Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Plasma bio-adrenomedullin is a marker of acute heart failure severity in patients with acute coronary syndrome.

BACKGROUND: The assessment of acute heart failure (AHF) in patients with acute coronary syndrome (ACS) is challenging. This study tested whether measuring plasma adrenomedullin in patients admitted for ACS provides valuable information regarding the presence of AHF at admission or its occurrence during hospitalization. METHODS AND RESULTS: The study population consisted of 927 prospectively enrolled patients with ACS. Blood samples for the measurement of plasma bio-adrenomedullin (bio-ADM) were collected at admission. Patients with alveolar pulmonary edema and interstitial pulmonary edema on chest radiography at admission had stepwise higher plasma concentrations of bio-ADM compared to patients with no or mild pulmonary congestion: 54.3 ±â€¯10.6 vs. 27.6 ±â€¯2.1 vs. 22.5 ±â€¯0.7 ng/L, overall P < 0.001. Patients with ACS complicated by AHF during the index hospitalization displayed higher plasma bio-ADM concentrations at admission compared to patients without AHF (33.8 ±â€¯2.7 vs. 21.8 ±â€¯0.7, P < 0.001): the higher the severity of AHF, the higher plasma bio-ADM concentrations at admission. Patients with cardiogenic shock displayed the highest values. Accordingly, bio-ADM concentrations at admission were associated with a higher risk of occurrence of AHF during index hospitalization (odds ratio 1.018, 95% confidence interval 1.011-1.026, P < 0.001). CONCLUSIONS: Plasma adrenomedullin is a marker associated with AHF severity in patients with ACS.

Prevalence, Temporal Evolution, and Impact on Survival of Ventricular Conduction Blocks in Patients With Acute Coronary Syndrome and Cardiogenic Shock.

Changes in QRS duration and pattern are regarded to reflect severe ischemia in acute coronary syndromes (ACS), and ventricular conduction blocks (VCBs) are recognized high-risk markers in both ACS and acute heart failure. Our aim was to evaluate the prevalence, temporal evolution, association with clinical and angiographic parameters, and impact on mortality of VCBs in ACS-related cardiogenic shock (CS). Data of 199 patients with ACS-related CS from a prospective multinational cohort were evaluated with electrocardiogram data from baseline and day 3. VCBs including left or right bundle branch block, right bundle branch block and hemiblock, isolated hemiblocks, and unspecified intraventricular conduction delay were assessed. Fifty percent of patients had a VCB at baseline; these patients were older, had poorer left ventricular function and had more often left main disease compared with those without VCB. One-year mortality was over 2-fold in patients with VCB compared with those without VCB (68% vs 32%, p<0.001). All types of VCBs at baseline were associated with increased mortality, and the predictive value of a VCB was independent of baseline variables and coronary angiography findings. Interestingly, 37% of the VCBs were transient, i.e., disappeared before day 3. However, 1-year mortality was much higher in these patients (69%) compared to patients with persistent (38%) or no VCB (15%, p<0.001). Indeed, a transient VCB was a strong independent predictor of 1-year mortality. In conclusion, our findings propose that any VCB in baseline electrocardiogram, even if transient, identifies very early patients at particularly high mortality risk in ACS-related CS.

Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?

OBJECTIVE: Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. METHODOLOGY, RESULTS: A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). CONCLUSION: Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.

Ventricular conduction abnormalities as predictors of long-term survival in acute de novo and decompensated chronic heart failure.

AIMS: Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long-term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). METHODS AND RESULTS: We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow-up. Half (51.5%, n = 506) of the patients had de novo AHF. LBBB, and IVCD were more common in ADCHF than in de novo AHF: 17.2% vs. 8.7% (P < 0.001) and 20.6% vs. 13.2% (P = 0.001), respectively, and RBBB was almost equally common (6.9% and 8.1%; P = 0.5), respectively. Mortality during the follow-up was higher in patients with RBBB (85.4%) and IVCD (73.7%) compared with patients with normal ventricular conduction (57.0%); P < 0.001 for both. The impact of RBBB on prognosis was prominent in de novo AHF (adjusted HR 1.93, 1.03-3.60; P = 0.04), and IVCD independently predicted death in ADCHF (adjusted HR 1.79, 1.28-2.52; P = 0.001). Both findings were pronounced in patients with reduced ejection fraction. LBBB showed no association with increased mortality in either of the subgroups. The main results were confirmed in a validation cohort of 1511 AHF patients with 5.9 years' mean follow-up. CONCLUSIONS: Conduction abnormalities predict long-term survival differently in de novo AHF and ADCHF. RBBB predicts mortality in de novo AHF, and IVCD in ADCHF. LBBB has no additive predictive value in AHF requiring hospitalization.

Natriuretic peptides in addition to Zwolle score to enhance safe and early discharge after acute myocardial infarction: A prospective observational cohort study.

BACKGROUND: The Zwolle score is recommended to identify low-risk patients eligible for early hospital discharge after ST-elevation myocardial infarction (STEMI), but since only one third of STEMI has low Zwolle score, hospital discharge is frequently delayed. B-type natriuretic peptide (BNP) also provides prognostic information after STEMI. The aim of the study was to test the hypothesis that patients with high Zwolle score associated with low BNP share similar outcomes than those with low Zwolle score. METHODS AND RESULTS: The study population consisted of 1032 consecutive STEMI patients in whom BNP was measured 24h after chest pain onset. The area under the curve of Zwolle score and plasma BNP for 30-day mortality were 0.82 and 0.87, p=0.39. A BNP threshold of 200pg/ml had sensitivity of 100% and specificity of 34% for predicting 30-day mortality. Patients with high Zwolle score and BNP≤200pg/ml (n=183) had similar mortality and hospital stay to those with low Zwolle score (0% vs. 0.5% and 5 vs. 5days, both p=1.0). By contrast, patients with high Zwolle score and BNP>200pg/ml had the highest mortality (6.7%) and the longest hospital stay (6days), both p<0.01. CONCLUSION: STEMI patients with high Zwolle score but low BNP share similar outcomes with those with low Zwolle score and should be eligible for early discharge. Hence, using the rule of "low-Zwolle or low-BNP" might increase the number of STEMI patients that might be eligible for early discharge.

Plasma Levels of Soluble CD146 Reflect the Severity of Pulmonary Congestion Better Than Brain Natriuretic Peptide in Acute Coronary Syndrome.

BACKGROUND: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. METHODS: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. RESULTS: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. CONCLUSIONS: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis.

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). DESIGN: Prospective observational cohort study. SETTING: One university/tertiary centre. PARTICIPANTS: A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. PRIMARY OUTCOME: 1-year mortality. SECONDARY OUTCOMES: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. STATISTICAL METHODS: Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). RESULTS: The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%. CONCLUSIONS: The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

["Stressful holiday" - takotsubo cardiomyopathy]. / "Stresová dovolená" aneb takotsubo kardiomyopatie.

Takotsubo cardiomyopathy (TTC) is an acute syndrome characterized by rapid onset of transient systolic dysfunction of the left ventricle. Symptoms, ECG and laboratory findings resemble acute coronary syndrome, from which TTC differs by the absence of coronary artery disease. In typical cases, TTC is triggered by exposure to unexpected stress and the clinical course and prognosis are very good. We present a case of a 63-year-old woman, in whom the onset of the disease was complicated by ventricular fibrillation. The patient recovered without sequelae thanks to immediate cardiopulmonary resuscitation and following care in a specialized cardiocenter, which involved also implantation of implantable cardioverter defibrillator to prevent sudden cardiac death. Takotsubo cardiomyopathy is an important entity in the differential diagnosis of acute coronary syndrome. Despite very good prognosis in most cases it should not be underestimated and it deserves careful attention and treatment which can prevent harmful complications.Key words: myocardial infarction - sudden cardiac death - takotsubo cardiomyopathy - ventricular fibrillation.