Publications by authors named "Bernard J Gersh"

669 Publications

Associations of Atrial Fibrillation After Noncardiac Surgery With Stroke, Subsequent Arrhythmia, and Death : A Cohort Study.

Ann Intern Med 2022 Jul 26. Epub 2022 Jul 26.

Department of Cardiovascular Medicine and Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota (A.M.C.).

Background: Postoperative atrial fibrillation (AF) after noncardiac surgery confers increased risks for ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after noncardiac surgery compare with those for AF occurring outside of the operative setting is unknown.

Objective: To compare the risks for ischemic stroke or TIA and other outcomes in patients with postoperative AF versus those with incident AF not associated with surgery.

Design: Cohort study.

Setting: Olmsted County, Minnesota.

Participants: Patients with incident AF between 2000 and 2013.

Measurements: Patients were categorized as having AF occurring within 30 days of a noncardiac surgery (postoperative AF) or having AF unrelated to surgery (nonoperative AF).

Results: Of 4231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients had an ischemic stroke or TIA and 2462 had subsequent AF; a total of 2565 deaths occurred. The risk for stroke or TIA was similar between those with postoperative AF and nonoperative AF (absolute risk difference [ARD] at 5 years, 0.1% [95% CI, -2.9% to 3.1%]; hazard ratio [HR], 1.01 [CI, 0.77 to 1.32]). A lower risk for subsequent AF was seen for patients with postoperative AF (ARD at 5 years, -13.4% [CI, -17.8% to -9.0%]; HR, 0.68 [CI, 0.60 to 0.77]). Finally, no difference was seen for cardiovascular death or all-cause death between patients with postoperative AF and nonoperative AF.

Limitation: The population consisted predominantly of White patients; caution should be used when extrapolating the results to more racially diverse populations.

Conclusion: Postoperative AF after noncardiac surgery is associated with similar risk for thromboembolism compared with nonoperative AF. Our findings have potentially important implications for the early postsurgical and subsequent management of postoperative AF.

Primary Funding Source: National Institute on Aging
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http://dx.doi.org/10.7326/M22-0434DOI Listing
July 2022

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

Circulation 2022 Jul 25;146(4):339-357. Epub 2022 Jul 25.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.122.057444DOI Listing
July 2022

Explaining unexplained syncope in hypertrophic cardiomyopathy: A clinical dilemma.

Int J Cardiol 2022 Sep 20;363:125-126. Epub 2022 Jun 20.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States of America.

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http://dx.doi.org/10.1016/j.ijcard.2022.06.051DOI Listing
September 2022

Newer P2Y Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis.

Mayo Clin Proc 2022 06;97(6):1074-1085

Section of Cardiovascular Medicine, Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC. Electronic address:

Objective: To evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).

Patients And Methods: MEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y inhibitors and clopidogrel in patients with AMI-CA/CS.

Results: Eight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).

Conclusion: In patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.
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http://dx.doi.org/10.1016/j.mayocp.2022.02.016DOI Listing
June 2022

Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model.

Am Heart J 2022 Sep 13;251:13-24. Epub 2022 May 13.

Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.

Methods: The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.

Results: Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.

Conclusions: In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.
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http://dx.doi.org/10.1016/j.ahj.2022.03.009DOI Listing
September 2022

Artificial Intelligence-Enabled Electrocardiogram for Atrial Fibrillation Identifies Cognitive Decline Risk and Cerebral Infarcts.

Mayo Clin Proc 2022 05;97(5):871-880

Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Objective: To investigate whether artificial intelligence-enabled electrocardiogram (AI-ECG) assessment of atrial fibrillation (AF) risk predicts cognitive decline and cerebral infarcts.

Patients And Methods: This population-based study included sinus-rhythm ECG participants seen from November 29, 2004 through July 13, 2020, and a subset with brain magnetic resonance imaging (MRI) (October 10, 2011, through November 2, 2017). The AI-ECG score of AF risk calculated for participants was 0-1. To determine the AI-ECG-AF relationship with baseline cognitive dysfunction, we compared linear mixed-effects models with global and domain-specific cognitive z-scores from longitudinal neuropsychological assessments. The AI-ECG-AF score was logit transformed and modeled with cubic splines. For the brain-MRI subset, logistic regression evaluated correlation of the AI-ECG-AF score and the high-threshold, dichotomized AI-ECG-AF score with infarcts.

Results: Participants (N=3729; median age, 74.1 years) underwent cognitive analysis. Adjusting for age, sex, education, and APOE ɛ4-carrier status, the AI-ECG-AF score correlated with lower baseline and faster decline in global-cognitive z-scores (P=.009 and P=.01, respectively, non-linear-based spline-models tests) and attention z-scores (P<.001 and P=.01, respectively). Sinus-rhythm-ECG participants (n=1373) underwent MRI. As a continuous measure, the AI-ECG-AF score correlated with infarcts but not after age and sex adjustment (P=.52). For dichotomized analysis, an AI-ECG-AF score greater than 0.5 correlated with infarcts (OR, 4.61; 95% CI, 2.45-8.55; P<.001); even after age and sex adjustment (OR, 2.09; 95% CI, 1.06-4.07; P=.03).

Conclusion: The AI-ECG-AF score correlated with worse baseline cognition and gradual global cognition and attention decline. High AF probability by AI-ECG-AF score correlated with MRI cerebral infarcts. However, most infarcts observed in our cohort were subcortical, suggesting that AI-ECG not only predicts AF but also detects other non-AF cardiac disease markers and correlates with small vessel cerebrovascular disease and cognitive decline.
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http://dx.doi.org/10.1016/j.mayocp.2022.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179015PMC
May 2022

Personalizing Choice of CABG vs PCI for Multivessel Disease: Predictive Model Falls Short.

J Am Coll Cardiol 2022 04;79(15):1474-1476

Department of Cardiovascular Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.jacc.2022.02.011DOI Listing
April 2022

The challenges of data safety monitoring for a pragmatic study: Lessons from the ADAPTABLE study.

Contemp Clin Trials 2022 04 15;115:106732. Epub 2022 Mar 15.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Data monitoring committees (DMCs) play a critical role in protecting the safety of participants and integrity of clinical studies. While there are well-established DMC guidelines for traditional, randomized controlled trials, the clinical trial community is still in the search for best practices in data and safety monitoring in pragmatic clinical trials. ADAPTABLE was a large, open label, pragmatic, randomized controlled trial, harnessing real world data from multiple sources and studying the comparative effectiveness of the two most common dosages of aspirin in patients with atherosclerotic cardiovascular disease. Specific issues arose in ADAPTABLE such as data quality, information latency, and protocol adherence, and these issues were both expected and unexpected features of the pragmatic study design. These issues imposed great challenges to the DMC members who were tasked to make critical decisions during the study. This article summarizes the unique experience of the ADAPTABLE DMC, including the internal debates and concerns, the concerted efforts to accomplish its mission, and the special contribution of the patient representatives. We also offer recommendations on data and safety monitoring for future pragmatic trials.
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http://dx.doi.org/10.1016/j.cct.2022.106732DOI Listing
April 2022

Management and Outcomes of Acute Myocardial Infarction-Cardiogenic Shock in Uninsured Compared With Privately Insured Individuals.

Circ Heart Fail 2022 05 4;15(5):e008991. Epub 2022 Mar 4.

Department of Cardiovascular Medicine (V.K., B.J.G., A.L., A.S.J., D.R.H., M.R.B., G.W.B.), Mayo Clinic, Rochester, MN.

Background: There are limited data on uninsured patients presenting with acute myocardial infarction-cardiogenic shock (AMI-CS). This study sought to compare the management and outcomes of AMI-CS between uninsured and privately insured individuals.

Methods: Using the National Inpatient Sample (2000-2016), a retrospective cohort of adult (≥18 years) uninsured admissions (primary payer-self-pay or no charge) were compared with privately insured individuals. Interhospital transfers were excluded. Outcomes of interest included in-hospital mortality, temporal trends in admissions, use of cardiac procedures, do-not-resuscitate status, palliative care referrals, and resource utilization.

Results: Of 402 182 AMI-CS admissions, 21 966 (5.4%) and 93 814 (23.3%) were uninsured and privately insured. Compared with private insured individuals, uninsured admissions were younger, male, from a lower socioeconomic status, had lower comorbidity, higher rates of acute organ failure, ST-segment elevation AMI-CS (77.3% versus 76.4%), and concomitant cardiac arrest (33.8% versus 31.9%; all <0.001). Compared with 2000, in 2016, there were more uninsured (adjusted odds ratio, 1.15 [95% CI, 1.13-1.17]; <0.001) and less privately insured admissions (adjusted odds ratio, 0.85 [95% CI, 0.83-0.87]; <0.001). Uninsured individuals received less frequent coronary angiography (79.5% versus 81.0%), percutaneous coronary intervention (60.8% versus 62.2%), mechanical circulatory support (54% versus 55.5%), and had higher palliative care (3.8% versus 3.2%) and do-not-resuscitate status use (4.4% versus 3.2%; all <0.001). Uninsured admissions had higher in-hospital mortality (adjusted odds ratio, 1.62 [95% CI, 1.55-1.68]; <0.001) and resource utilization.

Conclusions: Uninsured individuals have higher in-hospital mortality and lower use of guideline-directed therapies in AMI-CS compared with privately insured individuals.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008991DOI Listing
May 2022

Prognostic Relevance of Right Ventricular Remodeling after ST-Segment Elevation Myocardial Infarction in Patients Treated With Primary Percutaneous Coronary Intervention.

Am J Cardiol 2022 05 21;170:1-9. Epub 2022 Feb 21.

Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands; Turku Heart Center, University of Turku and Turku University Hospital, Turku, Finland. Electronic address:

ST-segment elevation myocardial infarction (STEMI) often leads to changes in right ventricular (RV) function and size over time. The prognostic implications of RV remodeling after STEMI, however, are unknown. RV remodeling in patients who underwent STEMI with primary percutaneous coronary intervention (PCI) was defined by RV end-systolic area (RV ESA) change at 6 months after STEMI compared with baseline. The optimal threshold of RV ESA change (≥40%) to define RV remodeling was derived from spline curve analysis. Long-term outcomes were compared between patients with and without RV remodeling. A total of 2,280 patients were analyzed (mean age 60 ± 11 years, 76% were men). RV remodeling was present in 315 patients (14%). After a median follow-up of 76 months (interquartile range 51 to 106 months), 271 patients (12%) died (primary end point) and the composite end point of all-cause mortality and HF hospitalization (secondary end point) was observed in 292 patients (13%). After adjustment for various risk factors, including tricuspid annular plane systolic excursion (TAPSE), post-STEMI RV remodeling was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] = 1.44, 95% confidence interval [CI] 1.02 to 2.02, p = 0.038) and the composite of all-cause mortality and HF hospitalization (HR = 1.41, 95% CI 1.02 to 1.96, p = 0.040). Finally, patients with RV remodeling had a significantly lower survival rate (Log-rank, p = 0.006) and event-free survival rate than those without RV remodeling during follow-up (log-rank, p = 0.006). RV post-infarct remodeling is associated with mortality and HF hospitalization, independent of RV systolic function.
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http://dx.doi.org/10.1016/j.amjcard.2022.01.015DOI Listing
May 2022

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Circulation 2022 02 31;145(5):392-409. Epub 2022 Jan 31.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø (M.L.L.).

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055018DOI Listing
February 2022

Functional classification of left ventricular remodelling: prognostic relevance in myocardial infarction.

ESC Heart Fail 2022 04 22;9(2):912-924. Epub 2022 Jan 22.

Department of Cardiology, Heart and Lung Centre, Leiden University Medical Centre, Albinusdreef 2, Leiden, 2300 RC, The Netherlands.

Aims: The current definition of post ST-segment elevation myocardial infarction (STEMI) left ventricular (LV) remodelling is purely structural (LV dilatation) and does not consider LV function (ejection fraction, EF), even though it is known to be a predictor of long-term post-STEMI outcome. This study aimed to reclassify LV remodelling after STEMI by integrating LV dilatation and function (LVEF) and to investigate the prognostic implications.

Methods And Results: Data from an ongoing registry of STEMI patients who were treated with primary percutaneous coronary intervention (PCI) were retrospectively evaluated. Four distinct remodelling subgroups were identified: (i) no LV dilatation, no LVEF impairment,(ii) no LV dilatation but LVEF impairment, (iii) LV dilatation but no LVEF impairment, and (iv) LV dilatation and LVEF impairment. The impact of functional LV remodelling on outcomes was analysed. A total of 2346 patients were studied (mean age 60 ± 11 years, 76% men). During a median follow-up of 76 (interquartile range 52 to 107) months, 282 (12%) died, while the composite of death and heart failure hospitalization occurred in 305 (13%) patients. Those with LV remodelling and LVEF impairment had a significantly lower survival rate (P < 0.001) and event-free survival rate (P < 0.001) compared with other functional LV remodelling groups.

Conclusions: Employing a functional LV post-infarct remodelling classification has the potential to improve risk stratification beyond structural LV remodelling alone. Identification of patients with the worst prognosis by using a functional LV remodelling approach may allow institution of early preventative therapies.
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http://dx.doi.org/10.1002/ehf2.13802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934947PMC
April 2022

Cardiac involvement in the long-term implications of COVID-19.

Nat Rev Cardiol 2022 05 22;19(5):332-341. Epub 2021 Oct 22.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.

Throughout 2021, the medical and scientific communities have focused on managing the acute morbidity and mortality caused by the coronavirus disease 2019 (COVID-19) pandemic. With the approval of multiple vaccines, there is a light at the end of this dark tunnel and an opportunity to focus on the future, including managing the long-term sequelae in patients who have survived acute COVID-19. In this Perspectives article, we highlight what is known about the cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome. To provide the greatest benefit to these survivors, prospective studies should begin now, with resources made available to monitor and study this population in the coming years.
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http://dx.doi.org/10.1038/s41569-021-00631-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532434PMC
May 2022

Improving Communication of Incidental Imaging Findings: Transforming Uncertainty Into Opportunity.

Mayo Clin Proc 2021 11 25;96(11):2753-2756. Epub 2021 Sep 25.

Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2021.06.021DOI Listing
November 2021

Myocardial contraction fraction by echocardiography and mortality in cardiac intensive care unit patients.

Int J Cardiol 2021 Dec 23;344:230-239. Epub 2021 Sep 23.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: The myocardial contraction fraction (MCF) is proposed as an improved measure of left ventricular (LV) systolic function that overcomes important limitations of the left ventricular ejection fraction (LVEF). We sought to determine whether a low MCF was associated with higher mortality in cardiac intensive care unit (CICU) patients.

Methods: We retrospectively analyzed unique Mayo Clinic CICU patients from 2007 to 2018 with MCF calculated as the ratio of the stroke volume to the left ventricular myocardial volume from a transthoracic echocardiogram within 1 day of CICU admission. Multivariable logistic regression analyzed the association between MCF and hospital mortality, after adjustment for LVEF and clinical variables.

Results: We included 4794 patients with a mean age of 68.0 ± 14.8 years (37.1% females). The mean MCF was 0.41 ± 0.16, and was lower in the 6.6% of patients who died in the hospital (0.32 ± 0.14 versus 0.42 ± 0.16, p < 0.001). On multivariable analysis, higher MCF remained associated with lower hospital mortality (adjusted OR 0.78 per 0.1 higher, 95% CI 0.69-0.89, p < 0.001), whereas LVEF was not significantly associated with hospital mortality (unadjusted OR 0.91 per 10% higher, OR 95% CI 0.82-1.02, p = 0.09). Patients with MCF <0.2 had the highest in-hospital mortality, and those with MCF ≥0.5 had the lowest in-hospital mortality, irrespective of admission diagnosis or LVEF.

Conclusions: MCF demonstrated a strong, inverse relationship with hospital mortality in CICU patients, even after adjusting for LVEF and clinical variables. MCF can be used to identify prognostically-relevant myocardial dysfunction at the bedside, even among patients with preserved LVEF.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.040DOI Listing
December 2021

Use of Artificial Intelligence Tools Across Different Clinical Settings: A Cautionary Tale.

Circ Cardiovasc Qual Outcomes 2021 09 16;14(9):e008153. Epub 2021 Aug 16.

Department of Cardiovascular Medicine (K.C.S., P.A.N., Z.I.A., P.A.F., B.J.G.), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.008153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455449PMC
September 2021

Cardiovascular Prevention in Individuals at High Risk of Developing Cancer.

JACC CardioOncol 2020 Sep 15;2(3):527-531. Epub 2020 Sep 15.

UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California, Los Angeles, California, USA.

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http://dx.doi.org/10.1016/j.jaccao.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352253PMC
September 2020

Defining the Proper SYNTAX for Long-Term Benefit of Myocardial Revascularization With Optimal Medical Therapy.

J Am Coll Cardiol 2021 07;78(1):39-41

Department of Cardiovascular Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.04.088DOI Listing
July 2021

Use of the HAVOC Score to Identify Patients at Highest Risk of Developing Atrial Fibrillation.

Cardiology 2021;146(5):633-640. Epub 2021 Jun 22.

Columbia University Medical Center, New York, New York, USA.

Background: Recent studies using insertable cardiac monitors (ICMs) show a high incidence of atrial fibrillation (AF). Further identifying subsets of patients who could benefit most from ICMs is desirable. We evaluated whether the HAVOC risk score which predicts AF in patients with cryptogenic stroke also predicts AF detection by ICMs in those without recent stroke.

Methods: Participants were included from the prospective, industry-sponsored REVEAL AF study assessing AF incidence in patients with CHADS2 scores ≥3 or =2 with 1 or more additional AF risk factors, who had ICM data and were not receiving anti-arrhythmic drugs. Ischemic stroke occurring less than 1 year prior to enrollment or documented AF were exclusion criteria. AF was defined as an adjudicated ICM-detected episode ≥6 min in duration. HAVOC scores were calculated by assigning 4 points for congestive heart failure, 2 points for each of hypertension, age ≥75 years, valvular disease, and coronary artery disease, and 1 point for each of peripheral vascular disease and obesity (body mass index >30). Scores classified risk as low (0-4), intermediate (5-9), or high (10-14); corresponding AF detection rates were compared using the log-rank test. AF incidence rates in patients with and without a history of remote stroke at baseline were also compared.

Results: Among 391 participants, the mean age was 71.5 ± 9.8 years and 186 (47.6%) were women. In total, 130 (33.2%) developed AF over 18 months. Stratification by HAVOC risk score was: 95 (24%) low, 241 (62%) intermediate, and 55 (14%) high. At 18 months, AF incidence in patients with low HAVOC scores (19.5%) was lower than in those with intermediate (32.1%) or high (34.2%) scores. AF incidence was similar among those with (n = 78) versus without (n = 313) remote stroke (27.3% vs. 29.8%; median time from stroke to ICM insertion was 4.2 [2.2-8.2] years).

Conclusions: The HAVOC risk score identified a subset of individuals at greatest risk of developing AF, while AF incidence rates were similar among those with and without remote stroke. The use of the HAVOC score could help identify those at greatest likelihood of manifesting AF during long-term monitoring.
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http://dx.doi.org/10.1159/000517827DOI Listing
December 2021

An under-recognized phenomenon: Myocardial volume change during the cardiac cycle.

Echocardiography 2021 08 4;38(8):1235-1244. Epub 2021 Jun 4.

Department of Cardiology, Mayo Clinic, Rochester, MN, USA.

Background: Myocardial volume is assumed to be constant over the cardiac cycle in the echocardiographic models used by professional guidelines, despite evidence that suggests otherwise. The aim of this paper is to use literature-derived myocardial strain values from healthy patients to determine if myocardial volume changes during the cardiac cycle.

Methods: A systematic review for studies with longitudinal, radial, and circumferential strain from echocardiography in healthy volunteers ultimately yielded 16 studies, corresponding to 2917 patients. Myocardial volume in systole (MVs) and diastole (MVd) was used to calculate MVs/MVd for each study by applying this published strain data to three models: the standard ellipsoid geometric model, a thin-apex geometric model, and a strain-volume ratio.

Results: MVs/MVd<1 in 14 of the 16 studies, when computed using these three models. A sensitivity analysis of the two geometric models was performed by varying the dimensions of the ellipsoid and calculating MVs/MVd. This demonstrated little variability in MVs/MVd, suggesting that strain values were the primary determinant of MVs/MVd rather than the geometric model used. Another sensitivity analysis using the 97.5th percentile of each orthogonal strain demonstrated that even with extreme values, in the largest two studies of healthy populations, the calculated MVs/MVd was <1.

Conclusions: Healthy human myocardium appears to decrease in volume during systole. This is seen in MRI studies and is clinically relevant, but this study demonstrates that this characteristic was also present but unrecognized in the existing echocardiography literature.
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http://dx.doi.org/10.1111/echo.15093DOI Listing
August 2021

Batch enrollment for an artificial intelligence-guided intervention to lower neurologic events in patients with undiagnosed atrial fibrillation: rationale and design of a digital clinical trial.

Am Heart J 2021 09 24;239:73-79. Epub 2021 May 24.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Background: Clinical trials are a fundamental tool to evaluate medical interventions but are time-consuming and resource-intensive.

Objectives: To build infrastructure for digital trials to improve efficiency and generalizability and test it using a study to validate an artificial intelligence algorithm to detect atrial fibrillation (AF).

Design: We will prospectively enroll 1,000 patients who underwent an electrocardiogram for any clinical reason in routine practice, do not have a previous diagnosis of AF or atrial flutter and would be eligible for anticoagulation if AF is detected. Eligible patients will be identified using digital phenotyping algorithms, including natural language processing that runs on the electronic health records. Study invitations will be sent in batches via patient portal or letter, which will direct patients to a website to verify eligibility, learn about the study (including video-based informed consent), and consent electronically. The method aims to enroll participants representative of the general patient population, rather than a convenience sample of patients presenting to clinic. A device will be mailed to patients to continuously monitor for up to 30 days. The primary outcome is AF diagnosis and burden; secondary outcomes include patients' experience with the trial conduct methods and the monitoring device. The enrollment, intervention, and follow-up will be conducted remotely, ie, a patient-centered site-less trial.

Summary: This is among the first wave of trials to adopt digital technologies, artificial intelligence, and other pragmatic features to create efficiencies, which will pave the way for future trials in a broad range of disease and treatment areas. Clinicaltrials.gov: NCT04208971.
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http://dx.doi.org/10.1016/j.ahj.2021.05.006DOI Listing
September 2021

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19.

J Am Coll Cardiol 2021 05;77(20):2466-2476

Cardiovascular Department, Manzoni Hospital, Lecco, Italy.

Background: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.

Objectives: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.

Methods: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).

Results: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).

Conclusions: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.
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http://dx.doi.org/10.1016/j.jacc.2021.03.309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128002PMC
May 2021

Temporal Trends, Management and Outcomes of Acute Myocardial Infarction with Concomitant Respiratory Infections.

Am J Cardiol 2021 07 15;150:1-7. Epub 2021 May 15.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

There are limited contemporary data on the management and outcomes of acute myocardial infarction (AMI) in patients with concomitant acute respiratory infections. Hence, using the National Inpatient Sample from 2000-2017, adult AMI admissions with and without concomitant respiratory infections were identified. We evaluated in-hospital mortality, utilization of cardiac procedures, hospital length of stay, hospitalization costs, and discharge disposition. Among 10,880,856 AMI admissions, respiratory infections were identified in 745,536 (6.9%). Temporal trends revealed a relatively stable tr end with a peak during 2008-2009. Admissions with respiratory infections were on average older (74 vs. 67 years), female (45% vs 39%), with greater comorbidity (mean Charlson comorbidity index 5.9 ± 2.2 vs 4.4 ± 2.3), and had higher rates of non-ST-segment-elevation AMI presentation (71.8% vs. 62.2%) (all p < 0.001). Higher rates of cardiac arrest (8.2% vs 4.8%), cardiogenic shock (10.7% vs 4.4%), and acute organ failure (27.8% vs 8.1%) were seen in AMI admissions with respiratory infections. Coronary angiography (41.4% vs 65.6%, p < 0.001) and percutaneous coronary intervention (20.7% vs 43.5%, p < 0.001) were used less commonly in those with respiratory infections. Admissions with respiratory infections had higher in-hospital mortality (14.5% vs 5.5%; propensity matched analysis: 14.6% vs 12.5%; adjusted odds ratio 1.25 [95% confidence interval 1.24-1.26], p < 0.001), longer hospital stay, higher hospitalization costs, and less frequent discharges to home compared to those without respiratory infections. In conclusion, respiratory infections significantly impact AMI admissions with higher rates of complications, mortality and resource utilization.
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http://dx.doi.org/10.1016/j.amjcard.2021.03.037DOI Listing
July 2021

To stent or not to stent? Treating angina after ISCHEMIA-introduction.

Eur Heart J 2021 04;42(14):1387-1388

Royal Brompton & Harefield Hospitals, Heart Division and Imperial College, National Heart & Lung Institute, London, UK

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http://dx.doi.org/10.1093/eurheartj/ehab069DOI Listing
April 2021

To stent or not to stent? Treating angina after ISCHEMIA-the impact of the ISCHEMIA trial on the indications for angiography and revascularization in patients with stable coronary artery disease.

Eur Heart J 2021 04;42(14):1389-1393

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

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http://dx.doi.org/10.1093/eurheartj/ehab069.001DOI Listing
April 2021

Stem Cells in Cardiovascular Diseases: 30,000-Foot View.

Cells 2021 03 9;10(3). Epub 2021 Mar 9.

Department of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Stem cell and regenerative approaches that might rejuvenate the heart have immense intuitive appeal for the public and scientific communities. Hopes were fueled by initial findings from preclinical models that suggested that easily obtained bone marrow cells might have significant reparative capabilities; however, after initial encouraging pre-clinical and early clinical findings, the realities of clinical development have placed a damper on the field. Clinical trials were often designed to detect exceptionally large treatment effects with modest patient numbers with subsequent disappointing results. First generation approaches were likely overly simplistic and relied on a relatively primitive understanding of regenerative mechanisms and capabilities. Nonetheless, the field continues to move forward and novel cell derivatives, platforms, and cell/device combinations, coupled with a better understanding of the mechanisms that lead to regenerative capabilities in more primitive models and modifications in clinical trial design suggest a brighter future.
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http://dx.doi.org/10.3390/cells10030600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001267PMC
March 2021

Dosing of Direct Oral Anticoagulants in Patients with Moderate Chronic Kidney Disease in US Clinical Practice: Results from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF II).

Am J Cardiovasc Drugs 2021 Sep 31;21(5):553-561. Epub 2021 Mar 31.

Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, 200 Morris Street, Durham, NC, 27701, USA.

Introduction: Direct oral anticoagulants (DOACs) have partial renal clearance and generally require dosage adjustments based on renal function. While current US and European guidance recommends dose adjustments in patients with moderate chronic kidney disease (CKD), it is unclear how often this is done appropriately in routine clinical practice.

Methods: We examined rates of appropriate and inappropriate dosing in patients with atrial fibrillation (AF) and moderate CKD, as determined by creatinine clearance (CrCl) of 30-50 mL/min calculated with the Cockcroft-Gault formula. Descriptive statistics were used to describe the rate of appropriate and inappropriate dosing as well as event rates.

Results: Among 1134 patients (8.5% of the overall ORBIT-AF II registry) with AF and CrCl 30-50 mL/min, the median age was 82 (25th, 75th percentile: 78, 86), 38% were male, and the median CHADSVASC score was 4 (25th, 75th percentile: 4, 5). At baseline, more than one-third (34%) of patients with moderate CKD were inappropriately dosed with DOACs. When evaluating the specific prescribed doses in those with moderate CKD, 15% (N = 170/1134) were underdosed, 66% (743/1134) were appropriately dosed, and 20% (N = 221/1134) were overdosed. There were no significant differences in comorbid medical conditions between patients with moderate CKD who were appropriately and inappropriately dosed with a DOAC.

Conclusion: In routine clinical practice, prescribing of DOACs in patients with AF with moderate CKD is often inconsistent with drug labeling, with up to one-third of patients being inappropriately dosed.
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http://dx.doi.org/10.1007/s40256-021-00473-xDOI Listing
September 2021

Risk of left atrial appendage thrombus and stroke in patients with atrial fibrillation and mitral regurgitation.

Heart 2022 01 25;108(1):29-36. Epub 2021 Mar 25.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Objective: To investigate the association of mitral regurgitation (MR) on thromboembolic risk of patients with non-valvular atrial fibrillation (NVAF) undergoing transoesophageal echocardiography (TEE)-guided cardioversion.

Methods: Data for consecutive patients who underwent TEE-guided cardioversion for NVAF between 2000 and 2012 were analysed. MR severity was assessed by Doppler echocardiography and classified as ≤mild, moderate or severe. Left atrial appendage emptying velocities were averaged for five consecutive cycles. Multivariable regression models were used to identify independent predictors of left atrial appendage thrombus (LAAT) and stroke.

Results: 2950 patients (age, 69.3±12.2 years, 67% men) were analysed. 2173 (73.7%) had ≤mild MR; 631 (21.4%), moderate MR; and 146 (4.9%), severe MR. Patients with moderate (age, 72.4±10.7 years) and severe (age, 72.8±12.1 years) MR were older than those with ≤mild MR (age, 68.2±12.5 years). The prevalence of LAAT was 1.5% (n=43). CHADS-VASc scores (≤mild MR, 3.0±1.6; moderate MR, 3.5±1.5; severe MR, 3.9±1.5; p<0.001) and heart failure frequency (≤mild MR, 38.4%; moderate MR, 48.0%; severe MR, 69.2%; p<0.001) were increasingly higher with greater MR severity. Multivariable logistic regression analysis showed no association of moderate MR (OR 0.77, 95% CI 0.38 to 1.56) or severe MR (OR 0.55, 95% CI 0.21 to 1.49) with LAAT. During a mean follow-up of 7.3±5.1 years (median 7.5, IQR, 2.7-10.9), 216 patients had an ischaemic stroke. Adjusted Cox regression analysis showed no significant association of moderate MR (HR 1.22, 95% CI 0.88 to 1.68) or severe MR (HR 0.73, 95% CI 0.31 to 1.46) with stroke.

Conclusions: Among patients with NVAF, the presence or severity of MR was not associated with a decreased risk of LAAT or stroke.
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http://dx.doi.org/10.1136/heartjnl-2020-317659DOI Listing
January 2022

Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas.

Open Heart 2021 03;8(1)

Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.

Objectives: Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions.

Methods: Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region.

Results: GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions.

Conclusions: In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.

Trial Registration Number: ClinicalTrials.gov Registry NCT00412984 and NCT00262600.
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http://dx.doi.org/10.1136/openhrt-2020-001471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986788PMC
March 2021
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