Prevention of Ventricular Desynchronization by Permanent Para-Hisian Pacing After Atrioventricular Node Ablation in Chronic Atrial Fibrillation: A Crossover, Blinded, Randomized Study Versus Apical ...Right Ventricular Pacing
Eraldo Occhetta, Miriam Bortnik, Andrea Magnani, Gabriella Francalacci, Cristina Piccinino, Laura Plebani, Paolo Marino
Para-Hisian pacing could improve cardiac function with respect to right ventricular apical pacing, preventing asynchronous ventricular contraction. We evaluated the feasibility, safety, and hemodynamic improvement induced by para-Hisian pacing (screw bipolar lead positioned near the His-bundle) in 16 patients with chronic atrial fibrillation and narrow QRS who underwent atrioventricular node ablation. Para-Hisian pacing allowed a shorter interventricular electromechanical delay and an improvement in New York Heart Association class, quality-of life-score, and 6-min walk test. Mitral and tricuspid regurgitations worsened during apical pacing and improved during para-Hisian pacing. Permanent para-Hisian pacing is feasible and safe.
The aim of our study was to evaluate the feasibility, the safety, and hemodynamic improvements induced by permanent para-Hisian pacing in patients with chronic atrial fibrillation and narrow QRS who underwent atrioventricular (AV) node ablation.
Right ventricular apical pacing, inducing asynchronous ventricular contraction, may impair cardiac function; permanent para-Hisian pacing could preserve interventricular synchrony and improve left ventricular function.
After AV node ablation, 16 patients were implanted with a dual-chamber pacemaker connected to a screw-in lead positioned in close proximity to the His bundle and to a right ventricular apical lead. Clinical and echocardiographic data were collected at baseline and after two randomized six-month periods (with para-Hisian and conventional pacing).
During para-Hisian pacing, the interventricular electromechanical delay improved as well (34 ± 18 ms) as during right apical pacing (47 ± 19 ms), p < 0.05. Para-Hisian pacing allowed an improvement in New York Heart Association functional class (1.75 ± 0.4 vs. 2.33 ± 0.6 at baseline and 2.5 ± 0.4 during apical pacing, p < 0.05 for both), in quality-of-life score (16.2 ± 8.7 vs. 32.5 ± 15.0 at baseline, p < 0.05), and in the 6-min walk test (431 ± 73 m vs. 378 ± 60 m at baseline and 360 ± 71 m during apical pacing, p < 0.5 for both). Mitral and tricuspid regurgitation improved during para-Hisian pacing (1.22 ± 0.8 and 1.46 ± 0.5 index, respectively, vs. 1.68 ± 0.6 p < 0.05 and 1.62 ± 0.7 p = NS index at baseline, respectively), with a slight worsening during apical pacing (1.93 ± 1 and 1.93 ± 0.7 index, respectively, p < 0.05 for both).
Permanent para-Hisian pacing is feasible and safe. Compared with conventional right apical pacing, it allows an improvement in functional and hemodynamic parameters over long-term follow-up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal ...failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (−0.6 ± 1.8%) as well as in BMI (−1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease due to motoneuron degeneration. Magnetic resonance imaging (MRI) is becoming a promising non-invasive approach to monitor the ...disease course but a direct correlation with neuropathology is not feasible in human. Therefore in this study we aimed to examine MRI changes in relation to histopathology in two mouse models of ALS (C57BL6/J and 129S2/SvHsd SOD1G93A mice) with different disease onset and progression. A longitudinal in vivo analysis of T2 maps, compared to ex vivo histological changes, was performed on cranial motor nuclei. An increased T2 value was associated with a significant tissue vacuolization that occurred prior to motoneuron loss in the cranial nuclei of C57 SOD1G93A mice. Conversely, in 129Sv SOD1G93A mice, which exhibit a more severe phenotype, MRI detected a milder increase of T2 value, associated with a milder vacuolization. This suggests that alteration within brainstem nuclei is not predictive of a more severe phenotype in the SOD1G93A mouse model. Using an ex vivo paradigm, Diffusion Tensor Imaging was also applied to study white matter spinal cord degeneration. In contrast to degeneration of cranial nuclei, alterations in white matter and axons loss reflected the different disease phenotype of SOD1G93A mice. The correspondence between MRI and histology further highlights the potential of MRI to monitor progressive motoneuron and axonal degeneration non-invasively in vivo. The identification of prognostic markers of the disease nevertheless requires validation in multiple models of ALS to ensure that these are not merely model-specific. Eventually this approach has the potential to lead to the development of robust and validated non-invasive imaging biomarkers in ALS patients, which may help to monitor the efficacy of therapies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predictive low-glucose suspend (PLGS) and hybrid closed-loop (HCL) systems may improve glucose control and quality of life in type 1 diabetic individuals. This is a cross-sectional, single-center ...study to compare the effect on metabolic control and glucose variability of PLGS and HCL systems as compared to standard sensor-augmented pump (SAP) therapy.
We retrospectively analyzed 136 adults (men/women 69/67, mean age 47.3 ± 13.9 years) with T1D on insulin pump therapy, divided accordingly to type of insulin pump system (
: SAP, 24 subjects;
: PLGS, 49 subjects;
: HCL, 63 subjects). The groups were matched for age, gender, years of disease, years of CSII use, and CGM wear time.
The analysis of CGM metrics, in the three groups, showed a statistically significant different percentage of time within the target range, defined as 70-180 mg/dl, with a higher percentage in group 3 and significantly less time spent in the hypoglycemic range in groups 2 and 3. The three groups were statistically different also for the glucose management indicator and coefficient of variation percentage, which were progressively lower moving from group 1 to group 3. In the HCL group, 52.4% of subjects reached a percentage of time passed in the euglycemic range above 70%, as compared to 32.7% in those with PLGS and 20.2% in those with SAP. A positive correlation between the higher percentage of TIR and the use of auto-mode was evident in the HCL group. Finally, the three groups did not show any statistical differences regarding the quality-of-life questionnaire, but there was a significant negative correlation between CV and perceived CSII-use convenience (r = -0.207, p = 0.043).
HCL systems were more effective in improving glucose control and in reducing the risk of hypoglycemia in patients with type 1 diabetes, thereby mitigating risk for acute and chronic complications and positively affecting diabetes technologies' acceptance.
Indication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom ...indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR.
We identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR.
At the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01–1.96; p = 0.041).
In heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, ...but lifestyle‐based weight loss strategies are not long‐term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes.
A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition.
Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%).
This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AIM: To evaluate the safety and efficacy of the permanent high interventricular septal pacing in a long term follow up, as alternative to right ventricular apical pacing. METHODS: We retrospectively ...evaluated:(1) 244 patients(74 ± 8 years; 169 men, 75 women) implanted with a single(132 pts) or dual chamber(112 pts) pacemaker(PM) with ventricular screw-in lead placed at the right ventricular high septal parahisian site(SEPTAL pacing);(2) 22 patients with permanent pacemaker and low percentage of pacing(< 20%)(NO pacing);(3) 33 patients with high percentage(> 80%) right ventricular apical pacing(RVA). All patients had a narrow spontaneous QRS(101 ± 14 ms). We evaluated New York Heart Association(NYHA) class, quality of life(Qo L), 6 min walking test(6MWT) and left ventricular function(end-diastolic volume, LV-EDV; end-systolic volume, LVESV; ejection fraction, LV-EF) with 2D-echocardiography. RESULTS: Pacing parameters were stable duringfollow up(21 mo/patient). In SEPTAL pacing group we observed an improvement in NYHA class, Qo L score and 6MWT. While LV-EDV didn’t significantly increase(104 ± 40 m L vs 100 ± 37 m L; P = 0.35), LV-ESV slightly increased(55 ± 31 m L vs 49 ± 27 m L; P = 0.05) and LV-EF slightly decreased(49% ± 11% vs 53% ± 11%; P = 0.001) but never falling < 45%. In the RVA pacing control group we observed a worsening of NYHA class and an important reduction of LV-EF(from 56% ± 6% to 43% ± 9%, P < 0.0001).CONCLUSION: Right ventricular permanent high septal pacing is safe and effective in a long term follow up evaluation; it could be a good alternative to the conventional RVA pacing in order to avoid its deleterious effects.
The aim of our study was to evaluate the feasibility, the safety, and hemodynamic improvements induced by permanent para-Hisian pacing in patients with chronic atrial fibrillation and narrow QRS who ...underwent atrioventricular (AV) node ablation.
Right ventricular apical pacing, inducing asynchronous ventricular contraction, may impair cardiac function; permanent para-Hisian pacing could preserve interventricular synchrony and improve left ventricular function.
After AV node ablation, 16 patients were implanted with a dual-chamber pacemaker connected to a screw-in lead positioned in close proximity to the His bundle and to a right ventricular apical lead. Clinical and echocardiographic data were collected at baseline and after two randomized six-month periods (with para-Hisian and conventional pacing).
During para-Hisian pacing, the interventricular electromechanical delay improved as well (34 +/- 18 ms) as during right apical pacing (47 +/- 19 ms), p < 0.05. Para-Hisian pacing allowed an improvement in New York Heart Association functional class (1.75 +/- 0.4 vs. 2.33 +/- 0.6 at baseline and 2.5 +/- 0.4 during apical pacing, p < 0.05 for both), in quality-of-life score (16.2 +/- 8.7 vs. 32.5 +/- 15.0 at baseline, p < 0.05), and in the 6-min walk test (431 +/- 73 m vs. 378 +/- 60 m at baseline and 360 +/- 71 m during apical pacing, p < 0.5 for both). Mitral and tricuspid regurgitation improved during para-Hisian pacing (1.22 +/- 0.8 and 1.46 +/- 0.5 index, respectively, vs. 1.68 +/- 0.6 p < 0.05 and 1.62 +/- 0.7 p = NS index at baseline, respectively), with a slight worsening during apical pacing (1.93 +/- 1 and 1.93 +/- 0.7 index, respectively, p < 0.05 for both).
Permanent para-Hisian pacing is feasible and safe. Compared with conventional right apical pacing, it allows an improvement in functional and hemodynamic parameters over long-term follow-up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with type 1 diabetes (T1D) may develop severe outcomes during COVID-19 disease, but their ability to generate an immune response against the SARS-CoV-2 messenger RNA (mRNA) vaccines remains ...to be established. Here we evaluated the safety, immunogenicity and glycometabolic effects of the SARS-CoV-2 mRNA vaccines in patients with T1D. A total of 375 patients, 326 with T1D and 49 non-diabetics, who received two doses of the SARS-CoV-2 mRNA vaccines (mRNA-1273, BNT162b2) between March and April 2021 at the ASST FBF-Sacco Milan, Italy, were included in this monocentric observational study (NCT04905823). Local and systemic adverse events were reported in both groups after SARS-CoV-2 mRNA vaccination without statistical differences between them. While both T1D patients and non-diabetic subjects exhibited a parallel increase in anti-SARS-CoV-2S titers after vaccination, the vast majority of T1D patients (70% and 78% respectively) did not show any increase in the SARS-CoV-2-specific cytotoxic response as compared to the robust increased observed in all non-diabetic subjects. A reduced secretion of the T cell-related cytokines IL-2 and TNF-alpha in vaccinated patients with T1D was also observed. No glycometabolic alterations were evident in patients with T1D using continuous glucose monitoring during follow-up. Administration of the SARS-CoV-2 mRNA vaccine is associated with an impaired cellular SARS-CoV-2-specific cytotoxic immune response in T1D patients.
J. Neurochem.
(2012)
120
, 765–778.
Abstract
Exposure to psychostimulants results in neuroadaptive changes of the mesencephalic dopaminergic system including morphological reorganization of ...dopaminergic neurons. Increased dendrite arborization and soma area were previously observed in primary cultures of mesencephalic dopaminergic neurons after 3‐day exposure to dopamine agonists via activation of D
3
autoreceptors (D
3
R). In this work, we showed that cocaine significantly increased dendritic arborization and soma area of dopaminergic neurons from E12.5 mouse embryos by activating phosphorylation of extracellular signal‐regulated kinase (ERK) and thymoma viral proto‐oncogene (Akt). These effects were dependent on functional D
3
R expression because cocaine did not produce morphological changes or ERK/Akt phosphorylation neither in primary cultures of D
3
R mutant mice nor following pharmacologic blockade with D
3
R antagonists SB‐277011‐A and S‐33084. Cocaine effects on morphology and ERK/Akt phosphorylation were inhibited by pre‐incubation with the phosphatidylinositol 3‐kinase inhibitor LY294002. These observations were corroborated
in vivo
by morphometrical assessment of mesencephalic dopaminergic neurons of P1 newborns exposed to cocaine from E12.5 to E16.5. Cocaine increased the soma area of wild‐type but not of D
3
R mutant mice, supporting the translational value of primary culture. These findings indicate a direct involvement of D3R and ERK/Akt pathways as critical mediators of cocaine‐induced structural plasticity, suggesting their involvement in psychostimulant addiction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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