Journal of the American Heart Association ORIGINAL RESEARCH Prognostic Impact of Nutritional Status After Transcatheter Edge-­to-­Edge Mitral Valve Repair: The MIVNUT Registry Berenice Caneiro-­Queija, MD; Sergio Raposeiras-­Roubin , PhD; Marianna Adamo, MD; Xavier Freixa, PhD; Dabit Arzamendi, PhD; Tomas Benito-­González , MD; Antonio Montefusco, MD; Isaac Pascual , PhD; Luis Nombela-­Franco , PhD; Josep Rodes-­Cabau , PhD; Mony Shuvy, PhD; Antonio Portolés-­Hernández , MD; Cosmo Godino , PhD; Dan Haberman , PhD; Laura Lupi , MD; Ander Regueiro, PhD; Chin Hion Li , MD; Felipe Fernández-­Vázquez , PhD; Simone Frea, MD; Pablo Avanzas, PhD; Gabriela Tirado-­Conte , MD; Jean-­Michel Paradis, MD; Alona Peretz, MD; Vanessa Moñivas, PhD; Jose A. Baz, MD; Michele Galasso, MD; Luca Branca, MD; Laura Sanchís , MD; Lluís Asmarats, PhD; Carmen Garrote-­Coloma , PhD; Filippo Angelini , MD; Victor León, MD; José A. de Agustín , MD; Alberto Alperi , MD; Ronen Beeri , MD; Gloria Maccagni, MD; Manel Sabaté , PhD; Estefanía Fernández-­Peregrina , MD; Javier Gualis, MD; Pier Paolo Bocchino , MD; Salvatore Curello, MD; Andrés Íñiguez-­Romo, PhD; Rodrigo Estévez-­Loureiro , PhD BACKGROUND: Malnutrition is associated with poor prognosis in several cardiovascular diseases. However, its prognostic impact in patients undergoing transcatheter edge-­to-­edge mitral valve repair (TEER) is not well known. This study sought to assess the prevalence, clinical associations, and prognostic consequences of malnutrition in patients undergoing TEER. Downloaded from http://ahajournals.org by on July 13, 2023 METHODS AND RESULTS: A total of 892 patients undergoing TEER from the international MIVNUT (Mitral Valve Repair and Nutritional Status) registry were studied. Malnutrition status was assessed with the Controlling Nutritional Status score. The association of nutritional status with mortality was analyzed with multivariable Cox regression models, whereas the association with heart failure admission was assessed by Fine-­Gray models, with death as a competing risk. According to the Controlling Nutritional Status score, 74.4% of patients with TEER had any degree of malnutrition at the time of TEER (75.1% in patients with body mass index <25 kg/m2, 72.1% in those with body mass index ≥25 kg/m2). However, only 20% had moderate–­severe malnutrition. TEER was successful in most of patients (94.2%). During a median follow-­up of 1.6 years (interquartile range, 0.6–­3.0), 267 (29.9%) patients died and 256 patients (28.7%) were admitted for heart failure after TEER. Compared with normal nutritional status moderate–­severe malnutrition resulted a strong predictor of mortality (adjusted hazard ratio [HR], 2.1 [95% CI, 1.1–­2.4]; P<0.001) and heart failure admission (adjusted subdistribution HR, 1.6 [95% CI, 1.1–­2.4]; P=0.015). CONCLUSIONS: Malnutrition is common among patients submitted to TEER, and moderate–­severe malnutrition is strongly as- sociated with increased mortality and heart failure readmission. Assessment of nutritional status in these patients may help to improve risk stratification. Key Words: CONUT ■ heart failure ■ malnutrition ■ mortality ■ transcatheter edge-­to-­edge repair Correspondence to: Sergio Raposeiras-­Roubin, MD, PhD, Department of Cardiology, University Hospital Alvaro Cunqueiro, C/Clara Campoamor 341, 36213 Vigo, Spain. Email: raposeiras26@hotmail.com Supplemental Material is available at https://www.ahajo​urnals.org/doi/suppl/​10.1161/JAHA.121.023121 For Sources of Funding and Disclosures, see page 9. © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. JAHA is available at: www.ahajournals.org/journal/jaha J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231211 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair replicating the procedure, after formal request to the CLINICAL PERSPECTIVE corresponding author. What Is New? Study Population • Most patients undergoing transcatheter edge-­ This study is based on a multicentric international to-­ edge mitral valve repair have malnutrition, MIVNUT (Percutaneous Mitral Valve Repair and even those who are overweight. Nutritional Status) registry, which included 1119 pa- • Moderate–­severe malnutrition is independently tients referred for TEER between 2012 and 2020 from associated with an increased probability of mortality and heart failure admission in patients 12 centers in Europe and Canada. Two hundred and undergoing transcatheter edge-­to-­edge mitral twenty-­seven patients were excluded by missing data valve repair. about nutritional status. Final cohort comprised 892 patients. All patients gave informed consent and the What Are the Clinical Implications? local ethics committee approved the protocol. • Improvement of preprocedural nutritional sta- Patients were classified according to nutritional tus may help improve the prognosis of patients status by the CONUT (Controlling Nutritional Status) undergoing transcatheter edge-­to-­edge mitral score11 which assess serum albumin, cholesterol, and valve repair. total lymphocyte count. A score of 0 to 1 was con- sidered normal; scores of 2 to 4, 5 to 8, and 9 to 12 reflected mild, moderate, and severe malnutrition, re- spectively. For this study, because of the low number Nonstandard Abbreviations and Acronyms of patients with severe degree of malnutrition (n=13), the moderate and severe categories were merged into CONUT Controlling Nutritional Status a single category (moderate–­severe malnutrition). MIVNUT mitral valve repair and nutritional status Body mass index (BMI) was calculated before the MR mitral regurgitation procedure for all patients, defined as the body mass TEER transcatheter edge-­to-­edge mitral valve (kilograms) divided by the square of the body height repair (in meters). Patients were classified according to BMI in 2 groups: normal weight (BMI <25 kg/m2) and over- Downloaded from http://ahajournals.org by on July 13, 2023 weight/obesity (BMI ≥25 kg/m2). T ranscatheter edge-­ to-­ edge mitral valve repair (TEER) has become an alternative to mitral valve Procedure surgery in patients with primary mitral regurgitation An interdisciplinary heart team in each institution dis- (MR) deemed at high-­risk or inoperable, being the first-­ cussed indication of TEER. The procedure was per- line strategy for those patients with secondary MR who formed according to standard practices, including remain symptomatic despite guideline-­directed medical fluoroscopic and transesophageal echocardiographic therapy.1 However, results are still not homogeneous in all guidance. The number of clips implanted and the selec- subgroups of patients; baseline, echocardiographic, and tion of the type of device were left to the operators’ dis- procedural characteristics may influence outcomes.2–­5 cretion, as well as medical treatment. Technical success Malnutrition is common in patients with heart fail- was defined as the successful deployment of at least ure (HF) leading to poor quality of life and increased one clip in the absence of procedural mortality. Acute mortality.6 Likewise, it has been linked to worse clinical procedural success was defined as reduction of MR to outcomes in patients with acute coronary syndromes,7 a grade ≤2+ with a mean transmitral gradient <5 mm Hg. and is getting increasing relevance in patients with val- vular heart disease.8–­10 Nonetheless, no information on nutritional status End Points has been provided for patients referred for TEER. Primary end point was all-­cause mortality. Secondary Therefore, we sought to assess the prevalence and end points were HF readmission and composite event prognostic relevance of malnutrition in a cohort of pa- of mortality and HF readmission. Patients were fol- tients referred for TEER. lowed up since the procedure date. In the absence of outcomes, time was censored at the last medical con- tact in primary or secondary care. METHODS The data, methods used in the analysis, and materi- Statistical Analysis als used to conduct the research are available to any Patients were analyzed separately according to nu- researcher for purposes of reproducing the results or tritional status. Continuous data were presented as J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231212 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair mean±SD and compared using unpaired t tests. Procedural Data Categorical data were presented as counts (propor- Procedural success was achieved in 94.2% of the pa- tions) and compared using Chi-­ square tests. The tients without significant difference between groups: incidence of mortality was estimated using Kaplan–­ 94.5%, 94.7% and 92.7%, respectively, for normal, Meier curves. We used Cox proportional hazard mild, and moderate–­severe malnutrition (P=0.080) and regression models to estimate the association of nu- significantly different compared with preprocedure for tritional status with all-­cause mortality. For HF admis- each nutritional status (Figure 2A). However, the per- sion, death served as a competing risk. Therefore, centage of grade 3–­4+ MR was higher as nutritional the incidence of HF admission was estimated using status worsened (10.5%, 14.1% and 17.5% in patients weighted cumulative incidence curves. Furthermore, with normal nutrition, mild malnutrition, and moderate–­ the association between nutritional status with the severe malnutrition, respectively). hazards and cumulative incidence of HF admission was modeled using Fine-­Gray proportional subdis- tributions hazards model. The proportionality as- Malnutrition and Outcomes sumption was verified by testing for an interaction During a median follow-­ up of 1.6 years, interquartile between the exposure variable and time, and no range of 0.6–­3.0, 267 patients (29.9%) died. Information relevant violations were found. All analyses were ad- about the variables associated with all-­cause mortality in justed for age, sex, and all those variables with a univariate analysis is shown in Table S1–­S11. After adjust- statistical association (P≤0.10) with outcomes in the ing for those variables, age and sex, moderate–­severe univariate analysis (see Table S1). To perfom parsi- malnutrition (but not mild) was independently associated monious multivariate models, continuous variables with all-­cause mortality during follow-­up after TEER (HR, were dichotomized and possible nonlinear associa- 2.07 [95% CI, 1.39–­3.07]) (Figure 3A). The complete mul- tions for the Cox proportional hazards model were tivariate analysis is shown in Tables S2 and S3. tested, without significant interactions were found During the follow-­ up, 256 patients (28.7%) were (Bonferroni-­corrected P value was >0.05). Effect es- admitted to hospital for HF. After a competing risk timates from Cox models were reported as hazard analysis, moderate–­ severe malnutrition emerged as ratios (HRs) while those from Fine-­Gray models were independent predictor of HF admissions (HR, 1.61 reported as subdistribution HRs (sHRs) along with [95% CI, 1.09–­2.37]) (Figure 3B). Univariate and mul- 95% CIs. Statistical analyses were conducted using tivariate analysis for HF admission is shown in Tables Downloaded from http://ahajournals.org by on July 13, 2023 STATA software, version 15 (Stata Corp, College S4 through S6. Station, Texas, USA). A 2-­sided P<0.05 was consid- Moreover, moderate–­severe malnutrition was asso- ered statistically significant. ciated with the combined end-­point of mortality and HF admission (Figure 3C; Tables S7 and S8). Despite the differences in patient characteristics be- tween the different hospitals (Table S9), there was no RESULTS variation in the results of the multivariate analysis after in- Malnutrition Prevalence and Baseline cluding the different hospitals as a confounding variable. Characteristics The analysis of the impact of malnutrition according According to nutritional status 237 patients (26.6%) BMI strata is shown in Tables S10 and S11. had a normal nutritional status, 477 patients (53.4%) The event rate of the combined end point (mortality had mild malnutrition, and 178 patients (20%) were and/or HF admission) was higher as the CONUT score classified as moderate–­severe malnutrition (Figure 1). increased (HR, 1.07 [95% CI, 1.02–­ 1.13]; P=0.008) We found malnutrition in 75.1% of normal weight (Figure 4). patients (BMI <25 kg/m2) compared with 72.1% Figure 2B shows the functional improvement at throughout overweight/obese patients (BMI>25 kg/ 6 months before and after the procedure for each nutri- m2) (P=0.312). Baseline characteristics of the study tional status. Although functional class at 6 months im- population according to nutritional status are pre- proved in all 3 nutritional groups it is greater for patients sented in Table. with mild malnutrition (81.5% of patients New York Heart Rate of functional MR was similar among the 3 Association I or II) compared with 74% and 67.4% for nutritional groups (134 patients with normal nutri- mild and moderate–­severe malnutrition (P<0.001). tional status (56.6%), 297 patients with mild malnutri- tion (62.3%) and 111 patients with moderate–­severe malnutrition (62.4%), P=0.299). Interestingly, anemia, DISCUSSION impaired renal function and poorer functional New To our knowledge, this is the first study to assess the York Heart Association class were significantly higher impact of malnutrition on TEER outcomes. The main among moderate–­severe malnourished patients. findings of our study can be summarized: J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231213 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair Downloaded from http://ahajournals.org by on July 13, 2023 Figure 1. Population distribution according to nutritional status. BMI indicates body mass index. 1. Most of the patients undergoing TEER have mal- 2. The risk of mortality and/or HF increases as the nu- nutrition, even in those overweight, and 1 out of tritional status worsens, making the CONUT score a 5 patients have moderate–­ severe malnutrition. good predictor of adverse events in this population. J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231214 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair Table 1. Baseline Characteristics of Percutaneous Mitral Valve Repair Population According to Nutritional Status Malnutrition Variables No Mild Moderate– ­Severe P value Age, y 72.3±11.2 73.9±10.2 74.2±9.0 0.081 Female sex, n (%) 96 (40.5) 143 (30.0) 54 (30.3) 0.014 Body mass index, kg/m2 26.7±4.9 26.2±4.7 25.6±4.3 0.054 Active smoking, n (%) 48 (20.3) 109 (22.9) 30 (16.9) 0.233 Arterial hypertension, n (%) 157 (66.2) 354 (74.2) 132 (74.2) 0.065 Dyslipidemia, n (%) 136 (57.4) 282 (59.1) 98 (55.1) 0.636 Diabetes, n (%) 62 (26.2) 186 (39.0) 72 (40.4) 0.001 Ischemic heart disease, n (%) 112 (47.3) 274 (57.4) 115 (65.0) 0.001 Peripheral artery disease, n (%) 22 (11.5) 81 (19.7) 37 (22.8) 0.013 Prior stroke, n (%) 22 (9.3) 52 (10.9) 20 (11.2) 0.758 COPD, n (%) 58 (24.5) 101 (21.2) 33 (18.5) 0.334 Atrial fibrillation, n (%) 135 (57.0) 286 (60.0) 107 (60.1) 0.717 Anemia, n (%) 90 (38.0) 262 (54.0) 134 (75.3) <0.001 Creatinine >1.5 mg/dL, n (%) 55 (23.2) 190 (39.8) 69 (38.8) <0.001 Functional MR, n (%) 134 (56.5) 297 (62.3) 111 (62.4) 0.299 LVEF ≦40%, n (%) 132 (55.7) 290 (60.8) 116 (65.2) 0.142 PAP ≧55 mm Hg, n (%) 77 (32.5) 135 (28.3) 61 (34.3) 0.258 NYHA class III-­IV, n (%) 184 (77.6) 423 (89.7) 164 (92.2) <0.001 B-­blocker, n (%) 189 (79.7) 383 (80.3) 128 (71.9) 0.058 ACEI/ARB, n (%) 136 (57.4) 261 (54.7) 79 (44.4) 0.022 ARNI, n (%) 22 (9.3) 45 (9.4) 13 (7.3) 0.684 Antialdosteronic, n (%) 130 (54.9) 232 (48.6) 87 (48.9) 0.268 Downloaded from http://ahajournals.org by on July 13, 2023 Diuretic, n (%) 182 (76.8) 400 (83.9) 150 (84.3) 0.047 Resynchronization therapy, n (%) 33 (13.9) 106 (22.2) 29 (16.3) 0.018 ICD, n (%) 58 (24.5) 168 (35.2) 46 (25.8) 0.004 ACEI indicates angiotensin-­converting enzyme inhibitors; ARB, angiotensin receptor blockers; ARNI, angiotensin receptor/neprilysin inhibitors; COPD, chronic obstructive pulmonary disease; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; and PAP, pulmonary artery pressure. 3. Moderate–­severe malnutrition is independently as- suggest screening for malnutrition in hospitalized pa- sociated with an increased probability of mortality tients16 since patients who are malnourished have more and HF admission complications, longer length of stay, and greater mor- tality.13,17,18 Different screening tools have been com- The relevance of malnutrition is given by the fact that pared to assess nutrition risk in patients with HF.14,19 is a common finding in patients admitted to hospitals by Nevertheless, simple malnutrition scores not consid- any cause and it is of special relevance in those linked ering anthropometric factors were more related to out- to the cardiovascular field.12 In patients undergoing valvu- comes than other scores including BMI, not only for lar heart surgery it has been reported to be in the range patients with HF but also for patients with acute coro- of 10% to 25%13 and it may increase up to 40% among nary syndrome.7,14Taking this into account we selected patients with transcatheter aortic valve replacements.9 the CONUT score as the tool for screening malnutri- Likewise, in patients with HF any degree of malnutrition tion in our population and simple measures including is described in 44%.14 In elderly populations of hospital- serum albumin, cholesterol, and lymphocyte count ized patients this percentage ranges from 30% to 50%.15 correlated accurately with malnutrition degrees.11 Of interest, in our study this percentage is even higher, It is well recognized that malnutrition has been around 70%, reflecting probably a more complex profile linked to poor prognosis in the cardiovascular of patients in which advanced HF, poorer functional class, scope.7–­10,20,21 Our population represents a special increased age, frailty, and comorbidities are merging. subset of patients with chronic HF, with a significant The Academy of Nutrition and Dietetics and the proportion of functional patients with MR in advanced American Society for Parenteral and Enteral Nutrition functional status, with frequent previous readmissions J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231215 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair Downloaded from http://ahajournals.org by on July 13, 2023 Figure 2. Improvement of the mitral regurgitation grade and functional class according to nutritional status. A, Change in mitral regurgitation grade before and after procedure for each nutritional status; B, Change in 6-­month New York Heart Association functional class for each nutritional group before and after the procedure. NYHA indicates New York Heart Association. and with symptoms uncontrolled under optimal med- thus creating a vicious circle that might be responsible ical therapy. It is in this type of patient with MR where for an impaired prognosis.23 Another potentially rele- malnutrition is more frequently found. Advanced HF in- vant factor connecting nutrition and adverse prognosis volves several mechanisms including the presence of is the link between nutritional status and frailty. Frailty chronic inflammation.22 Inflammation results in acute or concerns around 46% of patients undergoing TEER24 chronic-­related malnutrition6 and may be responsible and represents a complex syndrome involving physical for the wasting syndrome and hypoalbuminemia.23 It performance and nutrition.25 Frailty per se is associ- has been also described an improper activation of oxi- ated with 3-­times increased risk of death and twice dative processes in patients with chronic HF leading to the risk of death or HF hospitalization in patients with more tissue damage and more chronic inflammation, TEER.24 As malnutrition is one of the criteria included in J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231216 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair frailty can be successfully treated by TEER with signif- icant reduction of MR and improvement in New York Heart Association functional class and quality of life. According to nutritional status we can identify patients with greater mortality risk and work to ameliorate it. Therefore, although relevant, malnutrition per se must not be a contraindication for referring patients for per- cutaneous repair. The role of assessing malnutrition in our popula- tion is relevant because it can be a modifiable factor. It has been reported that nutritional interventions ap- pear to benefit hospitalized patients, by reducing hos- pital length and readmissions.26 In addition, there are preliminary data supporting a potential benefit from oral nutritional supplements in patients with HF, with significant reduction in the rate of mortality and hos- pital readmissions.27,28 It has been recently reported that those patients who are malnourished undergoing transcatheter aortic valve replacement that improve their nutritional status after the intervention have better prognostic outcomes.29 This fact may be seen as a signal for a potential target to improve outcomes both in aortic and mitral population, if the nutrition status can be optimized beforehand. Unfortunately, we did not assess nutritional status change after mitral repair, and this hypothesis is speculative. However, given the potential benefit of such strategy we should consider future trials based on nutritional interventions for opti- mizing TEER outcomes. Downloaded from http://ahajournals.org by on July 13, 2023 Study Limitations This is a multicenter retrospective investigation with the subsequent disadvantages secondary to its nature. In addition to this, data about nutritional status were available in 892 from 1119 patients (79.7%). This fact could be a source of selection bias. The rest of data for all analyzed variables were available in all patients. Since malnutrition is a complex issue, especially in older adults, because of diversity in cause and a wide range of determinants, a more complex comprehensive Figure 3. Primary, secondary, and combined end points nutritional assessment would be recommendable. We according to nutritional status. did not evaluate the association of malnutrition scores A, All-­cause mortality; B, heart failure readmission; C, mortality with inflammatory markers, nor with body composition. and heart-­failure readmission. However, CONUT score is easy to calculate and to im- plement as part of routine in clinical practice and does the frailty assessment, we can assume that a propor- not require specific anthropometric measurements or tion of our patients are overlapping those syndromes subjective questionnaires. In this sense, operators can therefore contributing to the increasing rates of mor- be more prone to use this tool because of the afore- tality and HF readmission. Thus, we speculate that mentioned advantages. Moreover, given that the nutri- these features might be responsible for the increased tional evaluation was conducted only in a single time adverse cardiovascular events in patients who are mal- point, we did not investigate the changes in nutritional nourished, irrespective of an adequate MR treatment. status over time and their relationship with cardiovas- On the other hand, it is important to stress that, as it cular outcomes. Information about frailty status and its was pointed out by our data and data by Metze and correlation with malnutrition would be interesting; how- colleagues,24 both patients with malnourished and ever, unfortunately, data about frailty were not available J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231217 Caneiro-­Queija et al Malnutrition and Edge-­to-­Edge Mitral Valve Repair Figure 4. Rate of mortality and heart failure admission according to Controlling Nutritional Status score. CONUT indicates Controlling Nutritional Status; and HF, heart failure. in the MIVNUT database. Moreover, we have no data Downloaded from http://ahajournals.org by on July 13, 2023 Disclosures about infective endocarditis during the follow-­up. And Dr Freixa is a consultant for Abbott Vascular. Dr Arzamendi is a consultant for Abbott Vascular and Edwards Lifesciences. Drs Nombela-­Franco and regarding medical therapy, we only had data about De Agustin have served as proctors for Abbott. Dr Rodés-­Cabau holds the treatment at discharge. Confirmation of our findings by Canadian Research Chair “Fondation Famille Jacques Larivière” for the de- other investigators and other countries with different velopment of structural heart disease. Dr Estevez-­Loureiro is consultant for Abbott Vascular, Boston Scientific, and Edwards Lifesciences. The remain- health care and social systems would be welcome. ing authors have no disclosures to report. Supplemental Material Tables S1–­S11 ARTICLE INFORMATION Received July 5, 2021; accepted August 1, 2022. Affiliations Hospital Álvaro Cunqueiro and Instituto de Investigación Sanitaria Galicia REFERENCES Sur, Vigo, Spain (B.C., S.R., J.A.B., M.G., A.Í., R.E.); Cardiac Catheteterization 1. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP III, Gentile Laboratory, Cardiothoracic Department, Spedali Civili Brescia, Brescia, F, Jneid H, Krieger EV, Mack M, McLeod C, et al. 2020 ACC/AHA guide- Italy (M.A., L.L., L.B., G.M., S.C.); Hospital Clinic, Barcelona, Spain (X.F., line for the management of patients with valvular heart disease: execu- A.R., L.S., M.S.); Interventional Cardiology Unit, Hospital Sant Pau i Santa tive summary: a report of the American College of Cardiology/American Creu, Barcelona, Spain (D.A., C.H.L., L.A., E.F.); Complejo Asistencial Heart Association joint committee on clinical practice guidelines. 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The influ- replacement. Circ Cardiovasc Interv. 2021;14:e009342. doi: 10.1161/ ence of nutritional status on complications after major intraabdominal CIRCINTERVENTIONS.120.009342 J Am Heart Assoc. 2022;11:e023121. DOI: 10.1161/JAHA.121.0231219 SUPPLEMENTAL MATERIAL Downloaded from http://ahajournals.org by on July 13, 2023 Table S1. Univariate analysis for all-cause mortality. Variables HR 95% CI P-value Age, per 1 year 1.03 1.01 - 1.04 <0.001 Male sex 1.32 1.01 - 1.73 0.046 BMI >= 25 kg/m2 0.83 0.65 - 1.06 0.131 Active smoking 0.83 0.62 - 1.10 0.196 Arterial hypertension 1.16 0.88 – 1.53 0.297 Dyslipidemia 1.06 0.83 – 1.35 0.650 Diabetes mellitus 1.38 1.08 – 1.76 0.009 Ischemic heart disease 1.52 1.19 – 1.95 0.001 Peripheral artery disease 2.29 1.74 – 3.03 <0.001 Prior stroke 1.19 0.83 – 1.71 0.349 COPD 1.21 0.92 – 1.59 0.180 Malnutrition 1.58 1.17 - 2.13 0.002 Atrial fibrillation 1.06 0.81 – 1.23 0.430 Anemia 1.91 1.48 – 2.46 <0.001 Creatinine > 1.5 mg/dL 1.55 1.22 – 1.98 <0.001 Functional MR 1.03 0.80 - 1.32 0.836 Downloaded from http://ahajournals.org by on July 13, 2023 LVEF <= 40% 1.39 1.07 – 1.80 0.015 Systolic PAP >= 55 mmHg 1.10 0.85 – 1.41 0.480 NYHA class III-IV 1.89 1.23 – 2.90 0.004 Successful procedure 0.59 0.31-0.76 0.002 B-blocker 0.83 0.63 – 1.10 0.194 ACEI/ARB 0.57 0.45 – 0.73 0.001 ARNI 0.71 0.38 – 1.35 0.303 Antialdosteronic 0.94 0.74 – 1.20 0.624 Diuretic 1.25 0.85 – 1.83 0.254 CRT 1.46 1.10 – 1.95 0.010 ICD 0.98 0.76 – 1.27 0.901 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter- Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S2. Multivariate analysis all-cause mortality. Variables HR 95% CI P-value Age, per 1 year 1.04 1.02 - 1.06 <0.001 Male sex 1.27 0.94 - 1.71 0.125 Diabetes mellitus 1.6 0.80 – 1.39 0.700 Ischemic heart disease 1.24 0.94 – 1.64 0.121 Peripheral artery disease 2.00 1.49 – 2.69 <0.001 Malnutrition Mild 0.98 0.69 - 1.39 0.900 Moderate-severe 2.07 1.39 – 3.07 <0.001 Anemia 1.22 0.92 – 1.62 0.162 Creatinine > 1.5 mg/dL 1.18 0.90 – 1.54 0.222 LVEF ≦ 40% 1.63 1.19 – 2.23 0.002 NYHA class III-IV 1.41 0.88 – 2.24 0.153 Successful procedure 0.68 0.41 - 1.12 0.128 ACEI/ARB 0.63 0.49 – 0.82 0.001 Resynchronization therapy 1.48 1.05 – 2.08 0.025 Downloaded from http://ahajournals.org by on July 13, 2023 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S3. Multivariate analysis all-cause mortality with CONUT. Variables HR 95% CI P-value Procedural success 0.65 0.39 – 1.06 0.085 Age, per 1 year 1.04 1.03 - 1.06 <0.001 Male sex 1.23 0.91 - 1.66 0.181 Diabetes mellitus 1.1 0.81 – 1.40 0.643 Ischemic heart disease 1.26 0.95 – 1.66 0.103 Peripheral artery disease 1.93 1.44 – 2.59 <0.001 Anemia 1.22 0.92 – 1.62 0.161 Creatinine > 1.5 mg/dL 1.14 0.88 – 1.49 0.325 LVEF ≦40% 1.69 1.24 – 2.32 0.001 NYHA class III-IV 1.35 0.85 – 2.16 0.208 Successful procedure 0.65 0.39-1.06 0.085 ACEI/ARB 0.66 0.50 – 0.85 0.002 CRT 1.37 0.98 – 1.93 0.068 CONUT score 1.13 1.06 - 1.21 <0.001 Downloaded from http://ahajournals.org by on July 13, 2023 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S4. Univariate Analysis of HF readmission. Variables sHR 95% CI P-value Age, per 1 year 1.00 0.99 - 1.01 0.877 Male sex 1.11 0.84 - 1.45 0.465 BMI >= 25 kg/m2 1.11 0.87 - 1.42 0.405 Active smoking 1.06 0.80 - 1.43 0.659 Arterial hypertension 1.26 0.94 – 1.69 0.114 Dyslipidemia 1.12 0.87 – 1.44 0.369 Diabetes mellitus 1.47 1.15 – 1.89 0.002 Ischemic heart disease 1.10 0.86 – 1.41 0.437 Peripheral artery disease 1.08 0.79 – 1.47 0.649 Prior stroke 1.14 0.78 – 1.67 0.502 COPD 1.28 0.96 – 1.70 0.087 Malnutrition 1.57 1.16 - 2.11 0.003 Atrial fibrillation 1.01 0.87 – 1.18 0.849 Anemia 0.95 0.75 – 1.22 0.707 Creatinine > 1.5 mg/dL 1.44 1.12 – 1.84 0.004 Downloaded from http://ahajournals.org by on July 13, 2023 Functional MR 0.93 0.72 - 1.20 0.588 LVEF ≦ 40% 1.24 0.96 – 1.61 0.100 PAP >= 55 mmHg 1.12 0.87 – 1.46 0.375 NYHA class III-IV 2.01 1.30 – 3.11 0.002 Successful procedure 0.52 0.32 – 0.85 0.008 B-blocker 0.96 0.72 – 1.29 0.800 ACEI/ARB 0.79 0.62 – 1.02 0.063 ARNI 1.52 0.99 – 2.32 0.051 Antialdosteronic 1.03 0.81 – 1.32 0.809 Diuretics 1.89 1.22 – 2.93 0.004 CRT 1.50 1.12 – 2.01 0.007 ICD 1.32 1.03 – 1.70 0.027 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S5. Multivariate analysis for HF readmission. Variables sHR 95% CI P-value Age, per 1 year 1.00 0.99 - 1.01 0.573 Male sex 0.94 0.71 - 1.26 0.693 Diabetes mellitus 1.45 1.12 – 1.87 0.005 COPD 1.37 1.03 – 1.83 0.031 Malnutrition Mild 1.18 0.86 - 1.65 0.304 Moderate-severe 1.61 1.09 - 2.37 0.015 Creatinine > 1.5 mg/dL 1.34 1.03 – 1.73 0.027 LVEF ≦ 40% 1.03 0.75 – 1.42 0.855 NYHA class III-IV 1.80 1.14 – 2.83 0.011 Successful procedure 0.56 0.34-0.92 0.021 ACEI/ARB 0.81 0.62 – 1.06 0.126 ARNI 1.36 0.85 – 2.18 0.196 Diuretic 1.68 1.06 – 2.66 0.027 Downloaded from http://ahajournals.org by on July 13, 2023 CRT 1.40 0.99 – 1.99 0.060 ICD 1.05 0.74 – 1.49 0.780 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S6. Multivariate Analysis of HF readmission with CONUT. Variables sHR 95% CI P-value Procedural success 0.55 0.33 - 0.90 0.020 Age, per 1 year 1.02 1.00 – 1.03 0.027 Male sex 1.06 0.79 - 1.41 0.716 Diabetes mellitus 1.38 1.07 – 1.79 0.015 COPD 1.19 0.89 – 1.59 0.248 Creatinine > 1.5 mg/dL 1.31 1.01– 1.70 0.042 LVEF ≦ 40% 1.12 0.81 – 1.53 0.495 NYHA class III-IV 1.64 1.04 – 2.59 0.034 Successful procedure 0.55 0.33-0.90 0.017 ACEI/ARB 0.80 0.61 – 1.05 0.112 ARNI 2.69 1.66 – 4.38 < 0.001 Diuretics 1.57 0.99 – 2.49 0.0053 Downloaded from http://ahajournals.org by on July 13, 2023 CRT 1.51 1.05 – 2.16 0.025 ICD 0.84 0.60 – 1.19 0.339 CONUT score 1.10 1.03 – 1.17 0.003 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S7. Multivariate analysis for mortality and HF readmission. Variables HR 95% CI P-value Age, per 1 year 1.01 1.00 - 1.03 0.022 Male sex 1.07 0.83 - 1.37 0.614 Diabetes mellitus 1.21 0.96 – 1.53 0.100 Ischemic heart disease 1.26 0.99 – 1.58 0.054 Peripheral artery disease 1.41 1.09 - 1.81 0.009 COPD 1.33 1.04 – 1.70 0.025 Malnutrition Mild 1.04 0.78 - 1.39 0.773 Moderate-severe 1.63 1.17 - 2.28 0.004 Anemia 1.00 0.79 – 1.26 0.993 Creatinine > 1.5 mg/dL 1.28 1.02 – 1.60 0.031 LVEF ≦ 40% 1.27 0.97 – 1.67 0.079 Downloaded from http://ahajournals.org by on July 13, 2023 NYHA class III-IV 1.54 1.05 – 2.25 0.028 Successful procedure 0.60 0.40 – 0-90 0.014 ACEI/ARB 0.67 0.54 – 0.84 <0.001 ARNI 0.91 0.58 – 1.40 0.655 Diuretic 1.48 1.02 – 2.13 0.037 CRT 1.65 1.21 – 2.26 0.002 ICD 0.91 0.67 – 1.23 0.532 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S8. Multivariate analysis for mortality and HF readmission with CONUT. Variables HR 95% CI P-value Procedural success 0.57 0.38 – 0.86 0.007 Age, per 1 year 1.02 1.01 - 1.04 < 0.001 Male sex 1.12 0.87 - 1.44 0.370 Diabetes mellitus 1.11 0.89 – 1.39 0.354 Ischemic heart disease 1.35 1.07 – 1.71 0.011 Peripheral artery disease 1.58 1.23 – 2.06 < 0.001 COPD 1.14 0.88 – 1.47 0.318 Creatinine > 1.5 mg/dL 1.17 0.93 – 1.46 0.173 LVEF ≦ 40% 1.41 1.08 – 1.85 0.012 NYHA class III-IV 1.40 0.96 – 2.06 0.082 Downloaded from http://ahajournals.org by on July 13, 2023 Successful procedure 0.57 0.38 – 0.86 0.007 ACEI/ARB 0.69 0.55 – 0.86 0.001 ARNI 1.42 0.91 – 2.20 0.120 Diuretics 1.35 0.94 – 1.95 0.105 CRT 1.73 1.26 – 2.37 0.001 ICD 0.77 0.57 – 1.05 0.099 CONUT score 1.12 1.06 – 1.18 < 0.001 ARNI: Angiotensin Receptor/Neprilysin Inhibitors; ACEI: Angiotensin-Converting Enzyme Inhibitors; ARB: Angiotensin Receptor Blocker; BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; CRT: Cardiac Resynchronization Therapy; ICD: Implantable Cardioverter-Defibrillator; LVEF: Left Ventricular Ejection Fraction; MR: Mitral Regurgitation; NYHA: New York Heart Association; PAP: Pulmonary artery pressure. Table S9. Descriptive information among centers. Age Female BMI CONUT Malnutrition Functional LVEF ≤ 40% Follow-up Mortality Center (years) (%) (kg/m2) (score) (%) MR (%) (%) (years) (%) Center 1 72.9±10.8 69.2 24.4±3.8 3.5± 2.2 79.2 69.2 65.8 2.6±2.2 40.0 Center 2 74.5±10.1 69.0 26.4±4.8 2.4±1.9 64.7 79.3 63.8 2.6±1.6 31.9 Center 3 69.4±10.4 61.5 26.6±4.5 2.6±1.5 78.0 60.6 62.4 2.5±1.6 33.9 Center 4 75.9±8.5 64.2 27.2±4.4 2.9±2.1 65.4 63.0 53.1 1.7±1.2 23.5 Center 5 76.8±10.7 65.1 27.0±4.4 3.3±2.0 81.9 43.4 42.2 1.9±1.8 30.1 Center 6 70.8±14.0 83.3 23.5±3.9 3.8±0.4 100.0 100.0 66.7 3.8±1.4 16.7 Downloaded from http://ahajournals.org by on July 13, 2023 Center 7 75.6±7.9 65.5 27.9±5.3 3.6±2.7 81.0 59.5 50.0 1.4±1.1 21.4 Center 8 68.2±9.8 80.6 25.2±4.0 2.8±1.6 86.1 80.6 72.2 1.1±0.7 27.8 Center 9 77.1±7.7 63.6 26.3±4.7 1.9±1.9 53.2 32.5 49.4 1.4±1.2 31.2 Center 10 77.2±8.3 66.7 26.4±4.1 2.8±1.8 80.4 49.0 58.8 0.2±0.1 0 Center 11 66.8±10.1 84.7 24.6±4.3 3,1±2.2 81.2 80.0 95.3 2.0±1.8 36.5 Center 12 75.4±11.3 43.2 27.2±5.9 2.2±2.2 52.3 25.0 40.9 2.8±2.4 38.6 Table S10. Univariate analysis for BMI categories and CONUT. BMI (kg/m2) Variable HR 95% CI P-value < 25 CONUT score 1.08 0.98 - 1.19 0.139 25-30 CONUT score 1.16 1.04 - 1.30 0.008 >30 CONUT score 1.23 1.03 – 1.48 0.022 Downloaded from http://ahajournals.org by on July 13, 2023 Table S11. Multivariate analysis for BMI categories and Malnutrition. BMI (kg/m2) Variable HR 95% CI P-value Non-malnutrition < 25 Mild malnutrition 1.46 0.77 – 2.73 0.243 Moderate-severe malnutrition 0.87 0.49 – 1.54 0.627 Non-malnutrition 25-30 Mild malnutrition 2.62 1.34-5.15 0.005 Moderate-severe malnutrition 0.958 0.53 – 1.72 0.886 Non-malnutrition >30 Mild malnutrition 6.16 1.83- 20.61 0.003 Moderate-severe malnutrition 1.25 0.52 – 2.99 0.621 Downloaded from http://ahajournals.org by on July 13, 2023