Introduction: There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients.
Method: A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals. The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data.
Results: There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0 years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30 days, 60 days, 180 days, and 1 year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT).
Conclusions: The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.
{"title":"Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients.","authors":"Thanita Boonyapiphat, Thidaporn Tangkittikasem, Artit Torpongpun, Vichai Senthong, Panyapat Jiampo","doi":"10.1007/s40119-024-00366-5","DOIUrl":"10.1007/s40119-024-00366-5","url":null,"abstract":"<p><strong>Introduction: </strong>There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients.</p><p><strong>Method: </strong>A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals. The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code \"I50.\" Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data.</p><p><strong>Results: </strong>There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0 years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30 days, 60 days, 180 days, and 1 year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT).</p><p><strong>Conclusions: </strong>The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"415-430"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Heart failure (HF) is one of the leading causes of hospitalization worldwide. In Thailand, data on HF burden remains limited. This study aimed to describe comprehensive evidence detailing the HF prevalence, hospital admission rates, in-hospital mortality, and overall mortality rates at the hospital level.
Method: All eligible adult patients' medical records from 2018 and 2019 were analyzed retrospectively at five hospitals in different regions. The patients were diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code I50. Descriptive statistics were used to examine the hospital burden as well as patients' clinical and outcome data.
Results: A total of 7384 patients with HF were identified from five tertiary hospitals. Around half of the patients were male. The mean age was 67 years, and the main health insurance scheme was the Universal Coverage Scheme. The prevalence of HF was 0.1% in 2018 and 0.2% in 2019. Heart failure with preserved ejection fraction (HFpEF) was the most common type of HF in both visits, followed by heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF). The proportion of HF hospitalizations was 1.2% in 2018 and 1.5% in 2019. The proportion of HF rehospitalizations versus hospitalizations in patients with HF was 22.7% in 2018 and 23.9% in 2019. The risk of rehospitalization was highest at 180 days after hospital discharge (87.8%). Among the patients with HF, the proportion of all-cause mortality was 9.1% in 2018 and 8.0% in 2019. Most of the deaths occurred within 30 days after hospitalization.
Conclusion: Our study demonstrated that the burden of HF in terms of hospitalization and in-hospital mortality was notably high when compared to similar studies conducted in Thailand and other countries.
{"title":"Real-World Heart Failure Burden in Thai Patients.","authors":"Panyapat Jiampo, Thidaporn Tangkittikasem, Thanita Boonyapiphat, Vichai Senthong, Artit Torpongpun","doi":"10.1007/s40119-024-00355-8","DOIUrl":"10.1007/s40119-024-00355-8","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure (HF) is one of the leading causes of hospitalization worldwide. In Thailand, data on HF burden remains limited. This study aimed to describe comprehensive evidence detailing the HF prevalence, hospital admission rates, in-hospital mortality, and overall mortality rates at the hospital level.</p><p><strong>Method: </strong>All eligible adult patients' medical records from 2018 and 2019 were analyzed retrospectively at five hospitals in different regions. The patients were diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code I50. Descriptive statistics were used to examine the hospital burden as well as patients' clinical and outcome data.</p><p><strong>Results: </strong>A total of 7384 patients with HF were identified from five tertiary hospitals. Around half of the patients were male. The mean age was 67 years, and the main health insurance scheme was the Universal Coverage Scheme. The prevalence of HF was 0.1% in 2018 and 0.2% in 2019. Heart failure with preserved ejection fraction (HFpEF) was the most common type of HF in both visits, followed by heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF). The proportion of HF hospitalizations was 1.2% in 2018 and 1.5% in 2019. The proportion of HF rehospitalizations versus hospitalizations in patients with HF was 22.7% in 2018 and 23.9% in 2019. The risk of rehospitalization was highest at 180 days after hospital discharge (87.8%). Among the patients with HF, the proportion of all-cause mortality was 9.1% in 2018 and 8.0% in 2019. Most of the deaths occurred within 30 days after hospitalization.</p><p><strong>Conclusion: </strong>Our study demonstrated that the burden of HF in terms of hospitalization and in-hospital mortality was notably high when compared to similar studies conducted in Thailand and other countries.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"281-297"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-04-30DOI: 10.1007/s40119-024-00367-4
Peeyush Jain, Santanu Guha, Soumitra Kumar, J P S Sawhney, Kamal Sharma, K P Sureshkumar, Ashwani Mehta, Rajnish Dhediya, Kumar Gaurav, Rajan Mittal, Bhavesh Kotak
Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.
心力衰竭是一项全球性的健康挑战,影响着数百万人的健康,而获得指南指导下的医疗治疗往往是有限的。造成这种限制的因素通常包括药物供应、采用缓慢、临床惰性和诊断延迟。尽管国际建议提倡在心力衰竭管理中使用指导性医疗疗法,但在资源有限的情况下,个性化方法至关重要。在印度,血管紧张素 II 受体阻滞剂肾利酶抑制剂和钠-葡萄糖共转运体 2 抑制剂等重要治疗手段尽管具有公认的安全性和有效性,但并未得到充分利用。为解决这一问题,包括心脏病专家、肾病专家和内分泌专家在内的 150 名专家达成了专家共识。他们就患者概况、监测和不良副作用等问题进行了讨论,并为心力衰竭管理中的指导性药物治疗提供了有针对性的建议。共识强调了对心力衰竭患者尽早启动指南指导下的药物治疗的重要性,尤其是钠-葡萄糖协同转运体2抑制剂,同时还探讨了维利奎特等创新疗法。为改善资源有限环境下的心衰治疗效果,专家们提出了多项措施,包括加强患者教育、心脏康复、改善药物获取途径以及改革医疗保健政策。
{"title":"Management of Heart Failure in a Resource-Limited Setting: Expert Opinion from India.","authors":"Peeyush Jain, Santanu Guha, Soumitra Kumar, J P S Sawhney, Kamal Sharma, K P Sureshkumar, Ashwani Mehta, Rajnish Dhediya, Kumar Gaurav, Rajan Mittal, Bhavesh Kotak","doi":"10.1007/s40119-024-00367-4","DOIUrl":"10.1007/s40119-024-00367-4","url":null,"abstract":"<p><p>Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"243-266"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-01-12DOI: 10.1007/s40119-023-00346-1
Krisztina Mária Szabó, Anna Tóth, László Nagy, Vivien Rácz, Zsófia Pólik, Katalin Hodosi, Attila C Nagy, Judit Barta, Attila Borbély, Zoltán Csanádi
Introduction: Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy.
Methods: CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared.
Results: A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II.
Conclusion: SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.
{"title":"Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.","authors":"Krisztina Mária Szabó, Anna Tóth, László Nagy, Vivien Rácz, Zsófia Pólik, Katalin Hodosi, Attila C Nagy, Judit Barta, Attila Borbély, Zoltán Csanádi","doi":"10.1007/s40119-023-00346-1","DOIUrl":"10.1007/s40119-023-00346-1","url":null,"abstract":"<p><strong>Introduction: </strong>Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy.</p><p><strong>Methods: </strong>CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared.</p><p><strong>Results: </strong>A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II.</p><p><strong>Conclusion: </strong>SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"149-161"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-02-13DOI: 10.1007/s40119-024-00354-9
Roos A Groen, J Wouter Jukema, Paul R M van Dijkman, Jeroen J Bax, Hildo J Lamb, M Louisa Antoni, Michiel A de Graaf
To enhance risk stratification in patients suspected of coronary artery disease, the assessment of coronary artery calcium (CAC) could be incorporated, especially when CAC can be readily assessed on previously performed non-gated chest computed tomography (CT). Guidelines recommend reporting on patients' extent of CAC on these non-cardiac directed exams and various studies have shown the diagnostic and prognostic value. However, this method is still little applied, and no current consensus exists in clinical practice. This review aims to point out the clinical utility of different kinds of CAC assessment on non-gated CTs. It demonstrates that these scans indeed represent a merely untapped and underestimated resource for risk stratification in patients with stable chest pain or an increased risk of cardiovascular events. To our knowledge, this is the first review to describe the clinical utility of different kinds of visual CAC evaluation on non-gated unenhanced chest CT. Various methods of CAC assessment on non-gated CT are discussed and compared in terms of diagnostic and prognostic value. Furthermore, the application of these non-gated CT scans in the general practice of cardiology is discussed. The clinical utility of coronary calcium assessed on non-gated chest CT, according to the current literature, is evident. This resource of information for cardiac risk stratification needs no specific requirements for scan protocol, and is radiation-free and cost-free. However, some gaps in research remain. In conclusion, the integration of CAC on non-gated chest CT in general cardiology should be promoted and research on this method should be encouraged.
{"title":"The Clear Value of Coronary Artery Calcification Evaluation on Non-Gated Chest Computed Tomography for Cardiac Risk Stratification.","authors":"Roos A Groen, J Wouter Jukema, Paul R M van Dijkman, Jeroen J Bax, Hildo J Lamb, M Louisa Antoni, Michiel A de Graaf","doi":"10.1007/s40119-024-00354-9","DOIUrl":"10.1007/s40119-024-00354-9","url":null,"abstract":"<p><p>To enhance risk stratification in patients suspected of coronary artery disease, the assessment of coronary artery calcium (CAC) could be incorporated, especially when CAC can be readily assessed on previously performed non-gated chest computed tomography (CT). Guidelines recommend reporting on patients' extent of CAC on these non-cardiac directed exams and various studies have shown the diagnostic and prognostic value. However, this method is still little applied, and no current consensus exists in clinical practice. This review aims to point out the clinical utility of different kinds of CAC assessment on non-gated CTs. It demonstrates that these scans indeed represent a merely untapped and underestimated resource for risk stratification in patients with stable chest pain or an increased risk of cardiovascular events. To our knowledge, this is the first review to describe the clinical utility of different kinds of visual CAC evaluation on non-gated unenhanced chest CT. Various methods of CAC assessment on non-gated CT are discussed and compared in terms of diagnostic and prognostic value. Furthermore, the application of these non-gated CT scans in the general practice of cardiology is discussed. The clinical utility of coronary calcium assessed on non-gated chest CT, according to the current literature, is evident. This resource of information for cardiac risk stratification needs no specific requirements for scan protocol, and is radiation-free and cost-free. However, some gaps in research remain. In conclusion, the integration of CAC on non-gated chest CT in general cardiology should be promoted and research on this method should be encouraged.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"69-87"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-02-21DOI: 10.1007/s40119-024-00353-w
Henriette Thau, Sebastian Neuber, Maximilian Y Emmert, Timo Z Nazari-Shafti
Numerous genetic and epidemiologic studies have demonstrated an association between elevated levels of lipoprotein(a) (Lp[a]) and cardiovascular disease. As a result, lowering Lp(a) levels is widely recognized as a promising strategy for reducing the risk of new-onset coronary heart disease, stroke, and heart failure. Lp(a) consists of a low-density lipoprotein-like particle with covalently linked apolipoprotein A (apo[a]) and apolipoprotein B-100, which explains its pro-thrombotic, pro-inflammatory, and pro-atherogenic properties. Lp(a) serum concentrations are genetically determined by the apo(a) isoform, with shorter isoforms having a higher rate of particle synthesis. To date, there are no approved pharmacological therapies that effectively reduce Lp(a) levels. Promising treatment approaches targeting apo(a) expression include RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran, which are currently in clinical trials. In this comprehensive review, we provide a detailed overview of RNA-based therapeutic approaches and discuss the recent advances and challenges of RNA therapeutics specifically designed to reduce Lp(a) levels and thus the risk of cardiovascular disease.
{"title":"Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?","authors":"Henriette Thau, Sebastian Neuber, Maximilian Y Emmert, Timo Z Nazari-Shafti","doi":"10.1007/s40119-024-00353-w","DOIUrl":"10.1007/s40119-024-00353-w","url":null,"abstract":"<p><p>Numerous genetic and epidemiologic studies have demonstrated an association between elevated levels of lipoprotein(a) (Lp[a]) and cardiovascular disease. As a result, lowering Lp(a) levels is widely recognized as a promising strategy for reducing the risk of new-onset coronary heart disease, stroke, and heart failure. Lp(a) consists of a low-density lipoprotein-like particle with covalently linked apolipoprotein A (apo[a]) and apolipoprotein B-100, which explains its pro-thrombotic, pro-inflammatory, and pro-atherogenic properties. Lp(a) serum concentrations are genetically determined by the apo(a) isoform, with shorter isoforms having a higher rate of particle synthesis. To date, there are no approved pharmacological therapies that effectively reduce Lp(a) levels. Promising treatment approaches targeting apo(a) expression include RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran, which are currently in clinical trials. In this comprehensive review, we provide a detailed overview of RNA-based therapeutic approaches and discuss the recent advances and challenges of RNA therapeutics specifically designed to reduce Lp(a) levels and thus the risk of cardiovascular disease.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"39-67"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Trinidad & Tobago has the highest prevalence of cardiovascular disease (CVD) in the Caribbean and clopidogrel is a ubiquitously used treatment. Yet, the extent of genetically mediated clopidogrel resistance is unknown. To determine this, we investigated whether the association between CYP2C19*2 and CYP2C19*3 genetic variants and clopidogrel resistance holds, and calculated the frequencies of these in the Trinidadian CVD population.
Methods: Demographic data, clinical data, and a saliva sample were collected under informed consent from 22 patients with CVD on dual anti-platelet therapy whose biochemical resistance to clopidogrel is known, and a further 162 patients accessing the main public CVD clinic in Trinidad and who are either currently being treated or are likely to be treated with clopidogrel. A polymerase chain reaction (PCR) and restriction enzyme digestion procedure was used to genotype each patient for the CYP2C19*2 and CYP2C19*3 allelic variants. Genotype was compared to known clopidogrel resistance in the 22 patients, and to disease status and clopidogrel usage in the larger cohort.
Results: CYP2C19*2 genotype was concordant with clopidogrel resistance. CYP2C19*2 was detected in 61.1% (99/162) of patients and CYP2C19*3 was undetected. Clopidogrel was the most prescribed antiplatelet therapy (42%). A total of 120 people presented with coronary artery disease (CAD) and 52.5% of these (n = 63/120) are currently prescribed clopidogrel. 63.5% (40/63) of patients with CAD who are prescribed clopidogrel carry the CYP2C19*2 allele; ten homozygous and 30 heterozygous. Indian patients comprised 65% of the cohort and were four times more likely to carry the CYP2C19*2 allele than African patients.
Conclusions: A large proportion of Trinidadian patients with CVD who are prescribed or may be prescribed clopidogrel carry genetic variants associated with clopidogrel resistance. These results emphasize the clinical need for further investigation into whether CYP2C19*2 genotype should guide clopidogrel use for the cardiovascular disease population in Trinidad & Tobago. A slide deck is available for this article.
{"title":"Prevalence of CYP2C19*2 and CYP2C19*3 Allelic Variants and Clopidogrel Use in Patients with Cardiovascular Disease in Trinidad & Tobago.","authors":"Daniele Jones, Shana Persad-Ramdeensingh, Sheherazade Crystal Abrahim, Naveen Seecheran, Rajini Rani Haraksingh","doi":"10.1007/s40119-024-00348-7","DOIUrl":"10.1007/s40119-024-00348-7","url":null,"abstract":"<p><strong>Introduction: </strong>Trinidad & Tobago has the highest prevalence of cardiovascular disease (CVD) in the Caribbean and clopidogrel is a ubiquitously used treatment. Yet, the extent of genetically mediated clopidogrel resistance is unknown. To determine this, we investigated whether the association between CYP2C19*2 and CYP2C19*3 genetic variants and clopidogrel resistance holds, and calculated the frequencies of these in the Trinidadian CVD population.</p><p><strong>Methods: </strong>Demographic data, clinical data, and a saliva sample were collected under informed consent from 22 patients with CVD on dual anti-platelet therapy whose biochemical resistance to clopidogrel is known, and a further 162 patients accessing the main public CVD clinic in Trinidad and who are either currently being treated or are likely to be treated with clopidogrel. A polymerase chain reaction (PCR) and restriction enzyme digestion procedure was used to genotype each patient for the CYP2C19*2 and CYP2C19*3 allelic variants. Genotype was compared to known clopidogrel resistance in the 22 patients, and to disease status and clopidogrel usage in the larger cohort.</p><p><strong>Results: </strong>CYP2C19*2 genotype was concordant with clopidogrel resistance. CYP2C19*2 was detected in 61.1% (99/162) of patients and CYP2C19*3 was undetected. Clopidogrel was the most prescribed antiplatelet therapy (42%). A total of 120 people presented with coronary artery disease (CAD) and 52.5% of these (n = 63/120) are currently prescribed clopidogrel. 63.5% (40/63) of patients with CAD who are prescribed clopidogrel carry the CYP2C19*2 allele; ten homozygous and 30 heterozygous. Indian patients comprised 65% of the cohort and were four times more likely to carry the CYP2C19*2 allele than African patients.</p><p><strong>Conclusions: </strong>A large proportion of Trinidadian patients with CVD who are prescribed or may be prescribed clopidogrel carry genetic variants associated with clopidogrel resistance. These results emphasize the clinical need for further investigation into whether CYP2C19*2 genotype should guide clopidogrel use for the cardiovascular disease population in Trinidad & Tobago. A slide deck is available for this article.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"191-203"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-02-02DOI: 10.1007/s40119-024-00352-x
João Presume, Jorge Ferreira, Regina Ribeiras
Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factor XI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factor XI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factor XI inhibition as a therapeutic target; (iii) an exploration of the various types of factor XI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.
抗凝疗法经历了重大演变,其标志是具有独特优势的直接口服抗凝剂的出现。尽管取得了这些进步,但在管理残余血栓和出血风险方面仍存在挑战,尤其是在易感人群中。对替代药物的追求已聚焦于因子 XI/XIa 抑制剂。本综述深入探讨了有关这一新靶点的几个关键方面:(i) XI 因子在凝血级联中的作用;(ii) 支持将 XI 因子抑制作为治疗靶点的遗传学证据和病理生理学原理;(iii) 探讨目前正在研究的各类 XI/XIa 因子抑制剂;(iv) 这些药物的潜在应用,包括矫形手术后的血栓预防、心房颤动的中风预防、急性冠状动脉综合征后的二级预防、非心肌栓塞性中风、异物植入后的血栓预防、终末期肾病和癌症患者;以及 (v) 正在进行的研究、最新发现和这些药物的未来研究轨迹概述。
{"title":"Factor XI Inhibitors: A New Horizon in Anticoagulation Therapy.","authors":"João Presume, Jorge Ferreira, Regina Ribeiras","doi":"10.1007/s40119-024-00352-x","DOIUrl":"10.1007/s40119-024-00352-x","url":null,"abstract":"<p><p>Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factor XI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factor XI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factor XI inhibition as a therapeutic target; (iii) an exploration of the various types of factor XI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"1-16"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan.
Methods: We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks.
Results: Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96-27.11) at baseline and 1.21 (0.45-6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy.
Conclusion: The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.
{"title":"Real-World Safety and Effectiveness of a 4-Factor Prothrombin Complex Concentrate in Japanese Patients Experiencing Major Bleeding: A Post-marketing Surveillance Study.","authors":"Masahiro Yasaka, Michiyasu Suzuki, Shigeki Kushimoto, Ayako Kiyonaga, Antoinette Mangione, Yuki Niwa, Naoki Terasaka","doi":"10.1007/s40119-024-00357-6","DOIUrl":"10.1007/s40119-024-00357-6","url":null,"abstract":"<p><strong>Introduction: </strong>Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan.</p><p><strong>Methods: </strong>We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks.</p><p><strong>Results: </strong>Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96-27.11) at baseline and 1.21 (0.45-6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy.</p><p><strong>Conclusion: </strong>The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"221-232"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01Epub Date: 2024-01-23DOI: 10.1007/s40119-024-00350-z
Sophia Calcara, Amanda Paeltz, Bernadette Richards, Tracey Sisk, Corey Stiver, Oluseyi Ogunleye, Karen Texter, May Ling Mah, Clifford L Cua
Introduction: Fetal echocardiograms (F-echo) are recommended in all pregnancies when maternal congenital heart disease (CHD) is present, even if there was a prior level II ultrasound (LII-US) that was normal. The goal of this study was to evaluate if any diagnosis of a critical CHD was missed in a fetus with maternal CHD who had a normal LII-US.
Methods: A retrospective chart review of all F-echoes where the indication was maternal CHD between 1/1/2015 to 12/31/2022 was performed. Fetuses were included if they had a LII-US that was read as normal and had an F-echo. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age.
Results: A total of 296 F-echoes on fetuses with maternal CHD were evaluated, of which 175 met inclusion criteria. LII-US was performed at 19.8 ± 2.9 weeks gestational age and F-echo was performed at 24.2 ± 2.8 weeks gestational age. No patient with a normal LII-US had a diagnosis of a critical CHD by F-echo (negative predictive value = 100%). Evaluating those patients that had a negative LII-US, ten patients were diagnosed with non-critical CHD postnatally (negative predictive value = 94.3%). F-echo correctly diagnosed two of the ten missed LII-US CHD.
Conclusions: Critical CHD was not missed with a normal LII-US in this at risk population. F-echo also missed the majority of CHD when a LII-US was read as normal. A cost-benefit analysis of screening F-echo in fetuses with maternal CHD should be conducted if a normal LII-US has been performed.
{"title":"The Utility of Screening Fetal Echocardiograms Following Normal Level II Ultrasounds in Fetuses with Maternal Congenital Heart Disease.","authors":"Sophia Calcara, Amanda Paeltz, Bernadette Richards, Tracey Sisk, Corey Stiver, Oluseyi Ogunleye, Karen Texter, May Ling Mah, Clifford L Cua","doi":"10.1007/s40119-024-00350-z","DOIUrl":"10.1007/s40119-024-00350-z","url":null,"abstract":"<p><strong>Introduction: </strong>Fetal echocardiograms (F-echo) are recommended in all pregnancies when maternal congenital heart disease (CHD) is present, even if there was a prior level II ultrasound (LII-US) that was normal. The goal of this study was to evaluate if any diagnosis of a critical CHD was missed in a fetus with maternal CHD who had a normal LII-US.</p><p><strong>Methods: </strong>A retrospective chart review of all F-echoes where the indication was maternal CHD between 1/1/2015 to 12/31/2022 was performed. Fetuses were included if they had a LII-US that was read as normal and had an F-echo. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age.</p><p><strong>Results: </strong>A total of 296 F-echoes on fetuses with maternal CHD were evaluated, of which 175 met inclusion criteria. LII-US was performed at 19.8 ± 2.9 weeks gestational age and F-echo was performed at 24.2 ± 2.8 weeks gestational age. No patient with a normal LII-US had a diagnosis of a critical CHD by F-echo (negative predictive value = 100%). Evaluating those patients that had a negative LII-US, ten patients were diagnosed with non-critical CHD postnatally (negative predictive value = 94.3%). F-echo correctly diagnosed two of the ten missed LII-US CHD.</p><p><strong>Conclusions: </strong>Critical CHD was not missed with a normal LII-US in this at risk population. F-echo also missed the majority of CHD when a LII-US was read as normal. A cost-benefit analysis of screening F-echo in fetuses with maternal CHD should be conducted if a normal LII-US has been performed.</p>","PeriodicalId":9561,"journal":{"name":"Cardiology and Therapy","volume":" ","pages":"163-171"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}