R. Meyer

Angioscopic evaluation of atherosclerotic plaques: Validation by histomorphologic analysis and association with stable and unstable coronary syndromes

OBJECTIVES We validated coronary angioscopic observations with histologic assessment of material removed by atherectomy. BACKGROUND Up to now, angioscopic findings have been primarily descriptive, and the clinical significance still needs to be substantiated. The proposed Ermenoville classification is relevant but has not yet been validated by histomorphologic analysis. METHODS We compared angioscopic findings in patients with different coronary syndromes and used atherosclerotic material retrieved by directional coronary atherectomy to validate the angioscopic observations. Coronary angioscopy was performed in 63 patients (56 men, 7 women) with stable (26 patients) and unstable angina (37 patients) before and after directional coronary atherectomy. The identity of atherectomized material was confirmed by ex vivo visualization with the angioscope and by postatherectomy angioscopy. Angioscopic and histologic findings could be compared in 44 of 63 patients. RESULTS Angioscopic findings were grouped into gray-white and yellow lesions (gray-yellow, deep yellow, yellow-red or yellow-pink). We found that patients with unstable angina had predominantly yellow lesions (89%). In patients with stable angina, gray-white (43%) or yellow (57%) lesions were similarly distributed. Ruptured yellow plaques and red or pink thrombi were identified in 11% of patients with stable angina and 39% of patients with unstable or early postmyocardial infarction angina. Histologically, gray-white lesions represented fibrous plaque without degeneration in 64% and with degeneration in 36% of patients. Gray-yellow lesions were associated predominantly with degenerated plaque (64%) and, to a lesser extent, with fibrous plaque (14%) or atheroma (14%). Deep yellow and yellow-red lesions represented either atheroma (53%) or degenerated plaque (42%). CONCLUSIONS Our study establishes a histomorphologic basis for classification and interpretation of angioscopic findings. Yellow plaque color is closely related to degenerated plaque or atheroma and is associated with unstable coronary syndromes.

Intramyocardial delivery of bone marrow mononuclear cells and mechanical assist device implantation in patients with end-stage cardiomyopathy.

In end-stage heart failure, mechanical ventricular assist devices (VAD) are being used as bridge-to-transplantation, as a bridge-to-recovery, or as the definitive therapy. We tested the hypothesis that myocardial implantation of autologous bone marrow mononuclear cells (BMNC) increases the likelihood of successful weaning from left VAD (LVAD) support. Ten patients (aged 14–60 years) with deteriorating heart function underwent LVAD implantation and concomitant implantation of autologous BMNC. Bone marrow was harvested prior to VAD implantation and BMNC were prepared by density centrifugation. Two patients received a pulsatile, extracorporeal LVAD and eight a nonpulsatile implantable device. Between 52 and 164 × 107 BMNC containing between 1 and 12 × 106 CD34+ cells were injected into the LV myocardium. There was one early and one late death. The median time on LVAD support was 243 days (range 24–498 days). Repeated echocardiographic examinations under increased hemodynamic load revealed a significant improvement of LV function in one patient. Three patients underwent heart transplantation, and four patients remain on LVAD support >1 year without evidence of recovery. Only one patient was successfully weaned from LVAD support after 4 months, and LV function has remained stable ever since. In patients with end-stage cardiomyopathy, intramyocardial injection of BMNC at the time of LVAD implantation does not seem to increase the likelihood of successful weaning from VAD support. Other cell-based strategies should be pursued to harness the potential of cell therapy in LVAD patients.

A Decade of Percutaneous Coronary Interventions in Cardiac Transplant Recipients: A Monocentric Study in 160 Patients

BACKGROUND Transplant vasculopathy is a long-term complication of cardiac transplantation. Percutaneous transluminal coronary angioplasty (PCI) is a method of choice for local revascularization that is also increasingly used in heart transplant patients. METHODS Between October 1989 and November 2006, 160 adult cardiac transplant recipients (19 women) with mean age at heart transplantation of 47 +/- 12 years underwent PCI in 502 coronary segments during 319 catheterizations (balloon only, 209; bare metal stents, 227, drug-eluting stents, 66). Concomitant medical therapy, procedural data, primary success, recurrence of stenosis, and cardiac events (cardiac death or repeat transplantation) were analyzed retrospectively. Multivariate Cox proportional hazards analysis was performed. RESULTS Stents reduced early and mid-term recurrence of stenosis but had no impact on graft survival. Drug-eluting stents did not improve the restenosis rate. Immunosuppression with mycophenolate mofetil and concomitant treatment with statins and clopidogrel were significantly associated with reduced recurrence of stenosis and prolonged graft survival. Low steroid dosage was associated with a positive impact on graft survival. CONCLUSIONS Stenting in heart transplant patients has no impact on graft survival despite high primary success and deferred recurrence of stenosis. Early reduction of steroids, immunosuppression by mycophenolate mofetil, and concomitant treatment with statins are likely to reduce recurrent stenosis and to improve graft survival in heart transplant patients needing PCI. Long-term treatment with clopidogrel deserves further assessment.

Noninvasive diagnosis of cardiac rejection through echocardiographic tissue characterization

Ultrasonic tissue characterization is based on the assumption that microscopic tissue structures are identifiable by their acoustic properties. Our study group consisted of 23 cardiac recipients. Two-dimensional images were obtained within 2 hours of endomyocardial biopsy. The end-diastolic echo frames were digitized into the matrix of an image-processing system. A region of interest was placed into the anteroseptal segment of the left ventricle. The texture within the region of interest was analyzed using four major groups of texture analysis (first-order histogram, co-occurrence matrix, run-length statistic, and power spectrum). A total of 408 echocardiographic examinations were compared with histologic findings. The 117 initially calculated texture parameters were reduced incrementally using a series of discriminant analyses. A set of three texture parameters (inverse difference moment undirected, run-length nonuniformity vertical, and sector sum) was able to describe changed echocardiographic texture when rejection occurred. Using these three parameters, echocardiographic sensitivity was 89.0% and specificity was 83.6% for moderate rejection. We conclude that cardiac rejection is associated with echocardiographic texture alterations and that serial echocardiographic texture analysis can reliably identify rejection.

Wall motion assessment by tissue Doppler imaging after heart transplantation: timing of endomyocardial biopsies and facilitation of therapeutic decisions during acute cardiac rejection.

The high temporal and velocity range resolution of pulsed-wave tissue Doppler imaging (PW-TDI) is particularly suited for the early detection of left ventricular (LV) dysfunction. We assessed the value of multi-parametric PW-TDI evaluations for the early diagnosis of acute cardiac rejection (ACR) and for ascertaining its functional severity in order to avoid routine endomyocardial biopsies (EB) and to improve anti-rejection therapeutic decisions. Methods: In 240 patients, 485 EB were performed after circumferential wall motion analysis by PW-TDI at the basal LV posterior wall. We measured the systolic and diastolic peak velocities Sm and Em, the systolic time TSm (onset of first heart sound to Sm) and the early diastolic time TEm (onset of second heart sound to Em). PW-TDI alterations were tested for relationships with morphological rejection grade (ISHLT classification). Results: With serial examinations, all parameters where significantly altered during ACR. As an expression of aggravation or the new appearance of relaxation disturbances during ACR, we found significant (p 5 0.0001) Em reductions and TEm extensions. Without such changes, rejection can be excluded and EB become unnecessary, whereas reductions of Em and/or TEm extensions of more than 10% should be clarified by EB. Sm reductions over 5% showed high sensitivity (91.0%) and specificity (96.5%) for clinically relevant, treatable ACR (equal or more than grade 2, plus those 1A and 1B rejections accompanied by clinical symptoms). The PW-TDI changes in symptomatic patients with 1A and 1B rejections were equivalent to those found during higher grade cellular ACR, which may be explained by the high incidence of vascular/humoral rejection components found in symptomatic patients with unexpectedly low degrees of cellular reaction. Asymptomatic patients with 1A and 1B rejection revealed no significant PW-TDI changes. Conclusions: Serial multiparametric PW-TDI can spare patients from unnecessary and very distressing routine EB. The early detection of clinically relevant ACR by PW-TDI can be a valuable guide for therapeutic decisions.

Clinical results of the Shelhigh® stentless bioprosthesis in patients with active infective endocarditis:

Despite improvements in medical care, the incidence of left-sided active infective endocarditis (AIE) has remained unchanged over the past few decades. As shown in a review of 26 publications on a total of almost 3800 patients treated between 1993 and 2003, it is reported to affect a median of 3.6–5.4/100 000 persons per year, increasing in individuals over 65 years old to 15.0/100 000 persons per year, with a male:female ratio of 2:1 [1]. This unchanging incidence may be explained by changes in both the spectrum of causative organisms and in the patients affected [2]. New groups at risk of endocarditis have emerged, for example, the increasingly aging population with heart valve sclerosis, patients with prosthetic valves, those exposed to nosocomial infections, hemodialysis patients, and intravenous drug abusers [3], while chronic rheumatic fever, which was a classic predisposing factor in the preantibiotics era, has become rare in industrialized countries. These developments reflect our experience of continuing high numbers of patients who have to be operated on for AIE each year: between May 1986 and December 2008 a total of 1313 AIE patients were operated on at the Deutsches Herzzentrum Berlin, 72.4% (n=1009) for native endocarditis and 27.6% (n=384) for prosthetic endocarditis (Fig. 1). Open image in new window Fig. 1. Operations for native and prosthetic active infective endocarditis at the Deutsches Herzzentrum Berlin from May 1986 to December 2008