Figure 14-1 shows a typical pressure-volume loop for a patient with aortic stenosis. Two differences from the normal curve are immediately apparent. First, the peak pressure generated during systole is much higher because of the high transvalvular pressure gradient. Second, the slope of the diastolic limb is steeper, reflecting the reduced left ventricular (LV) diastolic compliance that is associated with the increase in chamber thickness. Clinically, this means that small changes in diastolic volume produce relatively large increases in ventricular filling pressure.

Figure 14-1 Pressure-volume loop in aortic stenosis. LV = left ventricular.

(From Jackson JM, Thomas SJ, Lowenstein E: Anesthetic management of patients with valvular heart disease. Semin Anesth 1:239, 1982.)

This increased chamber stiffness places a premium on the contribution of atrial systole to ventricular filling, which in patients with aortic stenosis may account for up to 40% of the LV end-diastolic volume (LVEDV), rather than the 15% to 20% characteristic of the normal left ventricle. Echocardiographic and radionuclide studies have documented that diastolic filling and ventricular relaxation are abnormal in patients with hypertrophy from a variety of causes, with significant prolongation of the isovolumic relaxation period being the most characteristic finding. This necessarily compromises the duration and amount of filling achieved during the early rapid diastolic filling phase and increases the relative contribution of atrial contraction to overall diastolic filling. A much higher mean left atrial (LA) pressure is necessary to distend the left ventricle in the absence of the sinus mechanism. One treatment of junctional rhythm is volume infusion.

The systolic limb of the pressure-volume loop shows preservation of pump function, as evidenced by maintenance of the stroke volume (SV) and ejection fraction (EF). It is likely that use of preload reserve and adequate LV hypertrophy are the principal compensatory mechanisms that maintain forward flow. Clinical studies have confirmed that ejection performance is preserved at the expense of myocardial hypertrophy, and the adequacy of the hypertrophic response has been related to the degree to which it achieves normalization of wall stress, in accordance with the Laplace relationship. LV hypertrophy can be viewed as a compensatory physiologic response; however, severe afterload stress and proportionately massive LV hypertrophy could decrease subendocardial perfusion and superimpose a component of ischemic contractile dysfunction.

In aortic stenosis, signs and symptoms of CHF usually develop when preload reserve is exhausted, not because contractility is intrinsically or permanently impaired. This contrasts to mitral and aortic regurgitation, in which irreversible myocardial dysfunction may develop before the onset of significant symptoms. The major threat to the hypertrophied ventricle is its exquisite sensitivity to ischemia. Ventricular hypertrophy directly elevates basal myocardial oxygen demand (). The other major determinants of overall are heart rate, contractility, and, most important, wall tension. Increases in the latter occur as a direct consequence of Laplace’s law in patients with relatively inadequate hypertrophy. The possibility of ischemic contractile dysfunction in the inadequately hypertrophied ventricle arises from increases in wall tension, which directly parallels the imbalance between the elevated peak systolic pressure and the degree of mural hypertrophy. Although there is considerable evidence for “supply-side” abnormalities in the myocardial supply and demand relationship in patients with aortic stenosis, clinical data also support increased as important in the genesis of myocardial ischemia.

On the supply side, the higher LV end-diastolic pressure (LVEDP) of the poorly compliant ventricle inevitably narrows the diastolic coronary perfusion pressure (CPP) gradient. With severe outflow obstruction, decreases in SV and resultant systemic hypotension may critically compromise coronary perfusion. A vicious cycle may develop because ischemia-induced abnormalities of diastolic relaxation can aggravate the compliance problem and further narrow the CPP gradient. This sets the stage for ischemic contractile dysfunction, additional decreases in SV, and worsening hypotension.

Difficulty of Low-Gradient, Low-Output Aortic Stenosis

A subset of patients with severe aortic stenosis, LV dysfunction, and low transvalvular gradient suffers a high operative mortality rate and poor prognosis.² It is difficult to accurately assess the AVA in this low-flow, low-gradient aortic stenosis because the calculated valve area is proportional to forward SV and because the Gorlin constant varies in low-flow states. Some patients with low-flow, low-gradient aortic stenosis have a decreased AVA as a result of inadequate forward SV rather than anatomic stenosis. Surgical therapy is unlikely to benefit these patients because the underlying pathology is a weakly contractile myocardium. However, patients with severe anatomic aortic stenosis may benefit from valve replacement despite the increased operative risk associated with the low-flow, low-gradient hemodynamic state. Guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) call for a dobutamine echocardiography evaluation to distinguish patients with fixed anatomic aortic stenosis from those with flow-dependent aortic stenosis with LV dysfunction. Low-flow, low-gradient aortic stenosis is defined for a mean gradient of less than 30 mmHg and a calculated AVA less than 1.0 cm².

Timing of Intervention

In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop, but outcomes vary widely. The presence of moderate or severe valvular calcification along with a rapid increase in aortic-jet velocity identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than delaying until symptoms develop.

Echocardiography and exercise testing may identify asymptomatic patients who are likely to benefit from surgery.³ In a study of 58 asymptomatic patients, 21 had symptoms for the first time during exercise testing. Guidelines for AVR in patients with aortic stenosis are shown in Table 14-1.

Table 14-1 Recommendations for the Use of Aortic Valve Replacement in Patients with Aortic Stenosis

Replacement Indicated

• Patients with severe aortic stenosis and any of its classic symptoms (e.g., angina, syncope, dyspnea)

• Patients with severe aortic stenosis who are undergoing coronary artery bypass surgery

• Patients with severe aortic stenosis who are undergoing surgery on the aorta or other heart valves

Replacement Possibly Indicated

• Patients with moderate aortic stenosis who require coronary artery bypass surgery or surgery on the aorta or heart valves

• Asymptomatic patients with severe aortic stenosis and at least one of the following: ejection fraction of no more than 0.50, hemodynamic instability during exercise (e.g., hypotension), ventricular tachycardia; not indicated to prevent sudden death in asymptomatic patients who have none of the findings listed

Adapted from the American Heart Association web site (www.americanheart.org).

Functional outcome after aortic valve replacement in patients older than 80 years is excellent, operative risk is limited, and late survival rates are good. In patients with severe LV dysfunction and low transvalvular mean gradient, operative mortality is increased, but aortic valve replacement was associated with improved functional status. Postoperative survival was best in younger patients and with larger prosthetic valves, whereas medium-term survival was related to improved postoperative functional class.

Anesthetic Considerations

The foregoing pathophysiologic principles dictate that anesthetic management be based on the avoidance of systemic hypotension, maintenance of sinus rhythm and an adequate intravascular volume, and awareness of the potential for myocardial ischemia (Box 14-1). In the absence of CHF, adequate premedication may reduce the likelihood of undue preoperative excitement, tachycardia, and the resultant potential for exacerbating myocardial ischemia and the transvalvular pressure gradient. In patients with truly critical outflow tract obstruction, however, heavy premedication with an exaggerated venodilatory response can reduce the appropriately elevated LVEDV (and LVEDP) needed to overcome the systolic pressure gradient. In these patients in particular, the additional precaution of administering supplementary oxygen may provide worthwhile insurance.

BOX 14-1 Aortic Stenosis

Preload:	Increased
Afterload:	Increased
Goal:	Sinus rhythm
Avoid:	Hypotension, tachycardia, bradycardia

Intraoperative monitoring should include a standard five-lead ECG system, including a V₅ lead, because of the left ventricle’s vulnerability to ischemia. A practical constraint in terms of interpretation is that these patients usually exhibit ECG changes because of preoperative LV hypertrophy. The associated ST-segment abnormalities (i.e., strain pattern) may be indistinguishable from or at least very similar to those of myocardial ischemia, making the intraoperative interpretation difficult. Lead II should be readily obtainable for assessing the P-wave changes in the event of supraventricular arrhythmias.

Hemodynamic monitoring is controversial, and few prospective data are available on which to base an enlightened clinical decision. The central venous pressure (CVP) is a particularly poor estimate of LV filling when LV compliance is reduced. A normal CVP can significantly underestimate the LVEDP or pulmonary capillary wedge pressure (PCWP). The principal risks, although minimal, of using a pulmonary artery (PA) catheter in the patient with aortic stenosis are arrhythmia-induced hypotension and ischemia. Loss of synchronous atrial contraction or a supraventricular tachyarrhythmia can compromise diastolic filling of the poorly compliant left ventricle, resulting in hypotension and the potential for rapid hemodynamic deterioration. The threat of catheter-induced arrhythmias is significant for the patient with aortic stenosis. However, accepting a low-normal CVP as evidence of good ventricular function can lead to similarly catastrophic underfilling of the left ventricle on the basis of insufficient replenishment of surgical blood loss. To some extent, even the PCWP can underestimate the LVEDP (and LVEDV) when ventricular compliance is markedly reduced. Placement of a PA catheter also allows for measurement of cardiac output, derived hemodynamic parameters, mixed venous oxygen saturation, and possible transvenous pacing.

Intraoperative fluid management should be aimed at maintaining appropriately elevated left-sided filling pressures. This is one reason why many clinicians believe that the PA catheter is worth its small arrhythmogenic risk. Keeping up with intravascular volume losses is particularly important in noncardiovascular surgery.

Patients with symptomatic aortic stenosis are usually encountered only in the setting of cardiovascular surgery because of their ominous prognosis without aortic valve replacement. Few studies have specifically addressed the response of these patients to the standard intravenous and inhalation induction agents; however, the responses to narcotic and non-narcotic intravenous agents are apparently not dissimilar from those of patients with other forms of VHD. The principal benefit of a narcotic induction is the assurance of an adequate depth of anesthesia during intubation, which reliably blunts potentially deleterious reflex sympathetic responses capable of precipitating tachycardia and ischemia.

Many clinicians also prefer a pure narcotic technique for maintenance. The negative inotropy of the inhalation anesthetics is a theoretical disadvantage for a myocardium faced with the challenge of overcoming outflow tract obstruction. A more clinically relevant drawback may be the increased risk of arrhythmia-induced hypotension, particularly that associated with nodal rhythm and resultant loss of the atrium’s critical contribution to filling of the hypertrophied ventricle.

Occasionally, surgical stimulation elicits a hypertensive response despite the impedance posed by the stenotic valve and a seemingly adequate depth of narcotic anesthesia. In such patients, a judicious trial of low concentrations of an inhalation agent, used purely for control of hypertension, may prove efficacious. The ability to concurrently monitor cardiac output is useful in this situation. The temptation to control intraoperative hypertension with vasodilators should be resisted in most cases. Given the risk of ischemia, nitroglycerin seems to be a particularly attractive drug. Its effectiveness in relieving subendocardial ischemia in patients with aortic stenosis is controversial; however, there is always the risk of even transient episodes of “overshoot.” The hypertrophied ventricle’s critical dependence on an adequate CPP may be very unforgiving of even a momentary dip in the systemic arterial pressure.

Intraoperative hypotension, regardless of the primary cause, should be treated immediately and aggressively with a direct α-adrenergic agonist such as phenylephrine. The goal should be to immediately restore the CPP and then to address the underlying problem (e.g., hypovolemia, arrhythmia). After the arterial pressure responds, treatment of the precipitating event should be equally aggressive, but rapid transfusion or cardioversion should not delay the administration of a direct-acting vasoconstrictor. Patients with severe aortic stenosis in whom objective signs of myocardial ischemia persist despite restoration of the blood pressure should be treated extremely aggressively. This may mean the immediate use of an inotropic agent or simply accelerating the institution of cardiopulmonary bypass (CPB).

HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM, formerly known as hypertrophic obstructive cardiomyopathy) is a relatively common genetic malformation of the heart with a prevalence of approximately 1 in 500. The hypertrophy initially develops in the septum and extends to the free walls, often giving a picture of concentric hypertrophy. Asymmetric septal hypertrophy leads to a variable pressure gradient between the apical LV chamber and the LV outflow tract (LVOT). The LVOT obstruction leads to increases in LV pressure, which fuels a vicious cycle of further hypertrophy and increased LVOT obstruction.⁴ Various treatment modalities include β-adrenoceptor antagonists, calcium channel blockers, and surgical myectomy of the septum. For more than 40 years, the traditional standard treatment has been the ventricular septal myotomy-myomectomy of Morrow, in which a small amount of muscle from the subaortic septum is resected. Two new treatment modalities have gained popularity in recent years: dual-chamber pacing and septal reduction (ablation) therapy with ethanol.

Clinical Features and Natural History

Patients vary widely in their clinical presentation. The contribution of echocardiography to the diagnosis has unquestionably increased the number of asymptomatic patients who carry the diagnosis. Most patients with HCM are asymptomatic and have been seen by the echocardiographer because of relatives having clinical disease. Follow-up remains an important problem for cardiologists because sudden death or cardiac arrest may occur as the presenting symptom in slightly more than one half of previously asymptomatic patients.⁵

Less dramatic frequently presenting complaints include dyspnea, angina, and syncope. The clinical picture is often similar to that of valvular aortic stenosis. The symptoms may share a similar pathophysiologic basis (e.g., poor diastolic compliance) in the two conditions. The prognostic implications of clinical disease, however, are less certain for patients with HCM. Although cardiac arrest may be an unheralded event, other patients may have a stable pattern of angina or intermittent syncopal episodes for many years. Palpitations are also frequently described and may be related to a variety of underlying arrhythmias.

Pathophysiology

In HCM, the principal pathophysiologic abnormality is myocardial hypertrophy. The hypertrophy is a primary event in these patients and occurs independently of outflow tract obstruction. Unlike aortic stenosis, the hypertrophy begets the pressure gradient, not the other way around. Histologically, the hypertrophy consists of myocardial fiber disarray, and, anatomically, there is usually disproportionate enlargement of the interventricular septum.

A consensus exists that the disease is characterized by a wide spectrum of the severity of obstruction. It is totally absent in some patients, may be variable in others, or may be critically severe. Its most distinctive qualities are its dynamic nature (depending on contractile state and loading conditions), its timing (begins early, peaks variably), and its subaortic location. Subaortic obstruction arises from the hypertrophied septum’s encroachment on the systolic outflow tract, which is bounded anteriorly by the interventricular septum and posteriorly by the anterior leaflet of the mitral valve. In most patients with obstruction, exaggerated anterior (i.e., toward the septum) motion of the anterior mitral valve leaflet during systole accentuates the obstruction. The cause of this systolic anterior motion (SAM) is unclear. One possibility is that the mitral valve is pulled toward the septum by contraction of the papillary muscles, whose orientation is abnormal because of the hypertrophic process. Another theory is that vigorous contraction of the hypertrophied septum results in rapid acceleration of the blood through a simultaneously narrowed outflow tract. This could generate hydraulic forces consistent with a Venturi effect whereby the anterior leaflet of the mitral valve would be drawn close to or within actual contact with the interventricular septum (Fig. 14-2). This means that after the obstruction is triggered the mitral valve leaflet is forced against the septum by the pressure difference across the orifice. However, the pressure difference further decreases orifice size and further increases the pressure difference in a time-dependent amplifying feedback loop. This analysis is also consistent with observations that the measured gradient is directly correlated with the duration of mitral-septal contact. There appears to be good correlation between the degree of SAM and the magnitude of the pressure gradient. The SAM-septal contact also underlies the severe subaortic obstruction characteristic of HCM of the elderly, although the narrowing is usually more severe and the contribution of septal movement toward the mitral valve is usually greater.

Figure 14-2 Proposed mechanism of systolic anterior motion (SAM) in hypertrophic cardiomyopathy (HCM). A, Normally, blood is ejected from the left ventricle through an unimpeded outflow tract. B, Thickening of the ventricular septum results in a restricted outflow tract, and this obstruction causes the blood to be ejected at a higher velocity, closer to the area of the anterior mitral valve leaflet. As a result of its proximity to this high-velocity fluid path, the anterior mitral valve leaflet is drawn toward the hypertrophied septum by a Venturi effect (arrow). M.V. = mitral valve; L.V. = left ventricle.

(From Wigle ED, Sasson Z, Henderson MA, et al: Hypertrophic cardiomyopathy: The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 28:1, 1985.)

In addition to SAM, approximately two thirds of patients exhibit a constellation of structural malformations of the mitral valve. These malformations include increased leaflet area and elongation of the leaflets or anomalous papillary muscle insertion directly into the anterior mitral valve leaflet. HCM is not a disease process confined to cardiac muscle alone, because these anatomic abnormalities of the mitral valve are unlikely to be acquired or secondary to mechanical factors.

Three basic mechanisms—increased contractility, decreased afterload, and decreased preload—exacerbate the degree of SAM-septal contact and produce the dynamic obstruction characteristic of patients with HCM. The common pathway is a reduction in ventricular volume (actively by increased contractility, directly or reflexly in response to vasodilation, or passively by reduced preload), which increases the proximity of the anterior mitral valve leaflet to the hypertrophied septum. Factors that usually impair contractile performance, such as myocardial depression, systemic vasoconstriction, and ventricular overdistention, characteristically improve systolic function in patients with HCM and outflow tract obstruction. Diagnostically, these paradoxes are exploited by quantifying the degree of subaortic obstruction after isoproterenol (e.g., increased inotropy, tachycardia, and decreased volume) and the Valsalva maneuver (e.g., decreased venous return and ventricular volume), both of which reliably elicit increases in the pressure gradient. In the operating room, catheter-induced ectopy or premature ventricular contractions resulting from cardiac manipulation may also transiently exacerbate the gradient by increased inotropy from postextrasystolic potentiation. Therapeutically, volume loading, myocardial depression, and vasoconstriction should minimize obstruction and augment forward flow.

Poor diastolic compliance is the most clinically apparent manifestation of the relaxation abnormalities. LV filling pressures are markedly elevated despite enhanced systolic ejection and the normal or subnormal end-diastolic volume. This reduced ventricular volume reemphasizes the pivotal role played by the hypertrophied but intrinsically depressed myocardium. Reductions in afterload, mediated by hypertrophy, support the ventricle’s systolic performance, resulting in increased emptying and a small diastolic volume. However, hypertrophy also impairs relaxation, resulting in poor diastolic compliance and an elevated ventricular filling pressure. The key point is that the high filling pressure does not reflect distention of a failing ventricle, even though stress-volume relationships suggest that its contractility is intrinsically depressed. This disease is characterized by systolic and diastolic dysfunction.

As in patients with valvular aortic stenosis, relatively high filling pressures reflect the LVEDV (i.e., degree of preload reserve) needed to overcome the outflow obstruction. Intervention with vasodilators is therefore inappropriate. The poor ventricular compliance also means that patients with HCM depend on a large intravascular volume and the maintenance of sinus rhythm for adequate diastolic filling. The atrial contribution to ventricular filling is even more important in HCM than in valvular aortic stenosis, and it may approach 75% of total SV.