Lawrence S.C. Czer

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy : Role of increased fibrosis in the generation of reentry

OBJECTIVES We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND The role of increased fibrosis in reentry formation during human VF is unclear. METHODS Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Effect of prosthetic aortic valve design on the Doppler-catheter gradient correlation: An in vitro study of normal St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves

To evaluate the normal range of Doppler-derived velocities and gradients, their relation to direct flow measurements and the importance of prosthetic valve design on the relation between Doppler and catheter-derived gradients, five sizes of normal St. Jude bileaflet, Medtronic-Hall tilting disc, Starr-Edwards caged ball and Hancock bioprosthetic aortic valves were studied with use of a pulsatile flow model. A strong linear correlation between peak velocity and peak flow, and mean velocity and mean flow, was found in all four valve types (r = 0.96 to 0.99). In small St. Jude and Hancock valves, Doppler velocities and corresponding gradients increased dramatically with increasing flow, resulting in velocities and gradients as high as 4.7 m/s and 89 mm Hg, respectively. The ratio of velocity across the valve to velocity in front of the valve (velocity ratio) was independent of flow in all St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves when the two lowest flow rates were excluded for Hancock valves. Although Doppler peak and mean gradients correlated well with catheter peak and mean gradients in all four valve types, the actual agreement between the two techniques was acceptable only in Hancock and Medtronic-Hall valves. For St. Jude and Starr-Edwards valves, Doppler gradients significantly and consistently exceeded catheter gradients with differences as great as 44 mm Hg. Thus, Doppler velocities and gradients across normal prosthetic heart valves are highly flow dependent. However, the velocity ratio is independent of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Coronary Artery Bypass Surgery and Percutaneous Drug-Eluting Stent Implantation for Treatment of Left Main Coronary Artery Stenosis

OBJECTIVES The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND Expert guidelines recommend coronary artery bypass graft (CABG) surgery for the treatment of significant stenosis of the unprotected left main coronary artery (ULMCA) if the patient is eligible for CABG; however, treatment by percutaneous coronary intervention (PCI) is common. METHODS Details of patients (n = 343, ages 69.9 +/- 11.9 years) undergoing coronary revascularization for ULMCA stenosis (April 2003 to January 2007) were recorded. A total of 223 patients were treated with CABG (mean [interquartile range]: follow-up 600 [226 to 977) days) and 120 by PCI (follow-up 362 [192 to 586) days). The hazard ratios (HRs) for death and major adverse cardiovascular and cerebrovascular events (MACCE) were calculated incorporating propensity score adjustment. Survival comparisons were conducted in propensity-matched subjects (n = 134), and in low- and high-risk subjects for CABG. RESULTS Patients treated by PCI were more likely to be >or=75 years of age (49% vs. 33%; p = 0.005), and of greater surgical risk (Parsonnet score 17.2 +/- 11.2 vs. 13.0 +/- 9.3; p < 0.001) than patients treated by CABG. Overall, the propensity-adjusted HR for death was not statistically different (HR 1.93, 95% confidence interval [CI] 0.89 to 4.19, p = 0.10), but MACCE was greater in the PCI group (HR 1.83, 95% CI 1.01 to 3.32, p = 0.05). In propensity-matched individuals, neither survival nor MACCE-free survival were different. Survival was equivalent among low-risk candidates, but PCI had a tendency to inferior survival in high-risk candidates (Ellis category IV, log-rank p = 0.05). Interaction testing, however, failed to demonstrate a difference in outcomes of the 2 revascularization techniques as a function of baseline risk assessment. CONCLUSIONS Overall, the propensity-adjusted risk of mortality for treatment of ULMCA disease does not differ between PCI- and CABG-treated groups. There appears to be sufficient equipoise that a randomized clinical trial to compare the techniques would not be ethically contraindicated.

Assessment of aortic stenosis by three-dimensional echocardiography: an accurate and novel approach

Background: Accurate assessment of aortic valve area (AVA) is important for clinical decision-making in patients with aortic valve stenosis (AS). The role of three-dimensional echocardiography (3D) in the quantitative assessment of AS has not been evaluated so far. Objectives: To evaluate the reproducibility and accuracy of real-time three-dimensional echocardiography (RT3D) and 3D-guided two-dimensional planimetry (3D/2D) for assessment of AS, and compare these results with those of standard echocardiography and cardiac catheterisation (Cath). Methods: AVA was estimated by transthoracic echo-Doppler (TTE) and by direct planimetry using transoesophageal echocardiography (TEE) as well as RT3D and 3D/2D. 15 patients underwent assessment of AS by Cath. Results: 33 patients with AS were studied (20 men, mean (SD) age 70 (14) years). Bland–Altman analysis showed good agreement and small absolute differences in AVA between all planimetric methods (RT3D vs 3D/2D: −0.01 (0.15) cm2; 3D/2D vs TEE: 0.05 (0.22) cm2; RT3D vs TEE: 0.06 (0.26) cm2). The agreement between AVA assessment by 2D–TTE and planimetry was −0.01 (0.20) cm2 for 3D/2D; 0.00 (0.15) cm2 for RT3D; and −0.05 (0.30) cm2 for TEE. Correlation coefficient r for AVA assessment between each of 3D/2D, RT3D, TEE planimetry and Cath was 0.81, 0.86 and 0.71, respectively. The intraobserver variability was similar for all methods, but interobserver variability was better for 3D techniques than for TEE (p<0.05). Conclusions: The 3D echo methods for planimetry of the AVA showed good agreement with the standard TEE technique and flow-derived methods. Compared with AV planimetry by TEE, both 3D methods were at least as good as TEE and had better reproducibility. 3D aortic valve planimetry is a novel non-invasive technique, which provides an accurate and reliable quantitative assessment of AS.

Comparison of esmolol and nitroprusside for acute post-cardiac surgical hypertension

Abstract Because acute systemic hypertension early after cardiac surgery has been linked to catecholamine elevation, an open-label, randomized, crossover study was performed to compare the efficacy of esmolol, a new ultra-short-acting intravenous β-blocking agent, to nitroprusside, the standard therapy. Controlled drug infusions to maximal dosage (esmolol, 300 μg/kg/min, and nltroprusside, 10 μg/kg/min) were titrated to achieve at least a 15% reduction in systolic pressure. The blood pressure (BP) endpoint was achieved with esmolol (within 29 ± 14 minutes) in 18 of 20 patients (90%), compared with 19 of 20 (95%) with nitroprusside infusion (within 21 ± 15 minutes, difference not significant [NS]). Systolic BP decreased from 170 ± 13 to 136 ± 12 mm Hg (mean ± standard deviation) with esmolol and from 170 ± 13 to 141 ± 13 mm Hg with nitr roprusside infusion (both p

Use of esmolol in hypertension after cardiac surgery.

Systolic hypertension, which is common soon after cardiac surgery, increases cardiac work and may threaten fresh vascular anastomoses. Because postoperative hypertension is often associated with elevated catecholamines and preoperative use of beta-blocking agents, esmolol, an ultrashort-acting beta-blocking agent, was compared with nitroprusside in a crossover study in this setting. Twelve patients, 18 to 28 hours after cardiac surgery (coronary artery bypass graft in 9, aortic valve replacement in 2 and valved aortic conduit with reimplantation of coronary arteries in 1 patient) received controlled infusions of esmolol (mean dosage 142 +/- 100 micrograms/kg/min, range 50 to 300 micrograms/kg/min) and nitroprusside (mean dose 1.6 +/- 1.3 micrograms/kg/min, range 0.5 to 2.75 micrograms/kg/min). In this open-label study, choice of the first drug was randomized, after which patients were then crossed over to the other study drug. Therapeutic response (greater than or equal to 15% systolic blood pressure reduction) was achieved in 11 of 12 esmolol patients and 12 of 12 nitroprusside patients. Both drugs significantly lowered systolic and diastolic blood pressure, as well as left ventricular stroke work index. While the cardiac index was decreased by esmolol and increased by nitroprusside, neither drug significantly changed stroke volume index. Systemic vascular resistance, unchanged by esmolol, was decreased significantly by nitroprusside. Oxygen saturation and Pao2, unchanged with esmolol, were both significantly reduced with nitroprusside. Thus, for hypertension early after cardiac surgery, esmolol is safe, effective and rapid and, compared with nitroprusside, results in less unwanted decrease in diastolic blood pressure and oxygen saturation, but there is more decrease in heart rate and cardiac index.

A 6 year experience with the St. Jude Medical Valve: Hemodynamic performance, surgical results, biocompatibility and follow-up

After in vitro testing (confirmed in vivo) of three contemporary valve designs (St. Jude, Björk-Shiley and Carpentier-Edwards) demonstrated that the St. Jude valve possessed the most favorable hydrodynamic performance characteristics, a limited clinical trial was begun in high risk patients who might benefit from a prosthesis with improved hemodynamics. Between March 1978 and March 1984, 419 St. Jude prostheses (157 aortic, 156 mitral and 53 double aortic-mitral) were implanted in 366 patients. Ninety-six percent were in New York Heart Association functional class III or IV preoperatively. Early (30 day) mortality was 10.4% overall, and was lower after aortic (5.7%) or double (7.5%) than after isolated mitral valve replacement (16.0%). Forty-four prosthetic mitral valve recipients with severe ischemic mitral regurgitation experienced a 32% early mortality rate; without this group, mitral valve replacement carried a 10% early mortality rate (p less than 0.01). Multivariate logistic regression analysis confirmed that early death was strongly associated with three preoperative patient characteristics (p less than 0.05): ischemic mitral valve disease, depressed left ventricular function (ejection fraction less than 0.55) and advanced functional class (class IV). Late follow-up (7,055 patient-months, mean 22) was 99.7% complete (1 patient lost). Actuarial survival at 4 years was 80, 80 and 79% after aortic, mitral (nonischemic) and double valve replacement, respectively; in the subset with ischemic mitral regurgitation, actuarial survival was 34% (p less than 0.01). Eighty-six percent of survivors were in functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: Series of six patients and review of literature

BACKGROUND Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation. METHODS AND RESULTS The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2 g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7+/-7.5% at baseline to 50.3+/-8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53+/-6% (P not significant versus LVEF at discharge). CONCLUSIONS Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population.

Induction Therapy With Thymoglobulin After Heart Transplantation : Impact of Therapy Duration on Lymphocyte Depletion and Recovery, Rejection, and Cytomegalovirus Infection Rates

BACKGROUND This retrospective single-center study compared lymphocyte depletion in 144 heart transplant recipients using 2 different induction protocols with Thymoglobulin (Genzyme Transplant, Cambridge, MA). METHODS Thymoglobulin (1.5 mg/kg) was given to 105 patients for 7 days (Thymo7) and 39 patients for 5 days (Thymo5). RESULTS Patient clinical characteristics were similar except that the Thymo7 group had a higher prevalence of women (33% vs 15%, p = 0.04), gender mismatch (35% vs 19%, p = 0.07), donor African American race (19% vs 2%, p = 0.008), older donor age (35 +/- 13 vs 31 +/- 12, p = 0.08), and higher pre-transplant creatinine (1.43 +/- 0.67 vs 1.25 +/- 0.48 mg/dl, p = 0.095). Seventy-five percent of the Thymo7 group reached target (absolute lymphocyte count <or=200) and 42% at 21 days (p = 0.002). Thymo7 patients had significantly lower rejection rates (>or=1B) within the first year (7% vs 22%, p = 0.02). No humoral rejection occurred. At 1 year, freedom from rejection was 93% in the Thymo7 group vs 80% in the Thymo5 group (p = 0.007), and cytomegalovirus disease (9% and 5%, p = 0.5) and bacterial infection (26% vs 32%, p = 0.5) were similar. One-year actuarial survival was 92% +/- 3% in the Thymo7 and 100% in the Thymo5 group (p = 0.07), and at 3 years, 85 +/- 4% and 90 +/- 6%, respectively (p = 0.4). CONCLUSIONS Both Thymoglobulin regimens were well tolerated. The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.

Improved left atrial transport and function with orthotopic heart transplantation by bicaval and pulmonary venous anastomoses

Orthotopic heart transplantation (OHT) with bicaval and pulmonary venous anastomoses avoids the large atrial anastomoses of the standard biatrial technique. To determine whether the bicaval technique improves atrial performance, we used Doppler echocardiography to study 13 patients with bicaval OHT, 15 with biatrial OHT, and 8 normal subjects. All were in sinus rhythm and free of rejection. Left atrial size, transmitral (M) and late diastolic (A) mitral flow velocity integrals were measured. Atrial transport (A/M, %) and atrial ejection force (kilodynes, calculated from peak A-wave velocity and mitral orifice area) were assessed. Left atrial dimensions in the bicaval (4.3 +/- 0.5 cm) and biatrial groups (4.9 +/- 0.9 cm) were larger than in controls (3.3 +/- 0.8 cm, p < 0.05). Left atrial transport (37% +/- 12% and 35% +/- 12%) and ejection force (14.1 +/- 6.9 kdyne and 10.2 +/- 7.8 kdyne) were similar in the bicaval group and controls (p not significant) but were significantly lower in the biatrial group (20% +/- 19% and 3.6 +/- 4.0 kdynes, p < 0.05). The bicaval and pulmonary venous technique of OHT produces more physiologic atrial function compared with the biatrial technique as evidenced by greater atrial ejection force and more normal atrial transport.