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MacIver and Townsend's hypothesis predicts, based on a mathematical model of left ventricular contraction, that preserved absolute radial wall thickening (radWT) due to left ventricular hypertrophy is responsible for the normal ejection fraction in patients with heart failure with preserved ejection fraction (HFPEF).We tested the validity of this hypothesis by detailed echocardiography including evaluation of ventricular myocardial strain (S) using speckle tracking imaging in at least 60-year-old 18 controls and 94 hypertensive patients with normal ejection fraction.Echocardiography revealed no left ventricular diastolic dysfunction in 38 out of 94 (40%) patients with hypertension (HTDD-negative group), and 56 out of 94 (60%) patients had diastolic dysfunction (HTDD-positive groups). The absolute values of global longitudinal left ventricular peak systolic S were significantly reduced in both patient groups (P 0.05 for HTDD-negative, P 0.01 for HTDD-positive groups) vs. the controls. There were no significant between-groups differences in circumferential and radial peak left ventricular systolic Ss, radWT and ejection fraction. Left ventricular mass (LVM) (P 0.001), LVM/BMI (P 0.01) increased in the HTDD-positive group and ejection fraction/LVM/BMI decreased in both patient groups (P 0.01 for HTDD-negative, P 0.001 for HTDD-positive groups) vs. the controls. LVM increased, ejection fraction/LVM/BMI decreased in the HTDD-positive group vs. the HTDD-negative group (P 0.05 and P 0.01, respectively).We demonstrated decreased longitudinal left ventricular systolic function and showed that preserved ejection fraction was due to preserved absolute radWT and not due to increased radial or circumferential systolic function in patients with hypertension and normal ejection fraction, a potential HFPEF precursor condition. Instead of ejection fraction, rather ejection fraction/LVM/BMI might be used to detect subtle left ventricular systolic dysfunction in hypertension and HFPEF.

In this paper we examine the relations that may exist between the geometric variables most frequently used to describe left ventricular contraction. The left ventricle is represented by a thick-walled cylinder contracting both radially and longitudinally. For this model, wall thickening, mid-wall radius shortening and longitudinal axis shorteining can be shown to be uniquely related during contraction, whereas it can be demonstrated that internal radius shortening is not uniquely related to these variables, but is also determined by the specific geometry of the cylinder, expressed in terms of the mid-wall radius-to-wall thickness (R/h) ratio of the cylinder. Detailed analysis of the same variables in 44 normal subjects, 32 patients with aortic stenosis and 54 patients with valvular regurgitation (33 aortic and 21 mitral), strongly suggests that the same relations are also clinically applicable. For instance, ventricular longitudinal axis shortening can be estimated with some accuracy from the standard M-mode echocardiogram. Also, wall thickening can be viewed as the direct reflection of the shortening that occurs in the circumferential and longitudinal directions, whereas internal radius shortening is significantly influenced by the R/h ratio of the ventricle, a consideration which becomes important when analyzing results in patients with left ventricular hypertrophy.

A simulated randomized clinical trial in coronary artery disease was conducted to illustrate the need for clinical judgment and modern statistical methods in assessing therapeutic claims in studies of complex diseases. Clinicians should be aware of problems that occur when a patient sample is subdivided and treatment effects are assessed within multiple prognostic categories. In this example, 1073 consecutive, medically treated coronary artery disease patients from the Duke University data bank were randomized into two groups. The groups were reasonably comparable and, as expected, there was no overall difference in survival. In a subgroup of 397 patients characterized by three-vessel disease and an abnormal left ventricular contraction, however, survival of group 1 patients was significantly different from that of group 2 patients. Multivariable adjustment procedures revealed that the difference resulted from the combined effect of small imbalances in the distribution of several prognostic factors. Another subgroup was identified in which a significant survival difference was not explained by multivariable methods. These are not unlikely examples in trials of a complex disease. Clinicians must exercise careful judgment in attributing such results to an efficacious therapy, as they may be due to chance or to inadequate baseline comparability of the groups.

Vectorcardiograms (VCG) from a consecutive group of 77 patients with significant aortic valve disease were analyzed. All of the patients had complete left and right heart catheterization with normal coronary arteriograms and normal left ventricular contraction. Thirty-five (46%) patients met VCG criteria for anterior myocardial infarction (AMI-35%) and/or inferior myocardial infarction (IMI-14%). This was a significant increase in false positive diagnosis for both criteria compared to a group of 200 normal volunteers under age 30 and 100 patients with normal hearts by cardiac catheterization (P less than 0.01). It was found that if the VCG diagnosis of myocardial infarction was deferred when the maximal transverse plane magnitude was greater than 1.9 mV, the incidence of AMI false positive diagnosis decreased to 3% and the incidence of IMI false positive diagnosis decreased to 1%. The same rule was applied to the aortic valve disease cohort, a group of 124 patients with documented AMI and a group of 158 patients with IMI. This decreased the sensitivity of the AMI criteria from 93 to 83% and of the IMI criteria from 85 to 77%. The increase in average performance was statistically significant fro the AMI criteria (P less than 0.05) but not for the IMI criteria.

The quantitative approaches to the assessment of regional left ventricular (LV) function described in the preceding paper were applied in a well-defined population of patients with coronary artery disease. Two groups were chosen by electrocardiographic and angiographic criteria: group 1 had infarction and regional wall motion abnormalities and group 2 had no infarction and normal wall motion. Sensitivity to detect wall motion defects, specificity to correctly categorize normal segments, and overall predictive accuracy were evaluated for each two-dimensional echocardiographic approach. In addition, the ability of each method to localize regional contraction defects properly was evaluated. Area methods yielded better predictive accuracy than linear methods (87-95% vs 76-84%). No significant differences in accuracy were noted between quadrant and octant approaches. The fixed external-axis system was superior to a floating one for localizing contraction defects. We conclude that an area-based method, using a fixed-axis system and either octant or quadrant image subdivision, provides the best combination of predictive accuracy in categorizing LV segments as normal or abnormal and the greatest ability to localize LV regional abnormalities.

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 (V cf ) during ejection at maximum wall stress, average = 1.01 circumferences/sec (circ/sec) (range 0.64-1.47 circ/sec). Maximum and mean V cf 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. The mean regurgitant volume was 41% of the total stroke volume, of which an average of 46% was ejected into the left atrium prior to aortic valve opening. The ejection fraction and extent of fiber shortening were normal in all but two patients despite depressed shortening velocities in most. It is concluded that analysis of velocity in the ejecting phase of left ventricular contraction is useful in detecting apparent alterations in inotropic state in the face of the altered loading conditions accompanying chronic mitral regurgitation. Further, favorable unloading conditions early during systole in patients with mitral regurgitation appear to mask the effects of a depressed inotropic state on the pumping function of the heart.

Left ventricular (LV) shape change during systole was characterized in nine patients with typical clinical findings of the systolic click syndrome (SCS) by means of cineangiographic measurements of three segmental diameters of the LV cavity and of the mitral valve ring (MVR) and contrasted with findings in eight patients with normal LV function. In the latter group, shortening of the proximal, midventricular, and apical segment diameters was comparable, averaging 38.6, 40.3, and 46.8%, respectively; MVR shortening averaged 31.8%. The velocity of fiber shortening, estimated as mean circumferential fiber shortening rate (mean FSR), was also similar in the three segments (1.66, 1.84, and 2.09 circ/sec). In patients with SCS, the extent of shortening and mean FSR in the proximal ventricular segment were consistently reduced (average 22.2%, P < 0.005; and 0.96 circ/sec, P < 0.025 respectively), and the MVR exhibited either reduced extent of contraction (four patients) or was unchanged or increased in diameter during systole (five patients). However, shortening of the midventricular and apical segments was normal, averaging 37.5 and 40.5%, respectively, as was the mean FSR in these segments (averages 1.60 and 1.70 circ/sec). These findings are consistent with a primary disorder of the myocardium in SCS localized to the inflow region of the left ventricle.

The results presented are just the beginning of an attempt to study the reactions of the left coronary circulation in the unanesthetized dog to natural stresses of everyday life. They indicate in mild to moderate treadmill exercise, with little change in stroke cardiac output, that the flow and oxygen usage per heart beat does not greatly increase, so that the coronary circulation appears to be largely limited or monitored by the heart rate. During excitement and cardiac sympathetic nerve stimulation, the left coronary vascular bed undergoes massive dilatation, so that the left ventricle is able to increase its coronary circulation as the result of the combined effect of an increased number of heart beats and a greatly increased flow and oxygen usage per heart beat, the latter occurring despite a marked reduction in the duration of systole and of the cardiac cycle, and very little change in the pressure developed by the left ventricle. Although the left ventricular contraction imposes a large myocardial impediment to coronary flow, it permits a very sizable and variable contribution to systolic flow and to left coronary flow. In the resting dog, the left coronary inflow in systole generally approximates 15 to 60 per cent of that during diastole, and under different stress conditions, such as exercise, excitement, drug injections and irreversible hemorrhagic shock, both the systolic and diastolic flow per heart beat can increase by 300 to 400 per cent, the ratio between them remaining the same, or, at times, the volume of systolic flow can equal or exceed the diastolic flow. Evidence has been presented to show that much of this systolic flow represents intramural flow. These findings will, I believe, cause some recasting of our present views concerning the regulation of the coronary circulation.

Intramyocardial pressure was followed with the Johnson-DiPalma method in isolated hearts and in hearts in situ. Systolic intramyocardial pressure curves from hearts in situ exhibited two pressure peaks which were believed to coincide with peak contractile tension and with myocardial fiber shortening, respectively. The following factors influenced intramyocardial pressure: ventricular cavity volume, heart rate, coronary perfusion pressure, outflow resistance, and "epicardial" compression. The contractile strength of the left ventricle varied in proportion with the intramyocardial pressure; it did not appear to be regulated primarily by diastolic volume or by metabolic support. Intramyocardial pressure was believed to determine the contractile strength of the heart by controlling the release of a potentiating substance.

The apexcardiogram was analyzed in 41 patients with an altered pattern of left ventricular contraction. Four types were distinguished: type I, an early sustained systolic bulge which occurred in 12 patients, all of whom had large aneurysms and large enddiastolic volumes; type II, a bulge confined to midsystole which occurred in 13 patients, 11 of whom had some form of ventricular asynergy; type III, a late or end-systolic bulge which occurred in 12 patients, seven of whom had ventricular asynergy; type IV, a prominent spike during diastolic filling which occurred in four patients who had large zones of ventricular asynergy.

Review of our first 180 consecutive patients undergoing myocardial revascularization surgery at the Peter Bent Brigham Hospital shows that the over-all surgical mortality was 5.5%. Mortality in patients not in shock at the time of operation was 2.3%. The only major determinant of surgical survival appeared to be adequacy of left ventricular contraction, as indicated primarily by an ejection fraction above 40%. Of 116 patients operated on for relief of chronic angina pectoris or the intermediate coronary syndrome, 71% were free of angina 6 to 24 months (average 8.9) after surgery. The aggregate operative and late mortality in this group during the period of follow-up was 4.3%.

The exercise induced frequent ventricular premature beat (VPB) usually indicates the presence of frequent and complex forms of VPB on 24-hr ambulatory monitoring. While it is commonly associated with coronary heart disease (CHD) with abnormalities of left ventricular contraction (LVC) it is not specific for this condition. In the context of CHD with LVC, frequent or complex VPB substantially increase the risk of sudden cardiac death. No therapy is known to reliably suppress VPB and thereby prevent sudden death.