Cardiology

Généreux, P., Piazza, N., Alu, M.C., Nazif, T., Hahn, R.T., Pibarot, P., Bax, J.J., Leipsic, J.A., Blanke, P., Blackstone, E.H., Finn, M.T., Kapadia, S., Linke, A., Mack, M.J., Makkar, R., Mehran, R., Popma, J.J., Reardon, M., Rodes-Cabau, J., Van Mieghem, N.M., Webb, J.G., Cohen, D.J. and Leon, M.B. (2021). “Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.” Eur Heart J 42(19): 1825-1857.

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AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Kirschner, S.K., Deutz, N.E.P., Rijnaarts, I., Smit, T.J., Larsen, D.J. and Engelen, M. (2021). “Impaired intestinal function is associated with lower muscle and cognitive health and well-being in patients with congestive heart failure.” JPEN J Parenter Enteral Nutr May 22. [Epub ahead of print].

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BACKGROUND: Small and large intestinal perturbations have been described as prevalent extracardiac systemic manifestations in Congestive Heart Failure (CHF) but alterations in protein digestion and absorption and plasma short-chain fatty acid concentrations (SCFA), and the potential link with other systemic effects (e.g. lower muscle and cognitive health and well-being) have not been investigated in these patients. METHODS: We analyzed protein digestion and absorption with dual stable tracer method in 14 clinically stable, non-cachectic CHF outpatients (mean left-ventricular ejection fraction: 35.5 (95% CI [30.9, 40.1])% and 15 controls. Small intestinal non-carrier-mediated permeability and active carrier-mediated glucose transport were quantified by sugar permeability test. Plasma SCFA (acetate, propionate, butyrate, isovalerate, valerate) concentrations were measured as intestinal microbial metabolites. Muscle function was assessed by isokinetic dynamometry, cognition by a battery of tests, and well-being by questionnaire. RESULTS: Protein digestion and absorption were impaired by 29.2% (P = 0.001) and active glucose transport by 38.4% (P = 0.010) in CHF. Non-carrier-mediated permeability was not altered. While plasma propionate, butyrate and isovalerate concentrations were lower in CHF (P<0.05), acetate and valerate concentrations did not differ. Overall, intestinal dysfunction was associated with impaired leg muscle quality, emotional distress, and reduced cognitive function (P<0.05). CONCLUSIONS: We identified impaired protein digestion and absorption, and alterations in SCFA concentrations as additional intestinal dysfunctions in CHF that are linked to reduced muscle and cognitive health and well-being. More research is needed to implement strategies to improve intestinal function in CHF and to investigate the mechanisms underlying its link with the other systemic manifestations. This article is protected by copyright. All rights reserved.

Aldujeli, A., Hamadeh, A., Tecson, K.M., Krivickas, Z., Maciulevicius, L., Stiklioraitis, S., Sukys, M., Briedis, K., Aldujeili, M., Briede, K., Braukyliene, R., Pranculis, A., Unikas, R., Zaliaduonyte, D. and McCullough, P.A. (2021). “Six-Month Outcomes for COVID-19 Negative Patients with Acute Myocardial Infarction Before Versus During the COVID-19 Pandemic.” Am J Cardiol 147: 16-22.

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The Coronavirus disease 2019 (COVID-19) pandemic has changed the way patients seek medical attention and how medical services are provided. We sought to compare characteristics, clinical course, and outcomes of patients presenting with acute myocardial infarction (AMI) during the pandemic compared with before it. This is a multicenter, retrospective cohort study of consecutive COVID-19 negative patients with AMI in Lithuania from March 11, 2020 to April 20, 2020 compared with patients admitted with the same diagnosis during the same period in 2019. All patients underwent angiography. Six-month follow-up was obtained for all patients. A total of 269 patients were included in this study, 107 (40.8%) of whom presented during the pandemic. Median pain-to-door times were significantly longer (858 [quartile 1=360, quartile 3 = 2,600] vs 385.5 [200, 745] minutes, p <0.0001) and post-revascularization ejection fractions were significantly lower (35 [30, 45] vs 45 [40, 50], p <0.0001) for patients presenting during vs. prior to the pandemic. While the in-hospital mortality rate did not differ, we observed a higher rate of six-month major adverse cardiovascular events for patients who presented during versus prior to the pandemic (30.8% vs 13.6%, p = 0.0006). In conclusion, 34% fewer patients with AMI presented to the hospital during the COVID-19 pandemic, and those who did waited longer to present and experienced more 6-month major adverse cardiovascular events compared with patients admitted before the pandemic.

Medvedofsky, D., Milhorini Pio, S., Weissman, N.J., Namazi, F., Delgado, V., Grayburn, P.A., Kar, S., Lim, D.S., Lerakis, S., Zhou, Z., Liu, M., Alu, M.C., Kapadia, S.R., Lindenfeld, J., Abraham, W.T., Mack, M.J., Bax, J.J., Stone, G.W. and Asch, F.M. (2021). “Left Ventricular Global Longitudinal Strain as a Predictor of Outcomes in Patients with Heart Failure with Secondary Mitral Regurgitation: The COAPT Trial.” J Am Soc Echocardiogr May 8;S0894-7317(21)00184-X. [Epub ahead of print].

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BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) is a sensitive marker of LV function and may help identify patients with heart failure (HF) and secondary mitral regurgitation who would have a better prognosis and are more likely to benefit from edge-to-edge transcatheter mitral valve repair with the MitraClip. The aim of this study was to assess the prognostic utility of baseline LV GLS during 2-year follow-up of patients with HF with secondary mitral regurgitation enrolled in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation trial. METHODS: Patients with symptomatic HF with moderate to severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were randomized to transcatheter mitral valve repair plus GDMT or GDMT alone. Speckle-tracking-derived LV GLS from baseline echocardiograms was obtained in 565 patients and categorized in tertiles. Death and HF hospitalization at 2-year follow-up were the principal outcomes of interest. RESULTS: Patients with better baseline LV GLS had higher blood pressure, greater LV ejection fraction and stroke volume, lower levels of B-type natriuretic peptide, and smaller LV size. No significant difference in outcomes at 2-year follow-up were noted according to LV GLS. However, the rate of death or HF hospitalization between 10 and 24 months was lower in patients with better LV GLS (P = .03), with no differences before 10 months. There was no interaction between GLS tertile and treatment group with respect to 2-year clinical outcomes. CONCLUSIONS: Baseline LV GLS did not predict death or HF hospitalization throughout 2-year follow-up, but it did predict outcomes after 10 months. The benefit of transcatheter mitral valve repair over GDMT alone was consistent in all subgroups irrespective of baseline LV GLS.

Wang, C.H., Wu, M.C., Wu, C.Y., Huang, C.H., Tsai, M.S., Lu, T.C., Chou, E., Wu, Y.W., Chang, W.T. and Chen, W.J. (2021). “Blood gas phenotyping and tracheal intubation timing in adult in-hospital cardiac arrest: a retrospective cohort study.” Sci Rep 11(1): 10480.

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To investigate whether the optimal time to tracheal intubation (TTI) during cardiopulmonary resuscitation would differ by different blood gas phenotypes. Adult patients experiencing in-hospital cardiac arrest (IHCA) from 2006 to 2015 were retrospectively screened. Early intra-arrest blood gas analysis, performed within 10 min of resuscitation, was used to define different phenotypes. In total, 567 patients were included. Non-severe acidosis (pH≧7.15) was associated with favourable neurological outcome (odds ratio [OR]: 4.60, 95% confidence interval [CI] 1.63-12.95; p value = 0.004) and survival (OR: 3.25, 95% CI 1.72-6.15; p value < 0.001) in the multivariable logistic regression analyses. In the interaction analysis, normal blood gas phenotype (pH: 7.35-7.45, PCO(2): 35-45 mm Hg, HCO(3)(-) level: 22-26 mmol/L) × TTI ≦ 6.3 min (OR: 20.40, 95% CI 2.53-164.75; p value = 0.005) and non-severe acidosis × TTI ≦ 6.3 min (OR: 3.35, 95% CI 1.00-11.23; p value = 0.05) were associated with neurological recovery while metabolic acidosis × TTI ≦ 5.7 min (OR: 3.63, 95% CI 1.36-9.67; p value = 0.01) and hypercapnic acidosis × TTI ≦ 10.4 min (OR: 2.27, 95% CI 1.20-4.28; p value = 0.01) were associated with survival. Intra-arrest blood gas analysis may help guide TTI during for patients with IHCA.