Left ventricular reverse remodeling

Left ventricular reverse remodeling

Left ventricular remodeling which starts initially as a beneficial process becomes detrimental later on leading to progressive worsening of left ventricular dilatation and dysfunction. Reverse left ventricular remodeling is a beneficial process which occurs after optimal medical therapy or cardiac resynchronization therapy in heart failure. Similar reverse remodeling has been described after valve replacement and repair procedures.

Yu CM et al studied reverse left ventricular remodeling in 141 patients with advanced heart failure who received cardiac resynchronization therapy and was followed up for a mean period of 695 days [1]. There were 22 deaths in the study period, mostly due to heart failure and sudden cardiac death. They checked the relation between the reduction of left ventricular end systolic volume (LVESV ) at 3 to 6 months and long term clinical outcome. They found that a reduction of LVESV of 9.5% or more had a sensitivity of 70% and specificity of 70% for predicting all cause mortality. Corresponding figures for cardiovascular mortality were 87% and 69% respectively. This cut off value identified 61.7% as responders to reverse remodeling. All cause mortality was significantly lower in responders, 6.9% vs 30.6%. Cardiovascular mortality was 2.3% in responders compared to 24.1% in non-responders. Heart failure events were 11.5% in responders and 33.3% in non-responders. In this study, change in LVESV was the single most important predictor of all cause and cardiovascular mortality. Clinical parameters could not predict outcome events in this study.

Similar beneficial effect on left ventricular remodeling was demonstrated long back in the trials with angiotensin converting enzyme inhibitors. SOLVD (Studies of Left Ventricular Dysfunction) study showed that in patients with heart failure and reduced left ventricular ejection fraction, chronic treatment with angiotensin converting enzyme inhibitor enalapril prevented progressive left ventricular dilatation, systolic dysfunction and increase in end systolic volume [2]. Mean end systolic volume decreased from 106 to 93 ml/m² in the study group while it increased from 103 to 116 ml/m² in the control group.

Survival and Ventricular Enlargement (SAVE) trial with captopril showed that left ventricular end diastolic and end systolic areas at 1 year were larger in placebo group than in captopril group [3]. They noted that left ventricular enlargement and dysfunction after myocardial infarction were associated with the development of adverse cardiac events. Preventing ventricular enlargement with captopril was associated with a reduction in adverse events.

Left ventricular reverse remodeling after cardiac resynchronization therapy with more than 20% reduction in LVESV is considered to be much larger than that observed in medical therapy for heart failure [1]. Generally about one third of patients do not respond well to cardiac resynchronization therapy (CRT). Lack of clinical response and absence of left ventricular reverse remodeling has been included in the definition of non-responders to CRT.

A discord between those with and without left bundle branch block (LBBB) has been reported in a substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) [4]. Authors compared patients with CRT alone and those with CRT and defibrillator (CRT-D) who had echocardiograms available at 1 year. Patients in the substudy were stratified by the presence or absence of LBBB. In those with LBBB on CRT-D, a median reduction in LVESV of more than 35% significantly reduced the risk of long term mortality and heart failure events compared to patients with ICDs only. In patients without LBBB, there was no survival benefit despite a reduction of LVESV more than the median 27.6%. Those with LBBB and least reverse remodeling (quartile 1) had more than three fold risk for death compared with those with ICDs only. Authors concluded that despite left ventricular reverse remodeling with CRT-D, there was no survival benefit and potential harm in patients without LBBB.

Left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy on medical therapy has been reported in a study of 361 patients [5]. They defined left ventricular reverse remodeling as increase of left ventricular ejection fraction ≥10 U or a left ventricular ejection fraction ≥50% and a decrease in indexed left ventricular end diastolic diameter of ≥10% or indexed left ventricular end diastolic diameter of ≥33 mm/m². Left ventricular reverse remodeling was noted in 37% of the patients surviving 2 years. Left ventricular reverse remodeling on tailored medical therapy at mid term follow up predicted a lower rate of major cardiovascular events on long term follow up. Mean follow up period was 110 ± 53 months for the surviving patients after the mid term follow up at 24 months (range 9 to 36 months).

Left ventricular reverse remodeling has been documented in patients with severe aortic regurgitation undergoing aortic valve replacement [6]. They defined reverse remodeling of LV as ≥10% reduction in measures of LV volumes. They noted that left ventricular reverse remodeling as assessed by the Teichholz method was underestimated by a mean of 31 ml/m² compared to Simpson method. Echocardiographic parameters indicating reverse left ventricular remodeling at 1 year after aortic valve replacement are important predictors of long term outcomes after aortic valve replacement [7].

Left ventricular reverse remodeling was associated with significantly reduced event rate at 2 years after MitraClip procedure for mitral regurgitation [8]. In that study left ventricular reverse remodeling was defined as a ≥10% of the left ventricular end diastolic diameter after 12 months. This was noted in 49% of the patients. The study included both degenerative mitral regurgitation and functional mitral regurgitation. In degenerative mitral regurgitation, presence of recurrent or residual severe mitral regurgitation at 12 months inversely predicted left ventricular reverse remodeling. In functional mitral regurgitation, residual severe tricuspid regurgitation inversely predicted left ventricular reverse remodeling.

References

1. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005 Sep 13;112(11):1580-6.
2. Konstam MA, Rousseau MF, Kronenberg MW, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators. Circulation. 1992 Aug;86(2):431-8.
3. St John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S, et al. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation. 1994 Jan;89(1):68-75.
4. Naqvi SY, Jawaid A, Vermilye K, Biering-Sørensen T, Goldenberg I, Zareba W, McNitt S, Polonsky B, Solomon SD, Kutyifa V. Left Ventricular Reverse Remodeling in Cardiac Resynchronization Therapy and Long-Term Outcomes. JACC Clin Electrophysiol. 2019 Sep;5(9):1001-1010.
5. Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G. Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol. 2011 Mar 29;57(13):1468-76.
6. Ong G, Redfors B, Crowley A, Abdel-Qadir H, Harrington A, Liu Y, Lafrenière-Roula M, Leong-Poi H, Peterson MD, Connelly KA. Evaluation of left ventricular reverse remodeling in patients with severe aortic regurgitation undergoing aortic valve replacement: Comparison between diameters and volumes. Echocardiography. 2018 Feb;35(2):142-147.
7. Izumi C, Kitai T, Kume T, Onishi T, Yuda S, Hirata K, Yamashita E, Kawata T, Nishimura K, Takeuchi M, Nakatani S. Effect of Left Ventricular Reverse Remodeling on Long-term Outcomes After Aortic Valve Replacement. Am J Cardiol. 2019 Jul 1;124(1):105-112.
8. Nita N, Scharnbeck D, Schneider LM, Seeger J, Wöhrle J, Rottbauer W, Keßler M, Markovic S. Predictors of left ventricular reverse remodeling after percutaneous therapy for mitral regurgitation with the MitraClip system. Catheter Cardiovasc Interv. 2020 Sep 1;96(3):687-697.