Association Between Diastolic Dysfunction and Health Status Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement

Abstract

Objective:

To assess the association of baseline left ventricular diastolic dysfunction (LVDD) with health status outcomes of patients undergoing transcatheter aortic valve replacement (TAVR).

Background:

While LVDD in patients with aortic stenosis is associated with higher mortality after TAVR, it is unknown if it is also associated with health status recovery.

Methods:

In a cohort of 304 patients with interpretable echocardiograms, undergoing TAVR, LVDD was categorized at baseline as absent (grade 0), mild (grade 1), moderate (grade 2) or severe (grade 3). Disease-specific health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at baseline, 1-month and 12-month follow up. Association of baseline LVDD with health status at baseline and follow up after TAVR was assessed using a linear trend test and association with health status recovery (change in KCCQ OS) was examined using a linear mixed model adjusting for baseline KCCQ-OS.

Results:

Twenty-four (7.9%), 54 (17.8%), 186 (61.2%) and 40 (13.2%) patients had LVDD grades of 0, 1, 2 and 3 respectively. Baseline KCCQ OS was 61.3 ± 22.7, 51.0 ± 26.1, 44.7 ± 25.7, and 44.4 ± 21.9 (p=0.004) in patients with LVDD grade 0, 1,2 and 3. At 1 and 12 months after TAVR, LVDD was not associated with KCCQ-OS. Recovery in KCCQ-OS after TAVR was substantial and similar in patients across all severities of LVDD.

Conclusion:

While LVDD is associated with health status prior to TAVR, patients across all severities of LVDD have similar recovery in health status after TAVR.

CONDENSED ABSTRACT

Baseline LVDD is associated with higher mortality in patients undergoing TAVR for severe AS. To assess if LVDD before TAVR is also associated with patient’s health status before and after TAVR we examined the baseline and post-TAVR KCCQ-OS in a consecutive cohort of treated patients as a function of LVDD. LVDD was significantly associated with lower KCCQ-OS at baseline, however there was no association at 1and 12 month follow up. Improvement in KCCQ-OS after TAVR did not differ significantly in patients across all grades of LVDD.

INTRODUCTION

As aortic valve stenosis (AS) progresses and the left ventricle is exposed to increased afterload, compensatory left ventricle hypertrophy evolves to maintain cardiac output (1, 2). Increased afterload is also associated with development of adverse intramyicardial fibrosis (3, 4). These effects often result in left ventricular diastolic dysfunction (LVDD), which is present in ~70% of patients with symptomatic AS and is independently associated with mortality in patients undergoing surgical or transcatheter aortic valve replacement (TAVR) (5-10).

While the impact of LVDD on mortality outcomes after TAVR have been described, little is known regarding the association of pre-TAVR LVDD with health status prior to treatment, or whether LVDD impacts the benefits of TAVR in improving patients’ health status. Since, relief of symptoms and improvement in quality of life (QoL) are important goals of TAVR, understanding this association can help patients and providers weigh the overall risks and benefits of treatment in patients with LVDD. To address this gap in knowledge, we investigated the association between baseline LVDD with disease-specific health status of patients with severe AS before and after TAVR.

METHODS

Study Population

Data from all patients undergoing commercial TAVR at Saint Luke’s Mid America Heart Institute are submitted to the Transcatheter Valve Therapy (TVT) registry. The TVT registry is a national registry designed to serve as a platform for device and procedural surveillance, quality assurance and improvement initiatives, and to conduct studies that facilitate innovation and expansion of device labelling through evidence development (11). All patients who underwent commercial TAVR between January 2012 to October 2017 at Saint Luke’s Mid America Heart Institute (Kansas City, MO) were included in this analysis. Patients with significant mitral stenosis, greater than moderate mitral regurgitation, history of surgical mitral valve replacement, atrial fibrillation or paced rhythm at the time of transthoracic echocardiogram (TTE) or severe mitral annular calcification (MAC) were excluded from this analysis, due to inaccuracies in determining the severity of LVDD. MAC was deemed to be severe at the discretion of the echocardiographer interpreting the study at the initial read. This study was reviewed and approved by the local Institute Review Board and all study-related procedures were carried out in accordance with the Declaration of Helsinki.

Assessment of LVDD

Baseline TTEs performed within three months prior to TAVR were reviewed retrospectively by study investigators who are certified by the National Board of Echocardiography using Synapse™ Cardiovascular Imaging Software. For the acquisition of echocardiographic parameters, at least 3 consecutive heart beats were recorded and averaged for each parameter. Four variables were assessed to categorize LVDD grade in accordance with American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines (12, 13). The variables and individual cutoffs were; annular e’ velocity (septal e’ < 7cm/s or lateral < 10cm/s), average E/e’ > 14, Left Atrial Volume Index (LAVI) > 34ml/m² and peak tricuspid regurgitation (TR) velocity >2.8m/s. LVDD was defined by the presence of at least 3 of the aforementioned echocardiographic parameters. In patients with diastolic dysfunction, severity of LVDD was further categorized based on mitral inflow pattern using E/A ratio and peak E velocity. Grade 1 was defined as a mitral inflow pattern with an E/A ratio ≤ 0.8 and peak E velocity < 50cm/s. Grade 3 LVDD was defined as a mitral inflow pattern with an E/A ratio ≥ 2 in combination with an elevation of the left atrial pressure (E/e’ >14).

In instances when E/A ≤ 0.8 and E > 50cm/s or 0.8 < E/A <2, 3 additional criteria were evaluated, including TR velocity, LAVI, and average E/e’ using the above-mentioned thresholds. If all 3 parameters were available, and fewer than 2 met the cut off value, the LVDD was considered grade 1. If 2 or more parameters met the thresholds LVDD was considered grade 2. If only 1 parameter was available, or if there was a discrepancy between only 2 available parameters, LVDD grade was not classified. If only 2 parameters were available and met the cut off values, an adjudication of LVDD grade 2 was made, and if both did not meet the threshold, LVDD grade 1 was assigned. Supplemental figure 1 depicts the classification process.

A similar method was used to categorize LVDD from echocardiograms performed during follow-up after TAVR. Short-term follow-up was defined as 2 to12-weeks and long-term follow-up defined as 6 to24 months after TAVR respectively.

Study Outcomes

Disease-specific health status was evaluated at baseline, 1-month and 12-month followup using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). The 12-item version is a subset of the full, 23-item KCCQ, which captures 5 key domains of health status in patients with heart failure and has also been validated in patients with AS (14, 15). Domains are scored from 0 to 100, with higher scores indicating better health status (16). The individual domains of the KCCQ are converted into an overall summary score (KCCQ-OS), which was the primary outcome measure for this analysis. A 5-point change in KCCQ-OS represents a clinically important difference for individual patients (17). All-cause mortality over 12-months was assessed by review of electronic medical records.

Statistical Analysis

After excluding patients in whom an accurate assessment of LVDD could not be determined and patients with missing initial health status assessments, we compared baseline characteristics across LVDD grades (0-3, where 0 represents no LVDD) using linear trend tests for continuous variables and Mantel-Haenszel trend tests for categorical variables. We examined the association between LVDD grade and KCCQ-OS scores using a linear mixed model, which included time and LVDD grade as categorical effects, a time-by-LVDD interaction, and an unstructured within-patient covariance matrix. We used linear trend tests to compare mean KCCQ-OS across LVDD grades at each time point. We also analyzed change from baseline in KCCQ-OS at 1 month and 12 months using a linear mixed model that, in addition to a time-by-LVDD interaction, included adjustment for baseline KCCQ-OS. Time to all-cause mortality through 1 year was summarized using Kaplan-Meier (KM) estimates and compared across LVDD grades using the log-rank test. We also performed a series of analyses integrating both death and health status outcomes over 12 months. We calculated the proportion of patients for each LVDD group who were (1) alive with moderately large health status improvement (change ≥ 10 points from baseline KCCQ-OS), (2) alive with large health status improvement (change ≥ 20 points from baseline KCCQ-OS) and (3) “alive and well” as defined previously (KCCQ-OS ≥ 60 and no decline ≥10 points from baseline) (18). The proportion of patients in each LVDD group were compared using Mantel-Haenszel trend tests.

To assess the association of TAVR with health status as a function of patients’ LVDD, we categorized change in LVDD grade during short term (echocardiogram done at 2-12 weeks) and long term (echocardiogram done at 6-24 months) follow-up after TAVR. Finally, to examine the association between change in LVDD grade at short term follow-up with change in KCCQ-OS at 1-month and change in LVDD grade at long-term follow-up with change in KCCQ-OS at 12-months we developed another linear mixed model treating change in LVDD grade as a categorical effect and adjusting for baseline LVDD grade and baseline KCCQ-OS.

Missing Data

While our cohort included patients with baseline KCCQ-OS scores, many patients were missing follow-up scores. The rate of missing KCCQ data among survivors was 12.1% at 1 month and 41.3% at 12 months. We used inverse probability weighting (IPW) to examine the impact of missing data on our findings (19). We first constructed a multivariable logistic regression model among patients who were alive at follow-up, to determine the probability of having complete follow-up KCCQ data. The model included demographics, comorbidities, clinical characteristics and baseline KCCQ-OS. Each patient then received a weight, calculated as the reciprocal of the probability of having follow-up KCCQ data, so that those with follow-up data were reweighted to reflect the patient characteristics of the entire sample population. We calculated weights separately for 1-month and 12-month assessments (patients who died received a weight of 1.0). Weights were stabilized by dividing by the mean IPW. We then repeated the above analyses reweighting each patient by their IPW; the results were similar to the main findings. All statistical analyses were performed using SAS 9.4 (SAS Institute Inc, Cary, NC). All statistical tests were 2-tailed and significance was determined using α = 0.05.

RESULTS

Study Population

Among 587 patients who had TAVR for symptomatic AS, LVDD could be assessed in 335 patients, of whom 311 (92.8%) had some degree of LVDD at baseline (Supplemental figure 1). 31 patients who had LVDD could not be assigned a specific LVDD grade due to discrepant variables. These subjects were excluded from the analyses. Supplemental table 1 compares the demographic and clinical characteristics of patients who were excluded with those who were included in our analytical cohort. Compared to patients who were included, patients who were excluded had higher prevalence of chronic lung disease (60.3% vs 48.7% p=0.03). There were no other significant differences in demographics, comorbid conditions, health status assessment at each time point and mean aortic valve area and gradient.

In the final analytic cohort (n=304), the mean age was 81.1 ± 8.5 years, 41.1% were females, 48.7% had chronic lung disease, 24.9% had a history of myocardial infarction, and 10.9% had a history of stroke. Mean Society of Thoracic Surgeon risk score was 10.2 ± 4.3 and 74 (24%) patients underwent TAVR via alternative (non-femoral) access.

Table 1 shows a comparison of baseline demographic and clinical characteristics in patients according to LVDD grade. LVDD was grade 0 in 24 (7.9%) patients, grade 1 in 54 (17.8%) patients, grade 2 in 186 patients (61.2%) and grade 3 in 40 (13.2%) patient. Patients with higher grades of LVDD were more likely to be older, and to have had a prior myocardial infarction or prior coronary artery bypass graft surgery. There were no differences in aortic valve area or mean trans-valvular gradient across groups (Table 2). Patients with higher grades of LVDD were more likely to have lower ejection fraction, higher average peak TR velocity, and higher LAVI.

Table 1.

Comparison of baseline demographic, clinical and procedure characteristics in patients according to LVDD grade.

	LVDD grade
	0	1	2	3	P value
	n=24	n=54	n=186	n=40
Demographics
Age (Mean ± SD)	77.9 ± 10.7	79.0 ± 9.5	82.4 ± 7.7	82.5 ± 7.6	0.006
Female (%)	41.7	38.9	44.1	30.0	0.593
Caucasian Race (%)	100.0	100.0	97.8	100	0.591
Comorbidities (%)
Hypertension	91.7	88.9	96.8	90.0	0.462
History of MI	12.5	18.9	25.0	40.0	0.008
History of PCI	50.0	44.4	45.2	46.4	0.791
History of CABG	8.3	25.9	25.3	42.5	0.009
History of Stroke	8.3	9.3	13.4	2.5%	0.759
Chronic Lung Disease	33.3	45.3	49.7	57.5	0.056
Home Oxygen	4.2	3.7	7.5	5.0	0.561
Gait Speed (Mean ± SD)	1.5 ± 0.5	1.5 ± 0.5	1.6 ± 0.8	1.3 ± 0.4	0.656
STS Risk Score (Mean ± SD)	8.8 ± 4.8	9.8 ± 4.4	10.3 ± 4.3	10.9 ± 3.7	0.058
Femoral Access (%)	83.3	74.1	80.6	64.1	0.393
Study Outcomes
Mortality Rate at 12-month	0.0%	5.9%	7.7%	13.9%	0.289
KCCQ-OS (Mean ± SD)
Baseline	61.3 ± 22.7	51.0 ± 26.1	44.7 ± 25.7	44.4 ± 21.9	0.004
1-month	71.2 ± 22.1	72.1 ± 20.4	67.4 ± 23.7	66.9 ± 24.7	0.367
12-month	70.1 ± 22.4	74.5 ± 19.8	66.6 ± 26.4	65.4 ± 20.0	0.354

Table 2.

Comparison of echocardiographic parameters at baseline across study groups.

LVDD grade
	No LVDD n=24	1 n=54	2 n=186	3 n=40	P value
TVG [mm of Hg] (Mean ±SD)	45.6 ± 12.0	44.7 ± 11.8	46.3 ± 13.0	38.5 ± 13.2	0.005
Aortic Valve Area [cm2] (Mean ±SD)	0.7 ± 0.1	0.7 ± 0.1	0.7 ± 0.2	0.7 ± 0.	0.087
Ejection Fraction (Mean ±SD)	65.8 ± 5.6	60.5 ± 10.5	60.6 ± 12.1	48.0 ± 17.3	< 0.001
Average e’[cm/s] (Mean ±SD)	6.6 ± 1.6	6.0 ± 4.6	5.4 ± 1.5	6.2 ± 2.6	0.420
TR Velocity [m/s] (Mean ±SD)	2.2 ± 0.8	2.7 ± 0.4	3.1 ± 0.5	3.4 ± 0.5	< 0.001
LAVI [ml/m2] (Mean ±SD)	26.6 ± 6.1	33.9 ± 13.8	42.6 ± 12.5	45.4 ± 11.5	< 0.001
E/A ratio (Mean ±SD)	0.9 ± 0.4	0.7 ± 0.2	1.0 ± 0.4	2.6 ± 0.6	< 0.001
E/e’ ratio (Mean ±SD)	11.9 ± 3.5	13.9 ± 4.8	20.2 ± 7.3	21.0 ± 7.6	<0.001

Association of LVDD with mortality and health status

In the analytical cohort mean KCCQ-OS score was 47.1 ± 25.4 at baseline, 68.5 ± 23.1 at 1-month, and 68.4 ± 24.1 at 12-months after TAVR. Higher grades of LVDD were associated with worse baseline health status but similar KCCQ-OS at 1- and 12-months post-TAVR (Central Illustration Panel A). Recovery in health status in patients across all grades of LVDD was substantial and was similar in magnitude (Figure 1).

Central Illustration: Health status at baseline and follow up.

A) Comparison of health status in patients with severe AS across all grades of LVDD at baseline (before TAVR) and follow-up after TAVR. B) Composite health status and mortality outcomes for patients by LVDD grade. (total patients evaluated= 304 [LVDD 0=24, LVDD 1=54, LVDD2=186, LVDD3=40], error bars represent 95% confidence interval around the mean estimate).

[Aortic Valve Stenosis (AS), Left Ventricular Diastolic Dysfunction (LVDD), Transcatheter Aortic Valve Replacement (TAVR)]

Figure 1. Recovery in health status.

Comparison of recovery in health status after TAVR at 1-month and 12-month, according to baseline LVDD grade (total patients evaluated= 304 [LVDD 0=24, LVDD 1=54, LVDD2=186, LVDD3=40], error bars represent 95% confidence interval around the mean estimate).

[Left Ventricular Diastolic Dysfunction (LVDD), Transcatheter Aortic Valve Replacement (TAVR)]

Vital status at 12-months was available on all patients. Overall mortality rate at 12-months was 7.55% in our study population. Supplemental figure 2 shows the KM curves for mortality over 12-months stratified by LVDD grade. Patients with higher grades of LVDD at baseline had numerically higher mortality rate but it was not statistically significant (p=0.28).

Composite outcomes Central Illustration (Panel B) shows the proportion of patients who were alive with moderately large health status improvement (KCCQ-OS change ≥ 10), alive with large health status improvement (KCCQ-OS change ≥ 20) and “alive and well” (KCCQ-OS ≥ 60 and no decline ≥10 points from baseline) at 12-month follow-up. There was no difference across LVDD groups for the composite outcome of “alive and well”, or “alive with moderately large health status improvement.” However, patients with lower LVDD grade were less likely to be alive with a large health status improvement at 12-month follow-up (p =0.03).

Change in LVDD after TAVR and association with change in Health Status

Of the 304 patients in the final study cohort, 215 and 142 had an interpretable echocardiogram available at short term and long-term follow-up, respectively. Tables 3 and 4 depict the changes in LVDD grade following TAVR, at each follow-up timepoint. Among the 215 patients with an interpretable echocardiogram at baseline and short-term follow-up, LVDD grade improved in 55 (26%), worsened in 32 (14%), and was unchanged in 128 (60%) patients. Of the 142 patients with interpretable echocardiograms at both baseline and long-term follow up LVDD grade improved in 42(30%), worsened in 18 (12%), and was unchanged in 82 (58%) patients.

Table 3.

Change in left ventricular diastolic dysfunction grade among 215 patients with interpretable echocardiograms at baseline and short-term follow up.

	LVDD grade at short term follow-up
LVDD grade at baseline	0 (n=25)	1 (n=49)	2 (n=128)	3 (n=13)
0 (n=19)	10 (53%)	5 (26%)	4 (21%)	0
1 (n=38)	5 (13%)	15 (39%)	18 (48%)	0
2 (n=133)	9 (7%)	24 (18%)	95 (71%)	5 (4%)
3 (n=25)	1 (4%)	5 (20%)	11 (44%)	8 (32%)

Table 4.

Change in left ventricular diastolic dysfunction grade among 142 patients with interpretable echocardiograms at baseline and long-term follow up.

	LVDD grade at long term follow-up
LVDD grade at baseline	0 (n=22)	1 (n=27)	2 (n=87)	3 (n=6)
0 (n=12)	7 (58%)	2 (17%)	2 (17%)	1 (8%)
1 (n=25)	7 (28%)	6 (24%)	11 (44%)	1 (4%)
2 (n=86)	7 (8%)	12 (14%)	66 (77%)	1 (1%)
3 (n=19)	1 (5%)	7 (37%)	8 (42%)	3 (16%)

There was no association between improvement in LVDD grade at short-term follow-up with change in KCCQ-OS at 1-month (Mean estimate in KCCQ-OS change 0.28 ± 2.1 per 1-grade improvement in LVDD; p=0.89). Similarly, there was no association between improvement in LVDD grade at long-term follow-up with change in KCCQ-OS at 12-monhs (Mean estimate in KCCQ-OS change 1.7 ± 2.9 p=0.56, per 1-grade improvement in LVDD).

DISCUSSION

Although TAVR provides prompt and reliable reversal of valvular obstruction, some patients do not derive symptomatic benefit from the procedure (20, 21). One possible factor that could account for poor outcomes after TAVR is LVDD, which is commonly present in patients with AS (6). LVDD results from the severe afterload associated with AS, can worsen patients’ symptoms, and could conceivably result in worse health status after resolution of the aortic valve obstruction. To assess the recovery after TAVR in patients’ symptoms, function and QoL, we examined the baseline and post-TAVR KCCQ-OS in a consecutive cohort of treated patients as a function of LVDD. We found an association between increasing severity of LVDD grade and poorer health status at baseline, but no differences in health status 1-month or 12-months following TAVR. Rather, we found that the health status benefits from TAVR were robust and similar in patients across all grades of LVDD. Additionally, the benefit of TAVR in terms of composite outcomes of mortality and health status, was similar across LVDD groups. This suggests that there is no association between LVDD and the health status benefits of TAVR, and that LVDD should not be considered as a contraindication to treatment.

Our findings extend the previous literature on the relationship between LVDD and outcomes in patients undergoing TAVR to include patients’ health status. Several studies have reported higher mortality and cardiac rehospitalization following TAVR in patients with LVDD (7-10). Furthermore, in a prospective cohort of 166 patients with AS, LVDD was associated with increased myocardial fibrosis and was independently associated with mortality (22). Beyond mortality, patients are equally concerned about their symptoms, functional capacity and QoL. While the present study was not sufficiently powered to examine mortality, these findings enhance our understanding of the impact of baseline LVDD on outcomes after TAVR through assessment of health status and composite mortality and QoL outcomes.

It is unclear as to why the association between LVDD and QoL benefit of TAVR differs from that of mortality. One possible explanation is that the majority of symptoms in patients with LVDD are related to afterload mismatch, which improves rapidly after relief of valvular obstruction with TAVR. A second possible explanation is that LVDD may improve after relief of AS. Indeed, previous studies have shown that diastolic parameters improve as soon as 2 weeks after valve replacement, and improvement in LVDD after TAVR is associated with improvement in New York Heart Association functional status (23, 24). Although LVDD improved in a substantial number of patients in our study cohort, change in LVDD grade was not associated with change in health status after TAVR. Hence while both AS and LVDD impair patient’s health status, the impact of AS itself, on patient’s symptoms and QoL outweighs that of LVDD.

Our results should be interpreted in context of the following potential limitations. This was a single center study with a modest sample size, and it is possible that our study was underpowered to detect moderate differences in health status at follow-up. Only echocardiographic parameters were used to diagnose LVDD in this study, and hence LVDD could not be assessed in about 50% of patients (e.g. patient had atrial fibrillation, mitral stenosis, mitral valve repair etc.). It is possible that this introduced a selection bias in our observational study and other methods, such as measuring the time constant for isovolumic-pressure decline using an invasive manometer, could include additional patients and reduce this risk (25). Furthermore, we did not have data on amount of periprosthetic aortic regurgitation in patients across LVDD groups. However, previous studies have shown periprosthetic aortic regurgitation to be independent of baseline LVDD (6) and we do not expect that patients across LVDD groups in our study cohort would have significant differences in periprosthetic aortic regurgitation. Additionally, the severity of MAC was not quantitatively assessed using computed tomography and as MAC can influence LVDD parameters (26) this could have biased our results. However, patients with mitral valve disease including severe MAC on echocardiography were excluded based on the discretion of the echocardiographer interpreting the study if it was felt that the MAC was severe enough to influence assessment of LVDD (n=53). Finally, although it has been shown that myocardial fibrosis is associated with LVDD (22), other methods of assessing myocardial fibrosis such as global longitudinal strain or late gadolinium enhancement could be more sensitive and specific. Examining association of myocardial fibrosis using these markers with outcomes of patients with severe AS after TAVR remain important areas of further research.

CONCLUSIONS

In summary, in a large single-center study of patients undergoing TAVR, we found that baseline health status was inversely correlated with the extent of LVDD. Nonetheless, patients with all grades of LVDD had similar improvement in disease-specific health status after TAVR, which was immediate (at 1-month follow-up) and sustained (at 1-year follow-up). These findings suggest that baseline LVDD is not associated with the health status benefits of TAVR and that physicians and patients need not alter their expectations of health status benefit based upon patients’ extent of LVDD.

PERSPECTIVES.

WHAT IS KNOWN?

LVDD is associated with higher mortality in patients undergoing TAVR for severe AS. However, it is unknown whether LVDD is also associated with patients’ health status before TAVR and recovery in patient’s symptoms, function and QoL after TAVR.

WHAT IS NEW?

In this study on a consecutive cohort of patients undergoing TAVR we found a significant association of LVDD with poorer health status before TAVR. However, the improvement in health status and QoL after TAVR was robust and similar in patients across all grades of LVDD.

WHAT IS NEXT?

Larger multi-center studies are needed to confirm our results and to examine if myocardial fibrosis assessed by other modalities is also associated with health status of patients with AS before and after TAVR.

ABBREVIATIONS AND ACRONYMS

(AS)

Aortic Valve Stenosis

(LVDD)

Left Ventricle Diastolic Dysfunction

(TAVR)

Transcatheter Aortic Valve Replacement

(QoL)

Quality of Life

(TVT)

Transcatheter Valve Therapy

(TTE)

Transthoracic Echocardiogram

(MAC)

Mitral Annular Calcification

(LAVI)

Left Atrial Volume Index

(TR)

Tricuspid Regurgitation

(KCCQ)

Kansas City Cardiomyopathy Questionnaire