Screening of Diastolic Dysfunction With Impedance Cardiography in Hypertensive Patients
Condition: Hypertension; Diastolic Dysfunction
MeSH terms: Hypertension
Study type: Observational

Summary: 
      Arterial hypertension (AHT) is responsible for important morbidity and mortality. The cardiac
      repercussion of AHT is usually assessed by electrocardiography and echocardiography,
      time-consuming, technically demanding examinations that require experienced operators, which
      limits their use for screening diastolic dysfunction. Alternative tools for the screening of
      diastolic function in hypertensive patients are needed. Impedance cardiography (IC) is
      presently used in the study of AHT and in the optimization of antihypertensive therapy. It
      seems an attractive and economical option to change the clinical approach for screening;
      however, its validation in well-defined populations is required to sustain its use in
      clinical practice. The IMPEDDANS study aims to validate IC for screening left ventricular
      diastolic dysfunction in outclinic patients with AHT, using functional echocardiography as
      the clinical standard. Descriptive and analytical study with analysis of the agreement
      between the diagnosis of diastolic dysfunction and its degree, as well as the parameters
      obtained by impedance cardiography and echocardiography in patients with AHT.
    

Detailed description: 
      BACKGROUND. Impedance cardiography (IC) is a complementary diagnostic test used in the study
      of arterial hypertension (AHT) and in the optimization of antihypertensive therapy. It is
      easy-to-execute, non-operator-dependent and cost-effective. It analyses and registers
      hemodynamic changes through the measurement of electrical resistance changes in the thorax
      and translates them graphically as impedance and electrocardiogram waveforms. IC has evolved
      in recent years, making it an attractive and economical tool, particularly in screening
      settings and there is extensive published literature on its usefulness. More widespread use
      of IC has been limited due to limitations of the studies, mostly cross-sectional, with small
      samples, recruiting hemodynamically stable patients and providing inconsistent estimates of
      accuracy and reproducibility in different settings.

      AHT is responsible for high morbidity and mortality. In Portugal, according to PHYSA study,
      has overall prevalence of hypertension, in 2014, of 42.2% (44.4% in men, 40.2% in women). The
      progression of hypertensive heart disease involves myocardial fibrosis and changes in left
      ventricular geometry that precedes functional changes. Diastolic dysfunction is part of this
      continuum, and despite the growing recognition of its importance, it is generally undervalued
      because of the difficulty in its diagnosis and the absence of effective therapies. This
      reinforces the importance of finding alternative tests that provide important information for
      an initial assessment of diastolic function in hypertensive patients.

      This study intends to define the importance and usefulness of IC in the evaluation of LV
      diastolic dysfunction in patients with AHT.

      METHODS. Study Design. This is a validation study of a diagnostic method used in a new
      context, comparing it with the diagnostic method currently used for this effect in usual
      clinical practice. Its purpose is to determine the positive predictive value, negative
      predictive value, sensitivity and specificity of the presence of the D wave, the
      isovolumetric relaxation time, the systolic time ratio (STR) and thoracic fluid content (TFC)
      by IC, for the diagnosis of LV diastolic dysfunction (LVDD). To study the relationship
      between LV geometry, hemodynamic profile, diastolic dysfunction and its degree (confirmed by
      echocardiography) in hypertensive patients with diastolic dysfunction. We chose to perform a
      concordance study between IC and echocardiography, the validated , non-invasive test used for
      the clinical diagnosis of LVDD as well as for the characterization of hypertensive
      cardiopathy.

      To calculate the sample size we considered the primary endpoint (concordance of the diagnosis
      of diastolic dysfunction between IC and echocardiography). Thus, considering a hypothesized
      positive predictive value of 70 ± 5% of the parameters obtained by IC, 77 individuals are
      estimated to be able to verify the expected positive predictive value with 95% confidence.
      Since the prevalence of diastolic dysfunction in patients with AHT estimated to be
      approximately 50% in most studies, the sample size is doubled for 154 hypertensive patients.

      Evaluation. Participants will be systematically assessed by IC and echocardiography, with a
      maximum interval of 8 days between them, to obtain the parameters to be used in the
      validation and concordance studies. To ensure that both tests are performed under similar
      conditions, evaluations matching variations greater than 10% in BP or variations in excess of
      5% in HR will not be considered. These patients should, if possible, repeat one of the exams.
      If they maintain variations greater than those defined, they should be excluded from the
      study.

      Baseline Data. Ambulatory clinic protocol for patients followed for AHT require clinical
      evaluation, blood test, electrocardiogram and, eventually, 24 hours ambulatory blood pressure
      monitoring (AMBP). Data regarding the comorbidities and pharmacotherapy will be collected.
      Anthropometric data regarding adiposity and vital signs will be registed and body mass index
      calculated as weight (kg) divided by height (m) squared. Blood pressure will be measured in a
      quiet room with semiautomatic device (Omron HEM-907XL, Omron Healthcare, Bannockburn,
      Illinois, USA) with an appropriate cuff according with the established recommendations. If
      necessary 24 hours ABPM will be performed using an ABPM device - Spacelabs model 90207
      (Issaquah, Washington, USA) also according with current guidelines. Electrocardiogram will be
      performed per institutional protocol with a Page Writer TC 30, Philips, Eindhoven,
      Netherlands. The analytical screening evaluation includes complete blood count, haematocrit,
      urinalysis, urine microalbumin, serum sodium, potassium, creatinine (estimated or measured
      glomerular filtration rate [GFR]), and calcium, uric acid, glycated haemoglobin, lipid
      profile following a 9- to 12-hour fast (total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, and triglycerides), thyroid-stimulating
      hormone and brain natriuretic peptide.

      Impedance Cardiography. Impedance cardiography will be carried out in a single centre by a
      cardiopneumology technician with Niccomo continuous cardiac output monitor (Medis, GmbH,
      Ilmenau, Germany). This equipment uses the technique of four electrodes, two of current
      application and two others that detect the changes of voltage. As the current amplitude is
      constant, the voltage detected is proportional to the tissue impedance. Patients must present
      with fasting of 6 hours but must take their antihypertensive drugs and the examination is
      carried out in 4 phases after an initial 5 minutes hemodynamic stabilization period: 1.
      supine position I - 20 minutes continuous recording; 2. 70º orthostatism -with the help of
      the tilting table for 10 min in continuous recording; 3. tilt-back at 0º; 4. supine position
      II - 10 min continuous recording. The examination is interrupted if there is syncope or
      pre-syncope; dizziness, nausea and malaise associated with poorly tolerated hypotension and /
      or bradycardia; pain / precordial discomfort; ECG ST segment changes; Systolic blood pressure
      > 210mmHg.

      Transthoracic Echocardiography. Transthoracic echocardiography will be performed in Vivid E9
      and S5 devices (GE Healthcare, Chicago, Illinois, USA) by experienced cardiologists. The exam
      will be held in the echocardiography laboratories of two reference centers. To ensure
      uniformity of evaluation and correct evaluation all exams will be reviewed by a second
      cardiologist with experience in the technic. In order to define and grade diastolic
      dysfunction will be recorded left atrium volume index, the velocities E, A, septal e´,
      lateral e´, deceleration time (DT), isovolumetric relaxation time (IRVT), atrial reverse
      velocity (Ar) and E/A ratio variation with Valsalva maneuver (last two will only valued if
      the patient cooperates and if the images obtained have the necessary quality for analysis) as
      recommended by 2009 guidelines. Left ventricular geometry will be defined accordingly with
      international recommendations.

      Analytic Statistics. The diagnostic validity parameters will be calculated with 95%
      confidence intervals, using logistic regression models. The positive and negative predictive
      values will be calculated and the sensitivity and specificity will be estimated;
      receiver-operator curves (ROC) will also be analysed, with the calculation of the area under
      the curve. Diagnostic models with more than one parameter will be tested, using multivariable
      analysis, logistic and linear regression. For the analysis of agreement between the
      parameters obtained by ICG and echocardiography, the Bland-Altman method will be used with
      STATA® and R-project® software.
    

Intervention name(s): Diastolic function evaluation
Intervention type(s): Diagnostic Test
Intervention description(s): Diastolic function assessed by impedance cardiography (test to be validated) is compared with the assessment by echocardiography (clinical standard)
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Adult patients with arterial hypertension attending the outpatient clinic consultation
      
Keywords: hypertension; Diastolic Dysfunction; impedance cardiography; echocardiography