Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia
Condition: Thalassemia Major; Thalassemia Intermedia; Pulmonary Arterial Hypertension
MeSH terms: Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Thalassemia; beta-Thalassemia
Study type: Observational

Summary: 
      This is a multicenter observational case-control analysis lasting 12 months aimed at
      determining the prevalence of pulmonary hypertension (PAH) in patients with Thalassemia Major
      and Intermedia. The patients will be followed, treated and examined according to the best
      standard clinical practice dictated by the Italian Society for the study of
      Hemoglobinopathies (SITE), Thalassemia International Federation (TIF)and the Task Force for
      Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC);
      European Respiratory Society (ERS); International Society of Heart and Lung Transplantation
      (ISHLT) guidelines.
    

Detailed description: 
      The most recent International Classification of pulmonary arterial hypertension (PHA) include
      Hemoglobinopathies in Class I. At present there is no determination of the prevalence of this
      disease in a large population of thalassemic patients followed in a uniform way. The
      diagnostic criteria used for the normal population may not be suitable for a population such
      as thalassemia patients who present features like chronic anemia, iron overload, liver
      disease, endocrine disorders, etc.

      The criteria used to define the disease (PHA) will be those ones dictated by the above
      mentioned guidelines.

      Primary Objective of the study is the determination of the prevalence and severity of PHA in
      thalassemia syndromes, recently introduced in Class I of the Classification of PHA.

      Secondary objectives are:

      Critical evaluation of current diagnostic criteria derived from those applied to the general
      population, taking into account the peculiarities of the observed disease in the thalassemic
      population.

      Evaluation of sensitivity and specificity of echocardiogram versus right cardiac
      catheterization (RHC).

      Evaluation of the correlation between:

      echocardiography and RHC; resistance and heart rate determined both by RHC and
      echocardiography; Determination of the patients resulted vasoreactive during RHC. Validation
      of sensitivity and specificity (sens/spec) of 6 minutes walking test (6MWT) and brain
      natriuretic peptide (BNP) in Thalassemia Major (TM) and Intermediate (TI) with reference to
      specific pulmonary hypertensive disease

      In order to achieve the objectives of the study observed patients will be divided into group
      according to the following the criteria:

      group a)

        -  Pulmonary artery pressure (PAP) assessed (by echocardiogram) < 36 mmHg or a tricuspid
           regurgitant jet velocity (TG) < 3 m/sec and data on PAP and mean left ventricular
           ejection fraction (LVEF) > 50% group b)

        -  PAP estimated (by echocardiography)> 40 mmHg or TG > 3.2 m / sec and LVEF> 50%

        -  As indicated by the Guidelines, patients b) with increased PAP (TG > 3.2 m / sec or > 40
           mm Hg) will be further studied using RHC and vasoreactivity testing. Angio CAT, 6MWT and
           BNP.

      group c) - PAP estimated (by echocardiography) in the range of values > 3 m/sec (TG) and <
      3.2 m / sec or > 36 mm Hg and <40 mmHg and LVEF > 50% Each case included both in group b) and
      c) will be paired with two controls included in the group a) to make the groups more
      comparable.

      The group a) will serve as control group to compare the diagnostic methods evaluated as per
      protocol.

      In order to divide the patients into the three groups specified above first it will be
      evaluated: PAP, LVEF% and TG assessed by echocardiographic examination performed in the six
      months prior to the beginning of the study (thalassemic patients have to perform
      echocardiography once a year to monitor cardiac function according to the guidelines)

      Patients belonging to groups a), b) and c) will perform the following assessments:

      - Clinical cardiac evaluation according to the New York Heart Association (NYHA) (functional
      class I to IV)

      As per the International Guidelines, patients belonging to groups b) and c) have clinical
      indications to undergo Two-dimensional echocardiography-Doppler Duplex Scanner (PW) and color
      flow (CW) to determine the following parameters:

        -  End-systolic volume and left ventricular end diastolic, indexed according to body
           surface

        -  Percentage change of right ventricular areas (area diastolic/systolic area expressed as
           a percentage%)

        -  Tricuspid lateral annulus excursion Longitudinal (TAPS)

        -  Eccentricity Index (EI)

        -  TG

        -  Pulmonary resistance.

      Moreover, patients belonging to group b), according to the International Guidelines have
      clinical indication to undergo RHC, diagnostic evaluation to rule out the presence of
      associated diseases and to measure:

        -  Pulmonary pressures

        -  Mean atrial pressure

        -  Pulmonary resistance

        -  Cardiac rate

        -  Vasoreactivity test

      To compare the data derived from the RHC and the echocardiography the following
      echocardiographic parameters will be further evaluated:

      Right atrial pressure; Cardiac output; Pulmonary wedge pressure
    

Intervention name(s): Physician standard-of-care according to ESC/ERS Guidelines
Intervention type(s): Other
Intervention description(s): Physician standard-of-care
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with Thalassemia Major and Intermedia studied by echocardiography in the six
        months prior to the beginning of the study
      
Keywords: Thalassemia; Pulmonary Arterial Hypertension