Revista Societatii de Medicina Interna
Articolul face parte din revista :
Nr.2 din luna aprilie 2017
Autor Mădălina Ababei, Alexandru Cāmpeanu, Diana Cornelia Nistorescu, Andreea Hodorogea, Gabriela Uscoiu, Ioan Tiberiu Nanea
Titlu articolNONINVASIVE HEMODYNAMIC MONITORING IN ACUTE DECOMPENSATED HEART FAILURE
Cuvinte cheiebioimpedanță, insuficiență cardiacă acută, acid uric seric
Articol
Acute decompensated heart failure (ADHF), a heterogeneous and complex syndrome(1) with multiple pathophysiological mechanisms, is a major public health problem worldwide with increasing incidence and poor prognosis(2). Under the influence of some decompensation risk factor, such as infections, arrhythmias, lack of adherence to the treatment, patients with a history of heart failure may suffer a progressive symptomatology worsening; therefore, more than 70% of the cases of acute heart failure represent the clinical worsening of chronic heart failure - ADHF(3).
The increase of oxidative stress observed in ADHF, possibly exacerbated by systemic inflammation(4,5), leads to excessive free radical production, such as superoxide anion, that inactivates the NO(6,7). The sUA level is a witness increased production of superoxide(8)due to the XO activation(9–10). The imbalance between increasing oxidative stress and decreasing the NO amount induces endothelial dysfunction(11–12) and can activate other pro-inflammatory pathways and cytokine production, generating a vicious circle(13,14).
Hemodynamics studies the pump function of the heart and the forces needed for the blood flow throughout the vascular system(15). Measuring hemodynamic parameters using thoracic bioimpedance (ICG) is a cheap and non-invasive solution that brings important information for understanding the pathophysiological mechanisms(16)and hemodynamic consequences of acute heart failure that could help guiding therapy(17).
Blood pressure, the hemodynamic parameter used in clinical practice, does not identify changes of vascular resistance that occurs with disease progression or therapeutic interventions(18). Therefore, the peripheral resistance parameters can be used to optimize treatment and to improve functional status and life quality(19).
Several studies have shown that in invasive monitoring of patients with acute heart failure the risks outweigh the benefits(20). Therefore, the thoracic bioimpedance can be used instead, with reproducible results. The reference values were obtained from comparative studies with the invasive method that included patients in critical condition, with severe cardiovascular pathology that justified the risk associated with cardiac catheterization procedures(21–23). The standard of comparison in most cases was the measurement of cardiac output by thermo-dilution method using a catheter placed in the pulmonary artery(24).
The following parameters can be obtained using ICG: cardiac output, afterload (peripheral vascular resistance), contractility of left ventricle (LV) and volaemia; these parameters are represented as percentage variation from the ideal value(25).
In several pilot studies, the method was useful in diagnosing, severity stratification and optimizing treatment of patients with heart failure; therefore, this method could become a routine clinical tool in the future(26). Since the method is even faster than the determination of natriuretic peptides, it can be very useful in the emergency room for differential diagnosis of dyspnea(27). Moreover, it may be useful in assessing hemodynamic status in a state of apparent clinical stability(28), for treatment optimization and thus avoiding cardiac decompensation that would require costly hospitalization(29).
The PREDICT(30) study proved that ICG parameters have good predictive value in identifying ADHF patients with high risk of cardiovascular events. Furthermore, the study showed that the combined use of BNP and SSVRI, the vascular resistance parameter, shows a long-term prognosis in these patients(31). In another study conducted at the emergency room, the combination of BNP with ICG parameters could identify patients with increased risk of short-term mortality or re-hospitalization for ADHF patients(32).
Using this method is contraindicated in patients with extreme weight (below 30 kg or more than 120 kg), marked anxiety, severe aortic regurgitation, atrial fibrillation with rapid ventricular response or left bundle block(33). The thoracic electrical current could also influence the cardiac pacemakers’ activity(34).
The aim of the study was to assess the ICG parameters, highlighting a pathophysiological pattern and their relationship with the NT-proBNP and sUA levels and the endothelial function for ADHF patients at admission. Also, the effect of Allopurinol on hemodynamic parameters and endothelial function was assessed.
Method
The study group included 40 patients with ADHF caused by ischemic cardiomyopathy, treated according to 2012 ESC guidelines. The decompensation of heart failure was proved clinically: NYHA functional class III and IV and at least 2 signs of congestion and biologically: increasing of NT-proBNP level and required hospitalization.
Exclusion criteria were: marked anxiety, extreme weight (below 30 kg or more than 120 kg), atrial fibrillation with rapid ventricular response, severe aortic regurgitation, left bundle block, pacemaker, stroke in the last 3 months, cord pulmonale and severe pulmonary, renal or liver disease. None of the patients were taking Allopurinol before admission. All patients were informed about the purpose and methodology of the study and writing consent was obtained from every patient.
ECG, common laboratory tests, and echocardiography were performed for all patients, after a comprehensive clinical examination2. Also, the hemodynamic assessment using thoracic bioimpedance and NT-proBNP and sUA levels were determined for all patients during hospitalization (10±4 days).
The endothelial function was assessed by the flow-mediated vasodilatation method using the 2 dimensions vascular ultrasound of the brachial artery (FMD), as recommended by international guidelines35. Percentage variation in the diameter of the brachial artery before and after ischemic stimulus (tensiometer cuff inflation over 50 mmHg systolic BP value) was calculated and values below 10% indicated endothelial dysfunction.
FMD (%) = ((final diametre- initial diametre)*100)/( initial diametre)
The hemodynamic function was evaluated by the thoracic bioimpedance method using the HOTMAN® system (Hemosapiens Inc.)36, the parameters being played every 16 beats. The method is based on the resistance of the living tissue to very small intensity and high frequency current(37).
The hemodynamic status is influenced by "hemodynamic modulators": preload (volaemia), contractility (inotropism) and afterload (vascular resistance). If the hemodynamic status is evaluated for 1 minute, it is also influenced by the heart rate (chronotropism)(38).
Obtained parameters with ICG are:
CI - cardiac index (2.5-4 l/min/m²)
SI - index LV beat (33-47 mL/beat/m²)
ISI - inotropic status index (0.75-1.7 sec²)
LSWI - LV mechanical work index (50-62 g*m/m2)
SSVRI - systemic vascular resistance index (ideal value: 137.8 dyn.sec.cmˉ⁵.m2)
Twenty patients were randomly assigned to receive ALLO 300 mg/day, regardless of their sUA level added to the standard treatment (ALLO+ group). Another 20 patients were treated according to the ESC Guideline, forming the ALLO– group.
Statistical analysis. The results were presented as mean ± standard deviation for numeric variables and as absolute numbers and percentages for categorical variables. For the analysis of numeric variables, parametric (Student's t-test, ANOVA) or non-parametric (Mann-Whitney, Kruskal-Wallis) tests were used. Linear regression and Pearson correlation coefficient r were used for correlations between numerical variables. The statistical significance was considered for a p-value<0.05. The statistical analysis was performed using 20.0.SPSS.
Results
The baseline characteristics of the 2 study groups are presented in Table 1; they were similar in terms of age, clinical presentation, cardiovascular risk factors and paraclinics. The mean NT proBNP level was 5989 ± 8314 µg/dL, demonstrating decompensated heart failure. The mean sUA level was 7.15 ± 2.66 mg/dL at admission, 22 subjects having hyperuricemia. Also, the mean FMD was 7.18 ± 6.04%, 29 patients presenting endothelial dysfunction at admission.
The most common pathophysiological pattern identified with ICG was concomitant hypervolemia, hipoinotropism and vasoconstriction (>60% of the patients). Eighty-three percent of the patients had hipochronotropism, 85% hipointropism, 95% hypervolaemia and 85% peripheral vasoconstriction, probably due to decompensation factors such as ischemia, arrhythmia, or noncompliance to dietary or treatment.
Significant correlations between left ventricle (LV) mass and ISI (R =-0.324, p =0.041), LSWI (R =-0.316, p =0.041) and SSVRI (R =0.328, p =0.039) were noticed. Also, there were correlations between the E/E' ratio (a parameter for assessing the filling pressure in the left ventricle) and SI (R =0.654, p =0.029), ISI (R =0.713, p =0.014) and LSWI (R =0.644, p =0.032).
During hospitalization a significant improvement of myocardial contractility parameters was observed: CI, SI, ISI, LSWI and a marked decrease of peripheral vascular resistance, which was more pronounced in the ALLO+ group. Also, in this group was observed a greater improvement of the endothelial function and decrease of the sUA level were observed. NT-proBNP levels decreased for all subjects, with no difference between the groups.
During hospitalization, the presence of endothelial dysfunction (FMD<10%) was associated with SSVRI (R = -0.416, p=0.008), SI (R = 0.493, p = 0.001) and LSWI (R = 0.431, p = 0.006). Moreover, it was observed that vasoconstriction correlates with the sUA level, a witness of the oxidative stress level (R = 0.446, p = 0.004). Allopurinol reduces the oxidative stress by inhibiting the xanthine oxidase and thus increasing the NO level and improving endothelial dysfunction.
Discussions
The non-invasive hemodynamic evaluation could be a feasible and cheap solution to identify the dominant involved pathophysiological mechanisms that can be used in optimizing therapy(17).
In several pilot studies, the method was useful in diagnosing, severity stratification and optimizing treatment of patients with heart failure; therefore, in the future this method can become a routine clinical tool(39). However, there are no data on possible correlations between different non-invasive hemodynamic parameters and other cardiovascular risk markers.
The hemodynamic status is influenced by the following hemodynamic modulators: preload (volaemia), contractility (inotropism) and afterload (vascular resistance). The chronotropism brings additional information to clinically measured heart rate, indicating the compensation level of a low cardiac output(18). Also, blood pressure cannot identify the degree of vascular resistance; therefore, the ICG peripheral resistance parameters can be used to optimize treatment and improve functional status and life quality(19).
In this group of ADHF patients an overwhelming majority presented concomitant hypervolaemia, hipoinotropism and vasoconstriction (>60% of the patients). Eighty-five percent of the subjects presented vasoconstriction at admission, demonstrating that besides hypervolaemia, one of the major pathophysiological mechanisms in ADHF is peripheral vasoconstriction.
These results come in line with previous studies that showed that all patients with heart failure have alteration of at least one hemodynamic modulator, frequently presenting concomitant hypervolaemia and vasoconstriction(31). It is well known that the neurohormonal activation during a cardiac decompensation determines systemic vasoconstriction with increased preload and afterload, fluid retention and tachycardia with increasing myocardial oxygen consumption(40).
Although the average heart rate was 98 ± 28 beats/minute (with beta-blocker therapy), more than 80% of the subjects were having hipochronotropism, showing that an increased heart rate is not an effective compensatory mechanism to achieve a normal cardiac index.
Also, markers of oxidative stress and endothelial function were determined. The average sUA level was 7.15 ± 2.66 mg / dL, 55% of the subjects presenting hyperuricemia. These data come in line with previous studies(41)that have shown a high prevalence of hyperuricemia (>50%) in patients with ADHF. Hyperuricemia is a consequence of amplifying expression and activity of xanthine oxidase(42).
Endothelial dysfunction is another pathophysiological mechanism commonly found in ADHF, more than 70% of the subjects in this study group having endothelial dysfunction at admission, with a mean FMD percentage of 7.1±0.7 %.
Correlations between the LV mass and hemodynamic parameters were noticed. Apparently paradoxical, the inverse correlation between ISI, LSWI and LV mass can be explained by the high degree of interstitial fibrosis, by decreasing the oxygen supply due to intramural vessel compression, by lower metabolic efficiency fiber and by biochemical alterations in the fiber (less efficient and abnormal myosin synthesis)(43). Thus, decreased contractility in heart failure hypertrophies appears when a certain degree of hypertrophy is exceeded. This barrier seems to be last in this study group, with a mean LV mass of 270±79 g/m² (normal range: <95 g/m² in women and <115 g/m² in men). Lowering pump efficiency can also be due to contraction asynchrony and excessive geometry changes due to cavity dilation(44).
The results of the study also confirm the beneficial effect of Allopurinol on the hemodynamic parameters and endothelial function in ADHF patients. Even though the number of patients is insufficient for statistically significant results, it is clear that Allopurinol determined an important decrease of the peripheral vascular resistance and improvement of the endothelial function. Also, the presence of endothelial dysfunction (FMD<10%) was correlated with hemodynamic parameters, sUA level, SSVRI, SI and LSWI. Previous studies showed that the endothelial dysfunction is associated with hemodynamic abnormalities(45,46). It is thus confirmed that Allopurinol reduces the oxidative stress by inhibiting the xanthine oxidase, increases the NO level, improves endothelial function and has a vasodilatory effect; still, further larger studies are needed.
The improvement of the endothelial function did not correlate with the decrease of the sUA level, suggesting that the effect of Allopurinol on the endothelial function is at least in part independent of the sUA-lowering effect. Previous studies have shown that the effect of Allopurinol on the endothelial function is not secondary to the decrease of sUA level, but to reduction of the vascular oxidative stress(7). Using equivalent doses of Allopurinol and Probenecid, that produced similar reductions of the sUA level, the authors(47)proved that Probenecid practically had no effect on the endothelial function.
The NT-proBNP levels decreased with more than 50% from admission to release overall, with no difference between the groups; natriuretic peptides and vascular resistance and endothelial function parameters being complementary in the ADHF physiopathology(48): the natriuretic peptide level reflects disease progression and endothelial dysfunction and peripheral vascular resistance reflects the risk of sudden thromboembolic events, these being the main causes of death in heart failure(31).
Conclusions
The non-invasive hemodynamic evaluation could help identifying the dominant pathophysiological mechanisms involved in ADHF and optimizing therapy. The most common pattern observed in this study was concomitant hypervolaemia, hipoinotropism and vasoconstriction (>60% of the patients). Also, the high prevalence of hyperuricemia and endothelial dysfunction in ADHF was confirmed, these being markers of amplified oxidative stress.
Allopurinol (300 mg daily) increased contractility parameters, reduced peripheral resistance and improved the endothelial function, but did not influence the NT proBNP level (probably different pathophysiological mechanism).
References
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21. Kamath S, Drazner M, Tasissa G, Rogers J, Stevenson L, Yancy C. Correlation of impedance cardiography with invasive hemodynamic measurements in patients with advanced heart failure: The BioImpedance CardioGraphy (BIG) substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Eff. Am J Cardiol. 2002;89:993-995.
22. Sageman W, Riffenburgh R, Spiess B. Equivalence of bioimpedance and thermodilution in measuring cardiac index after cardiac surgery. J Cardiothorac Vasc Anesth. 2002;16:8-14.
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27. Havelka EG, Rzechula KH, Bryant TO, Anneken SM, Kulstad EB. Correlation between impedance cardiography and b-type natriuretic peptide levels in dyspneic patients. J Emerg Med. 2011;40(2):146-150. doi:10.1016/j.jemermed.2008.01.019.
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30. Packer M, Abraham WT, Mehra MR, et al. Utility of Impedance Cardiography for the Identification of Short-Term Risk of Clinical Decompensation in Stable Patients With Chronic Heart Failure. J Am Coll Cardiol. 2006;47(11):2245-2252. doi:10.1016/j.jacc.2005.12.071.
31. Castellanos LR, Bhalla V, Isakson S, et al. B-Type Natriuretic Peptide and Impedance Cardiography at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events. J Card Fail. 2009;15(1):41-47. doi:10.1016/j.cardfail.2008.09.003.
32. Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: Pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol. 2012;60(12):1031-1042. doi:10.1016/j.jacc.2012.01.077.
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Nr.2 din luna aprilie 2017
Acute decompensated heart failure (ADHF), a heterogeneous and complex syndrome(1) with multiple pathophysiological mechanisms, is a major public health problem worldwide with increasing incidence and poor prognosis(2). Under the influence of some decompensation risk factor, such as infections, arrhythmias, lack of adherence to the treatment, patients with a history of heart failure may suffer a progressive symptomatology worsening; therefore, more than 70% of the cases of acute heart failure represent the clinical worsening of chronic heart failure - ADHF(3).
The increase of oxidative stress observed in ADHF, possibly exacerbated by systemic inflammation(4,5), leads to excessive free radical production, such as superoxide anion, that inactivates the NO(6,7). The sUA level is a witness increased production of superoxide(8)due to the XO activation(9–10). The imbalance between increasing oxidative stress and decreasing the NO amount induces endothelial dysfunction(11–12) and can activate other pro-inflammatory pathways and cytokine production, generating a vicious circle(13,14).
Hemodynamics studies the pump function of the heart and the forces needed for the blood flow throughout the vascular system(15). Measuring hemodynamic parameters using thoracic bioimpedance (ICG) is a cheap and non-invasive solution that brings important information for understanding the pathophysiological mechanisms(16)and hemodynamic consequences of acute heart failure that could help guiding therapy(17).
Blood pressure, the hemodynamic parameter used in clinical practice, does not identify changes of vascular resistance that occurs with disease progression or therapeutic interventions(18). Therefore, the peripheral resistance parameters can be used to optimize treatment and to improve functional status and life quality(19).
Several studies have shown that in invasive monitoring of patients with acute heart failure the risks outweigh the benefits(20). Therefore, the thoracic bioimpedance can be used instead, with reproducible results. The reference values were obtained from comparative studies with the invasive method that included patients in critical condition, with severe cardiovascular pathology that justified the risk associated with cardiac catheterization procedures(21–23). The standard of comparison in most cases was the measurement of cardiac output by thermo-dilution method using a catheter placed in the pulmonary artery(24).
The following parameters can be obtained using ICG: cardiac output, afterload (peripheral vascular resistance), contractility of left ventricle (LV) and volaemia; these parameters are represented as percentage variation from the ideal value(25).
In several pilot studies, the method was useful in diagnosing, severity stratification and optimizing treatment of patients with heart failure; therefore, this method could become a routine clinical tool in the future(26). Since the method is even faster than the determination of natriuretic peptides, it can be very useful in the emergency room for differential diagnosis of dyspnea(27). Moreover, it may be useful in assessing hemodynamic status in a state of apparent clinical stability(28), for treatment optimization and thus avoiding cardiac decompensation that would require costly hospitalization(29).
The PREDICT(30) study proved that ICG parameters have good predictive value in identifying ADHF patients with high risk of cardiovascular events. Furthermore, the study showed that the combined use of BNP and SSVRI, the vascular resistance parameter, shows a long-term prognosis in these patients(31). In another study conducted at the emergency room, the combination of BNP with ICG parameters could identify patients with increased risk of short-term mortality or re-hospitalization for ADHF patients(32).
Using this method is contraindicated in patients with extreme weight (below 30 kg or more than 120 kg), marked anxiety, severe aortic regurgitation, atrial fibrillation with rapid ventricular response or left bundle block(33). The thoracic electrical current could also influence the cardiac pacemakers’ activity(34).
The aim of the study was to assess the ICG parameters, highlighting a pathophysiological pattern and their relationship with the NT-proBNP and sUA levels and the endothelial function for ADHF patients at admission. Also, the effect of Allopurinol on hemodynamic parameters and endothelial function was assessed.
Method
The study group included 40 patients with ADHF caused by ischemic cardiomyopathy, treated according to 2012 ESC guidelines. The decompensation of heart failure was proved clinically: NYHA functional class III and IV and at least 2 signs of congestion and biologically: increasing of NT-proBNP level and required hospitalization.
Exclusion criteria were: marked anxiety, extreme weight (below 30 kg or more than 120 kg), atrial fibrillation with rapid ventricular response, severe aortic regurgitation, left bundle block, pacemaker, stroke in the last 3 months, cord pulmonale and severe pulmonary, renal or liver disease. None of the patients were taking Allopurinol before admission. All patients were informed about the purpose and methodology of the study and writing consent was obtained from every patient.
ECG, common laboratory tests, and echocardiography were performed for all patients, after a comprehensive clinical examination2. Also, the hemodynamic assessment using thoracic bioimpedance and NT-proBNP and sUA levels were determined for all patients during hospitalization (10±4 days).
The endothelial function was assessed by the flow-mediated vasodilatation method using the 2 dimensions vascular ultrasound of the brachial artery (FMD), as recommended by international guidelines35. Percentage variation in the diameter of the brachial artery before and after ischemic stimulus (tensiometer cuff inflation over 50 mmHg systolic BP value) was calculated and values below 10% indicated endothelial dysfunction.
FMD (%) = ((final diametre- initial diametre)*100)/( initial diametre)
The hemodynamic function was evaluated by the thoracic bioimpedance method using the HOTMAN® system (Hemosapiens Inc.)36, the parameters being played every 16 beats. The method is based on the resistance of the living tissue to very small intensity and high frequency current(37).
The hemodynamic status is influenced by "hemodynamic modulators": preload (volaemia), contractility (inotropism) and afterload (vascular resistance). If the hemodynamic status is evaluated for 1 minute, it is also influenced by the heart rate (chronotropism)(38).
Obtained parameters with ICG are:
CI - cardiac index (2.5-4 l/min/m²)
SI - index LV beat (33-47 mL/beat/m²)
ISI - inotropic status index (0.75-1.7 sec²)
LSWI - LV mechanical work index (50-62 g*m/m2)
SSVRI - systemic vascular resistance index (ideal value: 137.8 dyn.sec.cmˉ⁵.m2)
Twenty patients were randomly assigned to receive ALLO 300 mg/day, regardless of their sUA level added to the standard treatment (ALLO+ group). Another 20 patients were treated according to the ESC Guideline, forming the ALLO– group.
Statistical analysis. The results were presented as mean ± standard deviation for numeric variables and as absolute numbers and percentages for categorical variables. For the analysis of numeric variables, parametric (Student's t-test, ANOVA) or non-parametric (Mann-Whitney, Kruskal-Wallis) tests were used. Linear regression and Pearson correlation coefficient r were used for correlations between numerical variables. The statistical significance was considered for a p-value<0.05. The statistical analysis was performed using 20.0.SPSS.
Results
The baseline characteristics of the 2 study groups are presented in Table 1; they were similar in terms of age, clinical presentation, cardiovascular risk factors and paraclinics. The mean NT proBNP level was 5989 ± 8314 µg/dL, demonstrating decompensated heart failure. The mean sUA level was 7.15 ± 2.66 mg/dL at admission, 22 subjects having hyperuricemia. Also, the mean FMD was 7.18 ± 6.04%, 29 patients presenting endothelial dysfunction at admission.
The most common pathophysiological pattern identified with ICG was concomitant hypervolemia, hipoinotropism and vasoconstriction (>60% of the patients). Eighty-three percent of the patients had hipochronotropism, 85% hipointropism, 95% hypervolaemia and 85% peripheral vasoconstriction, probably due to decompensation factors such as ischemia, arrhythmia, or noncompliance to dietary or treatment.
Significant correlations between left ventricle (LV) mass and ISI (R =-0.324, p =0.041), LSWI (R =-0.316, p =0.041) and SSVRI (R =0.328, p =0.039) were noticed. Also, there were correlations between the E/E' ratio (a parameter for assessing the filling pressure in the left ventricle) and SI (R =0.654, p =0.029), ISI (R =0.713, p =0.014) and LSWI (R =0.644, p =0.032).
During hospitalization a significant improvement of myocardial contractility parameters was observed: CI, SI, ISI, LSWI and a marked decrease of peripheral vascular resistance, which was more pronounced in the ALLO+ group. Also, in this group was observed a greater improvement of the endothelial function and decrease of the sUA level were observed. NT-proBNP levels decreased for all subjects, with no difference between the groups.
During hospitalization, the presence of endothelial dysfunction (FMD<10%) was associated with SSVRI (R = -0.416, p=0.008), SI (R = 0.493, p = 0.001) and LSWI (R = 0.431, p = 0.006). Moreover, it was observed that vasoconstriction correlates with the sUA level, a witness of the oxidative stress level (R = 0.446, p = 0.004). Allopurinol reduces the oxidative stress by inhibiting the xanthine oxidase and thus increasing the NO level and improving endothelial dysfunction.
Discussions
The non-invasive hemodynamic evaluation could be a feasible and cheap solution to identify the dominant involved pathophysiological mechanisms that can be used in optimizing therapy(17).
In several pilot studies, the method was useful in diagnosing, severity stratification and optimizing treatment of patients with heart failure; therefore, in the future this method can become a routine clinical tool(39). However, there are no data on possible correlations between different non-invasive hemodynamic parameters and other cardiovascular risk markers.
The hemodynamic status is influenced by the following hemodynamic modulators: preload (volaemia), contractility (inotropism) and afterload (vascular resistance). The chronotropism brings additional information to clinically measured heart rate, indicating the compensation level of a low cardiac output(18). Also, blood pressure cannot identify the degree of vascular resistance; therefore, the ICG peripheral resistance parameters can be used to optimize treatment and improve functional status and life quality(19).
In this group of ADHF patients an overwhelming majority presented concomitant hypervolaemia, hipoinotropism and vasoconstriction (>60% of the patients). Eighty-five percent of the subjects presented vasoconstriction at admission, demonstrating that besides hypervolaemia, one of the major pathophysiological mechanisms in ADHF is peripheral vasoconstriction.
These results come in line with previous studies that showed that all patients with heart failure have alteration of at least one hemodynamic modulator, frequently presenting concomitant hypervolaemia and vasoconstriction(31). It is well known that the neurohormonal activation during a cardiac decompensation determines systemic vasoconstriction with increased preload and afterload, fluid retention and tachycardia with increasing myocardial oxygen consumption(40).
Although the average heart rate was 98 ± 28 beats/minute (with beta-blocker therapy), more than 80% of the subjects were having hipochronotropism, showing that an increased heart rate is not an effective compensatory mechanism to achieve a normal cardiac index.
Also, markers of oxidative stress and endothelial function were determined. The average sUA level was 7.15 ± 2.66 mg / dL, 55% of the subjects presenting hyperuricemia. These data come in line with previous studies(41)that have shown a high prevalence of hyperuricemia (>50%) in patients with ADHF. Hyperuricemia is a consequence of amplifying expression and activity of xanthine oxidase(42).
Endothelial dysfunction is another pathophysiological mechanism commonly found in ADHF, more than 70% of the subjects in this study group having endothelial dysfunction at admission, with a mean FMD percentage of 7.1±0.7 %.
Correlations between the LV mass and hemodynamic parameters were noticed. Apparently paradoxical, the inverse correlation between ISI, LSWI and LV mass can be explained by the high degree of interstitial fibrosis, by decreasing the oxygen supply due to intramural vessel compression, by lower metabolic efficiency fiber and by biochemical alterations in the fiber (less efficient and abnormal myosin synthesis)(43). Thus, decreased contractility in heart failure hypertrophies appears when a certain degree of hypertrophy is exceeded. This barrier seems to be last in this study group, with a mean LV mass of 270±79 g/m² (normal range: <95 g/m² in women and <115 g/m² in men). Lowering pump efficiency can also be due to contraction asynchrony and excessive geometry changes due to cavity dilation(44).
The results of the study also confirm the beneficial effect of Allopurinol on the hemodynamic parameters and endothelial function in ADHF patients. Even though the number of patients is insufficient for statistically significant results, it is clear that Allopurinol determined an important decrease of the peripheral vascular resistance and improvement of the endothelial function. Also, the presence of endothelial dysfunction (FMD<10%) was correlated with hemodynamic parameters, sUA level, SSVRI, SI and LSWI. Previous studies showed that the endothelial dysfunction is associated with hemodynamic abnormalities(45,46). It is thus confirmed that Allopurinol reduces the oxidative stress by inhibiting the xanthine oxidase, increases the NO level, improves endothelial function and has a vasodilatory effect; still, further larger studies are needed.
The improvement of the endothelial function did not correlate with the decrease of the sUA level, suggesting that the effect of Allopurinol on the endothelial function is at least in part independent of the sUA-lowering effect. Previous studies have shown that the effect of Allopurinol on the endothelial function is not secondary to the decrease of sUA level, but to reduction of the vascular oxidative stress(7). Using equivalent doses of Allopurinol and Probenecid, that produced similar reductions of the sUA level, the authors(47)proved that Probenecid practically had no effect on the endothelial function.
The NT-proBNP levels decreased with more than 50% from admission to release overall, with no difference between the groups; natriuretic peptides and vascular resistance and endothelial function parameters being complementary in the ADHF physiopathology(48): the natriuretic peptide level reflects disease progression and endothelial dysfunction and peripheral vascular resistance reflects the risk of sudden thromboembolic events, these being the main causes of death in heart failure(31).
Conclusions
The non-invasive hemodynamic evaluation could help identifying the dominant pathophysiological mechanisms involved in ADHF and optimizing therapy. The most common pattern observed in this study was concomitant hypervolaemia, hipoinotropism and vasoconstriction (>60% of the patients). Also, the high prevalence of hyperuricemia and endothelial dysfunction in ADHF was confirmed, these being markers of amplified oxidative stress.
Allopurinol (300 mg daily) increased contractility parameters, reduced peripheral resistance and improved the endothelial function, but did not influence the NT proBNP level (probably different pathophysiological mechanism).
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