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Background: The impact of early-stage chronic kidney disease (CKD) on cardiovascular outcomes, particularly when albuminuria is present, remains unclear. This study examined the associations between early CKD (stages 1 and 2) with and without albuminuria and the incidence of major adverse cardiovascular events (MACEs), heart failure (HF) and all-cause mortality.

Methods: A cohort of 456 015 participants from the UK Biobank was categorised by CKD stage using serum creatinine to calculate estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (≥3 mg/mmol) to define albuminuria. Multivariable Cox proportional hazard models were applied to evaluate the associations between CKD stages and cardiovascular outcomes. Additionally, left ventricular mass (LVM), an intermediate cardiovascular risk marker, was assessed in a subset of participants using cardiovascular MRI.

Results: Compared with normal kidney function, the risk of adverse outcomes increased progressively with advancing CKD stages, except for stage 2 CKD without albuminuria. Stage 2 CKD with albuminuria was associated with higher risks of MACE (HR 1.32, 95% CI 1.25 to 1.38), HF (HR 1.79, 95% CI 1.67 to 1.92) and all-cause mortality (HR 1.51, 95% CI 1.44 to 1.58), comparable to stage 3A CKD without albuminuria. The presence of albuminuria significantly interacted with the relationships between CKD stages and outcomes. No significant differences in indexed LVM were observed between early-stage CKD with albuminuria and normal renal function.

Conclusions: In early-stage CKD, albuminuria is independently associated with increased risks of MACE, HF and mortality. These findings support the use of albuminuria over eGFR decline alone for cardiovascular risk stratification in early CKD.

Background: Treatment with implantable cardioverter-defibrillators (ICDs) effectively prevents sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Identifying patients most likely to benefit from a primary prevention ICD remains challenging. We aimed to investigate the long-term incidence of ICD therapy in patients with HCM according to SCD-risk at baseline.

Methods: The study retrospectively included all patients with HCM treated with an ICD for primary or secondary prevention between 1995 and 2022 in Eastern Denmark. Medical records for each patient were evaluated. Patients were stratified into risk groups according to the European Society of Cardiology HCM Risk-SCD score.

Results: We included 208 patients (66% male) with HCM and an ICD for primary (78%) or secondary prevention (22%). During a median 10-year follow-up, 66 patients (32%) received appropriate ICD therapy (antitachycardia pacing and/or shock), while 20 (10%) received inappropriate therapy. Patients with an ICD implanted for secondary prevention were almost twice as likely to receive appropriate therapy compared with patients with an ICD implanted for primary prevention (47% vs 28%, p=0.02). The 5-year cumulative incidences of appropriate shock therapy were 17% in patients with a high HCM Risk-SCD score, 16% in patients with an intermediate-risk score and 6% in patients with a low-risk score. A high-risk score was associated with higher cumulative incidence of appropriate shock therapy (p=0.012).

Conclusion: One-third of patients with HCM treated with an ICD experienced appropriate ICD therapy. The HCM-Risk SCD score adequately distinguished between low-risk and high-risk patients among those who underwent ICD implantation. Further improvements of risk-tools are needed to identify a larger proportion of the two-thirds of patients who did not benefit from ICD implantation after 10 years of observation.

Background: The upper reference limit of normal (ULN) of cardiac troponin (cTn) for older adults can be higher than for young adults, while the same ULN is used for both older and young adults in the current clinical practice.

Methods: In this multicentre longitudinal cohort study, non-acute myocardial infarction (non-AMI) inpatients with at least two cTn concentrations hospitalised between 2013 and 2022 in the Tianjin Health and Medical Data Platform were included. Multivariable Cox proportional hazards and landmark regression models were used to estimate the risk of in-hospital, 30-day and 1-year mortality in different cTn groups (normal, stable minor elevation (1-2×ULN with variation ≤20%), acute minor elevation (1-2×ULN with variation >20%) and apparent elevation (>2×ULN)).

Results: A total of 57 117 patients (mean age, 69.6 (13.6) years; 25 037 (43.8%) female) were included. Even minor elevation in cTn was associated with higher mortality risk. Compared with the normal cTn group, the adjusted HRs of in-hospital mortality for patients with steady minor elevation, acute minor elevation and >2× ULN in cTn were 1.70 (95% CI 1.25 to 2.33), 1.92 (95% CI 1.59 to 2.32) and 4.03 (95% CI 3.50 to 4.65), respectively. Similar trends were found for all-cause 30-day and 30-day to 1-year mortality. Among older adults, compared with the steady minor elevation group, patients with acute minor elevation in cTn had higher 30-day mortality risk (HR 1.30, 95% CI 1.02 to 1.65) but similar 30-day to 1-year mortality risk (HR 0.95, 95% CI 0.82 to 1.10), while among non-older adults, differences in short-term and 1-year mortality risks between the two groups were not statistically significant (p>0.05).

Conclusions: In non-AMI inpatients, including older adults, any stable or acute elevation in cTn, even minor, warrants attention. Further studies are needed to assess whether these patients can benefit from more aggressive treatment approaches.

Background: The aim of this study was to assess the presence of myocardial injury after COVID-19 infection and to evaluate the relation between persistent cardiac symptoms after COVID-19 and myocardial function in participants with known cardiovascular health status before infection.

Methods: In the prospective population-based Rotterdam Study cohort, echocardiography and cardiovascular magnetic resonance (CMR) were performed among participants who recovered from COVID-19 at home within 2 years prior to inclusion in the current study. Persistent cardiac symptoms comprised only self-reported symptoms of chest pain, dyspnoea or palpitations lasting >4 weeks after COVID-19 infection. We used linear regression and linear mixed models to estimate and test age-adjusted and sex-adjusted mean differences (95% CIs) of (1) post-COVID-19 CMR-derived and echocardiographic-derived parameters among participants with and without persistent post-COVID-19 symptoms and (2) pre-COVID-19 and post-COVID-19 echocardiographic assessments.

Results: 92 participants were included, with a mean age of 59±8 years of whom 52% were male. Normal post-COVID-19 CMR-derived left ventricular (LV) function and right ventricular ejection fraction were observed in 92% and 98% of participants, respectively. We observed normal native T1 relaxation times in 100%, normal extracellular volume in 98% and normal T2 relaxation times in 98% of the participants. Comparison of pre-COVID-19 and post-COVID-19 echocardiography revealed a significant but small decline in left ventricular ejection fraction (adjusted mean change -1.37% (95% CI -2.57%, -0.17%)) and global longitudinal strain (1.32% (95% CI 0.50%, 2.15%)). Comparing participants with and without persistent symptoms, there were no significant differences in adjusted CMR-derived ventricular volumes, LV function or presence of myocardial injury.

Conclusions: Almost all recovered non-hospitalised COVID-19 participants had normal CMR-derived ventricular volumes and function, without relevant myocardial injury.

Background: Statistical shape atlases have been used in large-cohort studies to investigate relationships between heart shape and risk factors. The generalisability of these relationships between cohorts is unknown. The aims of this study were to compare left ventricular (LV) shapes in patients with differing cardiovascular risk factor profiles from two cohorts and to investigate whether LV shape scores generated with respect to a reference cohort can be directly used to study shape differences in another cohort.

Methods: Two cardiac MRI cohorts were included: 2106 participants (median age: 65 years, 54% women) from the Multi-Ethnic Study of Atherosclerosis (MESA) and 2960 participants (median age: 64 years, 52% women) from the UK Biobank (UKB) study. LV shape atlases were constructed from 3D LV models derived from expert-drawn contours from separate core labs. Atlases were considered generalisable for a risk factor if the area under the receiver operating characteristic curves (AUC) were not significantly different (p>0.05) between internal (within-cohort) and external (cross-cohort) cases.

Results: LV mass and volume indices were differed significantly between cohorts, even in age-matched and sex-matched cases without risk factors, partly reflecting different core lab analysis protocols. For the UKB atlas, internal and external discriminative performance were not significantly different for hypertension (AUC: 0.77 vs 0.76, p=0.37), diabetes (AUC: 0.79 vs 0.77, p=0.48), hypercholesterolaemia (AUC: 0.76 vs 0.79, p=0.38) and smoking (AUC: 0.69 vs 0.67, p=0.18). For the MESA atlas, diabetes (AUC: 0.79 vs 0.74, p=0.09) and hypercholesterolaemia (AUC: 0.75 vs 0.70, p=0.10) were not significantly different. Both atlases showed significant differences for obesity.

Conclusions: The MESA and UKB atlases demonstrated good generalisability for diabetes and hypercholesterolaemia, without requiring corrections for differences in mass and volume. Significant differences in obesity may be due to different relationships between obesity and heart shapes between cohorts.

Background: Atrial fibrillation (AF) is a major and increasing burden on health services. This study aimed to evaluate the cost-effectiveness of digoxin versus beta-blockers for heart rate control in patients with permanent AF and symptoms of heart failure.

Methods: RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) was a randomised, open-label, blinded, endpoint trial embedded in the UK National Health Service (NHS) to directly compare low-dose digoxin with beta-blockers (ClinicalTrials.gov: NCT02391337). A trial-based cost-utility analysis was performed from a healthcare perspective over 12 months. Resource use in primary and secondary healthcare services, medications and patient-reported quality of life were prospectively collected to estimate differences in costs and quality-adjusted life years (QALYs).

Results: RATE-AF randomised 160 patients with mean age of 76 (SD 8) years and 46% women, of which 149 patients (n=73 digoxin, n=76 beta blockers) had complete data and survived to 12-month follow-up. Treatment with digoxin was significantly less costly, with a mean saving of £530.41 per patient per year (95% CI -£848.06 to -£249.38, p=0.001). This was principally due to substantially lower rates of adverse events, with less primary and secondary healthcare utilisation compared with beta-blocker therapy. There was no significant difference in QALYs (0.013; 95% CI -0.033 to 0.052, p=0.56). At the £20 000 per-QALY willingness to pay threshold, the probability of digoxin being cost-effective compared with beta-blockers was 94%, with potential annual savings to the NHS of £102 million/year (95% CI £48 million to £164 million saving, p=0.001).

Conclusions: Digoxin is a less costly option when compared with beta-blockers for control of heart rate in suitable patients with permanent AF, with larger cost-effectiveness studies warranted to advise on national and global policy-making.

Trial registration number: NCT02391337, EudraCT 2015-005043-13.

Background: Switching from a conventional to a high-sensitivity cardiac troponin (hs-cTn) assay enables detection of smaller amounts of myocardial damage, but the clinical benefit is unclear. We investigated whether switching to a hs-cTnI assay with a sex-specific 99th centile diagnostic threshold was associated with lower 1-year death or new myocardial infarction (MI) in patients with suspected acute coronary syndrome (ACS).

Methods: This pre-post study included nine tertiary hospitals in Australia. During the pre-hs-cTn period, all hospitals used conventional troponin assays, and during the postperiod, four switched to using hs-cTnI. Participants were ≥20 years old and presenting to emergency departments (EDs) with suspected ACS between March 2011 and November 2015. Outcomes were determined using linked administrative data and compared using Kaplan-Meier and Cox regression analyses.

Results: We identified 179 681 consecutive patients (62 (SD 19) years, 47% women), 87 019 (48%) during the preperiod, and 92 662 (52%) during the postperiod. Following the switch to hs-TnI, the proportion of patients diagnosed with new MI was not significantly different (3.9% postperiod vs 4.2% preperiod; p=0.08) while diagnoses of unstable angina were lower (1.5% postperiod vs 2.5% preperiod; p<0.0001). In non-switching jurisdictions, rates of new MI remained stable, while diagnoses of unstable angina increased. Switching to hs-cTnI assay was associated with lower mortality at 30 days (adjusted HR 0.88 (0.82, 0.95)) and 1 year (aHR 0.90 (0.85, 0.94)). The corresponding aHRs for non-switching jurisdictions were not statistically different.

Conclusion: The use of an hs-cTnI assay in an ED population with suspected ACS was associated with lower mortality at 1 year.