Tonny D.T. Tjan

Implantable Cardioverter/Defibrillator Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy Single-Center Experience of Long-Term Follow-Up and Complications in 60 Patients

Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of ventricular tachycardia (VT) and cardiac arrest in young patients. We hypothesized that treatment with implantable cardioverter/defibrillators (ICDs) is safe and improves the long-term prognosis of ARVC patients at high risk of sudden death. Methods and Results—Sixty patients with ARVC (aged 43±16 years) were treated with transvenous ICD systems. Despite a higher number of right ventricular sites tested for adequate lead positions (P <0.05), lower R-wave amplitudes (P <0.001) were achieved in ARVC patients compared with other entities. During follow-up of 80±43 months (396 patient-years), event-free survival was 49%, 30%, 26%, and 26% for appropriate ICD therapies and 79%, 64%, 59%, and 56% for potentially fatal VT (>240 bpm) after 1, 3, 5, and 7 years, respectively. Multivariate analysis identified extensive right ventricular dysfunction as an independent predictor of appropriate ICD discharge. Fifty-three adverse events occurred in 37 patients during the perioperative (n=10) or follow-up (n=43) period, mainly related to the leads (n=31 in 21 patients). No lead perforation was observed. Freedom from adverse events was 90%, 78%, 56%, and 42% and freedom from lead-related complications was 95%, 85%, 74%, and 63% after 1, 3, 5, and 7 years, respectively. Conclusions—These results strongly suggest an improvement in long-term prognosis by ICD therapy in high-risk patients with ARVC. However, meticulous placement and long-term observation of transvenous lead performance with focus on sensing function are required for the prevention and/or early recognition of disease progression and lead-related morbidity during long-term follow-up of ICD therapy in ARVC.

Milrinone Modulates Endotoxemia, Systemic Inflammation, and Subsequent Acute Phase Response after Cardiopulmonary Bypass (CPB)

BACKGROUND Compromised splanchnic perfusion and the resulting intestinal mucosal injury leads to a decreased mucosal barrier function, which allows translocation of intestinal flora and endotoxemia. The authors evaluated the effects of milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent acute-phase response in patients undergoing coronary artery bypass grafting. METHODS This open, placebo-controlled randomized clinical study enrolled 22 adult patients in two groups. Before induction of anesthesia, baseline values were obtained and patients were randomized to receive milrinone (30 microg/kg bolus administered progressively in 10 min, followed by a continuous infusion of 0.5 microg x kg(-1) x min(-1)) or saline. The following parameters were determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid A, and C-reactive protein. RESULTS Milrinone did not prevent gastrointestinal acidosis as measured by pHi, but its perioperative administration resulted in significantly higher pHi levels compared with control. Venous and hepatic venous endotoxin and the interleukin 6 concentration were reduced significantly in the milrinone group. Serum amyloid A values were attenuated in the milrinone group 24 h after surgery. No significant differences could be seen in routinely measured oxygen transport-derived variables. CONCLUSIONS Perioperative administration of low-dose milrinone may have antiinflammatory properties and may improve splanchnic perfusion in otherwise healthy patients undergoing routine coronary artery bypass grafting.

Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support

OBJECTIVES We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support. BACKGROUND Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process. METHODS The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support. RESULTS MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days. CONCLUSION Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.

Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction.

OBJECTIVE Aortic valve replacement for aortic valve stenosis (AS) and regurgitation (AR) in patients with severe left ventricular (LV) dysfunction contains an increased risk. Few data are available on the outcome of such patients. METHODS Fifty-five consecutive patients with severe LV dysfunction (ejection fraction, EF; <30%) and aortic valve replacement for AS (n=35) or AR (n=20) were investigated between 1994 and 2001. EF was 25+/-5%, mean transvalvular gradient 26+/-6mmHg (AS), aortic valve area 0.66+/-0.18cm(2) (AS), cardiac index (CI) 2.4+/-0.9l/min/m(2), enddiastolic LV diameter (LVEDD) 64+/-8mm and endsystolic LV diameters (LVESD) was 55+/-3mm. Ninety percent of patients were in New York Heart Association (NYHA) functional class III/IV at admission to the hospital. Concomitant coronary artery bypass grafts (CABG) were performed in 14 patients. Follow-up examinations including chest X-ray, echocardiography, exercise testing, were performed among survivors. RESULTS The survival rates for AS were: 1-year 76%, 2-year 68.8%, 5-year 64.2%; for AR: 1-year 94.4%, 2-year 86.5%, 5-year 74.2%. NYHA functional class improved from 90% in class III/IV to 45 (AR group) and 24% (AS group) at follow-up (P<0.02). The LVEDD decreased to 54+/-8mm after 1 year. The EF improved to 38+/-4 (AR group) and 40+/-5% (AS group) at follow-up. CONCLUSIONS Despite severe LV dysfunction, increased 1-year mortality especially in the AS group, aortic valve replacement was associated with improved functional status, symptoms and EF in both groups and in most patients. We, therefore, conclude that aortic valve replacement in patients with severe LV dysfunction can be performed with acceptable risk.

The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery☆

OBJECTIVES We hypothesized that a temporary cardiopulmonary bypass (CPB)-induced reduction of endotoxin antibody levels contributes to elevated endotoxin levels and the associated inflammatory consequences, with a significant influence on the postoperative ventilation time period. BACKGROUND Cardiac surgery using CPB induces a systemic inflammatory response syndrome with an associated risk of increased postoperative morbidity and mortality. METHODS A total of 100 consecutive patients undergoing elective coronary artery bypass graft surgery using CPB were prospectively investigated. Endotoxin core antibodies (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin, interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured serially from 24 h preoperatively until 72 h postoperatively. RESULTS Eighty-five patients had no complications (group 1), whereas 15 patients required prolonged ventilation (group 2). In both groups, there was a decrease of all antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2, preoperative antibody levels were lower (p < 0.01)--specifically, the decrease in IgM was significantly stronger and of longer duration (p < 0.002)--and levels of endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively. CONCLUSIONS We conclude that an CPB-associated temporary reduction of anti-endotoxin core antibody levels contributes to elevated endotoxin and IL-8 release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were associated with a greater rise in endotoxin and IL-8, as well as prolonged respirator dependence.

Cor triatriatum: short review of the literature upon ten new cases.

Cor triatriatum is defined as a membrane within the left atrium, which might lead to restricted pulmonary venous return. Diagnosis is usually achieved by echocardiography, therapy of choice is excision of the membrane. Upon ten new cases, the association with other congenital heart diseases (CHDs), clinical symptoms and the surgical approach are discussed. Eight of ten patients were children, six of them aged < 1 year. Additional CHDs included atrial and ventricular septal defects, partial anomalous pulmonary venous return and complex CHD. Surgery was performed in all cases. Prognosis is related to associated CHD.ZusammenfassungDas Cor triatriatum ist definiert als eine Membran innerhalb des linken Atriums, die zu reduziertem pulmonalvenösem Fluss führen kann. Die Diagnose wird üblicherweise echokardiographisch gestellt. Die Therapie der Wahl bei symptomatischen Patienten ist die chirurgische Exzision der Membran.Anhand zehn neuer Fälle werden die Assoziation mit anderen angeborenen Herzfehlern, die klinischen Symptome und der chirurgische Zugangsweg diskutiert. Acht der zehn Patienten waren Kinder, von diesen wiederum sechs < 1 Jahr alt. Assoziierte Herzfehler lagen bei neun Patienten vor: sieben Vorhofseptumdefekte, ein Ventrikelseptumdefekt, eine valvuläre Pulmonalstenose, eine bikuspide Aortenklappe, ein singulärer Ventrikel, eine partielle Lungenvenenfehlmündung und eine persistierende linke obere Hohlvene. Die Therapie war in allen Fällen chirurgisch, wobei in neun von zehn Fällen bei assoziierten Herzfehlern ein rechtsatrialer Zugang gewählt wurde, während bei isoliertem Cor triatriatum vom linken Atrium aus operiert wurde.

Skeletonization Versus Pedicle Preparation of the Radial Artery With and Without the Ultrasonic Scalpel

BACKGROUND The radial artery (RA) is increasingly used for myocardial revascularization because of its presumed advantageous long-term patency rates. The vessel can be harvested as a pedicle or skeletonized. The aim of this study was to compare the skeletonization technique with pedicle preparation using either an ultrasonic scalpel or scissors. METHODS Forty consecutive patients with coronary artery disease undergoing complete arterial revascularization were included in the study. In 20 patients the RAs were prepared using scissors and clips (group 1: skeletonization; group 2: pedicle). In another 20 patients the arteries harvested were prepared using an ultrasonic scalpel (group 3: skeletonization; group 4: pedicle). The RA was treated with papaverine to prevent spasm of the vessel during and after harvesting. Tissue specimens of each RA were taken to analyze endothelial morphology by scanning electron microscopy. After implantation of the RA, graft perfusion was measured with a flow probe. RESULTS Harvesting the RA as a skeletonized vessel took more time as compared with pedicle preparation (group 1 vs group 2: 37.1 +/- 3.5 minutes vs 24.4 +/- 3.9 minutes; p < 0.001 and group 3 vs group 4: 31.1 +/- 3.5 minutes vs 25.6 +/- 3.7 minutes; p < 0.01). The number of hemostatic titanium clips was similarly higher in group 1 as opposed to group 2 (58.7 +/- 7.1 vs 38.7 +/- 7.1; p < 0.01). However, there was no difference between groups 3 and 4 (p = 0.086). The length of the RA after skeletonization with scissors and clips was 20.8 +/- 1.5 cm in contrast with 19.1 +/- 0.9 cm (p < 0.01) after dissection as a pedicle. In the groups using the ultrasonic scalpel, there was no difference in graft length (p = 0.062). Mean blood flow through the graft after establishing the proximal anastomosis was similar among all groups (groups 1, 2, 3, and 4: 50 +/- 20.1 mL/min, 53.8 +/- 24.3 mL/min, 56.3 +/- 25.1 mL/min, and 51.8 +/- 23 mL/min, respectively). Scanning electron microscopy demonstrated endothelial damage in all patients in groups 1, 2, and 3 and in 7 patients of group 4. Most endothelial lesions were minor except in group 3 in which 1 of 5 endothelial lesions were severe. Statistically significant differences was found between groups 1 and 2, and 3 and 4 with respect to the degree of endothelial damage (p < 0.01). CONCLUSIONS Skeletonization using scissors and clips is more time consuming and technically more difficult, but yield significantly longer grafts. Skeletonization with an ultrasonic scalpel did not result in additional length and was more frequently associated with severe endothelial damage. Pedicle preparation using scissors or an ultrasonic scalpel is much simpler and faster, and does not jeopardize endothelial integrity.

A simple new model of physiologically working heterotopic rat heart transplantation provides hemodynamic performance equivalent to that of an orthotopic heart

BACKGROUND The widely used non-volume-loaded abdominal heterotopic heart transplant (NL) in rats undergoes atrophy after transplantation. Various techniques have been designed to load the transplanted heart because of its potential immunological impact. Our aim was to create a volume-loaded heterotopic heart transplantation model (VL) capable of ejection and practical for routine studies. Using this model, we tested the hypothesis that VL isografts would retain myocardial performance comparable to native hearts (NH). METHODS Heterotopic hearts were transplanted using and end-to-side anastomosis between the donors superior vena cava and the recipients abdominal inferior vena cava. The right ventricle loads the left ventricle (LV) via a direct anastomosis of the pulmonary artery to the left atrium. The LV ejects volume through an end-to-side anastomosis of the donors aorta to the recipients abdominal aorta. Hemodynamic data (systolic and diastolic LV pressures, dP/dt max and min, tau) were studied in-situ (at baseline and after adding volume) and in a Langendorff perfusion system (at baseline and after stimulation with isoproterenol) 2 weeks after transplantation. RESULTS In situ systolic pressure and diastolic function of VL was superior to NL, and beta-adrenergic stimulated performance in the Langendorff perfusion of VL showed hemodynamic performance equivalent to NH, unlike NL which had a diminished response. CONCLUSION This technique results in a volume-loaded ejecting heart transplant model that preserves anatomical structures. The VL can be evaluated in situ and after explantation in Langendorff perfusion system and may offer advantages if workload of the graft is of significance to the study performed.

Wound complications after left ventricular assist device implantation

BACKGROUND Wound necrosis and infection pose a tremendous risk for patients with left ventricular assist devices. METHODS We analyzed our database of patients with left ventricular assist devices for those who developed wound dehiscence and concomitant infection after left ventricular assist device implantation. RESULTS Three of our 66 patients (4.5%) with implantable ventricular assist devices had had severe wound complications with necrosis of the abdominal or thoracic wall uncovering part of the device. The predominant impact on the development of these complications was presumably related to multiple surgical interventions on the same site. CONCLUSIONS Nevertheless, these patients can recover and undergo successful heart transplantation if adequately managed.

The impact of the pro‐ and anti‐inflammatory immune response on ventilation time after cardiac surgery

Cardiac surgery using cardiopulmonary bypass (CPB) may induce a systemic inflammatory response syndrome (SIRS), which is associated with an increased risk of postoperative morbidity and mortality. The intention of this pilot study was to investigate the influence of the pro‐ and anti‐inflammatory cytokine responses as well as of released adhesion molecules and endotoxin on the time requirements for assisted postoperative respiration following CPB surgery.