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 <front>
  <journal-meta>
   <journal-id journal-id-type="nlm-ta">Ulutas Med J</journal-id>
   <journal-title-group>
    <journal-title>The Ulutas Medical Journal</journal-title>
    <abbrev-journal-title>Ulutas Med J</abbrev-journal-title>
   </journal-title-group>
   <issn pub-type="ppub">2149-0430</issn>
   <issn pub-type="epub">2149-388X</issn>
   <publisher>
    <publisher-name>Hayriye Zehra Ulutaş</publisher-name>
   </publisher>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="doi">10.5455/umj.20151225044952</article-id>
   <article-id pub-id-type="publisher-id">210730</article-id>
   <article-categories>
    <subj-group subj-group-type="heading">
     <subject>Original Research</subject>
    </subj-group>
    <subj-group subj-group-type="subject">
     <subject>Biochemistry</subject>
    </subj-group>
   </article-categories>
   <title-group>
    <article-title>Right ventricle diastolic function in high-normal and mildly elevated arterial blood pressure</article-title>
   </title-group>
   <contrib-group>
    <contrib contrib-type="author" corresp="yes">
     <contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0003-1838-2812</contrib-id>
     <name name-style="western">
      <surname>Hanboly</surname>
      <given-names>Noha Hassanin</given-names>
     </name>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Data curation" vocab-term-identifier="https://credit.niso.org/contributor-roles/data-curation/">Data curation</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Funding acquisition" vocab-term-identifier="https://credit.niso.org/contributor-roles/funding-acquisition/">Funding acquisition</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Project administration" vocab-term-identifier="https://credit.niso.org/contributor-roles/project-administration/">Project administration</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Resources" vocab-term-identifier="https://credit.niso.org/contributor-roles/resources/">Resources</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Software" vocab-term-identifier="https://credit.niso.org/contributor-roles/software/">Software</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Supervision" vocab-term-identifier="https://credit.niso.org/contributor-roles/supervision/">Supervision</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Validation" vocab-term-identifier="https://credit.niso.org/contributor-roles/validation/">Validation</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Visualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/visualization/">Visualization</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing – original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing – original draft</role>
     <role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing – review &amp; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing – review &amp; editing</role>
     <xref ref-type="aff" rid="aff1">1</xref>
    </contrib>
    <aff id="aff1">
     <label>1</label>
     <institution-wrap>
      <institution-id institution-id-type="ror">https://ror.org/03q21mh05</institution-id>
      <institution>Cardiovascular Department of Cairo University, Egypt</institution>
     </institution-wrap>
    </aff>
   </contrib-group>
   <pub-date publication-format="electronic" date-type="pub" iso-8601-date="2015-12-28">
    <day>28</day>
    <month>12</month>
    <year>2015</year>
   </pub-date>
   <pub-date publication-format="print" date-type="collection">
    <year>2015</year>
   </pub-date>
   <volume>1</volume>
   <issue>4</issue>
   <fpage>100</fpage>
   <lpage>103</lpage>
   <history>
    <date date-type="received" iso-8601-date="2015-11-30">
     <day>30</day>
     <month>11</month>
     <year>2015</year>
    </date>
    <date date-type="rev-recd" iso-8601-date="2015-12-14">
     <day>14</day>
     <month>12</month>
     <year>2015</year>
    </date>
    <date date-type="accepted" iso-8601-date="2015-12-25">
     <day>25</day>
     <month>12</month>
     <year>2015</year>
    </date>
   </history>
   <permissions>
    <copyright-statement>© 2015 The Author(s)</copyright-statement>
    <copyright-year>2015</copyright-year>
    <license>
     <ali:license_ref>https://creativecommons.org/licenses/by-nc/4.0/</ali:license_ref>
     <license-p>This is an open access article distributed under the CC BY-NC 4.0 licence.</license-p>
    </license>
   </permissions>
   <self-uri xlink:href="https://www.ulutasmedicaljournal.com/?mno=210730"/>
   <self-uri content-type="pdf" xlink:href="https://www.ulutasmedicaljournal.com/pdf/210730.pdf"/>
   <abstract>
    <p>Introduction: Many studies have evaluated left ventricle (LV) function in mildly increased arterial blood pressure; however, the right ventricle (RV) has received little attention because of its complex shape and orientation. This study aimed to evaluate RV diastolic dysfunction using pulsed and tissue Doppler echocardiography in untreated patients with blood pressure (BP) values ranging from optimal to mild hypertension. Materials and Methods: The study group consisted of 57 patients with high-normal and mildly increased arterial BP. Twenty healthy age- and sex matched subjects were recruited as controls. Conventional echocardiography was done to study LV dimensions and systolic function. Pulsed Doppler echocardiography was used to measure peak early and late tricuspid diastolic filling velocities. Tissue Doppler imaging was done to determine RV annular velocities. Results: Right ventricular hypertrophy was found in 28% of our patients with newly diagnosed systemic hypertension (n=16). Tricuspid E/A was 1.3 and 0.9 in the control and hypertensive groups, respectively. Tissue Doppler tricuspid E/A was significantly decreased in the hypertensive group (0.8 ±0.2 versus 1.2 ±0.1 in control, p&lt;0.001). Conclusions: right ventricular diastolic function deteriorates with a slight increase in systemic blood pressure. Right ventricular diastolic dysfunction may be an early clue to hypertensive heart disease.</p>
   </abstract>
   <kwd-group kwd-group-type="author">
    <kwd>Diastolic dysfunction</kwd>
    <kwd>Right ventricle</kwd>
    <kwd>tissue doppler echocardiography</kwd>
   </kwd-group>
   <funding-group>
    <funding-statement>No external source of funding was used for the current study.</funding-statement>
   </funding-group>
  </article-meta>
 </front>
 <body>
  <sec id="sec-1">
   <title>Introduction</title>
   <p id="b-1">Arterial systemic hypertension may determine impairment of both left ventricle (LV) diastolic and systolic functions, due to increased after load (    <xref ref-type="bibr" rid="ref1">1</xref>
). Also the right ventricle (RV) might be involved in this process by structural and functional abnormalities (    <xref ref-type="bibr" rid="ref2">2</xref>
). Left ventricular hypertrophy is often associated with hypertension and is an adaptive mechanism to maintain or normalize wall stress, sometimes at the expense of diastolic and long-axis systolic function (    <xref ref-type="bibr" rid="ref3">3</xref>
). This adaptive mechanism is associated with changes in left ventricular parameters and in chamber dimensions, geometry and function. These changes are progressive and can ultimately lead to heart failure with systolic and/or diastolic dysfunction (    <xref ref-type="bibr" rid="ref4">4</xref>
). Human heart functions as a unit that includes the right ventricle. The spectrum of changes in structure, function and shape of the left ventricle ultimately has an effect on the structure and function of the RV (    <xref ref-type="bibr" rid="ref5">5</xref>
).</p>
   <p id="b-2">Only a few publications concern echocardiographic assessment of the RV diastolic function in systemic hypertension, which is all more surprising as physical examination often demonstrates the features of RV pathology and dysfunction in hypertensive patients (    <xref ref-type="bibr" rid="ref6">6</xref>
). Purpose of the study was assessment of RV diastolic function in patients with untreated systemic hypertension using conventional and doppler echocardiography.</p>
  </sec>
  <sec id="sec-2">
   <title>Study Design</title>
   <p id="b-3">The study was carried out at the echocardiography laboratory of cardiovascular department at Cairo University hospitals. The Research Ethics Committee of the hospital reviewed and approved the study protocol. Fifty seven adult participants aged 54.8±14 years old with high-normal and mildly increased arterial blood pressure never treated with antihypertensive medications were compared with 20 age and gender matched control subjects .Patient written consent was given by all the participants. Hypertension was defined as persistent elevation of blood pressure above 140/90 mmHg on two or more occasions with the patient in a sitting position for at least five minutes (    <xref ref-type="bibr" rid="ref7">7</xref>
). Patients were subjected to history taking, physical examination and simple clinical investigations. Demographic parameters, including age, gender and associated symptoms were obtained. Subjects with ischemic heart disease, valvular heart disease and cor pulmonale were all excluded.</p>
   <sec id="sec-3">
    <title>Echocardiography</title>
    <p id="b-4">All subjects had echocardiography performed with the use of a Philips IE 33 (Andover, MA, USA) Ultrasound according to recommendations of the American Society of Echocardiography (     <xref ref-type="bibr" rid="ref8">8</xref>
). Left ventricle structure, dimensions and functions were studied. Right ventricle wall thickness was measured in diastole from the sub costal views wall and wall thickness ≥ 5 mm indicates RV hypertrophy (     <xref ref-type="bibr" rid="ref9">9</xref>
). Right ventricle diastolic function was assessed by recording tricuspid flow with standard pulsed wave Doppler and by measurements of early diastolic peak flow velocity (E), late diastolic peak flow velocity (A) and the ratio of early-to-late flow velocity peaks (E/A ratio).</p>
   </sec>
   <sec id="sec-4">
    <title>Tissue Doppler imaging (TDI)</title>
    <p id="b-5">In the apical four-chamber view, the sample volume was placed at the lateral tricuspid annulus to study early diastolic (E') and late diastolic (A') velocities. The use of E':A' ratio is one of the recommended indices approved by the American Society of Echocardiography for assessing right ventricle diastolic dysfunction (     <xref ref-type="bibr" rid="ref8">8</xref>
,     <xref ref-type="bibr" rid="ref10">10</xref>
).</p>
   </sec>
   <sec id="sec-5">
    <title>Statistical analysis</title>
    <p id="b-6">All statistical calculations were done using computer program SPSS (Statistical Package for the Social Science, SPSS Inc., Chicago, IL, USA) release 15 for Microsoft Windows (2006). All Data were statistically described in terms of mean ± standard deviation (± SD) Comparison of numerical variables between the study groups was done using Student t test for independent samples and one way analysis of variance (ANOVA) test when comparing 3 group. P-value less than 0.05 was considered statistically significant.</p>
   </sec>
  </sec>
  <sec id="sec-6">
   <title>Results</title>
   <p id="b-7">Fifty seven participants aged 54.8±14 years old (40 females and 17 males) with high-normal and mildly increased arterial blood pressure never treated with antihypertensive medications were compared with 20 age and gender matched control subjects free of any cardiac diseases. Systolic (SBP) and diastolic blood pressures (DBP) were significantly higher in hypertensive subjects compared to the controls (143.7±2.7 and 93.2±5.1 mmHg vs 119.4±8.1 and 72.3±6.9 mm hg, p-value &lt;0.001 for both)(    <italic>Table-1</italic>
).</p>
   <table-wrap id="tbl-1" position="float">
    <label>Table 1</label>
    <caption>
     <title>Demographic-clinical baseline data of study population</title>
    </caption>
    <graphic xlink:href="tbl-1.png">
     <alt-text>Table 1: Demographic-clinical baseline data of study population</alt-text>
    </graphic>
   </table-wrap>
   <sec id="sec-7">
    <title>Conventional Echocardiography</title>
    <p id="b-8">Interventricular septum thickness and right ventricle free wall thickness were significantly increased in patients with mild untreated systemic hypertension (1.2±0.2 and 0.5±0.1 vs.0.8±0.1 cm and 0.28±0.1cm among control group, P&lt;0.001for both).</p>
   </sec>
   <sec id="sec-8">
    <title>Pulsed and tissue Doppler imaging</title>
    <p id="b-9">Mitral E/A ratio 1.2±0.1 and 0.7±0.1 in the control and hypertensive group respectively (P value &lt; 0.001). While, tricuspid E/A was 1.3 and 0.9 in control and hypertensive groups respectively. Tissue Doppler tricuspid E' and E'/A' values were significantly decreased in hypertensive group (12±3.1 cm/s and 0.8 ±0.2 vs 15.3 ±1.3 cm/s and 1.2±0.1 in control group, p &lt;0.001 for both) (Figure-1).Positive significant correlation was found between mitral and tricuspid E/A ratio (p&lt;0.001, r: 0.842). Univariate regression analysis revealed that body mass index was found to be significant predictor of RV diastolic dysfunction (p:0.023).</p>
    <fig id="fig-1" position="float">
     <label>Figure 1</label>
     <caption>
      <p>Tissue Doppler imaging of right ventricle lateral tricuspid annulus in a normal subject E'/A' ratio is &gt;1(       <bold>a</bold>
) and in a hypertensive patient E'/A' ratio &lt;1(       <bold>b</bold>
).</p>
     </caption>
     <graphic xlink:href="fig-1.png">
      <alt-text>Figure 1: Tissue Doppler imaging of right ventricle lateral tricuspid annulus in a normal subject E'/A' ratio is &gt;1(a) and in a hypertensive patient E'/A' ratio &lt;1(b).</alt-text>
     </graphic>
    </fig>
   </sec>
  </sec>
  <sec id="sec-9">
   <title>Discussion</title>
   <p id="b-10">It was found that in middle-aged men central distribution of body fat is associated with increased BP, independently of body mass index and insulin resistance, thus suggesting a key role of central adiposity in the full expression of the “metabolic syndrome (    <xref ref-type="bibr" rid="ref11">11</xref>
). The current study showed that body mass indices and waist circumferences were increased in the hypertensive group. Moreover, body mass index was found to be significant predictor of RV diastolic dysfunction (RVDD). This is concordant with other studies that found that mitral annular E':A' ratio and body mass index were the only predictors of RVDD (    <xref ref-type="bibr" rid="ref10">10</xref>
). Concordant with other studies (    <xref ref-type="bibr" rid="ref12">12</xref>
), the present study used the ratio E':A' ratio alone to assess RVDD . However, this index was approved by the American Society of Echocardiography to assess the global RV diastolic function. Positive significant correlation was found between mitral and tricuspid E/A ratio (p&lt;0.001, r: 0.842) this is in accordance with other study that assessed RV DD in 100 adult Nigerian hypertensive subjects (    <xref ref-type="bibr" rid="ref13">13</xref>
).</p>
   <p id="b-11">Concordant with some studies that found that the prevalence of RV hypertrophy consistently varied among studies (17.0-80.0%) with an average of 28.6% in the pooled population (    <xref ref-type="bibr" rid="ref14">14</xref>
), the current study found that RV hypertrophy was prevalent in 28% of the high-normal and mildly increased blood pressure group. It was found that RV diastolic and systolic function deteriorates in response to slightly increased systemic BP (    <xref ref-type="bibr" rid="ref15">15</xref>
). It was found that increased pulmonary vascular resistance in systemic hypertension results from the activation of vasoconstriction pathways in both systemic and pulmonary vascular beds which may explain right ventricular hypertrophy from mild to moderate, uncomplicated hypertensive patients (    <xref ref-type="bibr" rid="ref16">16</xref>
).</p>
   <p id="b-12">Moreover, combination of increased thickness of the posterior wall, inter ventricular septum dimensions and right ventricular wall thickness will ultimately lead to at least progressive reduction in the right ventricular end-diastolic dimensions before progressive dilatation may occur in the right heart (    <xref ref-type="bibr" rid="ref17">17</xref>
).</p>
   <p id="b-13">A magnetic resonance imaging study to assess RV remodeling in systemic hypertension revealed that that systemic hypertension was associated with concentric RV remodeling and impaired diastolic function, confirming that the unstressed ventricle is not immune to the effects of systemic hypertension (    <xref ref-type="bibr" rid="ref18">18</xref>
).</p>
  </sec>
  <sec id="sec-10">
   <title>Conclusion</title>
   <p id="b-14">In arterial hypertension, increased systemic after load is transferred to RV, a structure not directly exposed to systemic BP but the inter ventricular septum is likely the candidate for that role. Right ventricle diastolic function could provide novel insights in RV function impairment in high-normal and mildly increased arterial blood pressure. Moreover, RV diastolic dysfunction may be an early clue to hypertensive heart disease.</p>
  </sec>
 </body>
 <back>
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