Cardiovascular outcome in type 2 diabetes and atrial fibrillation.

Diabetes is an independent risk factor for atrial fibrillation (AF). Frequently, it is part of the metabolic syndrome cluster, which includes obesity and hypertension that are independently associated with AF. The risk appears to be higher with longer duration of diabetes and inadequate glycemic control. Patients with diabetes and AF have a substantially increased risk of death and serious cardiovascular complications compared with those in sinus rhythm. Conversely, good metabolic control appears to be associated with maintenance of rhythm after successful therapeutic conversion to sinus rhythm by catheter ablation or electrical cardioconversion of AF. AF puts patients with type 2 diabetes at a high risk of cardiovascular complications and death, which could be successfully addressed by new classes of antidiabetic agents such as incretin analogues or sglt-2 inhibitors. Thus, a diagnostic strategy that addresses the increased risk for AF is urgently recommended, in addition to diabetes monitoring in routine outpatient practice. In order to prevent thromboembolic complications, which frequently determine the prognosis for this patient population, appropriate anticoagulation remains the mainstay of therapy, whereas the prognostic value of reinstalling sinus rhythm awaits further evidence.

Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group.

Patients with pulmonary hypertension are at risk of developing fatal right heart failure after heart transplantation. To evaluate this risk potential, candidates for heart transplantation are screened by measuring rest right heart pressures and the response to nitroprusside. To test the validity of this approach, the influence of pretransplantation right heart catheterization data on outcome after transplantation was analyzed in 293 of 301 consecutive patients. Patients with a pulmonary vascular resistance greater than 2.5 Wood units measured at baseline study had a 3-month mortality rate of 17.9% compared with 6.9% in patients with resistance less than or equal to 2.5 units (p less than 0.02). Patients with a pulmonary vascular resistance greater than 2.5 units at baseline study could be differentiated further according to their hemodynamic response to nitroprusside; those whose resistance could be reduced to less than or equal to 2.5 units with a stable systemic systolic pressure greater than or equal to 85 mm Hg had a 3-month mortality rate of only 3.8%. In contrast, patients whose pulmonary vascular resistance could not be reduced to less than 2.5 units, and those whose resistance could be reduced to less than or equal to 2.5 units but only at the expense of systemic hypotension (systolic pressure less than or equal to 85 mm Hg) had a 3-month mortality rate of 40.6% and 27.5%, respectively. Furthermore, all 10 patients who died of right heart failure belonged to the latter two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the AmpliSensor PCR and the SHARP signal detection system for the early prediction of symptomatic CMV infection in solid transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is associated with high morbidity and mortality in transplant patients. Specific antiviral treatment at an early stage of CMV infection may effectively ameliorate, but not eliminate CMV disease in these patients. Presently, the pp65 antigenemia test on peripheral leukocytes is the method most widely used for predicting and monitoring transplant patients for active CMV infection. Nucleic acid amplification methods are less well defined since they lack standardisation. OBJECTIVE: A seminested fluorometric PCR assay (AmpliSensor-CMV, BAG, Germany) and a one-step PCR with a signal-amplification step (SHARP, Abbott, Germany) specific for the fragments of the CMV UL 122 and UL 123 genes, respectively, were evaluated for the early diagnosis of CMV infection. DESIGN: A total of 26 recipients of heterogeneous solid organs were monitored prospectively for a median of 99 days after transplantation. By testing 371 clinical samples parallel with the pp65-antigen assay and IgM and IgG EIA assays the sensitivity, specificity, correlation and quantitation potential of both PCRs was evaluated. RESULTS: Eight out of 26 patients developed active CMV infection. A total of 48 samples of these patients exceeded a CMV-DNA load threshold of 15 genome equivalents/10(5) leukocytes (AmpliSensor-CMV) and 41 samples exceeded the critical cut-off for the SHARP system. The AmpliSensor PCR exceeded its threshold consistently before the clinical onset of CMV disease (median 8 days). There was very good agreement between symptomatic CMV infection in patients and AmpliSensor-PCR, SHARP PCR, and pp65-antigen results (kappa-coefficient > 0.900). IgM and IgG EIA showed moderate agreement (kappa-coefficient = 0.591 and 0.552, respectively). CONCLUSION: Both PCRs and pp65 antigen assay correlated significantly better with CMV disease than serodiagnosis. The AmpliSensor PCR allowed more precisely than the SHARP system a quantitative determination of viral load and an early and reliable prediction of active CMV infection. The use of AmpliSensor PCR may improve the diagnosis and management of active CMV infection in organ transplant recipients.

Cyclosporin A and transplant coronary disease after heart transplantation: facts and fiction.

From published data in the currently available literature on animal experiments, it can be concluded that CyA may be involved in the development of hypertension and renal dysfunction. These side effects are probably related to a disturbed vasomotor tone and a pathologic reaction to physiologic vasoconstrictive and vasodilative agents following administration of high doses of CyA. These effects are dose related and reversible and were undetected at clinically applied levels of immunosuppression. It therefore appears to be unlikely that this pathologic response is operative in precipitating or promoting TCD, which is supported by findings of in vivo and in vitro studies on human coronary arteries as well as by comparison of immunosuppressive protocols comparing series with and without application of CyA. Chronic graft dysfunction, as depicted by late mortality in heart and isolated lung transplant recipients and by loss of kidney allograft survival, yields an annual rate of between 4 and 6% per year. It is only in heart transplantation that TCD has been tried to be associated with CyA application. If CyA-related damage were to occur in coronary arteries independent from immunologic factors, the incidence of coronary disease should be similar in heart, lung, liver, and kidney transplants. This is not the case. Although continuous investigation on the side effects of immunosuppressive agents is definitely necessary, we should concentrate our research activities on potential prophylactic and therapeutic measures to overcome the single most important risk factor of long-term surviving patients after solid organ transplantation: chronic rejection.

Frequency-dependent antiarrhythmic drug effects on postrepolarization refractoriness and ventricular conduction time in canine ventricular myocardium in vivo.

Both conduction time (CT) and effective refractory period (ERP), absolute and relative to action potential duration (APD), are major determinants of re-entry arrhythmia circuits. We compared the effects of 3 commonly used class I antiarrhythmic agents, lidocaine, mexiletine and quinidine, and of the combination of the latter 2, on APD, ERP, ERP/APD ratio and interventricular CT in 26 in vivo canine hearts. To assess also the frequency dependence of these effects, each measurement was made at multiple steady-state cycle lengths ranging from 600 to 250 msec. A modified contact electrode technique was used to measure both APD and ERP simultaneously and at the same left ventricular site. Interventricular CT was measured as the interval from the stimulus of right ventricular paced beats to the upstroke of the ensuing left ventricular action potential. Lidocaine did not change APD, ERP and ERP/APD ratio significantly at any basic cycle length. In contrast, both mexiletine and quinidine increased the ERP/APD ratio, with progressively greater effects toward shorter cycle lengths. The quinidine/mexiletine combination increased the ERP/APD ratio significantly more than either drug alone (cycle length 350 msec: 8.3 +/- 2.2% quinidine; 17.6 +/- 7.0% mexiletine; 35.3 +/- 9.6% mexiletine/quinidine combination, P less than .01 vs. quinidine, P less than .05 vs. mexiletine). CT increased only with quinidine but not with mexiletine or lidocaine. Combination of mexiletine and quinidine caused no further slowing of conduction as compared to quinidine alone. Thus, although both ERP/APD ratio and CT are related to sodium channel conductance, drug effect on one parameter does not necessarily imply quantitatively similar effects on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

[Indication of myocardial "memory". Gradual, persisting modulation of myocardial decrease in excitation following change in the activation sequence]. / Hinweis auf myokardiales "Gedächtnis". Allmähliche, persistierende Modulation der myokardialen Erregungsrückbildung nach Anderung der Aktivierungssequenz.

It is well established that regional differences in electrical repolarization are responsible for the electrocardiographic T-wave. Regional differences in ventricular repolarization traditionally have been attributed to variance of action potential duration (APD), believed to be an intrinsic property of individual cardiac cells (17, 21, 24). To evaluate whether the excitation sequence influences ventricular repolarization we studied the effect of an altered excitation sequence on the APD distribution in isolated rabbit hearts. We found that APD is not primarily a function of the cell's location in the ventricle but rather is modulated by the sequence with which the ventricles are electrically excited. This excitation sequence-dependent modulation of APD occurs with a very slow time-course, requiring hours to develop and hours to dissipate after resumption of the original excitation sequence. Our findings suggest a new, as of yet unrecognized form of intercellular communication by which the myocardial cells adjust their repolarization sequence to a change in excitation sequence.

The influence of preoperative patient characteristics on early and late survival following cardiac transplantation.

In an attempt to identify the preoperative factors that influence survival following cardiac transplantation, we retrospectively analyzed multiple demographic, clinical, and hemodynamic data of 301 consecutive patients who underwent cardiac transplantation between December 1980 and July 1988 (cyclosporine era). Univariate and multivariate regression analyses revealed that the two most deleterious risk factors for premature death following transplantation were pulmonary hypertension not responsive to vasodilator challenge and preoperative requirement of hemodynamic support (intravenous inotropes or mechanical assistance). The combination of these two independent risk factors was an even stronger predictor of mortality (relative risk, 6:1; p less than 0.0001): the 3-month actuarial survival rate of the 20 patients with this combination was 30.3% versus 78.4% of the 47 patients with only pulmonary hypertension, 87.9% of the 42 patients with only the requirement of hemodynamic support, and 95.3% of the 172 patients with neither of these two risk factors. The difference in postoperative mortality between patients with versus those without these two risk factors is due to a higher rate of fatal infectious complications: six of 20 patients (30%) with both risk factors died from infection within 3 months after transplant compared with three deaths among 172 patients (1.7%) with neither of these risk factors. The majority of fatal infections were pulmonary. There were significantly more fatal and nonfatal infectious episodes in patients with one or both of these risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of intensified medical treatment and organ allocation on outcome of transplant candidates.

BACKGROUND: To test how the organization of a pre-transplant clinic and changes in organ allocation modus influence the survival of potential transplant candidates, the survival of patients referred for transplant evaluation between 4/93 and 4/96 (group A) was compared to that of patients referred from 5/96 to 7/00(group B). METHODS: After screening for transplant indication, group A was followed by the referring physician up to transplantation or 3-month reevaluation. Group B was closely followed by a specialized heart-failure clinic. Group A was transplanted according to Eurotransplant criteria, with waiting time being the strongest priority criterion. Due to an allocation partnership off our transplant centers, group B could be transplanted according to medical urgency regardless of waiting time. RESULTS: Overall one-year survival after referral was 69.8% for group A vs. 91 %for group B (p <0.0001). Transplantation within 1 year was required in more group A than group B patients (34% vs. 23%)with worse one-year post-transplant survival in group A (82%vs. 93%). CONCLUSIONS: Intensified treatment by a specialized heart failure program and an allocation system that allows for preferred transplantation of the 'sickest' patient improved over-all survival of transplant candidates and reduced the percentage of patients requiring transplantation.

Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts. Evidence for cardiac "memory".

Prolonged ventricular pacing induces T wave polarity changes that persist long after cessation of pacing. To examine how ventricular repolarization is modulated by prolonged changes in activation sequence, we studied the effect of ectopic pacing on the distribution of action potential durations (APDs) in nine isolated Langendorff-perfused rabbit hearts. A contact electrode probe was used to map right and left ventricular-epicardial monophasic action potentials during three consecutive changes in stimulus site, that is, 1) during 45 minutes of right atrial pacing, 2) during 120 minutes of right ventricular pacing, and 3) again, during 60 minutes of right atrial pacing. During each of these phases, the effect of activation sequence on repolarization was examined by linear-regression analysis of APD on activation time (AT). Results averaged for all nine hearts showed that during the initial atrial-pacing phase, APD was inversely related to AT (slope [S] = -1.63; r = 0.76), indicating that sites with earlier activation repolarized later. With the onset of ventricular pacing, the inverse correlation between AT and APD disappeared (S = -0.19; r = 0.31). Continuing ventricular pacing, however, produced slow changes in APD that restored the inverse relation (S = -0.71; r = 0.68 at 120 minutes; p less than 0.0002 versus 5 minutes). Switching from ventricular to atrial pacing again perturbed the inverse correlation (S = 0.28; r = 0.35) but at 60 minutes of atrial pacing, a significant inverse correlation was reestablished (S = -1.25; r = 0.53; p less than 0.01 versus 5 minutes). An inverse correlation between AT and APD tends to synchronize repolarization time (RT, the sum of AT and APD).(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission of malaria tertiana by multi-organ donation.

In this report, transmission of malaria via a liver, a kidney, and possibly a heart allograft from a single donor is described. The donor had immigrated from Cameroon to Germany 18 months before, but had no clinical signs of active malaria infection. The liver transplant recipient and one of the two kidney transplant patients developed febrile illness with the appearance of Plasmodium vivax in blood smears 5 and 6 wk after transplantation, respectively. In the heart transplant recipient, a subclinical malaria infection was suspected based on a rise of malaria antibodies late after transplantation, whereas the recipient of the second kidney allograft had no clinical or laboratory evidence of malaria. Both liver and kidney recipients with active malaria responded to medical treatment. However, the liver transplant patient developed progressive cholestasis and died 5 months after transplantation from liver failure possibly due to side effects of the malaria medication. Other cases of malaria in solid organ recipients are briefly reviewed.