Clinical assessment of VSR site and size and its relation to the severity of heart failure in post‐myocardial infarction ventricular septal rupture patients

Abstract Background Ventricular septal rupture (VSR) is a rare but well‐known mechanical consequence of an acute myocardial infarction (AMI). Even in the later stages of re‐perfusion therapy, the result of VSR remains poor. Our aim is to assess the site and size of VSR in relation to the severity of cardiac failure. Methods From January 2016 to December 2022, a total of 71 patients with a diagnosis of post‐myocardial infarction VSR were admitted to the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Data records were retrospectively included in this registry. In all patients, clinical and echocardiographic data were gathered, and statistical analyses were performed. Results A total of 71 consecutive patients (mean age: 66.27 ± 8.88 years); 50.7% male, 49.3% female, with (M:F) ratio of almost (1:1). Left ventricular ejection fraction (LVEF) was (48.55 ± 10.44%) on echocardiography, and apical VSR was the most common site (69.0%). Overall, the VSD site was strongly related to the VSD size (p = .016), LVEF (p = .012), AMI site (p = .001), and affected coronary vessel (p = .004). Prodromal angina (p = .041), intra‐aortic balloon pump (p = .002), affected coronary vessels (p = .020), pro‐BNP (p = .000), and LVEF (p = .017) were predictors of the severity of heart failure. Conclusions Diabetes mellitus is a common risk factor for post‐myocardial infarction VSR. VSR site and size had no relation to the severity of heart failure. A presentation with prodromal angina predicted severe heart failure and a worse prognosis.


| INTRODUCTION
A ventricular septal rupture (VSR) is an extremely serious and potentially fatal consequence of an acute myocardial infarction (AMI). 1,2 The incidence of VSR has drastically decreased since the introduction of effective reperfusion treatments (both pharmacological and mechanical). However, the fatality rate among patients with AMI and VSR is noted to be as high as 80% in a new sequence of cases with AMI undergoing immediate percutaneous coronary intervention (PCI), and appears relatively unaffected over the last few decades. 3 The incidence of VSR following AMI was as high as 1-3 percent before the advent of thrombolysis and PCI. [4][5][6][7][8] The incidence of VSR dropped to 0.17%-0.31% 9,10 after reperfusion therapies became the gold standard for treating AMI. The mortality rate from VSR remains exceedingly high, ranging from 45% to 80%, 11,12 despite advances in fast identification and treatment of both AMI and VSR.
As demonstrated by the SHOCK trial and confirmed by the GUSTO-I and APEX-AMI studies, VSR typically occurs much earlier, between 8 and 24 h after AMI, and the results did not differ substantially between those who received thrombolysis and those who did not. [9][10][11]13 However, the early detection of VSR may be the result of other factors, such as the widespread availability of echocardiography and changes in tissue pathology due to reperfusion injury and fibrinolysis. 3,9,14 Despite improvements and optimistic results in nonsurgical treatments for VSR, such as transcatheter closure techniques, 15 surgical repair of septal defects remains the primary treatment modality. The American College of Cardiology Foundation and American Heart Association's (ACCF/AHA) current guidelines suggest urgent surgical repair despite hemodynamic stability at the time of diagnosis. 16 Despite professional understanding of the necessity of surgical repair, the timing of VSR repair and perioperative therapeutic management remain controversial. 4,5,7,17,18 This research will evaluate the VSR site and size with particular regard to their relationship to the severity of heart failure.

| Medical ethics
This is a retrospective study involving data of human participants which is recruited from electronic medical records was reviewed and approved by The First Affiliated Hospital of Zhengzhou University and ethical number was not required.

| Study design and patient selection
Seventy-one patients who presented or were transferred to the First Affiliated Hospital of Zhengzhou University with VSR following AMI between January 2016 and December 2022 were analyzed retrospectively. Participants signed the patient permission form after a thorough description of the projects' aims, advantages, and even potential risks.
Any patient admitted for AMI who exhibited evidence of VSR on urgent cardiac catheterization or had hemodynamic compromise on echocardiography was considered for inclusion. Patients who did not survive their first hospital visit were not included; this included those who were rushed in for emergency cardiac catheterization but were unable to undergo it. Clinical symptoms and an elevation of serum troponin-T >0.1 mg/dL were used to diagnose AMI, and an electrocardiographic (ECG) showing >2 mm ST-segment elevation in the precordial leads or >1 mm ST-segment elevation in the limb leads was also considered diagnostic. We reviewed all of the patients' medical records and analyzed their clinical profiles, therapies (both nonsurgical and surgical), and final results. Each patient's clinical hemodynamics were derived from the earliest available vital signs.

| Cardiac catheterization
All patients who were diagnosed with AMI in the ER underwent immediate cardiac catheterization. The major goal of the coronary angiograms given to all patients was to initiate a primary intervention.
Some patients also had a left ventriculogram before echocardiographic confirmation. The level of obstruction was used to describe coronary artery disease (CAD). No narrowing of more than 20% showed that there was no CAD. Nonobstructive coronary artery disease was diagnosed when there was at least one lesion with a narrowing of more than 20% but less than 70%. Obstructive CAD was described as stenosis of more than 70% or stenosis of the left main artery of more than 50% that affected one, two, or three vessels.

| Variables
By reviewing the patient's medical records, we were able to learn about their demographic traits, medical co-morbidities (such as smoking history, hypertension, diabetes mellitus, and renal function), medical acuity (such as prodromal angina, LVEF, and Killip and NYHA classifications), the location of the infarction, the site and size of the septal rupture, and the peak cardiac enzymes. Prodromal angina is defined as typical chest pain bouts lasting 30 min or longer that occur within 24 h of the AMI's onset (either at rest or with exertion). 19 As additional variables for analysis, the intra-aortic balloon pump (IABP), early PCI (6 h after AMI), concurrent surgical operations, and calendar year of operation were also taken into consideration.

| Outcomes
The primary outcome was clinical correlation between the apex and middle VSR, defined as any factor that can differentiate the apical from the middle VSR based on clinical and statistical points. The secondary outcome was the indicators of severity of heart failure, defined as factors that can predict the severity of heart failure based on the clinical classification of cardiac failure and statistical analysis.
The New York Heart Association classification of heart failure (Table S1) can be used to describe the severity of heart failure and the symptoms of heart failure.

| Statistical analysis
Continuous variables were summarized as mean plus or minus the standard deviation (SD). Categorical variables were expressed as percentages of the sample. The comparison between apical VSR and middle VSR was performed by an independent sample test (Whitney U test) and the Chi-square test using Yates correction and Fisher's exact test for continuous and categorical variables, respectively. A two-tailed p < 0.05 was used to indicate statistical significance.

| RESULTS
A total of 71 subjects were diagnosed with VSR after MI between the years of 2016-2022 (   (Table 2).
From Table 3, age, gender, killip class, NYHA class, and Pro-BNP were not significantly different between the apical VSR group and the middle VSR group. The apical VSR group had a lower LVEF than the middle VSR group (46.08 ± 8.88% vs. 53.36 ± 11.72%, p = .012); a lower LVEF predicted severe heart failure. There was a significant difference in the size of the VSR among the two groups, which was smaller in the apical group than that in the middle one  difference predicted the severity of heart failure. There was a significant difference in the affected vessel among the 3 classes of heart failure (p = .020). Pro-BNP had also a strong variance between the 3 classes of heart failure, with a p value was (p = .000), which indicated that the higher the Pro-BNP value, the more severe the heart failure. And last, the LVEF was significantly different among the 3 classes of heart failure (p = .017), which predicted that the lower the LVEF, the higher the stage of heart failure ( Table 4) ( Figure 1B).

| DISCUSSION
While reading the research conclusions, individual points are worth pointing out. First, modern reperfusion strategies and more potent antiplatelet therapies have modified the epidemiology of VSR complicating AMI. 3 In fact, the frequency of this complication has greatly decreased and is accounted for as high as 0.2% in recent primary PCI studies. 20 In the current series, we found a slightly higher Age, gender, Killip class, NYHA class, and pro-BNP had no significant variance between the two groups (apical and middle VSR), which indicated no correlation between these factors and the site of the VSR. There was a significant difference in the size of the VSR among the two groups, which was smaller in the apical group than that in the middle one. LVEF can be used as an indicator to differentiate between apical and middle VSR, as it was lower in the apical VSR than that in the middle one, unless the size of the middle VSR was >10 mm, which is common as it is mentioned above, with a significant p value. The site of the AMI and the affected coronary proportionate to the severity of heart failure.
5. Diabetes mellitus is a common risk factor for post-myocardial infarction VSR.

AUTHOR CONTRIBUTIONS
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

ACKNOWLEDGMENTS
We would like to thank all the participants of our study. This work was supported in part by grants from the First affiliated hospital of Zhengzhou university.

CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Note: Definition: prodromal Angina: was defined as typical chest pain episodes (either at rest or upon effort) persisting <30 min and occurring within 24 h before the onset of the AMI. 19 Bold values indicate significant p value for the factors that showed clinical significance.