Abstract: Cell therapy is an adjunctive treatment to improve left ventricular function after myocardial injury. Multiple cell types have been tested experimentally in animal models of myocardial disease, with functional improvement as the primary endpoint. Regarding safety, the major concern has been that cell transplantation could generate an arrhythmogenic substrate as reported in clinical studies using myoblasts. The mechanism of these transplantation-related arrhythmias remains elusive but the cellular heterogeneity, resulting from differences in electrical membrane properties between recipient/donor cells, could provide a substrate for reentry circuits. The knowledge achieved from experimental studies on the substrate of arrhythmias in cell therapy gives useful information that could be translated into the development of a biological pacemaker or a non-pharmacological approach to atrial fibrillation. Limitations of current pharmacological and catheter ablation options to achieve rate control in patients with atrial fibrillation have motivated new strategies of cell therapy for non-pharmacological rate control without producing high-degree atrioventricular block. Although several issues remain to be addressed, some aspects of cell therapy are likely to be translated into clinical practice.
Abstract: BACKGROUND: Conversion of atrial fibrillation (A-Fib) to sinus rhythm is associated with transient mechanical dysfunction of left atrium and appendage, termed atrial stunning. OBJECTIVES: The aim of the present study was to evaluate the relationship between nutritional status and atrial stunning after conversion of A-fib. METHODS: Fifty-eight hemodynamically stable patients referred for cardioversion for lone AF were included in this study. To assess nutritional status and inflammation we measured: hemoglobin, erythrocyte mean cell volume, increased transferrin, decreased percent transferrin saturation and ferritin, albumin, CRP and Fe. Usual dietary intake was assessed with the use of a semi-quantitative food frequency questionnaire. LA function was assessed using peak atrial filling velocity, atrial ejection force and peak of emptying and filling velocities of left atrial appendage. RESULTS: Patients were categorized in 4 groups according to value of CRP and Fe. Patients with normal value of CRP and normal value of Fe and patients with elevated CRP but normal value of Fe showed no difference in parameters of atrial function. On contrary patients with reduced value of Fe showed significantly reduced parameters of atrial function. CONCLUSIONS: Data of the present study showed that patients with a reduction of Fe present a marked dysfunction of atrial contractility in comparison with other groups. We cautiously hypothesize an iron mechanism. The hemodynamic stress due to A-Fib can generate highly toxic hydroxyl radicals. These oxygen free radicals probably damage cells by oxidating various cell components and could be important in inducing myocardial stunning after A-Fib.
Abstract: The aim of the study was to evaluate the influence of left ventricular (LV) hypertrophy on left atrial (LA) electrical and mechanical function after cardioversion atrial fibrillation (A-Fib) of brief duration. Study group A included 100 patients with a first diagnosis of hypertension who had a moderate LV hypertrophy. The patient population included 64 men and 36 women with a mean age of 55 +/-7 years who were hospitalized because of A-Fib and were cardioverted with external DC shock. Control group B included 100 patients without cardiac hypertrophy cardioverted because of lone A-Fib. Atrial function and size were assessed by Doppler echocardiography and the following parameters were measured: transmitral peak A velocity, atrial filling fraction, atrial ejection force, peak E velocity, deceleration time, and isovolumic relaxation time, LA maximal and minimal volume, and LV cardiac mass index. Baseline echocardiography showed that LA diameters and volumes were enlarged in all patients during A-Fib. After the restoration of sinus rhythm LA diameters and volumes decreased and the reduction was more evident in group B compared to group A. LA function as a continuous variable was negatively related to LV mass index (r = -0.77), LA diameter (r = -0.66 and r = -0.69 for the superoinferior diameter), LA maximal volume (r = -0.61) and LA minimal volume (r = -0.55) (all p<0.01). Atrial ejection force as a continuous variable was positively related to age (r =0.78), peak A wave velocity (r =0.71), systolic blood pressure (r =0.51), and IVRT (r =0.41) (all p<0.01). Hypertrophy influenced the recovery of atrial function after cardioversion of A-Fib. Atrial function was reduced in patients with LV hypertrophy even after A-Fib of brief duration.
Abstract: Heparin-induced thrombocytopenia (HIT) is one of the most life-threatening adverse effects of heparin administration. It is characterized by thrombocytopenia and may also be associated with venous or arterial thrombosis. HIT type 2 is caused by the binding of antibodies, most likely IgG, to a complex of heparin and platelet factor-4, these complexes IgG/PF4/heparin activate platelets causing the release of pro-thrombotic particles that promote thrombin generation. HIT and HIT-thrombosis are associated with high morbidity and mortality. Thrombotic events are most frequently venous and may manifest as pulmonary embolism or cerebral venous thrombosis. Arterial thrombosis leading to limb damage and amputation and to myocardial infarction or stroke may also occur. HIT is a clinical syndrome that requires clinical and laboratory findings to confirm the diagnosis. All forms of heparin treatment should be stopped once HIT is suspected and patients should be treated with an alternative anticoagulant to treat and prevent thrombotic complications. Available alternative anticoagulants include argatroban and lepirudin, a recombinant form of hirudin.
Abstract: AIMS: The present study was designed to establish the relationship between personality factors, socio-economic factors and acute life stress with development, spontaneous cardioversion and recurrences of acute lone atrial fibrillation. METHODS: The study group consisted of 116 patients with lone atrial fibrillation cardioverted within 48h of the onset of arrhythmia; they underwent a series of cognitive tests to evaluate acute psychological stress and personality type. The socio-economic status and other covariates (alcohol consumption, smoking, and body mass index) were investigated. A control group, age- and sex-matched, was selected and compared. In the logistic regression analysis, the presence of spontaneous conversion to sinus rhythm was used as the dependent variable. Independent variables were indicator variables representing categories of stress, Type A behaviour pattern, coffee consumption and body mass index. Variables considered for logistic analysis were only those with independent prognostic value. RESULTS: Type A behaviour pattern was found in 23 (20%) patients with atrial fibrillation and in 11 (9%) controls (P<0.001). The mean score among patients with atrial fibrillation was 8+/-2.7, while in control subjects it was 5.5+/-2. The mean acute life stress score among patients with atrial fibrillation was 56+/-33, while in controls it was 34+/-27 (P<0.01). Spontaneous conversion of atrial fibrillation to sinus rhythm was observed in 72 patients (63%). In univariate analysis alcohol consumption, income, education and smoking habits did not affect spontaneous conversion. High coffee consumption (OR 0.3 95% CI 0.11-0.49; P<0.008) and high body mass index were associated with a significantly greater risk of atrial fibrillation (OR 1.5 95% CI 1.2-1.7). CONCLUSIONS: Type A behaviour pattern and acute life stress affect the development and spontaneous conversion of atrial fibrillation. Patients with acute stress showed the highest probability of spontaneous conversion followed by patients with Type A behaviour. Other socio-economic factors affect spontaneous conversion and recurrences of lone atrial fibrillation to a lesser extent.
Abstract: OBJECTIVES: The aim of the study was to evaluate the effect of regression of left ventricular (LV) hypertrophy on left atrial (LA) size and function in patients treated with telmisartan, an angiotensin II receptor blocker. METHODS: Patients population included 80 patients with mild-moderate LV hypertrophy treated with telmisartan. Patients were followed over a period of 12 months from the start of telmisartan treatment. LA size was measured during systole from the parasternal long-axis view from M-mode. Atrial function was assessed by Doppler-echocardiography and the following parameters were measured: transmitral peak A velocity, atrial filling fraction, atrial ejection force (AEF), peak E velocity, deceleration time and isovolumic relaxation time, LA maximal and minimal volume, and LV cardiac mass index (LVMI). RESULTS: All patients had an increased LVMI and decrease during follow-up. LA dimensions were greater at baseline and reduced after 1 year of treatment. LA volume indexes maximal volume, minimal volume and P volume were reduced compared with baseline value (maximal volume from 35+/-5 to 32+/-5, p<0.05; minimal volumes from 14+/-2 to 10+/-4, p<0.05). AEF, a parameter of atrial systolic function, increased from 12+/-3 to 15+/-2.4 (p<0.01). The reduction of LA volumes correlate with reduction of LVMI (LA maximal volume and LVMI r = 0.45; p<0.01; LA minimal volume and LVMI r = 0.34; p<0.05). A positive correlation was also found between LV mass index and P volume (r = 0.41; p<0.01), LV mass index and LA active emptying volume (r = 0.39; p<0.01), and LV mass index and LA total emptying volume (r = 0.38; p<0.05). CONCLUSIONS: The present study suggests that regression of LV hypertrophy due to telmisartan is associated with reduction of LA volumes that expresses variation of LV end-diastolic pressure. The reduction of LV end-diastolic pressure is associated with an increase in diastolic filling and with a significant reduction of active and passive emptying contribution of left atrium to LV stroke volume.
Abstract: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse effect of heparin treatment. HIT is mediated by antibodies directed at complexes that form between heparin and platelet factor 4 in plasma and are located on the platelet surface and on endothelium. HIT occurs in 1 to 2% of patients receiving unfractionated heparin (UFH) and with lower frequency in patients receiving low-molecular-weight heparins and heparinoids. Despite recent insights into the mechanisms of HIT, there remain important unresolved issues. For example, the reason for the wide difference in the frequency of HIT in patients treated with UFH in various clinical trials is not yet clear. There are patient population-dependent differences in the risk for HIT immunoglobulin G and the development of thrombotic episodes. The complex nature of this syndrome may relate to the composition of the responsible antigen. Patients with HIT need a more accurate evaluation of platelet counts and a better assessment of clinical evidence for thrombosis. Alternative anticoagulant therapy approaches are being studied, but there is at this time no firm clinical evidence for which treatment is best for patients with HIT and HIT-related thromboses.
Abstract: OBJECTIVES: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. METHODS: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mmHg, diastolic blood pressure [DBP] >90 mmHg) and mild-to-moderate LV hypertrophy (LV mass index related to body surface area [LVMI] 117-150 g/m2 for men and 105-150 g/m2 for women) treated with telmisartan monotherapy 40-80 mg once daily for 1 year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood pressure was also monitored at all visits. Diastolic function was assessed by examination of transmitral inflow and pulmonary vein flow patterns. RESULTS: Telmisartan reduced blood pressure; after 12 months, the mean+/-S.D. SBP and DBP were reduced from 144+/-10 to 126+/-8 mmHg (p<0.001) and from 98+/-8 to 86+/-7 mmHg (p<0.001), respectively. The LVMI was decreased from 119+/-7 to 109+/-3 g/m2 (p<0.001) after 12 months' telmisartan treatment. All patients had diastolic dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern of transmitral inflow was present in 21% of patients. The regression of LV hypertrophy observed after 12 months was associated with increased peak early diastolic velocity/peak late diastolic velocity ratio from 0.60+/-0.18 to 0.83+/-0.20 (p<0.001), shortened isovolumic relaxation time (IVRT) from 110+/-13 to 105+/-13 ms (p<0.001), and decreased deceleration time from 229+/-30 to 215+/-28 ms (p=0.002). Univariate analysis showed that shortened IVRT was related to a reduction in the LVMI and LA maximal and minimal volumes. In the multivariate analysis, the reduction in LVMI and the reduction in LA maximal and minimal volumes were independently associated with IVRT reduction. CONCLUSIONS: Telmisartan 40-80 mg is effective in LV hypertrophy regression in hypertensive patients. The reduction in LVMI due to telmisartan monotherapy was associated with a significant improvement of diastolic filling parameters and with a significant reduction of LA volumes.
Abstract: BACKGROUND: Atrial septal aneurysm (ASA) has been considered a potential source of cardiogenic embolism for many years. The ASA Multicenter Italian (ASA-MI) Study evaluated the prevalence and characteristics of ASA in patients with stroke and normal carotid arteries compared with control patients without stroke. The purpose of the present study was to evaluate the frequency of ASA and the association with patent foramen ovale (PFO) in the subgroup of younger patients (aged less than 55 years) included in the ASA-MI Study. METHODS: The ASA-MI Study included 606 patients, enrolled between November 1990 and December 1996: 245 patients with a previous cerebral embolic attack and normal carotid study and a control group of 316 patients. They all underwent transthoracic and transesophageal echocardiography. The subgroup of younger patients aged less than 55 years included 90 patients (61 men and 29 women of mean age 49 +/- 5 years) (group AY). This group was evaluated and compared with an age- and sex-matched control population (61 men; of mean age 48 +/- 6 years) (group BY). RESULTS: The prevalence of ASA was 48.8% (95% confidence interval 40-61) in group AY and 22.2% in the group BY (95% confidence interval 18-33) (chi(2) = 5.968; p = 0.01). Morphological features were similar in the 2 groups of patients. ASA involved the entire septum in 52% of patients of group AY, and in 47.2% of group BY. The prevalence of PFO was 58.8% (95% confidence interval 43-62) in group AY and 28.8% in group BY (95% confidence interval 17-35) (chi(2) = 5.811; p = 0.01). A strong association was found between ASA and PFO. Of the 90 younger patients with stroke, 39 of 44 (88.6%) with ASA also had PFO, compared with 14 of 46 (30.4%) without ASA (chi(2) = 7.370; p = 0.007). CONCLUSION: We found that ASA and PFO were independent predictive factors for stroke in younger patients with stroke and normal carotid arteries and that the association between ASA and PFO bore an increased odds risk.
Abstract: OBJECTIVE: The aim of this study was to evaluate the effect of external direct current (DC) shock on left atrial (LA) dimension and volumes after cardioversion for atrial fibrillation, and the relation between LA size and atrial function. METHODS: We evaluated 180 patients who were randomly cardioverted with DC shock (90 patients) or drugs (90 patients). Echocardiographic evaluations included LA size and volumes. LA passive and active emptying volumes were calculated, and LA function was measured as atrial ejection force. Changes in LA diameters and volumes were correlate with atrial systolic function. RESULTS: The LA was dilated in all patients during arrhythmia and decreased after the restoration of sinus rhythm. The entity of reduction was different in the 2 groups of patients. LA maximal and minimal volumes were increased after DC shock as compared with patients treated with drugs (LA maximal volume 34 +/- 4 vs 31 +/- 5; P <.01; LA minimal volume 18 +/- 2.6 vs 15 +/- 3.6; P <.01). The atrial function was also depressed after DC shock and the delay in the recovery of atrial contractility was related to LA dilation. Patients treated with drugs had a higher atrial ejection force that was associated with a more marked reduction in LA maximal volume after the restoration of in sinus rhythm. A relationship between LA volumes and atrial ejection force was observed in the group of patients with depressed atrial mechanic function (r = -0.78; P <.001). The active emptying fraction was lower, although not significantly, in this group, whereas the conduit volume was increased. CONCLUSION: External DC shock induced a depressed atrial mechanic function in many patients and this was associated with a persistence of LA dilation.
Abstract: BACKGROUND: The association between mitral valve prolapse (MVP) and cryptogenic stroke is controversial. The Atrial Septal Aneurysm Multicenter Italian (ASA-MI) Study is a prospective multicenter study evaluating the prevalence of atrial septal aneurysm (ASA) in patients with a recent stroke and normal carotid arteries. The aim of the present research was to evaluate the frequency of ASA and its association with MVP in the stroke population and in the subgroup of young patients (< 55 years) included in the ASA-MI Study. METHODS: The study group included 245 of the 606 patients referred for transesophageal echocardiography (168 men and 77 women, mean age 65.7 +/- 21 years). All patients were selected on the basis of a recent episode of unexplained cerebral ischemia and were included in the study if they had normal carotid arteries. The control population included 245 patients (mean age 64.7 +/- 23 years) who underwent transesophageal echocardiographic evaluation during the same period for indications other than cerebral ischemia. The subgroup of young patients (< 55 years) included 90 patients (61 men and 29 women, mean age 49 +/- 5 years). RESULTS: The prevalence of MVP was 18% (95% confidence interval 8 to 21%) in the stroke population and 15% (95% confidence interval 7 to 20%) in the control population (chi 2 = 2.1, p = NS). The prevalence of MVP did not differ between young stroke patients (28.8%) and young controls (20%) (chi 2 = 0.835, p = 0.3). MVP was not significantly associated with stroke. We found an association between ASA and MVP: there was a higher incidence of MVP in stroke patients with an ASA than in patients without stroke or an ASA (40.9 vs 25%, p < 0.05). There was also a higher frequency of MVP associated with ASA in the group of young patients than in all patients of the ASA-MI Study (28.8 vs 18%, chi 2 = 20.313, p < 0.001). CONCLUSIONS: We found an association between ASA and MVP in patients with recent stroke and this association bore a higher risk of cerebral events than in patients without these abnormalities.
Abstract: Pulmonary embolism (PE) and deep vein thrombosis are common causes of illness and death. The pharmacological approach to pulmonary embolism includes the use of anticoagulants, unfractionated heparin for the acute phase, and oral anticoagulants for prophylaxis. In massive PE, the use of thrombolytic agents is suggested to reduce systemic hypotension and right ventricular failure and increase cardiac output. Thrombolytic agents act on pulmonary vascular obstruction. In clinical practice, thrombolytic therapy is recommended in case of massive embolism with haemodynamic failure. Recent studies suggest the use of thrombolytic drugs in patients with normal systemic blood pressure who show right ventricular dysfunction at echocardiographic examination. A large randomised trial on lytic agents in submassive PE is therefore needed. Anticoagulants were primarily indicated for prevention of recurrences. Due to the development of low molecular weight heparin, the role of anticoagulants needs to be re-evaluated.
