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Búsqueda Bibliografica: hs TROPONINAS 2025 – Parte II

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30. Chin J Integr Med. 2025 Mar;31(3):206-214. doi: 10.1007/s11655-024-4000-5. Epub
2024 Dec 2.

Effect of Kuanxiong Aerosol on Perioperative Coronary Microcirculation in
Patients with Unstable Angina Undergoing Elective PCI: A Pilot Randomized
Controlled Trial.

Liu ZH(1), Xing WL(1), Liu HX(2), Shang JJ(1), Li AY(1), Zhou Q(1), Zhang ZM(1),
Li ZB(1), Chen KJ(3).

Author information:
(1)Cardiovascular Department, Beijing Hospital of Traditional Chinese Medicine,
Capital Medical University, Beijing, 100010, China.
(2)Cardiovascular Department, Beijing Hospital of Traditional Chinese Medicine,
Capital Medical University, Beijing, 100010, China. liuhongxu@bjzhongyi.com.
(3)Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091,
China.

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on
perioperative coronary microcirculation in patients with unstable angina (UA)
suffering from elective percutaneous coronary intervention (PCI).
METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone
in the left anterior descending (LAD) branch were included. Random numbers were
generated to divide patients into the trial group and the control group at a
ratio of 1:1. The index of coronary microcirculation resistance (IMR) was
measured before PCI, and the trial group was given two sprays of KXA, while the
control group was not given. IMR was measured again after PCI, cardiac troponin
I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h
after surgery, and major cardiovascular adverse events (MACEs) were recorded for
30 days. The data statistics and analysis personnel were blinded.
RESULTS: Totally 859 patients were screened, and 62 of them were involved into
this study. Finally, 1 patient in the trial group failed to complete the
post-PCI IMR and was excluded, 30 patients were included for data analysis,
while 31 patients in the control group were enrolled in data analysis. There was
no significant difference in baseline data (age, gender, risk factors, previous
history, biochemical index, and drug therapy, etc.) between the two groups. In
addition, differences in IMR, cTnI and CK-MB were not statistically significant
between the two groups before surgery. After PCI, the IMR level of the trial
group was significantly lower than that of the control group (19.56 ± 14.37 vs.
27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial
injury (PMI) was lower in the trial group, but the difference was not
statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in
either group.
CONCLUSIONS: KXA has the potential of improving coronary microvascular
dysfunction. This study provides reference for the application of KXA in UA
patients undergoing elective PCI. (Registration No. ChiCTR2300069831).

© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press
and Springer-Verlag GmbH Germany, part of Springer Nature.

DOI: 10.1007/s11655-024-4000-5
PMID: 39617867 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of Interest. All authors declare that
they have no conflict of interest.

31. N Engl J Med. 2025 Mar 6;392(10):972-983. doi: 10.1056/NEJMoa2412392. Epub 2024
Nov 18.

Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease.

Greenberg B(1), Taylor M(2), Adler E(1), Colan S(3), Ricks D(4), Yarabe P(4),
Battiprolu P(4), Shah G(4), Patel K(4), Coggins M(4), Carou-Keenan S(4),
Schwartz JD(4), Rossano JW(5)(6).

Author information:
(1)University of California, San Diego Medical Center, La Jolla.
(2)University of Colorado, Anschutz, Medical Center, Aurora.
(3)Boston Children's Hospital, Harvard Medical School, Boston.
(4)Rocket Pharmaceuticals, Cranbury, NJ.
(5)Children's Hospital of Philadelphia, Philadelphia.
(6)Perelman School of Medicine, University of Pennsylvania, Philadelphia.

BACKGROUND: Danon disease is a rare, X-linked, monogenic cardiomyopathy caused
by mutations in the lysosomal-associated membrane 2 gene (LAMP2), which encodes
the LAMP2 protein. In male patients, the predominant phenotype is progressive
cardiac hypertrophy, cardiac dysfunction, and early death. There are no directed
therapies for the disease.
METHODS: In this phase 1 study, we evaluated the safety and efficacy of a single
infusion of RP-A501, a recombinant adeno-associated virus serotype 9 containing
the transgene LAMP2B, which encodes an isoform of LAMP2. The primary outcomes
were the safety and toxic effects of RP-A501, myocardial LAMP2 transduction and
protein expression, stabilization of or reduction in heart-failure symptoms, and
stabilization of or improvement in cardiac structure and function. Key secondary
outcomes were sustained reduction in or stabilization of symptoms, immunologic
response to RP-A501, end-stage heart failure, and overall survival. Exploratory
outcomes included improvement in serologic markers of cardiac disease,
patient-reported outcomes, and quality-of-life assessments.
RESULTS: RP-A501 infusion was administered to seven male patients with Danon
disease: five who were 15 years of age or older and two who were between 11 and
14 years of age. All the patients received a transient immunomodulatory regimen
of prednisone, tacrolimus or sirolimus, and rituximab. Phase 1 data over 24 to
54 months, including interim data from a long-term follow-up study, are reported
here. One patient had complement-mediated thrombotic microangiopathy (grade 4)
with thrombocytopenia and acute kidney injury. Three patients had
glucocorticoid-related exacerbation (grade 3) of Danon disease-related skeletal
myopathy. One patient with left ventricular systolic dysfunction at baseline had
progressive heart failure and underwent transplantation 5 months after infusion.
In the six patients with normal left ventricular ejection fraction at baseline,
we observed cardiac LAMP2 protein expression and a reduction from baseline in or
stabilization of the left ventricular mass index, preservation of left
ventricular ejection fraction, and reduction in or stabilization of the levels
of cardiac troponin I and N-terminal pro-B-type natriuretic peptide. At 24 to 54
months, all the patients were alive, with complete resolution of side effects.
CONCLUSIONS: A single infusion of RP-A501 appeared to be safe and was associated
with cardiac LAMP2 expression and evidence of clinical improvement over a period
of 24 to 54 months. (Funded by Rocket Pharmaceuticals; ClinicalTrials.gov
number, NCT03882437.).

Copyright © 2024 Massachusetts Medical Society.

DOI: 10.1056/NEJMoa2412392
PMID: 39556016 [Indexed for MEDLINE]

32. N Engl J Med. 2024 Dec 12;391(23):2231-2241. doi: 10.1056/NEJMoa2412309. Epub
2024 Nov 16.

CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy.

Fontana M(1), Solomon SD(1), Kachadourian J(1), Walsh L(1), Rocha R(1), Lebwohl
D(1), Smith D(1), Täubel J(1), Gane EJ(1), Pilebro B(1), Adams D(1), Razvi Y(1),
Olbertz J(1), Haagensen A(1), Zhu P(1), Xu Y(1), Leung A(1), Sonderfan A(1),
Gutstein DE(1), Gillmore JD(1).

Author information:
(1)From the National Amyloidosis Centre, University College London, Royal Free
Hospital (M.F., Y.R., J.D.G.), and Richmond Pharmacology (J.T.) - both in
London; Brigham and Women's Hospital, Boston (S.D.S.), and Intellia
Therapeutics, Cambridge (J.K., L.W., R.R., D.L., D.S., J.O., A.H., P.Z., Y.X.,
A.L., A.S.) - both in Massachusetts; the University of Auckland, Auckland, New
Zealand (E.J.G.); Umea University, Umea, Sweden (B.P.); Centre
Hospitalo-Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris,
University Paris-Saclay, Le Kremlin-Bicêtre, France (D.A.); and Regeneron
Pharmaceuticals, Tarrytown, NY (D.E.G.).

BACKGROUND: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a
progressive, often fatal disease. Nexiguran ziclumeran (nex-z) is an
investigational therapy based on CRISPR-Cas9 (clustered regularly interspaced
short palindromic repeats and associated Cas9 endonuclease) targeting the gene
encoding transthyretin (TTR).
METHODS: In this phase 1, open-label trial, we administered a single intravenous
infusion of nex-z to patients with ATTR-CM. Primary objectives included
assessment of the effect of nex-z on safety and pharmacodynamics, including the
serum TTR level. Secondary end points included changes in N-terminal pro-B-type
natriuretic peptide (NT-proBNP) levels, high-sensitivity cardiac troponin T
levels, the 6-minute walk distance, and the New York Heart Association (NYHA)
class.
RESULTS: A total of 36 patients received nex-z and completed at least 12 months
of follow-up. Of these patients, 50% were in NYHA class III and 31% had variant
ATTR-CM. The mean percent change from baseline in the serum TTR level was -89%
(95% confidence interval [CI], -92 to -87) at 28 days and -90% (95% CI, -93 to
-87) at 12 months. Adverse events were reported in 34 patients. Five had
transient infusion-related reactions, and two had transient liver-enzyme
elevations that were assessed as treatment-related. Serious adverse events, most
of which were consistent with ATTR-CM, were reported in 14 patients. The
geometric mean factor change from baseline to month 12 was 1.02 (95% CI, 0.88 to
1.17) in the NT-proBNP level and 0.95 (95% CI, 0.89 to 1.01) in the
high-sensitivity cardiac troponin T level. The median change from baseline to
month 12 in the 6-minute walk distance was 5 m (interquartile range, -33 to 49).
A total of 92% of the patients had either improvement or no change in their NYHA
class.
CONCLUSIONS: In this phase 1 study involving patients with ATTR-CM, treatment
with a single dose of nex-z was associated with transient infusion-related
reactions and consistent, rapid, and durable reductions in serum TTR levels.
(Funded by Intellia Therapeutics and Regeneron Pharmaceuticals;
ClinicalTrials.gov number, NCT04601051.).

Copyright © 2024 Massachusetts Medical Society.

DOI: 10.1056/NEJMoa2412309
PMID: 39555828 [Indexed for MEDLINE]

33. J Am Coll Cardiol. 2025 Feb 11;85(5):489-500. doi: 10.1016/j.jacc.2024.11.004.
Epub 2024 Nov 15.

Intensive Lifestyle Intervention, Cardiac Biomarkers, and
Cardiovascular Outcomes in Diabetes: Look AHEAD Cardiac Biomarker Ancillary
Study.

Patel KV(1), Chunawala Z(2), Verma S(3), Segar MW(4), Garcia KR(5), Ndumele
CE(6), Wang TJ(2), Januzzi JL Jr(7), Bayes-Genis A(8), Butler J(9), Lam CSP(10),
Ballantyne CM(11), de Lemos JA(2), Bertoni AG(12), Espeland M(13), Pandey A(14).

Author information:
(1)Department of Cardiology, Houston Methodist DeBakey Heart and Vascular
Center, Houston, Texas, USA.
(2)Department of Internal Medicine, University of Texas Southwestern Medical
Center, Dallas, Texas, USA.
(3)Division of Cardiac Surgery, St Michael's Hospital, University of Toronto,
Toronto, Ontario, Canada.
(4)Department of Cardiology, Texas Heart Institute, Houston, Texas, USA.
(5)Department of Biostatistics and Data Science, Wake Forest University School
of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
(6)Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
(7)Massachusetts General Hospital, Harvard Medical School, Baim Institute for
Clinical Research, Boston, Massachusetts, USA.
(8)Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona,
Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades
Cardiovasculares (CIBERCV), Madrid, Spain.
(9)Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of
Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
(10)National Heart Centre Singapore, Duke-National University of Singapore,
Singapore.
(11)Department of Medicine, Baylor College of Medicine and Texas Heart
Institute, Houston, Texas, USA.
(12)Department of Internal Medicine, Wake Forest University School of Medicine,
Winston-Salem, North Carolina, USA.
(13)Department of Biostatistics and Data Science, Wake Forest University School
of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA;
Department of Internal Medicine, Wake Forest University School of Medicine,
Winston-Salem, North Carolina, USA.
(14)Department of Internal Medicine, University of Texas Southwestern Medical
Center, Dallas, Texas, USA. Electronic address:
ambarish.pandey@utsouthwestern.edu.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and
high-sensitivity cardiac troponin TÂ (hs-cTnT) are associated with cardiovascular
outcomes and are recommended for measurement in type 2 diabetes (T2D). However,
the effects of an intensive lifestyle intervention (ILI) targeting weight loss
on cardiac biomarkers and the prognostic association of changes in these
biomarkers with risk of adverse cardiovascular outcomes in T2D are not
well-established.
OBJECTIVES: This study sought to evaluate the effects of an ILI on cardiac
biomarkers and the association of changes in cardiac biomarkers with risk of
cardiovascular outcomes in T2D.
METHODS: Participants of the Look AHEAD (Action for Health in Diabetes) trial
underwent NT-proBNP and hs-cTnT measurement at baseline (NÂ =Â 3,984) and 1 and 4
years. The effects of the ILI (vs diabetes support and education [DSE]) on
cardiac biomarkers were assessed using adjusted linear mixed-effect models and
summarized as geometric mean ratios (GMRs). Associations of longitudinal changes
in cardiac biomarkers with risk of cardiovascular outcomes were assessed using
adjusted Cox models.
RESULTS: Average baseline NT-proBNP and hs-cTnT was 77 and 10.7Â ng/L,
respectively. The ILI (vs DSE) led to an increase in NT-proBNP at 1 year (GMR:
1.14; 95%Â CI: 1.08-1.20), but this difference was attenuated by 4 years (GMR:
1.01; 95%Â CI: 0.96-1.07). The ILI (vs DSE) led to lower hs-cTnT at 1 year (GMR:
0.94; 95%Â CI: 0.91-0.97) and 4 years (GMR: 0.93; 95%Â CI: 0.90-0.96).
Participants with meaningful weight loss by 1 year (≥5% vs <5%) had a
significant increase in NT-proBNP in the short term (year 1), which attenuated
in the long-term follow-up (year 4). Meaningful 1-year weight loss was
significantly associated with reduction in hs-cTnT in the long term. In adjusted
Cox models, increase in NT-proBNP was significantly associated with higher risk
of the composite atherosclerotic cardiovascular disease (ASCVD) outcome and
incident heart failure independent of baseline measure of the cardiac biomarker
and changes in risk factors. In contrast, longitudinal increase in hs-cTnT was
significantly associated with higher risk of the composite ASCVD outcome but not
incident heart failure in the most adjusted model.
CONCLUSIONS: Among adults with T2D, an ILI led to a significant reduction in
hs-cTnT on follow-up but a transient increase in NT-proBNP levels at 1 year that
attenuated over time. Longitudinal assessment of NT-proBNP and hs-cTnT provide
prognostic information for ASCVD risk, whereas only changes in NT-proBNP
predicted HF risk.

Copyright © 2025 American College of Cardiology Foundation. Published by
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jacc.2024.11.004
PMID: 39551169 [Indexed for MEDLINE]

Conflict of interest statement: Funding Support and Author Disclosures This
study was funded by an investigator-initiated grant from Roche Diagnostics
(principal investigator: Dr Pandey), which provided support for the reagents
used for measuring the cardiac biomarkers. Drs Patel and Pandey have received
research support from the National Heart, Lung, and Blood Institute
(R21HL169708). Dr Patel has served as a consultant to Novo Nordisk. Dr Verma has
received speaker and/or consulting fees from Abbott, Amarin, AstraZeneca, Bayer,
Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation
Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo
Nordisk, Pfizer, PhaseBio, and TIMI. Dr Segar has received nonfinancial support
from Merck, is on the advisory board of descendantsDNA; and is a founder of
ReCODE Medical. Dr Januzzi is a board member of Imbria Pharmaceuticals; has
received grant support from Abbott Diagnostics, Applied Therapeutics, HeartFlow,
and Novartis; has equity in JanaCare; has received consulting income from Abbott
Diagnostics, AstraZeneca, Beckman Coulter, JanaCare, Novartis, Prevencio, and
Roche Diagnostics; and participates in clinical endpoint committees/Data Safety
Monitoring Boards for AbbVie, Abbott, BridgeBio, Janssen, Pfizer, and Takeda. Dr
Bayes-Genis has received lecture and advisory fees from Abbott, AskBio,
AstraZeneca, Boehringer Ingelheim, Bayer, Medtronic, Novartis, Roche
Diagnostics, and Vifor. Dr Butler has served as a consultant to Abbott, American
Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer,
Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac
Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards,
Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria,
Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck,
Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain,
Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC
Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and
Zoll. Dr Lam is supported by a Clinician Scientist Award from the National
Medical Research Council of Singapore; has received research support from Novo
Nordisk and Roche Diagnostics; has served as a consultant or on the advisory
board/steering committee/executive committee for Alnylam Pharma, AnaCardio AB,
Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim,
Boston Scientific, Bristol Myers Squibb, Corteria, CPC Clinical Research, Eli
Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen
Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo
Nordisk, Quidel Corporation, Radcliffe Group Ltd., Roche, and Us2.ai; and serves
as co-founder and non-executive director of Us2.ai. Dr Ballantyne has received
grant/research support (all significant; all paid to institution, not
individual) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Ionis, Merck, New
Amsterdam, Novartis, Novo Nordisk, Roche Diagnostic, National Institutes of
Health, American Heart Association, and the American Diabetes Association; and
has served as a consultant to 89Bio, Abbott Diagnostics, Amarin, Amgen,
Arrowhead, AstraZeneca, Denka Seiken (significant), Esperion, Genentech,
Illumina, Ionis, Eli Lilly (significant), Merck (significant), New Amsterdam,
Novartis, Novo Nordisk, and Roche Diagnostic. Dr de Lemos has received grant
support from Abbott Diagnostics; has received consulting fees from Quidel
Cardiovascular, Inc; has received honoraria for participation in endpoint
committees from Beckman Coulter and Siemen’s Health Care Diagnostics; has
received fees for participation in data monitoring committees from AstraZeneca,
Novo Nordisk, Eli Lilly, Merck, Regeneron, Amgen, and Verve Therapeutics; and
has been named a co-owner on a patent awarded to the University of Maryland (US
Patent Application Number: 15/309,754) entitled: “Methods for Assessing
Differential Risk for Developing Heart Failure.” Dr Pandey has received research
support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01)
and the National Institute on Minority Health and Disparities (R01MD017529); has
received grant funding (to the institution) from Applied Therapeutics, Gilead
Sciences, Ultromics, Myovista, and Roche; has served as a consultant for and/or
has received honoraria outside of the present study as an advisor/consultant for
Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Sarfez
Therapeutics, Edwards Lifesciences, Merck, Bayer, Novo Nordisk, Alleviant, and
Axon Therapies; has received nonfinancial support from Pfizer and Merck; and is
a consultant for Palomarin Inc with stock compensation. All other authors have
reported that they have no relationships relevant to the contents of this paper
to disclose.

34. Sci Rep. 2024 Nov 1;14(1):26289. doi: 10.1038/s41598-024-77108-z.

Randomized trial of early exercise rehabilitation and its effects on patients
with acute coronary syndrome.

Miao X(#)(1), Jiang H(#)(2), Huang X(2), Zheng Y(2), Jin S(3)(4), Wang R(5).

Author information:
(1)Department of Cardiology/Endocrinolog, Fuzhou University Affiliated
Provincial Hospital, Shengli Clinical Medical College of Fujian Medical
University, Fuzhou, 350001, China.
(2)Department of Cardiology, Fuzhou University Affiliated Provincial Hospital,
Shengli Clinical Medical College of Fujian Medical University, No. 134 East
Street, Gulou District, Fuzhou, 350001, P.R. China.
(3)Department of Cardiology, Fuzhou University Affiliated Provincial Hospital,
Shengli Clinical Medical College of Fujian Medical University, No. 134 East
Street, Gulou District, Fuzhou, 350001, P.R. China. jins0305@163.com.
(4)Department of Nrusing, Fuzhou University Affiliated Provincial Hospital,
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001,
China. jins0305@163.com.
(5)Department of Cardiology, Fuzhou University Affiliated Provincial Hospital,
Shengli Clinical Medical College of Fujian Medical University, No. 134 East
Street, Gulou District, Fuzhou, 350001, P.R. China. rehuawang03@163.com.
(#)Contributed equally

To assess the psychological and physiological benefits of early exercise
rehabilitation in patients with acute coronary syndrome (ACS). Among 559
ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from
January to December 2021, 200 eligible participants were assigned to two groups.
The control group received standard care, while the experimental group received
early exercise rehabilitation in addition to standard care. The outcomes
measured included changes in depression levels (PHQ-9), fasting blood glucose,
and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)
levels. Data were analyzed using SPSS, with t tests and chi-square tests for
group comparisons. In comparison to the control group, the experimental group
demonstrated significant improvements in PHQ-9 scores (P < 0.001) and lower
fasting blood glucose levels before discharge (P = 0.046). Additionally, the
experimental group had notably reduced TnI levels at 72Â h after admission
(P = 0.001), especially among non-diabetic NSTEMI patients over 60 years old,
who showed decreased TnI levels at the 48-hour mark (P = 0.016). However, there
were no significant differences in NT-ProBNP change values between the two
groups (P > 0.05). Subgroup analysis revealed enhanced outcomes in the
intervention group for ACS patients without smoking or drinking history and no
heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has
notable benefits for ACS patients, including reduced depression, improved blood
glucose control, and enhanced myocardial protection, especially in nondiabetic
NSTEMI patients aged 60 and above.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-77108-z
PMCID: PMC11530432
PMID: 39487165 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

35. J Am Heart Assoc. 2024 Nov 5;13(21):e034367. doi: 10.1161/JAHA.123.034367. Epub
2024 Oct 25.

Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in
Patients With Chronic Coronary Heart Disease.

Stewart RAH(1), Robledo KP(2), Tonkin AM(3), Keech A(2), Kritharides L(4)(5),
Marschner I(2), Janus E(6), Thompson PL(7), Watts GF(8), Zeller T(9)(10), White
HD(1), Simes J(2).

Author information:
(1)Green Lane Cardiovascular Service, Auckland City Hospital, Te Toka Tumai, Te
Whatu Ora-Health New Zealand Auckland New Zealand.
(2)Faculty Medicine and Health, NHMRC Clinical Trials Centre University of
Syndey and The Royal Prince Alfred Hospital Camperdown NSW Australia.
(3)School of Public Health and Preventive Medicine Monash University Melbourne
VIC Australia.
(4)Department of Cardiology, Concord Hospital The University of Sydney Concord
NSW Australia.
(5)ANZAC Medical Research Institute, Faculty of Medicine, University of Sydney
Concord NSW Australia.
(6)Western Health Chronic Disease Alliance and Department of Medicine, Western
Health-Melbourne Medical School University of Melbourne Parkville Vic 3010
Australia.
(7)School of Population and Global Health The University of Western Australia
Perth WA Australia.
(8)Medical School The University of Western Australia Perth WA Australia.
(9)University Heart Centre Hamburg Hamburg Germany.
(10)Department of General and Interventional Cardiology, German Centre for
Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Campus
Research Hamburg Germany.

BACKGROUND: Protein biomarkers that reflect different pathophysiological
pathways have been associated with the risk of adverse cardiovascular events.
However, it is uncertain whether these associations are sustained with
increasing years after the biomarkers are measured.
METHODS AND RESULTS: In this cohort study, 7745 patients with coronary heart
disease who participated in the LIPID (Long-Term Intervention With Pravastatin
in Ischemic Disease) trial, BNP (B-type natriuretic peptide), troponin I,
cystatin-C, C-reactive protein, d-dimer and midregional proadrenomedullin were
measured at baseline and after 1 year. Discrimination of plasma biomarker
concentrations for cardiovascular death were evaluated in landmark analyses from
1 year for the next 5 years of the randomized trial, and for 10 additional years
after trial completion. All 6 biomarkers were associated with risk of
cardiovascular death (n=1903) both during and after the clinical trial (each
P<0.001). C-statistics for BNP were 0.706 and 0.704; cystatin-C, 0.686 and
0.693; troponin I, 0.686 and 0.689; C-reactive protein, 0.655 and 0.684;
d-dimer, 0.670 and 0.679, and midregional adrenomedullin, 0.686 and 0.688,
respectively. In multivariable models, adding all 6 biomarkers to models with
clinical risk factors increased the C-statistic for cardiovascular death from
0.709 to 0.775 during the clinical trial, and from 0.713 to 0.751 during 10-year
follow-up after the randomized trial (P<0.001 for both).
CONCLUSIONS: In patients with chronic coronary heart disease, biomarkers that
reflect different pathophysiological pathways are associated with the risk of
cardiovascular death for at least the next 15 years.

DOI: 10.1161/JAHA.123.034367
PMCID: PMC11935700
PMID: 39450716 [Indexed for MEDLINE]

36. J Physiol Pharmacol. 2024 Aug;75(4). doi: 10.26402/jpp.2024.4.05. Epub 2024 Oct
10.

The efficacy of levosimendan and dobutamine on reducing peripheral blood
interleukin-6 levels and improving cardiac function in patients with septic
cardiomyopathy: a comparative study.

Sun T(1), Sun QL(1), Liu Y(1), Zhang YY(1), Sheng P(1), Cui N(1), Zhang N(1),
Wang SH(1), Su D(2).

Author information:
(1)Department of Critical Care Medicine, Affiliated Hospital of Hebei
University, Baoding 071000, China.
(2)Department of Critical Care Medicine, Affiliated Hospital of Hebei
University, Baoding 071000, China. sudansd069@126.com.

In patients with severe septic cardiomyopathy, levosimendan has been found to
improve myocardial contractility more effectively than dobutamine, although the
underlying mechanisms remain unclear. This study aims to compare the effects of
levosimendan and dobutamine on cardiac function and inflammatory markers in
patients with septic cardiomyopathy, and to further investigate the advantages
and disadvantages of both treatments. We included 40 patients with septic
cardiomyopathy treated in the intensive care unit of our hospital from September
2020 to September 2023. The patients were randomly divided into a levosimendan
group (n=20) and a dobutamine group (n=20). Plasma concentrations of
interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha
(TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours,
and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by
chemiluminescence, and left ventricular ejection fraction (LVEF) was measured
using the Simpson method. After 24 hours of treatment, there were no significant
differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05).
However, at 48 hours, the IL-6 level in the levosimendan group was significantly
lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20
pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences
(P>0.05). Additionally, the cTnI level in the levosimendan group was
significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs.
1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan
group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that
levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and
improve myocardial contractility in patients with septic cardiomyopathy compared
to dobutamine.

DOI: 10.26402/jpp.2024.4.05
PMID: 39415525 [Indexed for MEDLINE]

37. BMC Pulm Med. 2024 Oct 10;24(1):500. doi: 10.1186/s12890-024-03325-x.

Effect of dexmedetomidine on postoperative high-sensitivity cardiac troponin T
in patients undergoing video-assisted thoracoscopic surgery: a prospective,
randomised controlled trial.

Xu CY(1), An MZ(1), Hou YR(1), Zhou QH(2).

Author information:
(1)Department of Anesthesiology and Pain Medicine, Affiliated Hospital of
Jiaxing University, No.1882, South Central Road, Jiaxing City, Zhejiang
Province, China.
(2)Department of Anesthesiology and Pain Medicine, Affiliated Hospital of
Jiaxing University, No.1882, South Central Road, Jiaxing City, Zhejiang
Province, China. zqh10980@zjxu.edu.cn.

BACKGROUND: One-lung ventilation and intrathoracic operations during
thoracoscopic surgery often result in intraoperative hypoxaemia and haemodynamic
fluctuations, resulting in perioperative myocardial injury. Dexmedetomidine, an
alpha-2 (α-2) agonist, has demonstrated myocardial protection. We hypothesize
that the routine intravenous administration of dexmedetomidine could reduce the
extent of myocardial injury during video-assisted thoracoscopic surgery (VATS).
METHODS: The study included patients aged ≥ 45 years, classified as American
Society of Anesthesiologists physical status I-III, who underwent general
anesthesia for video-assisted thoracoscopic surgery. The patients were randomly
assigned to either the intervention group, receiving general anesthesia with
dexmedetomidine, or the control group, receiving general anesthesia without
dexmedetomidine. Patients in the intervention group received a loading dose of
dexmedetomidine (0.5 µg·kg-1) before anesthesia induction, followed by a
continuous infusion (0.5 µg·kg-1·h-1) until the completion of the surgery.
Placebos (saline) were administered for the control group to match the
treatment. The primary outcome assessed was the high-sensitivity cardiac
troponin T on postoperative day 1. Additionally, the incidence of myocardial
injury after noncardiac surgery (MINS) was noted.
RESULTS: A total of 110 participants completed this study. The median
[interquartile range (IQR)] concentration of hs-cTnT on postoperative day 1 was
lower in the intervention group compared with the control group (7 [6-9] vs. 8
[7-11] pg·ml-1; difference in medians,1 pg·ml-1; 95% confidence interval [CI], 0
to 2; P = 0.005). Similarly, on postoperative day 3, the median [IQR]
concentration of hs-cTnT in the intervention group was also lower than that in
the control group (6 [5-7] vs. 7 [6-9]; difference in medians,1 pg·ml-1; 95%CI,
0 to 2; P = 0.011). Although the incidence of MINS was not statistically
significant (the intervention group vs. the control group, 3.8% vs. 9.1%,
P = 0.465), there was a decreasing trend in the incidence of MINS in the
intervention group.
CONCLUSION: The administration of perioperative dexmedetomidine in patients ≥ 45
years undergoing video-assisted thoracoscopic surgery could lower the release of
postoperative hs-cTnT without reducing incidence of myocardial injury.
TRIAL REGISTRATION: chictr.org.cn (ChiCTR2200063193); prospectively registered 1
September 2022.

© 2024. The Author(s).

DOI: 10.1186/s12890-024-03325-x
PMCID: PMC11465541
PMID: 39390494 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

38. Circ J. 2024 Dec 25;89(1):24-30. doi: 10.1253/circj.CJ-24-0479. Epub 2024 Oct 4.

Prospective Multicenter Screening With High-Sensitivity Cardiac Troponin T for
Wild-Type Transthyretin Cardiac Amyloidosis in Outpatient and Community-Based
Settings.

Arima N(1), Ochi Y(1), Kubo T(1), Murakami Y(2), Nishino K(3), Yamamoto H(4),
Satou K(5), Tamura S(6), Okawa M(7), Takata H(8), Shimizu Y(9), Baba Y(1),
Yamasaki N(1), Kitaoka H(1).

Author information:
(1)Department of Cardiology and Geriatrics, Kochi Medical School, Kochi
University.
(2)Murakami Clinic Murakami Naika Junnkannkika.
(3)Nishino Naika Clinic Junkanki Shinzounaika.
(4)Yamamoto Junkanki Naika Ganka Clinic.
(5)Satou Clinic.
(6)Tamura Cardio Clinic.
(7)Okawa-Naika.
(8)Aoyagi Clinic.
(9)Ryosekihotarugaoka Clinic.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a
simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed
exploratory systemic screening using hs-cTnT to detect wild-type transthyretin
CA (ATTRwt-CA) in outpatient and community-based settings.
METHODS AND RESULTS: This study was a prospective multicenter study including 8
internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals
aged ≥70 years who visited those clinics as outpatients were enrolled. Patients
with a prior diagnosis of CA or a history of heart failure hospitalization were
excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic,
and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed
examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was
confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the
study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent
further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2
men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22)
among patients with elevated hs-cTnT levels at two examinations, and at least
0.18% (2/1,141) in the whole study population.
CONCLUSIONS: Measurement of hs-cTnT will help to screen for patients with
undiagnosed ATTRwt-CA in primary care practice.

DOI: 10.1253/circj.CJ-24-0479
PMID: 39370278 [Indexed for MEDLINE]

39. Chron Respir Dis. 2024 Jan-Dec;21:14799731241289423. doi:
10.1177/14799731241289423.

The effects of inspiratory muscle training on biomarkers of muscle damage in
recovered COVID-19 patients after weaning from mechanical ventilation.

Iqbal M(1)(2)(3), Hassan K(4), Bliss E(1)(2)(3), Whiteside EJ(1)(3)(5), Hoffman
B(1)(3), Mills DE(1)(2)(3).

Author information:
(1)School of Health and Medical Sciences, University of Southern Queensland,
Ipswich, QLD, Australia.
(2)Respiratory and Exercise Physiology Research Group, School of Health and
Medical Sciences, University of Southern Queensland, Ipswich, QLD, Australia.
(3)Centre for Health Research, Institute for Resilient Regions, University of
Southern Queensland, Ipswich, QLD, Australia.
(4)Department of Physiotherapy, University of Lahore Teaching Hospital, Lahore,
Pakistan.
(5)Centre for Future Materials, University of Southern Queensland, Toowoomba,
QLD, Australia.

Background: COVID-19 patients experience respiratory muscle damage, leading to
reduced respiratory function and functional capacity often requiring mechanical
ventilation which further increases susceptibility to muscle weakness.
Inspiratory muscle training (IMT) may help mitigate this damage and improve
respiratory function and functional capacity. Methods: We studied the effects of
IMT on muscle damage biomarkers, respiratory function, and functional capacity
in COVID-19 recovered young adults, successfully weaned from mechanical
ventilation. Participants were randomly allocated to either an IMT (n = 11) or
control (CON; n = 11) intervention for 4Â weeks. The IMT group performed 30
dynamic inspiratory efforts twice daily, at 50% of their maximal inspiratory
mouth pressure (PMmax) while the CON group performed 60 inspiratory efforts at
10% of pMmax daily. Serum was collected at baseline, week two, and week four to
measure creatine kinase muscle-type (CKM), fast skeletal troponin-I (sTnI) and
slow sTnI. Results: Time × group interaction effects were observed for CKM and
slow sTnI, but not for fast sTnI. Both were lower at two and 4Â weeks for the IMT
compared to the CON group, respectively. Time × group interaction effects were
observed for forced expiratory volume in 1s, forced vital capacity, PMmax and
right- and left-hand grip strength. These were higher for the IMT compared to
the CON group. Conclusion: Four weeks of IMT decreased muscle damage biomarkers
and increased respiratory function and grip strength in recovered COVID-19
patients after weaning from mechanical ventilation.

DOI: 10.1177/14799731241289423
PMCID: PMC11457248
PMID: 39365635 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of conflicting interestsThe
author(s) declared no potential conflicts of interest with respect to the
research, authorship, and/or publication of this article.

40. J Gerontol A Biol Sci Med Sci. 2024 Nov 1;79(11):glae234. doi:
10.1093/gerona/glae234.

Associations of Hypertension and Orthostatic Hypotension With Subclinical
Cardiovascular Disease.

Petriceks AH(1)(2), Appel LJ(3)(4), Miller ER 3rd(3)(4), Mitchell CM(4), Schrack
JA(4), Wanigatunga AA(4), Michos ED(3)(4), Christenson RH(5), Rebuck H(5),
Juraschek SP(1)(2).

Author information:
(1)Division of General Medicine, Department of Medicine, Beth Israel Deaconess
Medical Center, Boston, Massachusetts, USA.
(2)Harvard Medical School, Boston, Massachusetts, USA.
(3)Department of General Internal Medicine, The Johns Hopkins University School
of Medicine, Baltimore, Maryland, USA.
(4)Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
Maryland, USA.
(5)Department of Pathology, University of Maryland School of Medicine,
Baltimore, Maryland, USA.

BACKGROUND: Orthostatic hypotension is associated with cardiovascular disease.
It remains unclear if low standing blood pressure or high seated blood pressure
is responsible for this association. We compared associations of orthostatic
hypotension and hypertension with high-sensitivity cardiac troponin I and
N-terminal pro-B-type natriuretic peptide.
METHODS: We performed a secondary analysis of the Study to Understand Fall
Reduction and Vitamin D in You, a randomized controlled trial funded by the
National Institute on Aging, between July 2015 and May 2019. Participants were
community-dwelling adults, 70 years or older. Blood tests for high-sensitivity
cardiac troponin I and N-terminal pro-B-type natriuretic peptide were drawn at
visits concurrent with blood pressure measurements. Secondary analysis occurred
in 2023. We determined associations between blood pressure phenotypes and
cardiac biomarkers.
RESULTS: Of 674 participants (mean age 76.5 ± 5.4 years, 43% female, 17.2% Black
race), 29.1% had prior cardiovascular disease. Participants with seated
hypertension had 10.1% greater high-sensitivity cardiac troponin I (95%
confidence interval = 3.8-16.9) and 11.0% greater N-terminal pro-B-type
natriuretic peptide (4.0-18.6) than those without seated hypertension.
Participants with standing hypertension had 8.6% (2.7-14.9) greater
high-sensitivity cardiac troponin I and 11.8% greater N-terminal pro-B-type
natriuretic peptide (5.1-18.9) than those without standing hypertension.
Hypotensive phenotypes were not associated with either biomarker.
CONCLUSIONS: Both seated and standing hypertension were associated with greater
high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic
peptide, but hypotensive phenotypes were not. Hypoperfusion may not be the
principal mechanism behind subclinical cardiac injury among older adults with
orthostatic hypotension.

© The Author(s) 2024. Published by Oxford University Press on behalf of The
Gerontological Society of America. All rights reserved. For commercial re-use,
please contact reprints@oup.com for reprints and translation rights for
reprints. All other permissions can be obtained through our RightsLink service
via the Permissions link on the article page on our site—for further information
please contact journals.permissions@oup.com.

DOI: 10.1093/gerona/glae234
PMCID: PMC11561395
PMID: 39292998 [Indexed for MEDLINE]

Conflict of interest statement: None.

41. Eur J Anaesthesiol. 2024 Nov 1;41(11):831-840. doi:
10.1097/EJA.0000000000002059. Epub 2024 Sep 12.

Mean arterial pressure versus cardiac index for haemodynamic management and
myocardial injury after hepatopancreatic surgery: A randomised controlled trial.

Abdullah T(1), Gökduman HC, Enişte İA, Kudaş İ, Ali A, Kinaci E, Özden İ, Gümüş
Özcan F.

Author information:
(1)From the Department of Anaesthesiology, Istanbul Başakşehir Çam&Sakura City
Hospital (TA, HCG, İAE, FGÖ), Department of General Surgery, Istanbul Başakşehir
Çam&Sakura City Hospital (İK), Department of Anaesthesiology, Istanbul Medical
Faculty, Istanbul University (AA), and Liver Transplantation &
Hepatopancreatobiliary Surgery Unit, Department of General Surgery, Istanbul
Başakşehir Çam&Sakura City Hospital (EK, İÖ).

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) frequently
complicates the peri-operative period and is associated with increased
mortality.
OBJECTIVES: We hypothesised that cardiac index (CI) based haemodynamic
management reduces peri-operative high-sensitive troponin-T (hsTnT) elevation
and MINS incidence in patients undergoing hepatic/pancreatic surgery compared to
mean arterial pressure.
DESIGN: A randomised controlled study.
SETTING: A single-centre study conducted in a university-affiliated tertiary
hospital between June 2022 and March 2023.
PATIENTS: Ninety-one patients, who were ≥ 65 years old or ≥ 45 years old with a
history of at least one cardiac risk factor were randomised to either mean
arterial pressure (MAP) based ( n  = 45) or CI-based ( n  = 46) management
groups, and completed the study.
INTERVENTIONS: In group-MAP, patients received fluid boluses and/or a
noradrenaline infusion to maintain MAP above the predefined threshold. In
group-CI, patients received fluid boluses and/or dobutamine infusion to keep CI
above the predefined threshold. When a low MAP was observed despite a normal CI,
a noradrenaline infusion was started.
MAIN OUTCOME MEASURES: The primary outcome was peri-operative hsTnT elevation.
The secondary outcomes were MINS incidence and 90-day mortality.
RESULTS: The median absolute troponin elevation was 4.3 ng l -1 (95% CI 3.4 to
6) for the CI-based group, and 9.4 ng l -1 (95% CI 7.7 to 12.7) for the
MAP-based group (median difference: 5.1 ng l -1 , 95% CI 3 to 7; P  < 0.001).
MINS occurred in 8 (17.4%) patients in the CI-based group and 17 (37.8%)
patients in the MAP-based group (relative risk: 0.46, 95% CI: 0.22 to 0.96; P
 = 0.029). Two patients in group-MAP died from cardiovascular-related causes.
One patient in group-CI and two in group-MAP died from sepsis-related
complications (for all-cause mortality: χ2  = 1.98, P  = 0.16). MAP-AUC and
CI-AUC values of the CI- and MAP-based groups were 147 vs. 179 min × mmHg ( P
 = 0.85) and 8.4 vs. 43.2 l m -2 min -1  × min ( P  < 0.001), respectively.
CONCLUSIONS: CI-based haemodynamic management assures sufficient flow and
consequently is associated with less peri-operative hsTnT elevation and lower
incidence of MINS compared to MAP.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05391087.

Copyright © 2024 European Society of Anaesthesiology and Intensive Care.
Unauthorized reproduction of this article is prohibited.

DOI: 10.1097/EJA.0000000000002059
PMID: 39262319 [Indexed for MEDLINE]

42. BMC Anesthesiol. 2024 Sep 11;24(1):324. doi: 10.1186/s12871-024-02684-6.

Efficacy of ozonated autohemotherapy for improvement of myocardial injury
following traumatic brain injury.

Wang C(#)(1), Zhu Y(#)(1), Liu W(1), Ren L(1), Wu Z(2), Chen J(3).

Author information:
(1)Department of Anesthesiology, Central Hospital of Wuhan, Huazhong University
of Science and Technology, Wuhan, 430000, Hubei Province, China.
(2)Department of Anesthesiology, Changzhou No.2 People's Hospital, Nanjing
Medical University, Changzhou, 213000, Jiangsu Province, China.
wuzhouquan2005@126.com.
(3)Department of Anesthesiology, Central Hospital of Wuhan, Huazhong University
of Science and Technology, Wuhan, 430000, Hubei Province, China.
chenjinli2001@sina.com.
(#)Contributed equally

BACKGROUND: Traumatic brain injury is a kind of injury caused by external
violence on the head. Its danger is not limited to life rescue in the early
stage of the disease. Moreover, the subsequent inflammatory reaction and the
change in its oxidative stress level will cause secondary myocardial injury. The
purpose of this study is to explore the myocardial protective effect of ozone
autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI).
METHODS: Forty patients with acute TBI were recruited and divided into The
treatment group (Group OA, n = 18) and the Control group (Group C, n = 19).
Patients in Group OA received OA before surgery and on the 1st and 2nd
postoperative days, while patients in Group C underwent autologous blood
transfusion. Venous blood was collected from all patients before (T0) and after
7Â days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and
amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1,
transthoracic cardiac ultrasound was performed to measure left ventricular
ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE),
and venous blood was sampled to determine the contents of superoxide dismutase
(SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale
(GCS) scores were calculated, and other clinical indexes were recorded.
RESULTS: (1) The levels of cTnT at T1 were significantly higher as compared with
that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable
decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2)
The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly
increased in Group OA as compared with those in Group C. (3) The length of
Intensive Care Unit and hospitalization time for patients in Group OA was
distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015,
respectively).
CONCLUSION: Perioperative OA treatment can alleviate the secondary myocardial
injury during the disease course of TBI, which might be associated with its
myocardial protective effect against oxidative stress.
TRIAL REGISTRATION: This study was approved by the Ethical Committee of
Changzhou NO.2 People's Hospital. The protocol was registered prospectively with
the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020.

© 2024. The Author(s).

DOI: 10.1186/s12871-024-02684-6
PMCID: PMC11389279
PMID: 39261798 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

43. Eur Heart J. 2024 Nov 8;45(42):4464-4478. doi: 10.1093/eurheartj/ehae590.

Cardiac biomarkers and effects of aficamten in obstructive hypertrophic
cardiomyopathy: the SEQUOIA-HCM trial.

Coats CJ(1), Masri A(2), Barriales-Villa R(3), Abraham TP(4), Brinkley DM(5),
Claggett BL(6), Hagege A(7), Hegde SM(6), Ho CY(8), Kulac IJ(6), Lee MMY(1),
Maron MS(9), Olivotto I(10), Owens AT(11), Solomon SD(6), Tfelt-Hansen
J(12)(13), Watkins H(14), Jacoby DL(15), Heitner SB(15), Kupfer S(15), Malik
FI(15), Meng L(15), Wohltman A(15), Januzzi JL(16)(17).

Author information:
(1)School of Cardiovascular and Metabolic Health, University of Glasgow,
Glasgow, UK.
(2)Division of Cardiology, Department of Medicine, Oregon Health & Science
University, Portland, OR, USA.
(3)Department of Cardiology, Complexo Hospitalario Universitario A Coruña,
INIBIC, CIBERCV-ISCIII, A Coruña, Spain.
(4)UCSF Adult Cardiac Echocardiography Lab, University of California San
Francisco, San Francisco, CA, USA.
(5)Division of Cardiovascular Medicine, Vanderbilt Heart & Vascular Institute,
Nashville, TN, USA.
(6)Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA, USA.
(7)Département de Cardiologie, Assistance Publique Hôpitaux de Paris, Hôpital
Européen Georges-Pompidou, Paris, France.
(8)Department of Medicine, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA, USA.
(9)Department of Cardiology, Lahey Hospital and Medical Center, Burlington, MA,
USA.
(10)Division of Cardiology, Meyer Children's Hospital, Istituto di Ricovero e
Cura a Carattere Scientifico, Florence, Italy.
(11)Center for Inherited Cardiovascular Disease, Division of Cardiovascular
Medicine, Department of Medicine, University of Pennsylvania Perelman School of
Medicine, Philadelphia, PA, USA.
(12)Section of Forensic Genetics, Department of Forensic Medicine, Faculty of
Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
(13)Department of Cardiology, Copenhagen University Hospital Rigshospitalet,
Copenhagen, Denmark.
(14)Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
(15)Clinical Research, Cytokinetics, Incorporated, South San Francisco, CA, USA.
(16)Division of Cardiology, Department of Medicine, Massachusetts General
Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
(17)Clinical Trials, Baim Institute for Clinical Research, Boston, MA, USA.

Comment in
doi: 10.1093/eurheartj/ehae600.
doi: 10.1093/eurheartj/ehae601.

BACKGROUND AND AIMS: The role of biomarker testing in the management of
obstructive hypertrophic cardiomyopathy is not well defined. This pre-specified
analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between
clinical characteristics and baseline concentrations of N-terminal pro-B-type
natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I
(hs-cTnI), and to evaluate the effect of treatment with aficamten on biomarker
concentrations.
METHODS: Cardiac biomarkers were measured at baseline and serially throughout
the study. Regression analyses determined predictors of baseline NT-proBNP and
hs-cTnI concentrations, and evaluated whether early changes in these biomarkers
relate to later changes in left ventricular outflow tract gradient (LVOT-G),
other echocardiographic measures, health status, and functional capacity.
RESULTS: Baseline concentration of NT-proBNP was associated with LVOT-G and
measures of diastolic function, while hs-cTnI was associated with left
ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was
reduced by 79% (95% confidence interval 76%-83%, P < .001) and hs-cTnI by 41%
(95% confidence interval 32%-49%, P < .001); both biomarkers reverted to
baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were
strongly associated with a lowering of LVOT-G, improvement in health status, and
increased peak oxygen uptake. N-Terminal pro-B-type natriuretic peptide
reduction strongly correlated with the majority of improvements in exercise
capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the
24-week change in key endpoints.
CONCLUSIONS: N-Terminal pro-B-type natriuretic peptide and hs-cTnI
concentrations are associated with key variables in obstructive hypertrophic
cardiomyopathy. Serial measurement of NT-proBNP and hs-cTnI appears to reflect
clinical response to aficamten therapy.

© The Author(s) 2024. Published by Oxford University Press on behalf of the
European Society of Cardiology.

DOI: 10.1093/eurheartj/ehae590
PMCID: PMC11544315
PMID: 39217447 [Indexed for MEDLINE]

44. J Am Heart Assoc. 2024 Sep 3;13(17):e035053. doi: 10.1161/JAHA.124.035053. Epub
2024 Aug 27.

Acute Myocardial Injury in Spontaneous Intracerebral Hemorrhage: A Secondary
Observational Analysis of the FAST Trial.

Rosso M(1), Stengl H(2), Scheitz JF(2), Lewey J(3), Mayer SA(4), Yaghi S(5),
Kasner SE(1), Witsch J(1).

Author information:
(1)Department of Neurology University of Pennsylvania Philadelphia PA USA.
(2)Department of Neurology and Center for Stroke Research Berlin Charité -
Universitätsmedizin Berlin Berlin Germany.
(3)Division of Cardiology, Department of Medicine University of Pennsylvania
Philadelphia PA USA.
(4)Department of Neurology and Neurosurgery New York Medical College Valhalla NY
USA.
(5)Department of Neurology Brown University Providence RI USA.

BACKGROUND: Acute myocardial injury is associated with poor outcomes in patients
with acute ischemic stroke, but its prognostic significance in patients with
spontaneous intracerebral hemorrhage remains unclear. We investigated whether
acute myocardial injury and the direction of the cardiac troponin I (cTnI)
change (rising versus falling) affect post-intracerebral hemorrhage outcomes.
METHODS AND RESULTS: We re-analyzed the FAST
(Factor-Seven-for-Acute-Hemorrhagic-Stroke) trial. Acute myocardial injury was
defined as at least 1 cTnI value above the upper reference limit with a
rise/fall of >20%. Logistic regression tested for associations (1) between acute
myocardial injury (presence versus absence) and poor outcome (modified Rankin
Scale 4-6) and mortality at 15 and 90 days; (2) among 3 groups (rising versus
falling versus no acute myocardial injury) and outcomes. Among the 841 FAST
participants, 785 patients were included. Acute myocardial injury was detected
in 29% (n=227); 170 had rising cTnI. At 15 and 90 days, respectively, those with
acute myocardial injury had higher odds of poor outcome (adjusted odds ratio)
([aOR] 2.3 [95% CI, 1.3-3.9]); and adjusted odds ratio 2.5 [95% CI, 1.6-3.9];,
and higher odds of mortality (adjusted odds ratio 2.4 [95% CI, 1.4-4.3]; and
adjusted odds ratio 2.2 [CI, 1.3-3.6]) than patients without. There was no
interaction between FAST group assignment and myocardial injury, and
associations between myocardial injury and outcomes were consistent across group
assignments. Rising cTnI was associated with the highest risk of poor outcomes
and mortality.
CONCLUSIONS: In this secondary analysis of the FAST trial, acute myocardial
injury was common and associated with poor outcomes. The direction of the cTnI
change might provide additional risk stratification after intracerebral
hemorrhage.

DOI: 10.1161/JAHA.124.035053
PMCID: PMC11646513
PMID: 39190583 [Indexed for MEDLINE]

45. Sci Rep. 2024 Aug 23;14(1):19574. doi: 10.1038/s41598-024-70470-y.

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an
interim analysis of randomized controlled clinical trial of early administration
of beta blockers.

El-Menyar A(1)(2), Asim M(3), Khan N(3), Rizoli S(4), Mahmood I(4), Al-Ani M(4),
Kanbar A(4), Alaieb A(4), Hakim S(4), Younis B(4), Taha I(4), Jogol H(4),
Siddiqui T(4), Hammo AA(4), Abdurraheim N(4), Alabdallat M(4), Bahey AA(4),
Ahmed K(4), Atique S(4), Chaudry IH(5), Prabhu KS(6), Uddin S(6), Al-Thani H(4).

Author information:
(1)Department of Surgery, Clinical Research, Trauma and Vascular Surgery, Hamad
Medical Corporation, Doha, Qatar. aymanco65@yahoo.com.
(2)Department of Clinical Medicine, Weill Cornell Medicine, P.O. Box 24144,
Doha, Qatar. aymanco65@yahoo.com.
(3)Department of Surgery, Clinical Research, Trauma and Vascular Surgery, Hamad
Medical Corporation, Doha, Qatar.
(4)Department of Surgery, Trauma Surgery, Hamad Medical Corporation, Doha,
Qatar.
(5)Department of Surgery, University of Alabama at Birmingham, Birmingham,
Alabama, USA.
(6)Translational Research Institute, Academic Health System, Hamad Medical
Corporation, Doha, Qatar.

This is an interim analysis of the Beta-blocker (Propranolol)Â use in traumatic
brain injury (TBI)Â based on the high-sensitive troponin status (BBTBBT) study.
The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical
trial with a target sample size of 771 patients with TBI. We sought, after
attaining 50% of the sample size, to explore the impact of early administration
of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines,
and the TBI biomarkers linked to the status of high-sensitivity troponin T
(HsTnT). Patients were stratified based on the severity of TBI using the Glasgow
coma scale (GCS) and HsTnT status (positive vs negative) before randomization.
Patients with positive HsTnT (non-randomized) received propranolol (Group-1;
n = 110), and those with negative test were randomized to receive propranolol
(Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered
within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic
blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and
ELISA-based immunoassays were used to quantify the serum levels of
pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI
biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three
hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and
gender were enrolled in the interim analysis. Group 1 had significantly higher
baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the
randomized groups (p = 0.001). Group 1 showed a significant temporal reduction
in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h
post-injury (p = 0.001). Patients with severe head injuries had higher baseline
levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01).
HsTnT levels significantly correlated with the Injury Severity Score (ISS)
(r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205,
p = 0.001). Early Propranolol administration showed a significant reduction in
cytokine levels and TBI biomarkers from baseline to 48Â h post-injury,
particularly among patients with positive HsTnT, indicating the potential role
in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov
NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29
December 2020 and is ongoing. The study was partly presented at the 23rd
European Congress of Trauma and Emergency Su