Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography.

AIMS: Off-line post-processing of colour tissue Doppler from digital loops may allow objective quantification of dobutamine stress echocardiography. We assessed the reproducibility of off-line measurements of regional myocardial velocities. METHODS AND RESULTS: Nine observers analysed 10 studies, each making 2400 observations. Coefficients of variation in basal segments from apical windows, at rest and maximal stress, were 9-14% and 11-18% for peak systolic velocity, 16-18% and 17-19% for time-to-peak systolic velocity, 9-17% and 18-24% for systolic velocity time integral, and 18-23% and 21-27% for systolic acceleration. Coefficients of variation for diastolic velocities in basal segments at rest were 11-40%. Coefficients of variation for peak systolic velocity were 10-24% at rest and 14-28% at peak in mid segments, and 19-53% and 29-69% in apical segments. From parasternal windows coefficients of variation for peak systolic velocity were 14-16% in basal posterior, and 19-29% in mid-anterior segments. High variability makes measurement unreliable in apical and basal anterior septal segments. The feasibility of obtaining traces was tested in 92 subjects, and >90% in all basal and mid segments apart from the anterior septum. CONCLUSION: Quantification of myocardial functional reserve by off-line analysis of colour tissue Doppler acquired during dobutamine stress is feasible and reproducible in 11 segments of the left ventricle. The most reliable measurements are systolic velocities of longitudinal motion in basal segments.

Diltiazem versus nitroglycerin for myocardial protection following coronary artery bypass grafting as assessed by dobutamine stress echocardiography.

BACKGROUND: Perioperative infusion of the calcium channel antagonist diltiazem reduces the occurrence and extent of postoperative myocardial ischemia. However, recent reports also mention nitroglycerin as the drug of choice to prevent conduit spasm after coronary bypass grafting. The diagnosis of myocardial ischemia in the perioperative setting is still problematic. Dobutamine stress echocardiography (DSE) is an established technique that combines inotropic stimulation with real-time myocardial imaging and delineates normal and abnormal regional contraction patterns. We assessed the perioperative anti-ischemic effects of diltiazem and nitroglycerin during hemodynamic stress using DSE. METHODS: 50 adult patients were included in a prospective randomized study. Diltiazem or nitroglycerin was used from the onset of extracorporeal circulation until 24 h postoperatively. Dobutamine stress echocardiography was performed in a stepwise fashion 2 to 3 h after elective coronary artery bypass grafting. RESULTS: In 42 of 49 patients, dobutamine stress echocardiography either reached a level of 40 micrograms/kg/min dobutamine or achieved the target heart rate. One patient improved in terms of segmental wall motion abnormalities and three patients developed new abnormalities without corresponding electrocardiographic changes. Analysis of ischemia-sensitive parameters showed lower creatine kinase MB (p = 0.032) and troponin I levels (p = 0.1) in the diltiazem group 24 h postoperatively. Heart rate was significantly lower in the diltiazem group (p = 0.0003). CONCLUSIONS: Under conditions of hemodynamic stress, DSE revealed no significant difference between diltiazem and nitroglycerin with regard to renewed ischemia.

Emergency angioplasty and stent deployment for acute occlusion of an anomalous single coronary artery (all three coronary arteries from one ostium in the right sinus of Valsalva).

A single coronary ostium is traditionally considered to be of little clinical significance. We report a case of a single ostium in the right sinus of Valsalva, giving rise to the right coronary artery, from which the left main coronary artery originated. Sudden death occurred seven days after acute gastrointestinal bleeding and subsequent interruption of aspirin therapy. Acute coronary angiography following successful resuscitation revealed an ascending thrombus in the right coronary artery. The patient underwent a complex percutaneous coronary angioplasty with stent deployment. We conclude that coronary artery disease may lead to severe ischemia with a large area at risk and major complications in patients with coronary anomalies. Patients with acute stent implantation might benefit from platelet aggregation even in cases of recent intestinal bleeding.

Effects of milrinone on pulmonary gas exchange in catecholamine-dependent heart failure.

Hemodynamic benefits of milrinone administration are accompanied by adverse effects on arterial oxygenation in mechanically ventilated patients with end-stage heart failure. Particular attention should be focused on pulmonary gas exchange variables after initiation of milrinone treatment in the critically ill patient.

[A simple method for AV-delay determination in dual chamber pacemakers]. / Eine einfache Methode zur Bestimmung des AV-Intervalls bei Zweikammerschrittmachern.

The individual adjustment of the AV intervals is a prerequisite for the hemodynamic advantages of dual-chamber pacing. The methods for the optimization of the AV-Delay (AVD) applied so far are time intensive. A simple and fast method is the approximate adjustment of the AVD with the surface-ECG. The aim of this work is the conception and validation of this new method. The optimal AVD is given if at the end of the atrial contraction the mitral valve is closed by the ventricular increase of pressure. In order to achieve this with pacemaker patients, the individually different atrial and ventricular conduction times must be considered. The different conduction times can be determined from the surface-ECG. Intra- and interatrial conduction times can be defined by the beginning of the atrial spike up to the end of the p-wave. The beginning of ventricular pressure increase corresponds to the peak of the stimulated QRS complex (beginning of the Iso-Volumetric Contraction time, ISVC) and depends on the interventricular conduction time.¶ In the case of 100 patients, who did not receive a cardiac pacemaker, the interval at the end of the p-wave (left atrial excitation, EP) up to the peak of the r-wave (ISVC) during rest and exercise was measured and an age referred average value of 100ms determined; this serves as standard value if no AV-conduction is available. The approximated optimized AVD is given if the interval of the end at the p-wave to the peak of the QRS-Complex amounts to 100ms. By means of a simple algorithm, the optimized AVD can, thus, be calculated:¶ After programming a long AVD, the interval at the end of the native or paced p-wave up to the peak of the stimulated QRS-Complex (EP/ISVC) is determined. This value EP/ISVC is then taken from the long AVD, the 100ms standard value is added and one receives the approximately optimized AVD.¶ In order to validate the described method, 13 consecutive patients (2 female, 11 male, average age 67±7.8 years) were included, and received for different indication (7 sick sinus syndrome, 4 AV block III, 2 binode disease) a DDD pacemaker (Affinity, St. Jude Medical).¶ About 8 weeks after implantation all patients underwent a PA catheter investigation, in order to optimize the AV-/PV-Delay of the pacemaker regarding the maximum cardiac output (CO). For CO measurement the thermo dilution method was applied. Altogether 17 complete hemodynamic measurements (9 times with different PVDs, 8 times with different AVDs) were executed. The patients 10-13 could be examined both in the VDD and in the DDD mode.¶ The minimum determined CO amounted to 3.5 l/min, the maximal CO 7.1 l/min and the average value was 5.62±0.98 l/min. In all patients not only one optimal AVD was found but, moreover, a varied interval of AVDs with which optimal CO results could be obtained. The comparison of surface ECG optimized AVD with the PA catheter optimized AVD showed a statistically significant correlation (0.825PV, 0.982 AV, P<0.01). Sixteen out of seventeen measurements were at an interval which enables hemodynamic optimal CO or stroke volume. Only one AVD determined from the surface ECG was situated slightly (10 ms) outside of a hemodynamic optimal determined AVD. Despite the encouraging test results represented here, further studies should examine the value of the new algorithm in comparison with the other techniques for AVD optimization.

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts.

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.

[Improved kidney function with intravenous prostaglandin E1 in patients with terminal heart failure]. / Verbesserung der Nierenfunktion durch intravenöses Prostaglandin E1 bei Patienten mit terminaler Herzinsuffizienz.

In end stage congestive heart failure activation of a series of compensatory mechanisms increase renal vascular resistance and impair renal function. Prostaglandin E1 is increasingly used in the treatment of severe heart failure for its vasodilating actions. In various experimental settings prostaglandin E analogues are known to improve renal function by modulating renal filtration pressure and redistribution of renal blood flow. However, prostaglandin E1 decreases systemic blood pressure and thus, also renal perfusion pressure, a fact by which renal function might be further compromized in heart failure patients. The aim of the study was to evaluate the effects of prostaglandin E1 on excretory renal function in patients with end stage heart failure and to prove the hypothesis, that the well known local actions of prostaglandins on renal microcirculation might outweigh the negative impact of an expected decrease in perfusion pressure. 25 patients with terminal congestive heart failure were investigated. 13 patients received prostaglandin E1 at a dose of 13.5 +/- 1.9 ng/kg/min in combination with constant rates of dopamine and dobutamine (group A), 12 patients received prostaglandin E1 at a dose of 10.3 +/- 1.7 ng/kg/min without catecholamines (group B). There was no significant difference in prostaglandin dosages between groups. Kidney function was assessed by measuring plasma creatinine and urea nitrogen, urinary output, creatinine clearance, osmotic and free water clearance at baseline and after 72 h of infusion therapy. Hemodynamic parameters were measured by using a balloon tipped pulmonary arterial catheter. Hemodynamic measurements during infusion showed a significant improvement in all patients. At the same time as expected mean arterial pressure decreased in both groups (p < 0.001). Nevertheless, in both groups a significant increase of creatinine clearance during infusion was observed (in group A from 45 ml/min to 78 ml/min., p < 0.05, in group B from 59 ml/min to 105 ml/min., p < 0.001). Creatinine clearance in group B (without catecholamines) reached higher levels than group A (p < 0.05). Urinary volumes did not change during infusion therapy, whereas free water clearance significantly decreased, as an indication of an improvement of renal concentrations ability. We conclude, that in patients with end stage heart failure continuous infusion of prostaglandin E1 improves excretory kidney function. These findings suggest that the local effects of prostaglandin E1 on renal microcirculation can counterregulate the negative impact of prostaglandins on renal perfusion pressure.

Effects of two different enalapril dosages on clinical, haemodynamic and neurohumoral response of patients with severe congestive heart failure.

Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 'high' in comparison to continued 'low' angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/- 1.1 years; 69 men, 14 women) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included. After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide, right heart catheterization at rest and exercise was performed. All patients presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35 mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P = 0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P = 0.01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.

The CarboMedics "top hat" supraannular prosthesis in the small aortic root.

Twenty-three patients, 11 men and 12 women, with a mean age of 64 (range, 34 to 78) underwent aortic valve replacement (AVR) with a CarboMedics "Top Hat" supraannular prosthesis between March 1993 and August 1994. The top hat supraannular prosthesis, a standard bileaflet valve with the cuff transferred to the valve inflow level, allowed implantation of 21-mm, 23-mm, and 25-mm valves, where a standard 19-mm or 21-mm valve would have usually been placed. One patient who had been in preoperative cardiogenic shock died in the perioperative period. Another had an intraoperative cerebral embolism with permanent impairment. Follow-up on 22 of 23 patients over a mean period of 9 months revealed mean Doppler gradients of 18 +/- 6 mmHg, 15 +/- 2.8 mmHg, and 11 mmHg, for the 21-mm, 23-mm, and 25-mm valves, respectively. Functional improvement was noted, with 17 patients in New York Heart Association (NYHA) Class I and 6 in NYHA Class II, postoperatively, compared with 0 in Class I, 9 in Class II, 10 in Class III, and 4 in Class IV, preoperatively. One patient showed reduced postoperative ventricular function with fractional shortening below 25%. Pandiastolic regurgitation intrinsic to the valve graded as slight was noted in all patients. Other postoperative complications included one patient with anticoagulant-related gastrointestinal bleeding and one other with prosthetic valve endocarditis successfully treated with antibiotics. The CarboMedics top hat valve allows a gain in prosthesis size of 2 mm to 4 mm in the aortic position over standard prostheses, resulting in favorable postoperative hemodynamics.

Diurnal variation of ventricular response to atrial fibrillation in patients with advanced heart failure.

Variability of ventricular rate was quantified by two measures of heart rate variability: the SD of the mean R-R interval (SDNN) and the SD of the 5-minute mean R-R interval (SDANN). In 35 patients with atrial fibrillation and advanced heart failure (left ventricular ejection fraction 20% +/- 9%, cardiac index 2.4 +/- 0.7 L/min/m2), SDNN and SDANN were compared to 13 preselected clinical and hemodynamic variables for prediction of outcome. During a 12-month follow-up period, 8 (23%) patients deteriorated clinically; 3 (9%) died, and 5 (14%) underwent heart transplantation. SDNN and SDANN correlated to the difference of the mean R-R interval between night (2 AM to 3 PM) and day (11 AM to noon) with r values of 0.62 and 0.77, respectively. From 15 preselected variables, only SDANN (chi 2 = 6.7, p = 0.01) was independently associated with survival on multivariate analysis. Dichotomized SDANN at 100 msec accurately predicted 12-month survival in 28 (80%) patients (relative risk = 9.77, p = 0.001). In conclusion, analysis of heart rate variability is useful in quantifying diurnal variation of ventricular rate in atrial fibrillation and might be useful in predicting survival in patients with advanced heart failure.

Sudden death and staged therapy for hemodynamic stabilization in patients enrolled in a heart transplantation program.

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14% +/- 5%, New York Heart Association Class II/III/IV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirty-seven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninety-nine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE1 for pre- and afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 +/- 9 months; patients who underwent staged therapy for 9 +/- 5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

OBJECTIVE: To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DESIGN: Prospective, placebo-controlled, randomized, single-blind study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). INTERVENTIONS: Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. MEASUREMENTS AND MAIN RESULTS: The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. CONCLUSION: PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.

Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension.

Plasma endothelin concentrations were evaluated in 53 chronic, congestive heart failure (CHF) patients with or without history of systemic hypertension, as well as in 9 with hypertension only and in 22 healthy control subjects. Plasma renin, aldosterone and atrial natriuretic peptide, as well as clinical and hemodynamic data were determined. In patients with CHF, big endothelin-1 was, independent of hypertension history, significantly greater than in hypertensive patients with normal cardiac function and in control subjects (both p < 0.0001). Patients with severe CHF had significantly greater big endothelin-1 values than did those with moderate CHF. During 12-month follow-up, 11 patients with CHF underwent heart transplantation, and 9 died; these patients had significantly greater big endothelin-1 concentrations than did the 33 clinically stable patients (p < 0.001). Big endothelin-1 and atrial natriuretic peptide correlated with right atrial pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction, effort capacity and severity of CHF (New York Heart Association functional class).

Clinical and neurohumoral response of patients with severe congestive heart failure treated with two different captopril dosages.

Although angiotensin converting enzyme inhibitor therapy is an established approach in the treatment of chronic heart failure, the required dosage remains unclear. This open 6 month study investigated the influence of different captopril dosages on the clinical course and neurohumoral activity of patients with severe heart failure (left ventricular ejection fraction < or = 20%). Eighty-five patients in New York Heart Association class II-IV despite treatment with digitalis, diuretics, and captopril (mean dose +/- SEM 28 +/- 2 mg.day-1 at baseline) for > or = 3 months received either 'low dose' captopril (< 75 mg.day-1, mean 32 +/- 2 mg.day-1; n = 46) or 'high dose' captopril (> or = 75 mg.day-1, mean 99 +/- 4 mg.day-1; n = 39) during the follow-up period. Both groups were comparable in clinical, haemodynamic and neurohumoral parameters at baseline. Functional state improved significantly only in the high dose group (P < 0.0001). Of 31 low dose and 20 high dose patients considered as heart transplantation candidates at baseline, 21 low dose and only six high dose patients remained on the waiting list (P < 0.0001). In patients in the low dose group, eight deaths were observed (P < 0.001). Seven patients remained on low dose captopril due to adverse effects. The initially elevated plasma levels of aldosterone and atrial natriuretic peptide decreased significantly only in high dose patients (P < 0.01). Renin increased significantly in both groups. These observations underline the necessity of suppressing neurohumoral overactivation with adequate doses of captopril reflected by sequential humoral plasma determination.

Prognostic value of heart rate variability in patients awaiting cardiac transplantation.

Time and frequency domain parameters of heart rate variability (HRV) were determined in patients with severe endstage heart failure awaiting cardiac transplantation (HTX). These parameters were then correlated with mortality to investigate the performance of HRV in discriminating between groups with high and low risk of death. The standard deviation of five consecutive RR intervals (SDANN) was found to be the parameter with the greatest sensitivity (90%) and specificity (91%). Patients with SDANN values of < 55 msec had a twenty-fold increased risk of death (90% confidence limits: 4-118, P < 0.001). The results furthermore suggest that measurements of HRV are superior to other prognostic markers such as left ventricular ejection fraction, pulmonary artery wedge pressure, cardiac index, and serum sodium levels. We conclude that HRV is a powerful, noninvasive tool to assess the risk of death in candidates for HTX. HRV measurements can therefore be used as a supplement to other markers of risk to determine the optimal therapeutic strategy in patients with severe congestive heart failure.