Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVES: Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). METHODS: It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. RESULTS: Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). CONCLUSIONS: Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

Intrapartum cardiotocography in pregnancies with and without fetal CHD.

OBJECTIVES: Congenital heart defects (CHD) are the most common inherited abnormalities. Intrapartum cardiotocography (CTG) is still considered a "gold standard" during labor. However, there is a lack of evidence regarding the interpretation of intrapartum CTG in fetuses with CHD. Therefore, the study aimed to compare intrapartum CTG in normal fetuses and fetuses with CHD and describe the association between CTG and neonatal outcomes. METHODS: The present study is a retrospective analysis of the CTG of 395 fetuses. There were three study groups: Group 1: 185 pregnancies with a prenatal diagnosis of CHD, Group 2: 132 high-risk pregnancies without CHD, and Group 3: 78 low-risk pregnancies without CHD. RESULTS: Abnormal CTG was present statistically OR=3.4 (95%CI: 1.61-6.95) more often in Group 1. The rate of the emergency CS was higher in this group OR=3 (95%CI: 1.3-3.1). Fetuses with CHD and abnormal CTG were more often scored ≤7 Apgar, with no difference in acidemia. The multivariate regression model for Group 1 does not show clinical differences between Apgar scores or CTG assessment in neonatal acidemia prediction. CONCLUSIONS: CTG in fetuses with CHD should be interpreted individually according to the type of CHD and conduction abnormalities. Observed abnormalities in CTG are associated with the fetal heart defect itself. Preterm delivery and rapid cesarean delivery lead to a higher rate of neonatal complications. Health practitioners should consider this fact during decision-making regarding delivery in cases complicated with fetal cardiac problems.

Paediatric and adult congenital cardiology education and training in Europe.

BACKGROUND: Limited data exist on training of European paediatric and adult congenital cardiologists. METHODS: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. RESULTS: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41). CONCLUSION: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Complete closure of the ductus arteriosus in the foetus with transposition of the great arteries.

Prenatal restriction of the ductus arteriosus can manifest as persistent pulmonary hypertension in the newborn, especially dangerous with the transposition of the great arteries. Its aetiology has long been related to maternal intake of non-steroidal anti-inflammatory drugs; however, some other substances, including polyphenols, may have similar properties. We describe a case of complete prenatal closure of the ductus arteriosus in the foetus with transposition of the great arteries. The newborn presented with pulmonary hypertension unresponsive to pharmacotherapy and died of multi-organ failure.

Fetal Cardiac Intervention for Pulmonary Atresia with Intact Ventricular Septum: International Fetal Cardiac Intervention Registry.

INTRODUCTION: Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience. OBJECTIVES: Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR). METHODS: We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics. RESULTS: Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9-31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (±0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%). CONCLUSIONS: Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients.

Spontaneous resolution of prenatally diagnosed isolated pleural effusion: An unusual early sign of a newborn disease.

We present a case report of a fetus with a diagnosed pleural effusion in the first trimester on nuchal translucency scan. The effusion resolved spontaneously by 17 weeks of pregnancy. Toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH) - negative. Array comparative genomic hybridization (aCGH) - normal. Serial Doppler scans normal - no prenatal signs of anemia. Maternal antibodies against red cell antigens - negative. Delivery at term by cesarean section because of macrosomia. Neonate suffered from prolonged jaundice. At 3 weeks of life diagnosed with hereditary spherocytosis. Literature review shows that this may be the first connection between this disease and prenatal life.

Fetal echocardiography gives a clue for the maternal diagnosis of tuberous sclerosis complex.

The detection of multiple cardiac tumors during fetal echocardiography allowed us to make the diagnosis of tuberous sclerosis complex in the mother and establish the reason of her first epileptic seizures.

Echocardiographic evaluation of right ventricular function in preterm infants with bronchopulmonary dysplasia.

AIM: To evaluate right ventricular function in preterm infants with and without bronchopulmonary dysplasia. METHODS: Eighty-nine preterm infants (<32 weeks) were divided into three groups: (1) no-bronchopulmonary dysplasia (n=32); (2) mild-bronchopulmonary dysplasia (n=35); (3) severe-bronchopulmonary dysplasia (n=15). Right ventricular echocardiographic parameters included the following: (1) pulsed-wave Doppler through the tricuspid valve (E/A ratio), pulmonary artery acceleration time, right ventricular ejection time, right ventricular velocity-time integral; (2) tissue Doppler measurements of myocardial velocities and atrioventricular conduction times; (3) pulsed-wave Doppler and tissue Doppler evaluation of myocardial performance index and E/E' ratio; and (4) M-mode detection of right ventricular end-diastolic wall diameter. RESULTS: The severe-bronchopulmonary dysplasia group had higher mean right ventricular myocardial performance index (on the 28th day of life by pulsed-wave Doppler) than the no-bronchopulmonary dysplasia (P=.014) or mild-bronchopulmonary dysplasia (P=.031) groups; no differences were found between no-bronchopulmonary dysplasia and mild-bronchopulmonary dysplasia groups (P=.919). A reduction in right ventricular myocardial performance index at later time points was observed in all three groups (P<.05). We found no differences between preterm infants with differing bronchopulmonary dysplasia severity in other right ventricular echocardiographic parameters. CONCLUSION: Right ventricular myocardial performance index measured by pulsed-wave Doppler indicates impaired right ventricular function in preterm infants with severe bronchopulmonary dysplasia.

Evaluation of left ventricular function in preterm infants with bronchopulmonary dysplasia using various echocardiographic techniques.

AIM: Echocardiographic evaluation of left ventricular function in preterm infants with and without bronchopulmonary dysplasia. METHODS: In 82 preterm infants (32 in no-bronchopulmonary-dysplasia group, 35 in mild-bronchopulmonary-dysplasia group, and 15 in severe-bronchopulmonary-dysplasia group), echocardiography was performed on the first day of life, at 28 days of life, and at 36 weeks postconceptional age. RESULTS: The mean E/A ratio at 36 PCA was 0.94±0.31 and 0.73±0.12 in the mild- and severe-bronchopulmonary-dysplasia groups, respectively (P=.037). The mean E'-wave velocity was 5.62±1.61 cm/s vs 4.32±1.11 cm/s at 1 day of life (P=.006) and 6.40±1.39 cm/s vs 5.34±1.37 cm/s at 28 days of life (P=.030) in the no-bronchopulmonary-dysplasia and mild-bronchopulmonary-dysplasia groups, respectively. This measure tended to be lower in the severe-bronchopulmonary-dysplasia group compared to the no-bronchopulmonary-dysplasia group (5.25±1.29 cm/s at 28 days of life; P=.081). The E/E' ratio differed between the no-bronchopulmonary-dysplasia (7.21±1.85) and mild-bronchopulmonary-dysplasia groups (9.03±2.56; P=.019) at 1 day of life. The left ventricle myocardial performance index decreased between 1 day of life and 36 postconceptional age in infants without bronchopulmonary dysplasia and those with mild bronchopulmonary dysplasia, but not in those with severe bronchopulmonary dysplasia. CONCLUSION: E/A and E/E' ratios are the most sensitive indicators of impaired left ventricle diastolic function in preterm infants with bronchopulmonary dysplasia.

Early vesico-amniotic shunting - does it change the prognosis in fetal lower urinary tract obstruction diagnosed in the first trimester?

OBJECTIVES: The aim of the study was to assess the outcome of vesico-amniotic shunting performed before 16 weeks of pregnancy in fetuses with severe megacystis diagnosed in the first trimester of pregnancy. MATERIAL AND METHODS: Between January 2008 and October 2012 severe megacystis with the bladder length > 15 mm was diagnosed in 17 fetuses. The procedure of early vesico-amniotic shunting (VAS) was offered to 8 patients with presumably isolated LUTO. The procedure of VAS was performed in 6 fetuses. Before the intervention one or two procedures of vesicocentesis and urine analysis were performed. RESULTS: In all treated cases shunts provided urinary tract decompression. All babies were born prematurely, 2 of them died due to premaurity, 3 of them survived and have normal renal function at the age of 5-6 years. In 4/5 children accompanying malformations were later diagnosed, in 1 born prematurely neonate necropsy was not performed. CONCLUSIONS: Our results suggest that early vesico-amniotic shunting in fetal LUTO is feasible and may potentially prevent not only pulmonary hypoplasia but also renal insufficiency. However, the rationale of the procedure needs further investigation due to a high risk of long-term morbidity and co-existing malformations in children Before offering the therapy detailed counseling of the parents about the possible pros and cons of the therapy is necessary.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.

[Familial congenital diaphragmatic hernia with anencephly-exencephaly and spina bifida]. / Rodzinne wystepowanie wrodzonej przepukliny przeponowej z wada dystroficzna i bezczaszkowiem.

Congenital Diaphragmatic Hernia (CDH) occurs with an estimated incidence of 1 to 2500 live births. Even though the exact etiology is still unknown, more and more often current research points out genetic factors as the possible cause of the defect. According to the latest data and the own experience 50-60% of CDH cases are isolated. The rest forms a group of CDH complicated by an additional anatomic defect or a genetic syndrome caused by a mutation of a single gene or the whole chromosome. We have presented a case study of a 32 years-old multigravida para 3, who has been referred to the Reference Centre of Prenatal Cardiology in 30 weeks of gestation due to the diagnosis of acrania with exencephaly, spina bifida and suspicion for CDH in a fetus. Although the patient's first child died due to CDH, the patient neither before nor during the pregnancy was getting a folic acid supplementation. Moreover, she has not agreed on a further cytogenetic testing or an advanced consultation with a clinical geneticist. The child died after delivery in a local hospital. The case was described to indicate the problem that the CDH diagnostic procedure is still missing a molecular genetic analysis especially in the cases of recurrent CDH. By saying that in the cases of CDH we should always strive to complete the molecular testing having in mind that by discovering pathogenesis and genes responsible for the formation of CDH we not only might improve the therapeutic methods but also find a way to prevent its development.

[Fetal cardiac interventions - are we ready for them?]. / Interwencyjne zabiegi kardiologiczne u plodów - czy jestesmy do nich przygotowani?

OBJECTIVE: The aim of the study was to analyze types and methods of intrauterine fetal cardiac interventions performed between June 2011 and December 2013, and to assess the perinatal management of the neonates. METHODS: The program was developed after analysis of the available literature, practical individual training in Linz, Austria, and simulation of the procedure in a dissecting-room. The rules for anesthesia in pregnant women and their fetuses were developed. The interventions were performed in fetuses with critical cardiac defects, in the operating room, under ultrasonographic control. The protocol was approved by the Local Bioethics Committee at the Centre of Postgraduate Medical Education. MATERIAL: We included fetuses with critical aortic stenosis (n=29), critical pulmonary stenosis (n=2), and closed or extremely restricted foramen ovale (n=7). Between June 2011 and December 2013, the team comprised of JD, MD and AK conducted 42 interventions in 35 fetuses, including 32 balloon aortic valvuloplasties (in 29 fetuses), 2 pulmonary valvuloplasties, 4 balloon atrial septostomies and 4 atrial septal stent placement. Three fetuses required both, aortic valvuloplasty and fenestration of the atrial septum. RESULTS: Out of the 42 procedures, 41 (97%) were technically successful. We recorded 3 cases of fetal demise associated with the intervention. We modulated the protocol of anesthesia given to pregnant women, switching from general to local anesthesia with intravenous sedation. We always provided additional fetal anesthesia with fentanyl and atracurium via the umbilical vein. CONCLUSIONS: Based on our 2.5-year experience, it seems safe to conclude that all types of fetal cardiac interventions may be successfully conducted at Polish centers. The procedures are safe for the pregnant women and improve fetal status. Most of the neonates treated prenatally were referred in good general condition to a tertiary pediatric cardiology and cardiac surgery center

[Increased nuchal translucency in chromosomally normal fetuses and pregnancy outcomes--a retrospective study]. / Przeziernosc karku powyzej 3,5 mm u plodów z prawidlowym karfiotypem--analiza wyników ciaz.

OBJECTIVES: The objective was to study the outcomes of fetuses with increased nuchal translucency > or = 3.5 mm and normal karyotype. MATERIALS AND METHODS: We performed a retrospective study on pregnancy outcomes and children development in 87 women with increased fetal nuchal translucency and normal karyotype who underwent chorionic villus sampling at our department. Mean observation period was 12 months after birth. Adverse pregnancy outcome was defined as miscarriage and intrauterine fetal demise, termination of pregnancy structural defect, neonatal death, genetic syndrome and other major abnormalities. RESULTS: The total incidence of adverse pregnancy outcome was 39.1% (n = 34). The likelihood of an adverse pregnancy outcome, a major structural defect or major heart defect increased significantly with nuchal translucency (OR 3.77). 68 children (78.2%) were born alive. Nuchal translucency was significantly higher in newborns with adverse pregnancy outcome than in healthy children [4.1 mm vs. 5.7 mm; p < 0.01]. After a normal anomaly scan at 20 weeks gestation the risk of adverse outcome was 14.5% (n = 9, 9/62) and increased with nuchal translucency thickness from 10.2% for NT 3.5-4.4 mm to 100% for NT > or = 6.5 mm [p < 0. 0 1]. There was no significant relationship of fetal gender maternal age and persistence of the nuchal fold with adverse pregnancy outcome. The rate of neurodevelopmental delay was 3.4 % and was not higher than in the general population. CONCLUSIONS: The overall risk of adverse pregnancy outcome was around 40% and was related to nuchal translucency thickness. After excluding structural defects, the chance of a favorable outcome was 85%. The rate of neurodevelopmental delay in fetuses with increased nuchal translucency normal karyotype and normal anatomy is not higher than in the general population.

Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients.

BACKGROUND: Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. METHODS AND RESULTS: We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. CONCLUSIONS: Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

The Polish National Registry for Fetal Cardiac Pathology: organization, diagnoses, management, educational aspects and telemedicine endeavors.

OBJECTIVE: We describe the National Registry for Fetal Cardiac Pathology, a program under the Polish Ministry of Health aimed at improving the prenatal diagnosis, care, and management of congenital heart disease (CHD). METHODS: An online database was created to prospectively record diagnosis, prenatal care, delivery, follow-up, and still images and video for fetuses with CHD. A certification program in fetal cardiac ultrasound was also implemented. Optimal screening and referral centers were identified by number of fetuses entered in the Registry yearly by each center. RESULTS: From 2004 to 2009, 2910 fetuses with CHD were registered (2473 structural, 437 functional anomalies). The most common reasons for referral for fetal echocardiography were abnormal four-chamber view (56.0%) and extra-cardiac anomalies (8.2% ), while the most common diagnoses were atrioventricular septal defects (10.2%) and hypoplastic left heart syndrome (9.7%). Prenatal diagnosis increased yearly, from 10.0% of neonatal diagnoses in 2003 to 38.0% in 2008. CONCLUSION: From inception of the registry up to 2009 there has been a fourfold increase in the number of neonates referred for cardiac surgery in whom the condition was prenatally diagnosed. Equally important achievements include the establishment of a certification program for fetal echocardiography and the organization of prenatal and neonatal management.

Therapeutic challenges and management of heart failure during pregnancy (part I).

Therapeutic management in pregnant patients with heart failure still remains a challenge, even though in most pregnant women with cardiac diseases an outcome is good. A 32-year-old woman, 17 weeks pregnant, was admitted to hospital with heart failure (HF) NYHA class III/IV. Echocardiography revealed enlarged LV, LVEF 13%, significant mitral insufficiency and pulmonary hypertension. The patient wished to continue the pregnancy. In a life-threatening condition, metoprolol, enalapril, spironolactone (for 5 days), furosemide, and digitalis were administered. Enalapril was continued for 42 days. Then the patient was switched to a dihydralazine and isosorbide mononitrate regimen. The fetus was controlled ultrasonographically. In the 19th week of pregnancy, the patient's condition improved (NYHA class II, LVEF 23%). The patient experienced 2 more episodes of HF exacerbation. In the 26th week of pregnancy, in a primary prevention of sudden cardiac death and because of 2nd-degree AV block, an ICD was implanted. In the 32nd week of pregnancy a cesarean section was performed. A male infant was delivered. The patient made a good recovery and was discharged on the 7th postoperative day. The newborn was discharged after 4 weeks, in good general condition. At 1-year follow-up the patient presented NYHA class II.

Therapeutic challenges and management of heart failure during pregnancy (part 2).

A particularly dangerous condition in pregnant women is already dilated left ventricle with severe functional impairment. Taking as an example the case of woman with dilated cardiomyopathy (DCM) first diagnosed in 17th week of pregnancy, the paper discusses diagnostic, therapeutic challenges and management of heart failure during pregnancy. Repeat measurements of brain natiuretic peptide levels should be helpful in diagnosing heart failure. To distinguish DCM from peripartum cardiomyopathy the time of manifestation should be considered. The risk of serious events is associated with NYHA class and impairment of left ventricular ejection fraction. Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin-II receptor blockers are contraindicated in pregnancy because of fetal toxicity. The incidence of sight effects is associated with time of administration of ACE-I and duration of treatment. Possible sight effects of drugs in fetus should be monitored (mainly ultrasonographically). ICD can be implanted during pregnancy if indicated. To assess the time and mode of delivery, a multidisciplinary team of different specialists is required. Subsequent pregnancy is contraindicated in a patient with DCM and low ejection fraction of left ventricle.