Long-term clinical and echocardiographic follow-up of the freestyle stentless aortic bioprosthesis: the Tel Aviv Medical Center experience.

BACKGROUND: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival. OBJECTIVES: To report the outcomes of patients after aortic valve replacement with the Freestyle stentless bioprosthesis at the Tel Aviv Medical Center followed for < or = 15 years. METHODS AND RESULTS: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 +/- 9.2 years, 4.2 +/- 1.5 and 10.2 +/- 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 +/- 29.1 vs. 22.8 +/- 9.6 mmHg, P < 0.0001; and 43.4 +/- 17.2 vs. 12.1 +/- 5.4 mmHg, P < 0.0001 respectively) during 3 months of follow-up. Mean overall follow-up was 4.9 +/- 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 +/- 2.5% and 57.2 +/- 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 +/- 2.3% vs. 76.0 +/- 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 +/- 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one. CONCLUSIONS: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients.

BNT162b2 mRNA COVID-19 vaccine three-dose safety and risk of COVID-19 in patients with myasthenia gravis during the alpha, delta, and omicron waves.

COVID-19 affects the respiratory parenchyma and may potentially contribute to the tendency of myasthenia gravis (MG) patients to develop respiratory failure. It is, therefore, important to study the safety of vaccines against SARS-CoV-2 and to assess the risk of COVID-19 in MG patients. The safety of the three-dose BNT162b2 mRNA vaccine and outcomes of COVID-19 during the alpha, delta, and omicron waves were studied in MG patients as well as the rate of exacerbations and safety for a period of up to 6 weeks from each vaccine dose and patient morbidity and mortality during COVID-19 compared to the general population. 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks of each vaccine dose. Both MG onset rate and exacerbation rate were similar to previous years. MG exacerbation rate among fifteen patients who had COVID-19 was significantly higher (40%) compared to the rate following vaccination. During the alpha and delta waves, COVID-19 mortality and severe disease were significantly higher (26.7%) compared to the general population (0.96%). All of them were unvaccinated and had generalized MG. During the omicron wave, all the MG patients who contracted COVID-19 were vaccinated and had mild disease. We concluded that COVID-19 is hazardous for generalized MG patients, while the vaccination did not raise the risk for either exacerbation or new onset of MG and was associated with a reduced risk for severe COVID-19. Hence, it is recommended for generalized MG patients to get vaccinated.

Low-dose ketamine via intravenous patient-controlled analgesia device after various transthoracic procedures improves analgesia and patient and family satisfaction.

Ketamine was recently shown to attenuate postoperative pain when used in combination with morphine in patients who had undergone general and orthopedic surgery. We assessed its effects in 46 patients undergoing minimally invasive direct coronary artery bypass, off-pump coronary artery bypass, or thoracotomy and correlated them with patient and family satisfaction. Patient-controlled analgesia (PCA) was available for 72 hours. One group received 2mg/bolus morphine randomly and double-blindly (group MO), and another group received 1mg morphine plus 5mg ketamine/bolus (group MK), both using IV-PCA. The patients' pain and satisfaction rates were assessed three times daily during hospitalization using a visual analog scale. Their families' satisfaction was assessed as well. Although the 3-day mean amount of morphine used by the MK patients was approximately 60% of that used by the MO patients, their levels of pain and satisfaction were better than those of the MO group. There was an inverted and statistically significant correlation between the patients' level of satisfaction on the second postoperative day (POD) and the satisfaction of their families on POD 2, 3, and 7 and the POD 3 patients' pain assessment in the MK group but not in the MO group. There were no differences in hemodynamic, respiratory, side effects, or complication rates between the groups. The conclusion is that the effects of adding a small ketamine dose to half of the standard morphine dose via IV-PCA after thoracotomy was superior to the standard morphine dose in terms of the patients' self-reported pain score and satisfaction, as well as the family satisfaction rate.

Single versus bilateral internal thoracic artery grafting in patients with low ejection fraction.

Coronary artery bypass grafting (CABG) is the standard of care for the treatment of complex coronary artery disease. However, the optimal surgical treatment for patients with reduced left ventricular function with low ejection fraction (EF) is inconclusive. In our center, left-sided coronary grafting with bilateral internal thoracic artery (BITA) is generally the preferred method for surgical revascularization, also for patients with low EF. We compared early and long-term outcomes between BITA grafting and single internal thoracic artery (SITA) grafting in patients with low EF.We evaluated short- and long-term outcomes of all patients who underwent surgical revascularization in our center during 1996 to 2011, according to EF ≥30% and <30%. Univariate and multivariate analyses were performed. In addition, patients who underwent BITA and SITA grafting were matched using propensity score matching.In total, 5337 patients with multivessel disease underwent surgical revascularization during the study period. Of them, 394 had low EF. Among these, 188 underwent SITA revascularization and 206 BITA grafting. Those who underwent SITA were more likely to have comorbidities such as chronic obstructive pulmonary disease, diabetes, congestive heart failure, chronic renal failure, and a critical preoperative condition including preoperative intra-aortic balloon pump insertion.Statistically significant differences were not observed between the SITA and BITA groups in 30-day mortality (8.5% vs 6.8%, P = .55), sternal wound infection (2.7% vs 1.0%, P = .27), stroke (3.7% vs 6.3%, P = .24), and perioperative myocardial infarction (5.9% vs 2.9%, P = .15). Long-term survival (median follow up of 14 years, interquartile range, 11.2-18.9) was also similar between the groups. Propensity score matching (129 matched pairs) yielded similar early and long-term outcomes for the groups.This study did not demonstrate any clinical benefit for BITA compared with SITA revascularization in individuals with low EF.

Does bilateral versus single thoracic artery grafting provide survival benefit in female patients?

OBJECTIVES: Bilateral internal thoracic artery (BITA) grafting is associated with improved survival, but this technique is reluctantly used in women due to an increased risk of sternal wound infection. The aim of this study was to compare the long-term survival of women who underwent BITA grafting and single internal thoracic artery (SITA) grafting. METHODS: We performed a retrospective analysis of 556 consecutive female BITA patients and 685 female SITA patients. RESULTS: SITA patients were older and more likely to have comorbidities (diabetes mellitus, chronic lung disease, chronic renal failure, peripheral vascular disease and cerebral vascular disease). Operative mortality showed a trend towards a benefit for BITA (2.9% vs 5.0% for SITA, P = 0.06). The sternal wound infection rates were similar (3.4% vs 2.9%, P = 0.6); however, the occurrence of stroke was significantly lower in the SITA group (3.4% vs 1.2%, P = 0.007). The median survival of the BITA group was significantly better {13.8 years [95% confidence interval (CI) 12.8-14.9] vs 10.3 years [95% CI 9.6-11.1], P = 0.001}. After propensity score matching (491 pairs), the assignment to BITA was not associated with increased early mortality or complication rates, and the choice of BITA grafting was associated with better survival [14.5 years (95% CI 13.3-15.6) vs 11.8 years (95% CI 10.7-12.9)]. Only the choice of conduits was associated with increased late mortality (multivariable analysis, hazard ratio 1.28, 95% CI 1.024-1.591; P = 0.03). CONCLUSIONS: The low early mortality and complication rate, and the long-term survival benefit of BITA compared to SITA grafting, support the use of BITA grafting in women.

Are two internal thoracic grafts better than one in patients with peripheral vascular disease?

BACKGROUND: The use of two bilateral internal thoracic artery grafting (BITA) was shown to lead to survival benefit. However, operators are reluctant to use BITA with peripheral vascular disease (PVD) because of concerns of increased rates of sternal wound infection and lack of studies supporting survival benefit compared with single internal thoracic artery (SITA) grafting. The aim of this study is to compare outcome BITA grafting versus of SITA and vein grafts in PVD patients. PATIENTS AND METHODS: Six hundred and twenty-one PVD patients who underwent BITA between 1996 and 2011 were compared with 372 patients who underwent SITA. RESULTS: SITA patients were older and more likely more likely to have comorbidities (female, insulin-dependent diabetes, chronic obstructive lung disease, congestive heart failure, previous coronary artery bypass grafting, renal insufficiency, cerebrovascular disease, and emergency operation). Operative mortality (5.1 vs. 4.5%, in the SITA and BITA, respectively, P=0.758), rate of sternal wound infection (5.1 vs. 3.9%, P=0.421), and strokes (4.8 vs. 7.4%, P=0.141) were not significantly different between groups. BITA patients did not have significantly better 10-year survival (52.6 vs. 45.9%, P=0.087) and after propensity score matching (302 well-matched pairs), BITA was not associated with improved survival (hazard ratio: 0.902; 95% confidence interval: 0.742-1.283; P=0.784) (Cox model). CONCLUSION: The routine use of BITA versus SITA in PVD patients does not improve long-term survival. Selective use of BITA in lower risk patients might unmask the benefits of BITA.

Are two internal thoracic grafts better than one in patients with chronic obstructive lung disease? Analysis of 387 cases between 1996-2011.

OBJECTIVES: Bilateral internal thoracic artery (ITA) grafting is associated with improved survival. However, potential survival benefit of using two ITA`s in patients with chronic lung disease (CLD) is questionable due to their increased risk of sternal wound infection (SWI) compared to operations incorporating single ITA (SITA). The purpose of this study is to compare early and long-term outcome of bilateral internal thoracic artery (BITA) grafting to that of grafting with single internal thoracic grafts and vein grafts or radial artery (SITA) in CLD patients with multi-vessels coronary disease. METHODS: One hundred and forty eight CLD patients who underwent BITA between 1996 and 2011 were compared with 239 who underwent SITA at the same period. RESULTS: SITA patients were more often female, more likely to have insulin treated diabetes (DM), DM with end organ damage, neurologic dysfunction and unstable angina. Despite of the difference in preoperative characteristics, early mortality (5.4% vs. 5.4%, in the SITA and BITA respectively, p = 0 < .999) and occurrences of SWI (6.3% vs 9.5%, p = 0.320) and strokes (3.8% vs 5.4%,p = 0.611) were not significantly different between groups. BITA patients did not have better Kaplan-Meier 10 year survival (52.8% vs. 42.6%, p = 0.088) and after matching, BITA and SITA had similar adjusted survival (HR 0.983[95%CI 0.755-1.280] p = 0.901) (cox model). CONCLUSION: Our study results suggest that in patients with CLD, the choice of BITA grafting technique did not provide survival benefit compared to SITA with other conduits.

Correction: Are two internal thoracic grafts better than one in patients with chronic obstructive lung disease? Analysis of 387 cases between 1996-2011.

[This corrects the article DOI: 10.1371/journal.pone.0201227.].

Should Bilateral Internal Thoracic Artery Grafting Be Used in Patients After Recent Myocardial Infarction?

BACKGROUND: Bilateral internal thoracic artery grafting (BITA) is associated with improved survival. However, surgeons do not commonly use BITA in patients after myocardial infarction (MI) because survival is good with single internal thoracic artery grafting (SITA). We aimed to compare the outcomes of BITA with those of SITA and other approaches in patients with multivessel disease after recent MI. METHODS AND RESULTS: In total, 938 patients with recent MI (<3 months) who underwent BITA between 1996 and 2011 were compared with 682 who underwent SITA. SITA patients were older and more likely to have comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, peripheral vascular disease), to be female, and to have had a previous MI. Acute MI and 3-vessel disease were more prevalent in the BITA group. Operative mortality of BITA patients was lower (3.0% versus 5.8%, P=0.01), and sternal infections and strokes were similar. Median follow-up was 15.21 years (range: 0-21.25 years). Survival of BITA patients was better (70.3% versus 52.5%, P<0.001). Propensity score matching was used to account for differences in preoperative characteristics between groups. Overall, 551 matched pairs had similar preoperative characteristics. BITA was a predictor of better survival in the matched groups (hazard ratio: 0.679; P=0.002; Cox model). Adjusted survival of emergency BITA and SITA patients was similar (hazard ratio: 0.883; P=0.447); however, in the nonemergency group, BITA was a predictor of better survival (hazard ratio: 0.790; P=0.009; Cox model). CONCLUSIONS: This study suggests that survival is better with BITA compared with SITA in nonemergency cases after recent MI, with proper patient selection.

One or Two Internal Thoracic Grafts? Long-Term Follow-Up of 957 Off-Pump Coronary Bypass Surgeries.

BACKGROUND: The potential survival benefit of bilateral internal thoracic artery (BITA) grafting in patients undergoing off-pump coronary artery bypass graft surgery (OPCABG) is controversial owing to the technical complexity of these operations. Our objective was to compare the outcome of patients undergoing OPCABG with BITA to the outcome of patients undergoing OPCABG with a single internal thoracic artery (SITA) and saphenous vein grafts or radial artery. METHODS: Five hundred and thirty-five consecutive patients who underwent OPCABG BITA at our institute between 2000 and 2008 were compared with 422 patients who underwent OPCABG with SITA. Propensity score matching was used to account for differences between groups in preoperative characteristics. RESULTS: Being female (20.9% versus 36.0%, p < 0.001), having diabetes mellitus (36.6% versus 55.7%, p > 0.001), recent myocardial infarction (23.6% versus 33.2%, p > 0.001), aged 70 years or more (41.1% versus 49.8%, p = 0.001), peripheral vascular disease (26.1% versus 46.7%, p > 0.001), and chronic renal failure (7.9% versus 15.9%, p > 0.001) were less frequent in the BITA group than in the SITA group, respectively. The European System for Cardiac Operative Risk Evaluation score was significantly higher for the SITA group (7.62, versus 5.46 for BITA group, p = 0.001), whereas operative mortality (1.7% BITA versus 2.6% SITA) and sternal wound infections (1.7% BITA versus 2.1% SITA) were similar. The mean follow-up was 11.6 ± 3.5 years. The BITA patients' 10-year survival (Kaplan-Meier) was better (72.2% versus 55.1% for SITA, p > 0.001). However, after propensity matching, survival for BITA and SITA were similar. CONCLUSIONS: This large cohort study suggests that long-term outcomes for patients undergoing OPCABG are not better with BITA grafting.

Comparison of radial and bilateral internal thoracic artery grafting in patients with peripheral vascular disease†.

OBJECTIVES: The composite T-graft with radial artery (RA) attached end-to-side to the left internal thoracic artery (ITA) provides arterial myocardial revascularization without the increased risk of deep sternal wound infection associated with harvesting 2 ITAs. However, many surgeons are reluctant to use RA in patients with peripheral vascular disease (PVD) due to concerns regarding the quality of the conduit in this subset of patients. The purpose of this study is to compare early- and long-term outcomes of arterial grafting with bilateral ITAs (BITA) to that of single ITA and RA in patients with PVD. METHODS: Between 1999 and 2010, 619 consecutive patients with PVD (500 BITAs and 119 single ITA and RA) underwent myocardial revascularization in our institution. RESULTS: Occurrence of following risk factors as female sex, age 70+, diabetes, unstable angina, emergency operation, cerebrovascular disease and chronic obstructive pulmonary disease was higher in the RA-ITA group. The RA-ITA group also had a higher logistic EuroSCORE (22.1 vs 13.3). Operative mortality and occurrence of deep sternal wound infection of the two groups was similar (4.2% vs 5.0% and 2.5% vs 4.0% for the radial and bilateral ITA, respectively). Median follow-up was 9.75 years. Unadjusted Kaplan-Meier 10-year survival of the two groups was similar (44.1% vs 49.6%, P = 0.7). After propensity score matching (100 pairs), assignment to BITA was not associated with better adjusted survival (hazard ratio 0.593, 95% confidence interval 0.265-1.327, P = 0.20, Cox model). CONCLUSIONS: In patients with PVD, complete arterial revascularization with left ITA and RA can be justified with regards to survival.

Impact of left ventricular filling parameters on outcome of patients undergoing trans-catheter aortic valve replacement.

AIM: To assess the impact of left ventricular (LV) filling parameters on outcomes following trans-catheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 526 TAVR patients were compared with 300 patients with severe aortic stenosis (AS) treated conservatively. Clinical variables were collected along with echocardiographic data at baseline, 1 month, and 6 months after study entry. End points included all-cause mortality and the combination of death and heart failure admission. LV filling parameters associated with mortality included reduced A wave velocity (P = 0.005) and shorter deceleration time (DT) (P = 0.0005). DT was superior to all other parameters (P = 0.05) apart from patients with atrial fibrillation in whom E/e' was better. Short DT (<160 ms) was associated with lower survival than long DT (≥220 ms; P = 0.002) or intermediate DT (P = 0.05), even after adjustment for age, gender, stroke volume index (SVI), and co-morbidities. However, patients with short baseline DT exhibited greater improvement in DT, E/A, and systolic pulmonary pressure at follow-up than patients with baseline DT ≥160 ms (P < 0.05 for all time x group interactions). Most importantly, among patients with short DT, TAVR was associated with better survival than conservative treatment (46 ± 7 vs. 28 ± 12% at 3 years, P = 0.05), even after adjustment for age, gender, and SVI (P = 0.05). CONCLUSION: Short DT is an independent predictor of adverse outcome following TAVR. Nevertheless, LV filling parameters improve in most patients post TAVR, and TAVR is associated with improved survival compared with conservative therapy, even in patients with evidence of elevated LV filling. Thus, evidence of elevated LV filling should not be viewed as a contraindication for TAVR.

Long-term outcome of revascularization with composite T-grafts: Is bilateral mammary grafting better than single mammary and radial artery grafting?

OBJECTIVE: Bilateral internal mammary artery (BIMA) grafting is associated with improved survival. However, many surgeons are reluctant to use this technique, owing to the potentially increased risk of sternal infection. The composite T-graft with radial artery (RA) attached end-to-side to the left internal mammary artery (IMA) provides complete arterial revascularization without increased risk of sternal infection. The purpose of this study is to compare outcomes of these 2 strategies. METHODS: Patients who underwent BIMA grafting using the composite T-graft technique, between 1996 and 2010 (n = 1329), were compared with 389 patients who underwent composite grafting with a single IMA + RA during the same time period. RESULTS: Patients undergoing single IMA grafting were older, more often women, and more likely to have diabetes, peripheral vascular disease, and COPD, and to need an emergency operation. Congestive heart failure, left main disease, and recent myocardial infarction were more prevalent with bilateral grafting. Propensity-score matching was used to account for differences between groups in preoperative patient characteristics. The 268 matched pairs had similar characteristics. The median follow-up time was 14.19 (95% confidence interval 13.43-14.95) years. Operative mortality and Kaplan-Meier 10-year survival of the 2 matched groups were similar (3.4% vs 3.7%, and 61.6% vs 64%, for the groups treated with BIMA and single IMA, respectively). Cox-adjusted survival was similar (P = .514). Age, chronic renal failure, and performance of <3 bypass grafts were independent predictors of decreased survival. CONCLUSIONS: This study suggests that long-term outcomes of arterial revascularization with a composite T-graft constructed using left IMA and RA are not inferior to outcomes after BIMA grafting.

Effect of tumor necrosis factor-alpha on endothelial and inducible nitric oxide synthase messenger ribonucleic acid expression and nitric oxide synthesis in ischemic and nonischemic isolated rat heart.

OBJECTIVES: The present study aimed to investigate the influence of endogenous tumor necrosis factor-alpha (TNF-alpha) that was synthesized during ischemia and exogenous TNF-alpha on endothelial and inducible nitric oxide synthase (eNOS and iNOS) messenger ribonucleic acid (mRNA) expression and nitric oxide (NO) production in the isolated rat heart. BACKGROUND: Tumor necrosis factor-alpha is recognized as being a proinflammatory cytokine with a significant cardiodepressant effect. One of the proposed mechanisms for TNF-alpha-induced cardiac contractile dysfunction is increased NO production via iNOS mRNA upregulation, but the role of NO in TNF-alpha-induced myocardial dysfunction is highly controversial. METHODS: Isolated rat hearts studied by a modified Langendorff model were randomly divided into subgroups to investigate the effect of 1-h global cardioplegic ischemia or the effect of 1-h perfusion with exogenous TNF-alpha on the expression of eNOS mRNA and iNOS mRNA and on NO production. RESULTS: After 1 h of ischemia, there were significant increases in TNF levels in the effluent (from hearts), and eNOS mRNA expression had declined (from 0.91 +/- 0.08 to 0.68 +/- 0.19, p < 0.001); but there were no changes in iNOS mRNA expression, and NO was below detectable levels. Perfusion of isolated hearts with TNF-alpha had a cardiodepressant effect and decreased eNOS mRNA expression to 0.67 +/- 0.04 (p < 0.002). Inducible nitric oxide synthase mRNA was unchanged, and NO was below detectable levels. CONCLUSIONS: We believe this is the first study to directly show that TNF-alpha does not increase NO synthesis and release but does downregulate eNOS mRNA in the ischemic and nonischemic isolated rat heart.

Use of intraoperative epiaortic ultrasonography to delineate aortic atheroma.

OBJECTIVE: A cerebrovascular accident (CVA) is a devastating complication of coronary artery bypass grafting (CABG) and a major cause for morbidity and mortality. Aortic manipulation, cannulation, and clamping during CABG may lead to release of atheromatous material from the ascending aorta, which may cause a CVA. This study assessed the hypothesis that the use of intraoperative epiaortic ultrasonography (EAUS) would supplement imaging information with that derived from manual aortic palpation and influence the surgical decision-making approach accordingly. METHODS: After undergoing a mid-sternotomy for CABG, 105 patients underwent EAUS with an 8-MHz transducer ordinarily used for conventional transthoracic echocardiography. The surgical strategy was decided on at three stages: preoperatively, after manual aortic palpation, and following EAUS. RESULTS: The preoperative strategy had assigned 105 patients to the "touched aorta" group that was planned for either on-pump or off-pump CABG (OPCAB) with proximal anastomosis to the aorta. Pathologic lesions of the atheromatotic ascending aorta were evident in 40 patients (38%), with the lesions detected in 22 patients (21%) by both palpation and EAUS, and in 18 patients (17%) by EAUS alone. The planned surgical strategy was changed in 29 patients (28%): 25 patients (24%) were converted from on-pump CABG to OPCAB, and the EAUS influenced the choice of the aortic cannulation, cross-clamping, and proximal anastomosis site in 4 patients (4%). Among the changes in surgical decision making, changes in 11 patients (10%) were based on lesion detection by both manual palpation and EAUS; in 18 patients (17%), changes resulted from pathologic evidence provided by EAUS alone. CONCLUSIONS: This study showed EAUS to be more sensitive in detecting atherosclerotic lesions than manual intraoperative palpation of the ascending aorta. This investigation contributes new data on the effect of EAUS on intraoperative surgical approach in the era of OPCAB. The use of EAUS has emerged as an important tool in intraoperative decision making, and we recommend its use routinely in CABG procedures.

Thermo-wrap technology preserves normothermia better than routine thermal care in patients undergoing off-pump coronary artery bypass and is associated with lower immune response and lesser myocardial damage.

OBJECTIVE: Perioperative hypothermia might be detrimental to the patient undergoing off-pump coronary artery bypass surgery. We assessed the efficacy of the Allon thermoregulation system (MTRE Advanced Technologies Ltd, Or-Akiva, Israel) compared with that of routine thermal care in maintaining normothermia during and after off-pump coronary artery bypass surgery. METHODS: Patients undergoing off-pump coronary artery bypass surgery were perioperatively and randomly warmed with the 2 techniques (n = 45 per group). Core temperature, hemodynamics, and troponin I, interleukin 6, interleukin 8, and interleukin 10 blood levels were assessed. RESULTS: The mean temperature of the patients in the Allon thermoregulation system group (AT group) was significantly ( P < .005) higher than that of the patients receiving routine thermal care (the RTC group); less than 40% of the latter reached 36 degrees C compared with 100% of the former. The cardiac index was higher and the systemic vascular resistance was lower ( P < .05) by 16% and 25%, respectively, in the individuals in the AT group compared with in the individuals in the RTC group during the 4 postoperative hours. End-of-surgery interleukin 6 levels and 24-hour postoperative troponin I levels were significantly ( P < .01) lower in the patients in the AT group than in the RTC group. The RTC group's troponin levels closely correlated with their interleukin 6 levels at the end of the operation ( R = 0.51, P = .002). CONCLUSIONS: Unlike routine thermal care, the Allon thermoregulation system maintains core normothermia in more than 80% of patients undergoing off-pump coronary artery bypass surgery. Normothermia is associated with better cardiac and vascular conditions, a lower cardiac injury rate, and a lower inflammatory response. The close correlation between the increased interleukin 6 and troponin I levels in the routine thermal care group indicates a potential deleterious effect of lowered temperature on the patient's outcome.

Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis.

OBJECTIVE: Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion. METHODS: Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion. RESULTS: Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s, P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03, P=0.2), while further increase was observed in the control group (from 1.0+/-0.1 to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart effluent in the control group was increased during reperfusion (79+/-30 and 200+/-22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked TNF-alpha immunostaining of left ventricular tissue was observed only in the control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A treated group at 40 min of reperfusion. CONCLUSION: Monophosphoryl lipid A-induced preconditioning renders the heart more tolerant to ischemia-reperfusion in terms of left ventricular diastolic and systolic function, and prevents tumor necrosis factor-alpha production during ischemia, through aborting the translation phase of tumor necrosis factor-alpha synthesis.

Added value of pulmonary venous flow Doppler assessment in patients with preserved ejection fraction and its contribution to the diastolic grading paradigm.

AIMS: To evaluate the prognostic role of pulmonary venous flow parameters and their role in patients with preserved ejection fraction (EF). METHODS AND RESULTS: Pulmonary venous flow parameters were measured in 365 patients in sinus rhythm, without significant mitral disease, and EF >50% (age 64.9 ± 19; 52% female) by a single sonographer. Survival, time to re-admission for heart failure, and to a combined cardiac end point (cardiac death, heart failure, and atrial fibrillation) were retrospectively analysed and correlated to echo parameters. Systolic (S) and diastolic (D) pulmonary vein flow were obtainable in 73% of patients and Ar in 65%. The lower peak S/D ratio and higher ΔAr-A time were associated with higher rate of heart failure readmission (P = 0.03 for both). The S/D integral ratio was the best pulmonary vein flow predictor of heart failure readmissions (P = 0.0009), better than the peak S/D ratio, or ΔA-Ar time (P < 0.01 for both), and independently predicted worse outcome even when adjusted for diastolic grading (using recent guidelines), left ventricle mass index, E/e', and left atrial volume index (P < 0.05 for all). The addition S/D ratio to diastolic grading recognized patients with pseudo-normal filling pattern and S/D ratio >1 with similar clinical outcomes to grade I (P > 0.5), but worse clinical outcomes than in the pseudo-normal patients with lower S/D ratio (P < 0.01). CONCLUSIONS: PVFP are obtainable in most patients, add prognostic information on top of routine diastolic parameters, and define an early stage of diastolic dysfunction resembling the pseudo-normal pattern in which S/D ratio is >1, and outcome is excellent.

Determinants of Effort Intolerance in Patients With Heart Failure: Combined Echocardiography and Cardiopulmonary Stress Protocol.

OBJECTIVES: The purpose of this study was to assess individual mechanisms of effort intolerance in patients with heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or normal cardiac function using combined echocardiography and cardiopulmonary stress testing. BACKGROUND: Combined stress echocardiography and cardiopulmonary tests visualize cardiac chambers in 4 well-defined activity levels (rest, unloaded, anaerobic threshold, and peak), allowing noninvasive assessment of cardiac function, hemodynamics, and arterial venous oxygen content difference (AVo(2)Diff) during all stages. METHODS: Left ventricular volumes, stroke volume (SV), S', E/e', oxygen consumption (Vo(2)), and AVo(2)Diff were measured in all effort stages using ramp semirecumbent cycle prolonged (≥8 min) exercise in 45 consecutive subjects evaluated for effort intolerance (14 normal cardiac function, 16 HFpEF, and 15 HFrEF patients; age 56.5 ± 16 years; 73% male). RESULTS: In HFpEF and HFrEF, the changes in Vo2 were attenuated (between group p = 0.003; group by time interaction p < 0.0001), as well as peak heart rate (p = 0.0001; p = 0.0001) and SV (p = 0.006; p = 0.0001). End-diastolic volume to E/e' ratio (measure of compliance) was superior in HFrEF and normal patients at baseline but worsened in HFpEF and HFrEF at peak exercise (8.3 ± 4 vs. 11.6 ± 5 vs. 19.1 ± 8; p = 0.004; p = 0.01). Functional mitral regurgitation worsened even during the unloaded stage, mostly in patients with HFrEF, but also in several patients with HFpEF. In multivariable analysis, heart rate response (p = 0.007), and AVo(2)Diff (p < 0.0001) were the most significant independent predictors of effort capacity; SV was not. CONCLUSIONS: Combined tests are feasible and allow noninvasive evaluation of effort intolerance. In HFpEF and HFrEF patients, exercise intolerance is predominantly due to chronotropic incompetence and peripheral factors. Combined stress echocardiography and cardiopulmonary tests may have potential for clinical management and selection of patients for trials.

Bilateral internal thoracic artery grafting in diabetic patients: short-term and long-term results of a 515-patient series.

BACKGROUND: Despite potential long-term benefits, bilateral internal thoracic artery grafting in diabetics remains controversial because of the risk of sternal infection. We sought to assess the short- and long-term outcome after left-sided bilateral internal thoracic artery grafting and to determine the configuration of choice in diabetic subsets. METHODS: Between 1996 and 2001, 515 diabetics underwent isolated left-sided skeletonized bilateral internal thoracic artery grafting. The outcome of 468 consecutive oral-treated diabetics and 47 selective insulin-treated patients was analyzed. Patients undergoing T-grafting were compared with those undergoing in situ bilateral internal thoracic artery arrangements. RESULTS: The respective rates for early mortality and sternal infections were 2.4% and 1.9% in oral-treated diabetics and 6.3% and 4.3% in insulin-treated diabetics. Multivariate correlates of sternal infection were chronic lung disease (odds ratio, 10), obesity (odds ratio, 7), reoperation (odds ratio, 22), and a creatinine level of 2 mg/dL or more (odds ratio, 8). Five-year survival was 82%. The T-graft (n = 437) and in situ (n = 162) subgroups had comparable baseline profiles. Freedom from cardiac mortality at 6.5 years was 95.6% and 87.6% (P =.277), and freedom from repeat revascularization was 91.5% and 92.7% (P =.860), respectively. The choice of bilateral internal thoracic artery configuration did not appear as a correlate of mortality, cardiac mortality, or major adverse cardiac events. Complementary right-sided gastroepiploic artery (hazard ratio, 0.36) and sequential (hazard ratio, 0.55) grafting were identified as protective factors against the occurrence of major adverse cardiac events. CONCLUSIONS: Routine skeletonized bilateral internal thoracic artery grafting can be implemented safely in oral-treated diabetics. This strategy is associated with a favorable late cardiac outcome and is thus recommended. Both left-sided bilateral internal thoracic artery configurations provide comparable short- and long-term outcomes.