A comprehensive understanding of the pathophysiologic characteristics and events of cardiogenic shock must be attained to impact the discouraging outcome of patients with this entity. The assiduous hemodynamic decline involves several interactive processes.
Early (initial 60 min) in the course of infarction autonomic disturbances have a predominant influence on a patient's hemodynamic status. As reported by Webb et al. (8) sympathetic overactivity (tachycardia and hypertension) occurred in 36% of patients (monitored within 30-60 min of infarction onset). However, the majority (55%) exhibited bradyarrhythmias and/or hypotension. This is a manifestation of the Bezold-Jarish reflex (20), which is expressed commonly during acute inferior-posterior infarction
(77%). Webb and colleagues also noted vagal effects in 32% of anterior infarctions. The likely mechanism of this response involves a mechanical stimulus of vagal afferents probably from systolic bulging of ischemic myocardium which results in vasodilation and bradycardia with additional inhibition of the arterial baroreflex (8,20,21).
An intravascular volume deficit has been recognized in up to 20% of patients with cardiogenic shock (22). This would be characterized as a Killip or hemodynamic class III state. Relative hypovolemia is most commonly encountered in the setting of right ventricular infarction. It has been shown that left ventricular performance is optimal during infarction with a pulmonary capillary wedge pressure of 14-18 mmHg (23). Although vol infusion can restore class I status to some patients initially categorized in class III, the majority do not appreciably improve reflecting evidence of primary cardiac compromise (24). In the SHOCK trial registry, 31% of patients presenting with shock did not exhibit signs of pulmonary congestion by radiographic or physical examination. Notably, the 28% of patients with clinical hypoperfusion without pulmonary congestion had a mean pulmonary capillary wedge pressure of 21.5 ± 6.7 mmHg vs 24.3 ± 8.1 mmHg in patients with hypoperfusion and pulmonary congestion. The hospital mortality in each of these groups was high at 70 and 60%, respectively (25).
The early development of cardiogenic shock in the course of infarction most commonly results from the loss of a large amount of myocardium. Autopsy studies have demonstrated that shock typically occurs after damage to >35-40% of left ventricular muscle (26-28). This may result from occlusion at a perilous site within a single coronary artery supplying a large region of myocardium or from cumulative damage after previous infarction. The elimination of the collateral function of an infarct-related artery could significantly enhance the destructive effect of a single vessel occlusion.
Later in the course, extension of infarct damage may occur as a result of multiple mechanisms. Infarct extension or reinfarction identified by enzyme elevation was reported in 23.3% of patients developing cardiogenic shock by the MILIS study group, compared with 7.4% of patients without shock (p < 0.001) (11). In the GUSTO-I trial, reinfarction occurred in 11% of patients with shock compared to 3% without shock (p < 0.001) (3). Reinfarction most commonly results from reocclusion, and this event has been shown to increase the risk of shock (29). Thrombus propagation or embolization might also result in reinfarction. Passive collapse and vasoconstriction at a second site within the coronary circulation can also result in ischemia or a second acute infarction (30). In the SHOCK registry, recurrent ischemia was more common in those with shock of late onset (>24 h) (38 vs 13.2%,p < 0.001) (17). Reinfarction was seen equally in early and late shock (8.2 and 8.3%).
Extension of infarction into the border zone in a subepicardial or lateral direction has been documented pathologically in the majority of patients with cardiogenic shock in some series (26,27). Factors which could adversely extend infarction into the border zone include impaired collateral flow, increased myocardial oxygen consumption by sympathetic activation or inotropic agents, changes in the balance of arterial driving pressure (aortic pressure—left ventricular diastolic pressure) from hypotension or congestive failure, and the possibility of reperfusion injury.
The phenomenon of reperfusion injury remains controversial (31-33). Investigation in experimental models has demonstrated pathologic evidence for progression to irreversible injury of viable myocardium in reperfused infarct zones and reduction of infarct size with agents that modify reperfusion injury. However, data are lacking to corroborate the importance of this phenomenon in a clinical situation. In fact, the GUSTO-I trial demonstration that rapid achievement of thrombolysis in myocardial infarction (TIMI) grade 3 flow by thrombolysis results in the lowest mortality would suggest that reperfusion injury is unlikely to have an important effect on outcome (34).
The pathologic picture of cardiogenic shock is characterized by progressive myocar-dial necrosis with an irregular extension of infarction not only into the border zone, but with focal regions of necrosis throughout both the left and right ventricles (26,27). This latter form of extension is a reflection of the hemodynamic state as it can be seen with other etiologies of circulatory shock.
Hypotension leads to ongoing myocardial injury. This progressive myocardial necrosis is confirmed by observation of a persistent elevation of creatine kinase isoenzyme-cardiac muscle subunit (CK-MB) (35). Left ventricular function is further impaired by the inefficiency of infarct zone expansion leading to increased wall stress (36). This progressive cardiac dysfunction leads to a "vicious cycle" of hypotension, declining coronary perfusion, and deteriorating left ventricular function culminating in an irreversible shock state. This shock state is potentiated by maladaptive compensatory mechanisms including sympathetic stimulation, fluid retention, and vasoconstriction. Lactic acidosis further impairs myocardial function.
In addition to ischemia-induced myocardial necrosis, recent data suggests a role for apoptosis in myocyte cell death during myocardial infarction. This process appears to predominate in areas of acutely distended myocardium remote form the infarct area or in the border zone in myocytes that are not rescued (37,38).
As stated earlier in this section, shock typically occurs when >35-40% of the left ventricular muscle is involved. There is not a threshold level of damage for defining patients with cardiogenic shock. A series of 16 patients with final infarct sizes of >40% of the left ventricle quantitated by Technetium-99m sestamibi tomography reported a 94% survival with development of cardiogenic shock in only one patient (39).
The variable neurohumoral response to left ventricular dysfuntion has often been implicated to explain the discrepancies in the clinical manifestations of similar size infarctions. However, the function of myocardium remote from the infarct region plays a pivotal role in hemodynamic response and has been recognized to be of considerable prognostic importance (40). Normally the noninfarct segments become hyperkinetic. An absence of hyperkinesis or asynergy of noninfarcted regions identify patients at high risk for early mortality (41). Diffuse hypokinesis has been recognized as a distinguishing feature for the development of cardiogenic shock in patients with similar size infarctions by echocardiography (42).
The corollary of abnormal remote myocardial function is multivessel coronary artery disease. In two autopsy series of patients dying from cardiogenic shock, 2 or 3 vessel disease (>75% obstruction) was identified in all patients (42,43). The left anterior descending artery is predominantly involved. Angiographic studies have reported left main and/or multivessel disease in 60-90% of patients with cardiogenic shock (18,42,44-48). The SHOCK registry reported multivessel disease in 77% (2 vessel disease, 21%; 3 vessel disease, 56%) with significant (>50%) left main disease in 16.2% of patients with ventricular failure (18). The left anterior descending is the predominant culprit vessel in patients with left ventricular power failure (Fig. 3).
A canine model of myocardial infarction simulating the presence of single or multi-vessel disease illustrates the devastating effect of additional coronary obstructive disease remote from the infarct artery. Beyersdorf et al. (49) demonstrated that, although animals with isolated left anterior descending occlusion exhibited a 100% 6-h survival of the acute infarction, those with a coexistent 50% left circumflex stenosis suffered a 57% mortality from cardiogenic shock or intractable ventricular fibrillation.
Shock can also result from distinct cardiac structural damage with a less extensive left ventricular infarction. Right ventricular infarction can be detected in 40-50% of patients with left ventricular inferior infarction. A deficit of right ventricular pump function from proximal occlusion of the right coronary artery leads to a decline in left ventricular preload as the principle mechanism of the shock state seen in approx 10% of patients with inferior wall infarction. The right ventricle dilates, and the pericardium further constrains left ventricular filling, resulting in hemodynamic parameters similar to pericardial constriction (diastolic equalization, right ventricle dip/plateau pressure configuration and ventricular interdependence). Abnormal interventricular septal function shifts toward the left ventricle in diastole contributing to the low-output state (50). Significant left ventricular damage is common with a clinically evident right ventricular infarction (51).
Rupture of the ventricular free wall, interventricular septum, and papillary muscle represent the major mechanical complications of myocardial infarction. These complications result from necrosis of critical cardiac structures and share a similar pathophys-iological substrate. They have been commonly associated with a first myocardial infarction (52-56). The infarction is usually small to moderate in size in patients with free wall or papillary muscle rupture (28,52). The majority of studies have reported less extensive coronary artery disease in patients with these complications compared to other patients with infarction (52,54,55,57). It has been proposed that patients with more severe coronary artery disease and left ventricular dysfunction cannot generate sufficient contractile stress to produce cardiac rupture. Infarct expansion has been demonstrated to be a harbinger of myocardial rupture (58).
Controversy remains over the possible accentuation of cardiac rupture by thrombolytic therapy (59). Honan et al. (60) reporting a meta-analysis of clinical trials suggested that while early thrombolysis decreases the risk of cardiac rupture, late therapy may enhance this potential complication. However, Late Assessment of Thrombolytic Efficacy (LATE) trial results did not show an increased risk of rupture in patients treated >12 h from onset, but thrombolysis did accelerate the time to rupture (61). In a report from the NRMI participants, data suggested that thrombolysis accelerated myocardial rupture typically within 24-48 h (62). Furthermore, the median time from myocardial infarction onset to diagnosis of interventricular septal rupture was 1 d in the GUSTO-I trial (63). Significantly, it has been shown that patients with cardiac rupture almost uniformly exhibit ineffective perfusion of the infarct artery (64).
Rupture of the free wall of the left ventricle can occur with left and, less commonly, right ventricular infarction (28,65). Rupture usually results from a transmural infarction
(28). Free wall rupture is often a sudden catastrophic event culminating in electromechanical dissociation and death. However a subacute presentation (approx 20%) manifested as hypotension, and right heart failure has been recognized perhaps representing an initial small hemopericadial accumulation (66,67). Patients may exhibit a transient episode of hypotension and bradycardia portending death in minutes to days.
The reported distribution of infarct location with an acute ventricular septal defect has been variable although more recent reports suggest a predominance of inferior wall involvement (68-70). A simple direct perforation or complex serpentine tracts may communicate between the two ventricles. The hemodynamic derangement is usually more substantial with inferior infarction reflecting associated right ventricular involvement and ineffective compensation for the shunt volume (71).
The complexity of the mitral valve apparatus and the subendocardial location of the papillary muscle blood supply explains the occurrence of papillary muscle dysfuntion during infarction. Cardiogenic shock occurs commonly in patients with partial or complete rupture of one of the papillary muscles (52,72). The posteromedial papillary muscle is more frequently involved because of the single vessel blood supply from the posterior descending branch of the right or left circumflex coronary artery. The antero-lateral muscle has a dual blood supply from the left anterior descending and left circumflex arteries (73).
It can appreciated that patients with preexisting severe valvular heart disease may have little reserve available to tolerate a large myocardial infarction, and like patients with previous infarction, they will be at higher risk for cardiogenic shock. Additionally, there have been several recent descriptions of patients presenting with an acute anteroapical infarction with compensatory hyperdynamic function of the preserved basal segments resulting in systolic anterior motion of the mitral valve leading to car-diogenic shock from left ventricular outflow tract obstruction (74-76). These patients have presented with a systolic murmur and shock in the setting of an acute infarction, often with only a small enzyme elevation. Recognition of this syndrome must be considered as common treatments for shock, including inotropic agents and afterload reduction including intra-aortic balloon counterpulsation, may lead to further clinical deterioration. Effective therapeutic measures include b-blockade and utilization of a-agonists (74).
Finally, it should be recognized that peripheral vasodilation may be seen in the seen in the terminal phase of shock from any cause. This could be manifest as a lower than expected systemic vascular resistance and a poor response to vasoconstrictor agents. Several mechanisms may play a role in this failure of vascular smooth cell contraction including activation of KATP channels by lactic acidosis, unregulated nitric oxide synthesis, and depletion of vasopressin stores (77).
Was this article helpful?