Right ventricular (RV) dysfunction, as evidenced by ventricular-arterial uncoupling, is “strongly and independently” associated with 2-year adverse outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR), according to a new analysis of trial data.
Published online Monday and in the Oct. 25 issue of JACC: Cardiovascular Interventions, the study noted that while it is established that RV contractile function and afterload influence outcomes in patients with SMR and HF, it is not known how RV afterload influences measures of contractile function and whether measures of contractile function indexed to afterload correlate with clinical outcomes.
Led by Michael I. Brener, MD, from the Columbia University Irving Medical Center, New York, the new analysis of data from the randomized COAPT trial found that advanced RV-pulmonary arterial (PA) uncoupling was strongly and independently associated with all-cause mortality or HF hospitalization within 24 months of follow-up.
“Patients with advanced RV-PA uncoupling experienced an approximate 2-fold increase in the risk for death or HF hospitalization at 2-year follow-up relative to patients with coupled RV contractile function and afterload,” the authors said, adding that the impact of RV-PA uncoupling was greater on mortality than HF hospitalization.
“Given these findings, HF with severe SMR should be added to the list of cardiovascular conditions in which RV dysfunction, specifically as defined by abnormal RV-PA coupling, is an important determinant of long-term prognosis,” they said.
Brener and colleagues set out to determine the prognostic impact of RV–PA coupling in patients with HF with severe SMR enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.
In the study, RV-PA coupling was assessed by the ratio of RV free-wall longitudinal strain (FWLS) derived from speckle-tracking echocardiography and noninvasively measured RV systolic pressure (RVSP) in 372 patients.
Advanced RV-PA uncoupling was defined as RV-FWSL/RVSP ≤0.5%/mmHg, while the primary endpoint was a composite of all-cause mortality or HF hospitalization at 24-month follow-up.
Initial results showed that 70.2% of patients had advanced RV-PA uncoupling, while multivariable analysis revealed that advanced RV-PA uncoupling was strongly associated with an increased risk for the primary 24-month endpoint of death or HF hospitalization (hazard ratio [HR]: 1.87; 95% confidence interval [CI]: 1.31-2.66; P = 0.0005).
The team noted that a similar association was present for all-cause mortality alone (HR: 2.57; 95% CI: 1.54-4.29; P = 0.0003), adding that the impact of RV-PA uncoupling was consistent in patients randomized to transcatheter edge-to-edge repair (TEER) versus guideline-directed medical therapy (GDMT).
They added that compared with GDMT alone, the addition of TEER improved two-year outcomes in patients both with (48.0% vs 74.8%; HR: 0.51; 95% CI: 0.37-0.71) and those without (28.8% vs 47.8%; HR: 0.51; 95% CI: 0.27-0.97) advanced RV-PA uncoupling (P interaction = 0.98).
Brener and colleagues concluded that the new analysis provides “robust evidence” for the prognostic utility of RV-PA coupling in patients with HF with severe SMR randomized to TEER versus GDMT.
“Perhaps most important, although the prognosis of patients treated with both TEER and GDMT alone was worse if advanced RV-PA uncoupling was present, TEER for severe mitral regurgitation improved clinical outcomes with a consistent effect regardless of RV-PA uncoupling,” they said.
They added that additional studies are needed to evaluate the durability of their finding in selected patient populations – such as those with marked pulmonary hypertension, who were excluded from the COAPT trial – and whether RV-PA coupling changes following TEER.
Writing in an accompanying editorial, Jörg Hausleiter, MD, from LMU Klinikum, Munich and the Munich Heart Alliance, and Nicole Karam, MD, PhD, from the Paris Cardiovascular Research Center at INSERM, said the results of the new study support the idea that evaluating the RV-PA coupling ratio is an important echocardiographic parameter for the identification and characterization of SMR patients with and without biventricular HF.
“The current study confirms the results of a previous analysis of the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, which revealed that the absence of RV-PA coupling is a major predictor for mortality in patients undergoing M-TEER for severe SMR,” said the expert commentators.
The editorialists noted that although the study adds important knowledge to the understanding of SMR, the results also open “a host of new questions.”
“First, considering the fact that the COAPT trial excluded patients with overt signs of severe right heart failure, the current study results imply that the RV-PA coupling parameter might identify patients with so far concealed right heart failure,” they suggested – adding that this is a phenomenon that needs to be replicated in future studies “because such patients may need more individualized treatments.”
Furthermore, they noted that the tricuspid annular plane systolic excursion (TAPSE)-to-RVSP ratio, which has been used in most previous studies on RV-PA coupling, was not analyzed in the current study. As such, the expert commentators noted that it remains unclear whether the use of the FWLS-to-RVSP ratio or RV fractional area change-to-RVSP ratio will provide a better identification of RV-PA coupling, and whether the use of the TAPSE-to-RVSP ratio would have provided the same outcome in this COAPT trial patient population.
Brener MI, Grayburn P, Lindenfeld J, et al. Right Ventricular–Pulmonary Arterial Coupling in Patients With HF Secondary MR: Analysis From the COAPT Trial. JACC Cardiovasc Interv 2021;14:2231-2242.
Hausleiter J, Karam N. Putting the Right Ventricle Into Perspective Before M-TEER: A Mandatory Step in the Decision Making? JACC Cardiovasc Interv 2021;14:2243-2245.
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