Quantification of myocardial iron deposition by two-dimensional speckle tracking in patients with ß-thalassaemia major and Blackfan-Diamond anaemia.

BACKGROUND: Cardiac disease related to transfusional iron overload is the leading cause of death in patients with ß-thalassaemia major. Early myocardial iron deposition predates decreased left ventricular dysfunction and currently is best assessed by cardiac magnetic resonance. METHODS: Echocardiographic speckle tracking-derived myocardial mechanics were compared with cardiac MRI T2 star (T2*) calculations in 45 chronically transfused patients with ß-thalassaemia major or Diamond-Blackfan anaemia (26 retrospectively and an additional 19 for validation). Two groups were studied: patients with presumed cardiac iron overload and interventricular T2* value ≤20 ms (low T2*) and patients with >20 ms (normal T2*). They were compared with a normal control group of 18 age- and gender-matched patients. RESULTS: Patients with low T2* had a uniform decrease in longitudinal and circumferential strain compared with normal controls (-16±3% vs -20±3% and -20±4% vs -23±5%, respectively; p<0.0005). Peak twist and peak apical rotation were lower in patients with low T2* than in those with normal T2* or normal control patients. Conversely, no significant difference was observed between patients with normal T2* and controls. There was a strong and direct logarithmic correlation between average global longitudinal strain and T2* values (r=-0.68, p=0.0007). Using a cut-off of ≤-17%, global longitudinal strain predicted a T2* value of <20 ms with a sensitivity of 76% and a specificity of 88%. CONCLUSION: Myocardial mechanics offers a simple alternative to cardiac MRI for assessing significant myocardial iron deposition.

Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis.

OBJECTIVES: To assess patients with different types of mutations of the beta myosin heavy chain (beta MHC) gene causing hypertrophic cardiomyopathy (HCM) and to determine the prognosis of patients according to the affected functional domain of beta MHC. DESIGN AND SETTING: Cohort study of subjects referred to an HCM clinic at an academic hospital. PATIENTS: 70 probands from the HCM clinic were screened for mutations of the beta MHC gene and 148 family members of the genotype positive probands were further assessed. The control group for the genetic studies consisted of 106 healthy subjects. MAIN OUTCOME MEASURES: Direct DNA sequencing was used to screen 70 probands for mutations of the beta MHC gene. Family members underwent genotypic and detailed clinical, ECG, and echocardiographic assessments. The survival of genotype positive subjects was evaluated according to the type of functional domain affected by the missense mutation and according to phenotypic characteristics. RESULTS: A mutation of the beta MHC gene was detected in 15 of 70 probands (21%). Of 148 family members studied in these 15 families, 74 were identified with a beta MHC defect. Eleven mutations were detected, including four novel mutations: Ala196Thr, Pro211Leu, Val404Leu, and Arg870Cys. Median survival was 66 years (95% confidence interval (CI) 64 to 77 years) in all affected subjects. There was a significant difference in survival between subjects according to the affected functional domain (p = 0.02). Significant independent predictors of decreased survival were the non-conservative (that is, associated with a change in the amino acid charge) missense mutations that affected the actin binding site (hazard ratio 4.4, 95% CI 1.6 to 11.8; p = 0.003) and those that affected the rod portion of beta MHC (hazard ratio 4.8, 95% CI 1.2 to 19.4; p = 0.03). No phenotypic characteristics were associated with decreased survival or cardiovascular morbidity. CONCLUSIONS: The type of beta MHC functional domain affected by the missense mutation is predictive of overall prognosis in HCM.

Contrast-enhanced quantitation of left ventricular ejection fraction: what is the best method?

The need to enhance the echocardiographic determination of left ventricular ejection fraction (LVEF) is greatest in patients with suboptimal images. We have previously demonstrated that in difficult-to-image patients, contrast-enhanced power harmonic imaging resulted in accurate calculation of LVEF by using Simpson's method. However, the incremental accuracy of contrast enhancement with other methods of determining LVEF has not been examined. This study prospectively assessed the comparative accuracy of LVEF determination by using the Quinones' method with fundamental imaging (FU), tissue harmonic imaging (TH), contrast-enhanced harmonic imaging [TH(CON)], as well as Quinones' method with contrast-enhanced power harmonic imaging [POW(QUIN)] in 62 patients with suboptimal images. LVEF was also calculated by using contrast-enhanced power harmonic imaging and Simpson's method [POW(SIMP)] in these patients. We demonstrated that LVEF calculated from the POW(QUIN) mode had the best agreement with radionuclide angiography (standard of comparison) compared with FU, TH, and TH(CON). However, POW(SIMP) was even more accurate. In conclusion, when the Quinones' method was used to calculate LVEF in difficult-to-image patients, POW(QUIN) mode was the most accurate. However, POW(SIMP) was even more accurate and should be the method of choice when a high degree of quantitative accuracy is required.

Dilation of the sinotubular junction causes aortic insufficiency after aortic valve replacement with the Toronto SPV bioprosthesis.

OBJECTIVE: This study was undertaken to examine the causes of late aortic insufficiency in patients who had aortic valve replacement with the Toronto SPV bioprosthesis (St Jude Medical, Inc, St Paul, Minn). METHODS: From 1991 to 1996, 174 patients with a mean age of 63 +/- 11 years underwent aortic valve replacement with the Toronto SPV bioprosthesis and were evaluated annually by Doppler echocardiographic studies to assess valve function. The diameters of the aortic root were retrospectively measured in all patients who had aortic insufficiency and also in a random sample of 23 patients without aortic insufficiency. The mean follow-up was 5.8 years (range 4 to 9 years). RESULTS: Aortic insufficiency greater than 1+ developed in 19 patients. The diameter of the sinotubular junction increased in these patients and did not change in those without aortic insufficiency. The ratio between the diameter of the sinotubular junction and the size of the Toronto SPV bioprosthesis increased in patients who had aortic insufficiency and did not change in those without aortic insufficiency. Both 2-way analysis of covariance and analysis by a mixed linear model demonstrated a significant difference in slopes between the patients with aortic insufficiency greater than 1+ and in those without insufficiency for the ratio of the diameter of the sinotubular junction/diameter of the Toronto SPV relationships over time (aortic insufficiency. Year; P <.001). Structural valve deterioration was observed in 5 valves, and in 4 of them the sinotubular junction of the aortic root had dilated. The freedom from structural valve deterioration was 99% +/- 1% for patients without aortic insufficiency and 82% +/- 12% for those with aortic insufficiency of more than 1+ at 8 years (P =.004). One patient had moderate aortic insufficiency without structural valve deterioration and dilation of the sinotubular junction. CONCLUSIONS: Dilation of the sinotubular junction causes aortic insufficiency after aortic valve replacement with the Toronto SPV bioprosthesis and increases the risk of structural valve deterioration. Banding the sinotubular junction may prevent dilation and enhance the durability of this valve.

Pulmonary valve injury: Swan-Ganz or surgery.

Pulmonary artery catheter (PAC) is a commonly used monitor in cardiac surgery. Pulmonary valve injury from the balloon of the pulmonary artery catheter is exceedingly rare; its description by transesophageal echocardiography is nonexistent in the literature. A patient is reported who developed a flail anterior pulmonary leaflet several days after successful myectomy for hypertrophic cardiomyopathy. The temporal sequence of PAC use and four transesophageal echocardiography studies over 13 days, with the first three showing normal pulmonary valves, suggested pulmonary valve trauma, most likely from a Swan-Ganz catheter, as the etiology. Partial damage to the pulmonary valve from the original surgery may have predisposed the patient to further damage when the PAC was reintroduced in the intensive care unit.

Mitral regurgitation in hypertrophic obstructive cardiomyopathy: relationship to obstruction and relief with myectomy.

OBJECTIVES: This study examined: 1) the impact of myectomy on postoperative mitral regurgitation (MR) and 2) the association between the severity of MR and the left ventricular outflow tract (LVOT) gradient. BACKGROUND: For patients with hypertrophic obstructive cardiomyopathy (HOCM) and MR, controversy exists as to whether myectomy alone is sufficient in eliminating MR. Furthermore, the relationship between the degree of MR and the LVOT peak gradient has not been well defined. METHODS: We performed pre- and postoperative transthoracic as well as intraoperative transesophageal studies in 104 consecutive patients with HOCM undergoing septal myectomy. Left ventricular outflow tract gradient and the nature of MR were assessed. RESULTS: In the 93 patients without independent mitral valve disease, a relationship was observed between MR severity and the LVOT gradient. Left ventricular outflow tract gradient (mean +/- standard deviation) for trivial, mild, moderate and severe MR were: 23.2+/-19.1, 43.8+/-25.4, 70.1+/-21.0 and 104+/-21.0 mm Hg (p < 0.001). Early postoperative, MR was absent or trivial in 80%, mild in 19% and moderate in 1%. None of these patients required additional mitral valve surgery. For patients with independent mitral valve disease (n = 11), five required mitral valve surgery as well as myectomy. The remainder had significant reductions in the degree of MR with myectomy alone. CONCLUSIONS: For patients with HOCM and MR not due to independent mitral valve disease, myectomy significantly reduced the degree of MR, without requirement for additional mitral valve surgery. In these patients the severity of MR was directly related to the magnitude of the LVOT gradient.

Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients.

The need to enhance the echocardiographic determination of left ventricular ejection fraction is greatest in patients with suboptimal images. Intravenous contrast (CON) and tissue harmonic imaging (THI) are 2 important methods for enhancing endocardial border definition. However, the comparative feasibility and accuracy of THI and contrast-enhanced power harmonic imaging in difficult-to-image patients have not been examined. We assessed the comparative accuracy of THI and CON in determining EF and ventricular volumes in patients with suboptimal fundamental images. We demonstrated that CON is feasible and exhibits a greater correlation with ejection fraction and ventricular volumes determined by radionuclide angiography (standard of comparison) than THI in this difficult-to-image population, with no reported side effects. For both ejection fraction and ventricular volumes, the observer variability was least for CON, intermediate with THI, and greatest for fundamental imaging.

Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study.

BACKGROUND: We evaluated distribution of warm antegrade and retrograde cardioplegia in patients undergoing coronary artery bypass grafting (CABG). METHODS: Myocardial perfusion was evaluated pre- and post-CABG using transesophageal echocardiography with injection of sonicated albumin microbubbles (Albunex) during warm antegrade and retrograde cardioplegia. The left ventricle (LV) was evaluated in five segments and the right ventricle (RV) was evaluated in two segments. Segmental contrast enhancement was graded as absent (score = 0), suboptimal or weak (score = 1), optimal or excellent (score = 2), or excessive (score = 3). RESULTS: Pre-CABG cardioplegic perfusion correlated weakly with severity of coronary artery stenoses (r = -0.331 and 0.276 for antegrade and retrograde cardioplegia, respectively). Antegrade cardioplegia administration resulted in 98% and 96% perfusion to the left ventricle pre- and post-CABG, respectively. Retrograde cardioplegic administration resulted in reduced LV perfusion, with 86% (p = 0.032 from antegrade) and 59% (p<0.001 from antegrade) pre- and post-CABG, respectively. The average LV perfusion score (mean +/- SEM) was greater with antegrade than retrograde cardioplegia both pre-CABG (1.93+/-0.04 vs. 1.53+/-0.11, p<0.001) and post-CABG (1.63+/-0.07 vs. 1.19+/-0.13, p = 0.004). RV perfusion was poor with both techniques pre-CABG, but improved significantly with antegrade cardioplegia post-CABG. CONCLUSIONS: We conclude that warm antegrade cardioplegia results in better left ventricular perfusion than warm retrograde cardioplegia. Right ventricular cardioplegic perfusion was suboptimal, but the best delivery was achieved with antegrade cardioplegia after coronary bypass. We therefore recommend construction of the saphenous vein graft to the right coronary artery early in the operative procedure.

Effect of a single bolus of intracoronary basic fibroblast growth factor on perfusion in an ischemic porcine model.

Basic fibroblast growth factor (bFGF) has been shown to induce angiogenesis in various animal models, but the methods of administration used experimentally are not clinically feasible. The objective of this study was to determine whether a single intracoronary bolus injection of bFGF would improve coronary perfusion in a porcine ischemic model that mimics clinical chronic ischemia. A copper coil studded with gold was delivered into the proximal right coronary artery of juvenile Yorkshire pigs and deployed by interventional techniques. After a four-week interval for stenosis maturation, bFGF (100 micrograms) was administered by bolus injection into the left coronary artery in five animals, and vehicle alone was administered in four animals. Angiogenesis and change in right coronary perfusion area were assessed two weeks later by angiography, myocardial contrast echocardiography and immunohistochemistry. The right coronary perfusion area increased significantly after treatment in all but one of the animals that received bFGF but not in any of the controls. Intimal hyperplasia was not induced by bFGF. Capillary density determined histochemically was not different in the two groups. In conclusion, in a porcine ischemic model, bFGF administered by a single bolus intracoronary injection into the contralateral artery improved antegrade perfusion into the ischemic territory although without histological evidence of angiogenesis. This preliminary work merits further investigation.

Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY).

BACKGROUND: Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies. METHODS AND RESULTS: This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with >/=50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline (P<0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82+/-32 mm Hg to 48+/-32 mm Hg (P<0. 001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22+/-5 mm) and 12 months (21+/-5 mm; P=NS). CONCLUSIONS: (1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) >/= 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients.

Will stentless valves be durable? The Toronto valve (TSPV) at 5 to 6 years.

The early hemodynamic benefits of stentless aortic valves have been well documented. The issue of long-term functional integrity remains unanswered. We report the clinical results of a multicenter registry with prospective data on 621 patients monitored for 7.1 years. Patient data were collected and analyzed at St Jude Medical Inc, St Paul, Minnesota. In all, 66% of patients were male; the average age was 65.9 years +/-11.0 years, with 39% older than 70 years. Native aortic valves were bicuspid in 40.6%, 91.5% were calcified and 65.7% stenotic. Most valves implanted (83.1%) were sizes 25, 27, or 29 mm. Concomitant coronary bypass was performed in 42% of patients. Total follow-up time for the 621 patients was 1,944.5 valve years (mean 3.1 years per patient). At 5 years, 86.1% (n = 137) and at 6 years 80.4% (n = 51) were in New York Heart Association class I, and 78% had no or trivial atrial insufficiency. The average mean systolic gradient for all valves at 6 years was 4.0 mm Hg, and the peak gradient was 8.6 mm Hg. The effective orifice area varied from 1.4 cm2 (23-mm valve) to 2.7 cm2 (29-mm valve). The decrease in left ventricular mass index was significant and sustained. Actuarial survival at 6 years was 84.2%, and freedom from cardiac-related deaths was 90.1%. Freedom from valve-related deaths was 95.7%, and freedom from prosthetic endocarditis was 98.6%. There were no instances of primary tissue valve failure during follow-up, with 97.2% freedom from reoperation. The early hemodynamic benefits of the TSPV are well maintained during more than 6 years of follow-up, without evident valvular dysfunction. Longer follow-up time is required to validate durability, but there is increasing evidence for well-maintained structural and functional integrity.

The Toronto SPV: hemodynamic data at 1 and 5 years' postimplantation.

The Toronto-SPV (T-SPV) bioprosthesis has been used for aortic valve replacement (AVR) since July 1991. There is no published data on its mid-term hemodynamic performance. This study compares the hemodynamic data of a consecutive series of patients at 1 and 5 years after AVR. The first 109 consecutive patients who had AVR with a T-SPV have been monitored for a minimum of 5 years and have had annual Doppler echocardiographic studies. There were 80 men and 29 women in the study; mean age was 62 years (range 34 to 80 years). Concomitant coronary artery bypass surgery was done in 35 patients. One operative and nine late deaths occurred. The mean systolic gradient across the T-SPV in all patients was 3.9+/-2.4 mm Hg at 1 year and 4.1+/-3.3 mm Hg at 5 years (P = .27). The mean aortic valve area was 2.2+/-0.6 cm2 at 1 year and 2.3+/-0.7 cm2 at 5 years (P = .43). The mean left ventricular mass index (LVMI) was 104+/-31 g/m2 at 1 year and 97+/-24 g/m2 at 5 years (P = .08). Multivariate linear regression analysis showed that preoperative coronary artery disease (P<.0001) and hypertension (P<.01) were independent predictors of higher LVMI over time. Aortic insufficiency was none/trivial in 94% of patients and mild in 6% at 1 year. At 5 years, aortic insufficiency was none/trivial in 88% of patients, mild in 10%, and moderate in 2%. The aortic leaflets remained thin and pliable in all patients as assessed by echocardiography. Most patients (85%) were in New York Heart Association functional class I. The hemodynamic performance of the T-SPV remained unchanged during the first 5 years after implantation. The LVMI continued to decrease after the first year and tended to normalize in most patients. The aortic valve remained competent, and the leaflets did not change their thickness or show evidence of calcification.

Hemodynamics and left ventricular mass regression following implantation of the Toronto SPV stentless porcine valve.

Stentless tissue valves may provide more favorable hemodynamics than conventional stented valves. Hemodynamic findings from a large multicenter trial have not been previously reported. The present report describes the hemodynamic findings from a multinational, multicenter study after implantation of the Toronto SPV valve. A total of 577 patients underwent aortic valve replacement with the Toronto SPV valve at 12 sites in 3 countries. Echocardiograms were recorded in the early postoperative period, 3 to 6 months after surgery, 1 year after surgery, and yearly thereafter, with follow-up to 3 years. Gradients decreased and effective orifice area increased in the months after surgery. One year after surgery, mean gradient for valve sizes 20 to 22, 23, 25, 27, and 29 mm was 7.3 +/- 4.4, 7.4 +/- 4.5, 6.1 +/- 3.3, 4.9 +/- 2.4, and 4.0 +/- 2.1 mm Hg, respectively; effective orifice area was 1.3 +/- 0.7, 1.5 +/- 0.5, 1.7 +/- 0.4, 2.0 +/- 0.4, and 2.4 +/- 0.6 cm2, respectively. There was a very low prevalence of significant aortic regurgitation at all time periods. There was significant left ventricular (LV) mass regression between the early and 3- to 6-month periods and between the 3- to 6-month and 1-year postoperative periods. The Toronto SPV valve has an excellent hemodynamic profile supported by significant regression of LV hypertrophy in the year after implantation. Data through 3 years demonstrates maintenance of low gradients and freedom from significant aortic regurgitation.