Jindřich Špinar

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.

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.

Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure

Abstract Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the 735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for nonhypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes. Clin Chem Lab Med 2003; 41(10):12991303

Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)

Background —Ezetimibe, when added to simvastatin, reduces cardiovascular events following acute coronary syndrome (ACS); we explored outcomes stratified by diabetes mellitus (DM). Methods —In IMPROVE-IT, 18,144 patients post ACS with LDL-C 50-125 mg/dL were randomized to ezetimibe/simvastatin-40mg (E/S) or placebo/simvastatin-40mg (P/S). The primary composite endpoint was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup. Results —The 4933 (27%) patients with DM were more often older, female, with prior MI and revascularization, and presented more frequently with non-ST segment elevation ACS compared to non-DM (each p interaction =0.02). The largest relative reductions in DM patients were in MI (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years had a 20% relative reduction in the primary endpoint regardless of DM (P interaction =0.91), while patients interaction =0.011). When stratified by the TIMI risk score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among non-diabetics, patients with a high risk score experienced a significant 18% relative reduction in the composite of cardiovascular death, MI, and ischemic stroke with E/S compared to P/S, whereas non-diabetics at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (P interaction 0.034). Conclusions —In IMPROVE-IT the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk non-diabetics. Clinical Trial Registration —URL: https://clinicaltrials.gov Unique Identifier: NCT00202878Background: Ezetimibe, when added to simvastatin, reduces cardiovascular events after acute coronary syndrome. We explored outcomes stratified by diabetes mellitus (DM). Methods: In IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), 18 144 patients after acute coronary syndrome with low-density lipoprotein cholesterol 50 to 125 mg/dL were randomized to 40 mg ezetimibe/simvastatin (E/S) or 40 mg placebo/simvastatin. The primary composite end point was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup. Results: The 4933 (27%) patients with DM were more often older and female, had had a prior myocardial infarction and revascularization, and presented more frequently with non-ST segment elevation acute coronary syndrome compared with patients without DM (each P<0.001). The median admission low-density lipoprotein cholesterol was lower among patients with DM (89 versus 97 mg/dL, P<0.001). E/S achieved a significantly lower median time-weighted average low-density lipoprotein cholesterol compared with placebo/simvastatin, irrespective of DM (DM: 49 versus 67 mg/dL; no DM: 55 versus 71 mg/dL; both P<0.001). In patients with DM, E/S reduced the 7-year Kaplan–Meier primary end point event rate by 5.5% absolute (hazard ratio, 0.85; 95% confidence interval, 0.78-0.94); in patients without DM, the absolute difference was 0.7% (hazard ratio, 0.98; 95% confidence interval, 0.91–1.04; Pint=0.02). The largest relative reductions in patients with DM were in myocardial infarction (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years of age had a 20% relative reduction in the primary end point regardless of DM (Pint=0.91), whereas patients <75 years of age with DM had greater benefit than those without (Pint=0.011). When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (Pint =0.034). Conclusions: In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Improvement in quality of life after catheter ablation for paroxysmal versus long-standing persistent atrial fibrillation: a prospective study with 3-year follow-up.

Background Changes in quality of life (QoL) after catheter ablation for long‐standing persistent atrial fibrillation (LSPAF) are not well described. We sought to compare QoL improvement after catheter ablation of paroxysmal atrial fibrillation (PAF) versus that after LSPAF. Methods and Results A total of 261 PAF and 126 LSPAF ablation recipients were prospectively followed for arrhythmia recurrence, QoL, hospital stay, and sick leave. In PAF versus LSPAF groups, 1.3±0.6 versus 1.6±0.7 procedures were performed per patient (P<0.00001) during a 3‐year follow‐up. Good arrhythmia control was achieved in 86% versus 87% of patients (P=0.69) and in 69% versus 69% of patients not receiving antiarrhythmic drugs (P=0.99). The baseline QoL was better in the PAF than in the LSPAF group (European Quality of Life Group instrument self‐report questionnaire visual analog scale: 66.4±14.2 versus 61.0±14.2, P=0.0005; European Quality of Life Group 3‐level, 5‐dimensional descriptive system: 71.4±9.2 versus 67.7±13.8, P=0.002). Postablation 3‐year increase in QoL was significant in both groups (all P<0.00001) and significantly lower in PAF versus LSPAF patients (visual analog scale: +5.0±14.5 versus +10.2±12.8, P=0.001; descriptive system: +5.9±14.3 versus +9.3±13.9, P=0.03). In multivariate analysis, LSPAF, less advanced age, shorter history of AF and good arrhythmia control were consistently associated with postablation 3‐year improvement in QoL. Days of hospital stay for cardiovascular reasons and days on sick leave per patient/year were significantly reduced in both groups. Conclusions Patients with LSPAF had worse baseline QoL. The magnitude of QoL improvement after ablation of LSPAF was significantly greater compared with after ablation of PAF, particularly when good arrhythmia control was achieved without the use of antiarrhythmic drugs.

Sinus rhythm restoration and arrhythmia noninducibility are major predictors of arrhythmia-free outcome after ablation for long-standing persistent atrial fibrillation: A prospective study

BACKGROUND The impact of restoring sinus rhythm (SR) by initial ablation in patients with long-standing persistent atrial fibrillation (LSPAF) is not fully established. OBJECTIVE The purpose of this study was to investigate the prognostic value of SR restoration at the initial procedure and arrhythmia noninducibility at the final repeat procedure for long-term outcome. METHODS A total of 203 patients (22% female; age 59 ± 9 years) underwent stepwise catheter ablation for LSPAF. RESULTS The procedural end-point of SR restoration was achieved in 50% of patients. During follow-up (median 48 months) and after 1.7 procedures per patient, 72% of patients were free from arrhythmia off antiarrhythmic drugs. Failure to restore SR was independently predicted by left atrial (LA) long-axis diameter ≥68 mm (relative risk [RR] 1.55, P = .03], proportion of high-voltage LA sites <20% (RR 1.62, P = .02), and left atrial appendage (LAA) atrial fibrillation cycle length (AFCL) <155 ms (RR 1.5, P = .05). Arrhythmia recurrence after the initial procedure was predicted by SR nonrestoration (RR 2.99, P <.000001) and LAA AFCL ≥155 ms (RR 1.90, P = .0002). Arrhythmia recurrence after the final procedure was predicted by SR nonrestoration at the initial procedure (RR 2.83, P = .0007), persistent AF duration ≥24 months (RR 2.74, P = .002), LAA outflow velocity <40 cm/s (RR 2.21, P = .006), and LAA AFCL ≥155 ms (RR 1.92, P = .02). In 115 patients with repeat procedure(s), failure to achieve arrhythmia noninducibility at the final procedure (19% of patients) was associated with arrhythmia recurrence (RR 8.9, P < .000001). CONCLUSION SR restoration at the initial procedure and arrhythmia noninducibility at the last repeat procedure were major predictors of arrhythmia-free outcome after ablation for LSPAF.

First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction

BACKGROUND First dose hypotension after the administration of an angiotensin-converting enzyme inhibitor in patients with acute myocardial infarction is one of the most important adverse events of this type of treatment. There is no information about first dose hypotension after angiotensin type 1-receptor blocker in this type of patient. AIM To compare the first dose responses to low dose captopril and losartan in patients with acute myocardial infarction. METHODS Single blind, randomised, multicentric, prospective study. Patients (n=320) with confirmed acute myocardial infarction, age >18 years, treated by direct percutaneous transluminal coronary angioplasty, thrombolysis and/or heparin, were randomised to receive a single dose of 6.25-12.5 mg captopril or 12.5-25 mg losartan within 24 h of hospital admission. Baseline laboratory and clinical examinations were performed before entering the study. Blood pressure monitoring started at hospital admission and continued for at least 8 h after the medication (second dose of captopril was given after 8 h). RESULTS The maximal blood pressure fall appeared about 1 h after the first dose of captopril and 3.5 h after the first dose of losartan. Patients in the captopril group had significantly higher incidence of asymptomatic hypotension (38%) than patients treated with losartan (24%) (P<0.001). No difference in hypotension requiring a change in medication was observed. CONCLUSION Low dose of losartan is safe for initiating therapy in patients with acute myocardial infarction within 24 h of hospital admission.

Does previous hypertension affect outcome in acute heart failure

BACKGROUND The effect of previous long-term hypertension on mortality in acute heart failure (HF), regardless of blood pressure values, has not been well studied. METHODS Acute Heart Failure Database (AHEAD) - Czech HF registry enrolled 4153 consecutive patients with acute HF. We excluded severe forms (cardiogenic shock, pulmonary oedema, right HF) and analysed 2421 patients with known presence or absence of previous hypertension. Demographic, clinical and laboratory profile, treatment and mortality rates were assessed and predictors of outcome were identified. RESULTS Patients with previous hypertension (71.5%) were older, more of female gender, with worse pre-hospitalisation NYHA class, increased incidence of co-morbidities and higher left ventricular ejection fraction (LVEF). Although in-hospital mortality was similar in both cohorts (2.6%), survival at 1, 2 and 3-year was worse in the hypertensive group (75.6%, 65.9% and 58.7% vs. 80.7%, 74.2% and 69.8%; P<0.001). Nevertheless, hypertension was not associated with mortality in multivariate analysis and stronger predictors of outcome were identified (P<0.05): new-onset acute HF [hazard ratio (HR) 0.62] and increased body mass index (HR 0.68) proved to have a protective role. Advanced age (HR 1.86), diabetes (HR 1.45), lower LVEF (HR 1.28) and admission blood pressure (HR 1.54), elevated serum creatinine (HR 1.63), hyponatremia (HR 1.77) and anaemia (HR 1.40) were associated with worse survival. CONCLUSION Antecedent hypertension is frequent in patients with acute HF and contributes to organ and vascular impairment. However its presence has no independent influence on short- and medium-term mortality, which is influenced by other related co-morbidities.

Neurohumoral Activity, Heart Failure and Prognosis in Patients with End-Stage Renal Disease Treated by Hemodialysis

Background: Chronic renal failure treated by regular hemodialysis is frequently accompanied by chronic heart failure; the mortality of both is high. Aim: To evaluate the role of markers of neurohumoral activation for the prognosis of patients treated with regular dialysis. Patients: 99 patients with end-stage renal disease were followed up for 3 years. Methods: Clinical evaluation, echocardiography, biochemistry including NT-proBNP and big endothelin (Big-ET). Results: The incidence of heart failure was 97% and the 3-year mortality was 50%. The sensitivity of NT-proBNP and Big-ET level for the prediction of death was 0.712 and 0.824, respectively, and specificity 0.642 and 0.695, respectively. The cut-off points were NT-proBNP ≧2,000 pg/ml and Big-ET ≧1.55 pmol/l. Neither NT-proBNP nor Big-ET could be incorporated in the multivariate model for overall survival, which means that although both parameters significantly influenced overall survival as single risk factors, they were not effective in competition with the other significant predictors. Conclusion: Overall survival seems to be influenced namely by age, hemoglobin, left atrium diameter or pulmonary congestion class on chest X-ray, while probability of early risk was associated with Big-ET, history of diabetes mellitus, C-reactive protein, uric acid and hemoglobin. The only intersection of the models is hemoglobin as a thoroughly significant predictor.

Functional improvement after successful catheter ablation for long-standing persistent atrial fibrillation

Aims Identifying patients who benefit from restored sinus rhythm (SR) would optimize the selection of candidates for ablation of long-standing persistent atrial fibrillation (LSPAF). This prospective study sought to identify the hitherto unknown factors associated with global functional improvement after successful radiofrequency catheter ablation of LSPAF. Methods and results In 171 LSPAF patients (84% of the total consecutive 203 patients) who were examined in SR 12 months after ablation, the individual per cent change from baseline value in maximum oxygen consumption at exercise test (VO2 max), left ventricular ejection fraction (LVEF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five-dimensional descriptive system (EQ-5D) of quality-of-life questionnaire were classified in quartiles by 0 (worse) to 3 (best) grades. The individual grades were summed into a composite score (SCORE, 0 … 12) reflecting global functional improvement. Significant improvement in VO2 max (3.4 ± 4.7 mL/kg/min), LVEF (7.5 ± 9.1%), NT-proBNP (-861 ± 809 pg/mL), and EQ-5D (0.7 ± 0.12) was observed (all P < 0.0001). On multivariable analysis, younger age (P = 0.001), male gender (P = 0.02), timely post-ablation left atrial appendage (LAA) outflow (P = 0.005) with improvement in outflow velocity (P = 0.0002), and withdrawal of Class I/III antiarrhythmic drugs (P < 0.05) were positively and independently correlated with the SCORE. Conclusions Younger male patients benefited most from catheter ablation of LSPAF. Delayed or non-improved LAA outflow and inability to discontinue Class I/III antiarrhythmic medication reduced the post-ablation functional improvement.