Cardiology

Beohar, N., Ailawadi, G., Kotinkaduwa, L. N., Redfors, B., Simonato, M., Zhang, Z., Morgan, L. G., Escolar, E., Kar, S., Lim, D. S., Mishell, J. M., Whisenant, B. K., Abraham, W. T., Lindenfeld, J., Mack, M. J. and Stone, G. W. (2022). “Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.” Eur Heart J.

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AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr. KEY QUESTION: Determine prognostic impact of baseline renal dysfunction (RD) in patients with heart failure (HF) with severe secondary mitral regurgitation (MR), including those treated medically or with transcatheter mitral valve repair (TMVr) in the COAPT trial. We examined the long-term impact of TMVr or incident end-stage renal disease (ESRD) or necessity for new renal replacement therapy (RRT). KEY FINDING: Renal dysfunction was common in patients with HF and severe secondary MR in the COAPT trial and portended worse 2-year outcomes. However, treatment with MitraCity reduced death, hospitalization, new-onset ESRD, and need for RRT regardless of baseline RD severity. TAKE-HOME MESSAGE: In HF patients with severe MR enrolled in COAPT, baseline RD was common and strongly predicted 2-year death and HF hospitalization. MitraClip treatment reduced incident ESRD and the need for RRT, contributing to the improved prognosis after TMVr.

Arnold, S. V., Zhao, Y., Leon, M. B., Sathananthan, J., Alu, M., Thourani, V. H., Smith, C. R., Mack, M. J. and Cohen, D. J. (2022). “Impact of Frailty and Prefrailty on Outcomes of Transcatheter or Surgical Aortic Valve Replacement.” Circ Cardiovasc Interv 15(1): e011375.

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BACKGROUND: Randomized trials have shown short- and mid-term benefits with transcatheter versus surgical aortic valve replacement (TAVR versus SAVR) for patients at intermediate or low-risk for surgery. Frailty and prefrailty could explain some of this benefit due to an impaired ability to recover fully from a major surgical procedure. METHODS: We examined 2-year outcomes (survival and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) among patients at intermediate or low surgical risk treated with transfemoral-TAVR or SAVR within the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial, SAPIEN 3 intermediate-risk registry, and PARTNER 3 trial. Frailty was examined as a continuous variable based on grip strength, gait speed, serum albumin, and activities of daily living. We tested the interaction of frailty markers by treatment (TAVR versus SAVR) in proportional hazards regression models (survival) and piecewise linear regression models (KCCQ), adjusting for patient demographic and clinical factors. RESULTS: Among the 3025 patients in the analytic cohort (2003 TAVR, 1022 SAVR; mean age 79.3 years, 61.6% men), 799 (26.4%) were nonfrail, 2041 (67.5%) were prefrail (1-2 frailty markers), and 185 (6.1%) were frail (3-4 frailty markers). Increasing frailty (none versus prefrail versus frail) was associated with higher 2-year mortality (5.5% versus 11.1% versus 22.8%; log-rank P<0.001) and worse 2-year health status among survivors (KCCQ scores adjusted for baseline: 84.8 versus 79.6 versus 77.4, P<0.001). In multivariable models, there were no significant interactions between frailty markers and treatment group for either survival (interaction P=0.39) or health status (interaction P>0.47 for all time points). CONCLUSIONS: In a cohort of older patients with severe aortic stenosis who were at low or intermediate surgical risk, increasing frailty markers were associated with worse 2-year mortality and greater health status impairment after either TAVR or SAVR, but there were no significant interactions between type of valve replacement and frailty with respect to either outcome.

Patlolla, S. S., Gong, T. and Hall, S. (2022). “Balancing the tug of war: intraoperative and postoperative management of multiorgan transplantation.” Curr Opin Organ Transplant 27(1): 57-63.

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PURPOSE OF REVIEW: Multiorgan heart transplants (MOHT) have steadily increased and account for approximately 4% of all heart transplants performed. Although long-term outcomes of MOHT are similar to heart transplant alone, perioperative management remains an issue with nearly double the rate of prolonged hospitalization. Better understanding of hemodynamic environments encountered and appropriate therapeutic targets can help improve perioperative management. RECENT FINDINGS: Accurate and precise hemodynamic monitoring allows for early identification of complications and prompt assessment of therapeutic interventions. This can be achieved with a multimodal approach using traditional monitoring tools, such a pulmonary artery catheter and arterial line in conjunction with transesophageal echocardiography. Specific targets for optimizing graft perfusion are determined by phase of surgery and organ combination. In some circumstances, the surgical sequence of transplant can help mitigate or avoid certain detrimental hemodynamic environments. SUMMARY: With better understanding of the array of hemodynamic environments that can develop during MOHT, we can work to standardize hemodynamic targets and therapeutic interventions to optimize graft perfusion. Effectively navigating this perioperative course with multimodal monitoring including transesophageal echocardiography can mitigate impact of complications and reduce prolonged hospitalization associated with MOHT.

Song, C., Madhavan, M. V., Lindenfeld, J., Abraham, W. T., Kar, S., Lim, D. S., Grayburn, P. A., Kapadia, S. R., Kotinkaduwa, L. N., Mack, M. J. and Stone, G. W. (2022). “Age-Related Outcomes After Transcatheter Mitral Valve Repair in Patients With Heart Failure: Analysis From COAPT.” JACC Cardiovasc Interv.

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OBJECTIVES: The aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. BACKGROUND: In the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients. METHODS: Patients (n = 614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression. RESULTS: Death or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patients <74 years of age (37.3% vs 64.5%; adjusted HR: 0.41; 95% CI: 0.29-0.59) and ≥74 years of age (51.7% vs 69.6%; adjusted HR: 0.58; 95% CI: 0.42-0.81) (P(int) = 0.17). Mortality was also consistently reduced with MitraClip treatment in young and elderly patients (P(int) = 0.42). In contrast, elderly patients treated with the MitraClip vs GDMT alone tended to have a lesser reduction of HFH than younger patients (P(int) = 0.03). Younger and older patients had similar improvements in quality of life after treatment with the MitraClip compared with GDMT alone. CONCLUSIONS: In the COAPT trial, MitraClip treatment of moderate to severe and severe SMR reduced the composite risk for death or HFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH.

Cimino, S., Agati, L., Filomena, D., Maestrini, V., Monosilio, S., Birtolo, L. I., Mocci, M., Mancone, M., Sardella, G., Grayburn, P. and Fedele, F. (2022). “3D Echo Characterization of Proportionate and Disproportionate Functional Mitral Regurgitation before and after Percutaneous Mitral Valve Repair.” J Clin Med 11(3).

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BACKGROUND: The impact of percutaneous mitral valve repair (PMVr) on long-term prognosis in patients with functional mitral regurgitation (FMR) is still unclear. Recently, a new conceptual framework classifying FMR as proportionate (P-MR) and disproportionate (D-MR) was proposed, according to the effective regurgitant orifice area/left ventricular end-diastolic volume (EROA/LVEDV) ratio. The aim was to assess its possible influence on PMVr efficacy. METHODS: A total of 56 patients were enrolled. MV annulus, LV volumes and function were assessed. Global longitudinal strain (GLS) was also calculated. Patients were divided into two groups, according to the EROA/LVEDV ratio. Echocardiographic follow-up was performed after 6 months, and adverse events were collected after 12 months. RESULTS: D-MR patients (n = 28, 50%) had a significantly more elliptical MV annulus (p = 0.048), lower tenting volume (p = 0.01), higher LV ejection fraction (LVEF: 32 ± 7 vs. 26 ± 5%, p = 0.003), lower LVEDV, LV end-systolic volume (LVESV) and mass (LVEDV/i: 80 ± 20 vs. 126 ± 27 mL, p = 0.001; LVESV/i: 60 ± 20 vs. 94 ± 23 mL, p < 0.001; LV mass: 249 ± 63 vs. 301 ± 69 gr, p = 0.035). GLS was more impaired in P-MR (p = 0.048). After 6 months, P-MR patients showed a higher rate of MR recurrence. After 12 months, the rate of CV death and rehospitalization due to HF was significantly higher in P-MR patients (46% vs. 7%, p < 0.001). P-MR status was strongly associated with CV death/rehospitalization (HR = 3.4, CI 95% = 1.3-8.6, p = 0.009). CONCLUSIONS: Patients with P-MR seem to have worse outcomes after PVMr than D-MR patients. Our study confirms the importance of the EROA/LVEDV ratio in defining different subsets of FMR based on the anatomical characteristic of MV and LV.