Blow-Out Cardiac Rupture Caused by Takotsubo Syndrome

Abstract

Background

Takotsubo syndrome (TTS) is generally considered a benign condition characterized by transient left ventricular (LV) dysfunction. However, a subset of patients may develop life-threatening complications such as blow-out cardiac rupture.

Case Summary

A 79-year-old woman presented with chest discomfort following a fall and was found to have ST-segment elevation, elevated cardiac biomarkers, and apical akinesis with basal hyperkinesis on echocardiography. Coronary angiography revealed no obstructive lesions, confirming the diagnosis of TTS. Despite stable hemodynamics, she suffered sudden cardiac arrest on day 4. Autopsy revealed LV apical rupture with transmural myocyte loss, contraction band necrosis, interstitial edema, and macrophage infiltration, while the basal segments appeared histologically intact.

Discussion

This case underscores the importance of recognizing high-risk features—such as advanced age, female sex, and persistent ST elevation—for early recognition of TTS patients vulnerable to cardiac rupture. Autopsy-based pathological evaluation continues to provide valuable insights into the underlying mechanisms of TTS.

Central Illustration

History of Presentation

A 79-year-old woman was referred to the orthopedic department of our hospital with restricted mobility due to bilateral knee pain following a fall down the stairs 2 days before admission. No preceding febrile or suspected viral illnesses were observed. On the day of the presentation, she also developed chest discomfort. Upon admission, her vital signs were as follows: heart rate, 83 beats/min; blood pressure, 109/70 mm Hg; body temperature, 36.9°C; and oxygen saturation, 98% on ambient air. Cardiac and respiratory examinations were unremarkable. Laboratory tests revealed elevated inflammatory markers (white blood cell count, 10,300/μL; C-reactive protein level, 11.6 mg/dL) and cardiac biomarkers (creatine-kinase level MB, 40.8 ng/mL; high-sensitivity troponin I level, 9,508 pg/mL; B-type natriuretic peptide level, 687 pg/mL). Chest radiography demonstrated cardiomegaly (cardiothoracic ratio, 60%) with mild pulmonary congestion. A 12-lead electrocardiogram (ECG) showed sinus rhythm with ST-segment elevation in multiple leads, including I, Ⅱ, aVL, aVF, and V₂ to V₆ with prolonged QTc interval (Figure 1A). Transthoracic echocardiography (TTE) revealed akinesis of the left ventricular (LV) apex with hyperkinesis of the basal segments. The LV was not dilated (diastolic and systolic dimensions: 41.8 mm and 33.5 mm, respectively), and the interventricular septal and posterior wall thickness measured 9.5 mm and 9.8 mm, respectively. The LV ejection fraction was reduced to 42%. No pericardial effusion was noted at this point (Figures 2A and 2B). Given the ST-segment elevation, acute coronary syndrome (ACS) was suspected, and the patient was referred to the cardiology department.

Take-Home Messages

• •While cardiac rupture is a rare complication of TTS, increased clinical vigilance may aid in the early detection of high-risk patients.
• •Clinicians should be aware of established risk factors, including female sex, advanced age, ST-segment elevation in the inferior leads, and the absence of T-wave inversion in the lateral leads.
• •Pathological evidence from autopsy cases offers critical perspectives that help bridge this gap in understanding the pathogenesis of TTS.

Figure 1.

Serial Changes of 12-Lead ECG Findings During Hospitalization

(A) The 12-lead ECG on admission (day 0) showed sinus rhythm with ST-segment elevation in leads I, II, aVL, aVF, and V₂ to V₆, along with a prolonged QTc interval (494 ms). Serial ECGs obtained on day 0 (A), day 1 (B), day 2 (C), and day 3 (D) continued to demonstrate ST-segment elevation in I, Ⅱ, aVL, aVF, and V₂ to V₆, although the elevations slightly attenuated over time. ECG = electrocardiogram; QTc = heart rate–corrected QT interval.

Figure 2.

Findings From TTE, CAG, and LVG on Admission

(A and B) Parasternal long-axis views on TTE during diastole (A) and systole (B) revealed akinesis of the LV apex with hyperkinesis of the basal segments. No pericardial effusion was observed. (C and D) CAG demonstrated no significant stenosis in the right (C) or left (D) coronary arteries. (E and F) LVG images (LAO view) during diastole (E) and systole (F) show the LV cavity outlined by a white dotted line. Akinesis of the mid-to-apical segments with preserved basal hyperkinesis was noted. CAG = coronary angiography; LV = left ventricle; LVG = left ventriculography; TTE = transthoracic echocardiography.

Past Medical History

The patient had a 10-year history of hypertension and was taking a calcium channel blocker (amlodipine 5 mg once daily).

Differential Diagnosis

The differential diagnosis included ACS, Takotsubo syndrome (TTS), acute myocarditis, and coronary spastic angina.

Investigations

Emergency cardiac catheterization was performed to evaluate for ACS. Coronary angiography revealed no significant stenosis or occlusion of the coronary arteries (Figures 2C and 2D). Left ventriculography demonstrated the classic ballooning pattern—akinesis of the mid-to-apical segments with preserved basal hyperkinesis (Figures 2E to 2F)—consistent with TTS. LV end-systolic and end-diastolic pressures were 112 and 14 mm Hg, respectively. No significant pressure gradient was detected in the LV outflow tract. In the absence of obstructive coronary disease and based on the characteristic wall motion abnormality, a diagnosis of TTS was made.

Management

The patient was managed in a high-care unit for close monitoring of TTS-related complications. On admission, hypokalemia was noted (serum potassium level, 3.4 mEq/L), and potassium supplementation was initiated to mitigate the risk of life-threatening ventricular arrhythmias. Due to oliguria (200 mL/day), intravenous furosemide (40 mg/day) was administered on hospital day 2. Overall, the patient's vital signs remained stable, and neither oxygen therapy nor vasopressor support was required. On day 3, follow-up TTE was performed to evaluate LV thrombus. Although no thrombus was identified, a smoke-like echo suggestive of blood stasis was observed. Intravenous anticoagulation with unfractionated heparin was initiated at 1,500 U/h and subsequently increased to 2,000 U/h based on activated partial thromboplastin time (APTT) monitoring. At midnight on day 3, the APTT was 24.8 seconds, prompting an increase in the heparin dose to 3,000 U/h. The 12-lead ECG continued to show ST-segment elevation, though slightly attenuated (Figures 1A to 1D).

On day 4, the patient experienced sudden cardiopulmonary arrest. Resuscitation was immediately initiated. Bedside TTE revealed a large pericardial effusion, raising concern for cardiac tamponade. Emergent pericardiocentesis was performed, and blood was aspirated from the pericardial space. Despite these efforts, pulseless electrical activity persisted, and resuscitation was unsuccessful. The patient was pronounced dead. An autopsy was performed with the consent of her family.

Autopsy Findings

Gross examination revealed a rupture at the apical region of the LV (Figures 3A to 3C), with approximately 170 mL of blood in the pericardial cavity. Pathologic observation demonstrated transmural myocyte loss, degeneration, and atrophy, accompanied by marked inflammation and interstitial edema in the mid-to-apical LV segments, most pronounced at the rupture site. In contrast, the basal LV segments showed little evidence of myocardial injury. The average diameter of myocytes in the apical region was 12.85 μm (11.18–15.80), while that in the basal region was 19.20 μm (16.40–20.63) (P < 0.001) (Figures 3D to 3I). No thrombotic occlusions or significant stenosis were found in epicardial coronary arteries or intramyocardial microvessels. Myocardial interstitial fibrosis was minimal in both apical and basal regions (Figures 4A and 4B). Immunohistochemistry revealed prominent infiltration of CD68⁺ and CD163⁺ macrophages surrounding damaged myocytes in the apical region. Aggregates of lymphocytes, neutrophils, eosinophils, or multinucleated giant cells were rarely observed (Figures 4C to 4F). These findings, which show myocardial necrosis with inflammation—including granulation tissue—that is regional but unrelated to coronary territories, support the idea that the condition aligns more with the subacute phase of TTS rather than myocarditis or myocardial infarction. Based on the clinical course and autopsy findings, blow-out cardiac rupture secondary to TTS was diagnosed as the cause of death.

Figure 3.

Pathologic Findings of the Autopsied Heart

(A) Gross examination revealed a rupture site at the apical lateral region of the LV, indicated by yellow arrowheads. Approximately 170 mL of blood was found in the pericardial cavity. (B and C) Gross transverse sections of the heart at the basal (upper section in B) and apical (lower section in B) levels. A high-power magnification view of the white rectangular area in (B) is shown in (C). Yellow arrowheads indicate the rupture site in the apicolateral region. (D to F) Microscopic images (H&E staining) of the areas outlined by white rectangles in (B and C). A fresh thrombus (Th) is visible near the rupture site in the LV apex. (G to I) High-power views of the black rectangular fields in (D to F), respectively. Marked myocyte loss, degeneration, and atrophy, along with prominent interstitial edema, are evident in the apical region, particularly at the rupture site (D and E, G and H). In contrast, the basal LV segments (F and I) show minimal histological evidence of myocardial injury. The average myocyte diameter in the apical region was 12.85 μm (11.18–15.80), compared to 19.20 μm (16.40–20.63) in the basal region (P < 0.001 by Mann-Whitney test, n = 30 in each region). No thrombotic occlusions were identified in the epicardial coronary arteries or intramyocardial microvessels. Black scale bars represent 500 μm in (D to F) and 100 μm in (G to I), respectively. H&E = hematoxylin and eosin; LV = left ventricle.

Figure 4.

Microscopic Findings of the Apical Area Near the LV Rupture Site

Representative high-power images of the LV apex are shown H&E (A), MT staining (B), and immunohistochemistry for CD3 (C), CD68 (D), CD163 (E), and CD79a (F). Atrophic and lost myocytes, interstitial edema, and infiltration of inflammatory cells were observed. Myocardial interstitial fibrosis was minimal. Immunohistochemistry revealed prominent infiltration of CD68⁺ (D) and CD163⁺ macrophages (E) surrounding damaged myocytes. Only minimal aggregation of T and B lymphocytes was detected (C and F). Black bars represent 100 μm. CD = cluster of differentiation; H&E = hematoxylin and eosin; LV = left ventricle; MT = Masson trichrome.

Discussion

This report presents a rare case of blow-out cardiac rupture as a complication of TTS with detailed histopathological correlation.

While TTS is typically considered benign with transient LV dysfunction in the absence of significant obstructive coronary artery disease, a subset of patients may experience serious complications. Among these, cardiac rupture is particularly rare—with an incidence of <1%—yet it carries a high mortality rate, ranging from 64% to 83%.^1,2 Recent review articles have summarized the clinical characteristics of TTS cases complicated by cardiac rupture.^1,2 Reported risk factors include female sex, advanced age, ST-segment elevation in the inferior leads, and the absence of T-wave inversion (ie, persistent ST-segment elevation) in the lateral leads²—all of which were present in the current case. Notably, the persistent ST elevation was particularly prominent (Figure 1). These findings underscore the importance of close clinical monitoring and vigilant in-hospital follow-up in high-risk TTS patients, as opposed to those with typical, uncomplicated presentations. Clinicians should be aware of these risk features to aid in the early detection of patients at increased risk for rupture.

The characteristic histopathological findings of TTS include reversible changes: contraction band necrosis, interstitial edema, and minimal inflammatory cell infiltration.³ In contrast, myocyte necrosis, considered an irreversible change, is widespread along with inflammation in severe cases. The literature review identified histopathological findings from 14 reported cases of TTS with cardiac rupture (Table 1), consistently showing extensive myocyte necrosis and inflammatory infiltrates composed of mononuclear and/or polymorphonuclear cells. The inflammatory pattern varies by phase; inflammatory cells seen in the acute phase of TTS are usually neutrophils and mononuclear cells, while in the subacute phase, macrophages are the primary cells with fewer lymphocytes. Although there is an inherent observational bias (ie, autopsy specimens allow comprehensive examination of the entire heart, whereas endomyocardial biopsies provide only limited sampling), ruptured TTS cases appear to exhibit more prominent myocyte necrosis and inflammatory cell infiltration compared to nonruptured cases. In our case, the striking regional differences between apical and basal segments reflect the characteristic wall motion abnormalities of TTS, with severe pathological changes concentrated in the akinetic apical region.

Table 1.

List of Pathologic Reports for Cases of Cardiac Rupture due to TTS

Patient #	Age, y	Sex	12-Lead ECG	TTE or LVG	Autopsy or Surgical Sample	Description of Pathological Findings	Time from IS of TTS to CR	Site of CR	Country	PMID
1	79	Female	STE in I, aVL, V1 to V5, STD in III, aVF, Q in V1 to V4	Apex akinesis	Autopsy	MN and inflammatory infiltrates	7 d	Apical LV AW	Japan	15849453
2	81	Female	STE in I, aVL, V2 to V6	Akinesis in midapex with hyperkinetic in basal wall	Autopsy	Transmural myocardial necrosis with Hem at CR site. Foci of coagulation and CBN with mononuclear lymphocyte infiltrations in other regions	5 d	Apical LV FW	Poland	17527000
3	73	Female	STE in V2 to V5	Akinesis in midapex with hyperkinetic in basal wall	Surgical	Myocardial necrosis	>16 d	Apical septum	Japan	18724037
4	74	Female	STE in I, aVL, V3 to V6	Akinesis in midapex with hyperkinetic in basal wall	Autopsy	Inflammatory cell infiltrations, interstitial fibrosis, Hem, and coagulation necrosis. No evidence of CBN	10 d	Apical LV AW	Japan	30532808
5	82	Female	STE in V1 to V5	Apical ballooning pattern	Autopsy	Hypertrophied and disarrayed myocytes surrounded by mononuclear inflammatory infiltration, loose connective tissue, and Hem	5 d	LV apex	Poland	22416075
6	62	Female	STE in I, II, V5 to V6	Akinesis in midapex with normokinetic in basal wall	Autopsy	MN along with polymorphonuclear cell infiltration and bundles of wavy myocardial fibers	2 d	Mid-LV PW	USA	22673027
7	70	Female	NA	NA	Autopsy	Diffuse coagulative MN with a number of CBN. Severe mixed inflammatory infiltration of Lym and Neut	1 d	LV apex	Italy	26363635
8	73	Male	Neg T in V2 to V5, Q in III aVF	Apical ballooning pattern	Surgical	Localized interstitial fibrosis with inflammatory cell infiltration and hemosiderin deposition	8 d	Apical septum	Japan	26632246
9	82	Female	NA	Normal LV function. Dilated and diffusely hypokinetic RV	Autopsy	Epicardial Hem and CBN with heavy polymorphonuclear leukocyte infiltrates	>3 d	Basal RV FW	Canada	28396614
10	73	Female	STE in V2 to V6, Q in V1 to V4	Akinesis in midapex with normokinetic in basal wall	Surgical	Disrupted myocytic integrity in multiple foci with lymphohistiocytic infiltrate and MN	5 d	Septum and RV FW	Korea	27873520
11	77	Female	STE in I, aVL, V2 to V6	Apical ballooning pattern with MR	Autopsy	Hem foci and Neut infiltration between the cardiac myocytes associated with hyper eosinophilic CBN	1 d	LV apex	USA	30116453
12	71	Female	STE in I, aVL, V2 to V5	Akinesis in midapex with hyperkinetic in basal wall	Surgical	Loss of myocytes and fibrosis with Lym and macrophages infiltration	9 d	Apical septum	Japan	29434120
13	75	Female	STE in V2 to V3, poor R and Q in V1 to V3	Akinesis in midapex with hyperkinetic in basal wall	Autopsy	CBN and Neut infiltration	1 d	Apical LV AW	USA	31428481
14	23	Female	STE in V5 and V6, STD in V1 and V2	Mid LV systolic dysfunction	Autopsy	Inflammatory infiltrates, MN, and subacute subendocardial Hem	>1 d	Mid-LV AW	USA	28802178

AW = anterior wall; CBN = contraction band necrosis; CR = cardiac rupture; ECG = electrocardiogram; FW = free wall; Hem = hemorrhage; IS = initial symptom; LVG = left ventriculography; Lym = lymphocytes; MN = myocyte necrosis; Neut = neutrophils; PW = posterior wall; STD = ST-segment depression; STE = ST-segment elevation; TTE = transthoracic echocardiography.

A literature search was conducted using PubMed to identify relevant cases.

Distinguishing TTS from acute myocarditis can be challenging. Although the 2 entities have distinct pathophysiological mechanisms—TTS is typically triggered by a catecholamine surge, whereas myocarditis results from infectious or immune-mediated injury—several case reports have described diagnostic confusion between the 2.^4,5 In the present case, pathological findings in the LV apex met the classic Dallas criteria for myocarditis, including myocyte necrosis and inflammatory cell infiltration. However, several observations support a diagnosis more consistent with TTS: 1) there was no history of preceding febrile or suspected viral symptoms; 2) the contralateral apical region to the rupture site exhibited extensive myocyte atrophy and some extent of necrosis with relatively less lymphocyte infiltration; 3) immunohistochemical analysis demonstrated abundant CD68⁺ and CD163⁺ macrophage infiltration at the rupture site, with only sparse CD3⁺ lymphocytes, suggesting that the macrophages had accumulated primarily for the clearance of necrotic myocytes due to catecholamine-mediated injury; and 4) the cardiomyocytes in the basal segments showed neither atrophy nor inflammatory cell infiltration (Figures 3 and 4). Taken together, these findings are consistent with the diagnosis of subacute phase TTS rather than myocarditis.

Conclusions

Although cardiac rupture is an uncommon complication of TTS, heightened clinical awareness may facilitate early identification of patients at elevated risk for this life-threatening event. While the mechanisms underlying TTS remain incompletely understood, accumulating pathological evidence from autopsy cases provides valuable insights into its pathogenesis, offering perspectives that cannot be fully captured by conventional clinical imaging modalities.

Funding Support and Author Disclosures

This study was supported by the Hamamatsu University School of Medicine Grant-in-Aid. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.