Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05271214 |
| Other study ID # |
0574-16-TLV |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2018 |
| Est. completion date |
January 2028 |
Study information
| Verified date |
February 2022 |
| Source |
Tel-Aviv Sourasky Medical Center |
| Contact |
Ofer Havakuk, MD |
| Phone |
+97236974250 |
| Email |
oferh[@]tlvmc.gov.il |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Left ventricular assist device (LVAD) candidates will be comprehensively evaluated at our
center, including clinical evaluation, echocardiography, right heart catheterization,
cardiopulmonary exercise test and laboratory exams. following this evaluation, patients will
be treated with inotropes, diuretics, uptitrated neurohormonal therapy. vitamin and iron
deficiencies will be corrected and the patients will be referred for coronary interventions
and cardiac resynchronization therapy appropriately. The need for LVAD implantation will be
reevaluated according to the patient's clinical condition, echocardiography and laboratory
findings.
Description:
Consecutive patients with advanced heart failure (HF) who will be referred for LVAD
implantation starting 01/2018. All patients will have severe left ventricular systolic
dysfunction (left ventricular ejection fraction < 30%) and severe HF symptoms (New York Heart
Association Class III-IV), with acute or gradual decompensation of HF.
All patients will be considered candidates for LVAD implantation. As such, they will undergo
extensive cardiac evaluation. This will include comprehensive echocardiography, right heart
catheterization and a cardio-pulmonary exercise test. Based on this initial evaluation,
patients will be graded according to the Interagency Registry for Mechanically Assisted
Circulatory Support (INTERMACS) profile. Individualized guideline-directed medical therapy
will be initiated. Following therapy optimization, evaluation will be repeatedly performed
during the next months in order to continuously reevaluate the need for a LVAD implantation.
Repeated evaluation will include clinical assessment, laboratory testing, comprehensive
echocardiography and cardio-pulmonary exercise test in all cases. Repeated right heart
catheterization will be done on an individual basis.
Our therapeutic goal will consist of initial stabilization during the index admission. Our
protocol includes intravenous furosemide (as needed) and continuous intravenous milrinone
0.25-0.5mcg/kg/min. Intravenous thiamine (500-1,000 mg) will be added. Beta blockers will be
continued or added within the first 24 hours and switched to HF-established beta blockers
within 48 hours. Hydralazine will be initiated within the first 48 hours and nitrates will be
added after reaching 60 mg hydralazine per day. A loading dose of digoxin (i.e. total 1mg)
was given during the first 48 hours. Low dose oral digoxin with an aim of maintaining digoxin
serum-levels of 0.4-0.8 ng/ml. Investigation for iron deficiency and vitamin D levels will be
done within 24 hours from admission and corrections will be initiated early. Low dose
spironolactone will be the first renin-angiotensin-aldosterone system inhibitor used,
followed by low dose valsartan with an aim to introduce sacubitril/valsartan shortly
thereafter. Type-2 sodium-glucose transporter inhibitors (SGLT2i) during the index admission
will be used with an aim of decreasing diuretic doses and reach early stabilization. Coronary
angiography will be routinely done and revascularization interventions will be considered on
an individual basis. Cardiac resynchronization therapy (CRT) will be used when appropriate.
After discharge, close follow up, at intervals of 3-14 days, will be performed at our
Outpatient HF Clinic, including clinical evaluation, laboratory testing and repeated cardiac
imaging. Patients will be planned to receive intravenous diuretics and inotropes
(levosimendan or milrinone). Drug up-titration will be rigorously pursued.
Cardiopulmonary exercise test: Symptom-limited graded ramp exercise tests performed with the
use of either bicycle ergometer (Ergoline, 100P) or treadmill ergometer (Ram, 770CE). The
work-rate increment protocol is tailored to the individual to yield fatigue-limited exercise
duration of about 8 to 12 min. The protocol includes 2 min of unloaded phase, a
symptom-limited ramp graded exercise, and 2 min of recovery. Breath-by-breath minute tidal
volume (TV), respiratory rate, VE, VCO2, and VO2 are measured using a Medical Graphics
Metabolic Cart (Cortex, Metalyzer 3B). Peak VO2 is the highest averaged 30-s VO2 during
exercise. Anaerobic threshold is determined manually using the modified V-slope method.
VE/VCO2 slope is calculated by linear regression with all exercise data obtained from the
progressive exercise test. The metabolic-chronotropic relationship is calculated from the
ratio of the HR reserve to the metabolic reserve during submaximal exercise. A
metabolic-chronotropic relationship slope <0.80 is considered indicative of chronotropic
incompetency. In patients receiving beta-blocker therapy, chronotropic incompetency is
considered to be present when <62% of HR reserve is reached.
Echocardiography: Echocardiographic evaluation performed in a standard manner, always using
the same equipment (iE33, Philips Medical Systems, Bothell, WA). LVEF is calculated by
Simpson's method. LV diameters, inter-ventricular septal diameter and LV posterior wall width
measured during systole and diastole as recommended (8). Forward stroke volume is calculated
from LV outflow tract with subsequent calculation of cardiac output. Left atrium volume is
calculated using the biplane area length method at end systole. All volumetric measurements
are adjusted to body surface area and reported as ml/m2. Pulsed-wave Doppler is performed in
the apical 4-chamber view to obtain mitral inflow velocities to assess left ventricular
filling. Recordings are averaged over 3 and ≥7 consecutive cardiac cycles during sinus rhythm
and atrial fibrillation respectively. Measurements of mitral inflow included the peak early
filling (E wave) and late diastolic filling (A wave) velocities, the E/A ratio, and
deceleration time (DT) of early filling velocity. Early diastolic mitral annular velocities
(e') measured in the apical 4-chamber view. The e' is measured from septal and lateral
annulus in all studies. The ratio of peak E to peak e' (septal, lateral and average) is
calculated (mitral E/e' ratio) from the average of at least 3 cardiac cycles (9). Apart from
qualitative grading, right ventricular function is evaluated using S' and tricuspid annular
plane systolic excursion (TAPSE). Hemodynamic assessment estimated tricuspid regurgitation
velocity and right atrial pressure using the inferior vena cava to calculate the systolic
pulmonary artery pressure.
Right heart catheterization. The catheterization is performed through a 7F sheath via the
right internal jugular or right femoral vein. Pressures in the right atrium, right ventricle,
pulmonary artery, and pulmonary capillary wedge position are measured at end expiration (mean
of ≥3 beats) using fluid-filled manometer. Mean pressures are calibrated at the beginning of
each case to avoid baseline drift. Transducers are zeroed at midaxillary level in each
patient. Pressure tracings from the entire study are stored for offline analysis. Mean right
atrium and pulmonary capillary wedged pressure (PCWP) taken at mid-A wave. PCWP position
verified by typical waveforms, appearance on fluoroscopy, and, when needed, by direct
oximetry (PCWP blood saturation ≥94%). Arterial blood pressure is measured noninvasively.
Arterial-venous O2 content difference (AVo2diff) measured directly as the difference between
systemic arterial and Pao2 content (=saturation × hemoglobin ×1.34). Oxygen consumption (Vo2)
measured from expired gas analysis to calculate cardiac output (CO), by the direct Fick
method (CO= Vo2÷AVo2diff).
