Anterior Left Ventricular Free Wall Research Articles

Phosphorylation of GATA4 at serine 105 is required for left ventricular remodelling process in angiotensin II-induced hypertension in rats.

In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and the importance of phosphorylation at serine 105 (S105) for the actions of GATA4 in an angiotensin II (AngII)‐induced hypertension rat model. Adenoviral constructs overexpressing wild‐type GATA4 or GATA4 mutated at S105 were delivered into the anterior LV free wall. AngII (33.3 µg/kg/h) was administered via subcutaneously implanted minipumps. Cardiac function and structure were examined by echocardiography, followed by histological immunostainings of LV sections and gene expression measurements by RT‐qPCR. The effects of GATA4 on cultured neonatal rat ventricular fibroblasts were evaluated. In AngII‐induced hypertension, GATA4 overexpression repressed fibrotic gene expression, reversed the hypertrophic adult‐to‐foetal isoform switch of myofibrillar genes and prevented apoptosis, whereas histological fibrosis was not affected. Overexpression of GATA4 mutated at S105 resulted in LV chamber dilatation, cardiac dysfunction and had minor effects on expression of myocardial remodelling genes. Fibrotic gene expression in cardiac fibroblasts was differently affected by overexpression of wild‐type or mutated GATA4. Our results indicate that GATA4 reduces AngII‐induced responses by interfering with pro‐fibrotic and hypertrophic gene expressions. GATA4 actions on LV remodelling and fibroblasts are dependent on phosphorylation site S105.

Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study.

Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mechanisms remain unclear. Previous experimental and modeling studies have investigated some of these mechanisms, including stretch-activated membrane currents, reduced gap junctional conductance, and altered cell membrane capacitance. In order to quantify the relative contributions of these mechanisms, we combined a monomain model of rabbit ventricular electrophysiology with a hyperelastic model of passive ventricular mechanics. First, a simplified geometric model with prescribed homogeneous deformation was used to fit model parameters and characterize individual MEF mechanisms, and showed good qualitative agreement with experimentally measured strain-CV relations. A 3D model of the rabbit left and right ventricles was then compared with experimental measurements from optical electrical mapping studies in the isolated rabbit heart. The model was inflated to an end-diastolic pressure of 30 mmHg, resulting in epicardial strains comparable to those measured in the anterior left ventricular free wall. While the effects of stretch activated channels did alter epicardial conduction velocity, an increase in cellular capacitance was required to explain previously reported experimental results. The new results suggest that for large strains, various mechanisms can combine and produce a biphasic relationship between strain and conduction velocity. However, at the moderate strains generated by high end-diastolic pressure, a stretch-induced increase in myocyte membrane capacitance is the dominant driver of conduction slowing during ventricular volume loading.

False lumen stent placement during iatrogenic coronary dissection

A 38-year-old woman without significant cardiovascular risk factors was admitted in the coronary care unit with the diagnosis of acute coronary syndrome without ST-segment elevation. In coronary angiography, left coronary artery system was normal in the first contrast injection, but acute occlusion of the left main coronary trunk (LCT) due to iatrogenic dissection was observed in the following. The patient presented marked ST elevation, severe hypotension, hemodynamic collapse, and loss of consciousness. Cardiopulmonary resuscitation (CPR) was initiated, and two drug-eluting stents were consecutively placed in the LCT and the left anterior descending coronary (LAD), but the patient died after 60 min of continuous CPR. The autopsy showed dissection of the LCT and LAD coronaries with both stents placed in the false lumen and hyperacute myocardial infarction in the anterior left ventricular free wall. This case underlines the importance of careful indication of invasive procedures and of taking in consideration their potential risks.

Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat

The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodeling. Corresponding changes in three-dimensional organization of cardiac extracellular matrix have not been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and morphological data, brain natriuretic peptide levels, and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure, and decompensated HF. Passive left ventricular (LV) pressure-volume relationships were determined in vitro. Transmural specimens from the anterior LV free wall were imaged using extended-volume confocal microscopy, and three-dimensional myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 mo and increased progressively thereafter. However, it was less than in controls for filling pressures <10 mmHg and not significantly different at ≥10 mmHg. Myocyte cross section was enlarged, with increased variability from 12 mo, while collagen fraction increased progressively. Perimysial collagen fraction remained unchanged with age, although endomysial collagen increased from 12 mo. Perimysial collagen between adjacent muscle layers fused at 12 mo and continued to thicken subsequently, while muscle layers became more dispersed and disordered. We conclude that LV dilatation, which accompanies decompensated HF in this model of HHD, is not due to LV "softening." While perimysial (and endomysial) collagen networks are substantially remodeled, they are not dissolved, as has been proposed. We argue that progressive disruption of the laminar organization of LV myocardium may contribute to impaired systolic function in HHD.

Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation

Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.

Hypertrophic Cardiomyopathy Phenotype Revisited After 50 Years With Cardiovascular Magnetic Resonance

Our purpose was to characterize the pattern and distribution of left ventricular (LV) hypertrophy by cardiovascular magnetic resonance (CMR) to more precisely define phenotypic expression and its clinical implications in hypertrophic cardiomyopathy (HCM). Based on prior pathologic and 2-dimensional echocardiographic studies, HCM has been regarded as a disease characterized by substantial LV wall thickening. Cine and late gadolinium enhancement CMR were performed in 333 consecutive HCM patients (age 43 +/- 17 years). Basal anterior LV free wall and the contiguous anterior ventricular septum were the most commonly hypertrophied segments (n = 256; 77%). LV hypertrophy was focal (involving < or = 2 segments [< or = 12% of LV]) in 41 patients (12%), intermediate (3 to 7 segments [13% to 49% of LV]) in 112 patients (34%), and diffuse (> or = 8 segments [> or = 50% of LV]) in 180 patients (54%); 42 patients (13%) showed hypertrophied segments separated by regions of normal thickness. The number of hypertrophied segments was greater in patients with LV outflow tract obstruction (> or = 30 mm Hg) than without (10 +/- 4 vs. 8 +/- 4 per patient; p = 0.0001) and was associated with an advanced New York Heart Association functional class (p = 0.007). LV wall thickness was greater in segments with late gadolinium enhancement than without (20 +/- 6 mm vs. 16 +/- 6 mm; p < 0.001). We also identified 40 (12%) of HCM patients with segmental LV hypertrophy largely confined to the anterolateral free wall, posterior septum, or apex, which was underestimated or undetected by echocardiography. Although diverse, patterns of LV hypertrophy are usually not extensive in HCM, involving < or = 50% of the chamber in about one-half the patients, and are particularly limited in extent in an important minority. Contiguous portions of anterior free wall and septum constituted the predominant region of wall thickening, with implications for clinical diagnosis. These observations support an emerging role for CMR in the contemporary evaluation of patients with HCM.

Role of tissue structure on ventricular wall mechanics.

It is well known that systolic wall thickening in the inner half of the left ventricular (LV) wall is of greater magnitude than predicted by myofiber contraction alone. Previous studies have related the deformation of the LV wall to the orientation of the laminar architecture. Using this method, wall thickening can be interpreted as the sum of contributions due to extension, thickening, and shearing of the laminar sheets. We hypothesized that the thickening mechanics of the ventricular wall are determined by the structural organization of the underlying tissue, and may not be influenced by factors such as loading and activation sequence. To test this hypothesis, we calculated finite strains from biplane cineradiography of transmural markers implanted in apical (n = 22) and basal (n = 12) regions of the canine anterior LV free wall. Strains were referred to three-dimensional laminar microstructural axes measured by histology. The results indicate that sheet angle is of opposite sign in the apical and basal regions, but absolute value differs only in the subepicardium. During systole, shearing and extension of the laminae contribute the most to wall thickening, accounting for >90% (transmural average) at both apex and base. These two types of deformation are also most prominent during diastolic inflation. Increasing afterload has no effect on the pattern of systolic wall thickening, nor does reversing transmural activation sequence. The pattern of wall thickening appears to be a function of the orientation of the laminar sheets, which vary regionally and transmurally. Thus, acute interventions do not appear to alter the contributions of the laminae to wall thickening, providing further evidence that the structural architecture of the ventricular wall is the dominant factor for its regional mechanical function.

Intramural Foci During Long Duration Fibrillation in the Pig Ventricle

For more than 50 years, it has been assumed that ventricular fibrillation (VF) is maintained solely by reentry in the working myocardium. This hypothesis has never been tested by recording VF with electrodes spaced sufficiently close to map activation sequences in 3D. We recorded the first 10 minutes of electrically induced VF from the anterior left ventricular (LV) free wall near the insertion of the anterior papillary muscle in 6 pigs. A 3D transmural unipolar electrode array consisting of a 9x9 array of needles with 2-mm spacing and 6 electrodes 2 mm apart on each needle was used for recordings. Automatic analyses were performed to recognize 3D reentry and foci. Our results showed that intramural reentry is present early but not late during VF in the mapped region. The incidence of reentry in working myocardium decreases almost to 0 after 3 minutes of VF. In contrast, intramural foci are present during early VF and, as VF continues, increase in incidence, so that by 10 minutes of VF, 27% of wavefronts arise from intramural foci. These results suggest that, particularly after the first 3 minutes of VF, mechanisms other than local reentry in the working myocardium maintain VF in the anterior LV free wall near the root of the anterior papillary muscle. Intramural foci may play an important role in later VF maintenance. It remains to be determined if these foci arise from Purkinje fibers attributable to abnormal automaticity, afterdepolarizations, or reentry.

Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium.

Previous studies suggest that the laminar architecture of left ventricular myocardium may be critical for normal ventricular mechanics. However, systolic three-dimensional deformation of the laminae has never been measured. Therefore, end-systolic finite strains relative to end diastole, from biplane radiography of transmural markers near the apex and base of the anesthetized open-chest canine anterior left ventricular free wall (n = 6), were referred to three-dimensional laminar microstructural axes reconstructed from histology. Whereas fiber shortening was uniform [-0.07 +/- 0.04 (SD)], radial wall thickening increased from base (0. 10 +/- 0.09) to apex (0.14 +/- 0.13). Extension of the laminae transverse to the muscle fibers also increased from base (0.08 +/- 0. 07) to apex (0.11 +/- 0.08), and interlaminar shear changed sign [0. 05 +/- 0.07 (base) and -0.07 +/- 0.09 (apex)], reflecting variations in laminar architecture. Nevertheless, the apex and base were similar in that at each site laminar extension and shear contributed approximately 60 and 40%, respectively, of mean transmural thickening. Kinematic considerations suggest that these dual wall-thickening mechanisms may have distinct ultrastructural origins.

Isolated left ventricular myocyte contractility in patients undergoing cardiac operations

Background: Because of methods required for obtaining isolated left ventricular myocytes, evaluation of the contractile function of isolated left ventricular myocytes in normal human patients has been limited. Accordingly, the goal of the present study was to develop a means to isolate human left ventricular myocytes from small myocardial biopsy specimens collected from patients undergoing elective coronary artery bypass operations and to characterize indices of myocyte contractile performance. Methods: Myocardial biopsy specimens were obtained from the anterior left ventricular free wall of 22 patients undergoing coronary artery bypass operations. Myocytes were isolated from these myocardial samples by means of a stepwise enzymatic digestion method and micro-trituration techniques. Isolated left ventricular myocyte contractile function was assessed by computer-assisted high-speed videomicroscopy under basal conditions and in response to β-adrenergic receptor stimulation with isoproterenol. Results: A total of 804 viable left ventricular myocytes were successfully examined from all of the myocardial biopsy specimens with an average of 37 ± 4 myocytes per patient. All myocytes contracted homogeneously at a field stimulation of 1 Hz with an average percent shortening of 3.7% ± 0.1% and shortening velocity of 51.3 ± 1.3 μm/s. After β-adrenergic receptor stimulation with isoproterenol, percent shortening and shortening velocity increased 149% and 118% above baseline, respectively ( P < .05). Conclusion: The unique results of the present study demonstrated that a high yield of myocytes could be obtained from human left ventricular biopsy specimens taken during cardiac operations. These myocytes exhibited stable contractile performance and maintained the capacity to respond to an inotropic stimulus. The methods described herein provide a basis by which future studies could investigate intrinsic and extrinsic influences on left ventricular myocyte contractility in human beings. (J Thorac Cardiovasc Surg 1998;116:495-502)

Intramural (“small vessel”) coronary artery disease in hypertrophic cardiomyopathy

Many patients with hypertrophic cardiomyopathy have signs and symptoms of myocardial ischemia and dysfunction. Although hypertrophy and increased left ventricular pressure can account for such abnormalities, altered small intramural coronary arteries have also been described in such patients. To determine the prevalence and extent as well as the clinical relevance of abnormal intramural coronary arteries, a histologic analysis of left ventricular myocardium obtained at necropsy was performed in 48 patients with hypertrophic cardiomyopathy (but without atherosclerosis of the extramural coronary arteries) and in 68 control patients with either a normal heart or acquired heart disease. In hypertrophic cardiomyopathy, abnormal intramural coronary arteries were characterized by thickening of the vessel wall and a decrease in luminal size. The wall thickening was due to proliferation of medial or intimal components, or both, particularly smooth muscle cells and collagen. Of the 48 patients with hypertrophic cardiomyopathy, 40 (83%) had abnormalities of intramural coronary arteries located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (9 patients); an average of 3.0 +/- 0.7 abnormal arteries were identified per tissue section. Altered intramural coronary arteries were also significantly more common in tissue sections having considerable myocardial fibrosis (31 [74%] of 42) than in those with no or mild fibrosis (31 [30%] of 102; p less than 0.001). Abnormal intramural coronary arteries were also identified in three of eight infants who died of hypertrophic cardiomyopathy before 1 year of age. In contrast, only rare altered intramural coronary arteries were identified in 6 (9%) of the 68 control patients (0.1 +/- 0.05 abnormal arteries per section; p less than 0.001) and those arteries showed only mild thickening of the wall and minimal luminal narrowing. Moreover, of those patients with abnormal intramural coronary arteries, such vessels were about 20 times more frequent in patients with hypertrophic cardiomyopathy (0.9 +/- 0.2/cm2 myocardium) than in control patients (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal intramural coronary arteries with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with hypertrophic cardiomyopathy studied at necropsy and may represent a congenital component of the underlying cardiomyopathic process.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of retrograde perfusion of cardioplegic solution in cardiac operations

The effects of continuous retrograde coronary perfusion of a cardioplegic solution were investigated in 42 patients. From each patient, a needle biopsy was taken on the anterior left ventricular free wall during cardiac operations and investigated by electron microscopy. With the use of our well-standardized ultrastructural criteria of ischemic injury, we found that the retrograde perfusion technique provides cardiac protection of a quality superior to that of antegrade perfusion. This finding applied to the state of the myocardial cells. The cardiac microvessels, on the other hand, were more severely injured by retrograde perfusion, and extracellular edema occurred more frequently. It is concluded, therefore, that the retrograde perfusion of a crystalline cardioplegic solution during cardiac operation has beneficial effects on the preservation of myocardial cells in comparison to the antegrade application. Unfortunately, we also conclude that the occurrence of extracellular edema and of microvascular damage represents a serious drawback in the clinical use of this method. This technique, therefore, needs to be improved before it may routinely be applied in patients undergoing cardiac operations.

Right ventricular infarction with electrocardiographic anterior left ventricular infarction and thrombosis of the left anterior descending coronary artery

At necropsy, right ventricular (RV) myocardial infarction secondary to coronary artery disease is observed only in patients with left ventricular (LV) infarction involving the LV posterior (inferior) wall. 1,2 The implication of this observation, of course, is that patients with electrocardiographic evidence of anterior wall LV infarction are spared from RV infarction. Although few reports describing patients with anatomically confirmed RV infarction have illustrated an electrocardiogram, 1–4 it is likely that more than 95% of patients with RV infarction have electrocardiographic evidence of posterior (inferior) LV infarction only. An occasional patient with electrocardiographic evidence of anterior wall myocardial infarction, however, has RV infarction. How can this be? The answer, demonstrated in the patient described herein, is: If the electrocardiogram indicates anterior wall LV infarction, but necropsy also shows RV infarction, the LV infarction in the basal third or so of the LV free wall is limited to the anterior LV free wall with or without involvement of the anterior portion of ventricular septum or lateral LV free wall or both; in the mid or apical third, or both, of the LV wall, however, the LV infarct is circumferential, or nearly so, such that the posterior (inferior) LV wall and posterior portion of ventricular septum indeed is infarcted. The RV infarct then represents an extension from the posterior portion of the ventricular septum.

Regional circumferential lengthening patterns in canine left ventricle.

We employed sonomicrometers in open-chest dogs to study lengthening of short segments of circumferentially oriented myocardium located at the base, midportion, and apex of the anterior left ventricular free wall. Left ventricular pressure was varied by inferior vena caval occlusion and volume expansion. Diastole was divided into rapid and slow lengthening phases. Rapid lengthening was completed first at the basal site at each of three successive levels of left ventricular diastolic pressure (LVDP). At the base, significant further lengthening occurred during the slow lengthening phase while at the apex virtually all lengthening was completed during the rapid phase. At low LVDPs, peak lengthening rates (dl/dt) were greatest at the apex. As LVDP was increased, regional differences in dl/dt diminished. These results indicate that there is regional variation in the timing of the phases of diastole and in lengthening patterns of the left ventricle. The volume-dependent variation in lengthening rates that we observed is consistent with the concept of regional differences in elastic recoil, which may contribute to active ventricular filling.

Regional dysfunction of the interventircular septum during acute coronary artery occlusion.

To compare the effects of local myocardial ischaemia on the dynamics of different portions of the interventricular septum (IVS), pairs of miniature ultrasonic crystals were implanted across the anterior and posterior portion of the IVS and the left ventricular free wall (LVFW) to measure wall thickness changes in open chest dogs. Following left anterior descending coronary artery (LAD) occlusion, the end-diastolic wall thickness decreased in all areas indicating significant chamber dilation. Systolic thickening was reduced from 19.2% to 0.8% in the anterior LVFW and from 16.0% to 4.1% in the anterior IVS, while a significant increase in thickening occurred in the posterior LVFW (from 17.1% to 21.0%) and in the posterior IVS (from 13.6% to 16.5%). Left circumflex artery (LCx) occlusion produced a greater distension of the ischaemic free wall and the magnitude of responses tended to be less in the IVS than in the free wall (percentage thickening being reduced from 15.3% to 7.2% in the posterior IVS, and from 17.4% to -4.4% in the posterior LVFW). Enhancement of the systolic thickening of the normal perfused area was more marked with LCx occlusion than with LAD occlusion. Percentage thickening increased from 19.0% to 26.9% in the anterior LVFW and from 17.2% to 28.6% in the anterior IVS. These findings indicate that the ischaemic responses of the IVS, as induced by ischaemia differed in the anterior and posterior portion of the septum. Thus, when attempting to assess clinical echocardiographic findings of an ischaemic septum, one should take into account these regional differences with regard to which area of the septum the ultrasonic beam had passed.

Regional myocardial dimensions following coronary artery bypass grafting in patients

The direct relationship between graft flow and regional midwall myocardial function has not been documented in patients. Therefore, the present study was designed to quantitate the effects of coronary artery bypass grafting on regional myocardial mechanics distal to a coronary artery obstruction. Twenty-one patients with subtotal or total occlusion of the left anterior descending (LAD) coronary artery underwent coronary artery bypass grafting. Following completion of the aortic and coronary anastomoses, two miniature ultrasonic dimension transducers (2.5 mm. diameter) were positioned within the minor axis of the anterior left ventricular free wall and were allowed complete freedom of movement. The transducers were placed at midwall depth, and areas of clinically apparent myocardial fibrosis were not utilized as sites of implantation. During control, 30 minutes following the termination of cardiopulmonary bypass, regional myocardial dimensions, pulmonary artery diastolic pressure, arterial pressure, and heart rate were recorded with all saphenous vein grafts open and after 30 seconds of single vein graft occlusion. These measurements were repeated during atrial pacing at a rate of 128 +/- 4 beats per minute. Data are mean +/- the standard error of the mean. During control, graft occlusion resulted in a regional decrease in systolic excursion from 1.3 +/- 0.1 to 1.0 +/- 0.2 mm. (p less than 0.01), as well as a decrease in the rate of shortening from 8.7 +/- 0.2 to 6.2 +/- 1.1 mm. per second (p less than 0.05); heart rate, mean arterial pressure, and diastolic pulmonary artery pressure remained unchanged. Graft occlusion with atrial pacing resulted in an exaggerated decrease in both regional systolic excursion, from 1.2 +/- 0.2 to 0.6 +/- 0.2 mm. (p less than 0.01), and rate of shortening, from 9.4 +/- 1.5 to 4.4 +/- 0.2 mm. per second (p less than 0.01). For the group of patients studied, end-diastolic lengths were unchanged with graft occlusion during control and atrial pacing. Moreover, with graft occlusion, isolated patients demonstrated regional dyskinesia as evidenced by holosystolic bulging. These studies in patients have documented for the first time that, despite a constant preload, afterload, and heart rate, regional myocardial function following coronary artery bypass grafting is dependent upon adequate graft flow, especially during stress.

In situ measurement of papillary muscle dynamics in the dog left ventricle.

In five open-chest dogs, pairs of ultrasonic dimension gauges were implanted in the anterior papillary muscle and in a circumferential subendocardial segment of the anterior left ventricular free wall, and simultaneous recordings were made with intracardiac pressure. The average shortening of the anterior segment in isovolumetric systole was 6% of end-diastolic length (EDL), with a total shortening of 19%. In the papillary muscles, isovolumetric shortening averaged 2%, total shortening was 10%, and shortening velocity was only 0.60 length/s. With acute pressure and volume overload, or inotropic interventions, changes in EDL were relatively less in papillary muscles than in the free wall. During acute occlusion of the anterior descending coronary artery, shortening of anterior segments and papillary muscles was replaced by holosystolic lengthening, and occlussion of the circumflex artery produced augmentation of shortening in both these regions, with lengthening of the posterior papillary muscle. The present study documents shortening of the anterior left ventricular papillary muscle throughout systole that is substantially less than that of the circumferential free wall, and demonstrates severe papillary muscle dysfunction with systolic elongation during regional ischemia.

Electrocardiographic changes associated with papillary muscle infarction in congenital heart disease

The electrocardiograms of 18 infants and children with congenital heart disease (4 with aortic stenosis and 14 with total anomalous pulmonary venous connection) and necropsy evidence of infarction of the papillary muscle or free wall, or both, were reviewed. In the presence of left ventricular hypertrophy, a Q wave in lead V 3R followed by a small R wave is strong evidence of infarction of the anterior left papillary muscle or anterior left ventricular free wall, or both. When associated with serially diminishing amplitude of the R wave in lead V 3R this is diagnostic of infarction. In the presence of right ventricular hypertrophy a Q wave in lead V 3R may be due to the hypertrophy. The finding of a serially diminishing R wave in this lead, however, is evidence of infarction of the anterior right papillary muscles or anterior right ventricular free wall. Hence, with left ventricular hypertrophy or right ventricular hypertrophy a Q wave in lead V 3R assumes diagnostic significance for infarction when accompanied by a diminishing R wave amplitude over the right precordial leads.