AIMS
To investigate the hemodynamic effects of increasing dosages of dobutamine infusion on
cardiac output and filling pressures in patients with symptomatic ATTRwt, assessed
simultaneously by right heart catheterization (RHC) and echocardiography.
To assess the safety of dobutamine infusion in ATTRwt patients.
HYPOTHESIS
Dobutamine infusion can increase myocardial contractility in patients with symptomatic
ATTRwt with an increase of CO by 10%.
The left ventricular filling pressure as expressed by the pulmonary artery wedge
pressure (PAWP) and/or mean pulmonary artery pressure (mPAP) will decrease by ≥ 10%
during increasing dobutamine dosages.
Dobutamine is well-tolerated and safe to use in symptomatic ATTRwt patients.
MATERIALS AND METHODS
Study population Symptomatic participants with ATTRwt, age ≥ 65 years, who have reduced left
ventricular ejection fraction (LVEF) and/or stroke volume index (SVI), without significant
valvular diseases or severe coronary artery diseases.
Study design
Eligible patients will be assessed in the trial day (one day) as following:
Step1; Baseline assessment: Blood pressure, pulse and ECG will be obtained. All participants
will also undergo a comprehensive resting transthoracic echocardiographic assessment
according to current guidelines.
Step 2; Invasive right heart catheterization (RHC): The subjects will be instructed not to
eat for 6 hours and not to drink for 2 hours before the procedure. RHC will be performed in
the cardiac invasive laboratory using right internal jugular vein access. Rarely, right
femoral vein access will be used, if the right internal jugular vein is difficult to
canulate, as a result of anatomical anomalies or local skin or muscle deformities. A 7 Fr
sheath will be inserted in the vein aseptic, and ultrasound guided in local anaesthesia.
Subsequently, a pulmonary catheter (Swan-Ganz) will be advanced through the sheath guided by
pressure waves and fluoroscopy, through the right atrium, the right ventricle, and ultimately
in a stable position in the pulmonary artery (PA). The standard Swan-Ganz catheter is
equipped with an inflatable balloon at the tip, which facilitates its placement into the PA
through the flow of blood. The balloon, when inflated, causes the catheter to "wedge" in a
small pulmonary blood vessel. While wedged, the catheter can provide an indirect measurement
of the mean left atrium pressure. Central oxygenation of the blood (SvO2) and N-terminal
pro-B-type natriuretic peptide (NT-proBNP) will be assessed from blood taken from the
pulmonary artery at rest and at peak dobutamine infusion according to the protocol.
The PA catheter location will be confirmed with fluoroscopy before leaving the laboratory and
both the sheath and the catheter will be fixed to the skin.
RHC is performed using a standard 7 Fr triple lumen Swan-Ganz catheter (Edwards Lifesciences,
Irvine, California, USA).
The following parameters will be measured by RHC:
PAWP
Mean right atrial pressure
Systolic and diastolic PA pressure
mPAP
CO All pressures at rest are measured at end-expiration as the average of five
measurements. CO is measured using thermodilution methods as the average of at least
four measurements not differing more than 10% and indexed to body surface area as the
Cardiac Index (CI). SV is calculated as CO divided by heart rate.
Step 3; Dobutamine challenge:
Step 4; Recovery period: The pulmonary catheter and sheath will be removed after a-5-minute
recovery period, right after obtaining the final images and invasive measurements. The
participants will be observed for 2 hours after the end of the test and will be discharged if
no complications arise. Blood sample will be taken to measure NT-proBNP after 1-2 hours after
the end of dobutamine challenge.
The investigators expect the study will last for about 6-7 hours, including preparations,
waiting time, the procedures themselves and the observation period.