High Left Atrial Pressure Research Articles

Panel 4 Other postoperative complications

MODERATOR PIERCE: We have here a panel of three members and myself, and I think we have all seen our share of problems and complications from the devices that we are talking about today. I would like to introduce the panel members: Dr Larry McBride, assistant professor of Surgery at St. Louis University; Dr Laman Gray, professor and chairman of the Department of Cardiac Surgery at the University of Louisville; and Dr Bud Frazier, professor of Surgery at the University of Texas at Houston and chief of the Transplant Program at the Texas Heart Institute. I would like to start off by saying first that our goal in the area of mechanical circulatory support is to prevent problems and complications. Sometimes when one gets into these problems and complications, it is simply not possible to get out of them in good fashion. Our goal, therefore, has to be to prevent these problems. By far the biggest problem that occurs in patients that have these devices, in my experience-and I think most people would agree with this-is bleeding. The problem is of such severity that, of course, the previous panel was devoted to that subject. We want to keep that in mind, and what we are going to talk about are other and in some ways lesser complications than bleeding. I would like to list what I consider to be six more or less generic problems that occur in patients on these devices. The first problem is that of an inadequate cardiac output in a patient who has a circulatory assist device in place. This problem may be very simple, that of hypovolemia; in this case, both atrial pressures are low and the cardiac index is less than 2 L/min/m2. We would try to improve the cardiac index by increasing the patient's blood volume. Another scenario is that of a patient who has a high left atrial pressure and a left ventricular assist device (VAD) that is not functioning properly. Well, the problem in that instance is some type of cannula obstruction. The surgeon has to look at that to find out what it is, reposition the cannula, and get the left atrial pressure down. The next scenario is that of a patient with an inadequate cardiac output in spite of a left VAD that seems to be functioning satisfactorily. There is a low left atrial pressure, and no one seems to be able to understand what the problem is. Well, the problem is that the patient has concomitant right ventricular failure that may have been unmasked by the insertion of the left VAD. What one has to do then is to get more blood over to the left side of the

Regional variation in pericardial contact pressure in the canine ventricle.

We studied eight open-chest dogs to determine whether there is regional variation in pericardial contact pressure (PCP). Flat, air-filled balloons were used to measure PCP simultaneously over the lateral walls of the right and left ventricles while cardiac volume was varied by dextran infusion. End-diastolic and mean PCP were significantly higher over the left than right ventricle at high (20.3 +/- 1.0 mmHg) and middle levels (13.7 +/- 0.9 mmHg) of left atrial pressure. At high left atrial pressures, the end-diastolic PCP over the lateral left ventricle was 9.1 +/- 2.4 mmHg compared with 4.3 +/- 2.3 mmHg over the lateral right ventricle (P less than 0.05). At middle levels of left atrial pressures, end-diastolic PCP was 6.2 +/- 3.5 mmHg over the left ventricle and 1.5 +/- 2.4 mmHg over the right ventricle (P less than 0.05). These variations in PCP persisted after severing the pericardial diaphragmatic attachments and after turning the dogs such that one or the other balloon was dependent. Regional distribution of PCP was studied by positioning a single balloon sequentially at multiple ventricular sites. PCP was consistently higher over the lateral wall of the left ventricle than either the anterior or posterior walls of the right or left ventricle. After aortic occlusion, end-diastolic PCP increased more over the left than right ventricle. In contrast, with pulmonary artery occlusion, end-diastolic PCP increased more over the right than left ventricle. Pericardial pressure varies regionally, and a single pericardial pressure may be an oversimplification when used to describe pericardial restraint on the cardiac volume.

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone

We have favored treatment of moderate mitral regurgitation and coronary disease with coronary bypass alone because of the high operative mortality of combined mitral valve replacement and coronary bypass. Between 1977 and 1983, coronary bypass alone was performed on 58 patients (mean age 63 +/- 8 years). Preoperatively, 90% had Canadian Cardiovascular Society class III or IV angina, and 10% had class III or IV congestive heart failure. In 72% mitral regurgitation had been caused by coronary disease. Hospital mortality was 3.4% (2/58). At follow-up (100% complete, mean 4.3 years) 66% of survivors were functional classes I and II (compared with 7% preoperatively, p less than 0.0001). Of those patients who worked preoperatively, 84% returned to work. There were no reoperations. The 5-year survival was 77%. In the same period combined mitral valve replacement and coronary bypass was required in 20 unmatched patients with moderate mitral regurgitation and coronary disease. Indications for valve replacement included congestive heart failure (10 cases), high left atrial pressure (three cases), and mitral stenosis (four cases). In these patients with more advanced symptoms the hospital mortality was 25%, and the 5-year survival was 31%. Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone achieved excellent hospital survival and long-term functional stability without a subsequent valve operation.

Valve-Incompetent foramen ovale in premature infants with ductus arteriosus: A Doppler echocardiographic study

In a 1 year period, 56 neonates with a clinical diagnosis of ductus arteriosus had Doppler echocardiographic confirmation of the ductus; 33 (59%) had additional, turbulent left to right flow at the atrial level through a valve-incompetent foramen ovale. Normalized left atrial dimensions in the group with the atrial shunt were significantly larger than when there was a competent foramen ovale; when the ductus closed and left atrial enlargement receded, the atrial shunt disappeared. However, several infants with large left chambers had no interatrial shunting. When the atrial shunt was present, there were up to three flow pulses, corresponding to atrial systole, ventricular systole and ventricular diastole, but these were frequently fused into two pulses or even one pulse per cycle. The atrial septal morphology provided supporting clues: general bowing of the septum or a localized bulge in the region of the foramen ovale indicated relatively high left atrial pressure, and frequently a slitlike dropout could be seen at the superior edge of the foramen. During the study, three additional neonates with a ductus arteriosus were found to have a secundum atrial septal defect with a typical echographic image, "matchhead" appearance of the septal rim of the defect, but the Doppler flow patterns were indistinguishable from those of a valve-incompetent foramen ovale. The hemodynamic effects of the interatrial shunt, from either cause, seemed slight during the hospital course, but the presence of a valve-incompetent foramen ovale indicated a relatively large ductal shunt. Quantification of the ductal shunt, however, continues to rely primarily on measurement of the left atrial and ventricular size.

VOLUME EXPANSION INCREASES CARDIAC OUTPUT (CO) BUT NOT OXYGEN DELIVERY (QO2) IN PIGLETS

Piglets (1-3 wks; n=12) were anaesthetized, intubated, and ventilated. Blood pressure (BP), pulmonary artery pressure (PAP), left atrial pressure (LAP), central venous pressure (CVP), and CO were measured directly. Arterial and mixed venous (PA) blood samples were obtained to determine QO2, O2 consumption (VO2), and O2 extraction. Six piglets (GENT) received 6% Gentran/0.9% NaCl to elevate LAP from approximately 5 to 15 mm Pig over 30 minutes. Six additional piglets (SAL) received 0.9% NaCl for 30 minutes. Cardiac index (CI) rose during GENT in each piglet, reaching a plateau (+54.2 +/- 38.5 (S.D.) cc/kg/min; p .01) at LAP between 12 - 15 mm Hg. CI fell at the highest LAP reading in 4/6 piglets. GENT raised LAP, PAP, and CVP equivalently (7.3 +/- 1-4, 7.2 +/- 2.6, 5.6 +/- 1.2 mm Hg; all p.01 vs SAL), but had no effect on BP or HR. Hb fell during GENT from 10.4 +/- 1.8 to 7.4 +/- 1.9 gm/dl (p .01) so that QO2 was not enhanced after GENT (17.6 +/- 1.5 vs 17.9 +/- 2.3 cc O2/kg/min) despite the rise in CO. VO2, O2 extraction, pH, and base excess did not change after GENT. Conclusions: 1. CO consistently rises with increased LAP from 5-12 mm Hg. At higher LAP, CO may fall. 2. QO2 does not rise and O2 extraction does not fall during GENT, as increased CO is opposed by hemodilution, 3. To the extent that improved QO2, not CO, is the endpoint of hemodynamic resuscitation, volume infusion without concurrent blood transfusion may be of little benefit.

Comparison of cardiac function in male and female diabetic rats

1. 1. To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week old male and female rats. 2. 2. Significantly lower values for +d P/d t occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. 3. 3. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. 4. 4. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats.

Acute Mitral Regurgitation

The mitral apparatus is a complex structure with many components. Diseases affecting any part of this apparatus may result in acute mitral regurgitation. The most common causes are ruptured chordae tendineae and ischemic dysfunction of the papillary muscles. Sudden disruption of the mitral apparatus markedly elevates pulmonary capillary pressure and results in acute pulmonary edema. Consequently, patients with acute mitral regurgitation usually are admitted to acute care facilities. The physical examination sometimes is misleading because the characteristic holosystolic murmur may be absent. In some patients with acute mitral regurgitation, such high left atrial pressures develop during the latter part of systole that the pressure gradient between the left ventricle and atrium is obliterated, resulting in cessation of the murmur in late systole. This regurgitant v wave in the left atrial or pulmonary capillary pressure tracing is the characteristic hemodynamic finding in acute mitral regurgitation, but it may not always be present. Currently, the best diagnostic technique is two-dimensional and Doppler echocardiography. The former provides anatomic detail of the mitral apparatus, and the latter confirms and quantifies the mitral regurgitation. Although left ventricular angiography can be used to make the diagnosis, Doppler echocardiographs provide more information, are equally sensitive, and are noninvasive. Cardiac catheterization is now largely used to define the coronary anatomy prior to valvar operation. Management of patients with acute mitral regurgitation includes the use of vasodilators, mechanical circulatory support, and finally valvoplasty or replacement.

Effects of coronary sinus pressure elevation on coronary blood flow distribution in dogs with normal preload.

Coronary sinus pressure (Pcs) elevation shifts the diastolic coronary pressure-flow relation (PFR) of the entire left ventricular myocardium to a higher pressure intercept. This finding suggests that Pcs is one determinant of zero-flow pressure (Pzf) and challenges the existence of a vascular waterfall mechanism in the coronary circulation. To determine whether coronary sinus or tissue pressure is the effective coronary back pressure in different layers of the left ventricular myocardium, the effect of increasing Pcs was studied while left ventricular preload was low. PFRs were determined experimentally by graded constriction of the circumflex coronary artery while measuring flow using a flowmeter. Transmural myocardial blood flow distribution was studied (15-micron radioactive spheres) at steady state, during maximal coronary artery vasodilatation at three points on the linear portion of the circumflex PFR both at low and high diastolic Pcs (7 +/- 3 vs. 22 +/- 5 mmHg; p less than 0.0001) (1 mmHg = 133.322 Pa). In the uninstrumented anterior wall the blood flow measurements were obtained in triplicate at the two Pcs levels. From low to high Pcs, mean aortic (98 +/- 23 mmHg) and left atrial (5 +/- 3 mmHg) pressure, percent diastolic time (49 +/- 7%), percent left ventricular wall thickening (32 +/- 4%), and percent myocardial lactate extraction (15 +/- 12%) were not significantly changed. Increasing Pcs did not alter the slope of the PFR; however, the Pzf increased in the subepicardial layer (p less than 0.0001), whereas in the subendocardial layer Pzf did not change significantly. Similar slopes and Pzf were observed for the PFR of both total myocardial mass and subepicardial region at low and high Pcs. Subendocardial:subepicardial blood flow ratios increased for each set of measurements when Pcs was elevated (p less than 0.0001), owing to a reduction of subepicardial blood flow; however, subendocardial blood flow remained unchanged, while starting in the subepicardium toward midmyocardium blood flow decreased at high Pcs. This pattern was similar for the uninstrumented anterior wall as well as in the posterior wall. Thus as Pcs increases it becomes the effective coronary back pressure with decreasing magnitude from the subepicardium toward the subendocardium of the left ventricle. Assuming that elevating Pcs results in transmural elevation in coronary venous pressure, these findings support the hypothesis of a differential intramyocardial waterfall mechanism with greater subendo- than subepi-cardial tissue pressure.

192 PROLONGED MECHANICAL VENTILATION OF INFANTS AFTER OPEN HEART SURGERY

Records of all 140 infants <2 years undergoing open heart surgery 7/80–9/84 were studied to evaluate the relationship between duration of mechanical ventilation (MV) and mortality, and risk factors for prolonged MV. MV was required for: 0–1 day (84), 2–6 days (37), >7 days (19). The 16% mortality in those with MV ≥7 days did not exceed that in infants with briefer MV (17%). Factors which prolong MV include: younger age (p<.005) (mean 10 mo), longer bypass time (p<.005) (mean 105 min), longer aortic cross clamp time (p<.01) (mean 51 min), and pre-op MV (p<.05). A predictive index (PI) for each patient was derived by assigning a +1 score for each factor when its value was worse than the mean. PI ≥2 predicted prolonged MV ≥7 days with 95% sensitivity and 57% specificity. MV ≥7 days occurred in 26% of infants with PI ≥2 and only in 1% with PI <2. Post-op factors including premature extubation requiring reintubation (p<.005) and requirement for a second surgical procedure (p<.005) also lengthened MV. The R2=.57 for combined significant variables in relation to duration of MV. While not predictive for the entire population, among the 19 requiring MV ≥7 days, 14 had pre-op elevation of pulmonary artery pressure, resistance, or blood flow, or high left atrial pressure. For patients predicted to have high risk of prolonged MV, early nutritional support, heightened vigilance for treatable complications and nosocomial infections, and avoidance of futile premature extubation are all suggested.

Effects of vascular pressure on the pulmonary microvasculature in isolated dog lungs.

The effects of short periods of high pulmonary vascular pressures on the filtration characteristics of the lung's microcirculation have been studied in isolated dog lungs. When left atrial pressures (Pla) were less than 30 cmH2O, the capillary filtration coefficient (Kf,c) was not different from that of controls (0.192 +/- 0.009 ml X min-1 X cmH2O-1 X 100 g-1). In 17 of 23 observations, where Pla exceeded 55 cmH2O, Kf,c was at least 1.5 times control. In 10 of 13 lungs, Kf,c returned to control values within 2 h after the Pla increase. However, in the other three experiments, Kf,c did not return to control values. These findings indicate that the filtration coefficient of pulmonary microvessels increases at high left atrial pressures (greater than 55 cmH2O) and may represent either a "stretching" of existing pores or opening of a few large pores.

Afterload reduction and cardiac output in patients after mitral valve surgery.

Thirteen patients who had mitral valve surgery were studied within 3 hours after operation. The patients were divided into 2 groups: group A with initial low cardiac index (1.70 +/- 0.25), elevated left atrial pressure (16.5 +/- 6.7) and high peripheral vascular resistance (2623 +/- 789); group B with initial normal cardiac index (3.71 +/- 0.54), normal left atrial pressure (13 +/- 3.5) and normal peripheral vascular resistance (1223 +/- 303). In both groups the mean arterial pressure was elevated (98 +/- 8.8, 96 +/0 15.8). An infusion of nitroprusside to reduce the mean arterial pressure to either 80 mmHg or 10% below the initial value had different effects in each group. In group A, cardiac index (CI) increased by 23%, left atrial pressure (LAP) decreased by 20%, pulmonary artery pressure (PAP) by 35%, and peripheral vascular resistance (PRV) by 32%. In group B, CI decreased by 8%, LAP by 32%, PAP by 30% and PVR by 13%. When LAP returned to initial values after an infusion of blood with continued infusion of nitroprusside, CI increased in both groups (27%, 11%) and the PVR remained lower (40%, 29%). The study demonstrates the favorable effect on cardiac output of vasodilator therapy on patients with elevated blood pressure, impaired by left ventricular function and high LAP, after surgery on mitral valve. The optimal effect is achieved by keeping the LAP within normal limits.

Afterload reduction with hydralazine following valve replacement

Impedance reduction with hydralazine was evaluated in 23 patients 1 to 3 hours after aortic or mitral valve replacement. Patients were randomly assigned to Group 1 (0.25 mg/kg) or Group 2 (0.5 mg/kg) and responses at 20, 60, and 120 minutes compared with control (paired t test) and mean values for each group compared (t test). In Group 1 significant responses were the fall in mean arterial pressure (78.3 +/- 3.0 to 66.7 +/- 2.2 mm Hg) and systemic vascular resistance (2,808 +/- 264 to 1,823 +/- 164 dynes-sec/cm5); the increase in cardiac index (2.07 +/- 0.13 to 2.71 +/- 0.21 L/min/m2), stroke volume index (26.9 +/- 2.3 to 34.0 +/- 3.3 ml/beat), and heart rate (80.8 +/- 5.8 to 84.2 +/- 6.6 beats/min). Central venous pressure did not change and left atrial pressure decreased at 120 minutes. Group 2 responses were similar except for higher central venous pressure at 20 minutes, higher left atrial pressures at control, 20, and 60 minutes, and lower left ventricular stroke work at control, 20, and 60 minutes. By selectively dilating the arterial system, hydralazine reduces mean arterial pressure and systemic vascular resistance and increases cardiac output with suble filling pressures.

Mechanism of reduction of mitral regurgitation with vasodilator therapy

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance to left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

Criteria for early extubation after intracardiac surgery in adults.

Of 142 adult patients undergoing open-heart surgery, 123 were extubated either in the operating room or within 3 hours after admission to the recovery room, to avoid the discomfort and risks of prolonged mechanical ventilation. The remaining 19 patients, who had impaired cardiac function, were mechanically ventilated for 1 to 7 days postoperatively. The most important criteria for cardiopulmonary malfunction indicating the need for continued mechnical ventilation were a low mixed venous O2 saturation (SVO2) of less than 60% and a high left atrial pressure (greater than 20 torr). Of the 123 patients, 118, had an uneventful postoperative recovery and 5 needed reintubation, 2 because of low SVO2 and 3 because of complications unrelated to respiratory management. Most adult patients can spontaneously breathe adequately immediately after or within 3 hours of completed open-heart surgery, but a thorough physiologic and clinical evaluation should precede extubation, to identify those who need prolonged mechanical ventilation in the postoperative phase. Criteria for selection of patients for early extubation are presented.

Effects of continuous positive-pressure ventilation in experimental pulmonary edema.

We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.

Computer-based analysis of preoperative and postoperative prognostic factors in 100 patients with combined aortic and mitral valve replacement.

From 1963 to 1971, aortic and mitral valves were replaced in 100 patients; 22 died in hospital. Follow-up in survivors is 100%. Catheterization was performed preoperatively in 99 patients and postoperatively in 85% of survivors. The influence of 19 preoperative potential risk factors on hospital mortality, postoperative symptomatic improvement, and long-term survival (assessed by monthly cohort-adjusted survival tables) was determined. Long-term survival was also assessed by comparing average values of the various risk factors in patients surviving 1, 2, and 3 years with values in patients who died during these intervals. In addition, changes induced by operation were studied 6 months postoperatively and their value in predicting subsequent longevity assessed. Significant ( P &lt; 0.05) findings were: a higher hospital mortality in patients with left atrial pressures ≥30 mm Hg or with fabric-covered valves; less postoperative symptomatic improvement in older patients; lower long-term survival rate in men and in patients with high left atrial, right atrial, pulmonary arterial, or right ventricular end-diastolic pressures. A decrease in radiographic heart size or a New York Heart Association class I or II status 6 months postoperatively was associated with a favorable subsequent prognosis. Postoperative hemodynamic values did not predict subsequent survival.

Effect of compromising right ventricular function in left ventricular failure by means of interatrial and other shunts: Right ventricular success versus left ventricular failure

The immediate advantages of a left to right interatrial shunt in the presence of a high left atrial pressure are evident from the experiments presented. The resultant reduction in left atrial pressure is shown to be proportional to the size of the shunt and to the initial height of left atrial pressure. When the initial left atrial pressure was high, this reduction in pressure was along the plateau of a ventricular function curve and was, therefore, associated with only a small drop in systemic flow. When shunt flow averaged 48.9 ml./min. per kg. and the ratio of shunt flow to systemic flow was 1.16, average left atrial pressure fell 30.7 per cent, from 18.1 mm. Hg to 12.5 mm. Hg; systemic flow fell only 5.3 per cent. Evidence that the right ventricle is well able to tolerate the increased flow burden is provided by the minor rise in right atrial pressure, which never exceeded 2 mm. Hg. A shunt from the pulmonary artery to the right atrium is shown to be similar in action, with a somewhat smaller effect on left atrial pressure for reasons which are discussed. The results reported are of acute experiments, and provide no information on the possible long-term benefits of a left to right interatrial shunt in left ventricular failure. However, situations analogous to this experimental preparation occur in nature in the form of Lutembacher's syndrome, the syndrome of partial anomalous pulmonary venous drainage with mitral stenosis, and tricuspid stenosis or insufficiency in association with left-sided heart lesions. These clinical syndromes are reviewed and the beneficial effect of the intracardiac or extracardiac shunt on high left atrial pressure discussed. It is further suggested that these syndromes support the view that the results of the studies presented are not mere artifacts of acute experiments but that a true reduction of left atrial pressure is likely to persist after blood pressures and flows have equilibrated. Finally, a mechanism of action of these shunts is postulated which relates the left atrial pressure to the characteristics of the right ventricular pump.

Intracardiac pressures during closed-chest cardiac massage.

During closed-chest cardiac massage, left-atrial and systemic arterial blood pressures are nearly equal. The former falls while the latter rises toward prearrest values with the resumption of effective cardiac activity. The high left-atrial pressures may explain pulmonary edema after prolonged closed-chest cardiac massage. An extremely critical state exists as long as there is no effective cardiac contraction even if a satisfactory systemic arterial blood pressure is maintained by closed-chest cardiac massage.

Intracardiac Pressures During Closed-Chest Cardiac Massage

During closed-chest cardiac massage, left-atrial and systemic arterial blood pressures are nearly equal. The former falls while the latter rises toward prearrest values with the resumption of effective cardiac activity. The high left-atrial pressures may explain pulmonary edema after prolonged closed-chest cardiac massage. An extremely critical state exists as long as there is no effective cardiac contraction even if a satisfactory systemic arterial blood pressure is maintained by closed-chest cardiac massage.

The natural history of ventricular septal defects in infancy

Sixty-two infants with ventricular septal defects were first catheterized under 1 year of age and followed up for one to five years; 40 were recatheterized. Thirty-six infants were born in the Bronx Municipal Hospital Center or Lincoln Hospital (local group). These patients were unselected, in that the decision to catheterize them was based only on the clinical diagnosis of a ventricular septal defect and not on an assessment of its size or the presence of symptoms. As far as we know, these infants include most if not all of the children born with ventricular septal defects in these hospitals during the period of study. With this assumption, the incidence of ventricular septal defects per 1,000 live births was 0.94 for full term infants, 4.51 for premature infants, and 1.35 for the whole group. Twenty-six other infants were referred from other hospitals or doctors (referred group), and, compared to the local group, they had larger defects, were more often in congestive heart failure and were more often catheterized after 6 months of age. In the whole series, 31 of 62 had congestive heart failure. This began before 6 months of age in all and occurred much earlier in premature than in full term infants. In the local group, spontaneous functional closure of the ventricular septal defect took place in 13 of 36 (36%); this was proved by recatheterization in 10 and autopsy in 1. Marked decrease in size of the defect took place in another 10 (28%). In the referred group (26 cases) there were 2 (8%) spontaneous closures and 7 (27%) reductions in defect size. For the whole series, 52 per cent of the patients had defects which were known to have closed or become smaller; 32 per cent were doing well clinically (most were not recatheterized so that some of these defects might have become smaller); and only 16 per cent of the infants were seriously affected by their lesions. Complete closure occurred between 7 and 12 months of age, most often when the defect was small, but it could occur with large defects. Decrease in defect size, however, occurred as frequently with large as with small defects, and was found in many children with congestive heart failure and pulmonary arterial hypertension. The 10 infants with large ventricular septal defects who did not do well included 4 who had pulmonary arterial banding for severe, uncontrolled congestive heart failure (2 died); 1 premature baby who died at 6 weeks of age with severe congestive heart failure; and 5 with a very high pulmonary vascular resistance. One of these 5 had a high pulmonary vascular resistance when 1 month old, and this did not change significantly at 5 and 13 months of age. The other 4, however, had low pulmonary vascular resistance when first catheterized at 3, 6, 6 and 11 months of age, respectively, and significant rises of resistance to pathologic levels when recatheterized at 9, 15, 26 and 40 months of age, respectively. This suggests that a rise in pulmonary vascular resistance in infancy is not rare when the ventricular septal defect is big and that, even in these children, the pulmonary vascular resistance does not usually persist at the high level present at birth but first falls post natally to normal levels before rising. These 5 infants all had large left to right shunts, high left atrial pressures and marked pulmonary arterial hypertension. In 3 out of the 4 whose pulmonary vascular resistances rose after the first catheterization, there were no distinctive clinical indications of this rise which was detected only at recatheterization. The other child had increasing right ventricular hypertrophy on the electrocardiogram. From these findings we suggest that, since in infancy spontaneous closure or reduction in size of the ventricular septal defect is so common, most infants should be treated conservatively in the hope that spontaneous improvement will occur. If the defect is very big and the child is in severe congestive heart failure which cannot be well controlled, then surgical closure of the defect or banding of the pulmonary artery should be done. If, however, the defect is big but congestive heart failure can be controlled medically, then the infant should be followed up with the hope that spontaneous improvement will occur. Whether clinical improvement occurs or not, the infant should be recatheterized six to nine months after the initial catheterization to determine if a rise in pulmonary vascular resistance has occurred; if it has then surgery should be advised.