Introduction

Papillary muscle rupture, ventricular septal rupture and free wall rupture complicating myocardial infarction are rare but devastating sequelae of myocardial necrosis. Although the incidence of mechanical complications has decreased owing to the development of reperfusion and adjunct medical therapies, these adverse events still go along with an exceptionally high mortality rate and constitute one of the major causes of death in the early phase after myocardial infarction. [1–6]

Most available data describing the frequency and characteristics of mechanical complications stem from the early reperfusion era evaluating fibrinolytic therapy. [1–4] The objective of the present study is to assess characteristics and outcomes of patients with a mechanical complication (MC) after ST-elevation myocardial infarction (STEMI) in a contemporary cohort of consecutive patients in the era of primary percutaneous coronary intervention.

Methods

Results

A total of 2508 patients were admitted to Bern University Hospital, Switzerland with STEMI between March 9, 2009 and June 30, 2014. Twenty-six (1.1%) of these patients suffered a mechanical complication (MC). During 1-year follow, two patients were lost to follow-up in the MC, and 107 in the no-MC group (Fig 1).

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Fig 1. Study flowchart.

2508 patients with ST-elevation myocardial infarction (STEMI) admitted for percutaneous coronary intervention at the University Hospital Bern between March 9, 2009 and June 30, 2014. 26 suffered a mechanical complication. STEMI, ST-elevation myocardial infarction; VSD, ventricular septal defect; VFWR, ventricular free wall rupture; PMR, papillary muscle rupture; * first patient lost to follow-up at day 26, second one at day 358; ^† regarding non-lethal clinical endpoints.

https://doi.org/10.1371/journal.pone.0209502.g001

Patients suffering a MC had a mean age of 74.5 years and were approximately ten years older than those without MC (Table 1). The proportion of women (42.3% versus 23.3%, p = 0.034) as well as the proportion of patients with renal failure on admission (66.7% versus 18.7%, p <0.001) was significantly higher in the MC group compared to the no-MC group. Left ventricular ejection fraction was slightly reduced in both groups (Table 1). Patients in the MC group frequently suffered from anemia (48%) or thrombocytopenia (20.8%) upon presentation. The majority of patients admitted with a MC (73.1%) were in cardiogenic shock (Killip class IV), whereas most patients (71.9%) without MC presented without signs of heart failure (Killip class I) (Table 1).

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Table 1. Baseline characteristics.

https://doi.org/10.1371/journal.pone.0209502.t001

In 50% of the patients with a MC PCI was not attempted or not completed (Table 2). In the MC group the time from symptom onset to balloon inflation or diagnostic angiography amounted to more than 24 hours in 42.3%, and only two patients (7.7%) underwent PCI within 6 hours, whereas almost half (48.2%) of the STEMI patients without mechanical complication were treated within 6 hours of symptom onset (Table 2). Only two patients had a history of PCI or CABG, for the remaining the STEMI leading to the MC was the first manifestation of coronary artery disease (Table 1). The right coronary artery was the most frequent culprit vessel in MC patients (13 (50%)), and multivessel disease was present in 77% (S1 Table). There was a significant difference in the proportion of patients with TIMI flow 0 or I between the MC group (82.4%) and the no-MC group (52.4%) (p = 0.014). At the end of coronary angiography TIMI flow III was documented in 82.4% of the culprit lesions in the MC group and achieved in 94.7% in STEMI patients without mechanical complications (Table 2). Circulatory support by means of intra-aortic balloon counter-pulsation (53.8% versus 4.6%, p < 0.001) or continuous vasopressor infusion (61.5% versus 9%, p < 0.001) was more frequently used in patients with MC compared to those without. Almost all patients with STEMI received a loading dose of a P2Y12 inhibitor (97.6%), whereas GPIIb/IIIa inhibitor use differed between groups (7.7% in the MC versus 22.6% in the no-MC group (Table 2)).

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Table 2. Coronary angiography: Lesion and procedural characteristics.

https://doi.org/10.1371/journal.pone.0209502.t002

Ventricular septal ruptures (VSR), two in combination with free wall rupture, accounted for the most frequent type of mechanical complication (17 of 26) in our cohort (Table 3). Seven of these patients were treated conservatively and died (median time to death: 0 days, IQR: 0–1 days). In six VSR patients an occluder device was implanted; three of them died within days due to residual shunt and persistent cardiogenic shock and the remaining three required surgical reconstruction. Overall, seven VSR patients underwent cardiac surgery; all but two survived beyond 30 days.

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Table 3. Mechanical complications: Management and 30-day mortality.

https://doi.org/10.1371/journal.pone.0209502.t003

The two patients with isolated ventricular free wall rupture (VFWR) underwent emergency surgery; one of them died within 30 days. Two patients with VSR and additional VFWR succumbed to their mechanical complication on the day of admission. All five patients with papillary muscle rupture (PMR) underwent surgical mitral valve replacement and survived.

If a MC was managed surgically, the surgery was generally conducted promptly after diagnosis of the MC (median time to surgery: 0.5 days (IQR 0–1 day)). Overall 30-day mortality in the MC group amounted to 58%, in the no-MC group to 7%. The ratio contrasting the hazard rate of death at 30 days in the MC to the no-MC group amounted to 11.86 (95%-confidence interval (95%-CI): 6.99–20.13, p <0.001)) (Fig 2). Associations between patient characteristics and mortality based on univariate Cox regression analysis in the total STEMI cohort are presented in S2 Table. None of the MC patients, for whom complete follow-up data was available and who survived beyond 30 days, died up to one-year follow-up. Two of the MC patients experienced a stroke during the one-year follow-up period (HR comparing MC to no-MC: 14.14, 95% CI 3.32–60.29).

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Fig 2. Survival curves.

Depicted are survival curves for all-cause mortality based on the product-limit estimator comparing patients with and patients without a mechanical complication in the context of an ST-elevation myocardial infarction.

https://doi.org/10.1371/journal.pone.0209502.g002

Discussion

In the present cohort study approximately one percent of the patients admitted with a STEMI suffered a MC. Patients with MC were older and more likely to be females as compared to STEMI patients without MC. Many of the MC patients sought delayed medical attention, almost half with a latency of more than 24 hours between symptom onset and angiography. Only two patients had a history of PCI or CABG; for the remaining patients, the STEMI leading to the MC was the first manifestation of coronary artery disease. At presentation three out of four patients were in cardiogenic shock. Patients with MC showed more lesions with TIMI 0 or I flow than patients without mechanical complications. Nine patients with ventricular septal rupture, two of them with additional VFWR, were conservatively treated due to futility and died. All three VSR patients, in whom an occluder device was implanted as definite treatment, died within 30 days. The remaining patients with VSR, VFWR and PMR were surgically treated and had 30-day mortality rates of 29%, 50% and 0%, respectively.

The incidence of mechanical complications observed in our cohort of patients admitted due to STEMI is in line with rates previously reported among patients undergoing primary percutaneous coronary intervention; [5–10] however, in contrast to our cohort, populations of these previous studies were largely restricted to patients, who presented within 24 hours of symptom onset.[5, 6, 8] Older age and female sex were associated with the occurrence of mechanical complications after myocardial infarction in previous studies conducted during the thrombolytic and the PCI era.[6, 10–15] The higher percentage of lesions with TIMI 0 or I flow observed in MC patients compared with no-MC patients may reflect the higher risk of developing a mechanical complication in the setting of a transmural infarction.[8, 9] A prolonged latency between symptom onset and hospitalization has been reported to be associated with the occurrence of MC in several studies conducted in the pre-primary PCI era; [16–18] our study supports the continual validity of this association.[10]

The introduction of reperfusion therapies, first thrombolysis, then percutaneous coronary intervention, has considerably decreased mortality after STEMI and the incidence of MC [1, 6, 8, 14, 19]; however, due to the nature of mechanical complications, mortality rates continue to be very high once such a complication develops. [1, 8, 15, 19, 20] This has been substantiated in a recent retrospective study from Spain, which assessed the temporal trends in incidence and outcomes of MC in elderly STEMI patients between 1988 and 2008.[19] Despite a decrease in overall in-hospital mortality rates (from 34.3% to 13.4%) as well as a reduction in the incidence of MC (from 11.1% to 4.3%) over the 30-year observation period, there was neither a significant decline in the proportion of deaths due to MC among all deaths (28.1% to 24.5%), nor the hospital fatality rate of patients suffering a MC (from 87.1% to 82.4%).[19]

Of note is that the proportion of patients undergoing surgical repair in the same study decreased from 45.2% to 17.6% (p = 0.04), with no differences in post-operative survival (28.6% to 33.3%; p = 0.74).[19] In a recent large-scale US study based on administrative data encompassing more than 10,000 patients with VSDs complicating STEMI between 2001 and 2013, the proportion of patients with an attempted corrective procedure was even lower (7.65%); post-procedural mortality rates were high (45.8% after surgery, 76.3% after minimal invasive interventions), particularly in relation to the reported overall in-hospital mortality rate of 30.5%.[15]

Nevertheless, public awareness campaigns to prevent long delays between symptom onset and medical presentation may help to lower the incidence of mechanical complications after myocardial infarction, and rapid echocardiographic evaluation of patients with signs of hemodynamic compromise or cardiac murmurs as well as mechanical circulatory support and subsequent surgical management may increase the chance of survival for individual patients with a MC. [9, 21–24]

The limitations of this study are related to its observational nature, which inherently bears the risk for selection and information biases. Findings of this study only allow inference with regard to STEMI patients surviving until hospital admission; however, a considerable proportion of mechanical complications may occur before presentation or after discharge and, in particular FWR, may lead to immediate death, which precludes identification of the underlying cause in the absence of an autopsy.[11, 25] Survivor bias also limits interpretation of differences in mortality observed in patients treated conservatively, interventionally or surgically. Finally, an assessment of the independent effect of mechanical complications on mortality or a sophisticated statistical evaluation of predictors of mortality within the MC group was precluded by the low event rate.

In this retrospective cohort study conducted in the PCI era, the incidence of mechanical complications after STEMI was low and associated with older age, female sex, and a prolonged latency period between symptom onset and angiography. Overall mortality of MC was high and only MC patients selected to undergo cardiac surgery had a chance of survival, in particular if suffering from papillary muscle rupture.

Supporting information