Beta-blocker Treatment Research Articles

Long-Term Follow-Up of Patients with Catecholaminergic Polymorphic Ventricular Arrhythmia.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited disorder causing life-threatening arrhythmias. Long-term outcome studies of the channelopathy are limited. Objective: The aim of the present study was to summarize our knowledge on CPVT patients, including the clinical profile treatment approach and long-term outcome. Methods: In this single center study, we retrospectively and prospectively collected data from nine CPVT patients and analyzed them. Results: We reviewed nine patients with CPVT in seven families (22% male), with a median follow-up time of 8.6 years. Mean age at diagnosis was 26.4 ± 12 years. Symptoms at admission were syncope (four patients) and aborted cardiac arrest (four patients). Family history of sudden cardiac death was screened in five patients. In genetic analyses, we found five patients with ryanodine type 2 receptor (RYR2) mutations. Seven patients were treated with beta-blockers, and if symptoms persisted flecainide was added (four patients). Despite beta-blocker treatment, three patients suffered from seven adverse cardiac events. An implantable cardioverter defibrillator was implanted in seven patients (one primary, six secondary prevention). Over the follow-up period, three patients suffered from ventricular tachycardia (ten times) and five patients from ventricular fibrillation (nine times). No one died during follow-up. Conclusion: Our CPVT cohort showed a high risk of cardiac events. Family screening, optimal medical therapy and individualized treatment are necessary in affected patients in referral centers.

Beta-blocker exposure for short-term outcomes following non-cardiac surgery: A meta-analysis of observational studies.

It remains uncertain whether there is a benefit to perioperative beta-blocker use on outcomes after non-cardiac surgery. This meta-analysis aims to update the evidence regarding the associations between beta-blocker exposure and patient major short-term outcomes following non-cardiac surgery. Pubmed, Embase, and the Cochrane Central Register from their inception to May 2019 were searched by two independent authors. Observational studies reporting associations between perioperative beta-blocker treatment and short-term outcomes including 30-day all-cause mortality (ACM), 30-day major adverse cardiovascular events (MACE) and 30-day stroke risk were selected for inclusion. Meta-analyses were carried out by using random effects models. Nineteen studies with a total of 1,711,766 participants were identified. Beta-blocker exposure was associated with reduced 30-day all-cause mortality (ACM) (RR 0.83, 95% CI 0.72 to 0.96). No evidence of publication bias was observed. Subgroup analyses revealed that significant 30-day survival benefits were observed in prospective, population-based studies, drug exposure period last till 1-2 months after surgery, patients having abdominal gastrointestinal surgery or having 3-4 cardiac risk factors. Beta-blocker exposure was associated with increased 30-day ACM among patients with no cardiac risk factors (RR 1.30, 95% CI 1.19 to 1.43). However, meta-analysis demonstrated a non-significant risk reduction in 30-day MACE (RR 1.03; 95% CI 0.85 to 1.25) or 30-day stroke risk (RR 0.86; 95% CI 0.44 to 1.68) with beta-blocker exposure. The results of the current meta-analysis indicate beta-blocker exposure may be a significant indicator for 30-day ACM, but not for 30-day MACE or 30-day stroke risk. The association between beta-blocker exposure and long-term outcomes deserves further investigation.

The Dark Purple Side of Ceftriaxone: A Case Report on Leucocytoclastic Vasculitis.

We present a case of an 85-year-old woman diagnosed with uncomplicated pyelonephritis, who was treated with intravenous ceftriaxone. Her chronic medications were phenprocoumon, diltiazem and bisoprolol. During the infectious phase, the patient presented tachycardia – despite high-dose beta-blocker treatment – and developed left acute heart failure, with acute renal failure (pre-renal origin). After introduction of furosemide diuretic therapy, clinical conditions improved and better control of the volemic status and heart rate was achieved. Several days after ceftriaxone and digoxin therapy initiation, worsening multiple non-blanching palpable purpuric lesions with bullae and papules, limited to the lower extremities, were noted. Skin biopsy was performed and a diagnosis of leucocytoclastic vasculitis, with associated panniculitis, was made. Ceftriaxone was discontinued and systemic corticosteroids were introduced, with a clear improvement in the cutaneous condition.LEARNING POINTSLeucocytoclastic vasculitis is a rare but significant side effect related to the administration of ceftriaxone.The importance of skin biopsy in the differential diagnosis of skin eruptions.

DECREASED MORTALITY WITH BETA-BLOCKER THERAPY IN PATIENTS WITH HFPEF INDUCED OR EXACERBATED BY ATRIAL FIBRILLATION

There are no proven effective treatments can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blockers treatment in patients with

Effect of resting heart rate on the risk of all-cause death in Chinese patients with hypertension: analysis of the Kailuan follow-up study

ObjectivePrevious studies have shown that an elevated heart rate is associated with a higher risk of cardiovascular events. This study aimed to prospectively examine the relationship between resting heart rate...

Myocardial Protection with Beta Blocker Treatment in Infants with Heart Failure Due to Congenital Heart Defects and Duchenne Muscular Dystrophy

Our first intention to treat infants’ heart failure with beta blockers was to improve the clinical condition as shown in our prospective randomized trial. We only use non-selective beta blockers in these infants, carvedilol in those with left ventricular dysfunction and propranolol in those with congenital heart disease without ventricular dysfunction. Despite a significant improvement of Ross’s heart failure score, we could not convince most colleagues within the last 25 years if the concept of neurohumoral activation in heart failure is not well-established pediatric cardiology. Recently, Honghai Liu et al. published that cardiomyocyte cytokinesis failure was increased in congenital heart disease. Inactivation of the beta adreno receptors genes and administration of the beta-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. We currently realize that propranolol in infants with congenital heart disease not only decrease highly elevated NT-Pro-BNP values but also decrease cardiac troponin T values that may indicate myocardial injury due to neurohumoral activation. We reproduce this observation, primarily seen in infants with congenital heart disease, in an infant with Duchenne muscular dystrophy. These observations were in good accordance with current data from H. Liu et al., who showed that treatment with non-selective beta blockers early after birth might rescue cytokinesis defects and prevent heart dysfunction in adulthood in a mouse model.

Propranolol for Surgeons in the Treatment of Infantile Hemangiomas.

Beta-blocker (Propanolol or Timolol maleate) treatment of infantile hemangiomas (IH) is a safe and effective treatment in the outpatient setting. The authors report a single surgeon's initial experience with setting up an outpatient service of beta-blocker treatment for head and neck IH at a tertiary children's hospital. A prospective study of children with head and neck IHs commenced in January 2015 with the end point being December 2018. Each child started either oral propranolol (2 mg/kg/day) or topical Timolol 0.5%. Thirty-eight patients commenced a beta-blocker during the study duration. The mean age at time of starting therapy was 9 months (range 3 weeks to 116 months). Four patients were older than 12 months at commencement. The mean duration of treatment was 9 months. The response to treatment was excellent or complete in 29% (n = 11), good in 50% (n = 18) and mild in 10% (n = 4). The non response rate was 10% (n = 4). No major adverse effects occurred but 29% (n = 11) experienced minor side effects. Low dose propranolol and topical Timolol is been safe and easy to use for surgeons who may not be regular prescribers or unfamiliar with treating children with IHs with beta-blocker therapy. In patient monitoring is unnecessary and parents can be taught easily to recognise side effects. Treating children from the start builds a trusting relationship with the family before the child requesting cosmetic revision of the fibro-fatty remnant.

Evaluation of central: peripheral blood pressure ratio in patients undergoing coronary angiography: A pilot study from North India

Aim: The study aimed to propose the ratio of central blood pressure:peripheral blood pressure as a novel index to predict cardiovascular risk. We additionally attempted to determine the impact of beta-blocker therapy on this ratio. Materials and Methods: This was a prospective, single-centre study conducted between August 2019__ and December 2019. A total of 102 patients undergoing cath-lab procedures such as coronary angiography (CAG), percutaneous coronary intervention were studied. Central blood pressure was invasively measured from the radial artery. Peripheral blood pressure was also measured from the right arm radial artery using invasive pressure transducer. Patients were divided into two groups as follows: (i) beta-blocker group to receive beta-blocker treatment (n = 82) and (ii) nonbeta-blocker group that did not receive beta-blocker treatment (n = 20). Results: The mean age of the study participants was 55.7 ± 10.0 years. Males constituted 80 (78.4%) patients of the study population. The central:peripheral blood pressure ratios for systolic and diastolic blood pressure were 0.88 ± 0.1 and 0.93 ± 0.2 (P = 0.004), respectively. Systolic blood pressure ratios for the beta-blocker and nonbeta-blocker groups were 0.89 ± 0.1 and 0.93 ± 0.2 (P = 0.016), respectively. Similarly, diastolic blood pressure ratios for the beta-blocker and nonbeta-blocker groups were 0.84 ± 0.1 and 0.95 ± 0.1 (P = 0.770), respectively. Conclusions: This novel ratio of central:peripheral blood pressure may serve as a precursor of cardiovascular risk. This ratio may give a clue to relationship between central and peripheral blood pressure.

T-Peak to T-End Improvements After Beta-Blocker Administration in Peripartum Cardiomyopathy Patients.

BackgroundMany studies have shown that T-peak to T-end (TPTE) interval was associated with sudden cardiac events. Peripartum cardiomyopathy (PPCM) causes reversible left ventricle systolic dysfunction which may deteriorate into sudden cardiac death. This study aimed to evaluate beta-blocker as an antiarrhythmic agent to improve TPTE interval as a prognostic value of sudden cardiac death.MethodsA cohort experimental prospective study was performed. The PPCM was diagnosed from the emergency ward. A total of 54 cases were identified from 2014 to 2016. Thirty-four patients were followed up for further analysis. Electrocardiograms were conducted in all the patients, and TPTE interval was measured. After a follow-up of 6 months of beta-blocker treatment, the echocardiography and TPTE interval were measured again to obtain the repolarization heterogeneity.ResultsThe mean age of subjects was 32 ± 6.4 years. The mean left ventricular ejection fraction (LVEF) was 32.24±6.3%. The mean TPTE interval was 123.7 ± 28.2 ms. After 6 months of beta-blocker administration, the mean LVEF was 58.26±4.4% and the mean TPTE was 98.7 ± 39.5 ms. The paired t-test showed a significant difference between TPTE interval pre- and post-administration of beta-blocker (P value < 0.001).ConclusionsThere is an improvement of TPTE in PPCM patients after 6 months of beta-blocker administration. Administration of beta-blocker in PPCM patients is expected to prevent sudden cardiac death in PPCM populations.

Prevalence and association of medication nonadherence with major adverse cardiovascular events in patients with myocardial infarction.

Current study was to evaluate the prevalence of guideline recommended medications adherence in myocardial infarction (MI) patients postpercutaneous coronary intervention (PCI) and the association of medication nonadherence and major adverse cardiovascular events (MACEs).MI patients who underwent PCI in the last 12 months were enrolled. Demographic and clinical characteristics were collected and guideline recommended medications were evaluated. Patients were divided into with and without MACEs groups.Compared to patients without MACEs, those with MACEs were older (54.8 ± 16.4 vs 51.1 ± 15.2 years), more likely to be smoker (40.2% vs 31.9%), have higher body mass index (BMI; 25.0 ± 6.1 vs 23.8 ± 5.7 kg/m2), diabetes (47.5% vs 37.8%), ischemic stroke (34.4% vs 25.6%), and estimated lower glomerular filtration rate (85.4 ± 9.6 vs 92.6 ± 10.7 mL/minute/1.73 m2). Patients with MACEs were also more likely to present with ST-elevation MI (STEMI; 54.1% vs 48.4%) and to undergo urgent PCI (62.3% vs 56.3%). Furthermore, patients with MACEs were less likely to adhere to dual antiplatelet therapy (77.9% vs 85.9%), renin−angiotensin system inhibitor (62.3% vs 69.7%), and beta-blocker (69.7% vs 72.8%) treatment. In unadjusted model, medication nonadherence was associated with 2-fold higher odds of MACEs. After adjustment for demographics, risk factors, comorbidities, and peri-PCI characteristics, medications nonadherence remained independently associated with MACEs, with odds ratio of 1.40 (95% confidence interval: 1.29–1.87).Medications adherence rate among MI patients post-PCI is suboptimal in China, which is independently associated with MACEs.

P331Effect of exercise stress test on platelet function in patients with recent acute myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation for coronary artery disease (CAD) is associated with lower cardiovascular mortality. On the other hand, acute strenuous exercise has been linked to cardiovascular complications such as acute myocardial infarction (AMI) and sudden cardiac death. One of the pathophysiological mechanisms involved in these outcomes might be an increase in platelet aggregability after exercise. Although previous studies showed higher platelet aggregability after exercise among stable CAD patients on aspirin treatment, there is no data regarding the effect of exercise on platelet activity in post-AMI patients on dual anti-platelet therapy (DAPT). Purpose To evaluate the effect of high-intensity exercise on platelet aggregability in sedentary post-AMI patients on DAPT. Methods Platelet function was analyzed immediately before and after maximal cardiopulmonary exercise test (CPET) on cycle ergometer utilizing a personalized ramp protocol and aiming to achieving peak exercise in around 10 min. The CPET was done within 31±4 days after uncomplicated AMI. Platelet aggregability was assessed by Multiplate®ADPtest (MP-ADP) and Multiplate® ASPItest (MP-ASPI) measured as area under the curve (AUC). Reticulated platelets were measured concomitantly to MP-ADP e MP-ASPI using a fully automated flow cytometer (Sysmex XN-2000®) to determine absolute immature platelet count (IPC) per 103/microliter. Continuous variables were expressed as means ±standard deviation or as median and 25th–75th percentiles if not Gaussian distributed. Comparisons between the pre- and post-CPET assessments were performed using Wilcoxon signed rank test. Results We analyzed 81 sedentary patients (mean age 58.3±10.1 years-old, 76.5% men) after AMI (50.6% with ST-elevation myocardial infarction, mean left ventricular ejection fraction after index event 55±11.7%, 98.8% on statin and 85.5% on beta-blocker treatment). Platelet aggregability, either by MP-ADP or MP-ASPI, and IPC were significantly increased after CPET (table). Platelet function after CPET Before CPET After CPET p-value Multiplate® ADPtest (AUC) – median (25th–75th percentiles) 32.0 (22.0–48.5) 37.0 (26.0–55.2) 0.003 Multiplate® ASPItest (AUC) – median (25th–75th percentiles) 17.0 (12.7–22.0) 22.0 (16.7–28.0) &lt;0.001 Immature platelet count (103/microliter) – median (25th–75th percentiles) 9.5 (6.8–13.8) 9.6 (6.6–16.5) 0.006 CPET: cardiopulmonary exercise test; AUC: area under the curve. Conclusion On this post-AMI population, platelet was hyperactivated after exercise stress test despite the use of DAPT. These findings suggest that, even when properly treated, post-AMI patients might be at higher risk of ischemic complications after high-intensity exercises, reinforcing the importance of tailoring exercise prescription in this population. Acknowledgement/Funding Sao Paulo Research Foundation, FAPESP

P3793Spironolactone in patients with permanent atrial fibrillation, possible heart failure protective potential

Abstract Background Atrial fibrillation (AF) promotes electrical, neurohormonal and structural remodeling of atria and ventricles. Long lasting AF leads to atrial interstitial fibrosis, apoptosis, loss of myofibrils and finally to heart failure (HF). Purpose The aim of the study was impact of aldosterone antagonist, spironolactone, on exercise tolerance and neurohormonal activity in patients with permanent AF without symptoms of HF. Methods In prospective, randomized study patients with permanent AF at least for 1 year, no signs and symptoms of HF and stable clinical condition were included. Patients were randomized to: beta-blocker plus spironolactone (dose: 25 mg) treatment and rate-control treatment with only beta-blocker. Propranolol, metoprolol and bisoprolol were used, doses were adjusted to achieve resting heart rate 60–80/min. Ergospirometry (CPX) and 6-minute walk (6-MWT) tests were performed during separate days. Results Study group consisted of 49 patients, 69% men, mean age 62.1±9.6 without structural and chronic active diseases, mean time of arrhythmia was 5.5 years, Q1: 2, Q3: 8 years. Follow-up was 11.2 months. All patients were treated with beta-blockers, 27 patients were treated with 25 mg spironolactone. Surprisingly physical capacity in 6-minute walk test (6-MWT) in studied patients was not significantly reduced in comparison with values ranges for healthy volunteers. After 11.2 months follow-up significantly longer exercise time (433±113 vs. 367±162 sec, p&lt;0.05) and lower maximal HR (159±25 vs. 165±22 beats/min, p&lt;0.0550) were observed in spironolactone treated group. Other CPX variables did not differ significantly between groups after 11,2 months: VO2: 20.7±5.1 vs. 20.1±4.8 [ml/kg/min]; VO2 as % of normal value: 78.4±15.2 vs. 76.8±15.2; O2 pulse: 12±2.8 vs. 12.7±3.6 [ml/beat]; AT: 1.4±0.3, 1.6±0.5 [L/min]; VE: 74.9±20.0, 72.6±17.9 [L/min]. All spirometric variables worsened after 11.2 months: VC: 4.3±1.1 vs. 3.8±0.8 [L], p&lt;0.0005, FVC: 4.2±1.1 vs. 3.8±1.0 p&lt;0.005 [L], FEV1: 3.1±0.8 vs. 2.8±0.7 [L], p&lt;0.01. In spironolactone treated group after 11.2 months BNP concentrations were significantly lower: Q1: 54, Q2: 83, Q3: 100 vs. Q1: 42, Q2: 93; Q3: 184 ng/L (p=0.025) and aldosterone levels were markedly increased: Q1: 216, Q2: 266; Q3:443 vs. Q1: 169; Q2: 228; Q3:294 ng/dL (p=0.0007). Conclusions In patients with permanent atrial fibrillation cardiopulmonary exercise responses were markedly abnormal, but exercise capacity was increased after spironolactone treatment. Deterioration of spirometry results might be due to beta-blocker treatment. In spironolactone treated group BNP levels were significantly lower what may correspond to its heart failure protective activity.

5037Drug treatment with beta-blockers and long-term outcome in patients with takotsubo syndrome: results from the takotsubo Italian network

Abstract Background Although generally considered a benign disease, Takotsubo syndrome (TTS) has recently been associated to a substantially comparable long-term outcome than acute coronary syndrome (ACS). The use of beta-blockers (BB) has been advocated in these patients for secondary prevention after the index event, considering the presumed role of catecholamine in TTS pathophysiology. However, the effect of BB on long-term outcome remains controversial due to the paucity of data and the lack of evidence from randomized studies. Purpose To investigate the impact of BB therapy on long-term outcome in patients with TTS. Methods The study included all TTS patients enrolled in the Takotsubo Italian Network multicenter registry. Patients were divided in two study groups according to the BB therapy after discharge. The following major adverse cardiac events (MACE) were assessed at the longest available follow-up: cardiac death, TTS recurrence, rehospitalization for cardiac cause, acute or worsening heart failure (HF) and ACS. Also, the composite of cardiac death and rehospitalization as well as the overall MACE were analyzed Results The study population included 548 patients (mean age 68.7±11.4 years; 44 males, 8%). Among them, BB treatment was reported in 368 (BB group, 67.2%) and 180 (no-BB group, 32.8%) patients, respectively. The baseline clinical characteristics were substantially comparable among groups with the only exception of COPD, which was prevalent in the no-BB group (10.3% vs 21.7%, p=0.001). During follow-up (median 18 months 25–75% c.i. 6–29), TTS recurrence was reported in 26 patients (4.7%), ACS in 10 (1.8%), acute or worsening HF in 39 (7.1%), cardiac hospitalization in 71 (13.0%) and cardiac death in 18 (3.3%). The rate of TTS recurrence and ACS was comparable between groups. Conversely, no-BB patients experienced more frequently acute or worsening HF (5.4% vs 10.6%, p=0.034), cardiac rehospitalization (10.9% vs 17.2%, p=0.042) and cardiac death (1.9% vs 6.1, p=0.018) than BB patients. Therefore, the MACE composite endpoint was significantly prevalent in the no-BB group (12.0% vs 20.6%, p=0.010). Kaplan-Meier curves for the composite of cardiac death and rehospitalization showed a statistically lower survival in the no-BB patients compared to the BB group (p=0.006). Moreover, landmark analysis showed a wider survival benefit in the BB patients after 2 years. Conclusions Although in absence of a secondary preventive effect on TTS recurrence, BB may improve the long-term cardiac outcome in patients with TTS. Prospective randomized studies are advisable to confirm these findings.

P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and &lt;50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF &lt;50% [HR 0.42, (95% CI 0.18- 0.99), p&lt;0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

P1588Beta-blocker therapy and risk of dementia: a population-based prospective study

Abstract Introduction Cerebral side effects have long been recognized as complications to beta-blocker treatment. However, evidence of a longitudinal relationship between the use of beta-blockers and incident dementiais still controversial. Objective To evaluate the longitudinal relationship between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer and mixed dementia. Methods From the prospective, population-based, Malmö Preventive Project, 18,063 individuals (mean age 68.2, males 63.4%) were included at baseline and followed for 84,506 person-years. Patients with prevalent cerebrovascular disease and dementia were excluded. In order to weight the risk of incident dementia associated with beta-blocker consumption, we performed propensity score matching analysis, resulting in 3,720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazardsregression. Results Overall, 122 study participants (1.6%) were diagnosed with dementia over the course of follow-up. Use of beta-blockers was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95% CI 1.01–3.78; p=0.048). Conversely, treatment with BB was not associated with increased risk of all-cause, Alzheimer and mixed dementia (HR: 1.15; 95% CI 0.80–1.66; p=0.44; HR: 0.85; 95% CI 0.48–1.54; P=0.59 and HR: 1.35; 95% CI 0.56–3.27; p=0.50, respectively). Conclusions and relevance We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta-blockers and increased risk of vascular dementia.

The Favourable Effects Of Betablockers Treatment On The Diabetic Hypertensive Patients With Nocturnal Non-Dipper Profile.

Background and Aims: This study wants to show the influence of the treatment on hypertension profiles and nocturnal heart frequency. We compare the mean heart rate (MHR) and mean arterial pressure (MAP) on hypertensive diabetic patients with different dipper profiles.

The Influence of Cardiovascular Medications on Iron Metabolism in Patients with Heart Failure.

Background and objectives: The etiology of anemia associated with heart failure is not fully understood, but there are data suggesting the involvement of multiple mechanisms, including various drug therapies used in patients with heart failure. Our primary objective was to evaluate the impact of beta blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers on iron metabolism in patients with heart failure. Materials and Methods: This was a prospective observational study that included patients diagnosed with heart failure and iron deficiency (defined by ferritin <100 μg/L, or 100–300 μg/L with transferrin saturation <20%). Patients with anemia secondary to a known cause were excluded. Results: We found a statistically significant correlation between beta-blocker treatment and ferritin values (p = 0.02). Iron, hemoglobin, and hematocrit levels were significantly lower in the patients using calcium-channel blockers than those who were not. We also found a statistically significant indirect correlation (p = 0.04) between the use of angiotensin-converting enzyme inhibitors and hematocrit levels. Conclusion: The contribution of our study arises from the additional data regarding the drug-induced etiology of iron deficiency. Practitioners should be aware of the potential impact of therapeutic recommendations and this should imply a close monitoring of the biochemical parameters of iron deficiency in this category of patients.

ANGIOTENSIN II INDUCES UCP1 IN ADIPOSE TISSUE OF AN EXPERIMENTAL MODEL OF CARDIO-RENAL CACHEXIA

Objective: Cachexia is a severe complication of advanced heart failure and chronic kidney disease. We previously reported that high dose Angiotensin II infusion in rats determined body weight reduction, prevented by an AT-1 receptor blocker treatment and beta-adrenergic non selective antagonism. The possible role of Ang II on UCP1 in white and brown adipose tissue, as a possible mechanism, was investigated in this study. Design and method: Male Sprague-Dawley rats, were implanted subcutaneously in the dorsal region with osmotic minipumps delivering Ang-II at high doses (525 ng/Kg/min) for 12 days to mimic heart failure and the development of cachexia. Five concurrent groups of rats were evaluated: 1) vehicle–infused rats (CTR-rat, n = 9); 2) Ang-II infused rats (n = 7); Ang- II rats receiving by oral gavage 2 days before minipump implantation until the 12th day of Ang-II infusion, either 3) bisoprolol (BIS,β1-adrenergic antagonist, 35 mg/Kg/day, n = 5), or 4) carvedilol (CVD,α1-non-selective-β1,2,3-adrenergic blocker, 90 mg/kg/day, n = 5) or 5) bupranolol (BPR,β3-antagonist, 200 mg/day/kg, n = 4). White adipose tissue (WATs) from retroperitoneal (RWAT), epidydimal (EWAT), dorsal (DWAT) and brown interscapular (IBAT) depot were withdrawn in order to determine UCP1 mRNA expression, norepinephrine tissue level (TNE) and tyrosine hydroxylase activity (THA) Results: THA and TNE were higher in Ang-II infused rats in all the white adipose tissue depots analyzed. CVD prevented TNE increase in all WATs, while BPR and BIS were effective in RWAT and EWAT but not DWAT. All the three beta adrenergic blocker treatments significantly reduced THA increased activity related to Ang-II infusion in all the WATs. UCP1 mRNA was increased in IBAT (+39%, p < 0.05) of Ang II-infused rat, significantly prevented by CVD and BPR but not by BIS. UCP1 was also increased in all the three WATs of Ang-II infused rats, with all the three beta blockers able to reduce the effect in RWAT and DWAT. No effect of beta-blockers treatment was observed in EWAT. Conclusions: High dose angiotensin II infusion determined an increase in UCP1 trascription in brown and white adipose tissue in rats. CVD and BPR were able to prevent UCP1 increase in brown and white adipose tissue more than beta-1 selective antagonist BIS.

Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital

Background: Considering the increasing burden of cardiovascular risk factors and recent advances on the management of acute coronary syndromes (ACS), we studied the epidemiological characteristics and treatment strategies of patients presenting with ACS. We also evaluated the lipid profile and attainment of lipid goals in a ‘real world’ clinical setting.Methods: This was a substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), a single-centre, prospective, randomised controlled trial. Baseline data from a total of 357 ACS patients were gathered using standardised methods.Results: Median age of patients was 60 years and 81.2% were males. Arterial hypertension and smoking were the most prevalent risk factors for coronary artery disease (CAD). Patients with ST-elevation myocardial infarction (STEMI) were heavier smokers, but were younger and exercised more compared to those with non-ST-elevation acute coronary syndrome (NSTE-ACS). Conversely, more NSTE-ACS patients had arterial hypertension, dyslipidaemia and diabetes mellitus. One-fifth of ACS patients was treated conservatively without a percutaneous coronary intervention (PCI). A combination of statin, dual antiplatelet therapy and beta-blockers were prescribed to 79.6% of patients upon discharge. A renin-angiotensin-aldosterone system inhibitor and a beta-blocker were prescribed to 67.3 and 91.8% of patients with LVEF ≤40%, respectively. Of patients with prior history of CAD, 63.1%, 71.4% and 58.3% received regularly statins, antiplatelets and beta-blocker treatment, respectively. Only 22.3% of these CAD patients had an optimal LDL-C of <70 mg/dl at admission.Conclusions: In hospitalised patients with ACS, management practices differed by ACS type and discharge medication was, mostly, in line with the latest guidelines. However, medication adherence and lipid lowering goals of secondary CAD prevention were largely unachieved.

Prior β-blocker treatment decreases leukocyte responsiveness to injury.

Following injury, leukocytes are released from hematopoietic organs and migrate to the site of damage to regulate tissue inflammation and repair, however leukocytes lacking β2-adrenergic receptor (β2AR) expression have marked impairments in these processes. β-blockade is a common strategy for the treatment of many cardiovascular etiologies, therefore the objective of our study was to assess the impact of prior β-blocker treatment on baseline leukocyte parameters and their responsiveness to acute injury. In a temporal and βAR isoform-dependent manner, chronic β-blocker infusion increased splenic vascular cell adhesion molecule-1 (VCAM-1) expression and leukocyte accumulation (monocytes/macrophages, mast cells and neutrophils) and decreased chemokine receptor 2 (CCR2) expression, migration of bone marrow cells (BMC) and peripheral blood leukocytes (PBL), as well as infiltration into the heart following acute cardiac injury. Further, CCR2 expression and migratory responsiveness was significantly reduced in the PBL of patients receiving β-blocker therapy compared to β-blocker-naïve patients. These results highlight the ability of chronic β-blocker treatment to alter baseline leukocyte characteristics that decrease their responsiveness to acute injury and suggest that prior β-blockade may act to reduce the severity of innate immune responses.