Medically refractory unstable angina pectoris. I. Long-term follow-up of patients undergoing intraaortic balloon counterpulsation and operation.

Of 82 patients with medically refractory unstable angina pectoris seen between October 1972 and January 1978, 60 patients underwent a combination of intraaortic balloon pump counterpulsation, cardiac catheterization and coronary revascularization. Most patients had atherosclerotic involvement of the vessels of the anterior left ventricular wall, 48 patients (80 percent) had abnormalities of left ventricular wall contraction and 22 patients (36 percent) had evidence of acute myocardial injury. One operative and one late death occurred. The perioperative infarction rate was 5 percent. Survivors, followed up for 3 to 63 months (mean 31 months), have done remarkably well; 77 percent are considered employable,and more than 90 percent are in functional class I or II.

Mitral valve replacement for isolated mitral regurgitation: analysis of clinical course and late postoperative left ventricular ejection fraction.

One hundred five patients underwent mitral valve replacement for relief of isolated mitral regurgitation between 1974 and 1979. There were 4 in-hospital deaths (4 percent) and 12 late deaths giving an 82 percent predicted 5 year survival rate. An age of 60 years or more at the time of surgery and a preoperative left ventricular ejection fraction of less than 0.40 were the only variables that correlated with decreased survival at 3 to 5 years after operation (p less than 0.05). Postoperatively, 87 (98 percent) of 89 long-term survivors were in New York Heart Association functional class I or II (68 in class I and 19 in class II). Survival did not differ between patients with porcine versus mechanical valve replacement, but patients with a mechanical valve had a greater incidence of postoperative cerebrovascular accident (8.6/100 patient years) than did patients with a porcine valve (2.8/100 patient years) (p less than 0.002). Ejection fraction at rest was determined with multigated cardiac imaging 12 to 75 months postoperatively in 34 of 89 long-term survivors. The mean preoperative ejection fraction was 0.62 +/- 0.09 (mean +/- 1 standard deviation) and the mean postoperative ejection fraction was 0.50 +/- 0.15 (p less than 0.001). When the preoperative value was compared with the postoperative value at rest the ejection fraction increased by 0.10 or more in 1 patient (3 percent), remained within +/- 0.09 of the preoperative value in 12 patients (35 percent) and decreased by 0.10 or greater in 21 patients (62 percent). Sixteen (94 percent) of 17 patients whose postoperative ejection fraction was greater than 0.50 were in functional class I postoperatively compared with 11 (65 percent) of 17 patients whose postoperative ejection fraction was 0.50 or less (p less than 0.05). No preoperative factor, including preoperative ejection fraction or cardiothoracic ratio, predicted the postoperative ejection fraction. A postoperative exercise ejection fraction was obtained in 29 patients, and an abnormal ejection fraction change with exercise (increase less than 0.05) was observed in 20 patients (69 percent). Patient age at the time of study correlated inversely with the change in ejection fraction from rest to exercise; no other variables were predictive. It is concluded that, in addition to age, only preoperative left ventricular function as measured by ejection fraction predicts survival in patients undergoing mitral valve replacement for isolated mitral regurgitation. Clinical recovery is good even though the majority of long-term survivors have a postoperative decrease in ejection fraction.

Myocardial protection with hypothermia and potassium cardioplegia during operation for ascending aortic aneurysms.

The operative management of aneurysms of the ascending aorta continues to present a technical challenge to the surgeon, and the results obtained provide a useful clinical assessment of the means of myocardial protection. We present a series of 35 consecutive patients who underwent operations for aneurysms of the ascending aorta during which myocardial protection was achieved with hypothermia and potassium cardioplegia. Twenty-three patients underwent aortic valve replacement and resection and grafting of a chronic ascending aortic aneurysm. Aortic valve replacement and aneurysmorrhaphy of a chronic ascending aneurysm were performed in five patients. Four patients underwent resection and grafting of a chronic ascending aortic aneurysm and three patients resection and grafting of acute aortic aneurysms. Aortic cross-clamp times varied from 48 minutes to 2 hours, 32 minutes, with a mean cross-clamp time of 1 hour, 29 minutes. There was one death in the hospital in this series of 35 patients for a mortality rate of 2.8%. Of the 34 survivors, there has been one late death from recurrent sternal wound infection. This clinical series documents the efficacy and safety of hypothermic potassium cardioplegia for protection of the myocardium during extended periods of ischemia attending operative correction of ascending aortic aneurysms.

Plasma vasopressin levels and urinary flow during cardiopulmonary bypass in patients with valvular heart disease: effect of pulsatile flow.

The effect of pulsatile flow on plasma vasopressin levels during cardiopulmonary bypass (CPB) was studied in 20 patients undergoing open valve replacement. Routine bypass was used in 10 patients and the AVCO pulsatile bypass pump was utilized in the other 10. In Group I (nonpulsatile) during CPB, the vasopressin level was markedly elevated (3.1 +/- 2 to 80 +/- 22 pg/ml) as was urine flow (0.6 +/- 0.2 to 5.9 +/- 2 ml/min) and urine Na+ concentration (69 +/- 19 to 116 +/- 7 mEq/L). In Group II (pulsatile) during CPB, the vasopressin level (3.8 +/- 3 to 54 +/- 14 pg/ml), urine flow (0.6 +/- 0.1 to 16.2 +/- 4.8 ml/min), and urine Na+ concentrations (61 +/- 13 to 97 +/- 10 mEq/L) were also elevated. The rise in vasopressin and urine Na+ was less in the pulsatile group (p less than 0.05) whereas the urine flow was higher (p less than 0.05). To maintain comparable blood pressure, the pulsatile flow group required significantly higher flows (4.5 +/- 0.2 compared to 3.8 +/- 0.2; p less than 0.05). These data suggest that CPB produces a marked vasopressin stress response which is beyond the physiological range for an antidiuretic effect on the kidney. At these levels vasopressin can exert a vasopressor effect to maintain resistance and affect renal blood flow, as well as producing an Na+ diuresis. The addition of pulsatile flow creates a more physiological situation attenuating the vasopressin response and producing a decrease in systemic resistance and a less pronounced Na+ diuresis.

Adrenocortical hormone levels during cardiopulmonary bypass with and without pulsatile flow.

To determine the effect of hypothermic pulsatile and nonpulsatile cardiopulmonary bypass (CPB) with hemodilution on adrenocortical function we measured plasma levels of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin in two groups of patients. Group I, comprising 11 patients had routine CPB (nonpulsatile), and Group II, comprising 12 patients, had pulsatile flow during CPB (pulsatile). Both groups demonstrated comparable increases in cortisol, ACTH, and aldosterone with operation. Levels for all three hormones appeared to decline during CPB and then rose again in the post-CPB period. There were no significant differences between groups. Plasma renin activity gradually declined in a comparable manner in both groups. In the post-CPB period, renin activity was slightly higher in the nonpulsatile group (1.7 +/- 0.5 versus 0.8 +/- 0.2 ng/ml/hr, p less than 0.05). Correction for the effect of hemodilution demonstrated no decrease in cortisol and a slight increase in ACTH in both groups during CPB. Significant increases occurred in both groups during CPB in urinary Na+ excretion rate and urinary Na+/K+ ratio, more so for the nonpulsatile group. There was no correlation between urinary Na+/K+ ratios and either plasma cortisol or aldosterone levels. Thus routine CPB demonstrates no evidence of adrenocortical hypofunction and the addition of pulsatile flow produces little improvement.

Mechanical valves: a comparative analysis of the Starr-Edwards and Björk-Shiley prostheses.

Despite the requirement of anticoagulation, mechanical valve prostheses offer the advantage of proven durability. We have compared the long-term results of 467 aortic valve replacements and 342 mitral valve replacements using the Starr-Edwards prosthesis with 110 aortic valve replacements and 105 mitral valve replacements using the Björk-Shiley prosthesis from 1973 through 1977. Improvement in New York Heart Association (NYHA) class was noted in greater than 80% of patients in all four groups. Long-term survival with mean follow-up over 5 years was not significantly different between respective groups. The probability of thromboembolic complications, however, was significantly higher (p less than 0.05) with the Starr-Edwards prosthesis in both the aortic and mitral positions. The probability of valve failure, although low for all groups, was significantly higher (p less than 0.05) in the Björk-Shiley mitral group due to late thrombotic occlusion. Use of the Starr-Edwards and Björk-Shiley prostheses is associated with satisfactory functional improvement and similar long-term survival rate. However, the increased risk of valve failure due to late thrombotic occlusion of the Björk-Shiley prosthesis should be considered when choosing a mechanical mitral prosthesis.

Isolated coronary artery bypass grafting in patients seventy years of age and older: early and late results.

Increasing longevity makes the consideration of coronary bypass common in elderly patients. Seventy-five patients 70 years of age or older undergoing coronary artery bypass grafting (CABG) for angina pectoris were compared to a control group of 75 patients under 70 years of age. The groups were matched for male:female ratio (46:29), previous infarction (28/75), unstable angina (27/75), and the requirement for preoperative intra-aortic balloon pumping (7/75). Patients under 70 years of age had an average preoperative New York Heart Association (NYHA) class of 3.0 +/- 0.6 (SEM) and an average left ventricular end-diastolic pressure of 15.5 +/- 0.8 mm Hg, compared to 3.3 +/- 0.6 and 12.9 +/- 1.1 mm Hg, respectively, for the older group. Average grafts per patient were 2.7 +/- 0.8 in the younger group and 2.8 +/- 0.1 in the older group. Overall operative mortality for patients under 70 was 4% (3/75) versus 12% (9/75) (p = 0.06) for patients 70 and older. The incidence of chronic stable angina was 2% (1/48) versus 6% (3/48) (p = 0.30). Perioperative infarctions occurred in 7% of those under 70 and 5% of those 70 or older (p = 0.54). Those under 70 averaged 13.8 +/- 0.6 postoperative hospital days versus 18.4 +/- 1.2 hospital days for the older group (p less than 0.05). Follow-up ranged from 2 to 94 months, averaging 22 months for patients under 70 and 24 months for those 70 or older. Late cardiac mortality rates were 4% (3/70) in the younger patients and 3% (2/66) in the older patients (p = 0.53). Current NYHA class was 1.3 +/- 0.7 for those under 70, with 9% reporting angina, and 1.4 +/- 0.7 for those who were 70 or older, with 6% reporting angina. CABG can be performed with acceptable risk in older patients and leads to encouraging symptomatic improvement and late survival.

Thromboxane and prostacyclin changes during cardiopulmonary bypass with and without pulsatile flow.

Nonpulsatile cardiopulmonary bypass, in patients with coronary artery disease, produces a significant increase in thromboxane, a potent platelet aggregant and putative coronary vasoconstrictor. Pulsatile flow may decrease the incidence of perioperative infarction and the hormonal stress response to bypass. This study assessed the effect of pulsatile blood flow on plasma thromboxane and prostacyclin profiles during cardiopulmonary bypass by serial measurement of their stable metabolites, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Two groups of eight patients each were studied before, during, and after cardiopulmonary bypass. Eight patients had routine (nonpulsatile) bypass and eight had pulsatile flow. In the nonpulsatile group, the TxB2 concentration significantly increased during bypass (65 +/- 39 to 1,224 +/- 306 pg/ml, p less than 0.01) and rapidly returned to control. Prostacyclin also rose (53 +/- 20 to 613 +/- 132 pg/ml, p less than 0.01). In the pulsatile group, TxB2 rose during bypass (53 +/- 18 to 693 +/- 130 pg/ml, p less than 0.01), but peak concentration was significantly lower than in the nonpulsatile group (1,224 +/- 306 versus 693 +/- 130 pg/ml, p less than 0.05). Prostacyclin rose sharply during cardiopulmonary bypass in the pulsatile group (53 +/- 22 to 1,033 +/- 136 pg/ml, p less than 0.01) and was higher than in the nonpulsatile group (1,033 +/- 136 versus 325 +/- 33 pg/ml, p less than 0.01). There were no intragroup differences of plasma hemoglobin, hematocrit, or platelet count. These data demonstrate that pulsatile flow significantly alters prostacyclin and thromboxane profiles during cardiopulmonary bypass and favors production of the coronary vasodilator and platelet disaggregant prostacyclin. This may be an important factor in some of the clinical advantages previously reported with this modality.

Serial changes in left ventricular ejection fraction in the early hours after aortocoronary bypass grafting.

To determine the course of left ventricular ejection fraction (LVEF) in the early hours after aortocoronary bypass grafting, 24 patients underwent serial gated bloodpool scanning. Twenty-two had received propranolol until the day of surgery. ECGs showed no evidence of perioperative infarction. Preoperatively, the mean (+/- SD) LVEF was 0.56 +/- 0.13; after bypass, it was 0.38 +/- 0.11 at 4 hours, 0.42 +/- 0.12 at 5 hours, 0.43 +/- 0.11 at 6 hours, 0.48 +/- 0.13 at 7 hours, 0.52 +/- 0.15 at 8 hours, and 0.54 +/- 0.15 at 10 to 14 days. The LVEFs at 4, 5, and 6 hours postoperatively were significantly lower than preoperatively (p less than 0.05). Postoperative mean heart rate was higher at all times; mean temperature was depressed at 4 and 5 hours and elevated at 7 and 8 hours; and mean arterial blood pressure was depressed at 7 hours, 8 hours, and 10 to 14 days (p less than 0.05). The degree of the early postoperative LVEF depression correlated with the daily preoperative propranolol dose (p less than 0.05) and was unrelated to bypass time, aortic cross-clamp time, or changes in temperature, heart rate, and blood pressure. The LVEF at 10 to 14 days postoperatively was not significantly different from the preoperative value. The LVEF is depressed in the early hours after aortocoronary bypass grafting and approaches the preoperative value with time. The magnitude of the early depression appears to be related to the preoperative propranolol dose, but does not significantly correlate with factors related to surgical technique.

Effect of cross-clamp time, temperature, and cardioplegic agents on myocardial function after induced arrest.

To evaluate the importance of time, temperature, and cardioplegia on the ability of the canine myocardium to maintain functional and ultrastructural integrity following induced arrest, we studied 220 dogs by varying myocardial temperature (34 degrees, 24 degrees, and 11 degrees C.), arrest time (0 to 120 minutes), and cardioplegic agents. Change in left ventricular function (LVF) was defined as the arithmetic difference in the center of mass between prearrest and postarrest LVF curves and was expressed as percent recovery of left ventricular stroke work. Left ventricular biopsies were obtained for semiquantitative electron microscopic analysis. After 90 minutes of cross-clamping, only hearts protected with combined hypothermia (H) and potassium-induced cardioplegia (K) significantly recovered prearrest function (24 degrees C.--80 percent, 11 degrees C.--99 percent). Hypothermia (H) alone for 90 minutes was less protective (24 degrees C.--49 percent, 11 degrees C.--59 percent). H preserved 84 percent of function after 60 minutes and 91 percent after 45 minutes. Normothermic arrest resulted in only 39 percent return of function at 45 minutes but could be extended with potassium-induced cardioplegia(K) to 78 percent at 60 minutes and 54 percent at 90 minutes. The addition of procaine plus HK improved protection over HK alone (95 percent versus 80 percent) but by itself was not effective. Neither hydrocortisone nor pretreatment with glucose-insulin-potassium, branched chain amino acids, or propranolol increased the protective effect of HK plus procaine. Inadequately protected groups (normothermia or H without K) showed more myocytic and capillary endothelial damage than the HK groups. No technique of myocardial protection studied completely preserved LVF, but the combination of HK plus procaine resulted in maximal recovery of LVF following cross-clamping for up to 120 minutes.

Hyperlipoproteinemia as a significant risk factor for pulmonary embolism in patients undergoing coronary artery bypass grafting.

A five-year (1975 through 1979) retrospective analysis of all cardiac surgical patients who sustained a postoperative pulmonary embolism was undertaken, and lipoprotein profiles of these patients were evaluated. Twenty-six patients (20 men and 6 women) were identified who had definite clinical, laboratory, and radiological evidence of pulmonary embolism in the postoperative period. Twenty had undergone coronary artery bypass grafting, and the remaining 6 had undergone other cardiac surgical procedures. Of the 20 patients who had coronary bypass, 19 (95%) were found to have hyperlipoproteinemia (14 patients with type II and 5 with type IV). There were 4 hospital deaths (15%), all related to pulmonary embolism. The 4 patients had undergone coronary bypass procedures, and all had type II hyperlipoproteinemia. Since patients with hyperlipoproteinemia made up less than 10% of the coronary bypass population, the incidence of pulmonary embolism in this group is highly significant (p less than 0.001). Experimental evidence has shown that patients with hyperlipoproteinemia, especially type II, have increased platelet adhesiveness and aggregation, and coagulation abnormalities consistent with a hypercoagulable state. This retrospective study clinically confirms that finding and suggests that early postoperative anticoagulation therapy may be indicated in patients with hyperlipoproteinemia, particularly type II, to reduce thromboembolic complications.

Extended evaluation of effects of anoxia on ventricular performance and compliance.

Eight dogs were prepared by implanting a left ventricular pressure transducer, aortic flow probe, and endocardial ultrasound crystals across the maximum transverse left ventricular diameter. In an unanesthetized state, the dogs were evaluated at rest and with acute volume loading, both before ischemic cardiac arrest and sequentially (2, 4, 6, 12, 24, and 48 hours) after 20 minutes of arrest during normothermic cardiopulmonary bypass. At a left ventricular end-diastolic diameter comparable to preoperative levels, left ventricular systolic pressure, heart rate, and rate of rise of left ventricular pressure were not changed, but at 2 to 6 hours there was a significant decrease in cardiac output (p less than 0.01), left ventricular stroke work (p less than 0.01), ejection fraction (p less than 0.05), maximum rate of systolic diameter shortening (p less than 0.05), and circumferential fiber shortening (p less than 0.05). They gradually returned to control levels by 24 hours postoperatively. Left ventricular compliance, as measured by left ventricular end-diastolic pressure at a set end-diastolic diameter and by left ventricular diastolic pressure/diameter, was reduced at 2 hours (p less than 0.01) and gradually returned to control values at 48 hours. Thus, reversible myocardial injury due to anoxia is associated with both decreased contractility and compliance, with resultant depressed left ventricular performance for 24 to 48 hours after injury.

Aortic valve replacement and coronary bypass in patients with severe stenosis of the left main coronary artery.

Adequate myocardial protection is difficult to achieve during operations for combined aortic valve disease and severe stenosis of the left main coronary artery. A double cross-clamp technique, which facilitates the delivery of cardioplegic solution to the myocardium, is described here. We reviewed the experiences of 11 patients, 6 of whom underwent operation using the new technique.

The effect of adding mannitol or albumin to a crystalloid cardioplegic solution: a prospective, randomized clinical study.

To determine if the myocardial protection afforded by a cold crystalloid potassium cardioplegic solution could be improved by the addition of either mannitol or albumin, a prospective clinical study was undertaken in which 58 patients undergoing elective aortocoronary bypass were randomized to one of three groups. Each group featured a different cardioplegic solution. The solutions were a standard potassium crystalloid solution, a solution containing mannitol sufficient to raise the osmolality by 20 to 30 mOsm, and a solution containing 5% albumin. Preoperative, intraoperative, and postoperative evaluation included serial measurements of ejection fraction, myocardial-specific isoenzyme, and hemodynamic indexes of performance. Electrocardiographic evaluation for perioperative myocardial infarction and the need for postoperative inotropic and mechanical support were also included. No differences were found among the groups. Therefore, although the use of mannitol or albumin has been shown to be beneficial in an experimental setting, superiority of either additive could not be demonstrated clinically.

Temperature gradients and rewarming time during hypothermic cardiopulmonary bypass with and without pulsatile flow.

Pulsatile perfusion during cardiopulmonary bypass (CPB) has been reported to have a number of beneficial effects, including attenuation of hormonal stress responses and improved organ blood flow and function. To determine the effect of pulsatile perfusion on temperature gradients and the time required for cooling and rewarming during CPB, we studied 21 patients scheduled for elective coronary artery operations. The patients were divided into two comparable groups: Group 1 (N = 11) had standard nonpulsatile perfusion, while in Group 2 (N = 10), a pulsatile pump was used. Rectal and esophageal temperatures were monitored, as were deltoid muscle temperatures and upper arm and finger skin temperatures in the same extremity. Ambient temperature, bypass flow and pressure, and bypass time were similar in both groups. Time required to cool to the lowest esophageal temperature was virtually identical for both groups (Group 1, 17 +/- 3 min; Group 2, 17.6 +/- 5 min), as was rewarming time (Group 1, 26.8 +/- 11 min; Group 2, 27.2 +/- 6 min). There were no significant differences in temperature measurements between groups except briefly during rewarming when finger skin temperature rose more rapidly in Group 1 (p less than 0.05). Temperature changes following CPB were the same for both groups, with rectal and esophageal temperatures showing an inverse relationships. These data demonstrate that pulsatile flow does not substantially alter rewarming time or temperature gradients during hypothermic CPB.

Correlation of patterns of subendocardial reperfusion and left ventricular performance after ischemia.

Ninety-three dogs were studied with normothermic or hypothermic ischemia for 60 or 90 minutes, with or without potassium cardioplegia. Radioactive-labeled microspheres (9 +/- 1) were injected into the aortic perfusion cannula just prior to aortic cross-clamping and at 2, 6, and 10 minutes after the clamp was released. Left ventricular (LV) function was analyzed with a right heart bypass model before and 45 minutes after the ischemia period. Changes in LV function were defined as the arithmetic difference in the center of mass between preischemia and postischemia computer-drawn Sarnoff curves. Regardless of technique of myocardial protection, increased subendocardial flow 2 minutes after ischemia correlated strongly with preservation of LV function (p less than 0.01). Well-preserved hearts showed a rapid return to normal levels of coronary blood flow (p less than 0.01). In contrast, a delay in the peaking of subendocardial flow to 10 minutes was associated with poor function (p less than 0.01). There was a high correlation between ultrastructural morphology and LV function. While well-preserved hearts showed early preferential subendocardial perfusion, the poorly protected myocardium is unable to restore adequate subendocardial flow early in the reperfusion period.

Plasma vasopressin levels and urinary sodium excretion during cardiopulmonary bypass with and without pulsatile flow.

The use of pulsatile perfusion during bypass should create a more physiological milieu and thus attenuate the vasopressin stress response. To determine this, 20 patients scheduled for elective coronary artery bypass operation were studied in two groups. Group 1 had a standard nonpulsatile perfusion, and in Group 2 a pulsatile pump was used. Measurements were made before and after anesthesia, after surgical incision, and at 15 and 30 minutes during and after cardiopulmonary bypass. In both groups, vasopressin levels were significantly elevated after sternotomy (4.5 +/- 1.5 to 37 +/- 10 pg/ml in Group 1 and 3.1 +/- 1.2 to 33 +/- 9 pg/ml in Group 2, p less than 0.05) and during bypass (198 +/- 19 pg/ml in Group 1 and 113 +/- 16 pg/ml in Group 2) but were higher in Group 1 (p less than 0.05). With comparable perfusion pressures in both groups, Group 2 required higher flow (4.2 +/- 0.2 versus 3.5 +/- 0.3 L/min, p less than 0.05) and had lower resistance (1,351 +/- 182 versus 1,841 +/- 229 dynes sec cm-5, p less than 0.05) and higher urine Na+ (123 +/- 5 versus 101 +/- 8 mEq/L, p less than 0.05). These data demonstrate that pulsatile flow can significantly attentuate the vasopressin stress response to bypass. Since vasopressin, at these concentrations, is a potent vasoconstrictor and is capable of producing a Na+ diuresis, this may partially explain the higher flow requirements and the decrease in Na+ excretion.

Perforation of congenitally deformed aortic valve resulting in aortic insufficiency. Report of case successfully treated by aortic valve replacement.

This 40-year-old male presented with the signs and the symptoms of acute aortic insufficiency and underwent aortic valve replacement. At surgery a deformed aortic valve with perforation was found. This represents a unique example of a congenitally deformed aortic valve complicated by acute perforation with resultant valvular incompetence.