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Heart Failure TreatmentA. Maslow, MD
Ventricular remodeling is a maladaptive dilation of both the injured myocardium and the surrounding tissue. Once begun ventricular remodeling becomes a self-perpetuating process in which continued dilation causes further increases in wall stress and subsequently greater dilation. The ventricle appears more spherical and the papillary muscles are displaced laterally and apical. This downward spiral results in impairment of atrio-ventricular valve function, increasing ventricular dysfunction, and progressive worsening of heart failure. Although medical therapies have helped to improve patient function and may even slow the remodeling, it does not halt or even reverse the progression. A number of therapies aimed at components of heart failure have been described (Table 1). 1,2,3
Transplantation is the only definitive therapy. Long term outcome after transplantation has improved significantly as a result of newer surgical techniques, organ preservation, anti-rejection therapies, and reduction in accelerated concentric coronary hypertrophy. However the combination of increased demand and reduced supply has driven the search for alternative treatments of heart failure. Mechanical assist devices have not yet provided a reliable long-term solution. Gene therapy, stem cell therapy, and tissue regeneration, although intriguing, are still in its infancy. Therefore, efforts are aimed at improving coronary artery perfusion, preventing, attenuating, or even reversing the remodeling process. Other options such as maintaining sinus rhythm, biventricular pacing, and AICDs are, for the most part, directed at treating the components and complications of heart failure, but are not necessarily directed at retarding its progression. A number of invasive and 'less' invasive surgical techniques have been described. Several investigations have demonstrated that ventricular resection and restoration with or without mitral repair reduces heart failure and improves patient function.4,5,6 Maxey et al retrospectively evaluated the benefits of performing coronary artery bypass grafting (CABG; n= 39) alone vs. CABG with ventricular resection and restoration (VR; n = 56) for patients with ischemic dilated (> 6 cm between tips of the papillary muscles) cardiomyopathy using standard forms of CABG and ventricular resection. Thirty-six patients underwent MVRepair (22 CABG, 14 in CAB/VR). For patients undergoing ventricular resection, the previously determined area of akinesis was resected, and the internal dimension of the ventricles was reduced to < 5 cm between the tips of the papillary muscles. A synthetic or pericardial patch was used to secure the closure of the ventricular defect. This patch not only aided in closure but was also sutured to change the shape of the ventricle from a spherical one to a more elliptical one. Both groups showed improvement in LVEF however the degree of LV functional improvement was greater in the CABG/VR group (33.4% from 22.1% vs. 29.0% from 25.8%). Twelve-month freedom from heart failure was greater in the CABG/VR (96.5%) vs. CABG (82%). There were no operative mortalities and both groups had similar long-term mortality. The authors concluded that patients with dilated ischemic cardiomyopathy may benefit from CABG and ventricular resection or remodeling. By reducing the ventricular volumes the authors postulate that they were able to reduce ventricular wall tension and improve oxygen supply-demand ratio. Other experiments have addressed the treatment of functional mitral regurgitation associated with ventricular remodeling and mitral leaflet tethering.5,6 Mitral repair in this patient population typically consists of performing a mitral annuloplasty alone. Although initial results were good, long term results consisted of recurrence of mitral regurgitation. Newer directions are aimed at the effects of remodeling and attempt to reduce leaflet tethering. This can be achieved by cutting the secondary chordae while leaving the basal chordae intact.5,6 This will reduce or eliminated leaflet tethering, improve leaflet mobility, and leaflet coaptation during ventricular systole. Although these techniques of ventricular restoration and valve repair improved function, they require cardiopulmonary bypass and open-heart surgery. Several relatively less invasive surgical techniques aimed directly at reducing mitral regurgitation, halting and even reversing remodeling of the ventricle have been recently described. These techniques include passive ventricular constraints, epicardial compression, and external mitral valve annuloplasty. In an attempt to halt the progression of ventricular remodeling a number of investigators have trialed a passive restraining device which is placed around the heart.7,8,9 The Acorn CorCap Cardiac Support Device (CSD; Acorn Cardiovascular Inc St Paul, Minn) is a high-strength mesh-like fatigue resistant fabric. When placed around the heart it provides both circumferential and longitudinal support for the ventricles. Circumferential support is greater than that from the base to the apex, thereby reshaping the failing spherical heart toward a more ellipsoidal one. The device is placed via a median sternotomy and placed around both ventricles and sutured above or below the atrio-ventricular groove. In addition to re-shaping the ventricle, the ACORN device may reduce the ventricular size by 10%. Although the CSD may be placed without cardiopulmonary bypass (CPB), CPB may be necessary for the less stable patient or for the patient who is scheduled to undergo additional surgical procedures (CABG, MVR, PLV etc etc). This device has been studied in animal models of pacing and ischemic dilated cardiomyopathy (8,9). One to two months after placement reductions in ventricular volumes, ventricular end diastolic pressure, and mitral regurgitation were noted, while left ventricular ejection fraction increased. Oz et al placed the CSD in 130 human with ischemia and idiopathic dilated cardiomyopathy.7 The following were the initial criteria used:
Initial exclusion criteria included:
Outcome was assessed using quality of life assessments, echocardiography, cardiac catheterization, ventriculography, and Doppler assessment of coronary flow reserve. The operative morality was 6% (8/130), and one-year mortality was 7% (9/122). Of these 1 of 8, and 4 of 9 were patients who underwent CSD placement alone. There were no complications as a result of the CSD placement. One-year data was available for only 25 patients. The placement of the CSD resulted in lower LVEDD (72.8 vs. 64.1 mm), LVESD (62.8 vs. 54.7 mm), and mitral regurgitation (1.6+ vs 0.5+). Left ventricular ejection fraction increased from 23.6% to 29.9%. Pressure-volume analysis did not demonstrate any evidence of restriction to filling. Coronary flow reserve was improved after the placement of the CSD. The initial experience helped form a list of high risk variables (below). If placement of the CSD were not permitted for patient with 4 or more of the following then 7 of the 8 early deaths would have been excluded.
The authors concluded that the CSD "halted ventricular dilation" and may "promote reverse remodeling". The CSD reduced ventricular wall stress, improved hemodynamics and may improve coronary flow reserve. Long term effects on cardiac function and patient outcome (> 1 year) have yet to be determined for a larger group of patients. Left ventricular remodeling results in posterior and lateral displacement of the papillary muscles causing apical and lateral tethering of the mitral leaflets and apical displacement of the coaptation point. Leaflet tethering restricts their return toward the mitral annulus during ventricular systole thereby impairing coaptation. Previous data demonstrate an early, but often transient benefit from mitral ring annuloplasty. Although early results may have been favorable, annuloplasty alone does not address the tethering of the leaflets associated with ventricular remodeling, which may still continue resulting in recurrence of mitral regurgitation. In other experiments investigators sought to reverse ventricular remodeling and improve mitral regurgitation by placing an external cardiac compression device. In two studies a 'Patch' was placed along the posterior lateral left ventricular wall.10,11 Advantages of these devices include; 1) attention to both valvular and subvalvular components of the mitral apparatus, 2) can be performed without CPB, 3) relatively simple repair, 4) adjustable on-line, 5) provides a stable repair s without impeding annular dynamics. These devices result in a 'septal-lateral cinching' of the mitral annulus. The authors hypothesize that repositioning of the papillary muscles using an external epicardial patch can reduce functional ischemic mitral regurgitation (IMR) by reverse remodeling, while repositioning the papillary muscles anterior, which reduces tethering of the mitral leaflets, mitral regurgitation, and ventricular volumes.10,11 In one study, papillary muscles were repositioned by placing a 'Patch-balloon' device along the infracted area, which was identified by discoloration and/or bulging of the myocardium. The Dacron patch was sewn over an inflatable balloon, which was in turn sewn over the infracted area. Inflation of the balloon caused anterior displacement of the myocardium and the papillary muscle. Incremental balloon inflation was guided by echocardiography until IMR was reduced and the mitral leaflets were seated normally during ventricular systole. Hung et al studied the benefit of the 'Patch-Balloon' in 6 sheep with chronic IMR and 4 sheep with acute IMR.10 After iatrogenic infarct, all animals had increases in ventricular volumes, reduction in left ventricular ejection fraction (LVEF), and mitral leaflet tethering due to displacement of the posterior medial papillary muscle (an increase in the posterior medial papillary muscle to mitral annular distance). Placement of the patch alone reduced IMR in three patients. In the remaining seven, inflation of the balloon was required to reduce IMR (mean 11 ml). With patch placement and balloon inflation the papillarymuscle was shifted anteriorly and the bend (tethering) of the anterior leaflet was reduced, resulting in improved coaptation. Patch-balloon therapy resulted in reductions in ventricular volumes, reduction or eliminating mitral regurgitation, without significantly changing LVEF. By applying the patch-balloon to the infarcted wall, the posterior medial papillary muscle was shifted anteriorly reducing tethering of the mitral leaflets. This improved coaptation of the mitral leaflets and reduced IMR significantly. The technique can be adjusted real-time with echocardiography without the need for cardiopulmonary bypass. There may have been an increase in ventricular stiffness as suggested by pressure-volume loops, however, since ventricular volumes were reduced, there were no significant increases in LVEDP. It remains to be determined what the long term effects are, especially with respect to ventricular diastolic function, which may be initially impaired. Another epicardial patch device was trialed in an animal model of pacing induced dilated cardiomyopathy.11 In this study the authors present preliminary data on the Coapsys device (Myocor Inc, Maple Grove Minn), which is designed to halt or reverse regional ventricular dilation, restore septal-lateral annular geometry and improve papillary muscle position, thereby reducing mitral regurgitation. The device consists of two Epicardial pads and an expanded polytetrafluoroethylene (ePTFE)-coated braided polyethylene subvalvular chord. The two pads are placed on the surface of the heart (Anterior and posterior) and attached via a trans-ventricular chord. The posterior pad has two heads which includes one placed at or about the level of the posterior mitral annulus and the second at or about the level of the papillary muscle tip. The anterior pad offers an anchor from which the posterior pad is pulled more anteriorly thereby partially or completely correcting the position of the posterior papillary muscle and reducing the annular diameter. The anterior pad was placed at the base of the RVOT 2 cm to the right of the LAD. The posterior pad was placed 2.5 cm from the AV groove midway between the papillary muscle and the annulus. Heart failure was induced by rapid ventricular pacing in 10 mongrel dogs. Placement of the Coapsys system resulted in significant reduction in mitral regurgitation (2.9+ to 0.6+) with 9/10 dogs having 1+ or less MR. The tenth dog had a significant reduction in MR. End diastolic and systolic left ventricular volumes were reduced approximately 30% while the LVEF was increased from 21.5% to 31.4%. There were no significant changes in central pressures, heart rate, or cardiac output. The authors concluded that the Coapsys device reduced MR in all animals and was easily placed off pump and adjusted on-line using echocardiography. Important comments include the lack of long term data regarding the effects of the device on both MR and ventricular function. There is no mention of the changes that occur in mitral annular area. Finally, there is some concern when reporting an increase in LVEF, a reduction in ventricular volumes but no change in LVEP. This would lead one to wonder what the effects on diastolic dysfunction that may be present with the placement of this device. Furthermore, there is no mention of the changes in right heart function except to say that the CVP did not change significantly. Placement of an epicardial patch immediately after a posterior lateral infarction may reduce subsequent ventricular remodeling and IMR by restraining the 'acute infarct expansion', preserving post-infarction ventricular geometry. This would reduce displacement of the papillary muscles and resultant IMR. Moainie et al induced a posterior-lateral infarction in twelve sheep by snaring the left circumflex artery.12 In six of the sheep a restricting Marlex mesh over the location of the posterior infarction. Data were collected at baseline, and at 30 minutes, 2, 5, and 8 weeks after infarction. Central venous pressures were significantly greater in the mesh treated animals. Otherwise, all hemodynamic data were similar. Ventricular volumes were significantly lower in mesh treated animals. Although calculated ejection fractions were similar between the two groups, there was significantly lower grades of mitral regurgitation in the mesh treated animals. Sonomicrometric data revealed expansion of both the infarct area and the peri-infarct areas in non-mesh treated animals, confirming the effect of ventricular strain on both infracted and non-infarcted tissue. The authors concluded that restraining infarct related expansion prevented remodeling and subsequent mitral regurgitation. The data also shows that the increase in myocardial strain after infarction affects both infarcted and non-infarcted tissue emphasizing the importance of assuring adequate coronary blood flow to areas surrounding an infarct. Higher central venous pressures in the mesh treated group may suggest some component of diastolic dysfunction as a result of the mesh. This would need to be further assessed. Since the cause of mitral regurgitation (relatively normal appearing leaflets) is multifactorial, it would seem reasonable that its treatment would involve manipulation of several features of the valve and subvalvular components. Ventricular remodeling and dilation results in displacement of the papillary muscles as well as dilation of the mitral annulus. The mitral annulus is a dynamic and important component of the mitral apparatus. It's shape and size change dramatically from systole to diastole. Mitral annular dilation may occur in association, and perhaps secondary to, left ventricular dilation. Although annular dilation, alone, may not result in significant mitral regurgitation, it is a significant contributor to the development of regurgitation. Kollar et al, report a technique in which the mitral annuloplasty was performed without cardiopulmonary bypass using external plication.13 After induction of anesthesia and median sternotomy the hearts of 12 canines were elevated to visualize the free wall of the left ventricle. A durable row of Prolene pledgeted suture was inserted subepicardial from the posterior descending artery to the left anterior descending artery, in parallel with the atrioventricular groove. The running suture encircled the LV free wall. Plication can then be performed and adjusted to achieve a desired reduction in annular size. Tightening of the suture was based on visual inspection of the myocardium for ischemia, which, based on experience, occurs within 1-2 minutes of 'overzealous' tightening. There was no evidence of hemodynamic instability. There was no injury to the coronary vessels. There was evidence in of nonocclusive compression of one vessel, which was not due to the suture, but instead a rubber tourniquet used to tighten and loosen the suture for the subsequent analysis. Assessment of the mitral annular dimensions showed a 17% and 31% reduction in mitral annular circumference and area respectively. Although the authors showed that the mitral annulus can be reduced in size and area, this experiment did not involve heart failure models with mitral regurgitation and therefore does not demonstrate the impact that this technique has on functional mitral regurgitation. The study also did not describe the impact of external annuloplasty on mitral leaflet function. Nevertheless, this technique is a potential 'off-pump' technique for mitral annuloplasty which may be a necessary component of the treatment of functional mitral regurgitation. Discussion and comment:New surgical techniques offer promising therapy for dilated cardiomyopathy and associated mitral regurgitation with or without the need for cardiopulmonary bypass. Furthermore, if performed without cardiopulmonary bypass (i.e. full beating heart) adjustments can be made while assessing the results in real time with transesophageal echocardiography. Such beating heart techniques may also allow assessment of repairs while manipulating different loading conditions. Currently there are few long-term results (> 1year) demonstrating persistent benefit and a lack of a negative effect on diastolic function. However, these experiments demonstrate potential therapies to attenuate, halt, or even reverse ventricular remodeling for both ischemia and idiopathic dilated cardiomyopathy. A continued benefit (> 1year) would offer either a bridge to more definitive therapy, or may be definitive enough to address the morbidity and mortality of heart failure. References:
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