René Géronimo Favaloro : pioneer of Cardiac Surgery

Dr. René G. Favaloro moved to the Cleveland Clinic in 1962 and proceeded to reshape the face of cardiac surgery as we knew it. Together with his colleagues at the Cleveland Clinic, Drs. Effler, Sones, Proudfit, Groves, Sheldon and countless others, he contributed to the double internal mammary arterymyocardial implantation by the Vineberg method, and by May 1967, he reconstructed the right coronary artery by the saphenous vein graft interposition. These landmark procedures paved the way for the aorto-coronary saphenous vein bypass graft in October 1967. Many similar breakthroughs ensued, with the application of the bypass technique to the left coronary artery, the combination of coronary artery bypass graft with left ventricular reconstruction and valve repair/replacement and finally, by December, a double bypass to the right coronary artery and anterior descending branch of the left coronary artery. In June, 1971, Dr. Favaloro decided to leave the Cleveland Clinic and return to Argentina where he created a medical centre, a teaching unit, a research department and finally an Institute of Cardiology and Cardiovascular Surgery. This was his greatest personal ambition. Over and above his brilliant mind and craft, Dr. Favaloro was a man of integrity, courage, honesty and humility, whose name will never cease to reverberate throughout the history of medicine.peer-reviewe

The use of attention-deficit hyperactivity disorder medications in cardiac disease

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset usually in childhood characterized by inattention, impulsivity, and hyperactivity causing a functional impairment. Untreated ADHD, or treatment delay is associated with adverse outcomes and poor quality of life. Although conservative management strategies such as behavioral and psychological interventions are important, pharmacological treatment has a strong evidence base with improved outcomes. ADHD medications are broadly divided into stimulant and non-stimulant medications. Stimulant medications are generally more effective than non-stimulants. Cardiovascular safety of ADHD medication has been a matter of debate for decades. Treatment guidelines advise the careful consideration of risks and benefits in people with cardiovascular diseases such as congenital heart disease or cardiomyopathy. Although stimulants can increase systemic blood pressure and heart rate, no significant associations were found between their use and serious cardiovascular events. Concerns regarding QT effects and attendant sudden cardiac death risks deter clinicians from initiating much-needed ADHD medications in patients with heart disease. This overly cautious approach is potentially depriving low-risk individuals from significant benefits associated with timely ADHD drug treatment. This review discusses the cardiovascular risks reportedly associated with ADHD medications, the evidence base for their safe usage in persons with established cardiovascular disease, and highlights future research directions

Therapeutic Dilemmas Faced When Managing a Life-Threatening Presentation of a Myocardial Bridge

Background. Myocardial bridges are congenital abnormalities, where a segment of coronary artery travels intramyocardially, rather than the typical epicardial course. The overlying muscle segment is termed “the bridge”. Most myocardial bridges are asymptomatic, but some can result in myocardial ischaemia, arrhythmias, and sudden cardiac death. Case Presentation. A 31-year-old male with no past medical history presented to our tertiary cardiac centre following an out-of-hospital ventricular fibrillation arrest. Coronary angiography and computed tomography of the coronary arteries revealed a 2 cm myocardial bridge overlying the left anterior descending (LAD) artery. An exercise echocardiogram demonstrated severe apical ballooning and hypokinesis during peak exercise, with corresponding ST-segment elevation, resolving on rest. Options for medical therapy of a symptomatic myocardial bridge include beta blockers, calcium channel blockers, ivabradine, or a combination thereof. Surgical interventions include deroofing the bridge and revascularisation of the affected region with bypass grafting. However, a lack of trial data comparing medical regimens and surgical interventions makes it difficult to ascertain the most effective management strategy for each patient. There was disagreement between experts at different tertiary centres over the optimal management of this patient. He was treated with multiple regimes of medical therapy with ongoing ischaemia on stress testing, before undergoing a negative stress test on amlodipine, diltiazem, and isosorbide mononitrate. It was felt that no further intervention was necessary at this time given his exercise test was now negative for ischaemia. However, after seeking a second opinion, he underwent surgical intervention with bypass grafting of his left anterior descending artery, followed by implantation of an implantable cardiac defibrillator. Subsequently, an angiogram postsurgery demonstrated concomitant spasm of the LAD and he was resumed on medical therapy with calcium channel blockers and nitrates. Discussion. Without randomised trials, it is impossible to determine the optimal management strategy for each patient. It is possible that some patients with myocardial bridges are not being trialled on optimal medical therapy prior to undergoing invasive and irreversible interventions

Parathyroid carcinoma : clinical course, diagnosis and management

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism often resulting in severe hypercalcaemia. It tends to follow a rather aggressive course with a high propensity for locoregional spread and distant metastasis. En bloc resection is the mainstay of treatment, with surgery also playing a role in the palliation of hypercalcaemia for recurrent and metastatic disease. While adjuvant chemotherapy and radiotherapy have shown disappointing outcomes, bisphosphonates and calcimimetic agents are effective in the management of recalcitrant hypercalcaemia in parathyroid carcinoma. We report a case of parathyroid carcinoma in a lady who initially presented with a neck mass, severe hypercalcaemia, a bony swelling over the shin and elevated parathyroid hormone levels. The diagnosis was confirmed histologically following a thyroid lobectomy, isthmectomy and parathyroidectomy. In the three years which followed the patient received two courses of palliative radiotherapy, two thoracotomies for pulmonary metastatectomy, an extensive neck re-exploration and fashioning of a tracheostomy for aggressive local recurrence with invasion of the larynx.peer-reviewe

Meta-analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease, as penetrance (proportion of G+ who develop disease) is variable, age-dependent, and not reliably predicted. METHODS: A systematic search of the literature was performed. We employed random effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere genes in two different contexts: clinically-based studies on patients and families with HCM versus population/community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up. FINDINGS: 455 full text manuscripts were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in non-proband relatives carrying P/LP variants identified during cascade screening was 57% (95% confidence interval [CI] [52,63]) and the mean age of HCM diagnosis was 38 years (95% CI [36, 40]). Penetrance varied from ~32% for myosin light chain (MYL3) to ~55% for myosin binding protein C (MYBPC3), ~60% troponin T (TNNT2) and troponin I (TNNI3), and ~65% for myosin heavy chain (MYH7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population, but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower; approximatively 11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ~8 years of follow up, starting from a mean age of ~16 years. However, short-term gene-specific phenotypic conversion varied between ~12% for MYBPC3 to ~23% for MYH7. CONCLUSIONS: The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve understanding of true lifetime penetrance in families and in the community, and to identify drivers of the transition from subclinical to overt HCM

Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort

BACKGROUND: As people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown. OBJECTIVES: To examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort. METHODS: Participants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60–64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60–64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60–64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation. RESULTS: One thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y with QTc prolongation [respectively: β −0.30 ms/nmol/L, (95% confidence intervals −0.44, −0.17), p < 0.001; β−28.9 ms/unit (-41.93, −15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β −0.04 ms/nmol/L (−0.08, −0.008), p = 0.019; β −2.44 ms/unit (-4.17, −0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y [β −0.21 ms/nmol/L (−0.39, −0.04), p = 0.017; β −20.14 ms/unit (−36.28, −3.99), p = 0.015], steeper decline in ΔIGF-I [β −0.05 ms/nmol/L/10 years (−0.10, −0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β −2.16 ms/unit/10 years (−4.23, −0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β −5.70 ms/mmol/L (−10.23, −1.18) p = 0.014]. CONCLUSIONS: Over a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted

Myocardial Fibrosis in Heart Failure: Anti-Fibrotic Therapies and the Role of Cardiovascular Magnetic Resonance in Drug Trials.

All heart muscle diseases that cause chronic heart failure finally converge into one dreaded pathological process that is myocardial fibrosis. Myocardial fibrosis predicts major adverse cardiovascular events and death, yet we are still missing the targeted therapies capable of halting and/or reversing its progression. Fundamentally it is a problem of disproportionate extracellular collagen accumulation that is part of normal myocardial ageing and accentuated in certain disease states. In this article we discuss the role of cardiovascular magnetic resonance (CMR) imaging biomarkers to track fibrosis and collate results from the most promising animal and human trials of anti-fibrotic therapies to date. We underscore the ever-growing role of CMR in determining the efficacy of such drugs and encourage future trialists to turn to CMR when designing their surrogate study endpoints

The Relationship of Left Ventricular Trabeculation to Ventricular Function and Structure Over a 9.5-Year Follow-Up The MESA Study

Left ventricular (LV) trabeculation is highly variable among individuals and is increased in some diseases (e.g., congenital heart disease or cardiomyopathies), but its significance in population-representative individuals is unknown

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis

Assessment of Microvascular Disease in Heart and Brain by MRI: Application in Heart Failure with Preserved Ejection Fraction and Cerebral Small Vessel Disease

The objective of this review is to investigate the commonalities of microvascular (small vessel) disease in heart failure with preserved ejection fraction (HFpEF) and cerebral small vessel disease (CSVD). Furthermore, the review aims to evaluate the current magnetic resonance imaging (MRI) diagnostic techniques for both conditions. By comparing the two conditions, this review seeks to identify potential opportunities to improve the understanding of both HFpEF and CSVD