Prognosis of mild/moderate chronic systolic heart failure

Abstract

⁎ Corresponding author. Tel.: +39 02 26437366; fax: +39 02 26437358. E-mail address: gabriele.fragasso@hsr.it (G. Fragasso). Despite many advances in diagnosis and therapy, heart failure (HF) is still apparently related to poor prognosis, with reported mortality rates at 5-year over 40% (9% per year) — a six-fold adverse rate compared with the general population [1–3]. To address this important public health issue, we sought to determine morbidity and mortality rates in our population of chronic HF out-patients, followed-up in the heart failure clinic of our Institution and compare them with rates reported in previous surveys. Of a total of 403 systolic heart failure patients attending our clinic from March 1992 to December 2005 and on optimal medical and device therapy, 372 (269 males, age at diagnosis 66±11 yrs) were considered eligible for study analysis. The remaining 31 patients could not be traced. Patients lost at followup were tested for baseline variables (age, gender, NYHA class, ejection fraction) and were not statistically different compared with the group with complete followup. Mean follow-up from first diagnosis was 67±44 months (median 58.50, Q1=40.75, Q3=80.25). The diagnosis of HF was ascertained according to European Society of Cardiology criteria: I) symptoms of heart failure and II) objective evidence (by echocardiography) of cardiac systolic dysfunction (at rest) and (in cases where the diagnosis was in doubt) III) response to treatment directed towards heart failure. Criteria I and II had to be fulfilled in all cases. Furthermore, we selected only patients with a baseline ejection fraction (EF)≤45% (Simpson biplane). Cardiovascular mortality was calculated as the number of events per 1000 person-year at risk. Mortality and morbidity were compared with the national population by using standardized mortality ratios, referring to national data classified by age and sex (data from the Italian Central Statistics Institute – ISTAT – We found that application twice of 4.3 MHz intracardiac ultrasound for 60 s at an intensity of 1.0 W/cm were suitable parameters for higher efficiency of transfection and low percentage of myocardial tissue impairment. Furthermore, the EGFP mRNA of EGFP+MB/US group was significantly higher than those of other groups, which confirmed that that the combination of intracardiac ultrasonic exposure and intramyocardial injection of microbubbles could enhance gene transfection. The main findings of this investigation were: 1) the intracardiac ultrasonic exposure technology and injection system provides an accurate and reliable means of delivering an injectate transendocardially into the LV, 2) this system allows for the injection of a naked DNA gene into designated myocardial sites and results in successful gene transfer and protein expression. This novel approach could also obviously reduce gene and microbubble dosage. In sum, intramyocardial injection microbubble combination of intracardiac ultrasonic exposure can enhance gene expression. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].