Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.

BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

Outcomes of patients with myocardial infarction and cardiogenic shock treated with culprit vessel-only versus multivessel primary PCI.

INTRODUCTION AND OBJECTIVES: Multivessel primary percutaneous coronary intervention (pPCI) is still often used in patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (CS). The study aimed to compare the characteristics and prognosis of patients with CS-STEMI and multivessel coronary disease (MVD) treated with culprit vessel-only pPCI or multivessel-pPCI during the initial procedure. MATERIAL AND METHODS: From 2016 to 2020, 23,703 primary PCI patients with STEMI were included in a national all-comers registry of cardiovascular interventions. Of them, 1,213 (5.1%) patients had CS and MVD at admission to the hospital. Initially, 921 (75.9%) patients were treated with culprit vessel (CV)-pPCI and 292 (24.1%) with multivessel (MV)-pPCI. RESULTS: Patients with 3-vessel disease and left main disease had a higher probability of being treated with MV-pPCI than patients with 2-vessel disease and patients without left main disease (28.5% vs. 18.6%; p < 0.001 and 37.7% vs. 20.6%; p < 0.001). Intra-aortic balloon pump, extracorporeal membrane oxygenation (ECMO), and other mechanical circulatory support systems were more often used in patients with MV-pPCI. Thirty (30)-day and 1-year all-cause mortality rates were similar in the CV-pPCI and MV-pPCI groups (odds ratio, 1.01; 95% confidence interval [CI] 0.77 to 1.32; p = 0.937 and 1.1; 95% CI 0.84 to 1.44; p = 0.477). The presence of 3-vessel disease and the use of ECMO were the strongest adjusted predictors of 30-day and 1-year mortality. CONCLUSIONS: Our data from an extensive all-comers registry suggests that selective use of MV-pPCI does not increase the all-cause mortality rate in patients with CS-STEMI and MVD compared to CV-pPCI.

Heart failure-related quality-of-life impairment after myocardial infarction.

AIMS: Recent advances in therapy led to a significant decrease in mortality and morbidity after myocardial infarction (MI). However, little is known about quality of life (QoL) after MI. We examined heart failure (HF)-related quality-of-life (QoL) impairment, its trajectories, and determinants after MI. METHODS: Data from a single-center prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were utilized. At 1 month and 1 year after hospital discharge, patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: In total, 850 patients (aged 65 ± 12 years, 27% female) hospitalized between June 2017 and October 2020 completed KCCQ at 1 month after discharge. Of these, 38.7% showed HF-related QoL impairment (KCCQ ≤ 75). In addition to characteristics of MI (MI size, diuretics need, heart rate), comorbidities as renal dysfunction and anemia were associated with QoL impairment. Of the 673 eligible, 500 patients (74.3%) completed KCCQ at 1 year after MI. On average, QoL improved by 5.9 ± 16.8 points during the first year after MI (p < 0.001); but, in 18% of patients QoL worsened. Diabetes control and hemoglobin level at the time of hospitalization were associated with QoL worsening. CONCLUSION: Two out of 5 patients after MI present with HF-related QoL impairment. In addition to guideline-directed MI management, careful attention to key non-cardiac comorbidities as chronic kidney disease, anemia and diabetes may lead to further augmentation of the benefit of modern therapies in terms of QoL.

Serum S100 Protein Is a Reliable Predictor of Brain Injury After Out-of-Hospital Cardiac Arrest: A Cohort Study.

Purpose: To evaluate serum S100 protein at hospital admission and after 48 h in early neuroprognostication of comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods: The study included 48 consecutive patients after OHCA, who survived for at least 72 h after the event. The patients were divided based on their best cerebral performance category (CPC) achieved over a 30 day follow-up period: favorable neurological outcome (CPC 1-2) vs. unfavorable neurological outcome (CPC 3-4). Predictors of an unfavorable neurological outcome were identified by multivariable regression analysis. Analysis of the receiver operating characteristic curve (ROC) was used to determine the cut-off value for S100, having a 0% false-positive prediction rate. Results: Of the 48 patients, 30 (63%) had a favorable and 18 (38%) had an unfavorable neurological outcome. Eleven patients (23%) died over the 30 day follow-up. Increased S100 levels at 48 h after OHCA, but not the baseline S100 levels, were independently associated with unfavorable neurological outcome, with an area under the ROC curve of 0.85 (confidence interval 0.74-0.96). A 48 h S100 value ≥0.37 µg/L had a specificity of 100% and sensitivity of 39% in predicting an unfavorable 30 day neurological outcome. Conclusion: This study showed that S100 values assessed 48 h after an OHCA could independently predict an unfavorable neurological outcome at 30 days.

Heart failure after myocardial infarction: incidence and predictors.

AIMS: The aim of the present paper was to provide an up-to-date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction. METHODS AND RESULTS: Based on literature review, several clinical risk factors and biochemical, genetic, and imaging biomarkers were identified to predict the risk of HF development after myocardial infarction. CONCLUSIONS: Heart failure is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development using a multimodality approach, and early initiation of guideline-directed HF therapy in these patients, can decrease the HF burden.

Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial.

BACKGROUND: Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. RESULTS: Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ±â€¯5.4%, placebo: 4.0% ±â€¯5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ±â€¯13.3 mL/m2, placebo: 5.1 ±â€¯18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ±â€¯11.2 mL/m2, placebo: 0.6 ±â€¯14.8 mL/m2, P = .56) were observed in both treatment arms. CONCLUSION: Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Heart rate as an independent predictor of long term mortality of acute heart failure patients in sinus rhythm according to their ejection fraction: data from the AHEAD registry.

BACKGROUND: Heart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF. METHODS: We analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded. RESULTS: Survival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months. CONCLUSION: Our study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease.

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.

Mid-term clinical outcomes of out-of-hospital cardiac arrest patients treated with targeted temperature management at 34-36 °C versus 32-34 °C.

BACKGROUND: Targeted temperature management (TTM) in comatose survivors of out-of-hospital cardiac arrest has been associated with improved neurological outcomes. However, the optimal temperature target for TTM remains unclear. OBJECTIVES: To compare a TTM protocol targeted at 34-36 °C with a protocol targeted at 32-34 °C with reference to both clinical outcomes and acute complications. METHODS: We analyzed a prospective registry of consecutive out-of-hospital cardiac arrest survivors who underwent TTM. We compared patients on a TTM protocol targeted at 34-36 °C (n = 59) with a historical cohort of patients treated at 32-34 °C (n = 116) according to the following parameters: six-month survival, cerebral performance category (CPC) scores, and acute complications. RESULTS: Survival and favorable neurological outcomes (CPC ≤ 2) at six months were 56% and 49%, respectively, in the higher target temperature group vs. 66% and 61%, respectively, in the lower target temperature group (p = 0.18 and 0.13). Acute clinical complications occurred in 1.5% vs. 12% of patients treated at the higher vs. the lower temperature range (p = 0.02). CONCLUSIONS: Patients treated with TTM at 34-36 °C had similar mid-term survival and neurological outcomes as patients treated with TTM at 32-34 °C. However, patients treated within the higher temperature range had fewer acute complications.

A Complex Heart Team's Approach to a Patient With Giant Cell Myocarditis.

Giant cell myocarditis is known as a rare and frequently fatal type of myocarditis that is usually characterized by progressive congestive heart failure and frequent ventricular arrhythmias. We report a rare case of giant cell myocarditis in a 64-year-old previously healthy woman. The case was complicated by the rapid development of progressive acute heart failure, which required the comprehensive care of our heart team. Using a broad spectrum of therapeutic approaches, the patient successfully underwent heart transplantation.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial.

AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial. METHODS AND RESULTS: A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable (n = 1361) and relax-non-comparable (n = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future. CONCLUSIONS: Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

Procalcitonin Dynamics After Long-Term Ventricular Assist Device Implantation.

BACKGROUND: Infectious complications (IC) are one of the main causes of worsening prognosis after long-term ventricular assist device (LVAD) implantation. Procalcitonin (PCT) is widely used for diagnosis of a bacterial infection. The objective of this study was to assess PCT dynamics after LVAD surgery and their relationship to the infectious complications. METHODS: A total of 25 consecutive patients indicated for LVAD implantation as a bridge to heart transplant were included. Procalcitonin levels were prospectively assessed before surgery and during the postoperative period (day 1, 2, 14 and 30). Values were compared according to the presence of IC. RESULTS: Procalcitonin levels were low before surgery, raised significantly within 1st and 2nd day after operation and decreased in the 14th and 30th days back to the baseline. There was no significant difference in PCT values between patients with or without IC as well as with or without right ventricle assist device (RVAD). Acute renal failure (ARF) increased PCT significantly only 14 days after LVAD implantation. In patients with ARF and/or RVAD we observed significantly higher PCT values in the 2nd, 14th and 30th day after operation. In subjects with IC and/or ARF and/or RVAD we also observed significantly elevated PCT concentrations 2 and 14 days after surgery. CONCLUSIONS: Our data show that the ability of PCT to detect IC in patients after LVAD implantation is limited and its concentrations more likely correlate with postoperative complications in general.

Clinical manifestations of infective endocarditis in relation to infectious agents: An 8-year retrospective study.

AIM: To compare clinical complications and outcomes of infective endocarditis (IE) episodes caused by Staphylococcus aureus (S. aureus) and other most frequent aetiological agents (streptococci, enterococci, coagulase-negative staphylococci, and culture-negative IE). METHODS: A total of 117 IE episodes assessed by all internal medicine services of a major teaching institution in the Czech Republic over an eight-year period were identified. RESULTS: We found that S. aureus IE episodes (n = 36) were significantly more associated with systemic embolism (41.7% vs 18.5%, P = 0.01), severe sepsis/septic shock (33.3% vs 3.7%, P < 0.0001), and in-hospital mortality (33% vs 12.3%, P = 0.01). No differences in local, structural, and/or functional complications (cardiac abscess formation, impaired integrity of the valvular apparatus, conduction disturbances, or incidence of heart failure) were observed between studied groups. Long-term survival estimates were significantly improved in patients with IE caused by agents other than S. aureus (13.78 median years vs 5.48 median years, P=0.03). CONCLUSIONS: IE episodes caused by S. aureus are associated with both increased short-term and long-term mortality. Of all the studied parameters, only systemic embolism and severe sepsis/septic shock predicted in-hospital mortality.

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.

Impact of urgent coronary angiography on mid-term clinical outcome of comatose out-of-hospital cardiac arrest survivors presenting without ST-segment elevation.

BACKGROUND: Timing of coronary angiography (CAG) is still controversial in the out-of-hospital cardiac arrest survivors who present without ST-segment elevation. METHODS AND RESULTS: We analysed a prospective registry of 158 comatose survivors of out-of-hospital cardiac arrest. For further analysis, we included 99 patients without ST-segment elevation on the initial electrocardiogram. All patients underwent temperature management. Urgent CAG (<2h from admission) was performed in 25% of the patients. A definite cause of the cardiac arrest could be identified during the index hospitalization in 82 patients: 36 had a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and 46 had a non-ACS diagnosis. Eighty-seven patients (88%) survived the index hospitalization and 65 (66%) were alive at six months. A favourable neurological status (cerebral performance category ≤ 2) was observed in 56% of the patients at discharge and in 56% after six months of follow-up. Neither the survival nor the neurological outcome differed between the patients in whom the CAG was performed urgently upon the admission and the patients in whom the CAG was initially not performed, regardless of the aetiology of the cardiac arrest. On the other hand, performing an urgent CAG was safe and it did not prolong the average time to achieve an effective hypothermia. CONCLUSIONS: Performing an urgent CAG in comatose cardiac arrest survivors without ST-segment elevation was not associated with better clinical and neurological outcome as compared to the initially conservative approach.

A clinical and laboratory approach used to elucidate discordant results of high-sensitivity troponin T and troponin I.

BACKGROUND: Careful interpretation of discordant results in high-sensitivity troponin measurements is necessary in cases of suspect immunoassay interferences. We describe several procedures taken in a case of a polymorbid patient with chest pain, without clear evidence of myocardial necrosis and with increased high-sensitivity cardiac troponin T (hs-cTnT). We checked the Vafaie's algorithm for the evaluation of suspect interference in troponin measurements. METHODS: We conducted a case report analysis, additional measurements, a dilution test and pretreatment of plasma with blocking agents. RESULTS: Concentration of hs-cTnT (99 th percentile of "healthy" population 14 ng/L) increased from 120.1 ng/L to 280.4 ng/L during an 8-month period and decreased to 216.3 ng/L during the following month with repeatedly negative troponin I (TnI), hs-cTnI, myoglobin and creatine kinase MB (CK-MB). Suspected false positivity of hs-cTnT was further confirmed by treatment of plasma with an antiheterophile blocking agent (hs-cTnT before treatment 280.4 ng/L, after 16.53/16.23 ng/L). This outcome was further confirmed by the manufacturer's experiments. CONCLUSIONS: The false-positive results of hs-cTnT were caused by the presence of extremely rare high molecular weight protein, presumably IgM, most likely HAMA (human anti-mouse antibody). Only the pre-treatment of plasma with a blocking agent provided a reliable indication of the interference. Cooperation among clinicians, laboratory personnel and the manufacturer is essential.

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.