Filip Malek

Baseline characteristics and hospital mortality in the Acute Heart Failure Database (AHEAD) Main registry

IntroductionThe prognosis of patients hospitalized with acute heart failure (AHF) is poor and risk stratification may help clinicians guide care. The objectives of the Acute Heart Failure Database (AHEAD) registry are to assess patient characteristics, etiology, treatment and outcome of AHF.MethodsThe AHEAD main registry includes patients hospitalized for AHF in seven centers with a Catheterization Laboratory Service in the Czech Republic. The data were collected from September 2006 to October 2009. The inclusion criteria for the database adhere to the European guidelines for AHF (2005) and patients were systematically classified according to the basic syndromes, type and etiology of AHF.ResultsOf 4,153 patients, 12.7% died during hospitalization. The median length of hospitalization was 7.1 days. Mean age of patients was 71.5 ± 12.4 years; men were younger (68.6 ± 12.4 years) compared to women (75.5 ± 11.5 years) (P < 0.001). De-novo heart failure was seen in 58.3% of the patients. According to the classification of heart failure syndromes, acute decompensated heart failure (ADHF) was reported in 55.3%, hypertensive AHF in 4.4%, pulmonary edema in 18.4%, cardiogenic shock in 14.7%, high output failure in 3.3%, and right heart failure in 3.8%. The mortality of cardiogenic shock was 62.7%, of right AHF 16.7%, of pulmonary edema 7.1%, of high output HF 6.1%, whereas the mortality of hypertensive AHF or ADHF was < 2.5%. According to multivariate analyses, low systolic blood pressure, low cholesterol level, hyponatremia, hyperkalemia, the use of inotropic agents and norepinephrine were predictive parameters for in-hospital mortality in patients without cardiogenic shock. Severe left ventricular dysfunction and renal insufficiency were predictive parameters for mortality in patients with cardiogenic shock. Invasive ventilation and age over 70 years were the most important predictive factors for mortality in both genders with or without cardiogenic shock.ConclusionsThe AHEAD Main registry provides up-to-date information on the etiology, treatment and hospital outcomes of patients hospitalized with AHF. The results highlight the highest risk patients.

A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial

BACKGROUND Heart failure with preserved ejection fraction (HFPEF) is a common, globally recognised, form of heart failure for which no treatment has yet been shown to improve symptoms or prognosis. The pathophysiology of HFPEF is complex but characterised by increased left atrial pressure, especially during exertion, which might be a key therapeutic target. The rationale for the present study was that a mechanical approach to reducing left atrial pressure might be effective in HFPEF. METHODS The REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) study was an open-label, single-arm, phase 1 study designed to assess the performance and safety of a transcatheter interatrial shunt device (IASD, Corvia Medical, Tewkesbury, MA, USA) in patients older than 40 years of age with symptoms of HFPEF despite pharmacological therapy, left ventricular ejection fraction higher than 40%, and a raised pulmonary capillary wedge pressure at rest (>15 mm Hg) or during exercise (>25 mm Hg). The study was done at 21 centres (all departments of cardiology in the UK, Netherlands, Belgium, France, Germany, Austria, Denmark, Australia, and New Zealand). The co-primary endpoints were the safety and performance of the IASD at 6 months, together with measures of clinical efficacy, including functional capacity and clinical status, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01913613. FINDINGS Between Feb 8, 2014, and June 10, 2015, 68 eligible patients were entered into the study. IASD placement was successful in 64 patients and seemed to be safe and well tolerated; no patient had a peri-procedural or major adverse cardiac or cerebrovascular event or need for cardiac surgical intervention for device-related complications during 6 months of follow-up. At 6 months, 31 (52%) of 60 patients had a reduction in pulmonary capillary wedge pressure at rest, 34 (58%) of 59 had a lower pulmonary capillary wedge pressure during exertion, and 23 (39%) of 59 fulfilled both these criteria. Mean exercise pulmonary capillary wedge pressure was lower at 6 months than at baseline, both at 20 watts workload (mean 32 mm Hg [SD 8] at baseline vs 29 mm Hg [9] at 6 months, p=0·0124) and at peak exercise (34 mm Hg [8] vs 32 [8], p=0·0255), despite increased mean exercise duration (baseline vs 6 months: 7·3 min [SD 3·1] vs 8·2 min [3·4], p=0·03). Sustained device patency at 6 months was confirmed by left-to-right shunting (pulmonary/systemic flow ratio: 1·06 [SD 0·32] at baseline vs 1·27 [0·20] at 6 months, p=0·0004). INTERPRETATION Implantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFPEF. The effectiveness of IASD compared with existing treatment for patients with HFPEF requires validation in a randomised controlled trial. FUNDING Corvia Medical Inc.

Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure

Heart failure with preserved or mildly reduced ejection fraction (HFpEF) is common and, to date, therapeutic options are limited. Increased left atrial pressure is a key contributor to the symptoms associated with HFpEF, particularly during physical activity. We report the 30‐day outcome of patients treated with a novel device intended to lower left atrial pressure by creating an 8 mm permanent shunt in the atrial septum.

Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure: IASD treatment of elevated filling pressures in HFpEF

Heart failure with preserved or mildly reduced ejection fraction (HFpEF) is common and, to date, therapeutic options are limited. Increased left atrial pressure is a key contributor to the symptoms associated with HFpEF, particularly during physical activity. We report the 30‐day outcome of patients treated with a novel device intended to lower left atrial pressure by creating an 8 mm permanent shunt in the atrial septum.

Long-term survival following acute heart failure: The Acute Heart Failure Database Main registry (AHEAD Main)

BACKGROUND The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged. METHODS The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival. RESULTS The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age>70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub-analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality. CONCLUSION The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival.

Uric acid, allopurinol therapy, and mortality in patients with acute heart failure—results of the Acute HEart FAilure Database registry

STUDY OBJECTIVE The aim of this study was to explore the prognostic role of serum uric acid (UA) measurement in the hospital and long-term mortality assessment in subjects with acute heart failure (AHF) from the Acute HEart FAilure Database registry (AHEAD). The AHEAD registry comprised 4153 patients with AHF syndromes hospitalized at the AHEAD participating centers. PATIENTS AND METHODS The study included 1255 patients who were admitted to the AHEAD participating centers with acute decompensated chronic heart failure, de novo heart failure, or cardiogenic shock between September 2006 and October 2009 and who had information about serum UA concentration available at the time of hospital admission. The hospital and long-term mortality was followed using the centralized database of the Ministry of Health, Czech Republic. The mean age of the cohort was 73.4 years, the female population represented 43%, the median hospital stay was 8 days, and the mean hospital mortality was 7.6%. RESULTS The median UA concentration of the patients with AHF was 432 μmol/L (7.26 mg/dL), the median estimated glomerular filtration rate (eGFR) was 49.0 mL/min, and N-terminal pro-brain natriuretic peptide level was 5510 pg/mL. Among other laboratory variables, UA concentration greater than 515 μmol/L (8.67 mg/dL) was associated with increased hospital mortality (P < .001), as well as eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and positive troponin. Uric acid concentration greater than 500 μmol/L (8.41 mg/dL) was associated with increased long-term mortality (P < .001), followed by eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and hemoglobin level lower than 130 g/L (P < .001). The 1-year survival rate of patients discharged from hospital (n = 1159) was 75.6%, and the 2-year rate was 66.8%. Survival of patients treated with allopurinol for hyperuricemia was significantly lower compared with untreated subjects (70.1 vs 77.2 for 1-year survival and 60.3 vs 68.5 for 2-year survival). CONCLUSION In patients with AHF, increased UA levels and documented allopurinol therapy for hyperuricemia were associated with increased hospital and long-term mortality. Allopurinol therapy is not a cause but the identifier of the subjects at risk.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUND The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 μmol/l), D--diabetes mellitus) scoring system. METHODS AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). RESULTS Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001). CONCLUSION The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

Prevalence and clinical significance of liver function abnormalities in patients with acute heart failure

AIMS Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). METHODS The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. RESULTS In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. CONCLUSIONS Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

Positive Influence of Being Overweight/Obese on Long Term Survival in Patients Hospitalised Due to Acute Heart Failure

Background Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the “obesity paradox” on a large cohort with long-term follow-up are lacking. Methods Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5–25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. Results In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26–1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09–1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11–1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. Conclusion These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Correlation of NT-proBNP, proANP and novel biomarkers: Copeptin and proadrenomedullin with LVEF and NYHA in patients with ischemic CHF, non-ischemic CHF and arterial hypertension

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