[Amyloidosis of the heart]. / Amyloidose des Herzens.

Amyloidosis is a heterogeneous group of diseases characterized by the pathological deposition of autologous proteins in an antiparallel ß-sheet confirmation forming non-branching linear fibrils of indefinite length and an approximate diameter of 10-12 nm. Cardiac amyloidosis is caused by deposits in the heart and may lead to cardiac arrhythmia and low output failure. Following the diagnosis, classification of the amyloid protein and evaluation of further organ involvement is mandatory. Treatment approaches are based on reduction of the production of amyloid precursor proteins. Standard heart failure treatment is usually not well tolerated and the underlying disease remains unaffected. Cardiac amyloidosis, especially of the light chain type, is associated with a poor outcome. The clinical picture is uncharacteristic, therefore correct diagnosis of cardiac amyloidosis is often delayed in many patients. Combination of clinical symptoms of different organ systems should alert the physician to the diagnosis of amyloidosis.

[Systemic amyloidoses]. / Systemische Amyloidosen.

Amyloidoses are rare protein folding disorders, in which proteins are deposited as insoluble fibrillar aggregates due to a conformational change. This can occur in a local or systemic form. Systemic amyloidoses are life-threatening complications of monoclonal gammopathy, chronic inflammatory diseases or within hereditary diseases. The causative treatment of amyloidosis is the reduction of the amyloid precursor protein by chemotherapy, anti-inflammatory treatment, or liver transplantation. Early diagnosis of the disease is essential in order to effectively treat patients and avoid further deterioration of organ functions.

Increased incidence of acute graft rejection on calcineurin inhibitor-free immunosuppression after heart transplantation.

BACKGROUND: Calcineurin inhibitor (CNI)-free immunosuppression is used increasingly after heart transplantation to avoid CNI toxicity, but in the absence of a randomized trial, concerns remain over an increased rejection risk. METHODS: We studied the incidence of graft rejection episodes among all cardiac graft recipients, beginning with the first introduction of CNI-free protocols. We compared events during CNI-free and CNI-containing immunosuppression among 231 transplant recipients of overall mean age 55.2 ± 11.8 years, from a mean 5.2 ± 5.4 years after transplantation through a mean follow-up of 3.1 ± 1.4 years. We considered as acute rejection episodes requiring treatment those of International Society for Heart and Lung Transplantation. RESULTS: During the total follow-up of 685 patient years (CNI-containing, 563; CNI-free, 122), we performed 1,374 biopsies which diagnosed 78 rejection episodes. More biopsies were performed in CNI-free patients: biopsies/patient-month of CNI-containing, 0.13 versus CNI-free, 0.22 (P < .05). The incidence of rejection episodes per patient-month was significantly higher on CNI-free compared with CNI therapy, among patients switched both early and later after heart transplantation, namely, within 1 year, 0.119 versus 0.035 (P = .02); beyond 1 year, 0.011 versus 0.004 (P = .007); beyond 2 years, 0.007 versus 0.003 (P = .04); and beyond 5 years: 0.00578 versus 0.00173 (P = .04). CONCLUSIONS: Rejection incidence during CNI-free immunosuppression protocols after heart transplantation was significantly increased in both early and later postoperative periods. Given the potentially long delay to rejection occurrence, patients should be monitored closely for several months after a switch to CNI-free immunosuppressive protocols.

[Return to work after heart transplantation]. / Berufliche Wiedereingliederung nach Herztransplantation.

Heart transplantation is the most effective treatment option for patients with end-stage heart failure to improve exercise tolerance and quality of life. This increase in quality of life may assume that heart transplant recipients are also able to return to their work. In general, there are no medical reasons to oppose a return to work. Despite enormous advances in medical rehabilitation after heart transplantation, the rate of working people among heart transplant recipients is very low. According to a survey at the Heidelberg Heart Transplant Center, only 37% of the heart transplant recipients return to work. This may be caused by tranplant-related problems as well as factors independent of heart transplantation. Furthermore, the psychological burden due to heart transplantation might hamper professional rehabilitation. Thus, psychotherapeutical support during transplant process appears to be appropriate. As a major issue for a return to work appears to be the patient's will, the voluntary nature of return to work step by step has to be limited. Programmes with close collaboration between physicians, health insurance companies, retirement insurance companies, employers, and especially the patients are necessary to increase the rate of professional rehabilitation and to underscore the health economic justification of heart transplant programmes.

[60-year old woman with round lesion of the right upper lobe of the lung after heart transplantation]. / 60-jährige Patientin mit Raumforderung im rechten Lungenoberlappen nach Herztransplantation.

We report on a woman presenting with fever and novel round lesion in the lung four months after heart transplantation. Microbiologic assessment of bronchial lavage and operative specimen revealed pulmonary nocardiosis. Furthermore, cerebral involvement has been observed. Antibiotic treatment according to the microbiological sensitivity test for eleven months resulted in complete remission of pulmonary and cerebral nocardiosis. Immunosuppressive treatment increases the risk for opportunistic infections early after transplantation as well as malignancies during the late course.

[Current diagnostic and therapy of light chain amyloidosis]. / Aktuelle Diagnostik und Therapie der Leichtkettenamyloidose.

Amyloidoses are protein-folding disorders in which soluble proteins are deposited as insoluble fibrillar aggregates due to a change in protein conformation. This might occur intra- or extracellularly, systemically or in a localized manner. The light chain type is the most common form of systemic amyloidoses and has the worst prognosis. The underlying disease is a monoclonal, mostly non-malignant plasma cell disorder. The causative treatment is the reduction of the amyloidogenic light chains with conventional or high-dose chemotherapy. Meanwhile, the"new drugs" used in multiple myeloma are also successfully applied. Early diagnosis is important to be able to treat patients effectively and to avoid further deterioration of organ function. Patients with newly diagnosed amyloidosis should be referred to a specialized center for consultation, diagnosis and treatment recommendation.

[Risk stratification and treatment of cardiac amyloidoses]. / Risikostratifizierung und Therapie kardialer Amyloidosen.

Cardiac amyloidoses are a heterogeneous group of cardiomyopathies that are resistant to treatment and are associated with a poor outcome. Standard heart failure treatment is usually not well tolerated and the underlying disease remains unaffected. The clinical picture is uncharacteristic. Cardiac amyloidosis is often associated with dysfunction of additional organs. Early cardiac amyloid involvement usually reveals left ventricular hypertrophy, impairment of longitudinal shortening and diastolic ventricular function. Without adequate therapy (bi-)ventricular hypertrophy will progress to severe systolic ventricular function decrease. The combination of low voltage pattern, left ventricular hypertrophy and granular sparkling is characteristic for advanced cardiac amyloid involvement. Cardiac magnetic resonance imaging and scintigraphy yield further information on the pattern and severity of cardiac involvement. In unclear cases (left ventricular) endomyocardial biopsy is necessary. Detection of early cardiac involvement and proper identification of patients at high risk for sudden cardiac death due to rapid progressive amyloidosis is still incompletely defined. Referral to specialized centers is strongly recommended.

[MR imaging in cardiac amyloidosis--morphology, function and late enhancement]. / Magnetresonanztomografie bei kardialer Amyloidose--Morphologie, Funktion und late enhancement.

PURPOSE: Since limited data is available using MR imaging in cardiac amyloidosis, the purpose of our study was to evaluate morphological and functional differences of the heart using cardiac MRI. MATERIALS AND METHODS: 19 consecutive patients (14 males, 5 females, mean age 59 +/- 6 years) with histologically proven cardiac amyloidosis were evaluated with MRI at 1.5 T. Results were compared with data of 10 healthy, age-matched control subjects (5 males, 5 females, mean age 60 +/- 6 years). Functional and morphological data including late enhancement (LE) was acquired. RESULTS: Compared to the control group, patients with cardiac amyloidosis had thickened atrial walls and dilated atriums. Both ventricles and the interventricular septum were thickened. The LV hypertrophy was focal in 11 / 19 (58 %) and global in 4 / 19 (21 %) of patients. A myocardial edema occurred in 2 / 19 patients with cardiac amyloidosis (11 %). An edema of the myocardium was visible in 2 / 19 (11 %) of patients. The LV ejection fraction was statistically significantly decreased. The prevalence of LE was 74 % (14 / 19 of patients). LE was detected predominantly in the LV anterior wall and in the interventricular septum. Within the segments LE was located predominantly in a subendocardial location. Between patients with and without LE no statistically significant differences of functional and morphological results were able to be established. CONCLUSION: There are three major outcomes of our assessment: 1. The LV hypertrophy is focal in the majority of patients with cardiac amyloidosis. 2. No statistically significant differences can be established in regard to the functional and morphological features between patients with and without LE. 3. Myocardial edema is a possible feature in cardiac amyloidosis.

Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.

Central hypercapnic chemoreflex modulation of renal sympathetic nerve activity in experimental heart failure.

Activation of the sympathetic nervous system plays an important role in the pathophysiology and progression of congestive heart failure (CHF). The precise mechanisms responsible for sympathetic activation in CHF are not yet clearly established. An altered central hypercapnic chemoreflex modulation of sympathetic nerve activity (SNA) might be an explanation. Therefore, the response of postganglionic renal SNA to elevation of CO2 concentration in the inspiratory air to 2, 4, and 6% was determined in anesthetized, artificially ventilated rats after denervation of peripheral baro- and chemoreceptors 2 weeks (group A; n=8) or 6 weeks (group B; n=11) after induction of an aorto-caval shunt, or 4 weeks after aortic banding (group C; n=7). In all CHF models, left ventricular enddiastolic pressure was increased (A 8 +/- 1, B 8 +/- 1, C 10 +/- 2 mmHg) as compared to sham operated controls (A 3 +/- 1, B 4 +/- 1, C 5 +/- 1 mmHg). Indicative of left ventricular hypertrophy and pulmonary congestion, wet weight of heart (A + 60%, B + 93%, C + 49%) and lungs (A + 15%, B + 36%, C + 12%) were also enhanced as compared to controls. Elevation of inspiratory CO2 concentration to 2,4, and 6% increased renal SNA by approximately 10, 20, and 30% from resting activity in all groups. The maximum SNA responses at 6% CO2 in the groups with CHF (A + 390 +/- 95, B + 425 +/- 133, C + 368 +/- 158 microVs) did not differ from those in the respective controls (A + 510 +/- 130, B + 570 +/- 180, C + 275 +/- 25 microVs). It is concluded that under these experimental conditions the central hypercapnic chemoreflex sensitivity is not altered in either of the employed models of CHF and therefore may not play a major role for the well-known elevation of SNA in CHF.