Heli Tolppanen

Causes of Death and Predictors of 5-Year Mortality in Young Adults After First-Ever Ischemic Stroke The Helsinki Young Stroke Registry

Background and Purpose— Data on mortality and its prognostic factors after an acute ischemic stroke in young adults are scarce and based on relatively small heterogeneous patient series. Methods— We analyzed 5-year mortality data of all consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the Department of Neurology, Helsinki University Central Hospital, from January 1994 to September 2003. We followed up the patients using data from the mortality registry of Statistics Finland. We used life table analyses for calculating mortality risks. Kaplan–Meier method allowed comparisons of survival between clinical subgroups. We used the Cox proportional hazard model for identifying predictors of mortality. Stroke severity was measured using the National Institutes of Health Stroke Scale and the Glasgow Coma Scale. Results— Among the 731 patients (mean age, 41.5±7.4 years; 62.8% males) followed, 78 died. Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7% (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender difference. Those ≥45 years of age had lower probabilities of survival. Among the 30-day survivors (n=711), stroke caused 21%, cardioaortic and other vascular causes 36%, malignancies 12%, and infections 9% of the deaths. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large artery atherosclerosis causing the index stroke independently predicted 5-year mortality adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype. Conclusions— Despite the overall low mortality after an ischemic stroke in young adults, several recognizable subgroups had substantially increased risk of death in the long term.

Clinical picture and risk prediction of short-term mortality in cardiogenic shock

The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short‐term mortality.

Physiological changes in pregnancy.

Abstract Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery. Some of these changes influence normal biochemical values while others may mimic symptoms of medical disease. It is important to differentiate between normal physiological changes and disease pathology. This review highlights the important changes that take place during normal pregnancy.

Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance

PurposeAcute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings.ResultsTissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries.ConclusionA multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.

Acute Heart Failure With and Without Concomitant Acute Coronary Syndromes: Patient Characteristics, Management, and Survival

BACKGROUND Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS. METHODS AND RESULTS Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03). CONCLUSIONS Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality.

Effect of precipitating factors of acute heart failure on readmission and long-term mortality

Acute heart failure (AHF) is one of the leading causes of unscheduled hospitalization and is associated with frequent readmissions and substantial mortality. Precipitating factors of AHF influence short‐term mortality, but their effect on outcome after hospital discharge is unknown. The present study assessed the effect of precipitating factors on readmission and long‐term survival in the overall population and in patients aged 75 years or younger.

Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study.

BACKGROUND Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF. METHODS In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years. RESULTS The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years. CONCLUSIONS Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.

Use of noninvasive and invasive mechanical ventilation in cardiogenic shock: A prospective multicenter study

BACKGROUND Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over non-invasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. METHODS 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24h into MV (n=137; 63%) , NIV (n=26; 12%), and supplementary oxygen (n=56; 26%) groups. We compared the clinical characteristics and 90-day outcome between the MV and the NIV groups. RESULTS Mean age was 67years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO2/FiO2 ratio, baseline hemodynamics or LVEF. MV patients predominantly presented with hypoperfusion, with more severe metabolic acidosis, higher lactate levels and greater need for vasoactive drugs, whereas NIV patients tended to be more often congestive. 90-day outcome was significantly worse in the MV group (50% vs. 27%), but after propensity score adjustment, mortality was equal in both groups. Confusion, prior CABG, ACS etiology, higher lactate level, and lower baseline PaO2 were independent predictors of mortality, whereas ventilation strategy did not have any influence on outcome. CONCLUSIONS Although MV is generally recommended mode of ventilatory support in CS, a fair number of patients were successfully treated with NIV. Moreover, ventilation strategy was not associated with outcome. Thus, NIV seems a safe option for properly chosen CS patients.

Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration.

AbstractRed blood cell distribution width (RDW) may serve as an integrative marker of pathological processes that portend worse prognosis in heart failure (HF). The prognostic value of RDW variation (&Dgr;RDW) during hospitalization for acute heart failure (AHF) has yet to be studied.We retrospectively analyzed 2 independent cohorts: Centro Hospitalar do Porto (derivation cohort) and Lariboisière hospital (validation cohort). In the derivation cohort a total of 170 patients (age 76.2 ± 10.3 years) were included and in the validation cohort 332 patients were included (age 76.4 ± 12.2 years). In the derivation cohort the primary composite outcome of HF admission and/or cardiovascular death occurred in 78 (45.9%) patients during the 180-day follow-up period.Discharge RDW and &Dgr;RDW were both increased when hemoglobin levels were lower; peripheral edema was also associated with increased discharge RDW (all P < 0.05). Discharge RDW value was significantly associated with adverse events: RDW > 15% at discharge was associated with a 2-fold increase in event rate, HR = 1.95 (1.05–3.62), P = 0.04, while a &Dgr;RDW >0 also had a strong association with outcome, HR = 2.47 (1.35–4.51), P = 0.003. The addition of both discharge RDW > 15% and &Dgr;RDW > 0 to hemoconcentration was associated with a significant improvement in the net reclassification index, NRI = 18.3 (4.3–43.7), P = 0.012. Overlapping results were found in the validation cohort.As validated in 2 independent AHF cohorts, an in-hospital RDW enlargement and an elevated RDW at discharge are associated with increased rates of mid-term events. RDW variables improve the risk stratification of these patients on top of well-established prognostic markers.

Mid-regional pro-atrial natriuretic peptide to predict clinical course in heart failure patients undergoing cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) induces reverse cardiac remodelling in heart failure (HF), but many patients receiving CRT remain non-responders. This study assessed the role of amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide (MR-proANP), and mid-regional-pro-adrenomedullin (MR-proADM) at the time of device implantation to predict favourable clinical course (CRT response and/or risk of MACE) in HF patients receiving CRT. Methods and results A total of 137 HF patients were prospectively included. Blood was drawn from the coronary sinus (CS) at CRT implantation, and from a peripheral vein (PV) simultaneously and after 6 months. Clinical CRT response at 6 months and major adverse cardiovascular events (MACE) at 2 years were assessed. Baseline PV-levels of MR-proANP (202 vs. 318 pmol/L, P = 0.009) and MR-proADM (843 vs. 1112 pmol/L, P = 0.02) were lower in CRT responders compared with non-responders. At 6 months, CRT responders showed a decrease in MR-proANP levels, compared with an increase in non-responders (-32 vs. +7 pmol/L, P = 0.02). During the same period, NT-proBNP decreased by a similar way in responders and non-responders, while MR-proADM was unchanged in both groups. High baseline MR-proANP, either in PV (OR 0.41, 95% CI 0.24-0.71, P = 0.002) or CS (OR 0.32, 95% CI 0.15-0.70, P = 0.005) was associated with reduced likelihood of CRT response. Furthermore, PV and CS levels of NT-proBNP, MR-proANP, and MR-proADM were all associated with increased risk of 2-year MACE (all P < 0.01). Conclusion Mid-regional-pro-atrial natriuretic peptide may assist prediction of clinical course in HF patients undergoing CRT implantation. Low circulating MR-proANP at the time of device implantation is associated with CRT response and more favourable outcome.