Cardiology

Agarwala, A., N. Bekele, E. Deych, M. W. Rich, A. Hussain, L. K. Jones, A. C. Sturm, K. Aspry, E. Nowak, Z. Ahmad, C. M. Ballantyne and A. C. Goldberg (2021). “Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.” J Am Heart Assoc 10(17): e020890.

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Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m(2) versus 29±6 kg/m(2); P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Kluis, A., J. Eisenga, J. Squiers, J. M. Dimaio, D. Gable, J. Kedora, W. Shutze and T. George (2021). “Extracorporeal membrane oxygenation for patients with pulmonary embolism undergoing thrombolysis.” Ann Thorac Surg.

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Patients with massive pulmonary embolism undergoing catheter-directed therapy are at high risk for cardiopulmonary arrest in the periprocedural period due to severe right ventricular dysfunction. We report the outcomes of three patients with massive pulmonary embolism treated successfully with catheter-directed thrombolytic therapy and veno-arterial extracorporeal membrane oxygenation.

Lawler, P. R., E. C. Goligher, J. S. Berger, M. D. Neal, B. J. McVerry, J. C. Nicolau, M. N. Gong, M. Carrier, R. S. Rosenson, H. R. Reynolds, A. F. Turgeon, J. Escobedo, D. T. Huang, C. A. Bradbury, B. L. Houston, L. Z. Kornblith, A. Kumar, S. R. Kahn, M. Cushman, Z. McQuilten, A. S. Slutsky, K. S. Kim, A. C. Gordon, B. A. Kirwan, M. M. Brooks, A. M. Higgins, R. J. Lewis, E. Lorenzi, S. M. Berry, L. R. Berry, A. W. Aday, F. Al-Beidh, D. Annane, Y. M. Arabi, D. Aryal, L. Baumann Kreuziger, A. Beane, Z. Bhimani, S. Bihari, H. H. Billett, L. Bond, M. Bonten, F. Brunkhorst, M. Buxton, A. Buzgau, L. A. Castellucci, S. Chekuri, J. T. Chen, A. C. Cheng, T. Chkhikvadze, B. Coiffard, T. W. Costantini, S. de Brouwer, L. P. G. Derde, M. A. Detry, A. Duggal, V. Džavík, M. B. Effron, L. J. Estcourt, B. M. Everett, D. A. Fergusson, M. Fitzgerald, R. A. Fowler, J. P. Galanaud, B. T. Galen, S. Gandotra, S. García-Madrona, T. D. Girard, L. C. Godoy, A. L. Goodman, H. Goossens, C. Green, Y. Y. Greenstein, P. L. Gross, N. M. Hamburg, R. Haniffa, G. Hanna, N. Hanna, S. M. Hegde, C. M. Hendrickson, R. D. Hite, A. A. Hindenburg, A. A. Hope, J. M. Horowitz, C. M. Horvat, K. Hudock, B. J. Hunt, M. Husain, R. C. Hyzy, V. N. Iyer, J. R. Jacobson, D. Jayakumar, N. M. Keller, A. Khan, Y. Kim, A. L. Kindzelski, A. J. King, M. M. Knudson, A. E. Kornblith, V. Krishnan, M. E. Kutcher, M. A. Laffan, F. Lamontagne, G. Le Gal, C. M. Leeper, E. S. Leifer, G. Lim, F. G. Lima, K. Linstrum, E. Litton, J. Lopez-Sendon, J. L. Lopez-Sendon Moreno, S. A. Lother, S. Malhotra, M. Marcos, A. Saud Marinez, J. C. Marshall, N. Marten, M. A. Matthay, D. F. McAuley, E. G. McDonald, A. McGlothlin, S. P. McGuinness, S. Middeldorp, S. K. Montgomery, S. C. Moore, R. Morillo Guerrero, P. R. Mouncey, S. Murthy, G. B. Nair, R. Nair, A. D. Nichol, B. Nunez-Garcia, A. Pandey, P. K. Park, R. L. Parke, J. C. Parker, S. Parnia, J. D. Paul, Y. S. Pérez González, M. Pompilio, M. E. Prekker, J. G. Quigley, N. S. Rost, K. Rowan, F. O. Santos, M. Santos, M. Olombrada Santos, L. Satterwhite, C. T. Saunders, R. E. G. Schutgens, C. W. Seymour, D. M. Siegal, D. G. Silva, Jr., M. Shankar-Hari, J. P. Sheehan, A. B. Singhal, D. Solvason, S. J. Stanworth, T. Tritschler, A. M. Turner, W. van Bentum-Puijk, F. L. van de Veerdonk, S. van Diepen, G. Vazquez-Grande, L. Wahid, V. Wareham, B. J. Wells, R. J. Widmer, J. G. Wilson, E. Yuriditsky, F. G. Zampieri, D. C. Angus, C. J. McArthur, S. A. Webb, M. E. Farkouh, J. S. Hochman and R. Zarychanski (2021). “Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.” N Engl J Med 385(9): 790-802.

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BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Smilowitz, N. R., R. Dubner, A. S. Hellkamp, R. J. Widmer and H. R. Reynolds (2021). “Variability of discharge medical therapy for secondary prevention among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) in the United States.” PLoS One 16(8): e0255462.

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BACKGROUND: Optimal medical therapy after myocardial infarction with nonobstructive coronary arteries (MINOCA; <50% stenosis) is uncertain. We evaluated variability in discharge prescription of angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACEI/ARB) and beta-blockers (BB) to MINOCA patients between hospitals to assess physician equipoise about secondary prevention. METHODS: Patients with MINOCA between 2007-2014 were identified in the NCDR Chest Pain-MI Registry. Those with prior revascularization or missing demographic, angiographic, or medication data were excluded. Analysis was limited to high-volume hospitals with ≥20 MINOCA total discharges. Discharge prescriptions for ACEI/ARB and BB after MINOCA were analyzed for each hospital. Clinical data on left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and diabetes mellitus status were extracted to identify other indications for ACEI/ARB or BB. RESULTS: Clinical data were available for 17,849 MINOCA patients, of whom 8,752 (49%) had LVEF <40%, GFR ≤60 mL/min, and/or diabetes. 5,913 patients without one of these indications for ACEI/ARB or BB were discharged from 156 high-volume hospitals. At discharge, ACEI/ARB was prescribed to between 16.0% and 88.8% of MINOCA patients (median 45.6%, IQR 38.0%-56.5%) and BB to between 28.0% and 97.5% (median 74.1%, IQR 64.7%-80.0%). CONCLUSION: There is marked variability between hospitals in the proportions of patients receiving ACEI/ARB and BB after hospitalization for MINOCA, suggesting clinical equipoise about the routine use of these agents. Randomized clinical trials are necessary to establish the benefit of ACEI/ARB and BB to improve outcomes after MINOCA.

Goligher, E. C., C. A. Bradbury, B. J. McVerry, P. R. Lawler, J. S. Berger, M. N. Gong, M. Carrier, H. R. Reynolds, A. Kumar, A. F. Turgeon, L. Z. Kornblith, S. R. Kahn, J. C. Marshall, K. S. Kim, B. L. Houston, L. P. G. Derde, M. Cushman, T. Tritschler, D. C. Angus, L. C. Godoy, Z. McQuilten, B. A. Kirwan, M. E. Farkouh, M. M. Brooks, R. J. Lewis, L. R. Berry, E. Lorenzi, A. C. Gordon, T. Ahuja, F. Al-Beidh, D. Annane, Y. M. Arabi, D. Aryal, L. Baumann Kreuziger, A. Beane, Z. Bhimani, S. Bihari, H. H. Billett, L. Bond, M. Bonten, F. Brunkhorst, M. Buxton, A. Buzgau, L. A. Castellucci, S. Chekuri, J. T. Chen, A. C. Cheng, T. Chkhikvadze, B. Coiffard, A. Contreras, T. W. Costantini, S. de Brouwer, M. A. Detry, A. Duggal, V. Džavík, M. B. Effron, H. F. Eng, J. Escobedo, L. J. Estcourt, B. M. Everett, D. A. Fergusson, M. Fitzgerald, R. A. Fowler, J. D. Froess, Z. Fu, J. P. Galanaud, B. T. Galen, S. Gandotra, T. D. Girard, A. L. Goodman, H. Goossens, C. Green, Y. Y. Greenstein, P. L. Gross, R. Haniffa, S. M. Hegde, C. M. Hendrickson, A. M. Higgins, A. A. Hindenburg, A. A. Hope, J. M. Horowitz, C. M. Horvat, D. T. Huang, K. Hudock, B. J. Hunt, M. Husain, R. C. Hyzy, J. R. Jacobson, D. Jayakumar, N. M. Keller, A. Khan, Y. Kim, A. Kindzelski, A. J. King, M. M. Knudson, A. E. Kornblith, M. E. Kutcher, M. A. Laffan, F. Lamontagne, G. Le Gal, C. M. Leeper, E. S. Leifer, G. Lim, F. Gallego Lima, K. Linstrum, E. Litton, J. Lopez-Sendon, S. A. Lother, N. Marten, A. Saud Marinez, M. Martinez, E. Mateos Garcia, S. Mavromichalis, D. F. McAuley, E. G. McDonald, A. McGlothlin, S. P. McGuinness, S. Middeldorp, S. K. Montgomery, P. R. Mouncey, S. Murthy, G. B. Nair, R. Nair, A. D. Nichol, J. C. Nicolau, B. Nunez-Garcia, J. J. Park, P. K. Park, R. L. Parke, J. C. Parker, S. Parnia, J. D. Paul, M. Pompilio, J. G. Quigley, R. S. Rosenson, N. S. Rost, K. Rowan, F. O. Santos, M. Santos, M. O. Santos, L. Satterwhite, C. T. Saunders, J. Schreiber, R. E. G. Schutgens, C. W. Seymour, D. M. Siegal, D. G. Silva, Jr., A. B. Singhal, A. S. Slutsky, D. Solvason, S. J. Stanworth, A. M. Turner, W. van Bentum-Puijk, F. L. van de Veerdonk, S. van Diepen, G. Vazquez-Grande, L. Wahid, V. Wareham, R. J. Widmer, J. G. Wilson, E. Yuriditsky, Y. Zhong, S. M. Berry, C. J. McArthur, M. D. Neal, J. S. Hochman, S. A. Webb and R. Zarychanski (2021). “Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.” N Engl J Med 385(9): 777-789.

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BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).