Left ventricular remodeling

Left ventricular remodeling

Left ventricular remodeling occurs in response to left ventricular stress and injury. It is progressive and occurs after large myocardial infarctions and dilated cardiomyopathy. Left ventricular volume increases and the normal elliptical shape becomes globular. Left ventricular remodeling is associated with changes at microscopic level which include myocyte hypertrophy, apoptosis and increased interstitial collagen deposition [1]. Left ventricular remodeling is a central pathophysiological mechanism in advancing heart failure. Reversal of remodeling with treatment is an important goal in the management of heart failure. Treatment modality could be either drugs or devices depending on the clinical scenario.

In post myocardial infarction remodeling, two processes are infarct expansion and enlargement of the rest of the left ventricle. Infarct expansion occurs in the process of fibrotic repair of the necrotic area with scar formation and thinning of the infarct zone. Increase in left ventricular volume is initially beneficial as the force of contraction increases according to Starling’s law. Volume overload hypertrophy occurs in the non infarcted segments [2]. But as the left ventricle assumes a spherical shape later, it leads to decline in performance.

In idiopathic dilated cardiomyopathy, there is elevated wall stress and left ventricle assumes a more spherical shape. A study comparing survivors and nonsurvivors showed that survivors had a small left ventricular end diastolic short axis dimension, but a similar long axis length [3]. Left ventricular cavity was more spherical in those with poorer survival. The study did not find any difference in systolic cavity dimension, wall thickness, cavity volume or fractional shortening between survivors and non survivors.

Pathologic left ventricular remodeling is associated with neuroendocrine activation which are triggered by the increased left ventricular wall stress and hemodynamic derangement [1]. Both angiotensin converting enzyme inhibitors and angiotensin receptor blockers are useful in prevention of adverse left ventricular remodeling. Reverse remodeling has also been documented by radionuclide ventriculograms [4]. This translates into reduced disease progression and mortality rates in patients with heart failure.

Similarly, treatment with betablockers can also prevent left ventricular remodeling after acute myocardial infarction [5]. Carvedilol treatment started early after acute myocardial infarction attenuated left ventricular remodeling in patients with persistent left ventricular dysfunction before discharge. Addition of carvedilol to standard therapy including angiotensin converting enzyme inhibitor was found to reduce clinical progression in patients who were only mildly symptomatic with well compensated heart failure [6]. This was a study by the US Carvedilol Heart Failure Study Group.

Angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan has been shown to be superior to enalapril in reducing cardiovascular mortality in the PARADIGM-HF (Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study [7]. A meta-analysis of twenty studies enrolling 10,175 patients concluded that ARNI was superior to angiotensin converting enzyme inhibitors and angiotensin receptor blockers in improving left ventricular remodeling in heart failure patients with reduced ejection fraction [8].

Cardiac resynchronization therapy is another treatment modality which has been shown to improve left ventricular remodeling. An analysis of the COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure) study showed that those with larger baseline left ventricular end diastolic dimension index had a reduction in all cause mortality and heart failure hospitalization with cardiac resynchronization therapy [9].

References

1. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 2011 Jan;4(1):98-108.
2. McKay RG, Pfeffer MA, Pasternak RC, Markis JE, Come PC, Nakao S, Alderman JD, Ferguson JJ, Safian RD, Grossman W. Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986 Oct;74(4):693-702.
3. Douglas PS, Morrow R, Ioli A, Reichek N. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1989 Feb;13(2):311-5. 
4. Konstam MA, Patten RD, Thomas I, Ramahi T, La Bresh K, Goldman S, Lewis W, Gradman A, Self KS, Bittner V, Rand W, Kinan D, Smith JJ, Ford T, Segal R, Udelson JE. Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy. Am Heart J. 2000 Jun;139(6):1081-7. 
5. Senior R, Basu S, Kinsey C, Schaeffer S, Lahiri A. Carvedilol prevents remodeling in patients with left ventricular dysfunction after acute myocardial infarction. Am Heart J. 1999 Apr;137(4 Pt 1):646-52.
6. Colucci WS, Packer M, Bristow MR, Gilbert EM, Cohn JN, Fowler MB, Krueger SK, Hershberger R, Uretsky BF, Bowers JA, Sackner-Bernstein JD, Young ST, Holcslaw TL, Lukas MA. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group. Circulation. 1996 Dec 1;94(11):2800-6. 
7. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. 
8. Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D. Effects of the Angiotensin-Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta-Analysis. J Am Heart Assoc. 2019 Jul 2;8(13):e012272. 
9. Shamoun F, De Marco T, DeMets D, Mei C, Lindenfeld J, Saxon LA, Boehmer JP, Leigh J, Yong P, Feldman AM, Bristow MR. Impact of Degree of Left Ventricular Remodeling on Clinical Outcomes From Cardiac Resynchronization Therapy. JACC Heart Fail. 2019 Apr;7(4):281-290.