Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia
Prevalence of Pulmonary Hypertension (PAH) in Patients With Thalassemia
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.
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
Inclusion Criteria:

 -  Patients with Thalassemia Major Patients or Intermediate referring to Centres using
 Web-Thal medical record (a clinical data sheet used for congenital anemias. Info:
 www.thalassemia.it)

 Exclusion Criteria:

 -  Patients who are considered potentially unreliable and/or not cooperative