H. H. Scheld

PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression

Background—Intergenic variations on chromosome 4q25, close to the PITX2 transcription factor gene, are associated with atrial fibrillation (AF). We therefore tested whether adult hearts express PITX2 and whether variation in expression affects cardiac function. Methods and Results—mRNA for PITX2 isoform c was expressed in left atria of human and mouse, with levels in right atrium and left and right ventricles being 100-fold lower. In mice heterozygous for Pitx2c (Pitx2c+/−), left atrial Pitx2c expression was 60% of wild-type and cardiac morphology and function were not altered, except for slightly elevated pulmonary flow velocity. Isolated Pitx2c+/− hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in Pitx2c+/− than in wild-type. Perfusion with the &bgr;-receptor agonist orciprenaline abolished inducibility of AF and reduced the effect on action potential duration. Spontaneous heart rates, atrial conduction velocities, and activation patterns were not affected in Pitx2c+/− hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing Pitx2c+/− with wild-type, for left atrial and right atrial tissue separately, identified genes related to calcium ion binding, gap and tight junctions, ion channels, and melanogenesis as being affected by the reduced expression of Pitx2c. Conclusions—These findings demonstrate a physiological role for PITX2 in the adult heart and support the hypothesis that dysregulation of PITX2 expression can be responsible for susceptibility to AF.

Selection and management of ventricular assist device patients : The Muenster experience

BACKGROUND Because of the growing discrepancy between the availability of donor organs and the number of patients with end-stage heart disease who need heart transplantation, a larger proportion of patients waiting for a suitable donor heart require pre-operative mechanical circulatory assistance. The criteria for the selection and management of these patients as applied at Muenster University Hospital are reviewed. METHODS The study population consists of 631 patients referred to our center for transplantation between January 1, 1990, and December 31, 1996. Two hundred ninety-seven patients were listed for transplantation and 157 were transplanted. Of 41 patients who underwent implantation of a ventricular assist device (n = 34, Novacor; n = 6, TCI HeartMate; n = 1, Medos), 39 received the device as a bridge to transplantation and 2 as permanent support. For the purpose of the analysis, the study population was divided into 3 groups (elective bridging, urgent bridging, emergency bridging) and compared with heart transplant candidates who did not require mechanical circulatory assistance. RESULTS Patients who underwent elective or urgent assist-device implantation were younger and had greater hemodynamic compromise than the remainder of patients waiting for heart transplantation, as suggested by a higher functional class and lower mean arterial pressure, cardiac index, serum sodium, and pulmonary artery wedge pressure. Survival of patients who electively underwent implantation of an assist device was better than that of patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. CONCLUSIONS This finding suggests that earlier implantation of assist devices may facilitate resolution of organ dysfunction before heart transplantation.

Operative techniques and strategies for minimally invasive fetoscopic fetal cardiac interventions in sheep.

AbstractBackground: Recent efforts to develop procedures for fetoscopic fetal cardiac interventions have been prompted by the development of severe secondary damage to the fetal heart due to semilunar valvar obstructions and the poor outcome of therapy-refractory fetal arrhythmias. The purpose of our manuscript is to analyze and share our experience with the creation of an operative setup for these procedures in sheep. Methods: We studied a total of 48 fetal sheep between 81 and 106 days of gestation (term, 145 days). After entering the amniotic cavity by a percutaneous approach, we performed various fetoscopic fetal cardiac procedures. We analyzed the success of percutaneous fetal access, methods of trocar support, the incidence and management of trocar dislodgement or accidental insertion into the chorioamniotic space, problems related to amniotic insufflation and trocar placement, as well as techniques for fetal posturing and uterine closure. Results: Percutaneous fetal access was achieved in all sheep. The use of resterilizable trocars substantially decreased the costs of our procedures. Utilizing a percutaneous transuterine purse-string suture for trocar support helped to minimize the number of nonabsorbable T-fasteners remaining inside the uterus postoperatively. As complications such as trocar dislodgement, insertion of the trocar into the chorioamniotic space, and problems with intraamniotic insufflation and gas loss were mastered, conversion to an open operative approach was never required. A novel strategy that we devised for percutaneous fetal posturing permitted adequate fetal posturing with ease and minimal trauma to the fetal skin. Conclusion: As operative techniques have become more refined, the feasibility of performing fetoscopic fetal cardiac interventions in human fetuses now depends mainly on technical improvements in imaging and interventional catheters, as well as advances in pacemaker equipment.

Surgical Management of Extensive Lipomatous Hypertrophy of the Right Atrium

Lipomatous hypertrophy of the right atrium is a rare lesion that is usually limited to the interatrial septum. The authors report on a patient that suffered from an extensive lipomatous hypertrophy, which protruded into the right and left atrium as well as the superior vena cava and caused inflow obstruction. Therapeutic management is discussed.

Myocardial ischaemia in patients with impaired left ventricular function undergoing coronary artery bypass grafting — milrinone versus nifedipine

Background and objective: Myocardial ischaemia and infarction are major complications immediately after coronary artery bypass grafting. They may be due to incomplete surgical revascularization, perioperative anaesthetic management or vasospasm of arterial grafts, e.g. the internal mammary artery. Infusions of nifedipine or milrinone have been advocated to prevent spasm of the mammary artery. The study compared the incidence of myocardial ischaemia after continuous infusion of either nifedipine (0.2 μg kg−1 min−1) or milrinone (0.375 μg kg−1 min−1) in patients with compromised left ventricular function scheduled for elective coronary artery bypass graft. Methods: After Institutional Review Board approval, this double-blinded randomized clinical study enrolled 30 adult patients with compromised left ventricular function (ejection fraction <0.4) scheduled for elective coronary artery bypass grafting after written informed consent had been obtained. Ischaemia was detected by Holter electrocardiographic monitoring. The incidence of myocardial cell death was monitored by serial determinations of the creatine kinase-MB (CK-MB) and troponin-I. Results: New ST elevation ⩾0.2 mV or new ST depression ⩽0.1 mV occurred in five of 15 patients in the milrinone group (33.3%) and in 13 of 15 patients (86.6%) in the nifedipine group (P < 0.05). There were increases in CK-MB and troponin-I in both groups. Twenty-four hours postoperatively, CK-MB (P = 0.003) and troponin-I (P = 0.001) were significantly higher in the nifedipine group. Conclusions: Perioperative continuous infusion of milrinone, compared with nifedipine, results in a significantly lower incidence of myocardial ischaemia and myocardial cell damage after elective coronary artery bypass grafting.

Clinical experience with nine patients supported by the continuous flow Debakey VAD.

Introduction: Pulsatile left ventricular assist devices (LVADs) have been established for bridging of selected patients with advanced congestive heart failure to transplantation. Their clinical application, however, has been complicated by bleeding, thromboembolic and infectious adverse events. Recently, continuous flow LVADs have been introduced. They are expected to be associated with a reduced risk for such complications. Here we report our experience with 9 patients on the continuous flow DeBakey VADTM. Patients and Methods: Since February 2000, 9 patients have been supported by the continuous flow DeBakey VADTM at our institution (all male, 38.6613.1 years, 3 DCM, 3 ICM, 1 congenital, 1 postcardiotomy, 1 myocardial infarction). Before implantation, patients were in severe heart failure (NYHA IV) requiring inotropic support. Cardiac index was 1.6460.49 l/min/m2. All patients fulfilled the requirements for listing to heart transplantation and were put on the waiting list at the time of LVAD implantation. Results: Current total support time (as of October 17, 2000) amounts to 900 patient days (14 2 232 days). One patient was transplanted 226 days following LVAD implantation, six patients are currently still on LVAD support. One patient died on postoperative day (POD) 14 due to multiorgan failure developing following preoperative cardiogenic shock due to myocardial infarction, one patient died on POD 15 after a thrombus generated from the left ventricle had caused the pump to stop. Bleeding complications requiring rethoracotomy occurred in 3 patients. There was no thromboembolic event. No driveline or device infection was observed. Moderate hemolysis was seen in 3 patients. In 4 patients, the LVAD was replaced (POD 76, 76, 137, 170) for another DeBakey VADTM. Device exchanges were associated with thrombus; however, its origin could not be determined. Conclusion: Our experience with the DeBakey VADTM indicates that it is associated with a low risk for bleeding, hemolysis, thromboembolic and infectious complications which makes it a valuable alternative to pulsatile LVADs. Thrombus in the pump may be addressed with improved anticoagulation and platelet inhibition.

Successful cardiac transplantation after 4 cases of DeBakey left ventricular assist device failure

Left ventricular assist devices (LVADs) are an established surgical therapy for patients with end-stage heart failure as a bridge to cardiac transplantation. Major disadvantages of these devices are thromboembolic events, bleeding complications, infections, and malfunctions. We report on our experiences with DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients underwent subsequent cardiac transplantation and are doing well now.

Pulmonary Palacos Embolism: A Case Report

Instrumentation with cement-augmented pedicle screws has expanded the therapeutic spectrum. This technique is useful for the palliation of bone metastases and in generalized osteoporosis. Serious complications such as pulmonary embolism have been described following percutaneous vertebroplasty, a frequently used technique. We report the case of a 55-year-old patient with a large central Palacos embolism of the right pulmonary artery after corporectomy of the lumbar vertebrae 3 and 4 and reconstruction using autologous pelvic bone. The large Palacos embolism was removed successfully from the right pulmonary artery with extracorporeal circulation.

Creation of a self-made total artificial heart using combined components of available ventricular assist devices.

We describe the case of a 39-year-old woman who received a self-made total artificial heart built of components from the Thoratec and ExCor Berlin Heart systems. The patient had a severe aortic/myocardial infection following replacement of the ascending aorta with a Shelhigh conduit due to type A aortic dissection. The surgical technique is described in detail in this article. This technique is feasible if a total artificial heart is not available and implantation of a biventricular assist device is not possible.

Outcome of women is impaired in patients undergoing emergency coronary artery bypass grafting for failed PTCA.

Es wird kontrovers diskutiert, ob Frauen eine erhöhte Letalität bei kardiovaskulären Erkrankungen oder Interventionen haben. Wir untersuchten diesen Aspekt bei weiblichen und männlichen Patienten, bei denen eine Notfallbypass-Operation nach nicht erfolgreicher PTCA durchgeführt wurde. Die klinischen und prozeduralen Parameter aller Patienten, die zwischen 1989 und 1998 eine Notfallbypass-Operation erhielten, wurden retrospektiv aus den Patientenakten erhoben. In diesen 10 Jahren wurden 6681 PTCAs in unserer Klinik durchgeführt, davon 1312 PTCAs bei Frauen (19,6%). Bei 110 dieser Patienten wurde eine Notfall-Bypassoperation durchgeführt, wovon 32 Frauen betroffen waren (29,1%). Postoperativ verstarben 9 Frauen und 5 Männer (Letalität 12,7%). Die weiblichen Patienten waren zum Zeitpunkt der Untersuchung älter (61,2±2,1 vs. 58,3±1,0 Jahre; n.s.), kleiner (1,61±0,01 vs. 1,76±0,01 m; p<0,0001), leichter (67,7±2,4 vs. 82,1±1,2 kg; p<0,0001), und hatten eine kleinere Körperoberfläche (1,70±0,04 vs. 1,98±0,02 m2; p<>;0,0001) sowie eine höhere Komorbidität ausgedrückt durch den sogenannten Cleveland Risikoscore (7,9±0,3 vs. 7,1±0,2 Punkte; p=0,013). Das Risiko für eine nicht-erfolgreiche PTCA mit nachfolgender Notfall-Bypassoperation war bei Frauen höher als bei Männern (2,4% vs. 1,5%; p=0,012; Odds Ratio 1,66) ebenso wie das Risiko für ein postoperatives Versterben (28,1% vs. 6,4%; p=0,004; Odds Ratio 4,39). Frauen verblieben postoperativ länger im Krankenhaus als Männer (19,7±4,2 vs. 12,9±1,3 Tage; p=0,044). Eine logistische Regressionsanalyse identifizierte niedrigeres Körpergewicht (p=0,003), eine höhere Anzahl erkrankter Koronararterien (p=0,024) und einen höheren Cleveland Score (p=0,023) als unabhängige Prädiktoren für ein postoperatives Versterben. In einem Kaplan-Meier Modell (Nachbeobachtungszeit 5,3±2,5 Jahre) zeigte sich eine höhere Krankenhaus-Sterblichkeit bei Frauen (p=0,0034; Log Rank Test), wobei das Langzeitüberleben vergleichbar war. Frauen hatten in dieser Untersuchung eine erhöhtes Risiko für eine nicht-erfolgreiche PTCA mit nachfolgender Notfall-Bypassoperation sowie eine dann deutlich erhöhte postoperative Letalität. In der multivariaten Analyse war weibliches Geschlecht jedoch kein unabhängiger Prädiktor sondern Körpergewicht, Anzahl erkrankter Koronararterien und Komorbidität. There is an ongoing debate whether female gender is associated with increased cardiovascular morbidity and mortality, especially after coronary interventions. The impact of gender on the outcome of patients undergoing emergency coronary artery bypass grafting (CABG) for failed PTCA was analyzed. Clinical and procedural data of all patients who underwent PTCA and subsequent emergency CABG at our institution from 1989 to 1998 were assessed. During these 10years, 6681 PTCA procedures were performed, 1312 in women (19.6%). Subsequently, 110 patients underwent emergency CABG of whom 32 were females (29.1%). Postoperatively, 9 women and 5 men died (mortality 12.7%). Women presented with higher age (61.2±2.1 vs. 58.3±1.0 years, n.s.), smaller height (1.61±0.01 vs. 1.76±0.01m, p<0.0001), lower weight (67.7±2.4 vs. 82.1±1.2 kg, p<0.0001), smaller body surface area (1.70±0.04 vs. 1.98±0.02m2, p<0.0001), and higher comorbidity as expressed by their Cleveland score (7.9±0.3 vs. 7.1±0.2, p=0.013). The risk for failure of PTCA with subsequent emergency CABG was higher in women than in men (2.4% vs. 1.5%, p=0.012, odds ratio 1.66) as well as for postoperative death (28.1% vs. 6.4%, p=0.004, odds ratio 4.39). Women had longer in-hospital stays (19.7±4.2 vs. 12.9±1.3 days, p=0.044). Logistic regression analyses found lower weight (p=0.003), higher number of diseased coronary vessels (p=0.024) and higher Cleveland score (p=0.023) to be independent predictors of operative mortality. A Kaplan-Meier model (follow-up 5.3±2.5 years) showed an increased in-hospital mortality in women (p=0.0034, log rang test), but a comparable long-term survival. Women had an increased risk for failure of PTCA and a markedly higher operative mortality after emergency CABG. In multivariate analyses, however, gender was not an independent predictor of postoperative death.