Sudden Death and Staged Therapy for Hemodynamic Stabilization in Patients Enrolled in a Heart Transplantation Program

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14%± 5%, New York Heart Association Class IIl/IIIIV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirtyseven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninetynine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE₁ for preand afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 ± 9 months; patients who underwent staged therapy for 9 ±5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure. Thus, patients who underwent staged therapy were at increased risk for sudden death (P = 0.01, relative risk 3.4, 95% confidence interval 1.2–9.7) but were at lower risk for death from pump failure (P = 0.009, relative risk 0.44, 95% confidence interval 0.22–0.84). In patients who underwent therapy with continuous outpatient PGE₁ (n = 7) or dobutamine (n= 21), risk for sudden death (P = NS by log rank test) did not increase. In conclusion, staged therapy significantly reduced death from pump failure; however, patients who could be stabilized and considered too well for heart transplantation were at increased risk for sudden death. Thus, overall survival did not improve. Of note, outpatient dobutamine did not increase the risk for sudden death.     

Active surfactant in pharyngeal aspirates of term neonates: lipid biochemistry and surface tension function

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air–liquid interface to values below 5 mN m^?1. In addition, it has been suggested that surfactant is also present in the airways, particularly in the perinatal period. We isolated surfactant from pharyngeal aspirates obtained from 33 neonates immediately after delivery and analysed it for both phospholipid (PL) composition and surface tension function. PL classes and phosphatidylcholine (PC) molecular species were determined by normal and reversed-phase high-performance liquid chromatography (HPLC), respectively. Static and dynamic surface properties of the surfactant were studied in a pulsating bubble surfactometer. Sample volume was 1.3 ± 0.5 mL (mean ± SD) with a total amount of 2.5 ± 1.3 μmol of PL and a concentration of 2.1 ± 1.0 μmol mL^?1 PL. HPLC analyses of PL classes revealed a composition identical with surfactant prepared from alveolar washes, i.e. PC 83.6 ± 2.1%, sphingomyelin 1.4 ± 0.5%, phosphatidylglycerol 8.1 ± 1.6%, phosphatidylethanolamine 2.1 ± 0.5% and phosphatidylinositol 2.6 ± 1.1%. Thin-layer chromatography showed almost identical results but was more time-consuming and needed more material for analysis. Analysis of PC molecular species revealed a composition typical of human alveolar surfactant with 54.7 ± 3.9% dipalmitoyl PC, 10.3 ± 1.9% palmitoyloleoyl PC and 9.1 ± 1.5% palmitoylmyristoyl PC. Minimal surface tension fell to values below 5 mN m^?1 within 5 min of cycling in all subjects. The methods used in this study allowed for complete PL and surface tension analyses of surfactant obtained during routine pharyngeal suctioning after delivery at term. Whether they are also applicable to preterm neonates with respiratory distress remains to be determined.     

The role of auxiliary dihydropyridine receptor subunits in muscle

The skeletal muscle dihydropyridine receptor is a slowly-activating calcium channel that functions as the voltage sensor in excitation-contraction coupling. In addition to the pore-forming α_1S subunit it contains the transmembrane α₂δ-1 and γ₁ subunits and the cytoplasmic β_1a subunit. Although the roles of the auxiliary subunits in calcium channel function have been intensively studied in heterologous expression systems, their functions in excitation-contraction coupling has only recently been elucidated in muscle cells of various null-mutant animal models. In this article we will briefly outline the current state of these investigations. * To whom correspondence should be addressed: Tel.: +43-512-507-3787; Fax: +43-512-507-2836; E-mail: bernhard.e.flucher@uibk.ac.at     

Rise of oxygenation in cervical lymph node metastasis during the initial course of radiochemotherapy

It has been hypothesized that during radiation treatment a reoxygenation of hypoxic tumor tissue takes place. To test this hypothesis, we have investigated whether reoxygenation in lymph node metastases could be determined by invasive PO (2) measurements. Through a hypodermic needle inserted transcutaneously into tumor-positive lymph nodes, polarographic oxygen determinations were made in 18 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx. These measurements were performed before therapy and a week after the onset of radiotherapy or radiochemotherapy, respectively. Low PO (2) values before treatment (mean value of the patient's median was 12.6 mm Hg PO (2)) and a mean hypoxic fraction (PO (2) < 5 mm Hg) of 39.6% indicated manifest tumor hypoxia. After 1 week of treatment, a significant increase in the median PO (2) (mean value of shift: 7.3 mm Hg) and a reduction in the hypoxic fraction (mean value of shift: 13.4% PO (2) < 5 mm Hg, P < 0.03) were observed after both radiotherapy and radiochemotherapy. Thus invasive PO (2) histography fulfills the requirements for a method to confirm tumor hypoxia in head and neck tumors. The results obtained indicate that reoxygenation occurs during the initial phases of radiotherapy and radiochemotherapy, and they will form the basis for future comparative investigations on the possible influence of hypoxic parameters on tumor responsiveness toward radiation and radiochemotherapy.     

Antibodies to Human Sinus Node in Sick Sinus Syndrome

The incidence of autoantibodies against human conducting tissue was studied in 45 pacemaker patients with sick sinus syndrome (SSS), in 17 patients with bradyarrhythmia, and jive patients with hypertensitive carotid sinus syndrome. Antibodies against the human sinus node were demonstrated in 29% of patients with SSS and in 24% of patients with bradyarrhythmia; a tenfold risk of SSS could be calculated in patients with this antibody as compared to age-matched controls. At least two subtypes of anti-sinus node antibodies were demonstrated: an antibody absorbable and another one not absorbable with ventricular myocardium. Patients with SSS and prior myocarditis of rheumatic fever have a threefold incidence of that antibody, demonstrating that anti-conducting tissue antibodies are etiologic indicators for former inflammatory heart disease. These antibodies may play a role in the secondary immunopathogenesis of sick sinus syndrome. This hypothesis emerges as an interesting new pathogenetic concept.     

Impact of Dual Chamber Pacing on the Incidence of Atrial and Ventricular Tachyarrhythmias in Recipients of Implantable Cardioverter Defibrillators

Recent observations suggest that frequent dual-chamber pacing in recipients of implantable cardioverter defibrillators (ICD) may adversely influence clinical outcomes. This prospective, multicenter study examined the relationship between the frequency of atrial (%AP) and ventricular pacing (%VP) and the incidence of atrial (AT) and/or ventricular tachyarrhythmias (VT) in a standard ICD population. A total of 141 consecutive patients with primary and secondary ICD indications were studied. Continuous arrhythmia detection with a dual-chamber ICD revealed paroxysmal AT in 60 (43%) and VT in 72 (51%) patients within 6 months of device implantation. Far-field oversensing of ventricular signals occurred in 13% of all "atrial tachy response" mode switches. Without adjustment for covariates, a higher %AP was associated with an increased incidence of AT (P < 0.05). However, this association remained only weakly significant after adjustment for covariates using a multivariate model. High New York heart failure functional classes correlated significantly with AT (P = 0.02) and VT (P = 0.007). Rate-modulated pacing, programmed in 1/3 of patients, correlated with occurrence of AT (P = 0.006), but not with occurrence of VT. With respect to dual-chamber pacing, a %AP ≥ 48% combined with a %VP > 40% was associated with an increased probability for VT. In conclusion, AT and VT occurred frequently within 6 months after dual-chamber ICD implantation. High rates of DDD/R stimulation were associated with a trend toward higher incidence of AT, VT, or both.     

Magnetic Resonance Imaging and Signal-Averaged Electrocardiography in Patients with Repetitive Monomorphic Ventricular Tachycardia and Otherwise Normal Electrocardiogram

Early or localized forms of arrhythmogenic right ventricular dysplasia (ARVD) have been proposed as the arrhythmogenic substrate of repetitive monomorphic ventricular tachycardia (RMVT) originating in the right ventricular outflow tract in patients without any underlying cardiac abnormality on clinical examination and echocardiography. To further examine this hypothesis, magnetic resonance imaging (MRI) and signal-averaged electrocardiography (SAECG) were performed on 23 patients with RMVT and normal 12-lead standard ECG of conducted sinus beats. MRI was performed using ECG-gated turbo spin-echo images of the heart in order to detect signs of early or localized forms of ARVD, such as localized wall thickness reductions, signal intensity increase indicating adipose tissue infiltrates, and regional bulgings or aneurysms. MRI was normal in 22 (96%) of 23 study patients. In the remaining patient (4%), MRI demonstrated signal intensity increase in the intraventricular septum but not in the right ventricular outflow tract. Time-domain analysis of the SAECG was normal in 21 (91 %) of 23 patients and revealed ventricular late potentials in 2 study patients (9%). Frequency-domain analysis of the SAECG was normal in 22 (96%) of 23 patients and revealed ventricular late potentials in one study patient (4 %). We conclude that normal MRI findings of the heart and absence of ventricular late potentials in the SAECC in most patients with RMVT and otherwise normal ECG do not support the hypothesis that early or localized forms of ARVD create the arrhythmogenic substrate in the majority of these patients.     

Relation Between Left Atrial Size and Secondary Atrial Arrhythmias After Successful Catheter Ablation of Common Atrial Flutter

Catheter ablation ptovides an effective cure for patients with typical atrial flutter. However, these patients may have the potential to develop atrial tachyarrhythmias other than common atrial flutter. This study examines clinical and echocardiographic predictors for the occurrence of uncommon atrial flutter or atrial fibrillation after abolition of common atrial flutter. The study population comprised 17 patients (12 men, 5 women, age 32–74 years) who underwent successful radiofrequency catheter ablation of common atrial flutter. Common atrial flutter did not recur in any patient during a median follow-up time of 8 (range 1–25) months. Within a median of 7 (range 1–223) days, however, symptomatic atrial tachyarrhythmias occurred in 8 of 17 patients (47%): uncommon atrial flutter (n = 4); atrial fibrillation (n = 3); and both uncommon atrial flutter and atrial fibrillation in one patient. Preablation left atrial volume was significantly larger in patients who developed secondary arrhythmias compared with patients who remained in sinus rhythm (57.9 ± 15.6 vs 43.7 ± 16.4 cm³, P < 0.05). Enlarged left atrial volume dichotomized at 51 cm³ independently predicted postablation atrial arrhythmias (x²=5.11, rel. risk = 5.3, P < 0.05). On Kaplan-Meier analysis, time to occurrence of postablation atrial arrhythmias was significantly shorter in patietits with enlarged left atrium (P < 0.02). In conclusion, symptomatic uncommon atrial flutter and atrial fibrillation develops in a substantial proportion of patients after successful ablation of common atrial flutter. Out of a series of clinical and echocardiographic parameters, preablation left atrial size is the best predictor for the occurrence of these postablation atrial arrhythmias.