Publications by authors named "Ankeet S Bhatt"

55 Publications

Epidemiology and Management of ST-Segment-Elevation Myocardial Infarction in Patients With COVID-19: A Report From the American Heart Association COVID-19 Cardiovascular Disease Registry.

J Am Heart Assoc 2022 May 26;11(9):e024451. Epub 2022 Apr 26.

Levine Cardiac Intensive Care Unit Thrombolysis in Myocardial Infarction (TIMI) Study Group Cardiovascular Division Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA.

Background Early reports from the COVID-19 pandemic identified coronary thrombosis leading to ST-segment-elevation myocardial infarction (STEMI) as a complication of COVID-19 infection. However, the epidemiology of STEMI in patients with COVID-19 is not well characterized. We sought to determine the incidence, diagnostic and therapeutic approaches, and outcomes in STEMI patients hospitalized for COVID-19. Methods and Results Patients with data on presentation ECG and in-hospital myocardial infarction were identified from January 14, 2020 to November 30, 2020, from 105 sites participating in the American Heart Association COVID-19 Cardiovascular Disease Registry. Patient characteristics, resource use, and clinical outcomes were summarized and compared based on the presence or absence of STEMI. Among 15 621 COVID-19 hospitalizations, 54 (0.35%) patients experienced in-hospital STEMI. Among patients with STEMI, the majority (n=40, 74%) underwent transthoracic echocardiography, but only half (n=27, 50%) underwent coronary angiography. Half of all patients with COVID-19 and STEMI (n=27, 50%) did not undergo any form of primary reperfusion therapy. Rates of all-cause shock (47% versus 14%), cardiac arrest (22% versus 4.8%), new heart failure (17% versus 1.4%), and need for new renal replacement therapy (11% versus 4.3%) were multifold higher in patients with STEMI compared with those without STEMI (<0.050 for all). Rates of in-hospital death were 41% in patients with STEMI, compared with 16% in those without STEMI (<0.001). Conclusions STEMI in hospitalized patients with COVID-19 is rare but associated with poor in-hospital outcomes. Rates of coronary angiography and primary reperfusion were low in this population of patients with STEMI and COVID-19. Adaptations of systems of care to ensure timely contemporary treatment for this population are needed.
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http://dx.doi.org/10.1161/JAHA.121.024451DOI Listing
May 2022

Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling.

J Cardiovasc Transl Res 2022 Mar 15. Epub 2022 Mar 15.

Division of Cardiology, Department of Medicine, Duke University, 2301 Erwin Road, Durham, NC, USA.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have evident cardiovascular benefits in patients with type 2 diabetes with or at high risk for atherosclerotic cardiovascular disease, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction (only empagliflozin and dapagliflozin have been investigated in this group so far), and chronic kidney disease. Prevention and reversal of adverse cardiac remodeling is one of the mechanisms by which SGLT2 inhibitors may exert cardiovascular benefits, especially heart failure-related outcomes. Cardiac remodeling encompasses molecular, cellular, and interstitial changes that result in favorable changes in the mass, geometry, size, and function of the heart. The pathophysiological mechanisms of adverse cardiac remodeling are related to increased apoptosis and necrosis, decreased autophagy, impairments of myocardial oxygen supply and demand, and altered energy metabolism. Herein, the accumulating evidence from animal and human studies is reviewed investigating the effects of SGLT2 inhibitors on these mechanisms of cardiac remodeling.
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http://dx.doi.org/10.1007/s12265-022-10220-5DOI Listing
March 2022

Prioritizing prevention of de novo and worsening chronic heart failure.

Eur J Heart Fail 2022 Apr 15;24(4):653-656. Epub 2022 Mar 15.

Duke Clinical Research Institute, Durham, NC, USA.

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http://dx.doi.org/10.1002/ejhf.2464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106859PMC
April 2022

Personalizing Comprehensive Disease-Modifying Therapy: Obstacles and Opportunities.

JACC Heart Fail 2022 02 8;10(2):85-88. Epub 2021 Dec 8.

Inova Heart and Vascular Institute, Falls Church, Virginia, USA.

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http://dx.doi.org/10.1016/j.jchf.2021.10.008DOI Listing
February 2022

Epidemiology of Acute Heart Failure in Critically Ill Patients With COVID-19: An Analysis From the Critical Care Cardiology Trials Network.

J Card Fail 2022 Apr 17;28(4):675-681. Epub 2022 Jan 17.

Levine Cardiac Intensive Care Unit, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation.

Methods: We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs without acute HF. Acute HF was subclassified as de novo vs acute-on-chronic, based on the absence or presence of prior HF. Clinical features, biomarker profiles and outcomes were compared.

Results: Of 901 admissions to an ICU due to COVID-19, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n = 45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin and natriuretic peptide levels and similar inflammatory biomarkers; patients with de novo HF had the highest cardiac troponin levels. Notably, among patients critically ill with COVID-19, illness severity (median Sequential Organ Failure Assessment, 8 [IQR, 5-10] vs 6 [4-9]; P = 0.025) and mortality rates (43.8% vs 32.4%; P = 0.040) were modestly higher in patients with vs those without acute HF.

Conclusions: Among patients critically ill with COVID-19, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation.
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http://dx.doi.org/10.1016/j.cardfail.2021.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762923PMC
April 2022

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes.

J Am Heart Assoc 2022 01 31;11(1):e022010. Epub 2021 Dec 31.

Division of Infectious Diseases, Brigham and Women's Hospital Boston MA.

Background Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.
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http://dx.doi.org/10.1161/JAHA.121.022010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075193PMC
January 2022

Cost and Value in Contemporary Heart Failure Clinical Guidance Documents.

JACC Heart Fail 2022 01 10;10(1):1-11. Epub 2021 Nov 10.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objectives: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

Background: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

Methods: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

Results: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most CGDs (27 of 33; 82%) included at least 1 cost/value statement, and 20 (61%) CGDs included at least 1 cost/value-related citation. Most of these statements were found in expert consensus documents (77.7%). Three (9%) documents reported estimated costs of recommended interventions, but only 1 estimated out-of-pocket cost. Of 179 cost/value-related statements observed, 116 (64.8%) highlighted the economic impact of HF or HF-related care, 6 (3.4%) advocated for cost/value issues, 15 (8.4%) reported gaps in cost/value evidence, and 42 (23.5%) supported clinical guidance recommendations. Over time, patterns of inclusion of statements and citations of cost/value have been largely stable.

Conclusions: Although most contemporary HF CGDs contain at least 1 cost/value statement, most CGDs focus on the high economic impact of HF and its related care; explicit inclusion of cost/value to support clinical guidance recommendations remains infrequent. These results highlight key opportunities for the integration of formalized cost/value considerations in future HF-focused CGDs.
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http://dx.doi.org/10.1016/j.jchf.2021.08.002DOI Listing
January 2022

Epidemiology of Cardiogenic Shock in Hospitalized Adults With COVID-19: A Report From the American Heart Association COVID-19 Cardiovascular Disease Registry.

Circ Heart Fail 2021 12 18;14(12):e008477. Epub 2021 Nov 18.

Levine Cardiac Intensive Care Unit, Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine (A.S.V., E.L.G., A.S.B., M.W.L., D.D.B., D.A.M., E.A.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767943PMC
December 2021

De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry.

J Card Fail 2021 10;27(10):1073-1081

Levine Cardiac Intensive Care Unit, TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.

Methods And Results: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02).

Conclusions: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.
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http://dx.doi.org/10.1016/j.cardfail.2021.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514080PMC
October 2021

Potential Implications of Expanded US Food and Drug Administration Labeling for Sacubitril/Valsartan in the US.

JAMA Cardiol 2021 12;6(12):1415-1423

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: The US Food and Drug Administration (FDA) expanded labeling for sacubitril/valsartan for use in individuals with chronic heart failure (HF) with left ventricular ejection fraction (LVEF) lower than normal. The population-level implications of implementation of sacubitril/valsartan at higher LVEF ranges is unknown. While the Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trial did not meet its primary end point, the trial may provide useful information in projecting expected clinical events among treated individuals.

Objective: To quantify newly eligible treatment candidates for sacubitril/valsartan under the expanded FDA labeling and to apply treatment effects and the number needed to treat (NNT) to prevent 1 worsening HF event derived from subgroups of the PARAGON-HF trial who fall under the revised FDA label.

Design, Setting, And Participants: Newly eligible treatment candidates were estimated by mapping the LVEF distribution from 559 520 adult patients hospitalized between 2014 and 2019 in the Get With The Guidelines-Heart Failure registry to adults self-identifying with HF in the National Health and Nutrition Examination Survey (2015 to 2018). The NNT with 3 years of treatment for 3 end points of interest (total HF hospitalizations, total HF hospitalizations and cardiovascular death, and total HF hospitalizations and urgent HF visits and cardiovascular death) were estimated from the PARAGON-HF trial. Data were analyzed from February to June 2021.

Main Outcomes And Measures: Number of worsening HF events prevented or postponed if eligible patients were treated with sacubitril/valsartan for 3 years.

Results: Of an estimated 4 682 098 adults, the mean (SE) age was 66.3 (0.8) years, 1 995 037 (42.6%) were women, and 748 045 (16.0%) were Black. The potential number of adults projected to be newly eligible varied by the definition of FDA labeling of lower than normal LVEF from 643 161 (95% CI, 534 433-751 888; LVEF of 41% to 50%) to 1 838 756 (95% CI, 1 527 911-2 149 601; LVEF of 41% to 60%). In the PARAGON-HF trial, the NNT to prevent a worsening HF event (range, 7 to 12 patients) was consistent irrespective of specific LVEF range selected. Comprehensive implementation of sacubitril/valsartan among newly eligible patients was empirically estimated to prevent up to 69 268 (95% CI, 57 558-80 978) worsening HF events (LVEF of 41% to 50%) to 182 592 (95% CI, 151 725-213 460) worsening HF events (LVEF of 41% to 60%).

Conclusions And Relevance: The expanded FDA labeling is positioned to substantially increase the potential HF population eligible for sacubitril/valsartan by up to 1.8 million individuals and has the potential to prevent or postpone as many as 180 000 worsening HF events, depending on the definition of normal LVEF.
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http://dx.doi.org/10.1001/jamacardio.2021.3651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444065PMC
December 2021

Adherence to Evidence-Based Therapies in Heart Failure: Deepening the Implementation Divide.

Authors:
Ankeet S Bhatt

JACC Heart Fail 2021 12 8;9(12):887-889. Epub 2021 Sep 8.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jchf.2021.07.007DOI Listing
December 2021

Hospitalization of Patients With (But Not for) Heart Failure: An Opportunity for Accelerated Guideline-Directed Medical Therapy Optimization?

J Card Fail 2021 08;27(8):910-912

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.cardfail.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750052PMC
August 2021

Contemporary Burden of Primary Versus Secondary Heart Failure Hospitalizations in the United States.

Am J Cardiol 2021 10 24;156:140-142. Epub 2021 Jul 24.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.amjcard.2021.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750211PMC
October 2021

Prioritizing Dissemination and Implementation Science in Cardiometabolic Medicine: CONNECTing the Dots.

JAMA 2021 07;326(4):311-313

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jama.2021.9847DOI Listing
July 2021

Evidence-Based Prescribing and Polypharmacy for Patients With Heart Failure.

Ann Intern Med 2021 08 29;174(8):1165-1166. Epub 2021 Jun 29.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (A.S.B., N.K.C.).

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http://dx.doi.org/10.7326/M21-1427DOI Listing
August 2021

Treatment Effects of Sacubitril/Valsartan Compared With Valsartan by Ejection Fraction in Patients With Recent Hospitalization.

J Card Fail 2021 09 13;27(9):1027-1030. Epub 2021 Jun 13.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.cardfail.2021.05.020DOI Listing
September 2021

Effect of sacubitril/valsartan vs. enalapril on changes in heart failure therapies over time: the PARADIGM-HF trial.

Eur J Heart Fail 2021 09 21;23(9):1518-1524. Epub 2021 Jun 21.

Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.

Aims: Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β-blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial.

Methods And Results: Patients with full data on medication use were included. We examined β-blocker and MRA use in patients randomized to sacubitril/valsartan vs. enalapril through 12-month follow-up. New initiations and discontinuations of β-blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β-blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of β-blocker and MRA were similar between treatment groups at baseline and at 6-month and 12-month follow-up. New initiations through 12-month follow-up were infrequent and similar in the sacubitril/valsartan and enalapril groups for β-blockers [37 (9.0%) vs. 42 (10.2%), P = 0.56] and MRA [127 (7.6%) vs. 143 (9.2%), P = 0.10]. Among patients on MRA therapy at baseline, there were fewer MRA discontinuations in patients on sacubitril/valsartan as compared with enalapril at 12 months [125 (6.2%) vs. 187 (9.0%), P = 0.001]. Discontinuations of β-blockers were not significantly different between groups in follow-up (2.2% vs. 2.6%, P = 0.26).

Conclusions: Initiation of sacubitril/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose down-titration of other key guideline-directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril/valsartan (when compared with enalapril) may promote sustained MRA use in follow-up.
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http://dx.doi.org/10.1002/ejhf.2259DOI Listing
September 2021

Accuracy of ICD-10 Diagnostic Codes to Identify COVID-19 Among Hospitalized Patients.

J Gen Intern Med 2021 08 7;36(8):2532-2535. Epub 2021 Jun 7.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Heart & Vascular Center and Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA.

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http://dx.doi.org/10.1007/s11606-021-06936-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183587PMC
August 2021

Prognostic Value of Natriuretic Peptides and Cardiac Troponins in COVID-19.

Circulation 2021 07 17;144(2):177-179. Epub 2021 May 17.

Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (J.W.C., B.L.C., K.S.J., M.V., A.S.B., S.D.S.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270227PMC
July 2021

Incidence and Outcomes of Pneumonia in Patients With Heart Failure.

J Am Coll Cardiol 2021 04;77(16):1961-1973

British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address:

Background: The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).

Objectives: This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials.

Methods: The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro-B-type natriuretic peptide).

Results: In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58).

Conclusions: The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711).
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http://dx.doi.org/10.1016/j.jacc.2021.03.001DOI Listing
April 2021

Virtual optimization of guideline-directed medical therapy in hospitalized patients with heart failure with reduced ejection fraction: the IMPLEMENT-HF pilot study.

Eur J Heart Fail 2021 07 13;23(7):1191-1201. Epub 2021 Apr 13.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Aims: Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF.

Methods And Results: Consecutive hospitalizations in patients with HFrEF (ejection fraction ≤40%) were prospectively identified from 3 February to 1 March 2020 (usual care group) and 2 March to 28 August 2020 (intervention group). Patients with critical illness, de novo heart failure, and systolic blood pressure <90 mmHg in the preceeding 24 hs prior to enrollment were excluded. In the intervention group, a pharmacist-physician GDMT Team provided optimization suggestions to treating teams based on an evidence-based algorithm. The primary outcome was a GDMT optimization score, the sum of positive (+1 for new initiations or up-titrations) and negative therapeutic changes (-1 for discontinuations or down-titrations) at hospital discharge. Serious in-hospital safety events were assessed. Among 278 consecutive encounters with HFrEF, 118 met eligibility criteria; 29 (25%) received usual care and 89 (75%) received the GDMT Team intervention. Among usual care encounters, there were no changes in GDMT prescription during hospitalization. In the intervention group, β-blocker (72% to 88%; P = 0.01), angiotensin receptor-neprilysin inhibitor (6% to 17%; P = 0.03), mineralocorticoid receptor antagonist (16% to 29%; P = 0.05), and triple therapy (9% to 26%; P < 0.01) prescriptions increased during hospitalization. After adjustment for clinically relevant covariates, the GDMT Team was associated with an increase in GDMT optimization score (+0.58; 95% confidence interval +0.09 to +1.07; P = 0.02). There were no serious in-hospital adverse events.

Conclusions: Non-cardiovascular hospitalizations are a potentially safe and effective setting for GDMT optimization. A virtual GDMT Team was associated with improved heart failure therapeutic optimization. This implementation strategy warrants testing in a prospective randomized controlled trial.
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http://dx.doi.org/10.1002/ejhf.2163DOI Listing
July 2021

Influenza vaccination: a 'shot' at INVESTing in cardiovascular health.

Eur Heart J 2021 05;42(20):2015-2018

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Sreet, Boston, MA 02115, USA.

The link between viral respiratory infection and non-pulmonary organ-specific injury, including cardiac injury, has become increasingly appreciated during the current coronavirus disease 2019 (COVID-19) pandemic. Even prior to the pandemic, however, the association between acute infection with influenza and elevated cardiovascular risk was evident. The recently published results of the NHLBI-funded INfluenza Vaccine to Effectively Stop CardioThoracic Events and Decompensated (INVESTED) trial, a 5200 patient comparative effectiveness study of high-dose vs. standard-dose influenza vaccine to reduce cardiopulmonary events and mortality in a high-risk cardiovascular population, found no difference between strategies. However, the broader implications of influenza vaccine as a strategy to reduce morbidity in high-risk patients remain extremely important, with randomized controlled trial and observational data supporting vaccination in high-risk patients with cardiovascular disease. Given a favourable risk-benefit profile and widespread availability at generally low cost, we contend that influenza vaccination should remain a centrepiece of cardiovascular risk mitigation and describe the broader context of underutilization of this strategy. Few therapeutics in medicine offer seasonal efficacy from a single administration with generally mild, transient side effects, and exceedingly low rates of serious adverse effects. Infection control measures such as physical distancing, hand washing, and the use of masks during the COVID-19 pandemic have already been associated with substantially curtailed incidence of influenza outbreaks across the globe. Appending annual influenza vaccination to these measures represents an important public health and moral imperative.
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http://dx.doi.org/10.1093/eurheartj/ehab133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083766PMC
May 2021

Clinical Outcomes in Patients With Heart Failure Hospitalized With COVID-19.

JACC Heart Fail 2021 01;9(1):65-73

Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objectives: The purpose of this study was to evaluate in-hospital outcomes among patients with a history of heart failure (HF) hospitalized with coronavirus disease-2019 (COVID-19).

Background: Cardiometabolic comorbidities are common in patients with severe COVID-19. Patients with HF may be particularly susceptible to COVID-19 complications.

Methods: The Premier Healthcare Database was used to identify patients with at least 1 HF hospitalization or 2 HF outpatient visits between January 1, 2019, and March 31, 2020, who were subsequently hospitalized between April and September 2020. Baseline characteristics, health care resource utilization, and mortality rates were compared between those hospitalized with COVID-19 and those hospitalized with other causes. Predictors of in-hospital mortality were identified in HF patients hospitalized with COVID-19 by using multivariate logistic regression.

Results: Among 1,212,153 patients with history of HF, 132,312 patients were hospitalized from April 1, 2020, to September 30, 2020. A total of 23,843 patients (18.0%) were hospitalized with acute HF, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 patients (75.6%) were hospitalized with alternative reasons. Hospitalization with COVID-19 was associated with greater odds of in-hospital mortality as compared with hospitalization with acute HF; 24.2% of patients hospitalized with COVID-19 died in-hospital compared to 2.6% of those hospitalized with acute HF. This association was strongest in April (adjusted odds ratio [OR]: 14.48; 95% confidence interval [CI]:12.25 to 17.12) than in subsequent months (adjusted OR: 10.11; 95% CI: 8.95 to 11.42; p <0.001). Among patients with HF hospitalized with COVID-19, male sex (adjusted OR: 1.26; 95% CI: 1.13 to 1.40) and morbid obesity (adjusted OR: 1.25; 95% CI: 1.07 to 1.46) were associated with greater odds of in-hospital mortality, along with age (adjusted OR: 1.35; 95% CI: 1.29 to 1.42 per 10 years) and admission earlier in the pandemic.

Conclusions: Patients with HF hospitalized with COVID-19 are at high risk for complications, with nearly 1 in 4 dying during hospitalization.
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http://dx.doi.org/10.1016/j.jchf.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833294PMC
January 2021

Treatment of HF in an Era of Multiple Therapies: Statement From the HF Collaboratory.

JACC Heart Fail 2021 01 9;9(1):1-12. Epub 2020 Dec 9.

Department of Medicine, University of Mississippi, Jackson, Mississippi, USA. Electronic address:

The treatment of heart failure with reduced ejection fraction (HFrEF) has changed considerably over time, particularly with the sequential development of therapies aimed at antagonism of maladaptive biologic pathways, including inhibition of the sympathetic nervous system and the renin-angiotensin aldosterone system. The sequential nature of earlier HFrEF trials allowed the integration of new therapies tested against the background therapy of the time. More recently, multiple heart failure therapies are being evaluated simultaneously, and the number of therapeutic choices for treating HFrEF has grown considerably. In addition, implementation science has lagged behind discovery science in heart failure. Furthermore, given there are currently >200 ongoing clinical trials in heart failure, further complexities are anticipated. In an effort to provide a decision-making framework in the current era of expanding therapeutic options in HFrEF, the Heart Failure Collaboratory convened a multi-stakeholder group, including patients, clinicians, clinical investigators, the U.S. Food and Drug Administration, industry, and payers who met at the U.S. Food and Drug Administration campus on March 6, 2020. This paper summarizes the discussions and expert consensus recommendations.
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http://dx.doi.org/10.1016/j.jchf.2020.10.014DOI Listing
January 2021

Discovery and care innovation amidst a pandemic.

Eur J Heart Fail 2020 12 14;22(12):2202-2204. Epub 2020 Dec 14.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1002/ejhf.2070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753523PMC
December 2020

Conduct of Clinical Trials in the Era of COVID-19: JACC Scientific Expert Panel.

J Am Coll Cardiol 2020 11;76(20):2368-2378

Inova Heart and Vascular Institute, Falls Church, Virginia; Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina. Electronic address: https://twitter.com/coconnormd.

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.
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http://dx.doi.org/10.1016/j.jacc.2020.09.544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836888PMC
November 2020
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