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Purpose: To determine the oxygen affinity for optimal tissue oxygen delivery with a hemoglobin-hydroxyethyl starch conjugate (HRC 101).Methods: Anesthetized rats were hemodiluted (180 ml kg(-1)) with low (P(50) approximately 70 mmHg) or high affinity (P(50) approximately 14 mmHg) HRC 101 at hemoglobin (Hb) concentrations near 100 or 70 g l(-1) (n = 6-8). Hippocampal tissue oxygen tension (P(Br)O(2)), blood flow, arterial blood gases, Hb, hematocrit (Hct) and lactate were measured. Data (mean +/- SD) were analyzed by two-way ANOVA.Results: Hemodilution reduced the hematocrit to 1 +/- 1% in all groups. P(Br)O(2) was best maintained after hemodilution with low affinity HRC 101 at Hb 100 and 70 g l(-1) (25.2 +/- 7.6 and 16.6 +/- 8.3 torr, respectively). P(Br)O(2) decreased (9.5 +/- 9.3 torr, P < 0.05) and serum lactate levels increased (5.0 +/- 1.7 mmol l(-1), P < 0.05) following hemodilution with the high affinity HRC 101 (Hb 100 g l(-1)).Conclusions: HRC 101 with a lower oxygen affinity favored tissue perfusion and maintained P(Br)O(2) after near complete blood volume exchange in rats. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about the long-term outcomes and costs of survivors of acute respiratory distress syndrome (ARDS).Objectives: To describe functional and quality of life outcomes, health care use, and costs of survivors of ARDS 2 yr after intensive care unit (ICU) discharge.Methods: We recruited a cohort of ARDS survivors from four academic tertiary care ICUs in Toronto, Canada, and prospectively monitored them from ICU admission to 2 yr after ICU discharge.Measurements: Clinical and functional outcomes, health care use, and direct medical costs.Results: Eighty-five percent of patients with ARDS discharged from the ICU survived to 2 yr; overall 2-yr mortality was 49%. At 2 yr, survivors continued to have exercise limitation although 65% had returned to work. There was no statistically significant improvement in health-related quality of life as measured by Short-Form General Health Survey between 1 and 2 yr, although there was a trend toward better physical role at 2 yr (p = 0.0586). Apart from emotional role and mental health, all other domains remained below that of the normal population. From ICU admission to 2 yr after ICU discharge, the largest portion of health care costs for a survivor of ARDS was the initial hospital stay, with ICU costs accounting for 76% of these costs. After the initial hospital stay, health care costs were related to hospital readmissions and inpatient rehabilitation.Conclusions: Survivors of ARDS continued to have functional impairment and compromised health-related quality of life 2 yr after discharge from the ICU. Health care use and costs after the initial hospitalization were driven by hospital readmissions and inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW: Pulmonary vasodilators are important in the management of pulmonary hypertension. Although systemic vasodilators may be effective in lowering pulmonary artery pressure, systemic vasodilation is the main limitation to dose titration. This review summarizes the latest research and developments in pulmonary vasodilators in the management of acute and chronic pulmonary hypertension. RECENT FINDINGS: Nitric oxide, the prototype of selective pulmonary vasodilators, remains an effective option in the management of pulmonary hypertension; however, cost and complexity of administration have led to consideration of other pulmonary vasodilators. Animal research suggests that nitric oxide may have an important role in the prevention of pulmonary hypertension after cardiopulmonary bypass. Experience with phosphodiesterase inhibitors, as monotherapy or as part of combination therapy, suggests that these agents improve cardiopulmonary hemodynamics and can be considered as alternatives and/or adjuncts to nitric oxide. Prostacyclins are a versatile class of pulmonary vasodilator as they have been shown to improve pulmonary hemodynamics administered intravenously or via inhalation. Endothelin receptor antagonists have been shown to be effective for long-term management of pulmonary hypertension. Several gene therapy strategies are currently undergoing evaluation. SUMMARY: Selective pulmonary vasodilation can be achieved through delivery of vasodilators directly to the lungs or targeting pulmonary specific processes. Several therapeutic options are available that demonstrate selectivity for the pulmonary vasculature. These agents can facilitate optimization of cardiopulmonary hemodynamics. [ABSTRACT FROM AUTHOR]

Background: As more patients survive the acute respiratory distress syndrome, an understanding of the long-term outcomes of this condition is needed.Methods: We evaluated 109 survivors of the acute respiratory distress syndrome 3, 6, and 12 months after discharge from the intensive care unit. At each visit, patients were interviewed and underwent a physical examination, pulmonary-function testing, a six-minute-walk test, and a quality-of-life evaluation.Results: Patients who survived the acute respiratory distress syndrome were young (median age, 45 years) and severely ill (median Acute Physiology, Age, and Chronic Health Evaluation score, 23) and had a long stay in the intensive care unit (median, 25 days). Patients had lost 18 percent of their base-line body weight by the time they were discharged from the intensive care unit and stated that muscle weakness and fatigue were the reasons for their functional limitation. Lung volume and spirometric measurements were normal by 6 months, but carbon monoxide diffusion capacity remained low throughout the 12-month follow-up. No patients required supplemental oxygen at 12 months, but 6 percent of patients had arterial oxygen saturation values below 88 percent during exercise. The median score for the physical role domain of the Medical Outcomes Study 36-item Short-Form General Health Survey (a health-related quality-of-life measure) increased from 0 at 3 months to 25 at 12 months (score in the normal population, 84). The distance walked in six minutes increased from a median of 281 m at 3 months to 422 m at 12 months; all values were lower than predicted. The absence of systemic corticosteroid treatment, the absence of illness acquired during the intensive care unit stay, and rapid resolution of lung injury and multiorgan dysfunction were associated with better functional status during the one-year follow-up.Conclusions: Survivors of the acute respiratory distress syndrome have persistent functional disability one year after discharge from the intensive care unit. Most patients have extrapulmonary conditions, with muscle wasting and weakness being most prominent. [ABSTRACT FROM AUTHOR]

Background: There is controversy surrounding the effectiveness of red blood cell (RBC) transfusion for treating anemia in patients hospitalized for acute coronary syndromes (ACS), particularly as hemoglobin levels (Hb) approach and drop below the range of moderate anemia., Methods: This population-based cohort study followed all adults hospitalized for ACS who experienced an in-hospital nadir Hb between 6.0-8.9g/dL between April 1, 2012 to March 31, 2021 in Ontario, Canada. Patients were excluded if they underwent coronary artery bypass graft surgery or had history of dementia, palliative care, or long-term care. Transfused patients were compared to non-transfused patients. The primary outcome was a composite of all-cause death and hospitalization for myocardial infarction (MI) within 30-days of hospital discharge. Overlap propensity score weighting was used to account for confounding and to emphasize the comparison in patients for whom there is clinical equipoise., Results: This study included 7,922 patients, of whom 3,498 were transfused and 4,424 were not transfused. In the propensity weighted cohort, the mean nadir Hb for each group was 7.75g/dL. The 30-day cumulative incidence rate for the primary outcome after application of propensity score weights was 28.6% in the transfusion group and 33.3% in the no-transfusion group (hazard ratio [HR]: 0.83, 95% confidence interval [CI] 0.75-0.91), which persisted at 1-year after hospital discharge and across sensitivity analyses., Conclusions: In patients hospitalized for ACS who experience nadir Hb levels between 6.0-8.9g/dL, RBC transfusion was associated with a reduction in the composite event of all-cause death and hospitalization for MI within 30-days after hospital discharge., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury., Methods: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65 mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m 2 ) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72 h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19)., Findings: Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n = 45) and 39.8% (n = 35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p = 0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3 mL/min/1.73 m 2 , 90% CI 0.51-8.12, p = 0.06; and MAKE 6.7% (n = 6) vs 15.9% (n = 14); RR: 0.41, 90% CI: 0.19, 0.88, p = 0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group)., Interpretation: In this proof-of-concept study, RMC-035 did not reduce AKI 72 h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes., Funding: Guard Therapeutics., Competing Interests: AZ received consulting and lecture fees and grants from German Research Foundation, BioMerieux, Baxter, Fresenius, Paion, Viatris, Bayer, Novartis, AM Pharma, and Alexion, received meeting and travel support from Sphingotec and held leadership and fiduciary roles at the German Interdisciplinary Association for Intensive and Emergency Medicine, the International Anesthesia Research Society and the journal “Der Anästhesist”. JLK received consulting fees from Biomerieux, Baxter, Alexion, SeaStar, Novartis, Guard Therapeutics and research funding from the NIH, Fresenius Medical and Biomerieux. TEL is a shareholder and employee of Guard Therapeutics. MR holds stock options and is a paid consultant to Guard Therapeutics. CDM received consulting fees from Alexion. AB was past-president of the German society for heart, thorax and vascular surgery, served on the DSMB for the INCREASE study and received consulting, lecture and advisory board fees from Guard Therapeutics, Marizyme, Abbott, and Abiomed, Data Monitoring Committee payments from Amopharma and patient fees from Guard Therapeutics. JoB received travel costs payments from Guard Therapeutics for an investigator meeting. DE is president of the ERAS Cardiac Society and was a member of Data Safety Monitoring Boards/Advisory Boards for Arthrex, Edwards Lifescience, Medella, Atricure, Pharmacosmos, Renibus, Alexion, and Genentech. AM, BdV, JaB, KM, ML, MT and NN declare no competing interests., (© 2024 The Author(s).)

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure., Objective: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function., Methods: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader., Results: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m 2 , minimum LA volume 11.1 ± 5.7mL/m 2 ) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m 2 , minimum LA volume 12.6 ± 5.0mL/m 2 ) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m 2 (95% CI: -1.7 to 3.7 mL/m 2 ; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m 2 (95% CI: -0.9 to 2.6 mL/m 2 ; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference - 0.01 (95% CI: -0.05 to 0.03, p = 0.59)., Conclusion: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970)., (© 2024. The Author(s).)

Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p -value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p -value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD.

Background: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia., Methods: Seventy statin-treated individuals with triglycerides ≥1.50 and <5.6 mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDH hi ) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The primary endpoint was the change in frequency of pro-vascular ALDH hi side scatter (SSC) low CD133 + progenitor cells. Change in frequencies of ALDH hi SSC mid monocyte and ALDH hi SSC hi granulocyte precursor subsets, reactive oxygen species production, serum biomarkers, and omega-3 levels were also evaluated., Findings: Baseline characteristics, cardiovascular risk factors, and medications were balanced between the groups. Compared to usual care, IPE increased the mean frequency of ALDH hi SSC low CD133 + cells (-1.00% ± 2.45% vs. +7.79% ± 1.70%; p = 0.02), despite decreasing overall ALDH hi SSC low cell frequency. IPE assignment also reduced oxidative stress in ALDH hi SSC low progenitors and increased ALDH hi SSC hi granulocyte precursor cell content., Conclusions: IPE-PREVENTION CardioLink-14 provides the first translational evidence that IPE can modulate VR cell content and suggests a novel mechanism that may underlie the cardioprotective effects observed with IPE in REDUCE-IT., Funding: HLS Therapeutics provided the IPE in kind and had no role in the study design, conduct, analyses, or interpretation., Competing Interests: Declaration of interests D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures, Hims, SFJ, and Youngene; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold & Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, who is assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo. B.B. reports receiving speaking honoraria from HLS Therapeutics and Pfizer. K.A.T. reports receiving honoraria and serving on the advisory boards for AbbVie, Allergan, Amgen, Astellas, Aspen, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lily, GlaxoSmithKline, Humber River Health, Lundbeck, Moderna, Novo Nordisk, Novartis, Pfizer, Takeda, and Eli Lily. E.J.F. is an employee of HLS Therapeutics. T.S.K. reports receiving honoraria from Abbott, Amgen, AstraZeneca, Bausch, Boehringer Ingelheim, the Canadian Medical and Surgical Knowledge Translation Research Group, the CPD Network Association, Eli Lily Canada, Janssen, Novo Nordisk Canada, and Sutherland Global Services Canada ULCA . He has served on advisory boards for Amgen, Eli Lily Canada, and Novo Nordisk. C.D.M. is supported by a Merit Award from the University of Toronto Department of Anesthesiology and Pain Medicine, holds the Cara Phelan Chair in Critical Care at St. Michael’s Hospital-Unity Health Toronto, and reports advisory board honoraria/consulting fees from Amgen, AstraZeneca, BioAge, Boehringer Ingelheim, and PhaseBio and DSMB stipends from Beth Israel Deaconess Medical Center, Cerus, and Takeda. L.A.L. has received research funding from, has provided CME on behalf of, and/or has acted as an adviser to Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Kowa, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. H.T. reports personal fees from the Canadian Medical and Surgical Knowledge Translation Research Group. S.V. holds a Tier 1 Canada Research Chair in Cardiovascular Surgery and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, and S&L Solutions; he is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine the association of intraoperative pulmonary artery catheter (PAC) use with in-hospital outcomes in cardiac surgical patients., Methods: MEDLINE, Embase, and Cochrane Library (Wiley) databases were screened for studies that compared cardiac surgical patients receiving intraoperative PAC with controls and reporting in-hospital mortality. Secondary outcomes included intensive care unit length of stay, cost of hospitalization, fluid volume administered, intubation time, inotropes use, acute kidney injury (AKI), stroke, myocardial infarction (MI), and infections., Results: Seven studies (25 853 patients, 88.6% undergoing coronary artery bypass graft surgery) were included. In-hospital mortality was significantly increased with PAC use [odds ratio (OR) 1.57; 95% confidence interval (CI) 1.12-2.20, P = 0.04]; PAC use was also associated with greater intraoperative inotrope use (OR 2.61; 95% CI 1.54-4.41) and costs [standardized mean difference (SMD) = 0.20; 95% CI 0.16-0.23], longer intensive care unit stay (SMD = 0.29; 95% CI 0.25-0.33), and longer intubation time (SMD = 0.44; 95% CI 0.12-0.76)., Conclusions: PAC use is associated with significantly increased odds of in-hospital mortality, but the amount and quality of the available evidence is limited. Prospective randomized trials testing the effect of PAC on the outcomes of cardiac surgical patients are urgently needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po 2 (P Br o 2 ) in a rat model. Changes in P Br o 2 (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, n = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at P < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; P = 0.014) and P Br o 2 (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; P < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in P Br o 2 (15.0 ± 6.3 mmHg, P = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, P = 0.003) that likely contributed to the observed reduction in P Br o 2 . This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, P < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved P Br o 2 . These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize P Br o 2 during acute anemia. NEW & NOTEWORTHY This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain Po 2 (P Br o 2 ), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in P Br o 2 , accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining P Br o 2 and initiating the increase in CO that optimized brain perfusion during acute anemia.

Sodium-glucose cotransporters 2 (SGLT2) are high-capacity, low-affinity transporters, expressed mainly in the early portion of the proximal renal tube, mediating up to 90% of renal glucose uptake, while SGLT1 receptors are found mainly in the small intestine, facilitating glucose absorption. SGLT2 inhibitors (SGLT2i) originally emerged as agents for the treatment of type 2 diabetes mellitus; however, they soon demonstrated remarkable cardio- and renoprotective actions that led to their licensed use for the treatment of heart failure and chronic kidney disease, regardless of the diabetic status. Cardiovascular remodelling represents an umbrella term that encompasses changes that occur in the cardiovascular system, from the molecular and cellular level, to tissue and organs after local injury, chronic stress, or pressure. SGLT modulation has been shown to positively affect many of these molecular and cellular changes observed during pathological remodelling. Among the different pathophysiological mechanisms that contribute to adverse remodelling, various stem and progenitor cells have been shown to be involved, through alterations in their number or function. Recent studies have examined the effects of SGLT2i on stem and progenitor cell populations and more specifically on endothelial progenitor cells (EPCs). Although some found no significant effect, others showed that SGLT2i can modulate the morphology and function of EPCs. These preliminary observations of the effect of SGLT2i on EPCs may be responsible for some of the beneficial effects of gliflozins on pathological remodelling and, by extension, on cardiovascular disease. The purpose of this narrative review is to critically discuss recent evidence on the cardioprotective effects of SGLT2is, in the context of cardiac remodelling., Competing Interests: TK has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, and Novo Nordisk, for advisory boards from Novo Nordisk and Boehringer Ingelheim, and has participated in sponsored studies by Eli-Lilly and Novo Nordisk. C. David Mazer reports advisory board honoraria and/or consulting fees from Amgen, AstraZeneca, BioAge, Boehringer Ingelheim, Cardior, PhaseBio and Sandoz; and reports stipends for serving on the Data and Safety Monitoring Board of Beth Israel Deaconess Medical Center, Cerus, and Takeda; Dr. Mazer is supported by a merit award from the University of Toronto Department of Anesthesiology, and holds the Cara Phelan Chair in Critical Care at St. Michael’s Hospital. TMS, KCC, FM, DM, DK have no conflicts of interest to report., (© 2024 The Author(s). Published by IMR Press.)

Modulation of the renin-angiotensin-aldosterone system is a foundation of therapy for cardiovascular and kidney diseases. Excess aldosterone plays an important role in cardiovascular disease, contributing to inflammation, fibrosis, and dysfunction in the heart, kidneys, and vasculature through both genomic and mineralocorticoid receptor (MR)-mediated as well as nongenomic mechanisms. MR antagonists have been a key therapy for attenuating the pathologic effects of aldosterone but are associated with some side effects and may not always adequately attenuate the nongenomic effects of aldosterone. Aldosterone is primarily synthesized by the CYP11B2 aldosterone synthase enzyme, which is very similar in structure to other enzymes involved in steroid biosynthesis including CYP11B1, a key enzyme involved in glucocorticoid production. Lack of specificity for CYP11B2, off-target effects on the hypothalamic-pituitary-adrenal axis, and counterproductive increased levels of bioactive steroid intermediates such as 11-deoxycorticosterone have posed challenges in the development of early aldosterone synthase inhibitors such as osilodrostat. In early-phase clinical trials, newer aldosterone synthase inhibitors demonstrated promise in lowering blood pressure in patients with treatment-resistant and uncontrolled hypertension. It is therefore plausible that these agents offer protection in other disease states including heart failure or chronic kidney disease. Further clinical evaluation will be needed to clarify the role of aldosterone synthase inhibitors, a promising class of agents that represent a potentially major therapeutic advance.

Background: This exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes., Methods: Cerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated., Results: Total cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004)., Conclusions: The innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: South Asian individuals shoulder a disproportionate burden of cardiometabolic diseases., Objectives: The purpose of this study was to determine if vascular regenerative cell content varies significantly between South Asian and White European people., Methods: Between January 2022 and January 2023, 60 South Asian and 60 White European adults with either documented cardiovascular disease or established diabetes with ≥1 other cardiovascular risk factor were prospectively enrolled. Vascular regenerative cell content in venous blood was enumerated using a flow cytometry assay that is based on high aldehyde dehydrogenase (ALDH hi ) activity and cell surface marker phenotyping. The primary outcome was the difference in frequency of circulating ALDH hi progenitor cells, monocytes, and granulocytes between the 2 groups., Results: Compared with White European participants, those of South Asian ethnicity were younger (69 ± 10 years vs 66 ± 9 years; P < 0.05), had lower weight (88 ± 19 kg vs 75 ± 13 kg; P < 0.001), and exhibited a greater prevalence of type 2 diabetes (62% vs 92%). South Asian individuals had markedly lower circulating frequencies of pro-angiogenic ALDH hi SSC low CD133 + progenitor cells (P < 0.001) and ALDH hi SSC mid CD14 + CD163 + monocytes with vessel-reparative capacity (P < 0.001), as well as proportionally more ALDH hi progenitor cells with high reactive oxygen species content (P < 0.05). After correction for sex, age, body mass index, and glycated hemoglobin, South Asian ethnicity was independently associated with lower ALDH hi SSC low CD133 + cell count., Conclusions: South Asian people with cardiometabolic disease had less vascular regenerative and reparative cells suggesting compromised vessel repair capabilities that may contribute to the excess vascular risk in this population. (The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion [ORIGINS-RCE]; NCT05253521)., Competing Interests: Funding Support and Author Disclosures The ORIGINS-RCE (The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion) study was supported in part by a Heart and Stroke Foundation of Canada Research Grant (G-23-0035127) to Dr Verma and Dr Hess and a Canadian Institute of Health Research Grant (MOP no. 379189) to Dr Hess. Dr Teoh has received personal fees from the Canadian Medical and Surgical Knowledge Translation Research Group. Dr Connelly holds the Keenan Chair in Research Leadership at St Michael’s Hospital and University of Toronto; is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure; has received research grants to his institution from AstraZeneca, Boehringer Ingelheim, and Servier; has received support for travel to scientific meetings from Boehringer Ingelheim; and has received honoraria for speaking engagements and ad hoc participation in Advisory Boards from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, and Servier. Dr Mazer is supported by a Merit Award from the University of Toronto Department of Anesthesiology and Pain Medicine; holds the Cara Phelan Chair in Critical Care at St Michael’s Hospital-Unity Health Toronto; has received Advisory Board honoraria/consulting fees from Amgen, AstraZeneca, BioAge, Biotest, Boehringer Ingelheim, Cardior, Cytosorbents, PhaseBio, Sandoz, and Trimedic Therapeutics; and has received Data Safety Monitoring Board stipends from Beth Israel Deaconess Medical Center, Cerus, and Takeda. Dr Bhatt has served on the Advisory Board for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier PracticeUpdate Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the Board of Directors for Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; was the inaugural chair of the American Heart Association Quality Oversight Committee; has served as a consultant for Broadview Ventures and Hims; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo, and for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT trial); has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, American College of Cardiology Accreditation Oversight Committee), Arnold and Porter law firm (for work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, RE-DUAL PCI Clinical Trial Steering Committee funded by Boehringer Ingelheim, AEGIS-II Executive Committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (Clinical Trial Steering Committees), Cowen and Company, Duke Clinical Research Institute (Clinical Trial Steering Committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (Continuing Medical Education [CME] Steering Committees), MJH Life Sciences, Oakstone CME (course director, “Comprehensive Review of Interventional Cardiology”), Piper Sandler, Population Health Research Institute (for the COMPASS Operations Committee, Publications Committee, Steering Committee, and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME Steering Committees), and Wiley (Steering Committee); has served as deputy editor of Clinical Cardiology, chair of the National Cardiovascular Data Registry ACTION Registry Steering Committee, and chair of the Veterans Affairs Cardiovascular Assessment, Reporting, and Tracking Research and Publications Committee; holds a patent for sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (editor, Braunwald’s Heart Disease); has served as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo and Takeda. Dr McGuire has received research support for Clinical Trials Leadership from AstraZeneca, Boehringer Ingelheim, CSL Behring, Esperion, Lilly USA, Lexicon, Merck & Co, Novo Nordisk, Pfizer, and Sanofi; and has received honoraria for consultancy from Altimmune, Applied Therapeutics, Bayer, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Intercept, Lilly USA, Merck & Co, Novo Nordisk, and Sanofi. Dr Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; has received research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, EOCI Pharmacomm Ltd, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, S&L Solutions, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; and is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment., Methods: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity., Results: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes., Conclusions: The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients., (© 2023. The Author(s).)

Background: This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity., Methods: EMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals., Results: Compared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m 2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m 2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (P interaction  = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction., Conclusions: There was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016)., (© 2023. The Author(s).)

Sodium glucose-cotransporter 2 (SGLT2) inhibitors have been reported to reduce cardiovascular events and heart failure in people with and without diabetes. These medications have been shown to counter regenerative cell exhaustion in the context of prevalent diabetes. This study sought to determine if empagliflozin attenuates regenerative cell exhaustion in people without diabetes. Peripheral blood mononuclear cells were collected at the baseline and 6-mo visits from individuals randomized to receive empagliflozin (10 mg/day) or placebo who were participating in the EMPA-HEART 2 CardioLink-7 trial. Precursor cell phenotypes were characterized by flow cytometry for cell-surface markers combined with high aldehyde dehydrogenase activity to identify precursor cell subsets with progenitor (ALDH hi ) versus mature effector (ALDH low ) cell attributes. Samples from individuals assigned to empagliflozin ( n = 25) and placebo ( n = 21) were analyzed. At baseline, overall frequencies of primitive progenitor cells (ALDH hi SSC low ), monocyte (ALDH hi SSC mid ), and granulocyte (ALDH hi SSC hi ) precursor cells in both groups were similar. At 6 mo, participants randomized to empagliflozin demonstrated increased ALDH hi SSC low CD133 + CD34 + proangiogenic cells ( P = 0.048), elevated ALDH hi SSC mid CD163 + regenerative monocyte precursors ( P = 0.012), and decreased ALDH hi SSC mid CD86  +  CD163 - proinflammatory monocyte ( P = 0.011) polarization compared with placebo. Empagliflozin promoted the recovery of multiple circulating provascular cell subsets in people without diabetes suggesting that the cardiovascular benefits of SGLT2 inhibitors may be attributed in part to the attenuation of vascular regenerative cell exhaustion that is independent of diabetes status. NEW & NOTEWORTHY Using an aldehyde dehydrogenase (ALDH) activity-based flow cytometry assay, we found that empagliflozin treatment for 6 mo was associated with parallel increases in circulating vascular regenerative ALDH hi -CD34/CD133-coexpressing progenitors and decreased proinflammatory ALDH hi -CD14/CD86-coexpressing monocyte precursors in individuals without diabetes but with cardiovascular risk factors. The rejuvenation of the vascular regenerative cell reservoir may represent a mechanism via which sodium glucose-cotransporter 2 (SGLT2) inhibitors limit maladaptive repair and delay the development and progression of cardiovascular diseases.

Purpose of Review: Anemia is prevalent in patients with acute coronary syndromes. In this setting, there is uncertainty and controversy surrounding the optimal transfusion strategy for managing anemia. The goal of this review is to summarize the current clinical evidence, guidelines, and future directions for managing transfusion in acute coronary syndromes., Recent Findings: There is limited evidence from randomized trials evaluating restrictive versus liberal transfusion in patients hospitalized with and/or for acute coronary syndromes. The results from these studies suggest clinical equipoise between transfusion strategies for short term outcomes, and a trend toward favoring a liberal strategy for long term major adverse cardiac events. There is inconsistency across clinical practice guidelines with respect to the optimal strategy for managing anemia and transfusion in acute coronary syndromes due to insufficient evidence., Summary: More evidence is urgently needed to conclusively establish the optimal strategy for transfusion management in the setting of acute coronary syndromes. These data will directly inform harmonization of clinical practice guidelines. Future investigations should explore alternative strategies to hemoglobin for quantifying the degree of anemic stress for personalizing transfusion therapy, the effects on functional outcomes, and managing anemia following hospital discharge., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study evaluated the use of a wearable, patch-based cardiac rhythm monitoring device in detecting postoperative atrial fibrillation (POAF) among cardiac surgical patients within 30 days after hospital discharge., Description: From the SEARCH-AF (The Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation) CardioLink-1 trial, this study examined rates of POAF according to surgery type and the incremental value of continuous cardiac rhythm monitoring among patients who underwent valve surgery. The primary outcome was cumulative atrial fibrillation or atrial flutter lasting for ≥6 minutes detected by continuous monitoring or atrial fibrillation or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization., Evaluation: The primary outcome occurred in 8.2%, 13.5%, and 21.2% of patients who underwent isolated coronary artery bypass grafting (CABG), isolated valve surgery, and combined CABG and valve surgery. Relative to patients who underwent isolated CABG, those patients who had valve surgery were more likely to experience POAF. A higher diagnostic yield was obtained when the patch-based cardiac rhythm monitor was applied in patients who underwent valve surgery., Conclusions: Use of a wearable, patch-based cardiac monitoring device was an effective detection strategy among patients undergoing valve surgery, given their higher risk of developing POAF., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits., Methods: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality., Results: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I 2 =72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I 2 =13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I 2 =35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I 2 =98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality)., Conclusions: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine., Systematic Review Protocol: PROSPERO CRD42019128144., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898., Competing Interests: RSK reports receiving grants from the NIH, speaker honorarium from the Cardiothoracic Research and Education Forum, and reports membership on an advisory board for Bio Products Laboratory. DF reports receiving grants financed by the Erasmus+ program, lecture; honoraria from Werfen Instrumentation Laboratory Comp., the American Society of Anesthesiology, University of Continuing Education Krems, Department for Health Sciences, Medicine and Research, Austria; leadership roles World Federation of Societies of Anesthesiologists, the Romanian Society of Anesthesia and Intensive Care, and European Sepsis Alliance; and has received equipment from Vifor Pharma Romania. AJG reports receiving consulting fees and honoraria from Edwards Lifesciences, and is a non-remunerated member of the executive board for the Society for Enhanced Recovery after Cardiac Surgery. JDL reports receiving grants or contracts from Edwards Lifesciences and the CTSA Seed Grant. SV holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, EOCI Pharmacomm Ltd, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. CDM reports advisory board honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, BioAge and PhaseBio; and DSMB honoraria from Cerus and Takeda. All other authors declare no competing interests., (© 2023.)

Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol (LDL-C) is still unclear. Recently in The Lancet, Ridker et al. demonstrated that residual inflammatory risk was a stronger predictor of fatal and non-fatal events compared to residual cholesterol risk, supporting the concept of inflammation testing to guide vascular risk reduction., Competing Interests: Declaration of interests S.V. is a national leader for the ZEUS trial and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S&L Solutions, and Sanofi; S.V. is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. C.D.M. reports advisory board honoraria/consulting fees from Amgen, AstraZeneca, BioAge, Biotest, Boehringer Ingelheim, Cytosorbents and PhaseBio and DSMB stipends from Beth Israel Deaconess Medical Center, Cerus, and Takeda. K.A.C. is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure and reports receiving research grants to his institution from AstraZeneca, Boehringer Ingelheim, and Servier; support for travel to scientific meetings from Boehringer Ingelheim; and honoraria for speaking engagements and ad hoc participation in advisory boards from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, and Servier., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: In the Canadian Mitral Research Alliance (CAMRA) Trial CardioLink-2 leaflet resection versus preservation techniques for posterior leaflet prolapse was investigated and no difference was shown in their effect on mean mitral gradient at peak exercise at 12 months postoperatively. The purpose of this subanalysis was to evaluate the effect of the 2 strategies on left ventricular (LV) reverse remodeling after repair., Methods: A total of 104 patients were randomized to either a leaflet resection or leaflet preservation strategy. Echocardiograms, performed at baseline (preoperative), predischarge, and 12 months postoperatively, were analyzed in a blinded fashion at a core laboratory., Results: All patients underwent successful mitral repair. At discharge, 3 patients showed moderate mitral regurgitation, whereas the remainder showed mild or less regurgitation. Compared with the baseline echocardiogram, the indexed end diastolic volume was reduced at the discharge echocardiogram (P < .0001) and was further reduced at the 12-month echocardiogram (P = .01). In contrast, the indexed end systolic volume did not significantly change from baseline assessed at the predischarge echocardiogram (P = .32) but improved at 12 months postoperatively (P < .0001), resulting in a corresponding improvement in ejection fraction at 12 months (P < .0001). The type of mitral repair strategy had no significant effect on LV reverse remodeling trends., Conclusions: The mitral repair strategies used did not influence postoperative LV reverse remodeling, which occurred in stages. Although LV end diastolic dimensions recovered before discharge, improvements in LV end systolic dimension were evident 12 months after repair., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)