1. Introduction
The progressive development of maternal and fetal circulation to maintain fetal growth can lead to heart failure in pregnant women who have reduced cardiac function.[1–3] The risk of heart failure during pregnancy exhibits a bimodal distribution,[1] being highest at 23 to 30 weeks of gestation and at delivery. During labor and delivery, cardiac afterload fluctuates due to pain, bearing down, interruption of the 600 to 700 mL/minute intervillous space shunting due to removal of placenta.[4] Moreover, cardiac preload can fluctuate by 300 to 500 mL due to autotransfusion from uterine contractions[5] and the relief of the compression on the inferior vena cava by the gravid uterus. In healthy pregnant women, cardiac hypertrophy is sufficient to tolerate this increased cardiac load.[3,6,7] However, women with dilated cardiomyopathy (DCM) may not tolerate this increased load due to morphological abnormalities, including a reduction in left ventricular wall thickness.[8]
Cardiomyocytes can adapt to an increased cardiac load via sarcomerogenesis and a 20% elongation during pregnancy.[7,9] As a reference, cardiomyocytes elongate by 47% during heart failure, lengthening from 120 µm (approximately 60 sarcomeres/cardiomyocyte) to approximately 160 µm.[8–11] Cardiomyocyte elongation results in ventricular dilation, leading to increased ventricular wall stress and reduced ventricular fractional shortening.[12,13] Cardiomyocyte remodeling during pregnancy is generally reversible within 40 days after delivery,[9,14] as opposed to pathological remodeling with exaggerated cardiomyocyte elongation (to approximately 200 µm), which is irreversible.[11] Ventricular diameter reduction after delivery depends on the rate of sarcomere elimination.[3,9] Functional mitral regurgitation (MR) disturbs left ventricular reverse remodeling after delivery.[15]
Structural heart disease increases the mortality rate among pregnant women undergoing emergency and urgent cesarean delivery (relative risk compared to vaginal delivery, 4.3; 95% confidence interval, 3.0 to 6.3[16]) and those with heart failure (4.8% vs 0.5% in patients without heart failure [17]). Improvements in the maternal mortality rate have been achieved by transitioning from general to regional anesthesia during cesarean delivery, thus avoiding the need for airway management.[18] The fact is that the safety of general anesthesia has improved overtime. General anesthesia could be the first choice of anesthesia even for patients with DCM, if anesthesiologists take precaution for aspiration pneumonia (through a fasting period for solids of 6–8 hours and use of antacids) and difficult airway management.[18] Thus, preterm evaluation of the cardiac function of pregnant women can improve anesthesia and intensive care management [19] as well as maternal and fetal survival. This observational study aimed to determine the relationship between progressive cardiac deterioration in pregnant women with DCM and the effect of perinatal interventions on delivery, maternal, and fetal outcomes.
2. Materials and methods
This retrospective longitudinal study was conducted from January 1984 to October 2016 and included pregnant women with DCM. Ethical approval for this study (M29-049) was provided by the ethics committee of the National Cerebral and Cardiovascular Center Hospital (Suita, Japan) on September 9, 2017. Study participants were informed of the study on the hospital website according to national legislation and could opt-out at any time. Acquisition of informed consent from patients was waived owing to the retrospective nature of this study. Anesthesia records were evaluated to determine the type of anesthesia used, invasive monitoring, and complications. The method of delivery and maternal cardiovascular outcomes were extracted from medical records. Events of significance included death, heart failure, stroke, transient ischemic attack, cardiac surgery, and arrhythmia from gestation to 42 days after delivery. Heart failure was excluded if the brain natriuretic peptide (BNP) level was < 100 pg/mL and was included if the BNP level was ≥ 400 pg/mL.[20] The BNP criterion was used as some patients were on bed rest during gestation, which may have masked symptoms of heart failure until cardiac functional capacity decreased below 1 metabolic equivalent (1 MET = 3.5 mL O2/kg/minute).[13] Arrhythmias included ventricular tachycardia, ventricular fibrillation, atrial fibrillation, atrial flutter, and bradycardia. The presence of 5 or more successive premature ventricular contractions was defined as ventricular tachycardia.[21]
Echocardiographic data were collected at baseline (within 1 year before pregnancy) and before 34 weeks gestation. Thirty-four weeks of gestation was considered a milestone for the fetus as the delivery of the fetus at 34 weeks is permissible when there are maternal cardiac complications and fetal developmental issues.[16] The highest echocardiographic measurement was included for left ventricular end-diastolic dimension/[height] and left ventricular end-systolic dimension/[height], and the lowest was included for ejection fraction (EF) and relative wall thickness (RWT). RWT was calculated using the following formula:
RWT = posterior wall thickness × 2 ÷ left ventricular end-diastolic dimension
Cardiac diameters were standardized according to the patient height because the body surface area changes during pregnancy.[22] Patients with severe diastolic dysfunction during the left ventricular diastolic period were identified (E/A > 2; deceleration time ≤ 130 ms).[23] The worst MR grades before 34 weeks gestation were collected. Pulmonary hypertension was evaluated by tricuspid insufficiency peak gradient (TIPG). Echocardiographic probability of pulmonary hypertension was high when TIPG was > 46 mm Hg, corresponding to peak tricuspid regurgitation velocity > 3.4 m/second.[24]
Neonatal outcomes were evaluated according to gestational age, body weight, sex, maternal parity, Apgar score, and blood gas of umbilical artery.
Patients with muscular dystrophy, congenital heart disease, peripartum cardiomyopathy, dilated phase of hypertrophic cardiomyopathy, or twin deliveries were excluded.
3. Results
We collected data on 37 deliveries from 32 patients. Among 7 patients, 8 deliveries met the exclusion criteria (muscular dystrophy, 3 patients; congenital heart disease, 2 patients; and dilated phase of hypertrophic cardiomyopathy, 3 patients). Fourteen patients delivered via cesarean section.
3.1. Anesthesia
There were 4 patients with heart failure. Two of them delivered preterm. All 4 patients had cesarean delivery under anesthesia (general anesthesia, 1 patient; combined spinal-epidural anesthesia [CSEA], 2 patients; epidural anesthesia, 1 patient). One woman with heart failure underwent a transition from epidural anesthesia alone to CSEA for cesarean delivery due to an insufficient dose. She subsequently required spinal supplementation (0.25% hyperbaric bupivacaine 2.2 mL [5.5 mg]). For the CSEA, another patient received 0.5% hyperbaric bupivacaine 2.2 mL (11 mg). Invasive monitoring was not used for the 2 patients who received CSEA. Central venous pressure was monitored in the 2 patients who were administered epidural anesthesia alone and the patient who received general anesthesia. Midazolam and propofol were administered to the patient under general anesthesia. She was monitored by transesophageal echocardiography. The remaining 10 patients who had cesarean delivery were administered anesthesia as follows: CSEA, 8 patients; general anesthesia, 1 patient; epidural anesthesia, 1 patient. Of these 10 patients, central venous pressure was monitored in 4. For CSEA, the dose of 0.5% hyperbaric bupivacaine was 0.8 mL (4 mg) to 2.5 mL (12.5 mg). Four patients had severe diastolic dysfunction: 3 had heart failure, and the 4th, who did not have heart failure, was administered labor epidural analgesia.
3.2. Complications
Four patients experienced heart failure within 42 days; three of these patients had severe diastolic dysfunction, whereas the remaining 1 had severe MR; one of these patients had ventricular tachycardia which did not require cardioversion. The remaining 25 patients did not experience heart failure within 42 days; four of these patients had arrhythmia while 1 patient had cardiac tamponade. The etiology of tamponade was not identified.
3.3. Neonatal data
The neonatal data are summarized in Table 1. No fetal death occurred. One newborn had a clavicle fracture and brachial plexus palsy due to forceps delivery.
| Outcome |
Heart failure (n = 4) |
No heart failure (n = 25) |
| Method of delivery |
|
|
| Cesarean |
4 (1) |
10 (0.4) |
| Vaginal |
0 (0) |
15 (0.6) |
| Neonatal data |
|
|
|
* Gestation at delivery (d) |
247.0 ± 2.9 |
260.4 ± 11.7 |
| ≥37 wk |
2 (0.5) |
15 (0.6) |
| 34–37 wk |
1 (0.25) |
9 (0.36) |
| 28–33 wk |
1 (0.25) |
1 (0.04) |
|
* Birth weight (g) |
2 391.5 ± 474.8 |
2 601.0 ± 376.5 |
| ≥2 000– < 2 500 |
3 (0.75) |
7 (0.28) |
| ≥1 500– < 2 000 |
0 (0) |
3 (0.12) |
| Apgar score (1 min) |
|
|
| 10 |
1 (0.25) |
0 (0) |
| 9 |
0 (0) |
7 (0.28) |
| 8 |
1 (0.25) |
16 (0.64) |
| 7 |
2 (0.5) |
2 (0.08) |
|
* Umbilical artery pH |
7.32 ± 0.03 |
7.31 ± 0.05 |
|
* Lactate (mmol/L) |
2.0 ± 0 |
2.3 ± 0.7 |
All other values are represented as number (proportion).
* Values are represented as mean ± SD.
3.4. Baseline values
The baseline data are summarized in Table 2. The New York Heart Association (NYHA) class ranged from I to II. The baseline NYHA class in 1 of 4 patients with heart failure was NYHA II, and that in the others was NYHA I.
Table 2 -
Baseline characteristics of the patients.
| Baseline |
Heart failure (n = 4) |
No heart failure (n = 25) |
|
* Age (yr) |
35.5 ± 4.1 |
30.0 ± 5.5 |
|
* Height (cm) |
156.9 ± 9.5 |
159.6 ± 4.8 |
|
* Body weight (kg) |
60.0 ± 16.7 |
53.7 ± 9.7 |
|
* Weight gain (kg) |
3.3 ± 4.4 |
5.4 ± 3.7 |
|
† Gravidity |
1 [0–1] |
0 [0–1] |
| 0 |
2 (0.5) |
18 (0.72) |
| 1 |
2 (0.5) |
5 (0.2) |
| 2 |
0 (0) |
1 (0.04) |
| 3 |
0 (0) |
1 (0.04) |
| History of cesarean delivery |
0 (0) |
1 (0.04) |
| Dates |
|
|
| 1984–2000 |
0 (0) |
5 (0.2) |
| 2001–2017 |
4 (1) |
20 (0.8) |
|
†NYHA |
1 [1–1.25] |
1 [1–1] |
| I |
3 (0.75) |
22 (0.88) |
| II |
1 (0.25) |
3 (0.12) |
| Arrhythmia |
1 (0.25) |
5 (0.2) |
| BNP (pg/mL) |
275.6 |
30.3 ± 28.8 |
| Hypertension |
0 (0) |
0 (0) |
| Diabetes mellitus |
0 (0) |
0 (0) |
| Medication |
|
|
| None |
2 (0.5) |
15 (0.6) |
| Diuretics |
0 (0) |
2 (0.08) |
| RAS inhibitor |
2 (0.5) |
5 (0.2) |
| β-blocker |
2 (0.5) |
7 (0.28) |
| Antiarrhythmic drug |
0 (0) |
2 (0.08) |
| Digoxin |
0 (0) |
4 (0.16) |
All other values are represented as a number (proportion).
BNP = brain natriuretic peptide, NYHA = New York Heart Association, RAS = renin-angiotensin system.
* Values are represented as mean ± SD (number).
† Values are represented as median [IQR].
3.5. Ultrasound echocardiography
The ultrasound echocardiography data are summarized in Table 3. The EF of the patients with heart failure was ≤ 35% (EF 35%, 2 patients; EF 33%, 1 patient; no data, 1 patient). Among the 25 patients without heart failure, 2 exhibited a left ventricular EF of ≤ 35% before 34 weeks gestation. The left ventricular posterior wall thickness in 4 patients decreased to 5 mm. No patient had a TIPG > 46 mm Hg.
Table 3 -
Ultrasound echocardiography data.
| Heart failure (n = 4) |
Baseline (n = 3) |
<34 weeks (n = 4) |
| LVDd (mm) |
52.0 ± 5.0 |
57.8 ± 3.7 |
| LVDd/height (mm/m) |
32.4 ± 1.5 |
36.8 ± 0.9 |
| LVDs (mm) |
37.7 ± 3.8 |
45.0 ± 3.9 |
| LVDs/height (mm/m) |
23.5 ± 1.3 |
28.8 ± 2.6 |
| Ejection fraction (%) |
51.0 ± 2.8 |
34.3 ± 1.2 |
| Wall thickness (mm) |
7.7 ± 1.5 |
7.6 ± 2.2 |
| RWT |
0.29 ± 0.03 |
0.26 ± 0.08 |
|
* MR grades |
1 [1–1] |
2 [2–2.25] |
| TR pressure gradients |
23.3 ± 4.2 |
29.8 ± 11.0 |
| No heart failure (n = 25) |
Baseline (n = 12) |
<34 weeks (n = 25) |
| LVDd (mm) |
52.3 ± 4.4 |
55.2 ± 5.2 |
| LVDd/height (mm/m) |
32.6 ± 2.6 |
34.7 ± 3.4 |
| LVDs (mm) |
35.7 ± 5.6 |
40.4 ± 5.7 |
| LVDs/height (mm/m) |
22.2 ± 3.2 |
25.4 ± 3.7 |
| Ejection fraction (%) |
54.4 ± 9.8 |
48.0 ± 12.1 |
| Wall thickness (mm) |
7.1 ± 1.4 |
6.9 ± 1.5 |
| RWT |
0.28 ± 0.06 |
0.25 ± 0.06 |
|
* MR grades |
1 [0–1] |
0 [0–1] |
| TR pressure gradients |
14.4 ± 10.3 |
14.6 ± 11.1 |
Left ventricular parameters at baseline, <34 weeks of gestation. The data at < 34 weeks of gestation are presented as the average of the highest values of the measured diameter (LVDd, LVDd/height, LVDs, and LVDs/height); the average of the lowest measured values of the EF, posterior wall thickness, and RWT; and the median of the worst MR value.
All other values are represented as mean ± SD.
LVDd = left ventricular end-diastolic dimension, LVDs = left ventricular end-systolic dimension, MR = mitral regurgitation, RWT = relative wall thickness.
* Values are represented as median [IQR].
4. Discussion
Airway management is the most important issue concerning anesthesia and intensive care. It is difficult to make a choice between general anesthesia and CSEA for patients with heart failure; however, it is reasonably certain that orthopneic patients cannot tolerate cesarean delivery under regional anesthesia in the supine position owing to hypoxemia and dyspnea. The rate of general anesthesia for cesarean delivery in patients who experienced heart failure is high (25%). The findings of this study indicate that a preoperative evaluation could optimize perinatal management when EF decreases to ≤ 35% before 34 weeks gestation in patients with dilated cardiomyopathy because preterm anesthetic evaluation allow anesthesiologists to take precaution for aspiration pneumonia and difficult airway management. EF ≤ 35% is associated with an increase in arrhythmia-related mortality.[25] For life-threatening arrhythmias, amiodarone might be relatively safe for ventricular tachycardia on the basis of its antiarrhythmic negative inotropic and chronotropic effects.[26] Some reports recommend that women with various heart diseases should not become pregnant when their EF is < 40% and mention that having an EF < 30% is a contraindication for pregnancy.[27–29] The criterion of EF ≤ 35% before 34 weeks gestation for anesthetic evaluation fits these reports. Thromboembolic complications must also be considered in patients with atrial fibrillation when EF is < 40%.[27] Anesthesiologists have to manage anticoagulants to perform epidural and spinal anesthesia.
In patients with DCM, afterload reduction may be beneficial. As the spinal anesthetic reaches the thoracic level, plasma noradrenaline concentrations and mean blood pressures tend to decrease.[30,31] The normal concentration of plasma noradrenaline is approximately 280 pg/mL (100–700 pg/mL)[30,32,33] and it decreases to approximately 100 pg/mL after spinal anesthesia.[30,33] The noradrenaline spillover from the sympathetic nervous system to the general circulation corresponds to 0.04 (µg/kg/minute),[34] which is depressed by spinal anesthesia. Blood pressure rapidly decreases after spinal anesthesia, which is lowest 4 to 6 minutes after administration.[35] Four to 6 minutes corresponds to 2 to 3 times of the half-life of noradrenaline (2–2.5 minutes).[36] To avoid rapid reduction of blood pressure, the sequential combined spinal-epidural technique might be beneficial. The sequential combined spinal-epidural technique is initiated with a low dose of an intrathecal anesthetic to prevent high spinal anesthesia and involves subsequent administration of a supplemental dose of a local anesthetic and an opioid through the epidural catheter. In spinal anesthesia, the superiority of intrathecal isobaric bupivacaine in the circulatory stability against hyperbaric bupivacaine is not clear.[37] The use of epidural anesthesia alone for cesarean delivery is not recommended due to insufficient analgesia of the sacral region.[38]
Anesthesiologists should improve the coupling between the left ventricular contractility and resistance to left ventricular ejection when afterload mismatch exists.[39,40] The ideal coupling occurs when their elastance are equal (EF 50%),[41,42] and anesthesiologists should reduce afterload as long as arterial pressure is maintained. The impact of the interruption of placental shunt after delivery corresponds to interruption of a mature arteriovenous fistula (shunt, blood flow rate: 600 mL/minute) for renal replacement therapy.[43] In this study, noradrenaline was not used in any case; however, the effectiveness of noradrenaline to maintain arterial pressure for cesarean delivery has been recently reported.[44] The reported effective doses to prevent blood pressure decline in healthy pregnant women was ED50 = 0.03 (µg/kg/minute),[45] ED80 = 0.07 (µg/kg/minute),[46] ED90 = 0.08 (µg/kg/minute),[45] and ED95 = 0.105 (µg/kg/minute).[46] The half-life of noradrenaline is 2 to 2.5 minutes,[37] and it takes 8 to 10 minutes for 94% of the steady state to be achieved.[47] Therefore, it might be necessary to modify the dose of noradrenaline if the blood pressure increases before 8 to 10 minutes of infusion. In a pregnant animal study, uterine artery resistance increased and uterine artery blood flow decreased when noradrenaline infusion rate exceeded 0.1 (µg/kg/minute) after spinal anesthesia.[48] The effective dose varies with patient status because noradrenaline spillover from sympathetic nervous system depends on patient status.[31,49–51] Pancaro et al[52] reported that a noradrenaline concentration of 20 µg/mL administered via a peripheral root is safe if observed cautiously. Pulmonary artery pressure was not monitored in any patient, but an indication of pulmonary artery catheter should be considered for patients with pulmonary hypertension. Regarding cardiac preload, the central venous pressure and pulmonary artery diastolic pressure can be assumed as the indicators of right and left heart preload, respectively.[53,54] In such cases, if pulmonary artery diastolic pressure and arterial blood pressure are maintained, a lower central venous pressure might be more desirable.[55]
The present study is not without limitations. The sample size was small because this study is a single center study and the prevalence of DCM was 1:2 500[28]; herefore, there is a possibility of selection bias and incomplete data bias. Furthermore, the prognosis for genetic DCM is thought to be the same as that for nongenetic DCM. However, some DCM variants are rapidly progressive. Therefore, it can be difficult to construct a standardized criteria to select the appropriate anesthetic method.
In conclusion, a preterm anesthetic evaluation may be warranted to optimize anesthetic management when EF decreases to ≤ 35% before 34 weeks gestation in patients with dilated cardiomyopathy.
Author contributions
Conceptualization: Makoto Sasaki, Yoshihiko Ohnishi.
Data curation: Makoto Sasaki.
Formal analysis: Makoto Sasaki.
Investigation: Makoto Sasaki.
Methodology: Makoto Sasaki.
Project administration: Makoto Sasaki.
Resources: Makoto Sasaki.
Supervision: Yoshihiko Ohnishi.
Validation: Makoto Sasaki, Yoshihiko Ohnishi.
Visualization: Makoto Sasaki.
Writing – original draft: Makoto Sasaki.
Writing – review & editing: Makoto Sasaki, Yoshihiko Ohnishi.
References
[1]. Ruys TP, Roos-Hesselink JW, Hall R, et al. Heart failure in pregnant women with cardiac disease: data from the ROPAC. Heart. 2014;100:231–8.
[2]. Weber KT, Kinasewitz GT, Janicki JS, et al. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation. 1982;65:1213–23.
[3]. Hunter S, Robson SC. Adaptation of the maternal heart in pregnancy. Br Heart J. 1992;68:540–3.
[4]. Brosens I, Pijnenborg R. What is defective: decidua, trophoblast, or both. In: Placental Bed Disorders. Cambridge, UK: Cambridge University Press; 2010:22–28.
[5]. Sanghavi M, Rutherford JD. Cardiovascular physiology of pregnancy. Circulation. 2014;130:1003–8.
[6]. Schannwell CM, Zimmermann T, Schneppenheim M, et al. Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology. 2002;97:73–8.
[7]. Eghbali M, Deva R, Alioua A, et al. Molecular and functional signature of heart hypertrophy during pregnancy. Circ Res. 2005;96:1208–16.
[8]. Reddy HK, Tjahja IE, Campbell SE, et al. Expression of matrix metalloproteinase activity in idiopathic dilated cardiomyopathy: a marker of cardiac dilatation. Mol Cell Biochem. 2004;264:183–91.
[9]. Yoshida M, Sho E, Nanjo H, et al. Weaving hypothesis of cardiomyocyte sarcomeres: discovery of periodic broadening and narrowing of intercalated disk during volume-load change. Am J Pathol. 2010;176:660–78.
[10]. Ryan TD, Rothstein EC, Aban I, et al. Left ventricular eccentric remodeling and matrix loss are mediated by bradykinin and precede cardiomyocyte elongation in rats with volume overload. J Am Coll Cardiol. 2007;49:811–21.
[11]. Zafeiridis A, Jeevanandam V, Houser SR, et al. Regression of cellular hypertrophy after left ventricular assist device support. Circulation. 1998;98:656–62.
[12]. Borow KM, Green LH, Grossman W, et al. Left ventricular end-systolic stress-shortening and stress-length relations in human. normal values and sensitivity to inotropic state. J Am Coll Cardiol. 1982;50:1301–8.
[13]. Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001;104:1694–740.
[14]. Allen VM, O’Connell CM, Liston RM, et al. Maternal morbidity associated with cesarean delivery without labor compared with spontaneous onset of labor at term. Obstet Gynecol. 2003;102:477–82.
[15]. Takeda K, Sakaguchi T, Miyagawa S, et al. The extent of early left ventricular reverse remodelling is related to midterm outcomes after restrictive mitral annuloplasty in patients with non-ischaemic dilated cardiomyopathy and functional mitral regurgitation. Eur J Cardiothorac Surg. 2012;41:506–11.
[16]. Lewis G. Section one: introduction. In: Why Mothers Die 2000–2002: the Sixth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. Plymouth, UK: Royal College of Obstetricians and Gynaecologists Press; 2004:1–57.
[17]. Guglielminotti J, Wong CA, Landau R, et al. Temporal trends in anesthesia-related adverse events in cesarean deliveries, New York State, 2003–2012. Anesthesiology. 2015;123:1013–23.
[18]. Liu S, Liston RM, Joseph KS, et al. Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. CMAJ. 2007;176:455–60.
[19]. Cole PJ, Cross MH, Dresner M. Incremental spinal anaesthesia for elective caesarean section in a patient with Eisenmenger’s syndrome. Br J Anaesth. 2001;86:723–6.
[20]. Chow SL, Maisel AS, Anand I, et al. Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association. Circulation. 2017;135:e1054–91.
[21]. Itsuo K, Yoshihusa A, Hirotsugu A. Guidelines for drug treatment of arrhythmias (Japanese Circulation Society 2009) [in Japanese]. 2009. Available at:
https://www.j-circ.or.jp/old/guideline/pdf/JCS2009_kodama_h.pdf [access date June 16, 2017].
[22]. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7:79–108.
[23]. Rossi A, Cicoira M, Golia G, et al. Amino-terminal propeptide of type III procollagen is associated with restrictive mitral filling pattern in patients with dilated cardiomyopathy: a possible link between diastolic dysfunction and prognosis. Heart. 2004;90:650–4.
[24]. Lau EM, Tamura Y, McGoon MD, et al. The 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: a practical chronicle of progress. Eur Respir J. 2015;46:879–82.
[25]. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225–37.
[26]. Krul SP, van der Smagt JJ, van den Berg MP, et al. Systematic review of pregnancy in women with inherited cardiomyopathies. Eur J Heart Fail. 2011;13:584–94.
[27]. Elkayam U, Goland S, Pieper PG, et al. High-risk cardiac disease in pregnancy: part II. J Am Coll Cardiol. 2016;68:502–16.
[28]. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39:3165–241.
[29]. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation. 2001;104:515–21.
[30]. LaPorta RF, Arthur GR, Datta S. Phenylephrine in treating maternal hypotension due to spinal anaesthesia for caesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaesthesiol Scand. 1995;39:901–5.
[31]. Pflug AE, Halter JB. Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in humans. Anesthesiology. 1981;55:120–6.
[32]. Neumark J, Hammerle AF. The influence of epidural analgesia on plasma norepinephrine, epinephrine and cortisol during labor and delivery. Eur Acad Anaesthesiol. 1983;32:208–12.
[33]. Puolakka J, Kaupplia A, Tuminala R, et al. The effect of parturition on umbilical blood plasma levels of norepinephrine. Obstet Gynecol. 1983;61:19–21.
[34]. Cohen G, Holland B, Sha J, et al. Plasma concentrations of epinephrine and norepinephrine during intravenous infusions in man. J Clin Invest. 1959;38:1935–41.
[35]. Hasanin A, Amin S, Refaat S, et al. Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: a randomized controlled trial. Anaesth Crit Care Pain Med. 2019;38:601–7.
[36]. Beloeil H, Mazoit JX, Benhamou D, et al. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005;95:782–8.
[37]. Sng BL, Siddiqui FJ, Leong WL, et al. Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2016;9:CD005143.
[38]. Mankowitz SK, Gonzalez Fiol AG, Smiley R. Failure to extend epidural labor analgesia for cesarean delivery anesthesia: a focused review. Anesth Analg. 2016;123:1174–80.
[39]. Kim IS, Izawa H, Sobue T, et al. Prognostic value of mechanical efficiency in ambulatory patients with idiopathic dilated cardiomyopathy in sinus rhythm. J Am Coll Cardiol. 2002;39:1264–8.
[40]. Kameyama T, Asano H, Ishizaka S, et al. Ventricular load optimization by unloading therapy in patients with heart failure. J Am Coll Cardiol. 1991;17:199–207.
[41]. Paul SP. Cardiac physiology. In: Kaplan JA, Reich DL, Savino JS (eds). Kaplan’s Cardiac Anesthesia. 6
th ed. Missouri, USA: Elsevier Saunders; 2011:98–131.
[42]. Sasayama S, Asanoi H. Coupling between ventricular and arterial properties. In: Sasayama S, Suga H (eds). Recent Progress in Failing Heart Syndrome. Tokyo, Japan: Springer; 1991:187–220.
[43]. Schmidli J, Widmer MK, Basile C, et al. Vascular access: 2018 clinical practice guidelines of the European society for vascular surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55:757–818.
[44]. Ngan KWD, Lee SWY, Ng FF, et al. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122:736–45.
[45]. Fu F, Xiao F, Chen W. A randomized double-blind dose-response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal-epidural anaesthesia for Caesarean delivery. Br J Anaesth. 2019;124:e108–14.
[46]. Wei C, Qian J, Zhang Y, et al. Norepinephrine for the prevention of spinal-induced hypotension during caesarean delivery under combined spinal-epidural anaesthesia: randomised, double blind, dose-finding study. Eur J Anaesthesiol. 2020;37:309–15.
[47]. Buston ILO, Benet LZ. Pharmacodynamics: absorption, distribution, metabolism, elimination. In: Brunton LL, Chabner BA, Knollman BC (eds). Goodman and Gilman’s the Pharmacological Basis of Therapeutics. 12th ed. in Japanese. Tokyo, Japan: Hirokawa Publishing Company; 2011: 22–52.
[48]. Clark KE, Irion GL, Mack CE. Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine. Am J Physiol. 1990;259:H197–203.
[49]. Lowes BD, Gilbert EM, Abraham WT, et al. Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. N Engl J Med. 2002;346:1357–65.
[50]. Porter TR, Eckberg DL, Fritsch JM, et al. Autonomic pathophysiology in heart failure patients. sympathetic-cholinergic interrelations. J Clin Invest. 1990;85:1362–71.
[51]. Swedberg K, Eneroth P, Kjekshus J, et al. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. Consensus trial study group. Circulation. 1990;82:1730–6.
[52]. Pancaro C, Shah N, Pasma W, et al. Risk of major complications after perioperative norepinephrine infusion through peripheral intravenous lines in a multicenter study. Anesth Analg. 2020;131:1060–1065.
[53]. Naeije R, Vachiery JL, Yerly P, et al. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41:217–23.
[54]. Rapp AH, Lange RA, Cigarroa JE, et al. Relation of pulmonary arterial diastolic and mean pulmonary arterial wedge pressures in patients with and without pulmonary hypertension. Am J Cardiol. 2011;88:823–4.
[55]. Drazner MH, Velez-Martinez M, Ayers CR, et al. Relationship of right to left-sided ventricular filling pressures in advanced heart failure insights from the ESCAPE trial. Circ Heart Fail. 2013;6:264–70.
