Evolution and Prognosis of Tricuspid and Mitral Regurgitation Following Cardiac Implantable Electronic Devices. A Systematic Review and Meta-analysis.

BACKGROUND: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIED) are increasingly recognized. However, uncertainty remains as to whether risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared to cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). AIMS: Synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases published until October 31st, 2023. Significant post-CIED TR and MR were defined as ≥ moderate. RESULTS: Fifty-seven TR studies (N=13,723 patients) and 90 MR studies (N =14,387 patients) were included. For all CIED, risk of post-CIED TR increased (pooled odds ratio (OR)=2.46 and 95% CI=1.88-3.22), while risk of post-CIED MR reduced (OR=0.74, 95% CI=0.58-0.94) after 12 and 6 months of median follow-up respectively. RVP via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR=4.54, 95% CI=3.14-6.57) and post-CIED MR (OR=2.24, 95% CI=1.18-4.26). Binarily, CSP did not alter TR risk (OR=0.37, 95% CI=0.13-1.02), but significantly reduced MR (OR =0.15, 95% CI=0.03-0.62). CRT did not significantly change TR risk (OR=1.09, 95% CI=0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR =0.49, 95% CI=0.40-0.61). There was no significant association of LP with post-CIED TR (OR=1.15, 95% CI=0.83-1.59) or MR (OR=1.31, 95% CI=0.72-2.39). CIED-associated TR was independently predictive of all-cause mortality (pooled hazard ratio (HR)=1.64, 95% CI=1.40-1.90) after median of 53 months. MR persisting post-CRT independently predicted all-cause mortality (HR=2.00, 95% CI=1.57-2.55) after 38 months. CONCLUSIONS: Our findings suggest that, when possible, adoption of pacing strategies which avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Atrial fibrillation and risk of adverse outcomes in heart failure with reduced, mildly reduced, and preserved ejection fraction: A systematic review and meta-analysis.

INTRODUCTION: Heart failure (HF) and atrial fibrillation (AF) frequently co-exist. Contemporary classification of HF categorizes it into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Aggregate data comparing the risk profile of AF between these three HF categories are lacking. METHODS: We conducted a systematic review and meta-analysis aimed at determining any significant differences in AF-associated all-cause mortality, HF hospitalizations, cardiovascular mortality (CV), and stroke between HFrEF, HFmrEF, and HFpEF. A systematic search of PubMed, EMBASE, and Cochrane Library databases until February 28, 2023. Data were combined using DerSimonian-Laird random effects model. RESULTS: A total of 22 studies comprising 248 323 patients were retained: HFrEF 123 331 (49.7%), HFmrEF 40 995 (16.5%), and HFpEF 83 997 (33.8%). Pooled baseline AF prevalence was 36% total population, 30% HFrEF, 36% HFmrEF, and 42% HFpEF. AF was associated with a higher risk of all-cause mortality in the total population with pooled hazard ratio (HR) = 1.13 (95% confidence interval [CI] = 1.07-1.21), HFmrEF (HR = 1.25, 95% CI = 1.05-1.50) and HFpEF (HR = 1.16, 95% CI = 1.09-1.24), but not HFrEF (HR = 1.03, 95% CI = 0.93-1.14). AF was associated with a higher risk of HF hospitalizations in the total population (HR = 1.29, 95% CI = 1.14-1.46), HFmrEF (HR = 1.64, 95% CI = 1.20-2.24), and HFpEF (HR = 1.46, 95% CI = 1.17-1.83), but not HFrEF (HR = 1.01, 95% CI = 0.87-1.18). AF was only associated with CV in the HFpEF subcategory but was associated with stroke in all three HF subtypes. CONCLUSIONS: AF appears to be associated with a higher risk of all-cause mortality and HF hospitalization in HFmrEF and HFpEF. With these findings, the paucity of data and treatment guidelines on AF in the HFmrEF subgroup becomes even more significant and warrant further investigations.

Persistence of significant secondary mitral regurgitation post-cardiac resynchronization therapy and survival: a systematic review and meta-analysis : Mitral regurgitation and mortality post-CRT.

Cardiac resynchronization therapy (CRT) significantly reduces secondary mitral regurgitation (MR) in patients with severe left ventricular systolic dysfunction. However, uncertainty remains as to whether improvement in secondary MR correlates with improvement with mortality seen in CRT. We conducted a meta-analysis to determine the association of persistent unimproved significant secondary MR (defined as moderate or moderate-to-severe or severe MR) compared to improved MR (no MR or mild MR) post-CRT with all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A systematic search of PubMed, EMBASE, and Cochrane Library databases till July 31, 2022 identified studies reporting clinical outcomes by post-CRT secondary MR status. In 12 prospective studies of 4954 patients (weighted mean age 66.8 years, men 77.8%), the median duration of follow-up post-CRT at which patients were re-evaluated for significant secondary MR was 6 months and showed significant relative risk reduction of 30% compared to pre-CRT. The median duration of follow-up post-CRT for ascertainment of main clinical outcomes was 38 months. The random effects pooled hazard ratio (95% confidence interval) of all-cause mortality in patients with unimproved secondary MR compared to improved secondary MR was 2.00 (1.57-2.55); p < 0.001). There was insufficient data to evaluate secondary outcomes in a meta-analysis, but limited data that examined the relationship showed significant association of unimproved secondary MR with increased cardiovascular mortality and heart failure hospitalization. The findings of this meta-analysis suggest that lack of improvement in secondary MR post-CRT is associated with significantly elevated risk of all-cause mortality and possibly cardiovascular mortality and heart failure hospitalization. Future studies may investigate approaches to address persistent secondary MR post-CRT to help improved outcome in this population.

Ongoing Risk of Ventricular Arrhythmias and All-Cause Mortality at Implantable Cardioverter Defibrillator Generator Change: A Systematic Review and Meta-Analysis.

[Figure: see text].

Risk of ventricular arrhythmia in cardiac resynchronization therapy responders and super-responders: a systematic review and meta-analysis.

AIMS: Response to cardiac resynchronization therapy (CRT) is associated with improved survival, and reduction in heart failure hospitalization, and ventricular arrhythmia (VA) risk. However, the impact of CRT super-response [CRT-SR, increase in left ventricular ejection fraction (LVEF) to ≥ 50%] on VA remains unclear. METHODS AND RESULTS: We undertook a meta-analysis aimed at determining the impact of CRT response and CRT-SR on risk of VA and all-cause mortality. Systematic search of PubMed, EMBASE, and Cochrane databases, identifying all relevant English articles published until 31 December 2019. A total of 34 studies (7605 patients for VA and 5874 patients for all-cause mortality) were retained for the meta-analysis. The pooled cumulative incidence of appropriate implantable cardioverter-defibrillator therapy for VA was significantly lower at 13.0% (4.5% per annum) in CRT-responders, vs. 29.0% (annualized rate of 10.0%) in CRT non-responders, relative risk (RR) 0.47 [95% confidence interval (CI) 0.39-0.56, P < 0.0001]; all-cause mortality 3.5% vs. 9.1% per annum, RR of 0.38 (95% CI 0.30-0.49, P < 0.0001). The pooled incidence of VA was significantly lower in CRT-SR compared with CRT non-super-responders (non-responders + responders) at 0.9% vs. 3.8% per annum, respectively, RR 0.22 (95% CI 0.12-0.40, P < 0.0001); as well as all-cause mortality at 2.0% vs. 4.3%, respectively, RR 0.47 (95% CI 0.33-0.66, P < 0.0001). CONCLUSIONS: Cardiac resynchronization therapy super-responders have low absolute risk of VA and all-cause mortality. However, there remains a non-trivial residual absolute risk of these adverse outcomes in CRT responders. These findings suggest that among CRT responders, there may be a continued clinical benefit of defibrillators.

Posttraumatic stress disorder and mortality in VA patients with implantable cardioverter-defibrillators.

BACKGROUND: The association between posttraumatic stress disorder (PTSD) and mortality in patients undergoing implantable cardioverter-defibrillator (ICD) placement has not been evaluated in US veterans. HYPOTHESIS: PTSD in veterans with ICD is associated with increased mortality. METHODS: We studied a retrospective cohort of 25 678 veterans who underwent ICD implantation between September 30, 2002, and December 31, 2011. Of these subjects, 3280 carried the diagnosis of PTSD prior to ICD implantation. Primary outcome was all-cause mortality between date of ICD implantation and end of follow-up (September 30, 2013). We used Cox proportional hazard models to compute multivariable adjusted hazard ratios with corresponding 95% confidence intervals for the relation between PTSD diagnosis and death following ICD placement. RESULTS: During a mean follow-up of 4.21 ± 2.62 years, 11 015 deaths were reported. The crude incidence rate of death was 87.8 and 103.9/1000 person-years for people with and without PTSD, respectively. We did not find an association between presence of PTSD before or after ICD implantation and incident death when adjusted for multiple risk factors (hazard ratio: 1.003, 95% confidence interval: 0.948-1.061). In secondary analysis, no statistically significant association was found. CONCLUSIONS: In this retrospective cohort study among more than 25 000 veterans undergoing ICD implantation, almost 13% had a diagnosis of PTSD. Subjects with PTSD were significantly younger, yet they had a higher incidence of coronary heart disease, major cardiac comorbidities, cancer, and mental health conditions. We found no association between presence of PTSD before or after ICD implantation and incident death when adjusting for all covariates.

ERRATUM: Unexpected Serious Cardiac Arrhythmias in the Setting of Loperamide Abuse.

Loperamide (Imodium) is a non-prescription opioid receptor agonist available over-the-counter for the treatment of diarrhea. When ingested in excessive doses, loperamide can penetrate the blood-brain barrier and is reported to produce euphoria, central nervous system and respiratory depression, and cardiotoxicity. There is an emerging trend in its use among drug abusers for its euphoric effects or for self-treatment of opioid withdrawal. We report a case of ventricular dysrhythmias associated with loperamide abuse in a 28-year-old man who substituted loperamide for the opioids that he used to abuse. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp, free with no login].

Unexpected Serious Cardiac Arrhythmias in the Setting of Loperamide Abuse.

Loperamide (Imodium) is a non-prescription opioid receptor agonist available over-the-counter for the treatment of diarrhea. When ingested in excessive doses, loperamide can penetrate the blood-brain barrier and is reported to produce euphoria, central nervous system and respiratory depression, and cardiotoxicity. There is an emerging trend in its use among drug abusers for its euphoric effects or for self-treatment of opioid withdrawal. We report a case of ventricular dysrhythmias associated with loperamide abuse in a 28-year-old man who substituted loperamide for the opioids that he used to abuse. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

Surface modification of copolymerized films from three-armed biodegradable macromers - An analytical platform for modified tissue engineering scaffolds.

The concept of macromers allows for a broad adjustment of biomaterial properties by macromer chemistry or copolymerization. Copolymerization strategies can also be used to introduce reactive sites for subsequent surface modification. Control over surface features enables adjustment of cellular reactions with regard to site and object of implantation. We designed macromer-derived polymer films which function as non-implantable analytical substrates for the investigation of surface properties of equally composed scaffolds for bone tissue engineering. To this end, a toolbox of nine different biodegradable, three-armed macromers was thermally cross-copolymerized with poly(ethylene glycol)-methacrylate (PEG-MA) to films. Subsequent activation of PEG-hydroxyl groups with succinic anhydride and N-hydroxysuccinimid allowed for covalent surface modification. We quantified the capacity to immobilize analytes of low (amino-functionalized fluorescent dye, Fcad, and RGD-peptides) and high (alkaline phosphatase, ALP) molecular weight. Fcad grafting level was controlled by macromer chemistry, content and molecular weight of PEG-MA, but also the solvent used for film synthesis. Fcad molar amount per surface area was twentyfive times higher on high-swelling compared to low-swelling films, but differences became smaller when large ALP (appr. 2:1) were employed. Similarly, small differences were observed on RGD peptide functionalized films that were investigated by cell adhesion studies. Presentation of PEG-derivatives on surfaces was visualized by atomic force microscopy (AFM) which unraveled composition-dependent domain formation influencing fluorescent dye immobilization. Surface wetting characteristics were investigated via static water contact angle. We conclude that macromer ethoxylation and lactic acid content determined film swelling, PEG domain formation and eventually efficiency of surface decoration. STATEMENT OF SIGNIFICANCE: Surfaces of implantable biomaterials are the site of interaction with a host tissue. Accordingly, modifications in the composition of the surface will determine cellular response towards the material which is crucial for the success of innovations and control of tissue regeneration. We employed a macromer approach which is most flexible for the design of biomaterials with a broad spectrum of physicochemical characteristics. For ideal analytical accessibility of the material platform, we cross-copolymerized films on solid supports. Films allowed for the covalent immobilization of fluorescent labels, peptides and enzymes and thorough analytical characterization revealed that macromer hydrophilicity is the most relevant design parameter for surface analyte presentation in these materials. All analytical results were combined in a model describing PEG linker domain formation and ligand presentation.

Artificial extracellular matrices support cell growth and matrix synthesis of human dermal fibroblasts in macroporous 3D scaffolds.

Surface modification of materials designed for regenerative medicine may improve biocompatibility and functionality. The application of glycosaminoglycans (GAGs) and chemically sulphated GAG derivatives is a promising approach for designing functional biomaterials, since GAGs interact with cell-derived growth factors and have been shown to support fibroblast growth in two-dimensional (2D) cultures. Here, coatings with artificial extracellular matrix (aECM), consisting of the structural protein collagen I and the GAG hyaluronan (HA) or sulphated HA derivatives, were investigated for their applicability in a three-dimensional (3D) system. As a model, macroporous poly(lactic-co-glycolic acid) (PLGA) scaffolds were homogeneously coated with aECM. The resulting scaffolds were characterized by compressive moduli of 0.9-1.2 MPa and pore sizes of 40-420 µm. Human dermal fibroblasts (dFbs) colonized these aECM-coated PLGA scaffolds to a depth of 400 µm within 14 days. In aECM-coated scaffolds, collagen I(α1) and collagen III(α1) mRNA expression was reduced, while matrix metalloproteinase-1 (MMP-1) mRNA expression was increased within 7 days, suggesting matrix-degradation processes. Stimulation with TGFß1 generally increased cell density and collagen synthesis, demonstrating the efficiency of bioactive molecules in this 3D model. Thus, aECM with sulphated HA may modulate the effectivity of TGFß1-induced collagen I(α1) expression, as demonstrated previously in 2D systems. Overall, the tested aECM with modified HA is also a suitable material for fibroblast growth under 3D conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Aspirin use and risk of atrial fibrillation in the Physicians' Health Study.

BACKGROUND: Inflammatory processes have been associated with an increased risk of atrial fibrillation (AF), potentially allowing for preventive therapy by anti-inflammatory agents such as aspirin. However, the effect of chronic aspirin on the incidence of AF has not been evaluated in a prospective cohort followed for an extended period. METHODS AND RESULTS: This study was comprised of a prospective cohort of 23 480 male participants of the Physicians' Health Study. Aspirin intake and covariates were estimated using self-reported questionnaires. Incident AF was ascertained through yearly follow-up questionnaires. Cox's regression, with adjustment for multiple covariates, was used to estimate relative risk of AF. Average age at baseline was 65.1±8.9 years. During a mean follow-up of 10.0 years, 2820 cases of AF were reported. Age-standardized incidence rates were 12.6, 11.1, 12.7, 11.3, 15.8, and 13.8/1000 person-years for people reporting baseline aspirin intake of 0, <14 days per year, 14 to 30 days per year, 30 to 120 days per year, 121 to 180 days per year, and >180 days per year, respectively. Multivariable adjusted hazard ratios (95% confidence interval) for incident AF were 1.00 (reference), 0.88 (0.76 to 1.02), 0.93 (0.76 to 1.14), 0.96 (0.80 to 1.14), 1.07 (0.80 to 1.14), and 1.04 (0.94 to 1.15) across consecutive categories of aspirin intake. Analysis of the data using time-varying Cox's regression model to update aspirin intake over time showed similar results. CONCLUSIONS: In a large cohort of males followed for a long period, we did not find any association between aspirin use and incident AF.

Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1α (SDF-1α) from surface modified polymer films.

Preparation of smart materials by coatings of established surfaces with biomolecules will lead to the next generation of functionalized biomaterials. Rejection of implants is still a major problem in medical applications but masking the implant material with protein coatings is a promising approach. These layers not only disguise the material but also equip it with a certain biological function. The anti-inflammatory chemokine stromal cell-derived factor 1α (SDF-1α) is well suited to take over this function, because it efficiently attracts stem cells and promotes their differentiation and proliferation. At least the initial stem cell homing requires the formation of a concentration gradient. Thus, a reliable and robust release mechanism of SDF-1α from the material is essential. Several proteases, most notably matrix metalloproteinases, are upregulated during inflammation, which, in principle, can be exploited for a tightly controlled release of SDF-1α. Herein, we present the covalent immobilization of M-[S4V]-SDF-1α on novel biodegradable polymer films, which consist of heterobifunctional poly(ethylene glycol) and oligolactide-based functionalized macromers. A peptidic linker with a trimeric matrix metalloproteinase 9 (MMP-9) cleavage site (MCS) was used as connection and the linkage between the three components was achieved by combination of expressed protein ligation and Cu(I) catalyzed azide/alkyne cycloaddition. The MCS was used for MMP-9 mediated release of M-[S4V]-SDF-1α from the biomaterial and the released SDF-1α derivative was biologically active and induced strong cell migration, which demonstrates the great potential of this system.

Regular physical activity and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Although previous studies have suggested that competitive athletes have a higher risk of atrial fibrillation than the general population, limited and inconsistent data are available on the association between regular physical activity and the risk of atrial fibrillation. METHODS AND RESULTS: A systematic, comprehensive literature search was performed using MEDLINE, EMBASE, and COCHRANE until 2011. Extracted data from the eligible studies were meta-analyzed using fixed effects model. Four studies, which included 95 526 subjects, were eligible for meta-analysis. For all of the studies included, the extreme groups (ie, maximum versus minimal amount of physical activity) were used for the current analyses. The total number of participants belonging to the extreme groups was 43 672. The pooled odds ratio (95% confidence interval) for atrial fibrillation among regular exercisers was 1.08 (0.97-1.21). CONCLUSIONS: Our data do not support a statistically significant association between regular physical activity and increased incidence of atrial fibrillation.

Intravascular ultrasound-assisted coronary sinus lead implant in patient with contrast anaphylaxis.

Ultrasound imaging has been used in a range of cardiac interventions. We describe the use of intravascular ultrasound to assist in coronary sinus lead implantation in a patient where contrast venography was contraindicated.

Pacing system malfunction is a rare cause of hospital admission for syncope in patients with a permanent pacemaker.

BACKGROUND: Few studies have examined the prevalence of permanent pacemaker (PPM) malfunction among patients with a previously implanted pacemaker admitted to the hospital with syncope. OBJECTIVE: This study sought to examine causes of syncope in patients with a previously implanted pacemaker admitted to our hospital with syncope. METHODS: We retrospectively reviewed our hospital admission database for patients who had both keywords "syncope" and "pacemaker" as their diagnoses from January 1, 1995 until June 1, 2012. One hundred and sixty-two patients who were admitted to the hospital because of syncope and had a PPM implanted prior to the index syncopal episode were included. All patients had pacemakers interrogated during the admission. Two independent physicians examined the discharge summary of each patient and determined the cause of syncope in each case. RESULTS: Of the 162 patients studied, eight (4.9%) were found to have pacemaker system malfunction as a cause of syncope. In 96 patients (59.2%), the cause of syncope could not be determined prior to hospital discharge. Among the identifiable causes of syncope, orthostatic hypotension was most prevalent (16%) followed by vasovagal (6%), severe aortic stenosis (4.3%), atrial arrhythmia (3.1%), acute and subacute infection (3.1%), and other less prevalent causes (3.1%). CONCLUSION: In this study, PPM system malfunction was rarely a cause of syncope in patients admitted to the hospital with a previously implanted device.

Do Omega-3 Fatty Acids Decrease the Incidence of Atrial Fibrillation?

Although atrial fibrillation is a very common medical problem in general population and has a high incidence in the setting of open heart surgery, there are very few therapies to prevent occurrence or recurrence of atrial fibrillation. N-3 polyunsaturated fatty acids have been shown to change basic physiologic properties of the atrial tissue to make it less susceptible to atrial fibrillation. In this review, we first describe basic physiological mechanisms thought to be responsible for these changes and then discuss observational and interventional studies evaluating the use n-3 polyunsaturated fatty acids for primary and secondary prevention of atrial fibrillation in the general population, in subjects undergoing open heart surgery, and in special subgroups of patients.

On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand for modification of poly(lactic-co-glycolic acid).

Cyclic Arg-Gly-Asp (RGD) peptides show remarkable affinity and specificity to integrin receptors and mediate important physiological effects in tumor angiogenesis. Additionally, they are one of the keyplayers in improving the biocompatibility of biomaterials. The fully biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) is frequently used for biomedical implants and can be applied as nanoparticles for drug delivery. The aim of this work was the generation of a lipidated c[RGDfK] peptide including a second functionality for coating of hydrophobic PLGA. Therefore, we established a general and straightforward strategy for the introduction of two different modifications into the same c[RGDfK] peptide. This allowed the generation of a palmitoylated integrin-binding lipopeptide that shows high affinity to PLGA. Additionally, we coupled 5(6)-carboxyfluorescein to the second site for modification to enable sensitive quantification of the immobilized lipopeptide on PLGA. In conclusion, we present a synthesis protocol that enables the preparation of c[RGDfK] lipopeptides with a strong affinity to PLGA and an additional site for modifications. This will provide the opportunity to introduce a variety of effector molecules site-specifically to the c[RGDfK] lipopeptide, which will enable the introduction of multifunctionality into c[RGDfK]-coated PLGA devices or nanoparticles.

T-wave inversion and diastolic dysfunction in patients with electrocardiographic left ventricular hypertrophy.

OBJECTIVES: The aim of this study was to investigate if T-wave inversion (TWI) in the settings of electrocardiogram (ECG)-left ventricular hypertrophy (LVH) is associated with advanced diastolic dysfunction (DD) in subjects with preserved ejection fraction (EF). BACKGROUND: Animal studies suggested that an abnormal transmural repolarization sequence from endocardium to epicardium may contribute to DD. However, little is known about abnormal repolarization sequence and DD in humans. METHODS: We studied 231 patients with ECG-diagnosed LVH and with an EF of 50% or greater (measured within 6 months of the index ECG). T-wave inversion was assessed on leads I, aVL, V(4), V(5), or V(6). Diastolic dysfunction was defined based on echocardiographic estimation of the left atrial pressure. We used multiple logistic regression to estimate the odds ratio of DD comparing patients with TWI with those without TWI. RESULTS: The average age was 65.0 ± 14.2 years, and 61% were women. The mean EF was 61.8% ± 6.6%. Patients with TWIs were more likely to have coronary artery disease (P = .013) and diabetes (P = .007). There was a 5.6-fold increased odds of DD in patients with TWI compared with those without TWI in a model adjusting for sex, age, relative wall thickness, body mass index, hypertension, coronary artery disease, diabetes, hyperlipidemia, and smoking. When comparing different echocardiographic estimates of the left atrial pressure, patients with TWI displayed higher values for septal and lateral E/e', left atrial volume index, and right ventricular/right atrial peak systolic gradient (P < .01 for each parameter). CONCLUSIONS: T-wave inversion is associated with increased odds of DD in patients with ECG-LVH with preserved systolic function. The reversal of the normal sequence of repolarization manifested on the 12-lead ECG as TWI may be a factor to DD.

Traumatic brain injury elicits similar alterations in α7 nicotinic receptor density in two different experimental models.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. Previous studies have shown alterations in the central cholinergic neurotransmission after TBI. We therefore determined α7 nicotinic acetylcholine receptor (nAChR) densities in newborn piglets and adult rats after experimental TBI. Thirteen newborn piglets (post-TBI survival time: 6 h) underwent fluid percussion (FP) injury (n = 7) or sham operation (n = 6). Furthermore, adult rats randomized into three groups of post-TBI survival times (2, 24, 72 h) received controlled cortical impact injury (CCI, n = 8) or sham operation (n = 8). Brains were frozen, sagittally cut and incubated with the α7-specific radioligand [(125)I]α-bungarotoxin for autoradiography. In injured newborn piglets, decreased α7 receptor densities were observed in the hippocampus (-38%), the hippocampus CA1 (-40%), thalamus (-30%) and colliculus superior (-30%). In adult rats, CCI decreased the receptor densities (between -16 and -47%) in almost any brain region within 2 and 24 h. In conclusion, widespread and significantly lowered α7 nAChR densities were demonstrated in both TBI models. Our results suggest that a nearly similar TBI-induced decrease in the α7 density in the brain of immature and adult animals is found, even with the differences in species, age and experimental procedures. The alterations make the α7 nAChR a suitable target for drug development and neuroimaging after TBI.