Abstract
OBJECTIVE
To evaluate the safety and efficacy of transcatheter mitral valve repair (TMVR) using MitraClip® devices in oldest-old patients compared to younger patients.
METHODS
The study retrospectively included 340 consecutive patients who underwent TMVR. Patients were classified according to age into the oldest-old (age ≥ 85 years) patient group or the younger (age < 85 years) patient group. Immediate results of the procedure, intrahospital outcomes and one-year outcomes were compared.
RESULTS
Oldest-old patients represented 15.9% (n = 54) of all patients. Procedure success was comparable for the oldest-old patient group and the younger patient group (92.6% vs. 95.8%, P = 0.30), and there was no difference in intrahospital mortality (9.2% vs. 4.2%, P = 0.12). At a one-year follow-up (interquartile range: 6–16 months), there was no significant difference in rehospitalization due to decompensated heart failure (25.5% vs. 34.3%, P = 0.24) or all-cause mortality (29.8% vs. 22.2%, P = 0.26) between the oldest-old patient group and the younger patient group. In patients with available echocardiographic follow-up, severity of residual mitral regurgitation was also comparable between the oldest-old patient group and the younger patient group.
CONCLUSIONS
TMVR seems to be feasible and effective in oldest-old patients and should be considered for oldest-old patients presenting with symptomatic severe mitral regurgitation and high surgical risk.
Mitral regurgitation (MR) is the most common valvular heart disease. Prevalence of MR increases with age.[1] If left untreated, severe degenerative MR is associated with adverse events.[2] The presence of secondary MR also worsens the prognosis of patients with heart failure (HF).[3] Life expectancy is increasing worldwide. For example, in 2020, more than 12 million adults in Europe were older than 85 years. This group, also referred to as ‘oldest-old’, currently represents about 3% of the general population.[4,5] Hence, oldest-old patients with MR are frequently seen in clinical practice. Due to comorbidities and other factors, mitral valve surgery in the elderly is associated with serious morbidity and mortality.[6] Transcatheter mitral valve repair (TMVR) has emerged as an alternative to surgery in patients with symptomatic severe MR and high surgical risk and has been shown to be superior to medical therapy alone in patients with HF.[7,8] However, oldest-old patients may have been underrepresented in dedicated trials, with the mean age of patients being 67.3 ± 12.8 years and 71.7 ± 11.8 years in the EVERST II trial and the COAPT trial, respectively.[7,8] Data about safety and efficacy of TMVR in ‘oldest-old’ patients are diverse. Although TMVR has been reported to be safe and feasible in octogenarians at short-term follow-up and mid-term follow-up,[9,10] worse outcomes of TMVR in oldest-old patients aged more than 85 years have also been reported.[11] Compared to young-old and middle-old patients, oldest-old patients exhibit generally more mortality, more morbidity, and longer hospital stays.[12] This study aims to assess safety and efficacy of TMVR among oldest-old patients.
METHODS
Study Population
All patients who underwent TMVR between January 1, 2014 and December 31, 2019 at the University Hospital RWTH Aachen, Aachen, Germany were retrospectively included (Figure 1). All patients had symptomatic severe MR as defined by the guidelines of European Society of Cardiology and the European Association of Cardiovascular Imaging.[13] All patients were evaluated by the heart team and were deemed to be non-operable. In all cases, the multidisciplinary heart team recommended proceeding with TMVR.
Figure 1.
Consort flow chart showing how the analytical sample was derived from the participants who were assessed for eligibility.
Patients were classified according to age into two groups: the oldest-old (age ≥ 85 years) patient group and the younger (age < 85 years) patient group. This study was approved by the Local Ethics Committee of the Faculty of Medicine, University Hospital RWTH Aachen, Aachen, Germany (EK 396/20) and was performed in accordance with the ethical standards laid down in the latest revision of the Declaration of Helsinki.
TMVR
All procedures were performed using MitraClip® devices (Abbott Vascular Structural Heart, Menlo Park, California, USA) under general anaesthesia with the guidance of fluoroscopy and transoesophageal echocardiography by an experienced interventional cardiologist. The steps of performing TMVR are described in detail elsewhere.[14]
Follow-up and Definition of Outcome
Intrahospital outcomes included procedure success defined as the successful implantation of at least one clip and reduction of severe MR to maximally moderate MR; vascular complications defined as arteriovenous fistula, pseudo aneurysm or relevant bleeding requiring operative or interventional management and intrahospital mortality.
One-year outcomes included New York Heart Association (NYHA) dyspnoea class, rehospitalization due to acute decompensated HF, all-cause mortality and a composite endpoint of rehospitalisation or all-cause mortality and severity of MR.
Follow-up data were obtained retrospectively from patients’ medical records. Patients who did not have follow-up data in our patient data management system were contacted by telephone and asked about their symptoms (NYHA dyspnoea category or need for rehospitalisation). In cases in which patients could not be reached, the primary care physician or patients’ family was contacted to achieve follow-up for all patients. In patients who needed hospitalization during the first year, the cause of rehospitalisation was investigated via medical charts or the primary care physician. In patients who did not survive, date of death was obtained through the primary care physician.
Statistical Analysis
Continuous variables were expressed as the median (interquartile range) and binary variables were expressed as the counts (percentages). Patients were classified according to their age into the oldest-old (age ≥ 85 years) patient group or the younger (age < 85 years) patient group. The Kolmogorov-Smirnov test for a normal distribution of age rejected normal distribution (P < 0.001). Continuous variables were compared using the Mann-Whitney U test and categorical variables were evaluated using the Pearson’s chi-squared test. Statistical analyses were performed using SPSS 25.0 (SPSS Inc., IBM, Armonk, NY, USA) and MedCalc Version 13.0.0.0 (MedCalc Software Ltd., Ostend, Belgium). Two-sided P-value < 0.05 were considered statistically significant.
RESULTS
Patients’ Characteristics
The study included 340 consecutive patients. Figure 2 shows the distribution of the patients’ ages. Oldest-old patients represented 15.9% (n = 54) of the study’s population. Degenerative MR was more prevalent in the oldest-old patient group, whereas ischemic cardiomyopathy was more patients in the younger patient group. Furthermore, younger patients had lower left ventricle ejection fraction and more dilatated left ventricle. Patients’ clinical characteristics and echocardiographic parameters are summarized in Table 1.
Figure 2.
Age distribution of patients who underwent transcatheter mitral valve repair.
Table 1. Clinical characteristics and echocardiographic parameters of the study population.
| Characteristics | All (n = 340) | Oldest-old (n = 54) | Younger (n = 286) | P-value |
| Data are presented as n (%). *Presented as median (interquartile range). NYHA: New York Heart Association. | ||||
| Clinical characteristics | ||||
| Age, yrs | 78 (73–82)* | 86 (86–88)* | 77 (71–81)* | < 0.001 |
| Male | 218 (64.1%) | 34 (62.9%) | 184 (64.3%) | 0.82 |
| Primary mitral regurgitation | 98 (28.8%) | 24 (44.4%) | 74 (25.8%) | 0.006 |
| Ischemic cardiomyopathy | 180 (52.9%) | 21 (38.9%) | 159 (55.6%) | 0.012 |
| Previous coronary artery bypass graft | 82 (24.1%) | 6 (11.1%) | 76 (26.6%) | 0.03 |
| Previous percutaneous coronary intervention | 166 (48.8%) | 27 (50%) | 139 (48.6%) | 0.96 |
| Non-ischemic cardiomyopathy | 68 (20%) | 9 (16.7%) | 59 (20.6%) | 0.43 |
| Diabetes mellitus | 106 (31.2%) | 10 (18.5%) | 96 (33.5%) | 0.019 |
| Arterial hypertension | 266 (78.2%) | 42 (77.8%) | 224 (78.3%) | 0.56 |
| Atrial fibrillation | 239 (70.2%) | 43 (79.6%) | 196 (68.5%) | 0.20 |
| Estimated glomerular filtration rate < 60 mL/min | 225 (66.1%) | 45 (83.3%) | 180 (62.9%) | 0.01 |
| Dialysis | 18 (5.3%) | 2 (3.7%) | 16 (5.6%) | 0.53 |
| Peripheral artery disease | 85 (25%) | 20 (37%) | 65 (22.7%) | 0.10 |
| Chronic obstructive pulmonary disease | 131 (38.5%) | 18 (33.3%) | 113 (39.5%) | 0.26 |
| NYHA class | 0.14 | |||
| I | – | – | – | |
| II | 40 (11.7%) | 6 (11.1%) | 34 (11.9%) | |
| III | 193 (56.7%) | 33 (61.1%) | 160 (55.9%) | |
| IV | 107 (31.4%) | 15 (27.8%) | 92 (32.2%) | |
| Imaging characteristics | ||||
| Left ventricle ejection fraction, % | 38 (28–53)* | 49 (35–55)* | 37 (27–50)* | 0.001 |
| Left ventricular end diastolic diameter, mm | 57 (51–64)* | 53 (46–59)* | 58 (51–65)* | < 0.001 |
| Left ventricular end systolic diameter, mm | 46 (37–56)* | 42 (33–50)* | 47 (38–57)* | 0.017 |
| Effective regurgitant orifice area, mm² | 31 (24–41)* | 30 (23–40)* | 31 (24–41)* | 0.65 |
| Regurgitant volume, mL | 51 (38–63)* | 59 (41–77)* | 51 (37–62)* | 0.05 |
| Left atrium area, cm² | 28 (23–34)* | 30 (23–35)* | 28 (23–34)* | 0.61 |
| Right atrium area, cm² | 23 (18–27)* | 23 (19–29)* | 23 (17–27)* | 0.28 |
| Tricuspid regurgitation | 0.31 | |||
| Mild | 139 (40.8%) | 18 (33.4%) | 121 (42.4%) | |
| Moderate | 162 (47.6%) | 22 (40.7%) | 140 (48.9%) | |
| Severe | 39 (11.6%) | 14 (25.9%) | 25 (8.7%) | |
| Systolic pulmonary artery pressure | 42 (34–55)* | 46 (37–60)* | 42 (34–53)* | 0.10 |
Intrahospital Outcome
The procedure was successfully completed with the implantation of a minimum of one clip and reduction of MR to maximally moderate MR in 324 patients (95.3%). Success of the procedure did not differ between the oldest-old patient group and the younger patient group (92.6% vs. 95.8%, P = 0.30). Occurrence of vascular complications also did not differ between the oldest-old patient group and the younger patient group (3.7% vs. 2.8%, P = 0.72). Similarly, intrahospital mortality did not differ significantly between the oldest-old patient group and the younger patient group (9.2% vs. 4.2%, P = 0.12) (Table 2).
Table 2. Intrahospital outcome of transcatheter mitral valve repair in oldest-old patients compared to younger patients.
| Variables | All (n = 340) | Oldest-old (n = 54) | Younger (n = 286) | P-value |
| Data are presented as n (%). *Presented as median (interquartile range). | ||||
| Success of procedure | 324 (95.2%) | 50 (92.6%) | 274 (95.8%) | 0.30 |
| Vascular complications | 10 (2.9%) | 2 (3.7%) | 8 (2.8%) | 0.72 |
| Intrahospital mortality | 17 (5%) | 5 (9.2%) | 12 (4.2%) | 0.12 |
| Number of clips | 1 (1–2)* | 1 (1–2)* | 1 (1–2)* | 0.31 |
| Mean transmitral pressure gradient after transcatheter mitral valve repair, mmHg |
3 (3–5)* | 3 (2–4)* | 4 (3–5)* | 0.33 |
One-year Outcome
At a one-year follow-up (interquartile range: 6–16 months), there was no significant difference in rehospitalization due to decompensated HF (25.5% vs. 34.3%, P = 0.24) or all-cause mortality (29.8% vs. 22.2%, P = 0.26) between the oldest-old patient group and the younger patient group. Consequentially, the composite endpoint of rehospitalization due to acute HF or all-cause mortality was comparable between the oldest-old patient group and the younger patient group (42.6% vs. 43%, P = 0.45) (Table 3). Both NYHA class and MR severity were also comparable between the oldest-old patient group and the younger patient group (Table 3). Figure 3 shows a comparison of NYHA class and MR severity at a one-year follow-up between the oldest-old patient group and the younger patient group.
Table 3. One-year outcome of transcatheter mitral valve repair in oldest-old patients compared to younger patients.
| Variables | All (n = 312) | Oldest-old (n = 47) | Younger (n = 265) | P-value |
| Data are presented as n (%). One-year outcome referred to patients with unsuccessful procedure or who did not survive to discharge were excluded from the follow-up analysis. *Referred to composite endpoint of death or hospitalization due to acute heart failure. **Referred to echocardiographic follow-up was available for 220 patients. NYHA: New York Heart Association. | ||||
| NYHA class | 0.57 | |||
| I | 45 (14.4%) | 4 (8.5%) | 41 (15.5%) | |
| II | 136 (43.6%) | 20 (42.6%) | 116 (43.8%) | |
| III | 105 (33.7%) | 20 (42.6%) | 85 (32.1%) | |
| IV | 26 (8.3%) | 3 (6.3%) | 23 (8.6%) | |
| Hospitalisation due to heart failure | 103 (33%) | 12 (25.5%) | 91 (34.3%) | 0.24 |
| One-year mortality | 73 (23.4%) | 14 (29.8%) | 59 (22.2%) | 0.26 |
| Composite endpoint* | 137 (40.3%) | 23 (42.6%) | 114 (43%) | 0.45 |
| Mitral regurgitation severity** | 0.11 | |||
| Mild | 127 (57.7%) | 13 (52%) | 114 (58.5%) | |
| Moderate | 79 (35.9%) | 8 (32%) | 71 (36.4%) | |
| Severe | 14 (6.4%) | 4 (16%) | 10 (5.1%) | |
Figure 3.
Comparison of NYHA class (A) and severity of MR (B) between the oldest-old patient group and the younger patient group at one-year follow- up.
MR: mitral regurgitation; NYHA: New York Heart Association.
DISCUSSION
The findings of our study suggest that the oldest-old (age ≥ 85 years) patients represent a considerable proportion of patients presenting with symptomatic MR and high surgical risk. In these patients, TMVR appears safe and can be performed with reasonable morbidity and mortality, comparable to those in younger patients. Furthermore, TMVR in these patients seems to be as effective as in younger patients in reducing MR and improving HF symptoms.
Our data show that about half of oldest-old patients present with degenerative primary MR. Surgical mitral valve repair is the therapy of choice for degenerative MR;[15] however, many elderly patients are not being referred for surgery.[16] Chivasso, et al.[17] reported a 30-day mortality rate of 14% in octogenarians (mean age: 83 years) undergoing mitral valve repair or replacement due to degenerative disease. Regarding the role of age in estimating surgical morbidity and mortality,[18–20] those endpoints are expected to be higher in patients older than 85 years. According to our results, TMVR may be an attractive alternative to surgery in this group of patients.
The outcomes of TMVR in octogenarians have been previously assessed.[8–10] At a short-term follow-up, Buzzatti, et al.[9] reported similar intrahospital mortality between patients older and younger than 80 years undergoing TMVR. However, they reported a higher rate of 30-day readmission in octogenarians. At a mid-term follow-up, Giordano, et al.[10] reported similar mortality between octogenarians and non-octogenarians and even lower rates of rehospitalisation and composite endpoints of mortality and rehospitalisation in octogenarians, suggesting the safety of TMVR in those patients. Although these two studies assessed the outcome in octogenarians and not in oldest-old patients, our results suggest that their findings also apply to oldest-old patients, as we found similar short- and mid-term outcomes in patients older and younger than 85 years. In contrast, Chen, et al.[11] reported that an age greater than 85 years was associated with a worse prognosis at one-year follow-up in patients undergoing TMVR. Although this study included fewer patients than ours, these differing results suggest the need for more research in this group of patients.
Furthermore, TMVR is reported to be safe and feasible in carefully selected nonagenarians.[21,22] Our study population included only six patients older than 90 years. TMVR was successful in those patients, and they all survived to discharge. However, this is an insufficient sample to obtain statistically relevant results.
Conclusively, our study suggests that TMVR can be safely performed and is effective in oldest-old patients. It also adds to our knowledge about this procedure in this group of patients.
LIMITATIONS
Although this study adds to the knowledge about TMVR in oldest-old patients, we acknowledge that it is limited by its retrospective observational nature. Furthermore, selection bias in oldest-old patients suffering from severe MR, who are being referred to TMVR evaluation cannot be excluded. In addition, this investigation suffers the usual shortcomings of a single center study.
CONCLUSIONS
Although morbidity and mortality rates among oldest-old patients are high after TMVR, their outcomes do not significantly differ from those of younger patients and TMVR seems to be similarly safe and effective. Therefore, very old age alone should not prevent performing TMVR.
ACKNOWLEDGMENTS
All authors had no conflicts of interest to disclose.
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