Search Results
within category "Heart and Vascular"
Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Contrast Ultrasound for Pediatric Trauma - Comparative Evaluation (CAPTURE Study)
This multicenter study aims to evaluate the accuracy of contrast-enhanced ultrasound (CEUS)
in diagnosing abdominal solid organ injuries in pediatric patients. Up to 130 subjects will
complete the study across approximately 5-10 sites in the US, with up to 30 patients in the
training phase (3 per site) and 100 patients in the treatment phase of the study. All
subjects will have had a CT scan as part of standard of care, confirming at least one solid
organ abdominal injury. The study procedure will occur within 48 hours from time of injury.
All subjects will have an abdominal ultrasound without contrast, followed by a
contrast-enhanced ultrasound using the contrast agent Lumason. Ultrasound and
contrast-enhanced ultrasound results will be compared to the CT scan results. The CT and
ultrasound scans will be read locally and will undergo central review.
1. Hemodynamically stable, as determined by the trauma team
2. Age 8 through 18 years (inclusive)
3. Interpretable CT of the abdomen and pelvis that demonstrates at least one solid organ
injury among the liver, spleen, pancreas, and kidneys
4. Plan for observation or admission to the hospital
5. Candidate for abdominal ultrasound based on body habitus, as determined by the
investigator
6. Glasgow Coma Score of 15
7. Able to complete the study procedures within 48 hours of injury
Exclusion Criteria:
1. Known cardiac abnormality
2. Pulmonary Hypertension
3. Known sensitivity to any Lumason components •including sulfur hexafluoride,
polyethylene glycol 4000, distearoylphosphatidylcholine (DSPC),
dipalmitoylphosphatidylglycerol sodium (DPPG-Na), or palmitic acid
4. Unable to be rolled onto side to allow lateral ultrasound windows if necessary
5. Unable to assent or consent
6. Pregnant
7. Lactating
8. CT images not available for transmission to central image repository
Drug: Lumason
Cardiovascular, Gall Bladder, Kidney, Liver, Pancreas, Soft Tissue, Abdominal Injury
A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction and Obesity (SUMMIT) (SUMMIT)
The main purpose of this study is to assess the efficacy and safety of Tirzepatide
(LY3298176) in participants with heart failure with preserved ejection fraction and obesity.
• Have a diagnosis of stable heart failure (NYHA class II-IV) and left ventricular
ejection fraction (LVEF) ≥50%
• Elevated NT-proBNP (N-terminal pro B-type natriuretic peptide) > 200 pg/ml for
participants without atrial fibrillation (AF), or >600 picogram/milliliter (pg/ml) for
participants with AF, Structural heart disease (Left atrial enlargement) or Elevated
left ventricular filling pressure
• Estimated glomerular filtration rate (eGFR) <70 milliliter (ml)/minute (min)/1.73m² at
screening, or HF decompensation within 12 months of screening,
• Stable dose of heart failure medications within 4 weeks of screening
• Body mass index (BMI) ≥30 kilograms per meter squared (kg/m²)
• 6MWD 100-425m
• KCCQ CSS ≤80
Exclusion Criteria:
• Have had a major cardiovascular event within the last 90 days of screening
• Have had acute decompensated heart failure within 4 weeks of screening
• Have non cardiac causes of functional impairment such as pulmonary arterial
hypertension (PAH), severe chronic obstructive pulmonary disease (COPD), anemia,
thyroid disease, musculoskeletal disease or orthopedic conditions
• Presence of cardiac amyloidosis, cardiac accumulation disease, cardiomyopathy and
severe valvular hear disease
• HbA1c ≥9.5% or uncontrolled diabetes
• History of proliferative diabetic retinopathy or diabetic maculopathy
• Have a history of pancreatitis
• eGFR <15 mL/min/1.73 m² or requiring dialysis at screening
Drug: Tirzepatide, Other: Placebo
Heart Failure With Preserved Ejection Fraction, Obesity
Heart Failure with Preserved Ejection Fraction (HFpEF)
AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA)
Objectives
- Primary: To test the hypothesis that apixaban is superior to aspirin for the prevention
of recurrent stroke in patients with cryptogenic ischemic stroke and atrial cardiopathy.
- Secondary: To test the hypothesis that the relative efficacy of apixaban over aspirin
increases with the severity of atrial cardiopathy.
• Age ≥ 45 years.
• Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
• Modified Rankin Scale (MRS) score ≤ 4.
• Ability to be randomized within 3 to 180 days after stroke onset.
• ESUS, defined as all of the following:
• Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a
subcortical (this includes pons and midbrain) infarct in the distribution of the
small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or
≤2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following
are not considered lacunes: multiple simultaneous small deep infarcts, lateral
medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar
stroke syndrome and no infarct on imaging are excluded.
• Absence of extracranial or intracranial atherosclerosis causing ≥50 percent
luminal stenosis of the artery supplying the area of ischemia. Patients must
undergo vascular imaging of the extracranial and intracranial vessels using
either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or
ultrasound, as considered appropriate by the treating physician and local
principal investigator.
• No major-risk cardioembolic source of embolism, including intracardiac thrombus,
mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors,
moderate or severe mitral stenosis, myocardial infarction within the last 4
weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or
infective endocarditis). Patent foramen ovale is not an exclusion. All patients
must undergo electrocardiogram, transthoracic or transesophageal echocardiography
(TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor
or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or
cardiac CT will be performed at the discretion of the local treating physician
and principal investigator. Additional cardiac rhythm monitoring, such as
monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor,
will be at the discretion of the treating physician and local principal
investigator.
• No other specific cause of stroke identified, such as arteritis, dissection,
migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as
toxicological screens, serological testing for syphilis, and tests for
hypercoagulability, will be performed at the discretion of the treating physician
and local principal investigator.
Exclusion Criteria:
• History of atrial fibrillation (AF), AF on 12-lead ECG, or any AF of any duration
during heart-rhythm monitoring prior to randomization.
• Clear indication for treatment-dose anticoagulant therapy, such as venous
thromboembolism or a mechanical heart valve.
• Need for antiplatelet agent, such as aspirin or clopidogrel
• History of spontaneous intracranial hemorrhage.
• Chronic kidney disease with serum creatinine ≥2.5 mg/dL.For Canadian sites only,
estimated creatinine clearance (eCrCl) <15 mL/min is also an exclusion criterion.
• Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.
• Clinically significant bleeding diathesis.
• Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).
• Clinically significant gastrointestinal bleeding within the past year (e.g., not due
to external hemorrhoids).
• At risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last
menses without a negative pregnancy test or not committing to adequate birth control,
which includes an oral contraceptive, two methods of barrier birth control such as
condom with or without spermicidal lubricant + diaphragm, or abstinence.
• Known allergy or intolerance to aspirin or apixaban.
• Concomitant participation in another clinical trial involving a drug or acute stroke
intervention.
• Considered by the investigator to have a condition that precludes follow-up or safe
participation in the trial.
• Inability of either participant or surrogate to provide written, informed consent for
trial participation.
Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
The global objective of this study is to determine the mechanisms of exercise intolerance and
dyspnea on exertion (DOE) in patients with HFpEF and based on this pathophysiology, test
whether specific exercise training programs (whole body vs single leg) will result in
improved exercise tolerance.
CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM
receiving available standard of care (SoC). For more information, please visit
https://www.cardio-ttransform.com.
• Females must be non-pregnant and non-lactating, and either surgically sterile or
post-menopausal or abstinent. If engaged in sexual relations of child-bearing
potential, agree to use 1 highly effective contraceptive method
• Males must be surgically sterile or, abstinent or, if engaged in sexual relations with
a woman of child-bearing potential, the participant or the participant's non-pregnant
female partner must be using a highly effective contraceptive method
• Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or
equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2-
propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m
Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the
absence of abnormal light chains ratio, centrally confirmed
• End-diastolic interventricular septum thickness of > 12 millimeters (mm) on Screening
echocardiogram
• New York Heart Association (NYHA) class I-III
Exclusion Criteria:
• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA),
coronary revascularization, cardiac device implantation, cardiac valve repair, or
major surgery within 3 months of Screening
• Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to
hypertension, valvular heart disease, or ischemic heart disease
• Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in
immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy
confirming the absence of light chain and the presence of TTR protein by mass
spectrometry or immunoelectron microscopy. For participants with chronic kidney
disease (CKD) and without presence of monoclonal protein in blood and urine, the
acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with
local hematologist, Investigator and Medical Monitor if the risks associated with the
biopsy outweigh the benefits
• Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or
anticipated liver transplant or LVAD within 1 year after randomization
• Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or
other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small
interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA]
vaccinations)
• Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid,
and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem).
Participants receiving any of these agents must respect a wash-out period of 14 days
before randomization.
Polypill Strategy for Heart Failure With Reduced Ejection Fraction
Heart failure with a reduced ejection fraction (HFrEF) represents a significant public health
burden in the United States, with a growing prevalence particularly among African Americans
and Hispanic Americans and individuals of low socioeconomic status (SES). Although effective
therapies exist, gaps in their uptake contribute substantially to the excess burden of heart
failure. The "polypill" is an inexpensive once daily pill containing three agents proven to
improve morbidity and mortality in heart failure and represents potential strategy for
increasing the utilization of proven HF therapies. The proposed study is a pragmatic,
single-center, randomized trial to test the feasibility and effectiveness of a polypill-based
strategy for the treatment of HFrEF in a low-income, racially diverse population.
• Adults age > = 18 years
• HF with left ventricular ejection fraction <= 40% within 3 months of screening who are
not on optimal guideline directed medical therapy
• New York Heart Association class II, III, or IV symptoms
Exclusion Criteria:
• Age < 18
• Systolic blood pressure < 120 mm Hg at enrollment
• Estimated glomerular filtration rate < 30 mL/min/1.73 m2 as measured by the simplified
• MDRD formula
• Serum potassium > 5.0 mEq/L
• Current need for inotropes
• Cardiac index < 2.2 L/min/m2
• History of revascularization within 30 days or plan for revascularization
• History of type 1 diabetes mellitus
• History of allergic reaction or contraindication to a beta-blocker (BB),
mineralocorticoid receptor antagonist (MRA), or sodium glucose cotransporter 2
inhibitor (SGLT2i)
• Contraindication to receive any of the components of the polypill
• Pregnancy
• < 12 month expected survival
• Inability to provide written informed consent
• Persistent or permanent atrial fibrillation who may not have optimal MRI imaging
• Extreme obesity (BMI > 45 kg/m2)
• ICD/PAcemaker devices that are incompatible with MRI
Drug: Polypill, Drug: Control Rx
Heart Failure, Heart
UT Southwestern; Parkland Health & Hospital System
A 12 Month Site Randomized Trial in Adults With Type 2 Diabetes Mellitus and History of Cardiovascular Disease (COORDINATE)
COORDINATE-Diabetes is a cluster-randomized clinical trial to test the effectiveness of an
innovative, clinic-level educational intervention to improve the management of patients with
type 2 diabetes mellitus and cardiovascular disease.
• Age ≥ 18 years old
• Diagnosis of Type 2 diabetes mellitus (T2DM)
• History of at least one of the following conditions:
1. Coronary artery disease (defined as prior MI, coronary revascularization (CABG or
PCI), and/or obstructive CAD (≥50%) as documented by angiography or CTA)
2. Stroke and/or carotid artery stenosis (≥50%)
3. Peripheral Arterial disease (defined as claudication with ABI<0.9, prior
peripheral revascularization, and/or amputation due to circulatory insufficiency)
• Ability to communicate with site staff and understand and provide written informed
consent and proof of Health Insurance Portability and Accountability Act (HIPAA)
authorization
Exclusion Criteria:
• Determined to be highly unlikely to survive and/or to continue follow-up in that
clinic for at least 1 year, as identified by site investigator
• GFR<30 mL/min/1.73m2
• Already on all guideline-recommended therapies for T2DM and CVD
• Absolute contraindication to any of the guideline recommended therapies for T2DM and
CVD
Other: Intense Education Intervention
Diabetes Mellitus, Type 2, Cardiovascular Diseases
COORDINATE-DIABETES, COORDINATE, T2DM, Diabetes Mellitus, Type 2, Cardiovascular Disease, Prevention
UT Southwestern; Parkland Health & Hospital System
Cancer and Blood Pressure Management, CARISMA Study
This phase II trial studies how well intensive blood pressure management works in decreasing
systolic blood pressure in patients with kidney or thyroid cancer that has spread to other
places in the body (metastatic) who are starting anti-angiogenic tyrosine kinase inhibitor
cancer therapy. This study is being done to find out if a systolic blood pressure to a target
of less than 120 mmHg (intensive systolic blood pressure management) can be achieved, well
tolerated, and beneficial as compared to the usual approach to a target of less than 140 mmHg
while taking an anti-angiogenic tyrosine kinase inhibitor. This study may help doctors
understand the best way to control blood pressure in kidney or thyroid cancer patients taking
anti-angiogenic tyrosine kinase inhibitor.
• English speaking
• Patient must have histologically or cytologically-proven advanced metastatic renal
cell cancer (mRCC) or medullary thyroid cancer initially treated with anti-angiogenic
tyrosine kinase inhibitors (AA-TKIs) including: sunitinib, sorafenib, pazopanib,
cabozantinib, lenvatinib, vandetanib, or axitinib)
• NOTE: If patient has a severe sulfa allergy (e.g. Stevens Johnson reaction), then
alternative non-sulfa medications can be considered in consultation with the
C-BAC. Patient with a noted severe allergic reactions to medications listed in
the algorithms is not necessarily excluded from this trial, as alternative
medications could be considered in consultation with the C-BAC. Moreover, the
patient treated with pre-existing medications that may interact with proposed BP
medications is not necessarily excluded, as alternative medications exist. The
clinical significance of any potential drug interactions can also be addressed
with the C-BAC.
• Prior exposure to another AA-TKI is permissible. Concurrent or prior treatment with
immunotherapy is also permissible
• Patient must have either clinical cardiovascular (CV) disease or evidence of increased
CV risk as defined by one or more of the following:
• Clinical CV disease (history of myocardial infarction [MI] acute coronary
syndrome, coronary revascularization, carotid endarterectomy or stenting greater
than 3 months prior to registration, peripheral artery disease, cerebrovascular
accident greater than 3 months prior to registration, abdominal aortic aneurysm
or heart failure [HF])
• An American College of Cardiology/American Heart Association (ACC/AHA) CV risk
score of at least 10%
• Chronic kidney disease (defined as an estimated glomerular filtration rate [eGFR]
between 30 and 60 ml/min per 1.73 m^2). Dialysis patients and patients with an
eGFR < 30 ml/min/1.73m^2 will be excluded. eGFR will be calculated according to
the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
• Patient must have systolic blood pressure (SBP) >= 130 mmHg on two or more occasions
according to any in-clinic visit in the 12 weeks prior to or during their initial 4
weeks of treatment with an AA-TKI. Patient who have a prior diagnosis of hypertension
or on pre-existing anti-hypertensive medications are eligible for enrollment. However,
patient must not be on more than 3 baseline blood pressure medications at time of
entry
• NOTE: If a patient has a single elevated SBP >= 130mmHg but not on repeat
assessment, an additional SBP assessment should be performed to confirm
ineligibility
• Patient must agree to comply with performing home blood pressure monitoring using an
Omron7250 oscillometric monitor at home, or equivalent models
• Women of childbearing potential and sexually active males must be strongly advised to
use accepted and effective methods of contraception or to abstain from sexual
intercourse for the duration of their participation in the study
• Patient must have internet access through a computer, tablet, or smart phone to use
EASEE-PRO and home BP monitoring. A valid phone number to receive text messages and
email address are also necessary
• Leukocytes >= 3,000/mcL (obtained within 14 days prior to registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 14 days prior to registration)
• Platelets >= 100,000/mcL (obtained within 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to
registration)
• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patient with a history of hepatitis C virus (HCV) infection must have been treated and
cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patient with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression
• Patient with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required during
the first cycle of therapy
• Patient with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Exclusion Criteria:
• Patient must not have end-stage renal failure on dialysis, history of repeated
hyperkalemia with a potassium > 5.5 mEq/l, or have a kidney transplant, or an eGFR <
30 ml/min/1.73 m^2
• Patient must not have coronary artery bypass grafting, MI acute coronary syndrome
severe/unstable angina, stroke, transient ischemic attack, clinically significant
bleeding requiring hospitalization or pulmonary embolism within 3 months prior to
registration
• Patient must not have brain surgery or radiotherapy within 2 weeks prior to
registration
• Patient must not have uncontrolled blood pressure defined by SBP > 160 mmHg on three
or more antihypertensives prior to TKI initiation
• Patient with an arm circumference too large (> 50 cm) or small (< 17 cm) to allow
accurate BP measurement with available devices will not be eligible
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with some
anti-hypertensives, including angiotensin receptor blockers. All females of
childbearing potential must have a blood test or urine study within 14 days prior to
registration to rule out pregnancy. A female of childbearing potential is defined as
any woman, regardless of sexual orientation or whether they have undergone tubal
ligation, who meets the following criteria: has achieved menarche at some point, has
not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing
potential) for at least 24 consecutive months (i.e., has had menses at any time in the
preceding 24 consecutive months)
This study will monitor device performance and outcomes of the SAPIEN 3 Transcatheter Heart
Valve (THV) System in subjects with a dysfunctional right ventricular outflow tract (RVOT)
conduit or previously implanted surgical valve in the pulmonic position with a clinical
indication for intervention.
1. Dysfunctional RVOT conduit or previously implanted surgical valve
2. RVOT/PV with ≥ moderate regurgitation and/or a mean RVOT/PV gradient of ≥ 35 mmHg
Exclusion Criteria:
1. Inability to tolerate an anticoagulation/antiplatelet regimen
2. Active bacterial endocarditis or other active infections
Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
The purpose of this study is to determine if intensive lowering of systolic blood pressure
(SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease
pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high
risk for memory decline or dementia.
• Age 60-80, all races/ethnicities, and both sexes are eligible;
• a) A positive family history of dementia defined as having at least one first-degree
relative with a history of AD or other type of dementia or
• b) having subjective memory complaints defined as a positive answer to BOTH of the
following questions:
1. "Are you worried about your memory or thinking abilities?
a) Not at all, b) A little bit, c) A lot"; B and C •includes
2. "Do you feel you have difficulty with your memory or thinking that is worse than
in the past?" b) Yes or No; Yes •includes
• Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical
judgment, may be rescreened in ≥ 7 days;
• Individuals with SBP ≥ 130 and SBP ≤ 180; Those on antihypertensives are eligible. If
an individual, not treated for HTN, has a SBP ≥ 125 mmHg, consider rescreening after
24 hours;
• Willingness to be randomized into the treatment groups and ability to return to clinic
for follow-up visits over 24 months;
• Fluency in English or Spanish or both, adequate visual and auditory acuity to allow
neuropsychological testing;
• Participants must have a regular healthcare provider.
Exclusion Criteria:
• Clinically documented history of stroke, focal neurological signs or other major
cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence
of infection, infarction, or other brain lesions;
• Diagnosis of AD or other type of dementia, or significant neurologic diseases such as
Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head
trauma or normal pressure hydrocephalus;
• Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or
longer if evidence of reactive depression or temporary mood disturbances) or
clinically significant psychopathology, (e.g., psychosis and schizophrenia); if
hospitalized in past year, can be rescreened in 6 months; or presence of a major
psychiatric disorder that in the investigator's opinion, could interfere with
adherence to research assessments or procedures.
• Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest,
cardiac bypass procedures within previous 6 months and congestive heart failure), or
other severe medical conditions;
• History of atrial fibrillation and evidence on ECG with any of the following: active
symptoms of persistent palpitation, dizziness, history of syncope, chest pain,
dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea
within the past 6 months; resting heart rate of < 30 or > 110 bpm; taking class I or
III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol,
dofetilide, and amiodarone; or clinical concerns for safely participating in lowering
blood pressure.
• Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than
110 mmHg, may be rescreened in 1 week.
• Orthostatic hypotension, defined as the third standing SBP < 100mmHg, may be
rescreened after 2 weeks;
• History of significant autoimmune disorders such as systemic lupus erythematosus,
rheumatoid arthritis or polymyalgia rheumatica;
• Significant history of alcoholism or drug abuse within the last five years;
• Uncontrolled diabetes mellitus, defined as hemoglobin A1C > 6.5%, or requiring insulin
treatment;
• Clinically diagnosed and untreated sleep apnea;
• Regularly smoking cigarettes within the past year;
• Pacemaker or other medical device of metal that precludes performing MRI;
• Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal
or surgically sterile to be considered not childbearing potential);
• Participant enrolled in another investigational drug or device study, either currently
or within the past 2 months;
• Severe obesity with BMI > 40 ; clinical judgment should be applied in all cases to
assess patient safety and anticipated compliance;
• Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix
"-sartan"; allergy to amlodipine;
• Abnormal screening laboratory tests (e.g., liver ALT and AST > 3 x ULN, GFR < 30 or
Hct < 28%); may be rescreened after 2 weeks or longer;
• A medical condition likely to limit survival to less than 3 years;
• Participant has any condition(s) judged by the study investigator to be medically
inappropriate, risky or likely to cause poor study compliance. For example:
1. Plans to move outside the clinic catchment area in the next 2 years;
2. Significant concerns about participation in the study from spouse, significant
other, or family members;
3. Lack of support from primary health care provider;
4. Residence too far from the study clinic site such that transportation is a
barrier including persons who require transportation assistance provided by the
study clinic funds for screening or randomization visits;
5. Residence in a nursing home; persons residing in an assisted living or retirement
community are eligible if they meet the other criteria;
6. Other medical, psychiatric, or behavioral factors that, in the judgment of the
site PI or clinician, may interfere with study participation or the ability to
follow the study Protocol.
7. Couples or significant partners who live together cannot be enrolled or
participate simultaneously in the study.
Drug: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine), Other: PCP
Hypertension, Cognitively Normal Older Adults, Subjective Cognitive Decline, Brain and Nervous System, Family History of Dementia
Dementia, Alzheimer's Disease, Cognitive Function, Blood Pressure, Amyloid, Tau
Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes (STEP HFpEF DM)
This study will look at how participants' daily life is affected by their heart failure. The
study will also look at the change in participants' body weight.
This study will compare the effect of semaglutide (a new medicine) compared to "dummy"
medicine on body weight and heart failure symptoms.
Participants will either get semaglutide or "dummy" medicine, which treatment participants
get is decided by chance.
Participants will need to take 1 injection once a week. The study medicine is injected with a
thin needle in a skin fold in the stomach area, thigh or upper arm.
During the study participants will have talks with the study staff about healthy lifestyle
and physical activity.
The study will last for about 59 weeks, that is a little more than 1 year. Participants will
have 12 clinic visits with the study doctor.
- At 6 of the visits participants will have blood samples taken.
- At 5 of the visits participants will be asked to fill in a questionnaire
- At 4 of the visits participants will have to do a 6-minute walking test
- At 3 of the visits participants will have a test to check the heart.
- participants will have their eyes checked before or at the start of the study and at the
end of the study
Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the
study period.
• Male or female, age above or equal to 18 years at the time of signing informed
consent.
• Body mass index (BMI) greater than or equal to 30.0 kg/m^2
• New York Heart Association (NYHA) Class II-IV
• Left ventricular ejection fraction (LVEF) greater than or equal to 45% at screening
• Diagnosed with T2D greater than or equal to 90 days prior to the day of screening
• HbA1c of below or equal to 10.0% as measured at the screening visit
Exclusion Criteria:
• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before
screening irrespective of medical records
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by
a fundus examination performed within 90 days prior to screening or in the period
between screening and randomisation. Pharmacological pupil-dilation is a requirement
unless using a digital fundus photography camera specified for non-dilated
examination.
Drug: Semaglutide, Drug: Placebo (Semaglutide)
Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) (ICECAP)
This is a multicenter trial to establish the efficacy of cooling and the optimal duration of
induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest.
The study team hypothesizes that longer durations of cooling may improve either the
proportion of children that attain a good neurobehavioral recovery or may result in better
recovery among the proportion already categorized as having a good outcome.
Inclusion criteria:
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to
maintain life support for 120 hours
Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or
norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of
Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance
Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Prisoner
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
• Pregnancy
Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction (MUSIC-HFrEF1)
It is believed that targeted SERCA2a enzyme replacement in HFrEF patients will correct
defective intracellular Ca2+ hemostasis, resulting in improved cardiac contractile function
and energetics which will, in turn, translate to improved clinical outcomes. Additionally, it
is hypothesized that correcting SERCA2a dysfunction will also improve coronary blood flow
through correction of the impaired endothelium-dependent nitric oxide-mediated vasodilatation
observed in heart failure.
• Chronic ischemic or non-ischemic cardiomyopathy
• NYHA class III/IV
• LVEF ≤35%
• Maximal, optimized heart failure therapy; ICD
Main
Exclusion Criteria:
• Restrictive cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis,
pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid
disease or discrete left ventricular (LV) aneurysm
• Prior heart transplantation, left ventricular reduction surgery (LVRS),
cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device),
mechanical circulatory support device (MCSD) or cardiac shunt
• Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS,
conventional revascularization procedure or valvular repair in the 6 months following
treatment
• Likely need for an immediate heart transplant or MCSD implant due to hemodynamic
instability
• Inadequate hepatic and renal function
• Diagnosis of, or treatment for, any cancer within the last 5 years except for basal
cell carcinoma or carcinomas in situ where surgical excision was considered curative
Innovative Support for Patients With SARS-COV2 Infections (COVID-19) Registry (INSPIRE) (INSPIRE)
The Innovative Support for Patients with SARS COV-2 Infections Registry (INSPIRE) study is a
CDC-funded COVID-19 project to understand the long-term health outcomes in recently tested
adults, both negative and positive, who have suspected COVID symptoms at the time of their
test. Participants will complete short online surveys every 3 months for 18 months, share
information about their health using a secure web-based platform, and are compensated for
their time.
INCLUSION CRITERIA
1. Fluent in English or Spanish;
2. Age 18 and over;
3. Self-reported symptoms suggestive of acute SARSCOV2 infection;
4. Under investigation for SARSCOV2 (defined as a patient who has received any screening
or diagnostic test used to detect the presence of COVID19 including any FDA approved
or authorized molecular or antigen-based assay) within the last 42 days.
EXCLUSION CRITERIA
1. Unable to provide informed consent;
2. Study team unable to confirm result of diagnostic test for SARSCOV2;
3. Does not have access to a hand-held device or computer that would allow for digital
participation in the study;
4. Individuals who are prisoners while participating in the study.
A Study of ISIS 678354 Administered to Participants With Severe Hypertriglyceridemia
The purpose of the study is to evaluate the efficacy of ISIS 678354 as compared to placebo on
the percent change in fasting triglycerides (TG) from baseline.
• Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
• Patients should be on standard of care lipid-lowering medications per local guidelines
unless intolerant. Lipid-lowering medications should be optimized and stabilized for
at least 4 weeks prior to Screening to minimize changes in these medications during
the study.
Key
Exclusion Criteria:
• Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
• Platelet count < 100K/cubic millimeters at Screening or Qualification
• Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
• Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
• Estimated GFR < 40 mL/min/1.73 m^2
• Healthy male and female individuals
• 18-35 years or 65+ years of age
• Free of any underlying moderate to serious medical conditions
Exclusion Criteria:
• Known heart disease; other chronic medical conditions requiring regular medical
therapy including cancer, diabetes, neurological diseases, uncontrolled hypertension,
and uncontrolled hypercholesterolemia.
• Taking of any medications (such as beta blockers and non-dihydropyridine calcium
channel blockers) that have known influences on either cardiac function or sweating
responses.
• Abnormalities detected on routine screening.
• Individuals who participate in a structured aerobic exercise training program at
moderate to high intensities.
• Current smokers, as well as individuals who regularly smoked within the past 3 years.
• Body mass index of greater than 30 kg/m^2
• Pregnant individuals
Physical Rehabilitation for Older Patients With Acute Heart Failure With Preserved Ejection Fraction (REHAB-HFpEF)
studyfinder@utsouthwestern.edu
All
60 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05525663
Show full eligibility criteria
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Inclusion Criteria:
1. Age >=60 years old
2. Ejection Fraction >=45%
3. In the hospital setting >24 hours for the management of acute decompensated heart
failure (ADHF), or diagnosed with ADHF after being hospitalized for another reason.
ADHF will be confirmed by the site physician, and will be defined according to the
Food and Drug Administration (FDA) definition of hospitalized heart failure as a
combination of symptoms, signs, and HF-specific medical treatments, and requires that
all 4 of the following are met:
• At least 1 symptom of HF which has worsened from baseline: a. dyspnea at rest or
with exertion; b. exertional fatigue; c. orthopnea; d. paroxysmal nocturnal
dyspnea (PND)
• At least 2 of the following signs of HF: a. Pulmonary congestion or edema on
physical exam (rales or crackles) or by chest X-ray; b. Elevated jugular venous
pressure or central venous pressure >=10 mm Hg; c. peripheral edema; d. wedge or
left ventricular end diastolic pressure >=15 mmHg; e. rapid weight gain (>=5
lbs.); f. Increased b-type natriuretic peptide (BNP) (>=100 pg/ml) or N-terminal
prohormone BNP (>=220pg/ml)
• Change in medical treatment specifically targeting HF, defined as change in dose
or initiation of or augmentation of at least 1 of the following therapies: a.
diuretics; b. vasodilators; c. other neurohormonal modulating agents, including
angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers (with
or without neprilysin inhibitor), beta-blockers, aldosterone inhibitors, direct
renin inhibitors, or sodium-glucose co-transporter-2 inhibitors
• The primary cause of symptoms and signs is judged by the investigator to be due
to HF
4. Adequate clinical stability to allow participation in study assessments and the
intervention Independent with basic activities of daily living, including the ability
to ambulate independently (with or without the use of an assistive device) prior to
admission
5. Able to walk 4 meters (with or without the use of an assistive device) at the time of
enrollment
Exclusion Criteria:
1. Acute myocardial infarction within the past 3 months, or planned coronary artery
intervention (percutaneous or surgical) within the next 6 months (Note: given that
cardiac biomarkers such as troponin are frequently elevated in HF patients, the
diagnosis of acute myocardial infarction should be based on clinical diagnosis, not
biomarkers alone)
2. Severe aortic or mitral valve stenosis
3. Severe valvular heart disease with planned intervention within next 6 months
4. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative
cardiomyopathy including amyloid heart disease (amyloidosis)
5. Planned discharge other than to home or a facility where the participant will live
independently
6. Terminal illness other than HF with life expectancy <1 year
7. Impairment from stroke or other medical disorders that preclude participation in the
intervention
8. Known dementia by medical record documentation, OR patients with Montreal Cognitive
Assessment (MoCA) <=18 AND without social support, OR MoCA <10 regardless of social
support
9. Advanced chronic kidney disease defined as estimated glomerular filtration rate <20
mL/min/1.73 m2 or on chronic or intermittent dialysis or dialysis anticipated within
the next 6 months
10. Already engaging in regular moderate to vigorous exercise conditioning defined as >30
minutes per day, >= twice per week consistently during the previous 6 weeks
11. Enrollment in a clinical trial not approved for co-enrollment
12. High risk for non-adherence as determined by screening evaluation
13. Inability or unwillingness to comply with the study requirements or give consent
Multicenter Trial of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent (ALTERRA)
To demonstrate the safety and functionality of the Edwards Alterra Adaptive Prestent in
conjunction with the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) System in patients with
a dysfunctional right ventricular outflow tract/pulmonary valve (RVOT/PV) who are indicated
for treatment of pulmonary regurgitation (PR).
1. The patient/patient's legally authorized representative has been informed of the
nature of the study, agrees to its provisions and has provided written informed
consent.
2. Pediatric or adult patent whose weight is ≥ 20 kg (44 lbs).
3. The patient has a dysfunctional RVOT/PV.
4. RVOT/PV proximal and distal landing zone diameter ≥ 27 mm and ≤ 38 mm and/or minimum
of 35 mm from contractile tissue to lowest pulmonary artery takeoff immediately prior
to Alterra Prestent insertion.
Exclusion Criteria:
1. Active infection requiring current antibiotic therapy (if temporary illness, patient
may be a candidate 2 weeks after discontinuation of antibiotics).
2. History of or active endocarditis (active treatment with antibiotics) within the past
180 days.
3. Leukopenia (WBC < 2000 cells/μL), anemia (Hgb < 7 g/dL), thrombocytopenia (platelets <
50,000 cells/μL) or any known blood clotting disorder.
4. Inappropriate anatomy for introduction and delivery of the Alterra Adaptive Prestent
or the SAPIEN 3 THV.
Device: Edwards Alterra Adaptive Prestent with SAPIEN 3 THV
• Ages 8 to ≤ 21 years
• Participant must be able to speak and understand English
• Be willing to participate and able to comply with the study protocol
• For participants with PE: Children with acute, radiologically confirmed pulmonary
embolism (PE) with our without DVT
• For control group: Children who are prescribed physical activity restrictions for 2 up
to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury
is referred to as "diagnosis" hereafter)
Exclusion Criteria:
• Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary
artery thrombosis
• Chronic kidney disease
• Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus,
juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
• A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
• History of or active cancer
• Pregnant
• Musculoskeletal limitations to exercise expected to be present uptil 4 months
post-diagnosis
• Weight ≥ 300 lbs
• Contraindications to magnetic resonance imaging
• Frequent severe exacerbations of asthma defined by two or more bursts of systemic
glucocorticoids (more than three days each) in the previous year or at least one
hospitalization, intensive care unit stay or mechanical ventilation in the previous
year. Patients should also be excluded if there are daily symptoms of asthma requiring
daily use of short-acting bronchodilators such as albuterol or levalbuterol
administration. The use of controller medications such as daily inhaled
corticosteroids for mild persistent asthma is not exclusionary.
• Has any other medical condition, which in the opinion of the investigator may
potentially compromise the safety or compliance of the patient or may preclude the
patient's successful completion of the clinical study
Additional exclusion criteria for participants with PE:
• Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and
abdominal thromboses encountered as a neonate are not exclusion criteria)
• Lack of anticoagulant treatment for the acute VTE due to contraindications
Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials (VERIFY)
VERIFY will validate biomarkers of upper extremity (UE) motor outcome in the acute ischemic
stroke window for immediate use in clinical trials, and explore these biomarkers in acute
intracerebral hemorrhage. VERIFY will create the first multicenter, large-scale, prospective
dataset of clinical, transmagnetic stimulation (TMS), and MRI measures in the acute stroke
time window.
• Age 18 years or older
• Unilateral stroke due to ischemia or intracerebral hemorrhage
• Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger
Extension (SAFE) score ≤ 8 out of 10 points (i.e., excluding full or nearly full motor
strength in both shoulder abduction and finger extension) within 48 to 96 hours of
stroke onset (or time last known well).
• Provision of signed and dated informed consent form within 48 to 96 hours of stroke
onset (or time last known well).
• Stated willingness to comply with all study procedures and availability for the
duration of the study
• Fluent in English or Spanish
Exclusion Criteria:
• UE injury or conditions on paretic side that limited use prior to the stroke.
• Legally blind.
• Dense sensory loss indicated by a score of 2 on NIHSS sensory item
• Unable to abduct the shoulder or extend the fingers of the non-paretic arm/hand/wrist
on verbal command
• Isolated cerebellar stroke
• Bilateral hemisphere acute strokes
• Co-enrollment in a trial of an intervention targeting the incident stroke (acute
treatment or rehabilitation/recovery intervention) after baseline assessments for
VERIFY are initiated
• Known or expected inability to maintain follow-up with study procedures through 90
days
• Cognitive or communication impairment precluding informed consent by the participant.
• Major medical, neurological, or psychiatric condition that would substantially affect
functional status
• Non-cerebrovascular diagnosis associated with unlikely survival at 90 days
• Pregnancy
• Contraindication to noncontrast MRI (i.e., certain metallic implants, metallic foreign
bodies or severe claustrophobia)
• Contraindication to TMS (i.e., cardiac pacemaker or other electronic devices in the
body at or above the level of the seventh cervical vertebra, such as cochlear implant,
cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine
epidural stimulator, or ventriculoperitoneal shunt; Skull defect related to current
stroke; Seizure after onset of current stroke; Seizure within the last 12 months while
taking anti-epileptic medications; Previous serious adverse reaction to TMS)
• Unable to perform behavioral assessments within 48-120 hours of symptom onset
• Unable to receive TMS or get MRI within 72-168 hours of symptom onset
• Anticipated inability to perform study procedures within 168 hours of symptom onset.
Diagnostic Test: Transcranial Magnetic Stimulation (TMS)
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of
mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of
schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However,
their clinical correlates, associated biomarker trajectories, and implications for treatment
are unknown. This study will investigate differential aspects of SZ neurobiology captured by
aging and disease course, in order to develop specific biomarkers which may offer actionable
targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic
Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints
within the anterior limbic system for aging and disease course in SZ: (1) alterations in the
circuit's function and structure that occur earlier in the lifespan and are larger in
magnitude than the alterations expected with normal aging (accelerated aging dimension); and
(2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent
transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of
SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will
ascertain a broad panel of biomarkers [via multimodal brain imaging: optimized 1H-MRS,
high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI],
along with comprehensive cognitive and clinical assessments. All measures will be acquired at
baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational
approaches, the study will examine (i) effects of aging and SZ course on anterior limbic
system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of
limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older,
Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs.
without accelerated aging profiles); and (iv) associations between biomarkers and cognitive
and clinical outcomes. This research will advance the field by providing novel biomarkers
that capture unique neurobiological contributions of aging and disease course in SZ, and will
motivate future studies on SZ mechanisms across the lifespan and development of precision
treatments.
• 18-65 years of age (SZ); 18-75 years of age (CON)
• Women and men
• All races and ethnicities
• Psychiatric diagnoses:
Patient participants (SZ): Meet DSM-5 criteria for schizophrenia or schizoaffective
disorder Healthy control participants (CON): No personal history of lifetime psychiatric
disorders, or a family history of psychotic disorders in 1st-or 2nd- degree relatives
• Able to read, speak, and understand English
• Able and willing to provide written informed consent; and willing to commit to the
study protocol, including 2-year longitudinal follow-up
Exclusion Criteria:
• Compromised cognitive function: Both SZ and CON participants: Estimated premorbid
intellectual ability <75 age-corrected score on Wide Range Achievement Test-4/Word Reading
Subtest (WRAT-4) CON participants: <26 score on the Montreal Cognitive Assessment (MoCA)
• Neurological or medical disorder that may affect brain function (history of stroke,
head injury with a loss of consciousness >10 min, seizure disorder, AIDS, poorly
controlled hypertension, poorly controlled diabetes, decompensated lung disease, etc.)
• Co-morbid DSM-5 diagnosis of drug/alcohol use disorder in prior 3 months
• Current treatment with benzodiazepine or non-benzodiazepine sedatives/hypnotics,
and/or anticonvulsants
• Presence of ferromagnetic objects in body
• Weight or body size exceeding MRI scanner capacity [>300 lbs]
• Claustrophobia in MRI scanner
• Pregnant women
• Breastfeeding women (VASO scan will not be administered. All other imaging modalities
are safe to administer.)
• Impaired kidney function: Glomerular Filtration Rate (GFR) < 30 ml/min/1.73m2 (VASO
scan will not be administered due to an association between Gadolinium-based MR
contrast use and Nephrogenic Systemic Fibrosis in individuals with severely impaired
renal function. All other imaging modalities are safe to administer.)
• History of hypersensitivity to any MRI contrast agent (VASO scan will not be
administered. All other imaging modalities are safe to administer.)
Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers
Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the
valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein.
Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac
amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and
premature death. Fortunately, new therapies that stabilize TTR improve morbidity and
mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is
often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic
specificity to detect early disease.
The overall objectives of this study are to determine the presence of subclinical hATTR-CA
and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The
central hypothesis of this proposal is that hATTR-CA has a long latency period that will be
detected through subclinical amyloidosis imaging and biomarker phenotyping.
The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the
association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim
1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2)
determine the association between amyloid-specific biomarkers and V122I TTR carrier status;
and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based
parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim
1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between
a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-,
and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and
non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and
compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing
amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched
non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our
clinical sites. These biomarkers detect and quantify different processes of TTR
amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic
stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers
to detect imaging evidence of subclinical hATTR-CA disease.
• Men and women ages 30-80 who are V122I TTR carriers (or matched non-carriers) without
history of HF (this will be assessed by study personnel) and defined as: a) No history
of hospitalization within the previous 12 months for management of HF; b) Without an
elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within
the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician
• Signed informed consent
Exclusion Criteria:
• A self-reported history or clinical history of HF
• Other known causes of cardiomyopathy
• History of light-chain cardiac amyloidosis
• Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction
{NSTEMI} or ST-elevation myocardial infarction {STEMI})
• Cardiac transplantation
• Body weight >250 lbs
• Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
• Inability to safely undergo CMRI
(For participants with symptomatic V122I hATTR-CA, we will enroll probands with HF from Aim
1 or patients with symptomatic V122I hATTR-CA from the three study sites.)
Inclusion Criteria:
• Men and women ages 30-80 who have symptomatic V122I hATTR-CA as determined by a
history of HF (this will be assessed by study personnel) and defined as: a) History of
hospitalization within the previous 12 months for management of HF; b) An elevated
B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the
previous 12 months; or c) A clinical diagnosis of HF from a treating clinician.
• Have an established diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo
red (or equivalent) staining with tissue typing with immunohistochemistry or mass
spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m
(99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory
criteria without abnormal M-protein.
• TTR gene sequencing confirming the V122I variant
• Signed informed consent
Exclusion Criteria:
• Other known causes of cardiomyopathy
• History of light-chain cardiac amyloidosis
• Cardiac transplantation
• Liver transplantation
• Previous Treatment with a TTR stabilizer (tafamidis, acoramidis) or TTR silencer
(inotersen, patisiran, eplontersen)
• Estimated glomerular filtration rate ≤30 mL/min/1.73 m2