What seemed to be true, was it?
The impact of new information
regarding the quantification of the left ventricle
Centro Privado de Cardiología (CPC) - Facultad de Medicina (UNT).
(T4000NIL) Tucumán, Argentina. E-mail
Recibido 31-OCT-2019 – ACEPTADO el 19-NOVIEMBRE-2019. There are no conflicts of interest to disclose.
There is a phrase by writer Mario Benedetti, that goes: “today’s truths constitute the errata of tomorrow”. These words clearly illustrate the content of these lines.
The value of left ventricular ejection fraction (LVEF) is, undoubtedly, the most significant data indicated in an echocardiogram report. This value is not only essential to define, for instance, the type of heart failure; but also as a variable for therapeutic indication and prognosis, in virtually all cardiological clinical scenarios. One should assume that such important information would be defined with marked thoroughness, and it would be known by all cardiologists, undoubtedly. Reality shows us that this is not so, by the observation of publications, scientific papers, or opinions by experts that propose values above 50% to 55% quite often, as if this 5% difference would have no impact. We should add to this, that based on these figures, we define abnormal values as variable as: less than 50%, less than 45%, less than 40%, less than 30%, to define different degrees of cardiac function compromise. The implication of this, not only lies in a proper diagnosis, but also has an impact on therapeutic decisions. There is a very significant number of trials that evaluated the use of some drugs assuming EF criteria. The first question that arises then is, both positive and negative results could be assumed as correct when the analysis variable is not defined?
The most recent guidelines from the American Society of Echocardiography jointly with the European Association of Cardiovascular Imaging, published in 2015, define values of 52% for men and 54% for women as inferior limit of normalcy . Based on this, we may infer that a 53% value would imply normalcy in a female patient, but would imply a certain degree of dysfunction in a male patient. In other words, if we assume a 50% value as inferior limit of normalcy for both genders, we would attribute a 4% drop and 2% drop as significant according to gender. These normalcy ranges were determined based on studies with a different population magnitude, mostly including white patients belonging to European countries or the US, and using different analysis methodologies. Are these values applicable to any population context then?
Considering these points, “The World Alliance Societies of Echocardiography (WASE) Normal Values Study” was generated. This study, recently published , included patients from 15 different countries (19 centers), among which two centers in Argentina were included (Instituto Cardiovascular Buenos Aires and Centro Privado de Cardiología de Tucumán). A total of 2262 normal patients were included (defined as patients with absence of any kind of cardiovascular, renal or pulmonary disease, from whom 2008 constituted the final population of the study, with an age range from 18 to 98 years, of White, Black, Hispanic, and Asian races). The population characteristics may be observed in detail in the published article. In this text, only the aspects considered most significant would be highlighted. Left ventricular volumes and diameters were greater in men than in women; however, EF values in women were higher (Table 1). In comparison to the mentioned guidelines, mass and diameter values were lower in WASE. Absolute indexed ventricular volumes were greater than those proposed in guidelines. Likewise, lower EF values were higher in WASE, with a much smaller range than that published in guidelines (57% vs 52% for men, and 58% vs 54% for women). Regional differences could be proven too. Mexico and Asian countries presented the lowest values of heart size (indexed volumes and mass); while USA, Argentina, Italy and Australia showed the highest figures. The average EF value was 56% to 58% in men (except Korea) and 58% to 60% in women (except Australia and Nigeria). The values obtained in Argentina may be visualized in Table 2, and the comparison of ejection fraction values between the different countries in Figure 1. Between 10 to 20% of patients in different countries present values outside the ranges established in guidelines. Normal values, excepting volumes, seem to be similar in all scenarios (races, countries, etc.).
Table 1. Comparative values obtained in WASE and their relation to those published in the ASE/EACVI 2015 guidelines
LVIDd: Left ventricular internal diameter at end diastole; LVIDs: Left ventricular internal diameter at end systole; IVSD: Interventricular septum thickness at end diastole; LVPWd: Left ventricular posterior wall thickness in diastole; LVEDV: Left ventricular end-diastolic volume; LVESV: Left ventricular end-systolic volume; LVEF: Left ventricular ejection fraction; LV GLS: Left ventricular global longitudinal strain; WASE: World Alliance Societies of Echocardiography. Modified from Asch F, et al.
Table 2. WASE values of individuals included in Argentina.
WASE: World Alliance Societies of Echocardiography; LVIDd: Left ventricular internal diameter at end diastole; LVIDs: Left ventricular internal diameter at end systole; IVSD: Interventricular septum thickness at end diastole; LVPWd: Left ventricular posterior wall thickness in diastole; LVEDV: Left ventricular end-diastolic volume; LVESV: Left ventricular end-systolic volume; LVEF: Left ventricular ejection fraction; i: Indexed. Modified from Asch F, et al.
Figure 1. Left ventricular ejection fraction values for both genders, comparing different countries. EF: Ejection fraction; EDV: End diastolic volume; ESV: End systolic volume; I: Indexed. Modified from Asch F, et al.
All these new results open the door to an interesting discussion. Taking into account the great overall representativeness of the data, should we take such values as normal? Should we modify cutoff values for ejection fraction to consider values as abnormal? Are the small differences associated to gender enough to consider different values in men and women? How does this information impact on scientific papers considering the values of previous guidelines? If we propose, only as an example, an investigation study that defined values below 40% as reduced left ventricular function, this means a 13-point value below the normal inferior value. According to the values obtained in WASE, 40% correspond to 17 points below the normal minimum value. How should we analyze this difference close to 5 points? Another clear example is the definition of severe ventricular dysfunction, as values below 30%. Should we continue considering this cutoff point or should we define a new one?
Undoubtedly, these are too many questions demanding a wide discussion and more investigation studies to obtain the proper answers; however, the need of a soon review of current guidelines is mandatory.
The WASE study since its publication is considered a pivotal study in cardiology, and it requires an exhaustive analysis and knowledge by all clinical cardiologists and particularly, those devoted to cardiology imaging tests.
Lang RM, Badano LP, Mor-Avi V,et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28 (1):1-39.e14.
Asch FM, Miyoshi T, Addetia K, et al. Similarities and Differences in Left Ventricular Size and Function among Races and Nationalities: Results of the World Alliance Societies of Echocardiography Normal Values Study. J Am Soc Echocardiogr 2019; 32 (11): 1396-1406.