The role of patient-oriented mHealth interventions in improving heart failure outcomes: A systematic review of the literature.

Heart failure (HF) is a debilitating disease with 26 million patients worldwide. Consistent and complex self-care is required on the part of patients to adequately adhere to medication and to the lifestyle changes that the disease necessitates. Mobile health (mHealth) is being increasingly incorporated in patient interventions in HF, as smartphones prove to be ideal platforms for patient education and self-help assistance. This systematic review aims to summarize and report on all studies that have tested the effect of mHealth on HF patient outcomes. Our search yielded 17 studies, namely 11 randomized controlled trials and six non-randomized prospective studies. In these, patients with the assistance of an mHealth intervention regularly measured their blood pressure and/or body weight and assessed their symptoms. The outcomes were mostly related to hospitalizations, clinical biomarkers, patients' knowledge about HF, quality of life (QoL) and quality of self-care. QoL consistently increased in patients who received mHealth interventions, while study results on all other outcomes were not as ubiquitously positive. The first mHealth interventions in HF were not universally successful in improving patient outcomes but provided valuable insights for patient-oriented application development. Future trials are expected to build on these insights and deploy applications that measurably assist HF patients.

Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction: Technique Principles, Current Evidence, and Future Perspectives.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.

Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

AIMS: The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). METHODS AND RESULTS: The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12 month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin ≥ 12 g/dL, ferritin ≥ 50 ng/L, and transferrin saturation > 20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6 min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72 years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12 months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. CONCLUSIONS: The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

Meta-analysis of cardiovascular outcome trials assessing the impact of glucagon-like peptide-1 receptor agonists on major cardiac arrhythmias.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a group of novel antidiabetic agents, demonstrated beneficial cardiovascular effects in recent large, placebo-controlled randomised clinical trials (RCTs); their clear antiarrhythmic benefit has not been yet underlined. The purpose of the present meta-analysis is to clarify the impact of GLP-1RAs on different types of cardiac arrhythmias. METHODS: We searched PubMed from its inception up to 8 October 2020 for all available cardiovascular and renal outcome, placebo-controlled RCTs utilising GLP-1RAs versus placebo. The present meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. RESULTS: We included data from 7 RCTs with GLP-1RAs in a total of 55,943 participants. Treatment with GLP-1RAs did not provide significant benefit in the risk for atrial fibrillation (RR = 0.81, 95%CI; 0.78-1.15, I2 = 51%), atrial flutter (RR = 0.79, 95%CI; 0.53-1.16, I2 = 0%), ventricular fibrillation (RR = 0.99, 95%CI; 0.48-2.04, I2 = 0%), ventricular tachycardia (RR = 1.41, 95%CI; 0.87-2.28, I2 = 10%), atrial tachycardia (RR = 0.63, 95%CI; 0.10-3.90, I2 = 24%), sinus node dysfunction (RR = 0.70, 95%CI; 0.40-1.23, I2 = 0%), ventricular extrasystoles (RR = 1.37, 95%CI; 0.56-3.30, I2 = 0%), second-degree atrioventricular block (RR = 0.96, 95%CI; 0.52-1.74, I2 = 0%) or complete atrioventricular block (RR = 0.78, 95%CI; 0.39-1.54, I2 = 38%). CONCLUSIONS: In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature.

High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

Syncope without prodromes is associated with excessive plasma release of adenosine at the time of syncope during head-up tilt table test.

BACKGROUND: In syncopal patients without underlying structural disease, we sought to investigate the association of Adenosine Plasma Levels (ADP) with the clinical presentation of neurally mediated syncope (NMS) and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT). METHODS: We studied 124 patients with different clinical types of NMS, i.e., Vasovagal (VVS, n=58), non-prodromes (NPS, n=18), or situational syncope (SS, n=48), using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting and in syncope. RESULTS: Baseline ADP did not differ among groups. ADP at syncope were higher in NPS (n=5) compared to VVS (n=20): 0.23 vs. 0.12 µΜ, p=0.03, and SS (n=22): 0.04 µΜ, p=0.02. In NPS, ADP increased from supine to syncope (n=5): 0.15 vs. 0.23 µΜ, p=0.04. In VVS, ADP increased only from supine to tilt position: 0.11 vs. 0.14 µΜ, p=0.02. In SS, ADP did not change during HUTT. In positive vasodepressor HUTT, ADP increased from supine to tilt position (p=0.002) and at syncope (p=0.01). In SS, 20.0% exhibited cardioinhibitory HUTT vs. 6.8% in other forms of syncope (p=0.04). In SS, 22.9% manifested positive ADT vs 6.6% in other types of syncope (p=0.012). CONCLUSION: The subset of NPS patients with positive HUTT, show excessive ADP release at the time of syncope. This may explain the lack of prodromes in this form of syncope. Such observations contribute to the understanding of distinct profiles of clinical forms of syncope and may differentiate the management approach accordingly.

Meta-analysis addressing the impact of cardiovascular-acting medication on peak oxygen uptake of patients with HFpEF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E' ratio study-end values (WMD - 1.64, 95%CI - 2.42 to - 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Cardiopulmonary exercise testing in patients with end-stage kidney disease: principles, methodology and clinical applications of the optimal tool for exercise tolerance evaluation.

Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), is associated with an increased risk for cardiovascular events and all-cause mortality. Exercise intolerance as well as reduced cardiovascular reserve is extremely common in patients with CKD. Cardiopulmonary exercise testing (CPET) is a non-invasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, neuropsychological and metabolic function during maximal or submaximal exercise, allowing the evaluation of functional reserves of these systems. This assessment is based on the principle that system failure typically occurs when the system is under stress and thus CPET is currently considered to be the gold standard for identifying exercise limitation and differentiating its causes. It has been widely used in several medical fields for risk stratification, clinical evaluation and other applications, but its use in everyday practice for CKD patients is scarce. This article describes the basic principles and methodology of CPET and provides an overview of important studies that utilized CPET in patients with ESKD, in an effort to increase awareness of CPET capabilities among practicing nephrologists.

Magnesium Disorders and Prognosis in Heart Failure: A Systematic Review.

Magnesium is an essential mineral for the human body and plays an important role in cardiovascular health. Hypomagnesaemia has been linked with increased cardiovascular mortality in heart failure; however, previous studies have yielded conflicting results. Even fewer studies have addressed the association between hypermagnesemia and prognosis in heart failure. The aim of the present systematic review was to investigate the association of serum magnesium levels with cardiovascular and all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF). Cardiovascular morbidity, referring to heart failure rehospitalizations and ventricular arrhythmias, was also investigated. Eligible studies were identified by searching PubMed and Scopus. The Quality in Prognosis (QUIPS) tool was used to assess the quality of included studies. Eight studies (total of 13,539 patients with HFrEF) that assessed the effects of serum magnesium levels on cardiovascular mortality, all-cause mortality, and cardiovascular morbidity met inclusion criteria. In half of the studies, hypomagnesemia was found to be an independent risk factor for cardiovascular mortality, including sudden cardiac death. Only 1 study reported that hypermagnesemia (serum magnesium levels above 2.4 mg/dL) is a prognostic factor for noncardiac mortality suggesting that hypermagnesemia is more likely an indicator of comorbidities rather than a true independent prognostic marker. Finally, low serum magnesium levels were not associated with readmissions for heart failure or ventricular arrhythmias in patients with HFrEF.

5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations.

BACKGROUND: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent that can cause cardiotoxicity manifesting, among others, as chest pain. Capecitabine is an oral prodrug of 5-FU, with reported preferential activation in malignant cells that may also cause cardiotoxic reactions. Standard treatment of 5-FU and capecitabine induced chest pain with vasodilators is mostly effective, but there are several cases of patients unresponsive to these agents. METHODS: We performed a PubMed search on 31st May 2020. We used a three keyword search strategy using Boolean search operators. More specifically, we included fluorouracil or 5-FU or capecitabine and chest pain or angina and mechanism or treatment or management. We included primary reports of clinical and non-clinical data, as well as systematic reviews. Narrative reviews, expert opinions, letters to the editor and other forms of non-primary literature were excluded. RESULTS: Our search yielded a total of 1595 reports. Of these, 1460 were narrative reviews or irrelevant to the topic and were excluded. A total of 135 reports were used for our review. We used 81 reports for data extraction, which included 13 clinical trials, 4 retrospective reports, 61 case reports, and 3 systematic reviews. CONCLUSION: We report the incidence and predisposing factors, the value of available diagnostic procedures, and standard medical and invasive treatments. We also speculate on the potential benefit of arginine as a promising option both in prevention as well as treatment of 5-FU-induced chest pain. Finally, gaps of evidence are identified and proposals are made in terms of future research.

Effects of different exercise programs on the cardiorespiratory reserve in HFpEF patients: a systematic review and meta-analysis.

HFpEF represents a heterogeneous syndrome with complex pathophysiological substrates and multiple clinical manifestations. Recently, much attention has been focused on cardiac rehabilitation programs for HFpEF patients, and several studies have examined the effects of exercise training on this specific population. This systematic review and meta-analysis included studies on adult patients with HFpEF and evaluated the impact of exercise on the cardiorespiratory fitness variables measured during CPET. The primary outcome was the difference in the change in the peak oxygen uptake (Δpeak VO2) between the groups. Literature search involved PubMed/MEDLINE, Cochrane/CENTRAL and Scopus databases. From an initial 5,143 literature records, we identified 18 studies fulfilling the inclusion criteria; 11 studies with 515 patients were finally included in the primary outcome analysis. Δpeak VO2 between baseline and study end was significantly higher in the groups of exercise training versus control (WMD 2.25 ml/kg/min, 95% CI 1.81-2.70). Exercise training resulted in greater change in the 6-minute walking test (6MWT) distance (WMD 2.25 m, 95% CI 1.81-2.70). Health-related quality of life (HRQoL) (WMD: -3.36, 95% CI -9.42 to 2.70, I2 = 14%, p = 0.33) and echocardiographic indices of diastolic function showed no differences between exercise and control groups at study end. In the subgroup analysis, no difference between resistance versus aerobic exercise was noted in Δpeak VO2, but high-intensity interval training showed a greater increase in peak VO2 versus aerobic exercise (WMD 1.62 ml/kg/min, 95% CI 0.96-2.29, I2 = 0%, p = 0.82). Exercise training in HFpEF results in significant improvements in peak VO2 and 6MWT distance as compared to those for controls. High-intensity interval training may offer greater enhancement of the exercise capacity of these patients than standard aerobic exercise.

Lung ultrasound-guided dry-weight reduction and echocardiographic changes in clinically euvolemic hypertensive hemodialysis patients: 12-month results of a randomized controlled trial.

OBJECTIVE: Left ventricular hypertrophy (LVH) and dysfunction are highly prevalent in hemodialysis patients and are independently associated with adverse outcomes. This study examines the long-term effects of dry-weight reduction with a standardized lung ultrasound (LUS)-guided strategy on echocardiographic indexes of left ventricular (LV) mass and function in hemodialysis patients. METHODS: Seventy-one clinically euvolemic hemodialysis patients with hypertension were randomized to dry-weight reduction guided by pre-hemodialysis LUS (n = 35) or standard-of-care treatment (n = 36) and were followed-up for 12 months. Two-dimensional and tissue-Doppler echocardiographies (TDI) were performed at the baseline and 12-month evaluations. RESULTS: During follow-up, dry-weight reduction took place in more patients in the active arm than in the control arm of the trial (71.4% vs 22.2%; p < 0.001). Left atrial (LA) surface (-1.37 ± 4.50 vs 1.28 ± 5.00 cm2; P = 0.006) and LA volume index (-3.22 ± 11.82 vs 4.76 ± 12.83 ml/m2; P = 0.009) decreased in the active and increased in the control group. LV end-diastolic volume (-0.94 ± 11.45 vs 6.58 ± 13.92 ml/m2; P = 0.015) decreased only in the active group. The LV mass index was unchanged in the active (134.21 ± 44.75 vs 133.57 ± 45.51; P = 0.844) and marginally increased in the control group (134.21 ± 40.96 vs 143.77 ± 50.04 g/m2; P = 0.089). The LV E/e' wave ratio was unchanged in the active (12.45 ± 4.69 vs 12.56 ± 4.89; P = 0.521) and increased in the usual-care group (10.91 ± 4.97 vs12.36 ± 6.43; P = 0.003). LV systolic function did not differ between the two study arms across the trial. CONCLUSION: Over 12 months, LUS-guided dry-weight reduction is associated with reverse LV and LA remodeling, myocardial hypertrophy regression, and improved LV diastolic filling properties.

Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors: A meta-analysis of cardiovascular outcome trials.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM: To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS: We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following "hard" efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS: We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I 2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I 2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I 2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I 2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I 2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I 2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I 2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I 2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION: DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors, except for those cases when newer antidiabetics (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) are not tolerated, contraindicated or not affordable for the patient.

The impact of atrial mechanical function on age-dependent presentation of neurocardiogenic syncope.

BACKGROUND: The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. HYPOTHESIS: We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. METHODS: We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head-up tilt test (HUTT). RESULTS: A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2 , p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05). CONCLUSIONS: Patients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.

Cardiorespiratory fitness assessed by cardiopulmonary exercise testing between different stages of pre-dialysis chronic kidney disease: A systematic review and meta-analysis.

AIM: The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown. METHODS: We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale. RESULTS: From 4944 records initially retrieved, six studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) [weighted-mean-difference, WMD: 2.46, 95% CI (1.15, 3.78)]. Oxygen consumption at ventilatory threshold (VO2 VT) was higher in Stages 2-3a compared with those in Stages 3b-5(pre-dialysis) [standardized-mean-difference, SMD: 0.59, 95% CI (0.06, 1.1)], while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results [WMD: 1.78, 95% CI (1.34, 2.22)]. Sensitivity analysis confirmed the robustness of these findings. CONCLUSION: VO2 peak and VO2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared with Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD.

A Patient-Oriented App (ThessHF) to Improve Self-Care Quality in Heart Failure: From Evidence-Based Design to Pilot Study.

BACKGROUND: Heart failure (HF) remains a major public health challenge, while HF self-care is particularly challenging. Mobile health (mHealth)-based interventions taking advantage of smartphone technology have shown particular promise in increasing the quality of self-care among these patients, and in turn improving the outcomes of their disease. OBJECTIVE: The objective of this study was to co-develop with physicians, patients with HF, and their caregivers a patient-oriented mHealth app, perform usability assessment, and investigate its effect on the quality of life of patients with HF and rate of hospitalizations in a pilot study. METHODS: The development of an mHealth app (The Hellenic Educational Self-care and Support Heart Failure app [ThessHF app]) was evidence based, including features based on previous clinically tested mHealth interventions and selected by a panel of HF expert physicians and discussed with patients with HF. At the end of alpha development, the app was rated by mHealth experts with the Mobile Application Rating Scale (MARS). The beta version was tested by patients with HF, who rated its design and content by means of the Post-Study System Usability Questionnaire (PSSUQ). Subsequently, a prospective pilot study (THESS-HF [THe Effect of a Specialized Smartphone app on Heart Failure patients' quality of self-care, quality of life and hospitalization rate]) was performed to investigate the effect of app use on patients with HF over a 3-month follow-up period. The primary endpoint was patients' quality of life, which was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 5-level EQ-5D version (EQ-5D-5L). The secondary endpoints were the European Heart Failure Self-care Behavior Scale (EHFScBS) score and the hospitalization rate. RESULTS: A systematic review of mHealth-based HF interventions and expert panel suggestions yielded 18 separate app features, most of which were incorporated into the ThessHF app. A total of 14 patients and 5 mHealth experts evaluated the app. The results demonstrated a very good user experience (overall PSSUQ score 2.37 [SD 0.63], where 1 is the best, and a median MARS score of 4.55/5). Finally, 30 patients (male: n=26, 87%) participated in the THESS-HF pilot study (mean age 68.7 [SD 12.4] years). A significant increase in the quality of self-care was noted according to the EHFScBS, which increased by 4.4% (SD 7.2%) (P=.002). The mean quality of life increased nonsignificantly after 3 months according to both KCCQ (mean increase 5.8 [SD 15] points, P=.054) and EQ-5D-5L (mean increase 5.6% [SD 15.6%], P=.06) scores. The hospitalization rate for the follow-up duration was 3%. CONCLUSIONS: The need for telehealth services and remote self-care management in HF is of vital importance, especially in periods such as the COVID-19 pandemic. We developed a user-friendly mHealth app to promote remote self-care support in HF. In this pilot study, the use of the ThessHF app was associated with an increase in the quality of self-care. A future multicenter study will investigate the effect of the app use on long-term outcomes in patients with HF.