Transcatheter aortic valve replacement in patients with systolic heart failure

Br J Cardiol 2019;26(4)doi:10.5837/bjc.2019.033 Leave a comment
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New York Heart Association (NYHA) class IV heart failure is one of the factors used in predicting in-hospital mortality in patients undergoing transcatheter aortic valve replacement (TAVR). The effect of systolic heart failure (SHF), aside from NYHA classification, on peri-procedural outcomes is unclear.

The study population was identified from the 2016 Nationwide Readmissions Data database using International Classification of Diseases-Tenth Revision codes for TAVR and SHF. Study end points included in-hospital all-cause mortality, the length of hospital stay, cardiogenic shock, acute myocardial infarction (AMI), acute kidney injury (AKI), mechanical complications of prosthetic valve, bleeding, and 30-day readmission rate. Propensity matching was used to create a control group of TAVR patients without a SHF diagnosis (TAVR-C).

A total of 5,674 patients were included in each group (mean age 79.9 years; 35.6% female). The groups were comparable in terms of baseline characteristics and comorbidities. TAVR-SHF was associated with significantly higher in-hospital all-cause mortality (2.7% vs. 1.9%, p<0.01), longer hospital stay (7.5 vs. 5.5 days, p<0.01), higher cardiogenic shock (5.1% vs. 1.6%, p<0.01), AMI (4.0% vs. 1.9%, p<0.01), AKI (18.7% vs. 12.4%, p<0.01) and mechanical complications of prosthetic valve (1.2% vs. 0.6%, p<0.01). There was no significant difference between TAVR-SHF and TAVR-C in terms of bleeding (19.5% vs. 18.2%, p=0.08) and 30-day readmission rate (10.8% vs. 10.2%, p=0.29).

Compared with TAVR-C, TAVR-SHF was associated with higher in-hospital peri-procedural complications and all-cause mortality.

Introduction

Systolic heart failure (SHF) in patients with severe aortic stenosis (AS) carries a worse prognosis, and aortic valve replacement improves ventricular systolic function and survival.1,2 Therefore, SHF is an indication for aortic valve replacement in severe AS.2 Both surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are associated with comparable survival and ventricular systolic function recovery in this group of patients.3 TAVR, however, is the recommended approach for patients with intermediate to prohibitive surgical risk; and SHF patients are often considered a high-risk group. As a result, SHF represents a significant proportion of the TAVR population.4,5

The Society of Thoracic Surgeons (STS) and the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) are the most commonly used risk score calculators to predict peri-operative mortality in cardiac surgery.6 Both scores consider ventricular function during peri-operative risk assessment for SAVR, which is highly dependent on pre-operative systolic function; however, studies have shown conflicting data on post-TAVR outcomes with pre-existing SHF, and none of these scores provide an acceptable predictive ability for post-TAVR outcomes.5,7,8

Method

Data source

The Nationwide Readmissions Data (NRD) is one of the largest collections of de-identified longitudinal hospital care data in the US. The NRD supports various types of analyses, including readmission rates, with safeguards to protect the privacy of individual patients, physicians, and hospitals. It contains clinical and nonclinical variables for each hospital stay, including patient linkage number for linking hospital visits across hospitals, International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) for principal and secondary procedures and diagnoses, age, gender, length of stay (LOS), and others.9,10

Study cohort

The ICD-10-CM/PCS codes were used to search discharges in the 2016 NRD who had TAVR during the index hospitalisation; SHF, baseline characteristics, comorbidities, and in-hospital post-procedural complications were subsequently extracted.10 The NRD excludes discharges with missing age, missing linkage numbers or from hospitals with more than 50% of their discharges excluded because of these criteria, as patients treated in these hospitals may not be reliably tracked over time.9 All best practices to use the NRD highlighted by Khera et al. were followed.11

Study end points

The study end points included in-hospital all-cause mortality, length of index hospital stay (LOS), cardiogenic shock, acute myocardial infarction (AMI), acute kidney injury (AKI), mechanical complications of prosthetic valve, bleeding, and 30-day readmission rate. Mechanical complications of prosthetic valve defined as TAVR valve embolisation, displacement, breakdown, or other mechanical complications (excluding peri-valvular leak, fibrosis, infection, stenosis, and thrombosis). AMI included any new post-procedural subendocardial or transmural myocardial infarction. AKI included any new post-procedural acute worsening of kidney function. Bleeding included any circulatory or central nervous system bleeding during or post-procedure, or post-haemorrhage/procedure anaemia.

The 30-day readmission rate was calculated based on the NRD recommendations. We identified all-cause readmissions (including first and subsequent admissions) within 30 days post-discharge to any hospital within the same state (as cross-state readmissions cannot be tracked by the NRD database). Transfers were not considered readmissions. We excluded TAVR patients whose age was less than 18 years, missing LOS or if TAVR procedure was done in the month of December as readmission rate cannot be calculated in two different years.12

Statistical analysis

Statistical Analysis System (SAS) software 9.4 (TS1M4, SAS Institute Inc., Cary, North Carolina) was used for propensity score matching and statistical analysis. The logistic regression was used to create propensity score, based on baseline characteristics for one-to-one parallel, balanced propensity score matching model using a caliper of 0.05. McNemar test was used to compare paired categorical variables, while paired-samples t-test was used to compare continuous variables. Pearson Chi-Square of Independence and unpaired-sample t-test were used in subgroup analysis to compare the end points of interest in TAVR-SHF to the overall TAVR group before propensity matching. The multi-variable logistic regression model was used to identify predictors of in-hospital all-cause mortality of the TAVR-SHF group. A two-tailed p value of <0.05 was used for statistical significance.13,14

Results

In the 2016 NRD database, there were around 17.2 million discharges. There were 23,604 discharges who had TAVR, 24.0% (5,674 patients) had had a diagnosis of SHF. The mean age of the overall TAVR cohort was 80.5 (standard deviation [SD] 8.3) years, 45.9% female. History of coronary artery disease, hypertension, hyperlipidaemia, and diabetes were the most common comorbidities. More than 96% of the TAVR were endovascular approach. After propensity matching, both TAVR-SHF and TAVR-C groups were comparable in terms of baseline characteristics (table 1).

Table 1. Demographics, baseline characteristics and comorbidities of overall all transcatheter aortic valve replacement (TAVR) group, and TAVR-systolic heart failure (TAVR-SHF) and control (TAVR-C) groups after propensity matching with p values for each variable

Baseline/group Overall TAVR* TAVR-SHF TAVR-C p value**
Number of patients 23,604 5,674 (24%) 5,674 (24%)
Mean age, years (SD) 80.5 (8.3) 79.7 (8.9) 80.1 (8.5) <0.01
Female 45.9% 35.5% 35.7% 0.72
Transapical TAVR 3.4% 3.6% 3.4% 0.50
Endovascular TAVR 96.6% 96.5% 96.7% 0.53
Hypertension 86.7% 86.0% 87.1% 0.09
Diabetes mellitus 36.1% 38.6% 37.7% 0.27
Hyperlipidaemia 69.0% 67.9% 68.3% 0.66
Chronic kidney disease 34.3% 43.1% 42.7% 0.65
Coronary artery disease 70.5% 77.9% 78.4% 0.41
Mitral regurgitation 6.9% 9.3% 9.3% 0.87
Chronic anaemia 23.4% 25.7% 24.9% 0.31
Atrial fibrillation 40.2% 47.6% 46.9% 0.45
Atrial flutter 4.1% 5.5% 5.0% 0.20
Long-term anticoagulation 18.6% 21.8% 21.9% 0.83
Long-term antiplatelet 10.1% 9.9% 10.0% 0.77
Aspirin 27.9% 26.9% 27.2% 0.69
Abnormal coagulation profile 0.4% 0.6% 0.3% 0.02
Peripheral vascular disease 25.7% 27.1% 26.3% 0.33
Chronic pulmonary disease 30.0% 32.8% 32.8% 0.93
Chronic liver disease 3.0% 2.8% 2.6% 0.44
Smoking 37.7% 38.2% 38.4% 0.82
Obesity 17.1% 15.8% 15.0% 0.21
A p value <0.05 indicates a statistically significant difference between TAVR-SHF and TAVR-C groups.
*Overall TAVR cohort characteristics before propensity matching.
**p value evaluating the statistical difference between the TACR-SHF and TAVR-C after propensity matching.
Key: SD = standard deviation

Table 2 shows, in comparison with TAVR-C, TAVR-SHF was associated with significantly higher in-hospital all-cause mortality (2.7% vs. 1.9%, p<0.01), two days longer hospital stay (7.5 vs. 5.5 days, p<0.01), higher cardiogenic shock (5.1% vs. 1.6%, p<0.01), AMI (4.0% vs. 1.9%, p<0.01), AKI (18.7% vs. 12.4%, p<0.01) and mechanical complications of prosthetic valve (1.2% vs. 0.6%, p<0.01). There was no significant difference between TAVR-SHF and TAVR-C in terms of bleeding (19.5% vs. 18.2%, p=0.08) and 30-day readmission rate (10.8% vs. 10.2%, p=0.29). Multi-variable analysis showed that hypertension, hyperlipidaemia, smoking, and long-term anticoagulation were predictors of increased mortality.

Table 1. Patient information and electrocardiogram (ECG) measurements

End point/group Overall TAVR* TAVR-C p value**
All-cause mortality 1.8% 1.9% <0.01
Mean LOS (SD) 5.6 (7.3) days 5.5 (6.9) days <0.01
Cardiogenic shock 2.4% 1.6% <0.01
Mechanical complication of prosthetic valve 0.7% 0.6% <0.01
AMI 2.3% 1.9% <0.01
AKI 12.0% 12.4% <0.01
Bleeding 18.4% 18.2% 0.08
Bleeding 18.4% 18.2% 0.08
Bleeding 18.4% 18.2% 0.08
Bleeding 18.4% 18.2% 0.08
Bleeding 18.4% 18.2% 0.08
End point/group Overall TAVR* TAVR-C p value**
Bleeding 18.4% 18.2% 0.08
30-day readmission 11.6% 10.2% 0.29
A p value <0.05 indicates a statistically significant difference between TAVR-SHF and TAVR-C groups.
*Overall TAVR cohort characteristics before propensity matching.
**p value evaluating the statistical difference between the TACR-CTO and TAVR-C after propensity matching.
Key: AKI = acute kidney injury; AMI = acute myocardial infarction; LOS = length of stay; PPM = need for a new permanent pacemaker; SD = standard deviation

Discussion

This study shows that TAVR-SHF was associated with a higher risk of in-hospital all-cause mortality and comorbidity, including development of post-procedural cardiogenic shock, and longer LOS in comparison with the overall TAVR group and with TAVR-C after propensity matching adjustment to baseline comorbidities. There were no significant differences in terms of 30-day readmission rates.

Severe AS patients undergoing TAVR, especially those with systolic dysfunction, have limited myocardial reserve and less tolerance to acute haemodynamic changes, which can lead to cardiogenic shock.15,16 Intra-procedural circulatory depression occurs in up to 20%, which may worsen coronary perfusion and start a vicious cycle of ischaemia and systolic dysfunction.16,17 It is the most common cause of early (i.e. within 30 days) post-TAVR death on autopsy studies.18 There are multiple reasons for post-TAVR cardiogenic shock including mechanical complications of the valve. Furthermore, SHF represents an independent risk factor for mechanical complications of TAVR valve, consistent with this study result.16,17,19 The increased cardiogenic shock in TAVR-SHF possibly contributed to the higher in-hospital mortality, morbidity, and subsequently longer LOS.

SHF in severe AS can be primarily driven by the increase in afterload, which has a high probability of recovery after valve replacement. It can also be secondary to other causes, such as myocardial ischaemia, which leads to scar-induced SHF where recovery is less certain and prognosis might not substantially improve with TAVR.5 These different mechanisms of SHF in TAVR patients might be responsible for the conflicting results in the literature.

Similar readmission rates may be attributed to excellent procedural success, systolic function recovery, reverse remodelling, improved haemodynamics and functional status in patients who survived to discharge, regardless of baseline systolic function, as most of the late post-TAVR mortality is secondary to non-cardiovascular causes.8,18,20 The similar bleeding rates were probably because of utilisation of similar procedural techniques and approaches.

This study has important clinical implications. It highlights a large high-risk subgroup of TAVR patients who are at higher risk of post-procedural mortality and morbidity, who require careful peri-procedural observation and familiarity with potential complications. It raises the question of whether routine pre-TAVR evaluation (such as myocardial strain and stroke volume index) is needed to assess which patients with SHF would benefit the most with respect to ventricular function recovery. Furthermore, it raises a question regarding the role of prophylactic mechanical circulatory support devices during TAVR in select SHF patients who are at higher risk for cardiogenic shock.

Limitations

This study is a retrospective study. The NRD database does not provide information about the symptomatic class, severity (some data have shown that emergent TAVR for decompensated severe AS was feasible but associated with higher complications and mortality rates),21,22 cause of SHF, the type of TAVR valve, echocardiographic haemodynamics and biomarkers of AS and SHF that all might affect post-TAVR outcomes and prognosis, as ejection fraction by itself might not completely reflect extent of myocardial damage and is not as sensitive as myocardial strain.5,23 The post-TAVR ejection fraction, functional status, and long-term outcomes could not be assessed.

Conclusion

The presence of SHF is associated with increased early post-TAVR mortality and morbidity. Further research is warranted to prospectively delineate the peri-procedural risks by using newer echocardiographic parameters and role of using prophylactic mechanical support devices.

Key messages

  • Systolic heart failure (SHF) is a common comorbidity in patients undergoing transcatheter aortic valve replacement (TAVR)
  • The effect of SHF on the TAVR outcomes is unclear
  • The presence of SHF is associated with increased early morbidity and mortality

Conflicts of interest

None declared.

Funding

None.

Study approval and consent

No ethical approval or consent was required.

References

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