New implantable cardiac monitor with three-lead ECG and active noise detection.

BACKGROUND: A new implantable cardiac monitor (BioMonitor, Biotronik) with a continuous remote monitoring option was prospectively implanted in patients with suspected arrhythmias or for therapy control after atrial fibrillation (AF) ablation. A three-lead ECG detection was intended to make the implantation more independent of the implantation site and the electrical heart axis. Because noise is a frequent problem in implantable cardiac monitors, an active noise detection algorithm was implemented. The aim of the trial was to evaluate the clinical performance of the device. METHODS: The device performance was evaluated in a prospective nonrandomized multicenter study with a follow-up of 12 months. Study endpoints were device-related serious adverse events at 3 months, appropriate QRS detection in direct comparison with synchronized Holter ECG recordings, sensitivity and positive predictive value of arrhythmia detection in comparison with Holter ECG and independent of it, and noise burden during the entire follow-up period. RESULTS: The implantation was successful in all 152 patients. Two device-related serious adverse events (pocket infections) occurred by 3 months. The mean QRS amplitude of 0.3 ± 0.2 mV at implantation remained stable over 12 months. QRS sensing performance indicated little over- and undersensing in most patients. More than 80 % of the patients had more than 22 h of noise-free monitoring per day. CONCLUSION: BioMonitor effectively detects patients with bradycardia, tachycardia, AF, or asystole. Active noise detection seems to reduce the transmission of meaningless data without diminishing the positive predictive value of the device.

Cardiac contractility modulation in non-responders to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) has become a standard therapy in cases of heart failure and asynchrony. Unfortunately, 20-30% of patients were non-responsive (NR) to CRT. In this report we used cardiac contractility modulation (CCM) as an adjunctive measure in NR patients. METHODS AND RESULTS: Sixteen NR patients, mean age 65 +/- 9 years, mean ejection fraction 27.3 +/- 7.4%, and New York Heart Association (NYHA) class III (n = 9) or IV (n = 7) despite CRT plus optimized medical therapy, received an additional CCM-implantation contra-lateral to the existing CRT system (OPTIMIZER III, Impulse Dynamics, Orangeburg, NY, USA). Cardiac contractility modulation delivers non-excitatory high-energy stimulatory impulses during the absolute refractory period, thus improving contractility [left ventricular (LV) dp/dt)] by stimulating the septum with two screw-in leads and one additional atrial lead for triggering the impulses. Acute LV dp/dt changes induced by CCM stimulation were measured by 5F Millar catheters placed in the LV during the implantation procedure in 14 of 16 cases. Patients were followed prospectively. Left ventricular dp/dt increased from a mean of 568 +/- 153 to 646 +/- 147 mmHg/s (+14%, P < 0.001) in the acute intraoperative testing. We noted the following complications and events during a follow-up of an average of 147 +/- 80 days (range 68-326) after CCM: intraoperative ventricular flutter needing cardioversion (n = 1), atrial lead dislocation (n = 1), coronary sinus (CS) lead dislocation (n = 1), painful stimulation requiring repositioning of septal leads (n = 1), true defibrillator shocks (n = 3), cardiac decompensations (n = 3), atrial fibrillation (n = 4), renal failure (n = 1), and pneumonia (n = 2). NYHA class improved from 3.4 to 2.8 (P < 0.01), and the ejection fraction increased from 27.3 +/- 5 to 31.1 +/- 6 (P < 0.01). Three patients (19%) died suddenly presumably due to electromechanical dissociation after 318, 104, and 81 days. No electrical interference was observed between the CCM and CRT systems, and in particular, at no time was the CRT-implantable cardioverter-defibrillator found to be delivering inadequate shocks. CONCLUSION: The CCM method is feasible and could be applied with calculated risks as a possible useful adjunct in CRT-NR when no other options are available; however, mortality and event rates are high in this very sick population.

Hemodynamic changes during cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a new method for the correction of inter- and/or intraventricular conduction delays of patients with heart failure. The long-term impact of CRT on central hemodynamics is not fully characterized. We performed complete right heart catheterization studies in 31 patients receiving a CRT device pre and 6 months after implantation. Most of the patients improved in their NYHA stage, their LVEF, and in parallel showed reduced right atrial (RA) pulmonary artery (PA) and pulmonary capillary wedge (PCW) pressures and pulmonary vascular resistance both at rest and at 25 watts. In addition, we found a reduction in heart rate accompanied by an increased mean arterial pressure both at rest and at 25 watts. Accordingly, brain natriuretic peptide levels (BNP) were lowered. It was concluded that, besides other well-known effects on ventricular coordination, central hemodynamics after 6 months were improved during CRT.

Rhabdomyolysis after addition of digitoxin to chronic simvastatin and amiodarone therapy.

Rhabdomyolysis is a well known side effect of statin therapy. Several drugs may increase its risk by drug-drug interactions. In particular, patients with heart disease receive more and more different compounds to cope with all the pathomechanisms involved and may therefore be of high risk for side effects. We report a case of rhabdomyolysis in a patient with heart failure on a multi-drug regimen caused by a drug interaction between chronic statin therapy (simvastatin), amiodarone and newly administrated digitoxin. The patient recovered fully after cessation of simvastatin therapy, the other drugs were given continuously. Potential mechanisms of this event are discussed. Most interesting in this case is that rhabdomyolysis occurred only after starting digitoxin after long-term therapy with the statin.

Inappropriate shock during left ventricular threshold measurement in a patient with coexisting ICD and a biventricular pacemaker.

Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads for biventricular stimulation is an established method for the therapy of congestive heart failure (CHF) in the case of inter- or intraventricular conduction delays. There are some patients having two separate devices: an ICD and a biventricular pacemaker. This case report describes an unusual interaction of these systems: an inappropriate VVI defibrillator shock during left ventricular threshold measurement in a biventricular pacemaker implanted on the other side.

What can happen during coronary sinus lead implantation: dislocation, perforation and other catastrophes.

Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is an established method for the therapy of congestive heart failure (CHF) in the case of asynchronous ventricular contractions. Successful therapy depends on the placement of left ventricular leads usually via the coronary sinus (CS), a technically more challenging procedure than regular pacemaker implantations. Without specific precautions CRT implantation can be the gateway to a time consuming nightmare. Therefore CS lead implantation methods, with a focus on complications, were reviewed according to the literature and own experience with approximately 500 procedures from 1999-2007.

Inappropriate ICD discharge induced by electrical interference from a physio-therapeutic muscle stimulation device.

This report illustrates the case of a patient with an implantable cardioverter defibrillator (ICD) who during physiotherapy with transcutaneous electrical stimulation of the lumbar musculature perceived a shock discharge by the ICD. Analysis of the stored electrogram showed inappropriate therapy due to electromagnetic interference with the external stimulation. Patients as well as physiotherapists should be informed about this potential interaction to avoid such iatrogenic, inappropriate ICD therapy.

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients.

INTRODUCTION: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. METHODS: From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64+/-12 years, range 14-90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. RESULTS: In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). CONCLUSION: Perioperative complications during CS lead implantation occur in 10-15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.

Long-term hemodynamic benefit of biventricular pacing depending on coronary sinus lead position.

BACKGROUND: Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. METHODS: In 45 heart failure patients with left bundle branch block and QRS >150 ms (age 59+/-10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n=15), lateral (L, n=19) or, if no other option available, anterior (A, n=11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. RESULTS: Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs groups P and L: Arterial pressure +8 and +9% vs +2%; PCWP -23 and -15% vs -4%, pulmonary pressure -18 and -12% vs -3% (p<0.01 for A vs P+L); cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). CONCLUSION: Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantly in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided.

Combination therapy with carvedilol and amiodarone in patients with severe heart failure.

BACKGROUND: Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis. METHODS AND RESULTS: In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6+/-11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1. 9+/-0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programmed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25%. Significantly, more patients were in sinus rhythm after 1 year than at study entry (85% vs. 63%, P<0.01). In 47 patients, under therapy over at least 1 year, the resting heart rate fell from 90+/-19 to 59+/-5 b.p.m. (P<0.001). Ventricular premature contractions in 24-h holter ECGs were suppressed from 1.0+/-3 to 0.1+/-0.3%/24 h (P167 b.p.m. detected by the pacemaker (1.2+/-2.8 episodes/patient/3 months vs. 0.3+/-0.8 episodes/patient/3 months after 1 year (P<0.01). The LVEF increased from 26+/-10 to 39+/-13% (P<0.001). NYHA class improved from 3. 17+/-0.3 to 1.8+/-0.6 (P<0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) developed symptomatic documented bradycardic rhythm disturbances requiring reprogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart transplants. The 1-year survival rate (Kaplan-Meier) without transplantation was 89%. Compared to historic control patients with amiodarone only (n=154) or without either agent (n=283) this rate was 64 and 57% (P<0.01). CONCLUSIONS: Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.

Sudden death and tailored medical therapy in elective candidates for heart transplantation.

BACKGROUND: Due to the shortage of donor organs there is a long waiting time for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored medical therapy optimized according to the individual patients demands was introduced to select responding HTx candidates for continued management without transplantation. The development of modes of death over time (heart failure, sudden arrhythmic) in this population is unknown. METHODS: In 434 elective candidates for heart transplantation, submitted to our institution in the years 1984-1997 (50% coronary artery disease, mean age 51.6 +/- 12 years, 86% males) medical therapy was adjusted according to the results of repeated right heart catherizations. Adjuncts to conventional therapy with ACE inhibitors, digitalis and diuretics were amiodarone, beta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. Only patients not responding to these measures were processed to HTx. Clinical events (death, mode of death, HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to patients characteristics by multivariance analysis. RESULTS: During the mean follow-up of 2.36 +/- 2.4 years only 113 patients (25%) received a donor heart. One hundred-sixteen patients (26%) died without transplantation. Eighty-three (72%) of the deaths were sudden, 24 (20%) due to progression of heart failure and 9 (8%) due to other reasons. A shift from heart failure to sudden death was observed. Including 8 successful resuscitations due to documented VT/VF, there is a 20% risk of having a major arrhythmic event during the first two years of observation. Long-term (>1 year) medical responders had better hemodynamics at entry. Patients who died suddenly had similar clinical and hemodynamic data at entry than patients who needed an early transplant, but were in a comparable NYHA stage before death than long-term medical responders (2.15 +/- 0.8 vs 1.82 +/- 0.6, NS). Patients dying suddenly had significant more ventricular premature beats (1.6 +/- 2.9%/24 hours vs 1.06 +/- 2.8%/24 hours, p < .01) and complex ventricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p < .01) than long-term responders. Seventy-five percent of all sudden death occurred during the first 2 observation years. CONCLUSIONS: The rate of heart failure death in elective candidates for heart transplantation under optimized medical therapy is low when patients are followed closely and transplant can be done rapidly after deterioration is recognized. Sudden death represents the highest risk for most patients. This event occurred predominantly in stable patients under tailored medical therapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic measures in this population.

Tumor marker determination after orthotopic heart transplantation.

BACKGROUND: Because the risk of developing malignant tumors after heart transplantation is approximately 100-fold higher, methods for rapid diagnosis must be developed to allow early and aggressive treatment in these patients. Although tumor markers have been used frequently for surveying already detected cancer, we studied their value in screening for tumors in heart transplant patients. METHODS: The levels of the tumor markers CEA, CA19-9, CA125, CA72-4, TPA, TPS, and CYFRA 21-1 were determined prospectively in 3-month intervals in 91 heart transplant patients between 1993 and 1998. RESULTS: In eight patients a definite diagnosis of cancer was made during the marker survey (mean observation time 2.85 +/- 1.3 years), including bronchogenic carcinoma in six, renal carcinoma in one, and colon cancer in one. All patients with bronchogenic carcinoma were smokers. The markers had a sensitivity below 60% to detect cancer. Given a 2-fold cutoff level (10 ng/mL), the CEA was the only marker with sufficient specificity (93.8%, only one false-positive result). Two patients were symptom-free even though they had elevated CEA levels. In one of those patients, disseminated intractable cancer was diagnosed at first evaluation, whereas no tumor was found in the other case at first evaluation. Subsequently, by means of fluorodeoxyglucose positron emission tomography, a hypermetabolic region was found in the right upper mediastinum. Control computed tomographic scan 4 weeks after the first investigation showed disseminated intractable disease also in this patient. Another heart transplant patient with colon cancer showed a normalization of the CEA after hemicolectomy and an increase in the CEA when liver dissemination developed. There was a relationship between cardiac death and CA125 and TPS in some heart transplant patients. CONCLUSIONS: We conclude that the CEA is the only tumor marker with adequate sensitivity and specificity to detect subclinical malignancies in the follow-up of heart transplant patients. However, because of several limitations (limited diagnostic and therapeutic possibilities and enormous costs), we cannot recommend screening by tumor markers on a regular basis. Because of the elevated risk of cancer in patients who had organ transplantation, further prophylactic measures, especially smoking cessation programs, must be developed. Once a malignancy is diagnosed, tumor markers can help target clinical decisions. Additionally, nonspecific increases in CA125 and TPS levels might be related to nonmalignant circulatory disturbances and cardiac death.

Heart transplantation in a patient with multiple sclerosis and mitoxantrone-induced cardiomyopathy.

We describe a 30-year-old man with end-stage heart failure after therapy with mitoxantrone for multiple sclerosis. A successful orthotopic heart transplantation was performed when intensified medical therapy failed to improve the patient's hemodynamics. In spite of the severe underlying disease he did well on dual immunosuppression with methylprednisone and cyclosporine. Neurologic symptoms remained stable throughout the procedure and, after 2 months, he resumed preoperative ambulatory status. Eight years after the operation, the patient is now in New York Heart Association (NYHA) Class I status. Using canes, he is able to walk short distances. Repeated urinary tract infections caused by Escherichia coli became a problem, but have been controlled by long-term oral antibiotic prophylaxis with trimethoprim.

Long-term hemodynamic benefit of atrial synchronization with A2A2D or A2A2T pacing in sinus node syndrome after orthotopic heart transplantation.

BACKGROUND: Exercise capacity after heart transplantation (HTx) may be limited by sinus node disease of the donor heart and atrioatrial dissociation. The role of pacemaker therapy in this setting is not well defined. The purpose of this study was to compare clinical and hemodynamic data of heart transplant recipients with acquired sinus node disease treated with atrial synchronized pacing and patients with other pacing modes or without pacemakers 1 year after operation. METHODS: Our cohort comprises a total of 112 HTx recipients from the years 1984 to 1996. Atrial synchronized pacing was performed in 21 patients with donor sinus node disease and recipient sinus rhythm. There was no associated morbidity or death for the pacemaker implantation. Fourteen patients received a dual-chamber pacemaker programmed with a short atrioventricular-Delay in A2A2D mode (donor atrial pacing triggered by recipient atrial sensing or both atria stimulated on demand); in the last 6 consecutive patients a single-chamber pacemaker was implanted with two unipolar leads to the atria connected with a Y adapter programmed in A2A2T mode (both atria were sensed and stimulated by triggering each other). RESULTS: Signals and thresholds remain stable over time. When clinical and hemodynamic data of 12 A2A2D/T patients with complete 1 year follow-up were compared to age- and sex-matched control HTx recipients with other pacing modes or without pacemakers, a significant benefit of atrial synchronization could be shown regarding rise in heart rate response to exercise (+38% vs 30% vs 16% at 50 watt), New York Heart Association classification (1.6 vs 1.8 vs 2.2), Roskamm staging (1.3 vs 2.5 vs 1.5), cardiac index at rest (3.2 vs 2.78 vs 3.1 L/min x m2), cardiac index at 50 watt (5.5 vs 4.5 vs 5.2 L/min x m2), stroke work at rest (51 vs 38 vs 42 pondmeter [PM]), stroke work at 50 watt (66 vs 48 vs 51 PM), pulmonary wedge pressure at rest (7 vs 13 vs 8 mm Hg) and pulmonary wedge pressure at 50 watt (14 vs 24 vs 18 mm Hg). CONCLUSION: It is concluded that electromechanical synchronization of the atria was of long-term benefit in heart transplant recipients with recipient sinus rhythm and donor sinus node disease.

LDL receptor activity in human leukocyte subtypes: regulation by insulin.

OBJECTIVES: LDL receptors of leukocytes play a key role in lipoprotein uptake, immunoregulation and the pathogenesis of atherosclerosis. Numerous studies with different methods of low reliability yielded conflicting results of its regulation in leukocyte subtypes. DESIGN AND METHODS: LDL receptors of human leukocytes were measured with use of the monoclonal antibody C-7. Specific C-7 binding was detected by FACS analysis using phycoerythrin-anti-mouse-IgG. Parallel incubations with FITC-labelled anti-LEU 4 (CD 3), anti-LEU 12 (CD 19) and anti-MY 4 (CD 14) antibodies were used to distinguish C-7 binding of specific cell types (T-, B-lymphocytes and monocytes). RESULTS: In contrast to monocytes, T and B-lymphocytes freshly isolated from healthy blood donors had no detectable binding capacity for C-7. After 24 and 48 h incubation of cells in a lipid-free medium, lymphocytes acquired some C-7 binding, albeit still much less than monocytes. Incubation with insulin for 24 h in a concentration of 0.5 microgram/mL led to an increase in C-7 binding for monocytes (up to 180%). Saturation experiments with the ligand suggests an increase in the number of receptors. In contrast the same insulin concentration inhibited C-7 binding of B- and T-lymphocytes by 35%. CONCLUSIONS: FACS analysis using monoclonal antibodies seems to be a feasible method for the investigation of lipid metabolism in leukocytes. The LDL receptor expression and its regulation by insulin differs in circulating monocytes and lymphocytes.

Metabolic changes during antihypertensive therapies.

There is controversy whether various classes of antihypertensive drugs can reduce significantly cardiovascular morbidity and mortality in primary prevention. A failure to show this in many studies was attributed, at least in part, to deleterious effects of these drugs on lipid metabolism. Especially adrenergic antihypertensives cause marked effects on lipoprotein levels in plasma. A review of the literature revealed that beta-blockers increase triglycerides and VLDL (very low density lipoprotein)-cholesterol and may lower plasma HDL (high density lipoprotein) levels. In contrast alpha 1-adrenergic inhibitors like prazosin, doxazosin and terazosin lower triglycerides, total cholesterol, LDL (low density lipoprotein)- and VLDL-cholesterol and increase plasma HDL levels. The mechanisms by which alpha- and beta-blockers may produce the observed effects on plasma lipids and lipoproteins are not well understood. It has been shown in our laboratory that the activity of the LDL receptor of peripheral cells, a major determinant of cholesterol levels in plasma, is regulated by catecholamines via alpha 2- and beta 2-adrenergic receptors. Accordingly, blockade of these adrenoceptors with alpha- and beta-adrenergic antagonists can reverse the catecholamine effect. In addition these agents may affect lipoprotein lipase, lecithin cholesteryl acyltransferase and cholesterol ester hydrolase. These data may explain, at least in part, the plasma effects. However, long-term studies are needed to clarify the clinical value of antihypertensives with different metabolic profiles.

Fluctuations of tumor markers in heart failure patients pre and post heart transplantation.

BACKGROUND: Elevated plasma levels of tumor markers may be caused by diseases other than malignancy, i.e. kidney, liver or circulatory disturbances. These conditions are not well defined, especially since there are only sparse reports on fluctuations of tumor markers related to cardiac function. PATIENTS AND METHODS: During our routine pre- and postoperative follow-up tumor marker determinations in heart failure patients were made in order to screen for possible occult neoplasm's which may either be a contraindication or a sequela of heart transplantation. The markers CA 12-5, CEA, CA 19-9, CA 72-4, TPA, TPS and CYFRA 21-1 were determined at three month intervals, besides clinical examination and hemodynamic measurements in a total of n = 118 patients pre- and n = 74 patients post heart transplantation. RESULTS: The results were grouped according the clinical status (NYHA-stage 1-4): CA12-5 (29.4 +/- 40.63 omega 151, 174 +/- 345 and 491 +/- 633 U/ml, p < 0.001 between all groups) and TPS (64 +/- 32, 118 +/- 153, 163 +/- 311 and 181 +/- 232 U/ml, p = 0.06 between all groups) were increasingly elevated in NYHA stages 1, 2, 3 or 4 respectively. A direct correlation to right atrial pressure (r = 0.41, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.27, p < 0.001) was only found for CA 12-5. After heart transplantation a normalization of elevated pre-OP levels could be found. Comparable to heart failure patients poor graft function was also associated with elevated levels of CA 12-5 (113 +/- 99 vs 21.6 +/- 31 U/ml, p < 0.0001), CA 72-4 (8.4 +/- 3 vs 3.6 +/- 4, U/ml p = 0.03) and TPS (154 +/- 133 vs 66 +/- 28 U/ml, p < 0.001). The individual time course of the markers, especially of CA 12-5, correlated nicely to clinical events and hemodynamic measurements in some patients. Another finding was that CYFRA 21-1 levels were correlated to renal function. CEA, CA 19-9 and CYFRA 21-1 serum levels were not influenced by circulatory disturbances. CONCLUSION: We concluded that the tumor markers CA 12-5 and TPS (but not CEA, CA 19-9 and CYFRA 21-1) are associated with congestion and the clinical course of heart failure and HTx patients. These "nonspecific" changes have to be considered when tumor markers are determined in cancer patients with heart failure. Whether CA 12-5 blood levels may yield additional prognostic information in the management of cardiovascular patients has to be determined in further studies.

Smoking after heart transplantation: an underestimated hazard?

OBJECTIVE: Risk factors for the development of vasculopathy and malignancies as the most important causes of morbidity and mortality after heart transplantation are not well defined. METHODS: Univariate and multivariate Cox regression analysis of the data derived from our 84 survivors of more than 3 months after orthotopic heart transplantation between 1984 and 1996. Measurement of carbonmonoxide-hemoglobin blood levels with an ABL 520 analyzer. RESULTS: Recipient or donor age, the mode of immunosuppression, total-, LDL- and HDL-cholesterol, the HDL/LDL-ratio, triglycerides, hypertension, diabetes mellitus, CMV status and rejection episodes had no independent influence on total mortality or the occurrence of graft vasculopathy or cancer. By means of an intensive questionnaire (in case of deceased patients, by their relatives) and measurement of CO-Hb blood levels we detected a high rate of patients who smoked after transplantation (22/84 = 26%). Four patients confessed smoking after undergoing the blood test. Non-smokers were defined as denying it in the questionnaire and having CO-Mb levels < 2.5% in repeated measurements. All but one were smokers before heart transplantation. Mean consumption was 11 cigarettes per day. Five and 10 years survival was significantly reduced in smokers vs. non-smokers (37 vs. 80% and 10 vs. 74%, respectively, P < 0.0001). Survival curves diverged dramatically after 4 years of observation. Smokers had a higher prevalence of transplant vasculopathy as revealed by coronary angiography and/or autopsy (10/22 smokers vs. 2/62 non-smokers, P < 0.00001) and a higher rate of malignancies (7/22 smokers developed cancer, as compared to 4 cancers in 62 non-smokers, P = 0.0001). The primary site of cancer was the lung in 5/6 smoking and lymphoma in all non-smoking cancer patients. CONCLUSIONS: Our data show that the prevalence of smoking after heart transplantation may be relatively high, especially in former smokers. Repeated measurements of CO-Hb could be helpful in its detection. Despite a relatively low cigarette count, smoking is a major risk factor of morbidity and mortality after heart transplantation (HTx). Approximately 4 years of exposure time is needed to uncover its negative influence. These findings should lead to aggressive smoking screening and weaning programs in every HTx center.

Analysis of terminal arrhythmias stored in the memory of pacemakers from patients dying suddenly.

AIMS: Stored electrograms or marker channels are available in most of modern cardiac pacemaker models. We sought to analyse these information to uncover terminal events of pacemaker patients dying suddenly. Method and results We made post-mortem pacemaker (PM) interrogations in 19 patients dying suddenly out of hospital between the years 1997 and 2005 (mean age 59 +/- 13 years, 90% males). The systems had activated arrhythmia monitoring algorithms. Indications of pacing were sick sinus syndrome in seven, AV-block in five, and heart failure due to asynchrony in seven cases. The interrogated pacemakers were CHORUS 7034 (n = 12), CONTAK TR (n = 2), and INSYNC III (n = 5). For interpretation stored marker channels and electrograms were analysed. The mean observation time after PM implantation prior death was 2.11 +/- 1.44 years, the mean left ventricular ejection fraction from the last available echo examination in the year prior death was 27.5 +/- 8%, mean age was 63 +/- 12 years. In 17/19 cases (89%), a tachycardia (most likely ventricular tachycardia) was found correlating to the time of death. The mean cycle length of the terminal arrhythmia was 307 +/- 144 (250-344) ms, corresponding to a heart rate of 195 +/- 95 (174-240) bpm. We found no evidence of specific pacemaker-related problems such as electronic failure, battery depletion, or undersensing. CONCLUSIONS: Post-mortem analysis of arrhythmia monitoring of pacemaker patients revealed tachycardias (most likely ventricular tachycardia) to be related to sudden death. These findings give some insight in mechanisms of terminal events in this group.

First experience with a new active fixation coronary sinus lead.

AIMS: Coronary sinus (CS) lead implantation is a technically challenging procedure owing to variable vein anatomies and a high dislocation rate. Therefore, CS lead technology has undergone evolutionary changes during the last 10 years. The mode of fixation has been a passive one up to now. We want to describe our first clinical experience with the newly available active fixation lead 4195 in terms of dislocation rate and stability of thresholds compared with conventional models. METHODS AND RESULTS: From 1999 to February 2007, we implanted 403 CS leads in 368 patients. Leads were categorized into three different groups on the basis of their fixation mechanism: straight (Easytrak I and Situs OTW; n = 54), curved (Attain 4193 and 4194, Corox, Aescula, Situs ULD; n = 308), and active (Attain 4195; n = 41). Operative and follow-up data were prospectively noted and checked for significance between groups during the first 3 months after implantation. Kaplan-Meier analysis of long-term lead function was also performed. Straight and curved CS leads suffered from significantly more dislocations compared with active fixation (P < 0.001). The active fixation lead (4195) has a stable threshold over time compared with a significant rise after 24 h and thereafter in straight (62%) and curved leads (20%). However, retraction of an active fixation CS lead may be a difficult issue as outlined in two cases requiring pullback of a 4195 lead owing to phrenic nerve stimulation (one unsuccessful despite vigorous traction). CONCLUSION: The active fixation lead 4195 using retention lobes yielded stable thresholds over time and seems to be superior to conventional leads in terms of dislocation. However, extraction may be a difficult or even impossible task.