JACC: RV failure associated with reversible reduction in LV free wall mass
Right ventricular failure (RVF) was associated with reversible reduction in left ventricular (LV) free wall mass in patients with chronic thromboembolic pulmonary hypertension (CTEPH), according to a study in the Feb. 22 Journal of the American College of Cardiology.
Additionally, when evaluating a rat model with RVF, researchers found that myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.
“Right ventricular failure secondary to chronic pressure overload determines survival in patients with chronic thromboembolic pulmonary hypertension and other forms of pulmonary arterial hypertension,” the authors wrote. “The mechanisms underlying the development of heart failure in these patients are not fully understood.”
To better add to previous data, Maxim Hardziyenka, MD, PhD, of the University of Amsterdam in the Netherlands, and colleagues evaluated LV mass via cardiac MRI in 36 CTEPH patients and 11 healthy volunteers. Additionally, the authors assessed whether LV atrophy is present in monocrotaline (MCT)-injected rats with right ventricular failure by measuring myocyte dimensions and in situ hybridization.
The results showed that CTEPH patients with RVF had an increased average pulmonary artery pressure, total pulmonary resistance, a lower cardiac index and six-minute walking distance compared with patients with preserved RV systolic function. The patients who exhibited RVF also had lower LV peak filling rates and LVEF compared with patients without RVF or the 11 volunteers.
In addition, CTEPH patients with a RVF had lower LV free wall mass indexes compared with patients without RVF, 35 g/m2 versus 44 g/m2. There was also no significant difference in RV ejection fraction, mass indexes of LV free wall or interventricular septum (IVS) between the patients without RVF and volunteers.
Pulmonary endarterectomy (PEA) significantly improved RVEF from 31 percent to 56 percent in RVF patients at baseline, and while LV free wall mass index increased from 38 g/m2 to 44 g/m2, IVS mass index decreased from 28 g/m2 to 22 g/m2 compared to that at baseline. Patients without RVF at baseline exhibited no significant changes in RVEF (54 percent to 56 percent) or LV free wall mass index, which increased from 46 g/m2 to 50 g/m2.
In the rat model, the researchers found that rats with RVF had reduced RV contractility and impaired LV early diastolic relaxation and diastolic filling, in addition to reduced LV free wall mass. Lastly, the rats with RVF had smaller LV free wall myocytes.
“Taken together, these findings indicate that LV remodeling that occurs in RVF due to chronic pulmonary hypertension may be explained by cardiac myocyte atrophy,” the authors wrote. “Although apoptosis and/or other mechanisms may also be responsible for the loss of myocardial mass in unloaded LV, atrophy may be the main mechanism.
“RVF in patients with CTEPH is associated with reduction in LV free wall mass. This reduction is reversible and can be restored after PEA,” the authors concluded. “Using a rat model of RVF secondary to PAH, we found that reduction in LV free wall mass can be, at least in part, explained by myocyte shrinkage due to atrophic remodeling.”
In an accompanying editorial, Louis J. Dell'Italia, MD, of the University of Alabama Center for Heart Failure Research in Birmingham, Ala., wrote, “It is of interest that in the patients without RV failure at the time of surgery, there are no significant differences in LV mass and function versus normals, and there are no changes after endarterectomy, albeit in a small number of patients.
“If one assumes that the extent of the pulmonary vasculopathy relates to the severity of pulmonary systolic pressure elevation, the question still remains to what extent LV structural and functional abnormalities are related to increased RV load alone and/or systemic factors released from the lungs.”
In addition, Dell’Italia wrote that the current findings provide insights into the mechanisms of ventricular interdependence on LV structure and function, but offered that future clinical studies will be necessary to further evaluate inflammatory biomarkers to predict the reversibility of LV dysfunction.
Additionally, when evaluating a rat model with RVF, researchers found that myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.
“Right ventricular failure secondary to chronic pressure overload determines survival in patients with chronic thromboembolic pulmonary hypertension and other forms of pulmonary arterial hypertension,” the authors wrote. “The mechanisms underlying the development of heart failure in these patients are not fully understood.”
To better add to previous data, Maxim Hardziyenka, MD, PhD, of the University of Amsterdam in the Netherlands, and colleagues evaluated LV mass via cardiac MRI in 36 CTEPH patients and 11 healthy volunteers. Additionally, the authors assessed whether LV atrophy is present in monocrotaline (MCT)-injected rats with right ventricular failure by measuring myocyte dimensions and in situ hybridization.
The results showed that CTEPH patients with RVF had an increased average pulmonary artery pressure, total pulmonary resistance, a lower cardiac index and six-minute walking distance compared with patients with preserved RV systolic function. The patients who exhibited RVF also had lower LV peak filling rates and LVEF compared with patients without RVF or the 11 volunteers.
In addition, CTEPH patients with a RVF had lower LV free wall mass indexes compared with patients without RVF, 35 g/m2 versus 44 g/m2. There was also no significant difference in RV ejection fraction, mass indexes of LV free wall or interventricular septum (IVS) between the patients without RVF and volunteers.
Pulmonary endarterectomy (PEA) significantly improved RVEF from 31 percent to 56 percent in RVF patients at baseline, and while LV free wall mass index increased from 38 g/m2 to 44 g/m2, IVS mass index decreased from 28 g/m2 to 22 g/m2 compared to that at baseline. Patients without RVF at baseline exhibited no significant changes in RVEF (54 percent to 56 percent) or LV free wall mass index, which increased from 46 g/m2 to 50 g/m2.
In the rat model, the researchers found that rats with RVF had reduced RV contractility and impaired LV early diastolic relaxation and diastolic filling, in addition to reduced LV free wall mass. Lastly, the rats with RVF had smaller LV free wall myocytes.
“Taken together, these findings indicate that LV remodeling that occurs in RVF due to chronic pulmonary hypertension may be explained by cardiac myocyte atrophy,” the authors wrote. “Although apoptosis and/or other mechanisms may also be responsible for the loss of myocardial mass in unloaded LV, atrophy may be the main mechanism.
“RVF in patients with CTEPH is associated with reduction in LV free wall mass. This reduction is reversible and can be restored after PEA,” the authors concluded. “Using a rat model of RVF secondary to PAH, we found that reduction in LV free wall mass can be, at least in part, explained by myocyte shrinkage due to atrophic remodeling.”
In an accompanying editorial, Louis J. Dell'Italia, MD, of the University of Alabama Center for Heart Failure Research in Birmingham, Ala., wrote, “It is of interest that in the patients without RV failure at the time of surgery, there are no significant differences in LV mass and function versus normals, and there are no changes after endarterectomy, albeit in a small number of patients.
“If one assumes that the extent of the pulmonary vasculopathy relates to the severity of pulmonary systolic pressure elevation, the question still remains to what extent LV structural and functional abnormalities are related to increased RV load alone and/or systemic factors released from the lungs.”
In addition, Dell’Italia wrote that the current findings provide insights into the mechanisms of ventricular interdependence on LV structure and function, but offered that future clinical studies will be necessary to further evaluate inflammatory biomarkers to predict the reversibility of LV dysfunction.