Echocardiography of right ventricular-arterial coupling predicts survival of elderly patients with heart failure and reduced to mid-range ejection fraction.

Echocardiography of right ventricular (RV)-arterial coupling obtained by the estimation of the ratio of the longitudinal annular systolic excursion of the tricuspid annular plane and pulmonary artery systolic pressure (TAPSE/PASP) has been found to be a remarkable prognostic indicator in patients with HF. Our aim was to evaluate the impact of TAPSE, PASP and their ratio in the prognostic stratification of outpatients with HF aged ≥70 years and reduced to mid-range ejection fraction (EF). A complete echocardiographic examination was performed in 400 outpatients with chronic HF and left ventricular (LV) EF ≤50% who averaged 77 years in age. During a median follow-up period of 25 months (interquartile range: 8-46), there were 135 cardiovascular deaths. Two different Cox regression models were evaluated, one including TAPSE and PASP, separately, and the other with TAPSE/PASP. In the first model, LV end-systolic volume index, age, no angiotensin converting enzyme (ACE) inhibitor use, TAPSE, PASP and gender were found to be independently associated with the outcome after adjustment for demographics, clinical, biochemical, echocardiographic data. In the second model, TAPSE/PASP resulted the most important independent predictor of outcome (hazard ratio [HR]:0.07, p<0.0001) followed by LV end-systolic volume index, no ACE inhibitor use, age and gender. The use of the variable TASPE/PASP improved the predictive value of the new multivariable model (area under the curve [AUC] of 0.74 vs AUC of 0.71; p<0.05). TASPE/PASP improved the net reclassification (NRI = 14.7%; p<0.01) and the integrated discrimination (IDI = 0.04; p<0.01). In conclusion, the study findings showed that assessment of RV-arterial coupling by TAPSE/PASP was of major importance to assess the prognosis of patients with chronic HF and LV EF ≤50% aged ≥70 years.

Combining echo and natriuretic peptides to guide heart failure care in the outpatient setting: A position paper.

BACKGROUND: Chronic heart failure (HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources. METHODS: This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were as follows: "heart failure, echocardiography, natriuretic peptides" in combination with "treatment, biomarkers, guidelines." RESULTS: Recent studies have supported the value of natriuretic peptides (NPs) and Doppler echocardiographic biomarkers of increased left ventricular (LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, that is to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce rehospitalization. CONCLUSION: We discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF.

A multiparametric clinical and echocardiographic score to risk stratify patients with chronic systolic heart failure: derivation and testing.

Although echo Doppler and biomarkers are the most common examinations performed worldwide in heart failure (HF), they are rarely considered in risk scores. In outpatients with chronic HF and left ventricular ejection fraction (LVEF) ≤45%, data on clinical status, echo Doppler variables, aminoterminal pro-type B natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and drug therapies were combined to build up a multiparametric score. We randomly selected 250 patients to produce a derivation cohort and 388 patients were used as a testing cohort. Follow-up lasted 29 ± 23 months. The univariable predictors that entered into the multivariable Cox model were as follows: furosemide daily dose >25 mg, inability to tolerate angiotensin converting enzyme (ACE) inhibitors, inability to tolerate ß-blockers, age >75 years, New York Heart Association (NYHA) >2, eGFR<60 mL/min, NT-proBNP plasma levels above the median, tricuspid plane systolic excursion (TAPSE) ≤14 mm, LV end-diastolic volume index (LVEDVi) >96 mL/m(2) , moderate-to-severe mitral regurgitation (MR) and LVEF <30%. The scores of prognostic factors were obtained with the respective odds ratio divided by the lower odd ratio: 4 points for furosemide dose, 3 points for age, NT-proBNP, LVEDVi, TAPSE, 2 points for inability to tolerate ß-blockers, inability to tolerate ACE inhibitors, NYHA, eGFR<60 mL/min, moderate-to-severe MR, 1 point for LVEF. The multiparametric score predicted all-cause mortality either in the derivation cohort (68.4% sensitivity, 79.5% specificity, area under the curve [AUC] 78.7%) or in the testing cohort (73.7% sensitivity, 71.3% specificity, AUC 77.2%). All-cause mortality significantly increased with increasing score both in the derivation and in the testing cohort (P < 0.0001). In conclusion, this multiparametric score is able to predict mortality in chronic systolic HF.

Prognostic value of pulsed tissue Doppler imaging for the assessment of left ventricular systolic function in patients with nonischemic dilated cardiomyopathy.

There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF.

Patterns of left ventricular remodeling in chronic heart failure: prevalence and prognostic implications.

BACKGROUND AND AIM: Many descriptors of left ventricular (LV) remodeling have important prognostic implications in patients with chronic systolic heart failure (HF). We sought to assess the prognostic value of the combination of increased LV mass with a disproportion between wall thickness and internal diameter. METHODS AND PATIENTS: Patients (n = 536) with chronic HF, ejection fraction <50% and LV end-diastolic volume index >91 mL/m(2), classified according to LV mass index and relative wall thickness (RWT), were followed up for 33 ± 21 months. Ventricular mass was determined using a standard M-mode echocardiographic method. Relative wall thickness was defined as the ratio of (sum of interventricular septum thickness in diastole + posterior wall thickness in diastole)/LV end-diastolic diameter. RESULTS: Prevalence of the pattern of increased LV mass index, defined as LV mass index >148 g/m(2) in men and >122 g/m(2) in women, and decreased RWT (<0.34) was 29%. Multivariable predictors of all-cause mortality were age >70 years (P < .0001), New York Heart Association class >2 (P < .0001), increased LV mass index, and decreased RWT (P = .003), E wave deceleration time ≤140 ms (P = .005), and male gender (P = .025). Patients with increased LV mass index and decreased RWT had a worse survival (33%) than patients with less LV mass index and normal to reduced RWT (log-rank 23.92; P < .0001). Comparisons of Cox models showed that the combination of increased mass index and decreased RWT added prognostic value to a model that included ejection fraction and end-systolic volume index. CONCLUSION: In patients with systolic HF, an independent and incremental risk of adverse outcome was associated with increased mass index and decreased RWT.

Combining blood flow and tissue Doppler imaging with N-terminal pro-type B natriuretic peptide for risk stratification of clinically stable patients with systolic heart failure.

AIMS: This study was designed to ascertain whether the combination of Doppler assessment of the ratio of mitral blood flow to myocardial early diastolic velocities (E/E(m) ratio) and plasma N-terminal pro-type B natriuretic peptide (NT-proBNP) testing is useful to better stratify patients with stable systolic heart failure (HF). METHODS AND RESULTS: A total of 362 outpatients with chronic systolic HF (left ventricular ejection fraction or=12), 77% in those with the E/E(m) ratio in the intermediate third, and 86% in those with the E/E(m) ratio in the lower third (

Value of tissue Doppler imaging for risk stratification of patients with chronic systolic heart failure with or without restrictive mitral flow.

AIMS: The aim of this study was to assess the prognostic value of tissue Doppler imaging (TDI) in patients with chronic systolic heart failure (HF) with or without restrictive mitral flow (RMF). METHODS AND RESULTS: Echocardiograms were obtained in 378 patients with chronic systolic HF [ejection fraction (EF) < or = 45%] in sinus rhythm. Restrictive mitral flow was defined by an E wave deceleration time (EDT) < or = 140 ms. Tissue Doppler imaging early (Em) diastolic and systolic (Sm) velocities were measured at the mitral annulus. Patients were followed-up for a median of 32 months. Endpoints were all-cause mortality and the combination of death or HF hospitalization. Mean left ventricular EF was 32 +/- 8%. Restrictive mitral flow and TDI annular velocities were all univariate predictors of the endpoints. Ejection fraction <25% was the only multivariate predictor of all-cause mortality. E wave deceleration time and Em < 8 cm/s were independently associated with the combined endpoint of death or HF hospitalization. At 48 months, survival was 61% in patients with RMF and 82% in patients with non-RMF (log-rank: 21.6; P < 0.0001). When patients were stratified according to Em at or above 8 cm/s or below 8 cm/s, those with RMF and Em < 8 cm/s exhibited the worst survival (log-rank: 27.16; P < 0.0001). Patients with Sm < or = 6 cm/s had a 58% survival rate, whereas it was 82% in patients with Sm > 6 cm/s (log-rank: 12.73; P = 0.0004). CONCLUSION: Doppler annular velocities provided useful information for prognostication of patients with systolic HF. Particularly, categorization of patients according to Em velocities allowed us to further stratify patients with RMF and non-RMF.

Effects of L-arginine on the Minnesota Living with Heart Failure Questionnaire quality-of-life score in patients with chronic systolic heart failure.

BACKGROUND: L-arginine, the precursor of nitric oxide, may restore nitric oxide levels and bioavailability and influence symptom severity, quality of life (QoL), physical performance, and left ventricular (LV) diastolic abnormalities in patients with chronic systolic heart failure (HF). The aim was to evaluate the effects of orally administered L-arginine in chronic HF patients. MATERIAL/METHODS: A parallel double-blind multicenter randomized study was performed in 68 patients (mean age: 64+/-11 years) with mild-to-moderate systolic HF (NYHA class II-III) and LV ejection fraction (EF)

Impaired Left Ventricular Global Longitudinal Strain among Patients with Chronic Kidney Disease and End-Stage Renal Disease and Renal Transplant Recipients.

BACKGROUND: Although heart failure is the most prevalent cardiovascular disease associated with adverse outcome in chronic kidney disease (CKD) and after kidney transplantation, left ventricular (LV) systolic function is often preserved in renal patients. The aim of this study was to evaluate global longitudinal strain (GLS), which is reportedly a more accurate tool for detecting subclinical LV systolic dysfunction, in patients with various degrees of renal function impairment, including kidney transplant recipients (KTRs). METHODS: This prospective study evaluated demographic, clinical, and ultrasound data, including the assessment of LV GLS and mitral E peak velocity and averaged ratio of mitral to myocardial early velocities (E/e'), of 70 consecutive renal patients (20 with stage 2-4 CKD, 25 with end-stage renal disease on hemodialysis [HD], and 25 KTRs). All patients had an LV ejection fraction ≥50% and no history of heart failure or coronary artery disease. We used multivariable logistic analysis to assess the risk of compromised GLS. One hundred and twenty control subjects with or without hypertension served as controls. RESULTS: A compromised GLS <-18% was shown in 55% of patients with stage 2-4 CKD, 60% of HD patients, and 28% of KTRs, while it was 32% in hypertensive controls and 12% in non-hypertensive controls (p < 0.0001). Patients with HD had higher systolic pressure and a significantly greater prevalence of increased LV mass and diastolic dysfunction. In renal patients, E/e' (p = 0.025), and LV mass index (p = 0.063) were independent predictors of compromised GLS at logistic regression analysis. E/e', systolic artery pressure, and LV mass also exhibited the greatest areas under the curve on receiver operating characteristic analysis to identify a compromised GLS. CONCLUSIONS: Renal disease proved to be associated with early and subclinical impairment of LV systolic function, which persists after starting dialysis and even in spite of successful kidney transplantation. An increased E/e' resulted to be the most powerful independent predictor of abnormal GLS.

Plasma N-terminal protype-B natriuretic peptide levels in risk assessment of patients with mitral regurgitation secondary to ischemic and nonischemic dilated cardiomyopathy.

BACKGROUND: Functional mitral regurgitation (MR) is a factor affecting prognosis of patients with chronic left ventricular (LV) dysfunction. The aim of the study was to investigate whether the evaluation of plasma N-terminal protype-B natriuretic peptide (NT-proBNP) concentrations is useful for prognostic assessment of patients with functional MR due to either ischemic or nonischemic chronic LV dysfunction. METHODS: Echocardiograms were obtained in 207 patients with chronic LV dysfunction (ejection fraction or=0.7 cm raised MR grade to severe. Median follow-up duration was 29 months. RESULTS: The NT-proBNP levels increased significantly with MR severity. At multivariate analysis, NT-proBNP was an independent predictor of cardiac death (hazard ratio 2.17, CI 1.10-4.30, P = .026) and the most powerful predictor of cardiac death or heart failure-related hospitalization (hazard ratio 3.19, CI 1.89-5.37, P < .0001). A progressively worse outcome was apparent when patients were stratified by a graded increase in MR severity and by quartiles of NT-proBNP levels. Increased NT-proBNP concentrations and more-than-mild MR identified patients with the highest risk of cardiac mortality. CONCLUSION: Assessment of plasma NT-proBNP allows for stratifying patients with functional MR regardless of their degree of valvular incompetence. Even in case of only mild or moderate MR, but increased NT-proBNP, patients have to face poor outcome.

Prognostic value of N-terminal pro-type-B natriuretic peptide and Doppler left ventricular diastolic variables in patients with chronic systolic heart failure stabilized by therapy.

Prognostication of patients with chronic heart failure (HF) stabilized by therapy may be difficult. Therefore, the aim was to evaluate whether combined assessment of plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) and Doppler left ventricular (LV) diastolic variables was relevant to the prognosis of patients with stable HF. Outpatients with LV systolic HF (ejection fraction < or =45%), classified using clinical criteria as decompensated (n = 94) and stable HF (n = 219), underwent a complete Doppler echocardiographic study. NT-pro-BNP was measured together with mitral wave velocities, E wave deceleration time, and tissue Doppler early septal annular velocity. Median follow-up was 22 months. Freedom from all-cause mortality or HF hospitalization at 24 months was worst (44%) in patients with decompensated HF, intermediate (58%) in patients with stable HF with NT-pro-BNP higher than the median (>1,129 pg/ml), and best (92%) in patients with lower NT-pro-BNP (log-rank p <0.0001). In patients with stable HF, NT-pro-BNP >1,129 pg/ml (hazard ratio [HR] 2.84, p = 0.003), E wave deceleration time <150 ms (HR 2.31, p = 0.004), and tissue Doppler early septal annular velocity <8 cm/s (HR 2.18, p = 0.01) were predictors of the end point at multivariate analysis. The addition of Doppler LV diastolic variables and NT-pro-BNP significantly improved the chi-square test for outcome prediction (from 14.4 to 46.4). In conclusion, NT-pro-BNP and spectral and tissue Doppler variables of LV diastolic dysfunction added independent and incremental contributions to prognostic stratification of patients with stable HF.

Prognostic significance of tricuspid annular motion and plasma NT-proBNP in patients with heart failure and moderate-to-severe functional mitral regurgitation.

BACKGROUND: The role of the right ventricle has been relatively neglected proportionate to its importance. We sought to evaluate the impact of right ventricular (RV) and NT-proBNP on the outcome of patients with heart failure (HF) and functional mitral regurgitation (MR). METHODS AND PATIENTS: Outpatients with left ventricular (LV) systolic HF (ejection fraction [EF] < or =45%) and moderate-to-severe MR measured by a vena contracta width > or =0.5 cm were prospectively enrolled (n=142). Indexes of LV and RV function, including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change and tissue Doppler RV acceleration at isovolumic contraction and NT-proBNP plasma levels were measured at the time of the index echocardiogram. RESULTS: Multivariate predictors of all-cause mortality included TAPSE<16 mm (hazards ratio [HR]: 2.64; p=0.009) and plasma NT-proBNP> or =3283 pg/ml (HR: 2.58; p=0.011). TAPSE<16 mm and plasma NT-proBNP> or =3283 pg/ml added incremental prognostic information to LV EF< or =25%, NYHA classes 3-4, coronary artery disease, elderly age and male sex. The 36-month Kaplan-Meier curve showed that survival was worst in the group with TAPSE<16 mm and NT-proBNP> or =3283 pg/ml (p<0.0001). CONCLUSION: This study demonstrates the significance of TAPSE and plasma NT-proBNP in predicting all-cause mortality in patients with systolic HF and moderate-to-severe functional MR.

[Evaluation of cardiovascular risk and perioperative management of patients undergoing noncardiac surgery. Results of an ANMCO web survey]. / Valutazione del rischio cardiovascolare e della gestione perioperatoria del paziente candidato a chirurgia non cardiaca. I risultati della web survey ANMCO.

BACKGROUND: Cardiovascular risk stratification and perioperative management of subjects undergoing non-cardiac surgery have recently been updated in the 2014 European Society of Cardiology guidelines. Nevertheless, and notwithstanding the epidemiological relevance of this condition, an underevaluation of the importance of perioperative risk stratification is a common feeling. METHODS: The ANMCO Cardiovascular Prevention Area organized, last year, a web-based survey with 15 questions to investigate perioperative management and care pathways in non-cardiac surgery and to evaluate guideline adherence of Italian cardiologists. Participation in the survey was anonymous. RESULTS: Respondents had a homogeneous geographical, as well as working (coronary care unit, post-intensive care unit, ambulatory service) distribution. Among respondents, 38% evaluated more than 20 patients each month, and 25% more than 20 patients aged >75 years. Local diagnostic guidelines were available according to 60% of respondents. Despite guideline recommendations, cardiological evaluation preceded the anesthesiologic one according to 36% of respondents, and 42% reported that it was performed independent of baseline risk. In addition, perioperative use of risk scores was low (1%), and functional capacity was reported from only 56% of respondents. Half of them used bridge therapy with heparin after stopping direct oral anticoagulants. CONCLUSIONS: The results of the ANMCO web-based survey confirm the need to promote educational programs on risk stratification and to raise awareness of Italian cardiologists on this matter in order to improve guideline adherence.

Right ventricular dysfunction is a major predictor of outcome in patients with moderate to severe mitral regurgitation and left ventricular dysfunction.

BACKGROUND: This study aimed to assess the prognostic value of right ventricular (RV) dysfunction in patients with secondary mitral regurgitation (MR) by simple methods of echocardiographic measurement. Although both RV dysfunction and functional MR may affect prognosis of patients with heart failure (HF) due to left ventricular (LV) dysfunction, information is lacking regarding the impact of RV dysfunction in patients with functional MR. METHODS: Among 356 consecutive patients with chronic HF due to LV dysfunction (ejection fraction < or = 45%), 107 met the entry criteria of moderate to severe MR as assessed by a vena contracta width > or = 0.5 cm. Tricuspid annular plane systolic excursion (TAPSE) was acquired to evaluate RV function. Median follow-up duration was 21 months. RESULTS: Among patients with a vena contracta width > or = 0.5 cm, 30 (28%) died and 28 (26%) were hospitalized for worsening HF. By multivariate analysis, TAPSE < or = 14 mm (hazard ratio [HR] 2.83, P = .027) and LV ejection fraction (HR 2.17, P = .099) were predictive of death from all causes. Independent predictors of freedom from all-cause mortality or hospitalization for worsening HF were New York Heart Association class (HR 2.15, P = .027), age (HR 1.98, P = .021) and TAPSE < or = 14 mm (HR 1.96, P = .031). At 24 months, survival was 45% in those with the worse TAPSE, whereas it was 82% in those with TAPSE > 14 mm (log-rank statistic = 0.0002). Aminoterminal pro-type B natriuretic peptide plasma levels were higher in patients with vena contracta width of > or = 0.5 cm and TAPSE < or = 14 mm. CONCLUSIONS: This study shows that RV function, assessed by TAPSE, plays a major role in the outcome of patients with functional moderate to severe MR.

Right heart failure due to a fistula between a giant aortic pseudoaneurysm and the left atrium: a late complication after cardiovascular surgery.

: A 69-year-old woman, treated 5 years before with mechanical aortic valve and vascular prosthesis of ascending aorta implantation for severe aortic regurgitation and dilation of ascending aorta, was referred to our center for dyspnea and peripheral edema. The transthoracic echocardiography showed a giant pseudoaneurysm incorporating the vascular prosthesis and a fistula of it with the left atrium. These findings were confirmed using the transesophageal echocardiogram, cardiac computed tomography, and during cardiac surgery, which was performed 5 days later. The reparative intervention consisted of suturing of both the connections; the patient survived the surgery, but she died 6 weeks later due to infectious complications.

[Clinical scores in chronic heart failure: does an ideal score exist?]. / Gli score clinici nell'insufficienza cardiaca cronica: esiste uno score ideale?

Numerous prognostic markers have shown to be predictive of patient outcome in heart failure (HF). The recent guidelines of the European Society of Cardiology for the diagnosis and treatment of acute and chronic HF have identified as many as 57 individual markers in patients with HF, including demographic data, etiology, comorbidities, clinical, radiological, hemodynamic, echocardiographic and biochemical parameters. If more accurate risk stratification is required, several scoring systems have been proposed. This article reviews scoring systems for HF prognostication. Although most of the models include readily available clinical information, usually NYHA functional class, left ventricular ejection fraction (LVEF) and comorbidities, quite a few of them comprise Doppler echocardiographic variables, other than LVEF, and circulating levels of natriuretic peptides. In order to achieve a better prediction of the outcome, an ideal score should be based on a comprehensive Doppler echocardiographic examination, the assessment of circulating biomarkers, and a more objective evaluation of exercise tolerance.

Double-chambered left ventricle in an asymptomatic adult patient.

This article shows a case of double-chambered left ventricle in asymptomatic 60-year-old man. This rare congenital entity is usually diagnosed in the neonatal or paediatric age, and it is characterized by the subdivision of the left ventricle in two chambers by an abnormal septum or muscle band. Differential diagnosis includes two other congenital left ventricular (LV) outpouching entities, such as diverticulum and aneurysm. As shown in our case, double-chambered left ventricle exhibits mixed features. A comprehensive cardiovascular magnetic imaging study is useful in the distinction of these closely related congenital diseases and, therefore, important for the correct final diagnosis.

Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy.

OBJECTIVE: Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients. METHODS: Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction ≤ 40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150 ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25 ± 17 months. RESULTS: Median value of MMP-9 was 714 ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5 ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure ≥ 35 mm Hg, N-terminal protype-B natriuretic peptide>1742 pg/ml, and glomerular filtration rate<60 ml/min/1.73 m(2). Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan-Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001). CONCLUSION: MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients.

Association of furosemide dose with clinical status, left ventricular dysfunction, natriuretic peptides, and outcome in clinically stable patients with chronic systolic heart failure.

In chronic heart failure (HF), high daily doses of furosemide have been associated with increased mortality. The authors sought to evaluate the relationships between orally administered furosemide doses, clinical status, left ventricular (LV) dysfunction, N-terminal proBNP (NT-proBNP), and outcome in 400 outpatients with chronic HF and LV ejection fraction (EF) ≤ 45%. Clinical status, NT-proBNP levels, and estimated glomerular filtration rate (eGFR) were evaluated. Median follow-up duration was 32 months. The median values of daily-dose furosemide and of furosemide dose normalized to body surface area were 25 mg (12.5-62.5 mg) and 15 mg/m(2) (13-34 mg/m(2)), respectively. A total of 32% of patients had decompensated HF according to Framingham score and criteria for congestion. In clinically stable patients, a multivariable Cox model, which included clinical and echocardiographic parameters plus NT-proBNP, hemoglobin, and eGFR, showed that normalized furosemide dose (P=.017), anemia (P=.060), age (P=.080), and New York Heart Association class (P=.080) were predictors of all cause-mortality. In patients with decompensated HF, LV end-systolic volume index (P=.018), NT-proBNP (P=.060), and reduced eGFR (P=.070) were independently related to the outcome. Normalized furosemide dose was a major determinant of prognosis in patients with chronic HF but without ongoing signs and symptoms, and this suggests a possible negative interaction of this drug in clinically stable patients.

Independent and incremental value of severely enlarged left atrium in risk stratification of very elderly patients with chronic systolic heart failure.

The authors sought to assess the impact on survival of demographic, clinical, and echo-Doppler parameters in patients with chronic heart failure due to left ventricular systolic dysfunction divided according to age groups. This study included 734 patients (age 69±11 years) who were classified into tertiles of age: I (22-66 years), II (67-76 years), and III (77-94 years). Severely enlarged left atrial size was defined as ≥52 mm in men and ≥47 mm in women. Multivariable analysis identified male sex (P=.018) and severely enlarged left atrium (P=.024) as significant correlates of all-cause mortality in the very elderly cohort, while restrictive filling pattern (RFP) (P=.004) and New York Heart Association class III or IV (P=.005) among patients of the first tertile and RFP (P=.028) among patients in the second tertile were independently associated with mortality after 30±21 months of follow-up. At the interactive stepwise model in the very elderly population, a severely enlarged left atrium, added to the model after clinical parameters and ejection fraction, moved the chi-square value from 20.7 to 25.8 (P=.048). RFP emerged as the single best predictor of all-cause mortality in the younger and intermediate ranges, whereas severely enlarged left atrium was the best predictor in the very elderly.