Acute myocardial infarction with ventricular septal rupture: Clinical characteristics, prognosis factors, and treatment strategies

Table 1 Epidemiological characteristics of acute myocardial infarction complicated by ventricular septal rupture before and after the implementation of emergency percutaneous coronary intervention, n (%)

Research object	Research center/country	Type of study population	AMI cases (n)	VSR incidence	Gender (male:female)	Implementation status of acute PCI	Year	Ref.
GUSTO Trial	International multicenter (Europe and United States)	AMI patients primarily receiving thrombolytic therapy	36303	798 (2.2)	1:1.2	Thrombolysis as the primary approach	1993	[84]
PAMI-1 and PAMI-2	Multicenter (America)	AMI patients	1295	4 (0.31)	-	PCI	1995	[85-87]
SHOCK Research	International multicenter (Europe and United States)	Patients with cardiogenic shock complicated by VSR after MI	939	55 (5.86)	-	Thrombolysis combined with IABP, partial PCI	1999-2006	[88]
MOODY Registered Study	China (multicenter)	AMI	9265	52 (0.56)	0.625:1	Thrombolysis combined with IABP, partial PCI	1999-2016	[89]
-	International multicenter	STEMI, NSTEMI	9126362	10344 (0.11)	0.71:1	Thrombolysis combined with IABP, partial PCI	2003-2015	[9]
Huazhong Fuwai Cardiovascular Hospital	China (single centre)	VSR with percutaneous closure	-	81	0.72:1	PCI and Percutaneous Septal Closure	2013-2020	[90]
Huazhong Fuwai Cardiovascular Hospital	China (single centre)	PIVSR patients	-	213	0.95:1	PCI	2018-2023	[91]
CAUTION study(NCT03848429)	International multicenter	Post-infarction MCs	-	720	1.46:1	Thrombolysis combined with IABP, partial PCI	2001-2019	[92]
Narayana Institute of Cardiac Sciences, India	India (single centre)	Patients diagnosed with post-AMI VSR and who underwent surgical closure of VSR by double patch technique	-	77	2.67:1	Thrombolysis combined with IABP, partial PCI	2002-2022	[93]
Karachi Tabba Heart Institute, Department of Clinical Research in Cardiology	Pakistan (multicenter)	AMI-VSR	11428	67 (0.6)	1.68:1	PCI	2011-2020	[94]
First Affiliated Hospital of Xi'an Jiaotong University	China (single centre)	AMI-VSR	5395	42 (0.78)	-	PCI	2016-2020	[95]
Beijing Anzhen Hospital, Capital Medical University	China (single centre)	AMI-VSR	-	180	0.94:1	PCI	2016-2023	[25]
Coronary Heart Disease Center, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College	China (single centre)	AMI-VSR	12354	70 (0.57)	0.89:1	Thrombolysis combined with IABP, partial PCI	2002-2010	[96]
Peking University People's Hospital Research	China (single centre)	STEMI	2057	16 (0.7)	1:1	11 cases of coronary angiography	1990-2004	[97]
-	China (multicenter)	AMI-VSR	-	127	1.12:1	61.4% drug therapy, 24.4% TCC, 14.2% surgical intervention	2012-2019	[98]
Shenyang Northern Theater General Hospital	China (single centre)	AMI-VSR	-	45	1.25:1	Surgery, IABP/ECMO	2012-2021	[99]
Cairo University	Egypt (single centre)	PIVSR	-	32	1:1	PCI	2015-2023	[100]
Nanjing First Hospital Affiliated with Nanjing Medical University	China (single centre)	AMI-VSR	-	50	0.63:1	PCI	2012-2021	[101]
National University of Singapore research	Singapore (single centre)	Analysis of Pathological Characteristics of VSR in Asian Populations	-	40	1.2:1	Histopathology combined with immunohistochemistry	2010-2020	[102]
A tertiary care center in South India	South India (single centre)	Patients undergoing TCC	-	21	2.5:1	PCI + TCC	2000-2014	[103]
Cleveland clinic	United States (single centre)	AMI-VSR	-	38	1.375:1	PCI + Ventricular septal repair	1976-2023	[104]

AMI-VSR: Acute myocardial infarction complicated by ventricular septal rupture; PCI: Percutaneous coronary intervention; IABP: Intra-aortic balloon pump; STEMI: ST - elevation myocardial infarction; NSTEMI: Non ST - elevation myocardial infarction; TCC: Transcatheter Closure; ECMO: Extraciroireal membrane oxygenation.

Table 2 Comparative table of clinical characteristics of acute myocardial infarction complicated by ventricular septal rupture

Clinical factors	Clinical manifestations	Diagnostic methods	Risk factors	Prevalence (%)	Treatment options	Ref.
Gender	The proportion of females was significantly higher than that in the control group (62.5% vs 36.4%)	Retrospective cohort analysis	Female is an independent risk factor	62.5 (VSR group)	Gender does not affect treatment selection, but women require closer hemodynamic monitoring	[6,105]
Age	Average age 66.85 years (VSR group) vs 60.79 years (control group)	Analysis of clinical data	Advanced age (> 65 years) significantly increases the risk	-	Elderly patients should be prioritized for interventional or surgical procedures	[6,105]
Inflammatory markers	CRP, D-dimer levels are significantly elevated	Serological testing (CRP, D-dimer)	Inflammatory response exacerbates myocardial necrosis	-	Anti-inflammatory therapy (such as glucocorticoids) may assist in stabilizing the condition	[106,107]
Myocardial injury markers	TnT significantly elevated	Troponin test	TnT levels are positively correlated with myocardial necrosis area	-	Early reperfusion therapy reduces peak TnT levels	[108]
Hemoglobin	Hb, Hct, and RBC were significantly lower than those in the control group	Complete blood count test	Anemia may increase the cardiac workload	-	Blood transfusion support to maintain tissue oxygen supply	[14]
Cardiac function classification	Killip classification ≥ grade III (78.1% in the deceased group vs 50% in the survival group)	Killip classification assessment	Deterioration of cardiac function is an independent risk factor for mortality	60 (Killip IV)	IABP support therapy	[25,34]
Myocardial infarction site	Anterior wall myocardial infarction accounts for 75%-84.6%	ECG, echocardiogram	Anterior wall infarction is prone to involve the blood supply area of the interventricular septum	75-84.6	Patients with anterior wall infarction require early screening for VSR	[14,109,110]
Location of ventricular septal perforation	Near the cardiac apex (anterior wall infarction) vs posterior interventricular septum (inferior wall infarction)	Echocardiography (ventricular septal echo dropout, left-to-right shunt)	Posterior perforation carries a worse prognosis	60 near the cardiac apex	Interventional closure is suitable for anterior perforations, while surgical repair is indicated for complex locations	[58]
Perforation diameter	Average 9.8 ± 3.9 mm, large perforation (> 15 mm) are associated with higher mortality rates	Echocardiography	The perforation diameter is positively correlated with the left-to-right shunt volume	-	Major perforations require emergency surgical intervention or occlusion	[10,110]
Reperfusion therapy	The proportion of reperfusion therapy was low (0% in the death group vs 50% in the survival group)	Coronary angiography (IRA completely occluded)	Failure to receive reperfusion therapy increases the risk of VSR	-	Emergency PCI or thrombolysis reduces the incidence of VSR	[10]
Comorbidity	Hypertension (60%); Diabetes (27.8%-46.9%)	Medical history collection	Hypertension and diabetes accelerate myocardial remodeling	60 (hypertension)	Control blood pressure and blood sugar to reduce cardiac workload	[14,110]
Hemodynamic status	CS (90% mortality group vs 33.9% survival group)	Hemodynamic monitoring (mean arterial pressure, heart rate)	CS is an independent risk factor for 30-day mortality. (OR = 24.112)	90 (mortality group)	VA-ECMO or IABP	[14]
Laboratory indicators	Elevated white blood cell count and lactate levels (survival group)	Complete blood count, lactate test	Elevated white blood cell count (OR = 1.619) is associated with mortality	-	Anti-infection and metabolic support therapy	[58]
MELD-XI Score	Patients with a score > 15 had a 3-year survival rate of 35.7% vs 85.1% for those with a score ≤ 15	MELD-XI score (Based on creatinine and bilirubin)	High score indicates hepatic and renal dysfunction with poor prognosis	-	Patients with a score > 15 should be prioritized for palliative care	[58]
Echocardiography parameters	LVEF is normal (66.7% of patients), but cardiac function continues to deteriorate	LVEF, LVEDD measurement	LVEF is normal but mechanical complications are prone to be missed in diagnosis	-	Comprehensive evaluation based on clinical symptoms	[14,93]
Coronary artery disease	Multivessel disease (62.5%), with the left anterior descending artery being the most common infarct-related vessel	Coronary angiography	Multivessel disease and absence of collateral circulation increase the risk of VSR	62.5 (multivessel disease)	CABG combined with VSR repair	[14,110]
Time	Patients with AMI to VSR time ≤ 4 days have higher mortality rates	Medical history review	Early perforation (≤ 4 days) presents fragile myocardial tissue and carries high surgical risks	-	Postpone the surgery for 3-4 weeks (if hemodynamically stable)	[94]
Timing of surgical intervention	Early surgery (≤ 7 days) mortality rate 43%, delayed surgery (> 4 weeks) mortality rate 65%	Analysis of Surgical Records	The timing of surgery is correlated with myocardial tissue stability	-	Hemodynamically stable patients are recommended for delayed surgery	[111,112]
Interventional occlusion procedure	The 30-day mortality rate after occlusion was 32%, with a 3-year survival rate of 73.8%	Percutaneous interventional occlusion (umbrella occluder)	Blockage failure is related to the perforation location and diameter	-	Applicable to patients with hemodynamic stability and suitable perforation site	[58]
Conservative treatment	The mortality rate of conservative treatment was 61.5% vs surgery/intervention at 14.3%	Medications (diuretics, vasodilators, positive inotropic drugs)	Conservative treatment is only suitable for those who cannot tolerate surgery	-	Short-term transitional therapy requires combination with IABP or ECMO	[113]
Merged ventricular aneurysm	30% of patients are complicated by ventricular aneurysm	Echocardiography or cardiac MRI	Ventricular aneurysm increases the risk of cardiac rupture	30	Resection of ventricular wall aneurysm combined with VSR repair	[21]
Renal insufficiency	Elevated serum creatinine (death group 138.5 μmol/L vs survival group 88.0 μmol/L)	Serum creatinine test	Renal insufficiency is an independent risk factor for postoperative mortality (OR = 1.78)	-	Preoperative hemofiltration or postoperative CRRT	[14,114]
Arrhythmia	The incidence of ventricular fibrillation and atrial fibrillation is relatively high	Electrocardiographic monitoring	Arrhythmia reflects instability in myocardial electrical activity	-	Antiarrhythmic drugs or ICDs	[115]
Thrombosis risk	D-dimer levels were significantly elevated (death group 2.2 μg/mL vs survival group 1.0 μg/mL)	D-dimer test	Hypercoagulability increases the risk of embolism	-	Anticoagulation therapy (such as heparin), but the bleeding risk needs to be balanced	[109,116]
Pulmonary artery systolic pressure	Pulmonary arterial hypertension (> 50 mmHg) is associated with right heart failure	Echocardiography (Tricuspid Regurgitation Velocity Method)	Pulmonary hypertension indicates increased right heart workload	-	Reduce pulmonary circulation resistance (such as inhaling NO)	[58,117]
Mitral regurgitation	Mitral regurgitation area shows no significant correlation with mortality	Echocardiography (regurgitant jet area measurement)	Mitral regurgitation is mostly secondary and not an independent risk factor	-	After VSR repair, mitral valve function can be indirectly improved	[118]
Hospitalization period	The death group had a shorter hospital stay (6 days vs the survival group's 22.5 days)	Medical record analysis	Short-term hospitalization reflects a sharp deterioration in the condition	-	Short-term hospitalization reflects a sharp deterioration in the condition	[6,109]
Long-term prognosis	3-year survival rate: Interventional closure 738%, surgical procedure 70%	Follow-up (survival rate, cardiac function classification)	Long-term mortality is often due to heart failure or reinfarction	-	Long-term anti-heart failure therapy postoperatively (such as ARNI, β-blockers)	[6,119]
Case distribution	VSR accounts for approximately 0.2%-1.57% of AMI	Epidemiological statistics	The incidence of VSR has decreased in the PCI era, but mortality rates remain high	0.2 - 1.57	Enhance the popularization rate of early reperfusion therapy to reduce the incidence rate	[98,110]

AMI: Acute myocardial infarction; CRP: C-reactive protein; TnT: Troponin T; Hct: Hematocrit; RBC: Red blood cell count; IABP: Intra-aortic balloon pump; ECG: Electrocardiogram; IRA: Infarct-related artery; PCI: Percutaneous coronary intervention; CS: Cardiogenic shock; VA-ECMO: Venous-arterial extracorporeal membrane oxygenation; LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic diameter; CABG: Coronary artery bypass graft; CRRT: Continuous renal replacement therapy; ICDs: Implantable cardioverter defibrillators; NO: Nitric oxide; ARNI: Angiotensin receptor neprilysin inhibitor; VSR: Ventricular septal rupture.

Table 3 Cardiac pathological characteristics and immunohistochemical results

Anatomic location	Pathologic feature	Immunohistochemical result	Perforation site	Complication	Probable cause of death	Ref.
Anterior left ventricle	Transmural necrosis, ventricular septal perforation (2.0 cm)	CD68 + macrophages densely packed, IL-1β highly expressed	Apical interventricular septum	Acute left heart failure, ventricular fibrillation	Cardiogenic shock	[20,21]
Basal part of the ventricular septum	Myocardial rupture with hematoma	Neutrophil infiltration, C3d complement deposition (++)	Near aortic valve at basal part	Third-degree atrioventricular block	Cardiac arrest	[22,23]
Anterior right ventricle	Necrosis extends to right ventricle, perforation slit-like	CD3 + T cell infiltration, IFN-γ positive	Anterior interventricular septum	Right heart failure, hepatic congestion	Multi - organ failure	[120,121]
Lateral left ventricle	Old infarct area calcified, fresh perforation (0.8 cm)	CD163 + M2 - type macrophages predominant, TGF-β highly expressed	Lateral edge of interventricular septum	Wall thrombus, cerebral embolism	Large - area cerebral infarction	[122,123]
Middle of the ventricular septum	Necrosis with abscess formation	CD15 + neutrophils aggregated, Gram-positive bacteria detected	Middle of the ventricular septum	Septic shock, infective endocarditis	Sepsis with DIC	[23,124]
Inferior left ventricle	Transmural necrosis with pericarditis	CD20 + B lymphocyte infiltration, focal IL-10 expression	Posterior - inferior part of interventricular septum	Cardiac tamponade, cardiac rupture	Acute cardiac tamponade	[125,126]
Papillary muscle root	Papillary muscle rupture with mitral valve prolapse	CD31 + neovessel growth, VEGF highly expressed	Posterior papillary muscle attachment area of interventricular septum	Acute mitral regurgitation, pulmonary edema	Acute pulmonary edema asphyxia	[127,128]
Apical left ventricle	Ventricular aneurysm formation, thrombus at perforation edge	CD68 + /CD206 + M2 - type macrophage polarization	Apical interventricular septum	Peripheral artery embolism (mesenteric)	Intestinal necrosis leading to septic shock	[129,130]
Upper part of the ventricular septum	Perforation with aortic valve ring tear	CD4 + helper T cell infiltration, HLA-DR overexpressed	Upper part of interventricular septum near aortic valve	Aortic valve regurgitation, coronary artery dissection	Acute circulatory collapse	[131,132]
Right ventricular outflow tract	Necrosis involving pulmonary valve	CD8 + cytotoxic T cell infiltration, PD-L1 negative in perforation area	Perforation in outflow tract of interventricular septum	Pulmonary hypertension, right ventricular failure	Acute right heart failure	[133,134]
Posterior left ventricle	Transmural necrosis extending to AV groove	IgG/IgM immune complex deposition, C1q positive	Posterior - basal part of interventricular septum	Complete atrioventricular block	Asystole syndrome	[135,136]
Anterior edge of the ventricular septum	Multiple small perforations (3 sites)	CD66b + NETs formed	Anterior 1/3 of interventricular septum	DIC, micro thromboembolism	Multi - organ microinfarction	[135,137]
Basal left ventricle	Transmural necrosis with ventricular wall rupture	TNF-α/IL-6 double - positive cells diffuse	Basal part of interventricular septum	Mediastinal hematoma, pericardial effusion	Hemorrhagic shock	[120,122]
Posterior right ventricle	Necrosis with fat infiltration	CD34 + microvessel density increased, Ang-2 highly expressed	Posterior - inferior part of interventricular septum	Pulmonary embolism, right atrial enlargement	Acute pulmonary embolism	[138,139]
Anterior interventricular septum	Ventricular aneurysm with mural thrombus	CD47 highly expressed (anti-phagocytosis signal), fibrosis at perforation edge	Middle of anterior interventricular septum	Thrombus detachment causing renal infarction	Acute renal failure	[130,140]
Junction of the septum and right ventricle	Granulation tissue growth in necrotic area	CD45RO + memory T cell infiltration, IL-17A positive in perforation area	Right ventricular face of interventricular septum	Refractory ventricular tachycardia	Electrical storm	[141,142]
Posterolateral left ventricle	Transmural necrosis involving posterior leaflet of mitral valve	Mixed CD68 + macrophage and CD3 + T cell infiltration	Posterior papillary muscle area of interventricular septum	Acute mitral regurgitation, pulmonary edema	Respiratory failure	[123,125]
Apical part of the septum	Perforation with left ventricular apical thrombus	CD14 + monocyte aggregation, MMP - 9 overexpression in perforation area	Apical interventricular septum	Cerebral embolism, lower limb artery embolism	Brainstem infarction	[22,143]
Right ventricular septal part	Necrosis extending to tricuspid valve ring	CD79a + B cell infiltration, IgA deposition	Right side of interventricular septum	Tricuspid regurgitation, hepatic and renal failure	Hepatorenal syndrome	[144,145]
Anterolateral left ventricle	Transmural necrosis with epicarditis	CD123 + plasmacytoid dendritic cell infiltration, IFN-α positive in perforation area	Anterolateral edge of interventricular septum	Pericarditis, pleural effusion	Cardiac tamponade	[122,123]
Middle of the septum	Necrotic area with eosinophilic infiltration	CD117 + mast cell activation, histamine release in perforation area	Middle 1/3 of interventricular septum	Anaphylactic shock, bronchospasm	Asphyxia	[124,146]
Posterior basal left ventricle	Old calcified lesion with fresh perforation	CD68 + macrophages and CD20 + B cell colocalization	Posterior - basal part of interventricular septum	Splenic infarction, sepsis	Septic cardiomyopathy	[147,148]
Apical right ventricle	Necrosis with fatty degeneration	CD36 + foam cell aggregation, ox - LDL positive	Apical part of right ventricle	Pulmonary infarction, ARDS	Respiratory failure with right heart failure	[149,150]
Anterior part of the left ventricle interventricular septum	Transmural necrosis with coronary artery fistula	CD144 + endothelial injury marker, VWF highly expressed in perforation area	Anterior interventricular septum near left anterior descending artery	Coronary artery - ventricular fistula, myocardial steal	Refractory hypotension	[151,152]
Junction of the septum and left ventricle	Necrosis with lymphatic dilation	CD68 + macrophages engulfing hemosiderin	Left ventricular face of interventricular septum	Chylothorax, protein - losing enteropathy	Hypoproteinemia causing multi - organ edema	[153,154]
Extensive anterior left ventricle	Large - area necrosis (> 40% left ventricle)	CD163 + M2 macrophages predominant, IL-10 highly expressed in perforation area	Anterior and middle parts of interventricular septum	Cardiogenic shock, lactic acidosis	Metabolic acidosis causing cardiac arrest	[155,156]
Posterior upper part of the septum	Perforation with chordae tendineae rupture	Mixed CD68 + macrophage and CD15 + neutrophil infiltration	Posterior upper part of interventricular septum near mitral valve	Acute mitral valve flail, pulmonary edema	ARDS	[124,157]
Free wall of the right ventricle	Necrosis with epicardial hemorrhage	CD11b + myeloid cell infiltration, MPO positive in perforation area	Free wall of right ventricle	Pericardial effusion, cardiac tamponade	Acute circulatory failure	[158,159]
Posterolateral left ventricle	Transmural necrosis involving left atrium	CD68 + macrophage polarization (M1 predominant), TNF-α/IL-1β co - expression in perforation area	Posterolateral edge of interventricular septum	Atrial fibrillation, left atrial thrombus	Cerebral embolism with brain herniation	[155,160]
Whole layer of the septum	Multiple perforations (5 sites) with myocardial dissolution	CD4+/CD8+ T cell ratio inverted, Fas/FasL highly expressed in perforation area	Anterior, middle, and posterior parts of interventricular septum	Whole - heart failure, hyperkalemia	Electromechanical dissociation	[161,162]

DIC: Disseminated intravascular coagulation; VEGF: Vascular endothelial growth factor; HLA-DR: Human leukocyte antigen-DR; PD-L1: Programmed death-ligand 1; AV: Atria and ventricles; NETs: Neutrophil extracellular traps; TNF-α: Tumor necrosis factor-α; IL: Interleukin; MMP-9: Matrix metalloproteinase-9; IgA: Immunoglobulin A; ox-LDL: Oxidized low-density lipoprotein; VWF: Von Willebrand factor; ARDS: Acute respiratory distress syndrome; MPO: Myeloperoxidase.

Table 4 Analysis of the Association between major prognostic factors and clinical outcomes

Prognostic factors	Clinical impact	Evidence-based basis	Severity level	Management strategies	Timeframe of impact	Population specificity	Intervention efficacy (%)	Ref.
Female	The 30-day mortality rate among female patients showed a significant increase (OR = 4.263)	Multicenter studies indicate that female patients account for 62.5% of VSR cases and represent an independent risk factor	High	Close hemodynamic monitoring with priority given to surgical intervention	Short-term (≤ 30 days)	Female, Elderly patients	The surgical survival rate has increased to 70%	[7,13,163,164]
Age > 65 years old	The mortality rate among elderly patients increased significantly (mean age of survival group: 57.4 years vs death group: 72.4 years)	Logistic regression analysis showed that age was an independent risk factor for 30-day mortality. (OR = 4.956)	High	Elderly patients are recommended to delay surgery (if stable) or undergo interventional occlusion	Short-term to medium-term (≤ 1 year)	Elderly patients	Delayed surgery mortality rate drops to 6.5%	[13,165-168]
Killip Class ≥ Ⅲ	The mortality rate reaches 78.1% in patients with deteriorating cardiac function (death group vs 50% survival group)	Killip classification ≥ grade III is significantly associated with 30-day mortality rate. (OR = 24.112)	Critical	IABP or VA-ECMO support, early surgical intervention	Short-term (≤ 30 days)	Merge patients with cardiogenic shock	IABP support increases survival rate by 20%	[13,20,119,165]
Anterior Wall AMI	Anterior wall infarction patients account for 75%-84.6% of VSR cases, with a higher mortality rate	Anterior wall infarction is prone to involve the blood supply area of the interventricular septum, increasing the risk of perforation. (P = 0.023)	High	Early screening for VSR, prioritizing PCI or CABG combined with repair surgery	Acute phase to short term	Patients with anterior wall AMI	PCI reduces mortality rate to 14.3%	[13,163,169-171]
VSR Diameter > 15 mm	The mortality rate of patients with large perforations (> 15mm) significantly increases	The diameter of the perforation is positively correlated with the left-to-right shunt volume, and large perforations require emergency surgery	Severe	Emergency surgical repair or interventional closure	Acute phase (≤ 7 days)	Hemodynamically unstable patient	The success rate of the occlusion procedure is 73.8%	[13,105,169,172]
Time to VSR Onset ≤ 4 Days	The 30-day mortality rate reaches 77.4% for patients who develop VSR within 4 days after AMI	Early perforation (≤ 4 days) presents with fragile myocardial tissue and carries high surgical risks. (OR = 12.646)	Critical	Postpone surgery until 3-4 weeks later (if stable), supplemented with mechanical circulatory support	Short-term (≤ 30 days)	Early-stage perforation patients	Delayed surgery mortality rate 65%	[6,13,163]
Elevated Inflammatory Markers	Elevated CRP and D-dimer levels are positively correlated with mortality (CRP 85 mg/L in the deceased group vs 27 mg/L in the survival group)	Inflammatory response exacerbates myocardial necrosis, and elevated CRP is associated with mortality (P < 0.05)	Moderate to High	Anti-inflammatory therapy (such as glucocorticoids), infection control	Short-term to medium-term	Patients with concurrent infections or systemic inflammation	Anti-inflammatory therapy improves prognosis by 30%	[13,166,173]
Cardiogenic Shock (CS)	The 30-day mortality rate for patients with combined CS reaches 90%	CS is an independent risk factor (OR = 4.288), requiring VA-ECMO support	Critical	VA-ECMO combined with IABP for hemodynamic maintenance	Acute phase (≤ 7 days)	Patients with hemodynamic collapse	ECMO support increases survival rate by 40%	[13,21,166,174]
LVEF < 40%	Patients with low LVEF showed significantly higher mortality (survivor group LVEF 45% vs deceased group 30%)	Left ventricular dysfunction exacerbates shunting, leading to multiple organ failure	High	Positive inotropic drugs combined with mechanical support to optimize cardiac function before surgery	Medium-term (≤ 1 year)	Patients with chronic heart failure	Postoperative survival rate 70%	[13,169,175]
No ventricular aneurysm	Patients without ventricular aneurysms have a higher mortality rate (OR = 12.646)	Ventricular aneurysm may alleviate perforation tension, while non-aneurysmal myocardium is prone to secondary rupture	Moderate	Ventricular aneurysm resection combined with VSR repair surgery	Long-term (> 1 year)	Patients with complex anatomical structures	Combined surgery survival rate 85%	[163,169,176]
Elevated TnT levels	TnT levels were positively correlated with mortality (3.56 ng/mL in the deceased group vs 0.31 ng/mL in the survival group)	Elevated TnT indicates extensive myocardial necrosis and poor prognosis (P = 0.011)	High	Early reperfusion therapy reduces peak TnT levels	Acute phase (≤ 72 hours)	Patients with extensive myocardial infarction	Reperfusion therapy reduces mortality by 50%	[13,165,177,178]
Delayed surgical timing	Early surgery (≤ 7 days) mortality rate 43% vs delayed surgery (> 4 weeks) 6.5%	The success rate of surgery is higher after myocardial tissue edema subsides	Moderate to High	Hemodynamically stable patients are recommended for delayed surgery, supplemented with temporary mechanical support	Mid-term (1-4 weeks)	Patients with stable condition	Delayed surgery survival rate 935%	[179,180]
Multiple coronary artery diseases	The mortality rate increased in patients with multivessel disease (62.5% vs single-vessel disease)	Multiple vessel disease leads to aggravated myocardial ischemia, making repair more difficult	High	CABG combined with VSR repair surgery	Long-term (> 1 year)	Patients with complex coronary artery lesions	CABG combined surgery survival rate 80%	[13,166,181,182]
Anemia (Hb < 10 g/dL)	Anemia increases cardiac workload and elevates mortality rates (survivor group Hb 12 g/dL vs deceased group 9 g/dL)	Low Hb reduces tissue oxygen supply and accelerates the progression of heart failure	Moderate	Blood transfusion support to maintain Hb > 10 g/dL	Short-term to medium-term	Patients with chronic kidney disease or bleeding tendency	Blood transfusion improves oxygen delivery with a 25% increase in survival rate	[13,99,183]
Renal insufficiency	Postoperative mortality rate increases in patients with renal insufficiency (OR = 1.78)	Elevated creatinine levels (> 138.5 μmol/L) are associated with postoperative mortality	High	Preoperative hemofiltration, postoperative CRRT support	Short-term to long-term	Patients with chronic kidney disease	CRRT support reduces mortality rate by 20%	[6,13,16]
Elevated Lactate Levels	A lactate level > 4 mmol/L indicates tissue hypoperfusion and is associated with significantly increased mortality	Elevated lactate levels reflect systemic hypoperfusion and are associated with multiple organ failure (P < 0.001)	Critical	Optimize perfusion (e.g., ECMO), correct metabolic acidosis	Acute phase (≤ 24 hours)	Patients with shock or sepsis	ECMO support increases survival rate by 35%	[13,166,184,185]
Diabetes Mellitus	Mortality rate increased in patients with combined diabetes (46.9% vs non-diabetic 27.8%)	Diabetes accelerate myocardial remodeling and impair healing (P < 0.05)	Moderate	Strictly control blood glucose (target HbA1c < 7%)	Long-term (> 1 year)	Diabetic patients	Blood sugar control reduces complication rates by 30%	[13,15,186]
Lack of Reperfusion Therapy	The mortality rate reaches 66.7% in patients who did not receive reperfusion therapy	Reperfusion therapy reduces the incidence of VSR (50% of the survival group received PCI vs 0% in the deceased group)	High	Emergency PCI or thrombolysis to restore coronary blood flow	Acute phase (≤ 12 hours)	AMI patients without contraindications	PCI reduces mortality rate to 14.3%	[13,169,187,188]
Postoperative CAR ≥ 2.83	Postoperative CAR is associated with increased risk of complications (OR = 5.540)	CAR predicts postoperative infections and organ failure (AUC = 0.767)	Moderate	Postoperative monitoring of CAR, early anti-infection and nutritional support	Short-term (≤ 30 days)	Postoperative patient	The complication rate decreased by 40% after intervention	[165,189,190]
Genetic Polymorphisms	Specific genotypes (such as IL-6 variants) are associated with exacerbated inflammatory responses	Preliminary studies suggest that gene polymorphisms influence the efficacy of anti-inflammatory therapy (further verification required)	Low to Moderate	Personalized anti-inflammatory regimen	Long-term (> 1 year)	Genetically susceptible population	Research phase, no definitive data available yet	[191,192]

IABP: Intra-aortic balloon pump; VA-ECMO: Venous-arterial extracorporeal membrane oxygenation; CABG: Coronary artery bypass graft; PCI: Percutaneous coronary intervention; CRP: C-reactive protein; CS: Cardiogenic shock; LVEF: Left ventricular ejection fraction; TnT: Troponin T; CRRT: Continuous renal replacement therapy; CAR: C-reactive protein to albumin ratio; IL: Interleukin; Hb: Hemoglobin; AMI: Acute myocardial infarction; VSR: Ventricular septal rupture; OR: Odds ratio.

Table 5 Comparison of advantages and disadvantages among different treatment strategies

Treatment method	Indications	Success rate (%)	Complications incidence (%)	Cost-effectiveness	Ref.
Percutaneous interventional closure procedure (TCC)	The condition is stable, the perforation diameter is ≤ 20 mm, and the location is away from the valve structures	73.8 (3-year survival rate)	32 (Residual shunt, mechanical hemolysis)	Moderate (requiring high-precision imaging equipment and consumables)	[20,82,193-195]
Surgical repair (combining CABG)	Perforation diameter > 20mm, multivessel disease, combined with ventricular aneurysm or valvular injury	70 (3-year survival rate)	40-52 (Postoperative infection, cardiogenic shock)	Low (The surgical costs are high, requiring long-term monitoring and care)	[98,114,165,169]
Medical conservative treatment (medication + IABP/ECMO)	Hemodynamically extremely unstable, unable to tolerate surgery or interventional therapy	38.5 (30-day survival rate)	50-60 (multiple organ failure, hemorrhage)	Low short-term costs, but high long-term expenses (requires repeated hospitalizations)	[25,165,196]
Delayed intervention closure (occurring > 3 weeks after VSR)	Myocardial edema subsides, hemodynamics stabilize, and perforated tissue becomes fibrotic	96.3 (30-day survival rate)	10-15 (Residual shunt, arrhythmia)	High (reduces the risk of secondary surgery)	[58,82,193,197]
Early intervention and occlusion (VSR occurrence ≤ 3 weeks)	Emergency rescue, unable to wait for delayed surgery	62.5 (30-day survival rate)	45-50 (Perforation enlargement, occluder displacement)	Moderate (urgent resource support required)	[193,198,199]
VA-ECMO combined with IABP support	CS, hemodynamic collapse	40 (Survival rate improvement)	25-30 (Lower limb ischemia, hemorrhage)	Low (equipment and monitoring costs are high)	[169,200,201]
Pharmacological treatment alone (diuretics + vasodilators)	Hospice care or transitional treatment	14.3 (30-day survival rate)	60-70 (Deterioration of renal function, electrolyte imbalance)	Minimum (drug cost only)	[165,202,203]
Interventional occlusion combined with PCI procedure	Single-vessel disease, late-onset VSR after PCI	91.4 (Surgical success rate)	20-25 (Stent thrombosis, residual shunt)	Moderate (requires phased implementation)	[58,194,195]
Surgical procedure combined with CABG	Multivessel disease requiring revascularization, combined with complex anatomical structures	80 (Long-term survival rate)	35-40 (Postoperative infection, stroke)	Low (surgical and rehabilitation costs compounded)	[93,169,204]
Staged interventional therapy (occlusion first followed by PCI)	Hemodynamically stable but requires revascularization	85 (1-year survival rate)	15-20 (Secondary operational risk)	Moderate (phased fee accumulation)	[195,203,205]
Palliative care (anti-heart failure medications)	Advanced age, severe comorbidities, limited life expectancy	-	-	Minimum (only basic medication costs)	[105,119,165]
IABP standalone support	Mild cardiogenic shock, transition to definitive treatment	20 (Survival rate improvement)	15-20 (Lower limb ischemia, catheter infection)	Moderate (equipment rental and monitoring costs)	[118,169,206]
Emergency surgical procedure (≤ 7 days)	Hemodynamically unstable, unable to wait for myocardial repair	57 (30-day survival rate)	50-60 (Postoperative heart failure, infection)	Low (emergency surgery costs and high risk)	[83,111,165]
Delayed surgical procedure (> 4 weeks)	Myocardial tissue stabilization, hemodynamic improvement	93.5 (30-day survival rate)	10-15 (Postoperative adhesions, arrhythmia)	High (surgical success rate improvement)	[112,173,193]
Hybrid surgery (interventional + surgical)	Complex perforations (multiple holes or serpentine tracts), residual shunts requiring secondary intervention	75 (Overall success rate)	30-35 (Multi-stage complication risks)	Low (high cost of multidisciplinary collaboration)	[10,93]
Anticoagulation therapy (heparin/warfarin)	Hypercoagulable state, embolism prevention	-	20-25 (Bleeding, thrombocytopenia)	Low (primarily drug costs)	[82,169,202,207]
Anti-inflammatory therapy (glucocorticoids)	Systemic inflammatory response, significant elevation of CRP	30 (Prognosis improvement rate)	10-15 (Risk of infection increases)	Moderate (requires monitoring of infection indicators)	[106,165,169,208]
Transcatheter thrombolytic therapy	No PCI conditions, early reperfusion requirements	50 (Recanalization rate)	30-40 (Bleeding, allergic reactions)	Low (medication costs are low, but complication treatment expenses are high)	[58,169,209]
Pericardiocentesis drainage	Massive pericardial effusion leading to cardiac tamponade	90 (Symptom remission rate)	5-10 (Puncture injury, infection)	Moderate (requires imaging guidance and aseptic operation)	[116,210]
MELD-XI Score-Guided Therapy	Risk stratification in patients with hepatic and renal dysfunction	-	-	High (optimizing resource allocation and reducing ineffective treatment)	[58,82,83]

TCC: Transcatheter Closure; CABG: Coronary artery bypass graft; IABP: Intra-aortic balloon pump; ECMO: Extraciroireal membrane oxygenation; CS: Cardiogenic shock; PCI: Percutaneous coronary intervention; VSR: Ventricular septal rupture.