Determinants of Slow Flow in Patients with Normal Coronary Arteries by MikeJenny

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									                                                                   Tel Aviv
                                                                 Medical Center


   Determinants of Slow Flow in
          Patients with
    Normal Coronary Arteries
Arbel Yaron, Rind Efrat, Halkin Amir, Mashav Noa, Berliner
     Shlomo, Herz Itzhak, Shevach Ayala , Keren Gad,
            Banai Shmuel and Finkelstein Ariel.
                Tel Aviv Medical Center
                     Tel Aviv, Israel
                This work was performed in partial fulfillment
                of the M.D. thesis requirements of Efrat Rind
             Conflict of Interest
   No conflict of interest to report.
                                            Introduction
   Angina pectoris is usually caused by
    atherosclerotic narrowing of the epicardial
    coronary arteries.
   In up to 20 percent of patients with anginal
    chest pain, the coronary angiogram does not
    reveal a significant narrowing of the epicardial
    coronary arteries1.
   1N                   1934-
         Engl J Med 346, 1934-1935 (2002)
                                      Introduction
   Slow Coronary Flow (SCF) is a phenomenon in
    which there is a delayed opacification of epicardial
    arteries in the absence of occlusive disease2.




   2 Am               66-
           Heart J 84, 66-71 (1972)
                                            Introduction
   Although the pathogenesis of this syndrome is
    controversial, several studies have suggested that
    it is mainly caused by endothelial microvascular
    dysfunction3-8. There is also a correlation
    between SCF and abnormal hemorheologic
    parameters9.


   3Circulation74, 964-972 (1986), 4Cathet Cardiovasc Diagn 37, 375-381 (1996), 5Coron Artery Dis 14, 155-161 (2003), 6Cardiovasc Revasc Med 9,
                     964-                                         375-                                   155-
    144-148 (2008), 7Coron Artery Dis 19, 591-595 (2008), 8Acta Cardiol 63, 579-584 (2008), 9Microcirculation 15, 451 - 459 (2008)
    144-                                  591-                              579-
                       Aims
   This study was designed to evaluate the factors
    affecting coronary blood flow, in patients who
    do not have a significant coronary narrowing.
                    Methods
   The data was collected from the Tel Aviv
    Prospective Angio Survey.
   TAPAS – a prospective, single center registry
    which enrolls all patients undergoing cardiac
    catheterization at the Tel Aviv Medical Center.
                    Methods
   For the present study, we recruited 114
    consecutive patients who underwent
    angiography, between October 2007 and
    January 2009, due to unstable angina or non
    specific chest pain, and were found to have
    normal coronaries per angiography.
          Dependent Variable:
          Coronary Blood Flow
   Each patient’s angiogram was evaluated by two
    blinded specialists who graded the patients’
    TIMI flow grade, TIMI frame count and
    Clearance scores.
                                  TIMI Flow Grade
   The TIMI flow-grading system is a subjective
    and categorical method classifies successful
    reperfusion10.
      Grade 0—No perfusion
      Grade 1—Penetration without perfusion

      Grade 2—Partial perfusion

      Grade 3—Complete perfusion

   10N                   932-
          Engl J Med 312, 932-936 (1985)
                                TIMI Frame Count
   The number of cineframes required for contrast
    to first reach standardized distal coronary
    landmarks.
   This is a more objective method to evaluate
    coronary flow as a continuous quantitative
    variable11.


   11Circulation       879-
                    93, 879-888 (1996)
Coronary Clearance Frame Count
   The opposite index to the TIMI Frame Count,
    since it is the number of cineframes required for
    the clearance of the contrast medium from the
    examined artery12.




   12J                        97-
      Thromb Thrombolysis 19, 97-100 (2005)
                                 173-
    PICTURE - Isr Med Assoc J 11, 173-177 (2009)
             Independent Variables
   Medical History:
       Diabetes Mellitus
       Hypertension
       Hyperlipidemia
       Current and Past Smoking
   Laboratory Variables:
       Lipids (Total Cholesterol, LDL, HDL, Triglycerides)
       Inflammatory Markers (WBC, CRP)
       Hematocrit
       Fibrinogen
       HbA1C
Clinical Characteristics

                  Number (%) of patients
     Age                  60 ± 11.5
 Male/Female           59/55 (52%/48%)
 BMI (kg/m2)            28 ± 5 (20-42)
Current Smokers           28   (24%)
 Past Smokers             37   (32%)
     DM                   28   (24%)
     HTN                  67 (58%)
Hyperlipidemia           75    (65%)
                     Results
   The Corrected TIMI Frame Count (CTFC)and
    the Clearance rate score were highly correlated
    (r=0.6, p=0.0001).
   There was also a high degree of correlation
    between the different blood vessels
    (r=0.6, p=0.0001).
                     Results
   These correlations support the assumption that
    slow flow is a systemic problem and give an
    extra verification to the used methods.
                      Results
   Since the Left Anterior Descending (LAD)
    artery is the most important artery and its blood
    flow is highly correlated to other coronary
    arteries’ flow, we continued the statistical
    analysis in reference to the CTFC of the LAD.
                     Results
   We created a linear regression in order to
    evaluate what are the factors that affect blood
    velocity.
   The only variable that was found to be
    significant was Hematocrit (beta=0.29, P=0.005)
                                         Results
   We divided our cohort into patients with normal
    versus slow flow.
   Slow Coronary Flow – two standard deviations
    above the normal published range for that
    particular vessel11.



   11Circulation       879-
                    93, 879-888 (1996)
                    Results
   Hematocrit and Current Smoking (15% vs. 39%)
    were the only variables that were found to be
    significant when comparing the two groups of
    patients.
                  Conclusions
   In patients with normal coronary arteries,
    coronary blood flow velocity is highly correlated
    between different blood vessels and the
    different measuring techniques.
   Slow flow is highly correlated to Hematocrit and
    Current Smoking.
                                                 Discussion
   Blood viscosity impairs blood flow.
   Hematocrit is the major determinant of whole
    blood viscosity13.
   These facts can explain the strong correlation
    that was found between the hematocrit level and
    the slow coronary flow.


   13Semin                     435-
              Thromb Hemost 29, 435-450 (2003)
                   Discussion
   The mechanism by which smoking may
    contribute to cardiovascular events before the
    development of significant coronary artery
    disease is not fully explored.
                                                   Discussion
   Smoking may involve the induction of
    endothelial dysfunction14.
   Moreover, smoking is known to elevate
    hematocrit level15.
   Perhaps, by doing so, it increases blood viscosity
    which slower the blood flow even more.


   14Circulation   115, 2621-2627 (2007), 15Can Med Assoc J 75, 520-523 (1956)
                         2621-                                   520-
                   Discussion
   Before conducting this study, our hypothesis
    was that suspected parameters, such as LDL
    Cholesterol, Fibrinogen and HbA1C, will be
    correlated to SCF.
   Surprisingly, the only correlated parameters were
    Hematocrit and Current Smoking.
           Take Home Message
   This study gives another reinforcement to the
    message many clinicians try to pass to their
    patients –
    The importance of smoking cessations.
              Tel Aviv
            Medical Center




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