Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.

BACKGROUND: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. METHODS: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. INTERPRETATION: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure.

OBJECTIVES: To create a valid, sensitive, disease-specific health status measure for patients with congestive heart failure (CHF). BACKGROUND: Quantifying health status is becoming increasingly important for CHF. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a new, self-administered, 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. METHODS: To establish the performance characteristics of the KCCQ, two distinct patient cohorts were recruited: 70 stable and 59 decompensated CHF patients with ejection fractions of <40. Upon entry into the study, patients were administered the KCCQ, the Minnesota Living with Heart Failure Questionnaire and the Short Form-36 (SF-36). Questionnaires were repeated three months later. RESULTS: Convergent validity of each KCCQ domain was documented by comparison with available criterion standards (r = 0.46 to 0.74; p < 0.001 for all). Among those with stable CHF who remained stable by predefined criteria (n = 39), minimal changes in KCCQ domains were detected over three months of observation (mean change = 0.8 to 4.0 points, p = NS for all). In contrast, large changes in score were observed among patients whose decompensated CHF improved three months later (n = 39; mean change = 15.4 to 40.4 points, p < 0.01 for all). The sensitivity of the KCCQwas substantially greater than that of the Minnesota Living with Heart Failure and the SF-36 questionnaires. CONCLUSIONS: The KCCQis a valid, reliable and responsive health status measure for patients with CHF and may serve as a clinically meaningful outcome in cardiovascular research, patient management and quality assessment.

An analysis of the effect of age on survival after heart transplant.

BACKGROUND: Advances in immunosuppression and reports of improved survival after cardiac transplantation have led to a liberalization of traditional recipient eligibility criteria, especially age. While age alone is not a contraindication to transplantation, conflicting data exists regarding long-term survival of the older transplant recipient. METHODS: One hundred-fifty three patients undergoing consecutive first time cardiac transplantation from June 7, 1985 through February 1, 1997 were studied. For purposes of analysis, patients were stratified according to age (<55 years vs. >55 years) and hospital and late outcomes determined. RESULTS: The incidence of early and late acute cellular rejection was not different based up on age. The freedom from infection at 12 months was 54+/-5% for patients < or =55 compared to 32+/-8% for patients >55 years old (p = .04). Five year estimated survival for patients >55 years old was only 56+/-9% compared to 78+/-5% for patients < or =55 years old (p = .005). The hazard for death was highest within the first post-transplant year for older patients and was most commonly due to infection. Both advanced age and pre-transplant diagnosis of ischemic cardiomyopathy were found to be independently and additively predictive of reduced late survival. CONCLUSIONS: In the present study, late survival was adversely influenced by advanced age. Older patients (>55 years) with pre-transplant diagnosis of ischemic cardiomyopathy were particularly at high risk (risk ratio 4.6:1) for death. Given little prospect of expanding the number of donor hearts, careful selection of patients over the age of 55 with pre-transplant ischemic cardiomyopathy is warranted.

Secular trends in cardiac transplant recipient and donor management in the United States, 1990 to 1994. A multi-institutional study. Cardiac Transplant Research Database Group.

BACKGROUND: The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. METHODS AND RESULTS: At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months (P < .0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% (P < .0001). Donor ischemic time increased from 150 to 166 minutes (P < .0001), and the proportion of donors requiring pressor support increased from 68% to 85% (P < .0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) (P = .08). CONCLUSIONS: The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.

Diagnostic use of adenosine in two pediatric patients.

We describe the successful diagnostic use of adenosine in two pediatric patients. In the first case, adenosine infusion enabled exclusion of accessory pathway conduction in a patient who had previous evidence of Wolff-Parkinson-White syndrome. In the second case, adenosine infusion aided in the diagnosis of a nonreciprocating reentrant atrial tachycardia in a postoperative Fontan patient. The transient atrioventricular nodal blocking effect of adenosine added diagnostic certainty which was not apparent from the surface 12-lead electrocardiograms or rhythm recording in both patients. As the therapeutic use of adenosine for reciprocating supraventricular tachycardia in children becomes more popular, clinicians should also recognize the situations in which its use may facilitate diagnosis of other supraventricular rhythms.

Matching the heart donor and heart transplant recipient. Clues for successful expansion of the donor pool: a multivariable, multiinstitutional report. The Cardiac Transplant Research Database Group.

Little information is available regarding donor-specific parameters that predict success or failure after heart transplantation. Furthermore, with increasing numbers of patients awaiting heart transplantation, there is tremendous pressure to expand the donor pool by stretching the margins of donor acceptability. To gain insight into donor-related and donor-recipient interrelated predictors of death after transplantation, 1719 consecutive primary transplantations performed at 27 institutions between Jan. 1, 1990, and June 30, 1992, were analyzed. Mean follow-up of survivors was 13.9 months, and actuarial survival was 85% at 1 year. By multivariable analysis, risk factors for death included younger recipient age (p = 0.006), older recipient age (p = 0.0005), ventilator support at time of transplantation (p = 0.0006), higher pulmonary vascular resistance (p = 0.02), older donor age (p < 0.0001), smaller donor body surface area (female donor heart placed into larger male patient) (p = 0.003), greater donor inotropic support (p = 0.01), donor diabetes mellitus (p = 0.01), longer ischemic time (p = 0.0003), diffuse donor heart wall motion abnormalities by echocardiography (p = 0.06), and, for pediatric donors, death from causes other than closed head trauma (p = 0.02). The overall 30-day mortality rate was 7% but increased to 11% when donor age exceeded 50 years and was 12% when inotropic support exceeded 20 micrograms/kg/min dopamine plus dobutamine and 22% with diffuse echocardiographic wall motion abnormalities. The interaction of donor risk factors was such that the heart of a smaller female donor given high-dose inotropes placed into a larger male recipient produced a predicted 30-day mortality rate of 26% and the heart of a 25-year-old male donor given high-dose inotropes with diffuse echocardiographic wall motion abnormalities transplanted into a 50-year-old male recipient led to a predicted 30-day mortality rate of 17%. This analysis supports cautious extension of criteria for donor acceptance but with an anticipated greater risk in the presence of diffuse echocardiographic wall motion abnormalities and long anticipated ischemic time, particularly in older donors given inotropic support.

Sex-related differences in patients undergoing direct angioplasty for acute myocardial infarction.

Important sex-related differences have been recognized in several coronary artery disease presentation and treatment subsets. Little data exist describing the relative findings and outcome in women versus men who received direct percutaneous transluminal coronary angioplasty for acute myocardial infarction. We studied 670 such patients of whom 464 (69%) were men and 206 were women. The women were significantly older (67 +/- 11 years vs 61 +/- 11, p < 0.001) but had undergone less prior coronary artery bypass graft surgery (6% vs 12%, p = 0.02), whereas prior myocardial infarction (17% women vs 22% men) and coronary artery disease distribution were not significantly different. Forty-one percent of women and 43% of men had single-vessel disease (p = NS). Both women and men had 1.5 lesions/patient dilated acutely, with similar success rates (95% women, 91% men; p = 0.08). Mean ejection fractions were similar (48% in both groups), and a similar percentage in each group had an ejection fraction < 30% (10% women vs 13% men). Over a mean follow-up period of 86 weeks, the need for repeat catheterization was frequent and was similar in both groups (44% women, 47% men; p = NS), whereas documented restenosis was less common in women (20% vs 28% of patients, p < 0.05). The need for coronary artery bypass grafting was similar (15% women, 17% men; p = NS), as was the need for repeat percutaneous transluminal coronary angioplasty in the infarct vessel (14% women, 18% men; p = NS) and overall mortality (7% women, 9% men; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise echocardiography after coronary artery bypass grafting.

Exercise echocardiography was used to assess the adequacy of regional myocardial perfusion in 125 patients who had undergone coronary artery bypass grafting. There were 108 men and 17 women (mean age 65 years) evaluated from 6 weeks to 16 years (mean 7 years) after surgery. Resting parasternal long- and short-axis and apical 4- and 2-chamber echocardiograms were recorded, digitized and stored. Maximal, symptom-limited upright treadmill exercise was then performed with continuous electrocardiographic monitoring. Repeat echocardiographic imaging and digitization were repeated within 1 minute of exercise termination. Resting and postexercise digitized echocardiograms were compared. A normal regional wall motion response to exercise consisted of improved segmental contraction and was used to predict uncompromised regional vascular supply. Unimproved or worsened segmental contraction after exercise was abnormal and was used as a predictor of regional vascular insufficiency. All patients underwent cardiac catheterization within 1 month after exercise testing. Regional coronary insufficiency was considered to exist when a segment's major vascular conduit exhibited greater than or equal to 50% luminal diameter reduction. Compared with the simultaneously acquired stress electrocardiogram, exercise echocardiography had superior sensitivity (98 vs 41%), specificity (92 vs 67%), positive predictive value (99 vs 91%), and negative predictive value (86 vs 12%) (p less than 0.001, 0.1, 0.01 and less than 0.001, respectively). In addition, exercise echocardiography correlated closely with the extent and regional distribution of compromised vascular supply. Exercise echocardiography is a highly sensitive, specific and accurate screening test for abnormal global and regional myocardial vascular supply in patients who have undergone coronary artery bypass grafting.

Histopathologic abnormalities of the sinus node compared with electrocardiographic evidence of sinus node dysfunction after the modified Fontan operation: an autopsy study of 14 cases.

Autopsy specimens from 14 patients who had undergone a modified Fontan operation were evaluated to correlate the extent of histopathologic disruption of the sinus node with electrocardiographic findings of sinus node dysfunction. Patients with sinus node dysfunction (n=7) and those without (n=7) were similar in age, complexity of cardiac malformation, and number of postoperative days at time of death. The degree of fibrosis, local hemorrhage, necrosis, lymphocytic infiltration, and focal calcification of the sinus node and perinodal tissue was also similar in both groups. These findings, which showed a comparable amount of sinus node disruption in patients with normal sinus rhythm and in those with sinus node dysfunction, indicate a lack of correlation between the extent of histopathologic abnormality of the sinus node and electrocardiographic evidence of sinus node dysfunction.

Antitachycardia pacemaker treatment of postoperative arrhythmias in pediatric patients.

An automatic antitachycardia pulse generator (Intertach 262-12) was implanted in each of six pediatric patients (mean age, 10 years) with drug-resistant and persistent postoperative supraventricular arrhythmias. Four had bradycardia-tachycardia syndrome, two after a Mustard procedure for transposition of the great arteries, one after a Senning procedure for the same anomaly, and one after a Fontan procedure for univentricular heart with transposition of the great arteries. Of the two remaining patients, one had atrial flutter after a modified Fontan procedure for univentricular heart and one had intra-atrial reentry tachycardia after a modified Fontan procedure for double-outlet right ventricle with pulmonary stenosis. During a mean follow-up interval of 31 months after implantation, pacemakers were activated on multiple occasions and functioned appropriately in all six patients. Complications necessitated six invasive interventions in three patients: erosion or infection of the system, adaptor fracture, and connector block fracture on one occasion each and lead dislodgment on three occasions. Four of the six patients continued to take drugs at the end of this study; however, all patients had their drug therapy reduced and one was taking digoxin only. The number of hospital admissions decreased after implantation. Despite a number of technical challenges, this newer multiprogrammable antitachycardia pacemaker appears to be a valuable addition to the treatment of refractory postoperative supraventricular tachyarrhythmias in pediatric patients.

The use of percutaneous transluminal coronary angioplasty in myocardial infarction.

To evaluate the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) in the treatment of myocardial infarction, we reviewed the records of 508 consecutive patients treated within 6 hours of pain onset. Two hundred fifty-eight patients received direct PTCA without thrombolytic therapy, and 250 received thrombolytic therapy followed by immediate PTCA (within 24 hours, n=73) or delayed PTCA (later than 24 hours, n=177). The direct-PTCA group had the lowest initial success rate (92%) and the highest 1-week (8.1%) and 1-year (14%) mortality rates. Immediate PTCA had a 96% success rate, and 6.8% 1-week and 8.2% 1-year mortality rates. Delayed PTCA had the same initial success (96%), but lower 1-week (1.7%) and 1-year (2.3%) mortality. We conclude that both direct PTCA and combination treatment (thrombolytic therapy followed by PTCA) result in high rates of recanalizing occluded coronary arteries, but that combination treatment has higher initial success and survival rates, with delay in the use of PTCA producing the best survival rates.

Pseudo-preexcitation in tricuspid atresia.

Because we have observed a relatively large number of tricuspid atresia patients with a short P-R interval and slurring of the initial QRS pattern suggesting preexcitation, we conducted a retrospective study to determine the frequency of this electrocardiographic pattern and whether or not this represented the presence of a true atrioventricular bypass tract. Three pediatric cardiologists reviewed the surface electrocardiograms of 183 consecutive tricuspid atresia patients who had been evaluated at the Mayo Clinic between 1980 and 1986. The patients' ages ranged from 4 months to 21 years; the male-to-female ratio was 5:4. The criteria for preexcitation included 1) a P-R segment <0.10 sec, 2) a QRS complex >0.10 sec, and 3) slurring of the upstroke of the QRS complex ("delta wave"). Of the 183 patients, 22 (12%) had P-R segments <0.10 sec, 9 of whom fulfilled the criteria for preexcitation. Five of these had a history of supraventricular tachycardia, and 4 of the 5 had undergone invasive electrophysiologic studies: 2 had enhanced atrioventricular-nodal conduction and 1 had normal atrioventricular-nodal conduction; only 1 had an accessory pathway. Our results indicate that, although many patients with tricuspid atresia meet the surface electrocardiographic criteria for preexcitation, many of these patients may not have an atrioventricular bypass tract; this state might be termed "pseudo-preexcitation." In these instances, invasive studies probably would not be necessary; regrettably, it may be difficult to distinguish between the presence and the absence of preexcitation in such patients without invasive electrophysiologic studies.

The effects of hypoxemia on myocardial blood flow during exercise.

We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryosurgical modification of atrioventricular conduction for treatment of atrioventricular node reentrant tachycardia.

Cryosurgical modification of atrioventricular (AV) node conduction was performed in five patients with AV node reentrant tachycardia that used dual AV nodal pathways and was refractory to drug therapy. The procedure alleviated the tachycardia in all patients without the development of complete heart block and without any associated surgical morbidity or mortality. These results suggest that cryosurgical modification of AV node conduction is a promising and potentially curative method of treating AV node reentrant tachycardia.

Results of the modified Fontan operation in adults.

The results of the modified Fontan procedure were examined in 77 patients 18 years of age and older who underwent operation at this institution between October 1973 and December 1986. This series represents 16% of the patients undergoing the modified Fontan operation during that period. Of the 77 patients (46 men and 31 women), 29 had tricuspid atresia, 30 had double-inlet ventricle and 18 had other complex lesions. There were 5 (6%) hospital deaths, compared with 67 (17%) for patients of all ages undergoing the Fontan operation during the same period. Patient age 18 years and older was not a significant risk factor. There were 8 late deaths. Detailed follow-up data were available on 61 (95%) survivors from 5 months to 12 years (mean 4 years) postoperatively. Fifty-seven (93%) of the patients were in New York Heart Association class I or II, 20 (33%) were taking no medication and 11 (18%) were taking digoxin alone. Seventeen (28%) patients complained of persistent ascites or edema. The study indicated that (1) the modified Fontan operation can be performed with low mortality in adults, (2) the long-term outcome is favorable and (3) persistent ascites or edema may be a problem in some patients.

Plasma atrial peptide concentration during acute changes in cardiac filling pressure induced by a contrast agent.

Left ventricular end-diastolic pressure and the concentration of atrial peptides in plasma were measured before and after the administration of contrast material into the left ventricle of 12 patients during cardiac catheterization. A positive relationship between changes in left ventricular end-diastolic pressure and the circulating level of atrial peptides was found in all 12 patients. Increases in plasma atrial peptide levels were detected within less than one minute after injection of the contrast agent. We conclude that the release of atrial peptides in the human is modulated rapidly by changes in atrial pressure. The rapid release of peptides from the atria in response to an increase in atrial pressure, coupled with evidence that atrial peptides reduce cardiac filling pressure, is consistent with the possibility that the atrial peptides may serve as part of a negative feedback system that enables the heart to influence its own filling pressure.