Prognostic Impact of Functional Mitral Regurgitation in Patients Admitted With Acute Decompensated Heart Failure

Abstract

Background: Functional mitral regurgitation (FMR) is a common complication of heart failure (HF) and worsens in acute decompensation. It is unclear whether FMR on admission or discharge determines the outcome. This study aimed to elucidate the prognostic significance of FMR on admission or discharge in patients admitted with acute decompensated HF.

Methods and Results: From 2006 to 2009, 349 patients admitted with acute decompensated HF were enrolled. They were followed with the composite endpoint of all-cause death and hospitalization for HF; 74 (21%) died and 113 (32%) developed the composite endpoint during 2.1±1.3 years. Moderate/severe FMR at discharge was associated with the composite endpoint (P=0.001), whereas that on admission was not. Multivariate Cox proportional hazard analysis showed that moderate/severe FMR (hazard ratio [95% confidence interval] =1.70 [1.03–2.73] P=0.04), logBNP, and NYHA class III/IV at discharge were independent determinants of the outcome. Moderate/severe FMR at discharge with BNP ≥200 pg/ml was prognostic, but BNP <200 pg/ml was no longer prognostic.

Conclusions: Residual moderate/severe FMR after medical therapy for acute decompensated HF was associated with poor outcome, suggesting a potential target for further treatment of HF. (Circ J 2016; 80: 139–147)

Heart failure (HF) is a complex clinical syndrome with a poor prognosis, which has imposed a considerable burden on nations from the public health perspective, despite recent advancements in medical treatment.^1–3 Patients with HF often experience acute decompensation (ADHF). The increased left ventricular (LV) filling pressure in ADHF produces myocardial injury and neurohumoral activation, further worsening cardiac function.⁴ Thus, the goals of therapy for ADHF should be not only to improve symptoms and hemodynamics, but also to remove accompanying deteriorating factors.⁴

Dilatation of the LV and mitral annulus often causes tethering of the intact mitral leaflets and functional mitral regurgitation (FMR), which in turn results in progressive LV and left atrial (LA) dilatation and a poor prognosis both in ischemic and non-ischemic HF.^5–7 Mitral valve (MV) surgery may be considered if severe HF symptoms caused by severe chronic FMR persist with optimal medical therapy;^8,9 however, an appropriate strategy for FMR is not fully established.

Patients with chronic HF often experience ADHF with deterioration of FMR,¹⁰ which may or may not improve at discharge following medical treatment.¹⁰ The prognostic significance of FMR severity on acute decompensation and that in a less symptomatic chronic state at discharge in patients with ADHF has not been determined. It has not been determined when is appropriate to evaluate the indication of FMR for more aggressive treatment. In this prospective cohort study of patients admitted for ADHF, we examined the hypothesis that the severity of FMR at discharge is more important than that on admission for predicting the long-term clinical outcome and for determining the indication of more aggressive treatment.

Methods

Study Population

From 2006 to 2009, 757 consecutive patients admitted with ADHF to the National Cerebral and Cardiovascular Center were registered in the n-CASCADE database, a single-center prospective registry for ADHF not caused by acute coronary syndrome. Of the 757 patients, 242 were not eligible because of poor quality echocardiographic recordings, and the remaining 515 patients were enrolled.

The exclusion criteria for this study were as follows: (1) organic MV disease, including mitral prolapse, rupture of chordae tendineae, rheumatic mitral disease, and infective endocarditis, (2) significant aortic valve disease, (3) congenital heart disease, (4) prior MV surgery, and (5) idiopathic pulmonary arterial hypertension except for secondary pulmonary hypertension caused by left-sided heart disease. We excluded 166 patients for the following reasons: organic MV changes (48 patients), concomitant significant aortic valve disease (68 patients), congenital heart disease (5 patients), post mitral surgery (42 patients), and idiopathic pulmonary arterial hypertension (3 patients). Finally, 349 patients were eligible for the study.

The study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the ethics committee and research department of the National Cerebral and Cardiovascular Center (M22-025). Written informed consent was given by all patients before registration. The investigators could not directly access the primary data.

Clinical Data Collection and Echocardiographic Study

The clinical background data of the patients, including age, sex, history of ischemic heart disease (IHD: history of myocardial infarction, angina, or vasospastic angina), atrial fibrillation, diabetes mellitus, and hypertension was collected by reviewing their charts.

LV and LA dimensions and diastolic function were evaluated by transthoracic echocardiography according to published recommendations.^11,12 LV ejection fraction (EF) obtained using the modified Simpson’s method and mitral inflow parameters (E-wave velocity, A-wave velocity, and deceleration time) were measured. Fractional shortening (%FS) calculated with the following formula was used when the LVEF value was not available: %FS=[(LV end-diastolic dimension−LV end-systolic dimension)/LV end-diastolic dimension] ×100. The severity of FMR was graded as previously reported.¹³ The grade of FMR was evaluated qualitatively (none, trace, mild, moderate, and severe) and scored in a semiquantitative fashion (none=0, trace-mild=1, moderate=2, severe=3). Trained sonographers blinded to the MR grade on admission recorded a comprehensive echocardiogram before discharge. To test the reliability of the semiquantitative method, we compared the results of the semiquantitative evaluation and proximal isovelocity surface area in 134 patients referred for evaluation of MR in a blinded fashion. The proximal isovelocity surface area was calculated by proximal flow convergence as previously described.¹⁴ The semiquantitative grading showed good correlation with the proximal isovelocity surface area analyzed by proximal flow convergence (r=0.74, P<0.001). LVEF was measured by scintigraphy in some patients.

Follow-up Study and Primary Endpoint

After discharge, patients were followed every year using a mail survey or outpatient visit. The endpoint of the study was composite cardiac events consisting of all-cause death and unexpected hospitalization for HF. Patients who underwent mitral surgery after enrollment were censored at the time of surgery.

Statistical Analysis

Numerical data are reported as either mean±SD or median and interquartile range, as appropriate. To compare numerical data between 2 groups, unpaired t-test or Wilcoxon’s rank sum test was used, as appropriate. Chi-squared test was used to compare the prevalence of characteristics between groups.

For survival analyses, patients were divided into groups based on FMR grade and other clinical characteristics. Kaplan-Meier survival curves were constructed for each subgroup and compared by log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to assess the predictive value of the factors for the composite endpoint after discharge. Plasma B-type natriuretic peptide (BNP) level was used after common logarithmic transformation. For multivariate analyses, we incorporated FMR grade and the variables that were significant in the univariate analyses. Subgroup analysis based on plasma BNP level at discharge was performed. A cut-off level of 200 pg/ml for plasma BNP level was selected based on a previous report.¹⁵ A 2-tailed probability (P) value less than 0.05 was accepted as significant. A software package (JMP 9.0; SAS Institute Inc, Cary, NC, USA) was used for statistical analysis.

Results

Patients Characteristics

Table 1 shows the baseline characteristics of the 349 enrolled patients. Mean age was 72±13 years, and 138 (40%) patients had a history of IHD. Mean %FS on admission was 19±10%. More than 70% of patients were prescribed an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) or β-blocker at discharge. A few patients were prescribed an oral inotropic agent, pimobendan, a compound similar to levosimendan.¹⁶

Table 1. Clinical Characteristics of ADHF Patients on Admission and at Discharge

	Admission (n=349)		Discharge (n=349)
	n*	Value†	n*	Value†
Age, years	349	72±13
Female, n (%)	349	121 (35)
BMI, kg/m2	348	23.4±4.3
NYHA III/IV, n (%)	319	319 (91)	325	17 (5)
SBP, mmHg	349	144±36		NA
DBP, mmHg	347	85±22		NA
Heart rate, beats/min	349	98±29	337	66±10
AF, n (%)	310	120 (34)	295	90 (26)
Prior HF hospitalization, n (%)	346	120 (34)
HTN, n (%)	349	267 (77)
DM, n (%)	338	154 (44)
CAD, n (%)	343	138 (40)
History of MI, n (%)	349	127 (36)
CRT implanted, n (%)	344	7 (2)		NA
Serum creatinine, mg/dl	349	1.37±1.28	346	1.42±1.30
Serum sodium, mEq/L	349	138±4	347	138±4
BNP, pg/ml	347	791 (429–1,345)	320	240 (128–423)
LAD, mm	278	45±8	326	46±8
LVDD, mm	344	56±11	344	57±11
LVDS, mm	343	46±13	342	45±13
FS, %	343	19±10	342	23±11
E-wave velocity, cm/s	254	90±29	309	75±27
E/A ratio	152	1.77±1.23	215	1.36±1.15
E deceleration time, ms	242	163±68	304	194±73
MR none-trivial, n (%)	349	40 (11)	349	56 (16)
MR mild, n (%)	349	182 (52)	349	215 (62)
MR moderate, n (%)	349	108 (31)	349	68 (19)
MR severe, n (%)	349	19 (5)	349	10 (3)
TRPG, mmHg	267	36±12	269	26±9
β-blocker, n (%)		NA	349	253 (72)
ACEI or ARB, n (%)		NA	349	258 (74)
Spironolactone, n (%)		NA	349	143 (41)
Oral inotrope, n (%)		NA	349	31 (9)
Oral diuretic, n (%)		NA	349	289 (83)

*Number of patients with data available; ^†values are presented as mean±SD, median and interquartile range (25–75th percentile), or n (%), as appropriate. ACEI, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; AF, atrial fibrillation; ARB, angiotensin-receptor blocker; BMI, body mass index; BNP, B-type natriuretic peptide; CAD, coronary artery disease; CRT, cardiac resynchronization therapy; DBP, diastolic blood pressure; DM, diabetes mellitus; FS, fractional shortening; HF, heart failure; HTN, hypertension; LAD, left atrial dimension; LVDD, left ventricular end-diastolic dimension; LVDS, left ventricular end-systolic dimension; MI, myocardial infarction; MR, mitral regurgitation; NA, not applicable; NYHA, New York Heart Association functional class; SBP, systolic blood pressure; TRPG, pressure gradient derived from tricuspid regurgitation.

Changes in FMR Grade

The changes in the grade of FMR in this cohort are shown in Figure 1. Of 349 patients, 127 (36%) patients had moderate/severe FMR on admission, of whom 64 (50%) showed improvement in the grade of FMR at discharge (none-trace, 4; mild, 60) and 63 (50%) had moderate/severe FMR at discharge after medical treatment (moderate, 68; severe 10). The average hospital stay was 38±35 days. Representative cases of the change in FMR grade in response to medical treatment are shown in Figure 2. Of 222 patients who had none/mild FMR on admission, 15 (7%) showed a worse grade of FMR at discharge (moderate, 14; severe, 1).

Figure 1.

Change in the grade of functional mitral regurgitation (FMR) between admission and discharge. On admission, 222 patients had none/mild FMR and 127 had moderate/severe FMR. After medical treatment, FMR improved to none/mild in 50% of the patients with moderate/severe FMR on admission, and remained moderate/severe in the remaining patients.

Figure 2.

Representative cases of a change in the grade of functional mitral regurgitation (FMR) after medical treatment. An 80-year-old woman with moderate FMR on admission (A) and mild FMR at discharge (B). A 50-year-old woman in atrial fibrillation with severe FMR on admission (C) and severe FMR at discharge (D). CRT failed to create a biventricular rhythm because of the atrial fibrillation with a rapid ventricular response (C). She was in an optimal atrial and biventricular pacing rhythm at discharge after a cardioversion (D). CRT, cardiac resynchronization therapy.

Prognostic Impact of FMR Grade

During the follow-up of 2.1±1.3 years, 74 (21%) patients died and 113 (32%) developed the composite endpoint, including death from any cause and readmission for HF; 5 patients who underwent MV surgery were censored at the day of the operation, of whom 2 had MV plasty in conjunction with ventricular reconstruction, 2 had tricuspid annular plasty, and 1 had ventricular reconstruction and coronary artery bypass grafting. Moderate/severe FMR at discharge was associated with a higher incidence of adverse cardiac events compared with none/mild FMR. The grade of FMR on admission was not associated with the long-term clinical outcome (Figure 3). Among patients with none/mild FMR at discharge, FMR severity on admission did not affect their prognosis (Figure 4). There were 15 patients who had none/mild FMR on admission and had developed moderate/severe FMR at discharge. This group showed a poor outcome, comparable to that of patients with moderate/severe FMR both on admission and at discharge (composite endpoint: 60.0% vs. 44.4%, P=0.672).

Figure 3.

Kaplan-Meier curves for composite endpoint. (A) Event-free curve for composite endpoint by FMR grade on admission. (B) Event-free curve for composite endpoint by FMR grade at discharge. FMR, functional mitral regurgitation.

Figure 4.

Kaplan-Meier curves for composite endpoint of patients with none/mild FMR at discharge by FMR grade on admission. Among patients with none/mild FMR at discharge, FMR severity on admission did not affect their prognoses. FMR, functional mitral regurgitation.

Predictors of Cardiac Events

Table 2 shows the results of univariate and multivariate Cox proportional hazard analyses for the composite endpoint. Age (hazard ratio [HR]: 1.03 per year, 95% confidence interval [CI]: 1.02–1.05, P<0.001), BNP at discharge (HR: 3.67 per logBNP, 95% CI: 2.29–5.86, P<0.001), NYHA functional class III/IV at discharge (HR: 6.99, 95% CI: 3.67–12.3, P<0.001), prior hospitalization for HF (HR: 1.90, 95% CI: 1.31–2.76, P<0.001), E-velocity at discharge (HR: 1.01, 95% CI: 1.00–1.01, P=0.042), moderate/severe FMR at discharge (HR: 1.91, 95% CI: 1.28–2.80, P=0.002), discharge prescription of ACEI/ARB (HR: 0.65, 95% CI: 0.44–0.97, P=0.035), and discharge prescription of oral inotrope (HR: 2.44, 95% CI: 1.45–3.90, P=0.001) were significant determinants of the development of composite cardiac events after discharge in the univariate analyses.

Table 2. Univariate and Multivariate Cox Proportional Hazard Analyses to Predict Composite Endpoint After Discharge of ADHF Patients

Variable	Univariate analysis			Multivariate analysis
	HR	95% CI	P value	HR	95% CI	P value
Age, years	1.03	1.02–1.05	<0.001	1.02	1.00–1.04	0.11
Female	1.19	0.80–1.74	0.368	1.35	0.83–2.16	0.23
Heart rate at discharge, beats/min	1.02	1.00–1.03	0.086
LogBNP at discharge	3.67	2.29–5.86	<0.001	2.46	1.24–4.95	0.01
NYHA III/IV at discharge	6.99	3.67–12.3	<0.001	3.34	1.38–7.50	0.01
AF at discharge	1.19	0.76–1.82	0.445
Prior hospitalization for HF	1.90	1.31–2.76	<0.001	1.57	0.96–2.56	0.07
LAD, mm	1.01	0.99–1.03	0.308
LVDD, mm	1.01	0.99–1.02	0.384
LVDS, mm	1.01	0.99–1.02	0.183
FS, %	0.98	0.96–1.00	0.063
LVEF, %	0.98	0.96–1.01	0.199
E-velocity at discharge	1.01	1.00–1.01	0.042	1.01	1.00–1.01	0.16
E/A ratio	1.15	0.97–1.31	0.106
E deceleration time at discharge, ms	1.00	0.99–1.00	0.051
MR grade ≥moderate	1.91	1.28–2.80	0.002	1.70	1.03–2.73	0.04
TRPG, mmHg	1.02	0.99–1.04	0.098
β-blocker	0.69	0.47–1.04	0.079
ACEI or ARB	0.65	0.44–0.97	0.035	0.94	0.57–1.59	0.82
Spironolactone	1.11	0.76–1.61	0.579
Oral inotrope	2.44	1.45–3.90	0.001	1.13	0.50–2.39	0.76

CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction. Other abbreviations as in Table 1.

A multivariate Cox proportional hazard model adjusted for age, sex, NYHA functional class, prior hospitalization for HF, medication, and plasma BNP level at discharge showed that residual moderate/severe FMR (HR: 1.70, 95% CI: 1.03–2.78, P=0.04), as well as logBNP level (HR: 2.46, 95% CI: 1.24–4.95, P=0.01) and NYHA class III/IV at discharge (HR: 3.34, 95% CI: 1.38–7.50, P=0.01), were independent determinants of the development of the composite endpoint after discharge.

In a subgroup analysis of patients with lower BNP level at discharge (<200 pg/ml), patients with persistent moderate/severe FMR at discharge had a comparable outcome to those with none/mild FMR (Figure 5A). In contrast, in patients with a persistently higher BNP level after medical treatment, persistent moderate/severe FMR adversely influenced the clinical outcome (Figure 5B).

Figure 5.

Kaplan-Meier curves for composite endpoint by BNP level at discharge. Event-free curve for composite endpoint by grade of FMR at discharge in patients with (A) lower BNP level (<200 pg/ml) and (B) higher BNP level (≥200 pg/ml) at discharge. BNP, B-type natriuretic peptide.

Comparison in Terms of FMR Grade at Discharge

Table 3 compares the characteristics of the patients with and without moderate/severe FMR at discharge. Both groups had similar age, sex ratio and prevalence of NYHA III/IV symptoms. IHD was more prevalent in the moderate/severe FMR group compared with the none/mild FMR group at discharge. Plasma BNP level, E-wave velocity, and E/A ratio were higher, and LA and LV dimensions were larger in patients with moderate/severe FMR at discharge. β-blockers, ACEIs/ARBs, and diuretics were similarly prescribed in the 2 groups, whereas oral inotropes and spironolactone were prescribed more frequently in the moderate/severe FMR group than in the none/mild FMR group at discharge.

Table 3. Clinical Parameters by FMR Grade at Discharge of ADHF Patients

	FMR≤Mild (n=271)		FMR≥Moderate (n=78)		P value
	n*	Values†	n*	Values†
Age, years	271	72±14	78	73±11	0.635
Female, n (%)	271	92 (34)	78	29 (37)	0.599
HTN, n (%)	271	207 (76)	78	60 (77)	0.921
DM, n (%)	260	113 (43)	78	41 (53)	0.158
CAD, n (%)	266	99 (37)	77	39 (51)	0.036
OMI, n (%)	271	89 (33)	78	38 (49)	0.011
NYHA III/IV at discharge (%)	258	13 (5)	67	4 (5)	0.764
AF at discharge, n (%)*	236	74 (27)	59	16 (21)	0.524
BNP at discharge, pg/ml	249	222 (112–399)	71	325 (184–468)	0.003
LAD at discharge, mm	254	45±9	72	47±8	0.030
LVDD at discharge, mm	267	55±10	77	64±10	<0.001
LVDS at discharge, mm	266	43±13	76	52±12	<0.001
FS at discharge, %	266	24±11	76	19±8	<0.001
LVEF at discharge, %	112	33±12	39	28±10	0.030
E-wave velocity, cm/s	243	71±26	66	87±28	<0.0001
E/A ratio	166	1.24±1.13	49	1.75±1.15	0.007
E deceleration time, ms	238	197±75	66	182±64	0.151
β-blocker, n (%)	271	194 (72)	78	59 (76)	0.476
ACEI or ARB, n (%)	271	206 (76)	78	52 (67)	0.104
Spironolactone, n (%)	271	103 (38)	78	40 (51)	0.0368
Oral inotrope, n (%)	271	16 (6)	78	15 (19)	0.001
Oral diuretic, n (%)	271	222 (82)	78	67 (86)	0.403

*Number of patients with data available; ^†values are presented as mean±SD, median and interquartile range (25–75th percentile), or n (%), as appropriate. OMI, old myocardial infarction. Other abbreviations as in Tables 1,2.

Discussion

In this prospective observational study of patients with ADHF, 36% of patients had moderate/severe FMR on admission. Although half of them showed improvement to none/mild FMR, the other half had persistent moderate/severe FMR at discharge. The severity of FMR at discharge had a prognostic effect on the long-term clinical outcome in spite of the improvement of HF symptoms, whereas severity of FMR on admission did not. Multivariate analysis revealed that moderate/severe FMR, as well as NYHA functional class and plasma BNP level, at discharge was an independent determinant of the composite endpoint of all-cause death and HF hospitalization, suggesting that residual FMR could be a potential target for further treatment of HF.

Although FMR is thought to play a key role in worsening HF, its prognostic significance after hemodynamic restoration in ADHF patients has not been elucidated. Mayer et al reported a prevalence of moderate/severe FMR of 21% in ADHF patients on admission and a strong association between FMR severity and BNP level.¹⁷ Nieminen et al also reported FMR prevalence of 43% in acute HF patients, including those with acute coronary syndrome, and found that FMR was more prevalent in recurrent chronic HF than in de novo HF.¹⁸ These reports did not focus on the timing of the evaluation of FMR and its prognostic significance.

FMR is caused by complex mechanisms, including imbalance of the tethering force and closing force,^19–21 dyssynchrony,^22,23 and annular dilatation, which interferes with coaptation of the mitral leaflets and further promotes the development of FMR.²⁴ Medical treatment restores the balance of forces, alleviates FMR and improves the clinical outcome of patients with HF;^25–27 however, FMR cannot be controlled by medical therapy in a considerable proportion of patients admitted for ADHF despite improvement of HF symptoms. Persistent moderate/severe FMR causes further LV remodeling and a worse outcome by increasing LV filling pressure, neurohumoral activation, and cellular modification.²⁸

FMR on admission did not affect outcomes in this study, partly because FMR on admission can ameliorate in response to the treatments correcting reversible factors such as hypervolemia, vascular resistance, or imbalance of neurohumoral factors. In the acute setting, FMR grading might be challenging because of tachycardia, limitations of the body position and the higher LA pressure might obscure the FMR jet on the color Doppler image. A minority of the patients experienced worsening FMR after treatments (n=15, 7%). These patients had a comparably poor prognosis to those with unchanged and persistent moderate/severe FMR (Figure S1). Their FMR might be underestimated in the acute setting. Thus, we recommend using the grade of FMR at discharge to predict the prognosis of patients admitted for acute HF.

Persistent FMR after ADHF could be further stratified. In the present study, patients with persistent moderate/severe FMR at discharge had a higher prevalence of IHD, larger LA and LV, worse LV systolic function and a higher plasma BNP level, indicating adverse cardiac remodeling with neurohumoral activation. The plasma BNP level is known to be a strong predictor for patients admitted with decompensated HF.²⁹ In the subgroup with plasma BNP level at discharge <200 pg/ml, patients with moderate/severe FMR at discharge had a comparable prognosis to patients with FMR of none/mild degree, suggesting that persistent FMR may be tolerated, as long as the plasma BNP level is controlled (Figure 5A). Contrarily, in the subgroup with a persistently higher BNP level, moderate/severe FMR at discharge had a worse outcome compared with those with FMR of none/mild degree at discharge (Figure 5B).

Prior hospitalization for HF is another important factor influencing the prognosis of patients admitted for ADHF.³⁰ Patients with recurrent HF had worse LV function and lower prescription rate of ACEI/ARB and a higher prescription rate of oral inotropes in recurrent HF (Table S1). Prior hospitalization for HF was a predictor of the composite endpoint in the univariate analysis, but not in the multivariate analysis in our study (Table 2). However, further analysis suggested that prior hospitalization might influence the effect of FMR associated with ADHF. In the majority of cases, moderate/severe FMR at admission ameliorated in de novo HF, whereas most of the cases of moderate/severe FMR in recurrent HF did not change severity in response to medical treatments (Table S1, Figure S2). In patients with de novo HF, those with moderate/severe FMR at admission and discharge had a comparable prognosis to patients with FMR of none/mild degree (Figure S3A). Contrarily, in patients with recurrent HF, those with moderate/severe FMR at discharge had a worse outcome than those with FMR of none/mild degree at discharge (Figure S3B).

These results suggest that persistent FMR may be a target for further treatment, especially when the plasma BNP level remains high after optimal medical therapy and in patients with recurrent HF.

In patients with severe FMR resistant to optimal medical therapy, non-pharmacological treatments such as cardiac resynchronization therapy (CRT) and surgical intervention are considered. Both CRT for patients with dyssynchrony and coronary artery bypass graft surgery for patients with IHD are reported to result in successful LV modification and FMR reduction in past studies.^31–33 However, no clear mortality benefit of MV surgery compared with medication and CRT has been reported, because of the high operative mortality in patients with FMR.³⁴ Therefore, the efficacy of surgical intervention for FMR has not been established.^35,36

Recently, percutaneous techniques for edge-to-edge repair have been developed. MitraClip^® is one of the most advanced mitral repair devices, and has started to be utilized for moderate/severe FMR.^37,38 The long-term durability of percutaneous mitral repair devices has not been determined; however, the survival rate was equivalent (88%,³⁹ 85%,³⁷ and 76%⁴⁰ for higher operative risk patients at 1-year follow-up) compared with surgical mitral repair or replacement. Although the results of randomized clinical trials are awaited, HF patients with persistent severe FMR in association with elevated plasma BNP level might be good candidates for this less invasive therapy.

Study Limitations

First, we graded the severity of FMR in a semiquantitative manner in this study. However, the grade of MR semiquantitatively evaluated in our institute showed satisfactory agreement with MR severity of the same patients quantified using proximal isovelocity surface area. We did not separate moderate FMR from severe FMR because of the limited number of patients with severe FMR at discharge. Second, we did not perform anatomical evaluation of the mitral apparatus in these cases. Evaluating the specific anatomical aberrations of the mitral apparatus might further clarify the subset suitable for MV repair surgery. Third, a considerable number of patients lacked data regarding diastolic function, which is reported to be a strong prognostic factor in patients with HF.⁴¹ Fourth, we used %FS instead of LVEF as a variable representing systolic function in most of the analyses in this study, because LVEF was not measured in a considerable number of patients on admission, mainly because of technical problems.

Lastly, because the institution is a specialized hospital in the cardiovascular field, the patient population might be biased; patients with reduced systolic function were dominant in this study. HF with preserved EF (≥45%) was 32% in the report on acute HF patients by Mayer et al,¹⁷ and 34% in Nieminen et al,¹⁸ but only 15% in our study. It has been reported that FMR associated with pulmonary hypertension is prevalent in HF with preserved EF and changes its grade in response to the loading status.^42,43 However, the prognostic impact of FMR in HF with preserved EF may be different from that in HF with reduced contraction. It is prudent to interpret the results of this study as mainly derived from patients with reduced contraction.

Conclusions

Patients with residual FMR after medical treatment for ADHF, especially those with higher BNP levels and recurrent HF, have a poor prognosis and may be candidates for further therapy, including invasive treatment of the MV.

Disclosures

The authors report that they have no relationship relevant to the contents of this paper to disclose.

Supplementary Files

Supplementary File 1

Figure S1. Kaplan-Meier curves according to changing pattern of FMR from admission to discharge.

Figure S2. FMR grade at admission and discharge in patients with de novo HF and recurrent HF.

Figure S3. Kaplan-Meier curves according to FMR grade at admission and discharge in patients with de novo HF and recurrent HF.

Table S1. Characteristics of de novo HF and recurrent HF

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-15-0663

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