Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure.

BACKGROUND: Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS: Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS: Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS: Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Heart transplantation in patients aged 70 years and older: a two-decade experience.

OBJECTIVE: Advanced age has been viewed as a contraindication to orthotopic heart transplantation (OHT). We analyzed the outcome of OHT in patients who were aged 70 years or older and compared the results with those in younger patients during a two-decade period. METHODS: A total of 519 patients underwent first-time single-organ OHT at our institution from 1988 to 2009. Patients were divided into three groups by age: ≥70-years old (group 1, n=37), 60 to 69-years old (group 2, n=206), and ≤60-years old (group 3, n=276). Primary endpoints were 30-days, and 1-, 5-, and 10-years survival. Secondary outcomes included re-operation for bleeding, postoperative need for dialysis, and length of postoperative intubation. RESULTS: There was no significant difference in survival between the greater than or equal to 70-year-old group and the two younger age groups for the first 10 years after OHT. Survival rates at 30 days, and 1-, 5-, and 10-years, and median survival in group 1 recipients were 100%, 94.6%, 83.2%, 51.7%, and 10.9 years (CI 7.1-11.0), respectively; in group 2 those numbers were 97.6%, 92.7%, 73.8%, 47.7%, and 9.1 years (CI 6.7-10.9), respectively; and in group 3 those numbers were 96.4%, 92.0%, 74.7%, 57.1%, and 12.2 years (CI 10.7-15.4; P=NS), respectively. There was no significant difference in secondary outcomes of re-operation for bleeding, postoperative need for dialysis, and prolonged intubation among the three age groups. CONCLUSIONS: Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients. Advanced heart failure patients who are aged 70 years and older should not be excluded from transplant consideration based solely on an age criterion. Stringent patient selection, however, is necessary.

Survival and allograft rejection rates after combined heart and kidney transplantation in comparison with heart transplantation alone.

BACKGROUND: The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. METHODS: We reviewed the clinical outcomes of patients undergoing HKT (n=30) or HT (n=440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. RESULTS: There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P<.001) and a greater incidence of hypertension (P=.04). No differences were found in cardiac allograft ischemic times, including cardiopulmonary bypass or cross-clamp times. Kidney allograft ischemic time was 14.6±9 hours (mean±SD; range, 4 hours to 49 hours). Kaplan-Meier survival estimates were similar for the HKT and HT groups at 30 days (93%±4.6% versus 98%±0.7%), 1 year (87%±6.2% versus 93%±1.2%), 5 years (68%±9.0% versus 76%±2.1%), and 10 years (51%±11% versus 53%±3.0%; P=.54 for all comparisons). Follow-up serum creatinine levels were similar after HKT and HT at 30 days (1.6±1.8 mg/dL versus 1.1±0.4 mg/dL), 1 year (1.4±0.6 mg/dL versus 1.5±0.6 mg/dL), and 5 years (1.8±1.8 mg/dL versus 1.8±1.2 mg/dL; P>.05 for all comparisons). CONCLUSIONS: HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Successful combined heart-bilateral lung-kidney transplantation from a same donor to treat severe hypertrophic cardiomyopathy with secondary pulmonary hypertension and renal failure: case report and review of the literature.

This study describes the first reported case of a combined heart-lung-kidney transplantation. Our patient suffered from hypertrophic cardiomyopathy due to long-standing hypertension with Dana Point Classification Group 2 pulmonary hypertension from the underlying cardiac disease, along with renal failure necessitating renal replacement therapy. Twenty months after the transplant procedure, she has stable pulmonary and renal function, plus has resumed a normal daily life with improving exercise tolerance. We propose that a combined heart-lung-kidney transplantation may be an acceptable therapeutic option for carefully selected patients with advanced, concomitant cardiac, pulmonary, and kidney disease.

Cardiac abnormalities in Anderson-Fabry disease and Fabry's cardiomyopathy.

Fabry's disease is an X-linked lysosomal storage disease most often associated with renal dysfunction and death due to renal failure in patients' fourth and fifth decades of life. However, cardiac manifestations including arrhythmias, angina and heart failure are common and probably underrecognized. Furthermore, Fabry's disease is now recognised as also affecting female carriers, who manifest signs later than males. A variant of Fabry's has been identified that only affects cardiac tissue, which presents as an unexplained hypertrophy of the left ventricle in middle-aged patients, possibly with women more affected than men. Given that epidemiological studies report a prevalence of Fabry's cardiomyopathy among middle-aged patients with cardiac hypertrophy to be anywhere from one to 12%, it is reasonable to screen these patients for alpha-galactosidase A deficiency. Although mortality data is lacking from randomised, controlled trials of galactosidase replacement therapy, there are some reports of improvement in cardiac endpoints. Therefore patients with known Fabry's disease should be screened early for cardiac involvement, as treatment benefit may not be seen once cardiac fibrosis has developed.

The clinical quandary of left and right ventricular diastolic dysfunction and diastolic heart failure.

Diastolic heart failure is a common clinical entity that is indistinguishable from systolic heart failure without direct evaluation of left ventricular function. Diastolic heart failure is a clinical diagnosis in patients with signs and symptoms of heart failure but with preserved left ventricular function and normal ejection fraction, and is often seen in patients with a long-standing history of hypertension or infiltrative cardiac diseases. In contrast, diastolic dysfunction represents a mechanical malfunction of the relaxation of the left ventricular chamber that is primarily diagnosed by two-dimensional transthoracic echocardiography and usually does not present clinically as heart failure. The abnormal relaxation is usually separated in different degrees, based on the severity of reduction in passive compliance and active myocardial relaxation. The question whether diastolic dysfunction ultimately will lead to diastolic heart failure is critically reviewed, based on data from the literature. Treatment recommendations for diastolic heart failure are primarily targeted at risk reduction and symptom relief. Currently, few data only are reported on diastolic dysfunction and its progression to systolic heart failure.

Amiodarone-induced QT prolongation in a newly transplanted heart associated with recurrent ventricular fibrillation.

Anti-arrhythmic drugs such as amiodarone have the potential to prolong QT intervals, which can result in torsades de point arrhythmia. It is unknown whether amiodarone, given to a recipient prior to cardiac transplantation, can cause arrhythmia in a newly transplanted donor heart. We report on a case of a 71-year-old male patient who had received intravenous and oral amiodarone prior to transplantation, which was associated with QT prolongation in the transplanted heart after re-exposure to the drug during subsequent episodes of ventricular fibrillation. An ICD was implanted, which has not been described that soon after cardiac transplantation. Amiodarone, given to a recipient, might cause QT prolongation in a donor heart after transplantation, possibly due to its long half-life and increased bioavailability caused by interaction with immunosuppressive drugs.

Reconciling Q waves and late gadolinium enhancement with no angiographic evidence of coronary disease: cardiac sarcoidosis presenting as decompensated heart failure.

Cardiac sarcoidosis is rare and subclinical involvement is four to five times more common than clinical involvement. Cardiac sarcoidosis is associated with a poor prognosis. ECG abnormalities are the most common presentation. However, as this case illustrates, it can also present as acute decompensated heart failure. Screening with cardiac positron emission tomography (PET) or magnetic resonance imaging (MRI) is highly suggested in patients with suspected disease. Diagnosis allows for early initiation of corticosteroids. Cardiac sarcoidosis is more common than previously thought. However, with treatment, survival may also be better than previously reported.

The prevalence and clinical relevance of sexual dysfunction in women and men with chronic heart failure.

Sexual dysfunction is a common problem of increasing incidence that is associated with multiple co-morbid conditions and chronic diseases. In heart failure, however, exact numbers are unknown, in part secondary to under-reporting and under-interrogating by health care providers. A gender-specific questionnaire was modified from established sexual dysfunction questionnaires to correspond to a non-randomized outpatient heart failure population, to assess the prevalence and demographic distribution of sexual dysfunction and potential treatments expectations. One-hundred patients in a stable hemodynamic condition in New York Heart Association classes I-III participated. Eighty-seven percent of women were diagnosed with female sexual dysfunction compared to 84% of men with erectile dysfunction. Eighty percent of women reported reduced lubrication, which resulted in frequent unsuccessful intercourse in 76%. Thirty-six percent of patients thought that sexual activity could harm their current cardiac condition; 75% of females and 60% of men stated that no physicians ever asked about potential sexual problems. Fifty-two percent of men considered sexual activity in their current condition as an essential aspect of quality of life and 61% were interested in treatment to improve sexual function. Sexual dysfunction appears to be high in prevalence in both men and women with chronic compensated heart failure and represents a reduction in quality of life for most. Despite the fact that most patients are interested in receiving therapy to improve sexual dysfunction, treatment options are rarely discussed or initiated.

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems.

Phosphodiesterase-5 (PDE-5) inhibitors selectively inhibit PDE-5 enzymes that are present in various tissues like penile tissue, platelets, vascular, and smooth muscle tissue. The drug's actions on these tissues have lead to the successful therapeutic use in patients suffering from conditions such as erectile dysfunction (ED) and pulmonary hypertension. PDE-5 inhibitors (PDE-5i) act on the erectile tissue causing penile smooth muscle relaxation and vasodilatation leading to penile erection. In addition, in particular when used in conjunction with prostaglandin inhibitors, PDE-5i cause vasodilatation in pulmonary vasculature hence decreasing both the pulmonary arterial pressure and resistance. PDE-5i have also shown to mildly decrease blood pressure, increase cardiac index, and increase coronary blood flow in experimental animals as well as in human studies. The Food and Drug Administration (FDA) has approved three PDE-5i for the treatment of ED: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) and one for pulmonary hypertension: sildenafil (Revatio). These agents are highly selective for PDE-5 enzymes as compared to other subclasses of PDE enzymes and have the almost identical pharmacological action but slightly different pharmacokinetics. Only little data exist about long-term use of PDE-5i and their effects on different organ system. This paper reviews the current information available on chronic PDE-5 inhibitor use.

Linking erectile dysfunction and coronary artery disease.

Coronary artery disease (CAD) and erectile dysfunction (ED) are both highly prevalent conditions that frequently coexist. Additionally, they share mutual vascular risk factors, suggesting that they are both manifestations of systemic vascular disease. The role of endothelial dysfunction in CAD is well established. Normal erectile function is primarily a vascular event that relies heavily on endothelially derived, nitric oxide-induced vasodilation. Accordingly, endothelial dysfunction appears to be a common pathological etiology and mechanism of disease progression between CAD and ED. The risk factors of diabetes mellitus, hypertension, hyperlipidemia, obesity and tobacco abuse contribute to endothelial dysfunction. This article reviews the role of vascular endothelium in health, the abnormalities resulting from vascular risk factors, and clinical trials evaluating the role of endothelial dysfunction in ED.

Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem.

Chronic heart failure (HF) is an increasingly common cardiovascular disorder. The goal of health-care providers is to optimize quality of life in this population, including sexual health. Up to 75% of patients with HF report erectile dysfunction (ED). As HF is a condition with distinct physiologic sequelae, some unique organic and psychological factors contributing to ED in this patient population have been identified, along with risk factors common to the development of coronary artery disease, HF and ED. This review describes contributing factors to ED in the setting of HF and highlights treatment considerations for this distinct patient population.

A multidisciplinary approach to assess erectile dysfunction in high-risk cardiovascular patients.

Erectile dysfunction (ED) is increasingly considered as one manifestation of systemic vascular disease. Accordingly, ED and coronary artery disease share mutual risk factors and frequently coexist. Sexual health is an important aspect of our patients' lives, and ED is a common concern of the cardiovascular patient. Despite this, sexual function is under-addressed in the cardiac patient. Even when this topic is broached by the primary care physician or urologist, ED frequently remains untreated due to safety concerns involving cardiac disease and other comorbidities. This article describes our experience with this unique patient population, as well as our approach to building a multidisciplinary clinic designed to specifically address the important issue of ED in the cardiac patient.

Sex and the heart.

Erectile dysfunction (ED) is a highly prevalent and increasingly common, mainly vascular disorder. Most patients with chronic cardiovascular diseases experience decreased libido and frequency of sexual activity, as well as ED. Some unique organic and psychological factors contributing to ED have been identified in patients with underlying cardiovascular problems. Certain risk factors are common to the development of coronary artery disease, heart failure and ED, including diabetes mellitus, hypertension, smoking and dyslipidemia. Additionally, the use of medications such as beta blockers, digoxin and thiazide diuretics might eventually cause but more likely worsen sexual dysfunction. These unintended consequences can lead to medical noncompliance in misguided efforts to retain satisfactory sexual activity, and thereby worsen cardiovascular problems. Accordingly, it is important for physicians dealing with patients with cardiovascular diseases to address sexual concerns in their patients. After careful evaluation, most patients with stable cardiac disorders can resume sexual activity and/or can be treated for ED.

Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease.

OBJECTIVE: To investigate whether blood flow in normal and post-stenotic coronary arteries is altered by therapeutic doses of the sulfonylurea agent glibenclamide. PATIENTS: 12 patients with a high grade stenosis of the left anterior descending coronary artery (n = 10) or left circumflex coronary artery (n = 2), and an angiographically normal corresponding left circumflex artery or left anterior descending artery, respectively. DESIGN: Two Doppler ultrasound wires were positioned in the "normal" and post-stenotic artery for simultaneous measurements of coronary blood flow velocity under baseline conditions and after intravenous glibenclamide, 0.05 mg/kg body weight. Local coronary blood flow was calculated from the average peak velocity and the cross sectional area derived from quantitative coronary angiographic analysis. Coronary flow reserve was determined after intracoronary injection of 30 microg adenosine and 12 mg papaverine. RESULTS: One hour after glibenclamide, serum insulin increased from (mean (SD)) 7.4 (2.0) to 44.8 (25.5) mU/l (p < 0.005), and C peptide from 1.4 (0.4) to 3.4 (1.2) ng/l (p = 0.005). In normal coronary arteries coronary flow reserve was 2.6 (0.4) after adenosine and 3.0 (0.4) after papaverine, while in post-stenotic arterial segments it was 1.2 (0.3) after adenosine (p = 0.005) and 1.3 (0.3) after papaverine (p = 0.005). There was no significant difference after glibenclamide. In non-stenotic arteries, average peak velocity (18.8 (5.2) cm/s) and calculated coronary blood flow (23.8 (10.7) ml/min) were not altered by glibenclamide (18.3 (5.2) cm/s and 22.8 (10.4) ml/min, respectively). In post-stenotic arteries, baseline average peak velocity was 13.3 (4.9) ml/min and coronary blood flow was 9.1 (3.0) ml/min, without significant change after glibenclamide (13.3 (5.2) cm/s, 9.0 (3.2) ml/min). CONCLUSIONS: Glibenclamide, 0.05 mg/kg intravenously, is effective in increasing serum insulin, suggesting a K(ATP) channel blocking effect in pancreatic beta cells. It does not compromise coronary blood flow and vasodilatation in response to adenosine and papaverine in post-stenotic and angiographically normal coronary arteries at rest.

[Application of radioactive substances in nuclear medicine research: current trends and radiation exposure of study subjects]. / Anwendung radioaktiver Stoffe in der nuklearmedizinischen Forschung: aktuelle Trends und Strahlenexposition der Probanden.

AIM: Analysis of the application of radioactive substances in research in the field of nuclear medicine in human beings and of the resulting radiation exposure to study subjects. METHODS: Assessment of applications for approval submitted in accordance with Paragraph 41 of the Radiation Protection Ordinance, evaluated by the Federal Office for Radiation Protection together with the Federal Institute for Pharmaceuticals and Medical Products, within the period from 1997 to 1999. RESULTS: The focus of the studies on the diagnostic application of radioactive substances in medicine evaluated has, since 1998, shifted from oncological to neurological and psychological aspects, while, at the same time, the number of PET studies increased constantly. The proportion of healthy study subjects included in the diagnostic studies increased from 7 to 22%. The number of therapeutic applications of radioactive substances has, since 1997, undergone a three-fold increase, and in the process of this, the focus of attention lay within the area of radioimmuno-therapy and endovascular brachytherapy. The effective dose was, among up to 49% of the investigated healthy study subjects higher than 5 mSv, and among up to 6% of these subjects was at levels of over 20 mSv. Up to 22% of the patients received, within the scope of diagnostic studies, an effective dose of between 20 and 50 mSv. An exceeding of the 50 mSv limit occurred among up to 3% of the patients. CONCLUSIONS: In spite of the increasing numbers of PET applications, conventional nuclear medicine has maintained its importance in the field of medical research. Further developments in the areas of radiochemistry and molecular biology led to an increase in the importance of radio-immuno therapy. The evaluation of new radiopharmaceuticals and the extension of basic biomedical research, resulted in an increase in the proportion of healthy study subjects included in the studies. The radiation exposure among subjects resulting directly from the studies showed, for the period of evaluation, an overall trend towards reduction.

Activation of ATP-sensitive potassium channels in hypoxic cardiac failure is not mediated by adenosine-1 receptors in the isolated rat heart.

BACKGROUND: Hypoxic cardiac failure is accompanied by action potential shortening, which in part might be a consequence of opening of cardiac ATP-sensitive potassium channels (K(ATP) channels). Coupling of the adenosine-1 receptor (A-1 receptor) to these channels has been described; however, the interaction of A-1-receptors and K(ATP) channels in different models of ischemia is still under debate. The hypothesis as to whether A-1 receptors are involved in hypoxic K(ATP) channel-activation in the saline-perfused rat heart was tested. METHODS AND RESULTS: Pharmacologic modulation of the K(ATP) channel by Glibenclamide (inhibitor) and Rimalkalim (activator) and of the A-1 receptor by R(-)-N6-(1-methyl-2-phenylethyl)-adenosine (R(-)-PIA, agonist) and 1,3-diethyl-3,7-dihydro-8-phenyl-purine-2,6-dione (DPX, antagonist) at different oxygen tensions (95% O2 and 20% O2) was performed in isolated Langendorff-rat hearts. Peak systolic pressure (PSP, intraventricular balloon), duration of monophasic action potential (epicardial suction electrode, time to 67% of repolarization: MAP(67%)), coronary flow, and heart rate (HR) were registered. Hypoxic perfusion resulted in a significant reduction of PSP (from 106 +/-11 to 56 +/-8 mmHg, P < 0.005) and shortening of MAP(67%) (from 37 +/-3 to 25 +/-4 ms, P < 0.005). With application of 1 microM Glibenclamide, MAP(67%) returned to normoxic values and PSP increased to 78 +/-9 mmHg (P < 0.005 vs hypoxia). In normoxia, 2 microM Rimalkalin resulted in reduction of MAP(67%) and PSP, which was reversed by Glibenclamide. Application of 0.1 microM R(-)-PIA in normoxia resulted in a decrease of HR (from 235 +/-36/min to 75 +/-41/min, P < 0.005), which was accompanied by an increase of PSP from 96 +/-7 to 126 +/-9 mmHg (P < 0.05) without changes in MAP(67%). These effects were reversible by 1 microM DPX and remained unaffected by application of 1 microM Glibenclamide. Application of 1 microM DPX in hypoxia had no effect on the measured parameters. CONCLUSION: In isolated rat hearts, the K(ATP) channel-system is activated in hypoxic cardiac failure and contributes to action potential shortening and reduced contractile performance. These effects seem to be independent of the A-1 receptor in this model.

Thrombosis in Behcet's disease: report of a case followed by a systematic review using the methodology of evidence-based medicine.

BACKGROUND: Behcet's disease (BD) is a rare systemic inflammatory disease of unknown aetiology with a variety of organ manifestations. METHODS: A case of Behcet's disease complicated by deep vein thrombosis (DVT) and inferior vena cava thrombosis referred to our institution is reported. In addition, a structured literature search using the methodology of evidence-based medicine for the localization of venous lesions, treatment modalities, and outcome of patients with Behcet's disease and concurrent thrombosis was performed. A modified validity score was assigned by established methods. RESULTS: In total, 214 citations were identified using our search strategy. Among these citations, 10 papers including a total of 32 patients (25 male, 7 female) met the inclusion criteria and were incorporated into this overview together with our patient. All studies consisted of serial case reports without control subjects. Neither localization of venous lesions, nor treatment modalities were homogeneous not allowing general recommendations. CONCLUSIONS: No data are available from controlled studies regarding treatment modalities of patients presenting with Behcet's disease complicated by concurrent thrombosis. This lack of evidence implicates the need for large scale and co-ordinated registries including data on the acute treatment as well as the prevention of future thrombotic events in this clinical setting. The diagnostic criteria of the "International Study Group for Behcet's Disease" may well serve as a basis for this approach.