Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Genetic predisposition in chemotherapy-induced cardiomyopathy in a 65-year-old female with metastatic breast cancer.

The prevention and management of cancer therapy-related cardiac dysfunction (CTRCD) have become increasingly important. Recent studies have revealed the crucial role of genetics in determining the susceptibility to development of CTRCD. We present a case of a 65-year-old woman with breast cancer who developed recurrent CTRCD following low-dose chemotherapy, despite lacking conventional cardiovascular risk factors. Her medical history included anthracycline-associated cardiomyopathy, and her condition deteriorated significantly after treatment with HER2-targeted therapies. Through the use of multimodal imaging, we detected severe left ventricular systolic dysfunction. Further investigation with genetic testing revealed a likely pathogenic variant in the TNNT2 gene, suggesting a genetic predisposition to CTRCD. This case implies the potential role of genetic screening in identifying patients at risk for CTRCD and advocates for personalized chemotherapy and cardioprotective strategies.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Temporal Trends, Risk Factors, and Clinical Outcomes of De Novo Lymphoproliferative Disorders After Heart Transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015. Multivariable analysis was done to identify risk factors for PTLD development after HTx. RESULTS: Among 28,136 HTx recipients, 1,069 (3.8%) developed PTLD within 10 years of transplantation. PTLD showed a bimodal age pattern with peak incidence in patients of pediatric age and late adulthood at transplantation. The early transplant era (2000-2007 vs 2008-2015), male recipient, and EBV donor-positive-recipient-negative match were independent risk factors of PTLD development within 3 years of transplantation, whereas maintenance therapy with cyclosporine vs tacrolimus at initial discharge was associated with a lower incidence. PTLD development within 3 years of transplantation was significantly associated with mortality (HR: 2.42 [95% CI: 2.01-2.91]; P < 0.001). Survival after PTLD diagnosis was higher in the recent transplant era. CONCLUSIONS: PTLD is relatively rare, but potentially fatal, post-transplant malignancy. PTLD incidence and mortality after HTx have decreased in the recent era. Strategies to minimize the risk of PTLD, and ensure early diagnosis and effective treatment are likely to improve outcomes in HTx.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Advanced and Acute Heart Failure.

The Korean Society of Heart Failure (KSHF) Guidelines provide evidence-based recommendations based on Korean and international data to guide adequate diagnosis and management of heart failure (HF). Since introduction of 2017 edition of the guidelines, management of advanced HF has considerably improved, especially with advances in mechanical circulatory support and devices. The current guidelines addressed these improvements. In addition, we have included recently updated evidence-based recommendations regarding acute HF in these guidelines. In summary, Part IV of the KSHF Guidelines covers the appropriate diagnosis and optimized management of advanced and acute HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Advanced and Acute Heart Failure.

The Korean Society of Heart Failure (KSHF) Guidelines provide evidence-based recommendations based on Korean and international data to guide adequate diagnosis and management of heart failure (HF). Since introduction of 2017 edition of the guidelines, management of advanced HF has considerably improved, especially with advances in mechanical circulatory support and devices. The current guidelines addressed these improvements. In addition, we have included recently updated evidence-based recommendations regarding acute HF in these guidelines. In summary, Part IV of the KSHF Guidelines covers the appropriate diagnosis and optimized management of advanced and acute HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Antihypertensive Medication Adherence and Cardiovascular Outcomes in Patients With Cancer: A Nationwide Population-Based Cohort Study.

Background Hypertension is an important cause of morbidity, which predisposes patients to major cardiovascular events and mortality. The aim of this study was to explore the association between adherence to antihypertensive medication and clinical outcomes in adult patients with cancer. Methods and Results Using the 2002 to 2013 Korean National Health Insurance Service-National Sample Cohort, we extracted adult patients with cancer treated with antihypertensive medications. Based on the medication possession ratio value, participants were divided into 3 groups: good (medication possession ratio ≥0.8), moderate (0.5≤ medication possession ratio <0.8), and poor (medication possession ratio <0.5) adherence groups. The primary outcomes were overall and cardiovascular mortality. The secondary outcome was cardiovascular events requiring hospitalization due to major cardiovascular diseases. Among 19 246 patients with cancer with concomitant hypertension, 66.4% were in the nonadherence group (26.3% were moderate and 40.0% were poor adherence group). Over a median of 8.4 years of follow-up, 2752 deaths and 6057 cardiovascular events occurred. Compared with the good adherence group, the moderate and poor adherence groups had a 1.85-fold and 2.19-fold increased risk for overall mortality, and 1.72-fold and 1.71-fold elevated risk for cardiovascular mortality, respectively, after adjustment for possible confounders. Furthermore, the moderate and poor adherence groups had a 1.33-fold and 1.34-fold elevated risk of new-onset cardiovascular events, respectively. These trends were consistent across cardiovascular event subtypes. Conclusions Nonadherence to antihypertensive medication was common in patients with cancer and was associated with worse clinical outcomes in adult patients with cancer with hypertension. More attention should be paid to improving adherence to antihypertensive medication among patients with cancer.

Systematic Review of the Economic Evaluation of Sodium-Glucose Cotransporter-2 Inhibitors Used as Treatment in Patients with Heart Failure.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently used as therapeutic agents for type 2 diabetes mellitus. Recent clinical trials have shown that they are beneficial for reducing the risk of cardiovascular mortality and hospitalization in patients with heart failure (HF). A comprehensive review regarding the cost-effectiveness of different SGLT2 inhibitors for HF treatment may be necessary to help clinicians and decision-makers select the most cost-effective HF treatment option. OBJECTIVE: This study conducted a systematic review of economic evaluation studies of SGLT2 inhibitors for the treatment of patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). METHOD: We searched PubMed, Cochrane, Embase, and EBSCOhost to identify published economic evaluation studies on SGLT2 inhibitors for HF treatment until May 2023. Studies on the economic evaluation of SGLT2 inhibitors in the treatment of HF were included. We extracted information such as country, population, intervention, type of model, health status, and conclusion of cost-effectiveness. RESULT: Of the 410 studies, 27 were finally selected. All economic evaluation studies used the Markov model, and commonly included health status as stable HF, hospitalization due to HF, and death. All dapagliflozin studies focused on patients with HFrEF (n = 13), and dapagliflozin was cost-effective in 14 countries, but not in the Philippines. All empagliflozin studies focused on the patients with HFrEF also showed the cost-effectiveness of empagliflozin (n = 11). However, empagliflozin use in patients with HFpEF was determined to be cost-effective in studies in Finland, China, and Australia studies but not in studies in Thailand and the USA. CONCLUSIONS: Most of the studies reported the cost-effectiveness of dapagliflozin and empagliflozin in patients with HFrEF. However, the cost-effectiveness of empagliflozin differed from country to country regarding patients with HFpEF. We suggest that further economic evaluation of SGLT2 inhibitors should focus on patients with HFpEF in more countries.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (EF), HF with mildly reduced EF, and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Treatment.

The Korean Society of Heart Failure (KSHF) guidelines aim to provide physicians with evidence-based recommendations for the management of patients with heart failure (HF). After the first introduction of the KSHF guidelines in 2016, newer therapies for HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction have since emerged. The current version has been updated based on international guidelines and research data on Korean patients with HF. Herein, we present Part II of these guidelines, which comprises treatment strategies to improve the outcomes of patients with HF.

Three year post heart transplant outcomes of desensitized durable mechanical circulatory support patients.

BACKGROUND: The risks and benefits of desensitization therapy (DST) in highly sensitized mechanical circulatory support (MCS) patients are not well known. We investigated 3 year post-transplant outcomes of desensitized durable MCS patients. METHODS: Among 689 consecutively enrolled heart transplantation recipients between 2010 and 2016, we categorized them into Group A (desensitized MCS patients, n = 21), Group B (desensitized non-MCS patients, n = 28) and Group C (all nondesensitized patients, n = 640). Post-transplant outcomes included the incidence of primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, antibody mediated rejection (AMR) and infectious complications. RESULTS: The types of DST in Groups A and B were similar and included combinations of rituximab/intravenous immunoglobulin and plasmapheresis/bortezomib. Group A, compared with Group B, showed significantly higher pre-DST panel reactive antibody (PRA) (92.2 ± 9.8 vs. 83.3 ± 15.6, P = 0.007) and higher PRA reduction after DST (-22.2 ± 26.9 vs. -6.3 ± 7.5, P = 0.015). Groups A and C showed comparable primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, and AMR. Although statistically not significant, Group A showed numerically higher 3-year freedom from AMR than Group B. Infectious complications were similar in both Groups A and B. CONCLUSIONS: DST for MCS patients showed significant PRA reduction, resulting in an expansion of the donor pool. The post-transplant outcome of desensitized MCS patients showed comparable clinical outcomes to non-desensitized control patients in the same study period, revealing the safety and efficacy of DST.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (EF), and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Treatment.

The Korean Society of Heart Failure (KSHF) guidelines aim to provide physicians with evidence-based recommendations for the management of patients with heart failure (HF). After the first introduction of the KSHF guidelines in 2016, newer therapies for HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction have since emerged. The current version has been updated based on international guidelines and research data on Korean patients with HF. Herein, we present Part II of these guidelines, which comprises treatment strategies to improve the outcomes of patients with HF.