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Biomedical subjects

L La Vecchia

Publications and source records attributed to L La Vecchia.

At least 19 recordsLinked to original sources

Left ventricular stroke work reserve as prognostic marker in severe heart failure.

AIM: We sought to determine whether an invasive approach based on Swan-Ganz catheterization, coupled with a pharmacologic stressor, might help stratify prognosis in patients with severe heart failure and uniformly depressed indices of cardiac function. METHODS: We studied 31 unselected consecutive patients with scalar doses of dobutamine (2.5-10 microg/kg/min) after baseline hemodynamic evaluation. Changes in stroke work index (SWI) from baseline to peak effect (stroke work reserve, SWR) were recorded, and patients classified as responders (SWR above the median) or non-responders to dobutamine (SWR below the median). One-year follow-up data were recorded. RESULTS: All patients completed the dobutamine challenge test without complications. Dobuta-mine increased SWI from 17+/-9 to 26+/-13 mg/ beat/m2 (P<0.0001 vs baseline), with a median increase of 6.4 g/beat/m2. Basal SWI was not related to stroke work reserve. The only predictor of response to dobutamine was a smaller left ventricular end-diastolic volume (135+/-28 vs 205+/-90 mL/m2; P=0.007). After 1 year, only 7 patients were alive, while 10 had successful transplantation. Transplant-free survival was 47% in responders vs 0% in non responders (P=0.007). At multivariate analysis, none of baseline hemodynamic parameters was predictive of survival. Only age and a SWR above the median were significant independent predictors of survival in this model. CONCLUSIONS: This study allows us to draw the following conclusions: 1) 1-year mortality in severe heart failure remains extremely high; 2) baseline hemodynamics dos not predict survival; 3) a positive response to dobutamine identifies a subgroup with significant lower mortality at 1 year; 4) this response is an independent predictor of survival and is more likely to occur in the presence of a less dilated left ventricle.

Female↗

Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism.

BACKGROUND: To investigate the frequency of cardiac troponin I (cTnI) increases in patients with pulmonary embolism (PE) and to assess the correlation between this finding, the clinical presentation, and outcomes. METHODS: Consecutive patients admitted to the coronary care unit with acute PE were prospectively enrolled between January 2000 and December 2001. cTnI was sequentially determined. Various cut off concentrations were analysed, but patients were categorised prospectively as having increased or no increased cTnI based on a cut off concentration of 0.6 ng/ml. The main outcome measure was in-hospital mortality. RESULTS: On admission, 14 of the 48 patients (29%) had cTnI concentrations greater than the receiver operating characteristic curve value used to diagnose acute myocardial infarction (> 0.6 ng/ml). Subsequently, six patients developed increases for an overall prevalence of 42% (20 of 42). The prevalence was higher when lower cut off concentrations were used: 73% (35 of 48) at the 99th centile and 60% (29 of 48) at the 10% coefficient of variability. Increased cTnI > 0.6 ng/ml was associated with a slower oxygen saturation (86 (7)% v 93 (4)%, p < 0.0001) and more frequent involvement of the main pulmonary arteries as assessed by spiral computed tomography (100% v 60%, p = 0.022). In-hospital mortality was 36% (5 of 14) of patients with increases > 0.6 ng/ml v 3% (1 of 42) of patients with lower concentrations (p = 0.008). Increased cTnI > 0.6 ng/ml on admission was the most powerful predictor of mortality (p = 0.046). CONCLUSIONS: In high risk patients with acute PE, cTnI was frequently detected on admission. It was the strongest independent predictor of mortality.

Acute Disease↗

Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides.

Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK(2) affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK(2) receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK(1)/NK(2) antagonist.

Animals↗

Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide.

High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose chemotherapy (HD-CHT) protocols. HD-CTX dose-limiting toxicity expresses itself as cardiac toxicity which is fatal in a minority of patients. The pathophysiology of HD-CTX-associated cardiotoxicity is still poorly understood. Autopsy studies in patients who died from acute HD-CTX-induced cardiac toxicity revealed hemorrhagic myocardial cell death and interstitial edema. Recently troponins, in particular troponin I (cTnI), have been found to represent a uniquely sensitive and specific marker of myocyte membrane integrity and therefore to increase in response to minimal myocardial cell damage in different settings, including doxorubicin-induced cardiotoxicity. We performed a multiparametric cardiologic monitoring in 16 consecutive breast cancer patients undergoing HD-CTX by means of serial ECG registrations and cardiac enzymes (CPK, CPK-MB and cTnI) determinations plus echocardiography in order to clarify acute cardiac events following HD-CTX administration. Neither overt cardiac toxicity nor cardiac enzymes elevation were recorded. Serial ECGs revealed in six cases little and reversible reduction of QRS voltage and/or ST abnormalities. Echo monitoring showed in four cases mild and transient increase of LV diastolic/systolic diameter/volume without decrease of FS% or EF% below normal values: in two of them abnormalities of diastolic function (E/A mitral doppler ratio) were also recorded. We conclude that our protocol of HD-CTX administration does not cause myocardial cell damage as analyzed by serum cTnI levels, thus suggesting that myocyte membrane injury may not be the first direct mechanism of HD-CTX cardiotoxicity. ECG (ie QRS voltages ) and Echo (ie E/A ratio) monitoring leads us to hypothesize that slight interstitial edema with reduction of LV diastolic compliance may be initial signs of cardiac dysfunction in this clinical setting.

Adult↗

Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction.

BACKGROUND: Evidence for the role of right ventricular (RV) function is emerging in patients with heart failure of different etiologies. Studies conducted in dilated cardiomyopathy (IDC) showed a high prevalence of RV dysfunction unrelated to the severity of pulmonary hypertension. The aim of the study was to investigate the role of RV dysfunction in ischemic versus nonischemic patients. METHODS: A series of 153 patients with left ventricular (LV) dysfunction (defined as a LV ejection fraction <45%) of either ischemic (n = 61, coronary artery disease [CAD] group) or nonischemic (n = 92, IDC group) origin were studied invasively. Besides routine catheterization data, RV volumes and ejection fractions were obtained angiographically. Reference data were collected in a control group of healthy subjects. RV dysfunction was defined as a RV ejection fraction <35% and ventricular concordance as a <10% difference between RV and LV ejection fraction. The LV/RV end-diastolic volume ratio was calculated to assess the relative dilatation of the ventricular chambers. Hemodynamic and angiographic data were compared in the 2 groups by univariate and multivariate logistic regression analysis. RESULTS: Patients with IDC and CAD had comparable LV ejection fractions (29% +/- 3% vs 31% +/- 8%, P not significant) and mean pulmonary pressures (27 +/- 12 mm Hg vs 26 +/- 11 mm Hg, P not significant); the LV/RV end-diastolic volume ratio was identical in the 2 groups (1.26 +/- 0.4 vs 1.24 +/- 0.4, P not significant). RV ejection fraction was significantly lower in IDC compared with CAD (33% +/- 10 % vs 46% +/- 11%, P <.0001), with a prevalence of RV dysfunction in the IDC group of 65% compared with 16% in the CAD group (P <.0001); similarly, the prevalence of ejection fraction concordance was 74% versus 33%, respectively (P <.0001). At multivariate analysis, a low RV ejection fraction was a powerful independent predictor of IDC compared with CAD (odds ratio 0.91, 95% confidence interval 0.87-0.94, P <.0001). RV dysfunction had a positive predictive value of 75% and a negative predictive value of 78% for the diagnosis of IDC; for ventricular concordance, these values were 81% and 69%, respectively. The correlation between mean pulmonary artery pressure and RV ejection fraction was weaker in the IDC group compared with the CAD group (R(2) = 0.032, P =.047 and R(2) = 0.172,P <.0001, respectively). CONCLUSION: In the presence of LV dysfunction, a reduced RV ejection fraction is a powerful marker for IDC compared with CAD, independent of age, pulmonary hypertension, LV function, and ventricular dimensions. These findings support the concept that IDC is frequently characterized by a biventricular involvement and that the presence of RV dysfunction represents a distinguishing feature of this disease.

Adult↗

Abciximab in rescue coronary angioplasty after full-dose tissue-type plasminogen activator.

BACKGROUND: Rescue angioplasty is a complex procedure because of frequent reocclusions secondary to a paradoxical pro-thrombotic effect brought about by thrombolytic therapy. Administration of abciximab may improve procedural results but its utilization in this setting is limited by the potential hemorrhagic risk. Very few data on this approach are currently available in the medical literature. METHODS: After failed full-dose tissue-type plasminogen activator (tPA), 30 patients (23 males, 7 females, mean age 64 +/- 13 years) referred for rescue angioplasty received abciximab (0.25 mg/kg bolus + 0.125 mcg/kg/min x 12 hour infusion) (Abc+ group). The procedural results, hemorrhagic complications and in-hospital outcome observed in these patients were compared to those of 35 patients submitted to rescue angioplasty in the same time period (1997-1999) who did not receive abciximab (Abc- group). RESULTS: In the Abc+ group, 11 patients (37%) were in Killip class 3-4, 14 (47%) had multivessel disease, and 4 (13%) had previous bypass surgery. In all Abc+ patients, factors suggestive of procedural failure were present (i.e. saphenous vein graft occlusion, intraluminal thrombus, dissection, reocclusion, slow flow). The periprocedural heparin dose was 5,000 IU in Abc+ and 100 IU/kg in Abc-patients (range 5,000-10,000 IU). The procedure was successful in 29 Abc+ (97%) and in 34 Abc- patients (97%). A hemoglobin drop > 5 g occurred in 3 Abc+ (10%) and in 4 Abc- patients (11%) with a similar incidence of blood transfusion in the two groups. In all these cases, significant bleeding occurred at the vascular access site. There were 2 in-hospital deaths in Abc+ and 1 in Abc- patients. CONCLUSIONS. Selected patients undergoing rescue angioplasty may be treated with abciximab without an undue increase in hemorrhagic complications. Larger studies are needed to confirm the feasibility of this approach and to assess its potential benefits.

Abciximab↗

Predictors of mortality at 30 days in high-risk patients treated with direct or rescue stenting for acute myocardial infarction: a single center experience.

BACKGROUND: Coronary stenting in acute myocardial infarction (AMI) is associated with a very low adverse event rate when performed at selected centers in clinical trials. However, because of exclusion criteria, a low-risk population is usually selected, while potential benefits of stenting should be investigated in an unselected population, including a larger proportion of high-risk patients. METHODS: We analyzed results obtained in 120 consecutive high-risk patients (mean age, 64 years; range, 38-95 years; 76% male), so defined according to the presence of 1 of the following: age > 75 years; Killip class 3; cardiogenic shock; 3-vessel or left main disease; ejection fraction < 45%; anterior AMI; previous bypass surgery; and/or out-of-hospital cardiac arrest. A primary procedure was performed in 63 patients and a rescue procedure in 57 patients. Stenting was attempted in all patients in which coronary occlusion could be crossed with the guidewire (117/120) and was successful in 115/117 (98%). RESULTS: Procedural success (TIMI 3 flow and residual stenosis < 20%) was obtained in 105 patients (88%), while a suboptimal result (TIMI 2 flow) was achieved in 9 patients (8%). At 30 days, twenty patients had died (17% mortality). For patients non in cardiogenic shock, 30-day mortality was 3.2%. At multivariate analysis, cardiogenic shock (p < 0.0001), peak CK-MB mass (p = 0.01), and suboptimal result (p = 0.018) were significant independent predictors of 30-day mortality. Rescue procedures were associated with a significant protective effect with respect to mortality (p = 0.033). CONCLUSION: In our series, high-risk patients treated with percutaneous intervention for AMI had a very high mortality rate in the presence of cardiogenic shock, despite the use of stents, intra-aortic balloon pumping and abciximab. In the remaining patients, acceptable results were obtained even in the presence of 1 or more risk factors. Rescue stenting does not seem to be associated with increased risk compared to primary stenting.

Adult↗

Appropriateness of the use of coronary angiography in a population of patients with ischemic heart disease.

BACKGROUND: Due to its pivotal role in the management of patients with ischemic heart disease, the use of coronary angiography has been continuously and progressively increasing over the years. However, an inappropriate rate of its utilization has been reported in 2 to 58% of cases. The aim of our study was therefore to evaluate the appropriateness of the indications for coronary angiography at our Institution. METHODS: All the patients undergoing coronary angiography at the catheterization laboratory of the Maggiore Hospital in Bologna during 1999 were evaluated. By retrospectively reviewing the data forms filled in at the time of insertion of the patient on the waiting list, the indications for coronary angiography were categorized as appropriate (class I/IIa), of uncertain value (class IIb) and inappropriate (class III), according to the guidelines of the American College of Cardiology/American Heart Association. In a blind fashion to this classification, the reports of coronary angiography were also reviewed to determine, both globally and in the different clinical subsets, the prevalence of significant coronary stenoses and of angiographically normal vessels. RESULTS: Class I/IIa indications were found in 72% of patients, as opposed to 28% in class lIb and none in class III. In the clinical subsets of stable angina, previous myocardial infarction and out-of-hospital cardiac arrest, the appropriateness was significantly higher, ranging from 74 to 100%, compared to recent myocardial infarction (63%) and unstable angina (59%) (accounting by itself for about one half of all class IIb indications). The overall prevalence of significant coronary artery disease was 87%, while in only 3% of cases did coronary angiography reveal normal vessels. CONCLUSIONS: In our population, the use of coronary angiography was highly appropriate and only seldom of uncertain value. The accurate noninvasive selection of patients which, in view of the limited access to the catheterization laboratory, we needed to perform before proceeding to coronary angiography probably played a major role in these results.

Aged↗

Outcome of percutaneous coronary angioplasty (PTCA) performed in a low-volume institution by low-volume operators, evaluated by means of the one-month major adverse cardiac event rate.

BACKGROUND: Since an inverse relationship between percutaneous coronary angioplasty (PTCA) case-load and in-hospital major adverse cardiac events (MACE) exists, we intended to evaluate the performance of low-volume PTCA operators, during the first year of our interventional program, by applying the more accurate index represented by the MACE rate within the first month. METHODS: The data relative to both the PTCA procedure and the control visit 3-4 weeks later, were retrospectively reviewed. Death, myocardial infarction and need for revascularization were the end-points evaluated, both globally and with respect to the individual operators. RESULTS: During 1999, 61 consecutive patients (53M, 8F; mean age: 59.9+/-10.4 years) were treated by two full-trained operators. Stable angina was the indication in 75% of cases. Comorbidities as diabetes and prior revascularization, were present in 16 and 5% of cases, respectively. Multivessel procedures were performed in 33% of cases, with a total number of lesions of 84 (77% A/B1 type). Stents were implanted in 70% of cases, as a bail-out in 12%. Procedural success rate was 93%. Overall one-month MACE rate was 3.3%, accounted for by 1 in-hospital emergency coronary surgery occurred to operator 1 (3.6% one-month MACE rate) and 1 elective coronary operation performed in a stable patient previously treated by operator 2 (3% one-month MACE rate). CONCLUSIONS: PTCA performed in a low-volume center by low-volume operators is not necessarily associated with a poor outcome, provided that adequate selection of low-risk cases is accomplished. Although only 52% of the Italian centers met in 1999 the recommended volume standards, reaching optimal case-load should anyway be pursued. Some time should however be conceded, provided that close monitoring of one-month MACE rate shows adequate performance of both the institution and the operators.

Angioplasty, Balloon, Coronary↗

Cardiac troponin I as diagnostic and prognostic marker in severe heart failure.

BACKGROUND: Cardiac cell death has been shown to occur in heart failure and has been implicated as one of the mechanisms responsible for progression of the disease. Cardiac Troponin I (cTnI) represents a highly sensitive marker for myocardial cell death. Based on previous studies reporting that cTnI may be detected in patients with heart failure, we evaluated the clinical correlates and prognostic implications of detectable cTnI in a consecutive series of patients with severe heart failure. METHODS: Thirty-four patients were examined. Upon admission, we measured serum levels of cTnI by conventional immunoenzymatic assay (Stratus Dade II). According to the results of this assay, patients were divided into 2 groups, based on the presence (cTnI+) or absence (cTnI-) of detectable cTnI. These 2 groups were compared by non-parametric analysis for their clinical characteristics, instrumental findings, and short-term outcome. RESULTS: The cTnI+ group included 10 patients (29%) with a mean serum cTnI of 0.7 +/- 0.3 ng/ml. Compared with the cTnI- group, these patients had significantly lower left ventricular ejection fractions (20% +/- 5% vs 26% +/- 7%, p = 0.023) and a trend for higher systolic pulmonary artery pressure (59 +/- 17 mm Hg vs 49 +/- 13 mm Hg, p = 0.08). In cTnI+ patients, the correlation between cTnI levels upon admission and ejection fraction was r = -0.530 (p = 0.11). We found ischemic etiology was equally present in the 2 groups, whereas we never found histologic signs of acute myocarditis. Other clinical characteristics (functional class, daily diuretic dose, need for intravenous inotropes) were not statistically different in the 2 groups. In cTnI+ patients who improved after admission, cTnI became undetectable after a few days; in patients with refractory heart failure who were hospitalized until death, cTnI persisted in detectable levels throughout the observation period. Using the Cox proportional hazard model, a positive cTnI was the most powerful predictor of mortality at 3 months (p = 0.013; hazard ratio 6.86; 95% confidence interval 1.32 to 35.4). CONCLUSIONS: These observations suggest that cTnI is detected in the blood of 25% to 33% of patients with severe heart failure; its presence may help to identify a high-risk sub-group who faces very poor short-term prognosis.

Adolescent↗

Procedural results, in-hospital course and six-month follow-up after rescue compared to primary stenting in acute myocardial infarction.

BACKGROUND: Although many previous reports showed a worse outcome after rescue compared to primary coronary angioplasty, a direct comparison of these two strategies in the era of stenting is lacking. METHODS: Fifty patients treated with rescue stenting were retrospectively compared to 61 patients treated with primary stenting during acute myocardial infarction over a 4-year period in our Laboratory. RESULTS: Baseline demographic and angiographic parameters were not significantly different in the two groups. Despite a significantly longer time-to-reperfusion in rescue stenting (4.7 +/- 2.7 vs 2.8 +/- 2.1 hours, p < 0.0001), procedural success rate (98 vs 97%), in-hospital mortality (6 vs 11%) and target vessel revascularization at 6 months (8 vs 10%) were similar in rescue compared to primary stenting. CONCLUSIONS: These data suggest that stenting may help improve results of rescue angioplasty, and support the concept that aggressive treatment after failed thrombolysis can be pursued with satisfactory results.

Adult↗

[Assessment of cardiotoxicity of high dose cyclophosphamide with electrocardiographic, echocardiographic, and troponin I monitoring in patients with breast tumors].

BACKGROUND: High-dose cyclophosphamide is the nucleus for virtually all high-dose chemotherapy protocols. Non-hematologic dose-limiting toxicity is represented by acute cardiomyopathy, even fatal in a minority of patients. The pathophysiology of such a cardiotoxicity is still poorly understood. Postmortem studies revealed hemorrhagic myocardial cell death, endothelial damage, and interstitial edema. Recently troponins, in particular troponin I, have been found to represent uniquely sensitive and specific markers of myocyte membrane integrity, thus to increase in response to myocardial cell damage in different clinical settings. METHODS: We performed a multiparametric monitoring in 16 consecutive breast cancer patients undergoing cyclophosphamide, by means of serial ECGs, cardiac enzymes determinations (creatine phosphokinase, MB mass and troponin I) through 0 to 72 hours, and echocardiography at baseline and after 48 hours. RESULTS: Neither overt cardiac failure nor enzyme elevation were recorded. Serial ECGs revealed a reduction in QRS voltage and/or ST segment abnormalities in 6 cases. Echocardiography showed an increase in left ventricular diastolic and/or systolic diameters and volumes in 4 cases but without any decrease in fractional shortening and ejection fraction under normal values: in 2 of them abnormalities of diastolic function (E/A mitral Doppler ratio, isovolumic relaxation time and deceleration time) were also recorded. CONCLUSIONS: Our protocol of cyclophosphamide administration did not cause cardiac toxicity by myocardial cell damage, as analyzed by troponin I levels, thus suggesting that myocyte membrane injury is not the first mechanism of it. ECG (i.e. QRS voltages) and echo-Doppler (i.e. E/A ratio) monitoring lead to hypothesize that endothelial injury and interstitial edema with subsequent reduction in left ventricular diastolic compliance may be the first signs of cardiac dysfunction in this clinical setting.

Adult↗

Isolation and synthesis of a novel immunosuppressive 17alpha-substituted dammarane from the flour of the Palmyrah palm (Borassus flabellifer).

The novel triterpene 1 with a dammarane skeleton and a hitherto unknown 17alpha-substitution pattern has been isolated from the Palmyrah palm in low yield and prepared by synthesis in larger quantities. 1 was shown to be an extremely potent immunosuppressant in vitro (MLR; IC50 = 10 ng/ml) and in vivo (DTH; ED50 = 0.01 mg/kg p.o.). A glucocorticoid like activity is excluded.

Humans↗

Left ventricular versus biventricular dysfunction in idiopathic dilated cardiomyopathy.

Eighty-five consecutive patients with idiopathic dilated cardiomyopathy were categorized according to the presence (biventricular dysfunction) or absence (left ventricular [LV] dysfunction) of reduced right ventricular ejection fraction (<35%) along with reduced LV ejection fraction (<50%). Compared with the 36 patients with LV dysfunction, the 49 patients with biventricular dysfunction had significantly worse New York Heart Association functional class (2.7+/-0.6 vs 1.9+/-0.5; p <0.001), LV ejection fraction (26+/-10% vs 34+/-8%; p <0.0001), and outcome (transplant-free survival, 55% vs 89%; p <0.001). Thus, dilated cardiomyopathy is frequently characterized by biventricular involvement, which identifies a more severe disease and a worse long-term prognosis.

Adult↗