AIM: We compared different demographic, clinical, and echocardiographic characteristics between patients with AF+HF and patients with AF only. Furthermore, we explored whether concurrent HF independently predicts several outcomes (all-cause mortality, cardiovascular mortality, ischemic stroke/systemic embolism (IS/SE), major bleeding, and clinically relevant non-major bleeding (CRNMB)).
MATERIALS AND METHODS: Comparisons between the AF+HF and the AF-only group were carried out. Multivariable Cox proportional hazard models were constructed for each outcome to assess whether HF was predictive of any of them while controlling for possible confounding factors.
RESULTS: A total of 2020 patients were included in this study: 481 had AF+HF; 1539 had AF only. AF+HF patients were older, more commonly males, and had a higher prevalence of diabetes mellitus, dyslipidemia, coronary artery disease, and chronic kidney disease (p≤0.05). Furthermore, AF+HF patients more commonly had pulmonary hypertension and low ejection fraction (p≤0.001). Finally, HF was independently predictive of all-cause mortality (adjusted HR 2.17, 95% CI (1.66-2.85) and cardiovascular mortality (adjusted HR 2.37, 95% CI (1.68-3.36).
CONCLUSION: Coexisting AF+HF was associated with a more labile and higher-risk population among Jordanian patients. Furthermore, coexisting HF independently predicted higher all-cause mortality and cardiovascular mortality. Efforts should be made to efficiently identify such cases early and treat them aggressively.
METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions.
RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive.
LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population.
CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.
METHODS: This systematic review searched MEDLINE, CINAHL+, Econlit, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database and the Cost-Effectiveness Analysis Registry from inception to 31 December, 2022, for relevant economic evaluations, which were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Bias in Economic Evaluation (ECOBIAS) criteria. The costs, quality-adjusted life-years, incremental cost-effectiveness ratios and cost-effectiveness thresholds were qualitatively analysed. Net monetary benefits at different decision thresholds were also computed. Subgroup analyses addressing the heterogeneity of economic outcomes were conducted. All costs were adjusted to 2023 international dollar (US$) values using the CCEMG-EPPI-Centre cost converter.
RESULTS: Thirty-nine economic evaluations that evaluated dapagliflozin and empagliflozin in patients with heart failure were found: 32 for the left ventricular ejection fraction (LVEF) ≤ 40% and seven for LVEF > 40%. Sodium-glucose cotransporter-2 inhibitors were cost-effective in all but two economic evaluations for LVEF > 40%. Economic outcomes varied widely, but favoured SGLT2i use in LVEF ≤ 40% over LVEF > 40% and upper-middle income over high-income countries. At a threshold of US$30,000/quality-adjusted life-year, ~ 90% of high to upper-middle income countries would consider SGLT2i cost-effective for heart failure treatment. The generalisability of study findings to low- and low-middle income countries is limited because of insufficient evidence.
CONCLUSIONS: Using SGLT2i to treat heart failure is cost-effective, with more certainty in LVEF ≤ 40% compared to LVEF > 40%. Policymakers in jurisdictions where economic evaluations are not available could potentially use this study's findings to make informed decisions about treatment adoption.
SYSTEMATIC REVIEW PROTOCOL REGISTRATION: This study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023388701).
METHODS: A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists.
RESULTS: A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold.
CONCLUSIONS: Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.
METHODS: We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity.
RESULTS: Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p
METHODS AND RESULTS: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).
CONCLUSION: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.
OBJECTIVE: To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up.
DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment.
INTERVENTIONS: In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years.
MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS).
RESULTS: A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group.
CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02771795.
METHODS: A total of 119 post-percutaneous coronary intervention ST elevation myocardial infarction patients with TIMI flow grade >2 were prospectively included in the study. Left ventricular global longitudinal strain was quantified by 2-dimensional speckletracking echocardiography, and left ventricular mechanical dispersion was determined at baseline and after 1 year to assess adverse cardiac remodeling. The levels of circulating biomarkers were measured at the baseline. TIMI score and the Global Registry of Acute Coronary Events score systems were used to evaluate the prognosis of patients.
RESULTS: Patients with high quartile versus low quartile of left ventricular mechanical dispersion exerted higher Global Registry of Acute Coronary Events and TIMI score grades, left ventricular endsystolic volume, global longitudinal strain, and levels of the N-terminal fragment of brain natriuretic peptide and lower left ventricular ejection fraction. Multivariate log regression showed that N-terminal fragment of brain natriuretic peptide > 953 pg/mL, global longitudinal strain > -8%, and high quartile of left ventricular mechanical dispersion remained independent predictors for adverse cardiac remodeling. Addition of left ventricular mechanical dispersion to the N-terminal fragment of brain natriuretic peptide improved the discriminative potency of the whole model.
CONCLUSION: Measurement of left ventricular mechanical dispersion might be useful in determining the risk of adverse cardiac remodeling in post-percutaneous coronary intervention ST elevation myocardial infarction patients.
METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
RESULTS: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.
DISCUSSION: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.
TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.
METHODS: LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk.
RESULTS: Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value.
CONCLUSIONS: In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.
METHODS: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported.
RESULTS: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059).
CONCLUSION: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.
METHOD: The annual cost of HF per patient was estimated using unweighted average and inverse probability weighting (IPW). Unweight average estimated the annual cost by considering all observed cases regardless of the availability of all the cost data, while IPW calculated the cost by weighting against inverse probability. The economic burden of HF was estimated for different HF phenotypes and age categories at the population level from the public healthcare system perspective.
RESULTS: The mean (standard deviation) annual costs per patient calculated using unweighted average and IPW were USD 5,123 (USD 3,262) and USD 5,217 (USD 3,317), respectively. The cost of HF estimated using two different approaches did not differ significantly (p = 0.865). The estimated cost burden of HF in Malaysia was USD 481.9 million (range: USD 31.7 million- 1,213.2 million) per year, which accounts for 1.05% (range: 0.07%-2.66%) of total health expenditure in 2021. The cost of managing patients with heart failure with reduced ejection fraction (HFrEF) accounted for 61.1% of the total financial burden of HF in Malaysia. The annual cost burden increased from USD 2.8 million for patients aged 20-29 to USD 142.1 million for those aged 60-69. The cost of managing HF in patients aged 50-79 years contributed 74.1% of the total financial burden of HF in Malaysia.
CONCLUSION: A large portion of the financial burden of HF in Malaysia is driven by inpatient costs and HFrEF patients. Long-term survival of HF patients leads to an increase in the prevalence of HF, inevitably increasing the financial burden of HF.
METHODS AND RESULTS: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients.
CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.