Mark Plunkett

Atrial Extracellular Matrix Remodeling and the Maintenance of Atrial Fibrillation

Background—Remodeling occurs in both ventricle and atrium in dilated cardiomyopathy and heart failure. However, the alteration of atrial extracellular matrix components during remodeling and its effect on the electrical remodeling and atrial arrhythmia have never been explored. Methods and Results—Atrial tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy and end-stage heart failure who underwent heart transplantation were examined. Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were used as controls (CNs). Western Blot analysis revealed a selective downregulation of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups compared with the NAF and CN groups and an upregulation of atrial metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type I collagen volume fraction (CVF-I) increased significantly in the PmAF group followed by the PsAF and NAF groups compared with that in CN. LA CVF-I significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the frequency of AF recurrence. Conclusions—Atrial extracellular matrix remodeling manifested by the selective downregulation of TIMP-2 along with upregulation of MMP-2 and CVF-I in the atrium is associated with the development of sustained atrial fibrillation in patients with cardiomyopathy and heart failure.

Use of assist devices and ECMO to bridge pediatric patients with cardiomyopathy to transplantation

BACKGROUND Pulsatile ventricular assist devices (VADs) are used to bridge adults with end-stage heart disease to transplantation. A combination of external implantable pulsatile and continuous-flow external mechanical support now can be used to bridge pediatric patients with end-stage cardiomyopathy to orthotopic heart transplantation (OHT). METHODS We reviewed consecutive pediatric patients with cardiomyopathy (n = 28) who required mechanical cardiac support from July 1995 to February 2001. All were OHT candidates with severe hemodynamic compromise despite maximal medical support. We excluded from this series patients who had undergone cardiotomy. RESULTS Nineteen patients received support from external continuous-flow devices, either with extracorporeal membrane oxygenation or with centrifugal VADs, and 9 patients received pulsatile support. Nineteen of 28 (68%) patients were successfully bridged to transplant (17) or weaned (2) from their devices after recovery. Of the patients successfully bridged to transplant or recovery, 89% are alive to date. Univariate analysis revealed that a lower bilirubin concentration after 2 days of support was associated with a favorable outcome (p = 0.006). As expected, the patients with pulsatile VADs had significantly higher rates of extubation and oral feeding. CONCLUSION Pulsatile and continuous-flow devices can complement each other to significantly extend the lives of a wide range of pediatric patients with severe cardiomyopathies.

Recent Trends in Early Outcome of Adult Patients after Heart Transplantation: A Single‐institution Review of 251 Transplants Using Standard Donor Organs1

Older age, prior transplantation, pulmonary hypertension, and mechanical support are commonly seen in current potential cardiac transplant recipients. Transplants in 436 consecutive adult patients from 1994 to 1999 were reviewed. There were 251 using standard donors in 243 patients (age range 18–69 years). To emphasize recipient risk, 185 patients who received a nonstandard donor were excluded from analysis. The indications for transplant were ischemic heart disease (n = 123, 47%), dilated cardiomyopathy (n = 82, 32%), and others (n = 56, 21%). One hundred and forty‐nine (57%) recipients were listed as status I; 5 and 6% were supported with an intra‐aortic balloon and an assist device, respectively. The 30‐d survival and survival to discharge were 94.7 and 92.7%, respectively; 1‐year survival was 89.1%. Causes of early death were graft failure (n = 6), infection (n = 4), stroke (n = 4), multiorgan failure (n = 3) and rejection (n = 2). Predictors were balloon pump use alone (OR = 11.4, p = 0.002), pulmonary vascular resistance > 4 Wood units (OR = 5.7, p = 0.007), pretransplant creatinine > 2.0 mg/dL (OR = 6.9, p = 0.004) and female donor (OR = 8.3, p = 0.002). Recipient age and previous surgery did not affect short‐term survival. Heart transplantation in the current era consistently offers excellent early and 1‐year survival for well‐selected recipients receiving standard donors. Early mortality tends to reflect graft failure while hospital mortality may be more indicative of recipient selection.

Seventeen-year experience with 1,083 heart transplants at a single institution

BACKGROUND Heart transplantation is the most accepted treatment for end-stage heart disease. A review of 1,083 consecutive transplants (1984 to 2001) was undertaken. METHODS Adult recipients were divided into quartiles. The last 540 transplants were combined. Three eras were created from these, 1984 to 1991, 1991 to 1995, and 1995 to 2001, with three age groups: 0 to 18 years, 19 to 61 years, and 62 to 74 years. All patients have at least 1 year of follow-up time. End points were survival, rejection, and graft coronary artery disease. RESULTS There were 1,012 patients. Donor age, graft ischemic time, and the proportion of elderly recipients and nonstandard donor hearts have increased in the current era. Actuarial 60-month survivals of recipients after 1995 were 80.7% (0 to 18 years); 75.3% (19 to 61 years); and 76.2% (>62 years). The current era children and younger adult groups demonstrated improved results when compared with previous eras (p = 0.003 and p = 0.05). Rejection episodes equal to or greater than ISHLT grade 3A per person per year improved to 0.15 in the current era (p < 0.001). During the three eras, older recipients (>62 years) demonstrated fewer episodes of rejection when compared with other adults (0.13 versus 0.58, p = 0.03). Deaths attributed to graft coronary artery disease decreased from 11% to 5% from era 2 to era 3. Regression analysis revealed a mild effect of donor age on survival and graft coronary artery disease (hazard ratio = 1.02, p = 0.001; hazard ratio = 1.039, p < 0.001, respectively). Recipient predictors of graft coronary artery disease were diagnosis of ischemic cardiomyopathy (hazard ratio = 1.6, p = 0.014) and congenital heart disease (hazard ratio = 3.41, p = 0.02). CONCLUSIONS Improved survival in the current era may be attributed to better organ preservation, improved immunosuppression and control of infection, and less life-threatening graft coronary artery disease.

Arrhythmia Recurrence in Adult Patients with Single Ventricle Physiology Following Surgical Fontan Conversion: Arrhythmia Recurrence Following Fontan Conversion

OBJECTIVES To evaluate the incidence of atrial tachy-arrhythmia (AT) recurrence following conversion from right atrial-pulmonary artery (RA-PA) Fontan to total cavopulmonary connection (TCPC) in adults. BACKGROUND AT is a recognized sequel of Fontan palliation, especially in RA-PA Fontans, and is associated with significant morbidity. While catheter ablation achieves fairly reliable short-term success with low morbidity, conversion to TCPC with arrhythmia surgery is a highly effective treatment option for the classical Fontan patients with incessant AT. METHODS Single center retrospective review. RESULTS Twenty-seven adults underwent Fontan conversion from RA-PA to TCPC, mostly for AT indications (n = 24). Nine (33%) underwent conversion to a lateral tunnel (LT) and 18 (67%) to an extracardiac (EC) Fontan. Two patients died <30 days post-operatively. Both had liver failure and had been turned down for cardiac/liver transplantation. In-hospital complications occurred in 15/27 patients (55%), including recurrence of AT requiring cardioversion in six patients (22%) and persistent pleural effusions in 4 (15%). Mean follow-up was 4.2 years (range 3 months-14 years). Functional capacity improved from mean New York Heart Association (NYHA) class 1.8 pre-conversion to 1.2 post-conversion (P= 0.008). Twenty-one patients had concomitant arrhythmia surgery (MAZE in 12 patients with IART and Cox-MAZE in nine patients with A-Fib +/- IART). Of these, 3/21 (14%) had AT recurrence >3 months following conversion. CONCLUSIONS Conversion from RA-PA Fontan to TCPC, with arrhythmia surgery, decreases AT recurrence and improves functional capacity. The risk of peri-operative mortality is highest in patients with cirrhosis. AT recurred in 14% of patients.

Results after transplantation using donor hearts with preexisting coronary artery disease.

OBJECTIVE Cardiac allografts with coronary artery disease may permit a selective expansion of the donor pool. Twenty-two recipients who received donor hearts with mild to moderate coronary artery disease on angiography were reviewed. All donor organs had preserved left ventricle function on echocardiogram. METHODS The procedure was explained to the patients in detail. All survivors have at least 1 year of follow-up. If the coronary arteries of the donor heart were significantly occluded, then the implanting surgeon performed coronary revascularization. Donors were allocated to patients facing imminent death (group I, n = 4) or to those who would otherwise not have been transplanted (group II, n = 18). Median recipient age was 57 years old for group I and 68 years old for group II. Median follow-up was 25 months for group I and 44 for group II. RESULTS Outcome was evaluated using survival and freedom from graft coronary disease as end points. In group I, 3 of the 4 hearts required revascularization. In group II, 10 of the 18 required revascularization. The majority of the revascularizations were recipient saphenous vein grafts (84.6%) to the donor left anterior descending artery (50%). The 1-month and 2-year actual survivals for group I are 75% and 50% and 87.5% and 81.3 for group II. One patient in group I who was in extremis and 3 in group II died at less than 90 days. Group II early deaths had donor risk factor combinations of coronary artery disease, left ventricular hypertrophy, and long distance. Freedom from new graft coronary artery disease was 100% at 2 years in group I and 87.5% in group II. CONCLUSIONS Selective use of donor hearts with coronary artery disease is acceptable. Early deaths are related to recipient factors as well as associated donor risk factors. Donor hearts with mild or moderate coronary artery disease and preserved function on echocardiogram can be used but may require revascularization with recipient conduit and/or percutaneous transluminal coronary artery angioplasty. Coronary disease in donor hearts requires grading and does not categorically preclude use, particularly in risk-matched recipients.

First successful bridge to cardiac transplantation using direct mechanical ventricular actuation.

Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patients native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under-utilized method of total circulatory support.

Surgical treatment of automatic atrial tachycardias.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term Outcomes of Heart Transplantation in Older Recipients

BACKGROUND Heart transplantation in the elderly is increasingly common. In the mid-1990s, 25% of recipients in our program were >62 years of age. We evaluated outcomes from one institution with the hypothesis that older recipients may be at higher risk of major complications associated with immunosuppression. METHODS We analyzed results for 182 patients aged 62 to 75 years (mean +/- SD: 66.3 +/- 11.4 years) who underwent heart transplantation between January 1995 and July 2001 at a single institution. They were compared with a control group of 348 contemporaneous adult recipients aged 18 to 62 years (mean +/- SD: 48.2 +/- 11.4 years). All recipients in this consecutive cohort had a follow-up of at least at least 5 years. End-points studied were Kaplan-Meier survival, freedom from dialysis and freedom from malignancy at 100 months. Follow-up was 100% at 100 months. RESULTS At 100 months, survival for the elderly was 55% (46 remaining at risk) and 63% (102 remaining at risk) for controls (p = 0.051, log-rank test). Re-transplant and dialysis, but not recipient age or malignancy, were predictive of survival by regression analysis (p = 0.003, p < 0.001, p = 0.53 and p = 0.84, respectively). Freedom from malignancy at 100 months was 68% for the elderly and 95% for controls (p < 0.001). Age predicted malignancy by regression analysis (p < 0.001). At 100 months, freedom from dialysis was 81% for the elderly and 87% for controls (p = 0.005). Pre-operative creatinine, but not age, was predictive of need for dialysis (p = 0.003 and p = 0.47, respectively). CONCLUSIONS Although long-term survival of older heart transplant recipients is acceptable, it is significantly lower than in young recipients. The increased risk of renal failure and malignancy among elderly patients likely influences the difference in survival observed between the two groups. Pre-operative renal function warrants careful consideration. As ventricular assist device technology improves, it may be used to complement heart transplantation to avoid immunosuppression and its side effect of malignancy in older patients with advanced heart failure.

Fontan Operation and the Single Ventricle

The Fontan operation has gone through multiple incarnations since Fontan and Baudets initial description in 1971. Through the medical dossier of a patient with a single ventricle, we plot the history of medical, surgical, and percutaneous interventions over the past 40 years, specifically focusing on the Fontan procedure, its development, indications, sequelae, and complications. Cardiac computed tomography with angiography is highlighted as a noninvasive imaging tool for the evaluation of the complex Fontan circulation.