Left ventricular surgical remodeling after the STICH trial.

Surgical treatment of anteroseptal scars has been, and still is, a challenging task for cardiac surgeons. Most patients are in heart failure and the infarcted areas can include different parts of the septum and the anterior wall. The core problem of ischemic congestive heart failure is the undue demand placed on the residual viable left ventricle myocardium. The surgical techniques used to correct the mismatch between contractile and asynergic areas differ, but the evolution of surgical techniques for left ventricular surgical remodeling (LVSR) is still a work in progress. The most popular one was proposed by Dor et al. in the 1980s and is still in general use. This technique addressed the problem of recovering a predictable volume but not necessarily the problem of rebuilding a physiologically conical shape. This anatomical aspect is becoming increasingly important, and the purpose of septal reshaping, as proposed by us in 2004, is more to recover a conical shape than to achieve volume reduction. Thus, we use the Dor operation only when septoapical scars are present. The need for a different surgical strategy is emphasized by the result of the STICH trial, which reports the data of 1000 patients randomized for coronary artery bypass grafting (CABG, n = 499) or CABG and LVSR (n = 501) and which failed to show any benefit of LVSR. However, the only surgical technique used was the classic Dor operation, where the purpose was to reestablish volume and not to recreate a physiological shape. This study, however, does not provide a definitive answer, as echocardiography results included only 212 patients in the CABG arm and 161 in the CABG and LVSR arm. Furthermore, previous myocardial infarction (MI) was not a prerequisite for study inclusion (13 % of patients in each group had no previous MI) and whether a previous MI was Q-wave or not was not specified. In conclusion, the long-term results after LVSR are satisfactory but appear to be better if a conical shape has been recreated. The role of preemptive surgery in selected cases and how to establish the limits of LVSR (grade of preoperative diastolic dysfunction, diastolic diameter, ventricular volumes, function of the remote zone, etc.) is still unclear. The impact of each individual treatment in the individual patient (medical treatment, CABG alone, CABG and LVSR) has still to be identified.

Age-dependence of risk factors for carotid stenosis: an observational study among candidates for coronary arteriography.

In order to identify subjects at higher risk for carotid stenosis and to provide insights into mechanisms of disease development at different age-intervals, a color duplex ultrasound of extracranial arteries was performed in 624 consecutive patients (mean age 62.9+/-10.7, 483 males) undergoing coronary angiography. Significant carotid atherosclerosis (> or =50% stenosis) was documented in 87 patients (14%): the disease was moderate (50/69% stenosis) in 51 patients (8%), severe (> or =70% stenosis) in 36 patients (6%). Age (P<0.0001), smoking (P<0.0001), diabetes (P=0.0002), renal dysfunction (P=0.0119) and hypertension (P=0.0202) were independent predictors of significant carotid atherosclerosis; age (P=0.0001), smoking (P=0.0009) and diabetes (P=0.0201) were independent predictors of severe disease. Among 262 candidates for cardiac surgery, significant carotid artery disease was identified in 57 cases (2.63 Relative Risk, 95% Confidence Intervals: 1.32/5.24). Correlation and regression tree analysis demonstrated that diabetes was associated with greater severity of carotid stenosis in younger patients and hypertension in older ones. In conclusion age is the primary determinant of carotid artery disease; diabetes and smoking accelerate progression of atherosclerosis in younger patients, hypertension and smoking in older ones. Among patients undergoing coronary angiography, carotid ultrasonography should be recommended in high risk subgroups of patients.

Composite lengthened arterial conduits: long-term angiographic results of an uncommon surgical strategy.

BACKGROUND: We sought to evaluate the long-term patency rate of composite lengthened conduits. METHODS AND RESULTS: From December 1991 to April 2000, 43 patients had a composite lengthened arterial conduit. There was a mean of 2.83 +/- 1.23 anastomoses per patient. No 30-day mortality occurred. Five patients died from 3 to 84 months after the operation (mean, 38.6 +/- 34.6 months). After a mean follow-up of 57.0 +/- 32.3 months (range, 3-99 months), all the survivors are asymptomatic. The only cardiac major events recorded were 2 (4.6%) late acute myocardial infarctions in the patients who died. Eight-year survival and event-free survival were both 80.4% +/- 9.1% (range, 3%-93%). In the early period (13.5 +/- 4.8 days) in 26 patients, 26 arterial composite lengthened conduits and 37 distal anastomoses had postoperative angiographic control; all the anastomoses were rates as grade A, according to Fitzgibbon classification. In the late period (29 +/- 30 months) in 23 patients, 23 arterial composite lengthened conduits and 34 distal anastomoses were checked; the patency rate was 22 (95.6%) of 23 for the composite lengthened conduits and 33 (97%) of 34 for the distal anastomoses. CONCLUSIONS: In particular situations, when the length of an arterial conduit is not enough to allow a correct use of the graft, lengthening of an arterial conduit can be a safe and effective technique.

Myocardial revascularization with and without cardiopulmonary bypass in multivessel disease: impact of the strategy on early outcome.

BACKGROUND: The impact of myocardial revascularization without cardiopulmonary bypass (CPB) was evaluated in a series of consecutive patients with multivessel disease. METHODS: From May 21, 1997 to November 30, 2000, 1,843 consecutive patients underwent isolated myocardial revascularization. From this total, 919 patients were done without CPB (group A, 49.9%) and 924 patients were done with CPB (group B, 50.1%). Patients that converted from without CPB to with CPB were included in group A. Thirty-three variables were evaluated with univariate and multivariate analysis to identify the independent variables predictive of higher incidence of early mortality, acute myocardial infarction, cerebrovascular accident, and early major events. RESULTS: Early mortality was 2.2% (group A, 1.4%; group B, 3.0%; p = 0.016), acute myocardial infarction incidence was 1.8% (group A, 1.1%; group B, 2.6%; p = 0.027), cerebrovascular accident incidence was 0.9% (group A, 0.8%; group B, 1.0%; p = not significant), and early major events incidence was 6.7% (group A, 5.3%; group B, 8.2%; p < 0.001). Stepwise logistic regression analysis showed that CPB was an independent risk factor for higher mortality (odds ratio, 2.2; p = 0.0217), higher incidence of acute myocardial infarction (odds ratio, 2.5; p = 0.0185), and higher incidence of early major events (odds ratio, 1.8, p = 0.0034). CONCLUSIONS: When CPB was not used, patients experienced lower early mortality and incidences of acute myocardial infarction were less complicated, both at univariate analysis and stepwise logistic regression analysis.

Radial artery for myocardial revascularization: long-term clinical and angiographic results.

BACKGROUND: To evaluate the long-term clinical and angiographic results of the radial artery (RA) as a graft in coronary artery bypass surgery. METHODS: One hundred sixty-four patients had a RA graft from July 1992 to July 1994. In 128 (group A) the RA was connected end to side (115) or end to end (13) to the left internal mammary artery. In 36 (group B) the proximal anastomosis was on the ascending aorta. RESULTS: Early mortality was 1.8% (group A 1.6% and group B 2.8%). Eight-year survival was 83.2%+/-3.2% (group A 82.1%+/-3.8% and group B 86.7%+/-6.2%, p = not significant [NS]), and event free survival was 80.1%+/-3.5% (group A 79.9%+/-4.4% and group B 80.2%+/-7.3%, p = NS). Sixty-one patients (37.2%) had an early angiography within 90 days from the operation. Patency rate of RA distal anastomoses were 98.9% (88 of 89), 98.7% in group A (77 of 78), 100% in group B (11 of 11; p = NS). After a mean of 48+/-27 months (6 to 96), 72 patients (51.1% of the survivors) had a new angiography. Patency rate of RA distal anastomoses was 95.6% (87 of 91), 93.8% in group A (61 of 65) and 100% in group B (26 of 26; p = NS). All the intermediate RA-LIMA anastomoses were patent at the early and late control. Patency rate for RA and IMAs was similar both early (88 of 89 versus 82 of 82; p = NS) and after 48+/-27 months (87 of 91 versus 93 of 93; p = NS). CONCLUSIONS: Long-term clinical results after RA grafting are satisfying. Angiographic patency rate, both early and after 48 months, is higher than 90% and is similar to that obtained with internal mammary arteries. The site of the proximal anastomosis does not influence early and late patency.

Paclitaxel and docetaxel enhance the metabolism of doxorubicin to toxic species in human myocardium.

Doxorubicin cardiotoxicity is a multifactorial process in which the alcohol metabolite doxorubicinol mediates the transition from reversible to irreversible damage. We investigated whether the tubulin-active taxane paclitaxel increases conversion of doxorubicin to doxorubicinol, thus explaining the high incidence of congestive heart failure when doxorubicin is used with paclitaxel. Specimens of human myocardium from patients undergoing bypass surgery were processed to obtain cytosolic fractions in which doxorubicin was converted to doxorubicinol by NADPH-dependent aldo/keto or carbonyl reductases. In this model, clinically relevant concentrations of paclitaxel (1-2.5 microM) increased doxorubicinol formation by mechanisms consistent with allosteric modulation of the reductases. Stimulation was observed over a broad range of basal enzymatic activity, and was accompanied by a similar pattern of enhanced formation of doxorubicinol aglycone, a metabolite potentially involved in the reversible phase of cardiotoxicity. The closely related analogue docetaxel had effects similar to paclitaxel, but increased doxorubicinol formation over a narrower range of enzymatic activity. The unrelated tubulin-active alkaloid vinorelbine had no effect. These results demonstrate that taxanes have a unique potential for enhancing doxorubicin metabolism to toxic species in human myocardium. The effects on doxorubicinol formation provide clues to explain the clinical pattern of doxorubicin-paclitaxel cardiotoxicity and also caution against the potential toxicity of combining docetaxel with high cumulative doses of doxorubicin.

Mitral valve procedure in dilated cardiomyopathy: repair or replacement?

BACKGROUND: Mitral valve (MV) procedure for dilated cardiomyopathy is becoming popular. We analyzed the indications to MV repair or replacement according to our 10-year experience. METHODS: From January 1990 to May 2000, 49 patients with dilated cardiomyopathy (12 idiopathic and 37 ischemic) underwent MV operation, 29 repair and 20 replacement. Preoperative evaluation included measurement of MV coaptation depth (CD) as a mirror of the abnormalities of MV apparatus leading to functional mitral regurgitation. RESULTS: Thirty-day mortality was 4.2% (2 patients). One-, 3-, 5-, and 10-year actuarial survival was, respectively, 90%, 87%, 78%, and 73%. The possibility of survival with at least one New York Heart Association functional class improvement was 88%, 76%, 71%, and 65%. Return of functional mitral regurgitation after MV repair was nearly inevitable; however, using a scale from 0 to 4, mean postoperative functional mitral regurgitation was 1.2+/-0.8 when preoperative MVCD was 10 mm or less and 2.5+/-0.7 when preoperative MVCD was 11 mm or higher (p < 0.05). Globally, functional results were not influenced by the strategy of treatment (MV repair or replacement). CONCLUSIONS: Mitral valve operation can give satisfying survival and good palliation of dilated cardiomyopathy. The MVCD can be helpful in the choice of the surgical strategy on the MV.

Early clinical experience with a new sutureless anastomotic device for proximal anastomosis of the saphenous vein to the aorta.

BACKGROUND: Avoiding aortic side clamping is useful to avoid local particulate embolization. A device that allows a saphenous vein graft to be anastomosed to the aorta without aortic manipulation is clinically evaluated. METHODS AND RESULTS: From July 1999 to March 2000, 17 patients who underwent myocardial revascularization had an aorta-saphenous vein graft anastomosis performed by means of an aortic anastomotic device. Eight were operated on with cardiopulmonary bypass and 9 without. The proximal anastomoses created by the aortic anastomotic device were performed before the institution of cardiopulmonary bypass or before the related distal anastomosis was performed. In 11 patients transcranial Doppler ultrasound was used. In 1 (6%) patient the saphenous vein graft was not deployed, and in 2 (12%) a single suture was added for minor bleeding. None of the 11 patients evaluated with transcranial Doppler ultrasound had evidence of particulate embolization during the procedure. No patient died or was reoperated on for bleeding. Six (35%) patients had a postoperative angiogram 48 +/- 26 days after the operation that showed widely patent proximal anastomoses. CONCLUSIONS: Use of an aortic anastomotic device allows a sutureless anastomosis to be created between the aorta and saphenous vein graft. The device could be used in totally endoscopic myocardial revascularization. A second-generation device is ready to solve the problems encountered and to increase the ease in handling the device.

Percutaneous interventions on arterial conduits.

Because of the extensive use of arterial conduits for coronary surgery and the increased risk of repeat surgery in cases of graft failure, there is a growing interest in percutaneous interventions (PI) for patients with conduit dysfunction. PI on arterial conduits is a challenge for the interventional cardiologist, due to anatomic and functional characteristics of the graft. There are no large-scale multicenter or randomized studies focusing on PI of arterial conduits. Few single-center experiences are available, and all report short-term encouraging results and < 20% restenosis rates. Procedural failures are mainly due to graft tortuosity or length. Spasm is not rarely reported in muscular conduits. Stents are effective for the treatment of ostial disease and in bail-out cases, but should be cautiously used in anastomotic lesions. In patients with patent internal mammary artery, large pectoralis branches are sometimes considered responsible for steal phenomena, but flow diversion is usually trivial and embolization should be accomplished only after careful functional evaluations. PI can safely be performed on arterial grafts, with careful planning and knowledge of conduit pathophysiology.

Anthracycline metabolism and toxicity in human myocardium: comparisons between doxorubicin, epirubicin, and a novel disaccharide analogue with a reduced level of formation and [4Fe-4S] reactivity of its secondary alcohol metabolite.

Secondary alcohol metabolites have been proposed to mediate chronic cardiotoxicity induced by doxorubicin (DOX) and other anticancer anthracyclines. In this study, NADPH-supplemented human cardiac cytosol was found to reduce the carbonyl group in the side chain of the tetracyclic ring of DOX, producing the secondary alcohol metabolite doxorubicinol (DOXol). A decrease in the level of alcohol metabolite formation was observed by replacing DOX with epirubicin (EPI), a less cardiotoxic analogue characterized by an axial-to-equatorial epimerization of the hydroxyl group at C-4 in the amino sugar bound to the tetracyclic ring (daunosamine). A similar decrease was observed by replacing DOX with MEN 10755, a novel anthracycline with preclinical evidence of reduced cardiotoxicity. MEN 10755 is characterized by the lack of a methoxy group at C-4 in the tetracyclic ring and by intercalation of 2, 6-dideoxy-L-fucose between daunosamine and the aglycone. Multiple comparisons with methoxy- or 4-demethoxyaglycones, and a number of mono- or disaccharide 4-demethoxyanthracyclines, showed that both the lack of the methoxy group and the presence of a disaccharide moiety limited alcohol metabolite formation by MEN 10755. Studies with enzymatically generated or purified anthracycline secondary alcohols also showed that the presence of a disaccharide moiety, but not the lack of a methoxy group, made the metabolite of MEN 10755 less reactive with the [4Fe-4S] cluster of cytoplasmic aconitase, as evidenced by its limited reoxidation to the parent carbonyl anthracycline and by a reduced level of delocalization of Fe(II) from the cluster. Collectively, these studies (i) characterize the different influence of methoxy and sugar substituents on the formation and [4Fe-4S] reactivity of anthracycline secondary alcohols, (ii) lend support to the role of alcohol metabolites in anthracycline-induced cardiotoxicity, as they demonstrate that the less cardiotoxic EPI and MEN 10755 share a reduction in the level of formation of such metabolites, and (iii) suggest that the cardiotoxicity of MEN 10755 might be further decreased by the reduced [4Fe-4S] reactivity of its alcohol metabolite.

Bilateral internal thoracic artery grafting: long-term clinical and angiographic results of in situ versus Y grafts.

BACKGROUND: We evaluated whether bilateral internal thoracic arteries provide the same long-term results when used as in situ grafts and as Y grafts. METHODS AND RESULTS: From October 1991 to February 2000, 1818 patients had bilateral internal thoracic arteries used as in situ (n = 1378, group A) or as Y grafts (n = 440, group B). The number of anastomoses per patient and the number of bilateral internal thoracic artery anastomoses per patient were higher in group B (3.1 +/- 0.9 and 2.7 +/- 0.9) than in group A (2.9 +/- 0.8 and 2.2 +/- 0.6) (both P <.001). The number of right internal thoracic artery anastomoses per patient rose from 1.0 +/- 0. 3 in group A to 1.4 +/- 0.6 in group B (P <.001), and the number of sequential anastomoses per right internal thoracic artery graft rose from 4.1% to 34.3% (P <.001). Thirty-day mortality was 2.0% in group A versus 2.5% in group B (P = not significant). No difference in postoperative course was detected. Eight-year survivals were 95.8% +/- 2.7% in group A versus 94.8% +/- 4.0% in group B (P = not significant), and event-free survivals were 95.2% +/- 2.9% in group A versus 93.6% +/- 4.4% in group B (P = not significant). Early angiograms were obtained in 295 patients (945 anastomoses, 863 distal and 82 proximal Y grafts), 213 patients (611) in group A and 82 patients (334) in group B. Patency rate was 98.8% in group A and 96.0% in group B (P = not significant), whereas grade A patency rate was 97.2% in group A and 96.4% in group B (P = not significant). Late angiograms were obtained in 88 patients (25 in group A and 63 in group B) at a mean of 17.5 +/- 18.4 months: patency rate was 100% in group A and 99.2 in group B (P = not significant), and grade A patency rate was 98.6% in group A and 98.8% in group B (P = not significant). No Y anastomosis was occluded or stenosed. COMMENT: Survival, incidence of cardiac events, and angiographic patency in the early and late phases are similar for bilateral internal thoracic arteries used either in situ or as Y grafts. However, Y grafting with bilateral internal thoracic arteries increases the number of anastomoses per bilateral thoracic artery, as well as the flexibility of the right internal thoracic artery.

Intravascular physiologic evaluation of the left anterior small thoracotomy operation: a novel approach to left anterior descending artery revascularization.

BACKGROUND: Efficacy and long-term patency rate of the left internal mammary artery (LIMA) conduits for revascularization of the left anterior descending coronary artery (LAD) has been demonstrated, with improved results as compared to the saphenous vein graft operation. Novel approaches to LAD revascularization including the use of the left anterior small thoracotomy (LAST) operation with persistence of the intercostal arteries compared to the traditional LIMA operation have not been reported. This study evaluated flow characteristics of LAST operation. METHODS: Phasic blood flow velocity in the proximal and distal arterial conduit segments was measured in 30 patients by intravascular Doppler flow wire after surgical revascularization of the LAD: 15 patients were revascularized by conventional operation using the LIMA (Group A), and 15 patients were submitted to the LAST operation (Group B). All patients underwent coronary angiography and ventriculography at 116 +/- 111 days after operation. Only angiographically normal grafts with normal left ventricular wall motion and coronary arteries free from significant distal stenosis were included for coronary flow velocity and reserve measurements. RESULTS: The diastolic/systolic velocity ratio in the proximal portion of the internal mammary artery was similar in the two groups (Group A 0.8 +/- 0.2 vs Group B 0.7 +/- 0.3, p = NS). Distal diastolic/systolic velocity ratio in Group A (1.7 +/- 0.1) was higher than Group B (0.9 +/- 0.3, p < 0.001). There were no differences in basal average peak velocity or coronary flow reserve between the proximal and distal segments for either groups. CONCLUSIONS: Although proximal phasic coronary flow patterns between the two groups were similar, distal diastolic/systolic velocity ratio was higher in the LIMA than in the LAST. This difference may be related to the persistence of the intercostal artery in the LAST operation. These data confirm the continued patency and similar functional flow patterns compared to the conventional LIMA operation, supporting further investigation and application of this novel approach to LAD revascularization.

Arterial revascularisation with two or more arterial conduits.

In the last decade arterial revascularisation has become more popular due to the routine use of the left internal mammary artery (LIMA). Left internal mammary artery grafting to the left anterior descending (LAD) coronary artery is widely recognised as the most important single determinant of improved results from coronary revascularisation. However, a question remains as to whether results can be further improved by using other arterial grafts in territories other than the LAD, or increasing the number of arterial anastomoses per patient. Although long-term results do not conclusively prove that arterial anastomoses to vessels other than the LAD increase the quality of late results, there are no results to disprove this hypothesis. In our institution we ensure that all mammary grafts are placed on the left coronary system. To achieve this we use skeletonised mammary conduits to increase graft length, and Y grafts to minimise the number of aortic anastomoses. We use the gastroepiploic artery as an in situ graft. With the radial artery we avoid aortic anastomoses by joining the radial artery to the internal mammary artery. With the increased use of skeletonised internal mammary arteries we use the inferior epigastric artery less frequently. This strategy for arterial revascularisation is based on results of 2236 patients undergoing myocardial revascularisation between October 1991 and June 2000. Of these, 75% had total arterial revascularisation where the early mortality was 2% and survival 93% at 7 years. We conclude that total arterial revascularisation using bilateral mammary grafts supplemented by other arterial conduits provides optimal results for myocardial revascularisation.

Off-pump myocardial revascularization using arterial conduits without cardiopulmonary bypass.

OBJECTIVE: The feasibility of myocardial revascularization via a median sternotomy with arterial conduits, without and with cardiopulmonary bypass (CPB), was evaluated. MATERIAL AND RESULTS: From May 21, 1997, to November 30, 1999, 721 patients had myocardial revascularization without CPB via median sternotomy using at least two arterial conduits. The procedure was performed without CPB in 322 patients (Group A); the remaining 399 patients (Group B) underwent the same operation with the aid of CPB. Group A patients were older, with a higher ejection fraction and less redo than Group B. There was no early death in Group A versus nine (2.3%) patients in Group B (p < 0.02). Incidence of cerebrovascular accident (CVA) and acute myocardial infarction (AMI) were similar in both groups. Early major events incidences were 1.2% versus 8.0% (p < 0.001) in Groups A and B, respectively. Postoperative angiographic controls showed a cumulative patency rate of 98.4% and a perfect patency rate of 96.7%. After 30 months, Groups A and B showed an actuarial survival of 98.1 +/- 0.7 and 96.5 +/- 2.8 (p = ns) and an event-free survival of 96.6 +/- 1.0 and 96.5 +/- 2.8 (p = ns), respectively. CONCLUSION: Myocardial revascularization without CPB using arterial conduits can be accomplished with the same quality of results obtained with the use of CPB.

Reoperative coronary surgery with and without cardiopulmonary bypass.

BACKGROUND: Reoperative coronary surgery without cardiopulmonary bypass (CPB) was analyzed to evaluate the technical profile of the patients studied and the benefit from this technique. MATERIAL AND METHODS: From November 21, 1994 to May 20, 1999, 166 patients had reoperative coronary surgery, 112 patients (Group A) with and 54 patients (Group B) without CPB. Median sternotomy was used in all the patients in Group A and in 13 patients in Group B. The remaining had a LAST (37 patients) or a posterolateral thoracotomy (4 patients). RESULTS: Anastomoses per patient were 2.4 +/- 0.8 in Group A and 1.1 +/- 0.4 in Group B (p < 0.001). When a single graft was needed, CPB was not used in 82.8% of the cases. However, when more than one graft was required, CPB was not used in only 5.6% of the cases. When a single territory had to be grafted, CPB was not used in 76.6% of the patients. If two territories were grafted, only 6.8% of the patients were in Group B, whereas no patient who needed a graft in all the three territories was in Group B. Overall mortality was 3.6% cerebrovascular accident (CVA) and acute myocardial infarction (AMI) incidence were 0.6% and 1.8%, respectively, and were similar in both groups. Incidence of early major events (overall 8.4%) was not different between groups. CONCLUSIONS: The primary endpoints (mortality, CVA rate, and AMI) were similar in both groups, but patients in Group B were less complicated. However, patients in the two groups were not the same, as the technical profile was quite different. As our results were similar to those obtained in the first operation, we think that consideration of different surgical possibilities, depending on territory to be grafted, will improve the results of redo coronary surgery, making them similar to those obtained in the first operation.