Robert J.M. Klautz

Restrictive Annuloplasty and Coronary Revascularization in Ischemic Mitral Regurgitation Results in Reverse Left Ventricular Remodeling

Background—Data on combined coronary artery bypass grafting (CABG) and restrictive annuloplasty in patients with ischemic cardiomyopathy are scarce, and the effect on reverse left ventricular (LV) remodeling is unknown. Methods and Results—51 patients with ischemic LV dysfunction (LV ejection fraction 31±8%) and severe mitral regurgitation (grade 3 to 4+) underwent CABG and restrictive annuloplasty with stringent downsizing of the mitral annulus (by 2 sizes, Physio-ring, mean size 28±2). Serial transthoracic echocardiographic studies were performed (before surgery and within 3 months and 1.5 years after surgery) to assess mitral regurgitation, transmitral gradient, leaflet coaptation, and left atrial and LV reverse remodeling. Clinical follow-up (New York Heart Association [NYHA] class, survival, events) was assessed at 2-year follow-up. Early operative mortality was 5.6%; at 2-year follow-up, all patients were free of endocarditis and thromboembolism, and 1 needed re-operation for recurrent mitral regurgitation; 2-year survival was 84%. NYHA class improved from 3.4±0.8 to 1.3±0.4 (P<0.01), with all patients in class I/II. Intraoperative transesophageal echo showed minimal (grade 1+) mitral regurgitation in 8 patients and none in 43, without stenosis. Leaflet coaptation was 0.8±0.2 cm. These values remained unchanged; all patients had no or minimal (grade 1+) mitral regurgitation at 2-year follow-up. LV end-systolic and end-diastolic dimensions decreased from 51±10 to 43±12 mm (P<0.001) and from 64±8 to 58±11 mm (P<0.001). Left atrial dimension decreased from 53±8 to 47±7 mm (P<0.001). Conclusion—Excellent results of combined restrictive annuloplasty and CABG were obtained. Residual mitral regurgitation was absent/minimal at 2-year follow-up, associated with a significant reduction in left atrial dimension and LV reverse remodeling.

Restrictive Mitral Annuloplasty Cures Ischemic Mitral Regurgitation and Heart Failure

BACKGROUNDnRestrictive mitral annuloplasty with revascularization is considered the best approach to ischemic mitral regurgitation with heart failure, but late results are controversial. We report late outcome in relation to preoperative left ventricular end-diastolic diameter (LVEDD) cutoff values, previously identified to predict intermediate-term left ventricular reverse remodeling.nnnMETHODSnOne hundred consecutive ischemic mitral regurgitation patients underwent restrictive mitral annuloplasty (stringent downsizing by two ring sizes; median size, 26) and coronary revascularization. Survivors were clinically and echocardiographically assessed at intermediate (18 months) and late (mean, 46 months) follow-up.nnnRESULTSnEarly mortality was 8%, and late mortality was 18%. Actuarial 1-, 3-, and 5-year survival rates were 87% +/- 3.4%, 80% +/- 4.1%, and 71% +/- 5.1%. Mortality predictors (Cox regression) were preoperative inotropic support (hazard ratio, 6.2; 95% confidence interval, 2.3 to 16.9) and preoperative LVEDD greater than 65 mm (hazard ratio, 4.5; 95% confidence interval, 1.9 to 10.9). Five-year survival rate for patients with LVEDD of 65 mm or less was 80% +/- 5.2%, versus 49% +/- 11% for LVEDD greater than 65 mm (p = 0.002). At 4.3 years follow-up, New York Heart Association functional class had improved from 2.9 +/- 0.8 to 1.6 +/- 0.6 (p < 0.01). Mitral regurgitation grade was 0.8 +/- 0.7, and was less than grade 2+ in 85% of patients. Left ventricular reverse remodeling was sustained with time for the LVEDD of 65 mm or less group. Late deaths did not show intermediate-term systolic left ventricular reverse remodeling, indicating a more extensive intrinsic left ventricular abnormality.nnnCONCLUSIONSnAt 4.3 years follow-up, intermediate-term cutoff values for left ventricular reverse remodeling proved to be predictors for late mortality. For patients with preoperative LVEDD of 65 mm or less, restrictive mitral annuloplasty with revascularization provides a cure for ischemic mitral regurgitation and heart failure; however, when LVEDD exceeds 65 mm, outcome is poor and a ventricular approach should be considered.

Relationship between Brain Blood Flow and Carotid Arterial Flow in the Sheep Fetus

ABSTRACT: The present study investigates whether changes in total brain blood flow can be reliably estimated by changes in carotid arterial blood flow in fetal and perinatal lambs. We therefore compared carotid arterial blood flow, measured with implanted transit-time ultrasound transducers, with brain blood flow, measured by radioactive microspheres in fetal lambs during normal oxygenation and during pulmonary ventilation with oxygen, with Po: ranging from levels normal for the healthy fetus to levels normally seen postnatally. Cerebral perfusion pressure was modified over a wide range to alter brain blood flow: it was decreased by balloon occlusion of the brachiocephalic trunk and increased by a balloon occluder around the aortic isthmus. Carotid arterial blood flow and brain blood flow were closely related (r = 0.97, p < 0.0001). The relationship was not altered at different levels of oxygenation. However, measurements during higher cerebral perfusion pressures, obtained during aortic isthmus occlusion, had a negative influence on the agreement between carotid arterial blood flow and brain blood flow. When excluding values obtained by aortic isthmus occlusion, changes of 20% or more in brain blood flow could be predicted with carotid arterial blood flow within a confidence limit of 95%. Blood flow measurements in the carotid artery may be useful to estimate changes in brain perfusion.

Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair

AIMSnDespite a successful surgical procedure and adherence to current recommendations, postoperative left ventricular (LV) dysfunction after mitral valve repair (MVr) for organic mitral regurgitation (MR) may still occur. New approaches are therefore needed to detect subclinical preoperative LV dysfunction. LV global longitudinal strain (GLS), assessed with speckle-tracking echocardiographic analysis, has been proposed as a novel measure to better depict latent LV dysfunction. The aim of this study was to investigate the value of GLS to predict long-term LV dysfunction after MVr.nnnMETHODS AND RESULTSnA total of 233 patients (61% men, 61 ± 12 years) with moderate-severe organic MR who underwent successful MVr between 2000 and 2009 were included. Echocardiography was performed at baseline and long-term follow-up (34 ± 20 months) after MVr. LV dysfunction at follow-up was defined as LV ejection fraction (EF) <50% and was present in 29 (12%) patients. A cut-off value of -19.9% of GLS showed a sensitivity and specificity of 90 and 79% to predict long-term LV dysfunction. By univariate logistic regression analysis, baseline LVEF ≤60%, LV end-systolic diameter (ESD) ≥40 mm, atrial fibrillation, presence of symptoms, and GLS >-19.9% were predictors of long-term LV dysfunction. By multivariate analysis, GLS remained an independent predictor of LV dysfunction (odds ratio 23.16, 95% confidence interval: 6.53-82.10, P < 0.001), together with LVESD.nnnCONCLUSIONnIn a large series of patients operated within the last decade, MVr resulted in a low incidence of long-term LV dysfunction. A GLS of >-19.9% demonstrated to be a major independent predictor of long-term LV dysfunction after adjustment for parameters currently implemented into guidelines.

Inhibition of the fetal stress response improves cardiac output and gas exchange after fetal cardiac bypass

Cardiac bypass in late-gestation fetal lambs causes severe placental vasoconstriction, which leads to fetal death from hypoxemia and respiratory acidosis. This response can be blocked by the administration of indomethacin; however, a fatal metabolic acidosis then gradually develops in the fetus. Because the fetus is known to mount an intensive catecholamine response to stress, and because the fetal myocardium is particularly sensitive to increased afterload, we hypothesized that elevated afterload as a result of fetal stress contributes to diminished cardiac output after bypass. Twenty fetal lambs at 80% gestation underwent 30 minutes of normothermic cardiac bypass at flow rates of 200 to 500 ml/kg per minute. All ewes received general anesthesia with ketamine. In 10 fetuses general anesthesia was specifically designed not to inhibit the release of stress-related catechols (ketamine); the remaining 10 fetuses received a high (cisterna magna) total spinal anesthetic with tetracaine, to block the fetal stress response. In each anesthetic group, 5 of the 10 lambs received indomethacin. During operation, normal hemodynamics were preserved in the spinal anesthetic group. Cardiac output, placental blood flow, and arterial carbon dioxide tension were all improved relative to results in the ketamine group. When spinal anesthesia and indomethacin are both given, hemodynamics also approach normal after bypass, and gas exchange is further improved. These data suggest that the inhibition of the stress response by spinal anesthesia improves the hemodynamic status of the fetus during operation and, in combination with indomethacin, allows maintenance of near-normal placental function after fetal cardiac bypass. Similar responses may also be possible in human fetuses with use of a high-dose narcotic technique.

Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial §

OBJECTIVEnTranexamic acid has been suggested to be as effective as aprotinin in reducing blood loss and transfusion requirements after cardiac surgery. Previous studies directly comparing both antifibrinolytics focus on high-risk cardiac surgery patients only or suffer from methodological problems. We wanted to compare the effectiveness of tranexamic acid versus aprotinin in reducing postoperative blood loss and transfusion requirements in the patient group representing the majority of cardiac surgery patients: low- and intermediate-risk patients.nnnMETHODSnWe conducted a non-sponsored, double-blind, randomised, placebo-controlled trial in which 298 patients scheduled for low- or intermediate-risk (mean logistic EuroSCORE 4.1) first-time heart surgery with use of cardiopulmonary bypass were randomised to receive either tranexamic acid, high-dose aprotinin, or placebo. All patients had preoperative normal renal function. End points of the study were monitored from the time of surgery until patient discharge. This trial was executed between June 2004 and October 2006.nnnRESULTSnBoth antifibrinolytics significantly reduced blood loss and transfusion requirements when compared with placebo. Aprotinin was about twice as effective as tranexamic acid in reducing total postoperative blood loss (estimated median difference 155 ml, 95% confidence interval (CI) 60-260; p < 0.001). Accordingly, aprotinin reduced packed red blood cell transfusions more than tranexamic acid, although the difference did not reach statistical significance. Only aprotinin significantly reduced the proportion of transfused patients when compared with placebo (mean difference -20.9%, 95% CI 7.3-33.5; p = 0.013), and only aprotinin completely abolished bleeding-related re-explorations (mean difference 6.8%, 95% CI 1.6-13.4%; p = 0.004). Neither antifibrinolytic agent increased the incidence of mortality (mean difference tranexamic acid -0.4%, 95% CI -4.6 to 4.4; p = 0.79, mean difference aprotinin -1.3%, 95% CI -6.2 to 3.5; p = 0.62) or other serious adverse events when compared with placebo.nnnCONCLUSIONnAprotinin has clinically significant advantages over tranexamic acid in patients with normal renal function scheduled for low- or intermediate-risk cardiac surgery.

Interaction Between Afterload and Contractility in the Newborn Heart: Evidence of Homeometric Autoregulation in the Intact Circulation

OBJECTIVESnWe undertook the present study to determine whether afterload and contractility interact in the hearts of newborn lambs. We specifically investigated whether stepwise increases in afterload increase contractility.nnnBACKGROUNDnSeveral studies in the isolated and intact adult dog heart have shown that afterload and contractility are not independent determinants of cardiac performance; rather, they interact. Afterload and contractility are unlikely to interact in the newborn heart because the factors that may mediate the interaction in the adult are missing in the newborn.nnnMETHODSnWe measured contractility at different steady state levels of afterload in seven newborn lambs under complete anesthesia. Contractility was measured by three different indexes: end-systolic pressure-volume relations (slope and volume position); preload-corrected first derivative of left ventricular pressure (dP/dtmax); and preload-corrected stroke work. Left ventricular pressure and volume were measured with a micromanometer and conductance catheter, respectively. Preload and afterload were manipulated by inflating or deflating a balloon catheter in the inferior vena cava and descending thoracic aorta, respectively. Data are expressed as mean value +/- 1 SD.nnnRESULTSnStepwise increases in afterload increased contractility, independent of which of the three indexes was used. The slope of the end-systolic pressure-volume relation increased from a mean baseline value of 4.44 +/- 2.43 to 6.69 +/- 2.89 kPa/ml at the highest level of afterload. Concomitantly, volume at 14 kPa of the end-systolic pressure-volume relation decreased from 3.34 +/- 1.52 ml at baseline to 1.12 +/- 0.83 ml at the highest afterload. The other two indexes showed qualitatively similar changes. Beats selected from unloading interventions on the basis of the same end-diastolic volume for each level of afterload showed no difference in stroke volume.nnnCONCLUSIONSnThis study in newborn lambs demonstrates that stepwise increases in afterload increase contractility considerably and that this enables the heart to maintain stroke volume at different levels of afterload. This forms direct evidence for the existence of homeometric autoregulation in the intact newborn heart.

The Influence of Indomethacin on the Autoregulatory Ability of the Cerebral Vascular Bed in the Newborn Lamb

ABSTRACT: Prevention of hyperperfusion of the brain in the perinatal period has been thought to be an important mechanism by which indomethacin reduces the risk for severe periventricular-intraventricular hemorrhage. The present study investigated whether an indomethacin-induced enhancement of the upper limit of cerebral vascular autoregulatory ability in the neonate contributed to this reduction in cerebral blood flow. In seven anesthetized newborn lambs, we measured temporal blood flow velocity (TMFV) in the carotid artery over a wide range of mean aortic blood pressures (MABP) before and 30 min after an i.v. dose of 1 mg/kg indomethacin. TMFV in the carotid artery was used as an estimate for changes in cerebral blood flow. Stepwise changes in MABP of approximately 10 mm Hg were achieved by progressive balloon occlusion of the thoracic aorta or by progressive bleeding. Multiple linear regression analysis of TMFV versus MABP, indomethacin, and the possible interactive effects confirmed that, at MABP values up to 86 mm Hg, indomethacin lowered TMFV of the carotid artery. Above 86 mm Hg, indomethacin reduced the slope of the TMFV-MABP relationship, indicating an improvement of the autoregulatory ability of the cerebral vascular bed. There was a significant interanimal variability. Thus, indomethacin may reduce the risk for PIVH by limiting cerebral blood flow, especially during increased cerebral perfusion pressures, which often occur after birth asphyxia.

Anatomic correction for transposition of the great arteries: first follow-up (38 patients).

SummaryBetween April 1983 and October 1985, 38 consecutive patients with transposition of the great arteries (TGA) underwent anatomic correction. Ages ranged from 1 day to 284 weeks (mean 26.2 weeks). Simple TGA was present in 17 patients, 17 had an associated ventricular septal defect, and the remaining four had a Taussig-Bing anomaly. Hospital mortality was 2 of 38, with 1 late death. Follow-up time varied from 6 to 35 months. Postoperative cardiac catheterization was performed in 34 of the 36 early survivors. Right ventricular outflow tract obstruction with a systolic gradient >20 mmHg was found in four. A residual left-to-right shunt was found in nine; Qp/Qs exceeded 2.0 in only one. In four, the pulmonary-to-systemic resistance ratio calculated was >0.3. All 35 survivors are in excellent condition. Only one patient has slight aortic insufficiency. Most pre- and postoperative electrocardiographic abnormalities disappeared in due course. Echocardiography revealed normal left ventricular dimensions and fractional shortening. The aortic root diameter showed in almost all a value above the 95th percentile of normal. Postoperatively, the aortic root has grown parallel to, but above, the 95th percentile and as yet has shown no tendency to normalization.

Single-beat estimation of the left ventricular end-diastolic pressure–volume relationship in patients with heart failure

Aims To test a method to predict the end-diastolic pressure–volume relationship (EDPVR) from a single beat in patients with heart failure. Methods and results Patients (New York Heart Association class III–IV) scheduled for mitral annuloplasty (n=9) or ventricular restoration (n=10) and patients with normal left ventricular function undergoing coronary artery bypass grafting (n=12) were instrumented with pressure-conductance catheters to measure pressure–volume loops before and after surgery. Data obtained during vena cava occlusion provided directly measured EDPVRs. Baseline end-diastolic pressure (Pm) and volume (Vm) were used for single-beat prediction of EDPVRs. Root-mean-squared error (RMSE) between measured and predicted EDPVRs, was 2.79±0.21u2005mm Hg. Measured versus predicted end-diastolic volumes at pressure levels 5, 10, 15 and 20u2005mm Hg showed tight correlations (R2=0.69–0.97). Bland–Altman analyses indicated overestimation at 5u2005mm Hg (bias: pre-surgery 44u2005ml (95% CI 29 to 58u2005ml); post-surgery 35u2005ml (23 to 47u2005ml)) and underestimation at 20u2005mm Hg (bias: pre-surgery −57u2005ml (−80 to −34u2005ml); post-surgery −13u2005ml (−20 to −7.0u2005ml)). End-diastolic volumes were significantly different between groups and between conditions, but these differences were not dependent on the method (ie, measured versus predicted). RMSEs were not different between groups or conditions, nor dependent on Vm or Pm, indicating that EDPVR prediction was equally accurate over a wide volume range. Conclusions Single-beat EDPVRs obtained from hearts spanning a wide range of sizes and conditions accurately predicted directly measured EDPVRs with low RMSE. Single-beat EDPVR indices correlated well with directly measured values, but systematic biases were present at low and high pressures. The single-beat method facilitates less invasive EDPVR estimation, particularly when coupled with emerging non-invasive techniques to measure pressures and volumes.