Usefulness of Left Atrial Remodeling in Predicting CardiacToxicity During Trastuzumab Therapy for Breast Cancer.

Trastuzumab is a key therapy for patients with human epidermal growth factor receptor 2 positive breast cancer (BC). However, it may cause left ventricular dysfunction, resulting in withdrawal of therapy. Left atrium (LA) enlargement has proven to cue subclinical ventricular dysfunction in various clinical setting. Aim of the study was to investigate the association between LA volume index (LAVI) change over time and the development of Cancer Therapeutics Related Cardiac Dysfunction (CTRCD). Consecutive human epidermal growth factor receptor 2 positive BC patients were retrospectively included. Transthoracic echocardiography was performed before starting Trastuzumab and at every 3 up to 12 months. LA volume was measured using the modified Simpson's rule and indexed for body surface area. Ninety patients formed the study population. All patients had a complete 12 months follow-up. Mean baseline LAVI was 27 ± 8 ml/m2 and it was dilated (≥34 ml/m2) in 10 patients (11%). During follow-up, CTRCD occurred in 19 (21%) patients and there was modest LAVI enlargement, with a mean increase of 3 ± 2 ml/m2 (p = 0.0002 vs. baseline). LAVI dilation was significantly higher in patients with CTRCD (average increase at the time of CTRCD vs. baseline: 7 ± 6 ml/m2, p = 0.008), versus patients without CTRCD (average increase at 12 months of follow-up 2±1, p = 0.02), p for comparison = 0.004. LAVI dilatation over time predicted CTRCD independently from baseline LAVI values and the presence of systemic arterial hypertension (OR for 5 ml/m2 dilation was 1.56 [95%CI 1.09 to 2.37], p = 0.01). Trastuzumab related CTRCD is associated with significant LAVI morphological remodeling in BC patients.

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.

Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.

BACKGROUND: Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients. METHODS: A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months. RESULTS: The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). CONCLUSIONS: The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.

The Sorin freedom stentless pericardial valve: clinical and echocardiographic performance at 10 years.

OBJECTIVE: The Sorin Pericarbon Freedom (SPF) is a stentless valve made of pericardium clinically available in 1990. We report the clinical and hemodynamic performance of the SPF at 10 years. METHODS: From April 2000 to December 2005, 85 patients with a mean age of 75 ± 6 years (range 57-86), underwent aortic valve replacement (AVR) with an SPF. Mean left ventricular ejection fraction was 58 ± 10% (range 29-86%) and mean peak transvalvular gradient (PG) 86 ± 24 mmHg. Clinical evaluation was performed at 3, 6, 12 months, and yearly thereafter. RESULTS: There were 2 operative deaths (2.4%). Follow-up ranged from 2 to 135 months (mean 78 ± 32 months) and was 99% complete. There were 35 late deaths, 7 of which were valve-related, with an actuarial survival of 45 ± 8% at 10 years. Structural SPF deterioration occurred in 2 patients, with an actuarial freedom of 96 ± 3%. A total of 4 patients were re-operated, 2 because of structural deterioration, 1 because of endocarditis, and 1 because of sinotubular junction dilatation; freedom from reoperation was 93 ± 4% at 10 years. At last clinical control, 41 patients (89%) were in NYHA class I or II. Mean SPF effective orifice area varied from 1.55 ± 0.66 cm2 for size 21 mm to 2.33 ± 0.86 cm2 for size 27 mm; PG varied from 19 ± 10 mmHg for size 21 mm to 11 ± 6 mmHg for size 27 mm. Left ventricular mass index decreased from 213 ± 51 gm/m2 to 157 ± 436 gm/m2 (p<0.001). CONCLUSIONS: The SPF has demonstrated overall good results in terms of valve durability and freedom from valve-related complications up to 10 years, with excellent hemodynamic performance.

A model of multi-disciplinary approach to the diagnosis and treatment of young patients with cryptogenic stroke and patent foramen ovale.

BACKGROUND: Treatment of patent foramen ovale in young patients with stroke is not supported by robust scientific evidence. In clinical practice, a pragmatic approach is needed to guide such therapeutic decisions. This study aims at standardising the diagnostic pathway for stroke patients younger than 55 years of age with a patent foramen ovale; elaborating a therapeutic algorithm; discussing every case in regular interdisciplinary counselling meeting; and setting up a follow-up schedule to assess clinical outcomes. METHODS: This is a cohort study on the effect of a standardised treatment of stroke patients with a patent foramen ovale. The primary endpoints include occurrence of recurrent ischaemic events, major bleeding, and device-related complications. The secondary endpoints include drug- or procedure-related side effects, persistence of right-to-left shunt, and persistent cardiac arrhythmia of new onset. RESULTS: A total of 103 patients have been enrolled. In all, 51 patients underwent percutaneous atrial septal repair; of these, one had minor post-procedural bleeding. At 12 months, 25% of this group of patients showed a latent I grade shunt, one patient a latent II degree shunt, and none had a persistent shunt. The remaining 52 patients were addressed to medical therapy; one of them experienced stroke recurrences while on medical therapy. CONCLUSIONS: This model of implementation of available evidence to clinical practice via a group-based, multi-disciplinary counselling provides a shared and coherent decision pathway and yielded a very low rate of recurrent events and therapy-related complications. This approach could be replicated in specific protocols for other complex or neglected clinical problems.

Prognostic value of myocardial fibrosis in patients with severe aortic valve stenosis.

OBJECTIVE: To evaluate whether myocardial fibrosis influences left ventricular performance in severe aortic stenosis and to assess its effect on long-term survival after aortic valve replacement. METHODS: Myocardial fibrosis was evaluated in biopsy specimens taken from the interventricular septum in 99 patients undergoing aortic valve replacement because of severe or prevalent aortic stenosis. Clinical and echocardiographic evaluations were performed at a mean follow-up of 6.2 ± 3.0 years. The patients were classified according to the myocardial fibrosis severity (none or mild in 28, moderate in 52, and severe in 19). RESULTS: Patients with severe myocardial fibrosis had a dilated left ventricle and positive association between the left ventricular end-diastolic diameter (R = 0.77, P < .001), left ventricular end-systolic diameter (R = 0.78, P < .001), left ventricular end-systolic wall stress (R = 0.74, P < .001) and the degree of myocardial fibrosis. Myocardial fibrosis was inversely related to left ventricular fractional shortening (R = -0.64, P < .001), left ventricular ejection fraction (R = -0.53, P < .001), and left ventricular relative wall thickness (R = -0.70, P < .001). Patients with a higher grade of myocardial fibrosis had a significantly lower freedom from cardiac death at 10 years (42% ± 19% vs 89% ± 6%, P = .002), with congestive heart failure the most common cause of death. At Cox regression analysis, patient age (P = .012), low preoperative transvalvular gradient less than 40 mm Hg (P = .040), preoperative end-systolic wall stress (P = .046), and preoperative myocardial fibrosis grade (P = .034) emerged as the strongest independent predictors of mortality. CONCLUSIONS: In patients with severe aortic valve stenosis, the amount of myocardial fibrosis appears to have significant effect on clinical status and long-term survival after aortic valve replacement. From these results, we believe that new strategies for the earlier detection of myocardial fibrosis are needed to achieve a better prognostic outcome.

Influence of myocardial fibrosis on left ventricular hypertrophy in patients with symptomatic severe aortic stenosis.

AIM: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. METHODS: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was <90 kdyn/cm(2), while those with end-systolic wall stress >90 kdyn/cm(2) were considered to have non-physiologic hypertrophy. RESULTS: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 ± 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. CONCLUSIONS: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload.

Physiopathologic correlates of intrathoracic impedance in chronic heart failure patients.

BACKGROUND: Increased plasma levels of amino-terminal fraction of brain natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described by Doppler transmitral flow pattern are well-known markers of decompensated heart failure (HF). Recently, some implantable defibrillators have allowed monitoring of intrathoracic impedance, which is related to lung water content, potentially indicating HF deterioration. The aim of this study was to assess the correlation between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow indexes. METHODS: Data were collected from 111 HF patients, in six Italian centers. All patients were on optimal medical therapy. Device diagnostics, echographic data, NT-proBNP determination, and clinical status as assessed by the Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and at unscheduled examinations due to HF decompensation or device alerts. RESULTS: Over a median follow-up of 413 days, 955 examinations were performed. Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013) and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At the time of confirmed alert events, NT-proBNP was significantly higher than during confirmed nonalert event examinations; DtE did not differ, whereas impedance was significantly lower. CONCLUSION: A decrease in intrathoracic impedance is inversely correlated with NT-proBNP and directly correlated with DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for being a useful tool to identify early HF decompensation.

Surgical treatment of postinfarction left ventricular free wall rupture.

BACKGROUND: Left ventricular free wall rupture (LVFWR) is still one of the often fatal complications of acute myocardial infarction. Surgical repair is mandatory even with high operative mortality. The optimal surgical technique is controversial since the results depend on type of rupture. We present our mid-term surgical experience according to the status of the left ventricular tear and type of surgical repair. METHODS: From January 1997 to December 2007, 19 consecutive patients with LVFWR were treated at our institution. The mean age was 72 +/- 8 ranging from 53 to 81 years; there were eight males and 11 females. According to the intraoperative findings, patients were divided into two groups: group 1 (eight patients), where no macroscopic tear of the LVFW could be detected with blood oozing from infarcted zone (Oozing type LVFWR); and group 2 (11 patients), where a macroscopic defect of the epicardium, with free communication between left ventricular cavity and pericardial space, was identified (Blow-out type LVFWR). The patch covering and glue technique was applied for group 1 patients, while closure of the ventricular tear either by direct suture or by patch repair was used for group 2 patients. RESULTS: The interval between diagnosis of LVFWR and surgery was 2.9 +/- 1.1 hours. However, reevaluation of echocardiographic studies showed an early missed diagnosis of LVFWR in three patients of group 1 and in eight of group 2. Thus, the mean interval between initial signs of rupture and surgery was 9 +/- 8 hours and 21 +/- 15 hours, respectively, for oozing and blow-out type rupture. On arrival in the operating room, four patients were on cardiopulmonary resuscitation, while four were in cardiogenic shock. The hospital mortality was 12% (one death) in group 1 and 36% (four deaths) in group 2 mainly due to multiorgan failure. Fourteen patients were discharged with a mean follow-up of 3.8 +/- 3.5 years. During follow-up, one patient in group 1 died after 7.5 years. No recurrence of free wall rupture or aneurysm formation was demonstrated in all cases. At last follow-up, all survivors showed excellent clinical results with a preserved left ventricular function. Patients with oozing type LVFWR and patch covering technique repair showed an absence of left ventricular-restricted motion at the echocardiographic study. CONCLUSION: In patients with LVFWR, early diagnosis and surgical treatment are crucial for successful outcome when excellent results can be achieved with a simple glued patch covering technique.

Ischemia induced by transesophageal atrial pacing stress echocardiography predicts long-term mortality.

OBJECTIVES: It was the aim of this study to investigate the long-term value of transesophageal atrial pacing in predicting death in patients with known or suspected coronary artery disease. BACKGROUND: Exercise, dobutamine and dipyridamole stress echocardiography are all effective in predicting cardiac death. Transesophageal atrial pacing stress echocardiography (TAPSE) is a safe alternative to pharmacologic tests, but no information is available on prognosis with TAPSE. METHODS: One thousand and ten TAPSE were performed in 975 consecutive patients. TAPSE was feasible in 970 tests (96%); after exclusion of the 35 patients with more than 1 TAPSE and those 42 lost at follow-up (mean 4.5 +/- 3.7 years, median 6 years), the final population consisted of 857 patients (675 males, 58 +/- 9 years old). The Cox model was used to analyze the association of clinical, resting and TAPSE variables with cardiac death. RESULTS: TAPSE was abnormal in 281 (32%) patients. There were 46 cardiac-related deaths (5%), 25 among the 281 patients with an abnormal test (8.9%) and 21 among the 576 patients with a normal test (3.6%). The predictors of cardiac death were age, previous revascularization, resting wall motion score index and its variation during TAPSE. Abnormal TAPSE significantly increases the value of models predicting cardiac death. Moreover, cardiac mortality increased progressively with the extent of the induced ischemia. CONCLUSIONS: TAPSE is a useful tool in predicting death in patients with known or suspected coronary artery disease and might be considered an alternative to pharmacologic stressors.

Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain?

BACKGROUND: Previous reports suggested a relationship between coronary artery disease (CAD) and aortic valve sclerosis (AVS). However, whether AVS can be used as a marker of obstructive CAD (obCAD) in patients with chest pain is unknown. We hypothesized that AVS is a predictive marker for obCAD in patients hospitalized for chest pain. METHODS: We studied 93 consecutive patients with chest pain undergoing coronary angiography. All had negative cardiac enzymes and no previous diagnosis of cardiac ischemic disease. AVS was detected by transthoracic echocardiography. Resting electrocardiography, left ventricular systolic function, wall-motion abnormalities, and stress test results were considered. We calculated the diagnostic value for obCAD of AVS, stress test, and combination of the two methods. RESULTS: ObCAD was present in 29 patients (31%). Patients with obCAD had a higher prevalence of AVS (38 vs 14%, P = .02) and positive stress test (67 vs 28%, P = .02). The odds ratio for obCAD in the presence of AVS was 3.7 (95% confidence interval 1.3-10.4, P = .01). AVS (P = .01) and a positive stress test (P = .002) were independent predictors for obCAD at the multivariate analysis. AVS had sensitivity of 38% and specificity of 86%. Stress test had sensitivity of 67% and specificity of 72%. When echocardiographic detection of AVS was combined with stress test, the sensitivity and negative predictive value improved to 93% and 96%, respectively. CONCLUSIONS: AVS is an independent predictor for obCAD in patients with chest pain, thus, it should be considered in the risk stratification of these patients.

Left atrial volume provides independent and incremental information compared with exercise tolerance parameters in patients with heart failure and left ventricular systolic dysfunction.

OBJECTIVE: Left atrial volume (LAV) is a powerful predictor of outcome in patients with chronic heart failure (CHF) independently of symptomatic status, age and left ventricular (LV) function. It is unknown whether LAV provides independent and incremental information compared with exercise tolerance parameters. METHODS: 273 patients with CHF (mean (SD) 62 (9) years; 13% female) prospectively underwent echocardiography and exercise testing with maximal oxygen consumption (Vo(2)). The primary end point was composite and included cardiac death, hospitalisation for worsening heart failure or cardiac transplantation. RESULTS: At Cox proportional hazard analysis, LAV normalised for body surface area (LAV/BSA) was strongly associated with mortality (hazard ratio (HR) = 1.027 (95% CI 1.018 to 1.04), p<0.001). The predictive value of LAV/BSA was independent of Vo(2) and LV ejection fraction (EF) (HR = 1.014 (1.002 to 1.025), p = 0.02; HR = 0.95 (0.91 to 0.99), p = 0.02; HR = 0.89 (0.82 to 0.98), p = 0.02 for LAV/BSA, EF and Vo(2), respectively). Receiver operator characteristic (ROC) curve analysis identified the best cut-off values for prediction of the end point. LAV/BSA >63 ml, EF <30% and Vo(2) <16 ml/kg/min were considered to be risk factors. Patients with three risk factors had an HR of 38 (95% CI 11 to 129) compared with patients with no risk factors. CONCLUSION: LAV provides powerful prognostic information incrementally and independently of Vo(2). LAV, EF and Vo(2 )can be used to build a risk prediction model, which can be used clinically.

Aortic stiffness correlates with an increased extracellular matrix turnover in patients with dilated cardiomyopathy.

BACKGROUND: An increased extracellular matrix (ECM) turnover has been associated with poor survival in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). However, the influence of the accelerated collagen turnover on the progressive large artery stiffening process characterizing CHF has not been clarified. This is relevant because aortic stiffening imposes an additional systolic load and impairs exercise tolerance in CHF patients. Therefore, we investigated whether the serum aminoterminal propeptide of type III collagen (PIIINP), an established marker of ECM turnover and tissue fibrosis in DCM, was associated with aortic stiffness in DCM patients. METHODS AND RESULTS: A total of 89 patients with clinical diagnosis of DCM (age 62 +/- 9 years, 80% men, mean ejection fraction 34% +/- 8%) were selected. Aortic pulse-wave velocity (PWV), a well-established marker of aortic stiffness, was measured by Doppler ultrasonography. Serum concentration of PIIINP was determined by radioimmunoassay. Mean aortic PWV was 5.7 +/- 2.3 m/s, and PIIINP was 5.0 +/- 1.3 microg/L. The variables correlated with aortic PWV were age (r = 0.33, P = .002), PIIINP (r = 0.30, P = .005), heart rate (r = 0.27, P = .02), stroke volume (r = -0.24, P = .03) and New York Heart Association class (r = 0.25, P = .02). In a multivariate analysis, age (P = .02) and PIIINP (P = .01) were independently related with aortic PWV, accounting for 27% of its variance. CONCLUSIONS: Higher serum PIIINP levels are independently associated with a stiffer aorta in DCM patients. This suggests that abnormalities in the ECM turnover might involve the proximal elastic vasculature and could partially explain the progressive large artery stiffening process characterizing CHF.

Comparison of the long-term survival benefits associated with revascularization or medical therapy in patients with known coronary artery disease undergoing transesophageal atrial pacing stress echocardiography.

Although the utility of stress echocardiography for the diagnosis and prognostic evaluation of patients with suspected coronary artery disease (CAD) has been widely reported, few studies have evaluated the role of revascularization in relation to the presence of inducible ischemia during stress in patients with known CAD. The study population consisted of 295 consecutive patients who underwent transesophageal atrial pacing stress echocardiography (TAPSE) in the echocardiographic laboratory of our division between January 1988 and September 1997, in whom coronary angiography was performed within 10 days of the test. Patients were then assigned to revascularization or medical treatment according to the treatment given within 60 days of TAPSE. Cardiac-related deaths were higher in medically treated (19 of 135) than in revascularized (8 of 160) patients (p = 0.03). Parameters measured with TAPSE, i.e., positivity of the test, change in wall motion score index (DeltaWMSI and peak WMSI) were significantly related to mortality in medically treated patients but not in revascularized patients. At multivariate analysis, DeltaWMSI remained the most powerful predictor of cardiac death in medically treated patients (p = 0.005). Mortality progressively increased with increments in extent of inducible ischemia among medically treated patients (5 of 71 patients in DeltaWMSI 0, 3 of 27 in DeltaWMSI 0 to 25, 11 of 37 patients in DeltaWMSI >25) but not among revascularized patients (3 of 58 patients in DeltaWMSI 0, 2 of 51 in DeltaWMSI 0 to 25, 3 of 51 patients in DeltaWMSI >25). The survival curve in medically treated patients with ischemia in a remote zone (24 patients, 8 deaths) was worse than in other groups of medically treated patients (41 patients, 6 deaths). In conclusion, in patients with known CAD, the presence and extent of ischemia as evaluated with TAPSE worsens survival, if revascularization is not performed. In patients without ischemia at TAPSE, revascularization or medical therapy are equally effective.

Chronic heart failure with preserved left ventricular ejection fraction: diagnostic and prognostic value of left atrial size.

BACKGROUND: Almost 40% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (EF) and prognosis similar to those with reduced EF. Data on prognostic markers in such patients are limited. We analyzed the prevalence and prognostic value of left atrial (LA) size in this condition. METHODS: 89 normal subjects (Group I), 38 asymptomatic hypertensive patients (Group II) and 183 HF patients with preserved EF (EF >45%) (Group III) were studied. LA diameter (LAD), LV diastolic (LVD) and systolic (LVS) dimensions and mass (LVmass) and EF were measured. E and A wave velocities and E/A were measured. The primary end point was all cause mortality in group III patients. RESULTS: Groups did not differ in age, gender or EF. Group III patients had larger LAD (4.6+-1.0 cm) compared with both Group I (3.7+/-0.6) and Group II (3.7+/-0.5 cm) (p<0.0001). A markedly enlarged (arbitrarily defined as LAD higher or equal 5 cm) had an odds ratio of 34 (95% CI 8-144) in distinguishing HF patients from normals. After a mean follow-up period of 29+/-27 months, 40 patients (21.9%) died. In Cox univariate analysis, NYHA class (HR 2.8 95% C.I. 1.8-4.3; p<0.0001), diastolic blood pressure (DBP) (HR 0.92 95% C.I. 0.88-0.96; p<0.0001), age (HR 1.059 95% C.I. 1.01-1.11; p=0.02) and LAD (HR 1.72 95% C.I. 1.27-2.3; p=0.0005) were predictors of mortality. LAD predicted survival independently of other variables. CONCLUSION: The left atrium is frequently dilated in HF patients compared with controls despite similar EF. LAD showed powerful prognostic value independent of clinical variables.

Carotid atherosclerotic plaque instability in patients with acute myocardial infarction.

UNLABELLED: The instability of atherosclerotic plaque is partly determined by local factors, but systemic factors such as infection, inflammation, autoimmunity or genes might also be important. We aimed to analyze whether patients with acute myocardial infarction (AMI) might have a higher proportion of unstable plaques in the carotid arteries compared with patients who had had no acute coronary events. METHODS: Sixty-nine consecutive patients with AMI (Group 1) and 95 patients without acute coronary events (Group 2) had carotid artery duplex ultrasounds. Carotid atherosclerosis was quantified by number of plaques in the two carotid arteries, intimal media thickening and degree of maximal stenosis. According to their morphology, plaques were divided into stable (fibrocalcific) and unstable (soft and/or not homogeneous). RESULTS: The two groups did not differ as regards age (66+/-8 vs. 68+/-19; p=0.3), female sex (13% vs. 21%; p=0.3), mean number of carotid plaques (2.8+/-1 vs. 2.5+/-2; p=0.2), degree of stenosis (59+/-2% vs. 36+/-1%; p=0.2) or intimal media thickening (1.04+/-0.2 vs. 1.06+/-0.2; p=0.8). However, Group 1 pts more frequently had unstable carotid plaques compared with Group 2 (43% vs. 15%; p=0.004), and had a greater number of unstable carotid plaques (0.51+/-0.6 vs. 0.16+/-0.4: p<0.0001) and a higher ratio of unstable to stable plaque (19% vs. 8%; p=0.005). In the overall population, logistic regression analysis showed that after adjustment for degree of maximal stenosis, the presence of coronary artery event (AMI pts) predicted the presence of unstable carotid plaque (OR: 4.3 95% CI: 2.0-9.2; p=0.0002). CONCLUSION: Patients with unstable coronary artery disease expressed clinically as AMI, frequently had unstable atherosclerotic plaques in other arterial sites such as carotid arteries. This finding supports the hypothesis that plaque instability might reflect a systemic process.

Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity.

BACKGROUND: Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. METHODS: Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). RESULTS: The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). CONCLUSIONS: Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.