Author + information
- Received October 11, 2012
- Revision received December 14, 2012
- Accepted December 21, 2012
- Published online May 1, 2013.
- Gidon Y. Perlman, MD,
- Sasa Loncar, MD,
- Arthur Pollak, MD,
- Dan Gilon, MD,
- Ronny Alcalai, MD,
- David Planer, MD,
- Chaim Lotan, MD and
- Haim D. Danenberg, MD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Haim D. Danenberg, Interventional Cardiology Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
Objectives This study sought to investigate the blood pressure (BP) response after transcatheter aortic valve implantation (TAVI) and its correlation with short- and mid-term clinical outcomes.
Background TAVI is an emerging therapy for aortic stenosis patients at high surgical risk. The acute hemodynamic sequelae of this procedure and their clinical relevance are yet unclear.
Methods Consecutive patients who underwent TAVI in a single center were prospectively monitored for BP response during 5 post-procedural days. Clinical parameters, adverse events, and medical treatment were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Patients were divided according to their post-procedural BP response into 2 groups: increased BP and stable BP.
Results One hundred and five patients were analyzed. Overall, systolic BP increased immediately after TAVI in the entire cohort by an average of 15 ± 31 mm Hg. This rise was sustained and led to intensification of antihypertensive treatment in 53 patients (51%); these patients were designated as the increased BP group. The increase in systolic BP after TAVI was associated with an increase in stroke volume and cardiac output and was not related to age, baseline cardiac function, or procedural outcomes. Patients with increased BP after TAVI had a significantly better prognosis with fewer adverse events in the hospital (21% vs. 62%, p < 0.01), after 30 days (30% vs. 71%, p < 0.01), and after 12 months (53% vs. 83%, p < 0.01) as compared with patients with stable BP.
Conclusions After TAVI, a substantial number of patients have a significant rise in systolic BP necessitating long-term treatment. This increase in BP is associated with an increase in cardiac output and predicts a better clinical outcome.
Severe aortic stenosis (AS) often presents with normal arterial systolic blood pressure (BP) in lieu of elevated intraventricular systolic pressure and, consequently, a pressure gradient across the aortic valve. Pre-procedural hypertension (HTN) is a risk factor and a predictor of increased mortality after aortic valve replacement (AVR) (1). Remodeling and reduction of left ventricular (LV) hypertrophy after AVR appear to correlate with a favorable clinical outcome (2). The disappearance of the pressure gradient across the aortic valve following surgical AVR often leads to dramatic hemodynamic changes and increased hypertension (3,4) that can challenge the post-procedural care and may further affect these patients in the chronic phase. The use of antihypertensive medications after surgery has been shown to improve LV remodeling in these patients (5,6).
Transcatheter aortic valve implantation (TAVI) is a novel approach for the treatment of severe AS patients who are inoperable or at high surgical risk. Unlike surgical AVR, TAVI is often performed under local anesthesia (7), and the post-procedural care takes place mainly in cardiac intensive care units. Studies that assessed the post-procedural hemodynamic sequelae of TAVI have focused on complications and hypotension rather than on the hypertensive response (7,8). Gotzmann et al. (9) described a rise in systolic BP immediately after TAVI, not related to a change in ejection fraction. Nevertheless, the causes, persistence, and clinical significance of this response are yet unclear. In this study, we prospectively investigated the in-hospital hemodynamic changes post-TAVI and their clinical correlations during 12 months of follow-up.
Study population and post-procedural monitoring
Consecutive patients who underwent TAVI at our institution were prospectively analyzed. All patients had severe symptomatic AS diagnosed clinically and confirmed by Doppler echocardiography. The study subjects were declined for surgery and referred to TAVI due to an increased surgical risk as assessed by an institutional heart team.
After TAVI, patients were transferred to the cardiac intensive care unit with continuous BP monitoring immediately after the procedure and during the following 5 days. The highest BP measurement was recorded every 8 h and used for analysis. Patients were initially kept on their pre-procedural antihypertensive therapy. Uncontrolled BP was promptly treated; treatment decisions were not restricted and were decided by the treating physicians. Baseline BP levels were measured in the pre-admission office visit.
All patients had echocardiograms performed after TAVI. Post-procedural aortic regurgitation was graded on a scale of 1 to 4 according to vena contracta width, jet diameter to left ventricular outflow tract (LVOT) diameter ratio and circumferential extent in the short-axis view. Valve areas, pressure gradients, stroke volume, and cardiac output were calculated using LVOT Doppler waveforms, LVOT diameter, heart rate, and the continuity equation as per standard techniques (10–12). Arterial compliance was calculated as stroke volume/pulse pressure (ml/mm Hg) (13). Procedural complications were recorded according to the Valve Academic Research Consortium definitions (14).
BP response after TAVI
Patients were divided into 2 groups according to the presence or absence of an increase in BP after TAVI.
Increased BP after TAVI was defined in the presence of one of the following:
1. A sustained (>48 h) systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg that was not present at baseline, before TAVI.
2. A need to increase more than 2-fold the dosage of an antihypertensive drug to achieve control of systemic BP.
3. A need to add an additional antihypertensive medicine to the pre-procedural regimen in order to achieve control of systemic BP.
Clinical outcomes were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Serious adverse events recorded during follow-up included: worsening heart failure; myocardial infarction; stroke; and recurrent hospitalization due to any cause and death.
Comparison of quantitative variables was performed using an unpaired Student t test whereas Fisher exact test was used to compare qualitative variables. Survival analysis was obtained by Kaplan-Meier estimates. Differences among the groups were compared with the log-rank test. All data were initially entered into a commercially available statistical program SPSS (version 17.0 for Windows, SPSS Inc., Chicago, Illinois).
One hundred and five consecutive patients were included in the study. Mean age was 80.7 ± 6.6 years and logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 23.3 ± 15.1. The baseline characteristics of the patients according to post-TAVI BP response are presented in Table 1. The 2 groups were similar in age, prevalence of HTN, logistic EuroSCORE, systolic and diastolic BP, ejection fraction, cardiac output, cardiac index, and aortic valve parameters. However, patients with increased BP were thinner (body mass index: 26.5 vs. 28.6 kg/m2, p < 0.05) and were using significantly less antihypertensive medications to achieve a similarly well-controlled BP at baseline before TAVI.
The 2 groups had similar systemic vascular resistance and arterial compliance at baseline. In accordance with the elderly age of our cohort and the high prevalence of HTN, arterial compliance was low in both groups (1.11 ± 0.47 ml/mm Hg vs. 1.26 ± 0.45 ml/mm Hg, p = 0.11).
There was no difference in the use of general anesthesia between the groups, nor the use of different approaches for valve delivery (transfemoral, trans-subclavian, and direct aortic). There was no difference between patients implanted with Medtronic CoreValve (Minneapolis, Minnesota) or Edwards Sapien XT valves (Edwards Lifesciences, Irvine, California) (Table 2).
Eighty-five patients (81%) had a prior diagnosis of HTN, and 16 additional patients (15%) were treated with antihypertensive medications for other diagnoses (e.g., heart failure and ischemic heart disease).
Systolic BP rose immediately after TAVI in the entire cohort by an average of 15 mm Hg (±31) and remained 8 mm Hg above baseline 5 days after the procedure despite medical treatment (p < 0.01 for both changes) (Fig. 1). Diastolic BP following TAVI was significantly reduced immediately after TAVI, and the diastolic BP was 7 mm Hg lower than baseline after 5 days (p < 0.01 for both changes).
Fifty-three patients (51%) had increased BP after TAVI and constituted the increased BP group. They all required intensification of antihypertensive therapy, including 27 patients in which parenteral BP lowering drugs were administered. In fact, 9 patients in this group (17%) had not been previously diagnosed as hypertensive. In the increased BP group, the number of antihypertensive drugs rose significantly by an average of 0.83 ± 1.03, whereas in the group of patients with stable BP after TAVI, the number of drugs decreased on average by 1.02 ± 1.30 (p < 0.01 for both changes).
Cardiac output, cardiac index, and stroke volume after TAVI were significantly increased in patients with increased BP versus patients with stable BP (p < 0.05). Patients with stable BP had, on average, a small reduction in stroke volumes and cardiac outputs (Table 3).
Elevated BP after TAVI was not associated with baseline arterial compliance, which was similar in both groups (Table 3). Systemic vascular resistance was largely unchanged after valve implantation with no association to BP response (Table 3).
There were 4 in-hospital deaths (3.8%), 5 deaths at 30 days (4.7%), and 13 deaths at 12 months (12.3%) (Fig. 2,Table 4). There was a trend toward more in-hospital deaths in patients with stable BP (0% vs. 8%, p = 0.056), but no significant differences in survival were seen after 12 months of follow-up.
The rates of in-hospital, 30 day, and 12-month serious adverse events were 21%, 30%, and 53%, respectively, for patients with increased BP as compared to 60%, 71%, and 83% for patients with stable BP (p < 0.01 for all differences between groups) (Fig. 3,Table 4). The majority of these events were episodes of worsening heart failure (Fig. 4), which were less frequent in the increased BP group than in the stable BP group (17% vs. 54% in-hospital, p < 0.01, and 23% vs. 60% at 12 months, p < 0.01). Adverse events possibly related to increased HTN such as stroke or transient ischemic attack, myocardial infarction, and acute kidney injury were rare and similar between the 2 groups. The adverse events reported in our cohort are detailed in Table 4 (and in Table 2 for acute kidney injury).
The rates of procedure-related complications with possible hemodynamic consequences including bleeding, vascular complications, pacemaker implantation, and post-procedural infections did not differ significantly between the 2 groups (Table 2). The severity of post-TAVI aortic regurgitation was likewise similar in both groups. We observed low rates of moderate or severe aortic regurgitation as shown in Table 5.
Hypertension following TAVI is frequent. In the study cohort, 53 of 105 patients (51%) had increased BP that led to intensification of antihypertensive therapy. Post-TAVI hypertension was associated with improved LV function, and a favorable in-hospital clinical outcome as well as at 30 days and at 12 months of follow-up. Mortality at 30 days in the entire cohort was relatively low or similar to other reported series (15–17). TAVI is a novel therapeutic option for patients with severe and symptomatic AS that are declined for surgery due to high surgical risk. These patients are often old with a multitude of major comorbidities. In our study, the average logistic EuroSCORE was 23.3 ± 15.1% and the prevalence of HTN was very high, approaching 81%, which is similar to other reports (17,18).
Interestingly, the increase in BP after TAVI predicted a favorable short- and mid-term clinical outcome independent of known risk factors for surgical AVR or TAVI such as age, LV dysfunction, ischemic heart disease, previous HTN, and chronic renal failure, which were common in our patients (1,15,16).
Increased BP after TAVI correlated with an increase in cardiac output, cardiac index, and stroke volume. The relative improvement of cardiac function in patients with increased BP may be the underlying mechanism for the BP response as the rise in BP was not associated with better baseline cardiac function parameters or procedural complications. Patients with increased BP were taking fewer antihypertensive drugs at baseline, but the level of BP control was similar before TAVI to that observed in patients in which BP was not elevated (Table 1); thus, the difference in the number of antihypertensives is probably not responsible for the different post-procedural response.
The association between good prognosis and increased BP, a potentially harmful response, is unexpected and its underlying mechanism is yet to be defined. The rise in BP may represent myocardial contractile reserve even in patients with reduced LV function at baseline. This possibility is supported by the fact that patients with increased BP had a significantly greater increase in both stroke volume and cardiac output than did stable BP response patients. A Pearson test for bivariate correlation between increased BP and an increase in cardiac output showed a significant (p = 0.015), though moderate, correlation (R2 = 0.28) with the combined outcome of death or worsening heart failure. The rise in BP may, in addition, represent a lack of adverse events that are associated with hypotension such as vascular injury and bleeding. However, there were no significant differences in the rates of procedural complications between the 2 groups in our study. Of note, 2 of our patients developed increased BP only after pericardiocentesis for tamponade, exemplifying that the absence of increased BP after TAVI might be a sign of a severe complication.
HTN is generally considered a marker of poor prognosis. Chronic HTN and accelerated HTN are well-described contributors to cardiovascular morbidity and mortality, especially in elderly patients (19–22). Baseline HTN has been found to be associated with worse outcomes after TAVI (18). The better prognosis associated with an increased BP response after TAVI persisted over 12 months of follow-up. Longer follow-up of these patients is needed to ascertain if increased HTN might also have negative effects on the very elderly patients undergoing TAVI.
Arterial stiffness and the resulting loss of blood pressure autoregulation are prevalent in elderly patients (23) and even more common in patients with cardiovascular disease (24,25). Reduced arterial compliance was present in our cohort, but arterial stiffness and peripheral vascular resistance cannot explain the rise in BP observed after TAVI, as these were similar in the 2 groups. However, reduced arterial compliance may explain the sustained nature of the elevated BP response recorded after TAVI due to the patients' inability to perform adequate arterial vasodilation after the relief of the aortic valve gradient. Of note, both groups had well-controlled BP before TAVI. Simultaneously with the increase in BP after TAVI we observed a slight reduction in diastolic pressure. This might represent mild aortic regurgitation after valve implantation. Diastolic BP was further decreased at day 5, probably by antihypertensive treatment administered for systolic HTN.
TAVI is often performed under local anesthesia and conscious sedation that do not afford the tight hemodynamic control that can be achieved under general anesthesia (26,27). We observed a BP surge immediately after valve implantation that required prompt treatment. Treating physicians should be aware of and alert to this response that is more challenging when patients are only mildly sedated.
The rapid and sustained BP changes after TAVI reported in this study for the first time are common and should be identified and treated throughout the procedure and the post-procedural phase. This is exemplified by a patient who had an abrupt rise of systolic BP to 220 mm Hg immediately after valve deployment and consequently developed severe pulmonary edema that necessitated mechanical ventilation.
TAVI is a novel therapy for a challenging population of patients. Treatment of these complex patients requires a dedicated multidisciplinary team of interventional cardiologists, intensive care specialists, and anesthesiologists to monitor their responses and promptly treat adverse events. The hemodynamic responses described herein may also bring insight to the recuperative capabilities of the myocardium in patients with AS.
The data we used for this study were prospectively collected but the cohort size is not large and a relatively short follow-up was used. As a result, we might have inherent biases between the 2 groups. In addition, the method we used for calculating cardiac output is indirect and could possibly have led to overestimation of the differences we observed. Nevertheless, the hemodynamic changes we noted were very significant, and we believe that these changes and the associated clinical outcomes are valid.
After TAVI, about one-half of the patients have a significant rise in systolic BP, necessitating immediate and long-term treatment. To our knowledge, this is the first study showing that an increase in BP after TAVI predicts a better recovery of cardiac function and favorable short- and mid-term clinical outcome.
Dr. Danenberg is a clinical proctor for Medtronic CoreValve. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- aortic stenosis
- aortic valve replacement
- blood pressure
- left ventricle
- left ventricular outflow tract
- transcatheter aortic valve implantation
- Received October 11, 2012.
- Revision received December 14, 2012.
- Accepted December 21, 2012.
- American College of Cardiology Foundation
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