Beta-blocker Therapy Research Articles

12-week Moderate-intensity Brisk Walking Improved Chronotropic Response In 40- To 69-year-old Patients With Hypertension

PURPOSE: The aim of this study was to investigate the effect of 12-week brisk walking on chronotropic response in 40- to 69-year-old hypertensive patients in order to provide a scientific theory for improving the prognosis of hypertension with exercise. METHODS: In this study, we included 68 hypertensive patients aged 40-69 in Beijing and Hebei Province in 12-week brisk walking intervention, and 34 hypertensive patients age- and gender-matched as control group. The patients included were free of beta blocker therapy. Participants in exercise group underwent 12-week brisk walking 3 times a week, with the intensity gradually increased from 40-49% to 50-59% heart rate reserve, and the duration gradually increased from 30 to 60 minutes each time. Resting blood pressure, resting heart rate and peak oxygen consumption (VO2peak) were measured. Chronotropic parameters were calculated according to the formula, including metabolic chronotropic relationship (MCR), chronotropic response index (CRI) at all stages. %Δ means the percentage of the difference of indicators between before and after intervention. RESULTS: (1) The systolic blood pressure of hypertensive patients was decreased after intervention of 12-week brisk walking (135.60 ± 13.08 vs 128.52 ± 12.62 mmHg, p < 0.0001) compared to the control group. (2) The %ΔMCR was increased in exercise group after intervention compared to the control group. ((-0.94 ± 25.20) vs (7.14 ± 27.11) %, p = 0.013). (3) The CRI at 50 W- and 75 W-load, CRI2 and CRI3, were decreased after 12 weeks in control group (CRI2: 0.87 ± 0.22 vs 0.77 ± 0.20, p = 0.033; CRI3: 0.96 ± 0.12 vs 0.89 ± 0.10, p = 0.022), while no statistical difference was seen in the exercise group. (4) VO2peak was increased in exercise group after intervention compared to the control group (29.23 ± 4.84 vs 30.52 ± 5.21 mL/kg/min, p = 0.008). (5) The %ΔVO2peak was positively correlated with the %ΔMCR in exercise group (r = 0.269, p = 0.027). CONCLUSIONS: The 12-week moderate-intensity brisk walking significantly reduced systolic blood pressure and improved chronotropic response in 40- to 69-year-old hypertensive patients. Furthermore, the improvement of chronotropic response was associated with increased cardiopulmonary fitness. Supported by National Key Research and Development Program in China (NO. 2016YFC1300202).

Prognosis of Patients with Advanced Liver Disease and Positive Stress Echocardiograms: Impact of Coronary Artery Disease, Non-alcoholic Steatohepatitis, and Beta-blocker Therapy

Background: In the general population, a positive dobutamine stress echocardiogram (DSE) in the absence of obstructive coronary artery disease (CAD) still identifies a high risk group. DSE is a widely employed screening method in candidates for liver transplantation. We investigated the prognostic impact of a positive DSE, CAD, and clinical factors in advanced liver disease. Methods: We obtained follow-up for cardiovascular events (angina requiring revascularization, heart failure, infarction, and cardiac death) in 61 liver transplant candidates who had positive DSE and coronary angiography. Event-free survival was compared between 22 patients with obstructive CAD (≥ 70% stenosis) and 39 patients with no obstructive CAD. Cox regression was used to identify factors associated with events. Results: Over a mean follow-up of 27 ± 28 months, 21% (8/39) of patients with positive DSE and no CAD had events compared with 45% (10/22) of patients with positive DSE and CAD (p = 0.04). Event free survival was better in those without CAD (p = 0.014) but one year cardiac mortality was similar in those with (9%) and without CAD (8%). Multivariable analysis showed that beta blocker use (HR: 4.1, 95% CI: 1.7 – 9.9, p-value = 0.010), CAD (HR: 4.4 95% CI: 1.8– 10.8, p-value = 0.008), and non-alcoholic steatohepatitis (NASH) (HR: 4.9, 95% CI: 2.0 – 11.7, p-value = 0.04) were independently associated with events. Conclusion: Advanced liver disease patients with positive DSE are at increased risk. CAD, beta blocker use and NASH are independently associated with cardiac events.

Beta receptor blocker therapy for the elderly in the COVID-19 era.

When the coronavirus disease 2019 (COVID-19) pandemic spread globally from the Hubei region of China in December 2019, the impact on elderly people was particularly unfavorable. The mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was highest in older individuals, in whom frailty and comorbidities increased susceptibility to severe forms of COVID-19. Unfortunately, in older patients, the course of COVID-19 was often characterized by significant cardiovascular complications, such as heart failure decompensation, arrhythmias, pericarditis, and myopericarditis. Ensuring that the elderly have adequate therapeutic coverage against known cardiovascular diseases and risk factors is particularly important in the COVID-19 era. Beta blockers are widely used for the treatment and prevention of cardiovascular disease. The clinical benefits of beta blockers have been confirmed in elderly patients, and in addition to their negative chronotropic effect, sympathetic inhibition and anti-inflammatory activity are theoretically of great benefit for the treatment of COVID-19 infection. Beta blockers have not been clearly shown to prevent SARS-CoV-2 infection, but there is evidence from published studies including elderly patients that beta blockers are associated with a more favorable clinical course of COVID-19 and reduced mortality. In this minireview, we summarize the most important evidence available in the literature on the usefulness of beta blocker therapy for older patients in the context of the COVID-19 pandemic.

Does sports participation increase risk in patients with long QT syndrome? Results from a large French cohort.

Sports practice, especially in competition, is usually restrained in patients diagnosed with long QT syndrome (LQTS). Although data are scarce, a low incidence of cardiac arrhythmic events (CAEs) during sports practice is reported. We aim to evaluate the incidence of CAE during sports practice in LQTS patients. All consecutive patients above 18 years of age diagnosed with LQTS and prospectively followed at the referral centre for inherited arrhythmia syndrome received a survey to retrospectively assess their sports practice prior to and after the diagnosis of LQTS. Two hundred and forty-six patients were included (57% females). The median age was 43 years, and the median QTc was 457 ms (428; 482). Patients reported a total of 4092 years [1376 (34%) after diagnosis] of sports practice: 2905 (77%) [1138 (39%) after diagnosis] years of leisure practice and 1187 (23%) [238 (20%) after diagnosis] years of competitive practice. One hundred and eighty (73%) patients practiced sport prior to the diagnosis of LQTS and 170 (69%) after. Prior to the diagnosis, four (2%) patients presented a CAE during leisure sports practice and one during competition. After diagnosis, only one patient presented a CAE, appropriately treated by an implantable cardioverter defibrillator discharge, in the context of beta-blocker non-compliance. The CAE event rate was 0.0007 events/year in the 1376 years of total sports practice after the diagnosis of LQTS. After the diagnosis of LQTS, the occurrence of CAE is very low during sports practice, even in competitive practice. There was no CAE in patients properly treated with beta-blocker therapy with good compliance.

Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers

ABSTRACT The congenital long QT syndrome (LQTS), one of the most common cardiac channelopathies, is characterized by delayed ventricular repolarization underlying prolongation of the QT interval of the surface electrocardiogram. LQTS is caused by mutations in genes coding for cardiac ion channels or ion channel-associated proteins. The major therapeutic approach to LQTS management is beta blocker therapy which has been shown to be effective in treatment of LQTS variants caused by mutations in K+ channels. However, this approach has been questioned in the treatment of patients identified as LQTS variant 3(LQT3) patients who carry mutations in SCN5A, the gene coding for the principal cardiac Na+ channel. LQT3 mutations are gain of function mutations that disrupt spontaneous Na+ channel inactivation and promote persistent or late Na+ channel current (INaL) that delays repolarization and underlies QT prolongation. Clinical investigation of patients with the two most common LQT3 mutations, the ΔKPQ and the E1784K mutations, found beta blocker treatment a useful therapeutic approach for managing arrhythmias in this patient population. However, there is little experimental data that reveals the mechanisms underlying these antiarrhythmic actions. Here, we have investigated the effects of the beta blocker propranolol on INaL expressed by ΔKPQ and E1784K channels in induced pluripotent stem cells derived from patients carrying these mutations. Our results indicate that propranolol preferentially inhibits INaL expressed by these channels suggesting that the protective effects of propranolol in treating LQT3 patients is due in part to modulation of INaL.

Beta-blocker use in patients with heart failure with preserved ejection fraction and sinus rhythm

IntroductionBeta-adrenergic receptor blockers (beta-blockers) are frequently used for patients with heart failure (HF) with preserved ejection fraction (HFpEF), although evidence-based recommendations for this indication are still lacking. Our goal was to assess which clinical factors are associated with the prescription of beta-blockers in patients discharged after an episode of HFpEF decompensation, and the clinical outcomes of these patients. MethodsWe assessed 1078 patients with HFpEF and in sinus rhythm who had experienced an acute HF episode to explore whether prescription of beta-blockers on discharge was associated with one-year all-cause mortality or the composite endpoint of one-year all-cause death or HF readmission. We also examined the clinical factors associated with beta-blocker discharge prescription for such patients. ResultsAt discharge, 531 (49.3%) patients were on beta-blocker therapy. Patients on beta-blockers more often had a prior diagnosis of hypertension and more comorbidity (including ischemic heart disease) and a better functional status, but less often a prior diagnosis of chronic obstructive pulmonary disease. These patients had a lower heart rate on admission and more often used angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and loop diuretics. One year after the index admission, 161 patients (15%) had died and 314 (29%) had experienced the composite endpoint. After multivariate adjustment, beta-blocker prescription was not associated with either all-cause mortality (HR=0.83 [95% CI 0.61-1.13]; p=0.236) or the composite endpoint (HR=0.98 [95% CI 0.79-1.23]; p=0.882). ConclusionIn patients with HFpEF in sinus rhythm, beta-blocker use was not related to one-year mortality or mortality plus HF readmission.

Association of pre-admission antihypertensive agents and outcomes in aneurysmal subarachnoid hemorrhage

BackgroundDelayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients. MethodsWe performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4–6. The secondary outcome was cVSP identified using transcranial Doppler (TCD). ResultsThe cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21–80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19–0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11–0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome. ConclusionPre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Efficacy and Safety of Ivabradine in Combination with Beta-Blockers in Patients with Stable Angina Pectoris: A Systematic Review and Meta-analysis.

IntroductionBeta-blockers are recommended by the European Society of Cardiology as first-line antianginal therapy for reducing heart rate (HR) and symptoms in patients with chronic coronary syndrome, despite a lack of data showing superiority to other antianginal agents. Most patients with angina pectoris require combination therapy to manage symptoms, with a second-line agent chosen to manage the predominant cardiovascular problem. Ivabradine, a selective sinus node If channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.MethodsThis systematic review and meta-analysis assessed the efficacy and safety of ivabradine in patients with stable angina pectoris who remained symptomatic despite receiving beta-blockers. Keyword searches of PubMed, The Cochrane Central Library Register, ClinicalTrials.gov, The World Health Organization International Clinical Trials Registry Platform (ICTRP) and Google Scholar identified studies comparing ivabradine plus beta-blockers with placebo or other first- or second-line antianginal agents in patients with stable angina pectoris. No date limits or language restrictions were applied. Outcomes were evaluated after 1 and 4 months of treatment, including changes in HR, angina attacks, use of short-acting nitrates, quality of life and safety. Risk of bias was evaluated on the basis of recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.ResultsSeven relevant studies were identified (N = 6821). Ivabradine plus a beta-blocker consistently reduced HR, anginal symptoms and short-acting nitrate consumption within 1 month of initiating therapy, with continued reductions for up to 4 months. Furthermore, ivabradine plus beta-blocker therapy was well tolerated, with bradycardia rarely reported (0.1% of patients overall). This study is limited by the inclusion of only two randomised studies, which may lead to result interpretation bias.ConclusionsIvabradine may be valuable for tailoring early antianginal treatment when used in combination with beta-blockers for chronic stable angina inadequately controlled by beta-blockers.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02222-1.

Left ventricular non-compaction in a juvenile systemic lupus erythematosus girl with Hashimoto’s thyroiditis: Case report and review of the literature

BackgroundLeft ventricular noncompaction (LVNC) is a structural abnormality of the left ventricular myocardium of unknown cause. Cardiovascular system involvement is an important manifestation in juvenile systemic lupus erythematosus (jSLE) and is a leading cause of morbidity and mortality. Aim of the workTo present a case of jSLE with LVNC and Hashimoto's thyroiditis. Case presentationA 15-year-old Tunisian girl with a history of Hashimoto's thyroiditis presented with paroxysmal chest pain, exertional dyspnea, headache, and polyarthralgia and was diagnosed with jSLE. Clinical examination revealed a febrile patient (39 °C). There was no tachypnea, no evidence of right heart failure, no audible murmurs on cardiac auscultation, and no edema of the lower limbs. Laboratory investigations revealed leucopenia (3500/mm3), anemia (10 g/dl), elevated erythrocyte sedimentation rate (ESR)(50 mm\\1sth), C-reactive protein (20 mg/l). Infections were excluded with multiple negative blood cultures and negative anti-streptolysin O antibodies. The antinuclear antibody (ANA) was positive homogenous at 1/10,000 and both anti-native DNA and anti-SSA were positive. The electrocardiogram (ECG) showed sinus tachycardia, the transthoracic echocardiography revealed pericarditis associated with a non-compacted LV and a small pericardial effusion. Thus, a cardiac magnetic resonance imaging (CMRI) was performed confirming LVNC with a hypertrabeculated sub-endocardium. There was no proteinuria, hypocomplementemia or cerebral vasculitis on cerebral magnetic resonance imaging (MRI). The patient received high-dose corticosteroids associated with beta-blocker therapy with a favorable outcome. ConclusionA rare case of LVNC which was accidentally discovered in a patient with jSLE and Hashimoto's thyroiditis is documented. Follow-up is needed for the development possible complications.

Tracheal Hemangioma: A Rare Cause of Hemoptysis in Children.

Tracheal hemangioma is a very rare benign vascular tumor. Few cases of tracheal hemangioma in children are reported in the literature. Chronic cough is the main symptom of the disease; however, hemoptysis is rarely reported as a symptom of tracheal hemangioma in children. Here, we report a case of tracheal hemangioma in an eight-year-old girl admitted to our pediatric department for recurrent hemoptysis. Routine biological and radiological investigations were normal. Diagnosis was made using computed tomography and bronchoscopy. Beta-blocker therapy was not efficient. Bronchoscopic treatment by electrical excision enables complete recovery. Tracheal hemangioma should be considered a cause of recurrent hemoptysis when routine biological and radiological investigations are negative.

Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity?

AimsPatients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis.MethodsThirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility.ResultsNineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02).ConclusionWe found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.

Standardizing Optimal Medical Therapy in Heart Failure Patients to Improve NCDR Metrics for ICD Implantation

Purpose: The Heart Rhythm Society recommends two medications to be prescribed after an ICD (Implantable Cardioverter Defibrillator) implantation for patients with EF < 40%. The recommended medications are beta blockers and angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) These medications have been well established as front line treatment in patients with heart failure who often need ICD implantation in prevention of sudden cardiac death. Long term beta blocker therapy can improve symptoms of heart failure, improve patient clinical status, and reduce hospitalizations and mortality.

Sympathetic and Vagal Nerve Activity in COPD: Pathophysiology, Presumed Determinants and Underappreciated Therapeutic Potential.

This article explains the comprehensive state of the art assessment of sympathetic (SNA) and vagal nerve activity recordings in humans and highlights the precise mechanisms mediating increased SNA and its corresponding presumed clinical determinants and therapeutic potential in the context of chronic obstructive pulmonary disease (COPD). It is known that patients with COPD exhibit increased muscle sympathetic nerve activity (MSNA), as measured directly using intraneural microelectrodes-the gold standard for evaluation of sympathetic outflow. However, the underlying physiological mechanisms responsible for the sympathoexcitation in COPD and its clinical relevance are less well understood. This may be related to the absence of a systematic approach to measure the increase in sympathetic activity and the lack of a comprehensive approach to assess the underlying mechanisms by which MSNA increases. The nature of sympathoexcitation can be dissected by distinguishing the heart rate increasing properties (heart rate and blood pressure variability) from the vasoconstrictive drive to the peripheral vasculature (measurement of catecholamines and MSNA) (Graphical Abstract Figure 1). Invasive assessment of MSNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training. A broad picture of the underlying pathophysiological determinants of the increase in sympathetic outflow in COPD can only be determined if a combination of these tools are used. Various factors potentially determine SNA in COPD (Graphical Abstract Figure 1): Obstructive sleep apnoea (OSA) is highly prevalent in COPD, and leads to repeated bouts of upper airway obstructions with hypoxemia, causing repetitive arousals. This probably produces ongoing sympathoexcitation in the awake state, likely in the "blue bloater" phenotype, resulting in persistent vasoconstriction. Other variables likely describe a subset of COPD patients with increase of sympathetic drive to the heart, clinically likely in the "pink puffer" phenotype. Pharmacological treatment options of increased SNA in COPD could comprise beta blocker therapy. However, as opposed to systolic heart failure a similar beneficial effect of beta blocker therapy in COPD patients has not been shown. The point is made that although MSNA is undoubtedly increased in COPD (probably independently from concomitant cardiovascular disease), studies designed to determine clinical improvements during specific treatment will only be successful if they include adequate patient selection and translational state of the art assessment of SNA. This would ideally include intraneural recordings of MSNA and-as a future perspective-vagal nerve activity all of which should ideally be assessed both in the upright and in the supine position to also determine baroreflex function.

Successful use of telemedicine for evaluation of infantile hemangiomas during the early COVID-19 pandemic: A cross-sectional study.

The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.

BLOOD PRESSURE VARIABILITY AT REST AND DURING AEROBIC EXERCISES IN WOMEN WITH ISCHEMIC CARDIAC DISESES

Objective: High visit-to-visit blood pressure (BP) variability increases the risk of cardiovascular disease in hypertension. In some earlier studies there was the hypothesis that exact same doses of exercise evokes the same response of BP and heart rate (HR). The aim of the study was to compare auscultatory measurements of SBP and DBP during cardiac aerobic exercise training twice a week, lasting three weeks in women with ischemic heart disease. Design and method: We examined 12 women with ischemic heart diseases, the age 60 ± 8.9 years, height 166 ± 6.7 cm, weight 78 ± 11.7 kg, ejection fraction was 46 ± 6 %. The cardiac patients were under therapy of betablockers. ACE inhibitors and statins. The intensity of aerobic training was determined individually according spiroergometric examination of the first ventilatory anaerobic threshold. BP measurements were provided using auscultatory measurement of BP at resting values, after warm-up period (10 minutes), at the peak of aerobic training period (40 minutes), at the cool-down period (10 minutes) twice a week, the training lasted 3 weeks. Results: Resting average values in the whole group of SBP were 129.0 ± 11.7 mmHg, of DBP 77.7 ± 8.5 mmHg, HR 71.7 ± 7.1 beat per minute. After warm-up period average values in the whole group of SBP were 126.7 ± 10.4 mmHg, of DBP 76.5 ± 7.0 mmHg, HR 84.4 ± 9.0 beat per minute. At aerobic peak - average values in the whole group of SBP were 135.1 ± 15.4 mmHg, of DBP 86.7 ± 10.9 mmHg, HR 86.6 ± 10.0 beat per minute. After cool-down period - average values in the whole group of SBP were 135.6 ± 13.3 mmHg, of DBP 87.8 ± 9.8 mmHg, HR 85.3 ± 11.6 beat per minute. Our results showed that SBP and DBP varies in resting values before exercise, after warm-up period, at the peak of aerobic exercise on the individual aerobic threshold value of load and after cool-down period from twenty mmHg to less mmHg. Conclusions: Aerobic exercise did not influence the values of this BP variability. Variability of the HR is also present at period of aerobic exercise training.

ORTHOSTATIC HYPOTENSION IN COVID 19 – CATCH IT IF YOU CAN!

Objective: The relationship between COVID-19 and blood pressure (BP) has raised great concern since the discovery of Angiotensin Convertase Enzyme 2 (ACE 2) – mediated mechanism of action for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2). Hypertension (HTN) itself proved to be a risk factor for more severe Coronavirus Disease 19 (COVID -19). However less studies focus on the trend of blood BP for patients with COVID-19 during the initial phase of disease. Design and method: We present the case of a 71 years old woman with grade 2 HTN previously controlled with diuretic and betablocker therapy that came to our hospital with dyspnea, cough and debilitating fatigue progressively worsened in the last 10 days. The patient also related the first episode of syncope in her life the night before the presentation. Results: The clinical evaluation revealed a conscious, euvolemic, with polypnea and a peripheral saturation in oxygen of 86%, corrected to 95% with 9 liters oxygen/minute via simple face mask and a BP of 110/70 mmHg with a ventricular rate of 45 beats per minute in supine position. The assessment of BP values while standing showed a value of 78/60 mmHg after 1 minute and 58/40 mmHg after 3 minutes, while the ventricular rate increased overall to 65 beats per minute. ECG was remarkable only for mild bradycardia and computed tomography pulmonary angiogram excluded pulmonary embolism. The patient was admitted with severe COVID-19 accompanied by severe orthostatic hypotension and bradycardia. Continuous telemonitoring showed only mild bradycardia. Under standard COVID 19 treatment, after 10 days, her symptoms had resolved with no residual orthostatic hypotension or bradycardia. Conclusions: In conclusion this case reflects the life-threatening dysautonomia caused by SARS-COV 2 infection. More concern should be placed on this type of fragile patients, taking into account both the macroscopic implications of being confined to bed for a long period of time and the microscopic butterfly effect caused by the binding of the virus on the widespread ACE 2 in the lungs, heart, kidneys and digestive tract.

Individualized Beta-Blocker Treatment for High Blood Pressure Dictated by Medical Comorbidities: Indications Beyond the 2018 European Society of Cardiology/European Society of Hypertension Guidelines.

Several hypertension guidelines have removed beta-blockers from their previous position as first-choice drugs for the treatment of hypertension. However, this downgrading may not be justified by available evidence because beta-blockers lower blood pressure as effectively as other major antihypertensive drugs and have solid documentation in preventing cardiovascular complications. Suspected inconveniences of beta-blockers such as increased risk of depression or erectile dysfunction may have been overemphasized, while patients with chronic obstructive pulmonary disease or peripheral artery disease, that is, conditions in which their use was previously restricted, will benefit from beta-blocker therapy. Besides, evidence that from early to late phases, hypertension is accompanied by activation of the sympathetic nervous system makes beta-blockers pathophysiologically an appropriate treatment in hypertension. Beta-blockers have favorable effects on a variety of clinical conditions that may coexist with hypertension, making their use either as specific treatment or as co-treatment potentially common in clinical practice. Guidelines typically limit recommendations on specific beta-blocker use to cardiac conditions including angina pectoris, postmyocardial infarction, or heart failure, with little or no mention of the additional cardiovascular or noncardiovascular conditions in which these drugs may be needed or preferred. In the present narrative review, we focus on multiple additional diseases and conditions that may occur and affect patients with hypertension, often more frequently than people without hypertension, and that may favor the choice of beta-blocker. Notwithstanding, beta-blockers represent an in-homogenous group of drugs and choosing beta-blockers with documented effect in prevention and treatment of disease is important for first choice in guidelines.

Prognostic value of 6-min walk test compared to cardiopulmonary exercise test in patients with severe heart failure.

The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are both predictive in heart failure (HFrEF). Although 6MWT substitutes for CPET in HFrEF patients, as submaximal testing may be preferable, its prognostic superiority still needs to be verified, particularly in regard to beta blockers (BBs). We aimed to compare the prognostic role of CPET and 6MWT and investigate whether BB therapy influences the predictive value. This is a single-center, retrospective study. Advanced HFrEF patients were followed up for 3 years: events were cardiovascular death or urgent heart transplantation. We analyzed the predictive capacity of CPET and 6MWT in patients, and subdivided according to use of BBs. In a group of 251 HFrEF patients, we found a correlation between meters and peak VO2 (r2 = 0.94). Over the 3-year follow-up, 74 events were recorded. Both CPET and 6MWT variables were correlated with outcome at univariate analysis (meter and VE/VCO2 slope, peak VO2, VO2 at ventilatory anaerobic threshold, percentage predicted of peak VO2), but only percentage predicted of peak VO2 (pppVO2) was an independent predictor. In 103 HFrEF patients on BBs (23 nonsurvivors), neither pppVO2 nor meter were predictive, while in 148 patients not treated with BB (51 with events) pppVO2 was selected as an independent prognostic parameter (P = 0.001). 6MWT is a valid alternative to CPET, although the percentage of predicted of peak VO2 emerged as the strongest predictor. Nonetheless, our results suggest that both functional derived parameters are not predictive among those patients treated with BBs. Further studies are necessary to confirm these findings.

Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial

Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized. Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes. For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure. Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up.

ECG descriptors of ventricular repolarization are associated with cardiac events in a gene-specific manner in long QT syndrome patients

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Assistance Publiques Hôpitaux de Paris (APHP) Background Congenital long QT syndrome (LQTS) is still associated with syncope and a risk of sudden cardiac death despite the dramatic reduction in mortality associated with beta-blocker therapy. Current risk stratification tools are imperfect. Objective To assess the contribution of automated scalar ECG descriptors of ventricular repolarization for arrrhythmic risk stratification in genotyped LQTS patients. Methods Patients with genotyped type 1, 2 or 3 LQTS with at least 1 digital ECG recording have been included in the study. History at diagnosis, and follow-up data were collected. Cardiac events included syncope, aborted cardiac arrest, appropriate implantable cardioverter-defibrillator therapy in VF zone, and sudden death. ECG were analyzed using the BRAVO algorithm embedded in the CalECG software, version 4.1.0. QT interval duration was manually checked but ECG descriptors of Ventricular Repolarization were fully automatic. Multivariate cox regression analysis were performed to identify parameters associated with cardiac events. Results 467 patients (58% female, median age at diagnosis=25, LQT1,2,3 54%, 39%, 7%) were followed-up during 15.2±9.2 years. Rate of cardiac event was 1.2/100 patients-year before diagnosis and 0.9/100 patients-year during follow-up. QTc duration was associated with the occurrence of cardiac events in the whole study population (HR=1.01 95%CI 1.0-1.01, p=0.03). Ventricular repolarization parameters associated with cardiac events were different according to LQTS type. Cardiac events were associated with increased time to accumulate 50% of T-wave energy (HR=1.53 95%CI 1.04-2.26, p=0.03) in LQT1 but with a decrease in T-wave slopes (ascending slope HR=0.63 95%CI 0.17-0.75, p&amp;lt;0.01) in type 2 LQTS patients. QTc duration was not independently associated with cardiac events in genotype specific multivariate models. Conclusions T-wave morphology parameters are associated with cardiac events in a gene-specific manner. Change in T-wave symmetry and T-wave flattening are associated with cardiac events in type 1 and type 2 LQTS respectively. The descriptors of ventricular repolarization are promising parameters or risk stratification beyond QTc duration in LQTS patients.