\u201cA randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer\u201d

The sequential doxorubicin \u2192 CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF 7 6 cycles (CMF); (b) doxorubicin 7 4 cycles followed by CMF 7 6 cycles (A \u2192 CMF); (c) CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (CMF \u2192 GT); and (d) doxorubicin 7 4 cycles followed by CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (A \u2192 CMF \u2192 GT). The study used a 2 7 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A 7 CMF or arms a + c vs b + d) and (2) the effect of adding GT after chemotherapy (arms a + b vs c + d). At a median follow-up of 72 months, A \u2192 CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR) = 0.740 (95% confidence interval (CI): 0.556-0.986; P = 0.040) and produced a nonsignificant improvement of overall survival (OS) (HR = 0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR = 0.74; 95% CI: 0.555-0.987; P = 0.040), with a nonsignificant improvement of OS (HR = 0.84; 95% CI: 0.54-1.32). A \u2192 CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. \ua9 2005 Cancer Research UK

A Computational Study of the Electrophysiological Substrate in Patients Suffering From Atrial Fibrillation

In the context of cardiac electrophysiology, we propose a novel computational approach to highlight and explain the long-debated mechanisms behind atrial fibrillation (AF) and to reliably numerically predict its induction and sustainment. A key role is played, in this respect, by a new way of setting a parametrization of electrophysiological mathematical models based on conduction velocities; these latter are estimated from high-density mapping data, which provide a detailed characterization of patients' electrophysiological substrate during sinus rhythm. We integrate numerically approximated conduction velocities into a mathematical model consisting of a coupled system of partial and ordinary differential equations, formed by the monodomain equation and the Courtemanche-Ramirez-Nattel model. Our new model parametrization is then adopted to predict the formation and self-sustainment of localized reentries characterizing atrial fibrillation, by numerically simulating the onset of ectopic beats from the pulmonary veins. We investigate the paroxysmal and the persistent form of AF starting from electro-anatomical maps of two patients. The model's response to stimulation shows how substrate characteristics play a key role in inducing and sustaining these arrhythmias. Localized reentries are less frequent and less stable in case of paroxysmal AF, while they tend to anchor themselves in areas affected by severe slow conduction in case of persistent AF

Transcatheter aortic valve replacement for aortic regurgitation after septal myectomy in patients with obstructive hypertrophic cardiomyopathy

Transaortic septal myectomy is currently considered to be the most appropriate surgical treatment for patients with obstructive hypertrophic cardiomyopathy (HCM) and heart failure symptoms unresponsive to medical therapy (1). However, a well-described late complication of this approach is the development of a substantial aortic regurgitation (AR), frequently requiring surgical aortic valve replacement (SAVR) (2). Post-myectomy AR may be secondary to the leaflet trauma at the time of surgery since septal myectomy is performed through the aortic valve after aortotomy; secondly, it may be related to the turbulent blood flow in the left ventricle outflow tract after surgery that in turn may cause recurrent trauma to the valve in systole; lastly, septal myectomy involves a piece of myocardium below the right coronary cusp and over time the derangement of septal structure may alter the support of the aortic valve causing gradual distortion of the aortic annulus. A redo SAVR is usually associated with an increased risk profile due to the presence of adherences and comorbidities. Although some studies reported encouraging results (3), TAVR is still an off-label indication for AR

Reply to the letter “Takotsubo syndrome: Any more covariates of its recurrence?”

No abstract availabl

Clinical characteristics of patients with takotsubo syndrome recurrence: An observational study with long-term follow-up

Background: Research investigating takotsubo syndrome (TTS) recurrence yielded conflicting results. Aim of the present study is to describe clinical characteristics of patients with TTS recurrence in a cohort with available long-term follow-up. Methods: The study population included 234 TTS patients enrolled in a prospective multicenter registry, median follow-up of 1328 (407, 2526) days. To investigate factors associated with TTS recurrence, we analyzed patients with recurrence (Group A) in comparison with a subgroup of TTS patients within the whole population (group B) who had similar age, sex and median follow-up length (Group A 2280 days vs Group B 2361 days). Results: We observed 9 TTS recurrences affecting 8 patients, all women, with a rate of 0.9% patients/year. Median time to first recurrence was 1593 days (interquartile range: 950, 2516). We detected no significant differences between patients with and without recurrences regarding cardiovascular risk factors, symptoms, ECG and echocardiographic findings at presentation, discharge therapy. Physical trigger and chronic obstructive pulmonary disease (COPD) were more prevalent in patients who experienced a recurrence (75% vs 27% and 50% vs 14% with p = 0.01 and p = 0.022 respectively). Univariable Cox regression analysis identified physical trigger and history of COPD to be both associated with TTS recurrence [hazard ratio (HR) 11.4, 95% confidence interval (CI) 2.29–56.8, p = 0.003 and HR 4.94, 95% CI 1.16–20.99 p = 0.031 respectively]. Conclusion: TTS recurrence is relatively uncommon. Association with physical trigger and COPD would suggest a closer follow-up in this subgroup of patients

Longitudinal changes of left and right cardiac structure and function in patients with end-stage renal disease on replacement therapy

Background: Few data are available regarding longitudinal changes of cardiac structure and function in end-stage chronic kidney disease (CKD). Aim of the present study is to describe serial echocardiographic findings in a cohort of dialyzed CKD patients. Methods: In this retrospective longitudinal study, we included n = 120 dialyzed CKD patients who underwent at least 2 echocardiograms either 1, 2 or 3 years apart. After baseline echocardiogram, n = 112 had a further examination at year 1, n = 76 at year 2 and n = 45 at year 3. Echocardiographic examination included Tissue Doppler Imaging of both left (LV) and right (RV) ventricle. Results: LV geometry and LV mass index did not significantly change over time. RV progressively dilated (mean change +1.3 mm, +1.1 mm and +3.1 mm at year 1, 2 and 3 respectively, p = 0.002, adjusted p = 0.003). Tissue Doppler parameters showed significant changes with regard to both LV (mean change of E/E’ +0.7, +1.3, +1.7 at year 1, 2 and 3 respectively p<0.001, adjusted p = 0.079) and RV (mean change of S wave (cm/sec) -1, -1.7, -2 at year 1, 2 and 3 respectively, p <0.001, adjusted p = 0.041). Decrease of RV S wave negatively correlated with E/E’ changes (r=-0.303, p = 0.002; r=-0.246, p = 0.049; r=-0.265, p = 0.089; at year 1, 2 and 3 respectively). LV ejection fraction (LVEF) progressively declined (p = 0.034, adjusted p = 0.140), albeit being significant lower against baseline only at year 3 (mean change -4.3%, p<0.05). Conclusions: In dialyzed CKD patients we observed parallel worsening of LV diastolic and RV systolic function accompanied by RV dilation. LVEF decreased less sharply

Outer loop and isthmus in ventricular tachycardia circuits: Characteristics and implications

Background: The isthmus of ventricular tachycardia (VT) circuits has been extensively characterized. Few data exist regarding the contribution of the outer loop (OL) to the VT circuit. Objective: The purpose of this study was to characterize the electrophysiological properties of the OL. Methods: Complete substrate activation mapping during sinus rhythm (SR) and full activation mapping of the VT circuit with high-density mapping were performed. Maps were analyzed mathematically to reconstruct conduction velocities (CVs) within the circuit. CV >100 cm/s was defined as normal and <50 cm/s as slow. Electrograms along the entire circuit were analyzed for fractionation, duration, and amplitude. Results: Six postmyocardial infarction patients were enrolled. The VT circuit was a figure-of-eight reentrant circuit in 4 patients and a single-loop circuit in 2 patients. The OL exhibited a mean of 1.9 ± 0.9 and 1.6 ± 0.5 corridors of slow conduction (SC) during VT and SR, respectively. SC in the OL were longer and faster than SC in the isthmus during SR. At the OL, SC sites showed local abnormal ventricular activity in 92%, and a bipolar voltage <0.5 mV was identified in 80.7%. Of the double-loop circuits, only 1 patient had fixed lines of block as isthmus boundaries, whereas in 3 patients the circuits were at least partially functional. Conclusion: In ischemic reentrant VT circuits, the OL contributes significantly to reentry with multiple corridors of SC. These corridors can result from structural or functional phenomena. Isthmus boundaries may correspond to functional or fixed lines of block

Incidence, determinants and prognostic relevance of dyspnea at admission in patients with Takotsubo syndrome: results from the international multicenter GEIST registry

Clinical presentation of Takotsubo syndrome (TTS) may range from acute chest pain to dyspnea: the prognostic role of clinical onset is still controversial. Aim of this study was therefore to investigate the prognostic relevance of dyspnea at presentation in patients with TTS. We analyzed 1,071 TTS patients (median age 72 years, 90% female) enrolled in the international multicenter GEIST registry. Patients were divided according to the presence or absence of dyspnea at hospital admission, as clinically assessed by the accepting physician. The primary endpoint was occurrence of in-hospital complications defined as a composite of pulmonary edema, cardiogenic shock and death. Overall, 316 (30%) patients presented with dyspnea at hospital admission. Diabetes, lower left ventricular ejection fraction and presence of pulmonary disease or atrial fibrillation were independently associated with dyspnea. In-hospital pulmonary edema, cardiogenic shock and death (17% vs. 3%, p < 0.001; 12% vs. 7%, p = 0.009; 5% vs. 2%, p = 0.004 respectively) and long-term overall mortality (22% vs. 11%, p < 0.001) occurred more frequently in patients with dyspnea than in those without. At multivariable analysis, dyspnea at presentation remained independently associated to both the composite primary endpoint [odds ratio 2.98 (95% confidence interval (CI) 1.95–4.59, p < 0.001] and all-cause mortality [hazard ratio 2.03 (95% CI 1.37–2.99), p < 0.001]. Dyspnea at presentation is common in TTS and is independently associated with in-hospital complications and impaired long-term prognosis. Thorough symptom assessment including dyspnea therefore represents a valuable tool to potentially optimize risk-stratification models for TTS patients