Figure 232-1. Patterns of ventricular hypertrophy. Specific patterns of ventricular remodeling occur in response to the imposed augmentation in work load. A pattern of hypertrophic growth characterized as concentric, in which increased mass is out of proportion to chamber volume, is particularly effective in reducing systolic wall stress (s) under conditions of heightened pressure load. In contrast, in volume overload conditions, in which the major stimulus is diastolic loading, a predominant finding is a great increase in the cavity size or volume. Although there can be extensive increases in mass, the relationship between mass and volume is either preserved or, in severe cases, reduced. The fundamental response is generated by cellular hypertrophy. However, the configuration of the new contractile tissue is specific and offsets the mechanical stimulus.[Modified from W Grossman et al in NR Alpert (ed): Perspectives in Cardiovascular Research. Myocardial Hypertrophy and Failure, vol 7. New York, Raven Press, 1993, with permission.]

Figure 231-9. Relationship between left ventricular end-diastolic volume and (1) end-diastolic pressure (top), describing the compliance of the left ventricle, i.e., its diastolic properties; and (2) left ventricular stroke work (bottom), describing the ventricle's systolic function curve. The normal left ventricle (left) reaches an end-diastolic pressure of 30 mmHg (pulmonary edema level) when its end-diastolic volume is elevated to 200 mL. The concentrically hypertrophied left ventricle (center) exhibits normal systolic function since the relation between left ventricular end-diastolic volume and stroke work is unchanged, but there is "diastolic failure" in that end-diastolic pressure reaches pulmonary edema level (i.e., 30 mmHg) at a lower level than normal (i.e., 130 mL). The dilated ventricle (right) exhibits "systolic failure" in that the maximal stroke work and the stroke volume at any level of end-diastolic volume are depressed. The left ventricle displays increased diastolic compliance, i.e., distensibility, with a higher than normal end-diastolic volume (280 mL) required to reach the pulmonary edema level.(Reprinted with permission from R Gorlin, Prim Cardiol 6:84, 1980.)

Figure 231-6. Diagram showing the interrelations among influences on ventricular end-diastolic volume (EDV) through stretching of the myocardium and the contractile state of the myocardium. Levels of ventricular EDV associated with filling pressures that result in dyspnea and pulmonary edema are shown on the abscissa. Levels of ventricular performance required when the subject is at rest, while walking, and during maximal activity are designated on the ordinate. The broken lines are the descending limbs of the ventricular-performance curves, which are rarely seen during life but which show the level of ventricular performance if end-diastolic volume could be elevated to very high levels. For further explanation see text.

(Modified from E Braunwald et al: Mechanisms of Contraction of the Normal and Failing Heart. Boston, Little, Brown, 1976.)

Figure 37-2. Sequence of events leading to the formation and retention of salt and water and the development of edema. ANP, atrial natriuretic peptide; RPF, renal plasma flow; GFR, glomerular filtration rate. Inhibitory influences are shown by broken lines. ADH, antidiuretic hormone.

Figure 232-CD1. Chest roentgenogram of patient with heart failure. This roentgenogram demonstrates cardiomegaly (cardiothoracic ratio 0.77), pulmonary congestion, and bilateral pleural effusions (note blunted costophrenic angles). [JB Young: Assessment of heart failure, in WS Colucci: Heart failure: Cardiac Function and Dysfunction, in E Braunwald (series ed): Atlas of Heart Diseases, vol 4. Philadelphia, Current Medicine, 1995, p 7.16.]

Figure 231-10. Scheme of interactions among various components that regulate cardiac activity. Solid lines indicate an augmenting effect; broken line represents an inhibiting effect.(From E Braunwald, N Engl J Med 290:1124-1129, 1420-1425, 1974.)

Figure 70-2. Time course of digoxin accumulation following repeated 0.25 mg/d oral maintenance dose administration (solid line), assuming bioavailability is about 85%. The smooth (dashed line) curve depicts the pattern of accumulation following administration of an equivalent dosing rate (150 ng/min) by continuous intravenous infusion. Note that accumulation and elimination are >90% complete after four half-lives and this is independent of the dosing regimen. Also, that steady state is proportional to the dosing rate (dose/dosing interval) and the ratio of bioavailability to clearance. The temporal relationships shown apply equally well to other drugs with linear pharmacokinetics and one-compartment distribution. For comparison, the plasma concentration-time curve if only the first dose were given is also shown (dotted line). Cmax,ss, maximum plasma concentration at steady state; Cavg, average plasma concentration; Cmin, minimal plasma concentration.

Figure 231-5. Effects of the addition of norepinephrine (NE) and the development of heart failure on the force-velocity relation of the cat papillary muscle. NE induces an increase in the velocity of shortening at any load, in the maximum force and isometric contraction (Po), and in the maximum velocity of zero load shortening (Vmax). Heart failure has the opposite effect. Key: o, control; -x-x, failure.(Modified from E Braunwald in Heart Disease, 4th ed. Philadelphia, Saunders, 1992.)

Figure 232-2. The natural history of congestive heart failure (CHF). Once left ventricular systolic dysfunction is present, it usually progresses, albeit not predictably. As left ventricular dysfunction progresses and symptoms increase, mortality rate increases and the process becomes inexorable. Myocyte loss and fibrosis become irreversible. An effective preventive measure must be introduced before onset or early in the course of progressive left ventricular dysfunction.(From Massie and Shah, with permission.)

Figure 231-CD3. The renin-angiotensin system. [JA Cusco, MA Creager: Neurohumoral, renal and vascular adjustments in heart failure, in WS Colucci: Heart failure: Cardiac Function and Dysfunction, in E Braunwald (series ed): Atlas of Heart Diseases, vol 4. Philadelphia, Current Medicine, 1995, p 6.8.

Adapted from: WC Paganelli et al: Cardiac regulation of renal function, in TO Cheng (ed): The International Textbook of Cardiology. New York, Pergammon Press, 1986, pp 1010-1020.]

Figure 231-CD2. Patterns of ventricular hypertrophy. Specific patterns of ventricular remodeling occur in response to the imposed augmentation in workload. In pressure overload, a pattern of hypertrophic growth characterized as concentric, in which increased mass is out of proportion to chamber volume, is particularly effective in reducing systolic wall stress (s) under conditions of heightened pressure load. In volume overload, a predominant finding is a great increase in the cavity volume. [MA Pfeffer: Cardiac remodeling and its prevention, in WS Colucci: Heart failure: Cardiac Function and Dysfunction, in E Braunwald (series ed): Atlas of Heart Diseases, vol 4. Philadelphia, Current Medicine, 1995, p 5.3.

Figure 231-CD1. The normal (N) relationship between LV wall thickness (h) and chamber radius (r) is shown (first panel). An acute increase in systolic pressure causes an increase in systolic wall stress, which can be approximated by the equation P ´ r/h, where P is LV systolic pressure. Diastolic wall stress is also increased when there is chamber dilatation or when diastolic pressure is elevated (second panel). If sufficient compensatory hypertrophy occurs, the increase in ventricular wall thickness may normalize the systolic and diastolic wall stresses (third panel). However, if additional chamber dilatation occurs or the increase in wall thickness is insufficient, systolic and diastolic wall stresses remain abnormally elevated. In this situation, further chamber dilatation may occur in association with hemodynamic failure (fourth panel).

Figure 231-11. Interplay between cardiac function and neurohumoral and cytokine systems. Myocardial injury, of many etiologies, can depress cardiac function, which in turn causes activation of the sympathoadrenal system (SAS) and the renin-angiotensin-aldosterone system (RAAS) and the elaboration of endothelin, arginine vasopressin (AVP), and cytokines such as tumor necrosis factor (TNF) a. In acute heart failure (left), these are adaptative and tend to maintain arterial pressure and cardiac function. In chronic heart failure (right), they cause maladaptive hypertrophic remodeling and apoptosis, which cause further myocardial injury and impairment of cardiac function. The horizontal line on the right (*) shows that chronic maladaptive influences can be inhibited by angiotensin converting enzyme inhibitors, b-adrenergic blockers, angiotensin type I receptor blockers, aldosterone antagonists, and endothelin type A blockers.

Table 232-1. Framingham Criteria for Diagnosis of Congestive Heart Failurea

MAJOR CRITERIA

Paroxysmal nocturnal dyspneaNeck vein distentionRalesCardiomegalyAcute pulmonary edemaS3 gallopIncreased venous pressure (>16 cmH2O)Positive hepatojugular reflux

MINOR CRITERIA

Extremity edemaNight coughDyspnea on exertionHepatomegalyPleural effusionVital capacity reduced by one-third from normalTachycardia (≥120 bpm)

MAJOR OR MINOR

Weight loss ≥4.5 kg over 5 days' treatment

a To establish a clinical diagnosis of congestive heart failure by these criteria, at least one major and two minor criteria are required.

SOURCE: KKL Ho et al, Circulation 88:107, 1993.

Table 232-2. Overview of Angiotensin-Converting Enzyme Inhibitors in Heart Failure

Odds Ratio 95% Confidence Interval  

Total mortality 0.77 0.67-0.88  

Mortality or hospitalization 0.65 0.57-0.74  

Progressive heart failure 0.69 0.58-0.83  

Sudden death 0.91 0.73-1.12  

Fatal myocardial infarction 0.82 0.60-1.11  

Total mortality  

Class 1 0.75 0.46-1.23  

Class 2 0.83 0.68-1.01  

Class 3 0.76 0.60-0.96  

Class 4 0.55 0.36-0.84  

EF >0.25 0.98 0.78-1.23  

EF £0.25 0.69 0.57-0.85  

NOTE: EF, ejection fraction

SOURCE: From Garg and Yusuf. Copyright 1995, American Medical Association.

Table 232-3. Clinical Trials in Heart Failure

Beta Blockade Aldosterone Antagonist

 

Trial name CIBIS II MERIT-HF RALES  

Drug Bisoprolol (B1 selective)

Metoprolol (B1 selective)

Spironolactone 

Age (avg, years) 61 64 65  

CAD% 50 65 54  

Male % 80 77 73  

NYHA II % 41  

III % 83 55 71  

IV 17 4 29  

ACE I % 90 90 95  

LVEF % 28 28 <35%  

Placebo  

Annual mortality, % 13 10 22  

Mortality reduction  

All cause 34 34 30  

Sudden death 42 41 29  

Pump failure death 26 49 36  

Hospital admissions for HF 32 35