Publications by authors named "Emily K Zern"

11 Publications

  • Page 1 of 1

Association of obesity-related inflammatory pathways with lung function and exercise capacity.

Respir Med 2021 Jul 30;183:106434. Epub 2021 Apr 30.

From the Cardiovascular Research Center, Division of Massachusetts General Hospital, Boston, MA, USA; Cardiology Division of Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Background: Obesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear.

Research Question: To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance.

Method: We examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006-June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression.

Results: Obesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV and FVC with a preserved FEV/FVC ratio suggesting a restrictive physiology pattern (P ≤ 0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV and FVC (beta -4.8, s.e. 0.9 for FEV1; beta -4.9, s.e. 0.8 for FVC; P < 0.0001 for both). Obesity-related inflammatory pathways were associated with worse pulmonary vascular distensibility (adiponectin, IL-6, and CRP, P < 0.05 for all), as well as lower pulmonary artery compliance (IL-6 and CRP, P ≤ 0.01 for both).

Interpretation: Our findings highlight the importance of obesity-related inflammatory pathways including inflammation and insulin resistance on pulmonary spirometry and pulmonary vascular function. Specifically, systemic inflammation as ascertained by CRP, IL-6 and insulin resistance are associated with restrictive pulmonary physiology independent of BMI. In addition, inflammatory markers were associated with lower exercise capacity and pulmonary vascular dysfunction.
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July 2021

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Aabnormal Left Ventricular Hemodynamic Responses During Exercise.

J Card Fail 2021 Jun 26;27(6):625-634. Epub 2021 Feb 26.

Corrigan Minehan Heart Center, Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Arterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise.

Methods And Results: A total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52-3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption.

Conclusions: Exercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular-vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.
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June 2021

Angiotensin Receptor-Neprilysin Inhibitor Therapy Reverses Pulmonary Hypertension in End-Stage Heart Failure Patients Awaiting Transplantation.

Circ Heart Fail 2020 02 14;13(2):e006696. Epub 2020 Feb 14.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (E.K.Z., S.C., M.A.H., M.M.K.).

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February 2020

Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort.

J Am Coll Cardiol 2020 01;75(1):17-26

Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear.

Objectives: This study sought to investigate the association of exPH with clinical determinants and outcomes.

Methods: The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality.

Results: Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both).

Conclusions: Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
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January 2020

Differential Clinical Profiles, Exercise Responses, and Outcomes Associated With Existing HFpEF Definitions.

Circulation 2019 07 28;140(5):353-365. Epub 2019 May 28.

Cardiology Division, Department of Medicine (J.E.H., L.W., C.S.B., T.C., A.S.E., K.M.H., P.P.P., R.M., M.N., G.D.L.), Massachusetts General Hospital, Boston.

Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF.

Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes.

Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met Heart Failure Society of America (HFSA) criteria for HFpEF. Clinical profiles and exercise capacity varied across definitions, with peak oxygen uptake of 16.2±5.2 (ACC/AHA), 14.1±4.2 (ESC), and 12.7±3.1 mL·kg·min (HFSA). A total of 243 patients had hemodynamic evidence of HFpEF (abnormal rest or exercise filling pressures), of whom 222 met ACC/AHA, 161 met ESC, and 41 met HFSA criteria. Over a mean follow-up of 3.8 years, the incidence of cardiovascular outcomes ranged from 75 (ACC/AHA) to 298 events per 1000 person-years (HFSA). Application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication.

Conclusions: Use of different HFpEF classifications variably enriches for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure highlights the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF subgrouping to test therapeutic interventions.
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July 2019

The Renal Challenge With Left Ventricular Assist Device Therapy-When Enough Is Enough.

JAMA Intern Med 2018 02;178(2):210-211

Division of Cardiac Surgery, Massachusetts General Hospital, Harvard Medical School, Boston.

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February 2018

A Pulmonary Embolism Response Team: initial experiences and future directions.

Expert Rev Cardiovasc Ther 2017 Jun 5;15(6):481-489. Epub 2017 Jun 5.

c Center for Vascular Emergencies, Department of Emergency Medicine , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.

Introduction: Acute pulmonary embolism (PE) is a common cardiovascular condition resulting in significant morbidity and mortality. Consensus recommendations suggest risk stratification of patients into three main categories: high-risk or 'massive' PE, intermediate-risk or 'submassive' PE, and low-risk PE. Given the relative dearth of prospective, randomized clinical trials delineating optimal selection of the diverse medical, interventional, and surgical treatment approaches, clinical care requires a multidisciplinary expert approach to patients with PE. Areas covered: The Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) was the first of its kind to create a multidisciplinary, rapid response team for acute PE, integrated within a research and educational framework. The MGH PERT has treated more than 700 patients with PE, the majority of which are in the 'massive' or 'submassive' categories. The PERT Consortium™ was founded in 2015 as a collaborative network between the growing number of PERT programs internationally, with greater than 80 institutions participating within one year of establishment. Expert commentary: Since its advent, the PERT model has expanded throughout the United States and internationally through a collaborative institutional and research network. PERT may represent a new standard for the care of patients with acute PE.
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June 2017

Utilization of palliative care services for cardiac arrest patients undergoing therapeutic hypothermia: A retrospective analysis.

Resuscitation 2017 03 21;112:22-27. Epub 2016 Dec 21.

Division of General Medicine and Public Health, Section of Palliative Care, Vanderbilt University Medical Center, United States.

Background: Palliative care (PC) services are integral to the care of patients with advanced medical illnesses. Given the significant morbidity and mortality associated with cardiac arrest, we sought to measure the use and impact of PC in the care of patients treated with therapeutic hypothermia (TH).

Methods: We conducted a retrospective study of 317 consecutive patients undergoing TH after cardiac arrest. We compared intensive care unit (ICU) characteristics and clinical outcomes of subjects who received PC consultation (n=125) to those who did not (n=192).

Results: The proportion of TH patients with PC consultations increased to greater than 60% by 2013, corresponding to our institution's expansion of PC services, development of a dedicated PC unit, and integration of this service into our published TH protocol. In the TH population, time to return of spontaneous circulation (ROSC) was associated with higher inpatient mortality (p<0.001) and placement of a PC consult (p=0.011). TH patients who received PC consultation had longer ICU stays (p=0.034), more ventilator days (p<0.001), and higher inpatient mortality (p<0.001). When these measures were analyzed cohort-wide comparing all TH patients pre- and post-2013, at which time the frequency of PC consultation had dramatically increased, there were no statistically significant differences in ICU care or outcomes.

Conclusion: In our population of cardiac arrest patients undergoing TH, the utilization of PC services has increased over time, particularly for those patients with high morbidity and mortality. Future randomized studies may further delineate optimal patient selection for PC consultation to better facilitate goals of care discussions and timely medical decision-making.
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March 2017

The Evaluation of Donor Site Pain After Harvest of Tricortical Anterior Iliac Crest Bone Graft for Spinal Surgery: A Prospective Study.

Spine (Phila Pa 1976) 2016 Feb;41(4):E191-6

*Department of Orthopaedics, Vanderbilt Orthopaedic Institute, Vanderbilt University School of Medicine, Nashville, TN†Texas Metroplex Institute for Sports Medicine and Orthopaedics, Arlington, TX‡Vanderbilt University School of Medicine, Nashville, TN§Oklahoma Sports, Science and Orthopaedics, Oklahoma City, OK||Department of Orthopaedics, University of Pittsburgh Medical Center, Pittsburgh, PA.

Study Design: A prospective cohort.

Objective: The aim of this study was to prospectively observe donor site pain, health-related quality-of-life outcomes, and complications following harvest of tricortical anterior iliac crest bone graft (AICBG) for anterior cervical discectomy and fusion (ACDF).

Summary Of Background Data: Persistent donor site pain from the anterior iliac crest has been reported to range between 2% and 40%. This morbidity has led surgeons to consider interbody alternatives for ACDF, which carry additional costs.

Methods: We prospectively enrolled 50 patients from 2 tertiary care centers over the course of 1 year observing complications and patient-reported outcomes. Patients filled out SF-12 and numeric rating scale (NRS) for pain in the arm, neck, and donor site pre-operatively and at 1 week, 2 weeks, 6 weeks, 3 to 6 months, and 1 year postoperatively. Outcomes were compared with a control group undergoing ACDF with allograft or Polyether ether ketone cages at 1 year.

Results: The mean ± SD donor site pain at 1 week was 5.6 ± 2.8 but decreased to 2.2 ± 2.4 at 6 weeks and 1.1 ± 1.8 at 1 year (P < 0.001). Including the 3 patients who were lost to follow-up, 10% of patients may have experienced persistent moderate or worse pain at 1 year. Linear regression analysis demonstrated that preoperative opioid use was an independent risk factor for increased donor site pain at 1 and 2 weeks (P < 0.05). There were no differences in outcomes at 1 year compared with the nonautograft group. There were 2 (4%) minor wound complications, both treated successfully with oral antibiotics.

Conclusion: Tricortical AICBG for ACDF is not associated with major complications and only 4% of patients (potentially, maximum of 10%) experienced moderate, persistent donor site pain at 1 year. There is no difference in health-related outcomes between patients who have autograft with those who did not at 1 year. Preoperative opioid use is associated with increased donor site pain within the first 2 weeks postoperatively but not in the long term. At 6 weeks postoperatively, patients can expect the majority of their donor site pain to be resolved.

Level Of Evidence: 2.
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February 2016

B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade.

PLoS One 2013 16;8(12):e84185. Epub 2013 Dec 16.

Department of Pathology, Microbiology and Immunology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America ; Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function.
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September 2014