Ventricular Septal Rupture (VSR) in Post-Acute Anterior Myocardial Infarction Patients: A Case Series

Case Summary: We present 2 cases of post-STEMI VSR. They had anterior AMI without reperfusion therapy because of patient delay and limited resources. Thereafter apical VSR occurs on 5 th day. VSR was suspected because of sudden hemodynamic deterioration and new holosystolic murmur (Grade III/VI) at left parasternal line of fourth-fifth ICS. Then it was confirmed by echocardiography. Both patients underwent hemodynamic stabilization while waiting for surgical therapy. Unfortunately, they deceased because of cardiogenic shock accompanied by other comorbidities. Discussion: VSR causes shunt from left to the right ventricle, which overloads the RV, leading to cardiogenic shock. The peak incidence of VSR in the first 24 hours or 3-5 days post-AMI. This fits both of our cases. VSR occurs in total coronary occlusion, which then causes coagulation necrosis in the ischemic area, characterized by neutrophils that trigger apoptosis and lytic enzymes, so that septum becomes thin, brittle then ruptures. VSR is most common in anterior AMI and the defect is at apical septum, as in our patients. Definitive therapy for VSR is surgical closure, but the best timing is still under debate. This article is expected to make us more aware of post-AMI VSR, so we can quickly diagnose and promptly treat the patients with multidisciplinary approach. This is very important to optimize patient’s outcomes even in limited resources area.


Introduction
Acute Myocardial Infarction (AMI) still remains one of the leading causes of death worldwide [1] . In myocardial infarction, mechanical complications can occur, although the incidence is relatively rare (<1% cases). One of the mechanical complications is cardiac rupture, which consists of free wall rupture (0.52%), ventricular septal rupture (0.17%), and papillary muscle rupture (0.26%). [2] This case series will discuss about ventricular septal rupture (VSR) in post-acute anterior MI Patients.
Ventricular septal rupture (VSR) is one of the fatal mechanical complications of AMI. Although it is rare, it has a very high mortality and morbidity rate [3][4][5] . The incidence of VSR in the prereperfusion era ranges from 1-2%. Currently, after various methods of reperfusion are available, the incidence of VSR is decreasing, ranging from 0.17 to 0.31% [3,4,6] . However, the mortality rate is still very high. For VSR patients who did not undergo surgery or device closure ranged from 46% -90%.

ARTICLE INFO
Even after surgery, it is still high at around 40%. [7] The purpose of this article is to expand our knowledge about post-infarction VSR in our work environment. Thus, we can know the clinical course, predictive factors and risk factors of VSR to be able to speed up the diagnosis even in places with limited resources. In addition, prompt treatment with multidisciplinary approach is also needed to provide better outcomes and decrease mortality rate,    The second patient came to the ER one day after the first patient was hospitalized and also a referral from the same hospital. Prior to being referred, she had been hospitalized for 3 days. She was referred with the diagnosis of Recent AMI anterior, cardiogenic shock, suspected VSR, acute heart failure, acute kidney injury, paroxysmal AF. A 51-

Case Presentation
year-old female with chief complaint of left-sided chest pain in the last 5 days before going to the ER.
It was like a burning sensation and radiated to the left shoulder. She complained of dyspnea that was getting worse and still persists even though she was at rest. She also complained of diaphoresis.
Chest pain and shortness of breath still persisted. There were no signs of anemia, jaundice and cyanosis. Besides that, JVP was not increase. On cardiac examination, there were single S1 and S2, with regular heart rhythm.
There was a new holosystolic murmur at the left parasternal line of fourth intercostal space and also at the midclavicular line of fifth intercostal space.
Grade III/VI murmur, not accompanied by thrill.
Therefore, it was suspected that VSR occurred due

Discussion
VSR is perforation of the interventricular septum, resulting in shunt from left to right ventricle [1,6] . It is fatal mechanical complications of AMI. Although it is rare, it has a very high mortality and morbidity rate [3][4][5] . Currently the incidence is decreasing due to reperfusion therapy [1,2,8,9] . However, the mortality rate is still very high, despite development of surgical therapy. VSR is often caused by delays in the diagnosis and treatment of AMI, especially in developing countries such as Indonesia due to limited resources and patient's knowledge [10] . This is also experienced by both of our patients.
Especially in the second patient who just dared to go to the hospital after 2 days of experiencing chest September 2022 | Vol 3 | Article 4 pain. Both patients were also unable to receive reperfusion therapy either invasively or pharmacologically due to limited resources and patients delay. This delay has also been extended because we are still in the era of the Covid-19 pandemic.
The peak of VSR incidence has a bimodal peak. It occurs 24 hours after AMI, and 3-5 days, with an average of 1-14 days after AMI [1,6] . This is match with our cases, as VSR in both patients occurred on 5 th day post AMI. Etiology of VSR is a total occlusion of the coronary arteries that supply interventricular septum, resulting in transmural myocardial infarction (full thickness infarction) [3,6,11] .
This can occur at any anatomic location of the interventricular septum. In the GUSTO-1 study, VSR was more common in anterior AMI (70%), than in inferior AMI (29%) [6,7] . The most common blockages occurred in the left anterior descending artery (64%) and right coronary artery (28%). VSR in anterior AMI tends to occur at the apical of septum, whereas inferior AMI is often associated with perforation of the basal septum and has a poorer prognosis [1,8] .  [4,7,8,12] . They are more than 50 years old, have never had AMI and reperfusion therapy. The first patient also had a history of CKD. This is in line with several previous studies which showed a higher incidence of VSR in this group. In people who have experienced MI or chronic ischemia, it will trigger the formation of new blood vessels (collateral circulations). This has a protective effect in case of total coronary artery occlusion. In addition, chronic ischemia can "prepare" the myocardium by forming myocardial fibrosis (preconditioned). So maybe our patient has no collateral or fewer collateral vessels and no myocardial fibrosis, but they need to be proven by further objective examination.
The influence of hypertension and diabetes on the incidence of VSR is still being debated until now.
According to several studies, diabetic patients will experience impaired angiogenesis or formation of collateral vessels caused by endothelial dysfunction and several other mechanisms. Therefore, there is a higher risk of VSR. But another study said that diabetes has no effect on the incidence of VSR. In a limited study said that CAD patients with hypertension will have more collateral than non-September 2022 | Vol 3 | Article 4 hypertension patient. In addition, there is cardiac hypertrophy and interstitial fibrosis (preconditioned heart) which is more resistant to damage due to MI so that the incidence of VSR is lower [1,13] . But there are different studies suggesting that high blood pressure during MI will increase the likelihood of VSR because this condition puts more stress on the weakening septum. Possibly, this happened in both of our cases, because their blood pressure was high at the beginning of MI. [1,[13][14][15] Non-smokers (as in our two patients) will have a higher incidence of post-infarction VSR than smokers. This is because in smokers often cause the formation of collateral circulation. But it is also still being debated and needs further investigation. [1,10,13,16] The mechanism of VSR is presence of coagulation necrosis of the ischemic tissue and characterized by neutrophil infiltration which can cause the septum to become thin and brittle. Neutrophils will trigger apoptosis and release of lytic enzymes. It causes disintegration of necrotic myocardial tissue.
This sub-acute process takes 3-5 days, which explains why VSR often occurs on 3 rd -5 th day post MI. Meanwhile, septal rupture that occurs within 24 hours post AMI is usually caused by dissection of an intramural hematoma or bleeding in the ischemic myocardium. This dissection occurs because of increased tension in the area of infarction and hypercontractility that weakens the myocardium. It usually occurs in inferior infarcts with a VSR at the basal septum. [1,3,6,17] Rupture of the interventricular septum causes a left to right shunt followed by RV overload, increased pulmonary blood flow which in turn causes LA and LV overload. If the process continues, it causes a decrease in the LV systolic function. Furthermore, the body will give negative feedback by increasing systemic vascular resistance through peripheral vasoconstriction. However, this mechanism can actually cause the shunt flow become more severe.
Over time, pump failure occurs and causes cardiogenic shock. [1,6,7] The clinical manifestations of VSR are diverse.
Generally, patients with VSR experience acute HF and cardiogenic shock, but there are asymptomatic patient, although this is very rare [2,8] . Therefore, all patients with AMI should be evaluated clinically, especially in patients with sudden hemodynamic deterioration and presence of a new, harsh, loud holosystolic murmur heard best at the lower left sternal border and may be accompanied by a thrill. [1,3,9,10] Clinical manifestations also depend on size of the septal defect, ongoing ischemia, presence of RV infarction, RV stunning due to volume overload, pulmonary hypertension and worsening cardiac output [1,8] . Other physical examinations obtained in patients with VSR are the presence of 3 rd heart sound, prominent 2 nd heart sound (pulmonary September 2022 | Vol 3 | Article 4 component), signs of pulmonary edema, RV and LV failure and also cardiogenic shock. [1,17] On chest x-ray, there were no specific signs indicating VSR. There may be LV enlargement and acute lung edema [1] . ECG can show the location of infarction, thus predicting the location of VSR. You can also find branch block due to damage to conduction pathway in the interventricular septum [3,8,18] .  [2,6,11,17] Management of VSR requires rapid diagnosis, aggressive oxygenation and hemodynamic stabilization of the patient with medication, mechanical support and surgery [1,10] .
Pharmacological therapy is given to stabilize hemodynamics before definitive therapy is taken. [10] The principle is to reduce afterload with intravenous nitroglycerin or other vasodilators and also reduce preload with intravenous diuretics. This can improve the condition of acute heart failure. Decreased afterload can also reduce left-to-right shunt so that LV stroke volume is more effective [6,10,17] . In addition, Inotropic is expected to reduce afterload and increase cardiac output thereby increasing tissue perfusion [10,14] . Mechanical support systems such as IABP (intra-aortic balloon counter pulsation), ECMO (extracorporeal Membrane Oxygenation), LVAD (left ventricular assist device) can be used to assist bridging therapy before definitive therapy. [1,10,19] Definitive therapy for VSR patients is surgical closure/repair of the septum accompanied by CABG. Transcatheter closure of the septal defect can be an alternative therapy. Surgical closure should be performed on all patients, even if the patient is hemodynamically stable, because the septal defect can increase in size at any time [1,2,10,13] . Even though, the exact time for surgical therapy is still much debated until now [2,4,5,10] . complications such as infection, respiratory distress syndrome, renal failure and many others. [2][3][4][5] Another conflicting opinion is the recommendation to postpone surgical intervention, because several studies show that surgery will provide optimal results if performed within 2-6 weeks from the onset of AMI when fibrotic tissue has formed. It helps maintain the suture, whereas if surgical procedure is performed during acute phase, infarcted myocardium is still weak and fragile, so the sutures are easily ruptured. The outcome of surgery is strongly influenced by size of the rupture, hemodynamic status and patient's surgical risk. [8,10,11,15] In both of our patients, due to limited resources and other considerations, surgical therapy was planned 2 weeks after the onset of AMI. Prior to that, hemodynamic stabilization and treating acute heart failure with appropriate pharmacological therapy were carried out, so that surgical therapy gave optimal results for the patient. However, unfortunately both of our patients deceased, due to cardiogenic shock. In addition, also accompanied by many other comorbidities, such as rapid deterioration of kidney function, urinary tract infection, acid-base imbalance and heart rhythm disturbance. The second patient had a worse clinical presentation due to a longer delay in AMI treatment, and more severe comorbidities than the first patient.

Conclusion
VSR is a fatal mechanical complication of AMI, which is rare and has a very high mortality and morbidity rate. Therefore, every doctor, especially in limited resources area like our hospital, should be aware of post-infarction VSR, especially in AMI with sudden deterioration of hemodynamic status. Early diagnosis and prompt treatment involving multidisciplinary approach are needed, especially before being referred for surgical therapy which is the definitive therapy for VSR. The timing of surgical therapy and the surgical technique must be individualized for each patient in order to provide optimal outcomes and decrease mortality.