Evaluation of Cardiopulmonary Diseases by Ultrasound

Study Purpose and Rationale

The purpose of this study is to assess the utility of noninvasive assessment of lung Doppler
signals performed via transthoracic parametric Doppler. The study has two major objectives
and is thus, divided into two phases, which are on a continuum.

Phase 1: The objective is to further evaluate LDS among patients presenting to the emergency
department with acute dyspnea, in order to determine the diagnostic value of this
non-invasive method to distinguish cardiac from pulmonary causes of dyspnea.

Phase 2: In addition, for those patients admitted to the hospital with a clinical diagnosis
of ADHF, we would like to further characterize changes in daily lung Doppler signal as a
surrogate biomarker of intravascular volume status, as assessed by clinical assessment.

Study Design and Methods:

1. Overall study design

Phase 1:

Prospective cohort study of patients presenting to the Massachusetts General Hospital
emergency department with acute dyspnea. . In addition, at MGH, pts admitted to the cardiac
floors (Ellison 9, 10, 11) and general medicine floors (White 9, 10, 11) with an admitting
diagnosis of heart failure, who presented with acute dyspnea, will be approached for
enrollment within 24 hours of hospital admission. All patients with acute dyspnea will
undergo routine clinical assessment, laboratory testing, and diagnostic imaging. In addition,
all patients will also undergo transthoracic parametric Doppler ultrasound based assessment
of LDS. Patients will be treated as usual, under the direction of the attending physician.
Two independent cardiologists will perform detailed chart review on all patients to determine
the etiology of acute dyspnea. They will be blinded to the results of the LDS. In the event
of discrepant findings, a third cardiologist will perform a final detailed chart review to
adjudicate the diagnosis.

Additionally, radiologist employed at MGH and who are independent to the study may perform
blinded adjudication of the study participants' chest x-rays (CXR) obtained in the Emergency
Department on the day of enrollment into the study

Phase 2:

In addition, patients diagnosed with ADHF (diagnosed based on the criteria described below),
will undergo daily TPD and assessment of LDS to further characterize changes in LDS over
time, until the day of discharge or up to day 7 of hospitalization, whichever comes first. In
addition to the initial inpatient scans, study staff will try to acquire a final scan within
72 hours of discharge for patients diagnosed with ADHF, regardless of the day of
hospitalization. This cohort of patients will also undergo daily clinical assessment of
volume status, weight measurement, and BNP assessment. In the event that repeat BNP or
NT-proBNP labs have not been drawn within 72 hours of discharge, study staff will coordinate
with the pathology laboratory (Dr. Kent Lewandrowski) to perform the assay as a research test
using excess clinical specimen from the subject's routine clinical blood draw if available.
Research subjects will not be charged for the cost of the BNP or NT-Pro-BNP assay.

Inclusion Criteria:

- Phase 1(ED):

Inclusion criteria:

Age > 18 years Acute onset dyspnea

- Phase 2 (Inpatient):

Age > 18 years Acute onset dyspnea: defined as SOB at rest or with minimal activity, with
onset within the past 14 days PLUS

The following criteria are required to be classified as heart failure (event has to meet
all of the following criteria):

a) The patient exhibits documented new or worsening symptoms due to heart failure on
presentation, including at least one of the following: i) Dyspnea (dyspnea with exertion,
dyspnea at rest, orthopnea) ii) Decreased exercise tolerance b) The patient has objective
evidence of new or worsening heart failure, consisting of at least two physical exam
findings (or one physical exam finding and one diagnostic criterion) including: i) Physical
exam findings considered to be due to heart failure, including new or worsened:

(1) Peripheral edema (2) Increasing abdominal distention or ascites (in the absence of
primary hepatic disease) (3) Increased jugular venous pressure and/or hepatojugular reflux
(4) Rapid weight gain thought to be related to fluid overload ii) Diagnostic findings
considered to be due to heart failure, including new or worsened:

1. Increased B-type natriuretic peptide/ NT-proBNP concentrations consistent with
decompensation of heart failure Note: In patients with chronically elevated
natriuretic peptides, a significant increase should be noted above baseline.

2. Radiological evidence of pulmonary congestion

Exclusion Criteria:

- Phase 1 (ED):

Pregnant women Inability to consent

- Phase 2 (Inpatient):

Pregnant women Pneumonia - currently, or within the past 30 days Non-cardiogenic pulmonary
edema (e.g. ARDS) Interstitial lung disease Inability to consent