Publications by authors named "Sanjay K Prasad"

Background: Serial perfusion cardiovascular magnetic resonance (CMR) in symptomatic patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic abnormalities of the myocardium.

Objectives: To assess how changes in cardiac reperfusion and remodelling associate with symptom improvement in patients undergoing CABG METHODS: Patients awaiting elective CABG completed serial quality of life questionnaires and detailed CMR at baseline and at 6-12 months post CABG as per protocol. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden.

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Genetic family screening following the detection of a pathogenic or likely pathogenic variant in a proband with dilated cardiomyopathy (DCM) remains one of the main applications of genetic testing. While cardiac screening is recommended for all first-degree relatives, the a priori risk among family members varies. Consequently, screening regimens should be tailored according to both genetic and clinical information at the individual and familial level.

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Background: Inflammatory, myocarditis-like episodes precede and are associated with higher risk of sustained ventricular arrhythmias and heart failure in patients with pathogenic or likely pathogenic desmoplakin (DSP) variants. Whether the recurrence and treatment of myocarditis-like episodes influence the outcomes in this population is unknown. This study aimed to assess the prognostic impact of the recurrence and treatment of myocarditis-like episodes in patients with pathogenic or likely pathogenic DSP variants.

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Diabetes increases the risk of cardiovascular disease (CVD) due to its multi-scale and diverse effects on cardiomyocyte metabolism and function, the circulation, and the kidneys. The complex relationship between organ systems affected by diabetes and associated comorbidities leads to challenges in estimating cardiovascular risk and stratifying optimal treatment strategies at the individual patient level. Most recently, sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists have been shown to offer substantial cardiac benefits.

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The prediction and management of sudden cardiac death risk continue to pose significant challenges in cardiovascular care despite advances in therapies over the last two decades. Late gadolinium enhancement (LGE) on cardiac magnetic resonance-a marker of myocardial fibrosis-is a powerful non-invasive tool with the potential to aid the prediction of sudden death and direct the use of preventative therapies in several cardiovascular conditions. In this state-of-the-art review, we provide a critical appraisal of the current evidence base underpinning the utility of LGE in both ischaemic and non-ischaemic cardiomyopathies together with a focus on future perspectives and the role for machine learning and digital twin technologies.

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Purpose Of Review: Dilated cardiomyopathy is an important contributor to heart failure burden worldwide. With an aging population and rising multimorbidity, in this review, we describe the prevalence of metabolic syndrome and renal failure in patients with dilated cardiomyopathy and focus on common underlying mechanisms, evaluate outcomes in these patients and highlight newer therapeutic strategies.

Recent Findings: A significant proportion of patients with dilated cardiomyopathy has concomitant metabolic syndrome and renal disease.

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Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by the presence of left ventricular dilatation and systolic dysfunction unexplained by abnormal loading conditions or coronary artery disease. However, a broad range of phenotypic manifestations, encompassing isolated scar, DCM with preserved ejection fraction, and overt DCM, should be regarded as a diagnostic classification representing a broad spectrum of underlying aetiologies, including both inherited and acquired heart muscle disorders. A multimodal non-invasive imaging approach is essential for accurate morpho-functional assessment of cardiac chambers and is key to establish the cardiac phenotype and to rule out an underlying ischaemic aetiology.

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Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. Here, we report results from a large genome-wide association study and multitrait analysis including 5,900 HCM cases, 68,359 controls and 36,083 UK Biobank participants with cardiac magnetic resonance imaging. We identified 70 loci (50 novel) associated with HCM and 62 loci (20 novel) associated with relevant left ventricular traits.

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Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality, with pathogenic variants found in about a third of cases. Large-scale genome-wide association studies (GWAS) demonstrate that common genetic variation contributes to HCM risk. Here we derive polygenic scores (PGS) from HCM GWAS and genetically correlated traits and test their performance in the UK Biobank, 100,000 Genomes Project, and clinical cohorts.

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Dilated cardiomyopathy (DCM) is extensively discussed in numerous expert consensus documents and international guidelines, with differing recommendations. To support clinicians in daily practice and decision-making, we conducted a systematic review of key guidelines and recommendations concerning the diagnosis and clinical management of DCM. Our research encompassed MEDLINE and EMBASE databases for relevant articles published, as well as the websites of relevant scientific societies.

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Article Synopsis
  • Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
  • Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
  • The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
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Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis.

Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

Design, Setting, And Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia.

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Article Synopsis
  • Hypertrophic cardiomyopathy (HCM) is a diverse heart condition that can lead to severe health issues and traditionally managed through symptom relief and the use of defibrillators to prevent sudden cardiac death.
  • There is a recognized need for treatments that modify the disease itself, and recently, new therapies like mavacamten, a myosin inhibitor, have gained regulatory approval.
  • Clinical trials for HCM face unique challenges, which include selecting patients based on their genetic and symptom profiles, measuring outcomes effectively, and considering factors like trial duration and sample size when interpreting results.
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Aims: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal.

Methods And Results: TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months.

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Article Synopsis
  • Pathogenic variants in the desmoplakin (DSP) gene lead to a unique type of cardiomyopathy that doesn't fit neatly into existing categories like DCM, NDLVC, or ARVC, with limited past studies on potential predictors of severe outcomes.
  • Researchers analyzed 800 patients with DSP variants from a global network over an average of 3.7 years, finding that 17.4% experienced sustained ventricular arrhythmias (VAs) and 9.0% had heart failure (HF) hospitalizations.
  • Key risk factors for developing VAs included female sex, history of non-sustained and sustained VAs, and lower left ventricular ejection fraction, while T-wave inversion was linked to HF
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Background: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).

Objectives: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).

Methods: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF.

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Aims: To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF).

Methods And Results: We conducted a prospective observational cohort study of patients with DCM and LV ejection fraction (LVEF) ≥40% assessed by CMR, including feature-tracking to assess LV GLS and late gadolinium enhancement (LGE). Long-term adjudicated follow-up included (i) HF hospitalization, LV assist device implantation or HF death, and (ii) SCD or aborted SCD (aSCD).

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Article Synopsis
  • Pathogenic variants in the desmoplakin (DSP) gene are linked to a specific type of arrhythmogenic cardiomyopathy, which increases the risk of serious heart rhythm issues, but current evaluation methods are unreliable for these patients.
  • A study was conducted with patients from the DSP-ERADOS registry to track the occurrence of sustained ventricular arrhythmia (VA) over time, using a detailed statistical analysis to create a new clinical prediction tool.
  • The research identified five key clinical factors that can help predict the risk of developing sustained VA, resulting in a new DSP risk score that demonstrated strong prediction capabilities in both the initial and external testing groups.
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Background: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters.

Objectives: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM.

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Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown.

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Aims: This study aimed to compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular death or non-fatal heart failure events in patients with non-ischaemic dilated cardiomyopathy (DCM).

Methods And Results: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm [median age 54 (interquartile range 44-64) years, 61% men, median left ventricular ejection fraction 42% (30-51%)] were analysed for measures of LA structure [LA maximum volume index (LAVImax) and LA minimum volume index (LAVImin)] and function (LA emptying fraction, LA reservoir strain, LA conduit strain (LACS), and LA booster strain]. Over a median follow-up of 7.

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Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.

Objectives: This study aims to investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.

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