Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. METHODS AND RESULTS: A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR < 60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR ≥ 60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup < 60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). CONCLUSION: Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

Uromodulin biology.

Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial and serum uromodulin. Among these, uromodulin modulates renal sodium handling through the regulation of tubular sodium transporters that reabsorb sodium and are targeted by diuretics, such as the loop diuretic-sensitive Na+-K+-2Cl- cotransporter type 2 (NKCC2) and the thiazide-sensitive Na+/Cl- cotransporter (NCC). Given these roles, the contribution of uromodulin to sodium-sensitive hypertension has been proposed. However, recent studies in humans suggest a more complex interaction between dietary sodium intake, uromodulin and blood pressure. This review presents an updated overview of the uromodulin's biology and its various roles, and focuses on the interaction between uromodulin and sodium-sensitive hypertension.

Cardiorespiratory fitness assessed with cardiopulmonary exercise testing in patients with juvenile idiopathic arthritis: a systematic review and meta-analysis.

OBJECTIVES: JIA is the most common type of arthritis in children and adolescents, causing joint damage, chronic pain and disability. Deconditioning is also prevalent in patients with JIA due to both inactivity and the disease progression, resulting in reduced cardiorespiratory fitness (CRF). We aimed to evaluate CRF of patients with JIA compared with healthy controls. METHODS: This is a systematic review and meta-analysis of studies using cardiopulmonary exercise testing (CPET) to examine differences in determinants of CRF between patients with JIA vs healthy controls. The primary outcome was peak oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and Scopus databases, manual search of article references and grey literature. Quality assessment was undertaken with Newcastle-Ottawa Scale. RESULTS: From 480 literature records initially retrieved, eight studies (538 participants) were included in final meta-analysis. VO2peak was significantly lower in patients with JIA compared with controls [weighted mean difference (WMD): -5.95 ml/kg/min (95% CI -9.26, -2.65)]. Exercise duration and VO2peak (% predicted) were found to be significantly impaired in patients with JIA compared with controls [standardized mean difference: -0.67 (95% CI -1.04, -0.29) and WMD: -11.31% (95% CI -20.09, -2.53), respectively], while no significant differences were found in maximum heart rate. CONCLUSION: VO2peak and other CPET variables were lower in patients with JIA compared with controls, indicating reduced CRF in the former. Overall, exercise programs for patients with JIA should be promoted as part of their treatment to improve physical fitness and reduce muscle atrophy. PROSPERO REGISTRATION: CRD42022380833.

Kidney transplantation and kidney donation do not affect short-term blood pressure variability.

PURPOSE: Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. MATERIALS AND METHODS: Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas. RESULTS: All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. CONCLUSION: Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

What is the context? Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.On the other hand, existing evidence suggests that kidney donors' BP levels do not change significantly after kidney donation.Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer.What is new? This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods.What is the impact?High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Effect of kidney transplantation on indices of cardiorespiratory fitness assessed with cardiopulmonary exercise testing: a systematic review and meta-analysis.

BACKGROUND: Patients with kidney failure often present with reduced cardiovascular reserve. Kidney transplantation (KT) is the optimal treatment for patients with end-stage kidney disease as it is associated with longer survival and improved quality of life compared to dialysis. METHODS: This is a systematic review and meta-analysis of studies using cardiopulmonary-exercise-testing to examine the cardiorespiratory fitness of patients with kidney failure before and after KT. The primary outcome was difference in pre- and post-transplantation values of peak oxygen uptake (VO2peak). Literature search involved three databases (PubMed-Web of Science-Scopus), manual search, and grey literature. RESULTS: From 379 records initially retrieved, six studies were included in final meta-analysis. A marginal, but not significant, improvement was observed in VO2peak after KT compared to pre-transplantation values (SMD: 0.32, 95%CI -0.02; 0.67). Oxygen consumption at anaerobic threshold was significantly improved after KT (WMD: 2.30 ml/kg/min, 95%CI 0.50; 4.09). Consistent results were shown between preemptive and after-dialysis-initiation transplantation and a trend for improvement in VO2peak was observed at least 3 months post-transplantation, but not earlier. CONCLUSION: Several major indices of cardiorespiratory fitness tend to improve after KT. This finding may represent another modifiable factor contributing to better survival rates of kidney transplant recipients compared to patients undergoing dialysis.

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.

Peridialytic and intradialytic blood pressure metrics are not valid estimates of 44-h ambulatory blood pressure in patients with intradialytic hypertension.

PURPOSE: In contrast to peridialytic blood pressure (BP), intradialytic and home BP measurements are accurate metrics of ambulatory BP load in hemodialysis patients. This study assessed the agreement of peridialytic, intradialytic, and scheduled interdialytic recordings with 44-h BP in a distinct hemodialysis population, patients with intradialytic hypertension (IDH). METHODS: This study included 45 IDH patients with valid 48-h ABPM and 197 without IDH. With 44-h BP used as reference method, we tested the accuracy of the following BP metrics: Pre- and post-dialysis, mean and median intradialytic, mean intradialytic plus pre/post-dialysis, and scheduled interdialytic BP (out-of-dialysis day: mean of 8:00am/8:00 pm readings). RESULTS: In IDH patients, peridialytic and intradialytic BP metrics showed at best moderate correlations, while averaged interdialytic SBP/DBP exhibited strong correlation (r = 0.882/r = 0.855) with 44-h SBP/DBP. Bland-Altman plots showed large between-method-difference for peri- and intradialytic-BP, but only + 0.7 mmHg between-method difference and good 95% limits of agreement for averaged interdialytic SBP. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP ≥ 130 mmHg were low for pre-dialysis (72.5/40.0%, κ-statistic = 0.074) and post-dialysis (90.0/0.0%, κ-statistic = - 0.110), mean intradialytic (85.0/40.0%, κ-statistic = 0.198), median intradialytic (85.0/60.0%, κ-statistic = 0.333), and intradialytic plus pre/post-dialysis SBP (85.0/20.0%, κ-statistic = 0.043). Averaged interdialytic SBP showed high sensitivity/specificity (97.5/80.0%) and strong agreement (κ-statistic = 0.775). In ROC analyses, scheduled interdialytic SBP/DBP had the highest AUC (0.967/0.951), sensitivity (90.0/88.0%), and specificity (100.0/90.0%). CONCLUSION: In IDH patients, only averaged scheduled interdialytic but not pre- and post-dialysis, nor intradialytic BP recordings show reasonable agreement with ABPM. Interdialytic BP recordings only could be used for hypertension diagnosis and management in these subjects.

SGLT-2 Inhibitors and Nephroprotection in Patients with Diabetic and Non-diabetic Chronic Kidney Disease.

For several years, blood pressure control and blocking of the renin-angiotensin system (RAS) represented the cornerstones of chronic kidney disease (CKD) treatment. Cardiovascular outcome trials with sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (DM) suggested that these agents can effectively delay the progression of CKD in these individuals. A major nephroprotective effect of canagliflozin was also shown in a renal outcome trial in patients with proteinuric diabetic CKD. The Study-to- Evaluate-the-Effect- of-Dapagliflozin-on-Renal-Outcomes-and-Cardiovascular- Mortality-in-Patients-With-Chronic-Kidney-Disease (DAPA-CKD) is a recent milestone in the field, as it included patients with both diabetic and non-diabetic proteinuric CKD and showed impressive reduction in the primary renal outcome of CKD progression, as well as the risk of hospitalization for heart failure and all-cause mortality on top of standard- of-care treatment. These benefits were consistent for patients with diabetic and non-diabetic CKD, including patients with ischemic or hypertensive nephropathy and glomerulonephritides (IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy). Based on the above, relevant guidelines should accommodate their recommendations to implement treatment with SGLT-2 inhibitors for CKD patients.

Sex-related short-term blood pressure variability differences in kidney transplant recipients.

OBJECTIVE: Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs. METHODS: In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods. RESULTS: Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men. CONCLUSION: In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients.

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave's disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto's thyroiditis two months post-vaccination. Grave's disease is uncommon in dialysis patients, whereas Hashimoto's thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against chronic kidney disease patients.

BACKGROUND: Hypertension is a major cardiovascular risk factor in both kidney transplant recipients (KTRs) and patients with chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard method for hypertension management in these subjects. This is the first study evaluating the full ambulatory blood pressure (BP) profile and short-term BP variability (BPV) in KTRs versus CKD patients without kidney replacement therapy. METHODS: Ninety-three KTRs were matched with 93 CKD patients for age, sex, and estimated glomerular filtration rate. All participants underwent 24-hour ABPM. Mean ambulatory BP levels, BP trajectories, and BPV indices (standard deviation [SD], weighted SD, and average real variability) were compared between the two groups. RESULTS: There were no significant between-group differences in 24-hour systolic BP (SBP)/diastolic BP (DBP) (KTRs: 126.9 ± 13.1/79.1 ± 7.9 mmHg vs. CKD: 128.1 ± 11.2/77.9 ± 8.1 mmHg, p = 0.52/0.29), daytime SBP/DBP and nighttime SBP; nighttime DBP was slightly higher in KTRs (KTRs: 76.5 ± 8.8 mmHg vs. CKD: 73.8 ± 8.8 mmHg, p = 0.04). Repeated measurements analysis of variance showed a significant effect of time on both ambulatory SBP and DBP (SBP: F = [19, 3002] = 11.735, p < 0.001, partial η2 = 0.069) but not of KTR/CKD status (SBP: F = [1, 158] = 0.668, p = 0.42, partial η2 = 0.004). Ambulatory systolic/diastolic BPV indices were not different between KTRs and CKD patients, except for 24-hour DBP SD that was slightly higher in the latter group (KTRs: 10.2 ± 2.2 mmHg vs. CKD: 10.9 ± 2.6 mmHg, p = 0.04). No differences were noted in dipping pattern between the two groups. CONCLUSION: Mean ambulatory BP levels, BP trajectories, and short-term BPV indices are not significantly different between KTRs and CKD patients, suggesting that KTRs have a similar ambulatory BP profile compared to CKD patients without kidney replacement therapy.

De novo Minimal Change Disease in an Adolescent after Pfizer-BioNTech COVID-19 Vaccination: A Case Report.

This is the first report in an adolescent of minimal change disease (MCD) after the first injection of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) with complete remission following steroid treatment. An 18-year-old white male with no prior medical history complained of gastrointestinal symptoms 11 days after his vaccination. Ascites and lower extremity edema were observed a few days later. He was admitted to a hospital as laboratory testing revealed proteinuria of 10.5 g/24 h, normal creatinine levels, and serum albumin of 1.8 g/dL, confirming the presence of nephrotic syndrome. Immunology and serology tests were unremarkable. A diagnostic kidney biopsy showed no significant glomerular or tubular abnormalities in light microscopy with negative immunofluorescence. Treatment with methylprednisolone 48 mg daily was initiated. A week after discharge, proteinuria declined to 1.2 g/24 h, and edema had disappeared, and 6 weeks later, complete remission was evident. As COVID-19 vaccination has been associated with the development of de novo and relapsing MCD, and this case provides additional support for this possible correlation.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against haemodialysis patients.

Background: Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. Methods: A total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed. Results: KTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P < 0.001); no significant differences were noted for diastolic blood pressure levels with the exception of the second nighttime. Repeated measurements ANOVA showed a significant effect of renal replacement therapy modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between them; the greatest between-group difference in BP (KTRs-HD in mmHg) was observed at the end of the second 24 h [-13.9 mmHg (95% confidence interval -21.5 to -6.2); P < 0.001]. Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD patients during all periods studied (24-h SBP average real variability: KTRs: 9.6 ± 2.3 mmHg; HD first 24 h: 10.3 ± 3.0 mmHg; P = 0.032; second 24 h: 11.5 ± 3.0 mmHg; P < 0.001). No differences were noted in dipping pattern between the two groups. Conclusions: SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges.

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions against the global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates of protection against severe disease and mortality. Barely a year after vaccines became available, the Omicron variant and its unprecedented speed of transmission has posed a new challenge. Overall, Omicron presents increased immune escape, transmissibility, and decreased pathogenicity. Vaccines do not offer a full protection against SARS-CoV-2 acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who may in turn spread the virus to others. Breakthrough infections may be causally related to the viral profile (viral variant and load, incubation period, transmissibility, pathogenicity, immune evasion), immunity characteristics (mucosal versus systemic immunity, duration of immunity, etc.), host determinants (age, comorbidities, immune status, immunosuppressive drugs) and vaccination properties (platform, antigen dose, dose number, dose interval, route of administration). Determining the rate of breakthrough infections may be challenging and necessitates the conduction of population-based studies regarding vaccine effectiveness as well as neutralizing antibody testing, a surrogate of immune protection. In this review, we analyze the causes of breakthrough infections, their clinical consequences (severity of infection and transmission), methods of determining their incidence as well as challenges and perspectives. Long COVID as well as multi-inflammatory syndrome in adolescents may be significantly reduced in breakthrough infections. The need for universal pancoranavirus vaccines that would aim at protecting against a plethora of SARS-CoV-2 variants as well as emerging variants is discussed. Finally, novel vaccine strategies, such as nasal vaccines, may confer robust mucosal and systemic protection, reducing efficiently transmission.

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 reserve examined with cardiopulmonary exercise testing in individuals with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) often present reduced physical activity and exercise tolerance due to factors relevant to co-existing disturbances of the cardiac, nervous and muscular systems. Cardiopulmonary exercise testing (CPET) is used for clinical evaluation of exercise limitation and related symptoms (i.e., dyspnea, fatigue) in several medical fields. OBJECTIVES: This is a systematic review and meta-analysis of studies using CPET technology to examine cardiopulmonary reserve in individuals with versus without CKD. METHODS: Literature search involved PubMed, Web of Science and Scopus databases; manual search of article references and of gray literature was also performed. Observational studies and randomized trials that used CPET for patients with CKD stage 1-5 versus controls were eligible. The primary outcome was peak oxygen uptake (VO2peak). The Newcastle-Ottawa Scale was used to evaluate the quality of retrieved studies. RESULTS: From an initial 4944 literature records, we identified 29 studies fulfilling the inclusion criteria; of these, 25 studies (2,213 participants) with complete data were included in the final meta-analysis. VO2peak was significantly lower in CKD patients than controls without CKD [standardized mean difference (SMD) -1.40, 95% confidence interval (CI) -1.68; -1.13)]. Values were lower for CKD than non-CKD individuals for oxygen consumption at anaerobic threshold (SMD -1.06, 95% CI -1.34; -0.79) and maximum workload [weighted mean difference (WMD) -58.26, 95% CI 74.14; -42.38]. In 3 studies, CKD patients had higher VO2peak than controls with heart failure without CKD (WMD 6.60, 95% CI 3.02; 10.18). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: VO2peak and other commonly analyzed CPET variables were lower in patients with CKD than controls, which indicates reduced functional cardiopulmonary reserve in CKD. In contrast, patients with CKD performed better than controls with heart failure without CKD. Overall, rehabilitation programs should be more widely applied to individuals with CKD. PROSPERO REGISTRATION NUMBER: CRD42021227805.

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.