Chronic kidney disease-related sarcopenia as a prognostic indicator in elderly haemodialysis patients.

BACKGROUND: The mortality of dialysis patients greatly exceeds that of the general population and identifying predictive factors for mortality may provide opportunities for earlier intervention. This study assessed the influence of sarcopenia on mortality in patients on haemodialysis. METHODS: This prospective, observational study enrolled 77 haemodialysis patients aged 60 years and over, of whom 33 (43%) were female, from two community dialysis centres. Baseline demographic and laboratory data were collected, and sarcopenia was diagnosed using grip strength, muscle mass by bioimpedance analysis (BIA) and muscle function by timed up-and-go according to European Working Group on Sarcopenia in Older People criteria. Nutritional status was assessed using a subjective nutritional assessment score, comprising functional changes in weight, appetite, gastrointestinal symptoms and energy.. A comorbidity score (maximum 7 points) was derived from the presence or absence of hypertension, ischaemic heart disease, vascular disease (cerebrovascular disease, peripheral vascular disease, and abdominal aortic aneurysm), diabetes mellitus, respiratory disease, a history of malignancy and psychiatric disease. Outcomes over six years were linked to the Australian and New Zealand Dialysis and Transplant Registry. RESULTS: The median participant age was 71 years (range 60-87). Probable and confirmed sarcopenia was present in 55.9% and severe sarcopenia with reduced functional testing in 11.7%. Over 6 years, overall mortality was 50 of the 77 patients (65%), principally from cardiovascular events, dialysis withdrawal and infection. There were no significant survival differences between patients with no, probable, confirmed, or severe sarcopenia, or between tertiles of the nutritional assessment score. After adjustment for age, dialysis vintage, mean arterial pressure (MAP) and the total comorbidity score, no sarcopenia category predicted mortality. However, the total comorbidity score [Hazard Ratio (HR) 1.27, Confidence Intervals (CI) 1.02, 1.58, p = 0.03] and MAP (HR 0.96, CI 0.94, 0.99, P = < 0.01) predicted mortality. CONCLUSION: Sarcopenia is highly prevalent in elderly haemodialysis patients but is not an independent predictor of mortality. Haemodialysis patients have multiple competing risks for mortality which, in this study, was predicted by a lower MAP and a higher total comorbidity score. TRIAL REGISTRATION: Recruitment commenced December 2011. The study was registered 10.01.2012 with the Australian New Zealand Clinical Trials Registry (ACTRN12612000048886).

Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?

BACKGROUND: In Australia, government-subsidised treatment of pulmonary arterial hypertension (PAH) is limited to monotherapy. Recent international guidelines advocate that initial combination therapy be considered for all symptomatic PAH patients. AIM: To characterise 'real-life' outcomes in PAH patients initiated on monotherapy. METHODS: We performed a retrospective analysis of 100 consecutive PAH patients at a single centre who were commenced on monotherapy for PAH between 2004 and 2015. The composite clinical end-point of 'treatment failure' was prospectively defined as (i) >15% fall in 6-min walk distance (6MWD) on follow up, (ii) physician judgement of inadequate treatment response, (iii) adverse drug effect requiring cessation and (iv) death or transplantation. RESULTS: At initiation of therapy, mean age was 54 ± 18 years, and underlying diagnoses included idiopathic (36%), connective tissue disease-associated (37%) and congenital heart disease-associated-PAH (25%). Baseline 6MWD was 360 ± 140 m, and 75% were in either the New York Heart Association functional classes III or IV. Over a median follow up of 38 months (interquartile range 20-67), 62% of the subjects met the criteria for a clinical failure event. Median time to monotherapy failure was 24 months (95% confidence interval 14-34), with death or transplantation being the most common clinical failure event. Estimated 1-, 3- and 5-year survival rates from time of treatment initiation were 92, 75 and 66%. CONCLUSION: The majority of patients failed initial monotherapy therapy within 2 years of treatment initiation. Broader access to approved PAH agents is needed to enable combination therapy in line with evidence-based international guidelines.

Mitral Regurgitation "Proportionality" in Functional Mitral Regurgitation and Outcomes After Mitral Valve Transcatheter Edge-to-Edge Repair: A Systematic Review and Meta-Analysis.

Background: Certain patients with functional mitral regurgitation survive longer with fewer heart failure hospitalizations after undergoing transcatheter edge-to-edge repair (TEER); however, clinical markers identifying who will benefit have not been established. The 'proportionality' of mitral regurgitation (MR) severity compared to left ventricular size has been hypothesized to predict clinical outcome. Methods: We sought to combine existing studies to compare outcomes between 'proportionate' MR and 'disproportionate' MR in patients undergoing TEER. PubMed and Medline were searched from January 2018 until May 2023. Data was extracted and synthesized by 2 independent authors using random effects models with risk ratios (RRs) for binary outcomes. The primary outcome was a combined endpoint of all-cause mortality or heart failure hospitalization (ACM/HFH). Other outcomes of interest included ACM and residual >2+ MR after TEER. Results: Six trials with a total of 1594 patients (mean age 71 years, 66% male) were included, which assessed MR proportionality using either a ratio of estimated regurgitant orifice area to left ventricular end-diastolic volume (EROA:LVEDV) or regurgitant fraction. Seven hundred and five (mean age 70 years, 75% male) were classified as proportionate MR, and 889 (mean age 72 years, 60% male) had disproportionate MR. There was no significant association between MR proportionality (by EROA:LVEDV) and ACM (RR 0.79, 95% confidence interval [CI] 0.44-1.42). Proportionality did not significantly associate with ACM/HFH, though there were divergent effect signals when proportionality was measured by EROA:LVEDV (RR 0.80, 95% CI 0.45-1.44) or regurgitant fraction (RR 1.48, 95% CI 0.53-4.11). Disproportionate MR showed a greater association with residual MR > 2+ post-TEER that did not meet statistical significance (RR 1.86, 95% CI 0.77-4.49). Conclusions: In patients undergoing TEER for functional mitral regurgitation, MR proportionality was not significantly associated with ACM/HFH, all-cause mortality, or residual MR.

Atrial functional mitral regurgitation: prevalence, characteristics and outcomes from the National Echo Database of Australia.

AIMS: Atrial functional mitral regurgitation (AFMR) is characterised by left atrial and consequent mitral annular dilatation causing mitral regurgitation. AFMR is likely to become more common with population ageing, alongside increases in atrial fibrillation and heart failure with preserved ejection fraction; conditions causing atrial dilatation. Here, we aim to define the prevalence and characterise the patient and survival characteristics of AFMR in the National Echocardiographic Database of Australia (NEDA). METHODS AND RESULTS: 14 004 adults with moderate or severe FMR were identified from NEDA. AFMR or ventricular FMR (VFMR) was classified by LA size, LV size and LVEF. AFMR was found in 40% (n=5562) and VFMR in 60% (n=8442). Compared with VFMR, the AFMR subgroup were significantly older (mean age 78±11 years), with a higher proportion of females and of AF. Participants were followed up for a median of 65 months (IQR 36-116 months). After adjustment for age, sex, AF, and pulmonary hypertension, the prognosis for VFMR was significantly worse than for AFMR (HR 1.57, 95% CI 1.47 to 1.68 for all-cause and 1.73, 95% CI 1.60 to 1.88, p<0.001 for both). After further adjustment for LVEF, mortality rates were similar in VFMR and AFMR patients (HR 0.93, p=NS), though advancing age and pulmonary hypertension remained independently associated with prognosis. CONCLUSIONS: AFMR is a common cause of significant functional MR that predominantly affects elderly female patients with AF. Advancing age and pulmonary hypertension independently associated with survival in FMR. Prognosis was better in AFMR compared with VFMR; however, this difference was accounted for by LV systolic impairment and not by MR severity.

One-Year Outcomes of Early, Compassionate Use of the PASCAL Ace Implant System for Transcatheter Mitral Valve Repair.

Background: Continued development of transcatheter mitral repair technologies is needed to address the large and diverse population of high-risk patients with symptomatic mitral regurgitation (MR). The new PASCAL Ace implant system, with its narrower profile, complements the original PASCAL transcatheter valve repair system. The aim of this study is to report 1-year outcomes from the early, compassionate-use observational experience with the novel PASCAL Ace implant system. Methods: After heart team assessment, adults with symptomatic moderate-to-severe (3+) or severe (4+) MR despite optimal medical therapy were treated under compassionate use at 3 hospitals internationally. Data were prospectively collected, and outcomes were assessed over a 12-month follow-up period. Results: Seventeen patients (mean age 76 years, 65% male, mean Society of Thoracic Surgeons Predicted Risk of Operative Mortality score 9.6) were treated. MR etiology was degenerative in 29%, functional in 65%, and mixed in 6%; 59% were in New York Heart Association (NYHA) class III-IV. Technical success was achieved in 100%, and procedural success in 94%. At 1 year, MR grade ≤2+ was achieved in 93% (p < 0.001) with 88% survival rate and 94% free from heart failure hospitalization. The composite major adverse event rate was 6% and 100% of patients had ≤NYHA class II symptoms (p < 0.001). Conclusions: At 1 year, the PASCAL Ace implant system demonstrated feasibility in this early, compassionate use experience in a small group of symptomatic patients with anatomically complex MR. The unique features of the PASCAL Ace implant may expand the treatable MR population.

Prevalence of Anderson-Fabry disease in a cohort with unexplained late gadolinium enhancement on cardiac MRI.

INTRODUCTION: Fabry disease is a rare X-linked genetic disorder in which cardiac manifestations include LVH, contractile dysfunction, and fibrosis, visible on cardiac MRI (cMRI) as late gadolinium enhancement (LGE) of the myocardium. Fabry's disease is an important diagnosis to make as treatment is available as lifelong replacement of the deficient enzyme. AIM: To define the prevalence of Fabry disease in a cohort of patients with unexplained LGE on cMRI. METHODS: The study population was recruited from patients aged >16 years who had cMRI performed between 2010 and 2018 to investigate LVH, idiopathic LV dysfunction and/or idiopathic ventricular arrhythmia. Patients with 'unexplained' LGE i.e. without a genetic diagnosis of an alternate cardiomyopathy such as HCM or biopsy-proven infiltrative cardiomyopathy such as sarcoid or amyloid, were tested for Fabry disease by either genetic testing or the Dried Blood Spot test (Sanofi-Genzyme). RESULTS: Of the 79 patients with unexplained LGE on cMRI, 2 patients tested positive for Fabry disease, both using genetic sequencing techniques. The prevalence of Fabry disease in this selected cohort was 2.5%. Specifically, 1 patient was a 65 year old male and the other patient a 75 year old female. In both cases, the pattern and distribution of LGE on cMRI was of patchy mid-wall enhancement in the inferoseptum. CONCLUSION: Unexplained LGE on cMRI may be an isolated manifestation of late-onset Fabry disease. This finding should prompt testing for Fabry disease given this is a potentially treatable condition.

Prognostic Value of Coronary Microvascular Function Measured Immediately After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: An International Multicenter Study.

BACKGROUND: The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease. METHODS: We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR≥25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated. RESULTS: During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16-2.105; P=0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11-2.28; P=0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76-3.35; P=0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67-6.63; P=0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77-2.54; P=0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99-2.43; P=0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96-3.36; P=0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events. CONCLUSIONS: IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.