`
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`
`Rev Esp Cardiol. 2012;65(10):879–884
`
`Original article
`
`Pulse Oximetry in the Diagnosis of Acute Heart Failure
`
`Josep Masip,* Maria Gaya` , Joaquim Pa´ ez, Antoni Betbese´ , Francisco Vecilla, Ruben Manresa, and Pilar Ruı´z
`
`Unidad de Cuidados Intensivos, Hospital Sant Joan Despı´ Moise`s Broggi, Consorci Sanitari Integral, Universidad de Barcelona, Sant Joan Despı´, Barcelona, Spain
`
`Article history:
`Received 12 February 2012
`Accepted 18 February 2012
`Available online 4 July 2012
`
`Keywords:
`Pulse oximetry
`Oxygen saturation
`Acute heart failure
`Myocardial infarction
`
`Palabras clave:
`Pulsioximetrı´a
`Saturacio´ n de oxı´geno
`Insuficiencia cardiaca aguda
`Infarto agudo de miocardio
`
`A B S T R A C T
`
`Introduction and objectives: Oxygen saturation by pulse oximetry is commonly used for monitoring
`critical patients, but its utility as a diagnostic marker of acute heart failure has not been assessed. This
`study analyzed the diagnostic role of oxygen saturation by pulse oximetry in a series of patients with
`acute myocardial infarction.
`Methods: In a prospective observational cohort study of 220 consecutive patients with acute myocardial
`infarction, data collection included baseline oxygen saturation by pulse oximetry (without oxygen),
`physiologic measurements, Killip class and data from portable chest radiography, recorded at the same
`hour on each of the first three days after admission. Patients were followed up for one year.
`Results: There were 612 assessments. Baseline oxygen saturation by pulse oximetry decreased
`progressively in relation to the presence and the severity of acute heart failure assessed by Killip
`classes 1 to 3 (mean: 95, 92 and 85, respectively; P<.001) or by radiology score 0 to 4 (95, 94, 92, 89 and
`83, respectively; P<.001), with a correlation coefficient of 0.66 and 0.63, respectively. Receiver operating
`characteristic curves disclosed the cut-off of oxygen saturation by pulse oximetry<93 to have the
`greatest area, with a sensitivity of 65%, specificity 90%, and overall test accuracy 83%. Patients grouped
`according to lowest oxygen saturation by pulse oximetry showed significantly different rates of one-year
`mortality or rehospitalization for heart failure.
`Conclusions: Baseline oxygen saturation by pulse oximetry is useful in establishing the diagnosis and
`severity of heart failure in acute settings such as myocardial infarction and may have prognostic
`<93.
`implications.The diagnosis may be suspected when baseline oxygen saturation by pulse oximetry is
` 2012 Sociedad Espan˜ ola de Cardiologı´a. Published by Elsevier Espan˜ a, S.L. All rights reserved.
`ß
`
`Pulsioximetrı´a en el diagno´ stico de insuficiencia cardiaca aguda
`
`R E S U M E N
`
`Introduccio´n y objetivos: La saturacio´ n de oxı´geno mediante pulsioximetrı´a se usa habitualmente en la
`monitorizacio´ n de pacientes crı´ticos, pero su utilidad como marcador diagno´ stico de insuficiencia
`cardiaca aguda no ha sido evaluada. Este estudio analiza el papel diagno´ stico de la saturacio´ n de oxı´geno
`mediante pulsioximetrı´a en una serie de pacientes con infarto agudo de miocardio.
`Me´todos: En un estudio observacional prospectivo, se incluyo´ a 220 pacientes consecutivos con infarto
`agudo de miocardio. Se registraron la saturacio´ n de oxı´geno mediante pulsioximetrı´a basal (sin oxı´geno),
`las constantes fisiolo´ gicas, la clase Killip y la puntuacio´ n radiolo´ gica a la misma hora, durante los
`primeros 3 dı´as del ingreso. Se siguio´ a los pacientes durante 1 an˜ o.
`Resultados: Se obtuvieron 612 valoraciones. La saturacio´ n de oxı´geno mediante pulsioximetrı´a basal
`disminuyo´ de forma progresiva respecto a la presencia y la gravedad de la insuficiencia cardiaca, tanto
`valorada con la clasificacio´ n de Killip 1-3 (medias, 95, 92 y 85, respectivamente; p
` 0,001), como con la
`<
`puntuacio´ n radiolo´ gica 0-4 (95, 94, 92, 89 y 83, respectivamente; p
` 0,001), con un cociente de
`<
`correlacio´ n de 0,66 y 0,63 respectivamente. Las curvas receiver operating characteristic para la saturacio´ n
`de oxı´geno mediante pulsioximetrı´a mostraron que el punto de corte
` 93 tenı´a la mayor a´ rea, con
`<
`sensibilidad del 65%, especificidad del 90% y precisio´ n diagno´ stica del 83%. Los pacientes agrupados
`segu´ n su saturacio´ n de oxı´geno mediante pulsioximetrı´a ma´ s baja, mostraron tasas significativamente
`distintas de mortalidad o rehospitalizacio´ n con insuficiencia cardiaca.
`Conclusiones: La saturacio´ n de oxı´geno mediante pulsioximetrı´a es u´ til para establecer el diagno´ stico y
`la gravedad de la insuficiencia cardiaca en situaciones agudas como el infarto de miocardio y puede tener
`implicaciones prono´ sticas. El diagno´ stico debe sospecharse cuando la saturacio´ n de oxı´geno mediante
`pulsioximetrı´a basal es
` 93.
`<
` 2012 Sociedad Espan˜ ola de Cardiologı´a. Publicado por Elsevier Espan˜ a, S.L. Todos los derechos reservados.
`ß
`
`SEE RELATED ARTICLE:
`http://dx.doi.org/10.1016/j.rec.2012.05.002, Rev Esp Cardiol. 2012;65:867–8
`* Corresponding author: Unidad de Cuidados Intensivos, Hospital Sant Joan Despı´ Moise` s Broggi, Consorci Sanitari Integral, Universidad de Barcelona, Jacint Verdaguer 90,
`08970 Sant Joan Despı´, Barcelona, Spain.
`E-mail address: jmasip@ub.edu (J. Masip).
`
` 2012 Sociedad Espan˜ ola de Cardiologı´a. Published by Elsevier Espan˜ a, S.L. All rights reserved.
`1885-5857/$ – see front matter
`http://dx.doi.org/10.1016/j.rec.2012.02.021
`
`ß
`
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`Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
`
`880
`
`J. Masip et al. / Rev Esp Cardiol. 2012;65(10):879–884
`
`Abbreviations
`
`AHF: acute heart failure
`AMI: acute myocardial infarction
`LB-SpO2: lowest baseline SpO2
`MB-SpO2: morning baseline SpO2
`SpO2: oxygen saturation by pulse oximetry
`
`INTRODUCTION
`
`Acute heart
`in
`frequent complication
`is a
`failure (AHF)
`patients with acute myocardial infarction (AMI).1,2 The inci-
`dence may be rather variable depending on the diagnostic
`criteria.3 In clinical practice, diagnosis
`is
`initially made on
`admission by anamnesis and physical examination.4 However,
`identification of this complication is frequently difficult and it is
`necessary to obtain complementary data from portable chest
`radiography5 or other techniques such as echocardiography,6
`pulmonary wedge catheter,7 or biological markers.8 Because
`AHF affects pulmonary function,9 gas exchange could be altered
`even in mild forms. Although AHF has been associated with
`hypoxemia,10 the diagnostic contribution of oxygen saturation
`by bedside pulse oximetry (SpO2) has not been analyzed. Most of
`the previous studies using this technique in AMI were limited to
`investigating the incidence of hypoxemia or nocturnal sleep
`apnea syndrome.11–15 Therefore, we conducted an observational
`study to assess the value of baseline SpO2 for the diagnosis and
`severity of AHF in patients with AMI, a homogeneous population
`with a high prevalence of this complication.
`
`METHODS
`
`Patient Population
`
`Our institutional ethics committee approved the study design
`and all patients gave their informed consent. All consecutive
`patients of any age with ST and non-ST segment elevation AMI
`admitted to our critical/semi-critical intensive care unit were
`considered for inclusion. AMI was defined by prolonged chest pain
`with ischemic electrocardiographic changes and elevated myo-
`cardial necrosis biomarkers. Patients were included irrespective of
`the treatment received prior to admission (primary coronary
`angioplasty, fibrinolytic or conventional treatment). Patients with
`moderate to severe chronic obstructive pulmonary disease (GOLD
`classes II-III) and those who developed cardiogenic shock were
`excluded.
`
`Study Design
`
`This was a prospective observational cohort study. Patients
`were continuously monitored by pulse oximetry during the first
`three days, using modular Hewlett-Packard (SpO2/Plet M1020A)
`pulse oximeters with a central station monitor. The target SpO2
`was ‘‘morning baseline SpO2’’ (MB-SpO2), which was registered
`by nurses in awake patients on the morning round, usually after
`chest radiography, and taking the most stable value on room air.
`In patients receiving oxygen therapy it was recorded when a
`
`steady value was reached, after several minutes of oxygen
`discontinuation.
`Physical examination data was recorded by staff physicians
`(Killip class)4 on admission and daily morning rounds thereafter.
`Portable chest radiographs were also obtained daily during rounds
`and were evaluated using a radiology score by consensus of
`2 observers and sometimes 3 in case of initial disagreement. This
`score was based on Battler et al. classification,5 establishing
`5 categories: (0) normal; (1) vascular redistribution to upper lung
`fields; (2) interstitial edema defined by B-Kerley lines or prominent
`and diffuse hiliar contour with vascular redistribution; (3) localized
`edema with alveolar infiltrates in less than 50% of the lung fields,
`mainly hilo-basal, and (4) diffuse alveolar edema with alveolar
`infiltrates in 3 or 4 quadrants.
`Data obtained on the first morning after admission was
`introduced as
`‘‘first day’’. Thus, the interval from the onset of
`AMI to that moment could be variable. However, data on the
`following days were also collected in the morning but at constant
`intervals up to 3 days. Oxygen therapy was administered if
`baseline SpO2 was lower than 93%. Cardiac necrosis markers (MB
`fraction creatine kinase/troponin T) were obtained on admission
`and every 6 h, until peak value was identified. Natriuretic peptides
`were not available in our center at the time of study recruitment.
`The variables registered during daily rounds were heart rate,
`respiratory rate, blood pressure, MB-SpO2, Killip class, and
`radiology score. The variable ‘‘lowest baseline SpO2’’ (LB-SpO2)
`was obtained retrospectively upon discharge from the intensive
`care unit (ICU), taking the lowest SpO2 value among those recorded
`during the whole acute cardiac care stay.
`Ventricular function was assessed by echocardiography, which
`was performed during hospitalization. After discharge, patients
`were followed up for one year and death or rehospitalization with
`AHF was registered.
`
`Diagnosis of Acute Heart Failure
`
`Patients with Killip classes 2 or 3 were initially considered to
`have AHF in the Bayesian analysis. However, an abnormal chest
`radiography was required to confirm this diagnosis in such a way
`that patients who presented normal radiology (score 0) were
`considered not to have AHF (Killip false positive) regardless of the
`assigned Killip class. Conversely, patients initially evaluated as
`Killip 1 on physical examination who presented unequivocal signs
`of pulmonary congestion on radiology (score 3-4) were considered
`to have AHF (Killip false negative).
`
`Statistical Analysis
`
`The total data registered during the 3 days of monitoring
`accounted for more than 600 determinations for every one of the
`6 study variables (Killip class, radiology score, MB-SpO2, heart rate,
`respiratory rate and blood pressure). Receiver operating char-
`acteristic (ROC) curves from these simultaneous determinations
`were used to analyze the test accuracy for the diagnosis of AHF for
`different cut-off levels of MB-SpO2, heart, and respiratory rates.
`When patients were analyzed, their LB-SpO2 was individually
`assigned. Comparisons between means were analyzed using the
`Student t test or analysis of variance (ANOVA). In variables with no
`normal distribution or no homogeneous variances, a nonpara-
`metric test (Kruskal-Wallis or Mann-Whitney) was used. Pair-wise
`multiple comparisons were performed by least-significant differ-
`ences or Tamhane test when variances were not equal. Non-
`test.
`continuous variables were analyzed by Fisher exact
`Continuous variables were reported as mean (standard deviation).
`All P values were for two-tailed comparisons.
`
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`
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`
`J. Masip et al. / Rev Esp Cardiol. 2012;65(10):879–884
`
`881
`
`logistic regression
`factors were analyzed by
`Independent
`analysis. Kaplan-Meier event-free (death or rehospitalization with
`AHF) survival analysis was used for the follow-up evaluation,
`assigning patients to one of three groups, according to their
`LB-SpO2. The range of LB-SpO2 for these groups was guided by
`the 95% confidence intervals (95%CI) of the mean SpO2 in each
`Killip class group. Consequently, these groups were: group 1
`(SpO2>93%); group 2 (SpO2=90%-93%), and group 3 (SpO2<90%).
`
`RESULTS
`
`Over a 2-year period, 220 consecutive patients with AMI, with
`and without ST segment elevation, were admitted to our intensive/
`semi-intensive care unit and accepted for participation in the
`study. The study was approved by our Ethics and Research
`Committee and was carried out in the year 2000. Fourteen patients
`(6%) developed cardiogenic shock or needed mechanical ventila-
`tion (invasive or noninvasive) and were subsequently excluded. In
`the remaining patients there were 122 with ST-segment elevation
`and 9 with left bundle branch block. Non-Q wave AMI was the final
`diagnosis in 106 patients.
`The characteristics of the patients based on the incidence of AHF
`are shown in Table 1. Overall, patients with AHF were older, less
`predominantly men, with higher rates of previous hypertension,
`diabetes, myocardial infarction and heart failure than patients
`without AHF.
`After 3 days the cumulative incidence of some degree of AHF
`was 35%. Two thirds of the patients presented AHF on admission
`whereas the rest of the patients developed this complication
`thereafter. Regarding symptoms, AHF was clinically silent in the
`majority of the patients and less than 20% showed some degree of
`shortness of breath. Mortality after 30 days and at 1 year was
`significantly greater in patients with AHF.
`in Table 1.
`Physiologic measurements are also presented
`Patients with AHF showed significantly higher respiratory and
`
`heart rates and lower LB-SpO2 and left ventricular ejection fraction,
`while there were no differences in blood pressure.
`Distribution of mean MB-SpO2 values in relation to the degree
`of AHF is shown in Figures 1 and 2. Median MB-SpO2 was
`significantly lower according to the degree of AHF measured either
`by Killip classes (n=612) or Battler scores (n=604). All intergroup
`pair- wise comparisons were also significantly different. There
`were also significant differences between respiratory rates for
`Killip classes 1 to 3 (19 [3], 21 [4], and 26 [8], respectively; P<.001)
`and for Battler scores 0 to 4 (19 [3], 20 [3], 21 [5], 24 [7], and 26 [7],
`respectively; P<.001). All intergroup pair-wise comparisons for
`respiratory rate were also significantly different.
`
`Diagnostic Accuracy
`
`Regarding measurements (n=612), the correlation coefficients
`between MB-SpO2 and Killip class and Battler score were 0.666
`and 0.619,
`respectively
`the
`(P<.001). Regarding patients,
`correlation coefficient between LB-SpO2 and
`left ventricular
`ejection fraction was 0.433; P <0.001.
`The MB-SpO2 measurements were plotted in a ROC curve for
`the diagnosis of AHF (Fig. 3). The cut-off level of SpO2<93 showed
`the greatest area under the curve with the highest test accuracy
`(83%). The cut-off value for patients with chronic bronchitis (n=45)
`with greater area was SpO2<93 as well. The ROC curves were also
`plotted for respiratory and heart rate. The cut-off with greater area
`for respiratory rate was >21 breaths/min (area, 0.64), with a test
`accuracy of 59% (odds ratio=2.19; 95%CI, 1.53-3.16). The cut-off
`value for heart rate was >76 bpm (area, 0.61) and the test accuracy
`73% (odds ratio=4.21; 95%CI, 2.8-6.3).
`There were 29 patients who were misclassified by Killip score,
`20 (10%) false negatives and 9 (4%) false positives. The combination
`of MB-SpO2<93 and Killip classes (2) or respiratory rate
`(>21 breaths/min) increased the specificity to 99.4% and 97%
`and the positive predictive value to 97.2% and 78%, respectively.
`
`Table 1
`Characteristics of 206 Patients With Acute Myocardial Infarction According to the Presentation of Acute Heart Failure
`
`No AHF (n = 133)
`
`AHF (n = 73)
`
`Characteristics
`
`Age, years
`
`Male
`
`Diabetes
`
`Hypertension
`
`Prior myocardial infarction
`
`Prior heart failure
`
`LBBB
`
`ST-Segment elevation
`
`Outcomes
`
`30-day mortality
`
`One-year mortality
`
`Physiologic measurements
`
`Lowest SpO2
`Systolic blood pressure,* mmHg
`
`Heart rate,* bpm
`
`Respiratory rate,* breaths/min
`
`LVEF, %
`
`End-diastolic diameter, mm
`
`61.512.4
`
`105 (79)
`
`34 (26)
`
`59 (45)
`
`19 (15)
`
`6 (5)
`
`1 (0.8)
`
`84 (63)
`
`0
`
`6 (4.9)
`
`93.42.1
`
`118.614.6
`
`71.711.7
`
`18.92.4
`
`60.18.7
`
`52.35.7
`
`709.4
`
`47 (64)
`
`35 (48)
`
`48 (69)
`
`28 (39)
`
`22 (31)
`
`8 (11)
`
`48 (66)
`
`9 (12.3)
`
`18 (26.1)
`
`87.96.3
`
`118.917.5
`
`81.113.5
`
`21.53.8
`
`45.810.5
`
`54.75.9
`
`AHF, acute heart failure; LBBB, left bundle branch block; LVEF, left ventricle ejection fraction; SpO2, oxygen saturation by pulse oximetry.
`Data are expressed as mean  standard deviation or no. (%).
`* Average values obtained on the 3 days of the study during the morning rounds.
`
`P
`
`<.001
`
`.031
`
`.002
`
`.002
`
`<.001
`
`<.001
`
`.001
`
`.760
`
`<.001
`
`<.001
`
`<.001
`
`.880
`
`<.001
`
`<.001
`
`<.001
`
`.010
`
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`
`
`Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
`
`J. Masip et al. / Rev Esp Cardiol. 2012;65(10):879–884
`
`882
`
`100
`
`96
`
`92
`
`88
`
`84
`
`80
`
`SpO2
`
`AUC-ROC, 0.85 (95%CI, 0.80-0.88)
`
`0.2
`
`0.4
`
`0.6
`
`0.8
`
`1
`
`Specificity
`
`1
`
`0.8
`
`0.6
`
`0.4
`
`0.2
`
`Sensitivity
`
`0
`
`0
`
`SpO2, % Sensitivity Specificity
`PPV
`
`
`
`
`
`
`
`
`
`
`
`
`NPV
`
`
`
`
`
`Accuracy
`
`
`
`
`
`AUC-ROC OR (95%
`CI)
`
`
`
`
`<90
`
`32
`
`98.2
`
`87.1
`
`79.1
`
`79.9
`
`0.65
`
`26 (12-54)
`
`27 (14-50)
`
`94.9
`
`91.7
`
`n=461
`
`1
`
`
`
`n=107
`
`2
`
`Killip class
`
`85.3
`
`n=44
`
`3
`
`Figure 1. Baseline oxygen saturation by pulse oximetry values in relation to
`the degree of heart failure assessed by physical examination (Killip classes) for
`all measurements. Squares are means; bars (standard deviation). SpO2, oxygen
`saturation by pulse oximetry.
`
`95.1
`
`94
`
`92.3
`
`89.2
`
`100
`
`96
`
`92
`
`88
`
`SpO2
`
`81.6
`
`83.7
`
`86.7
`
`89.5
`
`92.2
`
`83.3
`
`83.2
`
`78
`
`69.9
`
`0.69
`
`0.73
`
`0.77
`
`0.76
`
`0.74
`
`
`
`23 (13-39)
`
`17 (11-26)
`
`12 (8-18)
`
`11 (7-17)
`
`
`
`
`
`
`
`82.1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Figure 3. Receiving operating characteristics curve for oxygen saturation by
`pulse oximetry and acute heart failure. A table with information about
`different cut-off points is attached. 95%CI, 95% confidence interval; AUC, area
`under curve; NPV, negative predictive value; OR, odds ratio; ROC: receiver
`operating characteristic; SpO2, oxygen saturation by pulse oximetry; PPV,
`positive predictive value.
`
`<91
`
`<92
`
`<93
`
`<94
`
`<95
`
`42.6
`
`52.1
`
`64.5
`
`75.7
`
`85.8
`
`97.3
`
`95.4
`
`90.1
`
`78.9
`
`63.9
`
`85.7
`
`81.5
`
`71.7
`
`57.9
`
`47.5
`
`84
`
`80
`
`76
`
`n=314
`
`n=168
`
`n=61
`
`n=40
`
`0
`
`
`
`1
`
`
`2
`
`Battler class
`
`3
`
`
`82.7
`
`n=21
`
`4
`
`Figure 2. Baseline oxygen saturation by pulse oximetry values in relation to
`the degree of heart failure assessed by radiology score (Battler classes) for all
`measurements. Squares are means; bars (standard deviation). SpO2, oxygen
`saturation by pulse oximetry.
`
`Follow-up
`
`in
`follow-up was 13 months and was completed
`Mean
`192 patients (93%). Multivariate
`logistic regression analysis
`showed age and AHF to be the independent predictive variables
`for 1-year death or rehospitalization for AHF (Table 2). LB-SpO2
`was only an independent factor when AHF was not introduced in
`the analysis.
`Kaplan-Meier event-free (mortality and rehospitalization for
`AHF) survival curves for the 3 LB-SpO2 groups are shown in
`Figure 4. There were significant differences in the event-free rates
`between the 3 groups as well as in pair-wise group comparisons:
`group 1 vs group 2 (90.7% vs 76.1%; P=.01), group 2 vs group 3
`(76.1 vs 54.3%; P=.01) and group 1 vs group 3 (90.7 vs 54.3%; log
`rank test, P=.00005).
`
`DISCUSSION
`
`This study shows the utility of baseline SpO2 as a complementary
`tool to establish the diagnosis and severity of AHF. We chose to
`perform the study in patients with AMI because of the high
`prevalence of AHF in this population. The main advantage of SpO2
`lies in the fact that is noninvasive, it can be monitored continuously,
`and it is not affected by interobserver or intraobserver variability.
`The finding of a baseline SpO2 lower than 93 may be considered a
`signal of AHF and a warning to clinicians about this complication
`which may be especially useful between rounds. The lower the SpO2
`value, the higher the probability and severity of AHF.
`
`The results also stress the role of measuring respiratory rate and
`heart rate. These findings are relevant because respiratory rate is
`not usually considered a diagnostic marker of AHF. Although heart
`rate is commonly assessed for the diagnosis, it can be altered by the
`use of beta-blockers. The association of a decreasing SpO2 with an
`increasing respiratory rate may reinforce the suspicion of AHF in
`patients with doubtful diagnostic criteria.
`Our study found good correlations between baseline SpO2 and
`the degree of AHF or left ventricular ejection fraction. These findings
`were in accordance with previous trials analyzing oxygen saturation
`by CO-oximetry from arterial blood samples, which showed a close
`correlation between the defects in gas exchange and the severity of
`AHF or the pulmonary capillary wedge pressures,10,16–18 although
`this correlation decreased in chronic patients.19 Hypoxemia in AHF is
`explained by an increase in veno-arterial shunting and ventilation-
`perfusion imbalance.10,16–18 Despite this well-known interaction,
`however, the determination of oxygen saturation (SaO2) by arterial
`puncture as a diagnostic marker of AHF is not a common practice and
`this valuable information is frequently missed. Although SpO2
`values are closely related to SaO2 obtained by CO-oximetry, the
`accuracy of pulse oximetry may decrease in special situations such
`as severe hypoxemia, anemia, acidosis, pigmentation, low perfusion
`states, and the use of vasoactive drugs.20,21 Therefore, SpO2 and SaO2
`are not totally equivalent and the information in the literature about
`the role of SpO2 in AHF is scarce. Some authors have reported their
`experience with SpO2 in detecting Cheyne-Stokes respiration in
`patients with heart failure22 but, to our knowledge, no previous
`study has tested the utility of SpO2 for the diagnosis of AHF.
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`AliveCor Ex. 2025 - Page 4
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`Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
`
`J. Masip et al. / Rev Esp Cardiol. 2012;65(10):879–884
`
`883
`
`Table 2
`Risk Factors for One-year Death or Rehospitalization for Heart Failure
`
`Univariate analysis
`
`Multivariate analysis
`
`Acute heart failure
`
`Measurements
`
`a
`SpO2
`Left ventricular functionb
`
`Heart rateb
`
`Respiratory rateb
`
`Clinical characteristics
`
`History of heart failure
`
`Prior myocardial infarction
`
`Diabetes
`
`Hypertension
`
`Agec
`
`OR (95%CI)
`
`7.8 (3.6-17.1)
`
`5.5 (2.6-11.8)
`
`4.3 (1.9-9.6)
`
`2.5 (1.2-5)
`
`2.5 (1.2-5)
`
`5.5 (2.3-12.9)
`
`3.5 (1.7-7.4)
`
`2.5 (1.2-5)
`
`2.2 (1.05-4.6)
`
`1.13 (1.07-1.18)
`
`P
`
`<.001
`
`<.001
`
`.001
`
`.013
`
`.02
`
`<.001
`
`.001
`
`.015
`
`.049
`
`<.001
`
`OR (95%CI)
`
`7.1 (2.7-19)
`
`P
`
`<.001
`
`1.12 (1.05-1.18)
`
`<.001
`
`95%CI, 95% confidence interval; OR, odds ratio; SpO2, oxygen saturation by pulse oximetry.
`The OR reflects the odds for patients with the characteristic in question, as compared to those without the characteristic.
`a SpO2 is a categorical variable (cut-off
`<93) obtained by taking the lowest value registered on the rounds for each patient.
`b Categorical variables (cut-off: ejection fraction
`<0.50; heart rate
`>76 bpm; respiratory rate
`>21 breaths/min).
`c The OR for age represents the exponent for each year of age in the logistic equation.
`
`The diagnosis of AHF may be difficult in patients with AMI
`because it is often silent.23 In our series, the majority of patients
`with AHF did not show shortness of breath. Therefore, because AHF
`may be misdiagnosed in many cases by physical examination24,25
`(5%-10% of patients in our study were misclassified), the diagnostic
`criteria of AHF in this study required abnormal radiology because
`this technique enhances the sensitivity and diagnostic accu-
`racy.3,23 Chest radiography is considered a class I recommendation
`in the European Society of Cardiology guidelines on the diagnosis
`and treatment of AHF.26,27 In these guidelines, SpO2 also received
`the same consideration for monitoring, not for diagnosis.
`
`In recent decades the evaluation of ventricular function and
`filling pressures by echocardiography has become a widespread
`practice
`in the assessment of AHF, often replacing
`invasive
`like pulmonary catheter.27–29 Nevertheless,
`approaches
`the
`information provided by echocardiography is not continuous.
`Biochemical markers such as natriuretic peptides are frequently
`abnormally elevated on admission30 and have better prognostic
`than diagnostic value in patients with AMI.8 In this context, SpO2
`may become a complementary, continuous, and low-cost para-
`meter for assessing AHF with prognostic implications, as shown in
`the follow-up.
`
`Limitations
`
`This study had some
`lack of
`the
`including
`limitations,
`determination of natriuretic peptides, which were not commonly
`used in our institution when the study was performed, and the
`absence of a gold standard for the diagnosis of AHF in patients with
`AMI. Other limitations were the registry format that introduced
`data from each patient several times, the inability to achieve a
`completely blinded clinical assessment, and finally, the fact that
`patients with AHF were older and age might produce a decrease in
`SpO2 by itself. Furthermore, we assessed the merits of SpO2 as a
`diagnostic marker of AHF in patients with AMI, but this could not
`be tested in patients with significant chronic obstructive pulmon-
`ary disease or shock and it should be evaluated in the future in
`other acute care conditions. Finally, this series should not be
`considered as representative of the incidence of AHF in patients
`with acute coronary syndromes, as our population was recruited in
`a single community hospital with strongly biased admissions.
`
`CONCLUSIONS
`
`In this study, baseline SpO2 provided reliable information for
`establishing the diagnosis and severity of AHF as a complication of
`AMI with a warning cut-off value<93. The use of pulse oximetry
`for diagnosis purposes may be recommended when managing
`patients at risk of AHF.
`
`SpO2>93%
`
`SpO2 90-93%
`
`SpO2<90%
`
`Log rank test,
` P<.00005
`
`
`0
`
`
`
`2
`
`
`4
`
`
`6
`
`Months
`
`8
`
`10
`
`12
`
`1
`
`0.9
`
`0.8
`
`0.7
`
`0.6
`
`0.5
`
`0.4
`
`0.3
`
`0.2
`
`0.1
`
`0
`
`Event-free survival
`
`Patients at risk at the end of period
`
`86
`
`
`SpO2>93%
`
`
`SpO2 90-93% 71
`35
`SpO2<90%
`
`80
`
`56
`
`20
`
`71
`
`51
`
`16
`
`Figure 4. Kaplan-Meier event-free survival curves for three groups of oxygen
`saturation by pulse oximetry. Events are death or rehospitalization with heart
`failure within the first year. Numbers are patients at risk in each group after 1,
`6, and 12 months. SpO2, oxygen saturation by pulse oximetry.
`
`AliveCor Ex. 2025 - Page 5
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`Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.Document downloaded from https://www.revespcardiol.org/, day 28/03/2022. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
`
`884
`
`J. Masip et al. / Rev Esp Cardiol. 2012;65(10):879–884
`
`ACKNOWLEDGMENTS
`
`We thank physicians Gaieta` Permanyer, Xavier Bosch, Pilar
`Tornos, Jordi Otero, and Pere Codinach for their critical review of
`the paper; physicians Rosario Can˜ izares, Jaume Padro´ , and Josep
`Ballu´ s, as well as the entire nursing team of our intensive care unit,
`for their technical support in collecting data; the epidemiologist
`Montserrat Martin for statistical support; Mitsi Ito and Joshua
`Morris for help with language in writing the paper. All of them gave
`their consent to be mentioned in this section.
`
`FUNDING
`
`Our own institution financed the study.
`
`CONFLICTS OF INTEREST
`
`None declared.
`
`REFERENCES
`
`1. Spencer F, Meyer T, Goldberg R, Yarzebski J, Hatton M, Lessard D, et al. Twenty
`year trends (1975-1995) in the incidence, in-hospital and long-term death rates
`associated with heart
`failure complicating acute myocardial
`infarction.
`A community-wide perspective. J Am Coll Cardiol. 1999;34:1378–87.
`2. Hasdai D, Topol E, Kilaru R, Battler A, Harrington RA, Vahanian A, et al.
`Frequency, patient characteristics, and outcomes of mild-to-moderate heart
`failure complicating ST-segment elevation acute myocardial infarction: lessons
`from 4 international fibrinolytic therapy trials. Am Heart J. 2003;145:73–9.
`3. Hellermann J, Jacobsen SJ, Gersh BJ, Rodeheffer RJ, Redder GS, Roger VL. Heart
`failure after myocardial infarction: A review. Am J Med. 2002;113:324–30.
`4. Killip T, Kimball JT. Treatment of myocardial infarction in a coronary care unit.
`Am J Cardiol. 1967;20:457–64.
`5. Battler A, Karliner JS, Higgins CB, Slutsky R, Gilpin EA, Froelicher VF, et al. The
`initial chest x-ray in acute myocardial infarction. Prediction of early and late
`mortality and survival. Circulation. 1980;61:1004–9.
`6. Figenbaum H. Role of echocardiography in acute myocardial infarction. Am J
`Cardiol. 1990;66:H17–22.
`7. Forrester JM, Diamond G, Chatterjee K, Swan HJ. Medical therapy of acute
`myocardial infarction by application of hemodynamic subsets (first of two
`parts). N Engl J Med. 1976;295:1356–62.
`8. De Lemos J, Morrow D, Bentley J, Omland T, Sanatine MS, McCabe CH, et al. The
`prognostic value of B-type natriuretic peptide in patients with acute coronary
`syndromes. N Engl J Med. 2001;345:1014–21.
`9. Gehlbach NK, Geppert E. The pulmonary manifestations of left heart failure.
`Chest. 2004;125:669–82.
`10. Fillmore J, Shapiro M, Killip T. Arterial oxygen tension in acute myocardial
`infarction. Serial analysis of clinical state and blood gas changes. Am Heart J.
`1970;79:620–9.
`11. Galatius-Jensen S, Hansen J, Rasmussen V, Bildsøe J, Therboe M, Rosenberg J.
`Nocturnal hypoxaemia after myocardial infarction: association with nocturnal
`myocardial ischaemia and arrhythmias. Br Heart J. 1994;72:23–30.
`
`12. Saito T, Yoshikawa T, Sakamoto Y, Tanaka K, Inoue T, Ogawa R. Sleep apnea in
`patients with acute myocardial infarction. Crit Care Med. 1991;19:938–41.
`13. Wilson AT, Channer KS. Hypoxaemia and supplemental oxygen therapy in the
`first 24 h after myocardial infarction: the role of pulse oximetry. J R Coll
`Physicians Lond. 1997;31:657–61.
`14. Marin JM, Carrizo SJ, Kogan I. Obstructive sleep apnea and acute myocardial
`infarction: clinical implications of the association. Sleep. 1998;21:809–15.
`15. Stark R, Kohler D. The value and consequences of nocturnal pulse oximetry in
`severe heart failure, suspected myocardial infarct and acute cerebral ischemia.
`Pneumologie. 1989;Suppl 43:596–9.
`16. Sukumalchantra Y, Levy S, Danzig R, Rubin S, Alpem H, Swan HJ. Correcting
`arterial hypoxemia by oxygen therapy in patients with acute myocardial
`infarction. Effect on ventilation hemodynamics. Am J Cardiol. 1969;24:838–52.
`17. Fillmore SJ, Guimara¨ es AC, Scheidt SS, K