Improvement of left ventricular systolic function after intervention on right ventricular hemodynamics

Abstract

Background:

The importance of right–left ventricular interactions is increasingly recognized in patients with congenital heart disease. Interventions to improve right ventricular volume/pressure overloading may result in improvement of left ventricular systolic dysfunction. We hypothesized that patients with right ventricular volume or pressure overloading lesions and left ventricular dysfunction would have improvement in left ventricular function following isolated intervention to improve right ventricular hemodynamics.

Methods and Results:

Patient records were reviewed to identify participants. Patients with left ventricular dysfunction (left ventricular ejection fraction <55% by echocardiogram) who underwent interventions to improve right ventricular volume or pressure overloading conditions were included. Interventions to improve right ventricular volume/pressure overloading conditions included closure of an atrial septal defect (ASD) and pulmonary valve replacement (PVR). Seventeen patients were identified with right ventricular volume or pressure overloading lesions and left ventricular dysfunction who underwent interventions to improve right ventricular hemodynamics. The majority of patients demonstrated improvement in left ventricular function postprocedure. PVR was performed in 12 patients – 11 of whom were for pulmonary insufficiency and one for pulmonary stenosis (four surgical and eight transcatheter). Five patients had closure of an ASD – two of whom were closed with a transcatheter device and three closed surgically. Seven out of nine transcatheter interventions demonstrated improvement in left ventricular function within 24 h.

Conclusion:

Patients with left ventricular dysfunction who undergo interventions to alleviate right ventricular volume or pressure overloading lesions can have rapid improvement in left ventricular function.

INTRODUCTION

The importance of right–left heart interactions is being increasingly recognized in patients with congenital heart disease (CHD). Prior studies have demonstrated that left ventricular (LV) function plays an important role in right ventricular (RV) systolic performance.[1] Up to one-third of the work performed by the RV is a direct consequence of LV shortening.[2] RV dilation and/or dysfunction have been demonstrated to adversely affect LV systolic function and systemic cardiac output, and RV volume overloading has been demonstrated to worsen LV contraction.[2] Interventions to improve RV volume or pressure overloading may result in an improvement of LV systolic dysfunction. Experimental data in animals and studies in both children and adults corroborate this effect.[3]

Patients with tetralogy of Fallot (TOF) status postrepair can develop LV dysfunction over time as a consequence of long-standing dilation of the RV and increase in end-diastolic volume and end-systolic volume of both the RV and LV.[4] Surgical pulmonary valve replacement (PVR) in patients with repaired TOF was associated with an improvement in LV systolic function in a series of 32 patients, likely as a result of improved interaction between the RV and LV after reduction of RV volume load, and does not correlate with the use of preoperative heart failure medications.[5] However, there is a lack of published literature describing how interventions to improve RV hemodynamics in other volume or pressure loading lesions influence LV function. In addition, to date, there is a lack of studies demonstrating the impact of transcatheter interventions to reduce RV volume overload, such as transcatheter PVR, on LV function. Understanding the impact of interventions to improve RV–LV interactions is critical to the management of patients with RV volume or pressure overloading lesions who have LV systolic dysfunction.

The objective of this study was to identify patients with RV volume or pressure overloading lesions with associated LV dysfunction who underwent isolated intervention on their RV hemodynamics and assess the impact on LV function postprocedure. We hypothesized that right-sided volume and pressure overloading lesions with concurrent LV dysfunction would demonstrate improvement in LV function following intervention to improve RV hemodynamics.

METHODS

This was a single-center retrospective case series. Approval from the Scientific Review Committee and subsequent Institutional Review Board exemption was granted prior to study implementation. Surgical and interventional cardiac catheterization records were reviewed, and the EPiC database was queried to identify participants. Patients with LV dysfunction (LVEF <55% on echocardiogram) who underwent interventions to improve RV volume or pressure overloading conditions from January 1, 2018, to June 30, 2024, were identified and included in the case series.

Interventions to improve RV volume or pressure overloading conditions included both surgical and transcatheter closure of an atrial septal defect (ASD) and PVR (surgical or transcatheter). In addition to the intervention performed, demographic and clinical data including the patient’s age, sex, cardiac anatomy, prior interventions, cardiac medications, improvement in subjective patient symptoms pre- and postprocedure, preintervention left ventricular ejection fraction (LVEF) by two-dimensional (2D) bullet method on the most recent echocardiogram prior to the procedure, postintervention LVEF by 2D bullet method on echocardiogram, improvement in RV dilation pre- and postprocedure on echo, and the time interval from intervention to postintervention LVEF measurement by echocardiogram were collected. There was no age cutoff for enrollment. With the exception of one 17-year-old patient in the study group, all patients who met inclusion/exclusion criteria were adults.

For quality control, the LVEF on all echocardiograms in this study was independently reviewed and recalculated retrospectively by a pediatric cardiologist with advanced fellowship training in imaging and adult CHD to confirm accurate measurements.

Patients were excluded from the study if they had LV dysfunction due to other known causes (i.e., previously diagnosed ischemic or nonischemic cardiomyopathy), addition of a new medication to their guideline-directed medical therapy (GDMT), increase in dosing of an existing GDMT medication during the time period between cardiac imaging, had a pacemaker implanted or pacemaker settings optimized during the time period between cardiac imaging, or had an intervention directly targeting their LV myocardial health or hemodynamics during this time period (e.g., coronary intervention and aortic valve surgery).

Ethics approval

The study was granted exemption by the Institutional Review Board at Connecticut Children’s Medical Center. This retrospective chart review involving human participants was performed in accordance with the ethical standards as established in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Statistics

Demographic information was summarized using count (percentage). The median, mean, and range were calculated for the cohort’s age, preintervention LVEF, postintervention LVEF, change in LVEF, and time to improvement in LVEF. Interquartile range (IQR) for time to improvement in LVEF was included due to the wide range.

RESULTS

A total of 161 patients with ASD closure/repair or PVR were screened for eligibility. Of these patients, 144 were excluded, and 17 met inclusion/exclusion criteria for the study [Figure 1]. Of the 144 patients excluded, 135 were excluded for normal LV function prior to the procedure, 2 had a change to their GDMT regimen, 2 had preexisting cardiomyopathy, 2 had LV/coronary interventions performed during the procedure, and 3 did not have a preprocedure LVEF available.

Figure 1.

Flowchart of patients screened and enrolled in the study

Seventeen patients were identified with RV volume/pressure overloading conditions with concomitant LV dysfunction who had interventions, specifically to improve their RV hemodynamics. Male patients represented 58% of the participants (10/17), and 66% were receiving GDMT for heart failure (11/17), although their regimens differed. The mean age was 33 years with a range of 17–62 years. In all but one patient, the primary pathophysiology was RV volume overloading, with one patient who had right ventricle to pulmonary artery (RV to PA) conduit stenosis resulting in RV pressure overloading. Twelve patients had a PVR – 11 for severe pulmonary insufficiency and 1 for moderate pulmonary conduit stenosis (four surgical and eight transcatheter). Five patients underwent closure of an ASD – two of whom were closed with a transcatheter device and three underwent surgical closure (one secundum ASD and two sinus venosus ASDs). Of the total cohort, all 17 patients had improvement in LV function by 2D bullet on echocardiogram following intervention on a volume or pressure-loaded RV. One patient had subjective improvement in LV function by echocardiogram following intervention; however, his ejection fraction (EF) only increased from 50% to 52% after 365 days. One patient had a decrease in LV function 2 months later below his original baseline (33% preprocedure, 37% postprocedure, and 31% 2-month postprocedure). The remaining 15 patients all demonstrated long-standing improvement in LV function. The mean preintervention LVEF was 48% (range: 35%–54%), and the mean postintervention LVEF was 56% (range: 37%–68%) [Figure 2]. The mean change in LVEF was 9% with a range of 2%–15% [Figure 2]. The median time to echocardiogram-confirmed postintervention improvement was 2 days (IQR: 21 days) with a mean of 56 days and a range of 1–365 days. Seven out of nine transcatheter interventions for ASD closure or PVR showed an improvement in LVEF within 24 h (78%) [Table 1]. Symptom data were not well uniformly documented in all the patients pre- and postinterventions. However, in the 11 patients with documented symptoms of shortness of breath, fatigue, or exercise intolerance preintervention, nine reported an improvement in these symptoms after intervention (89%). There was preintervention RV dilation in 88% of patients (15/17), and 80% of those patients showed a subjective reduction in RV dilation on postprocedure echocardiogram (12/15), as described in the echocardiogram report.

Figure 2.

A graph of the pre- and postintervention left ventricular ejection fraction (LVEF) displayed by patient. The dotted line showing the mean pre- and postintervention LVEF of the entire cohort. LVEF: left ventricular ejection fraction

Table 1.

Demographic descriptors of all study participants grouped by primary anatomy/diagnosis

Sex	Age (years)	Diagnosis	Prior intervention	Medications	Intervention	Preintervention LVEF (%)	Postintervention LVEF (%)	Time to improvement (days)
Male	24	Secundum ASD	None	Carvedilol, empagliflozin, sacubitril-valsartan, furosemide, spironolactone	ASD device closure	35	44	1
Male	31	Secundum ASD, PS	Pulmonary valvuloplasty	Lisinopril	ASD device closure	45	59	1
Female	33	Secundum ASD	None	furosemide	ASD repair	53	63	2
Male	35	Sinus venosus ASD	None	None	Sinus venosus repair	54	68	7
Female	19	Sinus venosus ASD	None	None	Warden procedure	52	56	3
Female	62	PS	Pulmonary valvotomy	Lisinopril, carvedilol, furosemide	Surgical PVR	43	58	7
Female	28	TOF/PA	TOF repair, RV-PA conduit	Losartan, furosemide	Surgical PVR	53	57	300
Male	36	TOF	TOF repair	Lisinopril	Surgical PVR	50	52	365
Male	22	TOF	TOF repair, TAP	Metoprolol, sacubitril-valsartan	Surgical PVR	50	55	14
Male	40	TOF	BT shunt, RV–PA conduit	None	Transcatheter PVR	50	55	1
Female	31	TOF	Central shunt, RV–PA conduit	None	Transcatheter PVR	51	56	1
Female	56	TOF/PA	Waterston shunt, RV–PA conduit	Furosemide	Transcatheter PVR	52	59	1
Male	33	TOF	TOF repair, TAP	None	Transcatheter PVR	53	68	1
Female	33	TOF	BT shunt, RV–PA conduit	None	Transcatheter PVR (stenosis)	54	63	30
Male	36	TOF	TOF repair	Carvedilol, furosemide, losartan, spironolactone, metoprolol	Transcatheter PVR	33	37*	1
Male	17	DTGA	Rastelli	Lisinopril, metoprolol	Transcatheter PVR	41	50	210
Male	29	PA/IVS	Pulmonary valvotomy, TAP, RV–PA conduit	Atenolol	Transcatheter PVR	47	58	1

*Patient had a decrease in EF 2 months later below initial preintervention baseline. EF: Ejection fraction, PA: Pulmonary atresia, IVS: Intact ventricular septum, DTGA: D transposition of the great arteries, TAP: Transannular patch, RV to PA conduit: Right ventricle to pulmonary artery conduit, PVR: Pulmonary valve replacement, ToF: Tetralogy of Fallot, BT: Blalock–Taussig, ASD: Atrial septal defect, PS: Pulmonary stenosis, LVEF: Left ventricular ejection fraction, RV to PA: Right ventricle to pulmonary artery

DISCUSSION

In this case series, we present 17 patients who demonstrated improvement in LV systolic function after intervention to optimize RV hemodynamics, with the majority of interventions focusing on addressing RV volume overloading and one addressing RV pressure overloading. Prior experiments by Hoffman et al. and Brookes et al. demonstrated the negative effects of RV dilation on LV function.[2,6] In addition, findings by multiple studies have described improvement in LV systolic function following surgical PVR.[4,5,7] This case series reiterated the findings of improvement in LV function after surgical PVR and additionally described improvement in LV function after transcatheter PVR and both transcatheter and surgical ASD closure, for which there is a paucity of published cases in current literature. Relief of these RV volume or pressure overloading lesions may have led to improvement of RV dilation and/or normalization of septal contour, with subsequent improvement of LV function due to improved RV–LV interactions. Interestingly, most transcatheter interventions showed an improvement in LV function within 24 h, suggesting that the benefit on LV hemodynamics from alleviating these RV volume or pressure overloading lesions can be rapid. Surgical interventions were expected to take longer to see improvement in LV function due to the impact of cardiopulmonary bypass and recovery from myocardial dysfunction and postoperative low cardiac output; however, several of the surgical patients also showed rapid improvement in LV function.[8,9] This suggests that patients may experience a quick recovery of LVEF after optimizing RV volume or pressure overload, regardless of surgical versus transcatheter approach.

In this case series, RV volume or pressure overloading occurred in the context of an ASD or pulmonary insufficiency due to a congenital pulmonary valve abnormality or as a consequence of a prior intervention for pulmonary stenosis (such as transannular patch for TOF or pulmonary valvuloplasty for congenital pulmonary stenosis). There are other forms of congenital heart defects in which intervening on RV volume overloading lesions may positively impact LV function, including partial anomalous pulmonary venous return without ASD, unroofed coronary sinus, and large coronary to right heart fistulas; however, these diagnoses were not encountered in our series.

Although no significant changes were made to the patient’s heart failure regimens during the interval between pre- and postintervention EF changes, it is possible that the patients obtained benefit from these medications with regard to improvement in LV function. However, in a previous study of patients undergoing PVR for TOF, the use of heart failure medications preoperatively did not correlate with significant postoperative improvement in LVEF.[8] Given the majority of patients demonstrated a rapid improvement in LV systolic function postintervention, sometimes within 24 h, contributions from GDMT medications seem unlikely. In addition, there were several patients who were not on any GDMT yet demonstrated an improvement in LV function following the intervention.

In contrast to RV volume overloading, there are also patients who are subjected to significant RV pressure overloading conditions. RV pressure overloading and subsequent RV dysfunction can occur in pulmonary hypertension (PHTN).[10] While the most common group in adults is Group 2 PHTN from left heart disease, there also exists Group 1 or pulmonary arterial hypertension for which medical therapies are available.[11] Group PHTN can result from long-standing shunts from unrepaired congenital heart defects. Group 2 PHTN from LV systolic or diastolic dysfunction is also not uncommon in patients with CHD. It is conceivable that patients with PHTN regardless of etiology and concomitant LV dysfunction would show improvement in LV function after optimization of their pulmonary hypertensive regimens (in the case of Group 1 PHTN) and/or treatment of left heart dysfunction (in the case of Group 2 PHTN) due to improved RV–LV interactions.

In addition to PHTN, there are congenital cardiac lesions which can result in significant RV pressure overloading, including RV outflow tract obstruction from subvalvar, valvar, or supravalvar pulmonary stenosis; branch or distal PA stenosis; and double-chambered right ventricle.[12,13,14] One patient in this study had RV–PA conduit stenosis as the primary indication for transcatheter PVR and demonstrated improvement in LV function postprocedure. This reinforces the idea that intervening on lesions to relieve RV hypertension can improve LV function through improved RV–LV interactions.

A 36-year-old patient in the series with TOF and severe pulmonary valve insufficiency, accompanied by biventricular dilation and dysfunction (baseline EF of 33%), showed a modest improvement in EF to 37% following intervention. However, this gain was short lived, and LVEF declined back to preintervention levels at subsequent follow-up. Notably, the patient had been lost to follow-up for over a decade, and LV dysfunction was not significantly impacted by PVR. As suggested by the MADIT-CRT trial, an LVEF below 35% may necessitate cardiac resynchronization support (CRT), and offloading RV volume loading alone may not be sufficient.[15,16] This case may also represent irreversible LV cardiomyocyte mass loss from long-standing dysfunction, highlighting the importance of early intervention before progression to severe LV dysfunction. In patients with optimized hemodynamics, a recent study has demonstrated improvement in New York Heart Association functional class with CRT in patients with TOF.[17]

LV dysfunction in TOF may have many contributors. It may be noted in asymptomatic patients with TOF and could represent cardiomyocyte mass loss.[18,19] Adverse changes in the LV may be associated with worse clinical outcomes.[16] It is plausible that strategies targeting RV hemodynamics for early improvement of LV dysfunction may offer a protective effect on LV myocytes.[15] While larger studies are needed to understand the explicit impact of improving RV hemodynamics on LV function, it may offer an overall risk reduction in adverse outcomes.

In summary, this case series highlights a potential for improvement in LV systolic function once RV hemodynamics are optimized and further suggests that patients with LV dysfunction who undergo interventions to alleviate RV volume or pressure overloading lesions can have rapid improvement in LVEF. Larger prospective studies with standardized timeline for imaging pre- and postintervention are needed to understand interventricular hemodynamic alterations in patients undergoing treatment for varying RV volume and pressure overloading conditions, including impact on both LV systolic and diastolic function. Ideally, systolic function would be assessed not only by 2D bullet method on echocardiogram but also by additional function parameters such as global longitudinal strain.[20] It would be ideal to collect functional assessment by CMR, given the improved accuracy this modality demonstrates in calculating LVEF.[21] Unfortunately, CMR is not accessible in a timely a fashion compared to echocardiogram. Cardiac magnetic resonance imaging (CMR) is also less feasible in patients with pacemakers or behavioral issues who would require sedation to obtain the study. As a result of these limitations, only three patients in our study group had postprocedure CMR, and CMR data were not collected for this study.

Limitations

This study was subject to the limitations of a single-center retrospective study. Timing for preintervention and postintervention echo varied by patient. Interuser variability in echocardiogram interpretation was minimized by the review of all included echocardiograms by a pediatric cardiologist with advanced fellowship training in imaging and CHD, who confirmed that the calculated LVEF was accurate. There are known limitations of evaluation of LVEF by echocardiogram, but acquisition of CMR in a timely fashion postprocedure is not feasible in postoperative or postcatheterization patients.

CONCLUSIONS

In this case series of patients, intervention to alleviate RV volume or pressure overloading lesions resulted in improvement in LV function, sometimes within 24 h. Larger, prospective studies are necessary to better understand the responses of patients with various RV volume or pressure overloading lesions and concurrent LV dysfunction when RV hemodynamics are improved and to compare these effects between surgical and transcatheter interventions. Future research may help identify patients who will benefit from such interventions and potentially refine treatment guidelines. Additional studies are needed to understand the longevity of improved LV function after isolated interventions on RV hemodynamics.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.