Current barriers and recommendations on the diagnosis of transthyretin amyloid cardiomyopathy: a Delphi study.

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases. Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option. Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM. Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update.

Background: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice. Objectives: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management. Methods: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper. Results: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab. Conclusions: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. METHODS: We performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. RESULTS: Probable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18-29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. CONCLUSIONS: This nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Paediatric familial hypercholesterolaemia screening in Europe: public policy background and recommendations.

Familial hypercholesterolaemia (FH) is under-recognized and under-treated in Europe leading to significantly higher risk for premature heart disease in those affected. As treatment beginning early in life is highly effective in preventing heart disease and cost-effective in these patients, screening for FH is crucial. It has therefore now been recognized by the European Commission Public Health Best Practice Portal as an effective strategy. Model programmes exist in Europe to identify young individuals with FH, which are based on cascade screening of first-degree relatives of affected individuals, universal screening for high cholesterol, opportunistic screening of high-risk individuals, or a combination of the above approaches. Recommendations presented herein to improve identification of FH emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system, governments should provide financial support for these programmes and related care, and further research to optimize care and implementations should be conducted.

Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement.

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

The functional and structural evaluation of small fibers in asymptomatic carriers of TTR p.Val50Met (Val30Met) mutation.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Diet, Lifestyle, Smoking.

Cardiovascular disease is the leading cause of death globally The past few decades have shown that especially low- and middle-income countries have undergone rapid industrialization, urbanization, economic development and market globalization. Although these developments led to many positive changes in health outcomes and increased life expectancies, they all also caused inappropriate dietary patterns, physical inactivity and obesity. Evidence shows that a large proportion of the cardiovascular disease burden can be explained by behavioural factors such as low physical activity, unhealthy diet and smoking. Controlling these risk factors from early ages is important for maintaining cardiovascular health. Even in patients with genetic susceptibility to cardiovascular disease, risk factor modification is beneficial.Despite the tremendous advances in the medical treatment of cardiovascular risk factors to reduce overall cardiovascular risk, the modern lifestyle which has led to greater sedentary time, lower participation in active transport and time spent in leisure or purposeful physical activity, unhealthy diets and increased exposure to stress, noise and pollution have diminished the beneficial effects of contemporary medical cardiovascular prevention strategies. Therefore attenuating or eliminating these health risk behaviours and risk factors is imperative in the prevention of cardiovascular diseases.

Familial Hypercholesterolemia: Global Burden and Approaches.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is the most common genetic metabolic disorder characterized by markedly elevated LDL-C levels from birth leading to atherosclerotic cardiovascular disease (ASCVD) and premature deaths. The purpose of this review is to share the current knowledge in the diagnosis, risk estimation, and management of patients with FH in the light of recent evidence and guideline recommendations. RECENT FINDINGS: Recent registries underscored the prevalence of FH as 1/200-250 translating to an almost 1500 million subjects suffering from FH worldwide. However, only a minority of FH patients are identified early and effectively treated. In most cases, mutations in the LDL-receptor (LDLR) gene and to a lesser degree in the apolipoprotein B-100 (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL-receptor adaptor protein 1 (LDLRAP1) genes cause FH. Diagnostic scores such as Dutch Lipid Clinic Network criteria using clinical manifestations are helpful in identifying FH. Traditional risk factors and high lipoprotein(a) affect the course of the disease. Vascular ultrasound imaging and coronary calcium scoring are helpful for further risk estimation of these patients. Getting to LDL-C goals is possible with currently available treatments including statins, ezetimibe, and PCSK9 inhibitors, as well as lipoprotein apheresis, lomitapide, and mipomersen in more severe phenotypes. Additionally, novel agents bempedoic acid, inclisiran, and evinacumab expanded the treatment choices for some patients with FH. Early diagnosis and initiation of LDL-C lowering are still required to achieve the greatest reduction in ASCVD morbidity and mortality in patients with FH. FH is a common genetic disorder characterized by markedly elevated LDL-C levels from birth onward, resulting in significantly increased risk for ASCVD. Despite major advances in our understanding of the disease and effective therapies, FH is still underdiagnosed and undertreated. Early initiation of LDL-C lowering by increased awareness of FH among the healthcare professionals, patients, and the public is necessary to achieve meaningful reduction in ASCVD morbidity and mortality in these patients.

The landscape of preventive cardiology in Turkey: Challenges and successes.

Turkey, like many countries, is facing a growing burden of non-communicable disease (NCD)s and is among the countries with high cardiovascular mortality in Europe. Moreover, Turkey currently has the highest rate of premature cardiovascular disease (CVD) in Europe. During the last decades, Turkey made fundamental reforms in the health system to improve the treatment of risk factors to prevent CVD. The most outstanding success was in the area of tobacco control (13.4% decrease in smoking prevalence) and decreasing the salt consumption of the population (from 18 to 9.9 g/day) leading to a significant decrease in CVD mortality from 45% to 36.8% of all deaths. However, obesity and diabetes are increasing rapidly as a result of urbanization, low physical activity and unhealthy eating and the new generation is starting to take up smoking. The increase in cardiometabolic risk factors and aging of the population are expected to increase the number of CVD deaths. All CVD risk factors except smoking are significantly more prevalent in women. In addition, rare disease is a country specific problem with a significant contribution to the high rates of premature CVD in Turkey. Despite major improvements in management in acute coronary syndromes, sustained achievement in guideline recommended goals is suboptimal. In patients with a previous cardiovascular event smoking rate is 25.5%, 80.9% of these patients are overweight (BMI ≥25 kg/m2), 30% obese (BMI ≥30 kg/m2), and LDL-cholesterol targets of 70 mg/dL are attained in only 18%. Herein, we scrutinize the achievements and challenges of Turkey in establishing a 'National Heart Health Policy' aiming to decrease the burden of CVD and its risk factors.

Correlation of vascular risk age with pulse wave velocity in young patients with low absolute cardiovascular risk.

OBJECTIVE: The systematic coronary risk evaluation (SCORE) estimates the 10-year risk of fatal cardiovascular disease (CVD), and its application is recommended. The absolute risk of CVD, independent of risk factors, is relatively low in young individuals. Expressing the risk as their "risk age" may aid in understanding the risk. This study aimed to demonstrate a possible correlation between vascular risk age, SCORE risk value, and the level of subclinical atherosclerosis evaluated using a pulse wave velocity (PWV) device. METHODS: This work was designed to be a cross-sectional study. The SCORE 10-year fatal CVD risk and vascular risk age were calculated for patients below the age of 50 years and without any previous diagnosis of atherosclerotic disease or equivalents. The PWV of each patient was measured non-invasively using a PWV device. RESULTS: The study population included a total of 300 patients with a mean age of 35.1±9.5 years. The mean PWV and mean vascular age of the entire study population were 6.3±1.3 m/s and 44.3±5.5 years, respectively, and the median 10-year risk of fatal CVD score was 0.4 (0.04-2.74). There was a positive correlation between PWV and the 10-year risk of fatal CVD (r=0.613; P<0.001) and vascular risk age (r=0.684; P<0.001). CONCLUSION: Despite their young age and low to moderate 10-year risk of fatal CVD (<1%-5%) according to the SCORE chart, patients with a high vascular risk age were found to have high PWV values. These results show that calculations of vascular risk age might be used to assess the risk of fatal CVD in young patients and correlate with subclinical atherosclerosis.

Medical Treatment in Coronary Patients: Is there Still a Gender Gap? Results from European Society of Cardiology EUROASPIRE V Registry.

PURPOSE: This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). METHODS: Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80 years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6 months to < 2 years after hospitalization) was collected. RESULTS: Data was available for 8261 patients (25.8% women). Overall, no gender differences were observed in the prescription and use of cardioprotective medication like aspirin, beta-blockers, and ACE-I/ARBs (P > 0.01) at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P < 0.001). In contrast, at follow-up, women were more likely to use diuretics (31.5% vs. 39.5%; P < 0.001) and calcium channel blockers (21.2% vs. 28.8%; P < 0.001), whereas men were more likely to use anticoagulants (8.8% vs. 7.0%; P < 0.001). Overall, no gender differences were found in total daily dose intake (P > 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P < 0.001) or PCI (82.1% vs. 74.9%; P < 0.001) at follow-up. No gender differences were observed in prescribed (P = 0.10) and attended (P = 0.63) cardiac rehabilitation programs. CONCLUSION: The EUROASPIRE V results show only limited gender differences in the medical management of CHD patients. Current findings suggest growing awareness about risk in female CHD patients.

Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis.

BACKGROUND: Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS. METHODS: We consecutively recruited eligible subjects with moderate-severe CAS (n = 60), aortic sclerosis (ASc) (n = 49) and age and gender-matched control subjects (n = 48) in May 2016-December 2016. Plasma dietary and gut microbiota-related metabolite levels, namely choline, betaine, and trimethylamine N-oxide (TMAO), were measured using ultra-performance liquid chromatography-tandem mass spectroscopy method. Histopathological examinations were performed in patients that underwent aortic valve surgery. RESULTS: Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all p > 0.05). CAS patients had higher plasma choline levels compared to both control (p < 0.001) and ASc (p = 0.006). Plasma betaine and TMAO levels were similar (both p > 0.05). Compared to the lowest quartile choline levels (<11.15 µM), patients with the highest quartile choline levels (≥14.98 µM) had higher aortic valvular (p < 0.001) and mitral annular (p = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B ± SE:0.165 ± 0.060, p = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration (p < 0.001), neovascularization (p = 0.011), osseous metaplasia (p = 0.004), more severe tissue remodelling (p = 0.002) and calcification (p = 0.002). CONCLUSION: We found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.

Impact of the COVID-19 pandemic in patients with a previous history of premature myocardial infarction.

OBJECTIVES: The coronavirus-disease-2019 (COVID-19) pandemic has led to the restructuring of health-services to prioritize the treatment of COVID-19. The severe restrictions on daily life affected the management of chronic diseases. Patients with a previous history of premature myocardial infarction (MI) are a vulnerable group requiring frequent and continued medical attention both in the pandemic and non-pandemic era. The present study was conducted to provide insight into the impact of COVID-19 outbreak on heart-healthy lifestyle and management of patients with a history of premature MI. METHODS: This cross-sectional study included 170 consecutive patients with a history of premature MI who were already in regular follow-up in a tertiary out-patient prevention clinic before the pandemic. Inclusion criteria included age ≥18 years and being on regular follow up with the diagnosis of premature MI (documented MI before the age of 55 years) at least for one year. All patients were contacted by phone-call and replied to a 23-item questionnaire measuring the impact of the pandemic on the management, healthy lifestyle habits, and anxiety level. RESULTS: One patient died due to COVID-19 infection; therefore the analyses were conducted in 169 patients (age: 47.67 â€‹± â€‹11.84 years, 21.3% women). The median age at first MI was 39 (IQR 10) years and the median time elapsed since the first MI was 7 years (IQR 10). The study population was highly compliant with the follow-up visits (78.1%) and pharmacological therapy (97%) before the pandemic according to the medical files. The majority (82.2%) of the patients were aware that having a history of premature MI would increase the risk and harm of COVID-19. Anxiety level increased in 62.7% of the study patients. Overall, 65.7% of the patient group reported a disruption at least in ≥1 component(s) of healthy life-behaviors (non-compliance with the heart-healthy diet, an increase in alcohol intake, an increase in smoking, and/or reduced physical activity) since the emergence of the outbreak. The anxiety level (p â€‹= â€‹0.001) and the prevalence of appetite change (p â€‹< â€‹0.0001) and weight gain (p â€‹< â€‹0.0001) was lower in the lifestyle compliant group than the non-compliant group. Avoidance of seeking medical care was reported in 33.7% of the patients. Statin use was 99.4% before the pandemic and decreased to 89.9% (p â€‹< â€‹0.0001) â€‹despite the fact that medications were reimbursed and widely available. CONCLUSIONS: The COVID-19 pandemic significantly affected the heart-healthy lifestyle and anxiety levels of patients with a history of premature MI who were already in regular follow-up in a tertiary prevention clinic and led to significant avoidance of medical care. More rigorous follow-up, education, and reassurance of these patients with telemedicine are necessary for the prevention of further increase in their risk.