Highlights
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Pressure-Volume (PV) relationships reveal direct LV unloading after TAVR for severe aortic stenosis.
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LV unloading is associated with decreased LV myocardial metabolic demand, suggesting improved cardiac performance.
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LV contractility is reduced immediately after TAVR.
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The observed changes in PV relationships were irrespective of transcatheter valve platform, pre or postdilatation, rapid pacing or baseline LV EF.
Abstract
Background
Severe aortic stenosis (AS) induces a disproportional pressure gradient across the aortic valve causing increased left ventricular (LV) afterload. Transcatheter Aortic Valve Replacement (TAVR) aims to immediately alleviate the aortic pressure gradient and thereby changing LV cardiac mechanics. The aim was to describe by in-vivo assessment of LV pressure-volume (PV) relationships how TAVR acutely affects LV cardiac mechanics.
Methods
In this prospective observational study in patients with severe AS, LV cardiac mechanics were evaluated with an LV conductance catheter before and after TAVR. The effects of transcatheter valve design, pre and postdilatation, use of rapid pacing (≥180 bpm) and LV ejection fraction (EF) were specifically addressed.
Results
In-vivo LV PV reconstructions were obtained in 61 patients. Stroke work (SW) and pressure volume area (PVA) were significantly lower following TAVR (decrease from median [25th-75th percentile] of 10,935.6 [6877.5-13490.8] to 6,878.0 [4,870.8-8,613.8] mmHg/mL, P <.001 and from 17,831.5 [12,414.9-22,416.8] to 11,024.9 [8364.7-14705.0] mmHg/mL, P <.001, respectively) with stable SW/PVA ratios. Overall, end-systolic and end-diastolic pressures and volumes were significantly lower after TAVR. Arterial Elastance, as an index for LV afterload also decreased (2.66 [2.01-3.87]-1.96 [1.25-2.72] mmHg/mL, P <.001). LV contractility declined as illustrated by a reduction in End-systolic Elastance (2.22 [1.50-3.10]-1.58 [1.08-2.43] mmHg/mL, P <.001). The trends in changing LV cardiac mechanics were similar for balloon- and self-expanding valves and were not affected by pre/post dilatation, rapid pacing or LV EF.
Conclusions
TAVR for severe AS resulted in immediate LV unloading, lower myocardial metabolic demand and impaired contractility.
Trial Registration
This observational study was registered at URL: https://www.clinicaltrials.gov with unique identifier: NCT06204783.
Graphical abstract
Background
In the presence of severe aortic stenosis (AS), the left ventricle (LV) must overcome abnormally elevated afterload to maintain cardiac output. The LV gradually adapts through development of LV hypertrophy. Over time, LV-aortic uncoupling and systolic and diastolic dysfunction ensue. , Transcatheter aortic valve replacement (TAVR) is an established treatment for symptomatic patients with severe AS. Immediate reduction of the aortic valve pressure gradient may reverse the long-term negative effects of excessive LV afterload and may result in reverse LV remodeling (ie, normalizing LV end-systolic, end-diastolic dimensions and LV mass) within the first year after TAVR. , A plethora of transcatheter valve platforms and a variation of implantation techniques with or without rapid pacing exist but the immediate consequences on LV function are incompletely understood. , Echocardiographic studies describe short-term benefits of TAVR on LV unloading with corresponding improvements in LV-aortic coupling. , Hypotheses on changing cardiac mechanics are predominantly based on noninvasive imaging or simulations focusing on reconstructed ventricular volumes. However, more definitive in-vivo invasive assessments of LV mechanics surrounding aortic valve replacement are scarce but are critical to understand the immediate responses to TAVR.
Invasive measurement of pressure-volume (PV) relationships with a conductance catheter is considered the gold standard for assessing and quantifying critical aspects of cardiac contractile properties. , A previous in-vivo PV study described the effects of TAVR on LV cardiac mechanics, warranting confirmation in larger patient cohorts with particular attention to acute hemodynamic changes relevant to therapeutic optimization. The objective of this study was to determine how TAVR for severe AS affects LV cardiac mechanics and to assess the impact of valve platform (ie, balloon versus self-expanding valves), pre or postdilatation, rapid pacing and baseline LV ejection fraction (EF).
Methods
This single-center prospective observational study included patients who underwent nonemergent TAVR for severe AS at the Erasmus University Medical Center in Rotterdam, the Netherlands. The decision to proceed with TAVR and transcatheter valve platform selection was per heart team consensus. , All TAVR procedures were performed under local anesthesia. The use of balloon predilatation and postdilatation was determined on clinical need based on the decision of the treating physician. Nontransfemoral TAVR and planned concomitant coronary revascularization were exclusion criteria for study participation. A visual illustration of the patient selection process can be found in supplementary figure 1. The study protocol was approved by the local medical ethics committee (Medical Ethics Committee, Erasmus University Medical Center Rotterdam, registration number: MEC-2022-0132). Written informed consent was obtained for each patient prior to study enrollment. The data at the foundation of the findings of this study are available from the corresponding author upon reasonable request. No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents. More details on the study design can be found elsewhere.
Invasive pressure-volume measurements
A 7Fr conductance catheter (CD Leycom, Hengelo, the Netherlands) was positioned in the LV apex ( Figure 1 ). Apical seating of the conductance catheter was verified by fluoroscopy and visual inspection of segmental PV loops (version 3.18.1, Inca, CD Leycom, Hengelo, the Netherlands). PV data were recorded for a minimum of 10 seconds in steady state conditions prior to TAVR. Immediately after TAVR, the conductance catheter was re-inserted and positioned in the LV apex and PV recordings were repeated. Transthoracic echocardiographic (TTE) assessments were performed immediately before and after TAVR for the purpose of volume calibration of the conductance signal. Apical 2 and 4 chamber views were obtained to create a spherical three-dimensional model of the LV volume using dedicated software (version 1.1.1, Caas Qardia, Pie Medical, Maastricht, The Netherlands). Conductance signals were calibrated based on the reconstructed end-systolic and end-diastolic volumes.
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An appraisal of changing LV cardiac mechanics, as assessed by LV PV analysis, includes three main measures: The LV end-systolic and end-diastolic PV relations, including ventricular volumes (mL) and pressures (mmHg);
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LV metabolic demand and metabolic efficiency. The net metabolic demand is indexed by the LV pressure volume area (PVA, mmHg/mL) as the sum of stroke work (SW) and potential energy (PE) ( Figure 1 ). The ratio between SW and PVA is indicative of myocardial metabolic efficiency, ie, the fraction of the total myocardial work transferred as external work to propel blood through the vasculature;
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LV-aortic coupling, expressed by the ratio of E es (End-systolic elastance representing load-independent contractility) and E a (effective Arterial Elastance as measure for afterload in mmHg/mL.
Pressure-Volume (PV) reconstructions based on conductance catheter measurements before and after Transcatheter Aortic Valve Replacement (TAVR). A , Conductance catheter was introduced in the left ventricular (LV) apex allowing PV reconstructions immediately before TAVR. B , Insertion of the conductance catheter directly after TAVR to repeat PV measurements. C , Elementals of PV reconstructions, including ventricular volumes, pressures and LV-aortic coupling (ie, the ratio between E es and E a ). D , Cardiomechanics as a reflection of the myocardial metabolic demand (ie, the pressure volume area as the sum of SW and PE). E a , Arterial Elastance, EDPVR, End-Diastolic Pressure-Volume Relation; E es, End-Systolic Elastance; ESPVR, End-Systolic Pressure-Volume Relation; PE, Potential Energy; SW, Stroke Work .
The single-beat approach described by Chen et al. was applied to estimate the LV E es and corresponding V 0mmHg pre TAVR, with V 0mmHg representing the intersection of the end-systolic pressure volume relation trendline on the volume axis (ie, on 0 mmHg). For practical purposes (procedures under local anesthesia and in the context of a busy clinical program), a single-beat approach was chosen over a multi-beat approach. To overcome artefacts in contractility measurements due to outliers in V 0mmHg (ie, to overcome the intrinsic limitations of using single-beat algorithms), postprocedural E es was assessed with a fixed V 0mmHg (ie, using the V 0mmHg pre TAVR) and with E es = end-systolic pressure (ESP)/ (end-systolic volume (ESV)– V 0mmHg ) (supplementary figure 2) .
Statistics
Previous observational research, using noninvasive PV reconstructions, reported a mean decrease in PVA immediately after TAVR of 16,424 ± 6,268 mmHg/mL to 12,053 ± SD 5,260, P <.001. Based on that report, assuming normal distribution as well as a moderate to strong correlation, at least 65 patients were needed to detect a statistically significant change in PVA with 90% power and an alpha of 0.05.
Continuous variables (including SW, PE and PVA) were presented as means ± standard deviation (SD) or median and 25th to 75th percentile as appropriate. Normal distribution was assessed using the Shapiro-Wilk or Kolmogorov-Smirnov test dependent on group size. Measurements obtained directly before TAVR were compared with measurements immediately after TAVR. Paired t-tests or Wilcoxon signed rank tests were used for this comparison of the study outcome, according to normality of the variable distribution.
Predefined subgroup analyses evaluated changes in LV cardiac mechanics with (1) balloon-expandable and self-expanding transcatheter valves; (2) use of pre or postdilatation, (3) with or without rapid pacing (≥180 bpm); and (4) with or without depressed LV EF (ie, <50%). INCA software (version 3.18.1, CD Leycom, Hengelo, the Netherlands) and SPSS (version 28.01.0, IBM Corp., Armonk NY) were used for data processing and statistical analyses. Throughout the study, two-tailed P -values of <.05 were considered statistically significant.
Results
Between November 2022 and August 2023, 72 patients were included in this prospective study (supplementary figure 1). Two patients withdrew informed consent before study measurements. In 5 patients, procedural complications or inadequate echocardiographic images for volume calibration precluded successful reconstruction of PV relationships. Conductance catheter measurements were recorded in 65 patients. The PV loops of 4 patients were excluded from analysis because of uncorrectable calibration errors. This only slightly affected demonstrable effect size: with 61 patients, we had 90% power to demonstrate a decrease in PVA of 16,424 ± 6,268 mmHg/mL to 11,900 ± 5,260 with an alpha of 0.05.
Pre- and post-TAVR PV relationships were successfully reconstructed in 61 patients; average age was 79.0 (73.5-84.5 years) and 65.6% were male ( Table 1 , supplementary data). Rapid pacing was used in 49 of the procedures. Baseline LV EF was <50% in nine patients. TAVR was implanted successfully in all patients with an Accurate Neo2 (11/61, Boston Scientific, MA), Sapien S3 (22/61, Edwards Lifesciences, Irvine, CA), Evolut Pro+ (15/61, Medtronic, Minnesota), Navitor (11/61, Abbott, Illinois) or Myval (2/61, Meril Life Sciences, Gujarat, India) valve. Twenty-four patients received a balloon-expandable valve and 37 patients a self-expanding valve (demographics of patients in these 2 groups are further summarized in Table 1 ). Changes in LV cardiac mechanics after TAVR are summarized in Table 2 and the corresponding overall changes in the PV relationship is illustrated in the example of Figure 2 . Details on invasive pulmonary pressure measurements were available for a subset of patients and are presented in supplemental table A.
Table 1
Demographic and clinical details of included patients.
| TAVR (n = 64) | Balloon-expandable transcatheter valve (24/61) | Self-expanding valve (37/61) | P -value | |
|---|---|---|---|---|
| Age (y) | 79.0 (73.5-84.5) | 78.5 ± 6.0 | 80.0 (74.5-85.5) | P =.690 |
| M/F (%) | 40/21 (65.6/34.4) | 23/1 (95.8/4.2) | 17/20 (45.9/54.1) | P <.001 |
| Height (cm) | 172.9 ± 10.3 | 180.1 ± 8.4 | 168.2 ± 8.7 | P <.001 |
| Weight (kg) | 81.8 ± 15.6 | 87.7 ± 14.4 | 77.9 ± 15.3 | P =.015 |
| BMI (kg/m 2) | 27.5 ± 4.6 | 27.2 (24.2-30.4) | 27.9 ± 5.1 | P =.685 |
| NYHA class ≥III (%) | 47 (77.0) | 18 (75.0) | 29 (78.4) | P =.497 |
| Medical history | ||||
| COPD (%) | 9 (14.8) | 7 (29.2) | 2 (5.4) | P =.015 |
| Chronic kidney disease (%) | 21 (34.4) | 8 (33.3) | 13 (35.1) | P =.554 |
| (Previous) malignancy (%) | 15 (24.6) | 5 (20.8) | 10 (27.0) | P =.408 |
| Hypertension (%) | 36 (59.0) | 12.0 (50.0) | 24 (64.9) | P =.188 |
| Diabetes Mellitus (%) | 16 (26.2) | 4 (16.7) | 12 (32.4) | P =.142 |
| Stroke or TIA (%) | 9 (14.8) | 4 (16.7) | 5 (13.5) | P =.504 |
| Atrial fibrillation (%) | 22 (36.1) | 9 (37.5) | 13 (35.1) | P =.532 |
| Myocardial infarction (%) | 6 (9.8) | 4 (16.7) | 2 (5.4) | P =.158 |
| Coronary artery disease (%) | 38 (62.3) | 18 (75.0) | 20 (54.1) | P =.083 |
| Prior revascularization (%) | 19 (31.1) | 11 (45.8) | 8 (21.6) | P =.044 |
| Baseline echocardiography | ||||
| LV EF (%) | 54.7 ± 8.3 | 52.6 ± 7.5 | 56.0 ± 8.6 | P =.225 |
| Fractional shortening (%) | 31 (27-49) 47 | 33 ± 9 | 39 ± 12 | P =.312 |
| E/e’ ratio | 14 (11-16) | 14 ± 3 | 13 (11-17) | P =.384 |
| Aortic PG (mmHg) | 77.2 ± 19.3 | 78.9 ± 73.9 | 76.0 ± 16.0 | P =.598 |
| Aortic MG (mmHg) | 45.2 ± 12.1 | 45.9 ± 14.1 | 42.1 (36.8-49.2) | P =.727 |
| AVA (cm 2) | 0.79 ± 0.23 | 0.80 ± 0.21 | 0.79 ± 0.24 | P =.808 |
| Aortic V max (m/s) | 4.2 (4.0-4.8) | 4.4 ± 0.6 | 4.3 ± 0.5 | P =.479 |
| Concomitant AoI (≥moderate) (%) | 14 (23.0) | 10 (41.7) | 4 (10.8) | P =.007 |
| Baseline STS-score | 2.22 (1.77-3.42) | 1.94 (1.69-2.75) | 2.65 (1.77-3.75) | P =.094 |
| Agatston score (aortic) (CT) | 3,227 ± 1,595 | 4,291 ± 1,654 | 2,507 ± 1,082 | P <.001 |
| Baseline laboratory | ||||
| Haemoglobin (mmol/L) | 7.9 ± 1.0 | 7.8 ± 1.0 | 7.9 ± 1.0 | P =.450 |
| Creatinine (µmol/L) | 90.0 (77.0-119.0) | 95.5 (82.3-129.0) | 87.0 (75.0-109.5) | P =.116 |
| e-GFR (ml/min/1.73m 2) | 59.8 ± 19.9 | 59.1 ± 21.1 | 60.3 ± 19.3 | P =.816 |
| hs-TNT (ng/L) | 26.0 (17.0-41.0) | 27.5 (19.5-46.8) | 25.0 (15.0-35.0) | P =.244 |
| NT-pro BNP (pmol/L) | 141.0 (44.5-262.5) | 189.5 (60.8-254.3) | 108.0 (35.0-307.0) | P =.471 |
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