Krishnaraj Sinhji Rathod

William Harvey Research Institute | WHRI · Clinical Pharmacology

BACKGROUND Patients with previous coronary artery bypass grafting often require invasive coronary angiography (ICA). However, for these patients, the procedure is technically more challenging and has a higher risk of complications. Observational studies suggest that computed tomography cardiac angiography (CTCA) may facilitate ICA in this group, bu...

Background Cardiovascular events, driven by endothelial dysfunction, are a recognised complication of COVID-19. SARS-CoV-2 infections remain a persistent concern globally, and an understanding of the mechanisms causing endothelial dysfunction, particularly the role of inflammation, nitric oxide, and whether sex differences exist in this response, i...

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2⁻) reductase activity leading to...

Objective: To assess the safety and effectiveness of a novel pathway of deferrred invasive angiography in low-risk NSTEMI patients with concurrent COVID-19 infections; contrary to current UK guidelines recommending invasive coronary angiography in NSTEMI patients within 72 hours. Methods: This was a single-centre, observational study of all NSTE...

Introduction Stable angina affects 1.3 million people in the UK. Stent implantation in diseased coronary arteries helps to reduce the symptoms of angina and the long-term risk of heart attacks. we, and others, have shown that nitric oxide (NO) delivery utilising the nitrate/nitrite/NO pathway improves endothelial function, decreases platelet reacti...

Introduction Stable angina affects 1.3 million people in the UK. Stent implantation in diseased coronary arteries helps to reduce the symptoms of angina and the long-term risk of heart attacks. we, and others, have shown that nitric oxide (NO) delivery utilising the nitrate/nitrite/NO pathway improves endothelial function, decreases platelet reacti...

Background: It has been previously reported during the first COVID-19 outbreak that patients presenting with ST-segment elevation myocardial infarction (STEMI) and concurrent COVID-19 infection have increased thrombus burden and poorer outcomes. To date, there have been no reports comparing the outcomes of COVID-19-positive STEMI patients across a...

In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data wer...

Background: Drug eluting balloons (DEB) are a feasible method of rapid delivery of drug to a coronary vessel wall. Their efficacy has been established for the treatment of in-stent restenosis and small vessel disease but there is limited data for their use in bifurcation lesions. Objective: The aim of this study was to assess the effectiveness of...

Recently, there has been growing interest in the early discharge strategy for low-risk patients who have undergone primary percutaneous coronary intervention (PCI) to treat ST-segment elevation myocardial infarction (STEMI). So far findings have suggested there are multiple advantages of shorter hospital stays, including that it could be a safe way...

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O ·- and H O and nitrite (·NO ⁻ ) reductase activity leading to...

Background Refractory angina (RFA; limiting angina despite optimal medical therapy) is a growing, global problem, with limited treatment options. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effect of proangiogenic growth factor therapy (in the form of vascular growth factors delivered either as...

Background Left ventricular thrombus (LVT) complicates around one in six cases of acute and chronic left ventricular systolic dysfunction and is associated with an increased risk of stroke, major systemic embolism and death, believed to be ameliorated by anticoagulation. Off-label use of direct oral anticoagulants (DOACs) for LVT has steadily incre...

Background It has been previously reported during the first COVID outbreak that patients presenting with ST-Segment Elevation Myocardial Infarction (STEMI) and concurrent COVID-19 infection have increased thrombus burden and poorer outcomes [1]. Subsequently, there have been multiple further waves of the pandemic with the emergence of at least two...

Aspirin in combination with a P2Y12 inhibitor is the mainstay of treatment post percutaneous coronary intervention (PCI) for coronary artery disease (CAD). However, patients who are allergic to or intolerant to aspirin pose a therapeutic challenge especially when encountered in the setting of acute coronary syndrome. Aspirin desensitization strateg...

Aortic stenosis (AS) is a progressive disease that carries a poor prognosis. Patients are managed conservatively until satisfying an indication for transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) based on AS severity and the presence of symptoms or adverse impact on the myocardium. Up to 1 in 3 TAVIs are p...

Background The characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients with ST-Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) are still poorly known. Methods The PANDEMIC study was an investigator-initiated, collaborative, individual patient...

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised wit...

Background We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with...

Introduction Public reporting of 30-day mortality after percutaneous coronary intervention (PCI) imply that death after PCI is a complication for the interventional cardiologist and the hospital. However, in many cases mortality can occur despite receiving optimal care and achieving a successful PCI result. This is especially true in the context o...

Introduction Inflammation is implicated in endothelial dysfunction in CVD. A key mechanism mediating endothelial dysfunction is a reduction in bioavailable (eNOS-derived) nitric oxide (NO). Evidence has shown that increasing NO delivery via activation of the non-canonical pathway might increase anti-inflammatory and vascular protective NO. We hypot...

Emergency percutaneous coronary intervention of the left main (LM ePCI) coronary artery necessitated by acute coronary syndrome is associated with a high risk of mortality. However, optimal treatment strategies and related outcomes remain undefined in this group. We undertook a multi-center, retrospective, observational cohort study of consecutive...

Funding Acknowledgements Type of funding sources: None. Aim Elevated troponin levels have been shown to predict in-hospital outcomes in patients with COVID-19. However, whether this relates to or predicts longer-term outcomes is unknown. We aimed to investigate the effect of troponin elevation in patients with COVID-19, looking at resource utilisa...

Background Patients with AS are susceptible to myocardial ischemia and often present acutely, making it challenging to differentiate between a type 1 NSTEMI and acute decompensated aortic stenosis. This study aims to evaluate the diagnostic accuracy of Troponin T (TnT) (>5 fold above the upper limit of normal), ischemic ECG and angina, to predict a...

Background: Patients with previous coronary artery bypass graft (CABG) surgery typically have complex coronary disease and remain at high risk of adverse events. Quantitative myocardial perfusion indices predict outcomes in native vessel disease, but their prognostic performance in patients with prior CABG is unknown. Objectives: In this study,...

Objective The study aimed to determine the predictors of procedural failure (coronary cannulation) in patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) from the transradial (TR) approach. Methods We conducted an observational study of 20,315 consecutive patients undergoing TR angiography between 2016 and 2020. TR...

Length of hospital stay after acute myocardial infarction (MI) has fallen from 6 weeks or more in the 1950s to just a few days in contemporary practice.¹ Stepwise reductions in hospital stay were heralded by earlier mobilization, better risk stratification through echocardiography and exercise electrocardiogram testing, and lower complication rates...

Aims: The CREST tool was recently developed to stratify the risk of circulatory-aetiology death (CED) in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation myocardial infarction (STEMI). We aimed to validate the CREST score using an external cohort and determine whether it could be improved by the addition of serum lactate on admi...

Background Regional heart attack services have improved clinical outcomes following ST-segment elevation myocardial infarction (STEMI) by facilitating early reperfusion by primary percutaneous coronary intervention (PCI). Early discharge after primary PCI is welcomed by patients and increases efficiency of health care. Objectives This study aimed...

Background and purpose: Transient receptor potential cation channel subfamily V member 1 (TRPV1) is localised to sensory C-fibres and its opening leads to membrane depolarization, resulting in neuropeptide release and neurogenic inflammation. However, the identity of the endogenous activator of TRPV1 in this setting is unknown. The arachidonic aci...

Background Drug-eluting balloons (DEBs) are a feasible method of rapid delivery of drug to the vessel wall during a single balloon inflation without the need to leave a permanent implant. Their efficacy has been established for in-stent restenosis and small vessels but there are limited data for their use in bifurcation lesions. Methods We conduct...

Background: Outcome following ST-segment elevation myocardial infarction (STEMI) is thought to be worse in women than in age-matched men. We assessed whether such differences occur in the UK Pan-London dataset and if age, and particularly menopause, influences upon outcome. Methods: We undertook an observational cohort study of 26,799 STEMI pati...

Objectives: The clinical environment has been forced to adapt to meet the unprecedented challenges posed by the COVID-19 pandemic. Intensive care facilities were expanded in anticipation of the pandemic where the consequences include severe delays in elective procedures. Emergent procedures such as Percutaneous Coronary Intervention (PCI) in acute...

Background Inflammatory responses underlie the development of endothelial dysfunction in CVD, however, therapeutics that might target this pathway have not been forthcoming. A key pathogenic mechanism mediating endothelial dysfunction is a reduction in bioavailable (eNOS-derived) nitric oxide (NO). Activation of the non-canonical pathway for in-viv...

Introduction Chronic cardiovascular diseases are characterised by low-grade systemic inflammation and attenuated nitric oxide (NO) bioavailability resulting in endothelial dysfunction. Inorganic nitrate augments NO bioavailability and improves markers of vascular dysfunction in patients with cardiovascular risk factors. However, the exact mechanism...

Introduction Increasing evidence highlights the critical role of chronic inflammation in cardiovascular disease (CVD). Targeting inflammatory pathways in patients with CVD has been associated with improved CV function in pre-clinical (Gee, 2017), early clinical (Yndestad, 2006; Velmurugan 2013; Jones, 2016) and large phase III studies (Ridker, 2017...

Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist, with up to two thirds of patients with AS having significant CAD. Given the challenges when both disease states are present, these patients require a tailored approach diagnostically and therapeutically. In this review the authors address the impact of AS and aortic valve re...

Background: Patients with ischaemic heart disease and previous coronary artery bypass grafting (CABG) often need coronary evaluation by means of invasive coronary angiography (ICA). ICA in such patients is technically more challenging and carries a higher risk of complications including kidney damage, myocardial infarction, stroke and death. Impro...

Background and purpose: NO is a vasodilator and independent modulator of cardiac remodelling. Commonly, in cardiac disease (e.g., heart failure), endothelial dysfunction (synonymous with NO deficiency) has been implicated in increased BP, cardiac hypertrophy and fibrosis. Currently, no effective therapies replacing NO have succeeded in the clinic....

The transradial access approach is a well-established route for coronary angiography and percutaneous intervention, given its lower complication rate over the transfemoral route. However, complications are still apparent, some of which can lead to serious injury. We report a case of delayed diagnosis of localized compartment syndrome, caused by hae...

Background The response to COVID-19 has required cancellation of all but the most urgent procedures; there is therefore a need for the reintroduction of a safe elective pathway. Methods This was a study of a pilot pathway performed at Barts Heart Centre for the admission of patients requiring elective coronary and structural procedures during the...

Background: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need...

Intravascular imaging has evolved alongside interventional cardiology as an adjunctive tool for assessing plaque pathology and for guiding and optimising percutaneous coronary intervention (PCI) in challenging lesions. The two modalities which have dominated the field are intravascular ultrasound (IVUS), which relies on sound waves and optical cohe...

Background The international healthcare response to COVID-19 has been driven by epidemiological data related to case numbers and case fatality rate. Second order effects have been less well studied. This study aimed to characterise the changes in emergency activity of a high-volume cardiac catheterisation centre and to cautiously model any excess i...

Although COVID-19 is viewed primarily as a respiratory disease, cardiovascular risk factors and disease are prevalent among infected patients and are associated with worse outcomes. In addition, among multiple extra-pulmonary manifestations, there has been an increasing recognition of specific cardiovascular complications of COVID-19. Despite this,...

Background: Recent studies have suggested that the routine use of aspiration thrombectomy catheters during primary percutaneous coronary intervention (PCI) do not result in improved mortality and may be associated with an increased stroke rate. This study sought to investigate this hypothesis. Methods: This was an observational study analysing d...

Background: Out-of-hospital cardiac arrest (OHCA) is a major cause of death worldwide. Recent guidelines recommend the centralisation of OHCA services in cardiac arrest centres to improve outcomes. In 2015, two major tertiary cardiac centres in London merged to form a large dedicated tertiary cardiac centre. This study aimed to compare the short-te...

Background In patients presenting with non ST-segment elevation acute coronary syndromes (NSTE-ACS) an invasive approach has been shown to be superior to conservative management. Purpose We aimed to investigate the optimal timing of invasive coronary angiography and subsequent intervention. Methods We examined the impact ofearly (≤24h) versus del...

Coordinated molecular responses are key to effective initiation and resolution of both acute and chronic inflammation. Vascular inflammation plays an important role in initiating and perpetuating atherosclerotic disease, specifically at the site of plaque and subsequent fibrous cap rupture. Both men and women succumb to this disease process, and al...

Background: More than half of the patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have multi-vessel coronary artery disease. This is associated with worse outcomes compared with single vessel disease. Whilst evidence now exists to support complete revascularisation for bys...

Objective We aimed to assess the use of enhanced stent visualisation (ESV) on outcomes, after PCI with overlapping stents, specifically using CLEARstent technology. Background Stent underexpansion and overlap are both significant risk factors for restenosis and stent thrombosis. Enhanced stent visualisation (e.g. CLEARstent) systems could provide...

Aim: Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3 - 6 months for treatment of LV thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of Novel Oral Anti-Coagulant's (NOAC) compared to VKA for other indications such as DVT, PE and thrombo-embolic prevention in atria...

In contrast to nitric oxide, which has well established and important roles in the regulation of blood flow and thrombosis, neurotransmission, the normal functioning of the genitourinary system, and the inflammation response and host defense, its oxidized metabolites nitrite and nitrate have, until recently, been considered to be relatively inactiv...

Background Coronavirus disease 2019 (COVID-19) is thought to predispose patients to thrombotic disease. To date there are few reports of ST-elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in COVID-19 patients. Objectives The aim of this study was to describe the demographic, angiographic, and procedural characteristi...

Background Limited information exists regarding procedural success and clinical outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention ( PCI ). We sought to compare outcomes in patients undergoing PCI with or without CABG . Methods and Results This was an observational cohort study o...

Introduction We aimed to investigate the optimal timing of invasive coronary angiography and subsequent intervention in non-ST-segment elevation acute myocardial infarction (NSTEMI) patients. Methods We examined the impact of early (≤24 h) versus delayed (>24 h) intervention in a large observational cohort of 20,882 consecutive NSTEMI patients tre...

Computed tomographic coronary angiography (CTCA) is a non-invasive imaging modality, which allows plaque burden and composition assessment and detection of plaque characteristics associated with increased vulnerability. In addition, CTCA-based coronary artery reconstruction enables local haemodynamic forces assessment, which regulate plaque formati...

Background and aims In patients with ST-segment elevation myocardial infarction (STEMI), mortality is directly related to time to reperfusion with guidelines recommending patients be delivered directly to centres for primary percutaneous coronary intervention (PCI). The aim of this study was to describe the impact of inter-hospital transfer on repe...

Introduction Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might...

Objective To document UK rates of exercise treadmill testing, functional stress testing and CT coronary angiography (CTCA). Specific aims were to determine how rates have changed in the context of changing guideline recommendations within the UK and to identify regional inequalities in the utilisation of testing modalities. Secondary objectives wer...

Objective: Fractional flow reserve (FFR) is regarded as the gold standard for the physiological assessment of intermediate coronary artery stenoses. However, FFR does not allow assessment of plaque morphology and lesion geometry. Intracoronary imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can hel...

Aim Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3–6 months for the treatment of LV thrombus post- acute myocardial infarction (AMI). However based on evidence supporting the non-inferiority and potential superiority of Direct Oral Anti-Coagulation's (DOAC) compared to VKA for other indications such as atrial fibrill...

Introduction There has been an increasing focus on the development of scoring systems for patients admitted following resuscitation from out-of-hospital cardiac arrest (OHCA) to determine both prognosis and short-term management. One such system, the CREST score, has been shown to predict circulatory aetiology death in patients without ST-elevation...

Background Out-of-hospital cardiac arrest (OHCA) is a major cause of death in Europe and the United States. There has been recent literature to suggest that the centralisation of OHCA services may benefit patient outcomes. In 2015, two major tertiary cardiac centres in the UK agglomerated to form a large dedicated tertiary cardiac centre. The previ...

Background Limited information exists regarding procedural success and clinical outcomes in patients with previous CABG undergoing percutaneous coronary intervention (PCI). We sought to compare outcomes in patients undergoing PCI with or without previous coronary artery bypass grafts (CABG). Methods This was an observational cohort study of 123,78...

The human umbilical cord has recently emerged as an attractive potential source of mesenchymal stromal cells (MSCs) to be adopted for use in regenerative medicine. Umbilical cord MSCs (UC-MSCs) not only share the same features of all MSCs such as multi-lineage differentiation, paracrine functions and immunomodulatory properties, they also have addi...

Aims: Invasive Coronary angiography (ICA) is more complex and challenging in patients with previous CABG. Computerised Tomography Coronary Angiography (CTCA) may provide useful information prior to ICA to improve these procedures. Methods and results: This single-centre observational study included 835 patients with prior CABG undergoing invasiv...

Rationale: Cell-based therapies are a novel potential treatment for refractory angina and have been found to improve markers of angina. However, the effects on mortality and major adverse cardiac events (MACE) have not been definitively investigated. Objective: To investigate the efficacy and safety of stem cell treatment compared with optimal m...

Background: Despite advances in technology, patients with Cardiogenic Shock (CS) presenting with ST-segment myocardial infarction (STEMI) still have a poor prognosis with high mortality rates. A large proportion of these patients have multi-vessel coronary artery disease, the treatment of which is still unclear. We aimed to assess the trends in ma...

Introduction European guidelines recommend a primary PCI strategy in patients following out-of-hospital cardiac arrest (OHCA) with ST-segment elevation on the ECG. In those without ST elevation the decision to proceed to urgent angiography is recommended if there a high index of suspicion of ischaemia. Predicting which patients are likely to have a...

Aims: The public reporting of healthcare outcomes has a number of potential benefits; however, unintended consequences may limit its effectiveness as a quality improvement process. We aimed to assess whether the introduction of individual operator specific outcome reporting after percutaneous coronary intervention (PCI) in the UK was associated wi...

Cardiogenic shock remains a major problem affecting a large proportion of patients with acute coronary syndromes, with a persistent high mortality rate. Although mechanical reperfusion with percutaneous coronary intervention has improved outcomes following acute coronary syndromes, there is limited evidence supporting the other current treatments u...

Background: A large proportion of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) present with multivessel disease (MVD). There is uncertainty in the role of complete coronary revascularization in this group of patients. Objectives: The aim of this study was to investigate the outcomes of complete revascularizati...