Troponin I Release After High Diuretic Doses
Condition: ADHF
Study type: Interventional
Phase: Phase 4

Summary: 
      High values of cardiac troponin (Ct) in acute heart failure (ADHF) identify patients (pts) at
      higher risk and worsened prognosis. A Ct increase during therapy indicates the need for more
      appropriate intervention, aimed at compensating cardiac disease and effectively minimizing
      myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an
      intravenous high-dose of furosemide with or without small-volume hypertonic saline solution
      (HSS)on myocardial cytolysis in ADHF pts.
    

Detailed description: 
      After randomization, all patients included in the study underwent a complete physical
      examination, including a careful check of HF signs and symptoms, including BW measurement (in
      the morning before breakfast), supine and standing blood pressure (BP [the mean of 3
      measurements]), and heart rate (HR). Fasting blood samples were drawn to determine the serum
      levels of Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia on a
      daily basis during hospitalization, and this was continued until a clinically compensated
      state was obtained. The total daily output of urine was collected for measuring levels of
      creatinine clearance, urinary Na and K. A chest radiograph, electrocardiogram, and
      echocardiogram (prior to commencing therapy and again when discharged. In addition, BNP and
      TNI plasma levels will be evaluated for all patients on entry and at discharge. Each patient
      provided written informed consent prior to participating in the study.

      In order to determine GFR, the MDRD formula (Modification of Diet in Renal Disease),
      involving 4 parameters, was deployed. It provides an estimate of GFR comparable or superior
      to other formulae, with the advantage of not requiring any anthropometric measurements.
      According to the MDRD, GFR can be estimated using the following formula: GFR (ml/min/1.73m2)
      = 175 x {[serum creatinine (mg / dL or μmol/L/88.4)] -1.154 x {age (years) }-0.203 x 0.742 if
      female and 1.21 if Afro-American. The estimating of GFR by means of the MDRD formula is a
      useful and valid tool with which to obtain an index of kidney function.

      The echocardiography M / B mode color Doppler will be performed with a Vivid 7
      echocardiograph, with patients in a supine position and slightly left lateral decubitus. The
      mitral flow and the time taken for the wave to return to baseline (DTE) were evaluated from
      the apical 4 room positions, placing the sample volume of pulsed Doppler at the peak of the
      valve leaflets during the opening. Subsequently, the speed of early diastolic movement (Ea)
      of mitral annulus, obtained from the 4 room projection placing the sample volume of pulsed
      tissue Doppler onto lateral corner of the annulus, was assessed as an index of left
      ventricular relaxation. By measuring the Ea wave and the E / Ea ratio, the PCWP was evaluated
      in a quantitative way according to the following formulae:

      PCWP = 1.24 E / Ea + 1.91 for those in sinus rhythm PCWP = 0.821 E / Ea + 6.489 for those in
      atrial fibrillation. Calculating dp/dt. The calculating of dp/dt was performed by a spectral
      analysis of mitral regurgitation at CW Doppler. Two points were chosen on the mitral
      regurgitation curve for the correct calculation of echocardiographic dp / dt: A: speed 1 m /
      sec = 4 mm Hg; and B: speed 3 m / sec = 36 mm Hg. The pressure gradient between these two
      point was reported to be 32 mmHg (A - B = 36 - 4 = 32). dP/dT was calculated by dividing the
      pressure gradient between the two points for the temporal distance between them: dP / dT =
      32mmHg / T msec.

      Bioelectrical impedance variables will be detected with an impedance plethysmograph using a
      previously-described methodology (18). This emitted an alternating sinusoidal electric
      current of 800 mA and an operating single frequency of 50 kHz; it which was calibrated each
      morning using a standard resistor supplied by the manufacturer. BIA is a method for detecting
      whole-body fluid overload and pulmonary congestion, based on the theory that the accumulation
      of whole-body or intrathoracic fluid will conduct an electrical current passing across the
      body or trunk more easily, leading to a decrease in whole-body or pulmonary bioimpedance.
      Bioimpedance is a combination of resistance (Rz) (ie, the opposition of an alternating
      current flowing through intra- and extra-cellular ionic solutions) and reactance (Xc) (ie,
      the capacitative component of tissue interfaces, cell membranes, and organelles). As previous
      described, in standard whole-body tetrapolar BIA, sensing electrodes were placed on: the
      dorsum of the wrist, a line between the radial and ulnar styloid processes, the dorsum of the
      ipsilateral foot, and on a line between the medial and lateral malleoli. Source electrodes
      were placed to overlie the head of the third metacarpal on the dorsum of the hand and the
      third metatarsal on the dorsum of the foot, on the same side as the sensing electrodes. The
      measurements will be performed on the right side of the body with the patients in a
      semi-orthopneic or supine position. According to the RzXc graph method of the BIA vector, the
      impedance measurement will be standardized according to the height (H) of the subject,
      expressing both Rz/H and Xc/H in ohm/meters, to establish the hydration state. Bioelectrical
      impedance measurements will be assessed twice by the same experienced operator and paired
      measurements for each patient were used in the analysis.
    

Intervention name(s): Furosemide; Furosemide
Intervention type(s): Drug; Drug
Intervention description(s): 125-250 mg furosemide bid; 125-250 mf furosemide bid
Other intervention name(s): diuretics; diuretics
Intervention MeSH terms: Furosemide; Diuretics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: furosemide; hypertonic saline solution; troponin I