Topic: Heart Failure

Abstract

Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes.

Abraham WT, Lindenfeld J, Ponikowski P, Agostoni P, ... Salsali A, Anker SD
Aims
The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF).
Methods and results
HF patients with reduced EF (HFrEF) (≤40%,N = 312, EMPERIAL-Reduced) or preserved EF (>40%,N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were -4.0 m (-16.0, 6.0;P = 0.42) and 4.0 m (-5.0, 13.0;P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported.
Conclusion
The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

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

Eur Heart J: 21 Dec 2020; epub ahead of print
Abraham WT, Lindenfeld J, Ponikowski P, Agostoni P, ... Salsali A, Anker SD
Eur Heart J: 21 Dec 2020; epub ahead of print | PMID: 33351892
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial.

Butler J, Anker SD, Filippatos G, Khan MS, ... Packer M,
Aims
In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction.
Methods and results
Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models. Responder analyses were performed to assess the odds of improvement and deterioration in KCCQ scores related to treatment with empagliflozin. Empagliflozin reduced the primary outcome of cardiovascular death or heart failure hospitalization regardless of baseline KCCQ-CSS tertiles [hazard ratio (HR) 0.83 (0.68-1.02), HR 0.74 (0.58-0.94), and HR 0.61 (0.46-0.82) for <62.5, 62.6-85.4, and ≥85.4 score tertiles, respectively; P-trend = 0.10]. Empagliflozin improved KCCQ-CSS, total symptom score, and overall summary score at 3, 8, and 12 months. More patients on empagliflozin had ≥5-point [odds ratio (OR) 1.20 (1.05-1.37)], 10-point [OR 1.26 (1.10-1.44)], and 15-point [OR 1.29 (1.12-1.48)] improvement and fewer had ≥5-point [OR 0.75 (0.64-0.87)] deterioration in KCCQ-CSS at 3 months. These benefits were sustained at 8 and 12 months and were similar for other KCCQ domains.
Conclusion
Empagliflozin improved cardiovascular death or heart failure hospitalization risk across the range of baseline health status. Empagliflozin improved health status across various domains, and this benefit was sustained during long-term follow-up.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03057977.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 08 Jan 2021; epub ahead of print
Butler J, Anker SD, Filippatos G, Khan MS, ... Packer M,
Eur Heart J: 08 Jan 2021; epub ahead of print | PMID: 33420498
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: a Danish, nationwide cohort study.

Holt A, Blanche P, Zareini B, Rajan D, ... Gislason GH, Lamberts M

Listen to the audio abstract of this contribution at https://doi.org/10.1093/eurheartj/ehaa1058.
Aims
We aimed to investigate the long-term cardio-protective effect associated with beta-blocker (BB) treatment in stable, optimally treated myocardial infarction (MI) patients without heart failure (HF).
Methods and results
Using nationwide registries, we included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2018. Patients with prior history of MI, prior BB use, or any alternative indication or contraindication for BB treatment were excluded. Follow-up began 3 months following discharge in patients alive, free of cardiovascular (CV) events or procedures. Primary outcomes were CV death, recurrent MI, and a composite outcome of CV events. We used adjusted logistic regression and reported standardized absolute risks and differences (ARD) 3 years after MI. Overall, 30 177 stable, optimally treated MI patients were included (58% acute PCI, 26% sub-acute PCI, 16% CAG without intervention). At baseline, 82% of patients were on BB treatment (median age 61 years, 75% male) and 18% were not (median age 62 years, 68% male). BB treatment was associated with a similar risk of CV death, recurrent MI, and the composite outcome of CV events compared with no BB treatment [ARD (95% confidence intervals)] correspondingly; 0.1% (-0.3% to 0.5%), 0.2% (-0.7% to 1.2%), and 1.2% (-0.2% to 2.7%).
Conclusions
In this nationwide cohort study of stable, optimally treated MI patients without HF, we found no long-term effect of BB treatment on CV prognosis following the patients from 3 months to 3 years after MI admission.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 10 Jan 2021; epub ahead of print
Holt A, Blanche P, Zareini B, Rajan D, ... Gislason GH, Lamberts M
Eur Heart J: 10 Jan 2021; epub ahead of print | PMID: 33428707
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Redox-Resistant SERCA [Sarco(endo)plasmic Reticulum Calcium ATPase] Attenuates Oxidant-Stimulated Mitochondrial Calcium and Apoptosis in Cardiac Myocytes and Pressure Overload-Induced Myocardial Failure in Mice.

Goodman JB, Qin F, Morgan RJ, Chambers JM, ... Cohen RA, Colucci WS
Background
SERCA [sarco(endo)plasmic reticulum calcium ATPase] is regulated by oxidative posttranslational modifications at cysteine 674 (C674). Because sarcoplasmic reticulum (SR) calcium has been shown to play a critical role in mediating mitochondrial dysfunction in response to reactive oxygen species, we hypothesized that SERCA oxidation at C674 would modulate the effects of reactive oxygen species on mitochondrial calcium and mitochondria-dependent apoptosis in cardiac myocytes.
Methods
Adult rat ventricular myocytes expressing wild-type SERCA2b or a redox-insensitive mutant in which C674 is replaced by serine (C674S) were exposed to HO (100 µmol/Lμ). Free mitochondrial calcium concentration was measured in adult rat ventricular myocytes with 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 were subjected to chronic ascending aortic constriction.
Results
In adult rat ventricular myocytes expressing wild-type 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 wild-type cells, HO caused cytochrome c release and apoptosis, both of which were prevented in C674S-expressing cells. In myocytes from SERCA knock-in mice, basal SERCA activity and SR calcium content were decreased. To test the effect of C674 oxidation on apoptosis in vivo, SERCA knock-in mice were subjected to chronic ascending aortic constriction. In wild-type mice, ascending aortic constriction caused myocyte apoptosis, LV dilation, and systolic failure, all of which were inhibited in SERCA knock-in mice.
Conclusions
Redox activation of SERCA C674 regulates basal SR calcium content, thereby mediating the pathologic reactive oxygen species-stimulated rise in mitochondrial calcium required for myocyte apoptosis and myocardial failure.



Circulation: 21 Dec 2020; 142:2459-2469
Goodman JB, Qin F, Morgan RJ, Chambers JM, ... Cohen RA, Colucci WS
Circulation: 21 Dec 2020; 142:2459-2469 | PMID: 33076678
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes: Findings From the Look AHEAD Trial.

Patel KV, Bahnson JL, Gaussoin SA, Johnson KC, ... Pandey A,
Background
Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes. However, the contribution of baseline measures and longitudinal changes in fat mass (FM), lean mass (LM), and waist circumference (WC) to the risk of HF and myocardial infarction (MI) in type 2 diabetes is not well established.
Methods
Adults from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. FM and LM were predicted using validated equations and compared with dual-energy x-ray absorptiometry measurements in a subgroup. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in FM, LM, and WC over 1- and 4-year follow-up with risk of overall HF, HF with preserved ejection fraction (EF; EF ≥50%), HF with reduced EF (EF <50%), and MI.
Results
Among 5103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured FM/LM were highly correlated (=0.87-0.90; n=1369). FM and LM decreased over 4-year follow-up with greater declines in the intensive lifestyle intervention arm. In adjusted analysis, baseline body composition measures were not significantly associated with HF risk. Decline in FM and WC, but not LM, over 1 year were each significantly associated with lower risk of overall HF (adjusted hazard ratio per 10% decrease in FM, 0.80 [95% CI, 0.68-0.95]; adjusted hazard ratio per 10% decrease in WC, 0.77 [95% CI, 0.62-0.95]). Decline in FM was significantly associated with lower risk of both HF subtypes. In contrast, decline in WC was significantly associated with lower risk of HF with preserved EF but not HF with reduced EF. Similar patterns of association were observed for 4-year changes in body composition and HF risk. Longitudinal changes in body composition were not significantly associated with risk of MI.
Conclusions
In adults with type 2 diabetes, a lifestyle intervention is associated with significant loss of FM and LM. Declines in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HF with preserved EF but not HF with reduced EF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.



Circulation: 21 Dec 2020; 142:2420-2430
Patel KV, Bahnson JL, Gaussoin SA, Johnson KC, ... Pandey A,
Circulation: 21 Dec 2020; 142:2420-2430 | PMID: 33164570
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Myocardial Gene Expression Signatures in Human Heart Failure With Preserved Ejection Fraction.

Hahn VS, Knutsdottir H, Luo X, Bedi K, ... Kass DA, Sharma K
Background
Heart failure (HF) with preserved ejection fraction (HFpEF) constitutes half of all HF but lacks effective therapy. Understanding of its myocardial biology remains limited because of a paucity of heart tissue molecular analysis.
Methods
We performed RNA sequencing on right ventricular septal endomyocardial biopsies prospectively obtained from patients meeting consensus criteria for HFpEF (n=41) contrasted with right ventricular septal tissue from patients with HF with reduced ejection fraction (HFrEF, n=30) and donor controls (n=24). Principal component analysis and hierarchical clustering tested for transcriptomic distinctiveness between groups, effect of comorbidities, and differential gene expression with pathway enrichment contrasted HF groups and donor controls. Within HFpEF, non-negative matrix factorization and weighted gene coexpression analysis identified molecular subgroups, and the resulting clusters were correlated with hemodynamic and clinical data.
Results
Patients with HFpEF were more often women (59%), African American (68%), obese (median body mass index 41), and hypertensive (98%), with clinical HF characterized by 65% New York Heart Association Class III or IV, nearly all on a loop diuretic, and 70% with a HF hospitalization in the previous year. Principal component analysis separated HFpEF from HFrEF and donor controls with minimal overlap, and this persisted after adjusting for primary comorbidities: body mass index, sex, age, diabetes, and renal function. Hierarchical clustering confirmed group separation. Nearly half the significantly altered genes in HFpEF versus donor controls (1882 up, 2593 down) changed in the same direction in HFrEF; however, 5745 genes were uniquely altered between HF groups. Compared with controls, uniquely upregulated genes in HFpEF were enriched in mitochondrial adenosine triphosphate synthesis/electron transport, pathways downregulated in HFrEF. HFpEF-specific downregulated genes engaged endoplasmic reticulum stress, autophagy, and angiogenesis. Body mass index differences largely accounted for HFpEF upregulated genes, whereas neither this nor broader comorbidity adjustment altered pathways enriched in downregulated genes. Non-negative matrix factorization identified 3 HFpEF transcriptomic subgroups with distinctive pathways and clinical correlates, including a group closest to HFrEF with higher mortality, and a mostly female group with smaller hearts and proinflammatory signaling. These groupings remained after sex adjustment. Weighted gene coexpression analysis yielded analogous gene clusters and clinical groupings.
Conclusions
HFpEF exhibits distinctive broad transcriptomic signatures and molecular subgroupings with particular clinical features and outcomes. The data reveal new signaling targets to consider for precision therapeutics.



Circulation: 11 Jan 2021; 143:120-134
Hahn VS, Knutsdottir H, Luo X, Bedi K, ... Kass DA, Sharma K
Circulation: 11 Jan 2021; 143:120-134 | PMID: 33118835
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pulse Pressure, Prognosis, and Influence of Sacubitril/Valsartan in Heart Failure With Preserved Ejection Fraction.

Suzuki K, Claggett B, Minamisawa M, Nochioka K, ... McMurray JJV, Solomon SD

Arterial stiffness is increased with increasing age, and pulse pressure (PP), a marker of arterial stiffness, is a predictor of incident cardiovascular disease and mortality. However, the prognostic relevance of PP in heart failure (HF) with preserved ejection fraction has not been fully understood. We studied 4796 patients with HF with preserved ejection fraction from the PARAGON-HF trial. All patients underwent sequential run-in phases of valsartan and sacubitril/valsartan before randomization. We categorized patients by PP quartile and evaluated the influence of baseline PP on the PARAGON-HF primary end point (total HF hospitalizations and cardiovascular death). At screening, the median PP was 58 mm Hg (interquartile range, 50-69 mm Hg). There was a nonlinear, J-shaped association between PP and outcomes. Multivariable Cox proportional hazards models showed that patients in the highest PP quartile had a higher risk of the primary end point (adjusted hazard ratio, 1.39 [95% CI, 1.14-1.69]; =0.001), total HF hospitalizations (adjusted hazard ratio, 1.43 [95% CI, 1.15-1.79]; =0.001), and myocardial infarction (adjusted hazard ratio, 1.54 [95% CI, 1.06-2.23]; =0.022) compared with those in the second (lowest risk) PP quartile. Reductions in PP during sacubitril/valsartan run-in were associated with a decreased risk of the primary end point and total HF hospitalizations. One year after randomization, PP was significantly lower in the sacubitril/valsartan group compared with the valsartan group (3.0 mm Hg decrease [95% CI, 2.4-3.5]; <0.001). In conclusion, PP was an independent predictor of cardiovascular events in patients with HF with preserved ejection fraction enrolled in PARAGON-HF. Sacubitril/valsartan lowered PP compared with valsartan.



Hypertension: 27 Dec 2020:HYPERTENSIONAHA12016277; epub ahead of print
Suzuki K, Claggett B, Minamisawa M, Nochioka K, ... McMurray JJV, Solomon SD
Hypertension: 27 Dec 2020:HYPERTENSIONAHA12016277; epub ahead of print | PMID: 33356401
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Intrinsic Frequencies of Carotid Pressure Waveforms Predict Heart Failure Events: The Framingham Heart Study.

Cooper LL, Rong J, Pahlevan NM, Rinderknecht DG, ... Gharib M, Mitchell GF

Intrinsic frequencies (IFs) derived from arterial waveforms are associated with cardiovascular performance, aging, and prevalent cardiovascular disease (CVD). However, prognostic value of these novel measures is unknown. We hypothesized that IFs are associated with incident CVD risk. Our sample was drawn from the Framingham Heart Study Original, Offspring, and Third Generation Cohorts and included participants free of CVD at baseline (N=4700; mean age 52 years, 55% women). We extracted 2 dominant frequencies directly from a series of carotid pressure waves: the IF of the coupled heart and vascular system during systole (ω) and the IF of the decoupled vasculature during diastole (ω). Total frequency variation (Δω) was defined as the difference between ω and ω. We used Cox proportional hazards regression models to relate IFs to incident CVD events during a mean follow-up of 10.6 years. In multivariable models adjusted for CVD risk factors, higher ω (hazard ratio [HR], 1.14 [95% CI], 1.03-1.26]; =0.01) and Δω (HR, 1.16 [95% CI, 1.03-1.30]; =0.02) but lower ω (HR, 0.87 [95% CI, 0.77-0.99]; =0.03) were associated with higher risk for incident composite CVD events. In similarly adjusted models, higher ω (HR, 1.23 [95% CI, 1.07-1.42]; =0.004) and Δω (HR, 1.26 [95% CI, 1.05-1.50]; =0.01) but lower ω (HR, 0.81 [95% CI, 0.66-0.99]; =0.04) were associated with higher risk for incident heart failure. IFs were not significantly associated with incident myocardial infarction or stroke. Novel IFs may represent valuable markers of heart failure risk in the community.



Hypertension: 03 Jan 2021:HYPERTENSIONAHA12015632; epub ahead of print
Cooper LL, Rong J, Pahlevan NM, Rinderknecht DG, ... Gharib M, Mitchell GF
Hypertension: 03 Jan 2021:HYPERTENSIONAHA12015632; epub ahead of print | PMID: 33390053
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex differences in heart failure hospitalisation risk following acute myocardial infarction.

Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Objective
We evaluated the sex differences in 6-month heart failure (HF) hospitalisation risk in acute myocardial infarction (AMI) survivors.
Methods
For this retrospective cohort analysis, adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The primary outcome was a HF hospitalisation within 6 months. Secondary outcomes were fatal HF hospitalisation and the composite of index in-hospital HF or 6-month HF hospitalisation.
Results
Of 237 549 AMI survivors, females (37.9%) were older (70±14 years vs 65±13 years; p<0.001), had a higher prevalence of cardiac comorbidities and a lower revascularisation rate compared with males. The primary outcome occurred in 12 934 patients (5.4%), at a 49% higher rate in females (6.8% vs 4.6% in males, p<0.001), which was attenuated to a 19% higher risk after multivariable adjustment. Findings were consistent across subgroups of age, AMI type and major risk factors. In the propensity-matched time-to-event analysis, female sex was associated with a 13% higher risk for 6-month HF readmission (6.4% vs 5.8% in males; HR 1.13, 95% CI 1.05 to 1.21, p<0.001), and the increased risk was evident early on after the AMI. Fatal HF rate was similar between groups (4.7% vs 4.6%, p=0.936), but females had a higher rate of the composite HF outcome (36.2% vs 27.5%, p<0.001).
Conclusion
In a large all-comers AMI survivors\' cohort, females had a higher HF hospitalisation risk that persisted after adjustment for baseline risk differences. This was consistent across several clinically relevant subgroups and was evident early on after the AMI.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Jan 2021; epub ahead of print
Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Heart: 10 Jan 2021; epub ahead of print | PMID: 33431424
Go to: DOI | PubMed | PDF | Google Scholar |
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)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Dec 2020; 107:10-17
Mulder BA, Rienstra M, Blaauw Y
Heart: 30 Dec 2020; 107:10-17 | PMID: 33077503
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

Blacher M, Zimerman A, Engster PHB, Grespan E, ... Biolo A, Rohde LE
Objective
New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the(ReBIC)-1 Trial.
Methods
The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient\'s self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100).
Results
Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14).
Conclusions
Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.

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

Heart: 22 Dec 2020; epub ahead of print
Blacher M, Zimerman A, Engster PHB, Grespan E, ... Biolo A, Rohde LE
Heart: 22 Dec 2020; epub ahead of print | PMID: 33361353
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Greater admissions, mortality and cost of heart failure in adults with congenital heart disease.

Burstein DS, Rossano JW, Griffis H, Zhang X, ... Edelson JB, Menachem JN
Objective
Limited contemporary data exist regarding outcomes and resource use among adults with congenital heart disease and heart failure (ACHD-HF). This study compared outcomes, emergency department (ED) and hospital resource use, and advanced heart failure (HF) therapies in ACHD-HF versus non-ACHD with HF (HF-non-ACHD).
Methods
The Nationwide Emergency Department Sample and Nationwide Inpatient Sample were used to analyse outcomes and resource use among ACHD-HF ED visits and hospitalisations from 2006 to 2016. ACHD-HF was stratified by single-ventricle (SV) and two-ventricle (2V) disease.
Results
A total of 76 557 ACHD-HF visits (3.6% SV physiology) and 31 137 414 HF-non-ACHD visits were analysed. ACHD-HFs were younger (SV 33 years (IQR 25-44), 2V 62 years (IQR 45-76); HF-non-ACHD 74 years (IQR 63-83); p<0.001). ACHD-HFs had higher ED admissions (78% vs 70%, p<0.001), longer hospital length of stay (5 days (IQR 2-8) vs 4 days (IQR 2-7), p<0.001) and greater hospital costs ($49K (IQR 2K-121K) vs $32K (17K-66K), p<0.001). Mortality was significantly higher among ACHD-HFs with SV physiology (6.6%; OR 1.6, 95% CI 1.1 to 2.3) or 2V physiology (6.3%; OR 1.4, 95% CI 1.3 to 1.5) versus HF-non-ACHD (5.5%). ACHF-HF hospitalisations increased more (46% vs 6% HF-non-ACHD) over a 10-year period, but the proportion receiving ventricular assist device (VAD) (ACHD-HF -2% vs HF-non-ACHD 294%) or transplant (ACHD-HF -37% vs HF-non-ACHD 73%) decreased.
Conclusion
ACHD-HFs have significant ED and hospital resource use that has increased over the past 10 years. However, advanced HF therapies (VAD and transplantation) are less commonly used compared with those without adult congenital heart disease.

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

Heart: 22 Dec 2020; epub ahead of print
Burstein DS, Rossano JW, Griffis H, Zhang X, ... Edelson JB, Menachem JN
Heart: 22 Dec 2020; epub ahead of print | PMID: 33361349
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Remote monitoring in heart failure: current and emerging technologies in the context of the pandemic.

Mohebali D, Kittleson MM

The incidence of heart failure (HF) remains high and patients with HF are at risk for frequent hospitalisations. Remote monitoring technologies may provide early indications of HF decompensation and potentially allow for optimisation of therapy to prevent HF hospitalisations. The need for reliable remote monitoring technology has never been greater as the COVID-19 pandemic has led to the rapid expansion of a new mode of healthcare delivery: the virtual visit. With the convergence of remote monitoring technologies and reliable method of remote healthcare delivery, an understanding of the role of both in the management of patients with HF is critical. In this review, we outline the evidence on current remote monitoring technologies in patients with HF and highlight how these advances may benefit patients in the context of the current pandemic.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Jan 2021; epub ahead of print
Mohebali D, Kittleson MM
Heart: 10 Jan 2021; epub ahead of print | PMID: 33431425
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sacubitril/valsartan in the treatment of systemic right ventricular failure.

Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, ... Schalij MJ, Egorova AD
Objective
Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.
Methods
Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.
Results
Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).
Conclusions
We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Heart: 14 Jan 2021; epub ahead of print
Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, ... Schalij MJ, Egorova AD
Heart: 14 Jan 2021; epub ahead of print | PMID: 33452121
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

D-dimer and the incidence of heart failure and mortality after acute myocardial infarction.

Zhang X, Wang S, Liu J, Wang Y, ... Fang S, Yu B
Objective
D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.
Methods
We enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.
Results
Over a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.
Conclusions
D-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Jan 2021; 107:237-244
Zhang X, Wang S, Liu J, Wang Y, ... Fang S, Yu B
Heart: 30 Jan 2021; 107:237-244 | PMID: 32788198
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure.

Schrage B, Lund LH, Benson L, Stolfo D, ... Ferreira JP, Savarese G
Objective
It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort.
Methods
Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating).
Results
Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01).
Conclusions
In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Jan 2021; 107:229-236
Schrage B, Lund LH, Benson L, Stolfo D, ... Ferreira JP, Savarese G
Heart: 30 Jan 2021; 107:229-236 | PMID: 32769169
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Failure to vasodilate in response to salt loading blunts renal blood flow and causes salt-sensitive hypertension.

Wu J, Agbor LN, Fang S, Mukohda M, ... McCormick JA, Sigmund CD
Aims
Salt-sensitive (SS) hypertension is accompanied by impaired vasodilation in the systemic and renal circulation. However, the causal relationship between vascular dysfunction and salt-induced hypertension remains controversial. We sought to determine whether primary vascular dysfunction, characterized by a failure to vasodilate during salt loading, plays a causal role in the pathogenesis of SS hypertension.
Methods and results
Mice selectively expressing a peroxisome proliferator-activated receptor γ dominant-negative mutation in vascular smooth muscle (S-P467L) exhibited progressive SS hypertension during a 4 week high salt diet (HSD). This was associated with severely impaired vasodilation in systemic and renal vessels. Salt-induced impairment of vasodilation occurred as early as 3 days after HSD, which preceded the onset of SS hypertension. Notably, the overt salt-induced hypertension in S-P467L mice was not driven by higher cardiac output, implying elevations in peripheral vascular resistance. In keeping with this, HSD-fed S-P467L mice exhibited decreased smooth muscle responsiveness to nitric oxide (NO) in systemic vessels. HSD-fed S-P467L mice also exhibited elevated albuminuria and a blunted increase in urinary NO metabolites which was associated with blunted renal blood flow and increased sodium retention mediated by a lack of HSD-induced suppression of NKCC2. Blocking NKCC2 function prevented the salt-induced increase in blood pressure in S-P467L mice.
Conclusion
We conclude that failure to vasodilate in response to salt loading causes SS hypertension by restricting renal perfusion and reducing renal NO through a mechanism involving NKCC2 in a mouse model of vascular peroxisome proliferator-activated receptor γ impairment.

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

Cardiovasc Res: 31 Dec 2020; 117:308-319
Wu J, Agbor LN, Fang S, Mukohda M, ... McCormick JA, Sigmund CD
Cardiovasc Res: 31 Dec 2020; 117:308-319 | PMID: 32428209
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors: identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress.

Packer M

Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of serious heart failure events, even though SGLT2 is not expressed in the myocardium. This cardioprotective benefit is not related to an effect of these drugs to lower blood glucose, promote ketone body utilization or enhance natriuresis, but it is linked statistically with their action to increase haematocrit. SGLT2 inhibitors increase both erythropoietin and erythropoiesis, but the increase in red blood cell mass does not directly prevent heart failure events. Instead, erythrocytosis is a biomarker of a state of hypoxia mimicry, which is induced by SGLT2 inhibitors in manner akin to cobalt chloride. The primary mediators of the cellular response to states of energy depletion are sirtuin-1 and hypoxia-inducible factors (HIF-1α/HIF-2α). These master regulators promote the cellular adaptation to states of nutrient and oxygen deprivation, promoting mitochondrial capacity and minimizing the generation of oxidative stress. Activation of sirtuin-1 and HIF-1α/HIF-2α also stimulates autophagy, a lysosome-mediated degradative pathway that maintains cellular homoeostasis by removing dangerous constituents (particularly unhealthy mitochondria and peroxisomes), which are a major source of oxidative stress and cardiomyocyte dysfunction and demise. SGLT2 inhibitors can activate SIRT-1 and stimulate autophagy in the heart, and thereby, favourably influence the course of cardiomyopathy. Therefore, the linkage between erythrocytosis and the reduction in heart failure events with SGLT2 inhibitors may be related to a shared underlying molecular mechanism that is triggered by the action of these drugs to induce a perceived state of oxygen and nutrient deprivation.

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

Cardiovasc Res: 31 Dec 2020; 117:74-84
Packer M
Cardiovasc Res: 31 Dec 2020; 117:74-84 | PMID: 32243505
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Nox2+ myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1.

Molitor M, Rudi WS, Garlapati V, Finger S, ... Münzel T, Wenzel P
Aims
Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI.
Methods and results
HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery. Compared to sham, HF mice had significantly impaired endothelial function accompanied by enhanced mobilization of Sca-1+c-Kit+ haematopoietic stem cells and Sca-1-c-Kit+ common myeloid and granulocyte-macrophage progenitors in the bone marrow as well as increased vascular infiltration of CD11b+Ly6G-Ly6Chigh monocytes and accumulation of CD11b+ F4/80+ macrophages, assessed by flow cytometry. Using mice with Cre-inducible expression of diphtheria toxin receptor in myeloid cells, we selectively depleted lysozyme M+ myelomonocytic cells for 10 days starting 28 days after MI. While the cardiac phenotype remained unaltered until 38 days post-MI, myeloid cell depletion attenuated vascular accumulation of Nox2+CD45+ cells, endothelial dysfunction, oxidative stress, and vascular expression of adhesion molecules and angiotensin II receptor type 1 (AT1R). Pharmacological blockade of this receptor for 4 weeks did not significantly alter cardiac function, but mimicked the effects of myeloid cell depletion: telmisartan (20 mg/kg/day, fed to C57BL/6J mice) diminished bone marrow myelopoesis and myeloid reactive oxygen species production, attenuated endothelial leucocyte rolling and vascular accumulation of CD11b+Ly6G-Ly6Chigh monocytes and macrophages, resulting in improved vascular function with less abundance of Nox2+CD45+ cells.
Conclusion
Endothelial dysfunction in HF ensuing MI is mediated by inflammatory Nox2+ myeloid cells infiltrating the vessel wall that can be targeted by AT1R blockade.

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

Cardiovasc Res: 31 Dec 2020; 117:162-177
Molitor M, Rudi WS, Garlapati V, Finger S, ... Münzel T, Wenzel P
Cardiovasc Res: 31 Dec 2020; 117:162-177 | PMID: 32077922
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Inhibition of N-type calcium channels in cardiac sympathetic neurons attenuates ventricular arrhythmogenesis in heart failure.

Zhang D, Tu H, Wang C, Cao L, ... Wadman MC, Li YL
Aims
Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic post-ganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF.
Methods and results
Rat CHF was induced by surgical ligation of the left coronary artery. Lentiviral Cav2.2-α shRNA or scrambled shRNA was transfected in vivo into stellate ganglia (SG) in CHF rats. Final experiments were performed at 14 weeks after coronary artery ligation. Real-time polymerase chain reaction and western blot data showed that in vivo transfection of Cav2.2-α shRNA reduced the expression of Cav2.2-α mRNA and protein in the SG in CHF rats. Cav2.2-α shRNA also reduced Cav2.2 currents and cell excitability of CSP neurons and attenuated cardiac sympathetic nerve activities (CSNA) in CHF rats. The power spectral analysis of heart rate variability (HRV) further revealed that transfection of Cav2.2-α shRNA in the SG normalized CHF-caused cardiac sympathetic overactivation in conscious rats. Twenty-four-hour continuous telemetry electrocardiogram recording revealed that this Cav2.2-α shRNA not only decreased incidence and duration of ventricular tachycardia/ventricular fibrillation but also improved CHF-induced heterogeneity of ventricular electrical activity in conscious CHF rats. Cav2.2-α shRNA also decreased susceptibility to ventricular arrhythmias in anaesthetized CHF rats. However, Cav2.2-α shRNA failed to improve CHF-induced cardiac contractile dysfunction. Scrambled shRNA did not affect Cav2.2 currents and cell excitability of CSP neurons, CSNA, HRV, and ventricular arrhythmogenesis in CHF rats.
Conclusions
Overactivation of Cav2.2 channels in CSP neurons contributes to cardiac sympathetic hyperactivation and ventricular arrhythmogenesis in CHF. This suggests that discovering purely selective and potent small-molecule Cav2.2 channel blockers could be a potential therapeutic strategy to decrease fatal ventricular arrhythmias in CHF.

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

Cardiovasc Res: 31 Dec 2020; 117:137-148
Zhang D, Tu H, Wang C, Cao L, ... Wadman MC, Li YL
Cardiovasc Res: 31 Dec 2020; 117:137-148 | PMID: 31995173
Go to: DOI | PubMed | PDF | Google Scholar |
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)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Jan 2021; 107:208-216
Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
Heart: 30 Jan 2021; 107:208-216 | PMID: 33082175
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure.

Brumback LC, Andrews LIB, Jacobs DR, Duprez DA, ... Denenberg JO, Allison MA
Objectives
The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown.
Methods
Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure.
Results
Mean ± standard deviation PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure.
Conclusion
The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.



J Hypertens: 23 Dec 2020; epub ahead of print
Brumback LC, Andrews LIB, Jacobs DR, Duprez DA, ... Denenberg JO, Allison MA
J Hypertens: 23 Dec 2020; epub ahead of print | PMID: 33239550
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of exercise training on renal interstitial fibrosis and renin-angiotensin system in rats with chronic renal failure.

Yamakoshi S, Nakamura T, Mori N, Suda C, Kohzuki M, Ito O
Objective
To clarify the mechanisms of the renal protective effects of exercise training, we examined the effects of exercise training on the renal interstitial fibrosis and renin-angiotensin system (RAS) in rats with chronic renal failure.
Methods
Six-week-old male Sprague-Dawley rats were divided into three groups: sham operation; 5/6 nephrectomy + sedentary; 5/6 nephrectomy + exercise training. The 5/6 nephrectomy + exercise training group underwent treadmill running (20 m/min, 60 min/day, 5 days/week). After 12 weeks, renal function, histology and protein expression of collagen type I, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinase (TIMP) and RAS components in the renal cortex were examined.
Results
Exercise training ameliorated the 5/6 nephrectomy-induced hypertension, proteinuria, renal dysfunction, glomerular sclerosis and renal interstitial fibrosis. 5/6 Nephrectomy increased the expression of collagen type I, TGF-β1, MMP-2, MMP-9, TIMP-1, angiotensinogen, angiotensin-converting enzyme (ACE), (pro)renin receptor and angiotensin II type 1 receptor, and exercise training inhibited the 5/6 nephrectomy-increased expression of collagen type I, TGF-β1, TIMP-1, angiotensinogen and ACE expressions. 5/6 Nephrectomy decreased the expression of renin, ACE2, angiotensin II type 2 receptor and Mas receptor, and exercise training inhibited the 5/6 nephrectomy-decreased expressions.
Conclusion
These results indicated that exercise training attenuates the progression of glomerular sclerosis and renal interstitial fibrosis in chronic renal failure rats. The renal protective effects of exercise training may be mediated by ameliorating the renal collagen turnover and the exacerbation of renal RAS.



J Hypertens: 30 Dec 2020; 39:143-152
Yamakoshi S, Nakamura T, Mori N, Suda C, Kohzuki M, Ito O
J Hypertens: 30 Dec 2020; 39:143-152 | PMID: 32833922
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex-related differences in dynamic right ventricular-pulmonary vascular coupling in heart failure with preserved ejection fraction.

Singh I, Oliveira RKF, Heerdt PM, Pari R, Systrom DM, Waxman AB
Background
Right ventricle (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Females are more likely to have HFpEF but males have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary artery (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known.
Methods
We examined rest and exercise invasive pulmonary hemodynamics in 22 male HFpEF and 27 female HFpEF patients. In order to further investigate the discrepancy in RV-PA response between sex, we included 26 age matched control subjects (11 males and 15 females). Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was determined as the ratio of Ees/Ea.
Results
Both HFpEF groups experienced decreased peak VO2 (%predicted). However, male HFpEF patients experienced greater decrement in peak VO2 compared to females (58±16 vs. 70±15%; p<0.05). Male HFpEF had more pronounce increase in RV afterload, Ea (1.8 ± 0.6 vs. 1.3 ± 0.4 mmHg/mL/m; p<0.05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs. 1.2 ± 0.4; p<0.05) and resulting reduced stroke volume index augmentation. In contrast, female HFpEF patients were able to augment RV contractility in face of increasing afterload, preserving RV-PA coupling during exercise.
Conclusion
Male HFpEF patients were more compromised with regards to dynamic RV-PA uncoupling and reduced peak VO2 compared to females. This was driven by both RV contractile impairment and afterload mismatch. In contrast, female HFpEF patients had preserved RV-PA coupling during exercise and better peak exercise VO2 compared to male HFpEF.

Copyright © 2020. Published by Elsevier Inc.

Chest: 30 Dec 2020; epub ahead of print
Singh I, Oliveira RKF, Heerdt PM, Pari R, Systrom DM, Waxman AB
Chest: 30 Dec 2020; epub ahead of print | PMID: 33388286
Go to: DOI | PubMed | PDF | Google Scholar |
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 noninvasive 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, noninvasive estimate of volume status in these patient populations.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Dec 2020; 138:80-84
Vlismas PP, Wiesenfeld E, Oh KT, Murthy S, ... Jorde UP, Sims DB
Am J Cardiol: 31 Dec 2020; 138:80-84 | PMID: 33058805
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Relation Between Thyroid Function and Mortality in Patients With Chronic Heart Failure.

Samuel NA, Cuthbert JJ, Brown OI, Kazmi S, ... Rigby AS, Clark AL

Thyroid dysfunction is common in patients with chronic heart failure (CHF), but there is conflicting evidence regarding its prognostic significance. We investigated the relation between thyroid function and prognosis in a large, well characterized cohort of ambulatory patients with CHF. Heart failure was defined as signs and symptoms of the disease and either left ventricular systolic dysfunction (LVSD) mild or worse (heart failure with reduced ejection fraction [HFrEF]), or no LVSD and raised amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L; heart failure with normal ejection fraction [HFnEF]). Euthyroid state was defined as a thyroid-stimulating hormone (TSH) level between 0.35 and 4.70 mIU/l, hypothyroidism as TSH >4.70 mIU/l, and hyperthyroidism as TSH <0.35 mIU/l. 2997 patients had HFrEF and 1995 patients had HFnEF. 4491 (90%) patients were euthyroid, 312 (6%) were hypothyroid, and 189 (4%) were hyperthyroid. In univariable analysis, both hypothyroid patients (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.08 to 1.45) and hyperthyroid patients (HR 1.21, 95% CI 1.01 to 1.46) had a greater risk of death compared with euthyroid patients. There was a U-shaped relation between TSH and outcome. Increasing TSH was a predictor of mortality in univariable analysis (HR 1.02, 95% CI 1.01 to 1.03), but the association disappeared in multivariable analysis. The three strongest predictors of adverse outcome were increasing age, increasing NT-proBNP, and higher NYHA class. In conclusion, although thyroid dysfunction is associated with worse survival in patients with CHF, it is not an independent predictor of mortality.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Jan 2021; 139:57-63
Samuel NA, Cuthbert JJ, Brown OI, Kazmi S, ... Rigby AS, Clark AL
Am J Cardiol: 14 Jan 2021; 139:57-63 | PMID: 33115640
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Relation of Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Nutritional Status and Prognosis in Patients With Acute Heart Failure.

Maeda D, Sakane K, Kanzaki Y, Okuno T, ... Sohmiya K, Hoshiga M

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR<1.16 (n = 262); second tertile, 1.16≤AAR<1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p < 0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Jan 2021; 139:64-70
Maeda D, Sakane K, Kanzaki Y, Okuno T, ... Sohmiya K, Hoshiga M
Am J Cardiol: 14 Jan 2021; 139:64-70 | PMID: 33115639
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 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 × 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 4 years.
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 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:137-146
Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Am Heart J: 30 Dec 2020; 231:137-146 | PMID: 33039340
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left bundle-branch block is associated with asimilar dyssynchronous phenotype in heart failure patients with normal and reduced ejection fractions.

Friedman DJ, Emerek K, Kisslo J, Søgaard P, Atwater BD
Background
Few therapies improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). If left bundle-branch block (LBBB) is associated with left ventricular dyssynchrony and impaired cardiac performance in HFpEF, cardiac resynchronization therapy could be a promising treatment.
Methods
We performed a cross-sectional analysis of selected patients with HFpEF (ejection fraction ≥50%) with and without LBBB (normal conduction, NC) and patients with HFrEF and LBBB who were suitable cardiac resynchronization therapy candidates to describe and contextualize the mechanical phenotype of LBBB in HFpEF. Systolic and diastolic isovolumic times, ejection time(ET), and diastolic filling time(DFT) were measured on spectral tissue Doppler echocardiographic images and indexed to the heart rate. Dyssynchrony pattern was assessed using speckle-tracked longitudinal strain patterns. Comparisons were performed using analysis of variance and χ test with posthoc pairwise comparisons as indicated.
Results
Eighty-two HFpEF (50 with NC, 32 with LBBB) and 149 HFrEF (all with LBBB) patients met criteria. Overall, 84.4% with HFpEF/LBBB and 91.3% with HFrEF/LBBB had demonstrable mechanical dyssynchrony compared to 0% with HFpEF/NC. Compared to HFpEF/NC, HFpEF/LBBB had significantly prolonged isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and total isovolumetric time and significantly shorter ET (all indexed). LBBB/HFrEF patients, compared to LBBB/HFpEF patients, had increased ICT and IRT with decreased DFT but similar ET.
Conclusions
Patients with HFpEF and LBBB frequently have an LBBB dyssynchrony phenotype, prolonged ICT and IRT, and reduced ET compared to HFpEF patients with NC. The electromechanical dyssynchrony and disordered cardiac timing of HFpEF with LBBB are similar to HFrEF with LBBB.

Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; 231:45-55
Friedman DJ, Emerek K, Kisslo J, Søgaard P, Atwater BD
Am Heart J: 30 Dec 2020; 231:45-55 | PMID: 33098811
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk of heart failure following drug-eluting stent implantation in patients with non-ST-elevation myocardial infarction.

Lin CF, Chang YH, Yu FC, Tsai CT, ... Liu HY, Chien LN
Background:
and aims
The association between implanted stent types and heart failure in patients with non-ST-elevation myocardial infarction (NSTEMI) remains unknown. The current study aimed to investigate whether the implantation of a newer-generation drug-eluting stent (NG-DES) compared with that of a bare-metal stent (BMS) in patients with NSTEMI who receive an undefined duration of dual antiplatelet therapy (DAPT) reduces the risk of hospitalization for heart failure (HHF).
Methods
In this nationwide, population-based retrospective cohort study, propensity score matching was used on the Taiwan\'s National Health Insurance Research Database to select 8,644 pairs of patients with NSTEMI and similar baseline characteristics receiving NG-DES or BMS implantation between January 1, 2007 and December 31, 2016. A competing risk model was constructed to evaluate the risk of HHF in the NG-DES and BMS groups. Death was considered a competing risk.
Results
Rates of cumulative incidence competing risk for HHF at 1, 2, 3, 4, and 5-year follow-ups were lower in the NG-DES group (4.11%, 5.63%, 6.72%, 7.65%, and 8.89%, respectively) than in the BMS group (5.89%, 7.81%, 9.25%, 10.8%, and 11.9%, respectively). After adjustment for all clinical variables, NG-DES implantation was associated with a lower risk of HHF than BMS implantation after 5 years, with an adjusted subdistribution hazard ratio of 0.71 (95% CI = 0.64-0.79, p < 0.001). These results are in agreement with those of patients who received DAPT for >6 months.
Conclusions
NG-DESs may reduce HHF risk in patients with NSTEMI who receive an undefined duration of DAPT.

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

Atherosclerosis: 30 Dec 2020; 316:84-89
Lin CF, Chang YH, Yu FC, Tsai CT, ... Liu HY, Chien LN
Atherosclerosis: 30 Dec 2020; 316:84-89 | PMID: 33109336
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Alternative Echocardiographic Algorithm for Left Ventricular Filling Pressure in Patients with Heart Failure with Preserved Ejection Fraction.

Matsuhiro Y, Nishino M, Ukita K, Kawamura A, ... Sakata Y,

The American Society of Echocardiography / the European Association of Cardiovascular Imaging recommend a conventional algorithm for estimating left ventricular (LV) filling pressure in heart failure. However, several patients are classed as \"indeterminate\" due to their LV filling pressures being impossible to calculate. We investigated whether our new echocardiographic algorithm can predict clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). We enrolled 754 consecutive patients from the PURSUIT-HFpEF registry. We used the new algorithm to divide them into two groups; a normal LV filling pressure group (N group) and a high LV filling pressure group (H group). The H group consisted of 342 patients. Over a mean follow-up of 342 days, 185 patients reached the primary composite endpoint (157 readmissions for worsening heart failure and 43 cardiovascular deaths). In a multivariable Cox analysis, being in the H group was significantly associated with an increased rate of cardiac events compared to the N group (hazard ratio: 1.71; 95% confidence interval: 1.17 to 2.50, P = 0.006). There were 56 patients (7%) who were assigned to \"indeterminate\" with the conventional algorithm. Using the new algorithm, we reclassified 16 patients (29%) into the H group and 40 patients (71%) into the N group. The Kaplan-Meier curves showed the reclassified H group had a significantly higher incidence of cardiac events than those assigned to the N group (P < 0.01). In conclusion, the present study demonstrated LV filling pressure assessed by our algorithm can predict clinical outcomes in patients with HFpEF.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 21 Dec 2020; epub ahead of print
Matsuhiro Y, Nishino M, Ukita K, Kawamura A, ... Sakata Y,
Am J Cardiol: 21 Dec 2020; epub ahead of print | PMID: 33359198
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Unexpected high failure rate of a specific MicroPort/LivaNova/Sorin pacing lead.

Haeberlin A, Anwander MT, Kueffer T, Tholl M, ... Roten L, Noti F
Background
Pacing leads are the Achilles heel of pacemakers. Most manufacturers report a 3-year survival rate of >99% of their leads. We observed several failures of the Beflex/Vega leads (MicroPort, Shanghai, China; formerly Sorin/LivaNova).
Objective
The purpose of this study was to investigate failure rates of Beflex/Vega leads.
Methods
We analyzed the performance of Beflex/Vega leads implanted at our tertiary referral center. All-cause lead failures (any issues requiring reinterventions such as lead dislocations, cardiac perforations, and electrical abnormalities) were identified during follow-up. The Beflex/Vega lead was compared with a reference lead (CapSureFix Novus 5076, Medtronic, Minneapolis, MN) implanted within the same period and by the same operators.
Results
A total of 585 leads were analyzed (382 Beflex/Vega and 203 CapSureFix Novus 5076 leads). Cumulative failure rate estimates were 5.2%, 6.3%, and 12.4% after 1, 2, and 3 years for the Beflex/Vega lead. This was worse compared to the reference lead (1.5%, 1.5%, 3.7% after 1, 2, and 3 years; P = .001). Early failure manifestations up to 3 months occurred at a similar rate (Beflex/Vega vs CapSureFix Novus 5076 lead: 1.3% vs 0.5% for dislocations; 1.3% vs 1.0% for perforations). During follow-up, electrical abnormalities such as noise oversensing (P = .013) and increased pacing thresholds (P = .003) became more frequent in the Beflex/Vega group. Electrical abnormalities were the most common failure manifestation 3 years after implantation in this group (9.4% vs 2.2% for the CapSureFix Novus 5076).
Conclusion
The failure rate of the Beflex/Vega lead of >10% after 3 years was higher than that of a competitor lead. This gives rise to concern since >135,000 such leads are active worldwide.

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

Heart Rhythm: 30 Dec 2020; 18:41-49
Haeberlin A, Anwander MT, Kueffer T, Tholl M, ... Roten L, Noti F
Heart Rhythm: 30 Dec 2020; 18:41-49 | PMID: 32798776
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Comparison of Survival in Patients with Clinically Significant Tricuspid Regurgitation with and without Heart Failure (From the Optum Integrated File).

Barker CM, Cork DP, McCullough PA, Mehta HS, ... Mollenkopf S, Verta P

This study aimed to quantify survival rates for patients with Tricuspid Regurgitation (TR) using real-world data. Several clinical conditions are associated with tricuspid regurgitation (TR), including heart failure (HF), other valve disease (OVD), right-sided heart disease (RSHD), and others that impact mortality. Optum data from January 1, 2007, through December 31, 2018 included patients age ≥18 years with TR and 12 months of continuous health plan enrollment before TR. Exclusion criteria were end-stage renal disease or known/primary organ pathology. Cohorts were created hierarchically: (1) TR with HF; (2) TR with OVD (no HF); (3) TR with RSHD only (no OVD or HF); (4) TR only. Survival was estimated using a Cox hazard model with an interaction term for TR severity and adjusted for patient demographics and Elixhauser comorbidities. A total of 33,686 met study inclusion (1) TR with HF (26.6%); (2) TR with OVD (36.7%); (3) TR with RSHD only (17.1%); (4) TR only (19.6%). TR Patients (regardless of severity) with HF, OVD or RSHD had an increased risk of mortality compared to patients with TR alone. TR severity was also significantly associated (hazard ratio= 1.33; P=0.0002) with an increased risk of all-cause mortality. In conclusion, TR severity is significantly associated with an increased risk of all-cause mortality, independent of associated conditions including HF, OVD, or RSHD. In patients with severe TR, the mortality risk is most pronounced for patients who had RSHD without HF or OVD prior to their TR diagnosis.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 28 Dec 2020; epub ahead of print
Barker CM, Cork DP, McCullough PA, Mehta HS, ... Mollenkopf S, Verta P
Am J Cardiol: 28 Dec 2020; epub ahead of print | PMID: 33385352
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effectiveness and Safety of Extracorporeal Shockwave Myocardial Revascularization in Patients with Refractory Angina Pectoris and Heart Failure.

Martínez-Sánchez C, Azar-Manzur F, González-Pacheco H, Amezcua-Guerra LM, ... Gopar-Nieto R, Sandoval J

Extracorporeal shockwave myocardial revascularization (ESMR) is a therapy for refractory angina pectoris. Our aim was to assess the efficacy and safety of ESMR in the management of patients with stable coronary artery disease (CAD) and heart failure (HF) as well as its effects on inflammation and angiogenesis. In this single-arm prospective trial we included 48 patients with CAD, myocardial ischemia assessed by radionuclide imaging, echocardiographic evidence of left ventricular systolic dysfunction and without revascularization options. Changes in angina grading score, myocardial perfusion, left ventricular ejection fraction (LVEF), and six-minute walk test (6MWT) after ESMR therapy were used for efficacy assessment. Changes of inflammation and angiogenesis biomarkers were also evaluated. ESMR therapy was performed using a commercially available cardiac shockwave generator system (Cardiospec; Medispec). After 9 weeks of ESMR therapy, a significant improvement was found regarding the initial angina class, severity of ischemia, LVEF, and 6MWT in most patients. No deleterious side effects after treatment were detected. Regarding biomarkers, endothelial progenitor cells and angiopoietin-3 were significantly increased while IL-18 and TGF-β were significantly decreased after ESMR in the total group. Notably, VEGF, IL-1ß, and lipoxin A4 levels were significantly increased only in patients with myocardial ischemia improvement. In conclusion, ESMR therapy is safe and effective in most but not all patients with CAD and HF. ESMR is associated with increased markers of angiogenesis and decreased markers of inflammation. Myocardial ischemia improvement after ESMR is associated with increased markers of angiogenesis and pro-resolving mediators.

Copyright © 2020. Published by Elsevier Inc.

Am J Cardiol: 28 Dec 2020; epub ahead of print
Martínez-Sánchez C, Azar-Manzur F, González-Pacheco H, Amezcua-Guerra LM, ... Gopar-Nieto R, Sandoval J
Am J Cardiol: 28 Dec 2020; epub ahead of print | PMID: 33385348
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of Diabetes Mellitus and Left Ventricular Perfusion on Frequency of Development of Heart Failure and/or All-cause Mortality Late After Acute Myocardial Infarction.

Tomasik A, Nabrdalik K, Kwiendacz H, Radzik E, ... Nowalany-Kozielska E, Lip GYH

Type 2 diabetes mellitus (DM) has a detrimental impact on cardiovascular outcomes, with implications for prognosis following ST elevation myocardial infarction (STEMI).The aim was to evaluate the impact of DM and myocardial perfusion on the long-term risk of heart failure (HF) and/or all-cause mortality following primary percutaneous coronary intervention (pPCI) for STEMI. A total of 406 STEMI patients (104 with DM) treated with pPCI were enrolled in this observational study. Myocardial perfusion was reassessed with the Quantitative Myocardial Blush Evaluator. Follow-up data on HF (ICD10 [International Statistical Classification of Diseases] codes I50.0 - I50.9) and all-cause mortality were obtained from the National Health Fund. During a 6-year follow-up, 36 (35%) patients with DM died compared with 45 (15%) patients without DM (p <0.001). Also, 24 (23%) patients with DM developed HF compared with 51 (17%) patients without DM (p = 0.20). Patients with DM and HF had the highest mortality rate (75%), and those with DM and a QuBE score below the median value (9.0 arb. units) had significantly higher risk of HF (hazard ratio [HR] =1.96, 95% CI 1.18 to 3.27, p = 0.0099) and the composite of HF and/or all-cause mortality (HR = 1.89, 95% CI 1.33 to 2.69, p = 0.0004). In conclusion DM (type 2) and diminished myocardial perfusion increase the risk of HF and/or all-cause mortality during a 6-year follow-up after pPCI for STEMI.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Jan 2021; 140:25-32
Tomasik A, Nabrdalik K, Kwiendacz H, Radzik E, ... Nowalany-Kozielska E, Lip GYH
Am J Cardiol: 31 Jan 2021; 140:25-32 | PMID: 33144164
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Relation of Neighborhood Disadvantage to Heart Failure Symptoms and Hospitalizations.

Shirey TE, Hu Y, Ko YA, Nayak A, ... Patel S, Morris AA

Residence in socioeconomically deprived neighborhoods may influence patient\'s health-related behaviors and overall health. We evaluated the association of neighborhood disadvantage on heart failure (HF) symptom burden and hospitalization rates. We characterized neighborhood deprivation in 359 HF subjects (age 56 ± 13 years, 52% black) in metropolitan Atlanta using the Area Deprivation Index (ADI). ANOVA was used to compare HF symptoms measured using the Kansas City Cardiomyopathy Questionnaire, and HF Self-Care Index across ADI tertiles. Zero-inflated Poisson regression was used to compare rates of recurrent HF hospitalization (HFH) across ADI tertiles. Subjects living in more deprived neighborhoods were more likely to be black, have Medicare or Medicaid insurance, and have a lower ejection fraction than those living in less deprived neighborhoods (all p ≤ 0.005). Subjects in more deprived neighborhoods had more severe HF symptoms (p < 0.001), but there was no difference in HF Self-Care Index scores across ADI tertiles. Subjects living in more deprived neighborhoods had a higher odds of being hospitalized for HF than subjects in less deprived neighborhoods. Once subjects had experienced a HFH, however, the association between ADI and the risk of recurrent HFH varied by racial group. In whites, increasing ADI was associated with a marginally decreased risk of recurrent HFH, while there was no association between ADI and recurrent HFH in blacks. In conclusion, patients with HF living in more deprived neighborhoods have greater symptom burden and are more likely to experience a HFH than those living in less deprived neighborhoods.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Jan 2021; 140:83-90
Shirey TE, Hu Y, Ko YA, Nayak A, ... Patel S, Morris AA
Am J Cardiol: 31 Jan 2021; 140:83-90 | PMID: 33144159
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

Katbeh A, De Potter T, Geelen P, Di Gioia G, ... Van Camp G, Penicka M
Background
Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce.
Objective
To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF.
Methods
The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using HFPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides.
Results
Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e\', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF.
Conclusions
Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

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

Int J Cardiol: 14 Jan 2021; 323:161-167
Katbeh A, De Potter T, Geelen P, Di Gioia G, ... Van Camp G, Penicka M
Int J Cardiol: 14 Jan 2021; 323:161-167 | PMID: 32882295
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term performance and risk factors analysis after permanent His-bundle pacing and atrioventricular node ablation in patients with atrial fibrillation and heart failure.

Su L, Cai M, Wu S, Wang S, ... Vijayaraman P, Huang W
Aims
His-bundle pacing (HBP) combined with atrioventricular node (AVN) ablation has been demonstrated to be effective in patients with atrial fibrillation (AF) and heart failure (HF) during medium-term follow-up and there are limited data on the risk analysis of adverse prognosis in this population. In this study, we aimed to evaluate the long-term performance of HBP following AVN ablation in AF and HF.
Methods and results
From August 2012 to December 2017, consecutive AF patients with HF and narrow QRS who underwent AVN ablation and HBP were enrolled. The clinical and echocardiographic data, pacing parameters, all-cause mortality, and heart failure hospitalization (HFH) were tracked. A total of 94 patients were enrolled (age 70.1 ± 10.5 years; male 57.4%). Acute HBP were achieved in 89 (94.7%) patients with successful permanent HBP combined with AVN ablation in 81 (86.2%) patients. Left ventricular ejection fraction (LVEF) improved from 44.9 ± 14.9% at baseline to 57.6 ± 12.5% during a median follow-up of 3.0 (IQR: 2.0-4.4) years (P < 0.001). Heart failure hospitalization or all-cause mortality occurred in 21 (25.9%) patients. The LVEF ≤ 40%, pulmonary artery systolic pressure (PASP) ≥40 mmHg, or serum creatinine (Scr) ≥97 μmol/L at baseline was significantly associated with higher composite endpoint of HFH or death (P < 0.05). The His capture threshold was 1.0 ± 0.7 V/0.5 ms at implant and remained stable during follow-up.
Conclusion
His-bundle pacing combined with AVN ablation was effective in patients with AF and drug-refectory HF. High PASP, high Scr, or low LVEF at baseline was independent predictors of composite endpoint of all-cause mortality or HFH.

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

Europace: 25 Dec 2020; 22:ii19-ii26
Su L, Cai M, Wu S, Wang S, ... Vijayaraman P, Huang W
Europace: 25 Dec 2020; 22:ii19-ii26 | PMID: 33370800
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk prediction models for heart failure admissions in adults with congenital heart disease.

Cohen S, Liu A, Wang F, Guo L, ... Muhll IFV, Marelli AJ
Background
Heart failure (HF) is the leading cause of death in adult patients with congenital heart disease (ACHD). No risk prediction model exists for HF hospitalization (HFH) for ACHD patients. We aimed to develop a clinically relevant one-year risk prediction system to identify ACHD patients at high risk for HFH.
Methods
Data source was the Quebec CHD Database. A retrospective cohort including all ACHD patients aged 18-64 (1995-2010) was constructed for assessing the cumulative risk of HFH adjusting for competing risk of death. To identify one-year predictors of incident HFH, multivariable logistic regressions were employed to a nested case-control sample of all ACHD patients aged 18-64 in 2009. The final model was used to create a risk score system based on adjusted odds ratios.
Results
The cohort included 29,991 ACHD patients followed for 648,457 person-years. The cumulative HFH risk by age 65 was 12.58%. The case-control sample comprised 26,420 subjects, of whom 189 had HFHs. Significant one-year predictors were age ≥ 50, male sex, CHD lesion severity, recent 12-month HFH history, pulmonary arterial hypertension, chronic kidney disease, coronary artery disease, systemic arterial hypertension, and diabetes mellitus. The created risk score ranged from 0 to 19. The corresponding HFH risk rose rapidly beyond a score of 8. The risk scoring system demonstrated excellent prediction performance.
Conclusions
One eighth of ACHD population experienced HFH before age 65. Age, sex, CHD lesion severity, recent 12-month HFH history, and comorbidities constructed a risk prediction model that successfully identified patients at high risk for HFH.

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

Int J Cardiol: 31 Dec 2020; 322:149-157
Cohen S, Liu A, Wang F, Guo L, ... Muhll IFV, Marelli AJ
Int J Cardiol: 31 Dec 2020; 322:149-157 | PMID: 32798623
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cost-utility analysis of add-on dapagliflozin treatment in heart failure with reduced ejection fraction.

Krittayaphong R, Permsuwan U
Background
Dapagliflozin is an antidiabetic medication that has been shown to reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to determine the cost-utility of add-on dapagliflozin treatment for HFrEF.
Methods
An analytical decision model was constructed to assess lifetime costs and outcomes from a healthcare system perspective. The cohort comprised HFrEF patients with left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association (NYHA) class II-IV with an average age of 65 years. Clinical inputs were derived from the results of the Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure (DAPA-HF) trial. Risk of non-cardiovascular death data, readmission rate data, and treatment-related cost data were based on Thai population. The outcomes and costs were discounted at 3% annually. A series of sensitivity analyses were also conducted.
Results
The increased cost of dapagliflozin add-on treatment from 17,442 THB (559 USD) to 54,405 THB (1745 USD) was associated with a QALY gain from 6.33 to 6.92 compared to standard therapy, yielding an ICER of 62,090 THB/QALY (1991 USD/QALY). Sensitivity analyses revealed that the addition of dapagliflozin to the standard treatment demonstrated an 87% cost-effectiveness strategy at a level of willingness to pay (WTP) of 160,000 THB/QALY (5131 USD/QALY). ICER was higher in non-diabetes compared to diabetes (68,304 vs 47,613 THB/QALY or 2191 vs 1527 USD/QALY).
Conclusions
Dapagliflozin is a cost-effective add-on therapy for patients with HFrEF at a WTP of 160,000 THB/QALY (5131 USD/QALY).

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

Int J Cardiol: 31 Dec 2020; 322:183-190
Krittayaphong R, Permsuwan U
Int J Cardiol: 31 Dec 2020; 322:183-190 | PMID: 32800910
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Determinants of outcome in patients with heart failure with reduced ejection fraction & secondary mitral regurgitation.

Chasapi A, Karogiannis N, Zidros S, Patel K, Lloyd G, Bhattacharyya S
Background
The outcome of secondary mitral regurgitation (MR) in patients with heart failure is poor. Survival is related to the severity of MR. We sought to investigate the effect of left ventricular contractility, the ratio of left ventricular end-diastolic volume (LVEDV) to effective orifice area (EROA) and the ratio of regurgitant volume (RVol) to stroke volume (SV) on cardiovascular survival.
Methods
188 patients with a left ventricular ejection fraction (LVEF) < 50% and secondary MR were included. Groups were divided into tertiles. The Kaplan Meier method and log rank test were used to identify differences in survival between groups. Cox regression was used to identify independent predictors of cardiac mortality.
Results
Median follow-up was 30.4 months. Patients with a more abnormal global longitudinal strain (GLS) had lower survival, p = 0.001. There was no difference in survival between patients with an LVEF <30%, 30%-40% and >40%, p = 0.27. Patients with a higher RVol/SV ratio had lower survival than those with a lower ratio, p < 0.0001. Patients with a lower LVEDV/EROA ratio had worse survival than those with a higher ratio, p < 0.0001. Independent predictors of cardiovascular mortality were GLS (<5.6%) hazard ratio (HR) 2.7, the ratio of RVol/SV (>1.38) HR 4.96 and the ratio of LVDEV to EROA (<263) HR 4.49.
Conclusion
The main determinants of cardiovascular mortality in patients with secondary MR and heart failure are more abnormal GLS, lower LVEDV/EROA ratio and higher RVol/SV ratio. These may help risk stratify patients to help determine the optimal management strategy.

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

Int J Cardiol: 14 Jan 2021; 323:229-234
Chasapi A, Karogiannis N, Zidros S, Patel K, Lloyd G, Bhattacharyya S
Int J Cardiol: 14 Jan 2021; 323:229-234 | PMID: 32911003
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Characteristics, prognosis and treatment response in distinct phenogroups of heart failure with preserved ejection fraction.

Gu J, Pan JA, Lin H, Zhang JF, Wang CQ
Background
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups based on clinical features using machine learning, and to compare clinical characteristics, outcomes and treatment response across the phenogroups.
Methods
We applied model-based clustering to 11 clinical and laboratory variables collected in 970 HFpEF patients. An additional 290 HFpEF patients was enrolled as a validation cohort. During 5-year follow-up, all-cause mortality was used as the primary endpoints, and composite endpoints (all-cause mortality or HF hospitalization) were set as the secondary endpoint.
Results
We identified three phenogroups, for which significant differences in the age and gender, the prevalence of concomitant ischaemic heart disease, atrial fibrillation and type 2 diabetes mellitus, the burden of B-type natriuretic peptide level and HF symptoms. Patients with phenogroup 3 had higher all-cause mortality or composite endpoints, whereas patients in phenogroup 1 had less adverse events after 5-year follow-up. Moreover, it was indicated that beta-blockers or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) use was associated with a lower risk of all-cause mortality or composite endpoints in phenogroup 3, instead of the other phenogroups. This HFpEF phenogroup classification, including its ability to stratify risk, was successfully replicated in a prospective validation cohort.
Conclusion
Machine-learning based clustering strategy is used to identify three distinct phenogroups of HFpEF that are characterized by significant differences in comorbidity burden, underlying cardiac abnormalities, and long-term prognosis. Beta-blockers or ACEI/ARB therapy is associated with a lower risk of adverse events in specific phenogroup.

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

Int J Cardiol: 14 Jan 2021; 323:148-154
Gu J, Pan JA, Lin H, Zhang JF, Wang CQ
Int J Cardiol: 14 Jan 2021; 323:148-154 | PMID: 32860842
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Disproportionate functional mitral regurgitation predicts a favourable response after MitraClip implant in patients with advanced heart failure. Real-world evidence of a new conceptual framework.

Frea S, Pidello Md S, Boretto Md P, Rettegno Md S, ... Rinaldi M, De Ferrari GM
Introduction
Accurate predictors of good clinical response after MitraClip implant in patients with heart failure (HF) are still lacking. Aim of this study was to investigate the role of regurgitant fraction >50% as a marker of disproportionate functional mitral regurgitation (FMR) in identifying best responders to Mitraclip.
Methods and results
Data from 58 advanced HF patients (age 66 ± 8 years, 81% males, 63% NYHA class IV, LV ejection fraction (EF) 25.5 ± 5.5%) with disproportionate and proportionate FMR who underwent successful MitraClip implant were analyzed. After MitraClip all patient achieved mild (≤ 2+/4+) MR. During 12-month follow-up 18 patients (31%) had a major adverse cardiac event (MACE, i.e. cardiac death, urgent LVAD implant or heart transplantation, HF hospitalization). Disproportionate FMR (n = 48, 83%) was associated with a better clinical outcome (p = .003) while regurgitant volume and EROA were not. TAPSE ≤14 mm was associated with worse outcome (p = .018). At multivariable analysis only disproportionate MR and TAPSE ≤14 mm showed a significant association with MACE (p = .017 and p = .02, respectively). A reverse left ventricular remodeling (i.e., reduction on LV end-diastolic diameter and end-diastolic volume) was achieved only in the disproportionate FMR group.
Conclusions
In conclusion, disproportionate FMR assessed by regurgitant fraction and RV dysfunction assessed by TAPSE may help the selection of HF patients candidates for MitraClip therapy.

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

Int J Cardiol: 14 Jan 2021; 323:208-212
Frea S, Pidello Md S, Boretto Md P, Rettegno Md S, ... Rinaldi M, De Ferrari GM
Int J Cardiol: 14 Jan 2021; 323:208-212 | PMID: 32795480
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients With Coronavirus Disease-19.

Goerlich E, Gilotra NA, Minhas AS, Bavaro N, Hays AG, Cingolani OH
Background
Coronavirus disease-19 (COVID-19) has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain on speckle-tracking echocardiography in hospitalized patients with COVID-19 and subsequently aimed to identify characteristics of affected patients. We hypothesized that patients with COVID-19 with reduced basal LV strain would demonstrate elevated cardiac biomarkers.
Methods and result
Eighty-one consecutive patients with COVID-19 underwent speckle-tracking echocardiography. Those with poor quality speckle-tracking echocardiography (n = 2) or a known LV ejection fraction of <50% (n = 4) were excluded. Patients with an absolute value basal longitudinal strain of <13.9% (2 standard deviations below normal) were designated as cases (n = 39); those with a basal longitudinal strain of ≥13.9% were designated as controls (n = 36). Demographics and clinical variables were compared. Of 75 included patients (mean age 62 ± 14 years, 41% women), 52% had reduced basal strain. Cases had higher body mass index (median 34.1; interquartile range 26.5-37.9 kg/m vs median 26.9, interquartile range, 24.8-30.0 kg/m, P = .009), and greater proportions of Black (74% vs 36%, P = .0009), hypertensive (79% vs 56%, P = .026), and diabetic patients (44% vs 19%, P = .025) compared with controls. Troponin and N-terminal pro-brain natriuretic peptide levels trended higher in cases, but were not significantly different.
Conclusions
Reduced basal LV strain is common in patients with COVID-19. 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 The Authors. Published by Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:100-104
Goerlich E, Gilotra NA, Minhas AS, Bavaro N, Hays AG, Cingolani OH
J Card Fail: 30 Dec 2020; 27:100-104 | PMID: 32991982
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term Follow-Up of Patients with Heart Failure and Reduced Ejection Fraction 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 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:175-178
Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Int J Cardiol: 14 Jan 2021; 323:175-178 | PMID: 33038408
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Brain-Derived Neurotrophic Factor Improves Impaired Fatty Acid Oxidation Via the Activation of Adenosine Monophosphate-activated Protein Kinase-α - Proliferator-Activated Receptor-r Coactivator-1α Signaling in Skeletal Muscle of Mice With Heart Failure.

Matsumoto J, Takada S, Furihata T, Nambu H, ... Sabe H, Kinugawa S
Background
We recently reported that treatment with rhBDNF (recombinant human brain-derived neurotrophic factor) improved the reduced exercise capacity of mice with heart failure (HF) after myocardial infarction (MI). Since BDNF is reported to enhance fatty acid oxidation, we herein conducted an in vivo investigation to determine whether the improvement in exercise capacity is due to the enhancement of the fatty acid oxidation of skeletal muscle via the AMPKα-PGC1α (adenosine monophosphate-activated protein kinase-α-proliferator-activated receptor-r coactivator-1α) axis.
Methods
MI and sham operations were conducted in C57BL/6J mice. Two weeks postsurgery, we randomly divided the MI mice into groups treated with rhBDNF or vehicle for 2 weeks. AMPKα-PGC1α signaling and mitochondrial content in the skeletal muscle of the mice were evaluated by Western blotting and transmission electron microscopy. Fatty acid β-oxidation was examined by high-resolution respirometry using permeabilized muscle fiber. BDNF-knockout mice were treated with 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside, an activator of AMPK.
Results
The rhBDNF treatment significantly increased the expressions of phosphorylated AMPKα and PGC1α protein and the intermyofibrillar mitochondrial density in the MI mice. The lowered skeletal muscle mitochondrial fatty acid oxidation was significantly improved in the rhBDNF-treated MI mice. The reduced exercise capacity and mitochondrial dysfunction of the BDNF-knockout mice were improved by 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside.
Conclusions
Beneficial effects of BDNF on the exercise capacity of mice with HF are mediated through an enhancement of fatty acid oxidation via the activation of AMPKα-PGC1α in skeletal muscle. BDNF may become a therapeutic option to improve exercise capacity as an alternative or adjunct to exercise training.



Circ Heart Fail: 27 Dec 2020:CIRCHEARTFAILURE119005890; epub ahead of print
Matsumoto J, Takada S, Furihata T, Nambu H, ... Sabe H, Kinugawa S
Circ Heart Fail: 27 Dec 2020:CIRCHEARTFAILURE119005890; epub ahead of print | PMID: 33356364
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure.

Yurista SR, Matsuura TR, Silljé HHW, Nijholt KT, ... Kelly DP, Westenbrink BD
Background
Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models.
Methods
Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats. Seventy-five mice underwent a prevention treatment strategy with a KE comprised of hexanoyl-hexyl-3-hydroxybutyrate KE (KE-1) diet, and 77 rats were treated in either a prevention or treatment regimen using a commercially available β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG; KE-2) diet.
Results
The KE-1 diet in mice elevated β-hydroxybutyrate levels during nocturnal feeding, whereas the KE-2 diet in rats induced ketonemia throughout a 24-hour period. The KE-1 diet preventive strategy attenuated development of left ventricular dysfunction and remodeling post-transverse aortic constriction/MI (left ventricular ejection fraction±SD, 36±8 in vehicle versus 45±11 in KE-1; =0.016). The KE-2 diet therapeutic approach also attenuated left ventricular dysfunction and remodeling post-MI (left ventricular ejection fraction, 41±11 in MI-vehicle versus 61±7 in MI-KE-2; <0.001). In addition, ventricular weight, cardiomyocyte cross-sectional area, and the expression of ANP (atrial natriuretic peptide) were significantly attenuated in the KE-2-treated MI group. However, treatment with KE-2 did not influence cardiac fibrosis post-MI. The myocardial expression of the ketone transporter and 2 ketolytic enzymes was significantly increased in rats fed KE-2 diet along with normalization of myocardial ATP levels to sham values.
Conclusions
Chronic oral supplementation with KE was effective in both prevention and treatment of heart failure in 2 preclinical animal models. In addition, our results indicate that treatment with KE reprogrammed the expression of genes involved in ketone body utilization and normalized myocardial ATP production following MI, consistent with provision of an auxiliary fuel. These findings provide rationale for the assessment of KEs as a treatment for patients with heart failure.



Circ Heart Fail: 27 Dec 2020:CIRCHEARTFAILURE120007684; epub ahead of print
Yurista SR, Matsuura TR, Silljé HHW, Nijholt KT, ... Kelly DP, Westenbrink BD
Circ Heart Fail: 27 Dec 2020:CIRCHEARTFAILURE120007684; epub ahead of print | PMID: 33356362
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of dapagliflozin in heart failure with reduced ejection fraction, and COPD: An analysis of DAPA-HF.

Dewan P, Docherty KF, Bengtsson O, de Boer RA, ... Jhund PS, McMurray JJ
Aims
Chronic obstructive pulmonary disease (COPD) is an important comorbidity in HFrEF, associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. To examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).
Methods & results
We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening heart failure (HF) event or cardiovascular (CV) death. 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline NT-proBNP, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without 18.9 (95% CI 16.0-22.2) versus 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD versus no COPD 1.44 (1.21-1.72), P<0.001. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with (HR 0.67 [95%CI 0.48-0.93]) and without COPD (0.76 [0.65-0.87]); interaction p-value 0.47.
Conclusions
In DAPA-HF, one-in-eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all prespecified outcomes was consistent in patients with and without COPD.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 22 Dec 2020; epub ahead of print
Dewan P, Docherty KF, Bengtsson O, de Boer RA, ... Jhund PS, McMurray JJ
Eur J Heart Fail: 22 Dec 2020; epub ahead of print | PMID: 33368858
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Implantation of an Atrial Flow Regulator in a Child on Venoarterial Extracorporeal Membrane Oxygenator as a Bridge to Heart Transplant: A Case Report.

Piccinelli E, Castro-Verdes MB, Fraisse A, Bautista-Rodriguez C
Background
Balloon dilation and stenting of the atrial septum are techniques used to unload left heart cavities in acute or end-stage heart failure in children. However, they carry significant risks such as tamponade or device embolization.
Case presentation
We report the first case of a child with an end-stage mitochondrial cardiomyopathy on a venoarterial extracorporeal membrane oxygenator as a bridge to heart transplant where an atrial flow regulator device has been implanted.
Conclusions
This case illustrates the feasibility and safety of atrial flow regulator implantation in this setting. This procedure allowed to wean inotropic support while awaiting heart transplantation.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 23 Dec 2020; epub ahead of print
Piccinelli E, Castro-Verdes MB, Fraisse A, Bautista-Rodriguez C
J Card Fail: 23 Dec 2020; epub ahead of print | PMID: 33242607
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Multi-organ failure with abnormal receptor metabolism in mice mimicking Samd9/9L syndromes.

Nagamachi A, Kanai A, Nakamura M, Okuda H, ... Matsui H, Inaba T

Autosomal dominant \"sterile alpha motif domain containing 9 (Samd9) and Samd9L (Samd9/9L) syndromes\" are a large subgroup of currently established inherited bone marrow failure syndromes that include MIRAGE, ataxia pancytopenia, and familial monosomy 7 syndromes. Samd9/9L genes are located in tandem on chromosome 7 and have been known to be the genes responsible for myeloid malignancies associated with monosomy 7. Additionally, as interferon-inducible genes, Samd9/9L are crucial for protection against viruses. Samd9/9L syndromes are caused by gain-of-function mutations and develop into infantile myelodysplastic syndromes associated with monosomy 7 (MDS/-7) at extraordinarily high frequencies. We generated mice expressing Samd9LD764N, which mimic the MIRAGE syndrome presenting with growth retardation, a short life, bone marrow failure, and multi-organ degeneration. In hematopoietic cells, Samd9LD764N downregulates the endocytosis of transferrin and c-Kit resulting in a rare cause of anemia and a low bone marrow reconstitutive potential that ultimately causes MDS/-7. By contrast, in non-hematopoietic cells we tested, Samd9LD764N upregulated the endocytosis of EGFR by Ship2 phosphatase translocation to the cytomembrane and activated lysosomes, resulting in the reduced expression of surface receptors and signaling. Thus Samd9/9L is a downstream regulator of interferon that controls receptor metabolism, with constitutive activation leading to multi-organ dysfunction.



J Clin Invest: 28 Dec 2020; epub ahead of print
Nagamachi A, Kanai A, Nakamura M, Okuda H, ... Matsui H, Inaba T
J Clin Invest: 28 Dec 2020; epub ahead of print | PMID: 33373325
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of low-level tragus stimulation on endothelial function in heart failure with reduced ejection fraction.

Dasari TW, Csipo T, Amil F, Lipecz A, ... Yabluchanskiy A, Po SS
Background
Autonomic dysregulation in HFrEF plays a major role in endothelial dysfuction. Low level Tragus stimulation (LLTS) is a novel, non-invasive method of autonomic modulation.
Methods
We enrolled 50 HFrEF patients (LVEF≤40%) in a randomized, double-blinded, crossover study. Day 1: patients underwent 60 minutes of LLTS with a transcutaneous stimulator (20Hz, 200 μs pulse width) or sham (ear lobule) stimulation. Macrovascular function was assessed using flow mediated dilatation (FMD) in brachial artery and cutaneous microcirculation with laser speckle contrast imaging in hand and nail bed. Day 2: patients were crossed over to other study arm and underwent sham or LLTS; vascular tests were repeated pre- and post-stimulation.
Results
Compared to sham, LLTS improved FMD by increasing the %-change in brachial artery diameter (5 to 7.5, LLTS on day 1, p=0.02; 4.9 to 7.1, LLTS on day 2, p= 0.003), compared to no significant change in the sham group (4.6 to 4.7, p=0.84 on day 1 and 5.6 to 5.9, p=0.65 on day 2). Cutaneous microcirculation in hand showed no improvement and perfusion of nail bed showed a trend towards improvement.
Conclusion
Our study demonstrated beneficial effects of acute neuromodulation on macrovascular function. Larger studies to validate these findings and understand mechanistic links are warranted.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 29 Dec 2020; epub ahead of print
Dasari TW, Csipo T, Amil F, Lipecz A, ... Yabluchanskiy A, Po SS
J Card Fail: 29 Dec 2020; epub ahead of print | PMID: 33387632
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Case Reports of Implantable Cardiac Device Physiologic Sensor Changes in Subjects with COVID-19 Infection.

Shumway JL, Stolen CM, Ahmed R, Plumer M, Capodilupo RC

The SARS-CoV-2 pandemic has established a new set of challenges to healthcare delivery. Remotely monitored physiologic sensors on implantable cardiac devices can provide insight into the differential diagnosis of dyspnea in the heart failure population. We report on a unique pattern of sensor deviations that appear to occur specifically with SARS-CoV-2 infection.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 28 Dec 2020; epub ahead of print
Shumway JL, Stolen CM, Ahmed R, Plumer M, Capodilupo RC
J Card Fail: 28 Dec 2020; epub ahead of print | PMID: 33385524
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Right Atrial Remodeling in Heart Failure with Preserved Ejection Fraction.

Ikoma T, Obokata M, Okada K, Harada T, ... Kurabayashi M, Murakami M
Background
Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with a preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.
Methods and results
Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m in men and >33 mL/m in women). Compared to patients with normal RA size (n=234), patients with RA dilation (n=67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular (RV) systolic function, more severe pulmonary hypertension (PH), and higher prevalence of mild tricuspid regurgitation (TR), and impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, CI [4.00-26.1] current AF vs no AF and OR 3.38, CI 1.26-9.07, earlier AF vs no AF). Patients with RA dilation had more than two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted HR 2.01, 95% CI, 1.09-3.70-, p=0.02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.
Conclusions
These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 28 Dec 2020; epub ahead of print
Ikoma T, Obokata M, Okada K, Harada T, ... Kurabayashi M, Murakami M
J Card Fail: 28 Dec 2020; epub ahead of print | PMID: 33385523
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis.

Kittipibul V, Blumer V, Angsubhakorn N, Hernandez GA, ... Tedford RJ, Agarwal R
Background
Phosphodiesterase-5 Inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure (RVF) in patients with left ventricular assist devices (LVAD). Effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events (HRAE) are not well established.
Objective
This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes.
Methods
A comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020 to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I statistic were calculated.
Results
Thirteen observational studies were included in this analysis. Use of PDE5i was not significantly associated with lower postoperative RVF (OR 0.38, 95%CI 0.02-5.96, p=0.41). There was no significant association between PDE5i and gastrointestinal (GI) bleeding (OR 1.23, 95%CI 0.76-1.98, p=0.2), overall stroke (OR 0.60, 95%CI 0.21-1.68, p=0.17), ischemic stroke (OR 0.61, 95%CI 0.09-4.07, p=0.38), and pump thrombosis (OR 0.71, 95%CI 0.14-3.54, p=0.46).
Conclusions
Our meta-analysis showed no significant association between PDE5i and post-LVAD RVF. Despite the anti-platelet effects of PDE5i, there was no significant association between PDE5i and GI bleeding, overall stroke, ischemic stroke, and pump thrombosis. Randomized-controlled studies are warranted to evaluate the net benefits or harms of PDE5i in LVAD population.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 28 Dec 2020; epub ahead of print
Kittipibul V, Blumer V, Angsubhakorn N, Hernandez GA, ... Tedford RJ, Agarwal R
J Card Fail: 28 Dec 2020; epub ahead of print | PMID: 33385522
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pregnancy Associated Heart Failure with Preserved Ejection Fraction (HFpEF): Risk Factors and Maternal Morbidity: Pregnancy Associated HFpEF.

Briller JE, Mogos MF, Muchira JM, Piano MR
Background
Cardiovascular conditions are leading contributors to rising maternal morbidity and mortality. Heart Failure with preserved ejection fraction (HFpEF) results in the majority of heart failure admissions in women, yet its impact in pregnancy is unknown. We examined prevalence rates, risk factors and adverse pregnancy outcomes in women with HFpEF during pregnancy-related hospitalizations in the United States.
Methods
We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2002 through 2014 using the National Inpatient Sample. HFpEF cases were identified using the 428.3 International Classification of Diseases, 9 Edition, Clinical Modification code. Weighting variables were used to provide national estimates, unconditional survey logistic regression to generate odds ratios and 95% confidence intervals representing adjusted associations with adverse pregnancy outcomes and Joinpoint regression to estimate temporal trends.
Results
Among 58,732,977 hospitalizations, there were 3,840 HFpEF cases, an overall rate of 7 cases/100,000 pregnancy-related hospitalizations; 56% occurred postpartum, 27% during delivery and 17% antepartum. Temporal trend for hospitalization increased throughout the timeframe by 19.4% (CI: 13.9, 25.1). HFpEF hospitalizations were more common for Black, older, or poor women. Risk factors included hypertension (chronic hypertension and hypertensive disorders of pregnancy), anemia, obesity, diabetes, renal disease and coronary atherosclerosis; all known risk factors for HFpEF. Women with HFpEF were 2.61 to 6.47 times more likely to experience adverse pregnancy outcomes.
Conclusions
Pregnancy-related HFpEF hospitalization prevalence has increased and is associated with adverse pregnancy outcomes. Risk factors resemble those outside pregnancy, emphasizing the need for screening and monitoring women with risk factors during pregnancy for HFpEF.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 30 Dec 2020; epub ahead of print
Briller JE, Mogos MF, Muchira JM, Piano MR
J Card Fail: 30 Dec 2020; epub ahead of print | PMID: 33388469
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk Prediction for Peripartum Cardiomyopathy in Delivering Mothers: A Validated Risk Model: PPCM Risk Prediction Model.

Davis MB, Jarvie J, Gambahaya E, Lindenfeld J, Kao D
Background
Peripartum cardiomyopathy (PPCM) causes significant morbidity and mortality in childbearing women. Delays in diagnosis lead to worse outcomes; however, no validated risk prediction model exists. We sought to validate a previously described model and identify novel risk factors for PPCM presenting at the time of delivery.
Methods
Administrative hospital records from 5,277,932 patients from 8 states were screened for PPCM, identified by ICD-9 CM codes (674.5x) at the time of delivery. Demographics, comorbidities, procedures, and outcomes were quantified. Performance of a previously published regression model alone and with the addition of novel PPCM-associated characteristics was assessed using receiver operating characteristic area-under-the-curve (AUC) analysis. Novel risk factors were identified using multivariate logistic regression and the likelihood ratio test.
Results
In total, 1186 women with PPCM were studied, including 535/4,003,912 (0.013%) delivering mothers in the derivation set compared with 651/5,277,932 (0.012%) in the validation set. The previously published risk prediction model performed well in both the derivation (AUC 0.822) and validation datasets (AUC 0.802). Novel PPCM-associated characteristics in the combined cohort included diabetes mellitus (OR of PPCM 1.93 [1.23-3.02], p=0.004), mood disorders (OR 1.74 [1.22-2.47], p=0.002), obesity (OR 1.92 [1.45-2.55], p<0.001), and Medicaid insurance (OR 1.54 [1.22-1.96], p<0.001).
Conclusions
This is the first validated risk prediction model to identify women at increased risk for PPCM at the time of delivery. Diabetes mellitus, obesity, mood disorders, and lower socioeconomic status are risk factors associated with PPCM. This model may be useful for identifying women at risk and preventing delays in diagnosis.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 30 Dec 2020; epub ahead of print
Davis MB, Jarvie J, Gambahaya E, Lindenfeld J, Kao D
J Card Fail: 30 Dec 2020; epub ahead of print | PMID: 33388467
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Effect of Decongestion on Intrarenal Venous Flow Patterns in Patients With Acute Heart Failure.

Ter Maaten JM, Dauw J, Martens P, Somers F, ... Dupont M, Mullens W
Background
Discontinuous intrarenal venous flow patterns, as assessed by renal Doppler ultrasound examination, are associated with changes in hemodynamics such as volume expansion and poorer diuretic response in patients with heart failure (HF). We aimed to study intrarenal venous and arterial flow patterns after decongestive treatment in patients with acute HF.
Methods and results
Fifteen patients with acute HF were enrolled. Intrarenal venous and arterial flow patterns were assessed at baseline, 1 hour after administration of loop diuretics, at day 2 and day 3. Among patients hospitalized for acute HF, 13 (87%) had a discontinuous venous flow pattern at admission. After decongestive treatment, a significant improvement of the venous impedance index (P = .021) and venous discontinuity index (P = .004) was observed at day 3 compared with baseline. There was no effect on the intrarenal arterial flow patterns.
Conclusions
In patients who exhibit discontinuous renal venous flow patterns hospitalized for decongestive treatment owing to acute HF led to a normalization of intrarenal venous flow to a continuous pattern.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 30 Dec 2020; 27:29-34
Ter Maaten JM, Dauw J, Martens P, Somers F, ... Dupont M, Mullens W
J Card Fail: 30 Dec 2020; 27:29-34 | PMID: 32927066
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical and Imaging Response to Tumor Necrosis Factor Alpha Inhibitors in Treatment of Cardiac Sarcoidosis: A Multicenter Experience.

Gilotra NA, Wand AL, Pillarisetty A, Devraj M, ... Chen ES, Sheikh FH
Background
Cardiac sarcoidosis (CS) is an increasingly recognized cause of cardiomyopathy; however, data on immunosuppressive strategies are limited. Treatment with tumor necrosis factor (TNF) alpha inhibitors is not well described; moreover, there may be heart failure-related safety concerns.
Methods
Retrospective multicenter study of patients with CS treated with TNF alpha inhibitors. Baseline characteristics, treatments, and outcomes were adjudicated.
Results
Thirty-eight patients with CS (mean age 49.9 years, 42% women, 53% African American) were treated with TNF alpha inhibitor (30 infliximab, 8 adalimumab). Prednisone dose decreased from time of TNF alpha inhibitor initiation (21.7 ± 17.5 mg) to 6 months (10.4 ± 6.1 mg, P = .001) and 12 months (7.3 ± 7.3 mg, P = .002) after treatment. On pre-TNF alpha inhibitor treatment positron emission tomography with 18-flourodoxyglucose (FDG-PET), 84% of patients had cardiac FDG uptake. After treatment, there was a significant decrease in number of segments involved (3.5 ± 3.8 to 1.0 ± 2.5, P = .008) and maximum standardized uptake value (3.59 ± 3.70 to 0.57 ± 1.60, P = .0005), with 73% of patients demonstrating complete resolution or improvement of cardiac FDG uptake. The left ventricular ejection fraction remained stable (45.0 ± 16.5% to 47.0 ± 15.0%, P = .10). Four patients required inpatient heart failure treatment, and 8 had infections; 2 required treatment cessation.
Conclusions
TNF alpha inhibitor treatment guided by FDG-PET imaging may minimize corticosteroid use and effectively reduce cardiac inflammation without significant adverse effect on cardiac function. However, infections were common, some of which were serious, and therefore patients require close monitoring for both infection and cardiac symptoms.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:83-91
Gilotra NA, Wand AL, Pillarisetty A, Devraj M, ... Chen ES, Sheikh FH
J Card Fail: 30 Dec 2020; 27:83-91 | PMID: 32889044
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure.

Yamamoto M, Seo Y, Iida N, Ishizu T, ... Ohte N, Ieda M
Background
It remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression.
Methods and results
Patients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P < .001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 m, P = .013). A multivariable Cox proportional hazard model analysis revealed that the discontinuous pattern at follow-up (P < .001) and brain natriuretic peptide (P = .021) were significantly associated with the end points, independent of age, estimated glomerular filtration rate, and serum sodium level.
Conclusions
The IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:20-28
Yamamoto M, Seo Y, Iida N, Ishizu T, ... Ohte N, Ieda M
J Card Fail: 30 Dec 2020; 27:20-28 | PMID: 32652246
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

New measures of right ventricle-pulmonary artery coupling in heart failure: An all-cause mortality echocardiographic study.

Pestelli G, Fiorencis A, Trevisan F, Luisi GA, Smarrazzo V, Mele D
Aims
Right ventricle-pulmonary artery coupling (RVPAC) has emerged from pathophysiology to clinical interest for prognostic implication in heart failure and is commonly measured as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/SPAP). However, feasibility of SPAP is limited (down to 60% in trials, and maybe lower in clinical practice). We ought to assess the prognostic value of the TAPSE times pulmonary acceleration time product (TAPSE x pACT) and TAPSE to peak tricuspid regurgitation velocity (TAPSE/TRV) ratio as new alternative measures of RVPAC.
Methods and results
Two-hundred patients hospitalized with heart failure were followed-up (median time of 2.7 years) and 82 died. Non survivors had significantly lower TAPSE/SPAP, TAPSE x pACT and TAPSE/TRV than survivors (0.31 vs 0.40 mm/mmHg, 130 vs 156 cm·ms, 5.0 vs 5.8 ms, respectively). Four multivariate models were performed, each one including TAPSE, TAPSE/SPAP, TAPSE x pACT or TAPSE/TRV. TAPSE/SPAP resulted as the most powerful predictor of mortality (HR 0.74 per mm/mmHg increase, P < 0.001, C-Statistic 0.778), followed by TAPSE x pACT (HR 0.95 per 10 cm·ms increase, P = 0.013, C-Statistic 0.776), TAPSE/TRV (HR 0.76 per ms increase, P < 0.001, C-Statistic 0.774) and TAPSE (HR 0.91 per mm increase, P = 0.003, C-Statistic 0.769). Cutoffs of 140 cm·ms and 5.5 ms were respectively identified for TAPSE x pACT and TAPSE/TRV with receiving operating characteristic analysis for mortality.
Conclusion
TAPSE x pACT product and TAPSE/TRV ratio are valid alternative measures of RVPAC for prognostic assessment in heart failure that can be applied if TAPSE/SPAP is not feasible.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 21 Dec 2020; epub ahead of print
Pestelli G, Fiorencis A, Trevisan F, Luisi GA, Smarrazzo V, Mele D
Int J Cardiol: 21 Dec 2020; epub ahead of print | PMID: 33359279
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of a pharmacist-based multidimensional intervention aimed at decreasing the risk of hyperkalemia in heart failure patients: A Latin-American experience.

Gallo-Bernal S, Calixto CA, Molano-González N, Moreno MPD, ... Medina HM, Rodríguez MJ
Aims
Hyperkalemia is a potentially life-threatening condition associated with the use of heart failure (HF) medications, which can lead to increased morbidity and mortality. Novel approaches for hyperkalemia prevention are needed, especially in limited-resource settings. Despite multiple studies showing the beneficial impact of pharmaceutical-counseling in several outcomes, there is a knowledge-gap regarding its impact on hyperkalemia prevention.
Methods
A case-control study was performed in patients from the Adult Heart Failure Clinic Registry in our institution. Cases were selected using a definition of serum potassium K+ ≥5.5 mmol/L. To study the association between hyperkalemia and relevant risk factors, we performed a multivariate logistic regression analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) method for variable selection. We also fitted a Classification and Regression Tree (CART) to establish complex interactions and effect modifiers between the selected variables.
Results
We matched 483 controls (eligible HF patients without hyperkalemia) to 132 cases (eligible HF patients with hyperkalemia based on age and calendar, yielding a total sample size of 615 patients (270 females) for this study. Cases had statistically significant lower odds of receiving a pharmacist-based multidimensional intervention (PBMI) (OR 0.57; 95% CI, 0.43-0.80) or having HF with reduced ejection fraction (OR 0.56; 95% CI, 0.18-0.72). On the other hand, patients who presented hyperkalemia had statistically significant higher odds of having a history of chronic kidney disease stage 4 (OR 4.97; 95% CI, 2.24-11.01) or 5 (OR 6.73; 95% CI, 1.69-26.84) and being on enalapril at doses =40 mg/day (OR, 9.90; 95% CI 5.81-16.87).
Conclusions
PBMI is a practical approach to prevent hyperkalemia in HF patients in a limited-resource setting. However, clinical trials are needed to assess its effectiveness.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 03 Jan 2021; epub ahead of print
Gallo-Bernal S, Calixto CA, Molano-González N, Moreno MPD, ... Medina HM, Rodríguez MJ
Int J Cardiol: 03 Jan 2021; epub ahead of print | PMID: 33412183
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Circulating cardiovascular microRNAs in critically ill COVID-19 patients Short title: microRNA signatures in COVID-19.

Garg A, Seeliger B, Derda AA, Xiao K, ... Bär C, Thum T
Aims
Corona virus disease 2019 (COVID-19) is a still growing pandemic, causing many deaths and socio-economic damage. Elevated expression of the SARS-CoV-2 entry receptor ACE2 on cardiac cells of patients with heart diseases may be related to cardiovascular burden. We have thus analysed cardiovascular and inflammatory microRNAs (miRs), sensitive markers of cardiovascular damage, in critically ill, ventilated patients with COVID-19 or Influenza associated acute respiratory distress syndrome (Influenza-ARDS) admitted to intensive care unit (ICU) and healthy controls.
Methods and results
Circulating miRs (miR-21, miR-126, miR-155, miR-208a and miR-499) were analyzed in a discovery cohort consisting of patients with mechanically-ventilated COVID-19 (n = 18) and healthy controls (n = 15). A validation study was performed in an independent cohort of mechanically-ventilated COVID-19 patients (n = 20), Influenza-ARDS patients (n = 13) and healthy controls (n = 32). In both cohorts RNA was isolated from serum and cardiovascular disease/inflammatory-relevant miR concentrations were measured by miR-specific TaqMan PCR analyses. In both the discovery and the validation cohort, serum concentration of miR-21, miR-155, miR-208a and miR-499 were significantly increased in COVID-19 patients compared to healthy controls. Calculating the area under the curve (AUC) using ROC-analysis miR-155, miR-208a and miR-499 showed a clear distinction between COVID-19 and Influenza-ARDS patients.
Conclusion
In this exploratory study, inflammation and cardiac myocyte-specific miRs were upregulated in critically ill COVID-19 patients. Importantly, miR profiles were able to differentiate between severely ill, mechanically-ventilated Influenza-ARDS and COVID-19 patients, indicating a rather specific response and cardiac involvement of COVID-19.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Jan 2021; epub ahead of print
Garg A, Seeliger B, Derda AA, Xiao K, ... Bär C, Thum T
Eur J Heart Fail: 08 Jan 2021; epub ahead of print | PMID: 33421274
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac Myosin-Binding Protein C in the Diagnosis and Risk Stratification of Acute Heart Failure.

Kozhuharov N, Wussler D, Kaier T, Strebel I, ... Marber M,
Aims
Cardiac myosin-binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury versus high-sensitivity cardiac troponin (hs-cTn), and may therefore have diagnostic and prognostic utility.
Methods and results
In a prospective multicentre diagnostic study, cMyC, hs-cTnT, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver-operating characteristics curve (AUC). All-cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients versus patients with other final diagnoses (72 (IQR 39-156) versus 22 ng/L (IQR 12-42), p < 0.001)). cMyC\'s AUC was high (0.81, 95%CI 0.78-0.83), higher than hs-cTnT\'s (0.79, 95%CI 0.76-0.82, p = 0.081) and lower than NT-proBNP\'s (0.91, 95%CI 0.89-0.93, p < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95%CI 1.66-2.89; p < 0.001). cMyC\'s prognostic accuracy was comparable with NT-proBNP\'s and hs-cTnT\'s. cMyC did not independently predict all-cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge.
Conclusion
cMyC may aid physicians in the rapid triage of patients with suspected AHF.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Jan 2021; epub ahead of print
Kozhuharov N, Wussler D, Kaier T, Strebel I, ... Marber M,
Eur J Heart Fail: 08 Jan 2021; epub ahead of print | PMID: 33421273
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Peripheral and Pulmonary Effects of Inorganic-Nitrite during Exercise in Heart Failure with Preserved Ejection Fraction.

Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA
Aims
To determine whether inorganic nitrite improves peripheral and pulmonary O transport during exercise in heart failure with preserved ejection fraction(HFpEF).
Methods and results
Data from two invasive, randomized, double-blind, placebo-controlled trials with matched workload exercise of inhaled and intravenous sodium nitrite were pooled for this analysis(n=51). Directly measured O consumption(VO ), and blood gas data were used to evaluate the effect of nitrite on skeletal muscle O conductance(Dm), VO kinetics, alveolar capillary membrane O conductance(D ), and O utilization during submaximal exercise. As compared to placebo, treatment with nitrite resulted in an improvement in Dm (+4.9±6.5 vs -0.9±4.3 ml/mmHg*min, p=0.0008) as well as VO kinetics measured by mean response time (-5.0±6.9 vs -0.6±6.0 sec, p=0.03), with preserved O utilization despite increased convective O delivery through cardiac output (+0.4±0.7 vs -0.3±0.9 L/min, p=0.02). Nitrite improved D (+2.5 ± 6.3 vs -2.0 ± 9.0 ml/mmHg*min, p=0.05) with exercise, which was associated with lower pulmonary capillary pressures (r=-0.34, p=0.02), and reduced pulmonary dead space ventilation fraction (-0.01 ± 0.05 vs +0.02 ± 0.05, p=0.02).
Conclusion
Sodium nitrite enhances skeletal muscle O conductance during exercise as well as pulmonary O diffusion, optimizing O kinetics in tandem with increased convective O delivery through cardiac output augmentation. The favorable combined pulmonary, cardiac and peripheral effects of nitrite may improve exercise tolerance in people with HFpEF and requires further investigation.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Jan 2021; epub ahead of print
Reddy YNV, Stewart GM, Obokata M, Koepp KE, Borlaug BA
Eur J Heart Fail: 08 Jan 2021; epub ahead of print | PMID: 33421267
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Oral Sucrosomial iron improves exercise capacity and quality of life in heart failure with reduced ejection fraction and iron deficiency: A non-randomized, open-label, proof-of-concept study.

Karavidas A, Troganis E, Lazaros G, Balta D, ... Parissis J, Farmakis D
Background
Oral sucrosomial iron (SI) combines enhanced bioavailability and tolerance compared to conventional oral iron along with similar efficacy compared to intravenous iron in several conditions associated with iron deficiency (ID).
Methods and results
In this non-randomized, open-label study, we sought to evaluate prospectively the effects of SI on clinical parameters, exercise capacity and quality of life in 25 heart failure patients with reduced ejection fraction (HFrEF) and ID, treated with SI 28 mg daily for 3 months, in comparison to 25 matched HFrEF controls. All patients were on optimal stable HF therapy. Patients were followed for 6 months for death or worsening HF episodes. There were no differences in baseline characteristics between groups. At 3 months, SI was associated with significant increase in haemoglobin, serum iron and serum ferritin levels (all p ≤ 0.001) along with a significant improvement in 6-min walked distance (6MWD) and Kansas City Cardiomyopathy Questionnaire (all p < 0.01), even after adjustment for baseline parameters; these differences persisted at 6 months. Over the study period, there were no deaths, while 10 patients (20%) in total (4 in SI group and 6 in control group), experienced worsening HF (OR = 0.51, 95%CI, 0.41-6.79, p = 0.482). Drug-associated diarrhoea was reported by one patient in SI group and led to drug discontinuation; no other adverse events were reported.
Conclusions
In this proof-of-concept study, SI was well tolerated and improved exercise capacity and quality of life in HFrEF patients with ID. Randomized studies are required to further investigate the effects of this therapy.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Jan 2021; epub ahead of print
Karavidas A, Troganis E, Lazaros G, Balta D, ... Parissis J, Farmakis D
Eur J Heart Fail: 08 Jan 2021; epub ahead of print | PMID: 33421230
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex Differences in the Phenotype of Transthyretin Cardiac Amyloidosis Due to Val122Ile Mutation: Insights from Noninvasive Pressure-Volume Analysis.

Batra J, Rosenblum H, Defilippis EM, Griffin JM, ... Burkhoff D, Maurer MS
Background
Transthyretin cardiac amyloidosis (ATTR-CA) is an under-recognized cause of heart failure with preserved ejection fraction. In the United States, the valine-to-isoleucine substitution (Val122Ile) is the most common inherited variant. Data on sex differences in presentation and outcomes of Val122Ile associated ATTR-CA are lacking.
Methods and results
In a retrospective, single-center study of 73 patients diagnosed with Val122Ile associated ATTR-CA between 2001 and 2018, sex differences in clinical and echocardiographic data at the time of diagnosis were evaluated. Pressure-volume analysis using noninvasive single beat techniques was used to compare chamber performance. Compared with men (n = 46), women (n = 27) were significantly older at diagnosis, 76 years vs 69 years; P < .001. The end-systolic pressure-volume relationship, 5.1 mm Hg*m/mL vs 4.3 mm Hg*m/mL; P = .27, arterial elastance, 5.5 mm Hg*m/mL vs 5.7 mm Hg*m/mL; P = .62, and left ventricular capacitance were similar between sexes as was pressure-volume areas indexed to a left ventricular end-diastolic pressure of 30 mm Hg, a measure of overall pump function. The 3-year mortality rates were also similar, 34% vs 43%; P = .64.
Conclusions
Despite being significantly older at time of diagnosis with Val122Ile associated ATTR-CA, women have similar overall cardiac chamber function and rates of mortality to men, suggesting a less aggressive disease trajectory. These findings should be confirmed with longitudinal studies.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:67-74
Batra J, Rosenblum H, Defilippis EM, Griffin JM, ... Burkhoff D, Maurer MS
J Card Fail: 30 Dec 2020; 27:67-74 | PMID: 32829019
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical significance of reactive oxidative metabolites in patients with heart failure with reduced left ventricular ejection fraction.

Nishihara T, Tokitsu T, Sueta D, Oike F, ... Yamamoto E, Tsujita K
Background
We investigated the clinical significance of the derivative of reactive oxygen metabolites (DROM), a new marker of reactive oxygen species (ROS), in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF).
Methods and results
Serum DROM concentrations were measured in 201 consecutive patients with HFrEF (EF < 50%) in stable condition. DROM values were significantly higher in patients with HFrEF than in risk-matched patients without HF (P < 0.01). They also correlated significantly with high-sensitivity C-reactive protein and B-type natriuretic peptide. Kaplan-Meier analysis demonstrated significantly higher probabilities of HF-related events in the high-DROM group than in the low-DROM group (log-rank test, P < 0.01). Multivariable Cox hazard analysis revealed that DROM were independent and significant predictors of cardiovascular events. In a subgroup analysis, DROM levels were also measured at the aortic root and coronary sinus in 49 patients. The transcardiac gradient of DROM values was significantly higher in patients with HFrEF than in patients without HF (P = 0.04), indicating an association between DROM production in the coronary circulation and HFrEF development. Changes in DROM following optimal therapy were significantly associated with LVEF improvement (r = 0.34, P = 0.04).
Conclusions
The higher levels of DROM and their association with cardiovascular events suggest the clinical benefit of DROM measurements in the risk stratification of patients with HFrEF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:57-66
Nishihara T, Tokitsu T, Sueta D, Oike F, ... Yamamoto E, Tsujita K
J Card Fail: 30 Dec 2020; 27:57-66 | PMID: 32791184
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cystatin C and Muscle Mass in Patients With Heart Failure.

Ivey-Miranda JB, Inker LA, Griffin M, Rao V, ... Levey AS, Testani JM
Background
The estimated glomerular filtration rate (eGFR) from cystatin C (eGFRcys) is often considered a more accurate method to assess GFR compared with an eGFR from creatinine (eGFRcr) in the setting of heart failure (HF) and sarcopenia, because cystatin C is hypothesized to be less affected by muscle mass than creatinine. We evaluated (1) the association of muscle mass with cystatin C, (2) the accuracy of eGFRcys, and (3) the association of eGFRcys with mortality given muscle mass.
Methods and results
We included 293 patients admitted with HF. Muscle mass was estimated with a validated creatinine excretion-based equation. Accuracy of eGFRcys and eGFRcr was compared with measured creatinine clearance. Cystatin C and creatinine were 31.7% and 59.9% higher per 14 kg higher muscle mass at multivariable analysis (both P < .001). At lower muscle mass, eGFRcys and eGFRcr overestimated the measured creatinine clearance. At higher muscle mass, eGFRcys underestimated the measured creatinine clearance, but eGFRcr did not. After adjusting for muscle mass, neither eGFRcys nor eGFRcr were associated with mortality (both P > .19).
Conclusions
Cystatin C levels were associated with muscle mass in patients with HF, which could potentially decrease the accuracy of eGFRcys. In HF where aberrations in body composition are common, eGFRcys, like eGFRcr, may not provide accurate GFR estimations and results should be interpreted cautiously.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:48-56
Ivey-Miranda JB, Inker LA, Griffin M, Rao V, ... Levey AS, Testani JM
J Card Fail: 30 Dec 2020; 27:48-56 | PMID: 32750487
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Possible Association Between Body Temperature and B-Type Natriuretic Peptide in Patients With Cardiovascular Diseases.

Kang R, Nagoshi T, Kimura H, Tanaka TD, ... Kawai M, Yoshimura M
Background
In addition to various biological effects of natriuretic peptides (NP) on cardiovascular systems, we recently reported that NP raises intracellular temperature in cultured adipocytes. We herein examined the possible thermogenic action of NP in consideration of hemodynamic parameters and inflammatory reaction by proposing structural equation models.
Methods and results
The study population consisted of 1985 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of plasma B-type NP (BNP) to body temperature (BT) by excluding other confounding factors. A hierarchical path model showed increase in BNP, increase in C-reactive protein and decrease in left ventricular ejection fraction were mutually associated. As expected, C-reactive protein was positively correlated with BT. Importantly, despite a negative correlation between BNP and left ventricular ejection fraction, a decrease in the left ventricular ejection fraction was associated with BT decrease, whereas elevation in BNP level was associated with BT increase independently of C-reactive protein level (P = .007).
Conclusions
Patients with LV dysfunction tend to manifest a decrease in BT, whereas BNP elevation is associated with an increase in BT independently of inflammatory response. These findings suggest the adaptive heat-retaining property of NP (and/or NP-associated factors) when BT falls owing to unfavorable hemodynamic conditions in a state of impaired cardiac function.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:75-82
Kang R, Nagoshi T, Kimura H, Tanaka TD, ... Kawai M, Yoshimura M
J Card Fail: 30 Dec 2020; 27:75-82 | PMID: 32871239
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Differential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes.

Ivey-Miranda JB, Kunnirickal S, Bow L, Maulion C, ... Kransdorf EP, Bellumkonda L
Background
Sensitized patients awaiting heart transplantation spend a longer time on the waitlist and have higher mortality. We are now able to further characterize sensitization by discriminating antibodies against class I and II, but the differential impact of these has not been assessed systematically.
Methods and results
Using United Network for Organ Sharing data (2004-2015), we analyzed 17,361 adult heart transplant patients whose class I and II panel reactive antibodies were reported. Patients were divided into 4 groups: class I and II ≤25% (group 1); class I ≤25% and class II ˃25% (group 2); class II ≤25% and class I >25% (group 3); and both class I and II >25% (group 4). Outcomes assessed were treated rejection at 1-year mortality, all-cause mortality, and rejection-related mortality. Compared with group 1, only group 4 was associated with a higher risk of treated rejection at 1 year (odds ratio 1.31, 95% confidence interval [CI] 1.05-1.64), all-cause mortality (hazard ratio 1.24, 95% CI 1.06-1.46), and mortality owing to rejection (subhazard ratio 1.84, 95% CI 1.18-2.85), whereas groups 2 and 3 were not (P > .05).
Conclusions
Combined elevation in class I and II panel reactive antibodies seem to increase the risk of treated rejection and all-cause mortality, whereas risk with isolated elevation is unclear.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Dec 2020; 27:40-47
Ivey-Miranda JB, Kunnirickal S, Bow L, Maulion C, ... Kransdorf EP, Bellumkonda L
J Card Fail: 30 Dec 2020; 27:40-47 | PMID: 32750489
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Biomarkers and their relation to cardiac function late after peripartum cardiomyopathy.

Ersbøll AS, Goetze JP, Johansen M, Hauge MG, ... Gustafsson F, Damm P
Background
Angiogenic imbalance involving the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) and cleavage of the nursing-hormone prolactin by the enzyme cathepsin D (CD) both play a role in the pathogenesis of peripartum cardiomyopathy (PPCM). We hypothesized that angiogenic imbalance and increased activity of CD have a long-lasting impact in women with PPCM.
Methods and results
A nationwide Danish cohort of women with PPCM (PPCM-group, N=28), age-matched women with previous preeclampsia (PE-group, N=28) and uncomplicated pregnancies (UCP-group, N=28) participated in a follow-up study including biomarker analysis, exercise testing and cardiac magnetic resonance imaging (CMR). Eighty-four women participated. Median time to follow-up was 91 months (range 27-137) for the PPCM-group. Levels of sFlt-1, placental growth factor, N-terminal pro-natriuretic brain peptide and copeptin were all significantly higher in the PPCM-group. More women in the PPCM-group had detectable CD activity (68%) compared with the PE-group (29%) and UCP-group (36%) (p=0.0002). Levels of angiogenic factors and biomarkers correlated inversely with maximal exercise capacity and cardiac functional parameters assessed with CMR.
Conclusions
Women with PPCM had higher biomarker levels and CD activity up to seven years after diagnosis. Higher biomarker levels correlated inversely with maximal exercise capacity and markers of cardiac dysfunction suggesting that persistent angiogenic imbalance and increased CD activity is associated with residual cardiac dysfunction.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Jan 2021; epub ahead of print
Ersbøll AS, Goetze JP, Johansen M, Hauge MG, ... Gustafsson F, Damm P
J Card Fail: 06 Jan 2021; epub ahead of print | PMID: 33422687
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.

Schuldt M, Pei J, Harakalova M, Dorsch LM, ... van der Velden J, Kuster DWD
Background
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM). Genotype-specific differences have been reported in cardiac function. Moreover, HCM patients have later disease onset and a better prognosis than HCM patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.
Methods
A proteomics screen was performed in cardiac tissue from 39 HCM patients, 11HCM patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novelmouse model was used to confirm functional relevance of our proteomic findings.
Results
In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCM than in HCM and controls. Higher tubulin detyrosination was also found in 2 unrelatedmouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.
Conclusions
Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM, whereas a beneficial effect may be limited in patients with HCM.



Circ Heart Fail: 11 Jan 2021:CIRCHEARTFAILURE120007022; epub ahead of print
Schuldt M, Pei J, Harakalova M, Dorsch LM, ... van der Velden J, Kuster DWD
Circ Heart Fail: 11 Jan 2021:CIRCHEARTFAILURE120007022; epub ahead of print | PMID: 33430602
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Relationship between Body-Mass Index, Cardiovascular Biomarkers and Incident Heart Failure.

Suthahar N, Meems LMG, Groothof D, Bakker SJL, ... van Veldhuisen DJ, de Boer RA
Background
There are limited data examining whether body-mass index (BMI) influences the association between cardiovascular biomarkers and incident heart failure (HF).
Methods and results
Thirteen biomarkers representing key HF domains were measured: N-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-A-type natriuretic peptide (MR-proANP), cardiac troponin-T (cTnT), C-reactive protein, procalcitonin, galectin-3, C-terminal pro-endothelin-1 (CT-pro-ET-1), mid-regional pro-adrenomedullin, plasminogen activator inhibitor-1, copeptin, renin, aldosterone and cystatin-C. Associations of biomarkers with BMI were examined using linear regression models, and with incident HF using Cox regression models. We selected biomarkers significantly associated with incident HF, and evaluated whether BMI modified these associations.
Results
Among 8202 individuals, 41% were overweight (BMI 25-30kg/m ), and 16% were obese (BMI≥30kg/m ). Mean age of the cohort was 49 years (range 28-75), and 50% were women. All biomarkers except renin were associated with BMI: inverse associations were observed with NT-proBNP, MR-proANP, CT-pro-ET-1 and aldosterone whereas positive associations were observed with the remaining biomarkers (P ≤0.001). During 11.3±3.1 years follow-up, 357 HF events were recorded. Only NT-proBNP, MR-proANP and cTnT remained associated with incident HF (P<0.001), and a significant biomarker*BMI interaction was not observed (P >0.1). Combined NT-proBNP and cTnT measurements modestly improved performance metrics of the clinical HF model in overweight (ΔC-statistic=0.024; LHRχ =38; P<0.001) and in obese (ΔC-statistic=0.020; LHRχ =32; P<0.001) individuals.
Conclusions
Plasma concentrations of several cardiovascular biomarkers are influenced by obesity. Only NT-proBNP, MR-proANP and cTnT were associated with incident HF, and BMI did not modify these associations. A combination of NT-proBNP and cTnT improves HF risk prediction in overweight and in obese individuals. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 13 Jan 2021; epub ahead of print
Suthahar N, Meems LMG, Groothof D, Bakker SJL, ... van Veldhuisen DJ, de Boer RA
Eur J Heart Fail: 13 Jan 2021; epub ahead of print | PMID: 33443299
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Temporal trends in mortality and readmission after acute heart failure: A systematic review and meta-regression in the past four decades.

Kimmoun A, Takagi K, Gall E, Ishihara S, ... Javanainen T, Bastian K
Aims
Acute heart failure (AHF) is frequent and life-threatening disease. However, innovative AHF therapies have remained limited, and care is based on experts opinion. Temporal trends and benefits of long-term oral cardiovascular medications on AHF outcomes remain uncertain.
Methods and results
This study is registered with PROSPERO (CRD42018099885). A systematic review ranging from 1980 to 2017, searched AHF studies with more than 100 patients that reported death and/or readmission. Primary outcomes were temporal trends, assessed by meta-regression, for 30-day or one-year all-cause death and/or readmission rates. Secondary outcomes were temporal trends of oral cardiovascular therapies and their influence on primary outcomes. Among the 45143 studies screened, 285 were included, representing 15 million AHFs. In the past decades, though mortality and readmission remain high, there was a decline in 30-day all-cause death (OR for a 10-year increment: 0.74 (0.61-0.91); p=0.004) that persisted at one year (OR 0.86 (0.77- 0.96); p=0.007), while 30-day and one-year all-cause readmission rate remained roughly unchanged. Trends of primary outcomes were linear and did not differ among continents. Decline in one-year all-cause death rate correlated with high proportions of oral or beta-blockers, especially when combined with oral renin-angiotensin-aldosterone system inhibitors, but not with diuretics while trends in readmission remained unchanged with these therapies.
Conclusions
Though AHF outcomes remain poor, the present study revealed global favorable trends of survival after AHF episodes probably associated with greater use of oral neurohormonal antagonists. The present study urges to implement the combination of oral renin-angiotensin-aldosterone system inhibitors and beta-blockers in patients at risk of AHF. This article is protected by copyright. All rights reserved.

© 2021 European Society of Cardiology.

Eur J Heart Fail: 13 Jan 2021; epub ahead of print
Kimmoun A, Takagi K, Gall E, Ishihara S, ... Javanainen T, Bastian K
Eur J Heart Fail: 13 Jan 2021; epub ahead of print | PMID: 33443295
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Catabolic/anabolic imbalance is accompanied by changes of LV steroid nuclear receptor expression in tachycardia-induced systolic heart failure in male pigsSteroid hormones in pig model of heart failure.

Zacharski M, Tomaszek A, Kiczak L, Ugorski M, ... Janiszewski A, Ponikowski P
Background
Steroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data has revealed disordered steroidogenesis in male HF patients. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.
Methods and results
Male pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate and severe HF. Serum concentrations of dehydroepiandrosterone (DHEA), testosterone, dihydrotestosterone, estradiol, aldosterone and cortisol were assessed by ELISA. Androgen (AR), estrogen α (ERα), mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNAs levels in the left ventricle (LV) were determined by qPCR. The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The qPCR revealed the down-regulation of AR in consecutive stages of HF and increased expression of MR mRNA under these conditions.
Conclusions
In the HF pig model deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and down-regulation of androgen signaling on the ligand level was augmented by changes in steroid hormone receptor expression in the heart tissue.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 11 Jan 2021; epub ahead of print
Zacharski M, Tomaszek A, Kiczak L, Ugorski M, ... Janiszewski A, Ponikowski P
J Card Fail: 11 Jan 2021; epub ahead of print | PMID: 33450412
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Radio-contrast medium exposure and dialysis risk in patients with chronic kidney disease and congestive heart failure: A case-only study.

Wu MY, Chen TT, Wu MS, Tu YK
Background
Dialysis for end stage renal disease is considered a major public health challenge. Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization.
Method
This case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure.
Results
In total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1 week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval: 3.99-5.05). The ORs for acute-temporary (N = 23,418) and chronic dialysis (N = 13,291) were 5.57 (4.83-6.42) and 2.37 (1.90-2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N = 12,030) were 3.25 (2.53-4.19) and 4.85 (4.24-5.54) in early CKD patients (N = 24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57-5.48).
Conclusions
In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.

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

Int J Cardiol: 31 Jan 2021; 324:199-204
Wu MY, Chen TT, Wu MS, Tu YK
Int J Cardiol: 31 Jan 2021; 324:199-204 | PMID: 32926946
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diagnostic utility of right atrial reservoir strain to identify elevated right atrial pressure in heart failure.

Miah N, Faxén UL, Lund LH, Venkateshvaran A
Background
Accurate non-invasive estimation of right atrial pressure (RAP) is essential to assess volume status and optimize therapy in heart failure (HF). This study aimed to evaluate the utility of right atrial reservoir strain (RASr) assessed by speckle-tracking echocardiography to identify elevated RAP in HF and compare diagnostic performance with estimated RAP employing inferior vena cava size and collapsibility (RAP), in addition to RA area.
Method
Association between RASr and invasive RAP (RAP) was examined in 103 HF subjects that underwent standard echocardiography with speckle-tracking strain analysis directly followed by right heart catheterization. The discriminatory ability of RASr to identify RAP > 7 mmHg was evaluated and compared with RAP and RA area.
Results
RASr demonstrated association with RAP (β = -0.41, p < 0.001) and was an independent predictor when adjusted for potential confounders (β = -0.25, p < 0.001). Further, RASr showcased strong discriminatory ability to identify subjects with RAP > 7 mmHg (AUC = 0.78; 95% CI 0.68-0.87; p < 0.001). At a cut-off value of -15%, RASr displayed 78% sensitivity and 72% specificity to identify elevated RAP In comparison, RAP (AUC = 0.71; 95% CI 0.61-0.81; p < 0.001) demonstrated 89% sensitivity and 32% specificity with high false positive rate. RA area (AUC = 0.66; 95% CI 0.55-0.76, p = 0.005) displayed 64% sensitivity and 53% specificity.
Conclusions
RASr demonstrates good ability to identify elevated RAP and relatively stronger diagnostic performance when compared with conventional non-invasive measures. RASr may be useful as a novel noninvasive estimate of RAP in HF management.

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

Int J Cardiol: 31 Jan 2021; 324:227-232
Miah N, Faxén UL, Lund LH, Venkateshvaran A
Int J Cardiol: 31 Jan 2021; 324:227-232 | PMID: 32941871
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical impact of red blood cell transfusion on adverse clinical events in acute heart failure patients with anemia.

Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Background
Anemia has been recognized as an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear.
Method
This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2007 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated.
Results
Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (26%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality.
Conclusions
RBC transfusion was not associated with AHF readmission or all-cause mortality.

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

Int J Cardiol: 31 Jan 2021; 324:102-107
Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Int J Cardiol: 31 Jan 2021; 324:102-107 | PMID: 32946954
Go to: DOI | PubMed | PDF | Google Scholar |
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, Dimopoulos 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 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Jan 2021; 324:66-71
Surkova E, Segura T, Dimopoulos K, Bispo D, ... Gatzoulis MA, Li W
Int J Cardiol: 31 Jan 2021; 324:66-71 | PMID: 32987051
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Jan 2021; 324:90-95
Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Int J Cardiol: 31 Jan 2021; 324:90-95 | PMID: 33007325
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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 25.1years, 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: 31 Jan 2021; 324:115-121
Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Int J Cardiol: 31 Jan 2021; 324:115-121 | PMID: 33017630
Go to: DOI | PubMed | PDF | Google Scholar |
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 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Jan 2021; 324:205-213
Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Int J Cardiol: 31 Jan 2021; 324:205-213 | PMID: 33022289
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction.

Houard L, Amzulescu MS, Colin G, Langet H, ... Pouleur AC, Gerber BL


Background:
Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Methods We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, <0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; <0.001) but also the secondary composite endpoints (χ to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; <0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints.
Conclusions:
Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.



Circ Cardiovasc Imaging: 12 Jan 2021:CIRCIMAGING120011680; epub ahead of print
Houard L, Amzulescu MS, Colin G, Langet H, ... Pouleur AC, Gerber BL
Circ Cardiovasc Imaging: 12 Jan 2021:CIRCIMAGING120011680; epub ahead of print | PMID: 33438438
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic significance of cardiac I-123-metaiodobenzylguanidine imaging in patients with reduced, mid-range, and preserved left ventricular ejection fraction admitted for acute decompensated heart failure: a prospective study in Osaka Prefectural Acute Heart Failure Registry (OPAR).

Seo M, Yamada T, Tamaki S, Watanabe T, ... Sakata Y, Fukunami M
Aims
Cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging provides prognostic information in patients with chronic heart failure (HF). However, there is little information available on the prognostic role of cardiac 123I-MIBG imaging in patients admitted for acute decompensated heart failure (ADHF), especially relating to reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) < 40%], mid-range ejection fraction (HFmrEF; 40% ≤ LVEF < 50%) and preserved ejection fraction (HFpEF; LVEF ≥ 50%).
Methods and results
We studied 349 patients admitted for ADHF and discharged with survival. Cardiac 123I-MIBG imaging, echocardiography, and venous blood sampling were performed just before discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (late H/M) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The endpoint was cardiac events defined as unplanned HF hospitalization and cardiac death. During a follow-up period of 2.1 ± 1.4 years, 128 patients had cardiac events (45/127 in HFrEF, 28/78 in HFmrEF, and 55/144 in HFpEF). On multivariable Cox analysis, late H/M was significantly associated with cardiac events in overall cohort (P = 0.0038), and in subgroup analysis of each LVEF subgroup (P = 0.0235 in HFrEF, P = 0.0119 in HFmEF and P = 0.0311 in HFpEF). Kaplan-Meier analysis showed that patients with low late H/M (defined by median) had significantly greater risk of cardiac events in overall cohort (49% vs. 25% P < 0.0001) and in each LVEF subgroup (HFrEF: 48% vs. 23% P = 0.0061, HFmrEF: 51% vs. 21% P = 0.0068 and HFpEF: 50% vs. 26% P = 0.0026).
Conclusion
Cardiac sympathetic nerve dysfunction was associated with poor outcome in ADHF patients irrespective of HFrEF, HFmrEF, or HFpEF.

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

Eur Heart J Cardiovasc Imaging: 31 Dec 2020; 22:58-66
Seo M, Yamada T, Tamaki S, Watanabe T, ... Sakata Y, Fukunami M
Eur Heart J Cardiovasc Imaging: 31 Dec 2020; 22:58-66 | PMID: 32091079
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The relation of structural valve deterioration to adverse remodelling and outcome in patients with biological heart valve prostheses.

Issa IF, Dahl JS, Poulsen SH, Waziri F, ... Søgaard P, Møller JE
Aims
Native valve aortic stenosis is associated with adverse remodelling of the left ventricle and remodelling is stopped or even reversed with aortic valve replacement (AVR). However, the degeneration of bioprostheses and development of structural valve deterioration (SVD) may affect this.
Methods and results
To assess the association with SVD, remodelling and outcome 451 patients from a single surgical centre who had undergone AVR with a Mitroflow pericardial bioprosthesis were studied. All patients were assessed in 2014 and a subgroup of patients (N = 327) were re-exanimated again after at least 18 months [median time of 27 (interquartile range, IQR 26-33) months] including echocardiography, measurements of N-terminal pro-brain natriuretic peptide, and assessment of functional status. SVD was based on echocardiography. Moderate SVD was present in 63 patients (14%) and severe SVD in 19 (4%), in the subgroup with follow-up echocardiography 48 patients (15%) patients had moderate to severe SVD at first examination. Patients with SVD had significantly greater increase in left ventricular (LV) mass index [21.6 g/m2 (IQR 5.7-48.3 g/m2) vs. 9.1 g/m2 (-8.6 to 27.3 g/m2), P = 0.01]. Further, patients with SVD had lower LV ejection fraction [55% (IQR 51-62%) vs. 60% (IQR 54-63%), P = 0.01] at follow-up. During follow-up, 94 patients (21%) met the composite endpoint of death or reoperation due to SVD and 41 patient readmitted for heart failure. In multivariable Cox regression analysis, severe SVD [hazard ratio (HR) 2.64 (1.37-5.07), P = 0.004] was associated with composite endpoint, and readmission for heart failure [HR 3.82 (1.53-9.51), P = 0.004].
Conclusion
SVD in aortic bioprostheses is associated with adverse LV remodelling and adverse outcome.

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

Eur Heart J Cardiovasc Imaging: 31 Dec 2020; 22:82-91
Issa IF, Dahl JS, Poulsen SH, Waziri F, ... Søgaard P, Møller JE
Eur Heart J Cardiovasc Imaging: 31 Dec 2020; 22:82-91 | PMID: 31942609
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions.

Genovesi D, Vergaro G, Giorgetti A, Marzullo P, ... Volpi E, Emdin M
Objectives
This study aimed to test the diagnostic value of [18F]-florbetaben positron emission tomography (PET) in patients with suspicion of CA.
Background
Diagnosis of cardiac involvement in immunoglobulin light-chain-derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy.
Methods
Forty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection.
Results
Visual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUV) in patients with AL, sustained over the whole acquisition period (early SUV: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUV: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUV: 2.55; IQR: 1.80 to 2.97; vs. delayed SUV: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUV: 3.50; IQR: 1.60 to 3.37; vs. delayed SUV: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume.
Conclusions
Delayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Dec 2020; 14:246-255
Genovesi D, Vergaro G, Giorgetti A, Marzullo P, ... Volpi E, Emdin M
JACC Cardiovasc Imaging: 30 Dec 2020; 14:246-255 | PMID: 32771577
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prediction of AF in Heart Failure With Preserved Ejection Fraction: Incremental Value of Left Atrial Strain.

Jasic-Szpak E, Marwick TH, Donal E, Przewlocka-Kosmala M, ... Ponikowski P, Kosmala W
Objectives
This study sought to identify the factors associated with incident atrial fibrillation (AF) in a well-characterized heart failure with preserved ejection fraction (HFpEF) population, with special focus on left atrial (LA) strain.
Background
AF is associated with HFpEF, with adverse consequences. Effective risk evaluation might allow the initiation of protective strategies.
Methods
Clinical evaluation and echocardiography, including measurements of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA volume index (LAVI), were obtained in 170 patients with symptomatic HFpEF (mean age, 65 ± 8 years), free of baseline AF. AF was identified by standard 12-lead electrocardiogram, review of relevant medical records (including Holter documentation), and surveillance with a portable single-lead electrocardiogram device over 2 weeks. Results were validated in the 103 patients with HFpEF from the Karolinska-Rennes (KaRen) study.
Results
Over a median follow-up of 49 months, incident AF was identified in 39 patients (23%). Patients who developed AF were older; had higher clinical risk scores, brain natriuretic peptide, creatinine, LAVI, and LV mass; lower LA strain and exercise capacity; and more impaired LV diastolic function. PACS, PALS, and LAVI were the most predictive parameters for AF (area under receiver-operating characteristic curve: 0.76 for PACS, 0.71 for PALS, and 0.72 for LAVI). Nested Cox regression models showed that the predictive value of PACS and PALS was independent from and incremental to clinical data, LAVI, and E/e\' ratio. Classification and regression trees analysis identified PACS ≤12.7%, PALS ≤29.4%, and LAVI >34.3 ml/m as discriminatory nodes for AF, with a 33-fold greater hazard of AF (p < 0.001) in patients categorized as high risk. The classification and regression trees algorithm discriminated high and low AF risk in the validation cohort.
Conclusions
PACS and PALS provide incremental predictive information about incident AF in HFpEF. The inclusion of these LA strain components to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Imaging: 30 Dec 2020; 14:131-144
Jasic-Szpak E, Marwick TH, Donal E, Przewlocka-Kosmala M, ... Ponikowski P, Kosmala W
JACC Cardiovasc Imaging: 30 Dec 2020; 14:131-144 | PMID: 33413883
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Statin Exposure and Risk of Heart Failure After Anthracycline- or Trastuzumab-Based Chemotherapy for Early Breast Cancer: A Propensity Score‒Matched Cohort Study.

Abdel-Qadir H, Bobrowski D, Zhou L, Austin PC, ... Lee DS, Thavendiranathan P


Background:
Statins are hypothesized to reduce the risk of cardiotoxicity associated with anthracyclines and trastuzumab. Our aim was to study the association of statin exposure with hospitalization or emergency department visits (hospital presentations) for heart failure (HF) after anthracycline- and/or trastuzumab-containing chemotherapy for early breast cancer. Methods and Results Using linked administrative databases, we conducted a retrospective cohort study of women aged ≥66 years without prior HF who received anthracyclines or trastuzumab for newly diagnosed early breast cancer in Ontario between 2007 to 2017. Statin-exposed and unexposed women were matched 1:1 using propensity scores. Trastuzumab-treated women were also matched on anthracycline exposure. We matched 666 statin-discordant pairs of anthracycline-treated women and 390 pairs of trastuzumab-treated women (median age, 69 and 71 years, respectively). The 5-year cumulative incidence of HF hospital presentations after anthracyclines was 1.2% (95% CI, 0.5%-2.6%) in statin-exposed women and 2.9% (95% CI, 1.7%-4.6%) in unexposed women ( value, 0.01). The cause-specific hazard ratio associated with statins in the anthracycline cohort was 0.45 (95% CI, 0.24-0.85;value, 0.01). After trastuzumab, the 5-year cumulative incidence of HF hospital presentations was 2.7% (95% CI, 1.2%-5.2%) in statin-exposed women and 3.7% (95% CI, 2.0%-6.2%) in unexposed women ( value 0.09). The cause-specific hazard ratio associated with statins in the trastuzumab cohort was 0.46 (95% CI, 0.20-1.07;value, 0.07).
Conclusions:
Statin-exposed women had a lower risk of HF hospital presentations after early breast cancer chemotherapy involving anthracyclines, with non-significant trends towards lower risk following trastuzumab. These findings support the development of randomized controlled trials of statins for prevention of cardiotoxicity.



J Am Heart Assoc: 05 Jan 2021:e018393; epub ahead of print
Abdel-Qadir H, Bobrowski D, Zhou L, Austin PC, ... Lee DS, Thavendiranathan P
J Am Heart Assoc: 05 Jan 2021:e018393; epub ahead of print | PMID: 33401953
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ex situ heart perfusion: The past, the present, and the future.

Wang L, MacGowan GA, Ali S, Dark JH

Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening. Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability. This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:69-86
Wang L, MacGowan GA, Ali S, Dark JH
J Heart Lung Transplant: 30 Dec 2020; 40:69-86 | PMID: 33162304
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ventilation parameters and early graft function in double lung transplantation.

Schwarz S, Benazzo A, Dunkler D, Muckenhuber M, ... Klepetko W, Hoetzenecker K
Background
Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU).
Methods
A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (P), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest.
Results
In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (P, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679.
Conclusions
The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:4-11
Schwarz S, Benazzo A, Dunkler D, Muckenhuber M, ... Klepetko W, Hoetzenecker K
J Heart Lung Transplant: 30 Dec 2020; 40:4-11 | PMID: 33144029
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Older ...

This program is still in alpha version.