Hemostatic instantaneous coagulation on echocardiogram: a defining feature of the last heartbeat (a case report).

There is a paucity of detailed descriptions of echocardiographic features of the dying heart in the literature. A 64-year-old man on chronic hemodialysis presented with cardiac arrest after missing dialysis for three weeks. He received resuscitation efforts but died while his last heartbeats were fortuitously recorded by echocardiography. Rapid echo image acquisition during pulse check of a cardiopulmonary resuscitation attempt provided a unique opportunity for documenting the echocardiographic features of a dying heart. There was a rapid progressive dense echogenicity first in the left ventricular chamber and subsequently in all other chambers, which coincided with the final heartbeats. There is no prior documentation of this observation in the literature. We hereby illustrate and characterize this observation we term as Hemostatic Instantaneous Coagulation on Echo (HICE). HICE may be the defining feature of the dying heart and may guide the decision to discontinue resuscitation interventions.

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase ß: data from the Fabry Registry.

BACKGROUND: Agalsidase ß is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase ß cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase ß treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase ß. METHODS: The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase ß (average dose 1 mg/kg every 2 weeks) for up to 5 years. RESULTS: The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase ß was initiated. CONCLUSIONS: Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase ß 1 mg/kg every 2 weeks. TRIAL REGISTRATION NUMBER: NCT00196742.

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-ß: data from the Fabry Registry.

PURPOSE: The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-ß (recombinant human α-galactosidase A) on left ventricular hypertrophy. METHODS: Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-ß (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over ≥ 2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression. RESULTS: For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was -3.6 g/year (n = 31) compared with +9.5 g/year in untreated men of that age (n = 15) (P < 0.0001). Untreated men had a 3.4-fold higher risk of having faster increases in left-ventricular mass compared with treated men (odds ratio: 3.43; 95% confidence interval: 1.05-11.22; P = 0.0415). A baseline age of ≥ 40 years was also associated with left--ventricular hypertrophy progression (odds ratio: 5.03; 95% confidence interval: 1.03-24.49; P = 0.0457) compared with men younger than 30 years. CONCLUSION: Agalsidase-ß treatment for ≥2 years may improve or stabilize left-ventricular mass in men with Fabry disease. Further investigations may determine whether early intervention and stabilization of LVM are correlated with clinical outcomes.

Novel indices for left-ventricular dyssynchrony characterization based on highly automated segmentation from real-time 3-d echocardiography.

Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an invasive and expensive treatment option for left ventricular mechanical dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the unreliability of the current standard CRT indicators. Real-time three-dimensional (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time) information about the LV and is suitable for LVMD assessment. In this article, the complex left ventricle (LV) shape and motion of 50 RT3DE datasets are represented by novel 4-D descriptors - 4-D sphericity, volume and shape, from which novel indices were derived by principal component analysis (PCA) and subsequently analyzed by a support vector machine (SVM) classifier to assess their capability of LVMD characterization and CRT outcome prediction. These novel indices outperformed clinical indices and have promising capabilities in disease characterization and great potential in CRT outcome prediction. To enable efficient quantitative RT3DE analysis, a segmentation method was developed to combine the powers of active shape models and optimal graph search. Various aspects of the method were designed to handle varying RT3DE image quality among datasets and LV segments. An application with graphical user interface was developed to provide the user with simple and intuitive control. The developed method was robust to inter-observer variability and produced very good accuracy - 3.2±1.1 mm absolute surface positioning error, <1 mm mean signed error and <5% mean volume difference. The computer method's classification performance was compared with the independent standard, showing that the 4-D shape modal indices were not only the most capable of all tested options when employed for disease characterization but also the least sensitive to segmentation imperfections.

Cardiovascular events in patients with fabry disease natural history data from the fabry registry.

OBJECTIVES: These analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease. BACKGROUND: Fabry disease, a genetic disorder caused by deficiency of alpha-galactosidase A activity, is associated with CV dysfunction. METHODS: Major CV events (myocardial infarction, heart failure, or cardiac-related death) were analyzed in 2,869 Fabry Registry patients during the natural history period (i.e., before enzyme replacement therapy or among patients who never received therapy). Multivariate logistic regression analyses were performed to identify significant predictors of CV events. RESULTS: Eighty-three of 1,424 men (5.8%) and 54 of 1,445 women (3.7%) experienced CV events at mean ages of 45 and 54 years, respectively. Heart failure was the most common first CV event, reported by 50 men (3.5%) and 33 women (2.3%). Hypertension and left ventricular hypertrophy were the risk factors most strongly associated with CV events. When these parameters were used as covariates in logistic regression analyses, the odds ratio (OR) for hypertension in men was 7.8 (95% confidence interval [CI]: 2.1 to 28.6, p = 0.0019), and the OR for hypertension in women was 4.5 (95% CI: 1.6 to 12.3, p = 0.0037). The OR for left ventricular hypertrophy was 4.8 in men (95% CI: 1.03 to 22.2, p = 0.0463) and 8.2 in women (95% CI: 2.6 to 26.0, p = 0.0003). CONCLUSIONS: Major CV events occurred in approximately 5% of Fabry Registry patients during the natural history period. All patients with Fabry disease should be monitored for possible CV risk factors, particularly hypertension and left ventricular hypertrophy.

Increased vascular alpha1-adrenergic sensitivity in patients with renal failure: receiving recombinant erythropoeitin.

End stage renal disease (ESRD) is associated with altered hemodynamic regulation as a result of the pathophysiology or treatment of renal failure. Hypertension, common among dialysis patients, is a recognized complication of recombinant human erythropoietin (rHuEPO) therapy. We determined vascular adrenergic and nitric-oxide-mediated responsiveness in 7 patients with established ESRD on rHuEPO treatment and in 13 healthy volunteers using the dorsal hand vein technique. Sensitivity to the alpha1-adrenergic selective agonist phenylephrine was significantly increased in patients with ESRD on rHuEPO. The mean dose of phenylephrine producing 50% venoconstriction (ED50) was 38 +/- 1.6 ng/min in patients with ESRD and 135 +/- 1.3 ng/min in healthy volunteers-almost a 4-fold increase in dose, P = 0.01. In contrast, maximal venodilation mediated by bradykinin, an endothelium-dependent vasodilator, was not different in the 2 groups. To determine whether rHuEPO has a direct vasoconstrictor effect, we studied venous responsiveness to local infusions of rHuEPO in healthy volunteers. Increasing concentrations of rHuEPO produced no vasoconstriction in hand veins of healthy volunteers. These results suggest that vascular responsiveness to alpha-adrenergic stimulation in patients with ESRD on rHuEPO is increased whereas bradykinin-mediated venodilation remains intact. This increase in vascular alpha-adrenergic responsiveness may contribute to the increased peripheral vascular resistance and hypertension seen in patients with ESRD on rHuEPO.

Validity of revised Doppler echocardiographic algorithms and composite clinical and angiographic data in diagnosis of diastolic dysfunction.

BACKGROUND: Commonly used echocardiographic indices for grading diastolic function predicated on mitral inflow Doppler analysis have a poor diagnostic concordance and discriminatory value. Even when combined with other indices, significant overlap prevents a single group assignment for many subjects. We tested the relative validity of echocardiographic and clinical algorithms for grading diastolic function in patients undergoing cardiac catheterization. METHOD: Patients (n = 115), had echocardiograms immediately prior to measuring left ventricular (LV) diastolic (pre-A, mean, end-diastolic) pressures. Diastolic function was classified into the traditional four stages, and into three stages using a new classification that obviates the pseudonormal class. Summative clinical and angiographic data were used in a standardized fashion to classify each patient according to the probability for abnormal diastolic function. Measured LV diastolic pressure in each patient was compared with expected diastolic pressures based on the clinical and echocardiographic classifications. RESULT: The group means of the diastolic pressures were identical in patients stratified by four-stage or three-stage echocardiographic classifications, indicating that both classifications schemes are interchangeable. When severe diastolic dysfunction is diagnosed by the three-stage classification, 88% and 12%, respectively, were clinically classified as high and intermediate probability, and the mean LV pre-A pressures was >12 mmHg (P < 0.005). Conversely, the mean LV pre-A pressure in the clinical low probability or echocardiographic normal groups was <11 mmHg. CONCLUSION: Use of a standardized clinical algorithm to define the probability of diastolic function identifies patients with elevated LV filing pressure to the same extent as echocardiographic methods.

Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy.

We prospectively studied the effect of spironolactone, an aldosterone antagonist, on endothelial function in patients with advanced congestive heart failure (CHF) using the brachial artery reactivity method. Twenty patients optimized on conventional CHF therapy were treated with spironolactone, and brachial artery flow- mediated dilation was measured at baseline and at 4 and 8 weeks. Spironolactone improved endothelial function at 4 weeks, and sustained the improvement at 8 weeks, in patients with CHF on conventional medical therapy, presumably due to reversal of aldosterone impairment of endothelial nitric oxide activity.

Propafenone versus ibutilide for post operative atrial fibrillation following cardiac surgery: neither strategy improves outcomes compared to rate control alone (the PIPAF study).

BACKGROUND: It is unclear whether acute conversion of atrial fibrillation (AF) with anti-arrhythmic drugs following cardiac surgery restores and/or maintains sinus rhythm or reduces hospital length of stay (LOS). MATERIAL/METHODS: A randomized prospective pilot study was conducted in 2 teaching hospitals from 3/28/98 to 8/2/99 to study the effect of the early use of ibutilide or propafenone on the duration of AF, rhythm at discharge, and LOS. A total of 42 stable patients with new AF after surgery were randomized to oral propafenone (600mg, single dose; n=20), ibutilide (1 mg up to 2 doses if necessary; n=10), or rate control only (n=12). Agents used for rate control were left to the discretion of the primary physician but beta-blockers were encouraged. RESULTS: Pre-randomization distribution of diabetes, CHF, previous AF, and the use of beta-blockers were similar in all groups. At 24 hours 0%, 65% and 34% of patients in the ibutilide (p=0.01), propafenone (p=ns), and rate control groups respectively remained in AF. Although ibutilide decreased AF duration, recurrence rates were 90%, 41%, and 58% in those groups (p=ns compared to rate control). Of the 3 patients who did not convert, all received propafenone. There was no difference in LOS or rhythm at discharge. CONCLUSIONS: Ibutilide but not propafenone decreases the duration of AF after cardiac surgery and neither appears to affect LOS or rhythm at discharge. This data suggests that post operative AF is transient and routine anti-arrhythmic therapy is not necessary for the majority of patients.