Klose H
Background
Low partial pressure of blood carbon dioxide (PCO) is common in patients with pulmonary arterial hypertension (PAH) and may inform on clinical outcomes. We investigated whether PCO measurements could provide prognostic information in addition to standard risk assessment in this group of patients.
Methods
We conducted a retrospective observational cohort study on patients with newly diagnosed idiopathic, heritable or drug/toxin-induced PAH recruited from two European centres. Arterialised capillary blood gas analyses at diagnosis and follow-up were incorporated into standard risk assessment strategies and related to outcomes, defined as lung transplant or death. C statistics from receiver-operated characteristics and Cox regression models were used to assess the predictive value of models with and without PCO measurements. Unsupervised clustering was applied to assess the relation of PCO to haemodynamic and pulmonary function variables.
Results
Low PCO measured at diagnosis and follow-up was significantly associated with inferior outcomes in 204 patients with PAH. PCO provided prognostic information independent of established non-invasive variables. Integrating PCO in risk strata improved C statistics of non-invasive and mixed invasive/non-invasive models, and revealed more accurate outcome estimates in regression models. Pairwise correlation and unsupervised cluster analyses supported a link between PCO and haemodynamic variables, particularly with cardiac output, in PAH.
Conclusions
Measuring PCO at diagnosis and during follow-up in patients with PAH provided independent prognostic information and has the potential to improve current risk assessment strategies.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2020; 318:131-137
Harbaum L, Fuge J, Kamp JC, Hennigs JK, ... Hoeper MM, Klose H
Int J Cardiol: 31 Oct 2020; 318:131-137 | PMID: 32634498
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Impact:
Abstract

Cardiopulmonary exercise testing in chronic heart failure patients treated with beta-blockers: Still a valid prognostic tool.

Corrà U, Giordano A, Piepoli M
Background
The advent of beta-blockers (BBs) has revolutionized the treatment of heart failure due to left ventricular dysfunction (HFrEF), as these drugs increase survival and reduce hospitalization without a significant impact on exercise tolerance. In this new prognostic scenario, the predictive role of cardiopulmonary exercise testing (CPET) has been questioned.
Aim
To evaluate the predictive value of CPET and \"traditional\" derived and calculated risk parameters in HFrEF patients on BBs.
Methods
We retrospectively correlated 17 CPET risk parameters with hard events (cardiac death or urgent heart transplantation) over a 3-year follow-up in 744 HFrEF patients treated with BBs at our Institute from 2000 to 2013.
Results
Events were observed in 121/744 (16%) patients. Most CPET parameters were related to outcome at univariable analysis, but at multivariable analysis only exertional oscillatory ventilation (EOV), peak systolic blood pressure (SBP) and percentage of predicted peak VO2 (VO2%) resulted as significant. A CPET model using the dichotomized cut-off values of peak SPB ≤ 140 mmHg (HR = 2,27, p = .000, CI = 0.58-3.85), peak VO2% ≤ 50% (HR = 1.65, p = .008, CI = 1.14-2.38) and EOV = yes had a likelihood ratio of 45.27 (p = .000).
Conclusions
CPET confirmed its value as a prognostic tool in HFrEF patients treated with BBs, but different CPET parameters emerged as predictive (EOV, peak VO2% and peak SBP).

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2020; 317:128-132
Corrà U, Giordano A, Piepoli M
Int J Cardiol: 14 Oct 2020; 317:128-132 | PMID: 32611497
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Impact:
Abstract

Measurement, consequences and determinants of time to diagnosis in children with new-onset heart failure: A population-based retrospective study (DIACARD study).

Bichali S, Malorey D, Benbrik N, Le Gloan L, ... Baruteau AE, Launay E
Background
Time from first symptoms to diagnosis, called time to diagnosis, is related to prognosis in several diseases. The aim of this study was to assess time to diagnosis in children with new-onset heart failure (HF) and assess its consequences and determinants.
Methods
A retrospective population-based observational study was conducted between 2007 and 2016 in a French tertiary care center. We included all children under 16 years old with no known heart disease, and HF confirmed by echocardiography. With logistic regression used for outcomes and a Cox proportional-hazards model for determinants, analyses were stratified by HF etiology: congenital heart diseases (CHD) and cardiomyopathies/myocarditis (CM).
Results
A total of 117 children were included (median age [interquartile range (IQR)] 25 days (6-146), 50.4% were male, 60 had CHD and 57 had CM). Overall median (IQR) time to diagnosis was 3.3 days (1.0-21.2). The frequency of 1-year mortality was 17% and 1-year neuromotor sequel 18%. Death at 1 year was associated with low birth weight for all patients (adjusted odds ratio 0.24, 95% confidence interval [CI] 0.08-0.68) and time to diagnosis below the median with CM (0.09, 0.01-0.87) but not time to diagnosis above the median for all patients (0.59, 0.13-2.66). Short time to diagnosis was associated with clinical severity on the first day of symptoms for all patients (adjusted hazard ratio 3.39, 95% CI 2.01-5.72), and young age with CM (0.09, 0.02-0.41).
Conclusions
In children with new-onset HF presenting in our region, median time to diagnosis was short. Long time to diagnosis was not associated with poor outcome.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2020; 318:87-93
Bichali S, Malorey D, Benbrik N, Le Gloan L, ... Baruteau AE, Launay E
Int J Cardiol: 31 Oct 2020; 318:87-93 | PMID: 32553597
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Impact:
Abstract

Blockade of the neurohormonal systems in heart failure with preserved ejection fraction: A contemporary meta-analysis.

Gallo G, Tocci G, Fogacci F, Battistoni A, Rubattu S, Volpe M
Background
Although individual studies failed to demonstrate significant benefits with neurohormonal inhibitors in patients affected by heart failure (HF) with preserved ejection fraction (HFpEF), an evident trend towards a reduction in hospitalization and mortality has been previously documented in most cases. We aimed to conduct an updated meta-analysis on the effect of neurohormonal inhibitors [renin-angiotensin-aldosterone system (RAAS) inhibitors and angiotensin receptor neprilysin inhibitors (ARNi)] on the primary composite outcome of mortality and hospitalizations for HF and on the secondary outcomes of mortality and hospitalizations separately analyzed.
Methods and results
The extended literature search ended up with the identification of a total of 12 studies cumulatively including 30,882 patients, 16,540 in the treatment and 14,432 in the control groups. Eleven studies explored the outcome of death, 9 studies reported data about HF hospitalizations and 8 studies explored the composite outcome of death and HF hospitalizations. Our meta-analysis showed that treatment with neurohormonal inhibitors was significantly associated with a reduced risk of the primary composite outcome (OR 0.87, 95%CI: 0.82-0.93, p < .001; I = 2.2.) and with a decreased risk of HF hospitalizations (OR 0.84, 95%CI: 0.75-0.94, p = .002; I = 63%). In contrast, no significant effect on death was found (OR 0.79, 95%CI: 0.55-1.12, p = .184; I = 96.4%). Results remained substantially unchanged in the leave-one-out sensitivity analysis.
Conclusion
Our current work supports a beneficial effect of neurohormonal inhibitors (RAAS blockers and ARNi) on the primary composite outcome of death and HF hospitalizations and on the secondary outcome of HF hospitalizations in HFpEF patients. This finding provides support to the current prevalent clinical approach and to level of evidence reported in the Guidelines.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Sep 2020; 316:172-179
Gallo G, Tocci G, Fogacci F, Battistoni A, Rubattu S, Volpe M
Int J Cardiol: 30 Sep 2020; 316:172-179 | PMID: 32522678
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Abstract

Clinical significance of diastolic late mitral annular velocity in heart failure with preserved ejection fraction.

Oike F, Yamamoto E, Sueta D, Tokitsu T, ... Kaikita K, Tsujita K
Objectives
Because diastolic late mitral annular velocity (a\') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a\' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF).
Methods
We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a\' values were measured at septal mitral annuli.
Results
A\' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a\' and systolic mitral annular velocity (s\') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a\' plus s\' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a\' (<7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p < .01 by log-rank test) than those with high-a\' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a\' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714-0.949, p = .007) and HF-related events (HR: 0.551, 95% CI: 0.422-0.720, p < .001).
Conclusion
A\' value measurement is a non-invasive and useful method for risk stratification in HFpEF.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Sep 2020; 316:145-151
Oike F, Yamamoto E, Sueta D, Tokitsu T, ... Kaikita K, Tsujita K
Int J Cardiol: 30 Sep 2020; 316:145-151 | PMID: 32507393
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Abstract

Prevalence and incidence of various Cancer subtypes in patients with heart failure vs matched controls.

Schwartz B, Schou M, Gislason GH, Køber L, Torp-Pedersen C, Andersson C
Background
Patients with heart failure (HF) may be at increased risks of cancer, but the magnitude of risk for various cancer subtypes is insufficiently investigated.
Method
Using the Danish Nationwide administrative databases between 1997 and 2017, we estimated the prevalence, incidence and relative risk for all-cause cancer in new-diagnosed HF vs. age and sex-matched controls (up to 5 controls per HF case) before and after adjustment for comorbidities.
Results
Among the 167,633 people in the heart failure group and 837,126 individuals in the control group, there was a higher prevalence of several comorbidities, including cancer (17% vs. 10%) in the HF group; odds ratio 1.72 (1.70-1.75). Patients with heart failure also had higher cancer incidence (cancer incidence rate 3.02 [2.97-3.07] per 100 person-years), compared with controls (cancer incidence rate 1.89 [1.88-1.90]); hazards ratio 1.38 (1.36-1.40). However, after adjustment for comorbidities the increased risk of malignancy was greatly attenuated (hazards ratio 1.14 [1.12-1.16] for incident all-cause cancer) and dissipated altogether after additional adjustment for medications (multivariable adjusted hazards ratio 0.93 [0.91-0.96] for all-cause cancer). In a homogeneous cohort of patients with ischemic heart disease, the increased risk of all-cause cancer was only marginally increased after adjustment for baseline comorbidities (hazards ratio 1.05 [1.02-1.08]).
Conclusion
Patients with heart failure had a slightly increased risk of various cancer subtypes, but the risks were mainly driven by comorbidities.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Sep 2020; 316:209-213
Schwartz B, Schou M, Gislason GH, Køber L, Torp-Pedersen C, Andersson C
Int J Cardiol: 30 Sep 2020; 316:209-213 | PMID: 32446924
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Abstract

Altered Enhancer and Promoter Usage Leads to Differential Gene Expression in the Normal and Failed Human Heart.

Gacita AM, Dellefave-Castillo L, Page PGT, Barefield DY, ... Nobrega MA, McNally EM
Background
The failing heart is characterized by changes in gene expression. However, the regulatory regions of the genome that drive these gene expression changes have not been well defined in human hearts.
Methods
To define genome-wide enhancer and promoter use in heart failure, cap analysis of gene expression sequencing was applied to 3 healthy and 4 failed human hearts to identify promoter and enhancer regions used in left ventricles. Healthy hearts were derived from donors unused for transplantation and failed hearts were obtained as discarded tissue after transplantation.
Results
Cap analysis of gene expression sequencing identified a combined potential for ≈23 000 promoters and ≈5000 enhancers active in human left ventricles. Of these, 17 000 promoters and 1800 enhancers had additional support for their regulatory function. Comparing promoter usage between healthy and failed hearts highlighted promoter shifts which altered aminoterminal protein sequences. Enhancer usage between healthy and failed hearts identified a majority of differentially used heart failure enhancers were intronic and primarily localized within the first intron, revealing this position as a common feature associated with tissue-specific gene expression changes in the heart.
Conclusions
This data set defines the dynamic genomic regulatory landscape underlying heart failure and serves as an important resource for understanding genetic contributions to cardiac dysfunction. Additionally, regulatory changes contributing to heart failure are attractive therapeutic targets for controlling ventricular remodeling and clinical progression.



Circ Heart Fail: 29 Sep 2020:CIRCHEARTFAILURE120006926; epub ahead of print
Gacita AM, Dellefave-Castillo L, Page PGT, Barefield DY, ... Nobrega MA, McNally EM
Circ Heart Fail: 29 Sep 2020:CIRCHEARTFAILURE120006926; epub ahead of print | PMID: 32993371
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Abstract

Impact of predictive value of Fibrosis-4 index in patients hospitalized for acute heart failure.

Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Background
Abnormalities in liver function tests commonly occur in patients with acute heart failure (AHF). The Fibrosis-4 (FIB4) index, a non-invasive and easily calculated marker, has been used for hepatic diseases and reflects adverse prognosis. It is not clearly established whether the FIB4 index at admission can predict adverse outcomes in patients with AHF.
Methods and results
From a multicenter AHF registry, we retrospectively evaluated 1162 consecutive patients admitted due to AHF (median age 78 [69-85] years and 702 patients [60.4%] were male). The FIB4 index at admission was calculated as: age (yrs) × aspartate aminotransferase [U/L]/(platelets count [10/μL] × √alanine aminotransferase [U/L]. The median value of the FIB4 index at admission was 2.79. All-cause mortality and rehospitalization due to HF at 12 months were investigated as a composite endpoint and occurred in 142 (12.2%) patients and 232 (20%) patients, respectively. Kaplan-Meyer analysis shows a significant increase in the composite endpoint from the first to fourth quartile group of the FIB4 index values (log-rank, p < 0.001). Multivariate Cox regression model revealed the FIB4 index was an independent risk predictor for composite endpoint in patients with AHF (3 months: HR ratio 1.013 [95% Confidence interval (CI):1.001-1.025]; p = 0.03, 12 months: HR 1.015 [95% CI:1.005-1.025]; p = 0.003, respectively). However, neither aspartate aminotransferase, alanine aminotransferase, nor platelet count was found to be a significant predictor.
Conclusions
Hepatic dysfunction evaluated with the FIB4 index at admission is a predictor of the composite endpoint of all-cause mortality and rehospitalization in AHF patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 28 Sep 2020; epub ahead of print
Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Int J Cardiol: 28 Sep 2020; epub ahead of print | PMID: 33007325
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Abstract

Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients with Heart Failure with Reduced Ejection Fraction Treated with Sacubitril/Valsartan.

Ibrahim NE, Piña IL, Camacho A, Bapat D, ... Januzzi JL,

: Among patients with heart failure and reduced ejection fraction (HFrEF, left ventricular [LV] EF ≤40%) sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardiac remodeling. Data regarding racial and ethnic differences in response to S/V are lacking. : This was an analysis from the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure Study. Longitudinal changes in N-terminal pro B-type natriuretic peptide (NT-proBNP), cardiac reverse remodeling, and health status scores were compared between groups using multivariate latent growth curve modeling. : Among the 782 patients included in this study, 22.7% were Non-Hispanic Black (from herein referred to as Black), 14.9% were Hispanic, and 62.4% were Non-Hispanic White (from herein referred to as White). At baseline, compared to White patients, Black and Hispanic patients had lower NT-proBNP (g = 0.34) and differences between groups in baseline values for LVEDVi and LVESVi were negligible (g<0.10). Following S/V initiation, NT-proBNP decreased in all three groups (p<.0001) associated with improvements in LVEF, LVEDVi, and LVESVi. Although total improvement in LV measures was similar between groups, Black patients averaged larger gains in the first half of the trial while White patients averaged larger gains in the second half. Improvements in Kansas City Cardiomyopathy Questionnaire-23 Total Symptom scores were seen in all three groups. Treatment with S/V was well-tolerated. : Among Black, Hispanic, and White patients with HFrEF, treatment with S/V was associated with similar reduction in NT-proBNP, improvement in health status, and reverse remodeling. More data regarding racial and ethnic responses to HFrEF treatment are needed. : ClinicalTrials.gov; Unique Identifier: NCT02887183.



Circ Heart Fail: 02 Oct 2020; epub ahead of print
Ibrahim NE, Piña IL, Camacho A, Bapat D, ... Januzzi JL,
Circ Heart Fail: 02 Oct 2020; epub ahead of print | PMID: 33016100
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Abstract

Polygenic Score for Beta-Blocker Survival Benefit in European Ancestry Patients with Reduced Ejection Fraction Heart Failure.

Lanfear DE, Luzum JA, She R, Gui H, ... Li J, Williams LK

: Beta-blockers (BB) are mainstay therapy for heart failure with reduced ejection fraction (HFrEF). However, individual patient responses to BB vary, which may be partially due to genetic variation. The goal of this study was to derive and validate the first polygenic response predictor (PRP) for BB survival benefit in HFrEF patients. : Derivation and validation analyses were performed in n=1,436 total HF patients of European descent and with EF <50%. The PRP was derived in a random subset of the Henry Ford Pharmacogenomic Registry (HFPGR; n=248), and then validated in a meta-analysis of the remaining patients from HFPGR (n=247), the TIME-CHF (n=431), and HF-ACTION trial (n=510). The PRP was constructed from a genome-wide analysis of BB*genotype interaction predicting time to all-cause mortality, adjusted for MAGGIC score, genotype, level of BB exposure, and BB propensity score. : Five-fold cross-validation summaries out to 1000 SNPs identified optimal prediction with a 44 SNP score and cutoff at the 30th percentile. In validation testing (n=1188) greater BB exposure was associated with reduced all-cause mortality in patients with low-PRP score (n=251; HR=0.19 [95% CI=0.04-0.51], =0.0075), but not high-PRP score (n=937; HR=0.84 [95% CI=0.53-1.3], =0.448), a difference that was statistically significant ( interaction =0.0235). Results were consistent regardless of atrial fibrillation, EF (≤40% vs. 41-50%), or when examining cardiovascular death. : Among patients of European ancestry with HFrEF, a PRP distinguished patients who derived substantial survival benefit from BB exposure from a larger group that did not. Additional work is needed prospectively test clinical utility and to develop PRPs for other population groups and other medications.



Circ Heart Fail: 03 Oct 2020; epub ahead of print
Lanfear DE, Luzum JA, She R, Gui H, ... Li J, Williams LK
Circ Heart Fail: 03 Oct 2020; epub ahead of print | PMID: 33012170
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Abstract

Education and heart failure: New insights from the atherosclerosis risk in communities study and mendelian randomization study.

Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Introduction
We aim to characterize the nature and magnitude of the prospective association between education and incident heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them.
Methods
The final sample size was 12,315 in this study. Baseline characteristics between education levels were compared using 1-way ANOVA test, the Kruskal-Wallis test, or the χ2 test. We used the Kaplan-Meier estimate to compute the cumulative incident of HF by education levels and the difference in estimate was compared using the log-rank test. Cox hazard regression models were used to explore the association between education levels and incident HF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies (GWASs) was used to estimate the causal influence of the education and incident HF.
Results
During a median follow-up of 25.1 years, 2453 cases (19.9%) of incident HF occurred. After multiple adjustments in the final model, participants in the intermediate and advanced education levels were still associated with 18% and 21% decreased rate of incident HF separately. In MR analysis, we detected a protective causal association between education and HF (P = 0.005).
Conclusions
Participants with higher education levels were associated with a decreased rate of incident HF. There was a causal association between education and HF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 01 Oct 2020; epub ahead of print
Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Int J Cardiol: 01 Oct 2020; epub ahead of print | PMID: 33017630
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Abstract

Left Ventricular Systolic Ejection Time is an Independent Predictor of All-Cause Mortality in Heart Failure with Reduced Ejection Fraction.

Saed Alhakak A, Sengeløv M, Jørgensen PG, Bruun NE, ... Gislason G, Biering-Sørensen T
Background
Color Tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain the cardiac time intervals including the isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT+IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF), remains unknown.
Methods and results
A total of 997 patients with HFrEF (mean age 67±11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range, 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10ms decrease in SET (per 10 ms decrease: HR 1.09; 95% CI (1.06-1.13), p <0.001). The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10ms decrease: HR 1.06; 95% CI (1.01-1.11), p=0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06; 95% CI (1.16-8.06), p=0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between the IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, the SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF.
Conclusion
In patients with HFrEF, the SET provides independent and incremental prognostic information regarding all-cause mortality.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Oct 2020; epub ahead of print
Saed Alhakak A, Sengeløv M, Jørgensen PG, Bruun NE, ... Gislason G, Biering-Sørensen T
Eur J Heart Fail: 08 Oct 2020; epub ahead of print | PMID: 33034122
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Abstract

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

Ghuman J, Cai X, Patel R, Khan S, ... Isakova T, Mehta R
Background
Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy (LVH) and reduced exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D and iron homeostasis, is linked to LVH and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.
Methods
Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption (VO) and 6-minute walk distance (6MWD) in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population comprised of 172 individuals with available plasma for cFGF23 and iFGF23 measurements.
Results
Median (25-75 percentile) baseline cFGF23 and iFGF23 levels were 208.7 (132.1-379.5) RU/ml and 90.3 (68.6-128.5) pg/ml, respectively. After adjustment for cardiovascular disease, hematologic and kidney parameters, higher cFGF23 was independently associated with lower peak VO at baseline. Higher iFGF23 was independently associated with shorter 6MWD at baseline. No significant associations were appreciated with the longitudinal outcomes.
Conclusion
In patients with HFpEF, higher FGF23 levels are independently associated with reduced exercise capacity at baseline.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 05 Oct 2020; epub ahead of print
Ghuman J, Cai X, Patel R, Khan S, ... Isakova T, Mehta R
J Card Fail: 05 Oct 2020; epub ahead of print | PMID: 33035687
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Abstract

Validity of hemodynamic monitoring using inert gas rebreathing method in patients with chronic heart failure and those implanted with a left ventricular assist device.

Okwose NC, Bouzas-Cruz N, Fernandez OG, Koshy A, ... MacGowan GA, Jakovljevic DG
Objective
The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD).
Methods and results
Haemodynamic measurements were obtained in 42 patients: 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males; aged 50 ± 11 years). Measurements were performed at rest using thermodilution and inert gas rebreathing methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4±0.9 vs 4.7±0.8 l/min; P=0.27) or heart failure patients (4.4±1.4 vs 4.5 ± 1.3 l/min; P=0.75). There was a strong relationship between thermodilution and IGR cardiac index (r=0.81, p=0.001) and stroke volume index (r=0.75, p=0.001). Bland-Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR i.e. mean difference (lower and upper limits of agreement) for heart failure patients -0.002 (-0.65 - 0.66) l/min/m, and -0.14 (-0.78 - 0.49) l/min/m for patients with LVAD.
Conclusion
Inert gas rebreathing is a valid method for estimating cardiac output and should be used in clinical practice to complement evaluation and management of chronic heart failure and LVAD patients.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 05 Oct 2020; epub ahead of print
Okwose NC, Bouzas-Cruz N, Fernandez OG, Koshy A, ... MacGowan GA, Jakovljevic DG
J Card Fail: 05 Oct 2020; epub ahead of print | PMID: 33035686
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Abstract

HFPEF Score Reflects the Left Atrial Strain and Predicts Prognosis in Patients with Heart Failure with Preserved Ejection Fraction.

Hwang IC, Cho GY, Choi HM, Yoon YE, ... Kim HK, Kim YJ
Background
The HFPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the HFPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure (AHF).
Methods and results
In total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the HFPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range, 69-82). The median HFPEF score was 4 (interquartile range, 3-6). Patients with higher HFPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the LA (PALS), mitral E/e\' ratio, and peak tricuspid regurgitation velocity. PALS demonstrated a significant association with the HFPEF score, in patients without atrial fibrillation (AF) and those without AF. After adjustment for clinical factors and echocardiographic parameters, patients with higher HFPEF scores had higher risk of mortality and HF hospitalization regardless of the presence of AF.
Conclusions
HFPEF score reflects LA function in patients with HFpEF admitted for AHF. This association supports the clinical usefulness of the HFPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 05 Oct 2020; epub ahead of print
Hwang IC, Cho GY, Choi HM, Yoon YE, ... Kim HK, Kim YJ
J Card Fail: 05 Oct 2020; epub ahead of print | PMID: 33035685
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Abstract

VENTILATION DISPERSION INDEX AS AN OBJECTIVE EVALUATION TOOL OF EXERCISE OSCILLATORY VENTILATION IN PATIENTS WITH HEART FAILURE.

Corte RC, de Sá J, Carlos R, Felismino AS, ... Pereira E, Bruno S
Introduction
Exercise oscillatory ventilation (EOV) is related to worse prognosis in patients with heart failure (HF). However, its determination is subjective and there is no standard measure to identify it. The aim of the study was to evaluate and characterize the EOV of patients with HF using the ventilation dispersion index (VDI).
Methods
Patients underwent cardiopulmonary exercise testing (CPX), EOV was assessed by two reviewers and the VDI was calculated. The ROC curve analysis was used to assess the ability of the VDI to predict EOV. Pearson\'s correlation test was performed to determine the relationship between VDI and CPX variables.
Results
43 HF patients underwent CPX and were divided into two groups: with VDI<0.601; and VDI≥0.601. An AUC=0.759 was observed in the ROC curve analysis between VDI and EOV (p=0.008). The VDI showed a significant correlation with the ventilatory CPX variables. According to the cut-off point obtained on the ROC curve, patients with VDI≥0.601 had lower left ventricular ejection fraction (LVEF) and higher values of resting minute ventilation (VE) and peak VE.
Conclusion
VDI proved to be a good predictor of EOV in patients with HF.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 06 Oct 2020; epub ahead of print
Corte RC, de Sá J, Carlos R, Felismino AS, ... Pereira E, Bruno S
J Card Fail: 06 Oct 2020; epub ahead of print | PMID: 33038533
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Abstract

Plasma Volume Status and its Association with In-Hospital and Post-Discharge Outcomes in Decompensated Heart Failure.

Fudim M, Lerman JB, Page C, Alhanti B, ... O\'Connor CM, Mentz RJ
Background
Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV-status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and post-discharge clinical outcomes, in the ASCEND-HF trial.
Methods and results
KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. 6,373 (89.2%), and 6,354 (89.0%), patients had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with NT-proBNP, and with measures of decongestion such as body weight change and urine output (r<0.3 for all). Duarte-ePV was trending towards an association with worse 30-day (adjusted-OR 1.07, 95%CI 1.00-1.15, p=0.058), but not 180-day outcomes (adjusted-HR 1.03, 95%CI 0.97-1.09, p=0.289). Continuous KH-ePVS>0 (per 10 unit increase) was associated with improved 30-day outcomes (adjusted-OR 0.75, 95%CI 0.62-0.91, p=0.004). Continuous KH-ePVS was not associated with 180-day outcomes (adjusted-HR 1.05, 95%CI 0.98-1.12, p=0.139).
Conclusions
Baseline PV estimates had a weak association with in-hospital measures of decongestion. Duarte-ePV, trended towards an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 06 Oct 2020; epub ahead of print
Fudim M, Lerman JB, Page C, Alhanti B, ... O'Connor CM, Mentz RJ
J Card Fail: 06 Oct 2020; epub ahead of print | PMID: 33038532
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Abstract

sST2 and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction.

Espriella R, Bayés-Genis A, Revuelta E, Miñana G, ... Núñez J,
Background
Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24- and 72-hour in patients with AHF and concomitant renal dysfunction (RD).
Methods and results
This is a post-hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and RD [estimated glomerular filtrate rate (eGFR) <60 mL/min/1.73m2]. DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and diuretic efficiency was evaluated by using multivariate linear regression analysis. The median (interquartile range) cumulative DE at 24- and 72-hour was 747 ml (490-1167) and 1844 ml (1142-2625), respectively. The median (interquartile range) sST2, and mean eGFR were 72 ng/mL (47-117), and 34.0±8.5 ml/min/1.73m2, respectively. In a multivariable setting, higher sST2 were significant and non-linearly related to lower DE both at 24- and 72-hour (P=0.002 and P=0.019, respectively).
Conclusions
In patients with AHF and RD at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24- and 72-hour.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 07 Oct 2020; epub ahead of print
Espriella R, Bayés-Genis A, Revuelta E, Miñana G, ... Núñez J,
J Card Fail: 07 Oct 2020; epub ahead of print | PMID: 33038531
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Abstract

Longitudinal Strain Reflects Ventriculoarterial Coupling Rather Than Mere Contractility in Rat Models of Hemodynamic Overload-Induced Heart Failure.

Ruppert M, Lakatos BK, Braun S, Tokodi M, ... Kovács A, Radovits T
Background
Longitudinal strain (LS) is a sensitive marker of systolic function. Recent findings suggest that both myocardial contractility and loading conditions determine LS. The aim of this study was to investigate whether LS reflects the connection of cardiac contractility to afterload (termed ventriculoarterial coupling [VAC]) rather than mere contractility in rat models of hemodynamic overload-induced heart failure (HF).
Methods
Pressure overload-induced HF was evoked by transverse aortic constriction (TAC; n = 14). Volume overload-induced HF was established by an aortocaval fistula (ACF; n = 12). Age-matched sham-operated animals served as controls for TAC (n = 14) and ACF (n = 12), respectively. Pressure-volume analysis was carried out to compute contractility (slope of end-systolic pressure-volume relationship [ESPVR]), afterload (arterial elastance [E]), and VAC (E/ESPVR). Preload was evaluated by meridional end-diastolic wall stress. Speckle-tracking echocardiography was performed to assess LS.
Results
The TAC group presented with maintained ESPVR, increased E, and enhanced meridional end-diastolic wall stress. In contrast, the ACF group was characterized by reduced ESPVR, decreased E, and enhanced meridional end-diastolic wall stress. VAC increased in both HF groups. Furthermore, LS was also impaired in both HF models (-5.9 ± 0.6% vs -12.9 ± 0.5%, TAC vs Sham [P < .001], and -11.7 ± 0.7% vs -13.5 ± 0.4%, ACF vs Sham[P = .048]). Statistical analysis revealed that strain parameters were determined predominantly by afterload in the TAC group and by contractility in the ACF group, while preload had a minor effect. In the entire study population, LS showed a correlation with VAC (R = 0.654, P < .001) but not with ESPVR (R = 0.058, P = .668).
Conclusions
Under pathophysiologic conditions when both contractility and afterload become altered, LS reflects VAC rather than mere contractility.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 29 Sep 2020; 33:1264-1275.e4
Ruppert M, Lakatos BK, Braun S, Tokodi M, ... Kovács A, Radovits T
J Am Soc Echocardiogr: 29 Sep 2020; 33:1264-1275.e4 | PMID: 32778499
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Impact:
Abstract

Long-term follow-up of patients with heart failure and reduced ejection receiving autonomic regulation therapy in the ANTHEM-HF pilot study.

Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Background
The ANTHEM-HF pilot study was an open-label study that evaluated the safety and feasibility of autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) for patients with chronic HF with reduced EF (HFrEF). Patients in NYHA class II-III with EF ≤40% (n = 60) received ART for 6 months post-titration. ART was associated with sustained improvement in left ventricular (LV) function and HF symptoms at 6 and 12 months.
Methods
Continuously cyclic VNS was maintained to determine longer-term safety and chronic effects of ART. Echocardiographic parameters and HF symptoms were assessed throughout a follow-up period of at least 42 months.
Results
Between 12 and 42 months after initial titration, there were no device-related SAEs or malfunctions. There were 10 SAEs adjudicated to be unrelated to VNS, including 5 deaths. There were 6 non-serious adverse events that were adjudicated to be device-related (2 oropharyngeal pain, 1 implant site pain, 2 voice alteration, and 1 hoarseness). At 42 months, there was significant improvement from baseline in LVEF, NYHA class, 6-min walk distance, and MLHFQ score. However, these improvements at 42 months were not significantly different from mean values at 6 and 12 months.
Conclusions
In a 42-month follow-up, ART was durable, safe, and was associated with beneficial effects on LVEF and 6-min walk distance. Long term, chronic, open-loop ART continued to be well-tolerated in patients with HFrEF. The open label, randomized, controlled, ANTHEM-HFrEF Pivotal Study is currently underway to further evaluate ART in patients with advanced HF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 Oct 2020; epub ahead of print
Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Int J Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33038408
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Impact:
Abstract

Vagus Nerve Stimulation Provides Multiyear Improvements in Autonomic Function and Cardiac Electrical Stability in the ANTHEM-HF Study.

Nearing BD, Anand IS, Libbus I, DiCarlo LA, KenKnight BH, Verrier RL
Background
Patients with heart failure with reduced LVEF (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. ANTHEM-HF reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist long-term.
Methods and results
Effects of chronic VNS on heart rate, HRV, HRT, TWA, R-wave and T-wave heterogeneity (RWH, TWH), and nonsustained ventricular tachycardia (NSVT) incidence were evaluated in all ANTHEM-HF patients with ambulatory ECG data at 24 and 36 months (n=25). Autonomic markers improved significantly at 24 months and 36 months compared to baseline (heart rate, rMSSD, SDNN, HF-HRV, HRT slope, p<0.05). Peak TWA levels remained reduced at 24 and 36 months (p<0.0001). Reductions in RWH and TWH at 6 and 12 months persisted at 24 and 36 months (p<0.01). NSVT decreased at 12, 24, and 36 months (p<0.025). No sudden cardiac deaths, ventricular fibrillation, or sustained ventricular tachycardia occurred.
Conclusion
In symptomatic patients with HFrEF, chronic VNS appears to confer wide-ranging, persistent improvements in autonomic tone (HRV), baroreceptor sensitivity (HRT), and cardiac electrical stability (TWA, RWH, TWH).

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 09 Oct 2020; epub ahead of print
Nearing BD, Anand IS, Libbus I, DiCarlo LA, KenKnight BH, Verrier RL
J Card Fail: 09 Oct 2020; epub ahead of print | PMID: 33049374
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Impact:
Abstract

Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure.

Zhou B, Wang DD, Qiu Y, Airhart S, ... O\'Brien KD, Tian R

BackgroundWhile mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure (HF) is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level.METHODSWe compared the PBMC mitochondrial respiration of 19 hospitalized patients with stage D HF with that of 19 healthy participants. We then created an in vitro model of sterile inflammation by treating healthy PBMCs with mitochondrial damage-associated molecular patterns (MitoDAMPs) isolated from human heart tissue. Last, we enrolled patients with stage D HF and sampled their blood before and after taking 5 to 9 days of oral nicotinamide riboside (NR), a NAD precursor.RESULTSWe demonstrated that HF is associated with both reduced respiratory capacity and elevated proinflammatory cytokine gene expressions. In our in vitro model, MitoDAMP-treated PBMCs secreted IL-6 that impaired mitochondrial respiration by reducing complex I activity. Last, oral NR administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with HF.CONCLUSIONThese findings suggest that systemic inflammation in patients with HF is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in HF.TRIAL REGISTRATIONClinicalTrials.gov NCT03727646.FundingThis study was funded by the NIH, the University of Washington, and the American Heart Association.



J Clin Invest: 11 Oct 2020; epub ahead of print
Zhou B, Wang DD, Qiu Y, Airhart S, ... O'Brien KD, Tian R
J Clin Invest: 11 Oct 2020; epub ahead of print | PMID: 32790648
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Impact:
Abstract

Polypharmacy in Older Adults Hospitalized for Heart Failure.

Unlu O, Levitan EB, Reshetnyak E, Kneifati-Hayek J, ... Lachs MS, Goyal P
Background
Despite potential harm that can result from polypharmacy, real-world data on polypharmacy in the setting of heart failure (HF) are limited. We sought to address this knowledge gap by studying older adults hospitalized for HF derived from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke).
Methods
We examined 558 older adults aged ≥65 years with adjudicated HF hospitalizations from 380 hospitals across the United States. We collected and examined data from the REGARDS baseline assessment, medical charts from HF-adjudicated hospitalizations, the American Hospital Association annual survey database, and Medicare\'s Hospital Compare website. We counted the number of medications taken at hospital admission and discharge; and classified each medication as HF-related, non-HF cardiovascular-related, or noncardiovascular-related.
Results
The vast majority of participants (84% at admission and 95% at discharge) took ≥5 medications; and 42% at admission and 55% at discharge took ≥10 medications. The prevalence of taking ≥10 medications (polypharmacy) increased over the study period. As the number of total medications increased, the number of noncardiovascular medications increased more rapidly than the number of HF-related or non-HF cardiovascular medications.
Conclusions
Defining polypharmacy as taking ≥10 medications might be more ideal in the HF population as most patients already take ≥5 medications. Polypharmacy is common both at admission and hospital discharge, and its prevalence is rising over time. The majority of medications taken by older adults with HF are noncardiovascular medications. There is a need to develop strategies that can mitigate the negative effects of polypharmacy among older adults with HF.



Circ Heart Fail: 12 Oct 2020:CIRCHEARTFAILURE120006977; epub ahead of print
Unlu O, Levitan EB, Reshetnyak E, Kneifati-Hayek J, ... Lachs MS, Goyal P
Circ Heart Fail: 12 Oct 2020:CIRCHEARTFAILURE120006977; epub ahead of print | PMID: 33045844
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Impact:
Abstract

Five-year mortality and readmission rates in patients with heart failure in India: Results from the Trivandrum heart failure registry.

Harikrishnan S, Jeemon P, Ganapathi S, Agarwal A, ... Suresh K, Huffman MD
Introduction
Heart failure (HF) has emerged as an important and increasing disease burden in India. We present the 5-year outcomes of patients hospitalized for HF in India.
Methods
The Trivandrum Heart Failure Registry (THFR) recruited consecutive patients admitted for acute HF among 16 hospitals in Trivandrum, Kerala in 2013. Guideline-directed medical therapy (GDMT) was defined as the combination of beta-blockers (BB), renin angiotensin system blockers (RAS), and mineralocorticoid receptor antagonists (MRA) in patients with HF with reduced ejection fraction (HFrEF, EF < 40%) at discharge. We used Cox proportional hazards models and Kaplan-Meier survival plots for analysis. The MAGGIC risk score variables were included as exposure variables.
Results
Among 1205 patients [69% male, mean (SD) age = 61.2 (13.7) years], HFrEF constituted 62% of patients and among them, 25% received GDMT. The 5-year mortality rate was 59% (n = 709 deaths), and median survival was 3.1 years. Sudden cardiac death and pump failure caused 46% and 49% of the deaths, respectively. In the multivariate Cox model, components of GDMT associated with lower 5-year mortality risks were discharge prescription of BB, RAS blocker, and MRA. Readmissions, older age, lower systolic blood pressure, NYHA class III or IV, and higher serum creatinine were also associated with higher 5-year mortality.
Conclusions
Three out of every 5 patients had died during 5-years of follow-up with a median survival of approximately 3 years. Lack of GDMT in patients with HFrEF and frequent readmissions were associated with higher 5-year mortality. Quality improvement programmes with strategies to improve adherence to GDMT and reduction in readmissions may improve HF outcomes in this region.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 09 Oct 2020; epub ahead of print
Harikrishnan S, Jeemon P, Ganapathi S, Agarwal A, ... Suresh K, Huffman MD
Int J Cardiol: 09 Oct 2020; epub ahead of print | PMID: 33049297
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Impact:
Abstract

Obesity paradox in Korean male and female patients with heart failure: A report from the Korean heart failure registry.

Lee SY, Kim HL, Kim MA, Park JJ, ... Cho MC,
Background
Although the survival benefit of obesity has been suggested in patients with heart failure (HF), the impact of sex on obesity paradox is less clear. This study was performed to investigate whether there is a sex difference in the association between body mass index (BMI) and long-term clinical outcomes in patients hospitalized for HF.
Method
A total of 2616 patients hospitalized for HF (Mean age 66 years and 52% males) from the nation-wide registry database were analyzed. Patients were categorized using baseline BMI as normal (18.5 to 22.9 kg/m), overweight (23 to 27.4 kg/m) and obese (≥27.5 kg/m). Their all-cause mortality and long-term composite events, including all-cause mortality and HF readmission, were assessed according to the BMI groups.
Results
During the median follow-up period of 1499 days, there were 662 patients (25.3%) with all-cause mortality and 1071 patients (40.9%) with composite events. Compared to the normal weight group, the overweight (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.99; P = 0.045) and obese (HR, 0.53; 95% CI, 0.29-0.95; P = 0.032) group showed lower all-cause mortality rates even after adjusting for confounding factors in the male patients. Otherwise, BMI was not associated with composite events in males; it was not associated with all-cause mortality or composite events in females in the multivariable analyses (P > 0.05 for each).
Conclusions
Among patients with HF, a greater BMI was associated with low all-cause mortality in males, but not in females. Obesity paradox should be considered in the management of HF patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 08 Oct 2020; epub ahead of print
Lee SY, Kim HL, Kim MA, Park JJ, ... Cho MC,
Int J Cardiol: 08 Oct 2020; epub ahead of print | PMID: 33045277
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Impact:
Abstract

Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure.

Goyal P, Unlu O, Kennel PJ, Schumacher RC, ... Rich MW, Makam A
Background
To facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit/harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information.
Methods
We reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context.
Results
We examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update, and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations, and a quarter of ESC recommendations.
Conclusions
The majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 12 Oct 2020; epub ahead of print
Goyal P, Unlu O, Kennel PJ, Schumacher RC, ... Rich MW, Makam A
J Card Fail: 12 Oct 2020; epub ahead of print | PMID: 33065263
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Impact:
Abstract

Heart Failure Association of the European Society of Cardiology Update on Sodium Glucose Co-transporter-2 Inhibitors in Heart Failure (an update on the Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. The position paper of the Heart Failure Association of the European Society of Cardiology).

Seferović PM, Fragasso G, Petrie M, Mullens W, ... Coats AJS, Rosano GMC

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin have consistently demonstrated to be effective for the prevention of HF hospitalisation in patients with T2DM and established CV disease or at high CV risk. The specifically listed agents are recommended. Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalisation and CV death in symptomatic patients with HF and reduced ejection fraction, already receiving guideline directed medical therapy, regardless of the presence of T2DM.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 16 Oct 2020; epub ahead of print
Seferović PM, Fragasso G, Petrie M, Mullens W, ... Coats AJS, Rosano GMC
Eur J Heart Fail: 16 Oct 2020; epub ahead of print | PMID: 33068051
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Impact:
Abstract

Telemonitoring in patients with chronic heart failure and moderate depressed symptoms - results of the Telemedical Interventional Monitoring in Heart Failure (TIM-HF) study.

Koehler J, Stengel A, Hofmann T, Wegscheider K, ... Koehler F, Laufs U
Background
Depression is a frequent comorbidity in patients with chronic heart failure (CHF). Telemonitoring has emerged as a novel option in CHF care. However, patients with depression were excluded in most telemedicine studies.
Aims
This prespecified subgroup-analysis of the Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial investigates the effect on depressive symptoms over a period of 12 months.
Methods
The TIM-HF study randomly assigned 710 patients with CHF to either usual care (UC) or a telemedical intervention (TM) using non-invasive devices for daily monitoring electrocardiogram, blood pressure and body weight. Depression was evaluated by the Patient Health Questionnaire (PHQ-9) with scores ≥10 defining clinically relevant depressive symptoms. Mixed model repeated measures were performed to calculate changes in PHQ-9 score. Quality of life (Qol) was measured by the Short Form-36 (SF-36).
Results
At baseline, 156 patients had a PHQ-9 score ≥10 points (TM: 79, UC: 77) with a mean of 13.2 points indicating moderate depressiveness. Patients randomized to telemedicine showed an improvement of their PHQ-9 scores, whereas UC patients remained constant (p=0.004). Qol parameters were improved in the TM group compared to UC. Adjustment was performed for follow-up, NYHA class, medication, age, current living status, number of hospitalizations within last 12 months and serum creatinine. In the study population without depression the PHQ-9 score was similar at baseline and follow-up.
Conclusion
Telemedical care improved depressive symptoms and had a positive influence on quality of life in patients with CHF and moderate depression.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 14 Oct 2020; epub ahead of print
Koehler J, Stengel A, Hofmann T, Wegscheider K, ... Koehler F, Laufs U
Eur J Heart Fail: 14 Oct 2020; epub ahead of print | PMID: 33063412
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Impact:
Abstract

Association Between β-Blocker Use and Mortality/Morbidity in Patients With Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction and Advanced Chronic Kidney Disease.

Fu EL, Uijl A, Dekker FW, Lund LH, Savarese G, Carrero JJ
Background
It is unknown if β-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials.
Methods
Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between β-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate <60-30 mL/min per 1.73 m), for whom β-blocker trials demonstrate benefit. Second, we explored outcomes associated to β-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514).
Results
During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, β-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75-0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77-0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for β-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77-1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90-1.23]) or HFmrEF (death: 0.95 [0.79-1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90-1.31]).
Conclusions
In HFrEF patients with advanced CKD, the use of β-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF.



Circ Heart Fail: 18 Oct 2020:CIRCHEARTFAILURE120007180; epub ahead of print
Fu EL, Uijl A, Dekker FW, Lund LH, Savarese G, Carrero JJ
Circ Heart Fail: 18 Oct 2020:CIRCHEARTFAILURE120007180; epub ahead of print | PMID: 33070637
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Impact:
Abstract

Atrial fibrillation ablation in heart failure: What do we know? What can we do?

Chiocchini A, Terricabras M, Verma A

Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are two conditions that frequently impact reciprocally on each other. Patients with HFrEF have an increased risk of stroke, hospitalization and mortality after they develop AF and vice versa, AF causing deterioration of the ejection fraction is also associated to increased mortality. Catheter ablation has emerged as an effective alternative to antiarrhythmic drug treatment to maintain sinus rhythm and some randomized trials have shown a potential benefit in terms of mortality and hospitalization. This review discusses the available evidence regarding catheter ablation treatment in this specific patient group.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Europace: 20 Oct 2020; epub ahead of print
Chiocchini A, Terricabras M, Verma A
Europace: 20 Oct 2020; epub ahead of print | PMID: 33083820
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Impact:
Abstract

Clinical characteristics and outcomes of chronic heart failure in adult Takayasu arteritis: A cohort study of 163 patients.

Zhang Y, Fan P, Zhang H, Ma W, ... Luo F, Zhou X
Background
Chronic heart failure (CHF) is a serious complication and a major cause of mortality in patients with Takayasu arteritis (TA). We aimed to explore the clinical features and long-term outcomes in TA patients with CHF.
Methods and results
Adult TA patients admitted to our hospital between January 2009 to April 2018 were classified as HF and non-HF group. The adverse events were defined as a composite of all-cause mortality and hospitalization for HF. The outcome of the HF-group was further analyzed. A total of 61 HF patients and 102 non-HF patients were identified. In the HF group, the median age at assessment was 41.9 years, and female was predominant (82.0%). The multivariable logistic regression model revealed that pulmonary hypertension, aortic regurgitation, mitral regurgitation, level albumin, and uric acid were independently associated with CHF. After a median follow-up of 1347 days, 25 adverse events occurred in HF patients, and the 5-year event-free rate was 54.7%. The Cox model showed that coronary artery involvement, aortic regurgitation, without interventional treatment were related to adverse events.
Conclusions
The 5-year event-free rate was not satisfying. Aggressive intervention may decreased the likelihood of adverse events in patients with CHF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 17 Oct 2020; epub ahead of print
Zhang Y, Fan P, Zhang H, Ma W, ... Luo F, Zhou X
Int J Cardiol: 17 Oct 2020; epub ahead of print | PMID: 33086124
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Impact:
Abstract

Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort.

Raval AN, Johnston PV, Duckers HJ, Cook TD, ... Anderson RD, Pepine CJ
Aim
Heart failure following myocardial infarction (MI) is a potentially lethal problem with a staggering incidence. The CardiAMP Heart Failure trial represents the first attempt to personalize marrow-derived cell-based therapy to individuals with cell characteristics associated with beneficial responses in prior trials. Before the initiation of the randomized pivotal trial, an open-label \"roll-in cohort\" was completed to ensure the feasibility of the protocol\'s procedures.
Methods
Patients with chronic post-MI heart failure (NYHA class II-III) receiving stable, guideline-directed medical therapy with a left ventricular ejection fraction between 20 and 40% were eligible. Two weeks prior to treatment, a ~ 5 ml bone marrow aspiration was performed to examine \"cell potency\". On treatment day, a 60 mL bone marrow aspiration, bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNC\'s was performed in a single, point of care encounter. Patients were then followed to assess clinical outcomes.
Results
The cell potency small volume bone marrow aspirate, the 60 mL bone marrow aspirate, and transendocardial injections were well tolerated in 10 patients enrolled. There were no serious adverse events related to bone marrow aspiration or cell delivery. Improvement in 6-min walk distance was observed at 6 months (+47.8 m, P = 0.01) and trended to improvement at 12 months (+46.4, P = 0.06). Similarly, trends to improved NYHA heart failure functional class, quality of life, left ventricular ejection fraction and recruitment of previously akinetic left ventricular wall segments were observed.
Conclusion
All CardiAMP HF protocol procedures were feasible and well tolerated. Favorable functional, echo and quality of life trends suggest this approach may offer promise for patients with post MI heart failure. The randomized CardiAMP Heart Failure pivotal trial is underway to confirm the efficacy of this approach.
Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT02438306.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 18 Oct 2020; epub ahead of print
Raval AN, Johnston PV, Duckers HJ, Cook TD, ... Anderson RD, Pepine CJ
Int J Cardiol: 18 Oct 2020; epub ahead of print | PMID: 33091520
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Impact:
Abstract

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

Petrescu A, Bézy S, Cvijic M, Santos P, ... D\'hooge J, Voigt JU
Objectives
The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients.
Background
After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole.
Methods
52 HTx recipients that underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping.
Results
SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values.
Conclusions
End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 27 Sep 2020; epub ahead of print
Petrescu A, Bézy S, Cvijic M, Santos P, ... D'hooge J, Voigt JU
JACC Cardiovasc Imaging: 27 Sep 2020; epub ahead of print | PMID: 33004291
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Impact:
Abstract

Sex-specific differences in access and response to medical and device therapies in heart failure: State of the art.

Punnoose LR, Lindenfeld J

Women with heart failure (HF) are more symptomatic than their male counterparts. Despite deriving similar benefits from both medical and devices therapies, women continue to be underrepresented in clinic trials. Important sex-based disparities exist in enrollment in clinical trials and access to medical and device-based therapies, in part stemming from differences in medical and psychosocial comorbidities. Disparities in access to beneficial interventions likely contribute to the greater symptom burden identified in women with HF. Improved focus on the enrollment of women in clinical trials will allow a better understanding of the underpinnings of these disparities and improve the care of women with HF.

Copyright © 2020 Anesthesia History Association. Published by Elsevier Inc. All rights reserved.

Prog Cardiovasc Dis: 24 Sep 2020; epub ahead of print
Punnoose LR, Lindenfeld J
Prog Cardiovasc Dis: 24 Sep 2020; epub ahead of print | PMID: 32987026
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Impact:
Abstract

Sacubitril/Valsartan in Advanced Heart Failure With Reduced Ejection Fraction: Rationale and Design of the LIFE Trial.

Mann DL, Greene SJ, Givertz MM, Vader JM, ... Braunwald E,

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Sep 2020; 8:789-799
Mann DL, Greene SJ, Givertz MM, Vader JM, ... Braunwald E,
JACC Heart Fail: 29 Sep 2020; 8:789-799 | PMID: 32641226
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Abstract

Left Atrial Strain as a Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure.

Park JJ, Park JH, Hwang IC, Park JB, Cho GY, Marwick TH
Objectives
This study sought to identify whether left atrial strain can predict new-onset atrial fibrillation (NOAF) in patients with heart failure (HF) and sinus rhythm.
Background
Both HF and atrial fibrillation have common risk factors, and HF is a risk factor for the development of atrial fibrillation and vice versa.
Methods
Among 4,312 consecutive patients with acute HF from 3 tertiary hospitals, 2,461 patients with sinus rhythm and peak atrial longitudinal strain (PALS) were included in the study. Reduced PALS was defined as PALS ≤18%, and the primary endpoint was 5-year NOAF.
Results
During a 5-year follow-up, 397 (16.1%) patients developed NOAF. Patients with reduced PALS had higher NOAF than their counterparts (18.2% vs. 12.7%; p < 0.001). After adjustment for significant covariates, we identified 6 independent predictors of NOAF, including age >70 years (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.12 to 2.00), hypertension (HR: 1.45; 95% CI: 1.10 to 1.91), left atrial volume index ≥40 ml/m (HR: 2.03; 95% CI: 1.48 to 2.77), PALS <18% (HR: 1.60; 95% CI: 1.18 to 2.17), HF with preserved ejection fraction (HR: 1.47; 95% CI: 1.11 to 1.95), and no beta-blocker prescription at discharge (HR: 1.48; 95% CI: 1.14 to 1.92). A weighted score based on these variables was used to create a composite score, HAS-BAP (H = hypertension; A = age; S = PALS; B = no beta-blocker prescription at discharge; A = atrial volume index; P = HF with preserved ejection fraction [range 0 to 6] with a median of 3 [interquartile range: 2 to 4]). The probability of NOAF increased with HAS-BAP score.
Conclusions
In patients with HF and sinus rhythm, 16.1% developed NOAF, and PALS could be used to predict the risk for NOAF. The HAS-BAP score allows determination of the risk of NOAF. (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure [STRATS-AHF] Registry; NCT03513653).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 29 Sep 2020; 13:2071-2081
Park JJ, Park JH, Hwang IC, Park JB, Cho GY, Marwick TH
JACC Cardiovasc Imaging: 29 Sep 2020; 13:2071-2081 | PMID: 32682715
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This program is still in alpha version.