UDC 616.126.42-089.5
CORRECTION OF THE VALVULAR HEART DISEASE COUPLED WITH MULTIVESSEL CORONARY ARTERIES’ DISEASE REQUIRING CORONARY ARTERY BYPASS GRAFTING 
V.V. Popov, A.V.Kupchynsky, S.N. Solomka, A.N. Hurtovenko, A.I.Khrypachenko, A.A.Bolshak, L.V.Yakob, L.I.Tykhonenko, E.V.Khoroshkovata, E.V.Pukas

SI "N.M. Amosov National Institute of Cardiovascular Surgery of NAMS" (Kyiv)

The aim of this research is to study the possibilities of correction of valvular heart disease (VHD) coupled with multivessel coronary artery disease requiring coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CB).

	The study group included 75 patients with VHD undergoing treatment at the Department for surgical treatment of acquired heart defects at N.M. Amosov National Institute of Cardiovascular Surgery of NAMS of Ukraine.

There were 45 (60.0%) men and 30 (40.0%) women with a mean age at operation of 64,5 ± 5,7 years.  All patients pertained to the functional class IV by the New York classification (NYHA). All patients were performed VHD correction through valve replacement coupled with coronary artery bypass grafting (3 or more grafts).
   	1 patient out of the 75 operated died at the hospital stage (hospital mortality of 1.4%). The cause of death was multiple organ failure. There were no cases of significant acute cardiovascular failure. Inotropic support (dobutamine) was 3-4 mkrg  min/kg during early post-operative period within first 48 hours.  On the second postoperative day, MB-CPK group enzymes level amounted to 95.8 + 10.1 U/L. Single-stage correction of VHD and coronary artery bypass grafting (3 grafts and more) allow to adequately perform the defect correction at the hospital stage.
Key words: cardiopulmonary bypass, coronary artery bypass grafting, valvular heart disease correction, replacement, pharmaco-cold cardioplegia.
VHD correction with multivessel coronary bypass grafting requires a long -duration aortic cross-clamping.
In this regard, measures are taken for  anesthetic, resuscitation and perfusion support improvement without which "open" heart surgery of this level is impossible (Bunatyan A.A. et al., 2005).
Intraoperative myocardial protection for a period of reversible iatrogenic ischemia induced by clipping of the ascending aorta is an indispensable component of the anesthetic and perfusion support for operations of such complexity (Ursulenko V.I. et al., 2013, Knyshov G.V. et al., 2007, Buckberg G.D., 1995, Popov V.V. et al., 2015).

Despite a certain progress in solving the problem of intraoperative myocardial protection, a number of issues still require further study. In a number of cases there are complications associated with the clinical ischemic damage during cardiac surgery - namely, intra-operative myocardial infarction and a low cardiac output syndrome (Masse L., Antonacci M., 2005). This is due to both inadequate myocardial protection, inadequate reperfusion, and the initial significant myocardial damage due to the underlying disease (V.V. Popov et al., 2009, Susumu I. et al., 2006). This issue is  the subject of this publication which offers its own original version of its solution.
    Objectives.  Studying of VHD  efficiency correction coupled  with multivessel coronary artery bypass grafting.
MATERIALS AND METHODS
The analyzed group included 75 patients with valvular pathology coupled with multivessel coronary artery disease who were provided treatment at the Department for surgical treatment of acquired heart defects at the N.M. Amosov National Institute of Cardiovascular Surgery of NAMS of Ukraine from January 1, 2000 to March 1, 2016. In addition to the valvular pathology correction, all patients were performed bypassing of three or more coronary arteries. There were 45 (60.0%) men and (40.0%) women with a mean age at operation of 64.7±6.3 years. All patients pertained to functional class IV by the New York classification (NYHA).
 Atherosclerosis, hypertension (61.4%), bicuspid aortic valve (28.3%), rheumatism + lipoidoz  (18.3%), degenerative age-related changes (10.3%) were the etiologic cause of defects. Due to severe CHD symptoms, all patients were performed coronary bypass surgery: 3 coronary arteries (54 patients), 4 coronary arteries (20 patients) and 5 coronary arteries (1 patient). Isolated aortic valve lesion was noted in 43 (57.4%) cases, mitral - in 21 (28.0%). Combined mitral and aortic lesion occurred in 11 (14.6%) cases. In the presence of the narrow aorta mouth and aortic valve replacement, additional reconstruction of the aortic root was performed in 5 (6.7%) patients.
Atrial fibrillation occurred in 13 (17.3%) cases. The duration of atrial fibrillation in this case was 3,2 ± 0,3 years.
All operations were performed under cardiopulmonary bypass and mild hypothermia (30-32 C). Inserting of the venous aortocoronary bypass grafts operation stage was performed  jointly with the coronary surgery department staff. Before starting  cardiopulmonary bypass, setting of the retrograde cannula was controlled with the help of the finger and to a sufficient depth in the system of the coronary sinus.

"Custodiol" supply started from the moment of the aorta clamping, after the artificial heart fibrillation. Left heart chambers were drained through the left atrium. 
Retrograde cardioplegic solution supply was controlled: 1) by the pressure indicator at the coronary sinus inlet; 2) visually by the "Custodiol" leaking from the left coronary artery mouth (a cannula was set temporarily to control the lifting column height - 3-5 seconds). After aorta clamping, retrograde "Custodiol" supply started with the administration of 2/3 of the estimated amount under a pressure of about 40 mmHg for approximately 11-13 minutes, and then the next 1/3 of the amount was being injected antegradely under a pressure of about 60 mmHg for approximately 7 minutes (24 patients). Surgical procedures for the valve disease correction  started with the beginning of retrograde supply, and they stopped with the antegrade supply. 
With only retrograde method of cardioplegia supply (51 patients) "Custodiol" was being administered retrogradely with the introduction of 1/3 of the estimated amount under a pressure of about 40 mmHg for 4 minutes, and subsequent 2/3 of the amount – under a pressure of about 20 mm mmHg in order to extend the time of the cardioplegic agent impact on the myocardial tissue, as well as eliminate the rapid hemodilution.
In addition, tape occlusion around the cannulas of the vena cava contributed to a better cooling of the right heart chambers endocardium, especially of the right ventricle, due to the partial repayment of the coronary sinus cardioplegia (approximately 15%). Also, "Custodiol" flowing from the mouths of the coronary arteries cooled endocardium of the LV, and then evacuated.  In most cases, double-lumen cannulation of the vena cava was used (53 patients). We consider this phenomenon an important element of the adequacy of the heart protection.
Myocardial protection was carried out at permanent cardioplegia with the "Custodiol" solution of 25 ml /kg of the body weight (basic administration). With the period of aortic cross-clamping of more than 120 minutes the  initial dose increased to 5 ml\kg of the body weight, and for more than 150 minutes - 10 ml\kg. 
"Custodiol" was re-administered in each of the stents in the amount of 150 ml, as each  coronary anastomosis was applied. The heart was cooled externally. With basic administering of "Custodiol" immediately after aortic clamping, the presence of multifocal coronary arteries’ stenoses (inadequate protection due to short supply of "Custodiol" through the stenosis) significantly limited the possibility of using the antegrade cardioplegic solution supply in full, so the technique was not used by 100%. It was used supplementally in the amount of not more than one third from the basic after the primary retrograde supply. Over the last year period not more than 10% of total amount was pumped antegradely, and to a greater extent, it was used to protect the sinus node.
Following the procedure of introducing a basic cardioplegic solution, patients were divided into 2 groups (Table 1).

Table 1
Indicators of anoxia and reperfusion time, CPK-MB enzyme levels in different embodiments of the basic protection of the myocardium
Type of protection	Number of the operated	)
Type of enzyme (CPK-MB) (U/L)	Reperfusion time (min)	Anoxia time (min)	
 Retro-antegrade cardioplegia	24	135,7±13,1	85,7±9,2	177,5±23,1	
Retrograde cardioplegia	51	98,7±11,5	73,1±8,9	149,3±19,8	
Total:	75				

An extensive network of capillaries - cross-flows between the left and right coronary arteries’ basins allows through "Custodiol" retrograde introduction at low pressure to reach any myocardium area (Fig. 1), which made it possible to obtain a better CPK-MB enzyme level than in the combined form supply (p <0.05). The results are shown in Table 1.

Figure 1. Network of capillary venous cross-flows between the left and right coronary arteries’ basins.
Spontaneous recovery of cardiac function after removal of the clamp from the aorta was noted in 58.3% (n = 14/24) of cases with retro-antegrade baseline cardioplegia, and in 74.5% (n = 38/51) of cases with retrograde baseline cardioplegia  (p <0.05).
Following types  of the valvular correction have been performed: aortic valve replacement (37 - 62.7%), reconstruction of the aortic root at aortic mouth hypoplasia + aortic valve replacement (5 - 8.5%), mitral valve replacement (10 - 16.9%), MVC + operation "Labyrinth" (2 - 3.4%), combined mitral and aortic valves replacement (5 - 8.5%). Surgical correction of valvular pathology was performed by: Popov V.V (69 operations), Bolshak A.A. (4 operations) Antoshchenko A.A. (2 operations). 
Coronary artery bypass grafting was performed jointly with the surgeons of the Department of chronic coronary insufficiency surgery: A.V. Kupchynsky A.V. (45 operations), Solomka S.N. (14 operations), Ursulenko V.I. (12 operations), Jacob L.V. (2 operations), Mustafa Obeid (2 operations).
Access to the mitral valve was performed through the left atrium at the back and in parallel to interatrial sulcus. Bicuspid prostheses Carbomedics, Saint Jude Medical, ATS were used for implantation in the mitral position. Prostheses were fixed by separate U-shaped sutures with gaskets in the amount of 14-19 in the intra-annular (intermediate) position. 
 Access to the aortal valve was carried out through the aorta cross-section at the level of the sino-tubular junction. Bicuspid prostheses Carbomedics, Saint Jude Medical, ATS were used for implantation in the aortal position. Prostheses were fixed by separate U-shaped sutures with gaskets in the amount of 12 – 17 in the ventricular-aortic (25) or aorto-ventricular (2) position.  
  Adequate reperfusion period is an essential element for preservation  of the myocytes after myocardial protection. Thus, immediately prior to removing the aortic clamp, the perfusionist reduces the CB device performance to 300 ml/min, after which the aortic clamp is removed. At a given performance, every 5 seconds a repeated occlusion of the ascending aorta followed by a five-minute  declamping is performed within 60 seconds. Finally, the clamp is removed from the aorta. 
Following this manipulation, HLM performance increases within 5 minutes by adding 100-150 ml/min every 10 seconds and returning to the original performance. This maneuver is extremely important because it eliminates the haemodynamic and heat stroke for the coronary channel and myocardium which is in a low-pressure  and hibernation area caused by exposure to the cardioplegic solution and hypothermia. Only after reaching the estimated performance the patient rewarming begins.
Further, in the presence of an active or passive left ventricular drainage (100-200 ml/min), through the open LA in the right pulmonary veins area (about 1cm2 opening) the heart was allowed to " develop", without increasing its preload for 5-7 minutes, practically minimizing its shock  emissions into the aorta. Patient’s rewarming was performed with a gradient between bath and  HLM not exceeding 50C, which excluded the probability of gas bubbles formation. Once the heart "started running smoothly " at a minimum preload, passive drainage was removed  from the left ventricle, preload increased and inotropic support started within diuretic doses (2-4 mg/kg/min). It was strictly observed that reperfusion time period was within 1/2 of the aortic cross-clamping time, and at cardiomegaly, reduced myocardial contractility, reperfusion time increased.
After HLM stopping, CBV was replenished with the contents from the HLM through the arterial line, minimizing blood loss.
If it was not possible to return the contents of the HLM back into the patient through an aortic cannula at once, then the perfusate was collected in the container and re-infused through the central venous catheter.
                                                      
                                  RESULTS AND THEIR DISCUSSION
Out of 75 operated patients there was 1 in-hospital death (within 30 days after surgery), (in-hospital mortality 1.4%). Multiple organ dysfunction syndrome was the cause of death. It was a male patient of 68 years old, who was taken with overstated indications with a lasting rheumatic process (over 30 years), 25 kg overweight.
 He underwent mitral and aortic valves replacement, LA plastic. The tissues were in the condition of initially prolonged hypoxia (non-compact myocardium), so failed to endure surgical aggression.
Regardless of the method of cardioplegic solution supply, on the second post-operative day enzyme levels of CPK-MB group increased in proportion according to the extension of anoxia infarction (Table 2).                                                                                         
                                                                                              Table 2
The level of CPK-MB enzymes on the second post-operative day 
Cardioplegia option	CPK-MB enzymes level (U/L)	
	Aortic cross-clamping time (minutes)	
	< 120	121 – 140	141 –160	161–205	
Retro-antegrade cardioplegia	64,4±6,5	77,4±8,8	87,4±8,1	117,4±11,8	
Retrograde cardioplegia	61,4±6,7	72,4±7,3	85,5±8,4	109,4±10,5	
Number (n)	21	49	69	   155	

  In 5 (6.7%) patients during the first day was observed clinically significant acute cardiovascular failure which required higher doses of dobutamine of 7-8 mcg/kg/min in combination with noradrenaline in a dose of 0.05-0.07 mg/kg/min. Those patients were taken with overstated indications with sharply reduced myocardial contractility, and myocardial protection technique was not a determining factor in these cases. On the second day enzyme CPK-MB level day in this group amounted to 157.3 ± 16.4 U/L which was followed by its decline. In most cases, during the first 72 hours inotropic support (dobutamine) in the early postoperative period was 3.5 mcg/kg/ min in combination with noradrenaline at a dose of 0.02-0.03 g/kg/min in all groups.
 We consider it appropriate to use small doses of noradrenaline in the intensive care unit, particularly taking into account the expressed atherosclerosis and the presence of hypertension. Adequate vascular tone reflected favorably on hemodynamics and blood delivery for coronary anastomoses. Patients stayed in the intensive care unit within 76-96 hours. 
   At this stage, patients noted a rate change (%) and respiratory disorders (exacerbation of the smoker’s bronchitis) (%). On average, the patients were discharged in 15-17 days after the operation without clinically significant complications
                                               CONCLUSION
Simultaneous correction of the valve disease combined with multifocal coronary arteries’ lesions is a complex procedure providing a good hemodynamic effect, adequate re-vascularization of the myocardium. Myocardial protection operation is an important element of the operation. Pharmaco-cold cardioplegia solution "Custodiol" provides an adequate protection for the myocardium for more than 150 minutes, and it is a highly effective tool. Retrograde cardioplegic solution "Custodiol" flow path  allows you to safely perform myocardial protection with low risk of in-hospital mortality, reducing the probability of acute heart failure development. 
    Retrograde technique is simple, safe, it allows to significantly reduce the time of aorta clamping during cardiopulmonary bypass, lengthens the exposure time of the cardioplegic agent to the myocardium, as well as directly to the ventricular endocardium. CPK-MB level was directly proportional to the time of anoxia. A higher level of spontaneous recovery of cardiac function after removal of the clamp from the aorta in the group with retrograde flow path of "Custodiol" testifies to a deeper myocardial protection.

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