Incidence and predictors of new onset left ventricular diastolic dysfunction in asymptomatic patients with rheumatoid arthritis without overt cardiac disease.

Rheumatoid arthritis (RA) is associated with higher risk of heart failure. Several studies report that left ventricular (LV) diastolic dysfunction (LVDD), a silent precursor of heart failure, is widely present in RA patients. Very little is known about the factors related to the development of LVDD in this disease. In this study we assessed the incidence and the predictors of new-onset LVDD in RA patients. Two-hundred-ninety-five adults with RA without overt cardiac disease were prospectively analyzed from March 2014 to March 2015 by Doppler echocardiography. Among the 295 subjects evaluated, 217 (73.6%) had normal LV diastolic function and represented the final study population. At 1-year follow-up, 53 of 217 patients (24%) developed LVDD, which was of degree I (mild dysfunction) in all of them. By multivariate logistic regression analysis, lower E/A ratio of transmitral flow (ratio between the peak velocity of early diastolic "E" wave and late diastolic "A" wave of transmitral flow) was independently associated with new-onset LVDD [OR 0.17 (CI 0.09-0.57)], together with older age and higher systolic blood pressure. In a clinical predictive model derived from multivariate analysis, the new-onset LVDD rate event ranged from 0% (patients without any factor) to 75% (patients in whom the three predictors coexisted). A significant portion of patients with RA without overt cardiac disease develop LVDD at 1-year follow-up. This condition can be predicted by a simple clinical model which could improve the clinical management and the prognostic stratification of patients with RA.

Value of Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction to Predict Adverse Outcome in Patients with Asymptomatic Aortic Stenosis.

BACKGROUND AND AIM OF THE STUDY: Patients with asymptomatic aortic stenosis (AS) may have left ventricular systolic dysfunction (LVSD) defined as an impairment of the circumferential and/or longitudinal (C&L) myocardial fibers, despite a preserved left ventricular ejection fraction (LVEF). An assessment was made as to whether the combined LVSD of C&L fibers has a prognostic impact in asymptomatic AS. METHODS: A total of 200 asymptomatic AS patients was analyzed. Midwall shortening and mitral annular peak systolic velocity were considered as indices of C&L function and classified as low if <16.5% and <8.5 cm/s, respectively. The primary outcome was a composite of major cardiovascular events (MACE), including aortic valve-related and ischemic cardiovascular-related events. RESULTS: During a 25-month follow up period, MACE occurred in 69 patients (35%),while 46 of 72 patients (64%) had C&L LVSD and 23 of 128 patients (18%) had not (p <0.001). Cox analysis identified C&L LVSD as an independent MACE predictor, together with aortic transvalvular peak gradient, E/E' ratio and excessive left ventricular mass. C&L-LVSD also predicted the occurrence of aortic valve-related events and ischemic cardiovascular-related events analyzed separately. A receiver operating characteristic curve analysis showed that the area under the curve (AUC) for C&L LVSD in predicting MACE was 0.77, significantly higher (p = 0.002, z-statistic) than the AUCs of C&L fibers considered individually (0.64 and 0.63, respectively). CONCLUSION: C&L-LVSD provides additional prognostic information into traditional risk factors for patients with asymptomatic AS.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

BACKGROUND: Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. METHODS: Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. RESULTS: ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. CONCLUSIONS: In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Does treatment assignment influence the prognosis of patients with symptomatic severe aortic stenosis?

OBJECTIVE: Aortic valve replacement (AVR) is the standard therapy in patients with symptomatic aortic stenosis (AS). In high surgical risk patients, alternative therapeutic options to medical treatment (MT) such as trans-catheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) have been proposed. In this study we evaluated whether treatment assignment influences per se the prognosis of these subjects. PATIENTS AND METHODS: Criteria for treatment assignment were based on patient's clinical conditions, Logistic EuroSCORE and other co-morbidities ignored by EuroSCORE. Due to baseline clinical differences between patients with diverse treatment assignment, we used propensity score matching to achieve balance. RESULTS: 368 patients were studied: 141 underwent AVR, 127 TAVI, 49 BAV and 51 MT. 84 events (deaths for all causes) occurred during 14 months of follow-up: 11 AVR (8%), 26 TAVI (20%), 18 MT (35%), 29 BAV group (59%). Traditional Cox analysis identified treatment assignment as independent predictor of events (HR 1.82 [CI 1.10-3.25]) together with lower left ventricular ejection fraction, impaired renal function and history of heart failure. Matched Cox analysis by propensity score confirmed treatment assignment as an independent prognosticator of events (HR 1.90 [CI 1.27-2.85]), and showed similar rate events in TAVI and AVR patients, while it was significantly increased in BAV and MT patients. CONCLUSIONS: Treatment assignment may influence outcome of symptomatic patients with AS.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with asymptomatic aortic stenosis.

BACKGROUND: Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. METHODS: Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec, respectively (10th percentiles of controls). RESULTS: Combined C&L dysfunction was detected in 72 patients (36%). The variables associated with this condition were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak S' was linear and slightly significant in the whole population (r = 0.23; F statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns), negative (linear model) in the subgroup of patients without C&L dysfunction (r = -0.22; F = 0.02). CONCLUSIONS: C&L dysfunction is present in more than one-third of patients with asymptomatic AS and is associated with concentric LV geometry and higher degree of diastolic dysfunction. The relation between MS and peak S' largely varies in the subgroups with different C&L function.

Left atrial work in patients with stable chronic heart failure: factors associated and prognostic role.

BACKGROUND: Limited information is available on left atrial (LA) work in chronic heart failure (CHF) patients. We evaluated correlates and prognostic role of LA work in 243 CHF patients using as reference for normal LA work values 230 healthy controls. METHODS: Left atrial work was assessed by computation of LA kinetic energy (LAKE) from the formula: 0.5 × m × A(2) where m is LA stroke volume × blood density, and A is transmitral Doppler peak atrial velocity. The prespecified primary endpoint of the study was major cardiovascular (CV) events, a composite endpoint defined as CV death + hospitalization for heart failure (HF). RESULTS: Left atrial kinetic energy was 3.9 ± 2.7 in CHF patients and 2.6 ± 1.4 Kdynes/m(2) in controls (P < 0.001). Abnormally high LAKE (>5.4 Kdynes/m(2) = mean + 2 SD of the controls) was found in 19% of CHF patients and 4% of controls (P < 0.001). LAKE was independently associated with an increased shortening of left ventricular (LV) longitudinal fibers and renal dysfunction. CV death or hospitalization for decompensated HF occurred in 66% and 20% of patients with abnormally high and normal LAKE, respectively (P < 0.001). Abnormally high LAKE, not LA size, was an independent predictor of events hazard ratio (HR) 3.92 [95% CI 1.96-7.84] together with renal dysfunction and lower LV ejection fraction. CONCLUSION: In CHF patients, LAKE is significantly higher than in healthy controls, the prevalence of abnormally high LAKE is near fivefold higher in the former than in the latter. LAKE depends on systolic LV and renal function and is a strong predictor of CV death and hospitalization for HF. LA work has an incremental prognostic value over LA size.

Prognostic stratification by conventional echocardiography of patients with aortic stenosis: the "CAIMAN-ECHO score".

BACKGROUND AND AIM: Surgery is not recommended in asymptomatic patients with aortic stenosis (AS). However, prognosis of these patients is worse than retained. We built a simple score (named by the acronym "CAIMAN") for stratifying asymptomatic patients with AS according to the different risk for cardiovascular events. MATERIAL AND METHODS: Data from 141 patients with moderate-to-severe AS followed up for 36 months were analyzed. The end point "outcome" was defined as death of all causes or aortic valve replacement imposed by symptoms or hospital admission for myocardial infarction and/or heart failure. The score was validated in 143 patients prospectively recruited in 2 different centers. RESULTS: The 40 events occurred in the original cohort were associated with higher aortic transvalvular peak jet velocity, calcium score, and observed/predicted left ventricular (LV) mass ratio. Based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score 1-3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, 3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. After a mean period of 28 ± 18 months, event-free survival was 18%, 42%, 91%, and 96% in the 4 quartiles of echo score. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. CONCLUSIONS: The CAIMAN-ECHO score is a simple and feasible tool useful for an accurate prognostic stratification of patients with asymptomatic moderate-to-severe AS.

Analysis of left ventricular systolic function by midwall mechanics in patients with obstructive sleep apnoea.

AIMS: midwall mechanics reveal systolic dysfunction in obese and hypertensive patients with concentric left ventricular (LV) geometry, which is frequently detected in subjects with obstructive sleep apnoea (OSA). Midwall mechanics have never been studied in these patients, who frequently experience heart failure (HF). METHODS AND RESULTS: we analysed midwall stress-shortening relations by echocardiography in 150 controls and 200 patients with OSA (age 62 ± 13 years) without known cardiac disease. On the basis of the severity of OSA, patients were divided into mild OSA (n = 63), moderate OSA (n = 70), and severe OSA (n = 67). LV stress-corrected midwall shortening (scMS) was considered low if <87% in men and <90% in women. scMS was similar in controls and mild OSA (90 ± 13 and 91 ± 18%, respectively) and significantly lower in moderate and severe OSA (83 ± 14 and 83 ± 15%; all P < 0.001 vs. controls and mild OSA). Prevalence of low scMS was 40 and 39% in controls and mild OSA (P=NS), 62% in moderate and 61% in severe OSA (both P < 0.001 vs. controls and mild OSA). In logistic regression analysis, low scMS was associated with moderate-severe OSA (OR 3.82, P < 0.001) independent of significant associations with diabetes (OR 5.06, P < 0.01), LV hypertrophy (OR 1.89, P = 0.01), and LV concentric geometry (OR 2.79, P < 0.001). CONCLUSION: midwall mechanics are impaired in more than half of middle-aged patients with OSA without known cardiac disease. Moderate-severe OSA predicts LV systolic dysfunction independent of diabetes, LV hypertrophy, and concentric geometry. These relations may in part explain the increased rate of HF and cardiovascular events in these patients.

Changes in plasma N-terminal proBNP levels and ventricular filling pressures during intensive unloading therapy in elderly with decompensated congestive heart failure and preserved left ventricular systolic function.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels depend on left ventricular (LV) filling pressures and correlate with the state of neurohormonal modulation in patients with congestive heart failure (CHF). In these subjects, therapy of decompensated CHF can determine acute changes in BNP levels. METHODS AND RESULTS: We defined the sequential pattern of N-terminal (T) proBNP in elderly with decompensated CHF and preserved LV systolic function undergoing intensive unloading therapy, assessed the prevalence of patients who significantly reduced NTproBNP at the end of treatment, and verified the relations between changes in NTproBNP and ventricular filling pressures. NTproBNP was measured in 30 patients hospitalized for worsening CHF with LV ejection fraction >50% at admission and after 2 to 4 and 6 to 8 days from the start of treatment. Patients who exhibited a reduction in NTproBNP >35% from baseline to 8-day evaluation were defined as "responders." Twelve healthy subjects matched for age and sex were used as controls. NTproBNP was significantly higher in CHF patients than controls in all time points, to a greater extent in baseline evaluation (2982 [lower/upper quartile 1273/8146] versus 235 [150/280] pg/mL). A progressive, linear reduction of NTproBNP was detected in CHF patients during unloading. At Day 8, 18 patients (60%) resulted in "responders," whereas 12 (40%) were "nonresponders." The former could be predicted through higher pulmonary artery wedge pressure at baseline. Surprisingly, ventricular filling pressures similarly declined in responders and non responders. At Day 8, NTproBNP was yet 7-fold higher in CHF patients than controls. CONCLUSION: Intensive unloading therapy is associated with a significant short-term reduction in NTproBNP in elderly with CHF and preserved LV systolic function. This behavior is progressive and linear during the first week and parallels a reduction in ventricular filling pressures which, however, does not differ between patients who significantly reduce NTproBNP and those who do not. Thus the short-term changes in NTproBNP during intensive unloading therapy in our patients do not depend only on the acute improvement in hemodynamic conditions.

Does atrial fibrillation in very elderly patients with chronic systolic heart failure limit the use of carvedilol?

BACKGROUND AND AIMS: It is well known that beta-blockers are useful in patients with chronic heart failure (CHF). These favourable effects have recently been observed even in elderly CHF patients. Objectives of the present study were to evaluate the feasibility, tolerability and safety of carvedilol therapy in a cohort of patients > 70 years of age with CHF and left ventricular ejection fraction < 40% with chronic atrial fibrillation. For this purpose, we designed an observational, 12-month prospective study. RESULTS: Among 240 patients who were referred to our centers and met inclusion criteria, 64 had chronic atrial fibrillation (27%). Thirty-nine out of these 64 subjects (61%) were treated with carvedilol, while 25 patients (39%) had contraindications to such treatment. In the cohort of 176 patients with stable sinus rhythm (control group), carvedilol could be administered in 121 patients (69%), while it was not given in 55 (31%, p=ns). Airways disease was the main reason for exclusion from carvedilol in this setting of patients. No difference in 1-year tolerability of study drug was observed among patients with chronic atrial fibrillation (29 of 33 patients=87.9%) and stable sinus rhythm (95 of 102=93.1%). Adverse events leading to the discontinuation of carvedilol in these two populations were rare and never resulted in any disability, death or were life-threatening. CONCLUSION: In over-70 patients with systolic CHF, chronic atrial fibrillation does not limit the possibility of testing beta-blocker therapy. Carvedilol was equally tolerated and safe in patients with atrial fibrillation and sinus rhythm.

Influence of age on the relationship between left atrial performance and left ventricular systolic and diastolic function in systemic arterial hypertension.

BACKGROUND: Changes in left ventricular (LV) systolic and diastolic properties may generate variations in left atrial (LA) size and function in many pathophysiological models of LV overload. Besides these states, increasing age may independently influence and magnify LA changes. OBJECTIVE: To investigate the relation of LA size and function to increasing age in hypertensive patients, and to evaluate whether this relationship is influenced by LV function. METHODS: Three hundred thirty-six patients were evaluated using Doppler echocardiography. Maximal LA volume and ejection force were used as indexes of LA size and performance, respectively. RESULTS: Age was positively associated with LA ejection force (r=0.34, P<0.001) and maximal volume (r=0.25, P<0.001). The effect of age was independent of LV mass and LV concentric geometry, which independently influenced LA parameters. The relationship between age and LA ejection force was maintained in patients with and without LV systolic dysfunction, and in those with normal diastolic function, whereas it was lost in those with LV diastolic dysfunction. The relationship between age and LA size was not influenced by either LV systolic or diastolic function. LA ejection force was associated with LV mass and LV concentric geometry in all groups of patients 56 years or older, while no association was found between these variables in patients younger than 56 years. LV mass was systematically linked to maximal LA volume in all classes of age, together with LV end-diastolic volume in all groups of patients 56 years of age or older, and LV concentric geometry in patients 68 years of age or older. CONCLUSIONS: There is a positive relationship between age and LA size and performance in hypertensive patients, which is independent of LV mass and geometry. The effect of age on LA performance is insignificant when diastolic dysfunction occurs.

Reasons why patients suffering from chronic heart failure at very low risk for mortality die.

BACKGROUND: A proper prognostic stratification is crucial for organizing an effective clinical management and treatment decision-making in patients with chronic heart failure (CHF). In this study, we selected and characterized a sub-group of CHF patients at very low risk for death aiming to assess predictors of death in subjects with an expected probability of 1-year mortality near to 5%. METHODS: We used the Cardiac and Comorbid Conditions HF (3C-HF) Score to identify CHF patients with the best mid-term prognosis. We selected patients belonging to the lowest quartile of 3C-HF score (≤9 points). RESULTS: We recruited 1777 consecutive CHF patients at 3 Italian Cardiology Units (age 76±10years, 43% female, 32% with preserved ejection fraction). Subjects belonging to the lowest quartile of 3C-HF score were 609. During a median follow-up of 21 [12-40] months, 48 of these patients (8%) died, and 561 (92%) survived. The variables that contributed to death prediction by Cox regression multivariate analysis were older age (HR 1.03[CI 1.00-1.07]; p=0.04), male gender (HR 2.93[CI 1.50-5.51]; p=0.002) and a higher degree of renal dysfunction (HR 0.96[CI 0.94-0.98]; p<0.001). CONCLUSIONS: The prognostic stratification of CHF patients by 3C-HF score allows one to select patients at different outcome and to identify the factors associated with death in outliers with a very low mortality risk at mid-term follow-up. The reasons why these patients do not outlive the matching part of subjects who expectedly survive are related to a declined renal function and unmodifiable conditions including older age and male gender.

Pharmacological left ventricular reverse remodeling in elderly patients receiving optimal therapy for chronic heart failure.

BACKGROUND AND AIMS: In recent years, reversal of established left ventricular (LV) dilatation has been increasingly recognized in middle-aged patients with dilated cardiomyopathy receiving angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers. We performed this prospective study to evaluate whether optimized therapy for heart failure also induces LV reverse remodeling in older patients. METHODS: One hundred and twenty-four patients aged >70 years with LV ejection fraction <40% underwent clinical and echocardiographic evaluation at baseline and after 1 year. During the early stage of follow-up, pharmacological therapy was optimized. LV reverse remodeling was defined as a reduction in LV end-diastolic volume >25% from baseline to final evaluation. RESULTS: LV reverse remodeling was recognized in 32 patients (26%). Compared to the subjects who did not improve LV geometry, those with reverse remodeling had, at baseline, higher arterial blood pressure, lower serum creatinine levels, shorter duration of symptoms of heart failure, more frequently received beta-blocker therapy and had predominantly nonischemic aetiology. The variables associated with the development of reverse remodeling in the multivariate analysis were shorter duration of symptoms of heart failure (Odds ratio: 7.7; CI: 2.5-23.3, p=0.0001) and beta-blocker therapy (Odds ratio: 6.0; CI: 1.6-23.3, p=0.01). CONCLUSIONS: LV reverse remodeling takes place in elderly as well as in younger heart failure patients. A significant proportion of elderly patients undergoes this favourable process which occurs prevalently in patients receiving beta-blocker therapy with a short history of cardiac disease.

Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure.

BACKGROUND AND AIM: Mitral regurgitation (MR) has been demonstrated to be a powerful predictor of adverse outcome in middle-aged patients with chronic heart failure (CHF). In this study, we sought to define the prognostic impact of functional mitral regurgitation in a population of elderly patients with systolic CHF. METHODS: One hundred seventy-five outpatients aged >70 years with validated CHF and left ventricular ejection fraction <40% underwent clinical and echocardiographic evaluations at baseline. Mitral regurgitation was diagnosed by Color Doppler and quantified in 5 categorical values using a 0-4+ grading system. Outcome measures included 1-year mortality and hospitalization for worsening CHF. RESULTS: The distribution of patients according to the 5 different degrees of MR detected at baseline was: absent=11%, 1+=31%, 2+=38%, 3+=16%, 4+=4%. The relationship between MR and mortality was direct and approximately linear (r=0.39, p=0.00001). The prevalence of death in the 5 subgroups was 0%, 7%, 15%, 45%, 57%, respectively. Multivariate logistic regression analysis showed that MR was the strongest predictor of death (OR 4.47, 95% CI 1.50-13.0), independently of the presence of diabetes mellitus, older age and larger left ventricular end-diastolic volume. No association was found between MR and hospitalization for worsening CHF (r=0.08, p=0.41). CONCLUSIONS: This study establishes the direct and independent relationship between MR severity and one-year mortality among elders with systolic CHF. Conversely, MR does not provide useful information regarding the risk of subsequent hospitalization for worsening CHF.

Relationship between left ventricular geometry and left atrial size and function in patients with systemic hypertension.

BACKGROUND: Arterial hypertension determines distinct adaptive left ventricular geometric responses, which may differently affect left ventricular function and left atrial performance. OBJECTIVES: In this study, the effect of left ventricular geometry on left atrial size and function, and the relationship between left atrial size and left ventricular mass were assessed in 336 patients with systemic arterial hypertension who had undergone Doppler echocardiography. METHODS AND RESULTS: Patients were classified into concentric (110 patients with concentric left ventricular geometry defined as relative wall thickness > or = 0.44) and eccentric groups (226 patients with relative wall thickness < 0.44). Comparison to the latter, the former had greater left atrial size, left atrial ejection force, left ventricular mass and lower left ventricular midwall fractional shortening. Left ventricular concentric, rather than eccentric, geometry emerged by multivariate analysis as a factor independently associated with the highest degree of left atrial ejection force. Left atrial size was positively related to left ventricular mass in the whole population (r = 0.65, SEE = 6 ml, P < 0.00001). This relationship was maintained in the subgroups with concentric (r = 0.65, SEE = 6 ml, P < 0.00001) or eccentric geometry (r = 0.59, SEE = 6 ml, P < 0.00001). CONCLUSIONS: Our results indicate that the relationship of left ventricular geometry to both left atrial size and ejection force in hypertensive patients is relevant. Concentric left ventricular geometry is associated with greater left atrial size and ejection force than eccentric geometry, suggesting that increased left ventricular stiffness has a greater effect in stimulating left atrial performance than left ventricular end-systolic stress. The degree of left atrial enlargement similarly depends on left ventricular mass in patients with concentric and eccentric geometry.

Comparison of left ventricular geometry and left atrial size and function in patients with aortic stenosis versus those with pure aortic regurgitation.

Chronic aortic valve disease can result in distinct adaptive left ventricular (LV) geometric patterns, which has different effects on LV function and left atrial (LA) performance. In this study we assessed the effect of LV geometry on LA size and function, and we verified the relation between LA size and LV mass in patients with distinct LV overload subsets. We analyzed 183 patients with aortic valve disease who underwent a complete echocardiographic evaluation. Based on the type of valvular dysfunction, patients were classified into 2 groups: 141 patients with aortic stenosis (group AS) and 42 patients with pure aortic regurgitation (group AR). Each of these 2 groups were then divided into those with a concentric LV pattern and those with an eccentric pattern. Both LA size and LA ejection force were significantly greater in group AS than group AR, particularly in patients with a concentric LV pattern. The degree of LA enlargement depended on LV mass in the patients with a concentric LV pattern (group AS r = 0.61, p <0.00001; group AR r = 0.38, p = 0.04). In contrast, no relation was found between LA size and LV mass in the patients with an eccentric pattern, independently of the type of valve dysfunction. Our results indicate that the influence of LV geometry on LA size and function in patients with aortic valve disease is relevant. A concentric LV pattern is associated with greater LA size and higher ejection than an eccentric pattern, suggesting that chronic LV pressure overload more than volume overload has a greater effect on stimulating increases in LA performance. The degree of LA enlargement depends on LV mass in patients with a concentric LV pattern, whereas it was unpredictable in those with an eccentric LV pattern.

Hemodynamic response to intensive unloading therapy (furosemide and nitroprusside) in patients >70 years of age with left ventricular systolic dysfunction and decompensated chronic heart failure.

In patients with decompensated chronic congestive heart failure (CHF), intensive unloading therapy allows an acute decrease in ventricular filling pressures and improves long-term prognosis. Because elderly patients do not routinely undergo invasive hemodynamic evaluation, they are generally denied such a pharmacologic approach. We prospectively characterized the acute hemodynamic response to intensive unloading and its prognostic significance in a elderly population with CHF who were hospitalized for cardiac decompensation. Fifty-nine patients aged >70 years with left ventricular systolic dysfunction underwent intensive unloading therapy (furosemide and nitroprusside) tailored to reduce ventricular filling pressures to near-normal levels. The hemodynamic parameters were monitored by Doppler echocardiography. At baseline, left and right ventricular filling pressures were 21 +/- 3 and 10 +/- 3 mm Hg, respectively. Although all patients experienced a relevant improvement in clinical status during hospital stay, a significant reduction of ventricular filling pressures was detected at discharge in only 40 of them (68%) (responders), whereas 19 patients (32%) had a deficient response to therapy (nonresponders). This unfavorable behavior was predicted by the presence of renal dysfunction at admission. During 19-month follow-up, death due to cardiovascular causes occurred in 8 of 40 responders (20%) and in 9 of 19 nonresponders (47%) (p <0.005). Hospitalizations for cardiovascular causes were more frequent in the nonresponders (58% vs 8%, p <0.0001). Thus, a deficient hemodynamic response to intensive unloading treatment is not infrequent in elderly patients with decompensated CHF. This behavior is predicted by renal dysfunction at admission and is associated with poorer outcome.

Prevalence, predictors, and prognostic implications of improvement in left ventricular systolic function and clinical status in patients >70 years of age with recently diagnosed systolic heart failure.

In recent years, several clinical trials conducted on selected middle-aged patients have documented the positive effects of new pharmacologic and nonpharmacologic treatment on chronic heart failure (HF). More recently, some investigators reported cases of elderly patients who had improved clinical conditions and left ventricular (LV) systolic function, but neither the prevalence nor the clinical variables associated with this phenomenon have ever been characterized in this population. To assess the prevalence and the predictors of "improvement" of HF, we prospectively analyzed 87 patients with a recent diagnosis of HF and LV systolic dysfunction, aged >70 years, who were consecutively admitted to our center for functional class impairment (New York Heart Association class III and IV). After discharge, patients underwent clinical and echocardiographic evaluations every 6 months. During follow-up (17 +/- 9 months) improvement was documented in 31 subjects (36%). The variables associated with improvement in the multivariate analysis were the absence of diabetes (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.3 to 19.9, p = 0.007), history of arterial hypertension (OR 3.9, CI 1.3 to 11.1, p = 0.01), and beta-blocker therapy (OR 3.4, CI 1.1 to 10.8, p = 0.03). An improvement in clinical status and LV systolic function is not infrequently observed in patients >70 years of age who have a recent diagnosis of HF. This behavior occurs prevalently in patients receiving beta-blocker therapy who have a history of arterial hypertension, and is inversely related to the presence of diabetes mellitus.

Pre-discharge initiation of beta-blocker therapy in elderly patients hospitalized for acute decompensation of chronic heart failure: an effective strategy for the implementation of beta-blockade in heart failure.

BACKGROUND: Current guidelines recommend beta-blockers in patients with heart failure and left ventricular systolic dysfunction. These agents, however, are largely underused in elderly patients because of the perception of up-titration complexity and the fear of side effects. METHODS: We prospectively assessed the feasibility, safety, tolerability, and 1-year outcome of the in-hospital initiation of carvedilol in elderly patients admitted for worsening heart failure. RESULTS: Among 164 eligible subjects (age > 70 years, left ventricular ejection fraction < 40% and no sign of congestion), 120 (73%) received carvedilol, on average 4.5 days after admission. The drug was permanently withdrawn in 10 out of 116 survivors (9%) at 60 days: 5 did not tolerate the starting dose because of worsening heart failure (n = 1), bradycardia (n = 1), and bronchospasm (n = 3). Two discontinued carvedilol during the in-hospital dose titration phase because of increasing premature ventricular beats and transient second degree atrioventricular block. The remaining 3 dropouts (fatigue in 2 and symptomatic bradycardia in 1 case) occurred after discharge. During the period between 60 days and 12 months, carvedilol was discontinued in 2 patients because of a depressive syndrome and symptomatic bradycardia. In no case these adverse events lead to death or were life-threatening, required hospitalization or resulted in any disability. The 1-year tolerability was 89%, the mortality was 17.5%, the frequency of hospitalization for worsening heart failure was 21%. CONCLUSIONS: Thus, our results show that the in-hospital initiation of carvedilol is feasible and well-tolerated in elderly patients with recent worsening heart failure, and allows rapid identification of the most intolerant patients. The proportion of subjects taking carvedilol after 1 year from discharge was very high. This unconventional approach could significantly modify the use of beta-blockers in clinical practice.

Reasons why patients suffering from chronic heart failure at very high risk for death survive.

BACKGROUND: An accurate prognostic stratification is essential for optimizing the clinical management and treatment decision-making of patients with chronic heart failure (HF). Among the best available models, we used the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause mortality in patients with CHF. METHODS: we selected and characterized the subgroup of patients at very high risk with the worst mid-term prognosis belonging to the highest decile of 3C-HF score with the aim to assess predictors of survival in subjects with an expected probability of 1-year mortality near to 45%. METHODS AND RESULTS: We recruited 1777 consecutive chronic HF patients at 3 Italian Cardiology Units. Median age was 76 ± 10 years, 43% were female, and 32% had preserved ejection fraction. Subjects belonging to the highest decile of 3C-HF score were 246 (13.8% of total population). During a median follow-up of 21 [12-40] months, 110 of these patients (45%) survived and 136 (55%) died. The variables that contributed to survival prediction emerged by Cox regression multivariate analysis were the lower degree of renal dysfunction and higher body mass index. CONCLUSIONS: The prognostic stratification of chronic HF patients allows in daily practice to select patients at different risk for death and identify prognosticators of survival in outliers at very high risk of death. The reasons why these patients outlive the matching part of subjects who expectedly die are related to the maintenance of a satisfactory renal function and body mass index.