Aktuelle konservative Therapie der chronischen Herzinsuffizienz

Systolic heart failure and heart failure with preserved systolic function occur with similar prevalence rates in primary care. Nowadays we are equipped with drugs which effectively counteract the pathophysiological dysregulations in systolic heart failure and have resulted in significant reductions of morbidity and mortality. In recent years device therapy with implantable defibrillators and cardiac resynchronization devices has further supplemented and improved therapy. Due to the lack of dedicated randomized, controlled studies therapy of heart failure with preserved systolic function is mainly based on pathophysiological assumptions and targeted to symptom relief. Based on recent heart failure guidelines and latest studies this report gives an overview of the current recommendations for conservative treatment of both types of chronic heart failure.     

Comparison of cell therapy and cytokine therapy for functional repair in ischemic and nonischemic heart failure

Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and nonischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and nonischemic heart failure was induced by an IP injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2 x 10(5) c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p < 0.05 vs. control therapy). In the nonischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p < 0.05 vs. control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of nonischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.     

Effect of Oxygen Treatment on Heart Rate after Abdominal Surgery

Background: Cardiac complications are common during the postoperative period and may be associated with hypoxemia and tachycardia. Preliminary studies in high-risk patients after operation have shown a possible beneficial effect of oxygen therapy on arterial oxygen saturation and heart rate.

Methods: The authors studied the effect of oxygen therapy on arterial oxygen saturation and heart rate in 100 consecutive unselected patients randomly and double blindly allocated to receive air or oxygen therapy between the first and fourth day after major abdominal surgery.

Results: The median arterial oxygen saturation rate increased significantly from 96% to 99% (P < 0.0001) and the heart rate decreased significantly from 85 beats/min to 81 beats/min (P < 0.0001) during oxygen supplementation compared with air administered by a binasal catheter. The greatest decrease in heart rate occurred in patients with the lowest oxygen saturation or the highest heart rate values before oxygen supplementation. Overall, 73% of this unselected group of patients responded with decreased heart rate during supplemental oxygen therapy. No significant differences in changes in heart rate after oxygen supplementation were found between patients with or without an epidural catheter or between the postoperative day studied.     

Cardiac resurrection after bone-marrow-derived mononuclear cell transplantation during left ventricular assist device support

We describe a novel therapy of mononuclear cell transplantation combined with a left ventricular assist device (LVAD) for severe ischemic heart failure. Significant myocardial recovery by the LVAD rarely occurs in the severely failing heart. We undertook successful mononuclear cell transplantation in a patient who sustained an acute myocardial infarction that had resulted in the LVAD therapy. The heart regained good function after cell transplantation, and the LVAD was explanted 6 weeks later. These results suggest that this novel therapy could be an alternative to cardiac transplantation for severe ischemic heart failure.     

Heart transplantation for radiation-associated end-stage heart failure

Radiation-induced heart disease is an increasingly recognized late sequela of mediastinal radiation therapy for malignant neoplasms. We report four cases of heart transplantation for end-stage heart failure induced by mediastinal radiation therapy. Short-term and intermediate-term results are excellent with all four patients currently surviving a mean of 48 months after transplantation. Neither a second malignancy nor recurrence of the primary malignancy has been observed to date. The early results of heart transplantation for end-stage, radiation-induced heart disease are encouraging.     

Improvement of apparently fixed pulmonary hypertension with cardiac resynchronization therapy.

Many patients with advanced heart failure are ineligible for cardiac transplantation because of fixed pulmonary arterial hypertension. Cardiac resynchronization therapy, by stimulating the right atrium, and right and left ventricles, is a new therapy that effectively palliates symptoms in patients with heart failure. Cardiac resynchronization therapy increases cardiac output and decreases pulmonary capillary wedge pressure, thus partially reversing hemodynamic abnormalities that lead to secondary pulmonary hypertension in many heart failure patients. We describe a patient whose previously fixed pulmonary hypertension improved to the point that she was once again considered eligible for cardiac transplantation.     

Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema

Everolimus has recently received approval for immunosuppressive therapy in heart transplant recipients in Austria and Germany. At our heart center we have treated 114 patients with everolimus since January 2004. Here we describe 6 cases of lingual angioedema (corresponding to 5.3% of the patients). Symptoms occurred within 2 to 41 days after initiation of therapy. In 5 out of the 6 patients, lingual angioedema disappeared with anti-allergic treatment alone. However, in one patient, two severe recurrent episodes of lingual angioedema occurred so that therapy had to be discontinued. We conclude that the potentially life-threatening condition of lingual angioedema should be considered a severe drug reaction after initiation of everolimus therapy in heart transplant recipients.     

Heart block after coronary artery bypass--effect of chronic administration of calcium-entry blockers and beta-blockers

We evaluated risk of heart block after cardiopulmonary by-pass (CPB) in patients with normal conduction undergoing coronary artery bypass grafting who chronically received calcium-entry blockers, beta-blockers, or combined therapy. Before CPB, calcium-entry blockers alone produced an increase in P-R intervals but no change in heart rate; calcium-entry blocker effects were undetectable after CPB, beta-Blockers alone or with calcium-entry blockers produced lower heart rates and longer P-R intervals throughout the entire perioperative period when compared to no therapy (control) or calcium-entry blockers alone. Complete heart block did not occur; one control patient had transient second degree block after CPB. First degree block appeared transiently in 5% of the patients after anesthetic induction and in 15% on emergence from CPB, but was unrelated to drug therapy. We conclude that chronic calcium-entry blocker therapy has minimal effects on conduction perioperatively; beta-blocker effects persist for up to 10 hr after CPB; and the risk of heart block with either drug or combination is low and should not be a factor in their continued administration preoperatively.     

Management of heart failure: crossing boundary over to the surgical country

Pharmacologic therapy of heart failure appears to have reached its zenith. Few new agents are likely to replace conventional therapy. It is time for a paradigm shift in heart failure management. Aggressive surgical strategies to remodel the failing ventricle will shape heart failure therapy in the decade ahead. The articles that follow will describe in detail the advances that have been made in "crossing the boundary" to surgical treatment of advanced heart failure.     

Recent advances and limitations of medical treatment on heart failure

Main part of the management of chronic heart failure is pharmaceutical therapy. In patients with chronic heart failure due to left ventricular systolic dysfunction, enhanced activation of neurohormonal systems including sympathetic nerve and renin-angiotensin-aldosterone system plays the most important role in its progression and poor prognosis. Therefore, principle of treatment of chronic heart failure is inhibition of the elevated neurohormonal activity. Angiotensin converting enzyme inhibitors and beta blockers are class I drugs of choice. In patients who can not tolerate angiotensin converting enzyme inhibitors, angiotensin II receptor blockers are used as replacement. In patients with severe heart failure [New York Heart Association (NYHA) class > III], aldosterone antagonists are added. Diuretics are also class I drug necessary for an improvement of symptoms of heart failure. Recently, implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) are implanted more frequently, because volume of evidence indicates benefits of these non-pharmacological treatments. In this paper, recent advance in medical therapy for patients with heart failure and its limitation is discussed.     

Evidence that long-term survival of concordant xenografts is achieved by inhibition of antispecies antibody production.

Antibody and complement have been shown to be of primary importance in the rejection of hamster heart xenografts by rats. Very high anti-hamster antibody titers were detected at the time of rejection of hamster hearts transplanted into untreated or T cell deficient rats. This study demonstrates a method of inhibiting this antibody production by pulse therapy with cyclophosphamide (CyP) and continuous cyclosporine treatment, resulting in a median survival of the hamster heart of greater than 100 days. Controls and CsA-treated rats reject the transplanted hamster heart in a median of 3 days. CyP as a sole therapy resulted in a median survival of 14 days. Prolonged CyP therapy when combined with CsA was associated with increased death among rat recipients due to infection. Antispecies antibody production was suppressed during CyP and CsA therapy and did not recur after cessation of CyP therapy. Cessation of CsA therapy at 60 and 100 days posttransplantation resulted in subsequent rejection of the xenografts (median survival after cessation of therapy of 11 and 19.5 days, respectively) and was associated with production of rat anti-hamster antibodies.     

Ten-year follow-up after combined coronary artery bypass grafting and transmyocardial laser revascularization in patients with disseminated coronary atherosclerosis

Coronary artery disease involving heavily calcified lesions has been associated with worse short- and long-term outcomes including increased mortality. This paper aims to evaluate long-term survival benefit when CABG + transmyocardial laser revascularization (TMLR) are performed on the hearts of patients with disseminated coronary atherosclerosis (DCA). This novel retrospective study was conducted between 1997 and 2002 and followed 86 patients with ischemic heart disease and severe DCA who underwent TMLR using a Holmium:YAG laser and/or CABG. There were 46 patients who had CABG plus TMLR on at least one heart wall (“combined therapy group”) and 40 patients who had CABG or TMLR separately on at least one heart wall (“single therapy group”). For the whole group, actuarial survival at 10 years was 78.3% in the combined group compared to 72.5% in the single therapy group (p?=?0.535). Ten-year survival in the combined vs. single therapy group for the anterior heart walls was 100 vs. 72.2% (p?=?0.027). For the lateral and posterior heart walls were 73.7 vs. 73.3% (p?=?0.97) and 84.2 vs. 72% (p?=?0.27), respectively. Kaplan-Meier survival analysis showed benefit only for the anterior heart wall (F Cox test, p?=?0.103). Single therapy procedures on all heart walls (odds ratio 1.736, p?=?0.264) or on the anterior heart wall only (odds ratio 3.286, p?=?0.279) were found to be predictors of 10-year late mortality. Combined therapy (TMLR + CABG) provides benefit for perioperative mortality and long-term survival only when provided on the anterior heart wall. For patients with disseminated coronary atherosclerosis, cardiac mortality was found to be increased when followed up 6 years later, regardless of the therapy applied.     

Initial experience with bosentan therapy in patients considered ineligible for heart transplantation because of severe pulmonary hypertension

BACKGROUND: Pre-operative elevated pulmonary vascular resistance (PVR) has been associated with increased right ventricular failure and mortality after heart transplantation. The aim of this study was to assess the efficacy of bosentan, an oral endothelin-receptor antagonist, to reduce PVR in patients considered ineligible for heart transplantation because of severe pulmonary hypertension. METHODS: Seven patients with end-stage congestive heart failure and considered ineligible for heart transplantation because of severe pulmonary hypertension (PVR>2.5 Wood units after nitroprusside infusion) were included in the study. They received bosentan 62.5 mg b.i.d. for four wk and 125 mg b.i.d. thereafter. Right heart catheterization was repeated after six wk of therapy. RESULTS: After six wk of bosentan therapy, there was a significant decrease in PVR (6.0 +/- 2 vs. 3.8 +/- 2 Wood units, before vs. after bosentan; p = 0.02), in PVR during nitroprusside infusion (3.3 +/- 1 vs. 2.1 +/- 1 Wood units, before vs. after bosentan; p = 0.02) and in diastolic pulmonary artery pressure (33 +/- 7 vs. 23 +/- 7 mmHg, before vs. after bosentan; p = 0.04). No significant adverse events were observed. After bosentan therapy, five patients had PVR相似文献   

Current treatment of chronic heart failure

Cardiovascular diseases including heart failure represent a common disease in patients referred for anesthesia.In most cases, heart failure is caused by left ventricular dysfunction due to coronary heart disease. The aims of the treatment of chronic heart failure are the relief of symptoms, the improvement of prognosis and the prevention of the progression of heart failure. The first-line treatment involves the underlying heart disease such as myocardial revascularisation procedures in coronary heart disease or the correction of valve diseases. The pharmacological therapy depends on the stage of heart failure and symptoms of the patient. Heart failure therapy includes ACE-inhibitors, betablockers, diuretics und digitalis. Nitrates can be prescribed in patients with symptomatic heart failure despite adequate therapy but calcium antagonists are not recommended. Repeated or prolonged treatment with positive inotropic agents like phosphodiesterase inhibitors or beta-adrenergic drugs increases mortality but this is commonly used in acute stages of heart failure refractory to treatment. Interactions of ACE-inhibitors or AT1- antagonists with anesthetic agents can lead to severe hypotension especially in hypovolemic patients. Whether those drugs should be continued perioperatively or not has been controversially discussed. The use of betablockers has a positive impact on cardiac morbidity and mortality during and early after surgery. Chronic treatment with diuretics can be associated with hypovolemia and an imbalance of electrolytes leading to hypotension and arrhythmia during anesthesia but careful evaluation prior to anesthesia can avoid such complications. The continuation of digitalis during anesthesia has been controversially discussed due to the various interactions with anesthetics.     

Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound

The present study was performed to examine pressure transduction to the thoracic cavity during topical negative pressure (TNP) therapy of a sternotomy wound. Seven pigs underwent median sternotomy. Pressure transduction catheters were placed on the anterior surface of the heart (under the foam), in the pericardium (under the heart), in the left pleura and in the oesophagus at the level of the heart. The wound was sealed as for TNP therapy. The vacuum source was set to deliver negative pressures between -50 and -200 mmHg. The pressure on the anterior surface of the heart changed in a linear relationship with the applied negative pressure and was slightly lower than the applied negative pressure (-102 +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the pericardium (under the heart), in the left pleura and in the oesophagus, the wound pressure was only slightly affected by TNP therapy. In conclusion during TNP therapy, negative pressure is effectively transmitted to anterior portions of the heart. This may explain our recent findings that TNP increases microvascular blood flow in the myocardium. The pressure difference between the anterior and the posterior portions of the heart causes the right ventricle to be sucked up towards the posterior parts of the sternum, where it might be exposed to the sharp edges of the sternal bone, which may result in heart injury.     

Successful cardiac resynchronization therapy after cardiac surgery

Cardiac resynchronization therapy improves symptoms and survival in chronic heart failure patients, but has been poorly studied in the acute heart failure setting. We report the case of successful cardiac resynchronization therapy in the early postoperative period after cardiac surgery in a patient with left bundle branch block and proven ventricular dyssynchrony.     

Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat

BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778 and FK779) monotherapy and combination therapy were examined in prevention of acute heart and kidney allograft rejection and reversal of ongoing acute heart allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and kidney transplantation models. Immunosuppressants were administered orally from day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after transplantation for the reversal of ongoing acute rejection. RESULTS: In the prevention of acute heart rejection model, recipient rats treated with monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related prolongation of mean survival time (MST) compared with naive control rats (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and FK778 indicated that an additive to synergistic interaction was produced when compared with the respective monotherapies (combination index [CI]=0.631-1.022). These results were reproducible with tacrolimus and FK779 combination therapy (CI=0.572-0.846). Furthermore, similar results were also found in the prevention of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal of ongoing acute heart allograft rejection, combination therapy of tacrolimus and FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of acute heart and kidney rejection and reversal of ongoing heart allograft rejection in the rat.     

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy. One center's experience.

BACKGROUND: Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone. METHODS: A retrospective analysis of all heart transplant recipients at our institution who underwent surveillance coronary angiography for coronary allograft vasculopathy between 1995 and 2000 was performed. Patients with coronary allograft vasculopathy were stratified according to whether they received medical therapy or percutaneous coronary intervention. Baseline demographics, results of re-vascularization procedures and outcomes were analyzed. RESULTS: From 1995 to 2000, 301 patients underwent 602 coronary angiograms. Of the 79 patients who had angiographic evidence of coronary allograft vasculopathy, 53 were treated with aggressive medical therapy, while 26 underwent percutaneous coronary intervention in addition to aggressive medical therapy. At baseline, patients treated with aggressive medical therapy tended to be younger (54.6 +/- 13.8 years) than patients treated with percutaneous coronary intervention (62.6 +/- 7.6 years; p = 0.0079). Ejection fraction at time of diagnosis of coronary allograft vasculopathy was similar for both groups (medical therapy group, 44.4 +/- 13.4% vs percutaneous coronary intervention group, 47.2 +/- 12.7%; p = 0.38). In our cohort, heart transplant recipients with coronary allograft vasculopathy demonstrated greater mortality than heart transplant recipients without coronary allograft vasculopathy (p = 0.016). Patients who underwent percutaneous coronary intervention had a 60% re-stenosis rate at 6 months if they were treated with coronary angioplasty and an 18% re-stenosis rate if they received a coronary stent. Kaplan-Meier analysis showed no significant difference in survival in either treatment group at 1 year (80% for medical therapy group vs 95% for percutaneous coronary intervention group) or 3 years (68% for medical therapy group vs 79% for percutaneous coronary intervention group) after the angiographic diagnosis of coronary allograft vasculopathy. CONCLUSION: In this non-randomized trial, heart transplant recipients with coronary allograft vasculopathy were less likely to survive than patients without it. In addition, we found no statistical difference in mortality in heart transplant recipients with coronary allograft vasculopathy, regardless of whether they received percutaneous coronary intervention or aggressive medical therapy alone.     

Heart failure: state-of-the-art treatment and new therapeutic options

Heart failure is one of the most common health problems in Western countries. Untreated, the prognosis is very poor and there is no curative therapeutic approach yet. The gold standard for final stage congestive heart failure (CHF) is still heart transplantation. In recent years the medical therapy of heart failure has improved significantly. But still, beta-blockers, ACE inhibitors and diuretics are not offered to every patient with chronic heart failure. Currently, new therapeutic approaches are being evaluated: immunoadsorption and biventricular pacing. This article summarizes the latest recommendations for medical therapy of heart failure and will explain the mechanisms and clinical results of these new therapeutic options.     

The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure.

It has been reported that growth hormone (GH) deficiency induced cardiomyopathy responds to growth hormone replacement therapy. We describe the case of a middle-aged male with cardiomyopathic heart failure and growth hormone deficiency of the adult secondary to surgical panhypopituitarism. We demonstrate clinical and hemodynamic improvement of cardiac function with growth hormone replacement therapy despite underlying structural heart disease.