Four-year follow-up of a patient with mixed cardiomyopathy and an implanted cardiac contractility modulation device: a case report

The article presents a case report of a 28-year-old male patient with mixed dilated cardiomyopathy: myocardial noncompaction and chemotherapy-related cardiotoxicity, which led to severe heart failure (HF). With optimal drug therapy, the patient was implanted with a cardiac contractility modulation device in order to improve exercise tolerance, quality of life and relieve HF symptoms. Complex therapy has led to significant clinical and echocardiographic improvement. This case demonstrates a 4-year follow-up of a patient with a reduced left ventricular ejection fraction and an implanted cardiac contractility modulation device, whose condition, after several severe HF decompensations, was stabilized.

Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients After COVID-19

Background: Coronavirus disease 2019 (COVID-19) is a serious respiratory disease that results from infection with a newly discovered coronavirus (SARS-COV-2). Unfortunately, COVID-19 is not only a short-term infection but that patients (pts) recovering from SARS-CoV2 infection complain of persisting symptoms including: fatigue, diffuse myalgia and weakness, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements and/or physical exercise can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2. Methods: The study population was composed of pts after COVID-19, expressing subjective feelings of limited tolerance to exercise. The selected pts were randomized into two groups: GrM0 without supplementation; GrM1 with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fa-tigue assessment with Fatigue Severity Scale (FSS) was performed. After 1 month (Phase 1), a follow up FSS and 6MWT once more were performed in both groups. Results: A significant improvement in the mean distance covered in the 6MWT was noted among the pts in GrM1, compared to those in GrM0. We also noted that in GrM1 the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared to the beginning of the study (515.18 m in Phase 0 vs 557.8m in Phase 1; p = 0.000034). In GrM1, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 meters, compared to GrM0 (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS ≥ 4) compared to the group with supplementation (GrM1 = 5 pts (20%) vs GrM0 = 14pts (56%); p = 0.008). Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-minute walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, as well as activation of the SIRT1 enzyme, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19. Keywords: COVID-19, MNA, chronic fatigue syndrome, post-COVID syndrome

Breaking the Tie: How to Start Rehabilitation in Patients With Severe Limiting Intermittent Claudication

Intermittent claudication (IC) is the most common symptom of peripheral artery disease (PAD). IC affects the quality of life and results in marked exercise intolerance and limitation to daily activities with increased risk of cardiovascular complications. Exercise training is the first line of conservative management in PAD. However, patients with IC Patient cannot tolerate exercise because of leg discomfort induced by physical effort. This review will address alternative rehabilitation strategies to reduce exercise limitations and improve exercise tolerance in patients with IC.

Short-Term Perceptually Regulated Interval-Walk Training in Hypoxia and Normoxia in Overweight-to-Obese Adults

We compared the effects of short-term, perceptually regulated training using interval-walking in hypoxia vs. normoxia on health outcomes in overweight-to-obese individuals. Sixteen adults (body mass index = 33 ± 3 kg·m-2) completed eight interval-walk training sessions (15 × 2 min walking at a rating of perceived exertion of 14 on the 6-20 Borg scale; rest = 2 min) either in hypoxia (FiO2 = 13.0%) or normoxia during two weeks. Treadmill velocity did not differ between conditions or over time (p > 0.05). Heart rate was higher in hypoxia (+10 ± 3%; p = 0.04) during the first session and this was consistent within condition across the training sessions (p > 0.05). Similarly, arterial oxygen saturation was lower in hypoxia than normoxia (83 ± 1% vs. 96 ± 1%, p < 0.05), and did not vary over time (p > 0.05). After training, perceived mood state (+11.8 ± 2.7%, p = 0.06) and exercise self-efficacy (+10.6 ± 4.1%, p = 0.03) improved in both groups. Body mass (p = 0.55), systolic and diastolic blood pressure (p = 0.19 and 0.07, respectively) and distance covered during a 6-min walk test (p = 0.11) did not change from pre- to post-tests. Short term (2-week) perceptually regulated interval-walk training sessions with or without hypoxia had no effect on exercise-related sensations, health markers and functional performance. This mode and duration of hypoxic conditioning does not appear to modify the measured cardiometabolic risk factors or improve exercise tolerance in overweight-to-obese individuals.

Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure

Heart failure (HF) results in a myriad of central and peripheral abnormalities that impair the ability to sustain skeletal muscle contractions and, therefore, limit tolerance to exercise. Central to these abnormalities is the lowered maximal oxygen uptake, which is brought about by reduced cardiac output and exacerbated by O2 delivery-utilization mismatch within the active skeletal muscle. Impaired nitric oxide (NO) bioavailability is considered to play a vital role in the vascular dysfunction of both reduced and preserved ejection fraction HF (HFrEF and HFpEF, respectively), leading to the pursuit of therapies aimed at restoring NO levels in these patient populations. Considering the complementary role of the nitrate-nitrite-NO pathway in the regulation of enzymatic NO signaling, this review explores the potential utility of inorganic nitrate interventions to increase NO bioavailability in the HFrEF and HFpEF patient population. While many pre-clinical investigations have suggested that enhanced reduction of nitrite to NO in low PO2 and pH environments may make a nitrate-based therapy especially efficacious in patients with HF, inconsistent results have been found thus far in clinical settings. This brief review provides a summary of the effectiveness (or lack thereof) of inorganic nitrate interventions on exercise tolerance in HFrEF and HFpEF patients. Focus is also given to practical considerations and current gaps in the literature to facilitate the development of effective nitrate-based interventions to improve exercise tolerance in patients with HF.

Program «Smart ECG – ranolazin» - own experience and world approach

Purpose - comprehensive analysis of the world approach of the use of ranolazine in various clinical trials and the introduction of the program "Smart ECG" to assess the effectiveness of ranolazine.Matherial and methods. Evaluation of European guidelines, analysis of global randomized clinical trials of the ranolazine use, presentation of our own trial: we examined 40 patients with Q wave myocardial infarction (STEMI), were instituted basic therapy according to the modern recommendations which contained interventional treatment with restoration of patency of a heart attack-conditioned coronary artery, double antiplatelet therapy, statins, β-adrenergic blocker, angiotensin-converting enzyme inhibitors, aldosterone antagonists with addition of ranolazine (group I, 30 patients diagnosed STEMI), control - group II, 10 patients with STEMI, who received basic therapy without addition of ranolazine. Results. Analysis of clinical trials (CARISA, MARISA, ERICA, TERISA, MERLIN-TIMI, RIVER-PCI, RIMINI-TRIAL) proved the effectiveness of ranolazine as an antianginal and anti-ischemic drugs. The use of own program «Smart ECG» demonstrates the positive effect of ranolazine on STEMI and requires further implementation.Conclusion. In the European Society of Cardiology guidelines of the management of stable angina pectoris, ranolazine is given a class IIa (level of evidence B) recommendation as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects who cannot tolerate, have contraindications to, or whose symptoms are not adequately controlled by β- adrenergic blockers, calcium channel blockers and long-acting nitrates. In subjects with baseline low heart rate and low blood pressure, ranolazine may be considered as a first-line drug to reduce angina frequency and improve exercise tolerance - class IIa (level of evidence C) recommendation. Own study, which partially reflects the global approach according to the analyzed clinical studies, demonstrates the positive effect of ranolazine for patients with STEMI - analogue scale EQ–VAS indicates a positive effect, positive influence on the markers of electrical myocardial instability: decreasing of the probability of cases of SDNN decrease, depression of QT and maybe increase of ratio of maximum velocity for differentiated T wave.

Targeting the DPP-4-GLP-1 pathway improves exercise tolerance in heart failure patients: a systematic review and meta-analysis

Background The most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus. Methods An electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O2 consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death. Result After the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality. Conclusion Our results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.

P4699Gait pattern and muscle oxygen saturation changes act synergistically to improve exercise tolerance after multimodal training in patients with symptomatic lower extremity artery disease

Introduction Patients with atherosclerotic lower extremity artery disease (LEAD) have impaired walking capacities leading to decreased quality of life. Previous studies showed that LEAD patients also have altered gait pattern (decrease speed, cadence and step length, and increased stance phase). Reduced strength and endurance of lower limb muscles play a major implication in these adaptations. Supervised exercise training (SET) is effective in improving walking performances in symptomatic LEAD patients. However, there is no clear consensus whether SET also influences gait pattern. The aim of the present study was to investigate the effects of SET on gait pattern and calf muscle oxygen saturation (StO2) changes. Methods Fontaine stage II LEAD's patients following a 3-month multimodal (Nordic walking and lower limbs strengthening) SET were investigated. Constant-load treadmill incline walking test (2.5–3.2 km/h at 12%) was used to determine pain-free walking distance (PFWD) and maximal walking distance (MWD). During the treadmill test, spatiotemporal parameters (Physilogs®, GaitUp, Switzerland) and calf StO2 (NIRS, PortaMon, Artinis, The Netherlands) were assessed at baseline, PFWD and MWD. Ankle-brachial Index (ABI) and toe-brachial index (TBI) were also measured. All assessments were performed prior and after SET. Results Twenty stage II LEAD patients (62.7±2.4 yr, 80% men, 75% stage IIa) were included. Following SET, PFWD (98.5±10.0 pre- vs. 177.0±31.7m post-SET; P=0.012), and MWD (396.0±62.6 pre- vs. 633.0±107.4m post-SET; P=0.01) significantly increased. ABI (0.85±0.05 pre- vs. 0.85±0.03 post-SET; P=0.96) and TBI (0.61±0.03 pre- vs. 0.65±0.04 post-SET; P=0.07) did not change significantly. Following SET, patients had significantly shorter stride duration (−3%, P=0.05), higher cadence (+3%, P=0.04), longer double support (+10%, P=0.04), shorter swing (−3%, P=0.03), and longer stance duration phase (+2%, P=0.03). In addition, after SET patients also had significantly longer duration of the loading response (+9%, P=0.04) and foot-flat (+3%, P=0.04), and shorter duration of the push-off phase (−8%, P=0.01). Stride length was shorter although not significant (−2%, P=0.13). After SET, delta StO2 (baseline=0) was greater at PFWD (+33%) and at MWD (+68%; P=0.05, with no significant interaction effect). Conclusions These results confirm beneficial effects of SET on walking performances. After SET, the prolonged duration of loading response and foot-flat (stance sub-phases associated with limited calf muscles activation) may be a strategy to increase calf muscles oxygenation. The observed greater calf muscle oxygen desaturation (increased oxygen extraction) after SET may be related to an improved microvascular milieu leading to a better match between muscle oxygen delivery and utilization during exercise. Taken together, gait pattern and muscle oxygen desaturation changes may act synergistically to improve exercise tolerance in patients with LEAD. Acknowledgement/Funding None

Edward F. Adolph Distinguished Lecture. Contemporary model of muscle microcirculation: gateway to function and dysfunction

This review strikes at the very heart of how the microcirculation functions to facilitate blood-tissue oxygen, substrate, and metabolite fluxes in skeletal muscle. Contemporary evidence, marshalled from animals and humans using the latest techniques, challenges iconic perspectives that have changed little over the past century. Those perspectives include the following: the presence of contractile or collapsible capillaries in muscle, unitary control by precapillary sphincters, capillary recruitment at the onset of contractions, and the notion of capillary-to-mitochondrial diffusion distances as limiting O2 delivery. Today a wealth of physiological, morphological, and intravital microscopy evidence presents a completely different picture of microcirculatory control. Specifically, capillary red blood cell (RBC) and plasma flux is controlled primarily at the arteriolar level with most capillaries, in healthy muscle, supporting at least some flow at rest. In healthy skeletal muscle, this permits substrate access (whether carried in RBCs or plasma) to a prodigious total capillary surface area. Pathologies such as heart failure or diabetes decrease access to that exchange surface by reducing the proportion of flowing capillaries at rest and during exercise. Capillary morphology and function vary disparately among tissues. The contemporary model of capillary function explains how, following the onset of exercise, muscle O2 uptake kinetics can be extremely fast in health but slowed in heart failure and diabetes impairing contractile function and exercise tolerance. It is argued that adoption of this model is fundamental for understanding microvascular function and dysfunction and, as such, to the design and evaluation of effective therapeutic strategies to improve exercise tolerance and decrease morbidity and mortality in disease.