When a severe flare does not respond to iv corticosteroid therapy at full doses (1mg/kg body weight), it is necessary to switch to cyclosporine or infliximab. Etanercept is not approved in Europe for inflammatory bowel disease (for the time being).

A 37-year-old woman with extensive ulcerative colitis presents a severe flare-up for which treatment with prednisone at a dose of 1 mg/kg is started. After one week of treatment, the patient shows no improvement. What is the next therapeutic measure to be taken?

Emergency subtotal colectomy and in a second time prostectomy and ileoanal reservoir.

Associate an immunosuppressant such as azathioprine.

Associate mesalazine in doses of 4g per day orally and rectal triamcinolone 1 application every 12 hours.

Treatment with etanercept (an anti-TNFa antibody) should be considered.

Cyclosporine for the treatment of fulminant ulcerative colitis in children. Immediate response, long-term results, and impact on surgery.

Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine is effective for fulminant ulcerative colitis in adults, resulting in avoidance of immediate surgery in 75 percent of patients and a 55 percent long-term remission rate. Over the last five years, we studied the effectiveness of cyclosporine in children with fulminant colitis. Fourteen patients with ulcerative colitis (age, 7-20 years) received cyclosporine after satisfying the following criteria: 1) greater than five bloody diarrheal stools per day; 2) severe abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1-2 mg/kg/day); and 5) parenteral nutrition. Treatment was begun with oral cyclosporine (4.6-9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measured with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged on oral cyclosporine, prednisone, and a regular diet. Eleven of 14 patients (78 percent) responded within two to nine days and were able to consume a normal diet, had three or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedure. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2 to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while weaning from cyclosporine after 4 to 8 months. Three patients have been weaned from cyclosporine after 8 to 13 months and have remained in remission from six months to five years. One patient is about to complete a six-month course of cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P < 0.001), albumin (P < 0.01), erythrocyte sedimentation rate (P > 0.05), and prednisone dose (P < 0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subsequently underwent surgery. Cyclosporine is effective in achieving clinical remission in 80 percent of children with refractory fulminant colitis; however, within one year, most initial responders will require colectomy because of a flare up of the disease. In a majority of patients, the role of cyclosporine therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose leading to surgery in a well-prepared patient.

Continuously infused cyclosporine at low dose is sufficient to avoid emergency colectomy in acute attacks of ulcerative colitis without the need for high-dose steroids.

A dosage of 4 mg/kg/day intravenous cyclosporine as an adjunct to high-dosage hydrocortisone has been recommended to avoid colectomy in acute steroid-resistant ulcerative colitis. In treating eight such patients, four of whom presented with toxic megacolon, we immediately tapered the steroid dosage and infused a lower dosage of only 2 mg/kg cyclosporine for 15 days to fit a therapeutic range of 60-240 ng/ml, as previously designed for a kidney transplant program. Seven of the eight (87.5%), including three with megacolon, went into remission and started the chronic phase of treatment; the eighth patient underwent colectomy. Of the seven, one died on day 3 of the chronic phase because of pulmonary embolism while in clinical remission, and another discontinued treatment. The other five (62.5%) remain in remission on 6 mg/kg oral cyclosporine, or have already switched from cyclosporine to azathioprine. Two episodes of reversible nephrotoxicity appeared in the chronic phase only. These results emphasize the efficacy and safety of cyclosporine in acute ulcerative colitis, but there is still a need for further dose-response and drug association relationship studies.

The effectiveness and safety of rescue treatments in 108 patients with steroid-refractory ulcerative colitis with sequential rescue therapies in a subgroup of patients.

Among patients with steroid-refractory ulcerative colitis (UC) in whom a first rescue therapy has failed, a second line salvage treatment can be considered to avoid colectomy. To evaluate the efficacy and safety of second or third line rescue therapy over a one-year period. Response to single or sequential rescue treatments with infliximab (5mg/kg intravenously (iv) at week 0, 2, 6 and then every 8weeks), ciclosporin (iv 2mg/kg/daily and then oral 5mg/kg/daily) or tacrolimus (0.05mg/kg divided in 2 doses) in steroid-refractory moderate to severe UC patients from 7 Swiss and 1 Serbian tertiary IBD centers was retrospectively studied. The primary endpoint was the one year colectomy rate. 60% of patients responded to the first rescue therapy, 10% went to colectomy and 30% non-responders were switched to a 2(nd) line rescue treatment. 66% of patients responded to the 2(nd) line treatment whereas 34% failed, of which 15% went to colectomy and 19% received a 3(rd) line rescue treatment. Among those, 50% patients went to colectomy. Overall colectomy rate of the whole cohort was 18%. Steroid-free remission rate was 39%. The adverse event rates were 33%, 37.5% and 30% for the first, second and third line treatment respectively. Our data show that medical intervention even with 2(nd) and 3(rd) rescue treatments decreased colectomy frequency within one year of follow up. A longer follow-up will be necessary to investigate whether sequential therapy will only postpone colectomy and what percentage of patients will remain in long-term remission.

Infliximab salvage therapy after cyclosporine in an acute flare of chronic ulcerative colitis.

Although infliximab (Remicade, Schering Canada Inc, Quebec) therapy has been well studied in steroid refractory Crohn's disease, its use remains controversial in chronic ulcerative colitis. A 24-year-old woman with a 14-year history of well controlled left sided ulcerative colitis presented with an acute flare. Clinical, endoscopic and biopsy evidence of an acute flare of ulcerative pancolitis were present. There was no response to intravenous steroids but improvement was seen after receiving 14 days of intravenous cyclosporine (4 mg/kg/day continuous infusion). The patient was discharged from hospital with azathioprine (2.5 mg/kg/day) and low dose oral cyclosporine (4 mg/kg/day). She presented with worsening symptoms seven days after discharge. Because of the patient's unwillingness for surgery, she instead received two injections of infliximab 5 mg/kg at week 0 and week 2. An initial response occurred, but her clinical improvement was not durable. Colectomy was performed four weeks later. This is the first report of infliximab as a salvage therapy in an acute flare of chronic ulcerative colitis following failure of cyclosporine.

Successful use of infliximab and tacrolimus combination therapy in a patient with ulcerative colitis refractory to infliximab dose intensification plus azathioprine.

To report of a case successful use of infliximab (IFX) and tacrolimus (TAC) in a patient with ulcerative colitis (UC). A 22-year-old woman diagnosed with UC started treatment with azathioprine 2.5 mg/kg. After 3 years of therapy, she developed a severe relapse. A colonoscopy was performed showing diffuse continuous mucosal disease and multiple erosions (< 5 mm) with no signs of spontaneous bleeding. Treatment with IFX 5 mg/kg at weeks 0, 2, and 6 was started. After IFX induction, she remained with symptoms: six stools per day, as well as presenting bloody diarrhea, tenesmus, and no abdominal pain. An IFX dose intensification of 5 mg/kg every 6 weeks was prescribed. After 6 months of azathioprine plus IFX therapy, patient's clinical condition was improved: 3 - 4 stools per day, 20% of bloody diarrhea, tenesmus, and no abdominal pain. Her Mayo endoscopic subscore was 6.3 months later, and a severe relapse of ulcerative colitis was presented. The patient refused a surgical treatment. Azathioprine 2.5 mg/kg/day was suspended and TAC 0.2 mg/kg/day (12 mg/day) as a compassionate use was added to IFX dose intensification of 10 mg/kg every 8 weeks and mesalamine 800 mg 3 times daily. After the first month of combined therapy, the patient's clinical condition improved with no bloody stools and abdominal pain. After 6 months of combination therapy, the patient was in remission, with two stools per day, no tenesmus and no abdominal pain. Due to the patient's clinical remission, IFX was suspended. Tacrolimus was continued on 10 mg/day. After 6 months of TAC monotherapy, the patient continued without symptoms (1 - 2 normal stools per day). Based on our case, the combination therapy of IFX and TAC could be selected as an effective approach for the patients with UC refractory to IFX dose intensification plus AZA. However, further studies need to be performed to evaluate the efficacy of this combination therapy.

Cyclosporine A for induction of remission in severe ulcerative colitis.

Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Approximately 15% of patients have a severe attack requiring hospitalization at some time during their illness. These patients are traditionally treated with intravenous corticosteroids, with a response rate of approximately 60%. The patients who do not respond to steroid treatment usually require surgical removal of the large bowel (proctocolectomy or colectomy with an anal pouch). This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis. Few alternative treatments exist for severe ulcerative colitis: immunosuppressive medications (such as azathioprine) have a slow onset of action and are therefore usually ineffective. Antibiotics are not proven to be effective and biological treatments such as infliximab are still under investigation. The introduction of cyclosporine-A (CsA) for use in patients with severe ulcerative colitis (UC) has provided an alternative to patients previously facing only surgical options. Cyclosporine acts mainly by inhibiting T lymphocyte function, which is essential for the propagation of inflammation. Unlike most other immunosuppressive agents, CsA does not suppress the activity of other hematopoietic cells, does not cause bone marrow suppression and has a rapid onset of action. This reviews aims to systematically assess the effectiveness and safety of CsA for severe UC. This review aimed to evaluate the effectiveness of cyclosporine A for patients with severe ulcerative colitis. Electronic searches of The Cochrane Library (Issue 1, 2004), EMBASE (1980-2004), and MEDLINE (1966-2004); hand searching the references of all identified studies; contacting the first author of each included trial. Randomised clinical trials comparing cyclosporine A with placebo or no intervention to obtain and maintain remission of idiopathic ulcerative colitis. Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat analysis for the outcome measures. Only two randomized controlled trials were identified that satisfied the inclusion criteria. These two trials could not be pooled for analysis because of major differences in design and patient populations. In the first trial, 11 patients received intravenous cyclosporine (4 mg/kg) and 9 received placebo. Two of 11 in the treatment group failed to respond to therapy compared with nine of nine in the placebo group (RR 0.18, 95% CI 0.05 - 0.64). However, 3/11 and 4/9 eventually underwent colectomy in the treatment and placebo groups respectively and follow-up was less than a month. In the second trial 15 patients were treated with intravenous cyclosporine and 15 with intravenous methylprednisolone. Five of 15 patients in the cyclosporine group failed to respond to therapy as compared to 7/15 in the methylprednisolone group (RR 0.71, 95% CI 0.29 - 1.75). After 1 year 7/9 responders in the cyclosporine group were still in remission compared with 4/8 in the steroid group (p > 0.05) and the colectomy rate was similar in both groups. The mean time to response in the cyclosporine group in the 2 trials was short (7 days and 5.2 days). These results should be interpreted with caution given the small numbers of trials and patients evaluated for comparison, and limited follow-up (few weeks in one trial to a year in the other). The precise assessment of the occurrence of adverse events was difficult because the trials described different adverse reactions, which reversed after discontinuation of cyclosporine. There was no evidence in the trials reviewed that cyclosporine was more effective than standard treatment for preventing colectomy but this effect cannot be excluded due to the small sample size and rarity of this outcome. Additional limitations of current research include lack of data on quality of life, costs and long-term results of cyclosporine therapy. There is limited evidence that cyclosporine is more effective than standard treatment alone for severe ulcerative colitis. The relatively quick response makes the short-term use of cyclosporine potentially attractive, but the long-term benefit is unclear, when adverse events such as cyclosporine-induced nephrotoxicity may become more obvious. There is a need for additional research on quality of life, costs and long-term results from cyclosporine therapy in severe ulcerative colitis.

Treatment of severe steroid refractory ulcerative colitis.

Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg IV, 0-2-6 wk) or total colectomy. The choice between these three options is a medical-surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.

Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome.

Cyclosporine is a fungal metabolite and a powerful immunosuppressant. While response to intravenous steroids in severe ulcerative colitis is in excess of 60%, the remainder of patients are left with the options of curative panproctocolectomy or administration of intravenous rescue therapy with cyclosporine. There have been conflicting reports on the efficacy of intravenous cyclosporine in acute ulcerative colitis, and there are serious concerns about potential toxicity and opportunistic infections such as Pneumocystis carnii pneumonia. There are also concerns about early relapse and colectomy following cyclosporine rescue. To date there has been a paucity of data available to help guide the gastroenterologist in the use of cyclosporine and the maintenance of remission once achieved. Between 1994 and 2001, a total of sixteen patients who had received intravenous cyclosporine for acute exacerbation of their known UC (seven females, nine males, mean age 33 years) whose records were available for analysis. All patients were refractory to intravenous methylprednisolone (60 mg/24 h). Patients who responded to cyclosporine were discharged on a regimen of oral cyclosporine, oral steroids oral azathioprine and 5-aminosalicylate. Median disease duration was 5.4 years (range 0.9-25 years). All sixteen patients were initially treated with cyclosporine at a dose of 4 mg/kg/day. Nine patients were started on oral azathioprine (median dose 1.8 mg/kg). Seven patients underwent surgery (panproctocolectomy), although none had surgery after 6 months. Comparisons were made between patients with <7 days and >7 days intravenous steroid. Other parameters analysed were stool frequency at 3 days and CRP at 3 days. There were no significant differences between these groups. Median bowel frequency at day 3 was higher in patients who finally underwent surgery. At 3 years follow-up, 56% of the sixteen patients had avoided surgery by using azathioprine immunosuppression. The initial response rate to intravenous cyclosporine was high (69%). Side effects were documented in the majority of patients, but none of the patients had to discontinue treatment on account of these. Azathioprine has a useful role in maintaining the remission achieved by i.v. cyclosporine for acute ulcerative colitis patients. More than half the patients will avoid colectomy long-term when using triple immunosuppressive therapy including azathioprine adding support for its relative safety and another role for its use.

Successful use of golimumab in a patient with ulcerative colitis refractory to infliximab and adalimumab.

To report a case of successful use of golimumab (GLB) in a patient with ulcerative colitis (UC) refractory to infliximab (IFX) and adalimumab (ADA). A 60-year-old man was diagnosed with left UC and was given azathioprine 2.5 mg/kg to control UC symptoms and decrease corticosteroid patient dependence. Four years later, he developed adverse reaction to azathioprine and began treatment with mercaptopurine 1.5 mg/kg/day. Despite this treatment, he developed a severe relapse (Truelove-Witts modified: 15 points). Treatment with IFX 5 mg/kg at weeks 0, 2, 6, and every 8 weeks was started. After 1 year in clinical remission, the patient developed an infusion reaction to IFX, and IFX was suspended. The patient started treatment with ADA 40 mg every other week. After 2 years in clinical remission, ADA was suspended. 20 months after ADA discontinuation, the patient developed an acute episode of UC with a Truelove-Witts modified score of 16 points. ADA plus corticosteroid therapy was restarted. Despite these treatments, the patient's clinical condition did not improved. ADA 40 mg per week was started with not clinical improvement and with corticosteroid dependence after 4 months of ADA intensive therapy. The patient denied surgery, and cyclosporine was discarded because of its inability to be used as a maintenance drug. The patient started GLB with an induction dosage regimen of 200 mg subcutaneous at week 0, followed by 100 mg at week 2, and then maintenance therapy with 100 mg every 4 weeks (patient's weight = 84 kg), combined with mercaptopurine and corticosteroids. After 6 weeks of treatment, the patient achieved clinical remission, with just three non-bleeding stools per day, without stomach ache, apyretic, and no urgency or tenesmus rectal symptoms. One year later, the patient continued to be asymptomatic with a Truelove-Witts modified score of 2 points, corticoid-free treatment, and a complete clinical and endoscopic remission and normal calprotectin levels (< 15 µg/g). We decided to suspend mercaptopurine in order to avoid side effects derived from the combined treatment. After 1 year on GLB therapy, the patient continued in clinical remission. Based on our case, GLB could be selected as an effective approach for patients with UC refractory to IFX and ADA. However, further studies need to be performed to evaluate the efficacy of GLB therapy as a rescue treatment.

Management of ulcerative colitis

Refractory ulcerative colitis Refractory ulcerative colitis. Patients with toxic megacolon (colonic dilation > 6 cm and toxic appearing) who do not respond to steroid therapy within 72 hours should be consulted for colectomy. Those with less severe disease but do not respond to IV steroids within 7–10 days should be considered for colectomy or IV cyclosporine. IV cyclosporine at a rate of 2 mg/kg/day and if no response in 7–10 days, colectomy should be considered. If response is seen, oral cyclosporine at 8 mg/kg/day should be continued for 3–4 months while 6-MP or azathioprine is introduced. Those already on 6-MP or azathioprine should continue with these medications. A cholesterol level should be checked in patients taking cyclosporine as low cholesterol may predispose to seizures. Also, prophylaxis against PCP (Pneumocystis carinii) pneumonia is advised.

Review article: the management of mild to severe acute ulcerative colitis.

The goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high-dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first-line therapy, although the choice of 5-aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.

High-dose intravenous cyclosporine in steroid refractory attacks of inflammatory bowel disease.

To determin whether cyclosporine is effective in inducing remission in patients with severe active inflammatory bowel disease, refractory to steroids. Twenty-three patients with severe and steroid-refractory inflammatory bowel disease (15 ulcerative colitis and 8 Crohn's disease) were included. The Mayo Clinic Score and the CDAI were used to evaluate activity. Cyclosporine (4 mg/kg/day) was administered for a maximum of ten and a minimum of 7 days. Ten of the 15 ulcerative colitis patients achieved remission with a mean response lag time to onset improvement of 8 days. Seven of these patients remained stable with mesalazine 4 months after cyclosporine treatment. Two patients relapsed and underwent colectomy on the 50th and 200th day after treatment. Five patients presented no response and required urgent colectomy. Six of the 8 Crohn's disease patients achieved remission with a mean response lag time to onset improvement of 7 days. The 6 patients remained stable with mesalazine four months after cyclosporine treatment. The other 2 developed reversible renal failure and had to be released from the study. Intravenous high dose cyclosporine is effective and can be used as a rapid onset treatment for acute steroid refractory IBD.

[Acute severe ulcerative colitis treated with accelerated infliximab induction. Case report].

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

Management of acute severe ulcerative colitis.

The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.

Management of ulcerative colitis

Oral anti-inflammatory drugs require four to six weeks to work. Once remission is induced, maintenance levels can be used: sulfasalazine 2 g/day, mesalamine 1.2-2.4 g/day, or olsalazine 1 g/day. Patients on high dose sulfasalazine require folic supplementation (1 mg/day) because it inhibits folate absorption. If oral Mesalazine is still not working, prednisone is often given, starting at 40–60 mg/day. Prednisone often takes effect within 10–14 days. The dose should then be tapered by about 5 mg/week until it can be stopped altogether.

Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids.

The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P=0.007). Ten reversible adverse events occurred in 9 patients. This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a "bridge" until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.

[Treatment of acute a steroid-resistant ulcerative colitis with continuous venous infusion of cyclosporine].

Aim of this open study is to evaluate the efficacy and safety of a low-dose treatment of continuous intravenous infusion of cyclosporine. We treated twelve patients with severe active ulcerative colitis, that did not respond to high doses of intravenous steroid for at least ten days. We used a dose of 2 mg/kg/day for 15 days. After this period, if patients improved, cyclosporine was administered orally at the dose of 6 mg/kg/day for six months. The response rate to acute phase therapy was 92.8%. The mean response time was 5.8 days. Sixty-nine percent of patients responded within the first week. No adverse reaction was observed. The first five patients responding to acute phase therapy relapsed during or at the end of maintenance phase. Because of that, azathioprine was associated in the successive patients. Only 4 out of 12 patients (33%) were operated on. continuous intravenous infusion of cyclosporine at dosage of 2 mg/kg/day is a highly effective and safe therapy that may avoid or defer colectomy to eligible conditions.

Cyclosporin for severe ulcerative colitis attacks.

Cyclosporin-A is used as alternative medical therapy in steroid refractory ulcerative colitis with severe activity. In spite of known effectivity, the long term results of cyclosporin-A therapy is not clear for today. The results of 13 steroid refractory patients that treated with cyclosporin-A were retrospectively assessed. Cyclosporin-A was started as orally, 8 mg/kg/day in 4 patients and intravenously, 4 mg/kg/day in 9 patients. Intravenous therapy changed to oral therapy one week after beginning. Patients also received 5-ASA and azathioprine. Steroid was tapered. Ten patients responded to treatment in a mean of 9 days (range: 2-30 days). Three unresponded patients underwent total colectomy on 7, 11 and 19th day of therapy. Ten initially responded patients received the drug for average 4.9 months. Of these, four relapsed during and one relapsed soon after therapy. Four of 5 relapser patients underwent colectomy. One patient that not accepted surgical intervention is still receiving medical therapy. Remaining 5 patients, 38% of total group; 50% of patients that initially responded, maintain the remission at the end of average 17 months of follow up period. Cyclosporin-A therapy in severe ulcerative colitis that is refractory to steroids, provides initial remission in 80% of patients and allows 40% to retain their colon for 1 year.

Efficacy of cyclosporin in severe ulcerative colitis attack.

Cyclosporin-A is used as a alternative medical therapy in steroid resistant ulcerative colitis with severe activity. In spite of its known efficacy, the long term effects of are not entirely clear. The records of 13 steroid resistant patients treated with cyclosporin-A were retrospectively assessed. Cyclosporin-A had been prescribed orally at a dose of 8 mg/kg/day in four patients and intravenously, 4mg/kg/day in nine patients. Intravenous therapy was changed to oral therapy after one week and patients also received 5-ASA and azathioprine. Steroid treatment was tapered. Ten patients responded to treatment in a mean of nine days (range: 2-30 days). Three patients who did not respond underwent total colectomy on day seven, 11 and 19 of therapy. The 10 patients who initially responded received the drug for an average of 4.9 months; four of these relapsed during and one relapsed soon after discontinuation of therapy. Four of the five patients who relapsed underwent colectomy and the one patient who did not accept surgical intervention continued medical therapy. The remaining five patients (38% of the total group; 50% of the patients who initially responded) remained in remission at the end of an average 17 month follow up period. Cyclosporin-A therapy in severe ulcerative colitis that is resistant to steroids, provides initial remission in 80% of patients and allows 40% to retain their colon for one year.

Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis.

Cyclosporine A is highly effective in severe attacks of ulcerative colitis (UC) but is associated with important adverse effects that are mainly dose dependent. Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC. Primary end point was the proportion of patients with a clinical response. Secondary end points included time to response, colectomy rate, and adverse effects. Seventy-three patients were included. Day-8 response rates were 84.2% (32 of 38, 4 mg/kg) and 85.7% (32 of 35, 2 mg/kg) after a median of 4 days in both groups. Short-term colectomy rates were 13.1% (4 mg/kg) and 8.6% (2 mg/kg). Mean cyclosporine blood levels were 237 +/- 33 in the 2-mg/kg group and 332 +/- 43 ng/mL in the 4-mg/kg group. Active smoking was inversely correlated with clinical response (odds ratio, 0.06), but concomitant azathioprine or steroids were not predictive. A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group (23.7% vs. 8.6%, 2 mg/kg, P < 0.08). High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC. Although we did not observe differences in adverse effects on the short term, the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC.

[Cyclosporin for steroid refractory ulcerative colitis. Results of a study conducted at Turin General Hospital between 1990 and 1997].

Four every ten patients receiving high-dose parenteral steroids for severe ulcerative colitis fail and may have their colon removed. Intravenous followed by oral cyclosporin has been shown to initially rescue approx. 70% of these non-responder patients, but dosages and long term-efficacy are still debated. We reviewed the clinical outcomes of patients treated with cyclosporin for refractory ulcerative colitis at our Center in the last 7 years. Fifty-four patients destined to colectomy because of refractory ulcerative colitis (previous failure to respond to 7 days of 1 mg/kg/day steroids) were enrolled to initially receive a two-week continuous infusion of 2 mg/kg/day cyclosporin. Responders (showing at least a 50% reduction of activity) were meant to be treated with oral drug at 6-8 mg/kg/day for 6 months with the maintenance of remission and the spare of steroids being the end-points. Data are available for 47 patients followed-up for a minimum of 6 months up to 6 years. Of these 47, 14 did not respond to the intravenous drug and were submitted to surgery; of the remaining 33 responders (70%) entering the oral 6-month phase, 17 relapsed before end or on leaving the drug and were considered as failures. The remaining 16 (34% of the 47) left cyclosporin in remission and in need of less than 20 mg steroids daily. Of them, 12 avoided colectomy in a follow-up of 6 months-6 years. Intravenous cyclosporin may be rapidly effective in 7 every 10 patients whose acute ulcerative colitis fails a full-dose steroid course. However, only 3 of the initial 10 may maintain remission over a 6-month oral course. Further efforts should concentrate on improving the long term efficacy of cyclosporin.

Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level: A case report.

Acute severe ulcerative colitis (ASUC) is a complication of ulcerative colitis associated with high levels of circulating tumor necrosis factor alpha, due to the intense inflammation and faster stool clearance of anti-tumor necrosis factor drugs. Dose-intensified infliximab treatment can be beneficial and is associated with lower rates of colectomy. The aim of the study was to present a case of a patient with ASUC and megacolon, treated with hydrocortisone and accelerated scheme of infliximab that was monitored by drug trough level. A 22-year-old female patient diagnosed with ulcerative colitis, presented with diarrhea, rectal bleeding, abdominal pain, vomiting, and distended abdomen. During investigation, a positive toxin for <iClostridium difficile</i and colonic dilatation of 7 cm consistent with megacolon were observed. She was treated with oral vancomycin for pseudomembranous colitis and intravenous hydrocortisone for severe colitis, which led to the resolution of megacolon. Due to the persistent severe colitis symptoms, infliximab 5 mg/kg was prescribed, monitored by drug trough level (8.8 μg/mL) and fecal calprotectin of 921 μg/g (< 30 μg/g). Based on the low infliximab trough level after one week from the first infliximab dose, the patient received a second infusion at week 1, consistent with the accelerated regimen (infusions at weeks 0, 1, 2 and 6). We achieved a positive clinical and endoscopic response after 6 mo of therapy, without the need for a colectomy. Infliximab accelerated infusions can be beneficial in ASUC unresponsive to the treatment with intravenous corticosteroids. Longitudinal studies are necessary to define the best therapeutic drug monitoring and treatment regimen for these patients.

[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].

The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC). The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose. In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy. The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.

Inflammatory bowel disease

Medical therapies Medical treatment of IBD is individualised to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patient's disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptoms, with drugs such as prednisone, tumor necrosis factor inhibitors (TNF inhibitors), azathioprine, methotrexate, or 6-mercaptopurine.

Preliminary report: cyclosporin in treatment of severe active ulcerative colitis.

Intravenous cyclosporin (4 mg/kg daily) was given to fifteen patients with severe active ulcerative colitis, fourteen of whom had failed to respond to at least 10 days' treatment with intravenous steroids. In the acute phase of the open trial, eleven patients (73%) improved and avoided colectomy; the mean response time was 5.8 days. Patients who responded were maintained on oral cyclosporin (6-8 mg/kg daily) for a 6-month chronic phase. Six of the eleven patients have been weaned from steroids and remain in clinical and endoscopic remission 5-18 months after discontinuation of cyclosporin; three are well at 5 months and their steroid dose is being tapered; one patient relapsed after 5 months on oral cyclosporin and underwent colectomy; and one patient failed to show continued improvement with oral cyclosporin but is in clinical remission after changing to mercaptopurine treatment. Slight self-limiting adverse side-effects of cyclosporin were seen, but none necessitated withdrawal from the study. Cyclosporin seems to be an effective treatment for patients with severe active ulcerative colitis who have not responded to steroids.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Chronic relapsing inflammatory optic neuropathy

Five diagnostic criteria have been proposed: History of optic neuritis with one relapse Objectively measured visual loss NMO-IgG seronegative Contrast enhancement on imaging of acutely inflamed optic nerves Response to immunosuppressive treatment and relapse on withdrawal or dose reduction Treatment Treatment consists of three phases: 1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or plasmapheresis are given to restore visual function. 2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision. 3. Long-term phase: To avoid adverse effects of long-term steroids and to avoid relapse of disease, physicians can transition to a steroid-sparing agent. Azathioprine, methotrexate, cyclophosphamide, mycophenolate, IVIG, plasma exchange, cyclosporine, and infliximab have been used.

Outcome of a conservative approach in severe ulcerative colitis.

Severe ulcerative colitis is potentially life threatening even though a policy of intensive medical management and early colectomy in recent years reduced mortality to almost zero. However, colectomy, with or without ileal-anal anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no reliable prognostic index of surgical outcome has been developed. Intravenous steroids are still the mainstay of medical therapy but their maximal duration before stating a 'treatment failure' has not been defined. To evaluate the effectiveness, safety and outcome of an intensive medical approach in a series of patients with severe ulcerative colitis. One hundred and forty-nine episodes of severe ulcerative colitis in 115 patients admitted to a Gastroenterology Unit in a 7-year period were retrospectively evaluated. Intravenous glucocorticosteroids--methylprednisolone 1 mg/kg/day--and topical steroids were administered, and supportive treatments with intensive monitoring were extended to all the patients. Second-line strategies for steroid-refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab or surgery. The median number of Truelove criteria at admission was 3 (range 2-5), median CRP 34 mg/l (range 10-196). Median follow-up after discharge was 49 months. In 84 (57%) episodes an early response was noted, while 65 (43%) did not respond within 10 days to the standard steroid treatment. In the non-responders group, 28 patients went into remission with a prolonged steroid treatment (slow responders); 15 patients were treated with ciclosporin (eight responders) and 6 with infliximab (four responders). A total of 24 colectomies was performed in this group of patients (in 21 cases within 30 days from admission). Slow responders showed lower albumin levels (P = 0.02), higher cumulative dose of glucocorticosteroids in the year prior to admission (P = 0.02) and higher age (P = 0.03), in comparison with early responders. Major complications were noted in four episodes which responded to medical treatment. Disease-related mortality was zero. Medical treatment and use of second-line therapies were effective in the present series of patients. A group of slow responders has been identified and, if an intensive medical monitoring is guaranteed, steroids can be safely prolonged after the first 10 days of treatment. Cumulatively, about 80% of the patients responded to short-term medical treatment, only 5% of the patients underwent colectomy in the follow-up period. Major adverse events were recorded in four patients, who had recovered completely after adequate medical treatment.

[Triple immunosuppressive therapy in the treatment of severe ulcerative colitis].

Severe episodes of steroid-refractory ulcerative colitis (UC) were considered an indication for surgery until the introduction of new immunosuppressive agents such as cyclosporine. 1) To confirm the efficacy of intravenous cyclosporine in inducing remission in severe episodes of steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive therapy with cyclosporine, azathioprine and prednisone in the maintenance of remission induced by intravenous cyclosporine. Fourteen patients diagnosed with a severe episode of steroid-refractory UC were treated with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after response was induced, this regimen was substituted by oral cyclosporine plus azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids. Neoral cyclosporine was progressively reduced until discontinuation within 3 months, coinciding with a simultaneous decrease of oral steroids. All patients showed response to intravenous cyclosporine with a significant reduction in the Truelove index calculated before and after treatment. After remission was induced, all patients followed triple immunosuppressive therapy for 3 months. In the follow-up for a mean of 24 months (range: 14-34) only two patients required admission for a new episode of UC and colectomy was finally indicated in only one. None of the 14 patients treated with cyclosporine showed severe adverse effects attributable to the drug. Intravenous cyclosporine is a safe and effective alternative in the treatment of severe episodes of steroid-refractory UC. Early initiation of oral administration associated with azathioprine is useful in maintaining response, reducing subsequent relapses and the need for colectomy during the follow-up of these patients.

Cladribine

Two main approaches to multiple sclerosis treatment maintenance therapy are used – immunomodulation and immunosuppression and alternatively, immune reconstitution therapy. Classified as the latter, cladribine tablets are administered intermittently as a short treatment course without continuous immunosuppression. In contrast to maintenance therapies, clinical efficacy extends beyond the dosing period. Cladribine tablets are administered as 2 courses separated by 1 year (a maximum of 20 days of treatment). The recommended cumulative dose is 3.5 mg/kg weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (1 or 2 tablets) as a single daily dose based on body weight.

Ulcerative colitis: analyses of 116 cases (do extraintestinal manifestations effect the time to catch remission?).

Evaluation of clinical, demographic and epidemiologic features of ulcerative colitis and therapy response of these patients. Retrospectively, 116 patients (64.7% female) were enrolled in this study. Mean age and mean follow-up period were 36+/-16, 5+/-2 years, respectively. The most common anatomic involvement was pancolitis (60.3%) and the others were as follows: left side 25%, rectum 13.8% and ileum (backwash ileitis) 0.9%. Extraintestinal manifestations were observed in 42.2% of patients (sacroiliitis 12%, primary sclerosing cholangitis 7.6%, pyoderma gangrenosum 2.4%, peripheral arthropathy 1.6%, autoimmune hepatitis 1.6%, steatosis 12.9%, gallstone 0.8%, perianal fistulas 0.8%, sagittal sinus thrombosis 0.8%, psoriasis 0.8%). Multiple extraintestinal manifestations were observed (primary sclerosing cholangitis + pyoderma gangrenosum) in 2 patients. Colonic perforation due to toxic megacolon was observed in only one patient during follow-up period. The mean period for remission was 3.7 months in 72% of patients with pancolitis by the treatment of 5-aminosalicylic acid (5-ASA) (2-3 gr/day) + methylprednisolone (1 mg/kg/day) +/- (for maintenance of remission) azathioprine (AZT) (1.5-2 mg/kg/day); 3.7 months in 72% of left-sided colitis by 5-ASA +/- corticosteroid enemas +/- methylprednisolone (1 mg/kg/day) +/- (for maintenance of remission) AZT (1.5-2 mg/kg/day) and 3.7 months in 62.5% of patients with distal colitis by 5-ASA (p.o. +/- enema) +/- corticosteroid enemas. Colectomy was performed on 7 patients refractory to these treatments. Six patients (4 of them had pancolitis) were treated with cyclosporine (Cys) (4 mg/kg/day, p.o.). Only one patient, a non-responder to Cys therapy, had colectomy. The mean remission time was 4.7 months in 80.6% of patients with extraintestinal involvement and 3.2 months in 71.2% of patients without extraintestinal involvement (P=0.002). Medical therapy was generally enough for the treatment. Cys and/or surgery can be another choice for the patients that do not respond to the medical therapy. Extraintestinal manifestations do not change the remission rate, but prolong the time to catch remission.

Intravenous cyclosporine for the treatment of severe steroid refractory ulcerative colitis: what is the cost?

Intravenous cyclosporine often is used to treat patients with severe steroid refractory colitis secondary to ulcerative colitis in an attempt to avoid urgent total abdominal colectomy. The purpose of this study was to evaluate the success and cost of cyclosporine. A retrospective, chart review of all patients from 1996 to 2002 who were treated with cyclosporine and/or had a three-stage ileal pouch-anal anastomosis for severe steroid refractory colitis at our institution was performed. Patients were divided into three groups: TAC and CyA: patients who failed cyclosporine and had urgent total abdominal colectomy on the same admission; TAC no CyA: patients who had an urgent total abdominal colectomy without cyclosporine; and CyA only: patients treated successfully with cyclosporine and discharged without surgery. A subgroup of patients who had an ileal pouch-anal anastomosis was identified from each group. Cost data were obtained from the hospital's financial records. Forty-one patients (25 males) were identified. Twenty-nine patients received cyclosporine for severe steroid refractory colitis. Of these, 18 (62 percent) failed and underwent total abdominal colectomy on the same admission. Eleven (38 percent) responded to the cyclosporine and were discharged. Of the 11, 4 never had surgery, 1 had a three-stage ileal pouch-anal anastomosis, 5 had a two-stage ileal pouch-anal anastomosis, and 1 had a total abdominal colectomy only. Only 14 percent of patients avoided colectomy in the long-term. Complications of cyclosporine occurred in 8 patients (28 percent), and surgical complications occurred in 12 patients. The highest costs, highest length of stay, and highest number of overall complications were found in the group of patients who failed intravenous cyclosporine and required colectomy during the same hospitalization.


Something aortic. They give me a gradient, which without knowing the values seems somewhat high (55 mmHg!) and the area, which looks tiny to the naked eye: this is going to be aortic stenosis... And he has dyspnea. Symptomatic aortic stenosis, will the examiner want me to send him for surgery? With the guidelines in hand, that's right: this is a severe stenosis both in terms of area (<1 cm²) and mean gradient (>40 mmHg), with a preserved ejection fraction, and symptomatic. Surgical indication. If we do 1 we take away life expectancy, because we allow the ventricle to claudicate. 2 is outdated: balloon valvuloplasty? Only if the surgical risk is unaffordable, and in that case we would do 5, TAVI implantation (see [1]). But this is a 52-year-old man, who we assume has good bodywork because he walks to have dyspnea, so to the operating room. So to the operating room. A homograft? That's the Ross technique, I take the pulmonary and put it where the aortic. But it's rare, complex and only done in pediatrics. The correct thing to do is 3, without a doubt: replace with a prosthesis, preferably mechanical unless the patient has a contraindication for anticoagulation.

Something aortic. They give me a gradient, which without knowing the values seems somewhat high (55 mmHg!) and the area, which looks tiny to the naked eye: this is going to be aortic stenosis... And he has dyspnea. Symptomatic aortic stenosis, will the examiner want me to send him for surgery? With the guidelines in hand, that's right: this is a severe stenosis both in terms of area (<1 cm²) and mean gradient (>40 mmHg), with a preserved ejection fraction, and symptomatic. Surgical indication. If we do 1 we take away life expectancy, because we allow the ventricle to claudicate. 2 is outdated: balloon valvuloplasty? Only if the surgical risk is unaffordable, and in that case we would do 5, TAVI implantation (see [1]). But this is a 52-year-old man, who we assume has good bodywork because he walks to have dyspnea, so to the operating room. So to the operating room. A homograft? That's the Ross technique, I take the pulmonary and put it where the aortic. But it's rare, complex and only done in pediatrics. [HIDDEN], without a doubt: replace with a prosthesis, preferably mechanical unless the patient has a contraindication for anticoagulation.

A 52-year-old patient who has been complaining of dyspnea on medium exertion for 6 months. He has not presented angina or syncope. Physical examination and diagnostic tests show a mean aortic transvalvular gradient of 55 mmHg and a calculated area of 0.7 cm². Ejection fraction of 65%. The treatment to be indicated for this patient is:

Diuretics and more frequent check-ups by a specialist.

In case of increasing dyspnea on exertion, percutaneous dilatation of the aortic valve with a balloon catheter should be performed.

Replacement of the aortic valve with a prosthesis/bioprosthesis.

Replacement of the aortic valve with a homograft.

[Aortic stenosis is a common disease which requires individualized treatment].

Aortic stenosis is the most common valvular heart disease and the prevalence increases with age. Common symptoms include dyspnea, angina, and syncope. Echocardiography is a cornerstone in diagnosis of aortic stenosis. Severe aortic stenosis is defined as peak aortic jet velocity ≥4 m/s, a mean transvalvular gradient ≥40 mmHg, and/or an aortic valve area <1.0 cm2. The two-year mortality in patients with symptomatic aortic stenosis is 50 percent without intervention. The only efficient treatment is intervention, either open heart valve replacement or percutaneous transcatheter implantation of an aortic valve prosthesis (TAVI), which both provide symptomatic relief and improved survival. Many patients with aortic stenosis are elderly with comorbidities, thus making treatment decision challenging and requiring individual judgement.

Valvular heart disease

Aortic stenosis Treatment of aortic stenosis is not necessary in asymptomatic patients, unless the stenosis is classified as severe based on valve hemodynamics. Both asymptomatic severe and symptomatic aortic stenosis are treated with aortic valve replacement (AVR) surgery. Trans-catheter Aortic Valve Replacement (TAVR) is an alternative to AVR and is recommended in high risk patients who may not be suitable for surgical AVR. Any angina is treated with short-acting nitrovasodilators, beta-blockers and/or calcium blockers. Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers. Any heart failure is treated with digoxin, diuretics, nitrovasodilators and, if not contraindicated, cautious inpatient administration of ACE inhibitors. Moderate stenosis is monitored with echocardiography every 1–2 years, possibly with supplementary cardiac stress test. Severe stenosis should be monitored with echocardiography every 3–6 months.

Aortic valve replacement

Aortic stenosis Aortic stenosis is treated with aortic valve replacement in order to avoid angina, syncope, or congestive heart failure. Individuals with severe aortic stenosis are candidates for aortic valve replacement once they develop symptoms or when their heart function is impacted. Some people with asymptomatic aortic stenosis may also be candidates for aortic valve replacement, especially if symptoms appear during exercise testing. Patients with moderate aortic valve stenosis who need another type of cardiac surgery (i.e. coronary artery bypass surgery) should also have their valve addressed by the surgical team if echocardiography unveils significant heart problems.

Valvular heart disease

Aortic regurgitation Aortic regurgitation is treated with aortic valve replacement, which is recommended in patients with symptomatic severe aortic regurgitation. Aortic valve replacement is also recommended in patients that are asymptomatic but have chronic severe aortic regurgitation and left ventricular ejection fraction of less than 50%. Hypertension is treated in patients with chronic aortic regurgitation, with the anti-hypersensives of choice being calcium channel blockers, ACE inhibitors, or ARBs. Also, endocarditis prophylaxis is indicated before dental, gastrointestinal or genitourinary procedures. Mild to moderate aortic regurgitation should be followed with echocardiography and a cardiac stress test once every 1–2 years. In severe moderate/severe cases, patients should be followed with echocardiography and cardiac stress test and/or isotope perfusion imaging every 3–6 months.

[Therapy of aortic valve stenosis].

Calcific aortic stenosis is the most frequent valve disorder in the western world. It is a degenerative and chronic progressive disease in the elderly with increasing prevalence due to the demographic development in the population. As there is no medical therapy, the only option in severe aortic stenosis is valve replacement. Echocardiography is the diagnostic tool to assess aortic stenosis severity and morphology of the valve. Aortic stenosis is severe if the valve area is <1.0 cm(2), valve index <0.6 cm(2)/m(2) body surface, mean gradient >40 mmHg, and peak velocity >4.0 m/s. The entity of low flow, low gradient aortic stenosis is complex, and diagnosis and therapy are still challenging. Asymptomatic patients have a good prognosis, but must be reevaluated on a regular basis for the onset of symptoms or signs of progression. If one of the classical symptoms dyspnea and fatigue, angina pectoris or syncope occurs prognosis worsens dramatically and valve replacement is indicated. Gold standard therapy for aortic stenosis is surgical valve replacement. For high-risk patients (older age and severe comorbidities), transcatheter aortic valve implantation (TAVI) is established as standard therapy.

[Medium-term follow-up after percutaneous aortic valvuloplasty in the elderly. Clinical study apropos of 102 cases].

Percutaneous transluminal balloon aortic valvuloplasty was introduced in 1985 and, owing to its sometimes dramatic short-term results, it has rapidly become a useful procedure in the management of aortic stenosis in elderly subjects. The purpose of this study was to determine its clinical results at medium-term and to identify possible prognostic factors in order to improve the selection of patients suitable for this technique. Between January 1986 and December 1987, 78 patients (30 men, 48 women, aged from 60 to 93 years, mean 80 +/- 6.7 years) totalling 85 procedures were selected among 102 dilatations on the basis of a primary success without complications. Dilatation was performed by a technique similar to that described by Cribier et al. The follow-up period was 10 +/- 5.7 months (range: 1 to 27 months). The aortic valve area increased from 0.47 +/- 0.15 cm2 to 0.77 +/- 0.23 cm2, i.e. from 0.29 +/- 0.09 cm2/m2 to 0.48 +/- 0.13 cm2/m2 as regards the indexed area. The hospital mortality rate was 3.3 p. 100. At the end of the follow-up period 55 p. 100 of the patients were in NYHA class I or II; 29 p. 100 had died, 10 p. 100 had undergone a second dilatation and 13 p. 100 had had aortic valve replacement. This distribution into functional classes and major cardiac events was not significantly different in the subgroup of patients with an aortic valve area greater than 0.9 cm2 or in the subgroup of primary failure. The patients who died for cardiac reasons were older (p less than 0.01), had a lower cardiac output before and after dilatation (p less than 0.001) and a lower ejection fraction after dilatation (p less than 0.05) or even before in case of early death (p less than 0.05). Mortality and morbidity therefore were high at medium-term and unrelated to the haemodynamic effect of dilatation. On the other hand, the left ventricular systolic function was determinant, mainly because it could improve or remain stable when initially altered. These results suggest that only patients for whom aortic valve replacement is truly contra-indicated and who have a limited alteration of left ventricular function should be selected for aortic valvuloplasty.

Aortic regurgitation

Surgery A surgical treatment for AR is aortic valve replacement; this is currently an open-heart procedure. In the case of severe acute aortic regurgitation, all individuals should undergo surgery, if there are no absolute contraindications (for surgery). Individuals with bacteremia with aortic valve endocarditis should not wait for treatment with antibiotics to take effect, given the high mortality associated with the acute AI. Replacement with an aortic valve homograft should be performed if feasible. Prognosis The risk of death in individuals with aortic regurgitation, dilated ventricle, normal ejection fraction who are asymptomatic is about 0.2 percent per year. Risk increases if the ejection fraction decreases or if the individual develops symptoms.

Aortic valve replacement

Guidelines suggest TAVR for most patients aged 75 years and older, and surgical aortic valve replacement for most patients aged less than 75 years. Ultimately, the best treatment choice is a decision based on many individual factors. See also Aortic valve repair Artificial heart valve Valvular heart disease Minimally invasive cardiac surgery Pericardial heart valves Open aortic surgery References Sources External links The Society of Thoracic Surgeons – Aortic Valve Aortic Valve Replacement Animation Cardiology Cardiac surgery Implants (medicine) Prosthetics

AS can be asymptomatic or can cause symptoms of syncope, angina and heart failure. [6] Severe AS is fatal with a 50% mortality at 2 years. [7] As per The American College of Cardiology/American Heart Association (ACC/AHA) guidelines, AS is graded severe when the orifice area is less than 1.0 cm, the mean gradient is greater than 40 mmHg or the jet velocity is greater than 4 m/s. Prognosis is poor in symptomatic or severe cases unless the valve is replaced. Up to 30% of patients aged > 75 do not undergo surgical valve replacement either because of technical reasons; this may include porcelain aorta, general frailty, refusal to undergo surgery, and serious comorbid conditions. [8] The operative death risk for surgical aortic valve replacement (SAVR) is as high as 10% in patients with LV dysfunction, chronic renal disease, and advanced age. [9] Trans-catheter aortic valve replacement and trans-catheter aortic valve implantation (TAVR/TAVI) have emerged as a more feasible and less risky option for patients not suitable for surgery.

Aortic stenosis

Aortic valve replacement In adults, symptomatic severe aortic stenosis usually requires aortic valve replacement (AVR). While AVR has been the standard of care for aortic stenosis for several decades, aortic valve replacement approaches include open heart surgery, minimally invasive cardiac surgery (MICS) and minimally invasive catheter-based (percutaneous) aortic valve replacement. However, surgical aortic valve replacement is well-studied, and generally has a good and well-established longer-term prognosis. A diseased aortic valve is most commonly replaced using a surgical procedure with either a mechanical or a tissue valve. The procedure is done either in an open-heart surgical procedure or, in a smaller but growing number of cases, a minimally invasive cardiac surgery (MICS) procedure.

Percutaneous aortic valve replacement

Medical uses Patients with symptomatic severe aortic stenosis have a mortality rate of approximately 50% at 2 years without intervention. In patients who are deemed too high risk for open heart surgery, TAVR significantly reduces the rates of death and cardiac symptoms. At present, TAVR is not routinely recommended for low risk patients in favor of surgical aortic valve replacement, however it is increasingly being offered to intermediate risk patients, based on recent studies showing it to be non-inferior to surgical aortic valve replacement.

Aortic valve replacement

Low gradient aortic stenosis with concomitant left ventricular dysfunction poses a significant question to the anesthesiologist and the patient. Stress echocardiography (i.e. with dobutamine infusion) can help determine if the ventricle is dysfunctional because of aortic stenosis, or because the myocardium lost its ability to contract. Aortic insufficiency Many people with aortic insufficiency often don’t develop symptoms until they have had the condition for many years. Aortic valve replacement is indicated for symptoms such as shortness of breath, and in cases where the heart has begun to enlarge (dilate) from pumping the increased volume of blood that leaks back through the valve. Types of valves There are two basic types of replacement heart valve: tissue (bioprosthetic) valves and mechanical valves. Tissue valves

Mechanical Aortic Valve Replacement -- Indications

Transthoracic and transesophageal echocardiography are the two best tools to evaluate the aortic valve morphology. There are strict criteria outlined by the American Society of Echocardiography for severe aortic stenosis and the need for aortic valve replacement. Severe aortic stenosis is described as follows: [9] Aortic valve area of less than or equal to 1.0 cm2 Mean transvalvular aortic gradient greater or equal to 40 mmHg The maximum aortic jet velocity of greater than equal to 4 m/s across the valve The following are the stages and recommendations for aortic valve replacement in valvular stenosis: [10] [11]

Aortic valve replacement

Aortic stenosis most commonly is the result of calcification of the cusps. Other reasons for stenosis are the bicuspid valve (some patients have only two cusps at the aortic valve instead of the usual three) and rheumatic aortic stenosis (now rare in the West). Obstruction at the level of the aortic valve causes increased pressure within the heart's left ventricle. This can lead to hypertrophy and ultimately dysfunction of the heart. While x-ray and ECG might indicate aortic stenosis, echocardiography is the diagnostic procedure of choice. US findings also help in grading the severity of the disease. In cases of symptomatic severe aortic stenosis, AVR is warranted. In cases of asymptomatic but severe aortic stenosis, more factors should be taken into consideration.

Severe high-gradient aortic stenosis with symptoms by either history or on exercise testing (stage D1). Asymptomatic patients with severe AS (stage C2) and left ventricular ejection fraction (LVEF) <50 %. Patients with severe AS (stage C or D) undergoing other cardiac surgery. Asymptomatic patients with severe AS and low surgical risk. Asymptomatic patients with severe AS and decreased exercise tolerance or fall in systemic blood pressure. A mechanical valve is preferable over a bioprosthetic valve in the following patients: [12] Surgical aortic valve replacement in patients age < 55 years old. No contraindication to anticoagulation with Vitamin K antagonist. An existing indication for anticoagulation like a prosthetic mechanical valve at a different location. High risk of morbidity and mortality with reintervention. The following are predictors of poor outcome in patients undergoing aortic valve replacement: [13] [14]

Aortic valve

Aortic valve replacement Replacement of the aortic valve is done by replacing the native valve with a prosthetic valve. Traditionally, this has been a surgical procedure (surgical AVR or SAVR) but a non-surgical option called transcatheter aortic valve replacement (TAVR) or TAVI transcatheter aortic valve implantation delivers a prosthetic valve through a catheter. The choice between SAVR and TAVR often relies on the open-heart surgical risk and indications for other open heart surgeries (etc., coronary bypass, other valve dysfunction). The Bentall procedure is a type of surgical procedure when the aortic valve, aortic root, and ascending aorta are replaced in a single operation.

Aortic valve replacement

Indications for surgery Guidelines for aortic valve replacement As long-term data on the survival and quality of life of people following valve replacement have become available, evidence-based guidelines for aortic valve replacement have been developed. These help healthcare professionals decide when aortic valve replacement is the best option for a patient. Two widely accepted sets of guidelines used by surgeons and cardiologists are the American Heart Association and American College of Cardiology Guidelines for the Management of Patients with Valvular Heart Disease, and the European Society of Cardiology and the European Association for Cardio‑Thoracic Surgery Guidelines for the management of valvular heart disease. Aortic stenosis

[Aortic valve replacement in patients over 70: a Doppler echocardiographic study].

Aortic valve disease is known to be the most frequent valvular disease in the elderly and aortic valve replacement is often the best therapeutic strategy. Hemodynamic performance of prostheses is critical in this subset of patients to ensure an optimal quality of life. Moreover, old patients with small aortic ostia are getting more and more common in clinical practice, making often necessary to implant small prostheses. If a significant pressure drop is not achieved, hypertrophy persists and left ventricular function may not improve. Such conditions have not yet been extensively studied in the elderly. The aim of this study was firstly to assess echocardiographically the performance of aortic prosthetic heart valves in old patients (> or = 70 years) and compare the results obtained in patients with prostheses of different type and size, and secondly to evaluate the postoperative changes in left ventricular hypertrophy and function in a subset of patients with isolated or prevalent aortic stenosis. One hundred fifty-one patients were initially considered; global mortality was 9.3% at 20 +/- 12 months from intervention. In the 75 patients with a postoperative echocardiogram, transprosthetic gradient was 27 +/- 12 (max) and 15.1 +/- 6.6 (mean) mmHg. Mean functional prosthetic area (FPA) was 1.5 +/- 0.5 cm2. No statistically significant differences could be demonstrated between mechanical and biological prostheses. Three groups were identified, according to prosthetic size (Group 1: diameter < 23 mm, Group 2: diameter 23 mm, Group 3: diameter > 23 mm). Among groups, max and mean gradients as well as FPA were found to be significantly different. Respectively max gradient was 33.2 +/- 13, 26 +/- 11, 20.2 +/- 7.2 mmHg (p < 0.05), mean gradient was 17.2 +/- 6.1, 15.4 +/- 7.6, 11.7 +/- 4.3 mmHg (p < 0.01) and FPA was 1.2 +/- 0.3, 1.5 +/- 0.3, 1.8 +/- 0.7 cm2 (p < 0.05 between Group 1 and Group 3). In a subgroup of 31 patients with isolated or prevalent aortic stenosis, a significant interventricular septal thickness reduction was found postoperatively (14.3 +/- 2.3 vs 12.6 +/- 8.0 mm, p < 0.001). Posterior wall thickness decreased similarly, but to a lesser extent; left ventricular diameters and myocardial mass also significantly decreased (left ventricular mass: 186 +/- 45 vs 146 +/- 38 g/m2, p < 0.001). When prosthetic size was considered, septal thickness reduction was more evident in Group 1 and Group 2 (p < 0.05 and p < 0.01). On the contrary, a significant improvement in left ventricular diameters was observed only in Group 3 (p < 0.05). Left ventricular mass decreased significantly in Group 2 and Group 3 (p < 0.01 and p < 0.05). Such improvements could be demonstrated only in those patients (79%) who showed at least a 50% reduction in the transvalvular gradient. In this subset, left ventricular function also significantly improved (fractional shortening: 29 +/- 0.7 vs 33 +/- 0.7%, p < 0.02). In conclusion, aortic valve replacement in the elderly is a safe and effective therapeutic strategy. In patients with small aortic prostheses, the transvalvular gradient was found to be slightly but significantly higher as compared to that of larger prostheses. However, left ventricular function was good and similar in all subgroups. No significant differences were found between mechanical and biological prostheses. In old patients with isolated or prevalent aortic stenosis a significant reduction in left ventricular hypertrophy and mass is observed within 2 years from intervention. An increase in myocardial contractility can also be expected, if at least a 50% reduction in transvalvular gradient is obtained.

Aortic valve replacement

Patient–prosthesis mismatch When dealing with a small aortic annulus, the surgeon might be forced to insert a small prosthetic aortic valve, with an orifice that is too small in relation to the size of the patient. This is known as patient–prosthesis mismatch. It increases the pressure of the blood flowing through the valve and can negatively affect outcomes. Various techniques and stentless valves have been utilized to avoid this phenomenon. Less invasive procedures Minimally invasive cardiac surgery Since the late 1990s, some cardiac surgeons have been performing aortic valve replacement procedures using an approach referred to as minimally invasive cardiac surgery (MICS). Using this approach, the surgeon replaces the valve through a smaller chest incision (6–10 cm) than that for a median sternotomy. MICS typically involves shorter recovery times and more attractive cosmetic results.

Percutaneous aortic valve replacement

Severe symptomatic aortic stenosis carries a poor prognosis. No medical cure exists today, making the timing of aortic valve replacement the most important decision to make for these patients. Until recently, surgical aortic valve replacement was the standard of care in adults with severe symptomatic aortic stenosis. However, the risks associated with surgical aortic valve replacement are increased in elderly patients and those with concomitant severe systolic heart failure or coronary artery disease, as well as in people with comorbidities such as cerebrovascular and peripheral arterial disease, chronic kidney disease, and chronic respiratory dysfunction.

[Percutaneous transluminal aortic valvuloplasty using a balloon catheter. A new therapeutic option in aortic stenosis in the elderly].

Aortic valvular dilatation with a balloon catheter was performed in 44 patients, 20 men and 24 women, most of whom were very elderly (average age 77 years). The indication for valvular replacement had not been retained in these cases because of surgical contra-indications or a very high operative risk and in 3 cases because of patient refusal. Twenty-nine patients were in functional classes III or IV of the NYHA classification; 12 had syncopal episodes and 18 had invalidating angina. The dilatation was performed by a femoral arterial approach in 34 cases, and by a brachial arterial approach in 10 cases. MEDI-TECH catheters with 15, 18 or 20 mm diameters when inflated were used in the majority of cases. Several inflations lasting 10 to 240 seconds were performed in each case with balloons of increasing size. This was well tolerated in all but one patients who had a sharp syncope. The immediate results confirmed valvular dilatation. The average transvalvular pressure gradient fell from 76 +/- 25 mmHg to 30 +/- 13 mmHg (p less than 0.001). The aortic valve surface area calculated by the Gorlin formula increased from 0.5 +/- 0.18 cm2 to 1 +/- 0.42 cm2 (p less than 0.01). After dilatation the gradient was less than or equal to 40 mmHg in 37 cases; aortic valve surface area was greater than or equal to 1 cm2 in 14 cases and less than or equal to 0.7 cm2 in only 5 cases. The left ventricular ejection fraction increased immediately after valvuloplasty from 44 +/- 16 p. 100 to 49 +/- 15 p. 100 (p less than 0.01). In the 18 cases in which it was less than 40 p. 100 before valvuloplasty, it increased from 30 +/- 6 p. 100 to 36 +/- 9 p. 100 (p less than 0.02). Residual aortic regurgitation was only observed in one case. Two patients died in the hospital period (4.6 p. 100). There were no other serious complications. During an average follow-up period of 60 days (3 weeks to 6 months) there was a big improvement in symptoms in the great majority of cases and, in particular, syncopal and anginal attacks disappeared. Only 4 patients remained in functional classes III or IV after valvuloplasty. Percutaneous aortic valvuloplasty is a new, relatively simple, low risk, economic and very effective therapeutic procedure in all cases in which aortic valve replacement is contra-indicated or refused by the patient.(ABSTRACT TRUNCATED AT 400 WORDS)

[Results of isolated aortic valve replacement].

Progress in surgical technique and decreased early and late postoperative risk should lead to a modification in the indications for aortic valve replacement, before irreversible myocardial changes have definitively compromised the result of surgery. One hundred and seventy aortic valve replacements (100 pure or predominant aortic stenoses, 70 cases of aortic insufficiency) were carried out by the same surgeon over a period of 4 years with a minimum follow-up of one year and average of 25.4 months, using à Bjork prosthesis or a homograft. Early postoperative mortality was 5.3%, not differing from that associated with other types of valve replacement (mitral, polyvalvular). It is related more directly to surgical technique than to preoperative prognostic factors. Late mortality was 8.1%. Almost one third of these late deaths were related to the surgical technique or to the model of aortic prosthesis used. Stage IV cardiac failure plays a pejorative role in this late mortality, whilst no prognostic role could be demonstrated with respect to angina, meancardiac surface, Sokolow index, mean pulmonary artery pressure or diastolic pressure in the left ventricule. One year after surgery there was found to be a significantly important decrease in the Sokolow index and a modest decrease in mean radiological cardiac surface area. Beyond one year, no further improvement was seen. The majority of the patients surviving surgery had a good functional result since only 1% of the aortic stenosis patients and 7% of the aortic insufficiency group remained in stage III or IV cardiac failure. 78% of the patients who were working before operation were able to resume their professional activity after an average period of 6.2 months. However only 40% of the patients with stage IV failure who underwent surgery could return to work.

Mechanical Aortic Valve Replacement -- Introduction

Aortic valve stenosis is the most common type of valvular heart disease in the elderly. The incidence of aortic valve disease increases with age; one in eight people over the age of 75 have moderate to severe valvular heart disease. [1] The natural history of aortic stenosis usually begins with an asymptomatic period with the development of symptoms once the valve is critically stenosed. The progression of stenotic valve and time of onset of symptoms varies from patient to patient. Symptomatic patients with severe stenosis have a poor prognosis. Ross first described the higher mortality rate after the onset of cardiac symptoms in 1968. [2]

Valvular heart disease

Minor tricuspid insufficiency is common in healthy individuals. In more severe cases it is a consequence of dilation of the right ventricle, leading to displacement of the papillary muscles which control the valve's ability to close. Dilation of the right ventricle occurs secondary to ventricular septal defects, right to left shunting of blood, eisenmenger syndrome, hyperthyroidism, and pulmonary stenosis. Tricuspid insufficiency may also be the result of congenital defects of the tricuspid valve, such as Ebstein's anomaly. Signs and symptoms Aortic stenosis Symptoms of aortic stenosis may include heart failure symptoms, such as dyspnea on exertion (most frequent symptom), orthopnea and paroxysmal nocturnal dyspnea, angina pectoris, and syncope, usually exertional.

[The first 200 transcatheter aortic valve implantations in the Gottsegen Gyorgy Institute of Cardiology, Hungary].

Transcatheter aortic valve implantation is a therapeutic alternative for contraindicated and high surgical risk patients with severe symptomatic aortic stenosis. This intervention is part of daily routine in the Institute of the authors. In the present work the results of the first 200 patients are discussed. Until January, 2016, 200 patients (female 55%, mean age 79.9 years, average EuroSCORE 19.3%, left ventricular ejection fraction 54%, peak gradient 81.2 mmHg, mean aortic gradient 50.9 mmHg) underwent transcatheter aortic valve implantation. The procedure was performed with 99% success rate. Complications were evaluated according to VARC 2 definitions. Mortality was 5% at one month and 17.4% at one year. Cardiac mortality was 13.6 at one year. Cerebrovascular complications were 5% within one year, and 95% of patients were in NYHA I or II functional classes at one year. These findings are consistent with worldwide results. Orv. Hetil., 2016, 157(45), 1786-1792.

[A comparative evaluation of a prosthetic operation and balloon valvuloplasty in aortic valve stenosis in elderly people].

The results of surgical treatment of aortic stenosis (AS) in elderly patients were studied in a group of 602 patients aged from 70 to 90 years (average age 74.6 years) chosen from a total number of 1,643 persons who underwent operation for AS in 1975-1988. Total operative mortality with consideration for mortality connected with combined interventions was 11.4%, in the group of isolated prosthetics it was 10.4%. The late-term results were appraised in 96.6% of patients (in 3.6 years, on the average). According to actuarial charts, survival after 3 years was 75.9%, after 5 years--66.7%, and after 7 years--55.6%. There was no difference in the survival values of recipients of biological and mechanical prostheses. Significant improvement of the functional condition was noted (96.5% of patients belonged to NYHA classes I and II). Demographic and epidemiological studies showed this pathology in the elderly to be a new problem of surgery. Surgical treatment is justified by the quality of the results, prolonged survival, and an admissible risk level even at the age of 80-90 years. Comparison with the results of aortic balloon valvuloplasty studied on basis of a rich literature review shows these to be much poorer. On the whole, only surgery may be the real method of treatment allowing effective removal of AS. The operation can be carried out even on very old patients if there are no substantiated contraindications on the part of the brain and the patient's general condition.

InternalMed_Harrison

FIGURE 297e-12 After balloon valvuloplasty, the LV-AO mean pres-sure gradient decreased to 37.3 mmHg, indicating that the aortic valve area increased to 0.95 cm2. FIGURE 297e-14 Once the valve was deployed, the pressure gradi-ent between the LV and AO decreased to 11.6 mmHg, and the func-tional valve area is 1.34 cm2. The prevalence of calcific aortic stenosis is 2–3% in individuals age ≥75 years. Symptomatic aortic stenosis is associated with an average survival of 2–3 years and an increased risk of sudden death; aortic valve replacement improves both symptoms and survival. In high-risk patients with severe aortic stenosis who are not surgical candidates, 1and 5-year survival rates are ~62% and 38%, respectively. TAVR is approved in Europe and was recently approved in the United States as an alternative to surgical aortic valve replacement in high-risk patients. (Case contributed with permission by Dr. Andrew C. Eisenhauer.)

Aortic valve

There are alternatives to animal tissue valves. In some cases, a human aortic valve can be implanted. These are called homografts. Homograft valves are donated by patients and recovered after the patient expires. The durability of homograft valves is probably the same as for porcine tissue valves. Another procedure for aortic valve replacement is the Ross procedure (after Donald Ross) or pulmonary autograft. The Ross procedure involves going to surgery to have the aortic valve removed and replacing it with the patient's own pulmonary valve. A pulmonary homograft (a pulmonary valve taken from a cadaver) or a valvular prothesis is then used to replace the patient's own pulmonary valve. The first minimally invasive aortic valve surgery took place at the Cleveland Clinic in 1996. Endocarditis Endocarditis is infection of the heart and this often results in vegetations growing on valves. While it is possible for it to affect the aortic valve, it is not the most likely spot. Evaluation

Aortic valvuloplasty

Aortic valvuloplasty also known as balloon aortic valvotomy is the widening of a stenotic aortic valve using a balloon catheter inside the valve. The balloon is placed into the aortic valve that has become stiff from calcium buildup. The balloon is then inflated in an effort to increase the opening size of the valve and improving blood flow. According to the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease, balloon valvuloplasty (also referred to as balloon valvotomy) is not indicated for most patients with aortic stenosis. The preferred alternative, if available, is aortic valve replacement. However the guidelines noted specific settings in adults in which balloon valvotomy can be considered: As a "bridge" to surgery in hemodynamically unstable patients who are at high risk for aortic valve replacement. Use for palliation in patients with serious comorbid conditions that prevent performance of aortic valve replacement.

[Hemodynamic performance of mechanical aortic valves in narrow aortic annulus cases].

Small-sized prosthetic valves used in aortic valve position usually cause a high transvalvular gradient. This situation, especially in people with a high body surface area, causes a patient-prosthetic valve mismatch. In this study, hemodynamic performances of the two new generation bileaflet, small size mechanical valves were evaluated during rest and stress conditions. Eighteen patients with implanted 21-mm St. Jude HP (11 cases) and Sorin Bicarbon (7 cases) prosthetic valves in aortic position were evaluated at rest and during dobutamine infusion, 16.3+/-5.5 months after the operation. Dobutamine infusion was started at a dose of 5 microg/kg/min. The infusion rate was increased every 15 minutes up to 10-20-30 microg/kg/min. Maximum gradient, mean gradient, effective valve area (EVA), effective valve area index (EVAI) and performance index (PI) were calculated during rest and maximum dobutamine infusion rate. When the rest and dobutamine infusion measurements were compared, the maximum and mean gradients were found to be increased moderately, but EVA, EVAI, PI values did not change with increasing heart rates. For St. Jude valve; maximum gradient increased from 30.5+/-6.5 mmHg to 74.7+/-33.6 mmHg (p=0.03) and mean gradient increased from 17.9+/-3.8 to 40.8+/-23.8 mmHg (p=0.03). For Sorin Bicarbon valve; maximum gradient increased from 31.7+/-13.3 mmHg to 52.0+/-11.2 mmHg (p=0.01), mean gradient increased from 16.1+/-6.4 mmHg to 28.8+/-1.0 mmHg (p=0.01). The difference was not significant between the two valves with respect to measured parameters during rest and maximum dobutamine infusion. According to our findings, 21-mm Sorin Bicarbon and St. Jude HP mechanical bileaflet valves have good hemodynamic performance during exercise and these types of valves seem to be appropriate for patients with small aortic annulus.

Protected complex percutaneous coronary intervention and transcatheter aortic valve replacement using extracorporeal membrane oxygenation in a high-risk frail patient: a case report.

Transcatheter aortic valve replacement has become a routine procedure for patients with severe symptomatic aortic stenosis at increased surgical risk. Not much is known about using prophylactic support with venoarterial extracorporeal membrane oxygenation in patients undergoing transcatheter aortic valve replacement and eventually concomitant complex percutaneous coronary intervention. We present a successful procedure of transcatheter aortic valve replacement and high-risk percutaneous coronary intervention utilizing venoarterial extracorporeal membrane oxygenation for hemodynamic support in a very frail 88-year-old Caucasian woman with severe symptomatic aortic stenosis and coronary bypass grafting in the past. Echocardiography revealed a "low-flow low-gradient" aortic stenosis (mean transvalvular gradient 30 mmHg, aortic valve area 0.4 cm<sup2</sup, significant calcification), a left ventricular ejection fraction of 35%, severe mitral regurgitation with moderate stenosis (mean transvalvular gradient 7 mmHg), with a systolic pulmonary artery pressure of 80 mmHg. Moreover, pre-interventional coronary angiography exposed a severe left main ostial stenosis and sequential subtotal heavily calcified stenosis of the left anterior descending artery . Computed tomographic angiography showed no heavy tortuosity but moderate calcification of the iliofemoral arteries. The procedure was performed under general anesthesia in our hybrid operating room. Extracorporeal membrane oxygenation was established by left femoral percutaneous cannulation using a 21-Fr venous and 15-Fr arterial cannula. Subsequently, complex percutaneous coronary intervention with implantation of two drug-eluting stents from the left main into the left anterior descending artery was performed via a right femoral arterial 7F sheath. Thereafter, a 23-mm Sapien 3 aortic valve prosthesis (Edwards, Irvine, CA, USA) was implanted via right femoral artery in the usual manner, whereby the arterial pigtail catheter for marking the aortic annulus during transcatheter aortic valve replacement was inserted over a Check-Flo® Hemostasis Assembly (Cook Medical, Bloomington, IN, USA) on a Y-adapter via the arterial extracorporeal membrane oxygenation cannula. After extracorporeal membrane oxygenation decannulation, vascular closure was easily performed using the MANTA vascular closure device in order to reduce procedural time and risk of access site complications. In summary, we demonstrate the feasibility of elective prophylactic extracorporeal membrane oxygenation implementation in selected very high-risk and frail patients undergoing transcatheter aortic valve replacement and percutaneous coronary intervention in order to avoid intraprocedural complications.

[Comparative hemodynamic characteristics of Soviet-made mechanical heart valve prostheses in the mitral position].

The article deals with hemodynamic evaluation of Soviet-made, and heart valve prostheses in late-term periods after operation for mitral valve replacement. Fourty-six patients were examined: a ball prosthesis was implanted in 21 patients (1st group), as disk prosthesis--in 15 patients (2nd group) and a prosthesis--in 10 patients (3rd group). A good clinical result of the operation was achieved in all patients, they were referred to functional class I and II. Catheterization of the left and right parts of the heart, left ventriculography, and test with dosed physical exertion were carried out. Loading was continued till cardiac output increased approximately by 60 per cent in 6 patients of the 1st group, 12 patients of the second group, and in all 10 patients of the 3rd group. The study showed that the prostheses do not yield to foreign models of heart valves in hemodynamic characteristics and cause a lower stenosing effect than the prostheses do. No essential differences were detected between the prostheses.