Janusz Drzewiecki

Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions

Background—Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations. Methods and Results—We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P <0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P <0.0001) and from 20.2% to 4.7% in the MR cohort (P =0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P =0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients. Conclusions—Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions.

Incomplete Stent Apposition After Implantation of Paclitaxel-Eluting Stents or Bare Metal Stents Insights From the Randomized TAXUS II Trial

Background—The clinical impact of late incomplete stent apposition (ISA) for drug-eluting stents is unknown. We sought to prospectively investigate the incidence and extent of ISA after the procedure and at 6-month follow-up of paclitaxel-eluting stents in comparison with bare metal stents (BMS) and survey the clinical significance of ISA over a period of 12 months. Methods and Results—TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This intravascular ultrasound (IVUS) substudy included patients who underwent serial IVUS examination after the procedure and at 6 months (BMS, 240 patients; SR, 113; MR, 116). The qualitative and quantitative analyses of ISA were performed by an independent, blinded core laboratory. More than half of the instances of ISA observed after the procedure resolved at 6 months in all groups. No difference in the incidence of late-acquired ISA was observed among the 3 groups (BMS, 5.4%; SR, 8.0%; MR, 9.5%; P=0.306), with a similar ISA volume (BMS, 11.4 mm3; SR, 21.7 mm3; MR, 8.5 mm3; P=0.18). Late-acquired ISA was the result of an increase of vessel area without change in plaque behind the stent. Predictive factors of late-acquired ISA were lesion length, unstable angina, and absence of diabetes. No stent thrombosis occurred in the patients diagnosed with ISA over a period of 12 months. Conclusions—The incidence and extent of late-acquired ISA are comparable in paclitaxel-eluting stents and BMS. ISA is a pure IVUS finding without clinical repercussions.

Peristent Remodeling and Neointimal Suppression 2 Years After Polymer-Based, Paclitaxel-Eluting Stent Implantation: Insights From Serial Intravascular Ultrasound Analysis in the TAXUS II Study

Background— The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents. Methods and Results— TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49±1.12 mm2; SR, 0.94±0.76 mm2 [P=0.004]; and MR, 1.06±0.90 mm2 [P=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (&Dgr;, −0.22±1.05 mm2 [P=0.08]). In contrast, both the SR and MR groups exhibited an increase (&Dgr; SR, 0.30±0.76 mm2 (P=0.01); MR, 0.41±0.94 mm2 [P=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (&Dgr; between after the procedure and 2 years BMS, −0.34±1.28 mm2 [P=0.05]; SR, −0.02±1.40 mm2 [P=0.93]; MR, 0.32±1.56 mm2 [P=0.27]). Conclusions— The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.

Final 5-Year Results of the TAXUS II Trial: A Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for De Novo Coronary Artery Lesions

Background— The TAXUS II trial was designed to evaluate the safety and efficacy of the commercialized slow-release (SR) and an investigation-only moderate-release (MR) polymer-based TAXUS paclitaxel-eluting stent compared with a bare-metal stent for the treatment of de novo coronary lesions. Methods and Results— This prospective, randomized, double-blind, controlled trial enrolled 536 patients in 2 consecutive cohorts to compare TAXUS SR (n=131) and TAXUS MR (n=135) with an identical but uncoated bare-metal stent control (n=270). The present analysis reports final 5-year clinical outcomes of TAXUS II. At 5 years, both TAXUS SR and MR showed superior outcomes compared with control. The 5-year rates of major adverse cardiac events were 27.6%, 20.4%, and 15.1% (P=0.01); rates of target-vessel revascularization were 22.5%, 16.6%, and 9.0% (P=0.004); and rates of target-lesion revascularization were 18.4%, 10.3%, and 4.5% (P<0.001) for the control, TAXUS SR, and TAXUS MR groups, respectively. The rates of all-cause death and myocardial infarction were low and similar between groups, with 2 stent thromboses with bare-metal stents compared with no event beyond 2 years with either of the TAXUS stents. Conclusions— TAXUS II is the first large TAXUS trial to have reached 5-year follow-up. Both the SR and MR stents lowered the rates of target-vessel and target-lesion revascularization, which indicates their sustained efficacy. Furthermore, the low overall rates of all death, myocardial infarction, and stent thrombosis support the long-term safety of the TAXUS stent system.

Primary stenting versus MIDCAB: preliminary report–Comparision of two methods of revascularization in single left anterior descending coronary artery stenosis

BACKGROUND Percutaneous revascularization is a well-accepted method of treatment for a single left anterior descending coronary artery (LAD) stenosis. With the introduction of primary stenting, it has become the treatment of choice for a LAD lesion. In the last few years however, the introduction of minimally invasive cardiac surgery, video-assisted left internal thoracic artery (LITA) harvesting, and robotic surgery have raised the question as to whether minimally invasive surgical revascularization would be competitive with percutaneous coronary interventions in cases of single-vessel stenoses. METHODS A group of 100 patients with Canadian Cardiovascular Society class II to IV, and angiographically confirmed single critical stenosis of the LAD (type A or B), were treated with direct primary stenting (group 1, n = 50), or with endoscopic atraumatic coronary artery bypass grafting (group 2, n =50). RESULTS All patients in a group 1, obtained a very good angiographic and clinical effect. No acute postoperative complications were noted at 1 month of follow-up. However, at 1 month of follow-up, 3 patients (6%) developed restenosis of the LAD, and at 6 months follow-up, 6 patients (12%), developed restenosis of the LAD. In these cases, repeated percutaneous coronary interventions of the target vessel were successfully performed. In group 2, very good operative results were observed. In 1 and 6 months of follow-up, all patients remained asymptomatic. Critical stenosis of the left internal thoracic artery-LAD anastomosis was angiographically documented in 1 case (2%). This patient was successfully treated with balloon angioplasty. CONCLUSIONS The study results document the superiority of endoscopic atraumatic coronary artery bypass grafting over direct primary stenting in LAD revascularization, along with the slightly higher costs of the surgical procedure.

Integrated minimally invasive direct coronary artery bypass grafting and angioplasty for coronary artery revascularization

OBJECTIVE Minimally invasive direct coronary artery bypass (MIDCAB) through the anterolateral minithoracotomy has become a promising therapeutic option in patients with lesion in left anterior descending artery (LAD), especially in multimorbid, elderly and reoperated patients with type C or B lesions. To expand the benefits of MIDCAB concept to patients with multivessel disease, a hybrid myocardial revascularization procedure (HMR) combining surgery of the LAD with interventional procedures for additional coronary lesions has recently been introduced. METHODS Between January 1999 and September 2001, 50 patients (37 male, 13 female, mean age 54.8+/-20.1 years) underwent an HMR procedure. MIDCAB with endoscopic left internal thoracic artery (LITA) harvesting, followed by percutaneous coronary intervention (PCI) for additional coronary lesions and percutaneous transluminal coronary angioplasty (PTCA), was performed in 11 patients (22%) and stenting in 39 patients (78%). Angiographic assessment of graft patency was performed in all patients during the PCI procedure. The clinical follow-up period was 3-32 months. RESULTS There were no early and late deaths. Baseline Canadian Cardiology Society (CCS) class was 2.8+/-0.7 versus 1.1+/-0.9 (P<0.001) 30 days after HMR procedure. There were no major acute in-hospital cardiac events. Angiographic studies showed patent LIMA-LAD graft in 50 patients (100%). We showed good quality of anastomosis in 49 patients (98%). There was a moderate graft stenosis in one patient (2%). At long term follow-up, the rate of major cardiac events was 12%. Five patients (10%) developed restenosis after PCI, and one patient (2%) developed significant stenosis in site of LITA-LAD anastomosis; redo PCI was performed successfully. CONCLUSIONS The hybrid procedure is a safe and effective method for complete revascularization in selected patients with double-vessel coronary artery disease (patients with type B or C lesions in the proximal LAD). This method allows performance of complete revascularization with minimization of surgical trauma. So far, long-term results of HMR are limited by the results of PCI.

Long-term follow-up of the randomised controlled trial to evaluate the safety and efficacy of the zotarolimus-eluting driver coronary stent in de novo native coronary artery lesions: five year outcomes in the ENDEAVOR II study

AIMS We report here the final 5-year follow-up results from the ENDEAVOR II trial, which was the first randomised trial evaluating the Endeavor(tm) zotarolimus-eluting stent (ZES) compared with a bare metal stent (BMS) in patients with single, de novo coronary artery lesions. METHODS AND RESULTS Eligible patients were randomised 1:1 to receive ZES or BMS and were followed by telephone or clinic visit up to five years. We evaluated TVF and its components (target vessel revascularisation [TVR], Q-wave or non Q-wave myocardial infarction, or cardiac death attributed to the target vessel) at five years. Additionally, we report rates of MACE, TLR, and stent thrombosis (protocol- and ARC-defined) through five years. ENDEAVOR II enrolled 1,197 patients (598 ZES, 599 BMS). At five years of follow-up, the rates of TVF (15.4% vs 24.4%), TVR (10.7% vs 20.1%), MACE (15.4% vs 24.6%), and TLR (7.5% vs 16.3%) remained significantly lower in ZES patients compared with BMS patients. ARC definite and probable very late (>1 year) stent thrombosis remained low (0.2% ZES and 0.3% BMS) through five years. CONCLUSIONS After five years of follow-up, ZES demonstrated significantly improved clinical outcomes with sustained safety compared with BMS in patients with obstructive coronary artery disease.

Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation: A post hoc analysis of TAXUS II

Background and Method:Although direct coronary stenting does not improve angiographic outcome, it makes sense by reducing procedure times, radiation exposure and costs. Other potential advantages of direct stenting may be a reduction of myocardial ischemia time, which could be clinically relevant in high-risk patients. With the introduction of drug-eluting stents, however, concern arose that direct stenting would possibly damage the polymer coating and change or diminish the efficacy of the programmed drug release. Also, concerns about safety by preventing optimal apposition of single stent struts developed. It is the purpose of this paper to retrospectively analyze the data from the TAXUS-II Trial (536 patients) regarding patients with and without direct stenting. While predilatation was recommended per protocol, direct stenting was not forbidden: thus, direct stenting was performed in 49 patients (TAXUS n = 23, control n = 26).Results:In the TAXUS groups, there was no significant difference regarding major adverse cardiac events (MACE; 7.5% vs. 4.3%), angiographic restenosis in the analysis segment (4.8% vs. 4.3%), late loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cular ultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs. 5.61 ± 7.91%) at six months between the predilated and directly stented patients. The same was true for the patients receiving the control stent. Compared with the directly stented control group, the statistically significant positive effects of TAXUS direct stenting were maintained, regarding angiographic restenosis in the analysis segment (4.3% vs. 30.8%), late loss (0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volume obstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months. MACE was reduced from 19.2% to 4.3%; due to the small number of patients this trend did not reach statistical significance. After predilatation, all parameters were significantly improved by the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with or without predilatation revealed no differences in clinical, angiographic or IVUS parameters at six months. This suggests that direct stenting with the polymer-based paclitaxeleluting TAXUS stent is feasible, safe and equally effective. Randomized trials comparing stenting after predilatation versus direct stenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographische Kurz- und Langzeitergebnis nicht verbessert, macht es dennoch Sinn, da es die Prozedurzeiten, Strahlenexposition und die Kosten reduzieren kann. Andere mögliche Vorteile des Direkt-Stentings liegen in einer Reduktion der myokardialen Ischämiezeit, was bei Hochrisikopatienten klinisch relevant sein könnte. Mit der Einführung der Medikamente freisetzenden Stents kamen jedoch Bedenken auf, dass ein Direkt-Stenting möglicherweise die Polymerbeschichtung beschädigen könnte und somit die Wirksamkeit vermindert. Auch eine eventuelle Beeinträchtigung der Sicherheit und Wirksamkeit durch Malapposition einzelner Stentstreben wurde diskutiert. Ziel dieser Arbeit ist es, die Daten der TAXUS-II Studie (536 Patienten) hinsichtlich des Direkt-Stentings retrospektiv zu analysieren. In dieser Studie war die Vordehnung zwar empfohlen, ein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde ein Direkt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 in der Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen den prädilatierten und den direkt-gestenteten Patienten kein signifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %), angiographischer Restenose im analysierten Gesamtsegment (4,8 % vs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in der IVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95 ± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für die Patienten, die einen unbeschichteten Kontrollstent erhielten. Im Vergleich zur direkt gestenteten Kontrollgruppe waren die statistisch signifikanten positiven Effekte des TAXUS-Direkt-Stentings unverändert erhalten: angiographische Restenose im gesamten analysierten Segment (4,3 % vs. 30,8 %), late loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessene Volumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurde von 19,2 % auf 4,3 % reduziert, allerdings erreichte dieser eindeutige Trend aufgrund der kleinen Patientenzahl keine statistische Signifikanz. Nach Vordehnung waren in der TAXUS-Gruppe alle Parameter signifikant besser als in der Kontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mit oder ohne Vordehnung erhielten, ließ keinen Unterschied in den klinischen, angiographischen oder IVUSParametern nach 6-Monaten erkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mit dem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gut durchführbar, sicher und genauso wirksam ist wie nach Vordehnung. Randomisierte Studien zum Vergleich des Direkt-Stentings mit Stenting nach Vordehnung für Medikamente freisetzende Stents sind wichtig.

Direct Stenting with TAXUS Stents Seems to be as Safe and Effective as with Predilatation

Background and Method:Although direct coronary stenting does not improve angiographic outcome, it makes sense by reducing procedure times, radiation exposure and costs. Other potential advantages of direct stenting may be a reduction of myocardial ischemia time, which could be clinically relevant in high-risk patients. With the introduction of drug-eluting stents, however, concern arose that direct stenting would possibly damage the polymer coating and change or diminish the efficacy of the programmed drug release. Also, concerns about safety by preventing optimal apposition of single stent struts developed. It is the purpose of this paper to retrospectively analyze the data from the TAXUS-II Trial (536 patients) regarding patients with and without direct stenting. While predilatation was recommended per protocol, direct stenting was not forbidden: thus, direct stenting was performed in 49 patients (TAXUS n = 23, control n = 26).Results:In the TAXUS groups, there was no significant difference regarding major adverse cardiac events (MACE; 7.5% vs. 4.3%), angiographic restenosis in the analysis segment (4.8% vs. 4.3%), late loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cular ultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs. 5.61 ± 7.91%) at six months between the predilated and directly stented patients. The same was true for the patients receiving the control stent. Compared with the directly stented control group, the statistically significant positive effects of TAXUS direct stenting were maintained, regarding angiographic restenosis in the analysis segment (4.3% vs. 30.8%), late loss (0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volume obstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months. MACE was reduced from 19.2% to 4.3%; due to the small number of patients this trend did not reach statistical significance. After predilatation, all parameters were significantly improved by the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with or without predilatation revealed no differences in clinical, angiographic or IVUS parameters at six months. This suggests that direct stenting with the polymer-based paclitaxeleluting TAXUS stent is feasible, safe and equally effective. Randomized trials comparing stenting after predilatation versus direct stenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographische Kurz- und Langzeitergebnis nicht verbessert, macht es dennoch Sinn, da es die Prozedurzeiten, Strahlenexposition und die Kosten reduzieren kann. Andere mögliche Vorteile des Direkt-Stentings liegen in einer Reduktion der myokardialen Ischämiezeit, was bei Hochrisikopatienten klinisch relevant sein könnte. Mit der Einführung der Medikamente freisetzenden Stents kamen jedoch Bedenken auf, dass ein Direkt-Stenting möglicherweise die Polymerbeschichtung beschädigen könnte und somit die Wirksamkeit vermindert. Auch eine eventuelle Beeinträchtigung der Sicherheit und Wirksamkeit durch Malapposition einzelner Stentstreben wurde diskutiert. Ziel dieser Arbeit ist es, die Daten der TAXUS-II Studie (536 Patienten) hinsichtlich des Direkt-Stentings retrospektiv zu analysieren. In dieser Studie war die Vordehnung zwar empfohlen, ein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde ein Direkt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 in der Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen den prädilatierten und den direkt-gestenteten Patienten kein signifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %), angiographischer Restenose im analysierten Gesamtsegment (4,8 % vs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in der IVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95 ± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für die Patienten, die einen unbeschichteten Kontrollstent erhielten. Im Vergleich zur direkt gestenteten Kontrollgruppe waren die statistisch signifikanten positiven Effekte des TAXUS-Direkt-Stentings unverändert erhalten: angiographische Restenose im gesamten analysierten Segment (4,3 % vs. 30,8 %), late loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessene Volumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurde von 19,2 % auf 4,3 % reduziert, allerdings erreichte dieser eindeutige Trend aufgrund der kleinen Patientenzahl keine statistische Signifikanz. Nach Vordehnung waren in der TAXUS-Gruppe alle Parameter signifikant besser als in der Kontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mit oder ohne Vordehnung erhielten, ließ keinen Unterschied in den klinischen, angiographischen oder IVUSParametern nach 6-Monaten erkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mit dem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gut durchführbar, sicher und genauso wirksam ist wie nach Vordehnung. Randomisierte Studien zum Vergleich des Direkt-Stentings mit Stenting nach Vordehnung für Medikamente freisetzende Stents sind wichtig.

Correlation of Heart Rate Variability Parameters and QT Interval in Patients After PTCA of Infarct Related Coronary Artery as an Indicator of Improved Autonomic Regulation

The purpose of this study was to determine if PTCA of the infarct related coronary artery (IRA) in the late phase of myocardial infarction (MI) can improve autonomic regulation of sinus rhythm and electrical stability of the myocardium measured by heart rate variability (HRV), QT, QTc, and its dispersion (QTd) and if any correlation exists among these measures. The study was performed in 25 patients (21 male, age: 50 ± 9 years, EF: 52%± 11%) in the late phase of MI (2.5 ± 1.5 months). HRV parameters were calculated automatically. QT, QTc, and QTd were measured manually from a 12‐lead surface ECG (50 mm/s). All measurements were made before and 3–5 days after PTCA. Day and night parameters of HRV were sampled over two periods: 2 pm to 10 pm (day) and 10 pm to 6 am (night). Parameters of HRV measured from whole recordings were significantly higher after successful PTCA: SDRR (116 31 vs 128 ± 38 ms), SD (55 ± 17 vs 62 ± 22 ms), rMSSD (30 ± 13 vs 36 ± 14 ms) and HF (246 ± 103 vs 417 ± 224 ms2). Significant differences were found during daytime for SD, rMSSD, and HF, and during nighttime for SDRR, SDANN. QT interval duration, QT corrected to the heart rate, and QT dispersion were significantly lower after PTCA (QTd: 54 ± 15 vs 39 ± 12 ms). There was no correlation between HRV and QT values before PTCA. High correlations were found after the procedure, particularly between QTd and nighttime HRV. Conclusions: PTCA of IRA in the late phase of MI enhances sympathovagal regulation of the cardiac rhythm and the electrical stability of the heart, which may be prognostically important.