Pietro Barbieri

Prognostic indices in heart transplant candidates after the first hospitalization triggered by the need for intravenous pharmacologic circulatory support

BACKGROUND Patients with heart failure refractory to optimal oral pharmacologic therapy have a dismal short term prognosis. Heart transplantation is the only therapy shown to improve survival in these patients. Unfortunately, due to the critical shortage of donor organs, approximately 30% of listed patients with end-stage heart failure die before a suitable donor heart becomes available. The principal aim of this study was to determine whether intravenous pharmacologic circulatory support favorably influences the clinical course of heart transplant candidates or whether mechanical circulatory support should be instituted in this high risk patient population. METHODS Data from 154 consecutive hospitalizations in 125 patients 49+/-12 years were retrospectively reviewed. The product limit method was used to estimate survival. Multiple logistic regression analysis was used to identify the clinical and hemodynamic variables that independently predict outcome after each admission in which heart transplantation did not occur. RESULTS One year survival for the study population was 65%. This survival is significantly lower than the 91% 1 year survival in similarly ill patients undergoing heart transplantation. The Cox proportional hazard method identified serum bilirubin, blood urea nitrogen (BUN), serum sodium levels and right atrial pressure as independent prognostic indices. Serum bilirubin, BUN levels and duration of intravenous pharmacologic circulatory support were associated with a poor outcome. A composite index including serum bilirubin and BUN levels predicted outcome with a sensitivity and specificity of 79% and 77%, respectively. The addition of pharmacologic support duration increased the models sensitivity to 95%, but did not significantly alter specificity that was 74%. Of the 125 patients hospitalized due to the need to initiate intravenous pharmacologic support for the first time (index hospitalization), 69 (55%) were discharged after optimization of medical therapy. Of 21 patients who did not undergo transplantation during the follow-up period, 18 (86%) died within 2 years of the index hospitalization. The duration of intravenous pharmacologic support beyond which prognosis dramatically worsens without heart transplantation is 21 days. CONCLUSION Heart transplant candidates who require intravenous pharmacologic circulatory support for more than 21 days and do not receive a suitable donor heart within this period of time have a high mortality. Alternative therapies, such as implantation of a mechanical circulatory assist device should be considered in this high risk population.

Exploitation, integration and statistical analysis of the Public Health Database and STEMI Archive in the Lombardia region

We describe the nature and aims of the Strategic Program “Exploitation, integration and study of current and future health databases in Lombardia for Acute Myocardial Infarction”. The main goal of the Programme is the construction and statistical analysis of data coming from the integration of complex clinical and administrative databases concerning patients with Acute Coronary Syndromes treated in the Lombardia region. Clinical data sets arise from observational studies about specific diseases, while administrative data arise from standardised and on-going procedures of data collection. The linkage between clinical and administrative databases enables the Lombardia region to create an efficient global system for collecting and storing integrated longitudinal data, to check them, to guarantee their quality and to study them from a statistical perspective.

Determination of candidacy for mechanical circulatory support: importance of clinical indices

Heart transplantation is currently the most effective therapy for the treatment of advanced heart failure (CHF).1 However, its application is limited due to the lack of sufficient donor organs as well as the substantial incidence of post-transplant complications, such as rejection, infection, and cardiac allograft vasculopathy. Therefore, only a small minority of patients who suffer from advanced CHF are successfully treated with heart transplantation. Notwithstanding the strict criteria used in selection of heart transplant candidates, the number of patients listed for heart transplantation continues to increase because of the increasing incidence of chronic CHF2 resulting in ever increasing pre-transplant waiting time. Consequently, many ambulatory patients awaiting transplant experience progression of their disease, eventually become refractory to oral heart failure therapy.3 To address this issue, innovative surgical alternatives, such as left ventricular assist device (LVAD) implantation, have been explored, in an attempt to support patients who do not respond to traditional therapies until transplantation.4 Until recently, LVADs have generally been implanted in urgent or emergent situations, such as cardiogenic shock with related end-organ dysfunction or overt failure. Not surprisingly, the stress of surgery, when superimposed on the fragile underlying substrate, frequently contributes to poor outcomes, both in the short term as well as following transplantation in a candidate with ongoing medical complications. Recently there has been an increased tendency to insert mechanical circulatory support devices before the onset of frank end-organ dysfunction as an alternative to aggressive medical support, for example, maintenance inotropic therapy. Preliminary success with this approach has prompted some centers to consider “early” LVAD placement as a viable alternative to inotropic therapy as a bridge to heart transplant, particularly in patients thought to be at particularly high risk for progressive deterioration, or even as a potential alternative to transplantation itself. Although associated with shortterm risk and expense, LVADs can restore hemodynamic normalcy in patients with severe cardiac dysfunction and can maintain stability for months, thus preserving social autonomy, preventing costly hospitalizations, and allowing functional recovery of end-organ systems. Good post-transplant outcomes following prolonged LVAD support have been described.2,7 The advantages afforded by this pre-emptive approach must be weighed against the risks of the implantation surgery and devicerelated complications (hepatic and renal failure, thromboembolism, infections, bleeding, hemolysis, and mechanical device failure) as well as increased technical challenges at the time of the subsequent transplantation.2,6,7 This article will examine some of the current issues surrounding the role and implementation of LVAD support in managing patients with end-stage heart failure.

Trends in heart failure hospitalizations, patient characteristics, in-hospital and 1-year mortality: A population study, from 2000 to 2012 in Lombardy

BACKGROUND This study was undertaken to evaluate trends in heat failure hospitalizations (HFHs) and 1-year mortality of HFH in Lombardy, the largest Italian region, from 2000 to 2012. METHODS Hospital discharge forms with HF-related ICD-9 CM codes collected from 2000 to 2012 by the regional healthcare service (n=699797 in 370538 adult patients), were analyzed with respect to in-hospital and 1-year mortality; Group (G) 1 included most acute HF episodes with primary cardiac diagnosis (70%); G2 included cardiomyopathies without acute HF codes (17%); and G3 included non-cardiac conditions with HF as secondary diagnosis (13%). Patients experiencing their first HFH since 2005 were analyzed as incident cases (n=216782). RESULTS Annual HFHs number (mean 53830) and in-hospital mortality (9.4%) did not change over the years, the latter being associated with increasing age (p<0.0001) and diagnosis Group (G1 9.1%, G2 5.6%, G3 15.9%, p<0.0001). Incidence of new cases decreased over the years (3.62 [CI 3.58-3.67] in 2005 to 3.13 [CI 3.09-3.17] in 2012, per 1000 adult inhabitants/year, p<0.0001), with an increasing proportion of patients aged ≥85y (22.3% to 31.4%, p<0.0001). Mortality lowered over time in <75y incident cases, both in-hospital (5.15% to 4.36%, p<0.0001) and at 1-year (14.8% to 12.9%, p=0.0006). CONCLUSIONS The overall burden and mortality of HFH appear stable for more than a decade. However, from 2005 to 2012, there was a reduction of new, incident cases, with increasing age at first hospitalization. Meanwhile, both in-hospital and 1-year mortality decreased in patients aged <75y, possibly due to improved prevention and treatment.

Heart Diseases Registries Based on Healthcare Databases

The present study aims to promote incidence and prevalence estimates, to evaluate potential benefits and harms of specific health policies and to evaluate adherence to best practice by quality indicators based on administrative and textual databases (DB).

Methodological Issues in the Use of Administrative Databases to Study Heart Failure

Advantages and criticisms in using administrative data for clinical and epidemiological research are well discussed. These databases were originally designed for administrative aims rather than for clinical research. Several choices are necessary to make these databases suitable for clinical and epidemiological research. The choices have to be explicit and clearly declared, to let the reader know their possible effects. In this work we discuss methodological issues concerning the preliminary work on data from a regional project.

Gender Differences in Hospitalization for Acute Myocardial Infarction in Lombardy During the Years 2000–2010

The industrialized world is undergoing epidemiologic variations in acute coronary syndrome and the female gender is particularly involved in these changes. Our study was designed based on administrative databases of all hospital admissions in the Lombardy region during the years 2000–2010 which enabled us to obtain complete and updated information regarding the gender-related epidemiologic situation.