Efficacy and safety of nebivolol in Korean patients with hypertension by age and sex: a subanalysis from the BENEFIT-KOREA study.

BACKGROUND: BENEFIT-KOREA (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various comorbidities and treatment environments in Korea) study, an observational study in South Korea, demonstrated the efficacy and safety of nebivolol in Asian patients with essential hypertension with and without comorbidities in real-world settings. We present a subanalysis of the efficacy and safety of nebivolol across age and sex in the BENEFIT-KOREA cohort. METHODS: Adult South Korean patients with essential hypertension participated in the prospective, single-arm, open, observational BENEFIT-KOREA study; 3011 patients received nebivolol as monotherapy or add-on therapy. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and pulse rate at 12 and 24 weeks were evaluated. Participants were divided into three age groups-young males and females: < 50 years; middle-aged males and females: ≥50 years to < 70 years; and older males and females: ≥70 years. RESULTS: The mean age of study participants was 63.5 ± 12.9 years; majority were between 50 and 69 years of age and 40.4% were females. A significant decrease was observed in mean SBP, DBP, and pulse rate from baseline at 12 and 24 weeks in males and females across all age groups analyzed (all P < 0.001 vs. baseline), with no significant difference in mean reduction in SBP and DBP from baseline between sex within the age groups. Majority of reported adverse events were mild. The incidence of adverse events was lower in young participants versus middle-aged and older participants. CONCLUSIONS: Our subanalysis from the real-world BENEFIT-KOREA study in Asian patients with essential hypertension demonstrated the efficacy and safety of once-daily nebivolol across age groups with no between-sex differences. TRIAL REGISTRATION: Name of the registry: clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT03847350 . Date of registration: February 20, 2019 retrospectively registered.

Combined aerobic/resistance/inspiratory muscle training as the 'optimum' exercise programme for patients with chronic heart failure: ARISTOS-HF randomized clinical trial.

AIMS: An 'optimum' universally agreed exercise programme for heart failure (HF) patients has not been found. ARISTOS-HF randomized clinical trial evaluates whether combined aerobic training (AT)/resistance training (RT)/inspiratory muscle training (IMT) (ARIS) is superior to AT/RT, AT/IMT or AT in improving aerobic capacity, left ventricular dimensions, and secondary functional outcomes. METHODS AND RESULTS: Eighty-eight patients of New York Heart Association II-III, left ventricular ejection fraction ≤ 35% were randomized to an ARIS, AT/RT, AT/IMT, or AT group, exercising 3 times/week, 180 min/week for 12 weeks. Pre- and post-training, peakVO2 was evaluated with cardiopulmonary exercise testing, left ventricular dimensions using echocardiography, walking distance with the 6-min walk test (6MWT), quality of life by the Minnesota Living with HF Questionnaire (MLwHFQ), while a programme preference survey (PPS) was used. Seventy-four patients of [mean 95% (confidence interval, CI)] age 66.1 (64.3-67.9) years and peakVO2 17.3 (16.4-18.2) mL/kg/min were finally analysed. Between-group analysis showed a trend for increased peakVO2 (mL/kg/min) [mean contrasts (95% CI)] in the ARIS group [ARIS vs. AT/RT 1.71 (0.163-3.25)(.), vs. AT/IMT 1.50 (0.0152-2.99)(.), vs. AT 1.38 (-0.142 to 2.9)(.)], additional benefits in circulatory power (mL/kg/min⋅mmHg) [ARIS vs. AT/RT 376 (60.7-690)*, vs. AT/IMT 423 (121-725)*, vs. AT 345 (35.4-656)*], left ventricular end-systolic diameter (mm) [ARIS vs. AT/RT -2.11 (-3.65 to (-0.561))*, vs. AT -2.47 (-4.01 to (-0.929))**], 6MWT (m) [ARIS vs. AT/IMT 45.6 (18.3-72.9)**, vs. AT 55.2 (27.6-82.7)****], MLwHFQ [ARIS vs. AT/RT -7.79 (-11 to (-4.62))****, vs. AT -8.96 (-12.1 to (-5.84))****], and in PPS score [mean (95% CI)] [ARIS, 4.8 (4.7-5) vs. AT, 4.4 (4.2-4.7)*] [(.) P ≤ 0.1; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001]. CONCLUSION: ARISTOS-HF trial recommends exercise training for 180 min/week and supports the prescription of the ARIS training regime for HF patients (Clinical Trial Registration: http://www.clinicaltrials.gov. ARISTOS-HF Clinical Trial number, NCT03013270).

Risk markers of incident atrial fibrillation in patients with coronary heart disease.

BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.

A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

[Case Report] Stress induced (Takotsubo) cardiomyopathy triggered by the COVID-19 pandemic.

Stress induced (Takotsubo) cardiomyopathy (TC) represents an acute heart failure syndrome triggered by physical or emotional stressors. COVID-19 pandemic has caused an unprecedented health crisis resulting in fear, distress and anxiety, with emerging cardiovascular implications. COVID-19 related stress can act as potential trigger for TC. We present a case of an elderly female who developed TC due to stress surrounding COVID-19.

The effect of Mid-Day Sleep on blood pressure levels in patients with arterial hypertension.

STUDY OBJECTIVES: Lifestyle changes decrease blood pressure (BP) levels by 3-5 mmHg in hypertensive patients. We assessed the effect of mid-day sleep on BP levels in hypertensive patients. METHODS: We prospectively studied two hundred and twelve hypertensive patients. Mid-day sleep duration, lifestyle habits, anthropometric characteristics, office BP, ambulatory BP monitoring, pulse wave velocity (PWV), augmentation index (AI) were recorded. A standard echocardiographic evaluation was performed. RESULTS: 53.8% were females, mean age was 62.5±11.0 years and mean body mass index was 28.9±5.4kg/m2. Mean average 24h systolic and diastolic BP (SBP & DBP) was 129.9±13.2/76.7±7.9 mmHg respectively. The majority was non-smokers (70.3%) and did not have diabetes (74.7%). The mean midday sleep duration was 48.7±54.3 min. Average 24h SBP (127.6±12.9 mmHg vs 132.9±13.1 mmHg), average daytime SBP & DBP were lower in patients who sleep at midday, compared to those who do not (128.7±13/76.2±11.5 vs 134.5±13.4/79.5±10.4 mmHg) (p<0.005). The effect was not correlated to the dipping status. Midday sleep duration was negatively correlated with average 24h SBP & daytime SBP. In a linear regression model, for every 60 min of midday sleep, 24h average SBP decreases by 3 mmHg (p<0.001). There were no differences in the number of antihypertensive medications, PWV, AI or echocardiographic indices between study groups. CONCLUSIONS: Mid-day sleep significantly decreases average 24h and daytime SBP/DBP in hypertensives. Its effect seems to be as potent as other well-established lifestyle changes and is independent of dipping status.

COVID-19 pandemic and its impact on mental health of healthcare professionals.

In light of the unprecedented public health crisis of the COVID-19 pandemic, it is highly important to acknowledge the psychological impact of this mounting threat on healthcare professionals. Previous experience from smaller scale epidemics and emerging literature around COVID-19 show that the unparalleled amount of stress that healthcare workers are dealing with, is associated with increased psychological morbidities. We have depicted the psychological burden that the COVID-19 pandemic has posed on healthcare professionals in Greece and have reviewed the literature around the effect of previous epidemics on frontline healthcare staff. Moreover, we discuss potential triggers and the need for measures to minimise the psychological pressure on those at the frontline against this biothreat.

Recent advances in understanding and managing resistant/refractory hypertension.

The management of resistant hypertension presents several challenges in everyday clinical practice. During the past few years, several studies have been performed to identify efficient and safe pharmacological and non-pharmacological options for the management of such patients. The Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2) trial demonstrated significant benefits with the use of spinorolactone as a fourth-line drug for the treatment of resistant hypertension over doxazosin and bisoprolol. In addition, recent data support that spironolactone may demonstrate superiority over central acting drugs in such patients, as well. Based on the European guidelines, spironolactone is recommended as the fourth-line drug option, followed by amiloride, other diuretics, doxazosin, bisoprolol or clonidine.  Among several device-based approaches, renal sympathetic denervation had fallen into hibernation after the disappointing results of the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN) 3 trial. However, the technique re-emerged at the epicenter of the clinical and research interest after the favorable results of three sham-controlled studies, which facilitated novel catheters and techniques to perform the denervation. Significant results of iliac anastomosis on blood pressure levels have also been demonstrated. Nevertheless, the technique-related adverse events resulted in withdrawal of this interventional approach. Last, the sympatholytic properties of the carotid baroreceptor activation therapy were associated with significant blood pressure reductions in patients with resistant hypertension, which need to be verified in larger controlled trials. Currently device-based approaches are recommended only in the setting of clinical trials until more safety and efficacy data become available.

Real-world efficacy and safety of nebivolol in Korean patients with hypertension from the BENEFIT KOREA study.

OBJECTIVE: The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied. METHODS: Adult South Korean patients with essential hypertension, with or without comorbidities, were enrolled to participate in this prospective, single-arm, open, observational study; 3011 patients received nebivolol either as monotherapy or add-on therapy. Changes in SBP, DBP and heart rate (HR) at 12 and 24 weeks were evaluated. Subgroup analysis for BP changes in newly diagnosed (de novo) patients and those receiving other antihypertensives at study entry were also conducted. RESULTS: Nebivolol significantly decreased mean SBP and DBP at 12 and 24 weeks compared with baseline (P < 0.0001). A significant reduction in HR was also observed at 12 and 24 weeks (P < 0.0001). The reductions of SBP and DBP were notably greater when nebivolol was used as monotherapy in de novo patients (P < 0.0001) and as add-on therapy to existing antihypertensives (angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers; P < 0.0001). Majority of the reported adverse events were mild; the most common adverse events were dizziness (1.3%), headache (1.0%) and dyspnea (0.9%). CONCLUSION: Despite the limitations associated with observational studies, this real-world study in Asian patients with essential hypertension with and without comorbidities, demonstrated the efficacy and safety of once daily nebivolol, either as monotherapy or add-on therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03847350.SDC Callout: Video Abstract, http://links.lww.com/HJH/B172.

Impact of stable angina on health status and quality of life perception of currently treated patients. The BRIDGE 2 survey.

OBJECTIVE: to explore 1) the perception of stable angina (SA) - impact on quality of life (QoL) and current condition related to SA; 2) SA burden - symptoms and frequency of anginal episodes; 3) impairment attributable to SA - limitations in daily activities and impact on work; 4) characteristics that might affect the patients' perception." METHOD: a proprietary questionnaire was administered on-line to SA patients selected using a purpose-built screening program from general population panels collaborating with IQVIA in Italy, Germany, Spain, and the UK. Exploratory analyses were performed: descriptive statistics on the total sample and different stratifications (gender, age class, time since diagnosis) were provided; we used Chi-square tests to compare subgroups. RESULTS: of more than 25,000 subjects who accessed the survey, 268 were eligible and completed the questionnaire: mean age was 61 years and women accounted for 30%. Despite being treated, about 40% of patients reported that SA impacted "completely" or "very much" their QoL, 10% rated their condition as "not good", and 45.1% stated that they felt "Fair". The majority of patients were still symptomatic and many of them perceived that SA had a major impact on their working life. Women, younger patients and those with a more recent diagnosis reported a worse self-assessment of their condition, QoL and symptom burden. CONCLUSIONS: the results of our survey provide new insights on how patients with SA perceived their own health status and suggest that any patient with SA deserves a more detailed and accurate evaluation by their physicians.