Safety and tolerability of ß-blockers: importance of cardioselectivity.

Cardioselective ß-blockade is generally well tolerated in practice and contraindications to this therapy are uncommon. ß-blockers are a diverse therapeutic class, and their individual tolerability profiles are influenced strongly by their pharmacodynamic effects across different adrenergic receptors. Bisoprolol, probably the ß-blocker with the highest selectivity for blockade of ß1- vs. ß2-adrenoceptors, does not block ß2-adrenoceptors to an appreciable extent at doses in therapeutic use. Side-effects often attributed to ß-blockers, such as erectile dysfunction and adverse metabolic effects are uncommon with bisoprolol and other ß-blockers used at doses which only block ß1-adrenoceptors. Cautious use of a cardioselective ß-blocker is not contraindicated in people with chronic obstructive pulmonary disease or asthma and the outcomes benefits of ß-blockers in patients with coronary heart disease or heart failure are also apparent in patients with concurrent COPD. Starting with a low dose and titrating upwards carefully is important for optimising the tolerability of a ß-blocker. Most people with hypertension will receive combination antihypertensive therapy in practice, and the low-dose combination therapy approach provides a useful strategy for optimising the efficacy and tolerability of a regimen that includes a ß-blocker, compared with up-titrating an existing monotherapy.

Cardiovascular Complications in Patients with Heart Failure and COVID-19: CARDIO COVID 19-20 Registry.

Since early 2020, different studies have shown an increased prevalence of COVID-19 and poorer prognosis in older adults with cardiovascular comorbidities. This study aimed to assess the impact of heart failure (HF) on cardiovascular complications, intensive care unit (ICU) admissions, and in-hospital mortality in patients hospitalized with COVID-19. The CARDIO COVID 19-20 registry includes 3260 hospitalized patients with a COVID-19 serological diagnosis between May 2020 and June 2021 from Latin American countries. A history of HF was identified in 182 patients (5.6%). In patients with and without previous HF, the incidence of supraventricular arrhythmia was 16.5% vs. 6.3%, respectively (p = 0.001), and that of acute coronary syndrome was 7.1% vs. 2.7%, respectively (p = 0.001). Patients with a history of HF had higher rates of ICU admission (61.5% vs. 53.1%, respectively; p = 0.031) and in-hospital mortality (41.8% vs. 24.5%, respectively; p = 0.001) than patients without HF. Cardiovascular mortality at discharge (42.1% vs. 18.5%, respectively; p < 0.001) and at 30 days post-discharge (66.7% vs. 18.0%, respectively) was higher for patients with a history of HF than for patients without HF. In patients hospitalized with COVID-19, previous history of HF was associated with a more severe cardiovascular profile, with increased risk of cardiovascular complications, and poor in-hospital and 30-day outcomes.

Multifaceted Strategy Based on Automated Text Messaging After a Recent Heart Failure Admission: The MESSAGE-HF Randomized Clinical Trial.

Importance: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. Objective: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. Design, Setting, and Participants: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. Intervention: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. Main Outcomes and Measures: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. Results: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). Conclusions and Relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04062461.

Personalized care of patients with heart failure: are we ready for a REWOLUTION? Insights from two international surveys on healthcare professionals' needs and patients' perceptions.

AIMS: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient-centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. METHODS AND RESULTS: Anonymous online questionnaires co-developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline-mandated medications over up-titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline-recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. CONCLUSIONS: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient-centred, needs-driven quality improvement programmes.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

Autologous stem cell transplantation improves cardiopulmonary exercise testing outcomes in systemic sclerosis patients.

OBJECTIVES: Autologous haematopoietic stem cell transplantation (AHSCT) is a disease-modifying treatment for patients with severe SSc. Here, we aimed at assessing cardiopulmonary function outcomes of SSc patients after AHSCT. METHODS: Twenty-seven SSc adult patients treated with AHSCT were included in this retrospective study. Most had the diffuse cutaneous subset (93%) and pulmonary involvement (85%). Before and 12 months after AHSCT, patients underwent cardiopulmonary exercise testing, transthoracic echocardiography, pulmonary function test with diffusing capacity for carbon monoxide (DLCO), 6-min walk test (6MWT) and quality of life evaluations. RESULTS: After AHSCT, the peak VO2 increased from 954 to 1029 ml/min (P = 0.02), the percentage of predicted peak VO2 increased from 48.9 to 53.5 m (P = 0.01), and the distance measured by the 6MWT increased from 445 to 502 m (P = 0.01), compared with baseline. Improvements in peak VO2 correlated positively with improvements in 6MWT distance, and negatively with a decrease in resting heart rate. At baseline, patients with DLCO >70% had higher peak VO2 values than those with DLCO <70% (P = 0.04), but after AHSCT all patients showed improved VO2 values, regardless of baseline DLCO levels. Increases in VO2 levels after AHSCT positively correlated with increases in the physical component scores of the Short Form-36 quality of life questionnaire (r = 0.70; P = 0.0003). CONCLUSION: AHSCT improves the aerobic capacity of SSc patients probably reflecting combined increments in lungs, skeletal muscle and cardiac function.

The impact of the COVID-19 pandemic on heart failure management: Global experience of the OPTIMIZE Heart Failure Care network.

During the COVID-19 pandemic, reductions in heart failure (HF) hospitalizations have been widely reported, and there is an urgent need to understand how HF care has been reorganized in countries with different infection levels, vaccination rates and healthcare services. The OPTIMIZE Heart Failure Care program has a global network of investigators in 42 countries, with first-hand experience of the impact of the pandemic on HF management in different care settings. The national coordinators were surveyed to assess: 1) the challenges of the COVID-19 pandemic for continuity of HF care, from both a hospital and patient perspective; 2) the organizational changes enacted to ensure continued HF care; and 3) lessons learned for the future of HF care. Contributions were obtained from 37 national coordinators in 29 countries. We summarize their input, highlighting the issues raised and using the example of three very different settings (Italy, Brazil, and Taiwan) to illustrate the similarities and differences across the OPTIMIZE program.

Glucose-lowering Drugs and Hospitalization for Heart Failure: A Systematic Review and Additive-effects Network Meta-analysis With More Than 500 000 Patient-years.

BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2is) prevent hospitalization resulting from heart failure (HHF). However, patients with type 2 diabetes mellitus use multiple antihyperglycemic drugs to achieve glycosylated hemoglobin (HbA1c) targets. In these drug combinations, the risk of HHF is unpredictable and so is the parallel effect of glucose-lowering. PURPOSE: To examine the impact of antihyperglycemic drugs and their association on HHF. DATA SOURCES: Forty randomized controlled trials (RCTs) reporting HHF. STUDY SELECTION: Published RCTs were the data source. DATA EXTRACTION: Incidence rates of HHF. DATA SYNTHESIS: Random additive-effects network meta-analysis showed that metformin (P = 0.55), sulfonylureas (P = 0.51), glucagon-like peptide-1 receptor-agonist (P = 0.16), and dipeptidyl peptidase 4 inhibitors (DPP4is; P = 0.54) were neutral on the risk of HHF. SGLT2is and SGLT2is + DPP4is reduced the risk of HHF with a hazard ratio (HR) of 0.68 (95% CI, 0.60-0.76; P < 0.0001) and 0.70 (95% CI, 0.60-0.81; P < 0.0001), respectively. Increased risk of HHF was associated with thiazolidinediones (TZDs) as monotherapy or in combination with DPP4is (HR: 1.45; 95% CI, 1.18-1.78; P = 0.0004) and 1.49 (95% CI, 1.18-1.88; P = 0.0008), respectively. Regardless of the therapy, a 1% reduction in HbA1c reduced the risk of HHF by 31.3% (95% CI, 9-48; P = 0.009). LIMITATIONS: There are no data to verify drug combinations available for clinical use and to discriminate the effect of drugs within each of the therapeutic classes. CONCLUSIONS: The risk of HHF is reduced by SGLT2is as monotherapy or in combination with DPP4is and increased by TZDs as monotherapy or in combination. Glucose-lowering provides an additive effect of reducing HHF.

Serum potassium levels provide prognostic information in symptomatic heart failure beyond traditional clinical variables.

AIMS: Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF. METHODS AND RESULTS: Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non-ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow-up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut-point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m2 vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m2 , P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs. K > 4.7: 48%, P = 0.0029), and also higher MAGGIC score (K ≤ 4.7: 12.08 ± 5.7 vs. K > 4.7: 14.9 ± 7.9, P = 0.0089), without significant differences on the baseline pharmacological HF treatment. Both potassium levels [hazard ratio (HR) 4.26, 95% confidence interval (CI) 1.59-11.421, P = 0.003] and 6MWT distance (HR 0.99, 95% CI 0.993-0.999, P = 0.01) were independently associated with the primary outcome. After adjustments for MAGGIC score and 6MWT distance, potassium levels > 4.7 mmol/L maintained a significant association with outcomes (HR 3.57, 95% CI 1.305-9.807, P = 0.013). Patients with K > 4.7 mmol/L were more likely to present clinical events during the follow-up (log rank = 0.005). Adding potassium levels to the model including 6MWT and MAGGIC significantly improved the prediction of events over 2 years (integrated discrimination index 0.105, 95% CI 0.018-0.281, P = 0.012 and net reclassification index 0.447, 95% CI 0.077-0.703, P = 0.028). CONCLUSIONS: Potassium levels were independently associated with worse outcomes in patients with chronic symptomatic HF, also improving the accuracy model for prognostic prediction when added to MAGGIC score and 6MWT distance. The potassium levels above 4.7 mmol/L might identify those patients at an increased risk of cardiovascular events.

Advances in the Treatment of Cardiac Amyloidosis.

OPINION STATEMENT: Cardiac amyloidosis is associated with a high mortality rate, a long delay between the first signs and the diagnosis but a short interval between diagnosis and death. This scenario has changed recently due to improved disease awareness among doctors and significant progress in diagnosis thanks to multimodal imaging and a multidisciplinary approach. Therefore, during the last few years, we have had access to specific therapies for those patients. Those therapies are quite different depending on the type of amyloidosis, but there has been real progress. Systemic light chain amyloidosis (AL) with cardiac involvement is the most common form of cardiac amyloidosis. The severity of heart disease dictates the prognosis in AL amyloidosis. Advances in chemotherapy and immunotherapy that suppress light chain production have improved the outcomes. These recent improvements in survival rates have enabled therapies such as implanted cardiac defibrillators and heart transplantation that were usually not indicated for patients with advanced light chain amyloid cardiomyopathy to now be applied in selected patients. For transthyretin amyloidosis (ATTR), the second most common form of amyloidosis with cardiac involvement, there is also significant progress in treatment. Until recently, we had no specific therapy for ATTR cardiomyopathy (ATTR-CM), though now disease-modifying therapies are available. Therapies that stabilize transthyretin, such as tafamidis, have been shown to improve outcomes for patients with ATTR-CM. Modern treatments that stop the synthesis of TTR through gene silencing, such as patisiran and inotersen, have shown positive results for patients with TTR amyloidosis. Significant progress has been made in the treatment of amyloid cardiomyopathy, and hopefully, we will see even more progress with the spread of those treatments. We now can be optimistic about patients with this disease.

Circulatory and ventilatory power in diabetic patients: Secondary analysis of a randomized controlled trial.

BACKGROUND: Circulatory (CP) and ventilatory power (VP) have been used to improve the prognostic accuracy of cardiopulmonary exercise tests in cardiovascular disease, such as coronary artery disease. However, the effects of combined resistance and aerobic exercise program on VP and CP, especially in type 2 diabetes patients, have not been adequately investigated. Thus, this new parameter can be useful to prescribe exercise programs more assertive for this population. The present study aimed to assess the effect of 3 months of combined resistance and aerobic exercise training (CET) on CP and VP in patients with type 2 diabetes. METHODS: A randomized controlled trial was conducted involving 48 diabetic patients with an average age of 52.4 (±8.01) years old. The subjects were randomized into two groups: sedentary (SG, n = 15) and the CET group (n = 19). Cardiopulmonary exercise testing (symptom-limited incremental) was performed on a cycle ergometer, and the following parameters were measured: relative VO2 , VE /VCO2 slope, linear relationship between oxygen uptake and minute ventilation, and VCO2 . CET was performed with 30-min aerobic and 30-min resistance exercises three times a week for 12 weeks. RESULTS: Significant (p < .05) and clinical (d ≥ .80) differences were observed that favoured CET compared with SG for the following variables: heart rate, workload, VO2 relative peak, circulatory power peak, and VCO2 peak. Although no statistical difference was observed for ventilatory power, there was a clinical difference (p > .05 and d ≥ 0.80) that favoured CET. CONCLUSION: Three months of combined exercise training improved VP and CP indices in patients with type 2 diabetes when compared with a sedentary group.

A normal sodium diet preserves serum sodium levels during treatment of acute decompensated heart failure: A prospective, blind and randomized trial.

BACKGROUND: We tested the hypothesis that a normal sodium diet could be associated with preservation of serum sodium during treatment of acute decompensated heart failure (ADHF). METHODS AND RESULTS: Forty-four patients hospitalized for ADHF were blindly randomized by using block method to a low sodium diet (LS: 3 g/day of dietary sodium chloride; n = 22, 59.5 ± 11.9 y.o., 50% males. LVEF = 30.0 ± 13.6%); and a normal sodium diet (NS: 7 g/day; n = 22, 56.4 ± 10.3 y.o., 68% males; LVEF = 27.8 ± 11.7%), and both groups were submitted to fluid restriction of 1.000 mL/day. At the 7th day of intervention 16 patients of LS group and 15 patients of NS group were assessed for difference in serum sodium. Both groups had equivalent decongestion, reflected by similar percent reduction of body weight (LS: -5.0 ± 4.7% vs NS: -4.5 ± 5.2%. p = 0.41). Reduction of the N terminal fragment of type B natriuretic peptide (NT-proBNP) was significant only in the NS (-1497.0 [-18843.0 - 1191.0]. p = 0.04). The LS group showed lower levels of serum sodium (135.4 ± 3.5 mmol/L) compared to the NS group (137.5 ± 1.9 mmol/L; p = 0.04). Four cases of hyponatremia were observed only in the LS group (22%). The NS group exhibited higher mean blood pressure values (79.4 ± 2.4 mmHg vs 75.5 ± 3.0 mmHg. p = 0.03), and lower heart rate (73.2 ± 1.6 bpm vs 75.5 ± 2.1 bpm. p = 0.02). CONCLUSIONS: These results suggest that a normal sodium diet, when compared to a low sodium diet, is associated with similar degrees of decongestion, but with higher levels of natremia, blood pressure and lower neurohormonal activation during ADHF treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier no. NCT03722069.

Physical training improves myocardial perfusion but not left ventricular function response to exercise in patients with microvascular angina.

BACKGROUND: Patients with primary microvascular angina (PMA) commonly exhibit abnormal left ventricular function (LVF) during exercise, potentially owing to myocardial ischemia. Herein, we investigated in PMA patients the effect of the reduction of myocardial perfusion disorders, by using aerobic physical training, upon LVF response to exercise. METHODS: Overall, 15 patients (mean age, 53.7±8.9 years) with PMA and 15 healthy controls (mean age, 51.0±9.4 years) were studied. All subjects were subjected to baseline resting and exercise ventriculography, myocardial perfusion scintigraphy (MPS), and cardiopulmonary testing. PMA group members then participated in a 4-month physical training program and were reevaluated via the same methods applied at baseline. RESULTS: Baseline left ventricular ejection fraction (LVEF) determinations by ventriculography were similar for both groups (PMA, 67.7±10.2%; controls, 66.5±5.4%; P=0.67). However, a significant rise in LVEF seen in control subjects during exercise (75.3±6.2%; P=0.0001) did not materialize during peak exercise in patients with PMA (67.7±10.2%; P=0.47). Of the 12 patients in the PMA group who completed the training program, 10 showed a significant reduction in reversible perfusion defects during MPS. Nevertheless, LVEF at rest (63.5±8.7%) and at peak exercise (67.3±15.9%) did not differ significantly (P=0.30) in this subset. CONCLUSIONS: In patients with PMA, reduced left ventricular inotropic reserve observed during exercise did not normalize after improving myocardial perfusion through aerobic physical training.