Liver function monitoring in Fontan-procedure patients: audit of current practice across South Wales.

The Fontan procedure provides a palliative surgical repair for complex congenital heart disease, but it is associated with many long-term problems, including liver cirrhosis, and hepatocellular carcinoma. The current suggestion from international guidance is that end-organ surveillance should be carried out, with a particular focus on regular blood tests and imaging for liver function. In this study, retrospective analysis was performed on adult patients who had previously had a Fontan operation performed to determine the regularity of end-organ surveillance in regards to their liver function covering the three calendar years from 2016 to 2018, and the first six months of 2019. Eighty-six patients were identified in South Wales monitored by the adult congenital heart disease unit. We found that the number of investigations performed in the first six months of 2019 was comparable to other calendar years in their entirety. Liver function tests had been performed in 57% of patients throughout 2018, with only 8% having had an alpha-fetoprotein taken, and only 9% having had imaging of the liver performed. Over the course of their lifetime, 97% of patients had had a liver function blood test performed at some point, with 17% having had an alpha-fetoprotein taken, and 49% having their liver imaged. In conclusion, end-organ surveillance is an important follow-up for patients with a Fontan circulation, with guidelines proposing yearly blood test and imaging investigations. This study shows the opportunities to improve surveillance in this group of patients to highlight the development of liver cirrhosis, and/or hepatocellular carcinoma.

Echocardiographic Screening for Pulmonary Hypertension in Congenital Heart Disease: JACC Review Topic of the Week.

Echocardiography is the mainstay in screening for pulmonary hypertension (PH). International guidelines suggest echocardiographic parameters for suspecting PH, but these may not apply to many adults with congenital heart disease (ACHD). PH is relatively common in ACHD patients and can significantly affect their exercise capacity, quality of life, and prognosis. Identification of patients who have developed PH and who may benefit from further investigations (including cardiac catheterization) and treatment is thus extremely important. A systematic review and survey of experts from the United Kingdom and Ireland were performed to assess current knowledge and practice on echocardiographic screening for PH in ACHD. This paper presents the findings of the review and expert statements on the optimal approaches when using echocardiography to assess ACHD patients for PH, with particular focus on major subgroups: patients with right ventricular outflow tract obstruction, patients with systemic right ventricles, patients with unrepaired univentricular circulation, and patients with tetralogy of Fallot with pulmonary atresia.

The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging.

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age- and sex-matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long-axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end-diastolic wall thickness increased. However, absolute wall thickening (defined as end-systolic minus end-diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted ß-coefficient: 3.43 [2.60-4.26], P<.0001). Increasing end-diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

An audit of persistent foramen ovale closure in 105 divers.

INTRODUCTION: Right-to-left shunt across a persistent foramen ovale (PFO) has been associated with cutaneous, neurological and vestibular decompression illness (DCI). Percutaneous closure of a PFO has been used to reduce the risk of DCI. There are no randomised controlled trial data to support PFO closure for the prevention of decompression illness (DCI), so the need for audit data on the safety and efficacy of this technique has been recognised by the National Institute of Health and Clinical Excellence in the UK. METHOD: Retrospective audit of all transcatheter PFO closures to reduce the risk of DCI performed by a single cardiologist with an interest in diving medicine. RESULTS: A total of 105 eligible divers undergoing 107 procedures was identified. There was a low rate of procedural complications; a rate lower than a recent randomised trial of PFO closure for stroke. Atrial fibrillation required treatment in two patients. One patient with a previously repaired mitral valve had a stroke that was thought to be unrelated to the PFO closure. Sixteen divers had minor post-procedure symptoms not requiring any treatment. Two divers required a second procedure because of residual shunt; both subsequently returned to unrestricted diving. Eighty-one of 95 divers in whom follow-up bubble contrast echocardiography was available returned to unrestricted diving. CONCLUSIONS: The PFO closure procedure appeared to be safe and was associated with the majority of divers being able to successfully return to unrestricted diving.

Adaptations of aortic and pulmonary artery flow parameters measured by phase-contrast magnetic resonance angiography during supine aerobic exercise.

PURPOSE: Increased oxygen uptake and utilisation during exercise depend on adequate adaptations of systemic and pulmonary vasculature. Recent advances in magnetic resonance imaging techniques allow for direct quantification of aortic and pulmonary blood flow using phase-contrast magnetic resonance angiography (PCMRA). This pilot study tested quantification of aortic and pulmonary haemodynamic adaptations to moderate aerobic supine leg exercise using PCMRA. METHODS: Nine adult healthy volunteers underwent pulse gated free breathing PCMRA while performing heart rate targeted aerobic lower limb exercise. Flow was assessed in mid ascending and mid descending thoracic aorta (AO) and main pulmonary artery (MPA) during exercise at 180 % of individual resting heart rate. Flow sequence analysis was performed by experienced operators using commercial offline software (Argus, Siemens Medical Systems). RESULTS: Exercise related increase in HR (rest: 69 ± 10 b min(-1), exercise: 120 ± 13 b min(-1)) resulted in cardiac output increase (from 6.5 ± 1.4 to 12.5 ± 1.8 L min(-1)). At exercise, ascending aorta systolic peak velocity increased from 89 ± 14 to 122 ± 34 cm s(-1) (p = 0.016), descending thoracic aorta systolic peak velocity increased from 104 ± 14 to 144 ± 33 cm s(-1) (p = 0.004), MPA systolic peak velocity from 86 ± 18 to 140 ± 48 cm s(-1) (p = 0.007), ascending aorta systolic peak flow rate from 415 ± 83 to 550 ± 135 mL s(-1) (p = 0.002), descending thoracic aorta systolic peak flow rate from 264 ± 70 to 351 ± 82 mL s(-1) (p = 0.004) and MPA systolic peak flow rate from 410 ± 80 to 577 ± 180 mL s(-1) (p = 0.006). CONCLUSION: Quantitative blood flow and velocity analysis during exercise using PCMRA is feasible and detected a steep exercise flow and velocity increase in the aorta and MPA. Exercise PCMRA can serve as a research and clinical tool to help quantify exercise blood flow adaptations in health and disease and investigate patho-physiological mechanisms in cardio-pulmonary disease.

Use of radiofrequency perforation for lead placement in biventricular or conventional endocardial pacing after mustard or senning operations for D-transposition of the great arteries.

BACKGROUND: Endocardial pacemaker lead placement can be challenging after Mustard and Senning operations for transposition of the great arteries (D-TGA), if there is atresia of the systemic venous pathways and because the coronary sinus cannot be used for cardiac resynchronization therapy. Radiofrequency (RF)-assisted perforation techniques have been used in congenital heart disease but have not been reported for use in pacemaker implantation. METHODS AND RESULTS: We describe RF perforation of an atretic superior systemic venous pathway and systemic venous baffles in three patients after Senning and Mustard operations to implant endocardial pacing systems to achieve conventional or biventricular pacing. CONCLUSIONS: RF-energy-assisted perforation is feasible and effective tool to facilitate endocardial lead placement during dual-chamber and biventricular pacemaker implantation in patients with Mustard or Senning operations for D-TGA.

Drugs, gene transfer, signaling factors: a bench to bedside approach to myocardial stem cell therapy.

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction-myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs.

BACKGROUND: Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. OBJECTIVE: To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. METHODS: Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. RESULTS: Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. CONCLUSION: Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

[Stem cell therapy in cardiovascular diseases]. / Ossejtek alkalmazása a cardiovascularis betegségek kezelésében.

Myocardial infarction is the leading cause of congestive heart failure in the industrialized world. Current treatments fail to address the underlying scarring and cell loss, which are the causes of ischaemic heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes and endothelial cells. Myocardial regeneration is the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes were generated in what was previously considered a postmitotic organ. So far, candidates for cardiac stem cell therapy have been limited to patients with acute myocardial infarction and chronic ischaemic heart failure. Currently, bone marrow stem cells seem to be the most attractive cell type for these patients. The cells may be delivered by means of direct surgical injection, intracoronary infusion, retrograde venous infusion, and transendocardial infusion. Stem cells may directly increase cardiac contractility or passively limit infarct expansion and remodeling. Early phase I clinical studies indicate that stem cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of benefit and the effect on mortality after stem cell therapy.

[New medical therapies for the treatment of systolic heart failure]. / Uj lehetóségek a systolés szívelégtelenség gyógyszeres kezelésére.

Heart failure is characterized by sodium and fluid retention, sympathetic overactivation, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1000 patients in numerous clinical investigations, it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosteron receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.