Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

BACKGROUND AND AIMS: Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. METHODS AND RESULTS: The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). CONCLUSIONS: In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients.

Evaluation of the spatial aspects of T-wave complexity in the long-QT syndrome.

BACKGROUND: The duration of the QT interval is only a gross estimate of repolarization. Besides its limited accuracy and reproducibility, it does not provide information on the morphology of the T wave; thus, morphologic alterations such as notches can be only qualitatively described but not objectively quantified. METHODS AND RESULTS: To measure the complexity of repolarization in the long-QT syndrome (LQTS) patients, we previously applied principal component analysis to body surface mapping and found it useful in distinguishing normal from abnormal repolarization patterns (sensitivity, 87%). In the present study, we applied principal component analysis to 12-lead Holter recordings. The index of complexity of repolarization that we have developed (CR24h) reflects the average 24-hour complexity of repolarization and is mathematically defined as the average ratio between the second and the first eigenvalue. We studied 36 LQTS patients and 40 control subjects. A mean of 22+/-1.3 ECG recordings at 1-hour intervals was used in each patient, and a total of 1655 recordings were analyzed. CR24h was significantly higher in LQTS than in control subjects (34+/-12% versus 13+/-3%; P<.0001). A CR24h exceeding 2 SD above the mean of the control group (>20%) was present in 32 of 36 patients (88%). The negative predictive value of CR24h in LQTS was 88%, and the combination of prolonged QT and abnormal CR24h identified all LQTS patients from normal subjects, including 4 affected symptomatic individuals with a normal QT interval duration, suggesting that CR24h provides information independent of QT duration. CONCLUSIONS: Our data suggest that principal component analysis applied to 24-hour, 12-lead Holter recording adequately quantifies the complexity of ventricular repolarization and may become a useful noninvasive diagnostic tool in LQTS.

Molecular biology of the long QT syndrome: impact on management.

The long QT syndrome (LQTS) is a familial disease characterized by prolonged ventricular repolarization and high incidence of malignant ventricular tachyarrhythmias often occurring in conditions of adrenergic activation. Recently, the genes for the LQTS inked to chromosomes 3 (LQT3), 7 (LQT2), and 11 (LQT1) were identified as SCN5A, the cardiac sodium channel gene and as HERG and KvLQT1 potassium channel genes. These discoveries have paved the way for the development of gene-specific therapy for these three forms of LQTS. In order to test specific interventions potentially beneficial in the molecular variants of LQTS, we developed a cellular model to mimic the electrophysiological abnormalities of LQT3 and LQT2. Isolated guinea pig ventricular myocytes were exposed to anthopleurin and dofetilide in order to mimic LQT3 and LQT2, respectively. This model has been used to study the effect of sodium channel blockade and of rapid pacing showing a pronounced action potential shortening in response to Na+ channel blockade with mexiletine and during rapid pacing only in anthopleurin-treated cells but not in dofetilide-treated cells. Based on these results we tested the hypothesis that QT interval would shorten more in LQT3 patients in response to mexiletine and to increases in heart rate. Mexiletine shortened significantly the QT interval among LQT3 patients but not among LQT2 patients. LQT3 patients shortened their QT interval in response to increases in heart rate much more than LQT2 patients and healthy controls. These findings suggest that LQT3 patients are more likely to benefit from Na+ channel blockers and from cardiac pacing because they are at higher arrhythmic risk at slow heart rates. Conversely, LQT2 patients are at higher risk to develop syncope under stressful conditions, because of the combined arrhythmogenic effect of catecholamines with the insufficient adaptation of their QT interval. Along the same line of development of gene-specific therapy, recent data demonstrated that an increase in the extracellular concentration of potassium shortens the QT interval in LQT2 patients suggesting that intervention aimed at increasing potassium plasma levels may represent a specific treatment for LQT2. The molecular findings on LQTS suggest the possibility of developing therapeutic interventions targeted to specific genetic defects. Until definitive data become available, antiadrenergic therapy remains the mainstay in the management of LQTS patients, however it may be soon worth considering the addition of a Na+ channel blocker such as mexiletine for LQT3 patients and of interventions such as K+ channel openers or increases in the extracellular concentration of potassium for LQT1 and LQT2 patients.

[Diagnostic imaging of aortic pseudoaneurysm: study of 4 clinical cases]. / Diagnostica per immagini nello pseudoaneurisma dell'aorta: studio di quattro casi clinici.

Aortic pseudoaneurysm starts as small disruption of the aortic wall with an extravasation of blood into the mediastinum, contained only by fibrous tissue and by parietal pericardium. The most common cause of this condition is dehiscence or inflammatory processes of suture stitches after surgical interventions on aortic value or ascending sorts. Pseudoaneurysm represents about 40% of complications of cardiac surgery involving the ascending sorts. This complication occurs in about 1% of cases of aortic valve or ascending tract replacement. In this study, we evaluated, with different diagnostic techniques, 4 patients (all males, mean age 48 +/- 23 years, range 17-74) affected by aortic pseudoaneurysm occurring at different times after surgical intervention on the sorts. Clinically only 1 of the 4 patients referred chest pain. Repeated chest radiography and cardiac magnetic resonance were performed in every patient; 3 subjects were evaluated by transthoracic and transesophageal echocardiography; contrast-enhanced computed tomography was performed in 1 patients. Pseudoaneurysm diagnosis obtained by non invasive methods was later confirmed and better described by angiography. Our study demonstrated that transesophageal echocardiography and magnetic resonance are useful and reliable methods in the diagnosis of aortic pseudoaneurysm. However, in case of mediastinal he or pericardial effusion (suggestive of aortic pseudoaneurysm) by transesophageal echocardiography or magnetic resonance, angiography is necessary and may show the exact rupture site on the aortic wall. This diagnostic approach yields enough information for both diagnosis and surgical correction of this rare but high-risk pathological condition.

[Idiopathic ventricular fibrillation: from a collection of clinical cases to a prospective evaluation. The U-CARE Steering Committee. Unexplained Cardiac Arrest Registry of Europe]. / Fibrillazione ventricolare idiopatica: da una raccolta di casi clinica alla valutazione prospettica. Steering Committee di U-CARE.

BACKGROUND: The primary aim of U-CARE (Unexplained Cardiac Arrest Registry of Europe) is to collect clinical information on survivors about a documented episode of idiopathic ventricular fibrillation (IVF) and to follow these patients (pts) prospectively to acquire information on 1) recurrence of malignant arrhythmias or cardiac arrest, 2) development of a previously non obvious organic heart disease, 3) potential difference in outcome in pts treated with different drugs or devices. METHODS AND RESULTS: Within April 15th, 1994, eighty-six pts have been enrolled, 65 males and 21 females. The mean age at the time of the first cardiac arrest was 35 +/- 15 years. Clinical evaluation revealed "minor" functional or anatomical abnormalities in 14 subjects and they were excluded from the analysis. In the remaining 72 pts, no abnormalities were found at echocardiogram, Holter, angiography, exercise stress test. At the electrophysiologic study 35/68 pts were inducible. Thirty-eight pts received pharmacologic therapy, 28 an implantable defibrillator (ICD), three pts received both an ICD and drug therapy and three were left untreated. Follow-up data are available for 37 pts with a mean follow-up of 4.4 +/- 2.6 years. No patient had evidence of structural heart disease. Twenty-three pts remained asymptomatic, 12 (32%) had a recurrence of syncope or cardiac arrest: three died suddenly and 2 were defibrillated by the ICD. This study that represents the largest experience in IVF, shows: 1) all patients remained free from any organic heart disease at follow-up, 2) they have a high risk of recurrence of major arrhythmic events. CONCLUSIONS: An ICD implant would be appropriate in this population, at least until data on the efficacy of the pharmacologic therapy will be available.