Pompilio Faggiano

Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy

Background Functional mitral regurgitation (FMR) is a common finding in patients with heart failure (HF), but its effect on outcome is still uncertain, mainly because in previous studies sample sizes were relatively small and semiquantitative methods for FMR grading were used. Objective To evaluate the prognostic value of FMR in patients with HF. Methods and results Patients with HF due to ischaemic and non-ischaemic dilated cardiomyopathy (DCM) were retrospectively recruited. The clinical end point was a composite of all-cause mortality and hospitalisation for worsening HF. FMR was quantitatively determined by measuring vena contracta (VC) or effective regurgitant orifice (ERO) or regurgitant volume (RV). Severe FMR was defined as ERO >0.2 cm2 or RV >30 ml or VC >0.4 cm. Restrictive mitral filling pattern (RMP) was defined as E-wave deceleration time <140 ms. The study population comprised 1256 patients (mean age 67±11; 78% male) with HF due to DCM: 27% had no FMR, 49% mild to moderate FMR and 24% severe FMR. There was a powerful association between severe FMR and prognosis (HR=2.0, 95% CI 1.5 to 2.6; p<0.0001) after adjustment of left ventricular ejection fraction and RMP. The independent association of severe FMR with prognosis was confirmed in patients with ischaemic DCM (HR=2.0, 95% CI 1.4 to 2.7; p<0.0001) and non-ischaemic DCM (HR=1.9, 95% CI 1.3 to 2.9; p=0.002). Conclusion In a large patient population it was shown that a quantitatively defined FMR was strongly associated with the outcome of patients with HF, independently of LV function.

Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis

Objectives In patients with aortic stenosis (AS) left ventricular (LV) myocardial growth may exceed individual needs to compensate LV haemodynamic load leading to inappropriately high LV mass (iLVM), a condition at high risk of adverse cardiovascular events. The prognostic impact of iLVM was determined in 218 patients with asymptomatic severe AS. Methods iLVM was recognised when the measured LV mass exceeded 10% of the expected value predicted from height, sex and stroke work (prognostic cut-off assessed by a specific ROC analysis). For assessment of outcome, the endpoint was defined as death from all causes, aortic valve replacement or hospital admission for non-fatal myocardial infarction and/or congestive heart failure. Results At the end of follow-up (22+13 months) complete clinical data were available for 209 participants (mean age 75+11 years). A clinical event occurred in 81 of 121 patients (67%) with iLVM and in 26 of 88 patients (30%) with appropriate LV mass (aLVM) (p<0.001). Event-free survival in patients with aLVM and iLVM was 78% vs 56% at 1-year, 68% vs 29% at 3-year and 56% vs 10% at 5-year follow-up, respectively (all p<0.01). Cox analysis identified iLVM as a strong predictor of adverse outcome (Exp β 3.08; CI 1.65 to 5.73) independent of diabetes, transaortic valve peak gradient and extent of valvular calcification. Among patients with LV hypertrophy, those with iLVM had a risk of adverse events 4.5-fold higher than counterparts with aLVM. Conclusions iLVM is common in patients with asymptomatic severe AS and is associated with an increased rate of cardiovascular events independent of other prognostic covariates.

Rate of progression of valvular aortic stenosis in adults

Until recently the hemodynamic severity of valvular aortic stenosis (AS) was evaluated only by cardiac catheterization. Now, Doppler echocardiography allows a noninvasive and accurate assessment of AS severity and can be used to study its progression with time. The progression of AS was assessed during a follow-up period of 6 to 45 months (mean 18) by serial Doppler examinations in 45 adult patients (21 men and 24 women, mean age 72 +/- 10 years) with isolated AS. The following parameters were serially measured: left ventricular outflow tract diameter and velocity by pulsed Doppler, peak velocity of aortic flow by continuous-wave Doppler, to calculate peak gradient by the modified Bernoulli equation, and aortic valvular area by the continuity equation. At the initial observation, 13 of 45 patients (29%) were symptomatic (1 angina, 1 syncope and 11 dyspnea); during follow-up, 25 (55%) developed new symptoms or worsening of the previous ones (5 angina, 3 syncope and 17 dyspnea); 11 underwent aortic valve replacement and 3 died from cardiac events. Baseline peak velocity and gradient ranged between 2.5 and 6.6 m/s, and 25 and 174 mm Hg, respectively; aortic area ranged between 0.35 and 1.6 cm2. With time, mean peak velocity and gradient increased significantly from 4 +/- 0.7 to 4.7 +/- 0.8 m/s (p less than 0.01), and 64 +/- 30 to 88 +/- 30 mm Hg (p less than 0.01), respectively. A concomitant reduction in mean aortic area occurred (0.75 +/- 0.3 to 0.6 +/- 0.15 cm2; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Symptomatic Aortic Stenosis: Does Systemic Hypertension Play an Additional Role?

Abstract— Hypertension and aortic stenosis represent 2 different models of left ventricular systolic overload. Previous studies have observed different remodeling patterns in these conditions. There is, however, little information about patients with coexisting aortic stenosis and hypertension. Echocardiography was performed in 193 consecutive patients with symptomatic aortic stenosis (113 males, 80 females; mean age, 68±9 years). The prevalence of systemic hypertension was assessed. Left ventricular mass index and relative wall thickness were measured from M‐mode echocardiography. Four different left ventricular remodeling patterns were identified: normal remodeling, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. A history of hypertension was present in 62 patients (32%), whereas 131 patients were normotensive. No significant differences were found between hypertensive and normotensive patients with respect to age, male/female ratio, mean New York Heart Association class, distribution of symptoms, left ventricular systolic and diastolic function, and remodeling patterns. In hypertensive patients, however, symptoms were present with larger aortic valve areas and lower stroke work loss. Systemic hypertension is not rare in patients with symptomatic aortic stenosis (32% in our series). Left ventricular remodeling patterns are quite similar in hypertensive and normotensive aortic stenosis. Our results suggest that symptoms of aortic stenosis develop with larger valve area and lower stroke work loss in hypertensive patients, probably because of the additional overload due to hypertension itself. It could suggest that in patients with coexisting hypertension and aortic stenosis, hypertension should be treated more aggressively to delay the occurrence of symptoms, and these patients should be followed‐up more closely.

Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis.

OBJECTIVES The aim of this study was to evaluate the serum levels of carbohydrate antigen 125 (CA125) in patients with congestive heart failure (CHF). BACKGROUND CA125 is a glycoprotein produced by serosal epithelium, found to be increased in ovarian cancer. METHODS Serum levels of CA125 were obtained in 286 patients (122 males and 164 females; age 69 +/- 13 years) with CHF (left ventricular ejection fraction 30 +/- 11%). A non-invasive evaluation was obtained by Doppler echocardiography; right heart catheterization was performed in 88 patients. An attempt to adjust medical therapy to maximally tolerated doses was done, and CA125 was repeated after 18 days (range 7 to 40) in 80 patients. The mean follow-up duration was 6 +/- 3 months in 240 patients. RESULTS The mean value of CA125 was 68 +/- 83 U/ml (range 3 to 537): 71 +/- 85 in men and 56 +/- 64 U/ml in women (p = NS). CA125 above the normal value (<35 U/ml) was found in 152 (53%) of 286 patients; it was higher in patients with advanced New York Heart Association (NYHA) functional class (n = 140 in class I/II: 15 +/- 9 U/ml; n = 63 in class III: 57 +/- 18 U/ml; n = 83 in class IV: 167 +/- 94 U/ml; p < 0.005). CA125 was related to the deceleration time of early filling on transmitral Doppler (r = -0.63, p < 0.05) and to pulmonary artery wedge pressure (r = 0.66, p < 0.05) and right atrial pressure (r = 0.69, p < 0.05). During 6 +/- 3 months of follow-up, a combined end point of mortality and CHF hospitalization was observed in 16 of 127 patients with CA125 <35 U/ml, compared with 70 of 113 patients with CA125 >35 U/ml (p < 0.01). After medical treatment optimization, NYHA class decreased by more than one grade in 56 of 80 patients and was unchanged or increased in 24 patients: CA125 decreased from 125 +/- 98 to 53 +/- 61 U/ml (p < 0.001) in the former and changed from 130 +/- 81 to 153 +/- 61 U/ml (p = NS) in the latter. CONCLUSIONS Our data suggest that CA125 is related to CHF severity and short-term prognosis. Furthermore, fluctuations of CA125 serum levels over time may reflect changes induced by therapy. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of CHF patients.

Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure.

OBJECTIVES We studied whether direct assessment of the hemodynamic response to exercise could improve the prognostic evaluation of patients with heart failure (HF) and identify those in whom the main cause of the reduced functional capacity is related to extracardiac factors. BACKGROUND Peak exercise oxygen consumption (VO2) is one of the main prognostic variables in patients with HF, but it is influenced also by many extracardiac factors. METHODS Bicycle cardiopulmonary exercise testing with hemodynamic monitoring was performed, in addition to clinical evaluation and radionuclide ventriculography, in 219 consecutive patients with chronic HF (left ventricular ejection fraction, 22 +/- 7%; peak VO2, 14.2 +/- 4.4 ml/kg/min). RESULTS During a follow-up of 19 +/- 25 months, 32 patients died and 6 underwent urgent transplantation with a 71% cumulative major event-free 2-year survival. Peak exercise stroke work index (SWI) was the most powerful prognostic variable selected by Cox multivariate analysis, followed by serum sodium and left ventricular ejection fraction, for one-year survival, and peak VO2 and serum sodium for two-year survival. Two-year survival was 54% in the patients with peak exercise SWI < or = 30 g x m/m2 versus 91% in those with a SWI >30 g x m/m2 (p < 0.0001). A significant percentage of patients (41%) had a normal cardiac output response to exercise with an excellent two-year survival (87% vs. 58% in the others) despite a relatively low peak VO2 (15.1 +/- 4.7 ml/kg/min). CONCLUSIONS Direct assessment of exercise hemodynamics in patients with HF provides additive independent prognostic information, compared to traditional noninvasive data.

Assessment of oxygen uptake during the 6-minute walking test in patients with heart failure: Preliminary experience with a portable device

In patients with heart failure, the 6-minute walking test (6-MWT) is considered a useful measure of submaximal exercise capacity. Few data are available on oxygen uptake (VO2) during a standard 6-MWT. The aim of this study was to measure the 6-MWT VO2 by using a recently validated portable instrument in 26 patients (24 men, 2 women; mean age, 56 +/- 11 years) with mild to severe heart failure (New York Heart Association class II, 10 patients; III, 10 patients; IV, 6 patients; left ventricular ejection fraction: 22 +/- 6%). Peak VO2 was measured during a symptom-limited cardiopulmonary exercise test performed in a period of 1 to 3 days (10 watt/m increment). Peak VO2 was 15 +/- 4 ml/kg/m during the symptom-limited test and 12.9 +/- 4.4 ml/kg/m during the 6-MWT (p < 0.05), corresponding to 86% of peak VO2. Seven (27%) of 26 patients showed a 6-MWT VO2 equal to or higher than peak VO2. Anaerobic threshold (AT) was identified in 23 of 26 patients during maximal exercise and in 19 of 26 patients during the 6-MWT; VO2 at AT was similar in the two tests (12.2 +/- 3.5 ml/kg/m vs 11.9 +/- 4.2 ml/kg/m). The distance walked during the 6-MWT (mean, 418 +/- 20 m) significantly correlated with 6-MWT VO2 (r = 0.71) and peak VO2 (r = 0.63); the 6-MWT VO2 also showed a high correlation with peak VO2 (r = 0.86). Thus in patients with failing hearts, VO2 during 6-MWT (considered a classic submaximal exercise) is, on average, only 15% lower than peak VO2 and is largely supported by anaerobic metabolism (work above the anaerobic threshold).

The Challenge of Diagnosing Atheroembolic Renal Disease: Clinical Features and Prognostic Factors

Background— Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. Methods and Results— Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% >70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence. The risk of dialysis and death was 50% lower among those receiving statins. Conclusions— Clinical features of AERD are identifiable. These make diagnosis possible in most cases. Prognosis is influenced by disease type and severity.

Moderate alcohol use and health: a consensus document.

AIMS The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Long‐term prognosis of medically treated patients with functional mitral regurgitation and left ventricular dysfunction

To assess long‐term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy.