Short-Term Outcomes Following Total Correction of Tetralogy of Fallot in Adult Patients

doi:10.21203/rs.3.rs-2742406/v1

Objectivs:

Tetralogy of Fallot (TOF) is a common congenital heart disease which should be corrected. The recommended time for the Tetralogy of Fallot Total Correction (TFTC) surgery is during the infancy for the possible difficulties during the surgery and the related issues. However, sometimes TOF is diagnosed and managed during the adulthood.

Methods

This study is a descriptive and retrospective one which included all patients who underwent TFTC at age of 15-year and older in a 10 -year period (between the years 2010 and 2020) to identify short-term (including in-hospital mortality, ICU Length of stay, respiratory complications after the surgery such as: pulmonary edema, pneumonia and etc. and bleeding after the surgery) and one-year (including left ventricle ejection fraction (LVEF), right ventricle (RV) ejection fraction, severity of tricuspid regurgitation and aortic regurgitation after surgery) outcomes. All data were taken from medical records at Shahid Rajaei Hear Center. Data were analyzed using SPSS 22.

Results

94 patients with the mean age of 26.7 ± 9.6 years were enrolled. Most of them were male (59.6%) (P-value: 0.009). In-hospital mortality in our study were 5.3%. Tricuspid regurgitation (TR) was significantly resolved after the surgery (P-value: 0.006). Also, the correction of pulmonary size after the surgery was significant (P-value: 0.000).

Conclusion

This study showed that the surgery at older age is safe and the results are acceptable. Aging is not a contraindication for TFTC and surgery should be recommended if the patients are diagnosed with TOF at adulthood. Also, screening TOF in adult patients should be considered.

Tetralogy of Fallot

Tetralogy of Fallot Total Correction

Congenital Heart Disease

Adulthood

Mortality

Outcome

Complication

Tetralogy of Fallot (TOF) as a common congenital heart disease (CHD) (1), accounts for 7-10% of all congenital heart anomalies can be cyanotic or acyanotic (2). This disease includes four underlying structural abnormalities including pulmonary artery stenosis (PS), ventricular septal defect (VSD), right ventricular hypertrophy (RVH), and overriding of aorta which result of anterior and superior deviation of infundibular septum (3).

In developed countries TOF is usually diagnosed and treated at early ages by a surgery called Tetralogy of Fallot Total Correction (TFTC). In those settings, primary repair is the choice strategy (4). According to the previous studies the best time for TFTC is during the first year of the life. For instance, Starr et. al recommended 6 months of age (5) and several other studies suggested the age of 3 to 11 months for the TFTC surgery (6, 7) (6, 8). In contrast, in developing countries the patients might remain undiagnosed until adulthood (9). Furthermore, patients who do not have proper cardiac anatomy, suffer from severe cyanosis, have co-morbidities, undergo shunt implantation instead and complete surgery is delayed until they become older (4).

Addressing TOF at adult age is challenging not only for the complications of undiagnosed TOF during the years (e.g., Myocardial dysfunction, ventricular arrythmia, or even neurological complications) (9), but also for the possible difficulties during the surgery and the related issues(10). In these patients, due to the fact that they have been exposed to hypoxia for a long time, there is a possibility of multiorgan damage(11-16). In addition, due to the progressive hypertrophy of the right ventricle, there is a possibility of damage to the myocardium and a higher chance of arrhythmia (17) . Although the benefits of early and timely surgery are well known but there is a possibility that these patients will be referred at an older age, especially in developed countries. If surgery is not performed for who refer at older age, their survival would be as high as 24% according to a ten-year study (4).

For this reason, current guidelines recommend total correction of the disease, regardless of the patient's age (17). Hence, the present study aimed to study early outcome of TFTC, as well as possible complications in patients with tetralogy of Fallot who underwent surgery (TFTC) at the age of 15 and older in an Iranian tertiary heart center during a ten-year period (2010-2020).

Design: This study is a descriptive and retrospective study which was conducted on patients with tetralogy of Fallot aged over 15 years who underwent surgery. All data were taken from medical records at Shahid Rajaei Heart and Vascular Center (referral center for all types of heart diseases in Iran) between the years 2010 and 2020. Surgery including primary correction or second surgery after shunt palliation. All these patients were treated in the same center by the same surgical team, and their pre- and post-surgery evaluations were done by the adult congenital cardiologist. Before surgery, all patients underwent full evaluation (based on their condition) with CT-angiography; cardiac catheterization or echocardiography (with the Vivid 7 device).

The patients' medical records were examined and all necessary data were collected and recorded in the relevant checklist.

Inclusion criteria: All patients diagnosed with tetralogy of Fallot who were operated on at the age of 15 years or older in our center were included in the study.

Exclusion criteria: Patients whose medical records were incomplete were excluded from the study.

Instrument:

The data were collected from the patients' medical records and entered into the checklist in four groups:

1.Demographical information including age at surgery, sex, use of RVOT patch during surgery, different types of cardiac arrythmias including AF (atrial fibrillation), VT (Ventricular Tachycardia) and frequent PVCs (Premature ventricular contraction) before surgery, associated anomaly such as PDA (Patent Ductus Arteriosus), TGA (Transposition of Great Arteries), ASD (Atrial Septal Defect), coronary anomaly and MAPCAs (Major aortopulmonary collateral arteries greater than 3 mm(18)) were detected and recorded, right and left ventricle ejection fraction, severity of tricuspid and aortic regurgitation, pulmonary branch size (was defined as a small size of Mac Goon`s ratio<1.2) in echocardiography, the severity of pulmonary artery and pulmonary branch stenosis(RVOT obstruction).

2. Early outcome including in-hospital mortality, length of stay in the ICU (intensive care unit), respiratory complications after the surgery such as pulmonary edema, pneumonia and etc. and bleeding after the surgery.

3. One-year outcome including left ventricle ejection fraction (LVEF), right ventricle (RV) ejection fraction, severity of tricuspid regurgitation (TR) and aortic regurgitation (AI) after surgery.

Data analysis: For statistical analysis, we used Statistical Package for the Social Sciences (SPSS) software, version 22. We applied descriptive analysis for description of the data.

Ethical statement:

Considering that the patients whose information was used in the study were not available, the code of ethics was received from the ethics committee of the hospital (IR.RHC.REC.1400.003).

In this study, according to the mentioned inclusion and exclusion criteria, 94 adult patients who underwent TFTC from 2010 to 2020 in Rajai Cardiovascular, Medical, and Research Center were enrolled. The mean age of patients at surgery time was 26.7±9.6 years. Additionally, 56 patients were male (59.6%) and 38 patients were female (40.4%) and average age of male patients were significantly higher than female (P-value:0.009). Before surgery associated cardiac anomalies were found in 26 patients (27.7%) with right sidedness was found in 24 (25.5%). Also, 17 patients (18.1%) were diagnosed with AF arrhythmia. MAPCAs were found in 38 patients (40.4%) in cardiac catheterization (Table 1). In addition, in 91 (96.8%) of patients, surgeon used RVOT patch during correction.

Early outcome including in hospital mortality; ICU length of stay, bleeding after surgery and respiratory complication were investigated. In hospital mortality was 5.3%. The mean ICU length of stay was 87±30 hours. 97.9% of the patients were admitted in ICU for more than 48 hours and only 2.1% of them were discharged earlier than this time. Bleeding was reported in 20 patients (21.5%) and more than 90% of them needed surgery for bleeding control.

One-year outcome including right and left ventricular dysfunction, severity of AR, TR, RVOT obstruction. These data were compared in the patients before and after the surgery. The prevalence of TR was significantly decreased after the surgery (P-value: 0.006). Pulmonary branch size before and after the surgery were hypoplastic or small in 17 (18.1%) and 3 patients (3.2%), respectively and it was significantly acceptable after the surgery (P-value: 0.000). In the subgroup analysis for comparison of the small and hypoplastic pulmonary branches with the normal situation, no significant difference was found according to the patients' primary and secondary outcomes. (Table 3).

Before surgery, mild, moderate and severe RVOT obstruction were found in 2.1%, 3.1% and 94.6% of the patients, respectively. After the surgery RVOT obstruction was resolved in 50.5% of the patients. Also, mild and moderate RVOT obstruction were found in 39.3% and 12.7% of the patients, respectively. LV dysfunction changes in the patients before and after the surgery were not significant (P-value: 0.062). Also, there was not any significant difference in RV dysfunction before and after surgery (P-value: 0.338).

In this study, we intended to investigate short complications as well as the improvement of cardiac function factors in adult patients (older than 15 year) with Tetralogy of Fallot who underwent surgery. The mean age of the study group at the time of surgery was 26.7±9.6 years. Similarly, Atik et al. reported patients age of 26.6 ± 11.1 years at the time of TFTC (11), while, Presbitero et al. and Charles et al. reported higher mean age at the time of TFTC (14, 19) and Erdoğan et al. and Imran Khan et al. described younger patients who underwent the surgery (4, 20). This age difference in different studies can be due to the difference in diagnostic methods and the lack of awareness among patients for timely referral, which itself requires special attention.

In this study the prevalence of male patients was higher, the same as the most other previous studies (9, 11, 14, 20). Only in one study the prevalence of the female patients was higher (11). Right sidedness was found in 25.5% of our patients, but in the other studies, it was higher than our study (4, 19). Also, cardiac anomalies in our patients were higher than Clarles et al. study (19). In general, it is recommended that all patients with tetralogy of Fallot, especially at an older age, undergo a complete examination for associated anomalies before surgery, because it can have a significant impact on the type of surgery and the course of treatment.

Arrythmia was diagnosed in 18.1% of the patients. In two studies, the prevalence of arrythmia was higher than our study (11, 14). In the study of Imran et al. arterial arrythmia and heart block were found in 10% of the patients (4). In addition, in the study of Charles et. al, bundle branch block (BBB) was found in more than half of the patients (19). MAPCA was diagnosed in 40.4% of the patients and it was higher than Khan et al. and Khalid et al. studies (4, 9). One of the reasons for the higher prevalence of MAPCAs in our study could be the older age of our study patients compared to other studies, which increases the size of MAPCAs that can be identified in CT angiography.

In the first study on adult patients with TOF in 1972 by Charles et al. the mortality rate was high. Four deaths were reported from seventeen surgeries (23%) (19) that may be occurred due to the limited number of the patients and the status of techniques for surgeries at that time. During the recent decades the mortality rate of the TFTC surgery in the adult patients has decreased significantly (21). In the most of these studies the mortality rate ranged 1.8% to 8% (4, 9, 11, 14, 20, 22). In our study in hospital mortality was 5.3% but in children who underwent TFTC at the recommended time, the mortality rate is lower than 2 percent (5). In most of the recent studies the mortality rate was lower than our study and just in one study, the mortality rate was higher (4). In general, it can be said that based on the studies (23), if patients with tetralogy of Fallot are operated on time, the risk of mortality is lower and the long-term survival is excellent, compared to patients who are operated on at an older age. The most important issue in this field is the complete elimination of all defects and timely preservation of the myocardium, as well as the correct and timely treatment of surgical complications. According to these cases, it can be said that one of the reasons for the higher risk of mortality and surgical complications at older age is the prolongation of anatomical, hemodynamic, and physiological cardiac disorders (caused by the heart defects of the disease itself), which affects the right and left ventricular.

In our study, the mean ICU length of stay was 87±30 hours. The result of the other studies was approximately similar to our study (9, 20), but Atik et al. reported shorter ICU stay (11).

In our study, bleeding was reported in 21.5% of our patients and most of them needed a surgical approach for the bleeding control. In the study of Khalid et al. 2.9% of the patients needed another surgery due to tamponade or bleeding and residual VSD was reported in 8.7% of the cases, but none of them were moderate or severe (9). Bleeding was the reason of 3.8% of reoperations in the patients in Khan et al. study (4).

Respiratory complications were found in 14.9% of the patients. In the study of Erdoğan et al. 2.4% of the patients needed mechanical ventilation for more than three days (20). Atik et al. reported that 7.7% of the patients needed long mechanical respiratory support (11). As Khan et al. reported in his study, post operative complications encountered were low cardiac output syndrome (11.25%), pleural effusion requiring tapping (3.75%), reoperation for bleeding (3.8%), pulmonary regurgitation (moderate to severe) (25%) which occurred in the transannular patch group only and atrial arrhythmia (5%). In addition, most of the results of the surgery including the correction of TR, pulmonary size, RVOT obstruction and pulmonary branch size were successful.

This study showed that although the patients with TOF were diagnosed and underwent surgery too late in comparison with the guidelines, the results were acceptable. As mentioned above, TR was treated significantly. Also, the results of the surgery for improving the pulmonary stenosis, treatment of RVOT obstruction and pulmonary branch size were excellent. Before surgery, severe RVOT obstruction was found in most of the patients. After surgery it was resolved completely in about half of the patients. Also, severe obstruction was not found in any of the patients after the surgery. The results of the previous surgery for TFTC in the patients who were older than the recommended age, was successful (24, 25).

As mentioned in the previous parts, the gold standard time for management of the patients with TF is during the first year of life. Most of the patients with TF in the developed countries are diagnosed and managed in the childhood, so there is a lack of data about the newly diagnosed adult patients in these countries. In addition, studies about the management of TF in the adulthood in developing countries are limited, so this study can help us for choosing a better approach to this special group of the patients. Our study confirmed that the TFTC surgery in the adulthood is safe with acceptable outcomes and limited complications.

In a study conducted by Ignacio Lugones et.al (26), it was shown that the short-term results of surgery of TOF in adult patients depend on the cardiac anatomy and the clinical conditions of the patient before surgery, so it is recommended in adult patients, any types of the valvular heart diseases and cardiac defect should be corrected during the TFTC surgery. Although most of our patients were not in the advanced atherosclerosis ages, as the patients are becoming older, the normal population ischemic heart disease will play an important role in the long-term outcome of them. Although in an adult patient with a history of TFTC, the most important thing is the main disease, they must be evaluated as the other cardiovascular diseases that happen due to aging.

To sum up, although the best age for TFTC surgery is childhood, the result of the surgery in adulthood is acceptable, so advanced age should not be considered as a contraindication of the surgical management. In addition, according to the high rate of late diagnosis of TOF in developing countries, a screening program for all of the children and adults who refer to the clinics with an emphasize on the family physician program is recommended. In addition, due to the fact that accompanying anomalies can affect the course of the disease and the type of surgery, it is recommended to carefully assess the appropriate paraclinical burden before surgery.

Ethical statement: This study was approved by ethical committee of Rajaei heart center (IR.RHC.REC.1400.003).

Competing interests: The authors declare that there is no conflict of interest

Authors Contribution: MM, ZK, NM, YT, HT, AJ and SS managed the patients. MA, ZN, SM, MC drafted the paper, MA and ZK finalized the paper. All authors read and approved final version of the paper.

Funding: We did not receive any fund for this study.

Availability of data and materials: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Table 1: Demographic data

P-value

Frequency (Percent)

Variables of Demographic data

0.938

26.7±9.6 years

52 (55.3%)

27 (28.7%)

13 (13.8%)

2 (2.1%)

Age

Mean

Age groups

15-25

26-35

36-45

46-55

0.009

56 (59.6%)

38 (40.4%)

Gender

Male

Female

0.024

26 (27.7%)

68 (72.3%)

Cardiac anomalies

Yes

No

0.216

24 (25.5%)

70 (74.5%)

Sidedness

Right

Left

0.205

17 (18.1%)

77 (81.9%)

Arrhythmia

Yes

No

0.203

38 (40.4%)

56 (59.6%)

MAPCA (Major aortopulmonary collateral arteries)

Yes

No

91 (96.8%)

RVOT patch

Table 2: Outcomes

Frequency (Percent)	Variable
5 (5.3%)	In-hospital mortality
87±30 hours 92 (97.9%) 2 (2.1%)	ICU admission Mean More than 48 hours Less than 48 hours
14 (14.9%)	Respiratory complications
20 (21.5%)	Bleeding after surgery

Table 3: The results of the surgery

P-value

After surgery

Before surgery

Variable

0.338

1 (1.1%)

32 (34%)

54 (57.4%)

7 (7.4%)

6 (6.4%)

39 (41.5%)

44 (46.8%)

5 (5.3%)

RV dysfunction

Normal

Mild

Moderate

Severe

0.062

37 (39.4%)

52 (55.3%)

5 (5.3%)

52 (55.3%)

38 (40.4%)

4 (4.3%)

LV dysfunction

LVEF>50%

LVEF: 35-50%

LVEF<35%

0.006

53 (56.4%)

36 (38.3%)

5 (5.3%)

69 (73.4%)

23 (24.5%)

2 (2.1%)

Tricuspid Regurgitation (TR)

Mild

Moderate

Severe

18 (19.1%)

69 (73.4%)

6 (6.4%)

1 (1.1%)

30 (31.9%)

62 (66%)

2 (2.1%)

Aortic Regurgitation (AR)

Normal

Mild

Moderate

Severe

0.000

91 (96.8%)

3 (3.2%)

77 (81.9%)

17 (18.1%)

Pulmonary size

Acceptable

Hypoplastic or small

No competing interests reported.

Short-Term Outcomes Following Total Correction of Tetralogy of Fallot in Adult Patients

Status:

Journal Publication

Version 1

Abstract

Objectivs:

Methods

Results

Conclusion

Introduction

Methods

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Journal Publication

Version 1