Hans-Wilhelm Höpp

Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition

The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function.

Phosphodiesterase III inhibition or adrenoreceptor stimulation: Milrinone as an alternative to dobutamine in the treatment of severe heart failure

High levels of endogenous plasma catecholamines in patients with severe congestive heart failure induce a down-regulation of the myocardial beta-adrenoreceptors and thus cause adrenoreceptor agonists, such as dobutamine, to be less effective in the treatment of these patients. Phosphodiesterase III inhibitors work independent of adrenoreceptor activity and plasma catecholamine levels; thus these agents are likely to be more effective in the treatment of severe heart failure. The present study compares both the initial and late hemodynamic effects of dobutamine and milrinone during sequentially administered 24-hour infusions. Twenty patients with severe heart failure (New York Heart Association class III, n = 4; New York Heart Association class IV, n = 16) were investigated. Dobutamine could be administered at the prescribed maximum dose of 15 micrograms/kg/min for 24 hours in only 15 of 20 patients. In three patients the dose was reduced or dobutamine infusion completely stopped because of a drug-related increase in heart rate greater than 140 beats/min. Another 2 of 20 patients showed no hemodynamic improvement over 3 hours at the maximum dose of 15 micrograms/kg/min. Dobutamine administration was also discontinued in these patients on account of the existing unfavorable hemodynamic condition, and therapy with intravenous milrinone was started. All 20 patients responded to milrinone without side effects, although comparison of the hemodynamic effects during a 24-hour infusion was possible in only 15 patients. The 15 patients studied over both observation periods experienced an increase in heart rate from 88.8 to 105.6 beats/min (+ 1 hour; p less than or equal to 0.001) when receiving dobutamine but had no increase with milrinone. Stroke volume increased during dobutamine infusion from 19.3 to 28.9 ml/m2 (+49.6%) after 1 hour and then fell continuously to 25.2 ml/m2 after 12 hours; during milrinone therapy, stroke volume increased from 18.8 to 31.2 ml/m2 (+66%; p less than or equal to 0.001) and remained at this level until the end of the infusion (30.2 ml/m2). Pulmonary capillary wedge pressure (PCWP) decreased (p less than or equal to 0.001) immediately during milrinone therapy from 26.5 to 16.2 mm Hg after 30 minutes and stabilized at 20.1 mm Hg after 24 hours. During dobutamine infusion PCWP showed a delayed decrease from 27.8 to 19.0 mm Hg after 6 hours and subsequently rose to 22.7 mm Hg after 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis of left ventricular thrombi by magnetic resonance imaging and comparison with angiocardiography, computed tomography and echocardiography

Abstract Left ventricular (LV) thrombi are common in patients with acute and healed anterior myocardial infarction. Although the reported incidence of clinically diagnosed embolism varies widely,1–3 diagnosis of thrombus seems to carry an increased risk for this potentially life-threatening complication. It is not entirely clear whether long-term anticoagulation can reduce the embolism rate in patients with chronic aneurysms with an acceptable risk of bleeding. However, it is widely assumed that this is so; thus, the diagnosis of LV thrombus has far-reaching consequences. It is difficult to diagnose LV thrombus using currently available imaging techniques. LV angiography carries the risk of precipitating systemic emboli and has a low sensitivity in most reported studies.4 Echocardiography has been reported to be fraught with false-positive results.5,6 Indium-111 platelet scintigraphy reflects thrombus activity but has suboptimal sensitivity, especially for small thrombi.7 More recently, computed tomography (CT)8 and magnetic resonance imaging (MRI)9,10 have shown encouraging results in the detection of LV thrombi. However, the diagnostic accuracy of MRI has not been evaluated with independent confirmation by surgery or autopsy. This study describes the sensitivity and specificity of MRI in the diagnosis of LV thrombi in patients with LV aneurysms undergoing surgical aneurysmectomy, and compares the results with those of angiography, 2-dimensional echocardiography and CT performed in the same patients.

The effect of LDL apheresis on progression of coronary artery disease in patients with familial hypercholesterolemia

This study investigated the effect of extracorporal lipid-lowering therapy by low-density lipoprotein (LDL) apheresis on coronary artery disease in a population characterized by early development and rapid progression of atherosclerosis. We treated 32 patients aged between 15 and 63 years with drug-refractory familial hypercholesterolemia, treated once a week by immuno-specific LDL apheresis for 3 years in a controlled prospective and non-randomized trial; 25 patients (14 females and 11 males) completed the study. Noninvasive data were obtained by physical examination, 12-lead ECG and exercise testing. Invasive cardiological data were obtained by cardiac catheterization according to a standardized protocol in four cardiological centers. Left ventricular ejection fraction was calculated using planimetry. Coronary stenoses were measured quantitatively in 23 defined coronary segments by a panel of four investigators with an electronic digital caliper. In addition, overall coronary atherosclerosis was visually qualified. Final decisions on a classification into one of three groups (regression, no change, progression) of coronary atherosclerosis were based on panel consensus. Six cardiac events occurred throughout the study: percutaneous transluminal coronary angioplasty in one patient, coronary bypass grafting in three and two deaths. Statistical analysis of exercise testing yielded no significant change for maximum power and work capacity during the study period. Hemodynamic data revealed no significant change; mean ejection fraction was calculated as 65.8 ± 15.9% at study entry and 67.0 ± 12.7% at completion. Quantitative measurement of 111 circumscribed coronary stenoses showed a mean stenosis degree of 45 ± 26% at entry cineangio-film and 43 ± 22% at final cineangio-film demonstrating no significant change. Eight localized stenoses showed a regression of more than 10% and 11 stenoses a progression of more than 10%. Panel consensus decision for overall coronary atherosclerosis resulted in regression in no patients, no change in 16, questionable progression in 3, definite progression in 5, and undecided in one. We conclude that specific LDL-apheresis therapy can be used effectively for primary and secondary prevention of coronary artery disease in patients with familial hypercholesterolemia. Its beneficial effect was the prevention of further progression of coronary artery disease in the majority of the study population.

A synergistic approach to optimal stenting ☆: Directional coronary atherectomy prior to coronary artery stent implantation—the AtheroLink registry

OBJECTIVES The AtheroLink registry sought to observe the effect of plaque burden reduction by directional coronary atherectomy (DCA) prior to stenting on acute lesion success rate, on the clinical success rate and on the incidence of in-stent restenosis six months after intervention. BACKGROUND Although coronary stenting has reduced restenosis, its effect has been less favorable in complex lesions with a high plaque burden that results from suboptimal stent expansion. Therefore, plaque removal by DCA may improve the results of coronary stenting. METHODS A total of 167 patients with >60% stenosis in a native coronary artery of 2.8 to 4.0 mm in diameter were enrolled in 10 study centers on an intention-to-treat basis. All patients underwent DCA aimed at an optimal result (residual diameter stenosis <20%) followed by stenting. Angiographic follow-up was performed in 120 (71.8%) patients at 5.3+/-2.8 months. RESULTS Lesion success was achieved in 164/167 (98.2%) patients, and the clinical success rate was 95.2% (159/167 patients). The overall restenosis rate in the 120 patients with angiographic follow-up was 10.8% (13/120). Incidence of restenosis was lower (8.4%) in patients with optimal stent deployment following DCA compared to patients with a persisting caliber reduction >15% (restenosis rate 15.3.%) and restenosis occurred with a significantly higher frequency (p<0.04) in distal lesions (37.5%) compared to proximal stenoses (9.0%). CONCLUSIONS This observational multicenter registry points to a potential reduction in restenosis by a synergistic approach of DCA and stenting performed under routinely accessible angiographic guidance. Therefore, multicenter-based randomized clinical trials are clearly warranted to finally clarify the validity of this complex approach versus conventional angioplasty plus stenting.

In vivo uptake of azithromycin in human coronary plaques

Ten patients with symptomatic coronary artery disease received oral azithromycin for 3 days and underwent directional atherectomy on the third day. Azithromycin was found in all plaque samples with a median concentration of 284 ng/ml (95% confidence interval 163 to 517 ng/ml).

Coronary angioscopy during cardiac catheterization and cardiac surgery.

SummaryCoronary angioscopy (CA) was performed in 30 patients (pts) during cardiac catheterization (Group 1) and in 11 pts during coronary bypass surgery (Group 2) using ultrathin fiberoptic angioscopes (Ø1.2–1.8 mm). For percutaneous CA (Group 1) the angioscope was introduced through a 9F guiding catheter from the femoral artery. The viewing field was cleared by flushing Ringers solution and short-time occlusion of the coronary ostium by the guiding catheter. In Group 2 CA was performed retrogradely from the distal arteriotomy and through the bypass vein during flushing with cardioplegic solution. In Group 1 in 17/30 pts the coronary artery could be successfully examined by CA. In 13 pts the obstruction was eccentric and irregular shaped. In 2/5 pts, in whom CA was performed successfully pre and post balloon dilatation, CA after PTCA revealed an intimal rupture without clinical or angiographical signs of the intimal dissection. In Group 2 in 9/11 pts good visualization of stenoses could be achieved. At the obstruction site CA revealed thrombi in 3 pts and ulcer in 1 pts. In contrast to angiography, which estimates the lumen diameter of a segmental lesion, CA gives information about the luminal shape and the underlying substance of the obstruction (e.g. atheroma, thrombus, ulceration). The main problems in percutaneous CA are the insufficient intraluminal guidance, the insufficient depth of view of the angioscopes, and the limited examination time.

Assessment of Ventricular Vulnerability by Holter ECG, Programmed Ventricular Stimulation and Recording of Ventricular Late Potentials

In a total of 40 patients, 10 females and 30 males, aged 42 to 65 years (mean: 53 ± 6 years) the diagnostic accuracy of three methods that might indicate left ventricular vulnerability, has been tested. These methods comprise the spontaneous occurrence of complex ventricular arrhythmias (Lown’s classes IVa and b and ventricular tachycardias), the recovery of ventricular late potentials within the signal averaged surface ECG, and the induction of repetitive ventricular response during programmed right ventricular stimulation. The “gold standard” was the out-of-hospital documented spontaneous occurrence of ventricular tachycardias and/or fibrillation in each of these 40 patients, 21 of whom had to be resuscitated by DC shock.

Dynamic behavior of ventricular late potentials

In a series of 44 patients, 5 females and 39 males, the incidence and dynamic behavior of ventricular late potentials was studied. Using a home-built high resolution electrocardiogram equipment ventricular late potentials were found within the ST segment in 27/44 patients, and in 11 patients were the late potentials observed intermittently. In 21/44 patients late potentials were also present after the T wave, in 5 individuals intermittently.

The clinical significance of coronary angioscopy in patients with coronary heart disease

SummaryThe feasibility and safety of coronary endoscopy was evaluated in three sets of investigations: in 7 cadaver hearts, in 11 patients undergoing coronary bypass surgery, and in 30 patients during routine cardiac catheterization prior to coronary balloon angioplasty (PTCA). In three of the seven cadaver hearts the lumen of the arteries appeared normal. In three diffuse atherosclerotic lesions, and in one, a high-grade, tight stenosis were observed. In nine of eleven patients in the operation room, the lesions of interest could be visualized, and high-grade stenoses were found in all. In addition, in three patients with unstable angina pectoris, fresh thrombi were seen at the site of stenosis. In six of the nine patients, the periphery of the native coronary vessel was found to have no further stenotic regions. During cardiac catheterization in 17/30 patients, the lesion of interest could be examined angioscopically, and in 13 instances the stenosis appeared excentric and irregularly shaped. In three instances, multiple ulcerations were seen in the stenotic area. In two of the five patients, intimal ruptures were found following PTCA, which could not be documented angiographically. Coronary endoscopy provides valuable additional information on the nature and appearance of atherosclerotic lesions. It can be performed clinically without great harm to the patients. Despite some limitations, it will probably become a routine diagnostic tool in patients undergoing routine coronary angiography, balloon angioplasty or high-frequency angioplasty, and coronary bypass grafting.