Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Vasoactive drugs in chronic regurgitant lesions of the mitral and aortic valves.

This review examines the results of vasodilator therapy in patients with chronic regurgitant lesions of the aortic and mitral valves. The analysis includes those studies which provide data on hemodynamic measurements, left ventricular systolic function, ventricular volumes and regurgitant flow. In patients with chronic aortic or mitral regurgitation, the short-term administration of nitroprusside, hydralazine, nifedipine or an angiotensin-converting enzyme (ACE) inhibitor produces salutary hemodynamic effects. The major difference in the response to combined preload and afterload reduction (i.e., nitroprusside) in patients with aortic versus mitral regurgitation was that forward stroke volume generally increased and ejection fraction remained unchanged in mitral regurgitation, whereas ejection fraction generally increased and forward stroke volume remained unchanged in aortic regurgitation. These observations suggest that a reciprocal relation between regurgitant and forward flow characterizes the response to preload and afterload reduction in mitral regurgitation (through a preload-dependent dynamic regurgitant orifice), whereas correction of afterload mismatch dominates the response in aortic regurgitation. In studies of long-term vasodilator therapy in patients with chronic aortic regurgitation, a reduction in left ventricular volumes and regurgitant fraction, with or without an increase in ejection fraction, has been observed during treatment with hydralazine, nifedipine and ACE inhibitors. Patients with the largest, sickest hearts generally benefit the most from treatment with vasoactive drugs. Nonetheless, favorable ventricular remodeling has been reported in asymptomatic patients, and long-term nifedipine use has delayed the need for operation in asymptomatic patients with chronic aortic regurgitation. For patients with chronic mitral regurgitation, definition of the etiology of the lesion is a prerequisite for choosing appropriate therapy. Excluding patients with obstructive hypertrophic cardiomyopathy and mitral valve prolapse, and some with fixed-orifice (i.e., rheumatic) mitral regurgitation, the signal importance of preload reduction suggests that the preferred long-term therapy for symptomatic chronic mitral regurgitation is an ACE inhibitor. There are no long-term studies that support the use of vasodilator therapy in asymptomatic patients with chronic mitral regurgitation.

Geometric changes allow normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy.

OBJECTIVES: This study of hypertensive left ventricular hypertrophy 1) assessed myocardial shortening in both the circumferential and long-axis planes, and 2) investigated the relation between geometry and systolic function. BACKGROUND: In hypertensive left ventricular hypertrophy, whole-heart studies have suggested normal systolic function on the basis of ejection fraction-systolic stress relations. By contrast, isolated muscle data show that contractility is depressed. It occurred to use that this discrepancy could be related to geometric factors (relative wall thickness). METHODS: We studied 43 patients with hypertensive left ventricular hypertrophy and normal ejection fraction (mean +/- SD 69 +/- 13%) and 50 clinically normal subjects. By echocardiography, percent myocardial shortening was measured in two orthogonal planes; circumferential shortening was measured at the endocardium and at the midwall, and long-axis shortening was derived from mitral annular motion (apical four-chamber view). Circumferential shortening was related to end-systolic circumferential stress and long-axis shortening to meridional stress. RESULTS: Endocardial circumferential shortening was higher than normal (42 +/- 10% vs. 37 +/- 5%, p < 0.01) and midwall circumferential shortening lower than normal in the left ventricular hypertrophy group (18 +/- 3% vs. 21 +/- 3%, p < 0.01). Differences between endocardial and midwall circumferential shortening are directly related to differences in relative wall thickness. Long-axis shortening was also depressed in the left ventricular hypertrophy group (18 +/- 6% in the left ventricular hypertrophy group, 21 +/- 5% in control subjects, p < 0.05). Midwall circumferential shortening and end-systolic circumferential stress relations in the normal group showed the expected inverse relation; those for approximately 33% of the left ventricular hypertrophy group were > 2 SD of normal relations, indicating depressed myocardial function. There was no significant relation between long-axis shortening and meridional stress, indicating that factors other than afterload influence shortening in this plane. CONCLUSIONS: High relative wall thickness allows preserved ejection fraction and normal circumferential shortening at the endocardium despite depressed myocardial shortening in two orthogonal planes.

Right ventricular pacing reduces the rate of left ventricular relaxation and filling.

Right ventricular pacing alters left ventricular synchrony and loading conditions, each of which may independently influence left ventricular relaxation. Addition of a properly timed atrial contraction by using sequential atrioventricular (AV) pacing minimizes changes in left ventricular loading conditions, but ventricular asynchrony persists. To separate the effects of altered loading from those of asynchrony, the effects of right ventricular pacing and sequential AV pacing on the rate of isovolumic pressure decline (relaxation time constant), myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined. In 12 open chest anesthetized dogs, left ventricular pressure (micromanometer) and either left ventricular free wall segment length transients (n = 6) or minor axis dimension transients (n = 6) were measured during right atrial, right ventricular and sequential AV pacing; length and dimension were measured using ultrasonic crystals. Compared with right atrial pacing, right ventricular pacing produced a decrease in systolic pressure, a reduction in fractional shortening, a prolongation of the relaxation time constant (23.5 +/- 0.7 to 29.8 +/- 0.8 ms, p less than 0.05), slower peak segment lengthening rate (6.2 +/- 0.6 to 4.6 +/- 0.8 s-1, p less than 0.05) and a slower rate of increase in chamber dimension (3.5 +/- 0.1 to 2.7 +/- 0.1 s-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Systolic time intervals: assessment by isolated cardiac muscle studies.

To document the independent effects of acute changes in preload, afterload and inotropic state on the systolic time intervals, 10 isolated rat left ventricular muscle preparations were studied. Experiments were performed using physiologically sequenced contractions that simulate the loading conditions of the intact left ventricle. The preshortening period was measured from the time of the electrical stimulus to the onset of muscle shortening, and the isotonic contraction time was measured as the duration of shortening. These variables are analogous to the preejection period and the left ventricular ejection time in the intact heart. It was found that an isolated increase in preload shortened the preshortening period and prolonged the isotonic contraction time, whereas an increase in afterload prolonged the former and shortened the latter. Isoproterenol shortened both the preshortening period and the isotonic contraction time, while an increase in calcium shortened the preshortening period and lengthened the isotonic contraction time. All changes were significant (p less than 0.01) by analysis of variance. Thus, the similar dependence of preshortening period, isotonic contraction time and clinical systolic time intervals on changes in preload, afterload and inotropic state supports the derivation of systolic time intervals from fundamental principles of myocardial mechanics. These data provide an improved basis for the rational interpretation of systolic time intervals in patients with and without heart disease.

Chronic aortic regurgitation: prognostic value of left ventricular end-systolic dimension and end-diastolic radius/thickness ratio.

The prognostic value of preoperative echocardiographic data was assessed in 32 patients who underwent aortic valve replacement for chronic aortic regurgitation. All patients had preoperative studies and were followed up prospectively for 1 to 6 years after surgery. Postoperatively, 25 patients (Group A) achieved a normal left ventricular end-diastolic dimension and a significant regression of myocardial hypertrophy; 7 patients (Group B) had persistent left ventricular enlargement. During the follow-up period, the patients in Group A had fewer symptoms and used fewer medications than those in Group B. Moreover, survival at 4 years appeared to be better in Group A (96%) than in Group B (71%); two patients in Group B died with congestive heart failure; there were no such deaths in Group A. Preoperatively, a left ventricular dimension at end-diastole (DED) larger than 3.8 cm/m2 body surface area, a dimension at end-systole (DES) greater than 2.6 cm/m2 body surface area, an end-diastolic radius/wall thickness ratio (R/Th) greater than 3.8 or a product of R/Th and left ventricular systolic pressure (P X R/Th) exceeding 600 are predictive of a Group B result. If end-systolic dimension is greater than 2.6 and P X R/Th is greater than 600, all Group B patients can be identified; all but one patient in Group A had an end-systolic dimension less than 2.6 and P X R/Th less than 600. It is concluded that patients with chronic aortic regurgitation who are at risk of persistent postoperative left ventricular enlargement (with associated cardiac symptoms and reduced survival) can be identified by preoperative echocardiography.

Chronic mitral regurgitation: predictive value of preoperative echocardiographic indexes of left ventricular function and wall stress.

The effect of mitral valve replacement on left ventricular volume, mass, function and clinical symptoms was examined in 20 patients with chronic mitral regurgitation. Pre- and postoperative echocardiograms demonstrated that two outcomes could be defined. Left ventricular dimension at end-diastole was reduced to normal postoperatively in the 16 Group I patients, but was unchanged in the 4 Group II patients. The Group I response was associated with a dramatic reduction in left ventricular mass and a decrease in clinical symptoms; all 16 patients reached New York Heart Association functional class I. No change in left ventricular mass was seen in the Group II patients and all four remained symptomatic despite continued medical therapy. Examination of the preoperative echocardiographic measurements indicates that these data have significant prognostic value in predicting surgical outcome. When ventricular dimension at end-systole exceeds 2.6 cm/m2 or fractional shortening is less than 31% or end-systolic wall stress index exceeds 195 mm Hg, all Group II patients are identified and there are no false positive results in Group I. It is concluded that echocardiographic measurements of left ventricular size, function and wall stress can provide important prognostic information in patients with chronic mitral regurgitation. Such data may allow improved patient selection and a better definition of an optimal time for mitral valve replacement.

Left ventricular length-force-shortening relations before and after surgical correction of chronic mitral regurgitation.

OBJECTIVES: We tested the hypothesis that postoperative left ventricular (LV) systolic wall stress can be predicted from the change in LV diastolic dimension and ejection fraction (EF) after surgical correction of chronic mitral regurgitation (MR). We used a simple mathematic model to predict postoperative systolic stress from end-diastolic dimension and EF. The validity of this model was assessed using data from 21 patients undergoing mitral valve replacement (MVR) for chronic MR. BACKGROUND: The decline in EF after MVR for chronic MR is traditionally thought to be a consequence of a postoperative increase in afterload, caused by closure of a low resistance runoff into the left atrium. However, consideration of the Laplace relation suggests that afterload does not necessarily increase after the operation. METHODS: A spherical mathematical model of the left ventricle was used to define the relations between LV end-diastolic dimension, systolic wall stress and EF. To test the validity of this model, clinical and echocardiographic data were obtained from 21 patients with chronic MR before and 10 to 14 days after MVR. These echocardiographic data were examined with reference to plots derived from the mathematical model. RESULTS: Patients were categorized as those in whom end-diastolic dimension declined after the operation (group I, n = 15) and those with no reduction in end-diastolic dimension (group II, n = 6). Group I patients were subclassified into those undergoing MVR with chordal preservation (group Ia) and those undergoing MVR with chordal transection (group Ib). In groups Ib and II, there were significant reductions in EF (56 +/- 3% to 48 +/- 3% in group Ib and 50 +/- 2% to 40 +/- 3% in group II, both p < 0.05), but the changes in end-diastolic dimension and wall stress differed. In group Ib, end-diastolic dimension decreased and systolic wall stress was unchanged; in group II, end-diastolic dimension was unchanged and wall stress increased. In contrast, group Ia patients experienced a substantial reduction in end-diastolic dimension, no change in EF and a reduction in stress. The corresponding length-force-shortening coordinates closely approximate those predicted from a mathematic model relating end-diastolic dimension to EF and systolic wall stress. CONCLUSIONS: Concordant echocardiographic and mathematical model results indicate that postoperative changes in systolic stress are directly related to changes in chamber size and that LV afterload may fall when chordal preservation techniques are used in combination with MVR.

Asynchronous (segmental early) relaxation of the left ventricle.

Segmental early relaxation, a form of left ventricular asynchrony, refers to lengthening of a myocardial segment before mitral valve opening. This phenomenon may occur in normal and diseased hearts; when it is seen in a diseased ventricle it may occur in either the abnormally contracting segment or the normal segment. Experimental data indicate that altered loading conditions, especially nonuniform distribution of load or functional inhomogeneities (as may occur with regional ischemia), or both, may result in asynchronous relaxation of the left ventricle.

Left ventricular hypertrophy and mortality after aortic valve replacement for aortic stenosis. A high risk subgroup identified by preoperative relative wall thickness.

OBJECTIVES: We investigated the relation between the extent and pattern of left ventricular hypertrophy and surgical outcome in 54 patients undergoing aortic valve replacement for severe aortic stenosis. BACKGROUND: Previous work from our laboratory has demonstrated that a subgroup of patients, mostly elderly women with Doppler evidence of abnormal intracavitary flow acceleration, had an unexpectedly high in-hospital mortality rate after aortic valve replacement for aortic stenosis. We hypothesized that marked concentric hypertrophy, rather than the Doppler signal itself, was related to the poor outcome. METHODS: A retrospective analysis of the clinical, hemodynamic and echocardiographic data in patients who survived aortic valve replacement versus those who died in the hospital was performed. RESULTS: There were no differences between the 42 survivors and 12 nonsurvivors with regard to the clinical or hemodynamic variables. Of the echocardiographic variables analyzed, diastolic relative wall thickness was found to be significantly different between the two groups. Patients who died had significantly greater relative wall thickness (mean +/- SD) than those who survived (0.72 +/- 0.38 vs. 0.56 +/- 0.15, p = 0.04). Analysis by gender demonstrated that the relation between ventricular geometry and mortality held true only for women. CONCLUSIONS: We conclude that excessive ventricular hypertrophy, manifested as a markedly increased relative wall thickness, is associated with a significantly increased risk of postoperative mortality after aortic valve replacement for aortic stenosis.

Adult cardiology and the expanding supply of physicians.

The number of cardiologists can be projected with considerable accuracy into the next century. The total cardiology pool of physicians will increase until the year 2015 at which time those entering and leaving the pool will come into equilibrium. At that time the ratio of active cardiologists to the population will have greatly increased. This nation's future need for cardiologists is difficult to assess with any degree of precision. Therefore, this is the time for updating practice profile studies. Such studies today could be formulated in a manner to provide more detailed information on the cardiologist's daily activities. In addition, a data base developed through methodology such as the consensus formation approach must be developed and updated on a periodic basis. Through such analyses it will be possible to quantitate the future needs of cardiovascular manpower.

The class III antiarrhythmic effect of sotalol exerts a reverse use-dependent positive inotropic effect in the intact canine heart.

OBJECTIVES: We sought to study the rate related effects of sotalol on myocardial contractility and to test the hypothesis that the class III antiarrhythmic effect of sotalol has a reverse use-dependent positive inotropic effect in the intact heart. BACKGROUND: Antiarrhythmic drugs exert significant negative inotropic effects. Sotalol, a beta-adrenergic blocking agent with class III antiarrhythmic properties, may augment contractility by virtue of its ability to prolong the action potential duration (APD). METHODS: In 10 anesthetized dogs, measurements of left ventricle (LV) peak (+)dP/dt and simultaneous endocardial action potentials were made during baseline conditions and after sequential administration of esmolol and sotalol. In addition, electrical and mechanical restitution curves were constructed at a basic pacing cycle length of 600 ms by introducing a test pulse of altered cycle length ranging from 200 ms to 2,000 ms. RESULTS: In the steady state pacing experiments, sotalol prolonged the APD in a reverse use-dependent manner; such an effect was not seen with esmolol. At cycle lengths exceeding 400 ms, LV (+)dP/dt was significantly higher with sotalol than it was with esmolol. There was a direct relation between APD and LV (+)dP/dt with sotalol (r = 0.46, p < 0.001), but there was no significant relation between APD and LV (+)dP/dt with esmolol (r = 0.27, p = NS). Results in the single beat (restitution) studies were qualitatively similar to the steady state results; APD (at cycle length >400 ms) and LV (+)dP/dt (at cycle length >600 ms) were significantly higher with sotalol than they were with esmolol. CONCLUSIONS: The reverse use-dependent prolongation of APD by sotalol is associated with a positive inotropic effect.

When to intervene in chronic aortic regurgitation.

Symptomatic patients with chronic aortic regurgitation should undergo aortic valve replacement. Asymptomatic patients with normal left ventricular function are not surgical candidates, but aortic valve replacement should be performed in most patients with left ventricular dysfunction, even if symptoms are not yet present. The short-term administration of vasodilators is generally beneficial, but there is only meager evidence that the hemodynamic benefits are maintained; for this reason, the wide application of these agents should be postponed until well-designed clinical trials document a long-term benefit.

Force pattern of hypoxic myocardium applied to oxygenated muscle preparations: comparison with effects of regional ischemia on the contraction of non-ischemic myocardium.

OBJECTIVE: To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. METHODS: Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. RESULTS: Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. CONCLUSION: The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.

Left ventricular radius to wall thickness ratio.

Left ventricular relative wall thickness, expressed as the ratio of end-diastolic radius to wall thickness (R/Th ratio), has a constant relation with left ventricular systolic pressure in children and adults with a normal heart, subjects with physiologic forms of cardiac hypertrophy (athletes) and patients with compensated chronic left ventricular volume overload (chronic aortic regurgitation). Greatly increased values for the radius/thickness ratio, suggesting inadequate hypertrophy, indicate a poor prognosis in patients with chronic aortic regurgitation and in those with congestive cardiomyopathy; decreased values for this ratio are found in patients with hypertrophic cardiomyopathy (inappropriate hypertrophy) and in patients with compensated aortic stenosis (appropriate hypertrophy). In patients with compensated aortic stenosis, echocardiographic measurement of the left ventricular end-diastolic radius/wall thickness ratio has been used to estimate left ventricular systolic pressure. Measurement of left ventricular relative wall thickness appears to provide diagnostic and prognostic data in patients with a broad variety of cardiac disorders.

Assessment of the cardiac effects of hemodialysis with systolic time intervals and echocardiography.

The acute effects of hemodialysis on left ventricular (LV) function were studied with the use of externally recorded LV systolic time intervals and echocardiography; 10 patients with normal or near-normal predialysis LV function and no circulatory congestion were studied. Hemodialysis significantly decreased the LV ejection time (LVET) from 270 +/- 9 ms to 237 +/- 10 ms (p less than 0.001); no significant change was noted in the preejection period (PEP). The PEP/LVET ratio increased from 0.41 +/- 0.05 to 0.45 +/- 0.06 (p less than 0.05). The LV end-diastolic dimension decreased from 5.3 +/- 0.3 cm to 4.8 +/- 0.3 cm (p less than 0.001). Fractional shortening and ejection fraction did not change significantly, but hemodialysis slightly increased mean VCF from 1.2 +/- 0.1 s-1 to 1.4 +/- 0.1s-1 (p less than 0.005). Hemodialysis was associated with a 17% decrease (87 +/- 8 ml to 72 +/- 7 ml; p less than 0.001) in LV stroke volume as calculated from echocardiographic data. Small changes in heart rate and blood pressure were insignificant. We conclude that the postdialysis reduction in stroke volume was due primarily to an acute decrease in LV preload; dialysis also appears to be associated with a small increase in the LV contractile state.

Interval-dependent potentiation of left ventricular contractility is preserved in patients with atrial fibrillation and depressed ejection fraction.

Echocardiographic techniques were used to measure left ventricular isovolumic and ejection phase indexes of contractility in 54 patients with atrial fibrillation, and the relations between cycle lengths and contractility were compared in patients with normal and depressed ejection fractions. Data indicate that variations in contractility occur in a pattern that is consistent with postextrasystolic potentiation and that such interval-dependent potentiation is preserved in patients with atrial fibrillation and depressed ejection fraction.

Effect of propranolol on the left ventricular response to the Valsalva maneuver in normal subjects.

Ten normal subjects performed the Valsalva maneuver before and after the administration of propranolol (1 mg/kg). Changes in left ventricular (LV) size and function were assessed with noninvasive techniques (echocardiography and sphygmomanometer). Data were obtained at baseline, at 20 seconds of the strain phase (phase II) and 10 seconds after the release of strain (phase IV). In the control state (before propranolol), blood pressure decreased during phase II and exceeded baseline after the release of strain ("overshoot") in phase IV; after the administration of propranolol, the pressure overshoot characteristic of phase IV was no longer present. End-diastolic dimension decreased during the strain phase, but returned to baseline values during recovery in both control and propranolol states. LV stress-dimension and stress-shortening relations before and after propranolol indicate that an increase in LV contractility beginning during phase II and extending into phase IV was attenuated after propranolol. Although the absence of phase IV blood pressure overshoot may be clinically useful in identifying patients with impaired left ventricular function, beta-adrenergic receptor blocking agents can also produce this hemodynamic response in the presence of normal ventricular function.

Interval-dependent changes in left ventricular contractile state in lone atrial fibrillation and in atrial fibrillation associated with coronary artery disease.

In atrial fibrillation (AF), beat-to-beat changes in left ventricular (LV) systolic performance are caused by variations in filling (preload), aortic pressure (afterload), and ventricular inotropic or contractile state. These factors are known to be influenced by the preceding diastolic or RR interval (RR1), but the independent impact of variations in the pre-preceding RR interval (RR2) on contractile state is not well defined. This aspect was studied in 10 patients with lone AF and 8 with coronary artery disease by measuring LV peak ejection velocity (V[pe] Doppler echocardiography) in 80 to 100 consecutive cardiac cycles. V(pe) was plotted against RR1 for beats with a short RR2 and for beats with a long RR2. Such function-interval plots indicate a direct relation between V(pe) and RR1 (for RR1 = 500 to 1,000 ms). In lone AF, the slope (linear fit) of V(pe) versus RR1 was similar for short and long RR2 (slopes = 46 and 50 s[-1]). V(pe), calculated from best linear fit and a common RR1, was consistently higher when RR2 was short than when it was long. At an RR1 = 750 ms, V(pe) (% of max) was 87 +/- 6% when RR2 was short versus 76 +/- 6% when RR2 was long, p <0.05. Results were similar in patients with coronary artery disease and the observed interval-dependent potentiation of contractile state was preserved in patients with a low ejection fraction. By comparing V(pe) at a common RR1, the effects of time-dependent changes in LV preload and afterload are minimized if not abolished. Thus, differences in V(pe) reflect differences in contractile state caused by variations in RR2. Data confirm interval-dependent alterations in contractile state that are likely an expression of the force-frequency relation. Studies of LV function in AF should incorporate a consideration of cycle length-dependent changes in LV contractile state.

Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation.

Fourteen patients with biopsy-proved systemic amyloidosis underwent noninvasive cardiac testing to assess the presence and severity of cardiac amyloidosis. There was a clear tendency for electrocardiographic voltage to be low (sum of S wave in lead V1 plus R wave in lead V5 or V6 [SV1 + RV5 or V6] = 14.6 +/- 4.8 mm; normal range 15 to 35) and echocardiographic muscle cross-sectional area to be increased (11.4 +/- 2.7 cm2/m2; normal range 6 to 10). When the electrocardiographic or the echocardiographic data were examined individually, and especially when they were compared and contrasted with similar measurements from patients with pericardial disease (n = 8) or aortic valve disease (n = 24), it was apparent that the electrocardiogram and the echocardiogram had limited specificity in the diagnosis of amyloidosis. However, when the analysis combined these two techniques, a distinctive pattern emerged. There was an inverse correlation between voltage and muscle cross-sectional area (r = -0.79) in patients with amyloidosis; moreover, marked derangement of the voltage/cross-sectional area relation was associated with clinical symptoms and mortality. In addition, patients with amyloidosis and cardiac symptoms had abnormal left ventricular chamber radius to wall thickness ratios, consistent with infiltration of the myocardium as the primary abnormality in cardiac amyloidosis.