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This chapter assesses myocardial energetics. The heart requires very large amounts of energy, cycling many times its own weight in ATP daily, and uses a variable combination of carbohydrates, lipids, lactate, and amino acids as fuel. A key feature of the healthy heart is ‘metabolic flexibility’, i.e. the ability to use different substrates according to circumstances. As the syndrome of heart failure progresses, a steady downregulation of all aspects of cardiac metabolism may be seen. In extreme disease states, a fundamental deficiency in ATP can be demonstrated, but more subtle metabolic abnormalities are detectable at an earlier stage. Additionally, there are multiple downstream disturbances in mitochondrial function, in the high-energy phosphate pool and in excitation–contraction coupling. Ultimately, the detection of abnormalities of myocardial metabolism and energetics has spurred an interest in therapeutic modulation of metabolism in heart failure. This is attractive, as potentially such modulation would improve myocardial efficiency without the need for increased fuel delivery. Such therapies could have an additive effect to current heart failure management which generally relies on correction of the maladaptive neurohumoral consequences of the heart failure syndrome.

Inherited arrhythmia syndromes are rare, but collectively they are a major cause of loss of life in otherwise healthy young people. Several syndromes are described, and the pathogenic mechanisms and molecular genetics are increasingly well understood. Most of them affect ion currents and are termed “channelopathies.”

With the growing popularity of water-based sports, cases of swimming-induced pulmonary edema (SIPE) are becoming increasingly recognized. SIPE, a potentially life-threatening condition, is an acute cause of breathlessness in athletes. It has been described frequently in scuba divers, swimmers, and triathletes and is characterized by symptoms and signs of pulmonary edema following water immersion. It is important to recognize that athletes' symptoms can present with a spectrum of severity from mild breathlessness to severe dyspnea, hemoptysis, and hypoxia. In most cases, there is rapid resolution of symptoms within 48 hours of exiting the water. Recent advances in the understanding of the pathophysiology of SIPE, particularly regarding exaggerated pulmonary vascular pressures, have begun to explain this elusive condition more clearly and to distinguish its predisposing factors. It is essential that event organizers and athletes are aware of SIPE. Prompt recognition is required not only to prevent drowning, but also to implement appropriate medical management and subsequent advice regarding return to swimming and the risk of recurrence. This manuscript provides a current perspective on SIPE regarding the incidence rate, the current understanding of the pathophysiology, clinical presentation, medical management, recurrence rates, and advice on return to sport.

This chapter covers all areas of pacemaker programming and choices related to pacing. Methods of choosing rate limits, and related programming features are described for the lower rate interval, the upper rate interval, the atrioventricular interval, and refractory and blanking periods are described in detail. The anatomical and signal changes for each period are defined, and all descriptions are illustrated with example ECGs to show different programme outcomes. Rate response, programming rate response, and mode switching are covered. Automated functions and stored information are described, and algorithms to prevent atrial arrhythmias are explained. Finally, pacemaker-mediated tachycardia is outlined, including detection and methods of terminating the pacemaker-mediated tachycardia (PMT).

Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' - a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed.

We read with interest the study from van der Harst et al. [(1)][1]. The authors show an association between 52 genetic loci and various features of the resting 12-lead electrocardiograph (ECG). ECG-based criteria are notably poor in estimating myocardial mass. The Sokolow-Lyon criteria remain

Preliminary study to assess the risk profile and outcomes of patients aged over 90years at the time of percutaneous coronary intervention.A database search was performed to identify patients 90years or over at the time of percutaneous coronary intervention. Risk profile scores (Charlson Comorbidity Index, SYNTAX, Logistic clinical SYNTAX, New York PTCA score and frailty indices) were evaluated on 24 consecutive patients in order to determine the best predictor for survival. Between both groups (survivors and non-survivors) unpaired Student's t-test was used to determine statistical significance.The New York PTCA score was significantly higher in those patients that died in hospital (n=5) when compared to those who survived to discharge (n=19) (NY PTCA score of 20.9±5.4 vs. 4.5±0.8, p0.001) and this was also seen with mortality at 12months. The level of co-morbidity (Charlson index) was similar in patients who died in hospital (n=5) compared with those who survived to discharge (n=19, Charlson comorbidity index of 3.4±0.7 vs.3.9±0.6, p=0.70). This trend was also observed at 1year. The average level of frailty (by the CSHA Clinical Frailty Scale), SYNTAX score and logistic clinical SYNTAX were not significantly different between the two groups both at discharge and at 12months. Choosing an arbitrary New York PTCA score of 9%, nearly two thirds of patients above this level died, whereas no patient below this level of risk died in hospital.This small observational study found that nonagenarians who underwent PCI had relatively low comorbidity and SYNTAX scores. The specific coronary intervention (New York PTCA) risk score appears to have more predictive power in this small group of patients than the other three scores. Crucially, the factors that determine risk by New York PTCA score - haemodynamic instability, shock, pulmonary oedema, renal failure, etc. - are commonly encompassed by an "end-of-bed" assessment of the patient and these patients that pass this test ought not to be denied PCI on the basis of their advanced years.

Interventions to treat coronary artery disease are available but they must be targeted at the correct individuals (and indeed lesions), in order to gain maximal benefit with the minimal adverse effects. Coronary contrast angiography is not able to provide all the information required for the assessment of the effects of artery disease. Other imaging modalities are of growing importance as they can reduce radiation exposure and invasiveness of screening, as well as providing important extra information. The ideal 'multiparametric' imaging technique would assess anatomy, viability and lesion activity in a single quick scan. Currently, MRI is the technology closest to achieving this ideal, although the existing technology still has some limitations. This review discusses the currently available techniques for the imaging of coronary anatomy and of myocardial viability, and considers their benefits and limitations. We also discuss the developing field of imaging molecularly targeted to active coronary lesions. Finally we provide a 5-year view of the current and likely future optimal imaging strategies.

Background— Nitrite exhibits hypoxia-dependent vasodilator properties, selectively dilating capacitance vessels in healthy subjects. Unlike organic nitrates, it seems not to be subject to the development of tolerance. Currently, therapeutic options for decompensated heart failure (HF) are limited. We hypothesized that by preferentially dilating systemic capacitance and pulmonary resistance vessels although only marginally dilating resistance vessels, sodium nitrite (NaNO 2 ) infusion would increase cardiac output but reduce systemic arterial blood pressure only modestly. We therefore undertook a first-in-human HF proof of concept/safety study, evaluating the hemodynamic effects of short-term NaNO 2 infusion. Methods and Results— Twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO 2 at 10 μg/kg/min and 17 received 50 μg/kg/min with measurement of cardiac hemodynamics. During infusion of 50 μg/kg/min, left ventricular stroke volume increased (from 43.22±21.5 to 51.84±23.6 mL; P =0.003), with marked falls in pulmonary vascular resistance (by 29%; P =0.03) and right atrial pressure (by 40%; P =0.007), but with only modest falls in mean arterial blood pressure (by 4 mm Hg; P =0.004). The increase in stroke volume correlated with the increase in estimated trans-septal gradient (=pulmonary capillary wedge pressure–right atrial pressure; r =0.67; P =0.003), suggesting relief of diastolic ventricular interaction as a contributory mechanism. Directionally similar effects were observed for the above hemodynamic parameters with 10 μg/kg/min; this was significant only for stroke volume, not for other parameters. Conclusions— This first-in-human HF efficacy/safety study demonstrates an attractive profile during short-term systemic NaNO 2 infusion that may be beneficial in decompensated HF and warrants further evaluation with longer infusion regimens.

Mitochondrial aldehyde dehydrogenase-2 (ALDH-2) is involved in preconditioning pathways, but its role in remote ischaemic preconditioning (rIPC) is unknown. We investigated its role in animal and human models of rIPC. (i) In a rabbit model of myocardial infarction, rIPC alone reduced infarct size [69 ± 5.8 % (n = 11) to 40 ± 6.5 % (n = 12), P = 0.019]. However, rIPC protection was lost after pre-treatment with the ALDH-2 inhibitor cyanamide (62 ± 7.6 % controls, n = 10, versus 61 ± 6.9 % rIPC after cyanamide, n = 10, P > 0.05). (ii) In a forearm plethysmography model of endothelial ischaemia-reperfusion injury, 24 individuals of Asian ethnic origin underwent combined rIPC and ischaemia-reperfusion (IR). 11 had wild-type (WT) enzyme and 13 carried the Glu504Lys (ALDH22) polymorphism (rendering ALDH-2 functionally inactive). In WT individuals, rIPC protected against impairment of response to acetylcholine (P = 0.9), but rIPC failed to protect carriers of Glu504Lys polymorphism (P = 0.004). (iii) In a second model of endothelial IR injury, 12 individuals participated in a double-blind placebo-controlled crossover study, receiving the ALDH-2 inhibitor disulfiram 600 mg od or placebo for 48 h prior to assessment of flow-mediated dilation (FMD) before and after combined rIPC and IR. With placebo, rIPC was effective with no difference in FMD before and after IR (6.18 ± 1.03 % and 4.76 ± 0.93 % P = 0.1), but disulfiram inhibited rIPC with a reduction in FMD after IR (7.87 ± 1.27 % and 3.05 ± 0.53 %, P = 0.001). This study demonstrates that ALDH-2 is involved in the rIPC pathway in three distinct rabbit and human models. This has potential implications for future clinical studies of remote conditioning. © 2013 Springer-Verlag Berlin Heidelberg.

AIMS: This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle-indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. METHODS AND RESULTS: Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. CONCLUSION: Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.

Objective: To review the procedures, results and follow-up of patients who underwent percutaneous device closure of a patent foramen ovale (PFO) during pregnancy. We report modifications made to the established technique that allowed absolute minimization of radiation exposure. Relevant management issues of this unusual presentation of cardiac disease in pregnancy are discussed. Background: Stroke during or immediately prior to pregnancy is a catastrophic event. Paradoxical embolism may be more frequent due to the hypercoagulable state and increased incidence of venous thromboembolism. Treatment strategies must take into account the competing risks to mother and fetus. Methods: Three patients, aged 34, 27, and 39, presented with ischemic neurological events during or immediately preceding pregnancy. Due to evidence of recurrent events or relative contraindication to anticoagulation they proceeded to percutaneous device closure during the second trimester. The Helex device (WL Gore and Associates) was used in all patients. Procedures were performed with local anesthesia under intra-cardiac echocardiography guidance. Results: Successful closure was achieved with the Helex device in all three patients. Radiation doses, as assessed by dose area product, were 260, 58, and 19 cGy/cm2, with estimated uterine (fetal) dose of

A 71-year-old man was transferred to the extraction centre with Staphylococcus aureus endocarditis and a 3.5 × 1.7 cm vegetation adherent to the ventricular lead of his 7-year-old secondary-prevention dual chamber ICD (see Panel A and Supplementary material online, Videos S1–S3). He had been initially managed medically but the vegetation …

A 43-year-old woman having significant risk factors for ischaemic heart disease was admitted with an acute coronary syndrome (ACS). Coronary angiography revealed a non-flow limiting lesion in her right coronary artery with the rest of her arteries unremarkable. Risk stratification of the culprit lesion in the right coronary artery through intravascular ultrasound virtual histology demonstrated that the rupture plaque had less than 5% necrotic core with low vulnerability indices. This important finding suggested that the re-rupture risk was low so aggressive pharmacological treatment that can influence the plaque characteristics was instigated in preference to mechanical plaque sealing with a coronary stent. At a year of follow-up the patient was well and had no further events.

Sixteen years after a long admission for a serious occupational accident, a 38-year-old man presented with intermittent atypical chest pain. Upon investigations a retained fragment of a pulmonary artery catheter was found in the right ventricle. Throughout the years between his accident and the current presentation he did not have any symptoms or signs of complications associated with the retained catheter such as arrhythmia, sepsis or thromboembolism. Upon presenting his case at the medical/surgical multidisciplinary meeting it was decided that the probability of complications occurring at this stage was low as the catheter fragment would have endothelialised and the risk of retrieval would outweigh the benefits. This scenario highlighted the importance of understanding the possible long-term complications of retained catheter fragments, the importance of being aware of the limitation of these devices and the need to be more vigilant in the emergency setting.

Interrupted inferior vena cava (IVC) is a rare congenital abnormality often combined with cardiovascular and visceral malformations. We report the case of a 63-year-old male who presented in complete heart block with periodic absence of an escape rhythm requiring emergency temporary pacing. The trans-femoral …

The National Institute for Health and Care Excellence (NICE) CG95 clinical guideline on chest pain of recent onset was published in 2010. There is debate over whether the proposed strategy improves patient care and its implications on service costs. Following a six-month pilot, 472 consecutive patient records were audited for pre-test probability of significant coronary artery disease, investigations performed and outcomes. Low- and moderate-risk patients had an unexpectedly low rate of coronary disease and revascularisation. Computerised tomography coronary angiography (CTCA) and stress echocardiography performed similarly, though the latter was more resource intensive. High-/very high-risk patients frequently required revascularisation and greater than 10% of each group had prognostically significant disease, going against the recommendation that very high risk patients do not undergo angiography. There were frequent protocol deviations and training clinic staff in the new approach was challenging. In conclusion, implementing NICE CG95 is feasible but presents challenges. Staff require training to follow the protocol consistently. Functional testing had no benefits over anatomical testing with CTCA, which may allow cost savings in some departments.

Background: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. Methods: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. Results: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004–2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure ( P P P P =0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P =0.037), New York Heart Association class (HR, 2.00; P =0.015) at follow-up and baseline creatinine (HR, 8.19; P =0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P =0.002). Conclusion: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.