Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients.

BACKGROUND: Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS: Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS: Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION: Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

Acid-base balance in heart failure.

In end-stage heart failure, various acid-base disorders can be discovered due to the renal loss of hydrogen ions and hydrogen ion movements into cells, the reduction of the effective circulating volume, hypoxemia and renal failure. This justifies the occurrence of metabolic alkalosis, metabolic acidosis, respiratory alkalosis, as well as respiratory acidosis alone or in combination. Several studies have been published on the acid-base state in heart failure. In a 1951 study, Squires et al analyzed the distribution of body fluid in congestive heart failure by taking into consideration the abnormalities in serum electrolyte concentration and in acid-base equilibrium. A recent study by Milionis et al, analyzed 86 patients with congestive heart failure receiving conventional treatment; the majority of these patients exhibited hypokalemia, hyponatremia, hypocalcemia and hypophosphatemia. Disorders in acid-base balance were noted in 37.2% of patients. In a recent study, 70 patients with severe congestive heart failure before heart transplantation showed high-normal pH, slightly reduced pCO 2 and a slight loss of hydrogen ions. After heart transplantation, stability of blood pH and hydrogen ion concentrations was found. In contrast, bicarbonate and pCO 2 increased significantly. The data led us to formulate the diagnosis of a mixed acid-base disorder that includes respiratory alkalosis and metabolic alkalosis before heart transplantation. In heart failure, the presence of acid-base imbalance associated with the activation of mechanisms that lead to salt and water retention reveals evidence concerning the pivotal role of the kidney in determining the outcome of these patients.

Role of immunosuppressive regimen on the incidence and characteristics of cytomegalovirus infection in heart transplantation: a single-center experience with preemptive therapy.

OBJECTIVE: This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. PATIENTS AND METHODS: Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. RESULTS: The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). CONCLUSIONS: The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

The risk of stroke following CABG: one possible strategy to reduce it?

OBJECTIVE: Stroke remains a devastating complication of coronary artery bypass grafting (CABG): we evaluated whether a more aggressive diagnostic and therapeutic approach can reduce its incidence. METHODS: Between January 1998 and January 2002, 1388 consecutive patients underwent isolated on pump CABG with blood cardioplegia. Among the first 627 patients (Group A), Echo-Doppler study (DS) was performed only in selected patients (58) with history of cerebrovascular disease (CVD) and/or carotid bruit; in 761 patients (Group B), DS was performed routinely. Carotid endarterectomy (CEA) was performed in 45 patients in Group A associated to CABG during cardiopulmonary bypass (CPB) and in 90 patients in Group B under local anaesthesia before CABG. Brain CT scan was performed in all cases with postoperative neurological symptoms. RESULTS: The two groups were homogeneous for age, sex, associated diseases, history of CVD, number of graft and CPB time. There were no differences in terms of hospital mortality between Group A (22/627: 3.5%) and Group B (21/761: 2.75%); p=0.5. Postoperative stroke was observed in 24/627 (3.82%) patients of Group A and in 2/761 (0.26%) of Group B (p<0.001). Hospital mortality for stroke was higher in Group A (12/627: 1.91%) than in Group B (0/761; p<0.001) as well as the incidence of non-fatal stroke (Group A 12/627: 1.91% versus Group B 2/761: 0.26% p=0.006). CONCLUSIONS: Preoperative DS, performed in all cases of CABG, followed by CEA under local anaesthesia in patients with critical carotid stenosis reduces the incidence of postoperative stroke.

Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation.

OBJECTIVES: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated. METHODS AND RESULTS: Circulating N(epsilon)-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE-Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p < 0.01), and GFR (p < 0.01). CML was positively related to decreased total protein and serum albumin and negatively to body mass index (p < 0.01). In contrast, in the heart transplant group, impaired GFR was associated with a notable rise of both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6 (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum albumin (r = 0.394, p < 0.05) and lipofuscin (r = 0.651, p < 0.01) was found. CONCLUSIONS: The contrasting concentration of CML and AGE-Fl between patients with CHF and after heart transplantation in the presence of decreased GFR and oxidative stress are explained by lowered plasma proteins in CHF and higher concentrations in heart transplant recipients. In heart transplant recipients, in addition to myocardial inflammatory processes, immunosuppression may be important for enhanced formation of AGEs.

Evolving practice patterns in heart transplantation: a single-center experience over 15 years.

This analysis is a retrospective characterization of evolving patterns in donor and recipient risk factors for early and late outcomes (survival and freedom from rejection) along with determinants of hospital and 1-year mortality after heart transplantation over a 15-year experience in a single center. Profiles and outcomes were evaluated for procedures performed between 1988 and 1995 (group A, n = 105) versus 1996 and 2003 (group B, n = 218). The following parameters were considered: pretransplant diagnosis, recipient age UNOS status, donor age, total postretrieval ischemic time, donor/recipient size match, and degree of myocardial necrosis at biopsy. Recipients in group B were significantly more compromised as demonstrated by UNOS status (11.4% vs 19.3%; P =.05) and pretransplant pulmonary vascular resistance (2.3 +/- 1.5 vs 3.1 +/- 1.5; P =.04). Marginal donors were more frequently used for group B procedures (21.9% vs 47.7%; P <.0001). Outcomes were significantly more favorable among group B patients in terms of hospital mortality (18.1% vs 10.6%; P =.046), and 1- and 5-year actuarial survival (72.4% vs 83.4%, 60% vs 73.3%, respectively; P =.006). Analysis of the causes of death disclosed a significant reduction in fatal events due to graft failure and acute rejection in group B. No difference emerged with regard to actual freedom from acute rejection. Determinants of hospital mortality were pretransplant diagnosis, UNOS status, donor age, and cardioplegic solution. Transplant era, recipient age, infectious episodes, and ischemic necrosis at biopsy were risk factors for 1-year mortality. We conclude that despite extensive usage of marginal donors and selection of worse candidates, significantly better outcomes were achieved due to improvements in global management strategies.

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Treatment strategies for postinfarction left ventricular free wall rupture: stabilization with peri-operative IABP and off-pump repair.

BACKGROUND: Perioperative management of post-infarction left ventricular free wall rupture (LVFWR) is not clearly standardized and surgical repair is the only therapeutic option. Role of off-pump surgery and stabilization with perioperative intraaortic balloon pumping (IABP) were here analysed. METHODS: Seven patients underwent surgery for LVFWR between 1990 and 2002. Clinical picture included electromechanical dissociation (3 patients) and sudden hypotension (4 patients). Except in one patient who was reanimated through femoro-femoral cardiopulmonary bypass, off-pump repair through on-lay patching technique was always performed. IABP was employed in the immediate postoperative period in five cases. RESULTS: A satisfactory hemodynamic state was restored in all cases and there were no reoperations for bleeding or rerupture. Hospital survival was 100%. One patient underwent successful surgical myocardial revascularization two months after LVFWR. Two patients died at follow-up. The survivors present with good NYHA and CCS functional classes. CONCLUSIONS: When the anatomy of the LVFWR is favourable, off-pump external patching repair proves a good choice. Postoperative IABP provides satisfactory hemodynamic support.

Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass?

This study aimed to assess whether low doses of albumin in the priming solution for cardiopulmonary bypass (CPB) reduce postoperative bleeding. Three-hundred and seventy-seven patients undergoing CPB were retrospectively assigned to group A (154 patients, CPB primed with 20 ml/kg Ringer Lactate solution + 0.75 mg/kg albumin 20%) and group B (223 patients with 20 ml/kg Ringer Lactate). A significant difference was found in terms of reoperations for bleeding (group A 0/154 versus group B 9/223; P=0.033). The mean number of blood derivatives transfused per patient was higher in group B than in group A (P<0.001). Platelet count after CPB was higher in group A than in group B (175 +/- 52x10(3)/microl versus 131 +/- 70x10(3)/microl; P=0.045). The amount of postoperative bleeding was 525 ml versus 680 ml at 24 hrs (P<0.001), 819 ml versus 1102 ml at 48 hrs, (P<0.001), 963 ml versus 1294 ml at 72 hrs, (P<0.045) (group A versus group B respectively). Crystalloid priming with low-dose albumin reduces postoperative bleeding.

Protease removal by means of antiproteases immobilized on supports as a potential tool for hemodialysis or extracorporeal blood circulation.

This work studies protease concentration decrease in aqueous solutions in contact with a modified polyethersulphone graft membrane onto which antiproteases were immobilized. As a model of protease/antiprotease interaction, elastase and alpha1-antitrypsin were used. Experiments were carried out either under fixed amounts of immobilized antiproteases and variable protease concentration or under fixed protease concentration and variable amounts of immobilized antiproteases. In both cases, active protease concentrations decreased with increase in contact time with the membrane. Experimental conditions under which active elastase concentration becomes zero were also found. Occurrence of the same phenomenology has also been ascertained with protease solutions obtained from human blood neutrophils. The membrane activated with alpha1-antitrypsin showed differential inhibitory power on elastase and cathepsin G. This technology could open new perspectives in manufacturing new membranes to be used in hemodialysis and extracorporeal circulation when elastase is released.

Pilot study on prevention of lung injury during surgery for type A acute aortic dissection: no evident improvements with celsior flushing through the pulmonary artery.

OBJECTIVE: Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection. Experimental evidence suggests that pulmonary artery perfusion using hypothermic protective solutions helps prevent lung injury. The aim of this pilot prospective study was to evaluate the effect of pulmonary artery flushing during selective cerebral perfusion (SCP) on lung function. METHODS: Twenty patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to two treatment groups. Pulmonary flushing was performed during SCP in group P (10 patients), while conventional Kazui technique was applied in group N (10 patients). Lung perfusion consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung function was evaluated by intubation time, scoring of chest radiograms at 12 hours after CPB, and PaO2/FiO2 assessed from immediately before surgery to 72 hours after termination of cardiopulmonary bypass. RESULTS: Incidence of pre, intra and post operative determinants of lung dysfunction proved homogeneous in both groups. Lung oxygenation function showed a marked post operative decline followed by a slow improvement in both groups. Analysis of respiratory ratios did not disclose significant differences even though the flushed group had a better performance in all study patients. The incidence of prolonged ventilator support (longer than 72 hours) (30% vs 20%, p = NS) and severity of x-ray pulmonary infiltrate score were comparable (mean score 1.7 +/- 0.71 vs 1.6 +/- 0.68, p = NS). CONCLUSIONS: Pulmonary artery flushing with Celsior solution does not seem to provide an effective preservation of lung function.

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: a prospective randomized study on the timing of perioperative intraaortic balloon pump support.

In this prospective trial the results of preoperative and intraoperative IABP in coronary artery bypass graft (CABG) patients with low left ventricular ejection fraction (LVEF) were compared. Sixty CABG patients with preoperative LVEF < or = 0.30 were enrolled: in group A patients (n=30) IABP was started within 2 hours preoperatively; in group B (n=30) it was instituted intraoperatively before weaning from cardiopulmonary bypass. Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography. Hospital survival, length of IABP support, intubation, ICU and hospital stay, need for postoperative inotropic drugs and incidence of myocardial infarction were compared between the two groups. Survival in group A patients proved significantly higher (P=0.047). Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients (P<0.001). Doses of inotropic drugs (dobutamine, enoximone) were lower in group A (P=0.001; P=0.004) and duration shorter (P<0.001; P<0.001). No major IABP-related complication was observed.

Asymmetric medial degeneration of the intrapericardial aorta in aortic valve disease.

BACKGROUND: A geometrical and functional asymmetry in the normal aortic root has been recently demonstrated. Whether the distribution of medial degeneration (MD) within the wall of the dilated ascending aorta in adult patients reflects such asymmetry, still has to be assessed. METHODS: Nineteen patients with fibrocalcific aortic valve disease and dilatation of the intrapericardial aorta, without clinical signs and familiar history of primary elastic connective tissue disorders, underwent surgery. Biopsies (57 specimens) were taken in each patient from three areas of the ascending aortic wall distal to the three sinuses of Valsalva. MD lesions found at histology in each specimen were classified in three degrees. Comparisons were made between the three sites as to distribution of the three degrees and between one site and the other two as to incidence of the highest degree. RESULTS: A mild degree of MD was found in 26 specimens (45.6%), moderate in 14 (24.6%), severe in 17 (29.8%). The distribution of the three degrees of MD changes was significantly different between one of the three studied wall areas and the other two (P<0.001): a significantly greater incidence of the highest degree of involvement in the aortic wall distal to the non-coronary sinus than in the wall areas corresponding to the coronary sinuses was found (P<0.001). CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the wall area distal to the non-coronary sinus, likely due to haemodynamic stress asymmetry.

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.

Standard 19mm St Jude aortic valves in patients with body surface less than 1.7m2.

Although new models of bileaflet valves with improved orifice have been devised, aortic valve replacement with 19mm prostheses still raises concerns about long term effects of residual transprosthetic gradient. We reviewed our experience with 19 mm standard model St Jude prostheses in 68 patients operated on between January 1983 and December 1995. Clinical late assessment was performed to evaluate the incidence of valve related complications. Postoperative echocardiography was performed to evaluate hemodynamic performance of the prostheses. Mean body surface area was 1.66+/-0.14 m2. Late postoperative peak gradient was 53.85+/-7.16 mmHg; mean gradient was 34.80+/-5.55 mmHg; effective orifice area was 1.93+/-0.05 cm2. Thirteen-year actuarial survival has been 90.89+/-0.6%; thirteen-year freedom from embolism 89.41+/-0.7% and freedom from hemorrhage 98.25+/-0.02%. No case of prosthetic endocarditis, thrombosis, or reoperation was observed during follow-up.

Hemodialitic treatment of cardiac failure.

The various options for treatment of diuretic-resistant edema in heart failure and report on their experience with on line bicarbonate daily hemofiltration (135 min) in 16 patients with congestive heart failure IV class NYHA is discussed. The outcome was excellent. Only 6 patients died. Survival averaged 25 weeks in 4 patients. A total of 6 patients are still alive on dialysis after 18 to 52 weeks.

Bioelectrical impedance analysis in heart transplantation: early and late changes.

The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

Long term clinical and echocardiographic results of isolated aortic valve replacement in elderly patients.

Results after isolated aortic valve replacement with bileaflet prostheses in patients over 70 years old were reviewed. One-hundred-twenty-eight elderly patients were operated on between January 1988 and January 2000. Patients with associated heart disease were excluded from the study. Preoperative data, early and late postoperative mortality, all valve related complications and data concerning anticoagulation status were recorded. Hospital mortality was 9.3%. Mean follow-up time was 60.98 +/- 2.23 months. Twelve-year actuarial survival was 69.6 +/- 0.08%. Valve related and anticoagulation related complication rates (0.8% and 1.6% respectively) and actuarial freedom (99 +/- 0.009 both) were low, as well as the mean interval between consecutive INR checks (18.39 +/- 1.90 days) and the mean INR value (2.17 +/- 0.135). Late echocardiographic results showed low postoperative mean transprosthetic gradients (15.48 +/- 0.94). Bileaftlet prostheses in the elderly can achieve excellent results with a low incidence of anticoagulation related complications and low risk of reoperation. Older age can no longer be considered a contraindication to bileaftlet prosthesis implant.