Risk factors for clinical events at 1-year follow-up after drug-eluting stent implantation: results from the prospective multicenter German DES.DE registry.

BACKGROUND: Drug-eluting stents (DES) have substantially reduced target vessel revascularization (TVR) after percutaneous coronary interventions. Risk factors for clinical events need to be redefined with this treatment option. METHODS AND RESULTS: In the prospective DES.DE registry, baseline clinical and angiographic characteristics as well as in-hospital and follow-up events were recorded for all enrolled patients. Between October 2005 and May 2009, 21,774 patients receiving DES were enrolled at 98 DES.DE sites. The composite of death, myocardial infarction (MI) and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and TVR were predefined as primary endpoints. At 1-year follow-up rates for overall death, MI, stroke, MACCE, TVR and definite stent thrombosis were 2.7, 3.1, 1.4, 7.1, 11.5 and 0.6 %, respectively. Aside from well-known risk factors like age, diabetes mellitus and triple-vessel disease, stratification in patients with or without MACCE revealed atrial fibrillation, non-ST-segment elevation myocardial infarction, renal failure, impaired ejection fraction and peripheral vascular disease as strong predictors of MACCE at 1 year. CONCLUSION: Data collected in the DES.DE registry, reflecting the clinical practice in Germany, revealed favorable clinical outcomes after DES implantation in a real world setting but also identifying several high-risk populations.

Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention--the PASSAT Study.

BACKGROUND: The value of early therapy with beta-blocking agents in acute myocardial infarction (AMI) undergoing reperfusion is not yet well established. Newer beta-blocking agents such as carvedilol offer potential advantages in the setting of ischemia and reperfusion injury. METHODS: We randomized 100 patients with acute ST-elevation myocardial infarction (STEMI) to receive either 12.5 mg carvedilol or 50 mg metoprolol tartrate orally already before percutaneous coronary intervention (PCI) of the infarct-related artery, uptitrating to a daily target dose of 50 mg carvedilol or 150 mg metoprolol during the first week. Pts. were subjected to left ventricular (LV) angiography just before reperfusion and after 14 days to compare ejection fraction (EF) and regional wall motion abnormalities by quantitative LV analysis. Furthermore, kinetics of cardiac troponin T (cTnT), NT-proANP, NT-proBNP, endothelin, argenine vasopressin, epinephrine and norepinephrine were assessed during the first 12 hours and again at 2 weeks. In addition, reperfusion-induced rhythm abnormalities like VT, triplets, couplets, and bradycardic events were assessed continuously during the first 12 hours starting at reperfusion by Holter analysis. RESULTS: Both groups did not differ with respect to onset of pain, target vessel, extent of coronary heart disease, age, gender, rate of stenting or use of a GP IIb/IIIa inhibitor, pre- and postinterventional TIMI flow grade, time course of heart rate or blood pressure. There were neither significant differences in the cardiac and neurohumoral markers nor in the occurrence of arrhythmias between both treatment groups. Within 14 days, EF improved by 5.8+/-2.0% (mean+/-SEM) in the metoprolol group and by 5.2+/-2.1% in the carvedilol group (n.s.). Area of infarction was reduced by 6.1+/-2.9% in the metoprolol group and by 12.8+/-3.6% of total LV outline in the carvedilol group (n.s.). Maximum hypokinesia in the central infarcted region was diminished by 0.40+/-0.11 standard deviation (SD) in the metoprolol group and by 0.34+/-0.13 SD in the carvedilol group (n.s.). CONCLUSION: In the setting of direct PCI in acute STEMI, administration of carvedilol before reperfusion appears not to be superior to metoprolol with respect to myocardial injury and improvement of global and regional LV function. The study documents equivalent improvement of LV function and similar kinetics of cardiac and neurohumoral markers in pts. with acute STEMI undergoing direct PCI if the pts. were immediately treated with either carvedilol or metoprolol. Thus, superiority of carvedilol in experimental studies did not translate into a clinical benefit.

The extent of akinesis is predictive of the in-hospital mortality from endoaneurysmorrhaphy.

Endoaneurysmorrhaphy (EAR) has become an important therapeutic option in the treatment of patients with left ventricular (LV) aneurysm and congestive heart failure. Today, more and more patients are referred for EAR with a dilated akinetic LV rather than a classic dyskinetic LV aneurysm. Little is known about the contribution of the extent of akinesis to perioperative mortality. We reviewed the data of 147 patients with anterior left ventricular aneurysms undergoing EAR. Seventy percent of the patients were male; mean age was 62+/-9 years. Demographic, hemodynamic, angiographic and surgical variables were analyzed using univariate statistic tests in order to determine risk factors for in-hospital mortality.Eighty-two percent of the LV aneurysms had at least some dyskinesia, but 70% were mainly akinetic. 133 patients had additional bypass surgery, one had additional mitral valve replacement. In-hospital mortality was 4.1% (n=6). Risk factors for in-hospital mortality were the total extent of akinetic myocardium (p=0.027) in the 30 degrees RAO view and the duration of cardiopulmonary bypass (CPB, p=0.0068) which was itself dependent on the LV ejection fraction (p=0.001), the number of stenosed coronary arteries (p=0.004), and the extent of akinesis (p=0.023). The extent of dyskinesia was not associated with either perioperative mortality (p=0.36) or CPB duration. EAR can be performed with acceptable perioperative results. Because akinesis increases in many patients with time, and because the duration of ECC was dependent on variables reflecting the severity of the underlying heart disease, our findings underscore the importance of optimal timing for the surgical intervention.

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Effects of intracoronary low-dose enalaprilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction.

Bradykinin accumulation is a potent cardioprotective mechanism underlying angiotensin-converting enzyme (ACE) inhibition in ischemia and/or reperfusion injury. There is, however, concern about treatment with ACE inhibitors in the very early phase of acute myocardial infarction (AMI) due to adverse systemic hemodynamic effects. We tested the hypothesis that cardiac bradykinin metabolism can be influenced by very low doses of intracoronary ACE inhibitors without harmful systemic effects in patients with AMI. Twenty-two patients with AMI in Killip classes II to III who underwent primary percutaneous transluminal coronary angiography (PTCA) were randomized to intracoronary enalaprilat (50 microg) or saline, given immediately after reopening of the infarct-related artery. Hemodynamics and electrocardiograms were monitored continuously and samples for determination of ACE activity, angiotensin II, bradykinin, kininogen, and cardiac marker proteins were collected from pulmonary arterial and central venous blood. Enalaprilat had no adverse effects on systemic hemodynamics, but rather stabilized arterial pressure and cardiac rhythm during reperfusion. Enalaprilat induced a 70% reduction of ACE activity and a significant increase of bradykinin in pulmonary arterial blood. Angiotensin II was not significantly affected by enalaprilat either in pulmonary arterial or in central venous blood. Myoglobin release was lower and the duration of reperfusion arrhythmias was significantly reduced in the enalaprilat group (p <0.05). Thus, in this pilot study, intracoronary enalaprilat infusion in the infarct-related artery is feasible in the setting of primary angioplasty and is safe and well tolerated. Effective cardiac ACE inhibition can be achieved by low-dose intracoronary enalaprilat, which primarily causes a potentiation of bradykinin.

Incidence and predictors of pacemaker dysfunction with unipolar ventricular lead configuration. Can we identify patients who benefit from bipolar electrodes?

Unipolar ventricular leads were implanted in a considerable percentage of pacemaker recipients. There is little information on incidence and risk factors for unipolar pacemaker dysfunction using modern lead designs. Included in a cross-sectional analysis were 682 patients who fulfilled the following criteria: chronically implanted bipolar ventricular leads (> 1 year), intraoperative stimulation threshold < 1.0 V/0.5 ms, and potential amplitude > 6 mV. Incidences of chest wall stimulation (CWS) at an output of twice the amplitude threshold and of myopotential oversensing (MPO) at a sensitivity of half the sensing threshold were assessed. Energy (0.60 [0.72] vs 0.63 [0.81] microJ) and sensing thresholds (8.31 [3.18] mV vs 8.47 [3.47] mV) did not differ between uni- and bipolar modes. While all pacemakers worked properly during bipolar configuration, malfunctions were observed in 5.9% of patients during unipolar configuration (CWS = 1.9%, MPO = 4.2%). Patient age > 76 years (hazard ratio HR 8.2; P < 0.001), heart failure > or = NYHA Class II (HR 3.8; P < 0.001), and an antiarrhythmic therapy with Class I or III drugs (HR 3.3; P = 0.002) were independently associated with the occurrence of unipolar pacemaker dysfunction. Use of steroid-eluting leads reduced the probability of pacemaker dysfunction (HR 0.45; P = 0.03). Risk factors for unipolar ventricular pacemaker malfunction were higher age, heart failure, and antiarrhythmic drug therapy. Particularly in these patients, use of bipolar ventricular leads is beneficial.

Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction.

BACKGROUND: In ST-segment elevation myocardial infarction, a troponin T >/=0.1 microg/L on admission indicates poorer prognosis despite early reperfusion. To evaluate the underlying reason, we studied the value of cardiac troponin T (cTnT) for prediction of outcomes, epicardial blood flow, and myocardial reperfusion after primary percutaneous intervention. METHODS AND RESULTS: Patients (n=140) admitted within 12 hours after onset of symptoms were stratified by admission cTnT. Epicardial and myocardial reperfusion were graded by the TIMI score and by measurement of relative increases of myoglobin, cTnT, and creatine kinase (CK)-MB 60 minutes after recanalization, respectively. cTnT was positive in 64 patients (45.7%) and was associated with longer median time intervals to admission (5.5 versus 3.5 hours, P<0.001) and higher mortality rates after 30 days (12.5% versus 3.9%, P=0.06) and 9 months (14% versus 3.9%, P=0.005). cTnT independently predicted a 3.2-fold risk for incomplete epicardial reperfusion (P=0.03). In addition, cTnT >/=0.1 microg/L was associated with more severely impaired myocardial perfusion despite normal epicardial flow, as indicated by lower 60-minute ratios of myoglobin (2.6 versus 7.6, P=0.007), cTnT (6.6 versus 29.2, P<0.001), and CK-MB (3.5 versus 21.4, P=0.002) and a tendency for less resolution of ST-segment elevations (54% versus 60%, P=0.08). CONCLUSIONS: cTnT predicts poorer clinical outcomes, lower rates of postprocedural TIMI 3 flow, and more severely compromised myocardial perfusion despite normal epicardial flow. Thus, a cTnT-positive patient may require more aggressive adjunctive therapy when treated by percutaneous coronary intervention. The impact of preexisting or evolving microvascular dysfunction and the effect of therapies that target myocardial perfusion require further prospective evaluation.

Biomechanical hearts: muscular blood pumps, performed in a 1-step operation, and trained under support of clenbuterol.

BACKGROUND: As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now. METHODS AND RESULTS: In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5x150 microg/wk). During surgery, the mean stroke volume of BMHs was 53.8+/-22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P(MD)) and minimal diastolic (P(min)) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P(MD)=+2.9+/-1.1 mm Hg [P<0.04], P(min)=-2.4+/-0.9 mm Hg [P<0.04]). After BMH-supported heart contractions, the subsequent maximal rate of pressure generation, dP/dt(max), increased by 20.5+/-8.1% (P<0.02). One BMH, catheterized 132 days after surgery, shifted a volume of 34.8 mL per beat and 1.4 L/min with a latissimus dorsi muscle of 330 g. Depending on duration of training, the percentage of myosin heavy chain type 1 ranged between 31% and 100%. CONCLUSIONS: Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle.

Neurohumoral activation in percutaneous coronary interventions: apropos of ten vasoactive substances during and immediately following coronary rotastenting.

BACKGROUND: Ischemia, left ventricular dysfunction, endothelial damage and hemodynamic changes during percutaneous coronary intervention can lead to neurohumoral activation. This may partly explain the frequent episodes of coronary spasm, hypotension and bradycardia which occur during the procedure. Rotastenting, by employing the two basic mechanisms for coronary interventions-debulking and dilatation-epitomizes percutaneous coronary interventions in general. We sought to investigate the neurohumoral changes during and immediately following coronary rotastenting. METHODS AND RESULTS: Eighteen patients undergoing elective rotablator atherectomy followed by balloon predilatation and stenting for chronic stable angina were studied. Four femoral vein blood samples were drawn from each patient at the start of the intervention (baseline), and 2 (postdebulking-2), 10 (postdebulking-10) and 60 (postdebulking-60) minutes. respectively, after the first complete passage of the rotablation burr across the whole length of lesion. Levels of 10 neurohormones, namely, endothelin-1, bradykinin, arginine vasopressin, norepinephrine, dopamine, epinephrine, angiotensin II, serum angiotensin-converting enzyme activity. atrial natriuretic peptide and kininogen were estimated in each sample. Endothelin-1 and bradykinin attained their peak levels in the postdebulking-2 samples. and the rise from 0.34+/-0.07 pmol/ml and 235.8+/-17.7 pg/ml to 0.42+/-0.06 pmol/ml and 337.2+/-41.0 pg/ml, respectively, was statistically significant (p<0.05). The level of arginine vasopressin showed a significant (p<0.05) rise from baseline (108.5+/-31.8 pg/ml) to postdebulking-60 samples (136.5+/-39.4 pg/ml). The other neurohormones did not show significant changes. CONCLUSIONS: The results suggest a definite but differential neurohumoral activation during and immediately following rotastenting. These neurohumoral changes may have a role in untoward intra- and postprocedural vasomotor and hemodynamic effects. This study establishes the concept of neurohumoral activation during percutaneous coronary interventions.

Angiographic correlates of a positive troponin T test in patients with unstable angina.

OBJECTIVE: To study the angiographic correlates of cardiac troponin T (cTnT)-positive and -negative patients with unstable angina pectoris. BACKGROUND: A positive cTnT test identifies a high-risk subgroup of unstable angina pectoris patients. Only the high-risk cTnT-positive patients seem to benefit from a more aggressive antithrombotic treatment regimen. The underlying coronary pathology in cTnT-positive and -negative patients that explains the predictive power of cTnT on prognosis and response to antithrombotic therapy is largely unknown. METHODS: A total of 197 subsequently admitted patients with unstable angina pectoris underwent cTnT testing by a rapid bedside assay and early qualitative and quantitative angiography. Long-term follow-up was 12 months. RESULTS: Patients with cTnT-positive tests revealed more critical stenoses of culprit lesions (p =.041), more severe reductions of thrombolysis in myocardial infarction flow grades (p <.037), a higher prevalence of intracoronary thrombus (p =.079), and a poorer left ventricular function (p =.047). The odds ratio of cTnT was 5.8 (p <.0001) for presence of thrombus, reduced thrombolysis in myocardial infarction flow, and/or critical stenosis (>90%), and was 3.1 (p =.005) for presence of three-vessel disease, left main disease, and/or reduced left ventricular ejection fraction. Coronary bypass grafting was more frequently performed in the cTnT-positive group. However, event-free survival was not different in our cohort characterized by a high rate of percutaneous coronary interventions. CONCLUSIONS: A positive cTnT test in patients with unstable angina pectoris indicates presence of more severe coronary artery disease and poorer left ventricular function. This finding could explain the differences in short- and long-term outcome and treatment responses to antithrombotic regimens.

Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C.

It previously has been reported in ischemic rat hearts that local release of noradrenaline triggers ventricular fibrillation via alpha1A-adrenoceptor stimulation. In order to elucidate the intracellular pathway mediating ventricular fibrillation in this setting, we used inhibitors or activators of protein kinase C in the absence or presence of the alpha1A-adrenoceptor antagonist WB 4101. Regional ischemia was induced in isolated perfused rat heart byligature of the left coronary artery. Pharmacological interventions were tested by addition of drugs to the perfusate 10 min prior to ligature and throughout 30 min of ischemia while the epicardial electrocardiogram was continuously monitored. Blockade of protein kinase C by polymyxin B (1 micromol/l) significantly reduced ventricular fibrillation to 40% (from 87% in controls). Similar effects were seen with the protein kinase C inhibitors staurosporine 10 nmol/l (46% vs. 91%) and cremophor RH 40 100 micromol/l (33% vs. 77%). Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DOG, 10 micromol/l) or phorbol 12-myristate 13-acetate (PMA, 10 nmol/l) did not affect ventricular fibrillation. In the presence of the alpha1A-adrenoceptor antagonist WB 4101 (0.1 micromol/l), which per se suppressed ventricular fibrillation to 17%, both DOG and PMA increased the occurrence of ventricular fibrillation to 73% and 75%, respectively, whereas the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, 10 nmol/l) revealed no proarrhythmic effect. In summary, during regional ischemia in the isolated perfused rat heart, alpha1A-adrenoceptor stimulation induces ventricular fibrillation mainly by activating protein kinase C.

A novel strategy to overcome resistance in stent placement at lesion site after adequate predilatation.

Resistance was encountered in passing a 3 x 18 mm stent across a lesion in the proximal left anterior descending coronary artery. Successive changes in stent with repeated balloon dilatations did not succeed. Finally, a 9 mm stent was passed across the lesion and deployed at the site of maximal resistance. The 18 mm stent was then placed through this stent. A novel strategy to overcome resistance in the stent passage through the lesion after an adequate balloon predilatation is reported.

[Intermediate term clinical results after endoaneurysmorrhaphy in left ventricular aneurysm]. / Mittelfristige klinische Ergebnisse nach Endoaneurysmorrhaphie bei linksventrikulären Aneurysmen.

Endoaneurysmorrhaphy (EAR) in postinfarct ventricular aneurysms leads to excellent short-term results. However, the temporal response of EAR is widely unknown. Thus, the indication for surgical treatment of patients with ventricular aneurysms is not well defined. EAR was performed in 157 patients (6/1993-6/1999) with symptomatic ventricular aneurysms (median NYHA III). Factors influencing cardiac mortality and morbidity during follow-up were determined by univariate and multivariate analysis. Perioperative mortality was low: 5%. Mortality during follow-up was 3.3% per year, resulting in a 5-year survival rate of 78%. NYHA classification ameliorated significantly from the preoperative status compared to the follow-up period (median NYHA II; p < 0.001). Multivariate analysis identified preexisting arterial occlusive disease and advanced age (> 70 years) as significant factors influencing medium-term mortality. Implantation of the left internal mammary artery was associated with a better survival rate. Endoaneurysmorrhaphy can be performed with low perioperative mortality, will result in a significant amelioration of the cardiac clinical status and offers low medium-term mortality. Our data indicate that EAR seems to be the procedure of choice for patients with symptomatic ventricular aneurysms.

Risk factors for early reocclusion and luminal renarrowing in patients with acute coronary syndromes treated by direct PTCA with provisional stenting.

UNLABELLED: Angioplasty in acute coronary syndromes is complicated by a high rate of early vessel reocclusion and restenosis. Therefore, it is recommended to achieve a "stent-like" result by percutaneous transluminal coronary angioplasty (PTCA) or otherwise use coronary stenting (provisional stenting). This study sought to determine angiographic and patient-related factors that are associated with early target vessel reocclusion or luminal renarrowing after coronary intervention in acute coronary syndromes (ACS). In an observational prospective study we investigated 161 patients with ACS (acute myocardial infarction and unstable angina) submitted to PTCA. In 140 patients a follow-up angiography after 10 days was obtained. All angiograms were quantitatively evaluated by computerized measurements. Target vessel reocclusion and early luminal renarrowing was observed in 10 patients (7.1%) and 19 patients (13.6%), respectively. Using univariate analysis, significant risk factors (P < 0.05) for early reocclusion and renarrowing were diabetes mellitus (relative risk [RR] 6.1 and 5.0), arterial hypertension (RR 7.7 and 3.3), postprocedural lesion length > or = 2.5 mm (RR 6.8 and 7.1), postprocedural minimal lumen diameter < or = 2.5 mm (RR 9.0 and 5.8), residual stenosis > or = 25% (RR 4.8 and 3.5) and absence of stents (RR 4.1 and 3.2). Moreover, in multivariate analysis hypertension and postprocedural lesion length could be identified as independent risk factors for reocclusion and renarrowing. Diabetes mellitus was found to be an independent risk factor for renarrowing. CONCLUSIONS: In a consecutive series of patients with ACS undergoing PTCA with provisional stenting the occurrence of early target vessel reocclusion and luminal renarrowing is lower than previously reported for this subset of patients treated by PTCA alone. Adverse outcome is related to absence of stents, angiographic factors (residual stenosis, lesion length, minimal lumen diameter after procedure) and patient-related factors such as diabetes and hypertension.

Differential effects of carvedilol on norepinephrine release in normoxic and ischemic heart.

Carvedilol is a beta-adrenoceptor antagonist with multiple actions, which may contribute to superior cardioprotection in heart failure and myocardial infarction. We hypothesized that carvedilol may modulate presynaptic norepinephrine release in the heart. Therefore, we compared the effects of carvedilol (racemate and both enantiomers) and beta1-selective as well as nonselective beta-adrenoceptor blockers on norepinephrine release in isolated perfused rat hearts under normoxic and brief ischemic conditions. Exocytotic release of endogenous norepinephrine was induced by paired electric field stimulations to compare the release before (S1) and after (S2) beta-adrenoceptor blocker application. Metoprolol, bisoprolol, and pindolol (0.1-10 microM) had essentially no effect on exocytotic norepinephrine release under normoxic and ischemic conditions. In contrast, carvedilol exerted a biphasic concentration-response curve (increase followed by suppression) on norepinephrine release. The increase in norepinephrine release was more pronounced with R-carvedilol than with S-carvedilol, indicating an effect independent from beta-receptor antagonism. During ischemia, the facilitatory effect of carvedilol on norepinephrine release was lost, resulting in a concentration-dependent suppression of the release. These results indicate that carvedilol in contrast to classic beta1-selective and -nonselective beta-adrenoceptor blockers has pronounced effects on cardiac norepinephrine release with a remarkable difference between normoxic and ischemic conditions. Whereas a facilitation of norepinephrine release prevailed in normoxia, we observed a suppression of the release in ischemia. It remains to be established whether this unique action of carvedilol on cardiac sympathetic neurotransmission is of clinical relevance.

Atrial lead placement during atrial fibrillation. Is restitution of sinus rhythm required for proper lead function? Feasibility and 12-month functional analysis.

Unexpected atrial fibrillation (AF) during implantation of an atrial pacemaker lead is sometimes encountered. Intraoperative cardioversion may lengthen and complicate the implantation process. This study prospectively investigates the performance of atrial leads implanted during AF (group A) and compares atrial sensing and pacing properties to an age- and sex-matched control group in which sinus rhythm had been restored before atrial lead placement (group B). Patient groups consisted of 32 patients each. All patients received DDDR pacemakers and bipolar, steroid-eluting, active fixation atrial leads. In patients with AF at the time of implantation (group A), a minimal intracardiac fibrillatory amplitude of at least 1.0 mV was required for acceptable atrial lead placement. In patients with restored sinus rhythm (group B), a voltage threshold < 1.5 V at 0.5 ms and a minimal atrial potential amplitude > 1.5 mV was required. Patients of group A in whom spontaneous conversion to sinus rhythm did not occur within 4 weeks after implantation underwent electrical cardioversion to sinus rhythm. Pacemaker interrogations were performed 3, 6, and 12 months after implantation. In group A, implantation time was significantly shorter as compared to group B (58.7 +/- 8.6 minutes vs 73.0 +/- 17.3 minutes, P < 0.001). Mean atrial potential amplitude during AF was correlated with the telemetered atrial potential during sinus rhythm (r = 0.49, P < 0.001), but not with the atrial stimulation threshold. Twelve months after implantation, sensing thresholds (1.74 +/- 0.52 mV vs 1.78 +/- 0.69 mV, P = 0.98) and stimulation thresholds (1.09 +/- 0.42 V vs 1.01 +/- 0.31 V, P = 0.66) did not differ between groups A and B. However, in three patients of group A, chronic atrial sensing threshold was < or = 1 mV requiring atrial sensitivities of at least 0.35 mV to achieve reliable atrial sensing. Atrial lead placement during AF is feasible and reduces implantation time. However, bipolar atrial leads and the option to program high atrial sensitivities are required.

[Intracoronary stent implantation and left ventricular function in primary PTCA in acute myocardial infarct]. / Intrakoronare Stentimplantation und linksventrikuläre Funktion bei primärer PTCA im akuten Myokardinfarkt.

In acute myocardial infarction intracoronary stenting is superior to PTCA regarding interventional success and occurrence of cardiac events. It is, however, uncertain whether myocardial function also improves with stenting. We, therefore, assessed angiographic parameters of myocardial function in patients with acute myocardial infarction who were treated with primary PTCA and received additional stenting in case of an unsatisfactory angiographic result (provisional stenting). Nineteen patients with acute myocardial infarction, in whom a "stent-like" angiographic result was achieved by PTCA alone, were compared with an equal number of patients receiving provisional stenting. The groups were exactly matched with respect to severity of coronary heart disease, segment of coronary occlusion, Killip class, and TIMI flow after intervention. We only included patients without inhospital cardiac events, in whom repeat angiography after ten days revealed a patent target vessel. There were no differences between both groups regarding age, gender, enzymatic infarction size, duration of ischemia (< or = 12 h), and cardiac risk factors. Myocardial function was assessed by ventriculography and was analyzed quantitatively by the center-line method. The group treated by intracoronary stenting showed a significantly improved ejection fraction (60.3 +/- 2.1% vs. 52.6 +/- 2.9%). All parameters of regional wall motion also indicated significantly less functional disturbance in the stented group compared to PTCA alone (circumferential extend of hypokinesia: 7.4 +/- 2.4% vs. 16.1 +/- 3.4% chords, maximum hypokinesia in the central infarct region: -0.98 +/- 0.20 vs. -1.52 +/- 0.15 SD, severity of regional hypokinesia: 7.3 +/- 2.6 vs. 21.9 +/- 5.4 area). In summary, these results in patients undergoing primary PTCA in acute myocardial infarction indicate that intracoronary stenting is superior to PTCA alone with respect to myocardial recovery, even if an angiographically "stent-like" result can be achieved. Probably, stenting results in a more efficient reperfusion.

Heart rate variability in patients with acute myocardial infarction undergoing primary coronary angioplasty.

Depressed heart rate variability (HRV) has been associated with adverse outcome during and after acute myocardial infarction (AMI). The effects of reperfusion in AMI on the course of HRV have not been well characterized as yet. We analyzed 123 consecutive patients with a first AMI who underwent successful reperfusion (Thrombolysis In Myocardial Infarction grades 2 and 3) by primary percutaneous transluminal coronary angioplasty (PTCA). Time- and frequency-domain HRV was measured from 24-hour Holter monitoring, which began at hospital admission. Mean RR interval increased significantly after successful PTCA. Reperfusion immediately caused an immediate transient depression of HRV, which was followed by a significant increase of HRV. Quantitative markers of sympathetic activity and sympathovagal balance, such as SD of the averages of NN intervals in all 5-minute segments, and low- and/or high-frequency ratio continuously decreased within the observation period. Patients with anterior AMI exhibited the same pattern of temporal changes of HRV, with, however, lower absolute values for HRV and mean RR interval than patients with non-anterior AMI. Subgroup analysis in 21 patients with reperfusion > 12 hours after onset of pain showed that the biphasic profile of HRV and the marked increase of mean RR interval was absent. Furthermore, in patients with late reperfusion, HRV was significantly lower compared with those with early reperfusion. Thus, timely reperfusion in AMI leads to a biphasic effect on autonomic tone, characterized by a transient suppression, followed by a significant activation of the vagal tone, as well as an attenuation of sympathetic activity. Recovery of HRV may contribute to the benefits of early reperfusion in AMI.