Early Mechanical Circulatory Support for Cardiogenic Shock

Abstract

Reversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes cardiogenic shock is a crucial step in its early detection. Treatment of pre-cardiogenic shock is chiefly pharmacologic with intravenous administration of pressor, inotropic, and loop diuretic agents. Failure to reverse the preshock state with pharmacotherapy entails progression to cardiogenic shock and the need for prompt mechanical circulatory support with membrane oxygenation and possibly left ventricular decompression.

Cardiogenic shock (CS) is a clinical syndrome that may develop rapidly in patients with acute myocardial infarction/myocarditis or progressively in patients with advanced heart failure. The cause of CS is an acute myocardial infarction (AMI) in 30% of patients, and end-stage dilated or ischemic cardiomyopathy without AMI in 46% of patients.¹ With the underlying goal of improving communication between investigators and treatment outcomes, the society for cardiovascular angiography and intervention (SCAI) classified CS in 5 stages, as the American College of Cardiology and the American Heart Association (ACC/AHA) did for heart failure (HF).² The 5 stages are: at risk for CS (A), beginning (B), classic CS (C), deteriorating CS (D) and extremis(E). Not unexpectedly, the 5 stages of CS correlate with increasing in-hospital mortality in patients with HF and myocardial infarction.^3,4

The SCAI classification that was approved by the ACC/AHA, the society of critical care medicine (SCCM), and the society of thoracic surgeons (STS), underlines the likely benefit of prompt therapeutic interventions in CS. Critical care physicians, cardiothoracic surgeons, and interventional and advanced HF cardiologists have different viewpoints on CS and its management. However, an undeviating viewpoint is that early recognition of CS increased the likelihood of therapeutic success. The crucial step in early CS recognition is awareness of the clinical and hemodynamic deterioration that precedes CS.⁵ Proponents of the CS classification in 5 stages did emphasize the importance of the hemodynamic state that precedes the state of CS.⁶ Hypotensive patients without evidence of hypoperfusion (pre-shock) had lower in-hospital mortality than patients with hypotension and hypoperfusion (shock).⁶

The present review advocates pharmacologic management with intravenous administration of vasopressor, positive inotropic and loop diuretic agents in pre-CS, and mechanical circulatory support in CS with emphasis on prevention or early treatment of excessive left ventricular (LV) afterload.

RECOGNITION AND MANAGEMENT OF PRE-CARDIOGENIC SHOCK

Traditional symptoms, signs, and hemodynamic parameters of CS are unspecific identifiers of the pre-CS state. Patients with advanced HF may have clinical and hemodynamic profiles that emulate those of patients in pre-CS or CS. Hypertensive patients may be in pre-CS and have normal blood pressure, and patients receiving long-term beta-adrenergic receptor blockade may be in pre-CS and have a normal heart rate. Recognition of pre-CS rests on 2 pillars. A clinical deterioration over minutes to hours and evidence of a low cardiac output non-invasively by 2D Doppler echocardiography or invasively by superior vena cava (SVC) or pulmonary artery (PA) oxygen saturation <45%; with the caveat that patients do not have a mixed shock, such as CS and septic shock.

PRESSOR THERAPY

Norepinephrine (NE) is the preferred vasopressor in hypotensive patients in CS Other vasopressors include vasopressin, dopamine, and epinephrine. Norepinephrine increases systemic vascular resistance through stimulation of alpha-adrenergic receptors and improves cardiac output through beta-1 adrenergic receptors activation. Vasopressin is used in association with milrinone, in post-cardiac surgery patients with pulmonary hypertension and right ventricular (RV) failure.^7,8 Dopamine has a dose-dependent alpha-adrenergic receptor activation. Tachyarrhythmias limit its up-titration in CS patients.⁹ Compared to other vasopressor agents, epinephrine increases 90-day mortality in patients in CS.¹⁰ Compared to NE, epinephrine increases the incidence of refractory shock and lactic acidosis in CS.¹¹

LOOP DIURETIC THERAPY

Hypertrophy and hyperplasia of the epithelial cells of the distal convoluted tubule increase sodium reabsorption, and thereby reduce the effectiveness of loop diuretics in patients with advanced HF.¹² Increased concentrations of organic anions in patients with CS and acute kidney injury or chronic kidney disease also decrease the effectiveness of loop diuretic therapy as organic anions and loop diuretics compete for binding with Na⁺/K⁺/Cl⁺ co-transporters in the ascending loop of Henle. A standard recommendation is to start loop diuretic therapy at a dose equal to 2.5x the outpatient dose, either as an intravenous bolus or as a continuous intravenous infusion.¹³ Subsequent doses depend on the response to the initial dose. Inadequate response to the first dose warrants doubling the subsequent doses due to the logarithmic dose-response relationship of loop diuretics.¹⁴ Identifying diuretic resistance is helpful, as a combination strategy can be implemented to improve diuretic response, for example using loop diuretics with a thiazide like diuretic.¹⁵ Intravenous loop diuretic therapy is challenging in patients with RV failure due to AMI where excessive RV loading or unloading may contribute to shock.¹⁶

POSITIVE INOTROPIC THERAPY

The choice of positive inotropic agents is between milrinone and dobutamine. In-hospital mortality was 40% and similar in 192 patients with CS who were randomized 1:1 to phosphodiesterase 3 inhibition with milrinone and beta-adrenergic stimulation with dobutamine.¹⁷ Most patients (80%) were in full fledge CS and thus likely to be hypotensive and required pressor therapy.¹⁷ To minimize the need for pressor therapy, we prefer dobutamine over milrinone which has a stronger vasodilatory action. Further, the vasodilatory action of milrinone is unwanted and possibly harmful in patients with a mixed septic-cardiogenic shock that encompass 79.3 % of patients hospitalized for sepsis or septic shock in the Mayo Clinic cardiac intensive care unit.¹⁸ Due to its ease of titration and the above considerations, we generally choose dobutamine as a positive inotropic agent in pre-CS, except in patients with severe pulmonary hypertension or receiving beta-adrenergic receptor blockade. These patients are prime candidates for positive inotropic therapy with milrinone. To lessen the risk of tachyphylaxis and increased myocardial oxygen consumption we rarely increase the rate of dobutamine infusion over 5 mcg/kg/min.¹⁹ In brief, dobutamine is an effective and easy-to-titrate positive inotropic agent for the treatment of pre-CS.

The failure of pressor, inotropic, and loop diuretic therapy to promote diuresis and increase SVC or PA oxygen saturation likely entails progression from pre-CS to CS, and the need for further therapy including mechanical circulatory support or candidacy for a left ventricular assist device (LVAD) in patients with advanced HF and no or moderate RV failure.

MANAGEMENT OF CARDIOGENIC SHOCK

Mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is technically challenging and labor intensive²⁰.²¹ Patients with a terminal illness (< 2 years life expectancy), multiorgan failure, aortic insufficiency, coagulopathy, and central nervous system bleeding are ineligible for VA-ECMO. Classic indications for VA-ECMO are refractory CS or stages D and E of CS.² However, as CS progresses patients may develop a systemic inflammatory response syndrome (SIRS) including vasodilatation and unresponsiveness to catecholamines that contribute to end-organ dysfunction and thereby poor prognosis.¹⁶ Thus, we recommend considering VA-ECMO early in CS before the occurrence of end-organ dysfunction/failure that restoration of a normal cardiac output and membrane oxygenation may not reverse.

The most important consideration before implementing VA-ECMO is to entertain an exit strategy. Patients with acute myocarditis, iatrogenic shock, myocardial infarction, postcardiotomy, or coronary bypass surgery may regain sustainable LV function after the acute event/procedure. In contrast, patients with advanced HF who are not candidates for LVAD or cardiac transplantation are unlikely to benefit from VA-ECMO except when reversible comorbidity precipitates CS.

VA-ECMO AND LEFT VENTRICULAR UNLOADING

Due to retrograde blood flow toward the aortic valves, LV afterload commonly increases in patients on VA-ECMO.²¹ Thus, the cardiac output increase in VA-ECMO is associated with a rise in LV afterload. Limited aortic valve opening due to LV contractile dysfunction, increased afterload and residual bronchial and thebesian vein return to the left side contribute to LV distention and elevated filling pressure. Mitral regurgitation worsens the transmission of elevated left atrial pressures to the pulmonary circulation. Worsening pulmonary congestion, alveolar hemorrhage, and acute lung injury perpetuates a vicious cycle of systemic inflammatory response.^22–28 Left ventricular unloading aims at lowering LV end-diastolic pressure, mitral regurgitation, and preventing acute lung injury. Absence of aortic valve opening, moderate to severe mitral regurgitation, moderate to severe aortic regurgitation, LV spontaneous echo contrast, and increase in LV dimensions on echocardiogram suggest increased LV afterload during VA-ECMO support. Lack of pulsatility or narrow pulse pressure on the arterial line uncovers severe myocardial dysfunction and possible acute lung injury due to LV distention. Hemodynamic monitoring reliably detects early rise in LV filling pressure and the need for LV mechanical unloading. Continuous hemodynamic and echocardiographic assessment guides recovery and de-escalation of LV unloading.

The optimal timing, modality, and duration of LV unloading are under investigation in patients receiving VA-ECMO for CS. Data regarding the timing of LV unloading are scarce in VA-ECMO. Preliminary data indicate that LV unloading may have mortality benefits when carried out within the first 2–12 hours of VA-ECMO.^29–31 Figure 1 illustrates LV pressure-volume loops with different support modalities and the effect of Impella on LV unloading.

FIGURE 1.

Left ventricular pressure-volume (PV) loops in normal subjects, patients in CS, CS + VA-ECMO, and CS + VA-ECMO and Impella. Compared to normal subjects, cardiogenic shock (CS) patients have lower stroke volume (width of the PV loop) and contractility, and greater LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes (Shift of PV loop to the right) and LV end-diastolic pressure (LVEDP). The downward shift of the end-systolic elastance (Ees) slope (dashed straight red line) denotes low myocardial contractility in CS. The upward shift of the curvilinear pressure tracing denotes increased LVEDP compared to normal subjects. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) increases LV afterload, thereby further increasing LV volumes and reducing stroke volume in patients with CS. By unloading the LV, Impella reduces LV distension in CS patients on VA-ECMO.

LV UNLOADING MODALITIES

In the absence of head-to-head comparisons, the choice of an LV unloading modality depends on the patient’s clinical characteristics/course and exit strategy.³² Current LV unloading modalities are listed in table 1.

TABLE 1.

Invasive Strategies to Unload the LV in Patients on VA-ECMO

	Access/Effect	Advantage	Disadvantage
IABP	IABP placed via femoral artery access into the descending aorta Attenuates LV afterload in systole and enhances LV unloading	Bedside insertion Lower complication rates Reduces LV afterload Improves coronary perfusion	Requires regular rhythm Risk of vascular injury Partial unloading
Impella	Impella placed via femoral artery or axillary artery access into the LV Continuous LV unloading during systole and diastole	Direct LV unloading improves myocardial workload and reduces oxygen demand Reduces wedge pressure and RV afterload Axillary Impella helps with patient mobility	Risk of: Hemolysis Bleeding Thrombosis
Tandem heart	Drainage cannula placed in left atrium via femoral vein access and interatrial septal puncture Outflow cannula placed via femoral artery access, and returns blood to descending → ascending aorta	Improves native cardiac output up to 4-5L Does not require stable heart rhythm for insertion	Requires expertise in interatrial septal puncture Vascular injury Device migration Thromboembolism
LA-VA ECMO	Drainage cannula placed in right and left atria via femoral vein access Outflow cannula placed via femoral artery access, and returns blood to descending → ascending aorta	Indirect LV unloading and simultaneous venous drainage	Requires expertise in interatrial septal puncture Vascular injury Device migration Thromboembolism
Interatrial septostomy	Performed via femoral vein access under fluoroscopic and echocardiographic guidance using needle septal puncture and balloon dilation LA vents into the right atrium	Indirect LV unloading by reducing left atrial pressure	Requires expertise in interatrial septal puncture Thromboembolism
Surgical venting of LV	LV vent placed during surgical implantation of central VA-ECMO via trans-mitral or trans-apical approach	Direct LV unloading	Surgical approach which requires sternotomy or mini-thoracotomy
Percutaneous venting of LV	Trans-aortic venting catheter introduced percutaneously under echocardiographic guidance	Direct LV unloading	Insertion technique complications

IABP, intra-aortic balloon pump, LA, left atrium; LV, left ventricle; RV, right ventricle; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

CONCLUSION

Mortality remains elevated in CS. Whether mechanical circulatory support with extracorporeal oxygenation and LV unloading will reduce mortality in CS, has yet to be demonstrated in a randomized controlled trial. Early implementation of mechanical circulatory support with extracorporeal oxygenation and possibly LV unloading is likely to be the crucial factor in CS reversal.