To characterize the role of cardiac function in septic shock, serial radionuclide cineangiographic and hemodynamic evaluations were done on 20 patients with documented septic shock. Although all patients had a normal or elevated cardiac index, 10 patients had moderate to severe depression of their ejection fraction with values below 0.40. Thirteen of twenty patients survived their episode. Paradoxically, 10 of 13 survivors, but none of the 7 nonsurvivors, had an initial ejection fraction less than 0.40 (p less than 0.005). The mean initial ejection fraction for the survivors was 0.32 +/- 0.04, and their mean end systolic and end diastolic ventricular volumes were substantially increased with a normal stroke volume. The survivors' serial scans showed a gradual return to normal ejection fraction and ventricular volume by 10 days after the onset of shock. Nonsurvivors had normal initial ejection fractions and ventricular volumes that did not change during serial studies.

Profound but Reversible Myocardial Depression in Patients with Septic Shock

Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.

Septic Shock in Humans: Advances in the Understanding of Pathogenesis, Cardiovascular Dysfunction, and Therapy

BACKGROUND Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis." METHODS AND RESULTS Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001). CONCLUSIONS This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.

Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.

Background— The extent of the peri-infarct zone by magnetic resonance imaging (MRI) has been related to all-cause mortality in patients with coronary artery disease. This relationship may result from arrhythmogenesis in the infarct border. However, the relationship between tissue heterogeneity in the infarct periphery and arrhythmic substrate has not been investigated. In the present study, we quantify myocardial infarct heterogeneity by contrast-enhanced MRI and relate it to an electrophysiological marker of arrhythmic substrate in patients with left ventricular (LV) systolic dysfunction undergoing prophylactic implantable cardioverter defibrillator placement. Methods and Results— Before implantable cardioverter defibrillator implantation for primary prevention of sudden cardiac death, 47 patients underwent cine and contrast-enhanced MRI to measure LV function, volumes, mass, and infarct size. A method for quantifying the heterogeneous infarct periphery and the denser infarct core is described. MRI indic...

Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction.

Left ventricular dysfunction is common in respiratory-distress syndrome, asthma and obstructive lung disease. To understand the contribution of intrathoracic pressure to this problem, we studied the effects of Valsalva and Muller maneuvers on left ventricular function in eight patients. Implantation of intramyocardial markers permitted beat-by-beat measurement of the velocity of fiber shortening (VCF) and left ventricular volume. During the Muller maneuver, VCF and ejection fraction decreased despite an increase in left ventricular volume and a decline in arterial pressure. In addition, when arterial pressure was corrected for changes in intrapleural pressure during either maneuver it correlated better with left ventricular end-systolic volumes than did uncorrected arterial pressures. These findings suggest that negative intrathoracic pressure affects left ventricular function by increasing left ventricular transmural pressures and thus afterload. We conclude that large intrathoracic-pressure changes, such as those that occur in acute pulmonary disease, can influence cardiac performance.

https://www.nejm.org/doi/pdf/10.1056/NEJM197908303010901?listPDF=true

Effect of Intrathoracic Pressure on Left Ventricular Performance

Previously it was shown that left ventricular (LV) myocardial contractility can be assessed from the instantaneous relation between velocity of fiber shortening and maximum LV wall tension (VCF at max T). Such analysis is complex, requiring frame-by-frame correlation of LV dimensions with pressure, and a simpler approach was sought. In 50 patients the mean velocity of circumferential fiber shortening (mean VCF), determined from the systolic excursion of the LV internal minor equator obtained by cineangiography, was compared with instantaneous tension-velocity relations. In 13 subjects without LV disease, VCF at max T averaged 1.74 ± 0.31 (mean ± sd) circumferences (circ)/sec (range, 1.37-2.52); corresponding mean VCF was 1.50 ± 0.27 circ/sec (range, 1.23-2.03). In 22 patients with LV myocardial disease VCF at max T averaged 0.64 ± 0.29 circ/sec (range, 0.12-1.27); mean VCF averaged 0.68 ± 0.36 circ/sec (range, 0.15-1.29, P < 0.001 compared with normal subjects). Similar results were obtained in 15 patient...

Mean Velocity of Fiber Shortening A Simplified Measure of Left Ventricular Myocardial Contractility

Left ventricular (LV) myocardial contractility, or inotropic state, was characterized in terms of the instantaneous relations between velocity of circumferential fiber shortening (VCF), determined cineangiographically, and LV wall tension (hoop stress), calculated from LV dimensions and pressure, in five patients before and 7 to 10 mo after aortic valve replacement for free aortic regurgitation. Preoperatively the cardiac index was reduced or the LV end-diastolic pressure was markedly increased (or both occurred) in four patients, in each of whom depression of inotropic state was documented by a reduced VCF at maximum wall tension, ranging from 0.13 to 1.07 circumferences (circ)/sec (normal, > 1.40 circ/sec) at wall tensions of 318 to 464 g/cm2 (normal, 178 to 417 g/cm2). In one patient in whom LV end-diastolic pressure and cardiac index were normal preoperatively, VCF was 1.66 circ/sec at a maximum tension of 440 g/cm2. Following operation, LV end-diastolic pressure fell in the four patients with depress...

Left Ventricular Performance Following Correction of Free Aortic Regurgitation

In the past, assessment of cardiac function has centered on techniques that examined the heart's action as a pump. Hemodynamic analysis of cardiac function within the framework of the Fran...

Assessment of Cardiac Function

The mechanics of left ventricular contraction were studied during diagnostic cardiac catheterization using high-speed cineangiography in 11 patients with severe chronic mitral regurgitation. Compared with a group of previously studied normal subjects, most of the patients with mitral regurgitation demonstrated a reduced velocity of shortening (Vcf) during ejection at maximum wall stress, average = 1.01 circumferences/sec (circ/sec) (range 0.64-1.47 circ/sec). Maximum and mean Vcf values also were reduced in these patients, averaging 1.40 and 0.94 circ/sec, respectively. These findings are in contrast to those in acute experimental mitral regurgitation, and to observations of normal shortening velocities in chronic experimental volume overloading, in which left ventricular contraction velocity is augmented. Compared with normal subjects, patients with mitral regurgitation had significantly larger left ventricular end-diastolic circumferences and volumes, and higher total left ventricular stroke volumes. Th...

Mechanics of Left Ventricular Contraction in Chronic Severe Mitral Regurgitation

It has been suggested that the pulmonary arterial end-diastolic pressure (EDP) may accurately reflect the level of left ventricular EDP, and therefore be useful in the continuous monitoring of left...

Evaluation of Pulmonary Arterial End-Diastolic Pressure as an Estimate of Left Ventricular End-Diastolic Pressure in Patients with Normal and Abnormal Left Ventricular Performance

James H. Gault

Papers

Mean Velocity of Fiber Shortening A Simplified Measure of Left Ventricular Myocardial Contractility

Left Ventricular Performance Following Correction of Free Aortic Regurgitation

Assessment of Cardiac Function

Mechanics of Left Ventricular Contraction in Chronic Severe Mitral Regurgitation

Evaluation of Pulmonary Arterial End-Diastolic Pressure as an Estimate of Left Ventricular End-Diastolic Pressure in Patients with Normal and Abnormal Left Ventricular Performance