Profiles in Cardiomyopathy and Heart Failure

Profiles in Cardiomyopathy and Heart Failure

James C. Fang

Barry A. Borlaug

Heart failure (HF) is a chronic progressive condition that arises when the heart cannot provide adequate cardiac output to meet the systemic metabolic demands or cannot accommo-date the venous return without elevation of filling pressure. Thus, HF is a clinical syndrome that can be produced by a number of processes. Examples include any primary insult to the myocardium: infarction, chronic volume or pressure over-load, or a frank disorder of the heart muscle itself—a cardiomyopathy. Cardiomyopathies are generally divided into three categories, two of which are morphologic (dilated and hypertrophic); the third one is functional (restrictive). Alternatively, some authorities have divided patients based on whether the clinical syndrome of HF occurs in a patient with reduced ejection fraction (HFrEF or “systolic” HF) or with preserved EF (HFpEF or “diastolic” HF). Other nonmyocardial processes may cause the clinical syndrome of HF, such as valvular stenosis or pericardial disease, and these are reviewed elsewhere.

Heart failure occurs in part owing to the adverse effects of ongoing neurohormonal activation. There is a fairly good correlation between clinical manifestations and the hemodynamic profile. The most recent classification system emphasizes the progression of hemodynamic and neurohormonal stages rather than symptomatic status (which may wax and wane over time) as traditionally embodied by the New York Heart Association (NYHA) classification. Patients thus evolve from being at risk for developing heart failure (stage A), to structural heart disease (stage B), to symptomatic heart failure (stage C), and finally to medically refractory heart failure (stage D).1 Therapy is driven by both symptoms and the stage of disease and may include diuretic, vasodilator, and inotropic therapies that target the hemodynamic derangements of heart failure (low output, high resistance, elevated filling pressures) and thereby improve symptoms. Antagonism of the adrenergic and renin-angiotensin systems also helps to prevent further injury to the myocardium and thereby slow down the progression of heart failure, at least in the case of HFrEF.

Cardiac catheterization is performed in patients with heart failure for several reasons: (1) to assess etiology, (2) to define both resting and exercise hemodynamic status, and (3) to evaluate therapeutic interventions. In most patients with HF, all three goals can usually be addressed in a single procedure. The hemodynamic profile is generally characterized in the supine state, where resting and exercise conditions can be studied (see Chapter 20), although some centers prefer measurements in the upright state, especially if exercise is being used for diagnostic or prognostic purposes. After the hemodynamic assessment has been completed, angiography should be performed to define the coronary anatomy. Clinical criteria such as the presence or absence of angina are poor predictors of the presence or absence of clinically relevant coronary artery disease.2 Ventriculography should also be considered to assess systolic function, mitral regurgitation, and ventricular size and shape, although most patients will have had echocardiographic assessment prior to catheterization. If sufficient evidence of coronary artery disease is not present to explain the degree of ventricular dysfunction, an endomyocardial biopsy should be considered to help to define the etiology, especially when a specific diagnosis is suspected on clinical grounds3 (see Chapter 26).


There are many potential causes of HFrEF, with the most common one in the United States being coronary artery disease (roughly two-thirds of cases), and in most circumstances
this is clinically obvious based upon medical history, electrocardiography, and echocardiogram.1 Because coronary disease is so common, and because it represents a potentially reversible cause of HF (if viable myocardium is present), cardiac catheterization including coronary angiography is recommended for most patients with new-onset HFrEF. Noninvasive assessment of ischemic heart disease is advocated by some but can be misleading with both false positives and false negatives.2 Once coronary disease has been excluded, the differential diagnosis includes the various causes of dilated cardiomyopathy (DCM; Table 43.1). The noninvasive clinical assessment may suggest a specific diagnosis such as sarcoidosis or Chagas disease, but in most instances the cause will remain undefined (i.e., idiopathic). Most cases of idiopathic cardiomyopathy likely represent the sequelae of prior myocarditis4 or genetic mutations.5 Indeed, a recent study reported that ∽25% of patients with “apparent” DCM had mutations within the titin gene.6 Only a few etiologies of DCM have pathognomonic histologic findings, but endomyocardial biopsy may be helpful in confirming or excluding those diseases. In 1230 patients who underwent endomyocardial biopsy at the Johns Hopkins Hospital (Baltimore, MD) for unexplained HFrEF, a specific cause was eventually determined in 50% of the patients using the results of the endomyocardial biopsy in combination with clinical information, although only 15% had a specific histologic diagnosis3, but using the results of the endomyocardial biopsy in combination with clinical information, a specific cause was eventually determined in 50% of the patients. In addition to coronary angiography and biopsy, ventriculography allows assessment of mitral regurgitation and dyskinesis, both of which can be targeted surgically. Ventriculography is used predominantly when other imaging techniques such as echocardiography or MRI are inadequate or inconsistent with the clinical examination.

Table 43.1 Causes of Dilated Cardiomyopathies (in the Order of Decreasing Frequency)

Idiopathic cardiomyopathy



Occult Ischemic heart disease



Enteroviruses (e.g., Coxsackie A/B)



Drugs e.g., anthracyclines)




Rheumatologic disorders (e.g., lupus)

Endocrine disorders (e.g., pheochromocytoma, hypothyroidism)

Invasive hemodynamic assessment is also important, as physical examination may underestimate the degree of congestion7 and noninvasive methods are limited in accuracy.8, 9, 10 Many hemodynamic profiles are common to all forms of HF (e.g., elevated right and left heart filling pressure, pulmonary hypertension, low output) and not necessarily unique to particular cardiomyopathies.11 However, defining the hemodynamic profile in an individual patient can be used to optimally titrate vasodilators and diuretics.12 In some instances, this tailored management adjusted with an indwelling Swan-Ganz catheter over 48 hours can prolong or even obviate the need for cardiac transplantation.13 Furthermore, a detailed hemodynamic profile provides prognostic information.14,15 In a consecutive series of 152 advanced heart failure patients referred to the University of California, Los Angeles (UCLA) health system for cardiac transplantation, the presenting capillary wedge pressure (mean of 28 mmHg) was not predictive of survival, but the ability to reduce the pulmonary capillary wedge pressure to <16 mmHg by the end of the hospitalization was predictive of outcome with a 1-year survival of 83% (as compared with 38% if the filling pressures could not be so lowered by the end of hospitalization). The effect was independent of the final cardiac index achieved.14 Finally, while one of the key goals of inpatient management for decompensated HF remains volume removal, registry data have revealed that only ∽50% of patients achieve adequate diuresis.16 Part of this problem may relate to the inability to clinically estimate hemodynamic status.10 In select patients, catheterization to identify the presence or absence of an optimal volume status after aggressive treatment for decompensated HF may be useful and reduce subsequent risk for rehospitalization owing to inadequate treatment. However, the routine use of an invasive hemodynamic approach for decompensated heart failure does not appear to decrease mortality or rehospitalization.17

Responses to exercise, vasodilators, and inotropes are also optimally assessed with invasive hemodynamic measurements, although it should be noted that hemodynamics may improve significantly in the absence of drug therapy over time presumably owing to favorable changes in neurohormonal tone. In 21 patients who had their hemodynamics serially assessed over a 24-hour period, the cardiac index (CI) rose by an average of 0.23 L/minute per m2 and the left ventricular filling pressure decreased by 5.9 mmHg.18 Some patients even had spontaneous improvements that rivaled the effects of oral and intravenous vasodilator therapies. Postprandial improvements were also seen, confirming the importance of studying patients in the fasting state.


Despite the radical nature of replacing a human heart with another, cardiac allograft has emerged as an effective way of restoring essentially normal cardiovascular function in endstage heart failure. However, the transplanted heart is subject to a number of post-transplant factors that can influence cardiac function including denervation, organ preservation/ ischemic injury, myocardial rejection, donor/recipient size mismatch, allograft coronary artery disease, and hypertension/ ventricular hypertrophy. Initially the transplanted heart also demonstrates a restrictive hemodynamic profile; this resolves over days to weeks,48,49 although the less dramatic abnormalities in diastolic function may persist50, 51, 52 (Table 43.3). Resting contractility and ejection fraction are relatively normal,53 but total blood volume, cardiac volume, and end-systolic wall
stress increase even if myocardial mass is unchanged.48 In general, mild impairment of ventricular functional reserve is present, but it is demonstrable only with maximal exercise stress and may be in part a result of decreases in coronary flow reserve.54 The primary limitation in maximal cardiac output is owing to the denervated heart having a blunted heart rate response, and the Frank-Starling mechanism is exhausted early in the response to supine55,56 and upright exercise.57 This is partially offset by an increased sympathetic sensitivity, with dependence on circulating catecholamines for an adequate but delayed chronotropic exercise response.58

Figure 43.7 The hemodynamic effects of an inotropic agent, milrinone, in dilated cardiomyopathy. Milrinone increases contractility (positive dP/dt), improves lusitropy (negative dP/dt), and lowers preload (decreased left ventricular end-diastolic pressure [LVEDP]). The improvement in systolic and diastolic function occurs without an increase in systolic blood pressure. (Reproduced with permission from Baim DS, et al. Evaluation of a new bipyridine inotropic agent—milrinone—in patients with severe congestive heart failure. N Engl J Med 1983; 309:748.)

Figure 43.8 Effects of exercise on hemodynamics in dilated cardiomyopathy. Note the development of prominent V waves and dramatic increase of pulmonary capillary wedge pressure with exercise. This effect was achieved with supine arm exercise (moving bags of saline up and down in supine position) resulting in an almost twofold increase in heart rate (HR). The patient had an ejection fraction of 20%, an end-diastolic dimension of 7 cm, and moderately severe mitral regurgitation at rest. The lack of V waves and normal wedge pressure at rest are indicative of the chronic nature of the regurgitation. BP, blood pressure.

Although left ventricular responses to hypertension and acute increases in afterload are normal after cardiac transplantation, the denervated heart does not tolerate hypotension well, presumably because of lack of ventricular compliance and reflex sympathetic tone. Denervation also leads to several other clinically relevant hemodynamic abnormalities in addition to the obvious loss of cardiac pain sensation. Efferent parasympathetic denervation of the heart leads to a resting tachycardia of 90 to 110 beats per minute (bpm), lack of heart rate variability, and the ineffectiveness of atropine and digoxin; efferent sympathetic denervation leads to blunted
and delayed increases in heart rate in response to physiologic stress. Afferent denervation results in dysregulation of sodium and water homeostasis as well as in abnormalities in peripheral vascular responses.59

Table 43.3 Resting and Exercise Hemodynamics After Cardiac Transplantation




Right atrial pressure (mmHg)

6 ± 2

14 ± 7

Pulmonary artery pressure (mmHg)

18 ± 3

32 ± 9

Pulmonary capillary wedge pressure (mmHg)

10 ± 3

20 ± 6

Cardiac output (L/min)

5.0 ± 0.9

9.9 ± 1.7

Stroke volume (mL)

55 ± 9

77 ± 13

Heart rate (bpm)

90 ± 11

122 ± 18

Mean arterial pressure (mmHg)

91 ± 12

102 ± 14

Systemic vascular resistance (Wood)

17.7 ± 4.0

9.3 ± 2.4

Hosenpud, JD, Morton, MJ. Physiology and hemodynamic assessment of the transplanted heart. Cardiac Transplant 1986;180.

Right ventricular function is critical in the early post-transplant period. The normal right ventricle cannot accommodate significant acute pressure overload,60 and nowhere is this more apparent than in the post—cardiac transplant setting. Acute right heart failure accounts for 50% of all peri—and post—cardiac transplant complications and is a leading cause of early allograft failure and death. Not surprisingly, an elevated preoperative pulmonary vascular resistance predicts early postoperative death from acute right heart failure,61, 62, 63 and severe fixed pulmonary hypertension is a contraindication to cardiac transplantation.

Jun 26, 2016 | Posted by in CARDIOLOGY | Comments Off on Profiles in Cardiomyopathy and Heart Failure
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