Changes of the T-wave amplitude and angle: an early marker of altered ventricular repolarization in hypertension

BACKGROUND: The heterogeneity of ventricular repolarization is an important proarrhythmic factor. QT dispersion has been proposed to reflect the inhomogeneity of ventricular repolarization, but a poor reproducibility limits its clinical applicability. Reliable noninvasive methods to quantify abnormalities in ventricular repolarization are still lacking. The T-loop morphology analysis is a novel method aimed at quantifying ventricular repolarization. HYPOTHESIS: To test the ability of the T-loop morphology analysis to discriminate between hypertensive patients and healthy subjects, 105 hypertensive patients (mean age 63.6 +/- 12.3 years) and 110 healthy controls (mean age 49.7 +/- 14.3 years) were evaluated. METHODS: The maximum QT interval (QT maximum), the minimum QT interval (QT minimum), and their difference (QT dispersion) were calculated from a digitally recorded 12-lead electrocardiogram (ECG) in both study groups. X, Y, and Z leads were reconstructed from the 12-lead ECG, and the amplitude of the maximum T vector (T amplitude) and the angle between the maximum T vector and X axis (T angle) were calculated from the projection of the T loop in the frontal plane. RESULTS: T amplitude (p < 0.001), T angle (p = 0.05), and QT dispersion (p = 0.04) were significantly different between hypertensive patients and controls, while QT maximum (p = 0.14) and QT minimum (p = 0.35) did not differ between the groups. T amplitude was the only marker which differed between hypertensive patients without ECG criteria for left ventricular hypertrophy and controls (p = 0.002). CONCLUSIONS: T-loop features and particularly T amplitude are significantly different between hypertensive patients and healthy controls and may serve as early markers of repolarization abnormalities in a hypertensive population.     

Successful high‐risk percutaneous coronary intervention with the use of minimal extracorporeal circulation system

Minimal extracorporeal circulation (MECC) represents a contemporary system which integrates several advances in cardiopulmonary bypass technology in a single circuit. We challenged the efficacy of the MECC system to support the circulation in elective high‐risk percutaneous coronary intervention (PCI). A 78‐year‐old patient with complex coronary disease who would have been otherwise rejected for interventional therapy underwent PCI with rotablation on MECC support. The MECC system provided hemodynamic support at a flow of 1.8 L min^?1 m^?2 while perfusion pressure was kept at a minimum of 70 mm Hg. This allowed for successful angioplasty of the left main stem and a chronically occluded right coronary artery, which otherwise produced significant hemodynamic compromise. This case illustrates that mechanical circulatory support with the MECC system could provide a stable environment and a “safety net” for carrying out complex percutaneous coronary intervention in high‐risk patients. © 2012 Wiley Periodicals, Inc.     

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID trade mark ), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected. This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer.     

Intravenous administration of vitamin B12 in the treatment of hyperhomocysteinemia associated with end-stage renal disease

BACKGROUND: High serum levels of total homocysteine (tHcy) are common in dialysis patients with end-stage renal disease (ESRD). We assumed that these patients may have decreased response to conventional folic acid (FOL) and vitamin B12 (B12) administered orally. This study aimed to evaluate the efficacy of an intravenous (i.v.) B12 regimen in ESRD patients and compare it with the conventional regimen. METHODS: We designed an open label, crossover, non-randomized study of 72 ESRD patients. Our patients were hemodialyzed in two hospitals (HOSP1 and HOSP2). In HOSP1, patients were on 1 mg of FOL and 600 micog of B12 orally for 3 months, and then switching to 1 mg of B12 i.v. for 3 additional months, while the FOL dosage was constant. In HOSP2, patients received the same treatment in reverse. RESULTS: Patients in HOSP1 (n = 37) after i.v. B12 treatment, had significantly lower tHcy (p < 0.001) and FOL (p < 0.05) serum levels, compared with those at the end of oral B12 treatment. On the contrary in HOSP2 patients, serum tHcy levels increased significantly (n = 35, p < 0.0001) when i.v. was switched to oral treatment. There was a significant inverse correlation between tHcy and B12 (p < 0.0001) at the end of the i.v. treatment period; while treatment there was no correlation between tHcy and FOL serum levels. At the end of the oral treatment period, there was no significant correlation between tHcy and B12 serum levels, while tHcy and FOL serum levels had a significant inverse correlation (p = 0.002). CONCLUSIONS: Our results suggest that ESRD patients on dialysis have 'B12 resistance', and that they should have, in addition to their FOL therapeutic regimen, i.v. B12 treatment to reduce their elevated tHcy levels.