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Circulation
Lippincott Williams & Wilkins
Circulation

Lippincott Williams & Wilkins

0009-7322

Circulation/Journal CirculationSCIAHCIISTP
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    Collab, Virtualize, Democratize: A Conversation With the Founders of CardioNerds

    Farr, Maryjane
    7页
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Should Polypills Be Used for Heart Failure With Reduced Ejection Fraction?

    Pandey, AmbarishKeshvani, NeilWang, Thomas J.
    3页
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Effects of Empagliflozin on Symptoms, Physical Limitations, and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial

    Kosiborod, Mikhail N.Angermann, Christiane E.Collins, Sean P.Teerlink, John R....
    10页
    查看更多>>摘要：BACKGROUND: Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized). METHODS: Patients hospitalized for acute heart failure were randomized to empagliflozin 10 mg daily or placebo for 90 days. The KCCQ was assessed at randomization and 15, 30, and 90 days. The effects of empagliflozin on the primary end point of clinical benefit (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in KCCQ Total Symptom Score [TSS] change from baseline to 90 days) were examined post hoc across the tertiles of baseline KCCQ-TSS. In prespecified analyses, changes (randomization to day 90) in KCCQ domains, including TSS, physical limitations, quality of life, clinical summary, and overall summary scores were evaluated using a repeated measures model. RESULTS: In total, 530 patients were randomized (265 each arm). Baseline KCCQ-TSS was low overall (mean [SD], 40.8 [24.0] points). Empagliflozin-treated patients experienced greater clinical benefit across the range of KCCQ-TSS, with no treatment effect heterogeneity (win ratio [95% CIs] from lowest to highest tertile: 1.49 [1.01-2.20], 1.37 [0.94-1.99], and 1.48 [1.00-2.20], respectively; P for interaction=0.94). Beneficial effects of empagliflozin on health status were observed as early as 15 days and persisted through 90 days, at which point empagliflozin-treated patients experienced a greater improvement in KCCQ TSS, physical limitations, quality of life, clinical summary, and overall summary (placebo-adjusted mean differences [95% CI]: 4.45 [95% CI, 0.32-8.59], P=0.03; 4.80 [95% CI, 0.00-9.61], P=0.05; 4.66 [95% CI, 0.32-9.01], P=0.04; 4.85 [95% CI, 0.77-8.92], P=0.02; and 4.40 points [95% CI, 0.33-8.48], P=0.03, respectively). CONCLUSIONS: Initiation of empagliflozin in patients hospitalized for acute heart failure produced clinical benefit regardless of the degree of symptomatic impairment at baseline, and improved symptoms, physical limitations, and quality of life, with benefits seen as early as 15 days and maintained through 90 days.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)

    Schulze, P. ChristianBogoviku, JuergenWestphal, JulianAftanski, Pawel...
    10页
    查看更多>>摘要：BACKGROUND: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. METHODS: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51 +/- 19 versus 54 +/- 17 mL/min per 1.73 m(2); P=0.599) or injury (total urinary protein, 492 +/- 845 versus 503 +/- 847 mg/g creatinine; P=0.975; and urinary a1-microglobulin, 55.4 +/- 38.6 versus 31.3 +/- 33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups. CONCLUSIONS: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    SGLT2 Inhibitors: From Antihyperglycemic Agents to All-Around Heart Failure Therapy

    Anker, Stefan D.Usman, Muhammad ShariqButler, Javed
    4页
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial

    Fang, HaiXie, GaoqiangLin, Pao-HwaChen, Junshi...
    13页
    查看更多>>摘要：Background: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. Methods: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. Results: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5 +/- 9.8 years, and mean SBP and diastolic blood pressure of 139.4 +/- 8.3 and 88.1 +/- 8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. Conclusions: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Identification of Pathogenic Immune Cell Subsets Associated With Checkpoint Inhibitor-Induced Myocarditis

    Zhu, HanGaldos, Francisco X.Lee, DanielWaliany, Sarah...
    20页
    查看更多>>摘要：Background: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have the potential to cause immune-related adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Histologically, patients with ICI myocarditis have lymphocytic infiltrates in the heart, implicating T cell-mediated mechanisms. However, the precise pathological immune subsets and molecular changes in ICI myocarditis are unknown. Methods: To identify immune subset(s) associated with ICI myocarditis, we performed time-of-flight mass cytometry on peripheral blood mononuclear cells from 52 individuals: 29 patients with autoimmune adverse events (immune-related adverse events) on ICI, including 8 patients with ICI myocarditis, and 23 healthy control subjects. We also used multiomics single-cell technology to immunophenotype 30 patients/control subjects using single-cell RNA sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes by sequencing with feature barcoding for surface marker expression confirmation. To correlate between the blood and the heart, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing on MRL/Pdcd1(-/-) (Murphy Roths large/programmed death-1-deficient) mice with spontaneous myocarditis. Results: Using these complementary approaches, we found an expansion of cytotoxic CD8(+) T effector cells re-expressing CD45RA (Temra CD8(+) cells) in patients with ICI myocarditis compared with control subjects. T-cell receptor sequencing demonstrated that these CD8(+) Temra cells were clonally expanded in patients with myocarditis compared with control subjects. Transcriptomic analysis of these Temra CD8(+) clones confirmed a highly activated and cytotoxic phenotype. Longitudinal study demonstrated progression of these Temra CD8(+) cells into an exhausted phenotype 2 months after treatment with glucocorticoids. Differential expression analysis demonstrated elevated expression levels of proinflammatory chemokines (CCL5/CCL4/CCL4L2) in the clonally expanded Temra CD8(+) cells, and ligand receptor analysis demonstrated their interactions with innate immune cells, including monocytes/macrophages, dendritic cells, and neutrophils, as well as the absence of key anti-inflammatory signals. To complement the human study, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing in Pdcd1(-/-) mice with spontaneous myocarditis and found analogous expansions of cytotoxic clonal effector CD8(+) cells in both blood and hearts of such mice compared with controls. Conclusions: Clonal cytotoxic Temra CD8(+) cells are significantly increased in the blood of patients with ICI myocarditis, corresponding to an analogous increase in effector cytotoxic CD8(+) cells in the blood/hearts of Pdcd1(-/-) mice with myocarditis. These expanded effector CD8(+) cells have unique transcriptional changes, including upregulation of chemokines CCL5/CCL4/CCL4L2, which may serve as attractive diagnostic/therapeutic targets for reducing life-threatening cardiac immune-related adverse events in ICI-treated patients with cancer.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    An Immune Checkpoint Inhibitor Heart: How CD45RA(+) Effector Memory CD8(+) T Cells (Temra) Are Implicated in Immune Checkpoint Inhibitor Myocarditis

    Kallikourdis, MarinosCondorelli, Gianluigi
    3页
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Management of Atrial Fibrillation Across the Spectrum of Heart Failure With Preserved and Reduced Ejection Fraction

    Reddy, Yogesh N., VBorlaug, Barry A.Gersh, Bernard J.
    19页
    查看更多>>摘要：Atrial fibrillation (AF) is the most common arrhythmia among patients with heart failure (HF), and HF is the most common cause of death for patients presenting with clinical AF. AF is frequently associated with pathological atrial myocardial dysfunction and remodeling, a triad that has been called atrial myopathy. AF can be the cause or consequence of clinical HF, and the directionality varies between individual patients and across the spectrum of HF. Although initial trials suggested no advantage for a systematic rhythm control strategy in HF with reduced ejection fraction, recent data suggest that select patients may benefit from attempts to maintain sinus rhythm with catheter ablation. Preliminary data also show a close relationship among AF, left atrial myopathy, mitral regurgitation, and HF with preserved ejection, with potential clinical benefits to catheter ablation therapy. The modern management of AF in HF also requires consideration of the degree of atrial myopathy and chronicity of AF, in addition to the pathogenesis and phenotype of the underlying left ventricular HF. In this review, we summarize the contemporary management of AF and provide practical guidance and areas in need of future investigation.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Effect of Empagliflozin on Kidney Biochemical and Imaging Outcomes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)

    Lee, Matthew M. Y.Gillis, Keith A.Brooksbank, Katriona J. M.Allwood-Spiers, Sarah...
    4页
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins