On 3 legs shall we stand: Combined innovation for treatment of ischemic cardiomyopathy

Abstract

Central MessagePatients at high risk for ischemic cardiomyopathy progression may benefit from a combination of early coronary artery bypass grafting, mitral valve surgery, and/or ventricular restraint therapy.See Commentary on page 228.Feature Editor's Introduction—In the accompanying article, Kawabori and colleagues discuss new innovations in the treatment of ischemic cardiomyopathy. While surgeons are keenly aware of standard treatment options (guideline-directed medical therapy, revascularization, transplantation, and mechanical circulatory support), these authors explore the role of adjunctive therapies, including mitral valve surgery, ventricular restraint, and stem cell therapy in curbing the progression of this disease. They propose a future state where treatment for ischemic cardiomyopathy is more nuanced and tailored. This type of precision medicine would aim to treat patients earlier in their disease course with therapies that slow the progression to end-stage disease. Among the challenges we face is finding tools that achieve this goal. Given that revascularization and medical therapy are standard care for ischemic cardiomyopathy, the real question is do we have useful adjunctive therapies in 2021? To date, neither stem cell therapy nor ventricular restraint have shown efficacy in clinical trials. While the authors discuss how these concepts are being resurrected in new research, at this time, these particular therapies remain investigational. Patients at high risk for ischemic cardiomyopathy progression may benefit from a combination of early coronary artery bypass grafting, mitral valve surgery, and/or ventricular restraint therapy. See Commentary on page 228. Leora B. Balsam, MD In 1970, Burch and colleagues1Burch G.E. Giles T.D. Colcolough H.L. Ischemic cardiomyopathy.Am Heart J. 1970; 79: 291-292Google Scholar first described the term ischemic cardiomyopathy (ICM) in the literature as the degenerative changes and subsequent heart failure resulting from chronic coronary artery disease (CAD) and myocardial ischemia. In 2002, this definition was expanded to describe ICM as heart failure in patients with a previous myocardial infarction or coronary revascularization (either coronary angioplasty or coronary artery bypass graft [CABG] surgery), 75% or greater left main or proximal left anterior descending artery disease, or 75% or greater stenosis in multivessel disease.2Felker G.M. Shaw L.K. O’Connor C.M. A standardized definition of ischemic cardiomyopathy for use in clinical research.J Am Coll Cardiol. 2002; 39: 210-218Google Scholar Today, ICM is often further refined when used in clinical trials to include ejection fraction. ICM can be considered a chronic condition with reduced myocardial function in which patients have epicardial CAD and an ejection fraction <35%, despite optimal medical therapy.3Velazquez E.J. Lee K.L. Deja M.A. Jain A. Sopko G. Marchenko A. et al.Coronary-artery bypass surgery in patients with left ventricular dysfunction.N Engl J Med. 2011; 364: 1607-1616Google Scholar,4Mann D.L. Kubo S.H. Sabbah H.N. Starling R.C. Jessup M. Oh J.K. et al.Beneficial effects of the CorCap cardiac support device: five-year results from the Acorn Trial.J Thorac Cardiovasc Surg. 2012; 143: 1036-1042Google Scholar ICM continues to play a prominent role in the US health care landscape because those with CAD are at risk. CAD is the leading cause of cardiovascular death in the United States, and is estimated to account for 41.7% of deaths globally between 1990 and 2013.5Benjamin E.J. Muntner P. Alonso A. Bittencourt M.S. Callaway C.W. Carson A.P. et al.Heart disease and stroke statistics-2019 update: a report from the American Heart Association.Circulation. 2019; 139: e56-e528Google Scholar Thus, finding effective treatments for ICM remains of critical importance. The current gold standard treatment for end-stage ICM is heart transplantation (HTx) or the use of durable mechanical circulatory support (MCS), such as left ventricular (LV) assist devices, as destination therapy or as a bridge to transplant.6Peura J.L. Colvin-Adams M. Francis G.S. Grady K.L. Hoffman T.M. Jessup M. et al.Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association.Circulation. 2012; 126: 2648-2667Google Scholar However, these therapies have limited applicability, particularly in patients with underlying medical conditions such as high pulmonary vascular resistance in HTx, severe right heart dysfunction, or the inability to tolerate anticoagulation in MCS.6Peura J.L. Colvin-Adams M. Francis G.S. Grady K.L. Hoffman T.M. Jessup M. et al.Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association.Circulation. 2012; 126: 2648-2667Google Scholar Due to the limitations of HTx and MCS, there is increasing interest in treatments to alleviate disease burden for ICM patients before HTx and MCS become necessary. The efficacy of CABG in treating ICM is well established in the literature. The Surgical Treatment for Ischemic Heart Failure/Surgical Treatment for Ischemic Heart Failure Extension Study trials demonstrated definitive benefits for ICM patients undergoing CABG compared with those treated with medical therapy alone in both the short- and long-term. ICM patients who underwent CABG had lower rates of death or hospitalization from cardiovascular causes at a median of 56 months of follow-up.3Velazquez E.J. Lee K.L. Deja M.A. Jain A. Sopko G. Marchenko A. et al.Coronary-artery bypass surgery in patients with left ventricular dysfunction.N Engl J Med. 2011; 364: 1607-1616Google Scholar These benefits persisted even 10 years later. ICM patients who underwent CABG had fewer all-cause deaths, as well as better outcomes for all secondary outcomes recorded. A detailed subanalysis for death of any cause demonstrated a benefit from CABG for nearly all parameters measured.7Velazquez E.J. Lee K.L. Jones R.H. Al-Khalidi H.R. Hill J.A. Panza J.A. et al.Coronary-artery bypass surgery in patients with ischemic cardiomyopathy.N Engl J Med. 2016; 374: 1511-1520Google Scholar Of course, when applying these results to clinical practice, it is important to take into account individual factors such as myocardial variability, ejection fraction, LV volume, and heart failure stage when determining the benefit of a CABG for any single patient with ICM.8Bonow R.O. Maurer G. Lee K.L. Holly T.A. Binkley P.F. Desvigne-Nickens P. et al.Myocardial viability and survival in ischemic left ventricular dysfunction.N Engl J Med. 2011; 364: 1617-1625Google Scholar,9Panza J.A. Ellis A.M. Al-Khalidi H.R. Holly T.A. Berman D.S. Oh J.K. et al.Myocardial viability and long-term outcomes in ischemic cardiomyopathy.N Engl J Med. 2019; 381: 739-748Google Scholar For ICM patients with viable myocardium, Bax and colleagues10Bax J.J. Schinkel A.F.L. Boersma E. Rizzello V. Elhendy A. Maat A. et al.Early versus delayed revascularization in patients with ischemic cardiomyopathy and substantial viability: impact on outcome.Circulation. 2003; 108: II39-II42Google Scholar showed that early revascularization leads to lower mortality and significant functional improvement compared with those revascularized later. Non-viability limits the benefits of revascularization. Severely enlarged hearts with low ejection fraction may be nearing end-stage heart failure, and derive more benefit from end-stage heart failure surgeries, rather than revascularization. Risk stratifying individual patients based on likelihood of developing end-stage ICM, such as those with a strong family history of ICM, may lead to patient-specific preventative treatment. Higher-risk patients may benefit from frequent follow-up and early CABG to delay ICM progression. However, revascularization does not treat the full spectrum of complications associated with ICM. Ischemic mitral regurgitation (IMR) often occurs in ICM patients, and is associated with reduced survival, even after revascularization.11Milano C.A. Daneshmand M.A. Rankin J.S. Honeycutt E. Williams M.L. Swaminathan M. et al.Survival prognosis and surgical management of ischemic mitral regurgitation.Ann Thorac Surg. 2008; 86: 735-744Google Scholar Mitral valve replacement (MVR) or repair (MVr) provides more benefit for patients in earlier phases of ICM who have relatively preserved myocardial function because these surgeries decrease IMR and pulmonary congestion. Studies have also suggested that MVR may be more effective than MVr. In the well-known Cardiothoracic Surgical Trials Network randomized clinical trial where patients were randomized to receive MVR or MVr for severe IMR, there was more recurrent severe MR in the repair group after 1 year, despite no difference in LV reverse remodeling or mortality (P < .05).12Acker M.A. Parides M.K. Perrault L.P. Moskowitz A.J. Gelijns A.C. Voisine P. et al.Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.N Engl J Med. 2014; 370: 23-32Google Scholar However, performing MVR or MVr in end-stage heart failure patients with significantly decreased ventricular function may further stress the LV by increasing afterload via decreased MV regurgitation. An overloaded LV with high diastolic filling pressure does not eliminate elevated left atrial pressures, thereby reducing diastolic coronary flow and further worsening myocardial ischemia. End-stage ICM patients may derive more benefit from HTx or MCS to obtain a more physiological, unloaded LV. In addition to MVR and MVr, percutaneous therapy such as the MitraClip (Abbott, Abbott Park, Ill) may also play a role in treating ICM in the near future. A review by Takagi and colleagues13Takagi H. Ando T. Umemoto T. ALICE (All-Literature Investigation of Cardiovascular Evidence) GroupA review of comparative studies of MitraClip versus surgical repair for mitral regurgitation.Int J Cardiol. 2017; 228: 289-294Google Scholar suggests that MitraClip has similar survival outcomes to surgical mitral valve interventions. It is important to note that mitral valve interventions alone will not treat ICM. To further refine the indications for these procedures, individual investigations are required to determine how each aspect of ICM-stage, mitral valve anatomy, IMR severity, myocardial viability, predictions for progression of ICM, and the likelihood of developing end-stage heart failure, affect patient postoperative outcomes. Similar to revascularization, patients who are at high risk for developing end-stage ICM may benefit from early risk analysis and surgical procedures to slow disease progression. Ventricular restraint therapy (VRT) emerged in the 1980s with Carpentier's invention of the cardiomyoplasty procedure as a way to supplement current surgical therapies for ICM by providing diastolic support and preventing ventricular remodeling, without needing to be in direct contact with the patient's blood.14Kwon M.H. Cevasco M. Schmitto J.D. Chen F.Y. Ventricular restraint therapy for heart failure: a review, summary of state of the art, and future directions.J Thorac Cardiovasc Surg. 2012; 144: 771-777.e1Google Scholar, 15Lee L.S. Ghanta R.K. Mokashi S.A. Coelho-Filho O. Kwong R.Y. Bolman III, R.M. et al.Ventricular restraint therapy for heart failure: the right ventricle is different from the left ventricle.J Thorac Cardiovasc Surg. 2010; 139: 1012-1018Google Scholar, 16Naveed M. Han L. Khan G.J. Yasmeen S. Mikrani R. Abbas M. et al.Cardio-supportive devices (VRD & DCC device) and patches for advanced heart failure: a review, summary of state of the art and future directions.Biomed Pharmacother. 2018; 102: 41-54Google Scholar VRT has shown enough promise that 2 ventricular restraint devices were approved by the National Institutes of Health for human clinical trials to prevent adverse remodeling: the CorCap (Acorn Cardiovascular, Inc, St Paul, Minn) and the HeartNet (Paracor Medical, Sunnyvale, Calif). Initial results for these trials were promising: in 2012, the 5-year results from the Assessment of a Cardiac Support Device in Patients with Heart Failure trial showed that the CorCap is safe, improves quality of life, and decreases remodeling.4Mann D.L. Kubo S.H. Sabbah H.N. Starling R.C. Jessup M. Oh J.K. et al.Beneficial effects of the CorCap cardiac support device: five-year results from the Acorn Trial.J Thorac Cardiovasc Surg. 2012; 143: 1036-1042Google Scholar Similarly, in 2008 early clinical data for the HeartNet showed that it is safe and improves quality of life.17Klodell Jr., C.T. Aranda Jr., J.M. McGiffin D.C. Rayburn B.K. Sun B. Abraham W.T. et al.Worldwide surgical experience with the Paracor HeartNet cardiac restraint device.J Thorac Cardiovasc Surg. 2008; 135: 188-195Google Scholar Unfortunately, neither of these devices were ultimately used in clinical practice. The Food and Drug Administration felt there was not enough evidence to approve the CorCap, asit showed no survival benefit and there were some safety concerns, and the HeartNet clinical trial was halted, primarily due to a lack of evidence suggesting tangible benefit after 6 months and 1 year.14Kwon M.H. Cevasco M. Schmitto J.D. Chen F.Y. Ventricular restraint therapy for heart failure: a review, summary of state of the art, and future directions.J Thorac Cardiovasc Surg. 2012; 144: 771-777.e1Google Scholar The Assessment of a Cardiac Support Device in Patients with Heart Failure trial found that patients with an intermediate indexed LV end diastolic diameter derived the most benefit from the device, suggesting that ventricular size may affect the utility of VRT.18Mann D.L. Acker M.A. Jessup M. Sabbah H.N. Starling R.C. Kubo S.H. et al.Clinical evaluation of the CorCap cardiac support device in patients with dilated cardiomyopathy.Ann Thorac Surg. 2007; 84: 1226-1235Google Scholar The idea that ventricle size is important for determining outcomes after therapy has been previously hypothesized.19Menicanti L. Castelvecchio S. Left ventricular reconstruction concomitant to coronary artery bypass grafting: when and how?.Curr Opin Cardiol. 2011; 26: 523-527Google Scholar Ghanta and colleagues20Ghanta R.K. Rangaraj A. Umakanthan R. Lee L. Laurence R.G. Fox J.A. et al.Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure.Circulation. 2007; 115: 1201-1210Google Scholar began to investigate the idea that VRT must be carefully matched to patient ventricular parameters with their quantitative ventricular restraint device. In large animal testing, the quantitative ventricular restraint device showed superior efficacy over static pressure devices, suggesting that individualized VRT may be beneficial.21Lee L.S. Ghanta R.K. Mokashi S.A. Coelho-Filho O. Kwong R.Y. Kwon M. et al.Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy.J Thorac Cardiovasc Surg. 2013; 145: 824-831Google Scholar Perhaps an additional modality of ICM therapy lies in building off of the relative success of historical VRT devices, as many newer VRT devices have been showing promise in preclinical animal studies.22Naveed M. Wenhua L. Gang W. Mohammad I.S. Abbas M. Liao X. et al.A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.Biomed Pharmacother. 2017; 95: 701-710Google Scholar, 23Roche E.T. Horvath M.A. Wamala I. Alazmani A. Song S.E. Whyte W. et al.Soft robotic sleeve supports heart function.Sci Transl Med. 2017; 9: eaaf3925Google Scholar, 24Hord E.C. Bolch C.M. Tuzun E. Cohn W.E. Leschinsky B. Criscione J.C. Evaluation of the CorInnova heart assist device in an acute heart failure model.J Cardiovasc Transl Res. 2019; 12: 155-163Google Scholar The EpicHeart device (CorInnova, Houston, Tex) is designed to be implanted minimally invasively to provide systolic support for heart failure patients. It improves hemodynamic parameters in an ovine acute heart failure model.24Hord E.C. Bolch C.M. Tuzun E. Cohn W.E. Leschinsky B. Criscione J.C. Evaluation of the CorInnova heart assist device in an acute heart failure model.J Cardiovasc Transl Res. 2019; 12: 155-163Google Scholar A soft robot sleeve device developed by Roche and colleagues23Roche E.T. Horvath M.A. Wamala I. Alazmani A. Song S.E. Whyte W. et al.Soft robotic sleeve supports heart function.Sci Transl Med. 2017; 9: eaaf3925Google Scholar has also shown initial promise in small and large animal models as a way to support the heart by attempting to mimic native motion and biomechanical properties. The use of VRT technology does not preclude the inclusion of cellular or regenerative medicine in the quest for newer, less-invasive therapies for ICM. In fact, a 2010 small animal study showed increased efficacy of VRT when combined with cellular therapy.25Mokashi S.A. Guan J. Wang D. Tchantchaleishvili V. Brigham M. Lipsitz S. et al.Preventing cardiac remodeling: the combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia.J Thorac Cardiovasc Surg. 2010; 140: 1374-1380Google Scholar The idea of combination therapy is being tested with Naveed and colleagues22Naveed M. Wenhua L. Gang W. Mohammad I.S. Abbas M. Liao X. et al.A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.Biomed Pharmacother. 2017; 95: 701-710Google Scholar multifunctional Active hydraulic ventricular Support Drug delivery system (ASD, X. Zhou), which has shown improved heart function in small animal studies when the ASD device was used in conjunction with a therapeutic agent. The ASD represents the next generation of VRT, as it combines physical support with real-time heart monitoring and the ability to deliver targeted pharmacologic therapy.22Naveed M. Wenhua L. Gang W. Mohammad I.S. Abbas M. Liao X. et al.A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.Biomed Pharmacother. 2017; 95: 701-710Google Scholar Thus, it has the potential to adapt to a patient's heart in real time. The mesh-like design of the ASD also allows for the possibility of using it for patients undergoing cardiac surgery, such as CABG. This device gives rise to the idea that VRT may be able to augment already existing therapies, such as improving outcomes for patients who have had prior CABG or MVR or MVr. Among the major questions that remains as VRT continues to develop is how these devices may be used in conjunction with surgical or pharmacologic therapy to meet each patients' unique support needs and prevent progression of ICM. Since the early 2000s, cellular regenerative medicine has exploded, with the aim of treating ICM by using stem cells to preserve cardiac function, prevent scar formation, and regenerate healthy myocardium.26Pagano F. Picchio V. Chimenti I. Sordano A. De Falco E. Peruzzi M. et al.On the road to regeneration: “tools” and “routes” towards efficient cardiac cell therapy for ischemic cardiomyopathy.Curr Cardiol Rep. 2019; 21: 133Google Scholar Many aspects critical to the development of a successful cellular therapy remain under investigation, and it is unclear how the cells exert their effects on myocardium, if the stem cells effectively differentiate, or what the correct therapeutic dose should be.26Pagano F. Picchio V. Chimenti I. Sordano A. De Falco E. Peruzzi M. et al.On the road to regeneration: “tools” and “routes” towards efficient cardiac cell therapy for ischemic cardiomyopathy.Curr Cardiol Rep. 2019; 21: 133Google Scholar, 27Recchia F.A. Sharp T.E. Combination cell therapy for ischemic cardiomyopathy: is the whole greater than sum of its parts?.J Am Coll Cardiol. 2017; 70: 2516-2518Google Scholar, 28Curfman G. Stem cell therapy for heart failure: an unfulfilled promise?.JAMA. 2019; 321: 1186-1187Google Scholar Stem cells might exert their benefits through the release of signaling molecules to promote healing or revascularization and through differentiation to replace damaged myocytes.27Recchia F.A. Sharp T.E. Combination cell therapy for ischemic cardiomyopathy: is the whole greater than sum of its parts?.J Am Coll Cardiol. 2017; 70: 2516-2518Google Scholar Although preclinical studies show potential, current clinical trials of cell therapy have yet to show definitive benefits: a 2019 clinical trial using mesenchymal precursor cells to support patients with an LVAD found no difference in survival or in rates of LVAD weaning success between patients treated with mesenchymal precursor cells and those treated with a control solution.26Pagano F. Picchio V. Chimenti I. Sordano A. De Falco E. Peruzzi M. et al.On the road to regeneration: “tools” and “routes” towards efficient cardiac cell therapy for ischemic cardiomyopathy.Curr Cardiol Rep. 2019; 21: 133Google Scholar,29Yau T.M. Pagani F.D. Mancini D.M. Chang H.L. Lala A. Woo Y.J. et al.Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial.JAMA. 2019; 321: 1176-1186Google Scholar Other studies, such as the 2017 Intracoronary ALLogenic heart STem cells to Achieve myocardial Regeneration trial, have also shown no therapeutic effect with cellular therapy on ventricular remodeling after myocardial infarction.26Pagano F. Picchio V. Chimenti I. Sordano A. De Falco E. Peruzzi M. et al.On the road to regeneration: “tools” and “routes” towards efficient cardiac cell therapy for ischemic cardiomyopathy.Curr Cardiol Rep. 2019; 21: 133Google Scholar Similarly, cellular regenerative medicine has not yet shown applicable benefits to human patients. Although neonatal mice, rats, and piglets are all able to regenerate myocardium after injury within the first few days of life, the mechanism behind cardiac regeneration is still being elucidated and has not been studied in humans.30Porrello E.R. Mahmoud A.I. Simpson E. Hill J.A. Richardson J.A. Olson E.N. et al.Transient regenerative potential of the neonatal mouse heart.Science. 2011; 331: 1078-1080Google Scholar, 31Ye L. D’Agostino G. Loo S.J. Wang C.X. Su L.P. Tan S.H. et al.Early regenerative capacity in the porcine heart.Circulation. 2018; 138: 2798-2808Google Scholar, 32Wang H. Paulsen M.J. Hironaka C.E. Shin H.S. Farry J.M. Thakore A.D. et al.Natural heart regeneration in a neonatal rat myocardial infarction model.Cells. 2020; 9: 229Google Scholar, 33Das S. Goldstone A.B. Wang H. Farry J. D'Amato G. Paulsen M.J. et al.A unique collateral artery development program promotes neonatal heart regeneration.Cell. 2019; 176: 1128-1142.e18Google Scholar, 34Sadek H.A. Porrello E.R. Neonatal heart regeneration: moving from phenomenology to regenerative medicine.J Thorac Cardiovasc Surg. 2020; 159: 2451-2455Google Scholar Although there are high expectations for the future of this field, more evidence from double-blind, controlled, randomized trials is necessary to establish clinical outcomes, as stated by the European Society of Cardiology's consensus statement.35Mathur A. Fernández-Avilés F. Dimmeler S. Hauskeller C. Janssens S. Menasche P. et al.The consensus of the Task Force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for the treatment of acute myocardial infarction and heart failure: update 2016.Eur Heart J. 2017; 38: 2930-2935Google Scholar Although HTx or MCS therapy remains the mainstay of treatment for end-stage ICM, there is a substantial population of patient ineligible for these interventions. HTx opportunities are severely limited by donor availability and long waiting times.36Khush K.K. Cherikh W.S. Chambers D.C. Harhay M.O. Hayes Jr., D. Hsich E. et al.The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult heart transplantation report - 2019; focus theme: donor and recipient size match.J Heart Lung Transplant. 2019; 38: 1056-1066Google Scholar MCS also presents its own limitations—namely the need for anticoagulation, an external driveline, and the effects on patient quality of life—that may exclude certain patient populations from being supported on MCS.22Naveed M. Wenhua L. Gang W. Mohammad I.S. Abbas M. Liao X. et al.A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.Biomed Pharmacother. 2017; 95: 701-710Google Scholar Although no prior clinical trials have evaluated the efficacy of early combination therapy (CABG, mitral valve surgery, and/or VRT), each intervention has individually shown benefits and potential, and may be effective in preventing remodeling and slowing the disease progression of ICM (Figure 1). However, because these therapies are invasive, early intervention may be of the most benefit for the highest-risk patients. Thus, risk stratification that predicts the progression of ICM can inform optimal timing for surgical procedures to maximize the benefits to patients. Much like how combination chemotherapy for cancer attacks oncologic disease at different pathophysiology points and increases therapeutic efficacy, so too might a similar approach be effective for ICM.Tonight, I am launching a new precision medicine initiative to bring us closer to curing diseases… and to give all of us access to personalized information to keep ourselves and our families healthier.37Remarks by the President in State of the Union Address.https://obamawhitehouse.archives.gov/the-press-office/2015/01/20/remarks-president-state-union-address-january-20-2015Date accessed: January 14, 2021Google Scholar–Barak Obama In the 2015 State of the Union Address, US President Barak Obama ushered in the era of precision medicine.37Remarks by the President in State of the Union Address.https://obamawhitehouse.archives.gov/the-press-office/2015/01/20/remarks-president-state-union-address-january-20-2015Date accessed: January 14, 2021Google Scholar For the medical community, this meant sequencing individual genomes and utilizing trends in population genetic data to help tailor medicine and interventions to an individual's unique genetic profile.38Fact sheet: President Obama’s Precision Medicine Initiative.https://obamawhitehouse.archives.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiativeDate accessed: January 13, 2021Google Scholar During the past 5 years, precision medicine has evolved to include early genetic disease detection, risk stratification, and individual prevention. Multiple genetic risk factors have been identified for CAD, and polygenetic risk scores are being studied to assess risk for CAD and ICM.39Mosley J.D. van Driest S.L. Wells Q.S. Shaffer C.M. Edwards T.L. Bastarache L. et al.Defining a contemporary ischemic heart disease genetic risk profile using historical data.Circ Cardiovasc Genet. 2016; 9: 521-530Google Scholar,40Koyama S. Ito K. Terao C. Akiyama M. Horikoshi M. Momozawa Y. et al.Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease.Nat Genet. 2020; 52: 1169-1177Google Scholar With this information, it may be feasible to identify patients at risk for future ICM who may benefit from earlier surgical intervention. Perhaps then the future of treating ICM is "Precision Surgery," or utilizing patient physiology, anatomy, and genetic risk score to intervene early in the disease process and prevent remodeling and end-stage heart failure with a unique combination of effective therapies. Only time will tell what role "Precision Surgery" will play in the treatment of ICM. The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. Commentary: Combination surgery for ischemic cardiomyopathy: The preemptive strikeJTCVS OpenVol. 7PreviewIn this issue of JTCVS Open, Kawabori and colleagues1 present a commentary to the effect that a combination of coronary artery bypass grafting, mitral valve surgery, and ventricular restraint devices may be more effective than cellular therapy for the treatment of ischemic cardiomyopathy (ICM). The authors point out that there has been limited but real success in numerous studies applying coronary artery bypass grafting, mitral valve surgery, and ventricular restraint devices individually to treat ischemic cardiomyopathy. Full-Text PDF Open Access