Stanislaw Wos

Randomized Comparison of Stentless Versus Stented Valves for Aortic Stenosis Effects on Left Ventricular Mass

Background— Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. Methods and Results— The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus ≤25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176±62 and 182±63 g/m2, respectively) or at 6 months (142±49 and 131±45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. Conclusions— Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.

Influence of baseline left ventricular function on the clinical outcome of surgical ventricular reconstruction in patients with ischaemic cardiomyopathy.

AIMS The Surgical Treatment for Ischemic Heart Failure (STICH) trial demonstrated no overall benefit when surgical ventricular reconstruction (SVR) was added to coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy. The present analysis was to determine whether, based on baseline left ventricular (LV) function parameters, any subgroups could be identified that benefited from SVR. METHODS AND RESULTS Among the 1000 patients enrolled, Core Lab measures of baseline LV function with adequate quality were obtained in 710 patients using echocardiography, in 352 using cardiovascular magnetic resonance, and in 344 using radionuclide imaging. The relationship between LV end-systolic volume index (ESVI), end-diastolic volume index, ejection fraction (EF), regional wall motion abnormalities, and outcome were first assessed only by echocardiographic measures, and then by 13 algorithms using a different hierarchy of imaging modalities and their quality. The median ESVI and EF were 78.0 (range: 22.8-283.8) mL/m2 and 28.0%, respectively. Hazard ratios comparing the randomized arms by subgroups of LVESVI and LVEF measured by echocardiography found that patients with smaller ventricles (LVESVI <60 mL/m2) and better LVEF (≥33%) may have benefitted by SVR, while those with larger ventricles (LVESVI >90 mL/m(2)) and lower LVEF (≤25%) did worse with SVR. Algorithms using all three imaging modalities found a weaker relationship between LV global function and the effects of SVR. The extent of regional wall motion abnormality did not influence the effects of SVR. CONCLUSIONS Subgroup analyses of the STICH trial suggest that patients with less dilated LV and better LVEF may benefit from SVR, while those with larger LV and poorer LVEF may do worse. Clinical Trial Registration #: NCT00023595.

Influence of Crossover on Mortality in a Randomized Study of Revascularization in Patients With Systolic Heart Failure and Coronary Artery Disease

Background—To assess the influence of therapy crossovers on treatment comparisons and mortality at 5 years in patients with ischemic heart disease and heart failure randomly assigned to medical therapy alone (MED) or to MED and coronary artery bypass graft (CABG) surgery in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods and Results—The influence of early crossover (within the first year after randomization) on 5-year mortality was assessed using time-dependent multivariable Cox models. CABG was performed in 65/602 patients (10.8%) assigned to MED, and 55/610 patients (9.0%) assigned to CABG received MED only. Common reasons for crossover from MED to CABG were progressive symptoms or acute decompensation. MED-assigned patients who underwent CABG had lower 5-year mortality than those who received MED only (25% vs 42%; hazard ratio, 0.50; 95% confidence interval, 0.30–0.85; P=0.008).The main reason for crossover from CABG to MED was patient/family decision. Five patients did not undergo their assigned CABG within a year but died before receiving surgery without status change. They were deemed crossover to MED. The CABG-to-MED crossover population had higher 5-year mortality compared with those treated with CABG per-protocol (59% vs 33%; hazard ratio, 2.01; 95% confidence interval, 1.36–2.96; P<0.001). CABG was associated with lower mortality compared with MED in per-protocol and several time-dependent analyses (all P<0.05). Conclusions—CABG reduced mortality in both the per-protocol and crossover STICH patient populations. Crossover from assigned therapy, therefore, diminished the impact of CABG on survival in STICH when analyzed by intention to treat. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Comparison of retrograde versus antegrade cold blood cardioplegia: randomized trial in elective coronary artery bypass patients.

OBJECTIVE Myocardial areas distal to complete coronary artery occlusion are poorly protected by antegrade cardioplegia. Hence, retrograde cardioplegia becomes an important adjunct in myocardial protection. An aim of the study was to compare both methods prospectively. METHODS 158 coronary artery bypass grafting (CABG) patients were randomly assigned to two groups according to myocardial protection technique: 89 patients to group 1--retrograde cold blood cardioplegia (RCBC); and 69 patients to group 2--antegrade cold blood cardioplegia (ACBC). Preoperative parameters were similar but cross-clamp time and volume of cardioplegia needed were higher in the retrograde group. The results were assessed on the basis of: (1) clinical outcome; (2) ECG and enzymatic parameters of ischemia; (3) assessment of early systolic function by means of cardiac output (CO), stroke work index (SWI), left ventricular stroke work index (LVSWI) and right ventricular stroke work index (RVSWI) taken before, and 1 and 5 h after coming off bypass; (4) late systolic and diastolic function by echo assessment of segmental contractility of 17 segments and indexes of peak transmitral flow (TMI) taken 7 days and 6 months after operation. RESULTS Ischemic events, inotropes and ventricular fibrillation on reperfusion were significantly more frequent in the antegrade group. Sinus rhythm at an early stage postoperatively was found more frequently in the retrograde group. All these parameters became comparable 24 h after operation. Early myocardial recovery was better in the retrograde group where intraoperative improvement in CO and SWI was significant. At the same time, SWI decreased significantly in the antegrade group. RVSWI changes were similar in both groups. There were no differences in mortality and perioperative MI. Late myocardial performance by segmental contractility and diastolic transmitral flow were similar in both groups. CONCLUSIONS Retrograde continuous blood cardioplegia reduces ischemic injury and permits better early recovery of myocardial function. There is no difference, however, regarding long-term assessment of myocardial recovery.

Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction Results of the Biomarker Substudy of the Surgical Treatment for Ischemic Heart Failure Trials

Background—Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. Methods and Results—In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-&agr; receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: &khgr;2=40.6; P<0.0001 and sTNFR-1: &khgr;2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (&khgr;2=30.3) and sTNFR-1 (&khgr;2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (&khgr;2=6.0; P=0.049) and sTNFR-1 (&khgr;2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ⩽0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions—Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

Diazoxide provides protection to human myocardium in vitro that is concentration dependent

BACKGROUND Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro. METHODS The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation. RESULTS Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation. CONCLUSIONS This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.

Early Regional Assessment of LV Mass Regression and Function after Stentless Valve Replacement: Comparative Randomized Study

Early regional performance and hypertrophy regression after stentless aortic valve replacement are still incompletely characterized. We compared early postoperative changes of segmental thickness and function after stentless and stented aortic valve replacement as assessed by cardiac magnetic resonance (CMR). In 16 patients randomly assigned to stented (Mosaic, 8 patients) and stentless (Freestyle, 8 patients) groups, 4 parallel short-axis images at the level of the apex (slice 4), midventricle (slices 2-3), and mitral valve (slice 1) were obtained with a 1.5 T CMR scanner (Magnetom Sonata, Siemens) before and 1 month after surgery. Cine images were obtained using an echo gradient sequence. Left ventricle mass was calculated as the difference between the left ventricular end-diastolic volume at the epicardial and endocardial borders multiplied by a myocardium density factor (1.05). Each slice was divided into 8 segments (octants) from anterior (octant I-II) to septal (octant V-VIII). A total of 32 segments encompassed the entire heart. From each of these elements end diastolic thickness and systolic function (fractional thickening) were calculated. In stentless valves significant reduction of septal octant thickness on the midventricular slice was noted. There was no difference in regional systolic function-segment thickening. In stented valves no segmental thickness changes were observed. In stentless valves there was early postoperative thickness reduction of septal segments at the midventricular level. However, this finding did not coincide with changes in segmental function.

Gastric tonometry as a method of visceral oxygenation monitoring in patients undergoing coronary revascularisation.

OBJECTIVE The aim of the study was to assess gastric mucosal pH during certain parts of a major cardiac procedure (hypo- and normothermic), and then throughout the first postoperative day. METHODS Gastric mucosal pH was measured using a tonometer, in 15 patients subjected to elective CABG procedures. The patients were also assessed haemodynamically and serum lactate concentrations were measured. RESULTS It was found that cardiopulmonary bypass did not suppress visceral perfusion. The most critical was the period between 4th and 12th postbypass hour when a tendency towards decreased cardiac output and oxygen delivery was noted. At the same time oxygen consumption was increasing which resulted in triggering of anaerobic metabolic pathways, that was mirrored by significant rise in serum lactate levels. During this period of time the lowest, although not critical levels of gastric mucosal pH were recorded, suggesting a relative decrease in splanchnic perfusion. CONCLUSION Extracorporeal circulation does not significantly compromise splanchnic perfusion. Tonometry is a valuable, non-invasive method of visceral oxygenation monitoring. The first postoperative day is an especially critical time for a cardiac patient--a frequent control of haemodynamic and acid-base balance parameters is absolutely mandatory.

Left internal mammary artery improves 5-year survival in patients under 40 subjected to surgical revascularization.

BACKGROUND The population of young patients under 40 requiring coronary bypass surgery is characterized by an extremely and unusually rapid progression of coronary heart disease. The aim of the present study was to assess the clinical status and quality of life in these patients after surgery in relation to the type of conduit used to revascularize the left anterior descending artery (LAD). METHODS One hundred seventeen patients under 40 (range, 30-40 years) underwent coronary artery bypass grafting (CABG) at our institution between 1991 and 1999. Ninety-one patients received LIMA to LAD graft (group A), and in 26 patients the saphenous vein was used to graft this vessel (group B). Seventy-eight patients (63 in group A and 15 in group B) were assessed after a mean time of 71 +/- 26 months. They were asked to fill out a questionnaire aimed at their subjective assessment of their quality of life as compared with their preoperative status. RESULTS Five-year actuarial survival was higher in patients with LIMA to LAD graft (log rank test: P < .004). The functional status of patients in group B was significantly worse in comparison to group A: respectively, CCS 2.2 +/- 1.1 versus 1.5 +/- 0.7; (P = .02), NYHA 2.2 +/- 1.1 versus 1.3 +/- 0.5; (P = .002). Patients in group B more frequently required reinstitution of nitroglycerine treatment (93% versus 56%; P = .025). We failed to show differences between the 2 groups as far as subjective quality of life is concerned. In summary, 63% of patients perceived it to be worse, 29% to be better, and 8% felt it had not changed. CONCLUSION The use of LIMA is crucial in patients undergoing CABG under the age of 40 in order to achieve the best possible surgical results. Quicker recurrence of coronary disease symptoms is observed when a vein is used to graft the LAD. It may reflect an earlier progress of atherosclerosis in venous grafts.

Total arterial revascularization for multiple vessel coronary artery disease: with or without cardiopulmonary bypass.

BACKGROUND To assess the usefulness of off-pump technique for more technically demanding coronary artery bypass procedures using exclusively arterial conduits. METHODS Analysis of perioperative data of 324 consecutive patients in whom total arterial revascularization for multiple- vessel coronary artery disease was performed--181 cases on-pump and 143 cases off-pump. RESULTS On average in the on-pump group 2.7 +/- 0.8 (range, 2-5) grafts per patient were constructed versus 2.4 +/- 0.7 (range, 2-4) grafts per patient in the off-pump group (P < .001). Of the total number of 490 anastomoses performed on-pump, 83 (17%) were side-to-side and of 349 anastomoses performed off-pump, 51(15%) were side-to-side, a nonsignificant difference (P = .4). The aorta was used as a site for proximal anastomosis of 1 or more arterial conduits in 105 patients (58%) who underwent on-pump surgery and in 57 patients (40%) who underwent off-pump surgery (P = .002). In the off-pump group, the right internal thoracic artery (RITA) was rarely (12%) routed through the transverse sinus to circumflex branches compared with the on-pump group (34%) (P = .017). RITA in off-pump patients was more often used to revascularize the anterior wall (47% versus 29%; P = .08). We observed no difference in mortality (1.7% versus 0%; P = .3), incidence of perioperative myocardial infarction (8.8% versus 7.7%; P = .8), stroke (1.7% versus 1.4%; P = .8), or atrial fibrillation (24% versus 19%; P = .3). We observed less inotropic support and less blood-product use in off-pump patients. CONCLUSION Total arterial revascularization for multiple-vessel coronary artery disease may be safely performed off-pump. We observed tendency to somewhat smoother postoperative course in the off-pump group.