The Dynamic and Multifaceted Nature of Cardiovascular Disease and Using Genetic Testing to Inform Clinical Care: An International Perspective

Introduction: Atorvastatin is commonly prescribed to prevent cardiovascular disease; however, long-term adherence can be eroded by statin associated musculoskeletal symptoms (SAMS). Genetic variants in SLCO1B1 are associated with SAMS in patients using simvastatin; the association of these variants with adherence or SAMS has been less well characterized for atorvastatin. Methods: We tested the association between a loss of function genetic variant in SLCO1B1 and atorvastatin discontinuation in a large multi-specialty group practice. Using the electronic medical record (EMR) at Sanford Health, we defined a retrospective cohort of 8453 patients who were tested for SLCO1B1*5 (rs4149056, Val174Ala) through routine clinical care. Patients were included if they had received an atorvastatin prescription prior to genetic testing and had valid SLCO1B1 results. Patients were classified as discontinued (or not) based on their active medication list at the time of genetic testing. Clinical characteristics including demographics, diagnosis codes, smoking status, concomitant medications, and laboratory values for renal function and all creatine kinase (CK) values prior to testing, were extracted from the EMR. A Kruskal-Wallis test was used to compare longitudinal CK values vs. discontinuation. Logistic regression was used to test the relationship between SLCO1B1*5 and atorvastatin discontinuation for any reason. Results: There were 1752 patients available for analysis (mean age 64 years, 44% female, 2% non-Caucasian, 89% primary prevention indication). 1025 (58%) discontinued atorvastatin prior to SLCO1B1 testing. The number of SLCO1B1*5 alleles was associated with atorvastatin discontinuation (odds ratio per allele = 1.22, 95% confidence interval = 1.004 - 1.47, p = 0.04). Among the 495 patients with available CK levels, atorvastatin discontinuation was associated with higher mean CK levels than those who continued (Kruskal-Wallis test, p = 0.02). Conclusions: Atorvastatin discontinuation is common in real world patients at risk for cardiovascular disease. Carriers of SLCO1B1*5 are at increased risk for premature atorvastatin discontinuation - an effect which may reflect an excess risk of statin myopathy.

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A framework for the evaluation of patients with congenital facial weakness

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01736-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Bryn D. Webb ◽

Irini Manoli ◽

Elizabeth C. Engle ◽

Ethylin W. Jabs

Keyword(s):

Genetic Counseling ◽

Genetic Testing ◽

Patient Population ◽

Clinical Care ◽

Diagnostic Algorithm ◽

Accurate Diagnosis ◽

Facial Weakness ◽

The Core ◽

Follow Up Studies

AbstractThere is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.

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Challenges in genetic testing: clinician variant interpretation processes and the impact on clinical care

Genetics in Medicine ◽

10.1038/s41436-021-01267-x ◽

2021 ◽

Author(s):

Courtney Berrios ◽

Emily A. Hurley ◽

Laurel Willig ◽

Isabelle Thiffault ◽

Carol Saunders ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Care ◽

Variant Interpretation ◽

The Impact

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Management of Hypertension: A Bangladeshi Perspective

Bangladesh Medical Journal ◽

10.3329/bmj.v39i1.6232 ◽

1970 ◽

Vol 39 (1) ◽

pp. 40-43

Author(s):

SM Mustafa Zaman ◽

Mohammad Salman ◽

Kaniz Fatema

Keyword(s):

Cardiovascular Disease ◽

Fruits And Vegetables ◽

Lifestyle Modification ◽

Clinical Care ◽

Cost Effective ◽

Developed Countries ◽

Population Based ◽

Lifestyle Changes ◽

Optimum Level ◽

Lifestyle Modifications

Hypertension is a silent killer. Bangladeshis are racially predisposed to cardiovascular disease, and the increasing burden of hypertension has only added to the problem. Economic constraints and the allure of additional benefits without adverse effects have made lifestyle modifications an attractive proposition in developing and developed countries alike. Blood pressure is a continuum and any increase above optimum level confers additional independent risk of cardiovascular disease. We review screening, diagnosis and management using lifestyle measures and pharmacotherapy. We then discuss the barriers and challenges to implementing this approach and what can be done regarding prevention, screening, lifestyle modification and pharmacotherapy in our country. By adopting a comprehensive population based approach including policy level interventions directed at promoting lifestyle changes; a healthy diet (appropriate calories, low in saturated fats and salt and rich in fruits and vegetables), increased physical activity, and a smoking free society, properly balanced with a high risk approach of cost effective clinical care, Bangladesh can effectively control hypertension and improve public health. DOI: 10.3329/bmj.v39i1.6232 Bangladesh Medical Journal 2010; 39(1): 40-43

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Reference Standards for Cardiorespiratory Fitness by Cardiovascular Disease Category and Testing Modality: Data From FRIEND

Journal of the American Heart Association ◽

10.1161/jaha.121.022336 ◽

2021 ◽

Author(s):

James E. Peterman ◽

Ross Arena ◽

Jonathan Myers ◽

Susan Marzolini ◽

Philip A. Ades ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiorespiratory Fitness ◽

Clinical Care ◽

Cardiopulmonary Exercise Testing ◽

Age Groups ◽

Reference Standards ◽

National Database ◽

Disease Category ◽

Men And Women ◽

The Mean

Background The importance of cardiorespiratory fitness for stratifying risk and guiding clinical decisions in patients with cardiovascular disease is well‐established. To optimize the clinical value of cardiorespiratory fitness, normative reference standards are essential. The purpose of this report is to extend previous cardiorespiratory fitness normative standards by providing updated cardiorespiratory fitness reference standards according to cardiovascular disease category and testing modality. Methods and Results The analysis included 15 045 tests (8079 treadmill, 6966 cycle) from FRIEND (Fitness Registry and the Importance of Exercise National Database). Using data from tests conducted January 1, 1974, through March 1, 2021, percentiles of directly measured peak oxygen consumption (VO 2peak ) were determined for each decade from 30 through 89 years of age for men and women with a diagnosis of coronary artery bypass surgery, myocardial infarction, percutaneous coronary intervention, or heart failure. There were significant differences between sex and age groups for VO 2peak ( P <0.001). The mean VO 2peak was 23% higher for men compared with women and VO 2peak decreased by a mean of 7% per decade for both sexes. Among each decade, the mean VO 2peak from treadmill tests was 21% higher than the VO 2peak from cycle tests. Differences in VO 2peak were observed among the age groups in both sexes according to cardiovascular disease category. Conclusions This report provides normative reference standards by cardiovascular disease category for both men and women performing cardiopulmonary exercise testing on a treadmill or cycle ergometer. These updated and enhanced reference standards can assist with patient risk stratification and guide clinical care.

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Új lehetőség a szisztolés szívelégtelenség (HFrEF) kezelésében: omecamtiv-mecarbil

Cardiologia Hungarica ◽

10.26430/chungarica.2021.51.2.118 ◽

2021 ◽

Vol 51 (2) ◽

pp. 118-124

Author(s):

Arnold Péter Ráduly ◽

Attila Tóth ◽

Zoltán Papp ◽

Attila Borbély

Keyword(s):

Genetic Testing ◽

Expert Panel ◽

Clinical Care ◽

Cardiovascular Disorder ◽

Chain Gene ◽

Web Based ◽

Inherited Cardiomyopathy ◽

Omecamtiv Mecarbil ◽

Next Generation Sequencing Ngs ◽

Population Databases

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder worldwide which exhibits considerable genetic heterogeneity. Widespread utilization of next-generation sequencing (NGS) in HCM has uncovered substantial genetic variation and highlighted the importance of a standardized approach to variant interpretation. According to this, accurate and consistent interpretation of sequence variants is essential for effective clinical care for individuals and their families with HCM. With this regard, the 2015 guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) were widely applicable, but several elements lacked specificity for given genes or diseases. The latter guideline was adapted for the most frequent causative HCM gene, the beta myosin heavy chain gene (MYH7) by the ClinGen (Clinical Genome Resource) expert panel, the Inherited Cardiomyopathy Expert Panel. Due to the adaptation, the guideline became gene-specific, with general considerations which are widely adaptable for most of the causative genes in HCM. Based on the modified guideline, web-based interpretation algorithms have been developed which integrate data from population databases and define pathogenicity of different variants independent of the observer, therefore aiding standardized clinical interpretation of genetic testing. The latter approach serves as a basis for recommendation for genetic testing in the recent ACC/AHA HCM guideline published in 2020. The current review is meant to compile the latest advances in HCM genetic testing in clinical practice, while bringing into focus some of the ongoing challenges clinical geneticists are still facing. Although nowadays the interpretation of genetic findings is two steps closer to a more accurate approach due to gene adaptation and automatization, the multitude of putative causative genes have been once again reduced to the 8 sarcomere genes, a backward step.

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Indications for genetic testing in athletes and its application in daily practice

The ESC Textbook of Sports Cardiology ◽

10.1093/med/9780198779742.003.0020 ◽

2019 ◽

pp. 166-176

Author(s):

Andrea Mazzanti ◽

Katherine Underwood ◽

Silvia G. Priori

Keyword(s):

Cardiovascular Disease ◽

Genetic Testing ◽

Genetic Information ◽

Cardiac Death ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Daily Practice ◽

Polymorphic Ventricular Tachycardia ◽

Molecular Testing ◽

Long Qt ◽

Qt Syndrome

Genetic information is fundamental for the management of patients with primary arrhythmia syndromes (e.g. long QT syndrome or catecholaminergic polymorphic ventricular tachycardia) and cardiomyopathies (e.g. arrhythmogenic right ventricular cardiomyopathy or hypertrophic cardiomyopathy) which increase the risk of sudden cardiac death. Importantly, molecular testing can play a pivotal role in establishing a clinical diagnosis of an inherited cardiovascular disease, particularly when the phenotype in unclear and overlaps with the normal adaptations induced in the heart by chronic exercise. However, the decision to undergo genetic testing needs to be justified on a clinical basis and handled by professionals who are capable of framing the results in the correct perspective. In this chapter we will answer the following questions. When should genetic testing be performed in athletes? Which genetic tests should be requested for athletes? What impact should a positive genetic result have on sports eligibility?

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Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance

Life ◽

10.3390/life10040032 ◽

2020 ◽

Vol 10 (4) ◽

pp. 32

Author(s):

Katherine M. Spiech ◽

Purnima R. Tripathy ◽

Alex M. Woodcock ◽

Nehal A. Sheth ◽

Kimberly S. Collins ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Care ◽

Further Education ◽

Supporting Evidence ◽

Health Initiative ◽

Knowledge And Attitude ◽

Antihypertensive Response ◽

Clinician Attitudes ◽

Precision Health ◽

Strong Agreement

A precision health initiative was implemented across a multi-hospital health system, wherein a panel of genetic variants was tested and utilized in the clinical care of chronic kidney disease (CKD) patients. Pharmacogenomic predictors of antihypertensive response and genomic predictors of CKD were provided to clinicians caring for nephrology patients. To assess clinician knowledge, attitudes, and willingness to act on genetic testing results, a Likert-scale survey was sent to and self-administered by these nephrology providers (N = 76). Most respondents agreed that utilizing pharmacogenomic-guided antihypertensive prescribing is valuable (4.0 ± 0.7 on a scale of 1 to 5, where 5 indicates strong agreement). However, the respondents also expressed reluctance to use genetic testing for CKD risk stratification due to a perceived lack of supporting evidence (3.2 ± 0.9). Exploratory sub-group analyses associated this reluctance with negative responses to both knowledge and attitude discipline questions, thus suggesting reduced exposure to and comfort with genetic information. Given the evolving nature of genomic implementation in clinical care, further education is warranted to help overcome these perception barriers.

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Low‐Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events

Journal of the American Heart Association ◽

10.1161/jaha.119.016318 ◽

2020 ◽

Vol 9 (23) ◽

Author(s):

Peter Willeit ◽

Calvin Yeang ◽

Patrick M. Moriarty ◽

Lena Tschiderer ◽

Stephen A. Varvel ◽

...

Keyword(s):

Cardiovascular Disease ◽

Clinical Care ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cholesterol Content ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Lipoprotein A ◽

The Impact

Background Conventional "low‐density lipoprotein cholesterol (LDL‐C)" assays measure cholesterol content in both low‐density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of “LDL‐C” and corrected LDL‐C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline‐recommended LDL‐C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from “LDL‐C” to obtain corrected LDL‐C values (LDL‐C corr30 ). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual‐patient‐data meta‐analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow‐up). When comparing top versus bottom quartiles, the multivariable‐adjusted hazard ratio for cardiovascular disease was significant for “LDL‐C” (1.17; 95% CI, 1.05–1.31; P =0.005) but not for LDL‐C corr30 (1.07; 95% CI, 0.93–1.22; P =0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline‐recommended LDL‐C categories when using LDL‐C corr30 was assessed. In “LDL‐C” categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL‐C categories when LDL‐C corr30 was used: 30.2% (30.0%–30.4%), 35.1% (34.9%–35.4%), 32.9% (32.6%–33.1%), and 41.1% (40.0%–42.2%), respectively. Conclusions “ LDL‐C” was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL‐C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

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Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease

Cardiovascular Research ◽

10.1093/cvr/cvaa021 ◽

2020 ◽

Vol 116 (13) ◽

pp. 2040-2054 ◽

Cited By ~ 5

Author(s):

Evangelos K Oikonomou ◽

Musib Siddique ◽

Charalambos Antoniades

Keyword(s):

Artificial Intelligence ◽

Cardiovascular Disease ◽

Computational Models ◽

Cardiac Computed Tomography ◽

Clinical Care ◽

Cardiovascular Imaging ◽

Current Status ◽

Current Evidence ◽

Scientific Validity ◽

Non Invasive

Abstract Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.

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