Introduction

Multivessel coronary artery disease in non-ST elevation acute coronary syndrome (NSTE-ACS) occurs in more than 50% of patients [1, 2]. Indications for surgical or endovascular revascularization are often not established in some patients with NSTE-ACS due to high risk of intraoperative complications [3]. As a rule, these patients undergo therapy. Cardiac surgeons refuse coronary bypass surgery due to high perioperative risk (Euroscore II), and endovascular surgeons refrain from percutaneous coronary intervention (PCI) due to high SYNTAX score (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery).

SYNTAX score facilitates optimal treatment selection by identifying patients with high risk of adverse events after PCI. This index also reflects prohibitive risk of unfavorable outcomes following difficult PCI. Therapeutic treatment of patients with NSTE-ACS and multivessel coronary artery disease who are denied revascularization is accompanied by high in-hospital mortality (about 28%) and poor quality of life [4].

Preliminary data on high-risk PCI under support of extracorporeal circulation in patients with NSTE-ACS and multivessel coronary artery disease who were denied conventional revascularization show encouraging clinical results. Case fatality rate/mortality rate within 12 months is 5.5–6.2% / 8.7–11% [5].

Modern extracorporeal support systems are quite diverse (intra-aortic balloon counterpulsation (IABP), Impella (2.5; 3.5; 5.0), TandemHeart, iVAC 2L). However, only parallel cardiopulmonary bypass maintains blood circulation and oxygenation [6, 7].

In our work, extracorporeal support was ensured by heart-lung machine. There are two options for its intraoperative application. The first option is complete artificial circulation characterized by complete replacement of cardiac output. The second option is partial replacement with effective intrinsic cardiac output (parallel CPB). In this case, perfusion rate is adjusted considering hemodynamic and metabolic needs. In this work, we used parallel CPB.

A 84-year-old patient B. (resident of St. Petersburg) was hospitalized with angina pectoris and shortness of breath when walking on a flat surface within 20–30 m. Symptoms disappeared at rest after 3–5 minutes. There was also feeling of lack air in horizontal position with relief in sitting position. After examination, we established the following diagnosis: coronary artery disease, NSTE-ACS, post-infarction cardiac sclerosis (previous myocardial infarction with recurrent infarction in December 2018); stage III hypertension with high risk of cardiovascular complication; severe degenerative aortic stenosis, moderate mitral insufficiency, mild aortic insufficiency; cerebrovascular disease, previous stroke, hypoxic-ischemic encephalopathy stage II; atherosclerosis of the aorta and cerebral arteries, lower limb arteries; previous angioplasty and stenting of the right coronary artery in December 2018. Complications: moderate pulmonary hypertension; chronic heart failure stage Iib class IV. Concomitant diseases: chronic pyelonephritis without exacerbation, gastroesophageal reflux disease, chronic gastritis, impaired glucose tolerance; previous surgery for basal cell carcinoma of the forehead skin (June 29, 2018); mild anemia; diffuse nodular toxic goiter, euthyroidism.

Echocardiography data: impaired contractility of the left ventricle (ejection fraction 28%), severe aortic stenosis (blood flow velocity 4.2 m/s, maximum pressure gradient 80 mm Hg, mean pressure gradient 44 mm Hg, orifice area 0.7 cm²), pulmonary artery pressure 46 mm Hg.

Coronary angiography revealed stenosis of the left main coronary artery 80%, proximal subocclusion of the left anterior descending artery with diffuse lesions of its walls, subocclusion of diagonal artery, middle third of circumflex artery, proximal stenosis 60% of obtuse marginal artery (Fig. 1).

Fig. 1. Coronarography. Stenosis of the left main coronary artery 80%, subocclusion and diffuse lesions of the proximal third of the left anterior descending artery, subocclusion of the first diagonal artery, subocclusion of the middle third of circumflex artery, proximal stenosis 60% of the obtuse marginal artery.

Determining treatment strategy, we considered age (84 years), coronary lesion (severe multivessel coronary artery disease with involvement of the left main coronary artery), concomitant diseases and complications (previous myocardial infarction within 90 days before the present surgery, post-infarction cardiac sclerosis), RCA stenting in December 2018, severe aortic stenosis (blood flow velocity 4.2 m/s, maximum pressure gradient 80 mm Hg, mean pressure gradient 44 mm Hg, orifice area 0.7 cm2) with reduced ejection fraction (28%), moderate mitral insufficiency, mild aortic insufficiency, previous stroke in August 2018, moderate pulmonary hypertension, chronic heart failure class IV, impaired glucose tolerance, mild anemia, decreased glomerular filtration rate (50 ml/min/1.73 m2). Both endovascular intervention (SYNTAX score 33, PTCA score 16) and open cardiac surgery were rejected due to high risk of unfavorable outcomes (Euroscore II 40.76%).

Considering high mortality following drug therapy and vital indications for myocardial revascularization, we scheduled stenting of the left main coronary artery, LAD, circumflex artery, balloon valvuloplasty of the aortic valve under general anesthesia and parallel CPB. ASA grade 4 was determined by severe systemic disease, permanent threat to life and high risk of sudden cardiac death.

We established perioperative management considering objective status, underlying and concomitant diseases, diagnostic data and some other features. First, influence of preload on stroke volume is limited by severe atherosclerosis, and overload could lead to dilatation of the left chambers, left atrium, left ventricle and mitral annulus, as well as aggravation of mitral regurgitation. With this in mind, we planned to replenish intravascular volume in accordance with the target hemodynamic parameters and clinical response to volemic load. The second feature is the need to maintain heart rate within a narrow range (60–80 beats/min), since high rate is accompanied by decrease in coronary perfusion, and low rate is associated with limitation of cardiac output in a patient with a fixed stroke volume. It was important to maintain sinus rhythm for ensuring sufficient systolic ejection time through the stenotic aortic valve.

When choosing the method of anesthesia, we considered the following circumstances. Cardiac output cannot be increased in response to decrease in heart rate in patients with severe aortic stenosis. These ones require alpha-adrenergic receptor agonists to prevent blood pressure decrease and potential sudden death. This is because LV afterload is primarily determined by aortic stenosis, so this component remains constant. Blood pressure decrease is followed by only mild decrease in LV afterload. Thus, arterial hypotension can quickly develop in response to injection of most anesthetics. In this case, hypertrophied myocardium is at high risk of ischemia, since coronary blood flow depends on systemic diastolic pressure. Moreover, most patients with severe mitral regurgitation develop pulmonary hypertension due to increased left atrial pressure and pulmonary resistance. Hypercapnia and nitrous oxide sedation should be avoided in patients with elevated pulmonary vascular resistance due to the risk of reactive pulmonary vasoconstriction. Therefore, we used total intravenous anesthesia. Anesthetic strategy had certain features (Fig. 2).

Fig. 2 Anesthetic card.

Mild oral premedication with hydroxyzine hydrochloride 25 mg the day before provided peace of mind for the patient and prevented tachycardia. Upon admission to the operating theatre, the patient had normal heart rate and mild arterial hypotension (BP 90/60 mm Hg) without clinical signs of hypoperfusion (SHOCK stage B) [8]. However, analyzing oxygen delivery (DO₂) and consumption (VO₂), we found oxygen debt (DO₂/VO₂ ratio = 490 ml/min : 190 ml/min = 2.5 : 1.0, norm 5 : 1). The extraction index was 39% (norm 20–25%) that also indicated insufficient tissue perfusion and confirmed the need for CPB. An experienced surgeon and perfusionist were ready for emergency CPB in case of severe hemodynamic disorders.

Under aseptic conditions and local anesthesia, an introducer was inserted into the right femoral artery to measure blood pressure. Invasive BP monitoring was necessary for immediate recognition and correction of hemodynamic changes, as well as serial sampling of arterial blood gases.

Preoperative blood test: WBC = 5.06×10⁹ /L; Neu = 3.4×10⁹ /l; Hb = 112 g/l; Ht = 35.1%; RBC = 3.62×10¹² /L; PLT = 190×10⁹ /L; AST = 36 U/l; ALT = 24 U/l; creatinine = 86 µmol/l; total bilirubin = 19.5 µmol/l; potassium = 4.0 mmol/l; sodium = 138 mmol/l; glucose = 6.24 mmol/l; activated partial thromboplastin time = 33.9 s; INR = 1.06; prothrombin = 95%; prothrombin time = 11.8 s. Arterial blood gases: pH = 7.249; pCO₂ = 45.7 mm Hg; pO₂ = 53.6 mm Hg; BE = -7; HCO₃¯ = 18.5 mmol/l; SpO₂ = 82.7%.

Induction of anesthesia was followed by intubation and mechanical ventilation. We injected propofol (2 µg/ml) and fentanyl (5 µg/kg/hour) to maintain anesthesia. Deep muscle relaxation was provided by bolus intravenous pipecuronium bromide 2 mg every 40 min.

Mechanical ventilation was performed in CMV mode (Vte = 500 ml, f = 12/min, MV = 6.0 l/min, PEEP = 5 cm H₂O, Preak = 19 cm H₂O, Pplato = 12, I:E = 1:2, FiO₂ = 50%). Parameters were corrected considering arterial and venous blood gases. Hemodynamic support during anesthesia was maintained by intravenous infusion of noradrenaline (0.03–0.06 μg/kg/min). Anemia following intraoperative blood loss and hemodilution was compensated by RBC and fresh frozen plasma transfusion.

Central venous catheter was inserted through internal jugular vein under ultrasound guidance, and electrode for temporary pacing was passed to the apex of the right ventricle. Left femoral artery and vein were used to establish CPB.

Considering short-term surgery and cost feasibility, we preferred on-pump surgery. We established perfusion rate at 4.9 l/min considering growth and weight of the patient.

Priming solution for heart-lung machine included isotonic Sterofundin 500 ml, sodium chloride 0.9% 500 ml, sodium bicarbonate 3% 150 ml, Mannitol 15% 400 ml, furosemide 20 mg, heparin 5000 IU, potassium chloride 10% 10 ml. The total filling volume was 1550 ml.

Auxiliary circulation was performed under mild hypothermia (35°C) with standard hemodilution (Ht 25-28%) and perfusion rate of 36–60% of the calculated one (1.8–3.0 l/min) to maintain target systolic blood pressure 60-70 mm Hg. Mean BP during CPB was 50–80 mm Hg, central venous pressure 0-5 mm Hg, SpO₂ 95-100%. Unfractionated heparin 300 U/kg was injected before perfusion (total dose 23,000 IU). After that, we controlled ACT (target value > 400 s) to determine the need for additional dose of heparin (Table 1, 2).

Table 1. Intraoperative parameters of cardiopulmonary bypass

Table 2. Intraoperative arterial and venous blood gases

At the first surgical stage under CPB, we implanted 2 stents in the left anterior descending artery, 1 stent in circumflex artery and 1 stent in the left main coronary artery. Control angiography (TIMI III) is presented in Fig. 3.

Fig. 3. Balloon angioplasty of the left anterior descending artery with implantation of 2 stents.

Balloon angioplasty of the circumflex artery with implantation of 1 stent. Stenting of the left main coronary artery with 1 stent and post-dilatation with a balloon. TIMI III.

Balloon valvuloplasty of the aortic valve was performed under parallel perfusion and RV stimulation (180/min) (Fig. 4).

Fig. 4. Right ventricular pacing by external pacemaker (180 per a minune) with simultaneous balloon aortic valve valvuloplasty under cardiopulmonary bypass.

After stabilization of blood pressure, the patient was transferred to normothermic perfusion. Then, we gradually decreased extracorporeal support considering spontaneous cardiac output, blood pressure, heart rate and signs of hypoperfusion (diuresis, peripheral blood flow, laboratory data). Arterial blood gases early after CPB (perfusion rate 1 l/min): pH = 7.326; pCO₂ = 38 mm Hg; pO₂ = 156 mm Hg; BE = -6.3; HCO₃¯= 19.1 mmol/l; SpO₂ = 99.2%. Invasive monitoring demonstrated stable BP (100/60 mm Hg) under alpha-adrenomimetic support with norepinephrine 0.06 μg/kg/min. There were no ultrasound signs of bleeding into pericardial cavity. CPB was stopped. Heparin was neutralized with protamine sulfate 230 mg. CPB time was 185 min, fluid balance during perfusion period — 950 ml (+).

Acute decrease in pressure gradient on the aortic valve was followed by immediate reduction of LV end-diastolic pressure with simultaneous increase in stroke volume. Left atrial and pulmonary artery pressure decreased. Myocardial function improved rapidly, although hypertrophied ventricle still required preload and afterload control.

In early postoperative period, we observed arterial hypotension and the need for vasopressor support with norepinephrine. Doses decreased from 0.10 to 0.05 μg/kg/min. Elevation of troponin I with peak values after 3-4 days and no ECG abnormalities or impaired LV contractility was due to surgical intervention. Agitation, disorientation in space and time, as well as no adequate verbal contact (RASS score 3) were observed on the first day after surgery. Sedation with propofol 100 mg/h under respiratory support was continued for a day. The patient was weaned from ventilator using the RSBI protocol in 2 postoperative days after assessing the consciousness and severity of agitation (RASS score 0-1).

Blood test in ICU: WBC = 13.9×10⁹ /L; Neu = 12.9×10⁹ /L; Hb = 82 g/l; Ht = 23.1%; RBC = 2.66×10¹² /L; PLT = 122×10⁹ /L; AST = 36 U/l; ALT = 20 U/l; creatinine = 119 µmol/l; total bilirubin = 25 µmol/l; potassium = 4.1 mmol/l; sodium = 145 mmol/l; glucose = 9.0 mmol/l; troponin I = 946.8 pg/ml; APTT = 39.6 s; INR = 1.35; prothrombin = 66%; prothrombin time = 15.1 s. Arterial blood gases: pH = 7.35; pCO₂ = 33 mm Hg; pO₂ = 128 mm Hg; BE = -6.7; HCO₃¯ = 18.2 mmol/l; SpO2 = 99%; sodium = 138 mmol/l; potassium = 3.9 mmol/l; calcium = 1.07 mmol / l.

The main postoperative problems were anemia, hemodynamic instability and transient agitation with RASS score +3. Intensive care included transfusion of 3 doses of packed RBC and 1 dose of fresh frozen plasma (Hb 95 g/l and Ht 28.3% at discharge). Hemodynamic support was canceled after 4 postoperative days. We constantly assessed consciousness throughout the entire ICU-stay. There was a wave-like changes in consciousness (RASS score from 0 to +3). Measures were taken to organize circadian rhythm (sedation only at night). Visits of relatives and constant contact of patient with staff for medical and domestic issues were essential. Consciousness was normalized after 6-day intensive care. The patient was sociable, friendly, fully oriented in space and own personality, as well as ready to cooperate with the staff. Clinical state improved under therapy. After 7 postoperative days, the patient was transferred to the specialized department. Angina pectoris did not recur, and circulatory insufficiency regressed. The patient was discharged in 21 days after surgery.

LV ejection fraction increased from 28 to 48%, LV contractility increased, LV end-diastolic volume decreased from 210 to 110 ml. Mean pressure gradient on the aortic valve decreased from 44 to 23 mm Hg. Pulmonary artery pressure decreased from 46 to 29 mm Hg. Moreover, blood flow velocity through the aortic valve decreased from 4.2 to 3.3 m/s, maximum pressure gradient decreased from 80 to 47 mm Hg, mean gradient decreased from 44 to 33 mm Hg. Aortic valve orifice area increased from 0.7 to 2.3 cm².

A month later, the second stage of surgical treatment was performed (transcatheter aortic valve implantation).

Discussion

Cardiac patients with multivessel coronary artery disease, severe comorbidities and high risk of perioperative mortality have poor adaptive cardiovascular capacity. Surgery may be followed by abnormal processes with decrease in cardiac output, progressive ischemia, cardiogenic shock or malignant ventricular arrhythmia. In some cases, cardiogenic shock develops before surgery.

Mechanical circulatory support (in this case, parallel cardiopulmonary bypass) effectively replaces heart function in case of cardiac arrest or life-threatening arrhythmia. Oxygenator may be required in patients with respiratory dysfunction. The disadvantage of this method is increase in afterload that may be critical in patients with reduced LV contractility, for example, in cardiogenic shock. This disadvantage can be corrected by optimizing circulatory support with adjusting perfusion rate. More invasive technique is puncture of atrial septum for left heart decompression.

There are literature data on the positive impact of extracorporeal circulation providing cardiopulmonary support in patients with refractory cardiac arrest and cardiogenic shock.

Radsel P. et al. [9] analyzed 3 scenarios (extracorporeal support before intervention, during and after surgery when hemodynamic instability progresses). The authors concluded that emergency veno-arterial extracorporeal support provides immediate hemodynamic stabilization and saves time for PCI in patients with refractory cardiac arrest undergoing chest compressions and in patients with cardiogenic shock refractory to standard therapy. The authors report 83% success rate for PCI and describe successful on-pump transcatheter aortic valve implantation in 4 patients with low LV ejection fraction. Successful radiofrequency ablation followed by pacemaker implantation under extracorporeal support was described. Overall in-hospital survival was 44%. Takayama H. et al. [10] reported survival rate of 49% in patients with cardiogenic shock undergoing treatment under extracorporeal support. However, the authors note that 50% of survivors require heart transplantation in the future.

Vereshchagin I.E. et al. [11] compared the results of high-risk PCI in patients with acute coronary syndrome supported by extracorporeal membrane oxygenation and intra-aortic balloon counterpulsation. The study recruited 34 patients including 18 ones after PCI under extracorporeal membrane oxygenation and 16 patients after PCI under intra-aortic balloon counterpulsation. Long-term (12 months) results showed the advantage of intraoperative ECMO.

To date, there are no clear recommendations that would definitely answer the question of the need for extracorporeal support in ACS. Our clinical case demonstrates the possibility of parallel CPB in the treatment of high-risk patients with ACS scheduled for PCI.

Conclusion

This clinical observation confirms that CPB-assisted endovascular interventions may be effective in patients with severe coronary artery disease and high risk of mortality. The main features of perioperative intensive care were the need for multidirectional correction of intravascular volume at different stages of surgery and cardiopulmonary bypass in accordance with the target hemodynamic parameters and clinical response, timely correction of anemia and blood loss, correction of ventilation parameters under control of blood gases, early intraoperative use of alpha-agonists, careful monitoring of blood clotting parameters and surgical hemostasis under total heparinization during cardiopulmonary bypass and after heparin reversal, careful cardiorespiratory monitoring at all stages of intensive care.

Author contribution:

Concept and design of the study — Volchkov V.A., Zhuravlev M.M., Shakh B.N., Boyarkin A.A.

Collection and analysis of data — Zhuravlev M.M.

Writing the text — Volchkov V.A., Zhuravlev M.M., Shakh B.N., Boyarkin A.A.

Editing — Volchkov V.A., Zhuravlev M.M., Shakh B.N.

The authors declare no conflicts of interest.