Use of Sodium–Glucose Cotransporter 2 (SGLT-2) Inhibitors Beyond Diabetes: On the Verge of a Paradigm Shift?

The sodium–glucose co-transporter 2 (SGLT2) inhibitors have proven effective in glycemia control in patients with type 2 diabetes (T2D) by increasing urinary glucose excretion. However, the beneficial effects of SGLT2 inhibition extend beyond glycemic control, with new studies demonstrating beneficial effects that lead to improved cardiovascular (CV) (cardioprotection) and renal outcomes (renoprotection) in patients with T2D. Pivotal CV outcomes trials have demonstrated a 27-35% reduction in heart failure (HF) hospitalizations in patients with T2D. Importantly, a variety of pleiotropic effects of these new agents have been identified that include, but are not limited to, anti-atherosclerotic, anti-inflammatory, and anti-oxidant effects, decreased vascular stiffness and improved endothelial function, weight loss, reduction in sympathetic activity and in cardiac arrhythmogenesis. Ongoing studies are investigating these actions in patients with and without diabetes. Such results, if positive, may lead to a paradigm shift in the management of CV, renal and even other diseases beyond diabetes. Rhythmos 2020;15(1):67-71

Hybrid Heart Failure Treatment

A case of refractory heart failure (HF) is presented in a 64-year-old gentleman with ischemic cardiomyopathy and severe left ventricular dysfunction, who availed himself of currently available hybrid HF treatment, like optimal medical treatment, electrical and interventional therapies comprising drugs, an implantable cardiac resynchronization therapy defibrillator (CRT-D) effected via alternate route (middle cardiac vein) for left ventricular lead placement combined with percutaneous mitral valve therapy (MitraClip) that prolonged his life to ~10 years. Rhythmos 2021; 16(1):99-101

Cardiology News / Recent Literature Review / Last Quarter 2019

HCS Working Groups: Thessaloniki, 20-22/2/2020 ACC Meeting: Chicago, IL, USA, 28-30/3/2020 EHRA Meeting: Vienna, 29-31/3/2020 HRS Meeting: San Diego, 6-9/5/2020 EuroPCR: Paris, 19-22/5/2020 ESC Meeting: Amsterdam, 29/8-2/9/2020 Childhood Secondhand Smoke Exposure Predicts Increased Risk for Adulthood Atrial Fibrillation (AF) After Adjustment for AF Risk Factors A study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring’s childhood, evaluated every 2-8 years and being under routine surveillance for incident AF. Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio - HR: 1.18; p=0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio - OR: 1.34; p<0.001). Offspring smoking mediated 17% of the relationship between parental smoking and offspring AF (Groh CA et al, J Am Coll Cardiol 2019; 74:1658-64). When Left Untreated, Severe Aortic Stenosis (AS) is Associated With Poor Long-Term Survival / But Also Moderate AS Confers Poor Survival Rates Among 16,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively, on an adjusted basis (vs. no AS; 5-year mortality 19%), patients with mild to severe AS had an increasing risk of long-term mortality (adjusted hazard ratio: 1.44-2.09; p<0.001 for all comparisons). The 5-year mortality was 56% and 67%, respectively, in those with moderate AS (mean gradient 20.0-39.0 mmHg/peak velocity 3.0-3.9 m/s) and severe AS (≥40 mmHg, ≥4 m/s, or AV area<1 cm2 in low-flow, low-gradient severe AS). A markedly increased risk of death from all causes (5-year mortality >50%) and CV disease was evident from a mean AV gradient >20 mmHg (moderate AS) after adjusting for age, sex, LV systolic or diastolic dysfunction, and aortic regurgitation (Strange G et al, J Am Coll Cardiol 2019; 74:1851-63). Premature (Age≤45 Years) Acute or Stable Obstructive Coronary Artery Disease (CAD) is an Aggressive Disease Despite the Currently Recommended Prevention Measures, With High Rates of Recurrent Events and Mortality Among 880 patients with premature CAD, aged 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia, at baseline presentation, 91% underwent coronary revascularization, predominantly for acute MI (79%). Over 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n=131 of 264), mostly related to new coronary lesions (17% vs 8%; p=0.01; hazard ratio - HR: 1.45 for new vs initial culprit lesion). All-cause death (n=55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted HR - adjHR: 1.95; p=0.02), inflammatory disease (adjHR: 1.58; p=0.03), and persistent smoking (adjHR: 2.32; p<0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis (Collet J-P et al, J Am Coll Cardiol 2019; 74:1868-78)... (excerpt

Eggshell Calcification of the Heart

   A case of a patient with extensive egg-shell calcification of the pericardium is presented without signs of constriction. This was imaged by fluoroscopy during an ablation procedure performed for persistent atrial fibrillation.  Rhythmos 2022; 17(1):105-106

Cardiology News / Recent Literature Review / Last Quarter 2019

HCS Working Groups: Thessaloniki, 20-22/2/2020 ACC Meeting: Chicago, IL, USA, 28-30/3/2020 EHRA Meeting: Vienna, 29-31/3/2020 HRS Meeting: San Diego, 6-9/5/2020 EuroPCR: Paris, 19-22/5/2020 ESC Meeting: Amsterdam, 29/8-2/9/2020 Childhood Secondhand Smoke Exposure Predicts Increased Risk for Adulthood Atrial Fibrillation (AF) After Adjustment for AF Risk Factors A study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring’s childhood, evaluated every 2-8 years and being under routine surveillance for incident AF. Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio - HR: 1.18; p=0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio - OR: 1.34; p<0.001). Offspring smoking mediated 17% of the relationship between parental smoking and offspring AF (Groh CA et al, J Am Coll Cardiol 2019; 74:1658-64). When Left Untreated, Severe Aortic Stenosis (AS) is Associated With Poor Long-Term Survival / But Also Moderate AS Confers Poor Survival Rates Among 16,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively, on an adjusted basis (vs. no AS; 5-year mortality 19%), patients with mild to severe AS had an increasing risk of long-term mortality (adjusted hazard ratio: 1.44-2.09; p<0.001 for all comparisons). The 5-year mortality was 56% and 67%, respectively, in those with moderate AS (mean gradient 20.0-39.0 mmHg/peak velocity 3.0-3.9 m/s) and severe AS (≥40 mmHg, ≥4 m/s, or AV area<1 cm2 in low-flow, low-gradient severe AS). A markedly increased risk of death from all causes (5-year mortality >50%) and CV disease was evident from a mean AV gradient >20 mmHg (moderate AS) after adjusting for age, sex, LV systolic or diastolic dysfunction, and aortic regurgitation (Strange G et al, J Am Coll Cardiol 2019; 74:1851-63). Premature (Age≤45 Years) Acute or Stable Obstructive Coronary Artery Disease (CAD) is an Aggressive Disease Despite the Currently Recommended Prevention Measures, With High Rates of Recurrent Events and Mortality Among 880 patients with premature CAD, aged 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia, at baseline presentation, 91% underwent coronary revascularization, predominantly for acute MI (79%). Over 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n=131 of 264), mostly related to new coronary lesions (17% vs 8%; p=0.01; hazard ratio - HR: 1.45 for new vs initial culprit lesion). All-cause death (n=55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted HR - adjHR: 1.95; p=0.02), inflammatory disease (adjHR: 1.58; p=0.03), and persistent smoking (adjHR: 2.32; p<0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis (Collet J-P et al, J Am Coll Cardiol 2019; 74:1868-78)... (excerpt

Dronedarone: the Hope and the Hype

Atrial fibrillation (AF) is the commonest cardiac arrhythmia afflicting ~1% of the total population in an age-dependent manner with 2.3% of individuals older than 40 years of age, or 5.9% of people older than 65. Approximately 70% of persons with AF are between 65 and 85 years of age. Patients with AF experience significantly higher mortality rates than patients without AF; adjusted relative mortality risk has been found approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < 0.05). One sixth of all strokes are attributable to AF and the percentage of strokes due to AF increases dramatically with age; of course the risk of stroke is significantly decreased with anticoagulation therapy by 60-70%, but this has its own inherent problems. Unfortunately, the use of antiarrhythmic drugs (AADs) employed thus far to maintain sinus rhythm is severely problematic with treatment being occasionally worse than the disease. Nevertheless, the goal is still to maintain sinus rhythm, since teleologically this is the optimal rhythm man is born and should live with, but the means to effect and sustain this, have inherent potentially prohibitive risks, as shown in the AFFIRM, RACE and other trials. However, even in the AFFIRM trial, which showed that AADs may be associated with increased mortality, overall maintenance of sinus rhythm (with or without AADs) was associated with improved survival compared with persistent AF. This observation supports the long-recognized mortality risk associated with AF, and hence the continued quest for development of new and safer antiarrhythmic agents and methods to maintain sinus rhythm. In this endeavor, newer pharmacological agents have recently emerged but not yet fulfilled this expectation. Among them, dronedarone, a modified molecule of amiodarone devoid of the iodine moiety, was heralded as the agent with the new hope... (excerpt

Focal Ablation of Atrial Fibrillation: The Target Remains Elusive

Contemporary technology using mapping tools and algorithms in animal and computer models has suggested discrete atrial fibrillation (AF)-sustaining mechanisms in the form of electric rotors as focal areas of AF perpetuation. When these focal sites were targeted, ablation initially appeared promising in reducing the recurrence rates of AF. However, many other investigators have been unable to reproduce this kind of success with focal impulse and rotor modulation (FIRM)-guided ablation, and have cast doubts on the effectiveness of this novel technique that could have led to a paradigm-shift in our approach to AF ablation. A single randomized trial that was recently published in a high-impact cardiology journal indicating poor results of rotor ablation was subsequently retracted amidst a cloud of controversy and doubt about the flaws and conflicts of current medical publishing. Thus, until further evidence from ongoing and future randomized studies becomes available, the target of focal ablation for AF patients continues to remain elusive. Rhythmos 2017;12(2):21-25

TAVI in Bicuspid Aortic Valve Stenosis: Cautiously Feasible

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation with a prevalence of 0.4% to 2%. For a long time, a BAV has not been considered an indication for transcatheter aortic valve implantation (TAVI) due to insufficient technology and poor procedural results conferred by a challenging valvular anatomy leading to poor stability of the prosthetic valve and/or paravalvular regurgitation due to distorted native valve leaflets. Large randomized controlled TAVI trials typically excluded bicuspid aortic stenosis (AS) because of its unique anatomic features. However, current technological advancements are apparently changing this landscape, and over the last few years, TAVI appears technically feasible, albeit a demanding procedure, and has been used to treat severe bicuspid AoV stenosis with promising results, as shown, apart from earlier case reports and patient series, in several recent observational studies and comparative trials between patients with tricuspid and patients with BAV. Thus, current literature cautiously supports a role of TAVI in selected BAV AS patients; however, the final role of this technique in this challenging group of patients will need to be determined from randomized controlled trials comparing TAVI with surgical replacement and studies comparing TAVI in bicuspid and tricuspid aortic valves. Technological advancements appear to play a significant and crucial role in rendering the transcatheter approach feasible, efficacious and safe. Rhythmos 2017;12(3): 40-44

Management of Cryptogenic Strokes by Percutaneous Closure of Interatrial Communications

In patients with a cryptogenic stroke the prevalence of a patent foramen ovale (PFO) is increased to approximately 50% compared with a 25%-30% prevalence rate in the general population. This leads to a plausible assumption that a considerable number of strokes could potentially be attributed to a PFO, most likely due to paradoxical embolism. It is estimated that the risk for an embolic stroke due to the presence of a PFO may be 9-fold higher than that related to hypertension, diabetes or hypercholesterolemia. Furthermore, in the presence of an interatrial septal aneurysm (IASA), this risk may even be 30-fold higher. The management of patients with a cryptogenic stroke and a PFO is currently based on antithrombotic or anti-platelet therapy, however the recurrence rate remains high (4-25%), and this has led to the recommendation of percutaneous PFO closure, which is now effected via a simple and relatively safe technique, which appears to reduce recurrences to 0-5%. However, the studies which provide such favorable data are only retrospective, which means that we are in dire need of prospective randomized studies that compare the two therapeutic approaches, before the interventional method is more widely adopted. In addition to cryptogenic stroke, the presence of a PFO has been also associated, among other conditions, with bouts of migraine and its percutaneous closure has been shown, albeit via retrospective and observational data, to eliminate or significantly improve this common condition. The only prospective randomized trial available (MIST trial) failed to show conclusively the superiority of PFO closure to medical treatment with regards to elimination of migraine.Another large group of patients undergoing percutaneous closure of an interatrial communication are those with a secundum atrial septal defect (ASD). The majority of these patients, at least those having defects as large as 35-38 mm and an adequate rim to support a closure device, can now be successfully submitted to the percutaneous technique and thus avoid surgery. Certainly, these patients could also suffer from cryptogenic strokes and migraine, however, most of them usually require intervention because of hemodynamic reasons.The technique of percutaneous closure of a PFO or an ASD performed by adult interventional cardiologists is indeed a relatively simple and swift procedure of right heart catheterization, carried out from the groin area via the femoral vein with use of local anesthesia. Complications related to the procedure are limited to ≤1-3.4%. Due to this paradigm of technological progress, a rapid growth of procedures of percutaneous closure of ASD and PFO has been noted over the last decade, particularly over the recent 4-5 years. Nevertheless, one has to resist in widely and hastily adopting such methods before further strong evidence becomes available via randomized prospective studies

Vitamin D and Cardiovascular Disease

Vitamin D exists in several forms comprising steroid-like fat-soluble molecules (secosteroids). Cholecalciferol (vitamin D3) is synthesized in the skin in response to ultraviolet irradiation producing photochemical cleavage of a cholesterol precursor (7-dehydro-cholesterol). Irradiation of ergosterol, a membrane sterol found in the Ergot fungus, produces ergocalciferol (vitamin D2). Dietary sources of vitamin D include fish oils (D3), egg yolk (D3), mushrooms (D2), and fortified cereals and dairy products (D2 or D3). Vitamin D derived from all different sources undergoes two successive hydroxylation steps, first in the liver (25-hydroxyvitamin D) and then the kidney (1, 25-hydroxyvitamin D2 / calcitriol). The former form has a longer half-life than the latter (weeks vs. several hours). The biologic effects of vitamin D result largely from its binding to the vitamin D receptor (VDR), a nuclear steroid hormone found in almost every tissue. Calcitriol (D2) appears to have the greatest affinity for the receptor. The prevalence of vitamin D deficiency is estimated around 30–50% in the adult population in developed countries, mostly the result of insufficient cutaneous production due to decreased exposure to sunlight, and to a less degree from low dietary intake. Serum levels of 25-hydroxyvitamin D >30 ng/mL are considered adequate, while levels < 20 ng/mL are diagnostic of vitamin D deficiency.The endocrine functions of vitamin D in relation to bone metabolism and mineral ion homoeostasis are well known. Vitamin D deficiency results in reduced intestinal absorption of calcium, which stimulates the production of parathyroid hormone with an ensuing accelerated bone de-mineralization to maintain serum calcium concentration, with all these alterations leading to the clinical effects of hypocalcemia. These may rarely result in tetany, but due to gradual and insidious development, more commonly produce local, or diffuse musculo-skeletal aches and pains.Importantly, more recent epidemiological studies have linked vitamin D deficiency with the pathogenesis of cardiovascular disease (CVD) and an attendant increase in cardiovascular morbidity and mortality, but data for a causal relationship are still missing... (excerpt