A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1-1q1.

Longitudinal evaluation of a seven generation kindred with an inherited conduction system defect and dilated cardiomyopathy demonstrated autosomal dominant transmission of a progressive disorder that both perturbs atrioventricular conduction and depresses cardiac contractility. To elucidate the molecular genetic basis for this disorder, a genome-wide linkage analysis was performed. Polymorphic loci near the centromere of chromosome 1 demonstrated linkage to the disease locus (maximum multipoint lod score = 13.2 in the interval between D1S305 and D1S176). Based on the disease phenotype and map location we speculate that gap junction protein connexin 40 is a candidate for mutations that result in conduction system disease and dilated cardiomyopathy.

Prevention of bedrest-induced physical deconditioning by daily dobutamine infusions. Implications for drug-induced physical conditioning.

The effects of intermittent infusions of dobutamine were studied in young normal male subjects during a period of bedrest deconditioning to determine whether this synthetic catechol affects physical conditioning processes in humans. 24 volunteers were placed at bedrest and randomized to daily 2-h treatments of saline infusions (control), dobutamine infusions, or maintenance exercise (control). Exercise, hemodynamic, and metabolic studies were performed at base line and at the termination of the 3-wk treatment period. Maximal exercise (duration, oxygen consumption, and workload) fell for the saline group and remained unchanged for the dobutamine and exercise groups. Hemodynamics during exercise were maintained the same as pretreatment base line for the dobutamine and exercise groups, whereas stroke volume and cardiac output dropped and heart rate rose for the saline group. The metabolic profile showed an increased blood lactate response at rest and during submaximal exercise after 3 wk of bedrest for the saline group, and essentially no change for the exercise and the dobutamine groups. Extraction of oxygen across the exercising lower limb rose for the dobutamine group, as did the activity of the skeletal muscle oxidative enzymes, citrate synthetase, and succinate dehydrogenase. In contrast to the exercise control group, the saline and dobutamine groups developed orthostatic hypotension, tachycardia, and accentuation of the renin-aldosterone response over the 3-wk treatment period; for the saline group, this is best explained by the observed fall in blood volume and for the dobutamine group, by the blunting of vascular vasoconstrictive responses. During a period of bedrest deconditioning in humans, infusions of dobutamine maintain many of the physiologic expressions of physical conditioning.

Atrial septal defect: attenuation of respiratory variation in systolic and diastolic time intervals.

The effects of pathologic states on right and left ventricular function have been studied extensively. However, there have been few studies on the interrelations between right and left ventricular function in normal human subjects and in patients with disease. Respiratory effects on ventricular interrelations reflected by diastolic time, right or left ventricular systolic time and ventricular performance (pre-ejection period/ejection time ratio) were studied in 12 normal subjects and 15 patients with a normal pressure-large shunt atrial septal defect. Simultaneous pulmonary artery (intracardiac manometer recordings) and left ventricular external recordings were performed in both groups. Left ventricular diastolic time increased with inspiration in the normal subjects and decreased in the patients with atrial septal defect (12.6 +/- 2.39 [1 SE] versus -13.4 +/- 3.48 ms, p less than 0.001). Left ventricular systolic time and ejection time decreased with inspiration in the normal group and remained unchanged in the patient group (-7.6 +/- 0.95 versus -0.9 +/- 0.77 ms, p less than 0.001 and -10.4 +/- 1.09 versus -1.7 +/- 0.80 ms, p less than 0.001, respectively). Left ventricular pre-ejection period/ejection time ratio increased with inspiration in the normal subjects and remained unchanged in the patients with atrial septal defect (0.03 +/- 0.008 versus 0 +/- 0.01, p less than 0.01). Right ventricular diastolic time decreased with inspiration in normal and patient groups (-8.8 +/- 1.6 versus -17 +/- 3.87 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Postural exercise abnormalities in symptomatic patients with mitral valve prolapse.

The hemodynamics of the supine and upright exercise response in 16 symptomatic women with mitral valve prolapse (Group I) was compared with that in 8 asymptomatic normal control women (Group II). All subjects had supine and upright echocardiography and phonocardiography at rest and none demonstrated mitral regurgitation. All participants then underwent same day graded bicycle exercise, with simultaneous radionuclide angiography in both the upright and the supine posture. Catecholamines were measured, and a variety of volumetric and hemodynamic data were obtained. Group I (patients with mitral valve prolapse) demonstrated a reduced exercise tolerance, especially during upright exercise, as measured by both total exercise duration and maximal work load achieved. Mean total catecholamine measurements were similar between the two study groups at comparable mean heart rate, mean blood pressure and mean rate-pressure (double) product. No difference was observed in the ratio of right to left ventricular stroke counts at rest or during exercise regardless of posture, suggesting that exercise-induced mitral regurgitation did not occur. A difference was noted, however, in left ventricular end-diastolic volume index. At rest, Group I patients exhibited a 42% decrease in this index when sitting upright, and this difference from supine values persisted at submaximal (300 kpm/min) and peak work loads (34 and 29% difference, respectively). This contrasted with the control subjects whose upright end-diastolic volumes at rest, at 300 kpm/min and at peak exercise were reduced 21, 10 and 3%, respectively, compared with supine values. Cardiac index measurements reflected the reduced left ventricular end-diastolic volume observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The Marfan syndrome: abnormal aortic elastic properties.

Aortic distensibility and aortic stiffness index were measured at the ascending aorta (3 cm above the aortic valve) and the mid-portion of the abdominal aorta from the changes in echocardiographic diameters and pulse pressure in 14 patients with the Marfan syndrome and 15 age- and gender-matched normal control subjects. The following formulas were used: 1) Aortic distensibility = 2(Changes in aortic diameter)/(Diastolic aortic diameter) (Pulse pressure); and 2) Aortic stiffness index = ln(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic diameter)/Diastolic aortic diameter. Pulse wave velocity was also measured. Compared with normal subjects, patients with the Marfan syndrome had decreased aortic distensibility in the ascending and the abdominal aorta (2.9 +/- 1.3 vs. 5.6 +/- 1.4 cm2 dynes-1, p less than 0.001 and 4.5 +/- 2.1, vs. 7.7 +/- 2.5, cm2 dynes-1, p less than 0.001, respectively) and had an increased aortic stiffness index in the ascending and the abdominal aorta (10.9 +/- 5.6 vs. 5.9 +/- 2.2, p less than 0.005 and 7.1 +/- 3.1 vs. 3.9 +/- 1.2, p less than 0.005, respectively). Aortic diameters in the ascending aorta were larger in these patients than in normal subjects, but those in the abdominal aorta were similar in the two groups. Linear correlations for both aortic distensibility and stiffness index were found between the ascending and the abdominal aorta (r = 0.85 and 0.71, respectively). Pulse wave velocity was more rapid in the patients than in the normal subjects (11.6 +/- 2.5 vs. 9.5 +/- 1.4 m/s, respectively, p less than 0.01). Thus, aortic elastic properties are abnormal in patients with the Marfan syndrome irrespective of the aortic diameter, which suggests an intrinsic abnormality of the aortic arterial wall.

Clinical characteristics of sudden death victims in heritable (chromosome 1p1-1q1) conduction and myocardial disease.

OBJECTIVES: The purpose of this study was to identify the clinical characteristics of family members at risk of sudden death. BACKGROUND: The significance of sudden death in heritable cardiac disorders with delayed expression is incompletely understood. Additional insights come from a four-decade experience of seven generations of a family of German origin with autosomal dominant (chromosome 1p1-1q1) cardiac conduction and myocardial disease. METHODS AND RESULTS: A total of 38 family members (20 males; 18 females) were identified with sudden death. Twenty-eight family members (mean age 48+/-8 years) from earlier generations had no pacemaker at the time of sudden death. In this group, 15 subjects were asymptomatic prior to sudden death. Ten family members with sudden death, from later generations, had chronically implanted pacemakers for high grade atrioventricular block. This group was older (mean age 57+/-2 years), with decreased functional status (New York Heart Association class II to IV), enlarged left atria, dilated left ventricles with reduced systolic function and documented ventricular fibrillation in three members. Twenty-eight family members with sudden death were descendants of sib lineages 2 or 6; 21 family members with sudden death were offspring of a parent who also suffered sudden death. CONCLUSION: Sudden death is an important late outcome in heritable (chromosome 1p1-1q1) cardiac conduction and myocardial disease. Pacemaker therapy is important for the treatment of symptomatic bradycardia, but it does not prevent sudden death. Family members who are beyond the third decade of life with reduced functional capacity, left ventricular dysfunction, pacemakers and who are the offspring of a parent with sudden death appear to be at greatest risk

Medial necrosis and acute alterations in aortic distensibility following removal of the vasa vasorum of canine ascending aorta.

OBJECTIVE: It is known that the outer layers of the thoracic aorta receive substantial blood flow through vasa vasorum. This study was undertaken to test the hypothesis that removal of vasa vasorum flow will alter the elastic properties of the ascending aorta. METHODS: Distensibility of the ascending aorta was determined before and 30 min after careful removal of the periaortic fat network which contains the vasa vasorum in 10 acutely instrumented dogs (experimental group) and the results were compared with those obtained from six weight matched sham operated control dogs. Aortic distensibility was measured using the formula: distensibility = 2 x pulsatile changes in aortic diameter divided by (diastolic aortic diameter x pulse pressure). Aortic pressures were measured directly from the ascending aorta by a pressure gauge. Aortic diameters were simultaneously determined by an elastic air filled ring connected to a transducer. The efficacy of the technique for the interruption of vasa vasorum blood supply to the aortic wall was proved in six additional animals by histology of transverse blocks of aortic wall from the area of interest. Histology was performed before vasa vasorum removal in two animals, 30 min after vasa vasorum removal in another two, and 15 d after vasa vasorum removal in the remainder. RESULTS: At baseline, there was no difference in the measured variables between the two groups. Aortic distensibility decreased significantly in the experimental group after vasa vasorum removal by 0.90(SEM 0.17) 10(-6).cm2.dyn-1 (p < 0.001), while it remained unchanged in the control group during the experiment. Complete removal of vasa vasorum of the ascending aorta was found in experimental group animals which were killed 30 min after operation, while ischaemic medial necrosis was observed in those killed 15 d after operation. CONCLUSIONS: Vasa vasorum removal led to an acute decrease in the distensibility of the ascending aorta. Lack of blood supply to the outer part of the aortic wall is most likely to have accounted for these findings.

Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep.

Symptoms suggesting autonomic instability and increased adrenergic effect were identified in 53 patients with primary disorders of impaired wakefulness. Urine and plasma catecholamine concentrations were significantly increased in patients with sleep apnea. Excessive increases in heart rate during isoproterenol infusions suggested adrenergic hyperresponsiveness as an alternative explanation for symptoms of catecholamine excess in some individuals. Twenty-two patients demonstrated mitral valve prolapse (MVP), implicating primary neurologic disturbances as potential factors in the fatigue and lassitude often associated with MVP. The catecholamine abnormalities may explain some of the difficulties frequently encountered in using stimulants to treat sleep disorders.

Sleep apnea: treatment with protriptyline.

Fourteen patients with an average of more than 60 episodes of upper airway obstruction during night sleep were treated with a nonsedating tricyclic antidepressant, protriptyline. Frequency and duration of recorded apneas decreased in 11 cases, and satisfactory control of sleep apnea was maintained with medical therapy alone in 8 of these 11 patients for 7 to 15 months. Potential adverse effects of protriptyline, particularly on the cardiovascular system, limit its use in this illness. These results indicate the possibility of pharmacologic reversal of sleep-induced incoordination of the upper airway.

Cardiovascular disease of connective tissue origin.

Inherited abnormalities of connective tissue elements often cause changes in the structure and function of the cardiovascular system. Well-known heritable disorders of connective tissue in which cardiovascular abnormalities are prominent include the Marfan syndrome and the Ehlers-Danlos syndrome. Connective tissue abnormalities also occur without the associated features of a recognized syndrome. These include isolated valvular prolapse and anuloaortic ectasia. In this review, the cardiovascular features of connective tissue abnormalities--both the recognized syndromes and the isolated abnormalities--are described, important concepts in the diagnosis and treatment of these disorders are reviewed, and the classification of inherited connective tissue abnormalities of the cardiovascular system is discussed.

Ascending aorta distensibility abnormalities in hypertensive patients and response to nifedipine administration.

PURPOSE: The purpose of the present investigation was to study the distensibility of the ascending aorta in patients with arterial hypertension and normal subjects before and after administration of a calcium antagonist, nifedipine. PATIENTS AND METHODS: The distensibility of the ascending aorta was measured before and after nifedipine administration in 22 male hypertensive patients and 12 age-matched male normotensive subjects. Aortic distensibility was calculated as a function of changes in aortic diameter and pulse pressure, using the formula: 2 x (pulsatile change in aortic diameter)/[(diastolic aortic diameter) x (aortic pulse pressure)]. Aortic diameters were measured by echocardiography and aortic pressures were obtained by catheterization of the ascending aorta. RESULTS: In the basal state, the distensibility of the ascending aorta and aortic strain were lower in hypertensive patients than in normotensive subjects (p < 0.001); the lower aortic distensibility, however, was associated with a greater distending pressure. A good inverse correlation (r = -0.81) was found between mean aortic pressure and aortic distensibility. The aortic distensibility was increased after nifedipine administration in both groups; this increase in aortic distensibility, however, was lower in the patients with hypertension compared with normotensive subjects (p < 0.001). CONCLUSIONS: Aortic distensibility is decreased in patients with arterial hypertension. Nifedipine administration increased the distensibility of the ascending aorta both in patients with arterial hypertension and in normotensive subjects. The increase of aortic distensibility after nifedipine administration was lower in hypertensive patients.

Left ventricular mass and systolic performance in chronic systemic hypertension.

This study was undertaken to define the relation between the extent of left ventricular (LV) hypertrophy and ventricular systolic performance in patients with chronic systemic hypertension. Ninety patients with chronic systemic hypertension were compared with 41 normal subjects as determined by angiography. LV mass was estimated from the M-mode echocardiogram. Patients were separated into 3 groups: those with LV mass of less than 2 (group I, n = 58), 2 to 4 (group II, n = 21) and more than 4 (group III, n = 11) standard deviations above mean normal. The ratio of preejection period to LV ejection time (PEP/LVET), percent shortening of the echocardiographic internal diameter (% delta D) and velocity of circumferential shortening (Vcf) were used as indexes of LV systolic performance. The frequency of abnormality, expressed as percent of patients in groups I, II and III, was 33%, 55% and 85% for PEP/LVET, 15%, 35% and 72% for % delta D, and 0%, 15% and 55% for Vcf. For each group PEP/LVET was the most frequently abnormal measure and Vcf was the least frequent abnormality. Calculation of peak and end-systolic wall stress was used as an index of the adequacy of LV hypertrophy. This index was significantly reduced in group I, did not differ from control in group II and was significantly increased in group III, indicating that hypertrophy was appropriate to wall tension in groups I and II. It is concluded that the occurrence of LV dysfunction with increasing LV mass in patients with moderate LV hypertrophy (group I and II) reflects a deficiency in intrinsic contractile performance of the hypertrophied myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction.

Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (p<0.001), with maximal effect on the ratio (p<0.0001) between 02.00 to 04.00 A.M., 08.00 to 11.00 A.M., and 19.00 to 22.00 P.M. (delta% ratio -30%, -32%, and -26%, respectively). Metoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, p<0.001). Heart rate variability indexes in the placebo group and controls remained unchanged 30 days after the baseline study. In conclusion, quinapril increased parasympathetic, and decreased sympathetic and partially restored sympathovagal interaction in patients with uncomplicated AMI during the entire 24-hour period, with peak effect in the early and late morning and evening hours. Metoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.

Usefulness of systolic time intervals in coronary artery disease.

This review summarizes current knowledge concerning the value of systolic time intervals in coronary artery disease. Although the usual pattern of prolongation of the preejection period (PEP) and shortening of the left ventricular ejection time (LVET) characteristic of left ventricular failure is seen in acute myocardial infarction, the systolic time intervals (as well as all other measures) are profoundly influenced by adrenergic hyperactivity characteristics of this disorder. Adrenergic stimulation normally shortens both the PEP and LVET indexes and decreases the PEP/LVET ratio. The degree of shortening of electromechanical systole (QS2) is directed related to the excessive adrenergic tone. Patients with the greatest systolic time interval abnormalities have a poorer prognosis, a greater incidence of congestive heart failure and more abnormalities of directly measured indexes of left ventricular performance. The systolic time intervals are useful for assessing left ventricular performance in chronic coronary artery disease as well. In chronic coronary artery disease the PEP/LVET ratio and angiographically determined left ventricular ejection fraction are closely correlated ( r = -0.76), but the level of this correlation is less than that in other forms of left ventricular disease. The left ventricular ejection time index is prolonged after exercise in patients with angina pectoris when compared with findings in normal subjects. Failure of the ischemic ventricle to respond to adrenergic stimulation is the most likely mechanism. Addition of the postexercise left ventricular ejection time to standard treadmill stress testing identifies a significant number of patients (23 percent) who would have had false negative results by electrocardiographic criteria alone. In addition, this index provides confirmatory evidence in those with apparently positive electrocardiographic test data. The systolic time intervals have been useful in assessing both medical and surgical therapy in coronary artery disease. The test can be performed repeatedly and provides a measure of both left ventricular performance and extent of adrenergic hyperactivity. Thus, evaluation of therapy represents the most useful future application of systolic time intervals.

The equilibrium position of the mitral valve: an accurate model of mitral valve motion in humans.

A "semiopen" diastolic equilibrium position of the mitral valve that is assumed in the absence of transmitral flow has been demonstrated in instrumented dogs. It has been suggested that the papillary muscles and chordae tendineae play an integral role in returning the valve to this position after initial diastolic opening. To determine whether such a model of mitral valve motion is valid in noninstrumented humans without underlying valvular disease, M-mode and Doppler ultrasound studies were performed in 6 subjects who underwent prolonged periods of ventricular diastole and atrial inactivity. After maximal opening, the mitral valve assumed a stable open position in which mean separation of the anterior and posterior mitral leaflets was 52% of maximal separation. This position was maintained for a mean duration of 585 ms, during which time transmitral flow fell to 0 m/s. Peak mitral valve opening preceded the early transmitral flow peak by an average of 42 ms, suggesting an active closure of the mitral valve as flow continued to accelerate. It is concluded that a semiopen equilibrium position of the mitral valve is assumed during prolonged diastolic periods in the absence of transmitral flow and is an accurate model describing diastolic mitral valve motion in noninstrumented humans. The chordae tendineae and papillary muscles may actively participate in the genesis and maintenance of the equilibrium position.

Aortic distensibility abnormalities in coronary artery disease.

Vasodilatory capacity of nonstenotic arteries in experimental animals with atherosclerosis is decreased. It was postulated that aortic distensibility may be abnormal in patients with coronary artery disease (CAD). Aortic distensibility was determined in 24 normotensive patients with CAD and an angiographically normal aorta and values were compared with those in 18 age-matched normal subjects. Aortic diameters were measured at 3 levels--2, 4 and 6 cm above the aortic valve--by angiographic techniques. The area of the first 6 cm of the aorta above the aortic valve was planimetered and mean aortic diameters were calculated. Distensibility was calculated using the formula: [2 X (changes of the aortic diameter)/(diastolic aortic diameter) X (changes of the aortic pressure)]. CAD patients had similar aortic pressures but markedly lower distensibility than normal subjects: 0.7 +/- 0.2 vs 1.7 +/- 0.3 (p less than 0.02); 1.5 +/- 0.3 vs 4.0 +/- 0.6 (p less than 0.02); and 1.2 +/- 0.2 vs 5.3 +/- 0.6 (p less than 0.001) at 2, 4 and 6 cm above the aortic valve, respectively. Distensibility was also calculated from the mean aortic diameters and was greater in normal subjects than in CAD patients (3.4 +/- 0.4 vs 1.6 +/- 0.1, p less than 0.001). Decreased aortic distensibility in CAD may be related to the common atherosclerotic process or to reduced ascending aorta vasa vasorum flow from coronary arteries.

Prolonged electrical systole and QT greater than QS2 secondary to coronary artery disease.

Dyssynchronous depolarization-repolarization in the left ventricular (LV) myocardium may produce QT greater than QS2 or long QT. In 41 patients with coronary artery disease (CAD) and LV aneurysm, 46 patients with CAD and a history of acute myocardial infarction (AMI) but no LV aneurysm, and 52 patients with CAD without previous AMI, QT and QS2 were measured simultaneously at a speed of 100 mm/s within 48 hours of cardiac catheterization. Patients receiving class I antiarrhythmic drugs were excluded. The incidence of QT greater than QS2 was significantly greater in patients with LV aneurysm (71%) than in those with previous AMI (22%) and those with CAD but no previous AMI (20%) (p less than 0.001). Likewise, the incidence of long QT corrected for heart rate was significantly greater in patients with LV aneurysm (54%) than in those with previous AMI (7%) and those with CAD and no previous AMI (6%) (p less than 0.0001). The incidence of QT greater than QS2 in another 19 patients with previous AMI who were receiving digitalis therapy was significantly greater (65%) than in those with previous AMI but not receiving digitalis therapy (22%) (p less than 0.001). The incidence of long QT corrected for heart rate and QT greater than QS2 was not statistically different between patients with previous AMI and those with CAD but no previous AMI. The QT greater than QS2 or long QT in patients with aneurysm is probably a result of dyssynchronous depolarization or repolarization within or in the border zone of the LV aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Rest and exercise cardiovascular effects of terazosin in congestive heart failure.

This study investigated the acute effects of the alpha 1 antagonist terazosin on myocardial circulatory responses at rest and during exercise. Ten patients with congestive heart failure (class III and IV) underwent hemodynamic evaluation before and after a 5-mg oral dose of terazosin. At rest and during exercise, terazosin significantly decreased pulmonary capillary wedge pressure, systemic vascular resistance and mean arterial pressure while cardiac index increased. Stroke volume index increased (p less than 0.01) during exercise while left ventricular stroke work index remained unchanged in both experimental conditions. Terazosin administration significantly decreased both rest and exercise myocardial oxygen consumption while exercise coronary sinus oxygen content increased and arterial-coronary sinus oxygen difference diminished (p less than 0.05). Parallel with these changes, alpha blockade decreased the ratio of coronary blood flow to total cardiac output. Coronary vascular resistance remained unaltered with alpha blockade both at rest and during exercise. Coronary blood flow tended to diminish with decreased myocardial oxygen demand. Alpha 1 blockade induces systemic vasodilation and improves myocardial circulatory parameters without inducing coronary dilation or altering metabolic autoregulation.

Exercise-induced S-wave prolongation in left anterior descending coronary artery stenosis.

Myocardial ischemia may decrease conduction velocity and produce QRS prolongation in the surface electrocardiogram. In cases with normal intraventricular conduction, areas of the myocardium contributing to the development of the S wave receive blood from all 3 major coronary arteries, whereas in left anterior hemiblock or right bundle branch block, most of the blood supply to the areas of the myocardium contributing to the development of the S wave is from the left anterior descending (LAD) coronary artery. To test the hypothesis that the S wave will be prolonged with exercise only in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block, 88 patients with normal intraventricular conduction, 66 with left anterior hemiblock and 36 with right bundle branch block were studied. Sixty-four, 32 and 21 patients had LAD, right and left circumflex coronary artery stenoses, respectively. In patients with normal coronary arteries, S-wave duration decreased with exercise regardless of the status of ventricular conduction. In patients with coronary artery disease and normal intraventricular conduction, the S wave was prolonged slightly with exercise, but in those with left anterior hemiblock and right bundle branch block, it was prolonged significantly (12.5 +/- 6 and 10.4 ms, respectively) only in those with LAD, but not in those with circumflex or right coronary artery stenosis. S-wave prolongation in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block most likely is related to exercise-induced ischemia in the areas of the myocardium contributing to the development of the S wave.