Is hypertensive left ventricular hypertrophy a cause of sustained ventricular arrhythmias in humans?

Sudden cardiac death (SCD) is most commonly secondary to sustained ventricular arrhythmias (VAs). This review aimed to evaluate if left ventricular hypertrophy (LVH) secondary to systemic hypertension in humans is an isolated risk factor for ventricular arrhythmogenesis. Animal models of hypertensive LVH have shown changes in ion channel function and distribution, gap junction re-distribution and fibrotic deposition. Clinical data has consistently exhibited an increase in prevalence and complexity of non-sustained VAs on electrocardiographic monitoring. However, there is a dearth of trials suggesting progression to sustained VAs and SCD, with extrapolations being confounded by presence of co-existent asymptomatic coronary artery disease (CAD). Putatively, this lack of data may be due to the presence of more homogenous distribution of pathophysiological changes seen in those with hypertensive LVH versus known pro-arrhythmic conditions such as HCM and myocardial infarction. The overall impression is that sustained VAs in the context of hypertensive LVH are most likely to be precipitated by other causes such as CAD or electrolyte disturbance.

A simple adaptation of a handheld ECG recorder to obtain chest lead equivalents.

Hand held ECG recorders are transforming the way we detect and diagnose heart rhythm disorders. The Kardia 6 L was launched in 2019 to detect and diagnose heart rhythm disorders recording a six lead (limb lead) ECG. Recording and analysis of precordial leads are currently not supported by the Kardia 6 L. In this study we aim to assess if reliable chest lead data can be obtained using a simple modification to the recording system.

Restoration of sinus rhythm results in early and late improvements in the functional reserve of the heart following direct current cardioversion of persistent AF: FRESH-AF.

BACKGROUND: The improvement in cardiac physiological parameters after restoration of sinus rhythm in patients with persistent atrial fibrillation (AF) can be challenging to quantify. Overall cardiac function assessment is better assessed by peak cardiac power output (CPOpeak), rather than indirect measures of cardiac performance such as peak oxygen consumption (VO2peak). CPO was used to quantify improvement in cardiac function early and later following electrical cardioversion. METHODS AND RESULTS: 29 patients with persistent AF underwent maximal treadmill cardiopulmonary exercise (CPEx) testing within 14days (±3) 8weeks (±3) following electrical cardioversion (DCCv). This enabled measurement of VO2peak, cardiac output (COpeak) and calculation of CPOpeak. Quality of life (QoL) data (EQ5D) was also recorded. Three patients attended for 2 CPEx tests and 3 were lost to follow-up (total n=26). Fourteen were successfully cardioverted and 12 remained in AF. In patients successfully cardioverted exercise duration increased significantly between all tests. CPOpeak, VO2peak, CO peak and QoL were improved significantly between Tests 1 and 2 (p<0.02) and Tests 1 and 3 (p<0.05). QoL improved by 15%. CONCLUSIONS: Restoration of SR confers significant, early and sustained cardiac functional improvement following DCCv with a significant 14% increase in the calculated peak power output of the heart. Such increase in functional reserve suggests that pursuit of a rhythm control strategy in the treatment of AF may be warranted in terms of both improving quality of life and cardiac function with objective improvement of cardiac function.

Development Of A Novel Scoring System That Determines The Success Of Atrial Fibrillation Ablation As Part Of Cardiac Surgery.

BACKGROUND: Radiofrequency ablation therapy for the treatment of atrial fibrillation (AF) can be performed as a concomitant procedure alongside cardiac surgery, but carries the risks of increased bypass time and damage to the sinoatrial node. This study aims to assess the efficacy of concomitant surgical AF ablation and develop a novel scoring system to predict post-procedural return to sinus rhythm. METHODS: A review of the Leeds General Infirmary surgical database was conducted to list all patients who had undergone valvular or coronary bypass surgery with concomitant AF ablation between Jan 2012 - Dec 2013 (n = 76). Follow-up was obtained retrospectively using patient notes, clinic letters and echocardiographic data. Primary outcome was freedom from AF at median follow up (383 days). A novel scoring system was created through analysis of previous literature and evaluated using a receiver operating characteristic (ROC) curve. RESULTS: At median follow up 50.9% of patients undergoing the procedure were free from AF. The novel scoring system was shown to adequately predict post-procedural return to sinus rhythm (ROC AUC = 0.7708). CONCLUSION: A novel scoring system was shown to predict procedural success in patients undergoing concomitant AF ablation alongside cardiac surgery. These results can be further validated using larger patient cohorts.

During ablation for atrial fibrillation, is simultaneous renal artery ablation appropriate?

Over the past few decades, the mainstay of hypertension management has been pharmacological therapy; however, there is now a growing body of evidence that drug-resistant hypertension can be managed effectively by renal artery ablation. Several studies have documented the feasibility and safety of this treatment, although data regarding long-term outcomes are still emerging. Atrial fibrillation (AF) and hypertension commonly coexist, and recent work has demonstrated improved outcomes from catheter ablation of AF with concomitant renal artery denervation at little extra cost in terms of time and resource. The aim of this review is to explore the link between hypertension and AF, the synergistic effect of renal artery ablation on AF ablation, explain how this may work and address unanswered questions.

Role of coronary revascularisation among patients receiving implantable defibrillators: a review.

Patients with coronary artery disease (CAD) can present with spontaneous ventricular arrhythmias occurring outside the context of an acute coronary syndrome with no apparent identifiable reversible cause. In addition to secondary prevention medications, implantable cardiac defibrillator (ICD) remains the main therapeutic intervention to reduce the risk of subsequent mortality and morbidity. Investigations prior to ICD implantation may identify the presence of angiographically significant epicardial coronary stenoses in previously asymptomatic patients, alongside other arrhythmic substrates such as myocardial scar and impaired left ventricular systolic function. So does coronary revascularisation in these patients reduce the occurrence of appropriate ICD shocks in the long run? In this article we comprehensively review the literature to answer the primary question of whether coronary revascularisation reduces recurrent ventricular arrhythmia burden among patients with CAD receiving an ICD, with focus on those presenting with ventricular arrhythmias outside the context of acute coronary syndrome. With growing evidence of the adverse prognostic impact of appropriate ICD discharges and an ever-increasing number of ICD implants world-wide, we believe that this question is of paramount importance. We summarise the available evidence to draw conclusions about the appropriate management strategy and also highlight areas of uncertainty that require attention in future research.

South Asians are Under-Represented in a Clinic Treating Atrial Fibrillation in a Multicultural City in the UK.

The Leeds rapid access atrial fibrillation (AF) clinic was set up to streamline and standardise management of patients with newly diagnosed AF. Anecdotal evidence suggests that there is under-representation of south Asians in these clinics.All patient attendances between June 2007 and June 2011 were documented and combined with ethnicity data from patient administration records. Local population demographics for 2009 were obtained from the office of national statistics. This was used to estimate the expected prevalence of AF across the different ethnic groups in Leeds taking age into account. One thousand two hundred and ten patients were referred. The study sample included 992 patients, and the number of south Asians attending was 88% less than expected (Chi squared analysis; p<0.0001). These results suggest that there is an under-representation of south Asians in a large centre that serves a cosmopolitan population. Potential reasons for this discrepancy including barriers to accessing treatment for this population or a lower prevalence of AF in south Asians due to an as yet unidentified genetic factor.

Extracellular matrix turnover and disease severity in Anderson-Fabry disease.

BACKGROUND: Anderson-Fabry Disease (AFD) is an inherited metabolic disease associated with premature death secondary to cardiovascular and renal disease. Patients with AFD develop progressive left ventricular (LV) remodelling and heart failure. We hypothesized that altered extracellular matrix (ECM) turnover contributes to the pathophysiology of cardiac disease in AFD. METHODS AND RESULTS: Twenty-nine consecutive patients (44.1 +/- 11.7 years, 15 male) with AFD and 21 normal controls (39.7 +/- 11.3 years, 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 and -2 (TIMP-1, TIMP-2). All patients underwent clinical assessment, echocardiography and Mainz Severity Score Index (MSSI) measurement, a validated severity score in AFD. MMP-9 levels were significantly higher in patients than controls (1003.8 +/- 337.8 ng/ml vs 576.7 +/- 276.3 ng/ml respectively, p < 0.001). There were no differences in TIMP levels between patients and controls. There was a positive correlation between MMP-9 levels and MSSI (r = 0.5, p = 0.01). There was a negative correlation between MMP-9 and endocardial fractional shortening (FS) (r = -0.5, p = 0.01) and mid-wall FS (r = -0.6, p = 0.001). There was no correlation between other echocardiographic parameters and MMP-9 levels. These relations were independent of age and sex using stepwise linear regression analysis. CONCLUSIONS: Patients with AFD have abnormal ECM turnover compared to normal controls. The correlation between MMP-9 levels and systolic function suggests that altered ECM turnover is important in cardiac remodelling. The association between MMP-9 and overall disease severity suggests that circulating levels of MMP-9 may provide a useful marker for assessing the response of patients with AFD to enzyme replacement treatment.

Tissue inhibitor of metalloproteinse-1 is a marker of diastolic dysfunction using tissue doppler in patients with type 2 diabetes and hypertension.

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is associated with increased fibrosis of the extracellular matrix (ECM). Myocardial stiffness is a feature of diastolic dysfunction. We assessed circulating TIMP-1 as a marker of diastolic dysfunction in patients with type 2 diabetes mellitus (DM) and hypertension, who were compared with healthy controls. METHODS: We recruited 54 patients (43 males; mean age 68 +/- 5 years) with treated type 2 DM (i.e. controlled glycaemia, hypertension, hyperlipidaemia), 35 (30 males; 69 +/- 8 years) treated nondiabetic hypertensives, and 31 healthy controls (18 males; 66 +/- 5 years). Circulating TIMP-1 was measured by ELISA. Using transthoracic echocardiography, the early (E) diastolic mitral inflow velocity was measured with pulse wave Doppler, and the early mitral annular velocity (e'), a recognized index of diastolic relaxation, was measured with tissue Doppler. The E/A ratio was also calculated and isovolumic relaxation time measured. RESULTS: Mean e' levels differed significantly between controls, diabetics and hypertensives (P < 0.0001). Circulating TIMP-1 was significantly different between patients and controls (P = 0.006), but there was no statistically significant difference between the DM and hypertension group. In both groups, only e' was negatively correlated with TIMP-1 levels, with a stronger correlation among the hypertensive patients (Spearman r = -0.544, P = 0.001) when compared with the diabetic group (r = -0.341, P = 0.011). CONCLUSION: Diastolic relaxation is impaired in diabetes and hypertensive patients. The relationship between TIMP-1 and e' may reflect increased myocardial fibrosis and consequent diastolic dysfunction, which may be more prominent in hypertension.

What role do extracellular matrix changes contribute to the cardiovascular disease burden of diabetes mellitus?

Matrix metalloproteinases (MMP) and their inhibitors (TIMP) are central factors in the control of extracellular matrix turnover. They are important in normal physiology and also during a range of pathological states. In this review, we have systematically identified clinical articles relevant to cardiovascular disease in diabetes from the last 10 years. Our aim was to outline the structure, function and regulation of metalloproteinases and their key roles in cardiomyopathy and vasculopathy in diabetes. We also explore the effects of drug intervention on both human subjects with diabetes and experimental animal models. The modulation of MMP and TIMP activity using drugs that affect the expression and function of these proteins may provide us with new ways to treat this serious and disabling disease, and we explore potential mechanisms and treatments.

Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels.

BACKGROUND: The commonest cause of mortality in patients with Type 2 diabetes is atherothrombosis, which can be related to abnormalities in the coagulation and fibrinolytic pathways, as well as in platelet function. Platelet microparticles (PMPs) may contribute to the prothrombotic state and may promote the progression of atherosclerosis. We hypothesized that PMPs are elevated in Type 2 diabetes and that patients with Type 2 diabetes and clinically apparent atherosclerosis would have the highest levels. Similarly, we hypothesized that soluble plasma P-selectin (sPsel) and CD40L (both molecules which are released by activated platelets), as well as %CD62P (P-selectin) and %CD63 positivity on platelets quantified by flow cytometry, would be highest in patients with Type 2 diabetes and clinically apparent atherosclerotic disease, and might be correlated to PMP levels. METHODS: Venous blood was obtained from 21 Type 2 diabetic patients without atherosclerotic complications, 18 diabetic patients with clinically apparent atherosclerotic disease and 21 non-diabetic control subjects. PMPs, as well as %CD62P and %CD63 positivity on platelets, were quantified by flow cytometry. sPsel and CD40L were measured using ELISA. RESULTS: Patients with Type 2 diabetes and clinically apparent atherosclerotic disease had the highest PMP (P=0.045) and sPsel (P=0.046) levels, compared with patients without complications (who had intermediate PMP levels) and control subjects. Control subjects had the lowest CD40L levels (P<0.001) when compared with patients with Type 2 diabetes, with no difference in sCD40L levels between the two diabetic subgroups. %CD62P and %CD63 positivity did not differ between the groups. PMP levels correlated with %CD62P positivity (P=0.026) but not to %CD63 positivity (P=0.089), sCD40L (P=0.407) or sP-sel (P=0.163); sCD40L levels did not correlate with any other marker of platelet activation. CONCLUSION: PMPs are elevated in Type 2 diabetes. In addition, patients with clinically apparent atherosclerosis had the highest levels of PMPs and sPsel. Thus, PMPs may be a marker of symptomatic atherosclerotic vascular disease in Type 2 diabetes, and may both represent a useful risk stratification tool as well as a novel therapeutic target for anti-thrombotic drugs.

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity.

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.

Autonomic reflexes in heterotopic heart transplantation.

Heterotopic heart transplantation (HHT) is useful in the setting of irreversible pulmonary hypertension or donor/recipient size mismatch. The resulting pump is composed of two hearts attached to one another. Autonomic tone can be lost in orthotopic heart transplantation, but HHT is unique in that the donor heart lacks an autonomic nervous supply. This is relevant in terms of increasing cardiac output for example during exercise. We document altered autonomic tone in two of our patients who underwent HHT, and discuss the bearing this has on cardiac function.

Collateralization and the response to obstruction of epicardial coronary arteries.

Occlusive coronary disease is an important cause of global morbidity and mortality. While mechanical revascularization is effective, some individuals are not amenable to such interventions, and have a poorer prognosis. However, collateral circulation can protect and preserve myocardium around the time of coronary occlusion, contribute to better residual myocardial contractility, and lessen symptoms. We describe the anatomy and physiology of coronary collateralization, its component parts (angiogenesis and arteriogenesis), the current methods for definition of the collateral response and how this might be manipulated. The manipulation of this process is a realistic possibility for future adjuvant treatment of coronary artery disease.

Psychological interventions for depression in adolescent and adult congenital heart disease.

BACKGROUND: Adult and adolescent congenital heart disease is increasing in prevalence as better medical care means more children are surviving to adulthood. People with chromic disease often also experience depression. There are several non-pharmacological treatments that might be effective in treating depression and improving quality of life for adults and young adults with congenital heart disease. The aim of this review was to assess the effects of treatments such as psychotherapy, cognitive behavioural therapies and talking therapies for treating depression in this population. OBJECTIVES: To assess the effects (both harms and benefits) of psychological interventions for treating depression in young adults and adults with congenital heart disease. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CCTR) (on The Cochrane Library issue 4, 2002), MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), PsycLIT (1887 to August 2002), the Database of Abstracts of Reviews of Effectiveness (DARE) (Issue 4, 2002 of the Cochrane Library), Biological Abstracts (January 1980 to August 2002), and CINAHL (January 1980 to August 2002). Abstracts from national and international cardiology and psychology conferences and dissertation abstracts were also searched. SELECTION CRITERIA: Randomised controlled trials comparing psychological interventions with no intervention for people over 15 years with depression who have congenital heart disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles and abstracts of studies that were potentially relevant to the review. Studies that were clearly ineligible were rejected. Two reviewers independently assessed the abstracts or full papers for inclusion criteria. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility. MAIN RESULTS: No randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: Depression is common in patients with congenital heart disease and can exacerbate the physical consequences of the illness. There are effective pharmacological and non-pharmacological treatments for depression, but we have not been able to identify any trials showing the effectiveness of non-pharmacological treatments. A well designed randomised controlled trial is needed to assess the effects of psychological interventions for depression in congenital heart disease.

Pyramidal neurones in pathological human motor cortex express nitric oxide synthase.

The enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH diaphorase) is widely used as a sensitive marker for indicating the presence of nitric oxide synthase in neurones. Pyramidal neurones in the healthy neocortex do not contain detectable levels of nitric oxide synthase. However, in the precentral gyrus of brains showing pathological damage, a high proportion of Betz cells (11-50%) and some smaller pyramidal neurones contained low to moderate levels of NADPH diaphorase. They were located in layers V and VI and were present in a newborn baby, older children and elderly adults. Thus, under pathological conditions, some pyramidal neurones are apparently capable of synthesising nitric oxide and this may have a neuroprotective function.