Severe aortic stenosis is common among elderly patients with a prevalence of 3.4% and associated with acute heart failure [1, 2, 3], cardiogenic shock and death . In high-risk patients mortality without aortic valve replacement is around 50% within one year . Due to the development of transcatheter aortic valve replacement (TAVR), more patients are nowadays eligible for aortic valve replacement . TAVR interventions have been increasing continuously over the last years, with a similar in-hospital mortality compared to surgical aortic valve replacement (SAVR) after excluding emergencies and favourable long-time outcomes [7, 8, 9].
Initially only recommended for elderly and inoperable patients, rates of death, stroke and re-hospitalizations were seen to be lower for TAVR compared to SAVR in the PARTNER 3 trial of patients with low risk and a mean age of 73 years . Nevertheless, SAVR remains an important alternative option with good long-term results for younger patients at low operative risk and in cases where TAVR is unfavourable due to anatomic reasons [10, 11].
Patients with critical stenosis may present as an emergency with a beginning cardiogenic shock or multiple organ failure . In these cases the operative risk for SAVR is increased and patients are often inoperable . Accordingly, the first TAVR in men was performed by Alain Cribier in an emergency patient, who was rejected for SAVR . Minimal invasive procedures, e. g. transcatheter aortic valve replacement (TAVR) and balloon valvuloplasty (BV) offer alternative treatment options in these unstable and endangered patients . BV might be used as bridge-to-replacement or as destination therapy (BV only) . However, BV only has been associated with high restenosis rates and increased mortality [5, 17, 18]. Therefore, the relevance of BV only as a destination therapy declines. Nevertheless, some BV only may be performed for palliative indications or in emergencies, where a TAVR or SAVR is not possible due to anatomic reasons or availability of TAVR or SAVR e.g. in certain smaller hospitals [19, 20]. Emergency situations in particular make it difficult to decide on one of the three different treatments.
To our knowledge no registry studies evaluating larger numbers of symptomatic patients with emergency interventions such as TAVR, SAVR, or BV only have been performed yet. We therefore analysed clinical characteristics, comorbidities and outcomes of all three treatment options in acutely admitted patients undergoing interventions in a large nationwide cohort from Germany in order to provide more evidence for treatment of acute admitted cases with aortic valve stenosis.
Since 2005, data on all hospitalizations in Germany have been available for scientific use via the Diagnosis Related Groups (DRG) statistics collected by the Research Data Center of the Federal Bureau of Statistics (DESTATIS). These data include diagnoses and procedures of nationwide in-hospital treatment of patients, reimbursed according to the DRG system. From this database we extracted data on all BV only, TAVR or SAVR procedures that were conducted among symptomatic patients with severe aortic valve stenosis, classified as acutely admitted admissions according to the DRG system (occasion of admission: emergency ‘aufn_anl N’). BV only, TAVR or SAVR procedures were defined including the respective procedures (OPS code 8837a0, 535a0, 53510) but excluding concomitant procedures (coronary artery bypass grafting, tricuspid valve or mitral valve replacement as defined by Reinöhl et al. ). For the BV only group, a TAVR or SAVR procedure within the same hospital stay were excluded.
Our study did not involve direct access to data on individual patients by the investigators but only access to summary results provided by the Research Data Center. Therefore, approval by an ethics committee and informed consent were not required, in accordance with German law. All summary results were anonymized by DESTATIS. In practice, this means that any information allowing the drawing of conclusions regarding a single patient or a specific hospital is censored by DESTATIS to guarantee data protection. Especially the use of the anonymous and persistent ‘institute indicator of hospitals’ is restricted in order not to publish any information directly attributable to a single hospital.
Continuous variables are reported as means ± standard deviations (SD) and frequencies were presented with percentages. Time trends were calculated using linear regression models.
In order to determine the impact of different procedures on the outcomes, multivariable logistic or linear regression analyses were carried out. A total of 21 baseline patient characteristics were included as potential confounders (all covariates listed in Table 1). In order to account for the correlation of error terms of patients treated in the same hospital, a random intercept was added at the centre level. All analyses were carried out using Stata 16.0 (StataCorp, College Station, Texas, USA).
|Patients treated with SAVR
(n = 1873)
|Patients treated with TAVR
(n = 8184)
|Patients treated with balloon valvuloplasty
(n = 970)
SAVR vs. TAVR
SAVR vs. BV
TAVR vs. BV
|Age, years ± SD||66.9 ± 10.8||81.3 ± 6.6||81.3 ± 7.0||<0.001||<0.001||1.000|
|In-hospital mortality, %||3.5||5.1||20.7||0.002||<0.001||<0.001|
|Reimbursement, mean ± SD||23.127€ ± 16.888€||34.781€ ± 11.096€||31.378€ ± 22.350€||<0.001||<0.001||<0.001|
|Cardiogenic shock, %||4.8||4.6||22.2||0.752||<0.001||<0.001|
|EuroSCORE||9.4 ± 7.5||24.4 ± 14.2||23.2 ± 13.9||<0.001||<0.001||0.013|
|NYHA class II, %||10.3||7.7||5.6||<0.001||<0.001||0.018|
|NYHA class III or IV, %||35.5||55.8||65.6||<0.001||<0.001||<0.001|
|Coronary artery disease, %||22.0||52.2||91.8||<0.001||<0.001||<0.001|
|Previous myocardial infarction <4 months, %||0.6%||1.9%||1.3%||<0.001||0.058||0.191|
|Previous myocardial infarction <1 year, %||0.2||0.8||0.9||0.007||0.007||0.629|
|previous myocardial infarction >1 y, %||2.5||5.5||4.2||<0.001||0.012||0.094|
|Previous CABG, %||2.0||11.2||5.9||<0.001||<0.001||<0.001|
|Previous cardiac surgery, %||5.3||17.2||10.3||<0.001||<0.001||<0.001|
|Carotid disease, %||4.6||6.3||6.2||0.004||0.068||0.862|
|Pulmonary hypertension, %||13.6||25.8||23.5||<0.001||<0.001||0.115|
|Severe renal insufficiency (GFR <15 ml/min), %||1.8||3.4||4.4||<0.001||<0.001||0.106|
|Renal insufficiency (GFR <30 ml/min), %||1.8||6.3||7.8||<0.001||<0.001||0.065|
|Atrial fibrillation, %||41.0||50.7||47.3||<0.001||0.001||0.048|
|Diabetes mellitus, %||24.6||33.8||36.6||<0.001||<0.001||0.078|
The results were provided by the German Data Research Center. The aim of the collaboration of DESTATIS with public research institutes is to give the possibility to assess medical treatment in clinical practice in a nationwide cohort. Therefore, the collaboration is a tool for researchers to investigate clinical important problems, beyond that it serves as a quality control for public health.
We analysed characteristics and outcomes of 11,027 patients acutely admitted who underwent procedures in Germany for severe symptomatic aortic valve stenosis between 2014 and 2018. Over this time, 1,873 patients were treated with SAVR, 8,184 patients with TAVR and 970 patients with BV only (Table 1).
Figure 1 reflects the number of emergency patients treated with SAVR, TAVR or BV only in Germany from 2014 until 2018. There was an increase in TAVR interventions (1,294 to 1,827, p = 0.014) and for BV only interventions (170 to 233, p = 0.054) per year. However, surgical aortic valve replacements decreased from 426 to 316 (p = 0.009).
Baseline characteristics are shown in Table 1. Patients treated with TAVR or BV only were substantially older than patients treated with SAVR (81.3 versus 66.9 years). They also had a higher EuroSCORE and more often fell into NYHA class III or IV than patients with SAVR. Nearly 50% of TAVR and BV only patients were women, in comparison to 31.2% of the SAVR group. TAVR patients had significantly more comorbidities than SAVR patients (see Table 1).
Table 1 shows the outcomes of patients undergoing emergency treatment strategies for acute symptomatic aortic valve stenosis. Patients treated with BV only had the highest mortality rate (20.9%) while patients treated with TAVR were associated with the highest reimbursement (€34,781) without risk-adjustment.
After risk adjustment, substantial differences were found for in-hospital mortality and reimbursement. In comparison to BV only, SAVR (OR 0.26 [96% CI 0.16; 0.45], p < 0.001) and TAVR (OR 0.38 [0.29; 0.49], p < 0.001) were associated substantially lower risk for in-hospital mortality (Figure 2). At the same time, the procedure-related increases in reimbursement are moderate. Compared to BV only, hospitalization costs of patients undergoing SAVR are reduced by €5,578 ([95% CI €8,023; €3,133], p < 0.001), despite the resource-intensive surgical procedure. TAVR procedures are associated with higher hospitalization costs (€4,143 [€2,330; €5,926], p < 0.001) (Figure 3).
To our knowledge, this is the first large registry study of acutely admitted patients undergoing emergency treatment strategies with SAVR, TAVR or BV only for severe aortic valve stenosis.
Our results expand the recently published study of Gaede et al. by comparing BV only therapy to TAVR and SAVR in patients with urgent need for treatment and analysing the costs of all three procedures . BV only was associated with a substantially increased risk of in-hospital mortality. TAVR procedures for acutely admitted patients are increasing with similar outcome risks compared to SAVR and therefore promising for inoperable patients.
Patients with severe aortic valve stenosis who were admitted to the hospital acutely were mostly elderly patients at increased operative risk. This confirms the scientific consensus that even in emergency settings severe aortic valve stenosis is mainly a disease of elderly patients .
In accordance with several nationwide registries [23, 24], we also observed a trend towards more TAVR than SAVR procedures, but with an additional reference to emergency admissions with severe aortic valve stenosis from 2014 until 2018. Interestingly, despite a widely described high complication rate of BV only [5, 17, 18], the number of BV only procedures increased even within the TAVR era in Germany. Of note, we included only cases into the BV only group, which did not receive TAVR or SAVR. The unfavourable in-hospital outcomes of BV only were confirmed in the present analysis.
Since reasons of treatment decisions are not documented, we can only speculate, why an aortic valve replacement was declined. Some BV only could have resulted from palliative indications and the increase of BV only could also be the result of increasing experience in transcatheter procedures , which even led to an increased use of similar techniques such as BV. Moreover, in some emergencies TAVR or SAVR may not have been possible due to anatomic reasons. Another cause may be restrictions in the availability of TAVR or SAVR. Hospitals without a department of cardiac surgery or low volume are not allowed to perform TAVR in Germany. In these smaller hospitals, BV only may be used as a rescue therapy [19, 20]. However, even if some patients are referred for definitive replacement the mortality after BV only is still high.
Procedures for acutely admitted patients with symptomatic and severe aortic valve stenosis are challenging and Bongiovanni and his colleagues already reported a 30-day cardiovascular mortality rate of 23.8% for TAVR and 33.0% for BV . In our own cohort, the mortality after SAVR was 3.5%, after TAVR 5.1%, and after BV only 20.7%. In comparison to both aortic valve replacement therapies, BV only patients had the worst outcomes in terms of in-hospital mortality even after risk adjustment. However, it is necessary to mention that these patients were sickest and there is likely a lot of residual confounding which cannot be completely covered by our registry study. A poor left ventricular function, advanced comorbidities and significant frailty could therefore lead to BV as a diagnostic tool to assess ‘therapeutic response’ instead of TAVR or SAVR, but also to symptom palliation in the context of cardiogenic shock . Our results are in line with a report of Ben-Dor et al. who found a worse long-term survival in patients undergoing BV only compared to those who had BV to bridge for TAVR or SAVR . High complication and restenosis rates have already been described for BV, but its method has improved and it still has a role as a bridging strategy to TAVR or SAVR . Even though we are unable to tell if BV only patients might have benefited from bridging to valve replacement, we can provide evidence that BV only without definitive valve replacement is associated with high complication rates within a hospital stay. Therefore, if possible, a definitive aortic valve replacement should be planned within the hospital stay after BV, provided a life expectancy over one year according to current guidelines .
The shift towards TAVR is still associated with an increase of in-hospital costs . The present study confirms that treatment costs were highest in the TAVR group in emergency settings. From an economic view BV only has no advantages: it has similar costs but significantly higher length of hospital stay and mortality compared to TAVR.
The strengths of this study include a large study population of acutely admitted patients with symptomatic severe aortic valve stenosis, first time comparison of clinical characteristics and outcome risk analyses according to the three treatment groups SAVR, TAVR or BV. Several limitations need to be considered. Analyses were performed in a registry study setting from a national database according to ICD and OPS codes. Important clinical factors of patients such as a decision to palliative care might therefore not have been considered. Furthermore, there was no follow-up to evaluate long-term outcomes of the three treatment groups. We examined BV only therapy and therefore cannot make any statement on its use in bridging to SAVR or TAVR.
Patients acutely admitted with severe aortic valve stenosis undergoing BV are at increased risk of in-hospital mortality. They were also sicker than TAVR and SAVR patients which probably influenced our results. Thus, our findings support the concept of a definitive aortic valve replacement within the hospital stay whenever possible and indicated. Since outcomes of TAVR and SAVR were comparable in acutely admitted patients, an individual decision should be made in accordance to current guidelines.
|DESTATIS||Research Data Center of the Federal Bureau of Statistics|
|DRG||Diagnosis Related Groups|
|LoS||Lengths of stay|
|SAVR||surgical aortic valve replacement|
|TAVR||transcatheter aortic valve replacement|
This work was supported by German Heart Foundation/German Foundation of Heart Research.
The authors have no competing interests to declare.
Peter Stachon and Constantin von zur Mühlen share the last authorship.
Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolving epidemiology of valvular aortic stenosis. The Tromso study. Heart. 2013; 99(6): 396–400. DOI: https://doi.org/10.1136/heartjnl-2012-302265
Osnabrugge RL, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: Disease prevalence and number of candidates for transcatheter aortic valve replacement: A meta-analysis and modeling study. J Am Coll Cardiol. 2013; 62(11): 1002–12. DOI: https://doi.org/10.1016/j.jacc.2013.05.015
Ross J, Jr., Braunwald E. Aortic stenosis. Circulation. 1968; 38(1 Suppl): 61–7. DOI: https://doi.org/10.1161/01.CIR.38.1S5.V-61
Essa M, Aneni E, Bernardi C, et al. A Systematic Review of Cardiogenic Shock in the Setting of Severe Aortic Stenosis: Prevalence, Management and Outcomes. J Card Fail. 2019; 25(8): S51. DOI: https://doi.org/10.1016/j.cardfail.2019.07.143
Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010; 363(17): 1597–607. DOI: https://doi.org/10.1056/NEJMoa1008232
Reinohl J, Kaier K, Reinecke H, et al. Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice. N Engl J Med. 2015; 373(25): 2438–47. DOI: https://doi.org/10.1056/NEJMoa1500893
Gaede L, Blumenstein J, Husser O, et al. Aortic valve replacement in Germany in 2019. Clin Res Cardiol. 2021. DOI: https://doi.org/10.1007/s00392-020-01788-6
Baron SJ, Magnuson EA, Lu M, et al. Health Status After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2019; 74(23): 2833–42. DOI: https://doi.org/10.1016/j.jacc.2019.09.007
Gaede L, Blumenstein J, Kim WK, et al. Trends in aortic valve replacement in Germany in 2015: Transcatheter versus isolated surgical aortic valve repair. Clin Res Cardiol. 2017; 106(6): 411–9. DOI: https://doi.org/10.1007/s00392-016-1070-1
Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017; 38(36): 2739–91. DOI: https://doi.org/10.1093/eurheartj/ehx391
Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation. 1982; 66(5): 1105–10. DOI: https://doi.org/10.1161/01.CIR.66.5.1105
Christ G, Zehetgruber M, Mundigler G, et al. Emergency aortic valve replacement for critical aortic stenosis. A lifesaving treatment for patients with cardiogenic shock and multiple organ failure. Intensive Care Med. 1997; 23(3): 297–300. DOI: https://doi.org/10.1007/s001340050331
Scott WC, Miller DC, Haverich A, et al. Determinants of operative mortality for patients undergoing aortic valve replacement. Discriminant analysis of 1,479 operations. J Thorac Cardiovasc Surg. 1985; 89(3): 400–13. DOI: https://doi.org/10.1016/S0022-5223(19)38789-6
Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: First human case description. Circulation. 2002; 106(24): 3006–8. DOI: https://doi.org/10.1161/01.CIR.0000047200.36165.B8
Huang H, Kovach CP, Bell S, et al. Outcomes of Emergency Transcatheter Aortic Valve Replacement. J Interv Cardiol. 2019; 2019: 7598581. DOI: https://doi.org/10.1155/2019/7598581
Smedira NG, Ports TA, Merrick SH, Rankin JS. Balloon aortic valvuloplasty as a bridge to aortic valve replacement in critically ill patients. Ann Thorac Surg. 1993; 55(4): 914–6. DOI: https://doi.org/10.1016/0003-4975(93)90116-Y
Cribier A, Savin T, Saoudi N, Rocha P, Berland J, Letac B. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: An alternative to valve replacement? Lancet. 1986; 1(8472): 63–7. DOI: https://doi.org/10.1016/S0140-6736(86)90716-6
McKay RG, Safian RD, Lock JE, et al. Balloon dilatation of calcific aortic stenosis in elderly patients: Postmortem, intraoperative, and percutaneous valvuloplasty studies. Circulation. 1986; 74(1): 119–25. DOI: https://doi.org/10.1161/01.CIR.74.1.119
Kamperidis V, Hadjimiltiades S, Ziakas A, et al. Balloon valvuloplasty as destination therapy in elderly with severe aortic stenosis: A cardiac catheterization study. J Geriatr Cardiol. 2015; 12(3): 218–25.
Oettinger V, Kaier K, Heidt T, et al. Outcomes of transcatheter aortic valve implantations in high-volume or low-volume centres in Germany. Heart. 2020. DOI: https://doi.org/10.1136/heartjnl-2019-316058
von Zur Muhlen C, Reiss S, Krafft AJ, et al. Coronary magnetic resonance imaging after routine implantation of bioresorbable vascular scaffolds allows non-invasive evaluation of vascular patency. PLoS One. 2018; 13(1): e0191413. DOI: https://doi.org/10.1371/journal.pone.0191413
Bach DS, Siao D, Girard SE, Duvernoy C, McCallister BD, Jr., Gualano SK. Evaluation of patients with severe symptomatic aortic stenosis who do not undergo aortic valve replacement: The potential role of subjectively overestimated operative risk. Circ Cardiovasc Qual Outcomes. 2009; 2(6): 533–9. DOI: https://doi.org/10.1161/CIRCOUTCOMES.109.848259
Kundi H, Strom JB, Valsdottir LR, et al. Trends in Isolated Surgical Aortic Valve Replacement According to Hospital-Based Transcatheter Aortic Valve Replacement Volumes. JACC Cardiovasc Interv. 2018; 11(21): 2148–56. DOI: https://doi.org/10.1016/j.jcin.2018.07.002
Stachon P, Kaier K, Zirlik A, et al. Development and Results of Transcatheter and Surgical Aortic Valve Replacement in Germany 2014 and 2015. Dtsch Med Wochenschr. 2018; 143(23): e206–e12. DOI: https://doi.org/10.1055/a-0655-6218
Keeble TR, Khokhar A, Akhtar MM, Mathur A, Weerackody R, Kennon S. Percutaneous balloon aortic valvuloplasty in the era of transcatheter aortic valve implantation: A narrative review. Open Heart. 2016; 3(2): e000421. DOI: https://doi.org/10.1136/openhrt-2016-000421
Bongiovanni D, Kuhl C, Bleiziffer S, et al. Emergency treatment of decompensated aortic stenosis. Heart. 2018; 104(1): 23–9. DOI: https://doi.org/10.1136/heartjnl-2016-311037
Saia F, Marrozzini C, Ciuca C, et al. Emerging indications, in-hospital and long-term outcome of balloon aortic valvuloplasty in the transcatheter aortic valve implantation era. EuroIntervention. 2013; 8(12): 1388–97. DOI: https://doi.org/10.4244/EIJV8I12A212
Ben-Dor I, Pichard AD, Satler LF, et al. Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv. 2010; 3(11): 1150–6. DOI: https://doi.org/10.1016/j.jcin.2010.08.014
Saia F, Moretti C, Dall’Ara G, et al. Balloon aortic valvuloplasty as a bridge-to-decision in high risk patients with aortic stenosis: A new paradigm for the heart team decision making. J Geriatr Cardiol. 2016; 13(6): 475–82.
Kaier K, von Zur Muhlen C, Zirlik A, et al. Estimating the additional costs per life saved due to transcatheter aortic valve replacement: A secondary data analysis of electronic health records in Germany. Eur J Health Econ. 2019; 20(4): 625–32. DOI: https://doi.org/10.1007/s10198-018-1023-x