T. Bordonali

Worsening renal function in patients hospitalised for acute heart failure: Clinical implications and prognostic significance

Renal function is a powerful prognostic variable in patients with heart failure (HF). Hospitalisations for acute HF (AHF) may be associated with further worsening of renal function (WRF).

The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT‐proBNP and cardiac troponin‐T

Brain natriuretic peptide (BNP), NT‐proBNP and troponins are useful for the assessment of patients with heart failure. Few data exist about their serial changes and their prognostic value in patients with acute heart failure (AHF).

Effect of Spironolactone on Left Ventricular Ejection Fraction and Volumes in Patients With Class I or II Heart Failure

The beneficial effects of spironolactone in chronic heart failure (HF) have been demonstrated in patients with New York Heart Association (NYHA) class III to IV HF. This study examined the effect of spironolactone on left ventricular (LV) function and functional capacity of patients with mild to moderate HF (NYHA class I to II). One hundred sixty-eight patients with NYHA class I to II HF and LV ejection fraction ≤40% were randomized to spironolactone or placebo and assessed by echocardiography, gated single-photon emission computed tomography, technetium-99m sestamibi single-photon emission computed tomographic radionuclide ventriculography, and cardiopulmonary exercise testing at baseline and after 6 months of treatment. In the spironolactone group LV ejection fraction increased from 35.2 ± 0.7% to 39.1 ± 3.5% (p <0.001), with a decrease in LV end-diastolic and end-systolic volumes and myocardial mass and an improvement in LV diastolic filling pattern. Cardiopulmonary exercise testing parameters did not change. In conclusion, administration of spironolactone to patients with NYHA class I to II HF has beneficial effects on LV remodeling and diastolic function.

Hemodynamic Progression and Outcome of Asymptomatic Aortic Stenosis in Primary Care

The prognostic relevance of a rapid rate of hemodynamic progression of aortic stenosis (AS) has been predominantly investigated in tertiary centers. We reviewed the clinical and echocardiographic data from 153 asymptomatic patients with AS (age 77 ± 9 years; 65% men), with normal left ventricular function and paired echocardiograms ≥4 months apart (mean 2.9 ± 2.1 years), evaluated in a nonreferral echocardiographic laboratory. The severity of AS was graded by the peak aortic velocity (Vmax) and progression was classified as slow or fast according to a cutoff value of 0.3 m/s increase annually. The end points were all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR). At baseline, 135 patients (88%) had mild-to-moderate and 18 (12%) severe AS. Of the 153 patients, 49 (32%) showed fast progression (0.61 ± 0.32 m/s/yr) and 104 (68%) had slow progression (0.10 ± 0.16 m/s/yr). Among the 144 patients (94%) with clinical follow-up data, 40 died and 48 underwent AVR. The mortality rate was greater than that of the general population (p <0.001). On multivariate analysis, the independent predictors of mortality were the yearly change in Vmax (hazard ratio [HR] 13.352 per m/s increase, 95% confidence interval [CI] 5.136 to 34.713, p <0.001) and age (HR 1.122 per year, 95% CI 1.0728 to 1.735, p <0.001). The predictors of the composite end point of death and AVR were the yearly change in Vmax (HR 12.307, 95% CI 6.024 to 25.140, p <0.001) and Vmax on the initial echocardiogram (HR 2.684, 95% CI 1.921 to 3.750, p <0.001). In conclusion, primary care patients with asymptomatic AS are usually elderly and frequently develop rapid hemodynamic progression, which independently predicts, not only AVR, but also overall mortality.

Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure

OBJECTIVE Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (β-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. METHODS Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6 MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. RESULTS Patients receiving orodispersible L-carnosine had an improvement in 6 MWT distance (P = 0.014) and in quality-of-life (VAS score) (P = 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6 MWT and quality-of-life assessed by the EQ-5D test and the VAS score. CONCLUSION This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.

Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease

The clinical, genetic or biological variables which regulate long-term efficacy of cholinesterase inhibitors (ChEIs) in Alzheimer disease (AD) are still unknown and it is not possible to predict who will benefit from the treatment. In this study we showed that high cholesterol levels correlated with faster decline at 1-year follow-up in AD patients on ChEIs. These findings suggest that serum cholesterol is a modulating factor of treatment response and additional therapies aimed at reducing treatable high cholesterol levels may represent an alternative strategy to improve ChEIs efficacy and slow down disease progression over time.

Long-term prognostic value of the right ventricular myocardial performance index compared to other indexes of right ventricular function in patients with moderate chronic heart failure.

Background: The ventricular myocardial performance index (MPI) is a feasible echocardiographic parameter for the evaluation of patients with chronic heart failure (CHF). The long‐term prognostic role of right ventricular MPI (RV MPI) has been already assessed in patients with more advanced CHF but data are lacking in moderate CHF. The aim of the study is to evaluate the possible prognostic role of RV MPI in moderate CHF patients compared to others traditional RV parameters. Methods: From 2003 to 2004 we enrolled 95 consecutive NYHA class II CHF patients (65 males and 30 females), with the mean age of 66 ± 11 years with left ventricular ejection fraction (LVEF) <40%, on optimal medical treatment. All patients were evaluated clinically and by echocardiography with a follow‐up of 5 years (combined end point: cardiovascular mortality and hospitalization for HF). Results: RV MPI was 0.45 ± 0.36, tricuspid annular plane systolic excursion was 21 ± 8 mm, RV fractional area change was 42 ± 12%, systolic pulmonary artery pressure was 33 ± 9 mmHg, and acceleration time of pulmonic flow was 115.5 + 22.62 msec. After the 5 year follow‐up the total mortality was 24.2% and HF hospitalization rate was 33%. At Cox multivariate analysis only an RV MPI superior to median value (>0.38) and tricuspid annular plane systolic excursion inferior to median value (<18 mm) had shown a significant prognostic role. Conclusion: The RV MPI in a population of moderate CHF showed to have a more long‐term powerful prognostic value than other conventional and traditional echocardiographic right ventricular functional parameters.

ACUTE MYOCARDIAL INFARCTION PRESENTING WITH TRANSIENT GLOBAL AMNESIA

To the Editor: Despite the definition of benign disease, transient global amnesia (TGA) is never a benign event. The case reported here highlights the importance of taking into account possible malignant comorbidities related to TGA attack. A 72-year-old man presented with sudden onset of clearcut anterograde amnesia. He appeared to be confused, agitated with repetitive queries, and without any other neurological symptoms or signs. In the emergency department, physicians found high arterial blood pressure levels (180/ 110 mmHg), no accompanying focal neurological symptoms or epileptic features, no clouding of consciousness, and no loss of personal identity. The clinical finding were consistent with the diagnostic criteria for TGA, although it was apparently not related to the known TGA precipitant factors. Thus, the patient was referred to the neurological department for routine evaluation, but laboratory analyses revealed creatine kinase and troponin I alterations. An electrocardiogram was immediately performed, and signs of acute myocardial anterolateral infarction (AMI) were detected. Thus, the patient was admitted to the intensive care unit. Diagnostic examination to exclude other causes of amnesia was then completed using a brain computed tomography scan and electroencephalogram, which did not show any abnormality; the amnesic gap resolved within 8 hours from the onset. Although the patient did not indicate chest pain at admission, it was subsequently found that complaints of a few episodes of angina pectoris had been reported in the 3 months before the admission. Hypertension and chronic cardiac ischemic disease were detected for the first time during this admission. This is the first description of the presentation of TGA along with AMI. Several different causes of TGA have been proposed, including transient ischemia, migraine, epileptic seizure, and venous congestion, but none of these fully explains the disease mechanism. A common feature of TGA episodes is the presence of triggering events, such as immersion in cold water, sexual intercourse, painful experience, and physical exertion. All these triggers share an increased sympathetic activity, leading to increased central venous return along with transient retrograde high-pressure venous flow to bilateral hippocampal and diencephalic structures. Patients with AMI are known to have impaired autonomic function. In particular, sympathetic hyperactivity has been shown to occur early in AMI. Experimental evidence demonstrated that sympathetic afferents are distributed throughout anterior and inferoposterior walls of the left ventricle, and anterior ischemia leads to sympathetic activation reflex through their activation. Thus, it might be speculated that AMI triggered this TGA event. As previously reported in a TGA case associated with concomitant aortic dissection, this work further confirms that a benign event such as a TGA can sometimes mask a life-threatening disease. This study suggests that particular attention to cardiacrelated pathology should be taken into consideration in emergency department evaluation of TGA patients.

Measurement of the myocardial performance index in ambulatory patients with heart failure: correlation with other clinical and echocardiographic parameters and independent prognostic value.

Background: Many echocardiographic parameters have been proposed for the assessment of the patients with heart failure (HF). Recently, the myocardial performance index (MPI) has been shown to be an accurate index of myocardial function. We assessed the correlation with other clinical and echocardiographic measurements and the prognostic value of MPI in patients with HF. Methods and results: The MPI was assessed in 112 consecutive patients with persistent symptoms of HF (II–III NYHA class), sinus rhythm, LV systolic dysfunction (defined by an ejection fraction ≤ 45%). At multivariable analysis, only NYHA class and ejection fraction were independently related to MPI. The severity of mitral regurgitation and MPI were the only parameters independently related to the incidence of death or cardiovascular hospitalizations. A MPI > 0.55 (median value) and medium to severe mitral regurgitation were associated with a relative risk of cardiovascular events of 18.7 (95% confidence interval [CI], 16.6–20.7; P < 0.005) and of 3.03 (95% CI, 2–4.1; P = 0.035), respectively. Conclusions: In our patients with HF, MPI was the best predictor of cardiovascular events. Mitral regurgitation was the only other variable which had an additive prognostic value at multivariate analysis. (ECHOCARDIOGRAPHY 2010;27:123‐129)

β-blocker therapy of heart failure: an update

The beneficial effects of β-blocker therapy in patients with heart failure have been consistently shown by multi-center randomised trials. These agents are effective and also relatively well tolerated in the elderly and in patients with diabetes and advanced heart failure – traditionally considered as relative contraindications to their administration. However, the use of β-blockers in clinical practice remains low. The difficulties in their initiation and up-titration may be overcome by patient and physician education, as well as by their initiation during hospitalisation and/or the involvement of non-physician providers (i.e., a nurse facilitator). Forthcoming advances in the pharmacokinetic and pharmacodynamic characteristics of some β-blockers, and testing of novel methods for patient and drug selection may be based on genetic testing, and may allow further improvement of β-blocker therapy in the next future.