|Year : 2021 | Volume
| Issue : 1 | Page : 9-14
Taurine as an adjunct therapy for early left ventricular recovery in peripartum cardiomyopathy
Hany V Zaki1, Mohamed S Sweed2, Rania M Ali1, Mohamed A Abdelhafeez2
1 Departments of Anesthesia, Critical Care and Pain Management, Ain Shams University, Cairo, Egypt
2 Departments of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt
|Date of Submission||26-Apr-2020|
|Date of Acceptance||22-Jul-2020|
|Date of Web Publication||16-Apr-2021|
Dr. Mohamed S Sweed
Department of Obstetrics and Gynecology, Ain Shams University, Cairo 16646
Source of Support: None, Conflict of Interest: None
Background and Aims: The pathophysiology of peripartum cardiomyopathy is not fully understood. Despite standard medical therapy, both morbidity and mortality remain high. Restoration of inflammatory cytokine balance may hold promise for therapy. Taurine has a powerful immune-modulatory and anti-inflammatory in addition to positive inotropic effect. This study evaluates the effect of taurine infusion on clinical status, left ventricular function, circulating plasma levels of N-terminal brain natriuretic peptide and C-reactive protein in women with peripartum cardiomyopathy. Methods: Forty women with peripartum cardiomyopathy admitted postpartum to the ICU were randomly assigned to one of two groups (20 in each group): Group T received taurine infusion and Group C received normal saline infusion over 24 hours for 5 days. Both groups received standard heart failure therapy according the institutional treatment protocol. Results: In the taurine group on day 5, there was a significant reduction in LVEDD and LVESD and significant increase in LVEF. All patients had an improvement in LVEF of at least 10% and 5 patients had recovery of LVEF to ≥50% on day 5 while the other 15 patients had LVEF 45- 50%. In the control group on day 5, there was non-significant change in LVEDD, LVESD and LVEF and no patient had recovery of LVEF to ≥50% or showed improvement in LVEF more than 10%. NYHA functional class showed significant increase on day 5 in the taurine group compared to the control group. Seventeen patients (85%) in the taurine group showed improvement of the NYHA functional class at day 5. In contrast, only 2 patients (10%) in the control group showed improvement of NYHA functional class at day 5. Conclusion: Early addition of taurine infusion to standard heart failure therapy improves both; echocardiographic parameters and laboratory parameters but without clinically significant changes in women with peripartum cardiomyopathy.
Keywords: C-reactive protein, left ventricular function, N-terminal brain natriuretic peptide, peripartum cardiomyopathy, taurine
|How to cite this article:|
Zaki HV, Sweed MS, Ali RM, Abdelhafeez MA. Taurine as an adjunct therapy for early left ventricular recovery in peripartum cardiomyopathy. J Obstet Anaesth Crit Care 2021;11:9-14
|How to cite this URL:|
Zaki HV, Sweed MS, Ali RM, Abdelhafeez MA. Taurine as an adjunct therapy for early left ventricular recovery in peripartum cardiomyopathy. J Obstet Anaesth Crit Care [serial online] 2021 [cited 2021 Oct 24];11:9-14. Available from: https://www.joacc.com/text.asp?2021/11/1/9/313908
| Introduction|| |
Peripartum cardiomyopathy (PPCM) is characterized by new onset heart failure within 1 month before and 5 months after delivery in a previously healthy woman. Only 23% to 54% of patients show cardiac function recovery within 6 months. Despite standard medical therapy, both morbidity and mortality remain high.,,
The pathophysiology of PPCM is not fully understood. Restoration of inflammatory cytokine balance may be an area that holds promise for therapy. Pentoxifylline, an inhibitor of TNFα, has been shown to improve the functional class and left ventricular function in patients with PPCM. However, whether similar results can be achieved with other immune modulators remains to be established.
Taurine is the most abundant intracellular sulphur-containing amino acid. Taurine is involved in many diverse biological and physiological functions., It has a powerful immunomodulatory and anti-inflammatory effect., It also has a positive inotropic effect, which could be due to its effect on intracellular Ca2+ concentrations in cardiomyocytes. Many clinical trials revealed beneficial actions of taurine during different pathophysiological conditions including diabetic cardiomyopathy, ischemic heart disease, hypertension and congestive heart failure.,,,,,,
This study evaluates the effect of taurine infusion on; clinical status, left ventricular function, circulating plasma levels of N-terminal brain natriuretic peptide (NT-pro BNP) and CRP in patients with PPCM.
| Methods|| |
This randomized double-blind placebo-controlled study was conducted in the intensive care unit (ICU) of Ain-Shams University Maternity Hospital from January 2015 to January 2020. The study was approved by the institutional Ethical Research Committee and all participants provided written informed consent. The study was registered on ClinicalTrials.gov Protocol Registration and Results System I.D.: NCT03907267.
Women eligible for this study were aged between 20-40 years old and having PPCM. PPCM was diagnosed by symptoms of congestive heart failure that developed in the last month of pregnancy and continued to present postpartum or during the first month postpartum with no other identifiable cause for heart failure, and LVEF <45% by transthoracic echocardiography. Exclusion criteria were low LVEF ≤25%, sepsis, autoimmune disease, severe chronic disease, malignancy and conditions that prevent the completion of the calculated study fluid volume.
A total of 40 patients with PPCM were admitted postpartum to the ICU. They were randomly assigned to one of two groups (20 in each group): Group T received 10 ml/kg taurine solution 10% (Aminoven®, Fresenius-Kabi, Egypt) infusion over 24 hours (1 gm/kg body weight/day) through central vein catheter for 5 days. Group C received 10 ml/kg normal saline infusion over 24 hours through central vein catheter for 5 days. Randomization was performed in a 1:1 ratio using a computer-generated sequence using MedCalc version 13.2.2 (MedCalc Software, Ostend, Belgium). Study solutions volume was subtracted from the daily calculated maintenance dose and both groups were followed up by the central venous pressure and the clinical signs of pulmonary congestion. Both solutions were prepared in similar packages so that the investigators and data analysts were blinded to groups' intervention till end of data analysis.
Women in both groups received full intensive care treatment for PPCM according to the standard protocol of the obstetric ICU of Ain Shams University. All patients received treatment with the diuretic furosemide and the angiotensin-converting enzyme inhibitor enalapril. All patients were followed up throughout their ICU stay. Vital signs were monitored at admission and until patients were discharged from the ICU using ECG, pulse oximetry and continuous invasive arterial blood pressure monitoring through radial artery, central venous pressure monitoring and an indwelling catheter for urine output assessment.
Data were collected on admission to the ICU as baseline values and on day 5 after the end of the study solution for evaluation of the drug effect; demographic data including age, parity, and the time of presentation, whether prepartum or postpartum, clinical data including New York Heart Association (NYHA) functional class, heart rate, systolic and diastolic blood pressure. The functional class was considered to improve if it increased by at least 1 grade of the NYHA classification. Echocardiographic parameters including LVEDD, LVESD and LVEF were recorded. Laboratory parameters including NT-pro BNP and C-reactive protein (CRP) were also recorded.
The primary end point was improvement of the left ventricular ejection fraction >10% and the secondary end point was improvement of the laboratory parameters.
Using PASS 21 and based on data from previous studies, it was calculated that a sample size of 17 patients per group would achieve 81% power to detect a difference of 10% in ejection fraction between both groups and with a significance level (alpha) of 0.05 using a two-sided two-sample t-test. Twenty patients were included to replace any missed data.
The statistical analysis was performed using SPSS software package version 17 (Chicago, IL). Normally distributed numerical data are presented as mean ± SD and differences between groups were compared using the independent Student's t-test, data not normally distributed were presented as median (IQR) and compared using Mann-Whitney test and categorical variables were presented as number (%) and analysed using the χ2 test or Fisher exact test. P < 0.05 is considered statistically significant.
| Results|| |
Forty women with PPCM admitted postpartum to the ICU were randomly assigned to one of two groups [Figure 1]. The baseline characteristics of patients in both groups were similar in terms of demographic data [Table 1]. The clinical parameters on day 1 (baseline values) were comparable between both groups [Table 2]. In the taurine group, systolic blood pressure on day 5 was significantly lower compared to day 1 and similarly was significantly lower compared with group C. On the other hand, changes in diastolic blood pressure at day 1 and day 5 were insignificant in the 2 groups regarding intra- and inter group comparison [Table 2], whereas heart rate values on day 5 were significantly lower compared to day 1 in each of the 2 groups and significantly lower in group T compared with group C on day 5 [Table 2].
NYHA functional class showed significant increase on day 5 in the taurine group compared to the control group. Seventeen patients (85%) in the taurine group showed improvement of the NYHA functional class at day 5. In contrast, only two patients (10%) in the control group showed improvement of NYHA functional class at day 5 [Table 2].
As regards Echocardiographic parameters, on day 1, LVEDD, LVESD and LVEF values were comparable between both groups. In the taurine group on day 5, there was a significant reduction in LVEDD and LVESD and significant increase in LVEF. All patients had an improvement in LVEF of at least 10% and 5 patients had recovery of LVEF to ≥50% on day 5 while the other 15 patients had LVEF 45-50%. In the control group on day 5, there was non-significant change in LVEDD, LVESD and LVEF and no patient had recovery of LVEF to ≥50% or showed improvement in LVEF more than 10% [Table 3].
Concerning laboratory parameters, the baseline NT-proBNP and CRP values were comparable between both groups on day 1. Taurine group showed significant reduction in NT-proBNP as well as CRP on day 5 as compared to the baseline values on day 1 and as compared to the control group. Also, the control group on day 5 showed significant reduction in CRP only [Table 4].
| Discussion|| |
This study showed that the early addition of taurine to standard heart failure therapy in women with PPCM resulted in significantly greater improvements of left ventricular function measured by NYHA functional class, LVEDD, LVESD and LVEF in addition to reduction of values of NT-pro BNP and CRP more than seen with standard therapy alone. Despite numerous researches, the aetiology of PPCM is still unknown. There are many hypotheses including myocarditis, genetic susceptibility, and auto-immune response.,,
Since the cause of PPCM is unknown, there is still no specific treatment of this serious disease. The management of PPCM is basically the same as other types of heart failure through conventional supporting therapies. Whereas enhancing the cure rate through the administration of targeted therapies is still under research. Understanding of pathogenesis could represent a breakthrough in the treatment of PPCM. From that aspect, studies that investigated inflammation, prolactin, and oxidative stress as a possible cause of PPCM reported promising results. PPCM-targeted therapies (such as intravenous immunoglobulin, pentoxifylline, and bromocriptine) have shown promise in small trials but require further evaluation.,,,
Surprisingly, only 103 PPCM patients have been included in randomized trials. PPCM needs further high-quality investigation to ultimately guide disease-specific therapy recommendations. Data from researches related to the pathogenesis of PPCM and that inflammation might have a role in it, were the basis for the design of the present study for investigating taurine as PPCM-targeted therapy. There is positive correlation between inflammatory markers – CRP, interleukin-6, tumor necrosis factor-α (TNFα) and LVEDD and LVESD, as well as inverse correlation between these markers and LVEF. Plasma marker of apoptosis Fas/apoptosis antigen 1 (Fas/Apo-1) in patients with PPCM is also a predictor of mortality.,
Taurine is involved in many diverse biological and physiological functions. The potential health benefits of taurine in cardiovascular disease are rapidly emerging. Heart failure is characterized by defects in Ca2+ homeostasis. Experimental studies have shown that in cases of ischemic heart disease, the beneficial actions of taurine in heart failure can be attributed to its effects on Ca2+, its antioxidant properties and its membrane-stabilization effect.,,,,, Taurine can prevent intracellular Ca2+ overload under conditions of oxidative stress and may improve or prevent defects in Ca2+ handling in cardiomyocytes during heart failure.
Clinical studies have shown that taurine can be beneficial to patients that are unresponsive or resistant to digitalis or diuretics. Taurine has also been reported that it can lower left ventricular end-diastolic pressure in patients with heart failure.
In the current study, there was significant reduction of the heart rate to reach clinically desirable levels that are almost within the normal range. This beneficial effect was more evident in the taurine group. Regarding the systolic blood pressure, the changes were statistically significant but clinically insignificant in the taurine group.
NT-pro BNP, an unspecific marker for pregnancy complications such as preeclampsia as well as for heart failure, is markedly elevated in most PPCM patients with little overlap to healthy peripartum women. NT-pro BNP is strong predictors of clinical outcomes in all stages of HF. HF therapies that improve mortality and morbidity reduce NT-pro BNP values. This led to the concept of biomarker-guided HF management using NT-pro BNP to supplement clinical judgment. Meta-analyses suggest a 20-30% mortality reduction with biomarker-guided HF care over standard HF care and prospective studies have demonstrated that serial outpatient assessment of natriuretic peptides leads to more up- titration of HF medications and decrease in natriuretic peptides.,,,
Follow-up echocardiography is also recommended to monitor the left ventricular function in PPCM patients. Follow-up studies have revealed that higher LVEF at presentation has better cure rates and shorter recovery times. Moreover, incidence of mortality or complications that are life threatening or resulted in long-term morbidity is higher in women with left ventricular ejection fraction ≤25%. For that reason, patients with LVEF ≤25% were excluded from the study.
PPCM is not an indication for delivery except in cases of hemodynamic unstable patient or rapidly decompensating patient. However, PPCM is characterized by a probability for spontaneous recovery. To control these factors, the study medications were started at the post-partum period to evaluate the patient condition under the same circumstances after reevaluating the condition of the patients after delivery.
Recovery from PPCM is defined as recovery of LVEF to ≥50%. Recovery usually occurs between 3 to 6 months postpartum, but might occur as late as 48 months postpartum. Only about a quarter to a half of cases have complete recovery of left ventricle ejection fraction. The prognosis is best when PPCM is diagnosed and treated early. Fortunately, in the present study, patients were enrolled immediately postpartum.
The present study shows many strength points to be considered, being a randomized controlled trial with double-blinding gives the study more strength and increases the reproducibility of its results. Also, the number of recruited participants, taking in consideration that only 103 PPCM patients have been included in randomized trials before is adequate to produce reliable comparable results. Still, more studies on larger scales and meta-analysis are needed before using taurine as a standard treatment for PPCM.
| Conclusion|| |
The early addition of taurine infusion to standard heart failure therapy improves the echocardiographic parameters and the laboratory parameters but without clinically significant changes in patients with PPCM.
Ain Shams University.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006;368:687-93.
Elkayam U, Akhter MW, Singh H, Khan S, Bitar F, Hameed A, et al
. Pregnancy-associated cardiomyopathy: Clinical characteristics and a comparison between early and late presentation. Circulation 2005;111:2050-5.
Fett JD, Christie LG, Carraway RD, Murphy JG. Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 2005;80:1602-6.
Brar SS, Khan SS, Sandhu GK, Jorgensen MB, Parikh N, Hsu JW, et al
. Incidence, mortality, and racial differences in peripartum cardiomyopathy. Am J Cardiol 2007;100:302-4.
Dinic V, Markovic D, Savic N, Kutlesic M, Jankovic RJ. Peripartum cardiomyopathy in intensive care unit: An update. Front Med (Lausanne) 2015;2:82.
Sliwa K, Skudicky D, Candy D, Bergemann A, Hopley M, Sareli P. The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy.
Eur J Heart Fail 2002;4:305-9.
Boucknooghe T, Remacle C, Reusens B. Is taurine a functional nutrient? Curr Opin Clin Nutr Metab Care 2006;9:728-33.
Warskulat U, Heller-Stilb B, Oermann E, Zilles K, Haas H, Lang F, et al
. Phenotype of the taurine transporter knockout mouse. Methods Enzymol 2007;428:439-58.
Grimble RF. The effects of sulfur amino acid intake on immune function in humans. J Nutr 2006;136 (6 Suppl):1660S-5S.
Marcinkiewicz J, Kurnyta M, Biedron R, Bobek M, Kontny E, Maslinski W. Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanisms. Adv Exp Med Biol 2006;583:481-92.
Xu YJ, Arneja AS, Tappia PS, Dhalla NS. The potential health benefits of taurine in cardiovascular disease. Exp Clin Cardiol 2008;13:57-65.
Azuma J, Sawamura A, Awata N. Usefulness of taurine in chronic congestive heart failure and its prospective application. Jpn Circ J 1992;56:95-9.
Jeejeebhoy F, Keith M, Freeman M, Barr A, McCall M, Kurian R, et al
. Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction. Am Heart J 2002;143:1092-100.
Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, et al
. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids 2004;26:267-71.
Mizushima S, Nara Y, Sawamura M, Yamori Y. Effects of oral taurine supplementation on lipids and sympathetic nerve tone. Adv Exp Med Biol 1996;403:615-22.
Hayes KC, Pronczuk A, Addesa AE, Stephan ZF. Taurine modulates platelet aggregation in cats and humans. Am J Clin Nutr 1989;49:1211-6.
Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, et al
. Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: Effects of taurine supplementation. Am J Clin Nutr 1995;61:1115-9.
Militante JD, Lombardini JB. Treatment of hypertension with oral taurine: Experimental and clinical studies. Amino Acids 2002;23:381-93.
Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema JP, Becker A, et al
. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: A proof-of-concept pilot study. Circulation 2010;121:1465-73.
Felker GM, Jaeger CJ, Klodas E, Thiemann DR, Hare JM, Hruban RH, et al
. Myocarditis and long-term survival in peripartum cardiomyopathy. Am Heart J 2000;140:785-91.
Midei MG, DeMent SH, Feldman AM, Hutchins GM, Baughman KL. Peripatum myocarditis and cardiomyopathy. Circulation 1990;81:922-8.
Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon M, Sundstrom JB. Autoimmune mechanisms as the basis for human peripartum cardiomyopathy. Clin Rev Allergy Immunol 2002;23:301-24.
Bhattacharyya A, Basra SS, Sen P, Kar B. Peripartum cardiomyopathy: A review. Tex Heart Inst J 2012;39:8-16.
Cardona-Guarache R, Kron J. Treatment of peripartum cardiomyopathy: A call to action. Can J Cardiol 2015;31:1418-20.
Bozkurt B, Villaneuva FS, Holubkov R, Tokarczyk T, Alvarez RJ Jr, MacGowan GA, et al
. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol 1999;34:177-80.
Sliwa K, Skudicky D, Candy D, Bergemann A, Hopley M, Sareli P. The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy. Eur J Heart Fail 2002;4:305-9.
Sliwa K, Skudicky D, Bergmann A, Candy G, Puren A, Sareli P. Peripartum cardiomyopathy: Analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1. J Am Coll Cardiol 2000;35:701-5.
Sliwa K, Förster O, Libhaber E, Fett JD, Sundstrom JB, Hilfiker-Kleiner D, et al
. Peripartum cardiomyopathy: Inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J 2006;27:441-6.
Belanger MC, Ouellet M, Queney G, Moreau M. Taurine-deficient dilated cardiomyopathy in a family of golden retrievers. J Am Anim Hosp Assoc 2005;41:284-91.
Shiny KS, Kumar SH, Farvin KH, Anandan R, Devadasan K. Protective effect of taurine on myocardial antioxidant status in isoprenaline-induced myocardial infarction in rats.
J Pharm Pharmacol 2005;57:1313-7.
Franconi F, Stendardi I, Matucci R, Failli P, Bennardini F, Antonini G, et al
. Inotropic effect of taurine in guinea-pig ventricular strips. Eur J Pharmacol 1984;102:511-4.
Ohta H, Azuma J, Onishi S, Awata N, Takihara K, Kishimoto S. Protective effect of taurine against isoprenaline-induced myocardial damage. Basic Res Cardiol 1986;81:473-81.
Satoh H, Nakatani T, Tanaka T, Haga S. Cardiac functions and taurine's actions at different extracellular calcium concentrations in forced swimming stress-loaded rats. Biol Trace Elem Res 2002;87:171-82.
Xu YJ, Arneja AS, Tappia PS, Dhalla NS. The potential health benefits of taurine in cardiovascular disease. Exp Clin Cardiol 2008;13:57-65.
Junus K, Wikström AK, Larsson A, Olovsson M. Placental expression of proBNP/NT-proBNP and plasma levels of NT-proBNP in early- and late-onset preeclampsia. Am J Hypertens 2014;27:1225-30.
Gaggin HK, Januzzi JL Jr. Biomarkers and diagnostics in heart failure. Biochim Biophys Acta 2013;1832:2442-50.
Januzzi JL Jr, Rehman SU, Mohammed AA, Bhardwaj A, Barajas L, Barajas J, et al
. Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol 2011;58:1881-9.
Shah MR, Califf RM, Nohria A, Bhapkar M, Bowers M, Mancini DM, et al
. The STARBRITE trial: A randomized, pilot study of B-type natriuretic peptide-guided therapy in patients with advanced heart failure. J Card Fail 2011;17:613-21.
Fett JD, Sannon H, Thelisma E, Sprunger T, Suresh V. Recovery from severe heart failure following peripartum cardiomyopathy. Int J Gynaecol Obstet 2009;104:125-7.
Goland S, Modi K, Bitar F, Janmohamed M, Mirocha JM, Czer LS, et al
. Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Fail 2009;15:645-50.
Amos AM, Jaber WA, Russell SD. Improved outcomes in peripartum cardiomyopathy with contemporary. Am Heart J 2006;152:509-13.
[Table 1], [Table 2], [Table 3], [Table 4]