Cardiac Exercise Research Articles

Why Does Rivaroxaban Not Work in Severe Mitral Stenosis?

Mitral stenosis is not a rare disease. Rheumatic fever is the principal cause of mitral stenosis. Anulus calcification and congenital heart disease are recognized as other causes of mitral stenosis.[1] In developed countries, the prevalence is approximately 0.6 in 1,000 in the United States, but it is much higher in developing nations: 21 cases per 1,000 in Asia, 15 cases per 1,000 in Africa, and 17 cases per 1,000 in South America.[2] Atrial fibrillation occurs in approximately 32% of symptomatic patients, thus decreasing cardiac output and exercise capacity, and greatly increasing the risk of thromboembolism.[3] Oral anticoagulation is therefore mandatory in these patients. Although direct oral anticoagulants (DOACs) have been found to be noninferior or superior versus vitamin K antagonists (VKAs; e.g., warfarin) in preventing cardioembolism in patients with atrial fibrillation,[4] patients with atrial fibrillation and rheumatic heart disease were not enrolled in earlier trials, thus excluding this pathological condition from approved indications.[5] Since ensuring adequate anticoagulation with laboratory monitoring while using VKAs may be difficult in developing countries, DOACs have the potential to improve the extension of oral anticoagulation without the need of any laboratory control. The commitment to plan a superiority trial (DOAC vs. VKA) came in 2016 from the cardiology community, which aimed to design a superiority trial involving a single-dose DOAC (no laboratory monitoring) versus VKA (with laboratory monitoring), and since the latter showed a poor time in the therapeutic range in countries of Asia, Africa, and Latin America.[6] Thus, a multicenter, randomized, noninferiority trial to evaluate the efficacy and safety of the factor Xa inhibitor, rivaroxaban, in comparison with VKA was planned and recently completed (INVICTUS trial). The trial involved patients with rheumatic heart disease from Africa, Asia, and Latin America,[7] enrolling patients with atrial fibrillation and echocardiographically documented rheumatic heart disease. Eighty-five percent of trial participants had mitral-valve stenosis, which was moderate-to-severe in 82%. These participants had a CHA2DS2VASc score of at least 2, a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast (SEC), or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban (20 mg/day) or dose-adjusted VKA (INR: 2.0–3.0). The mean ± standard deviation (SD) duration of follow-up was 3.1 ± 1.2 years. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. The primary safety outcome was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH).[8] A total of 4,531 participants were included in the final analysis. Mean age of the patients (72.3% women) was 50.5 years.

Effect of a 12-week high-intensity exercise intervention: a comparison of cardiac exercise adaptations during biological disease-modifying antirheumatic drug treatment (TNF inhibitors vs IL-6 signalling inhibitors) in patients with rheumatoid arthritis – study protocol for a randomised controlled trial

IntroductionThe chronic inflammatory state in rheumatoid arthritis (RA) augments the risk of cardiovascular disease (CVD), with pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin 6 (IL-6) playing a vital role....

Beneficial effects of exercise initiated before development of hypertrophic cardiomyopathy in genotype-positive mice.

The effect of exercise on disease development in hypertrophic cardiomyopathy (HCM) genotype-positive individuals is unresolved. Our objective was to test the effect of exercise training initiated before phenotype development on cardiac fibrosis, morphology, and function in a mouse model of HCM. Genotype-positive Myh6 R403Q mice exposed to cyclosporine A (CsA) for induction of HCM (HCM mice) were allocated to high-intensity interval treadmill running or sedentary behavior for 6 wk. CsA was initiated from week 4 of the protocol. Cardiac imaging and exercise testing were performed at weeks 0, 3, and 6. After protocol completion, arrhythmia provocation was performed in isolated hearts, and left ventricles (LVs) were harvested for molecular biology and histology. Exercised HCM mice ran farther and faster and exhibited attenuated left atrial (LA) dilatation compared with sedentary mice. Exercised HCM mice had no difference in fibrosis compared with sedentary HCM mice despite lower expression of key extracellular matrix (ECM) genes collagen 1 and 3, fibronectin, and lysyl oxidase, accompanied by increased activation of Akt, GSK3b, and p38. Exercise did not have negative effects on LV function in HCM mice. Our findings indicate mild beneficial effects of exercise initiated before HCM phenotype development, specifically lower ECM gene expression and LA dilatation, and importantly, no detrimental effects.NEW & NOTEWORTHY Genotype-positive hypertrophic cardiomyopathy (HCM) mice had beneficial effects of exercise initiated before phenotype development. Exercised HCM mice had increased exercise capacity, smaller left atria, no increase in hypertrophy, or reduction of function, and a similar degree of fibrosis despite reduction of central extracellular matrix (ECM) genes, including collagens, compared with sedentary HCM mice.

Cardiac exercise imaging using a 3-tesla magnetic resonance-conditional pedal ergometer: Preliminary results in healthy volunteers and patients with known or suspected coronary artery disease.

Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR METHODS: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. Median subjective image quality of real-time cine at rest was 1 (interquartile range [IQR] 1-2) and 2 (IQR 2-2.5) for post-exercise real-time cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62-73] to 111 [104-143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m2, respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution postexercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

Cardiac transplant and exercise cardiac rehabilitation.

Cardiac transplantation is the final therapeutic option for patients with end-stage heart failure. Most patients experience a favorable functional ability post-transplant. However, episodes of acute rejection, and multiple comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and cardiac allograft vasculopathy are common. The number of transplants has increased steadily over the past two decades with 3,817 operations performed in the United States in 2021. Patients have abnormal exercise physiologic responses related to surgical cardiac denervation, diastolic dysfunction, and the legacy of reduced skeletal muscle oxidative capacity and impaired peripheral and coronary vasodilatory reserve resulting from pre-transplant chronic heart failure. Cardiorespiratory fitness is below normal for most patients with a mean peak VO2 of approximately 60% of predicted for healthy persons. Cardiac transplant recipients are therefore excellent candidates for Exercise-Based Cardiac Rehabilitation (CR). CR is safe and is a recommendation of professional societies both before (pre-rehabilitation) and after transplantation. CR improves peak VO2, autonomic function, quality of life, and skeletal muscle strength. Exercise training reduces the severity of cardiac allograft vasculopathy, stroke risk, percutaneous coronary intervention, hospitalization for either acute rejection or heart failure, and death. However, there are deficits in our knowledge regarding CR for women and children. In addition, the use of telehealth options for the provision of CR for cardiac transplant patients requires additional investigation.

Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs-A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial.

This study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective. Young male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p < 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p < 0.001). The ST-segment resolution (>80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p < 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p < 0.001). Early intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI.

Differences in Cardiac Mechanics and Exercise Physiology Among Heart Failure With Preserved Ejection Fraction Phenomapping Subgroups

Unsupervised machine learning (phenomapping) has been used successfully to identify novel subgroups (phenogroups) of heart failure with preserved ejection fraction (HFpEF). However, further investigation of pathophysiological differences between HFpEF phenogroups is necessary to help determine potential treatment options. We performed speckle-tracking echocardiography and cardiopulmonary exercise testing (CPET) in 301 and 150 patients with HFpEF, respectively, as part of a prospective phenomapping study (median age 65 [25th to 75th percentile 56 to 73] years, 39% Black individuals, 65% female). Linear regression was used to compare strain and CPET parameters by phenogroup. All indicies of cardiac mechanics except for left ventricular global circumferential strain worsened in a stepwise fashion from phenogroups 1 to 3 after adjustment for demographic and clinical factors. After further adjustment for conventional echocardiographic parameters, phenogroup 3 had the worst left ventricular global longitudinal, right ventricular free wall, and left atrial booster and reservoir strain. On CPET, phenogroup 2 had the lowest exercise time and absolute peak oxygen consumption (VO2), driven primarily by obesity, whereas phenogroup 3 achieved the lowest workload, relative peak oxygen consumption (VO2), and heart rate reserve on multivariable-adjusted analyses. In conclusion, HFpEF phenogroups identified by unsupervised machine learning analysis differ in the indicies of cardiac mechanics and exercise physiology.

Sudden cardiac death in sports

Problem and objective: To inform about the incidence, causes and prevention measures of sudden cardiac death in sports. Methods: A literature search was performed (PubMed, Web of Science, Researchgate) using the terms sudden cardiac death (SCD), sudden cardiac arrest (SCA), sudden death, cardiopulmonary resuscitation, sport, exercise and athlete. Observational studies, systematic reviews and meta-analyses that examined SCD/SCA during exercise or up to one hour afterwards in recreational, competitive or elite athletes were considered. Results: Of 6350 study titles and abstracts 11 full-text studies were included in this clinical review. When the incidence was calculated based on multiple sports, it varied between populations and ranged from 0.1 to 2.9/100,000 athlete-years (AY). The incidence was highest in male professional basketball players, with 19/100,000 AY. The most frequent cause of SCD/SCA in athletes &gt;35 years was coronary artery disease (CAD), while in younger athletes the predominating underlying pathologies (autopsy-negative sudden unexplained death, myocarditis, cardiomyopathies, coronary artery anomalies and premature CAD) differed by region. The most effective screening tool for cardiovascular disease in athletes is the ECG. Survival after CPR is substantially influenced by the use of an automated external defibrillator (AED). Discussion: SCD/SCA in athletes is a rare but very tragic event. Incidence rates in athletes differ among populations, studies, and sports. Some degree of underreporting can be assumed as there is no mandatory reporting of sports-related SCD/SCA in most countries and few scientific registries exist. Potentially, primary screening measures could be adapted to the regionally different causes of SCD/SCA. In addition, training athletes and staff in the use of an AED is paramount to improving survival rates.

Importance of Systematic DiagnosticTesting in Idiopathic Ventricular Fibrillation: Results From the Dutch iVF Registry.

Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized. The purpose of this study was to investigate the importance and consistency of systematic diagnostic testing in iVF. This study included 423 iVF patients from 11 large secondary and tertiary hospitals in the Netherlands. Clinical characteristics and diagnostic testing data were ascertained. IVF patients experienced the index event at a median age of 40 years (IQR: 28-52 years), and 61% were men. The median follow-up time was 6 years (IQR: 2-12 years). Over the years, "high yield" diagnostic tests were increasingly performed (mean 68% in 2000-2010 vs 75% in 2011-2021; P< 0.001). During follow-up, 38 patients (9%) originally labeled as iVF received an alternative diagnosis. Patients in whom "high-yield" diagnostic tests were consistently performed during the initial work-up received an alternative diagnosis less frequently during follow-up (HR: 0.439; 95%CI: 0.219-0.878; P = 0.020). Patients who received an alternative diagnosis during follow-up had a worse prognosis in terms of cardiac death (P = 0.012) with a trend toward more implantable cardioverter-defibrillator therapy (P = 0.055). Although adherence to (near) complete diagnostic testing in this population of iVF patients increased over the years, patients with iVF still undergo varying levels of diagnostic evaluation. The latter leads to initial underdiagnosis of alternative conditions and is associated with a worse prognosis. Our results underscore the importance of early systematic diagnostic assessment in patients with apparent iVF.

Abstract P512: Association Between Resting Rate Pressure Product and All-Cause Mortality Among United States Adults

Background: Rate pressure product (RPP) is a measure of myocardial oxygen consumption and often used to quantify cardiac exercise workload. We sought to determine whether resting RPP was associated with all-cause mortality in healthy U.S. adults. Methods: This was a nationally representative, retrospective cohort study of the 1999-2018 National Health and Nutrition Examination Survey (NHANES), linked to the National Death Index through 2019. We included adult, non-pregnant participants without cardiovascular disease, kidney dysfunction, hypertension, diabetes, or current chronotropic agent use. RPP was calculated as the product of mean systolic BP (of 3 sitting BPs) and resting heart rate, and classified into quintiles (Q1≤7300, Q2 [Ref]: 7300-8250, Q3: 8250-9200, Q4: 9200-10400, Q5: &gt;10400). We used multivariable Cox regression to estimate risk of all-cause mortality, adjusting for demographics, CVD risk factors, and comorbidities, and accounting for the survey design. Results: Among 19,954 participants (mean age 40y; 9,653 [48%] female; 8,056 [66%] non-Hispanic White), 1,013 died over a median follow-up of 10.3 years (IQR, 5.6-15.5). Adults in Q3-Q5 had significantly increased unadjusted risk of all-cause mortality compared to Q2 (HR [95% CI], Q1: 0.89 [0.50,1.58], Q3: 1.69 [1.06,2.72], Q4: 1.97 [1.16,3.34], Q5: 2.69 [1.71,4.22]). Adjustment for covariates attenuated risks of mortality but remained 61% higher for Q5 (Q2 [Ref], Q1: 1.02 [0.77,1.36], Q3: 1.09 [0.85,1.40], Q4: 1.22 [0.93,1.59], Q5: 1.61 [1.25,2.07]). When stratifying by gender, men, but not women, demonstrated increased risk of mortality in Q4 and Q5 (Women, Q4: 0.84 [0.54,1.31], Q5: 1.33 [0.89,1.98]; Men, Q4: 1.53 [1.07,2.18], Q5: 1.79 [1.30,2.46]). Conclusion: Healthy adult participants with a resting RPP greater than 10,400 had 61% higher risk of all-cause mortality compared to a RPP less than or equal to 7,300. This effect seems to be more pronounced in men than women. Further longitudinal studies are needed to understand the independent, predictive value of RPP and factors (e.g. aerobic activity) driving RPP.

Diagnostic evaluation of unexplained ventricular tachyarrhythmias in younger adults.

The diagnostic work-up for cardiac arrest from ventricular tachyarrhythmias occurring in younger adults and structurally normal hearts is variable and often incomplete. We reviewed records for all recipients of a secondary prevention implantable cardiac defibrillator (ICD) younger than 60 years at a single quaternary referral hospital from 2010 to 2021. Patients with unexplained ventricular arrhythmias (UVA) were identified as those with no structural heart disease on echocardiogram, no obstructive coronary disease, and no clear diagnostic features on ECG. We specifically evaluated the adoption rate of five modalities of "second-line"cardiac investigations: cardiac magnetic resonance imaging (CMR), exercise ECG, flecainide challenge, electrophysiology study (EPS), and genetic testing. We also evaluated patterns of antiarrhythmic drug therapy and device-detected arrhythmias and compared them with secondary prevention ICD recipients with a clear etiology found on initial assessment. One hundred and two recipients of a secondary prevention ICD under the age of 60 were analyzed. Thirty-nine patients (38.2%) were identified with UVA and were compared with the remaining 63 patients with VA of clear etiology (61.8%). UVA patients were younger (35.6 ± 13.0vs. 46.0 ± 8.6 years, p < .001) and were more often female (48.7% vs. 28.6%, p = .04). CMR was performed in 32 patients with UVA (82.1%), whereas flecainide challenge, stress ECG, genetic testing, and EPS were only performed in a minority of patients. Overall, the use of a second-line investigation suggested an etiology in 17 patients with UVA (43.5%). Compared to patients with VA of clear etiology, UVA patients had lower rates of antiarrhythmic drug prescription (64.1% vs. 88.9%, p = .003) and had a higher rate of device-delivered tachy-therapies (30.8% vs. 14.3%, p = .045). In this real-world analysis of patients with UVA, the diagnostic work-up is often incomplete. While CMR was increasingly utilized at our institution, investigations for channelopathies and genetic causes appear to be underutilized. Implementation of a systematic protocol for work-up of these patients requires further study.

Intracardiac Flow Analysis of the Right Ventricle in Pediatric Patients With Repaired Tetralogy of Fallot Using a Novel Color Doppler Velocity Reconstruction

Repaired tetralogy of Fallot (RTOF) patients will develop right ventricular (RV) dysfunction from chronic pulmonary regurgitation (PR). Cardiac magnetic resonance sequences such as four-dimensional flow can demonstrate altered vorticity and flow energy loss (FEL); however, they are not as available as conventional echocardiography (echo). The study determined whether a novel, vendor-independent Doppler velocity reconstruction (DoVeR) could measure RV intracardiac flow in conventional echo of RTOF patients. The primary hypothesis was that DoVeR could detect increased vorticity and diastolic FEL in RTOF patients. Repaired tetralogy of Fallot patients with echo were retrospectively paired with age-/size-matched controls. Doppler velocity reconstruction employed the stream function-vorticity equation to approximate intracardiac flow fields from color Doppler. A velocity field of the right ventricle was reconstructed from the apical 4-chamber view. Vortex strength (VS, area integral of vorticity) and FEL were derived from DoVeR. Cardiac magnetic resonance and exercise stress parameters (performed within 1year of echo) were collected for analysis. Twenty RTOF patients and age-matched controls were included in the study. Mean regurgitant fraction was 40.5%±7.6%, and indexed RV end-diastolic volume was 158±36mL/m2. Repaired tetralogy of Fallot patients had higher total, mean diastolic, and peak diastolic VS (P=.0013, P=.0012, P=.0032, respectively) and higher total, mean diastolic, and peak diastolic body surface area-indexed FEL (P=.0016, P=.0022, P<.001, respectively). Peak diastolic indexed FEL and peak diastolic VS had weak-to-moderate negative correlation with RV ejection fraction (r=-0.52 [P=.019] and r=-0.49 [P=.030], respectively) and left ventricular ejection fraction (r=-0.47 [P=.034] and r=-0.64 [P=.002], respectively). Mean diastolic indexed FEL and VS had moderate-to-strong negative correlation with percent predicted maximal oxygen consumption (r=-0.69 [P=.012] and r=-0.75 [P=.006], respectively). DoVeR can detect alterations to intracardiac flow in RTOF patients from conventional color Doppler imaging. Echo-based measures of diastolic VS and FEL correlated with ventricular function. DoVeR has the potential to provide serial evaluation of abnormal flow dynamics in RTOF patients.

Renal denervation in management of heart failure with reduced ejection fraction: A systematic review and meta-analysis

BackgroundSome, but not all, recent studies have shown that renal denervation (RDN) can improve cardiac function and exercise tolerance in people who have heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of RDN as a treatment for HFrEF. MethodsThe Medline, Cochrane Library, Embase, and PubMed databases were searched through to September 28, 2022 for clinical studies that evaluated the effect of RDN on HFrEF. The primary endpoints were changes in left ventricular ejection fraction (LVEF) and 6-min walk distance (6MWD). Secondary endpoints were changes in echocardiographic parameters, including left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA) class, heart rate, and systolic and diastolic blood pressure were also evaluated. Major adverse events were defined as death and rehospitalization for heart failure during follow-up. The estimated glomerular filtration rate (eGFR) and serum creatinine level were extracted as measures of renal function. ResultsEleven trials comprising 313 patients were eligible for quantitative analysis. Pooled analyses showed a mean increase in LVEF of 4.25 % (95 % CI 1.77–6.72; p < 0.001, I2 = 69 %) and an increase in 6MWD (mean difference 50.28 m, 95 % CI 8.78–91.78; p = 0.02; I2 = 81 %) after RDN. Left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness also improved after RDN. NT-proBNP, NYHA class, and heart rate were significantly decreased after RDN. There were no significant changes in blood pressure after RDN. Mortality and HF-related hospitalization rates were relatively low. There was no significant change in eGFR or creatinine after RDN. ConclusionsOur findings suggest that RDN can effectively increase LVEF and 6MWD in patients with HFrEF but require confirmation in studies with larger sample sizes and longer follow-up durations.

A remarkable adaptive paradigm of heart performance and protection emerges in response to the constitutive challenge of marked cardiac-specific overexpression of adenylyl cyclase type 8

Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an increased cAMP-induced cardiac workload (∼30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TGAC8, and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TGAC8 vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TGAC8 did not differ from WT. Unbiased omics analyses identified more than 2,000 transcripts and proteins, comprising a broad array of biological processes across multiple cellular compartments, which differed by genotype; compared to WT, in TGAC8 there was a shift from fatty acid oxidation to aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, marked overexpression of AC8 engages complex, coordinate adaptation “circuitry” that has evolved in mammalian cells to defend against stress that threatens health or life (elements of which have already been shown to be central to cardiac ischemic pre-conditioning and exercise endurance cardiac conditioning) that may be of biological significance to allow for proper healing in disease states such as infarction or failure of the heart.

SGLT2 Inhibition in Heart Failure with Preserved Ejection Fraction - The New Frontier.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with high morbidity and increasing socio-economic burden, compounded by the lack of effective treatment options available to treat this disease. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have previously been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes and patients with heart failure with reduced ejection fraction (HFrEF). Recent major clinical trials with SGLT2 inhibitors, both empagliflozin and dapagliflozin, have now demonstrated improved cardiovascular outcomes in patients with HFpEF and a significant reduction in heart failure hospitalization. Current evidence shows a potential for cardiovascular benefits with SGLT2 inhibition that is consistent across the spectrum of ejection fraction, age, New York Heart Association (NYHA) functional class, natriuretic peptide levels and diabetes status. Although the cardioprotective mechanisms behind SGLT2 inhibition remain unclear, ongoing clinical studies aim to clarify the role of SGLT2 inhibitors on biomarkers of cardiac metabolism, diastolic function and exercise capacity in HFpEF. This article analyzes current clinical evidence from randomized controlled trials and meta-analyses and explores the potential cardioprotective mechanisms of SGLT2 inhibitors, while also looking towards the future of SGLT2 inhibition in HFpEF.

The effect of dance on rehabilitation training after COVID-19.

This study aims at investigating the effect of dance on rehabilitation training after COVID-19. In this study, a total of 112 patients with COVID-19 were recruited for rehabilitation training. Before enrollment, a neurologist conducted medical history inquiry, basic information collection, MMSE (MiniMental State Examination), MoCA (Montreal Cognitive Assessment) and MHIS (Mental Health Information Systems) assessment. In the end, 68 patients with COVID-19 who met the entry criteria and signed the informed consent were included in the training. 8 patients with greater exercise risk after the ECG exercise test were not included in the group. Therefore, 60 patients were finally included in the group. The improved BMCE (Basic Medicine Comprehensive Examination) protocol was used to evaluate the cardiac function and exercise adaptability of the patients. The 12 lead ECG and gas metabolism instrument were used to monitor the changes of ECG and gas metabolism, and the blood pressure was measured at the same time. The exercise intensity was evaluated by subjective fatigue degree. The patient stopped the exercise test and rested for 15 minutes under the following conditions: (1) complained of any discomfort or intolerable fatigue; (2) horizontal or oblique ST segment pressure in ECG not shorter than 3 mm; (3) moderate to severe angina pectoris or reduction of systolic blood pressure greater than 10 mmhg. The heart rate when stopping the test was the maximum heart rate of the patient. The average participation times of MCI patients in the aerobic dance group were 33.9 (IQR = 34, 36), 89.7% of MCI patients participated in 90% of aerobic dance training, and only 3.4% of MCI patients participated in less than 80% of aerobic dance courses. Compared with the control group, the 3-month change value of Wechsler's logical memory of MCI patients in the aerobic dance group was significantly improved (p < 0.01). The 3-month change value of digital connection test B score was significantly improved (mean value of difference between groups = -32. The treatment speed was significantly shortened at 6 months (P300 latency 6 months change value = -20 ms). The intensity and frequency of aerobic dance play a key role in the effect of cognitive improvement, requiring long-term persistence and ensuring the intensity and frequency of training. Second, the patient's processing speed (P300 latency) tends to gradually extend with the passage of time, and aerobic dance intervention helps shortening the P300 latency, suggesting that patients can delay the decline of their cognitive function through early aerobic dance intervention.

Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: a potential therapeutic option

Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.

Increasing diabetes testing adherence with incentives in rural Northwestern Ontario.

The health outcomes of rural Canadians have been described as poor and can in some part be related to diabetes mellitus. Despite the high mortality and morbidity rates associated with the disease, compliance with management remains low. Research has shown that a small financial incentive used to modify patient behaviour, can improve outcomes in cardiac disease and exercise adherence. This study aims to evaluate if a small financial incentive awarded to rural Northwestern Ontario patients with diabetes who complete an haemoglobin A1c (HbA1c) test, would result in greater compliance in test completion. Patients were recruited through two Northern rural clinics. Participants were divided into two groups: Group A received a financial incentive, whereas Group B received a letter of reminder. HbA1c tests were recorded every 6 months for 2 years and compliance was analysed using a t-test and Chi-square. One hundred and forty-six participants were recruited with 30 lost to follow-up. Overall, the incentive group completed a statistically significantly higher number of HbA1c tests compared to those in the control group. In addition, it was noted that there was an increase in test adherence for participants that received reminder letters, although not an initially expected outcome of the study. The results suggest that either a financial incentive or a reminder directed towards rural Canadians could have a benefit in promoting health behaviours to subsequent medical management of diabetes mellitus.

Feasibility of Cardiac Exercise Rehabilitation in Patients with Cardiac Amyloidosis

Objective: We aimed to determine if prescribed exercise programs in rehabilitation of patients with cardiac amyloidosis was feasible and beneficial. Methods: This prospective monocentric pilot study was proposed to all adult patients, diagnosed with cardiac amyloidosis, and referred to the cardiac rehabilitation centre at the Henri Mondor University hospital (Créteil, France) between 2011 to 2015. All patients had clinical evaluations, laboratory tests, and echocardiographic examinations upon recruitment to the study. The cardiac exercise rehabilitation programme, in this study, comprised a baseline incremental system-limited exercise test followed by 20 endurance training sessions at a constant workload intensity. Cardiac exercise rehabilitation was deemed feasible if the patient completed the baseline test and 10 sessions without an adverse event. Patients with a relative increase of 16% in VO2max and/or maximal workload were considered to have benefited from cardiac exercise rehabilitation. Results: Overall, 27 cardiac amyloidosis patients were recruited. Cardiac exercise rehabilitation was feasible in 19 (70%) and not feasible in 8 (30%). Of the 19 patients whom cardiac exercise rehabilitation was feasible, cardiac exercise rehabilitation benefited 9 (47%). This benefit was significantly associated with lower N-type pro-brain natriuretic peptide levels, lower creatinineamia, and higher left ventricular ejection fraction at baseline. Conclusion: Cardiac exercise rehabilitation is feasible and beneficial in selected patients with cardiac amyloidosis.

1013 RADIOFREQUENCY CATHETER ABLATION OF IDIOPATHIC VENTRICULAR FIBRILLATION: A CURRENT SINGLE-CENTRE EXPERIENCE

Abstract Short-coupled idiopathic ventricular fibrillation (SC-IVF) is a rare, life-threatening arrhythmia, accountable for 5–10% of out-of-hospital cardiac arrests (OHCA). Catheter ablation of the short-coupled premature ventricular contraction (PVC) that triggers VF has been shown to prevent VF recurrences in outdated case series. Aim To evaluate the clinical outcome and summarize the recent experience of 3D electrophysiological mapping and radiofrequency catheter ablation (RFCA) of SC-IVFs in a tertiary high-volume referral centre. Methods from January 2016, we enrolled all consecutive patients diagnosed with SC-IVF and treated by RFCA. Structural heart disease was excluded in all patients by means of echocardiography, cardiac magnetic resonance, coronary angiography, and exercise test. Brugada syndrome and long QT syndrome were excluded by Ajmaline and Epinephrine tests, respectively. The CARTO system was used to construct detailed 3D electroanatomic maps of the right and left ventricle. Mapping and ablation were performed with a standard 3.5- irrigated tip catheter. The PVCs were localized by mapping the earliest bipolar electrogram relative to the onset of the ectopic surface QRS (confirmed by QS complex in the unipolar configuration). Pace mapping was used in patients with infrequent PVCs. The origin of PVCs from fascicles/Purkinje network was indicated by initial sharp potentials preceding the ectopic QRS complex. The procedural end point was the abolition of all clinical PVCs. Outcome (freedom from SC-PVCs and VF episodes) was assessed by Holter monitoring and defibrillator memory interrogation. Results eleven consecutive patients [8 men, 3 women; median age 41 (± 5 years)] were enrolled. 10/11 patients (91%) were asymptomatic prior the index VF event, while 1 patient (9%) experienced recurrent syncope. An aborted OHCA was the index event in all patients. Arrhythmic storm was observed at the index presentation in 2 patients (18%). No patient had family history of sudden cardiac death. All patients were implanted with an ICD after the index event. The delay in SC-IVF diagnosis was 3 (± 2 years) from the index event. 2 patients (18%) had ≥ 2 SC-PVC morphologies. The mean coupling interval (CI) of the SC-PVCs ranged from 230 to 330 msec (mean 303 ± 26 msec). The CI/QT ratio ranged from 0.6 to 1 (mean 0.81 ± 0.15). 10 patients underwent RFCA for recurrent VF/ICD shocks and 1 patient for refractory electrical storm. RFCA was based on activation mapping, pace-mapping, and both in 1 (9%), 1 (9%), and 9 (82%) patients, respectively. The sites of ablation were LV Purkinje, RV Purkinje, RV non-Purkinje (RV outflow tract and tricuspid annulus), and LV non-Purkinje (LV Summit) in 3 (27%), 4 (36%), 3 (27%), and 1 (9%) patient, respectively. The first ablation was acutely successful in all patients. 1 patient experienced recurrence of SC-PVCs and VF episodes after 5 days from the first ablation and underwent a second RFCA. There were no peri-procedural complications. After a median follow-up of 22 months (ranging from 6 to 39 months) all patients were free from sustained ventricular arrhythmia recurrences: 10 patients (91%) were free from VF and PVCs; 1 patient (9%) had recurrent SC-PVCs without VF episodes. Conclusions this retrospective study explored the effectiveness of RFCA combined with the advanced electroanatomic mapping in a current cohort of patients with history of OHCA diagnosed with SC-IVF. RFCA of SC-PVCs was safe and highly effective in abolishing VF episodes in all patients.