Ronald E. Drusin

Diagnosis and Classification of Myocarditis by Endomyocardial Biopsy

Myocarditis was diagnosed by endomyocardial biopsy in 34 patients with otherwise unexplained heart failure. On the basis of both clinical and histologic findings these patients were divided into three groups. Seven patients had acute myocarditis (mean age, 20 years; mean ejection fraction, 22 per cent) characterized by an interstitial inflammatory infiltrate and extensive, acute cell damage. Five of these patients died after a mean duration of illness of eight weeks. Eighteen patients had rapidly progressive myocarditis (mean age, 35 years; mean ejection fraction, 19 per cent) characterized by patchy acute and healing cell damage and fibrosis; 17 of them died after a mean duration of illness of 23 months. Nine patients had chronic myocarditis (mean age, 31 years; mean ejection fraction, 31 per cent) characterized by focal inflammation and cell damage. All nine were alive after a mean follow-up period of 39 months. In four of these nine, clinical and hemodynamic improvement occurred after one month of immunosuppressive therapy. Our study suggests that a clinically useful classification of myocarditis can be accomplished by endomyocardial biopsy.

Cyclosporine-associated end-stage nephropathy after cardiac transplantation : Incidence and progression

BACKGROUND The salutary immunosuppressive effects of cyclosporine in extending cardiac allograft survival may be curtailed by its nephrotoxic effects. We reviewed our first 9 years of experience with cyclosporine after cardiac transplantation, to evaluate the incidence and progression of cyclosporine-associated end-stage renal failure necessitating chronic hemodialysis. METHODS Retrospective computer-based file review and personal interview when possible. RESULTS The population at risk was comprised of all adult cardiac recipients surviving at least 3 years (n=293). Of these, 19 (6.5%) developed end-stage renal failure requiring chronic hemodialysis. There were 17 men and 2 women (mean age of 45 +/- 11 years). The mean creatinine clearance for the study group decreased by 38% (P<0.001 vs. before transplant) by 6 months after transplantation and by 48% by 3 years postoperatively (P<0.001 vs. before transplant). The mean serum creatinine rose by 80% (P< 0.001 vs. before transplant) by 6 months after transplantation and by 125% by 3 years postoperatively (P<0.001 vs. before transplant). Time elapsed from transplantation to hemodialysis ranged from 3.7 to 9.5 years (mean 6.4 +/- 2). Actuarial 1- year survival after onset of hemodialysis was 75%. CONCLUSIONS Although cyclosporine remains the central immunosuppressive agent for cardiac allograft recipients, its use leads to a greater than one-third decrease in creatinine clearance by 6 months after transplantation and progression to end-stage renal failure, requiring hemodialysis in 6.5% of cardiac transplant recipients. Moreover, these patients are at increased risk of death compared with other cardiac allograft recipients. This data warrants the search of alternative or adjunctive agents that would allow decreased dosing or reduced nephrotoxicity of cyclosporine, while maintaining equivalent survival.

Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure.

Background. Systemic amyloidosis complicated by heart failure is associated with high cardiovascular morbidity and mortality. Heart transplantation for patients with systemic amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. Methods. All patients with systemic amyloidosis and heart failure referred for heart transplant evaluation from 1997 to 2004 were included in this retrospective cohort analysis. An interdisciplinary protocol for cardiac transplantation using extended-donor criteria organs, followed in 6 months by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for familial (ATTR) amyloidosis, was developed. Survival of the transplanted amyloid cohort was compared to survival of those amyloid patients not transplanted and to patients transplanted for other indications. Results. A total of 25 patients with systemic amyloidosis and heart failure were included in the study; 12 patients received heart transplants. Amyloid heart transplant recipients were more likely female (58% vs. 8%, P=0.02) and had lower serum creatinine (1.3±0.5 vs. 2.0±0.7 mg/dL, P=0.01) than nontransplanted amyloid patients. Survival at 1-year after heart transplant evaluation was higher among transplanted patients (75% vs. 23%) compared to patients not transplanted (P=0.001). Short-term survival posttransplant did not differ between transplanted amyloid patients and contemporaneous standard and extended-donor criteria heart transplant patients (P=0.65). Conclusions. Cardiac transplantation for amyloid patients with extended-donor criteria organs followed by either stem cell or liver transplantation is associated with improved survival compared to patients not transplanted. Short- to intermediate-term survival is similar to patients receiving heart transplantation for other indications. This clinical management strategy provides cardiac amyloid patients a novel therapeutic option.

Factors Affecting Long-Term Survival (.10 Years) After Cardiac Transplantation in the Cyclosporine Era

OBJECTIVES The aim of this study was to determine long-term survival (>10 years) after cardiac transplantation in the cyclosporine era and identify risk factors influencing long-term survival. BACKGROUND Despite the availability of newer modalities for heart failure, cardiac transplantation remains the treatment of choice for end-stage heart disease. METHODS Between 1983 and 1988, 195 patients underwent heart transplantation at a single center for the treatment of end-stage heart disease. Multivariable logistic regression analysis of pretransplant risk factors affecting long-term survival after cardiac transplantation included various recipient and donor demographic, immunologic and peritransplant variables. RESULTS Among the group of 195 cardiac transplant recipients, actuarial survival was 72%, 58% and 39% at 1, 5 and 10 years respectively. In the 65 patients who survived >10 years, mean cardiac index was 2.91/m2 and mean ejection fraction was 58%. Transplant-related coronary artery disease (TRCAD) was detected in only 14 of the 65 patients (22%). By multivariable analysis, the only risk factor found to adversely affect long-term survival was a pretransplant diagnosis of ischemic cardiomyopathy (p = 0.04). CONCLUSIONS Long-term survivors maintain normal hemodynamic function of their allografts with a low prevalence of TRCAD. It is possible that similar risk factors that lead to coronary artery disease in native vessels continue to operate in the post-transplant period, thereby contributing to adverse outcomes after cardiac transplantation. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of coronary atherosclerosis and enable long-term survival after cardiac transplantation.

Respiratory Complications of Cardiac Transplantation

The authors evaluated all respiratory complications of cardiac transplantation in a 10-year study of 94 consecutive recipients. Mean follow-up time was 20 +/- 17 months. The initial 20 patients were treated with azathioprine and prednisone, while the subsequent 74 patients received cyclosporine and prednisone. In the azathioprine group, respiratory infections accounted for 24 of 60 (40%) infections. Two-thirds of the respiratory infections occurred in the first 3 postoperative months and were generally localized processes (focal pneumonitis, nodule(s), abscess, or empyema). Gram-positive and gram-negative bacteria (8/30) and aspergillus (8/30) were the predominant pathogens. Respiratory failure occurred in 29% of infectious episodes. In the cyclosporine group, there were significantly fewer respiratory infections. There was also a reduction in the number of nonrespiratory infections; hence, the percentage of total infections due to respiratory causes, 26 of 50 (52%), was not significantly different. In contrast, however, nearly two-thirds of the respiratory infections in cyclosporine-treated patients occurred after the first 3 postoperative months, and were usually diffuse processes. Despite diffuse disease, respiratory failure was observed with similar frequency (19%). Pneumocystis carinii (9/31) and cytomegalovirus (CMV) (7/31) were the predominant pathogens. CMV pneumonitis tended to occur earlier than that due to P. carinii (2.9 +/- 1.9 mo vs. 9.8 +/- 11.2 mo, respectively), but there was considerable overlap. In comparison with infectious processes, there were 50% fewer noninfectious respiratory complications in both groups. These were primarily pleural (46%) or thromboembolic (18%) disorders. Four of five pulmonary emboli occurred in patients with intercurrent cardiorespiratory illness, and were detected only at autopsy. The authors conclude that respiratory infections account for one-half of all infections observed in cardiac transplant recipients, despite the reduced infection rate associated with the use of cyclosporine. Furthermore, respiratory infections in cyclosporine-treated patients exhibit different clinical and etiologic features than those seen in azathioprine-treated patients. Finally, occult thromboemboli may be difficult to recognize in cardiac transplant recipients because of the high incidence of coexisting cardiorespiratory disease.

Dobutamine in the rejecting transplanted heart.

Dopamine is commonly used to improve cardiac output and to maintain peripheral perfusion after myocardial injury. It has several advantages over other catecholamines. At effective inotropic dose levels, dopamine produces less peripheral vasoconstriction than norepinephrine. Dopamine also causes fewer arrhythmias than isoproterenol. This is a case report of a heart transplant patient who began rejecting and developed heart failure. In addition to the immunosuppressive agents, dopamine was used initially as the vasopressor with marked deterioration in the patients condition. Dobutamine, a new inotropic agent, was substituted for dopamine with subsequent improvement in cardiac function. The authors concluded that dobutamine may be the most appropriate agent to use in the rejecting transplanted heart because of the formers direct action on the heart. Dobutamine may also be preferred for support of the cardiac outputs of patients with chronic heart failure.

Simultaneous intermittent intraatrial and intraventricular conduction defects mimicking trifascicular conduction delay

Both intermittent rate related left bundle branch block and intermittent rate related trifascicular conduction delay (left bundle branch block with marked H-V interval prolongation) have been previously described. However intermittent rate related intraatrial block with left bundle branch block has not. No only does the case presented herein reveal intermittent rate related intraatrial block with left bundle branch block, but also PR prolongation secondary to the intraatrial block. This combination mimicked intermittent trifascicular conduction delay. Electrophysiological testing allowed differentiation of this pseudotrifascicular defect from true trifascicular conduction delay.

When is it safe to operate following myocardial infarction

BACKGROUND History of recent myocardial infarction (MI) is known to be a significant risk factor for postoperative complications following elective, noncardiac surgery (NCS). Recommendation regarding the optimal time for elective surgery following MI has changed over time as additional data have become available. Herein, we examine the current evidence and recommendation regarding the most appropriate time interval for elective NCS following MI to minimize morbidity and mortality.

When is it safe to operate following myocardial infarction? (TrioBP)

BACKGROUND History of recent myocardial infarction (MI) is known to be a significant risk factor for postoperative complications following elective, noncardiac surgery (NCS). Recommendation regarding the optimal time for elective surgery following MI has changed over time as additional data have become available. Herein, we examine the current evidence and recommendation regarding the most appropriate time interval for elective NCS following MI to minimize morbidity and mortality.

Quinidine-Digoxin Interaction-Reply

We would like to reply to the comments by Matzke and Burkle and those by Cisneros. Matzke and Burkle have reservations regarding the incidence of the interaction. We have made no attempt to state the actual incidence of this interaction; a retrospective study of hospitalized cardiac patients cannot possibly establish a true incidence. We have simply reported the finding of 25 cases in a single medical center in a single year, which suggests to us that the interaction must be common. Based on their mathematical model, Drs Matzke and Burkle expected higher serum digoxin concentrations than we found. The implication of this comment is that serum digoxin concentration may have risen merely from institution of a higher dose, enforced patient compliance in the hospital, or increased absorption from changes in other medications. We do not belive this to be the case for the following reasons: First, the baseline