Left bundle branch block cardiomyopathy (LBBB-CMP): from the not-so-benign finding of idiopathic LBBB to LBBB-CMP diagnosis and treatment.

Introduction Idiopathic left bundle branch block (iLBBB) is an uncommon finding. Its benignity has been increasingly questioned, though its natural history remains poorly clarified. Similarly, LBBB-cardiomyopathy (LBBB-CM) has been also increasingly recognized as a distinct entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development. Still, it remains a scarcely studied topic. There is an urgent need for investigation and evidence reinforcement in these areas. OBJECTIVES: two main objectives: (1) to explore the natural history of "asymptomatic" iLBBB carriers; (2) to characterize the outcomes and therapeutic approach used in a "real-world" cohort of possible LBBB-CMP patients (pts). METHODS: tertiary care centre retrospective study of pts with iLBBB and possible LBBB-CMP, screened from a large hospital electrocardiographic database from 2011 to 2017 (LBBB = 347). To assign the 1st objective, only pts with left ventricular ejection fraction (LVEF) ≥ 50% and available follow-up (FU) data were included (n = 152). Regarding the 2nd objective, possible LBBB-CMP pts were selected and defined as iLBBB pts with LVD (LVEF < 50%) and no secondary causes for LVD (n = 53). Data were based on pts' careful review of medical records. RESULTS: focusing our 1st objective, 152 iLBBB carriers were identified. Median FU time were 8 years, and 61% were female. During FU, approximately 25% developed LVD, 20% needed ≥ 1 cardiovascular (CV) hospitalization, and 15% needed a cardiac device implantation. The majority (2/3) of pts with LVD on FU (n = 35) had no secondary causes for LVD, being classified as possible LBBB-CMP pts. Time-to-LVD analysis showed no differences between pts with a known cause for LVD vs LBBB-CMP pts (Log-rank = 0.713). Concerning the 2nd objective, 53 possible LBBB-CMP pts were identified. Median FU time were 10 years, and 51% were female. During the FU, 77% presented heart failure (HF) symptoms, and 42% needed ≥ 1 CV hospitalization, mainly due to HF. Half presented severe LVD at some point in time, and 55% needed a cardiac device, most of them a cardiac resynchronization therapy (CRT) device. Comparing CRT with non-CRT pts, no differences were found in terms of medical therapy, but better outcomes were observed in CRT group: LVEF improvement was higher (median LVEF improvement of 11% in non-CRT vs 27% in CRT; p < 0.001), and fully recovery from LVD was more frequent (50% of CRT vs 14% non-CRT; p = 0.028). CONCLUSION: our data strengthen current evidence on natural history of iLBBB, showing significant CV morbidity associated with the presence of iLBBB, and reinforces the need for a serial and proper FU of these carriers. Our data on "real-world" possible LBBB-CMP pts shows high rates of CV events, namely HF-related events, and supports the growing evidence pointing out CRT as this subgroup of pts' cornerstone of treatment. In conclusion, our work sheds additional light on these largely unknown topics and underlines the urgent need for larger and prospective studies addressing the identification of LVD development predictors in iLBBB carriers, as well as the establishment of diagnostic criteria and therapeutic approach for LBBB-CMP.

Loop diuretic discontinuation in chronic heart failure patients: A retrospective study.

INTRODUCTION AND OBJECTIVES: The use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. METHODS: This retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. RESULTS: Among 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. CONCLUSIONS: In our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.

The association between pre-existing heart failure and cancer incidence: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Cardiovascular diseases (CVD) and cancer are some of the most recognized causes of mortality and morbidity worldwide. Cancer is the second leading cause of death in heart failure (HF) populations. Recent studies have hypothesized that HF might promote the development and progression of cancer. We aim to analyze and discuss the most recent evidence on the relationship between HF and cancer development. METHODS: From inception to November 2022, we searched PubMed, Web of Science and ClinicalTrials.gov for relevant articles on patients with HF and a subsequent cancer diagnosis that reported outcomes of overall and site-specific cancer incidence, or mortality. RESULTS: Of 2401 articles identified in our original search, 13 articles met our criteria. Studies reporting risk rate estimates were summarized qualitatively. Studies reporting hazard ratios (HRs), or relative risks were combined in a meta-analysis and revealed that HF was associated with an increased overall cancer incidence with a HR=1.30 (95% CI: 1.04-1.62) compared with individuals without HF. Subgroup analyses by cancer type revealed increased risk for lung cancer (HR=1.87; 95% CI: 1.28-2.73), gastrointestinal cancer (HR=1.22; 95% CI: 1.03-1.45), hematologic cancer (HR=1.60; 95% CI: 1.23-2.08) and female reproductive cancer (HR=1.67; 95% CI: 1.27-2.21). Mortality from cancer was higher in HF patients compared with non-HF subjects with a HR=2.17 (95% CI: 1.23-3.84). CONCLUSIONS: Our systematic review and meta-analysis revealed that HF may result in a subsequent increase in cancer incidence as well as in cancer-related mortality. The most common cancer subtypes in HF patients were lung, female reproductive system, and hematologic cancers. Further research is needed to understand this association better and to provide the best cardiological and oncological care.

Left bundle branch block-induced dilated cardiomyopathy: Definitions, pathophysiology, and therapy.

Left bundle branch block (LBBB) is a frequent finding in patients with heart failure (HF), particularly in those with dilated cardiomyopathy (DCM). LBBB has been commonly described as a consequence of DCM development. However, a total recovery of left ventricular (LV) function after cardiac resynchronization therapy (CRT), observed in patients with LBBB and DCM, has led to increasing acknowledgement of LBBB-induced dilated cardiomyopathy (LBBB-iDCM) as a specific pathological entity. Its recognition has important clinical implications, as LBBB-iDCM patients may benefit from an early CRT strategy rather than medical HF therapy only. At present, there are no definitive diagnostic criteria enabling the universal identification of LBBB-iDCM, and no defined therapeutic approach in this subgroup of patients. This review compiles the main findings about LBBB-iDCM pathophysiology and the current proposed diagnostic criteria and therapeutic approach.

First-degree atrioventricular block in hypertrophic cardiomyopathy patients: an easy and worthy prognostic marker?

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Recently, a connection has been observed between the presence of first-degree atrioventricular block (FDAVB) and cardiovascular outcomes, although the pathophysiology of this association remains poorly understood. Considering the period 2000-2023, we retrospectively included HCM patients at sinus rhythm at the first appointment and sought possible interactions of FDAVB (defined as PR interval >200 ms) with different clinical and imaging variables and with the occurrence of cardiovascular events, including atrial fibrillation (AF). A total of 97 patients were included, of whom 57 (58.8%) were men, with a mean age of 51±19 years, and 14 (14.4%) had FDAVB. During a median of 4.29 (P25 1.92, P75 7.67) years of follow-up, 35 cardiovascular events occurred, including 13 de novo diagnoses of AF, 8 hospitalizations due to heart failure, 8 new-onset strokes, 4 myocardial infarctions, and 2 implantations of cardio defibrillators in secondary prevention; no HCM-related death occurred. We did not find any association between outcomes and the presence of FDAVB. The role of FDAVB as a prognostic marker in HCM patients requires further investigation. We found that FDAVB patients were older, more frequently reported dyspnea, had a larger QRS duration, a higher E/e' ratio, and lower maximal left ventricle wall thickness by magnetic resonance (p<0.05). After multivariable analysis, FDAVB was independently associated with a higher echocardiographic E/e' ratio (p=0.039) (odds ratio=1.588). This is the first paper to document an independent association between FGAVB and a higher E/e' ratio in HCM patients.

Association of Mycobacterium avium paratuberculosis serostatus with age at first calving, calving interval, and milk production in dairy cows.

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of bovine paratuberculosis, also known as Johne's disease. This infection is responsible for negative effects, ranging from reduction of milk production to reproductive compromise and increased susceptibility to other diseases such as mastitis. Contradictory information on the association between this infection and reproductive performance has been reported in dairy cows. The aim of this work was to investigate associations between individual cow MAP seropositivity and lifetime reproduction and production performance. The MAP serum ELISA (IDEXX MAP Ac) results from all the 13,071 adult cows present on 191 farms and corresponding birth- and calving-date records obtained from the National Association for Genetic Improvement of Dairy Cattle were used. Cows and farms were classified as positive or negative, based on ELISA results. Outcomes assessed were age at first calving (AFC), intercalving intervals (ICI) from first to fourth interval, and average milk production per day of productive cycle (Milk-305/ICI, a ratio between 305-d corrected milk production and the number of days of the respective calving interval). Multilevel mixed models were used to investigate the association of cow MAP status with AFC, ICI, and Milk-305/ICI. Three levels were considered in the models: "measurement occasion," the first level, was nested within cows and cows were nested within farms. The "measurement occasion" is the time point to which all the observed measures (between 2 successive parturitions, such as milk production and somatic cell count) were referred. Our results indicate that MAP-positive cows have a significantly lower 14-d mean AFC than MAP-negative cows. The overall average ICI in our study was 432.5 d (standard deviation: 94.6). The average ICI, from first to fourth, was not significantly affected by MAP seropositivity. No significant effect of MAP positivity was found on the overall ICI. In relation to Milk-305/ICI, MAP-positive cows did not produce significantly less milk than negative cows across their productive lifetime. We observed higher but nonsignificant Milk-305/ICI (kg/d) in MAP-positive cows. In our study, the proportion of MAP-positive cows within lactations remained similar across all lactations, suggesting that seropositivity did not increased drop-off rate.

Cardiovascular magnetic resonance in muscular dystrophies: looking ahead.

Cardiac magnetic resonance (CMR) is an established tool for risk stratification in several cardiomyopathies, and its role in muscular dystrophies (MuD) looks promising. We sought to assess how CMR performs in predicting cardiac events in a real cohort of MuD patients. A prospective single-center study with the enrollment of consecutive adult MuD patients referred to cardiac screening from 2012 to 2018 with the collection of clinical and CMR data. During follow-up (FUP), major adverse cardiac events were considered a composite of device implantation, ventricular tachycardia (VT), hospitalization due to heart failure, and death. Sixty-five patients were included (mean age of 32±16, 51% female); the majority had myotonic dystrophy (34; 52.3%); most were asymptomatic (60; 92.3%) and at sinus rhythm (64; 98.5%). CMR was abnormal in 23 (43.3%) patients: left ventricle ejection fraction (LVEF) <55% was found in 7 patients, and late gadolinium enhancement (LGE) was present in 23 patients, mainly intra-myocardial or subepicardial (10 and 8 patients, respectively). During a median FUP of 77 months (interquartile range: 33), there were 7 deaths, 8 implanted devices, and one sustained VT. LVEF<55% and the presence of LGE were associated with the occurrence of all events (log rank test, p=0.002 and p=0.045, respectively). LVEF<55% was associated with a 6-fold higher risk of events (crude hazard ratio of 6.15; 95% confidence interval of 1.65-22.93), that remained significant after adjusting for LGE presence (adjusted hazard ratio of 4.81, 95% confidence interval of 1.07-15.9). In our cohort, CMR LVEF<55% and the presence of LGE were significantly associated with adverse events during follow-up, reinforcing the role of this technique on risk stratification of MuD populations.

Cardiovascular Magnetic Resonance Versus Histopathologic Study for Diagnosis of Benign and Malignant Cardiac Tumours: A Systematic Review and Meta-Analysis.

BACKGROUND: The gold standard for diagnosis of cardiac tumours is histopathological examination. Cardiovascular magnetic resonance (CMR) is a valuable non-invasive, radiation-free tool for identifying and characterizing cardiac tumours. Our aim is to understand CMR diagnosis of cardiac tumours by distinguishing benign vs. malignant tumours compared to the gold standard. METHODS: A systematic search was performed in the PubMed, Web of Science, and Scopus databases up to December 2022, and the results were reviewed by 2 independent investigators. Studies reporting CMR diagnosis were included in a meta-analysis, and pooled measures were obtained. The risk of bias was assessed using the Quality Assessment Tools from the National Institutes of Health. RESULTS: A total of 2,321 results was obtained; 10 studies were eligible, including one identified by citation search. Eight studies were included in the meta-analysis, which presented a pooled sensitivity of 93% and specificity of 94%, a diagnostic odds ratio of 185, and an area under the curve of 0.98 for CMR diagnosis of benign vs. malignant tumours. Additionally, 4 studies evaluated whether CMR diagnosis of cardiac tumours matched specific histopathological subtypes, with 73.6% achieving the correct diagnosis. CONCLUSIONS: To the best of our knowledge, this is the first published systematic review on CMR diagnosis of cardiac tumours. Compared to histopathological results, the ability to discriminate benign from malignant tumours was good but not outstanding. However, significant heterogeneity may have had an impact on our findings.

Recommendations for the Management of Cardiomyopathy Mutation Carriers: Evidence, Doubts, and Intentions.

Cardiomyopathies may be hereditary and associated with a familial predilection. Morbidity and mortality can be caused by heart failure, sudden death, or arrhythmias. Sometimes these events are the first manifestations of cardiovascular disease. Hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy are perhaps most thoroughly studied in that context. Dilated cardiomyopathy, although most frequently of secondary etiology, has a significant familial cluster. Noncompaction of the left ventricle can sometimes be seen in healthy individuals and, in other instances, is associated with severe LV dysfunction. Genetic testing is of utmost importance, since it might allow for the identification of individuals carrying mutations predisposing them to these diseases. In addition, certain variants may benefit from tailored therapeutic regimens, and thus searching for a causal mutation can impact clinical practice and is recommended for all patients with HCM or ACM. Patients with DCM and positive family history should be included as well. Regular follow-ups are advised, even in those with negative phenotypes, because these disorders are often age dependent. During pregnancy and in the case of athletes, special consideration should be made as well. We intend to summarize the most current evidence regarding their management.

First description of Portuguese patients with cardiac amyloidosis and p.Val142Ile: more evidence of an "African variant" in Caucasians.

Objectives. Hereditary transthyretin amyloidosis caused by the (ATTRv) p. Val142Ile variant is a common cause of cardiac amyloidosis among Western African countries and Afro-Americans populations. However, in recent years, Caucasian patients have been identified in greater numbers, raising the question of whether this variant has been undeappreciated in this population. We now have new cases of cardiac amyloidosis caused by the p.Val142Ile from a center in northern Portugal. In addition, we reviewed and discussed the published data concerning p.Val142Ile in Caucasians. Design. Patients diagnosed with cardiac amyloidosis underwent genetic testing using TTR gene sequencing and their relatives were recommended for genetic counsellingand testing if a pathogenic TTR variant was found. In our center, we reviewed the clinical data of patients who had the p.Val142Ile variant. A review of published cases of p.Val142Ile in Caucasians was also performed, to which our data was compared. Results. We found three ATTRv patients with the p.Val142Ile variant (one homozygotic), all Caucasian males with a median age at diagnosis of 69 years old. All of them had heart failure and arrhythmias. During the follow-up period, two patients died. There were 47 unrelated unrelated Caucasian cases of ATTRv p.Val142Ile variant reported worldwide until May 2022. Conclusions. Our findings add to the mounting evidence that the global prevalence of p.Val142Ile is likely understated. This highlights the importance of the systematic screening of the TTR gene in amyloidosis and phenocopies, as well as larger epidemiologic studies to determine the true ATTRv p.Val142Ile prevalence in non-African communities.

Takotsubo Syndrome in a Rheumatoid Arthritis Patient Under Tofacitinib: A Case Report.

We describe a case of a 57-year-old white woman treated for rheumatoid arthritis (RA) with tofacitinib 10mg daily (started one year ago) and prednisolone 5mg daily. She presented to the emergency department with a tight squeezing chest pain and shortness of breath for 7h and the clinical evaluation revealed regional systolic dysfunction of the left ventricle, mimicking a myocardial infarction, in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. All changes were transient and resolved completely within 4 days. The diagnosis of Takotsubo cardiomyopathy (TKM) was established. This is, as far as we know, the first report of a case of TKM in a RA patient taking tofacitinib. Although the association has not been previously described and the precise cause cannot be identified in this patient, the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.

Mavacamten, a novel revolutionizing therapy in hypertrophic obstructive cardiomyopathy: A literature review.

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiac diseases, defined as a left ventricular wall thickness of ≥15 mm, in the absence of other causes of abnormal ventricular loading. A major hallmark of this disease is the presence of left ventricular outflow tract obstruction, which develops in up to three quarters of patients, referred to as obstructive hypertrophic cardiomyopathy. Current treatment is offered to symptomatic patients, based on the presence of documented left ventricular obstruction, aimed at reducing symptoms and disease progression. This is achieved through pharmacological empirical therapy, surgery, alcohol ablation and/or pacing. Mavacamten is a first-in-class allosteric inhibitor of cardiac myosin that promises to provide clinicians with targeted therapy for these patients. The aim of this review is to provide a general overview of the modern approach to the diagnosis and management of HCM, as well as to integrate all the current knowledge on mavacamten, in anticipation of a future change in the treatment algorithm of patients with HCM.

Characteristics of Streptococcus agalactiae Colonizing Nonpregnant Adults Support the Opportunistic Nature of Invasive Infections.

The prevalence and lineages of Streptococcus agalactiae (group B streptococci [GBS]) colonizing pregnant women are well studied, but less is known about colonization of nonpregnant adults. We characterized GBS colonization in adults as a potential reservoir for infections and tested for the presence of clones with a potentially higher invasive disease potential. We evaluated GBS gastrointestinal, genitourinary, and oral colonization among 336 nonpregnant adults in the community. We characterized the isolates by serotyping, multilocus sequence typing, profiling of surface protein genes and pili, and antimicrobial susceptibility and compared them with contemporary invasive isolates. The colonization rate (n = 107, 32%) among nonpregnant adults was like that of pregnant women. Colonization increased with age (~25% in the 18 to 29 and 30 to 44 years old groups and >42% in the ≥60 years old group), potentially explaining the higher incidence of disease with older age. Participants who were colonized at multiple sites (73%) were frequently carrying indistinguishable strains (93%), consistent with the existence of a single reservoir of colonization and transfer of GBS between sites within the same individual. The most frequent lineages found were serotype Ib/CC1 (n = 27), serotype V/CC1 (n = 19), serotype Ia/CC23 (n = 13), serotype III/ST17 (n = 13), and serotype Ib/CC10 (n = 11). Comparison with contemporary isolates causing invasive infections in Portugal did not reveal any lineage associated with either asymptomatic carriage or invasive disease. Asymptomatic colonization of nonpregnant adults is significant and could act as a reservoir for invasive disease, but in contrast to infant disease, we found no GBS lineages with an enhanced potential for causing invasive disease in adults. IMPORTANCE The increasing incidence of Streptococcus agalactiae (group B streptococci [GBS]) infections in adults and the inability of antimicrobial prophylaxis peripartum to control late-onset infections in infants motivate the study of the asymptomatic carrier state in nonpregnant adults. We found an overall carriage rate like that of pregnant women, increasing with age, potentially contributing to the higher incidence of GBS infections with age. Colonization of diabetic participants was not higher despite the higher number of infections in this group. Comparison between contemporary genetic lineages causing infections and found in asymptomatic carriers did not identify particularly virulent lineages. This means that any prophylactic approaches targeting colonization by particular lineages are expected to have a limited impact on GBS disease in adults.

Does the type of seizure influence heart rate variability changes?

OBJECTIVE: Heart rate variability (HRV), an index of the autonomic cardiac activity, is decreased in patients with epilepsy, and a low HRV is associated with a higher risk of sudden death. Generalized tonic-clonic seizures are one of the most consistent risk factors for SUDEP, but the influence (and relative risk) of each type of seizure on cardiac function is still unknown. Our objective was to assess the impact of the type of seizure (focal to bilateral tonic-clonic seizure - FBTCS - versus non-FBTCS) on periictal HRV, in a group of patients with refractory epilepsy and both types of seizures. METHODS: We performed a 48-hour Holter recording on 121 patients consecutively admitted to our Epilepsy Monitoring Unit. We only included patients with both FBTCS and non-FBTCS on the Holter recording and selected the first seizure of each type to analyze. To evaluate HRV parameters (AVNN, SDNN, RMSSD, pNN20, LF, HF, and LF/HF), we chose 5-min epochs pre- and postictally. RESULTS: We included 14 patients, with a median age of 36 (min-max, 16-55) years and 64% were female. Thirty-six percent had cardiovascular risk factors, but no previously known cardiac disease. In the preictal period, there were no statistically significant differences in HRV parameters, between FBTCS and non-FBTCS. In the postictal period, AVNN, RMSSD, pNN20, LF, and HF were significantly lower, and LF/HF and HR were significantly higher in FBTCS. From preictal to postictal periods, FBTCS elicited a statistically significant rise in HR and LF/HF, and a statistically significant fall in AVNN, RMSSD, pNN20, and HF. Non-FBTCS only caused statistically significant changes in HR (decrease) and AVNN (increase). SIGNIFICANCE/CONCLUSION: This work emphasizes the greater effect of FBTCS in autonomic cardiac function in patients with refractory epilepsy, compared to other types of seizures, with a significant reduction in vagal tonus, which may be associated with an increased risk of SUDEP.

Heart rate variability in patients with refractory epilepsy: The influence of generalized convulsive seizures.

OBJECTIVE: Patients with epilepsy, mainly drug-resistant, have reduced heart rate variability (HRV), linked to an increased risk of sudden death in various other diseases. In this context, it could play a role in SUDEP. Generalized convulsive seizures (GCS) are one of the most consensual risk factors for SUDEP. Our objective was to assess the influence of GCS in HRV parameters in patients with drug-resistant epilepsy. METHODS: We prospectively evaluated 121 patients with refractory epilepsy admitted to our Epilepsy Monitoring Unit. All patients underwent a 48-hour Holter recording. Only patients with GCS were included (n = 23), and we selected the first as the index seizure. We evaluated HRV (AVNN, SDNN, RMSSD, pNN50, LF, HF, and LF/HF) in 5-min epochs (diurnal and nocturnal baselines; preictal - 5 min before the seizure; ictal; postictal - 5 min after the seizure; and late postictal - >5 h after the seizure). These data were also compared with normative values from a healthy population (controlling for age and gender). RESULTS: We included 23 patients, with a median age of 36 (min-max, 16-55) years and 65% were female. Thirty percent had cardiovascular risk factors, but no previously known cardiac disease. HRV parameters AVNN, RMSSD, pNN50, and HF were significantly lower in the diurnal than in the nocturnal baseline, whereas the opposite occurred with LF/HF and HR. Diurnal baseline parameters were inferior to the normative population values (which includes only diurnal values). We found significant differences in HRV parameters between the analyzed periods, especially during the postictal period. All parameters but LF/HF suffered a reduction in that period. LF/HF increased in that period but did not reach statistical significance. Visually, there was a tendency for a global reduction in our patients' HRV parameters, namely AVNN, RMSSD, and pNN50, in each period, comparing with those from a normative healthy population. No significant differences were found in HRV between diurnal and nocturnal seizures, between temporal lobe and extra-temporal-lobe seizures, between seizures with and without postictal generalized EEG suppression, or between seizures of patients with and without cardiovascular risk factors. SIGNIFICANCE/CONCLUSION: Our work reinforces the evidence of autonomic cardiac dysfunction in patients with refractory epilepsy, at baseline and mainly in the postictal phase of a GCS. Those changes may have a role in some SUDEP cases. By identifying patients with worse autonomic cardiac function, HRV could fill the gap of a lacking SUDEP risk biomarker.

Group B streptococcal infections in infants in Iceland: clinical and microbiological factors.

Introduction. Group B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7-89 days), with different GBS clonal complexes (CCs) associated with different disease presentations.Hypothesis. Different GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia).Aim. To study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland?Methodology. All culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records.Results. A total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001).Conclusion. CC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.

Temporal trends of lipid control in very high cardiovascular risk patients.

INTRODUCTION: Since 2011, the European guidelines have included a specific low-density lipoprotein cholesterol (LDL-C) target, <70 mg/dl, for very high cardiovascular risk (CVR) patients. However, registries have shown unsatisfactory results in obtaining this level of adequate lipid control. OBJECTIVES: To assess temporal trends in the use of lipid-lowering therapy (LLT) and attainment of adequate control in very high CVR patients since 2011. METHODS: We performed a retrospective observational study including very high CVR patients admitted in two periods: the first two years since the 2011 guidelines (2011/2012) and five years later (2016/2017). Lipid values, LLT, clinical variables and adequate lipid control rates were analyzed. RESULTS: A total of 1314 patients were reviewed (2011/2012: 638; 2016/2017: 676). Overall, 443 patients (33.7%) were not under LLT and only a slight improvement in drug prescription was observed from 2011/2012 to 2016/2017. In LLT users, the proportion of high-intensity LLT increased significantly in the later years (6.4% vs. 24.0%; p<0.001), but this was not associated with adequate lipid control. Overall, mean LDL-C was 95.4±37.2 mg/dl and adequate control was achieved in 320 patients (24.4%), without significant differences between 2011/2012 and 2016/2017 (p=0.282). Independent predictors of adequate control were male gender, older age, diabetes, chronic kidney disease, prior acute coronary syndrome, prior stroke and LLT, while stable coronary artery disease was associated with higher risk of failure. CONCLUSION: Even after the introduction of specific LDL-C targets, these are still not reached in most patients. Over a five-year period, LLT prescription only improved slightly, while adequate lipid control rates remained unchanged.

Takotsubo Syndrome in a Rheumatoid Arthritis Patient Under Tofacitinib: A Case Report.

We describe a case of a 57-year-old white woman treated for rheumatoid arthritis (RA) with tofacitinib 10mg daily (started one year ago) and prednisolone 5mg daily. She presented to the emergency department with a tight squeezing chest pain and shortness of breath for 7h and the clinical evaluation revealed regional systolic dysfunction of the left ventricle, mimicking a myocardial infarction, in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. All changes were transient and resolved completely within 4 days. The diagnosis of Takotsubo cardiomyopathy (TKM) was established. This is, as far as we know, the first report of a case of TKM in a RA patient taking tofacitinib. Although the association has not been previously described and the precise cause cannot be identified in this patient, the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.

Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast ß-Glucans in Bovine Monocytes.

Yeast-derived products containing ß-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. ß-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified ß-glucans, and also to Zymosan. Our results show that particulate, but not soluble ß-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate ß-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary ß-glucans.

Recommendations for genetic testing in cardiology: Review of major international guidelines. / Recomendações para a realização de testes genéticos em cardiologia ­ revisão das principais diretrizes internacionais.

In recent years, the importance of genetic causes of cardiovascular diseases has been increasingly recognized, as the result of significant advances in molecular diagnosis techniques. This growing knowledge has enabled the identification of new phenotypes and the subclassification of clinical syndromes, impacting the therapeutic approach and genetic counseling offered to affected families. This paper describes the state of the art of genetic testing in the main cardiovascular diseases, aiming to provide a useful tool to help cardiologists and other health professionals involved in the care of individuals with hereditary heart diseases and their families.