Failure Of Drug Therapy Research Articles

Atrial Fibrillation Ablation: First-Line Therapy?

Background: Ablation for atrial fibrillation (AF) is a widely-accepted treatment for this arrhythmia. Ablation is traditionally reserved for second-line therapy in patients who have failed drug therapy, but it may be ready for first-line treatment. Objective: This article outlines the rationale for using ablation as first-line therapy for AF. Findings: AF increases both morbidity and mortality. Unfortunately, drug-based therapy for AF is very ineffective and may contribute adversely to both patient morbidity and mortality. Ablation addresses the root causes of AF and thus may be curative. The technique for ablation has become quite consistent and the outcomes better than those with drug therapy. The complication risk is also acceptably low. There is even preliminary evidence to suggest that AF ablation is superior as first-line treatment compared to drugs. Conclusion: AF ablation is rapidly evolving towards becoming first-line therapy for some patients with this debilitating arrhythmia.

Radioiodine treatment of juvenile Graves disease.

Ablation of the thyroid gland with radioactive iodine-I131 is an effective and safe method of therapy for older children and adolescents, as with adults, to treat hyperthyroidism of Graves disease (Graves-Basedow disease). The use of radioiodine as initial therapy or, as more often, the second line of therapy following antithyroid drug treatment is highly efficacious and rarely associated with short-term or long-term side effects. The indications for radioiodine therapy are failure of antithyroid drug therapy, idiosyncratic hypersensitivity reactions to antithyroid drugs, contraindications for surgical therapy including patients who refuse surgery, and the desirability to permanently prevent the development of hyperthyroidism. The treatment will induce permanent primary hypothyroidism within months after the use of ablative doses of radioiodine. The safety and simplicity of clinical management with L-thyroxine therapy for hypothyroidism favor radioiodine therapy for Graves disease over the potential risks from treatment with antithyroid drugs or surgery, and from untreated or relapsing hyperthyroidism. Radioiodine therapy is associated with the lowest morbidity and mortality among the currently available methods of therapy for Graves disease.

Abstract 4092: Initial Experience with Subxiphoid Percutaneous Epicardial Ventricular Tachycardia Ablation in Patients with Prior Cardiac Surgery

Introduction: Epicardial ablation via subxiphoid percutaenous access improves VT ablation success rate and is growing in popularity. However, it is unclear if this technique is feasible in patients with prior cardiac surgery because of pericardial adhesions. We describe results in our initial 12 patients with previous cardiac surgery. Methods: A total of 27 patients (11 women) underwent an epicardial VT ablation after failed antiarrhythmic drug therapy and at least one endocardial ablation. Twelve patients had undergone previous cardiac surgery (7 CABG, 3 valve only, 2 combined). The pericardium was accessed using a Tuohy needle. Then a guidewire and an irrigated tip catheter were used to free up adhesions. VT was mapped and ablated. We compared the results in patients with and without prior surgery. Results: There was no difference in the age (62±11 vs 58±13 years, p=ns), percent women (41 vs 40%, p=ns), EF (30±9 vs 27±11, p=ns), NYHA class (2.4±1.0 vs 2.1±0.9, p=ns) or use of beta-blockers (100 vs 93%, p=ns) or ACE inhibtors (100 vs 93%, p=ns) among patients with and without prior cardiac surgery. However, patients with prior surgery were more likely to have CAD (100 vs 66% p=0.02) and be on ASA (100 vs 73%, p=0.04.) The mean procedure (298±90 vs 178±45 min, p=0.01) and fluoroscopy time (106±24 vs 45±11 min, p=0.01) was longer in patients with prior surgery versus without surgery. The entire epicardium was mapped in 15/15 (100%) of the nonsurgical patients but only in 7/11 (64%) of the surgical patients due to adhesions (p=0.02.) The acute success rate, defined as elimination of all clinical VTs, was lower in the surgical group (75 vs 100%, p=0.02). Elimination of all VTs was achieved less often in post-surgical patient than non-surgical patients (58 vs 80%, p=0.04.) There were two occurrences of RV perforation in each group both treated with conservative therapy. There were no other complications. After 7±2 months, 66% of surgical patients and 80% of non-surgical patients were VT free (p=0.04) as monitored by ICD or 1, 3, and 6 month monitor. One patient in non-surgical group died of heart failure. Conclusion: Prior cardiac surgery does not preclude epicardial VT ablation but is associated with longer procedure times and lower success rates.

Management of failures of first line treatments

Up to 70% of the patients treated to prevent rebleeding will experience a bleeding episode within 2 years. The response should be adapted to the delay after the index bleed, the source and the severity of the haemorrhage, the underlying liver disease and the initial treatment to prevent rebleeding. Bleeding can be caused by endoscopic techniques themselves, which should incitate to complete obliteration rather than to switch to another therapy. Failure of drug therapy can be secondary to ineffectiveness, to a lack of compliance, or to an insufficient dosage. The two latter conditions may be corrected. Whenever a patient rebleeds in spite of optimal treatment, liver transplantation should be considered. When such a procedure is contra-indicated and in patients on the waiting list, a Transjugular intra-hepatic porto-systemic shunt (TIPS) should be performed.

Bridging the Divide in Heart Failure

Heart failure largely affects the elderly, with an average age at first diagnosis of 75 years in most developed countries. Many of these patients have comorbidity, such as chronic airways disease, diabetes, hypertension and renal dysfunction. Although the prognosis has improved dramatically in the past 10 years – largely owing to the more widespread introduction of drug therapies such as angiotensin-converting enzyme (ACE) inhibitors and β-blockers – recent surveys have shown that only a small minority of patients admitted to hospital with heart failure are seen by a specialist heart failure team, and less than 20% are followed up in a specialist clinic. The vast majority of patients in the UK are followed up in primary care, with some input of care from the elderly physicians. The use of drugs known to improve symptoms and prognosis remains less than ideal. The first session of the meeting was a detailed discussion of the role of the primary care physician in the diagnosis and treatment of heart failure. Applying the guidance from NICE, with a normal ECG and normal plasma brain natriuretic peptide (BNP) measurement making heart failure very unlikely, was often difficult – access to BNP testing is still very limited in the UK. In addition, ECG interpretation is also of variable quality and, in the elderly, the ECG is rarely completely normal. Data from the Quality and Outcomes Framework suggest that the quality of diagnosis in primary care varies markedly, and this is supported by a recent Health Care Commission survey that demonstrates marked variation in speed of access to diagnostic tools such as echocardiography. General practitioners with a specialist interest (GPSI) in cardiovascular disease are playing an increasing role in the diagnosis and management of more complex cardiac problems, including heart failure. This is observed to be most effective where there are good links to the secondary care-based cardiologists. Evidence was presented to show the improvement in the time-todiagnose heart failure and better uptake of appropriate drug therapy in areas where a GPSI had been established. Primary care physicians also play a key role in ensuring uptitration of medication, such as ACE inhibitors, angiotensin-receptor blockers and β-blockers. Measuring blood pressure, pulse rate and renal function can easily be carried out in primary care, saving the patient a journey to the local hospital, but does require an interested primary-care physician and practice nurse. Increasingly, heart failure specialist nurses are working in the community, often funded by the British Heart Foundation or Primary Care Trusts. Evidence was presented demonstrating that this initiative has reduced inappropriate hospital admissions and is cost effective. Multidisciplinary work is the best model of care, a point emphasized throughout the meeting. Increasingly, the competence and knowledge of the healthcare professional is more important than where they work. Heart failure patients benefit from good access to medical and

Pharmacogenetics in Laboratory Diagnostics

Pharmacogenetics (PGt) is a fast evolving field in medical science, since adverse drug reactions (ADR) and therapy failure may be due to variations in the genes of drug metabolizing enzymes, drug transporters and drug targets. There are many different techniques available for the detection of mutations, Single Nucleotide Polymorphisms (SNPs) and gene copy number variations (CNVs) that allow the scientist to apply the best suited method for defined diagnostic questions. This article reviews some of the most important genes of pharmacogenetic relevance, gives an overview of several methods frequently used for genotyping and provides insight into routine pharmacogenetic testing in the clinical laboratory.

Atrial-fibrillation ablation should be considered first-line therapy for some patients

Ablation for atrial fibrillation has become a widely accepted and practiced treatment for this arrhythmia. While this treatment has traditionally been reserved for second-line therapy in patients who have failed drug therapy, ablation is now being contemplated for first-line treatment. This review outlines the argument in favor of using ablation as first-line therapy for atrial fibrillation. Contrary to trials suggesting that rate control is equivalent to rhythm control, atrial fibrillation increases both morbidity and mortality. Unfortunately, drug-based therapy for atrial fibrillation is very ineffective and may also contribute adversely to both patient morbidity and mortality. Ablation has emerged as a curative therapy that addresses the root causes of atrial fibrillation. The technique for ablation has become quite consistent and the outcomes are far superior to those achievable by drug therapy. The complication risk is also acceptably low. There is also evidence to suggest that atrial-fibrillation ablation is superior to drug therapy as first-line treatment. Given all of the above-mentioned arguments, it is not unreasonable that atrial-fibrillation ablation be used as a first-line option for selected patients with this disease.

How to engage Cofilin

In HIV-infected people, resting CD4+ T cells are the main reservoir of latent virus and the reason for the failure of drug therapy to cure HIV infection. Still, we do not have a complete understanding of the factors regulating HIV replication in these cells. A recent paper in Cell describes a new trick that the virus uses to infect resting T cells. Interaction between the viral gp120 and cellular HIV co-receptor, CXCR4, during viral entry initiates signaling that activates cofilin, the main regulator of actin polymerization. As a result of this activation, actin is depolymerized, thus destroying the natural barrier to HIV replication. I discuss implications of this study for our understanding of HIV biology and development of novel anti-HIV therapeutic approaches.

Catheter Ablation for Ventricular Tachycardia

Sustained ventricular tachycardia (VT) is an important cause of morbidity and sudden death in patients with heart disease.1 Implantable cardioverter-defibrillators (ICDs) terminate VT episodes, reducing the risk of sudden death. Recurrent VT develops in 40% to 60% of patients who receive an ICD after an episode of spontaneous sustained VT. A first episode of VT occurs in ≈20% of patients within 3 to 5 years after ICD implantation for primary prevention of sudden death in high-risk groups.2–4 ICD shocks reduce quality of life and are associated with an increased risk of death.2–4 Antiarrhythmic drug therapy with amiodarone or sotalol reduces VT episodes but with disappointing incidence of side effects and efficacy.2 Catheter ablation is useful for reducing VT episodes and can be life-saving when VT is incessant.1,5,6 Idiopathic VTs occur in patients without structural heart disease and rarely cause sudden death. Electrophysiological study with catheter ablation is often warranted to confirm the diagnosis, to provide further evidence for the absence of ventricular scar or other disease, and often to cure the arrhythmia. Ablation is also an option for symptomatic nonsustained VT and frequent ventricular ectopy in these patients.1 The appearance of the VT on ECG often suggests its likely cause and associated heart disease (Figure 1). Monomorphic VT has the same QRS complex from beat to beat, indicating repetitive ventricular activation from a structural substrate or focus that can be targeted for ablation. Most are due to reentry through regions of ventricular scar.7 Figure 1. ECG types of VT and most common causes are shown with characteristic ECG features of selected VTs. LBBB indicates left bundle-branch block; LVOT, LV outflow tract; RBBB, right bundle-branch block; L, left; and R, right. Polymorphic VTs have a changing ventricular activation sequence that can be due to …

DRUG‐RELATED HOSPITAL ADMISSIONS IN A GENERIC PHARMACEUTICAL SYSTEM

1. Generically based pharmaceutical systems exist in a few countries of the world, such as Iran. Most developed countries have free market pharmaceutical systems. Drug-related problems (DRP) have been reported mostly in the Western world but few data are available for generic systems. In this study, we tried to measure the prevalence of drug-related problems leading to hospital admissions in Isfahan, Iran. 2. One thousand consecutive hospital admissions in three major teaching hospitals were studied for a period of 6 months for the presence of DRP as a cause of hospital admissions. Two subcategories of DRP were considered: (i) drug therapy failure; and (ii) adverse drug reactions. Preventability and outcome measures were also assessed. Medications responsible for DRP were classified according to the Anatomic Therapeutic Chemical (ATC) classification of the World Health Organization. 3. Of the 1000 admissions studied, 115 (11.5%) were owing to DRP, 81% as a result of drug therapy failure and 19% as adverse drug reactions. A total of 106 out of the 115 DRP cases (92%) were either preventable or probably preventable, most of which had to do with either prescriber or patient error. An overview of DRP showed that 58.3% resulted in complete recovery, 33.9% in relative recovery and 7.8% in death. Close to 1% of hospital admissions resulted in DRP-related deaths. 4. The overall prevalence of hospital admissions caused by DRP is similar to that in free market pharmaceutical systems. The high preventability rate of these problems should alert clinicians and policy makers to design strategies to curtail this. Also, reasons for differences in subtypes of DRP between the results of this study and those of the literature from free market systems needs to be investigated further.

Sustained improvement in symptoms of GERD and antisecretory drug use: 4-year follow-up of the Stretta procedure

Approximately 20% of patients with GERD do not respond to medical therapy. The Stretta radiofrequency antireflux procedure represents an alternative to failed drug therapy for GERD. The aim of this study was to assess symptom and medication changes after the Stretta procedure during a 4-year follow-up period. Prospective case series on intent-to-treat basis. Community practice. Patients with GERD with persistent symptoms despite twice-daily proton pump inhibitor (PPI) medications. The Stretta procedure was performed in drug-refractory patients with GERD diagnosed by the presence of endoscopically evidenced esophagitis or abnormal esophageal pH testing. Symptom assessment was performed with a validated health-related quality-of-life questionnaire (with and without medication) at baseline and 6, 12, 24, 36, and 48 months after treatment. Complications of the procedure and medication usage were analyzed. Significant changes in symptom scores, GERD quality-of-life parameters, and medication usage on the basis of clinical outcomes. We report on a series of 109 consecutive patients treated with the Stretta procedure who have reached 4-year follow-up. Complete long-term follow-up assessment was available in matched data for 109 patients at 12 months, 108 patients at 24 months, 102 patients at 36 months, and 96 patients at 48 months. A second procedure was performed in 13 patients. Heartburn scores decreased from 3.6 to 1.18 (P < .001), total heartburn score (GERD health-related quality-of-life questionnaire) decreased from 27.8 to 7.1 (P < .001), and patient satisfaction improved from 1.4 to 3.8 (P < .001) (see ). Medication usage decreased significantly from 100% of patients on twice-daily PPI therapy at baseline to 75% of patients showing elimination of medications or only as-needed use of antacids/over-the-counter PPIs at 48 months (P < 0.005). There were no serious complications of the procedure. This is an uncontrolled, nonrandomized case series in consecutive patients that does not include long-term pH or motility studies. This study in drug-refractory patients with GERD found the Stretta procedure to be a safe, effective, and durable treatment that produced significant improvements in heartburn and quality of life and decreased medication usage during a 4-year period of follow-up.

Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillation

The angiotensin-converting enzyme (ACE) deletion allele, ACE D, is associated with increased ACE activity and adverse outcomes in cardiovascular disease. Although activation of the renin-angiotensin-aldosterone system (RAAS) now appears to play a role in the pathophysiology of atrial fibrillation (AF), it remains to be determined if ACE genotype impacts response to conventional AAD therapy in patients with AF. The purpose of this study was to investigate whether response to antiarrhythmic drug (AAD) therapy in patients with AF is modulated by the ACE I/D polymorphism. We studied 213 patients (147 men, 66 women; ages 52 +/- 15 years) prospectively enrolled in the Vanderbilt AF Registry. AAD therapy outcome was defined prospectively as response if there was a >or=75% reduction in symptomatic AF burden or nonresponse if AF burden was unchanged, necessitating a change in drugs or therapy. Lone AF (age <65 years, no identifiable cause) was present in 72 (34%) patients, whereas hypertension was the most common underlying disease in the remaining 141 (41%). AF was paroxysmal in 170 (80%) and persistent in 43 (20%). The frequencies of the DD, ID, and II genotypes were in Hardy-Weinberg equilibrium. Lone AF and DD/ID genotypes were highly significant predictors of failure of drug therapy (P <.005). In patients with lone AF, failure of drug response was 5%, 41%, and 47% in patients with II, ID, and DD genotypes, respectively, (P <.005, II vs. ID/DD). These results provide further evidence for a role of RAAS activation in the pathophysiology of AF and point to a potential role for stratification of therapeutic approaches by ACE genotype.

Video-assisted subtotal or near-total thyroidectomy for Graves' disease

Surgery remains the treatment of choice for patients with Graves' disease. The purpose of the present study was to assess the usefulness and efficacy of video-assisted subtotal or near-total thyroidectomy in patients with Graves' disease. Between March 2000 and December 2004, 63 patients with Graves' disease underwent video-assisted subtotal, near-total or total thyroidectomy. Fifty-three patients (84 per cent) were considered for surgery after failure of antithyroid drug and radioiodine therapy, whereas the other ten patients were initially selected for surgical treatment based on their own preference. Treatment outcome was evaluated, including surgical complications, thyroid function, quality of life and patient satisfaction with the surgical result. All patients were operated on using a video-assisted technique, with some modifications depending on time and experience. There were no conversions to open surgery. Three patients (5 per cent) had temporary recurrent laryngeal nerve palsy that recovered spontaneously. Most patients were satisfied with the surgical results, particularly regarding the placement of the surgical scars. Video-assisted subtotal or near-total thyroidectomy is a safe and effective procedure for treatment of Graves' disease.

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol

Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1-9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of < or = 7.0%. If confirmed HbA1c rises to > or = 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.

HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug treatment

The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Drug Resistance, Virus Fitness and HIV-1 Mutagenesis

The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of drug resistance mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Características clínicas y electrofisiológicas de pacientes fulgurados con radiofrecuencia por taquicardia por reentrada nodal típica

AV nodal reentry tachycardia (AVNRT) is the most common cause of paroxysmal supraventricular tachycardia. Radiofrequency ablation is today the treatment of choice. To report our experience in patients who underwent slow pathway ablation. Fifty six consecutive patients (68% female, mean age 43 years old) that underwent slow pathway ablation are reported. Sixty four percent of patients had failed drug therapy. During electrophysiological study, AVNRT was induced in 55 patients. Isoproterenol was required for induction in 36%. Programmed atrial stimulation revealed dual AV nodal pathway in only 64% of the patients; 29% had AVNRT with single nodal curve and 7% only prolongation of AH interval. The slow pathway was ablated in 55 patients. One patient refused ablation because of risk of AV block. All patients had immediate success post ablation. Sixty four percent of patients persisted with partial evidence of dual curve manifested by sudden AH prolongation and single echoes. Isoproterenol is essential for ruling out AVNRT, since 29% of the patients had baseline single nodal curve and in only 64% was tachycardia induced without isoproterenol. Persistence of residual dual physiology does not rule out the success of ablation.

Successful Pulmonary Resection Combined with Chemotherapy for the Treatment ofMycobacterium aviumPulmonary Disease: A Case Report

The Mycobacterium avium complex (MAC) is the most common pathogen causing nontuberculous mycobacterial pulmonary disease. Despite the introduction of newer, more effective agents for the treatment of MAC, such as clarithromycin, the response to drug therapy in MAC pulmonary disease remains poor, and often frustrating. When MAC pulmonary disease has not been successfully eradicated using drug treatment alone, surgical management is still recognized to play a significant role. A case of MAC pulmonary disease, in a patient whose MAC disease was successfully treated by pulmonary resection, following the failure of drug therapy containing clarithromycin, is reported. To our knowledge, this is the first case report in Korea that the patient underwent a pulmonary resection for the treatment of MAC pulmonary disease.(Tuberculosis and Respiratory Diseases 2003, 54:621-627)

Surgery for ventricular tachycardia of left ventricular origin: risk factors for success and long-term outcome.

To review 26 consecutive patients with sustained monomorphic ventricular tachycardia (VT) of left ventricular origin, who underwent direct VT surgery. Economic factors precluded the use of an implantable cardioverter defibrillator (ICD) in the majority of these patients, and the indication for surgery in 81% of patients was for failed medical drug therapy and 27% of patients had frequent or incessant life-threatening VT. The principles of direct VT surgery included intraoperative mapping, extended endocardial resection, cryoablation, left ventricular aneurysm repair by left ventricular remodelling and endoaneurysmorrhaphy, as well as coronary artery bypass grafting. Two patients with non-ischaemic VT were significantly younger (37.7 +/- 19.4 years, P = 0.03), had lower preoperative New York Heart Association class (P = 0.03), and had better left ventricular ejection fractions of 59.5 +/- 2.1% (P = 0.001) than the 24 ischaemic patients. No operative mortality or recurrence of VT occurred in this group. Ischaemic VT patients had an operative mortality of 8.3%; risk factors were concomitant valve surgery (P = 0.02), and perioperative intra-aortic balloon pump (P = 0.02). Surgery improved the left ventricular ejection fraction from 28.4 +/- 9.8% to 43.2 +/- 8.2% (P = 0.0001). Freedom from recurrence or inducibility of VT in operative survivors was 78.8 +/- 9.6% at 10 years; risk factors were arrhythmic focus remote to the left ventricular aneurysm (P = 0.015), and simple cryoablation or endocardial resection alone and not in combination (P = 0.003). Survival was 54.1 +/- 11.6% and 43.3 +/- 13.4% at 5 and 10 years, respectively, and there were no arrhythmic or sudden cardiac deaths. Patients with immediately life-threatening VT unsuitable for ICD implantation requiring urgent or emergent VT surgery had a 10-year survival of 22.2 +/- 13.9% compared to the more elective surgical group with a rate of 73.3 +/- 13.9% (P = 0.08). Direct VT surgery should remain an objective for symptomatic drug refractory VT of left ventricular origin.

Surgery for Mycobacterium avium complex lung disease in the clarithromycin era.

Since the introduction of clarithromycin, it has been assumed that pulmonary Mycobacterium avium complex (MAC) disease can be treated with medication alone. This study examines whether surgery can still play an important role in the management of MAC lung disease in the current era. Between April 1993 and January 2001, 21 patients (11 men and 10 women) underwent a pulmonary resection for MAC infection. The median age of the patients was 56 years (range: 27-67 years). None of the patients were immunocompromised. Regimens employing clarithromycin were initiated preoperatively in all patients. The indications for surgery were failure of drug therapy in 19 patients and discontinuation of chemotherapy because of drug toxicity in two patients. The pulmonary resections (19 right lung, 2 left lung) performed included lobectomy in 16 patients, pneumonectomy in three, bilobectomy in one, and lobectomy plus segmentectomy in one. All of the patients survived the surgery. Six major postoperative complications occurred in six patients (28.6%) and these included two bronchopleural fistulas after right pneumonectomy, two space problems, one prolonged air leak, and one case of interstitial pneumonia. All postoperative complications were manageable, and four of these were treated surgically. All patients had sputum-negative status after their operation. Relapse occurred in two patients (9.5%) at six months and two years postoperative, respectively. The first patient, who originally had a right upper lobectomy, underwent a left upper lobectomy during the follow-up period, attaining sputum conversion. The second patient underwent a right pneumonectomy and then died of respiratory failure four years postoperatively. This one late death was the only fatality. Although it is associated with relatively high morbidity, surgery provides a high sputum conversion rate for patients whose MAC disease responds poorly to drug therapy. Even in the present clarithromycin era, pulmonary resection remains the treatment of choice when MAC lung disease has not been successfully eradicated by drug treatment alone.