Predicting impaired cardiopulmonary exercise capacity in patients with atrial fibrillation using a simple echocardiographic marker.

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis.

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials. Objectives: We aim to investigate the change in global longitudinal strain (GLS) of A97S ATTR-CM patients after 12 months of tafamidis treatment. Methods: We retrospectively analysed a prospective cohort of patients with A97S ATTR-CM who received tafamidis meglumine (61 mg/day) at the National Taiwan University Hospital. Echocardiography with speckle tracking strain analysis was performed at baseline and 12 months after treatment. Results: In all, 20 patients were included in the cohort. The baseline left ventricular ejection fraction (LVEF) and interventricular septum (IVS) thickness were 59.20 ± 13.23% and 15.10 ± 3.43 mm, respectively. After 12 months of tafamidis treatment, the LVEF and IVS were 61.83 ± 15.60% (p = 0.244) and 14.59 ± 3.03 mm (p = 0.623), respectively. GLS significantly improved from -12.70 ± 3.31% to -13.72 ± 3.17% (p = 0.048), and longitudinal strain (LS) in apical and middle segments significantly improved from -16.05 ± 4.82% to -17.95 ± 3.48% (p = 0.039) and -11.89 ± 4.38% to -13.58 ± 3.12% (p = 0.039), respectively. Subgroup analysis showed that patients with LVEF < 50% had a better treatment response and improvement in GLS. The patients with an IVS ⩾ 13 mm had an improvement in two-chamber LS from -10.92 ± 4.25% to -13.15 ± 3.87% (p = 0.042) and an improvement in apical left ventricular LS from -15.30 ± 5.35% to -17.82 ± 3.99% (p = 0.031). Conclusion: Tafamidis significantly improved GLS, and particularly apical and middle LS in A97S ATTR-CM patients.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis Transthyretin cardiomyopathy (ATTR-CM) is a severe heart condition that has gained attention due to recent advancements in treatments. One of these treatments, called tafamidis, has been shown to be effective in maintaining heart function and quality of life. However, there has been limited research on a specific genetic variation of ATTR-CM: A97S. Our aim was to determine whether A97S ATTR-CM patients experienced improved heart function after one year of tafamidis treatment. We conducted this study at the National Taiwan University Hospital, where we enrolled 20 A97S ATTR-CM patients. We used echocardiography to evaluate their heart function, focusing on a parameter called global longitudinal strain. The results showed that after one year of tafamidis treatment, these patients experienced a significant improvement in their global longitudinal strain, particularly in the apical and middle regions of the heart. In conclusion, tafamidis appears to be beneficial for A97S ATTR-CM patients by enhancing their heart's global longitudinal strain, which is a positive sign for their cardiac health.

Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study.

BACKGROUND: Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM. METHODS: We retrospectively analyzed a prospective cohort of ATTR-CM patients, including 14 with hereditary A97S ATTR-CM and 17 healthy controls with baseline CMR data. All ATTR-CM patients received tafamidis treatment and received CMR with extracellular volume (ECV) at baseline and after 1 year of follow-up. RESULTS: Baseline N-terminal pro-B-type natriuretic peptide, left ventricular (LV) mass, LV ejection fraction, global radial, circumferential and longitudinal strain, T1 mapping and ECV were significantly worse in the patients with ATTR-CM compared with the healthy controls. After 1 year of tafamidis treatment, ECV decreased from 51.5 ± 8.9% to 49.0 ± 9.4% (P = 0.041), however there were no significant changes in LV mass, LV ejection fraction, global radial strain, global circumferential strain, global longitudinal strain and T1 mapping. CONCLUSIONS: After a one-year treatment period, tafamidis exhibited subtle but statistically significant reductions in ECV, potentially indicating a decrease in amyloid deposition among patients diagnosed with hereditary A97S ATTR-CM.

Efficacy of Tafamidis in Patients with Ala97Ser Hereditary Transthyretin Cardiac Amyloidosis: A Six-Month Follow-Up Study.

Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. Objectives: This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. Methods: We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Results: Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m2, and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. Conclusions: The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.

Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals.

BACKGROUND: The main target of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the sodium-glucose cotransporters 2, is found in the kidneys, and their activity is reduced in patients with chronic kidney disease (CKD). How the efficacy of SGLT2i may vary in patients with different levels of renal impairment has not been fully elucidated. METHODS: We searched the PubMed databases for relevant studies published through May 25, 2022. Randomized control trials comparing SGLT2i with placebo and reporting cardiovascular or renal outcomes were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), which were defined as cardiovascular death (CV death), nonfatal myocardial infarction (MI), and nonfatal ischemic stroke. Secondary outcomes included the components of MACE, all-cause mortality, hospitalization for heart failure (HHF), the composite of CV death and HHF, and composite renal outcomes. Linear meta-regression analysis was used to assess the effects of estimated glomerular filtration rate (eGFR) on the risks associated with SGLT2i treatment vs placebo for all outcomes. Nonlinear meta-regression analysis was also performed for MACE to investigate the combined influence of reduced drug efficacy in CKD but possible greater risk reduction in a population with higher risk at baseline. Further analyses were performed by including additional study-level covariates, including the prevalence of diabetes mellitus (DM), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). RESULTS: Risk ratios for MACE, CV death, nonfatal MI, HHF, and composite renal outcomes associated with SGLT2i treatment were not significantly related to baseline eGFR values. A positive association was observed between eGFR values and the risk of stroke with SGLT2i use (regression coefficient ß = .0109, 95% confidence interval [CI] 0.0029-0.0188). A similar positive association was observed between eGFR values and the composite outcome of CV death and HHF (ß = .0025, 95% CI 0.0000-0.0051). The results of the meta-regression analyses, including the additional covariates of DM, HF, and ASCVD, were consistent with the results of the primary analyses for most outcomes. CONCLUSION: The protective effects of SGLT2i for reducing most adverse cardiovascular and renal outcomes persisted in patients with variable degrees of renal impairment. The observed benefits such as preventing CV death, HF worsening, or stroke may be greater for patients with more severe CKD. Considering the cardiovascular and renal benefits associated with SGLT2i treatment, patients with CKD should be treated aggressively to improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42021273500.

Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

The Imposter Dance of Alternating QRS Complexes.

This case report describes a patient in their late 50s with acute onset chest pain with diaphoresis.

Major adverse cardiovascular and limb events in people with diabetes treated with GLP-1 receptor agonists vs SGLT2 inhibitors.

AIMS/HYPOTHESIS: This study aimed to assess the real-world outcomes of people with diabetes mellitus treated with glucagon-like peptide-1 receptor agonists (GLP1RAs) compared with those treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in terms of major adverse cardiovascular and limb events. Peripheral artery disease is a common cause of morbidity in people with diabetes. Previous cardiovascular outcome trials have demonstrated the benefits of GLP1RAs and SGLT2is for reducing various cardiovascular events, but the safety and efficacy of these drugs on limb outcomes remain subject to debate and ambiguity. METHODS: A retrospective cohort study was conducted in which data were collected from the Taiwan National Health Insurance Research Database. In total, 379,256 individuals with diabetes receiving either GLP1RA or SGLT2i with treatment initiated between 1 May 2016 and 31 December 2019 were identified. The primary outcome was major adverse limb events (MALE), defined as the composite of newly diagnosed critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for peripheral artery disease, and non-traumatic amputation. The secondary outcome was major adverse cardiac events, which was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Other examined outcomes included death from any cause and hospitalisation for heart failure. Propensity score matching was performed at a 1:4 ratio between the GLP1RA and SGLT2i groups to mitigate possible selection bias. RESULTS: A total of 287,091 patients were eligible for analysis, with 81,152 patients treated with SGLT2i and 20,288 patients treated with GLP1RA after matching. The incidence of MALE was significantly lower in the GLP1RA group than in the SGLT2i group (3.6 vs 4.5 events per 1000 person-years; subdistribution HR 0.80; 95% CI 0.67, 0.96), primarily due to a lower incidence of critical limb ischaemia. The reduced risks of MALE associated with GLP1RA use were particularly noticeable in people with diabetic peripheral neuropathy (subdistribution HR 0.66 vs 1.11; p for interaction 0.006). CONCLUSIONS/INTERPRETATION: In people with diabetes, GLP1RA use was associated with significantly reduced risks of MALE compared with SGLT2i within the first 2 years after initiation, especially among people with diabetic neuropathy.

Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals.

OBJECTIVES: The "obesity paradox" - in which patients with obesity exhibit superior survival than normal-weight counterparts - has been reported for several diseases. However, obesity is a well-known risk factor for cardiovascular disease, and whether the obesity paradox is present in peripheral artery disease (PAD) is unknown. METHODS: A comprehensive search for studies that reported mortality in patients with PAD grouped by BMI identified 12 studies. We compared the survival of underweight patients with those who were not underweight, and patients with obesity against those without. Underweight was defined by a BMI value of <18.5 kg/m2 in most studies and obesity by BMI ≥ 30 kg/m2. Subgroup analyses were performed according to length of follow-up, presentation of PAD, and mode of revascularization. Meta-regression analyses were conducted, with covariates including age, sex, presence of coronary artery disease (CAD) and diabetes mellitus (DM). RESULTS: The mortality risk of underweight patients with PAD was significantly higher compared to those who are not underweight (HR 1.72, 95% CI 1.38-2.14; I2 = 84.2%). In contrast, the mortality risk of patients with obesity with PAD was significantly lower than those without (HR 0.78, 95% CI 0.62-0.97; I2 = 89.8%). These findings remained consistent regardless of the presentation of PAD, revascularization, age, sex, or presence of CAD. The risk of death in the short-term of underweight patients (HR 1.50, 95% CI 0.47-4.72) and patients with obesity (HR 0.86, 95% CI 0.66-1.13) were not significantly different from their counterparts. The meta-regression showed that of the association between obesity and better survival was more pronounced in studies with a greater proportion of patients with concomitant CAD (regression coefficient -0.029, 95% CI -0.054 to -0.004). CONCLUSIONS: In patients with PAD, mortality is higher among underweight patients and lower among patients with obesity. The mechanisms underlying the obesity paradox in patients with PAD remain to be elucidated, and further evidence is required to guide optimal weight control strategies in these patients.

A Dose Response Association Between Body Mass Index and Mortality in Patients with Peripheral Artery Disease: A Meta-analysis Including 5 729 272 Individuals.

OBJECTIVE: Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD. METHODS: A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT). RESULTS: The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/m2 to approximately 33 - 34 kg/m2. The risk of mortality increased slightly thereafter. This relationship was consistent with that of long term mortality but was not apparent in short term mortality. A U shaped relationship was also observed between BMI and mortality in patients who received EVT with the lowest mortality observed at around 30 kg/m2. CONCLUSION: The obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality.