Chronotropic Competence Research Articles

Abstract MP08: Higher Fitness Level and Favorable Hemodynamic Responses to Submaximal Exercise Test in Young Adults are Associated With Lower Risk of Chronic Kidney Disease in Later Life: The Framingham Heart Study

Introduction: Studies have demonstrated that higher cardiorespiratory fitness (CRF) and a favorable heart rate (HR) and blood pressure (BP) response to submaximal exercise, including during the recovery period, are associated with lower cardiovascular disease (CVD) risk. However, there are limited studies examining the association of CRF and hemodynamic response to exercise test with incidence of chronic kidney disease (CKD). Hypothesis: We hypothesized that high CRF and a favorable HR and BP response to submaximal exercise test and during recovery will be associated with lower risk of CKD prospectively. Methods: We evaluated 3,535 Framingham Offspring Study participants (mean age 43.5 yrs, 52.1% women) without CKD, who completed a submaximal exercise test between 1979-1983. CKD incidence was defined as eGFR <60ml/min/1.73m 2 on follow-up. Multivariable-adjusted Cox regression models with discrete time intervals were used to relate CRF and hemodynamic responses to exercise test at baseline with the incidence of CKD on follow-up. Results: At baseline, 23% of participants had chronotropic incompetence and 19.6% had impaired HR recovery after exercise (Δ HR 1 < 12 bpm). On follow-up (median 25.7 years), 801 individuals (22.8%; 434 women) developed CKD. Participants in the second and third tertile of CRF (defined based on age and sex-specific treadmill exercise duration) had lower risk of CKD compared to those in the first tertile of CRF ( Table ). Participants with chronotropic incompetence, higher peak SBP during exercise and impaired HR recovery had higher risk of CKD, compared to those with chronotropic competence, lower peak SBP during exercise, and normal HR recovery post-exercise ( Table ). Conclusions: Higher CRF and favorable HR and BP responses to exercise test in young adulthood may be a marker of lower risk of CKD in later life. The biological mechanisms underlying the observed association warrant further investigation.

Abstract 16657: Role of Exercise Induced Mitral Regurgitation and Its Prevalence in Functional Limitation of Heart Failure Patients With Preserved Ejection Fraction

Background: Functional limitation in heart failure (HF) patients recognize multiple mechanisms. Exercise-induced mitral regurgitation (Ex-MR) has been extensively studied in HF population with reduced ejection fraction (HFrEF, EF < 40%), as responsible of right ventricle (RV) to pulmonary circulation (PC) uncoupling phenomenon. The relative role of this hemodynamic determinant has not been investigated so far in HF patients with preserved (HFpEF, EF > 50%) and mid-range EF (HFmrEF, EF 40 - 49%). Aim: To describe functional phenotypes and cardiac response to exercise in HF patients, with respect to the development of Ex-MR. Methods: 179 HF patients and 23 controls were tested with cardiopulmonary exercise test (CPET) combined with exercise-echocardiography. Based on current guidelines, we identified 114 HFrEF, 34 HFmrEF and 31 HFpEF, further divided according with the presence of at least moderate (>2+/4+) Ex-MR. Results: Ex-MR rate was 58%, 41% and 42% in HFrEF, HFmrEF and HFpEF, respectively. Ex-MR was associated with echocardiographic signs of RV-PC uncoupling (TAPSE/PASP ratio), particularly enhanced by the exercise in HFpEF patients. HFpEF with Ex-MR showed a distinct phenotype with chronotropic competence and increased peripheral oxygen extraction, compared to Ex-MR - cohort, possible expression of a compensatory mechanism to significant reduction in contractile reverse. The Ex-MR was associated with lower peak VO2 and workload in HFrEF and HFmrEF, while there were no differences related to HFpEF. The presence of Ex-MR significantly compromised also ventilatory efficiency (VE/VCO2) in all HF classes. Conclusion: Ex-MR emerged as a new mechanism of functional limitation in HFpEF, sharing a common pathophysiological basis with other HF patients. The RV-PC uncoupling is the best haemodynamic correlate of Ex-MR.

Laser Catheter Modulation of the Sinus Node in the Treatment of Inappropriate Sinus Tachycardia: Experimental and Clinical Results.

Inappropriate sinus tachycardia (IST) is a rare type of arrhythmia that is currently difficult to treat successfully. The effects of laser catheter applications aimed at the sinus nodal area were tested experimentally and the technique was used for the treatment of IST. Continuous-wave, mapping-guided 1,064 nm neodymium-doped yttrium aluminum garnet laser applications at 15 W (9.5 W/mm2) per 15 seconds (142.5 J/mm2) and an irrigation flow of 30 mL/min were aimed at the sinus nodal area in five dogs (three applications each) and one human patient (two applications) by use of an 8-French open-irrigated electrode-laser mapping and ablation (ELMA) catheter provided with three miniature pin electrodes (0.5 mm × 4.0 mm) with interelectrode distances of 2.0 mm arranged symmetrically and radially around the endhole of the catheter tip. Laser application was aimed at the largest and earliest atrial potentials recorded in the focused local electrograms 30 ms to 45 ms prior to the onset of the P-wave in the surface lead electrocardiogram. Lesions were evaluated morphometrically. Holter monitoring in the patient was performed prior to and after treatment. During laser application in the dogs, sinus nodal potential amplitudes dwindled gradually from a mean of 42 mm ± 24 mm to 5.0 mm ± 3.0 mm and sinus cycle lengths lengthened from 452 ms ± 35 ms to 634 ms ± 35 ms (p < 0.0001 for both). In the patient, electrical potential amplitudes in the local electrograms dwindled from 41.0 mm to 5.0 mm and, in the Holter monitor, heart rate decreased from 109 bpm ± 29 bpm to 79 bpm ± 26 bpm (p < 0.0001). IST ablation was painless and without complications. During a follow-up of 4.9 years, the patient was asymptomatic and her heart rate and chronotropic competence remained normal. In conclusion, ablation of IST was achieved by substrate mapping-guided laser application while using the open-irrigated EMLA catheter RytmoLas (LasCor GmbH – Laser Medical Devices, Taufkirchen, Germany). However, this is a proof-of-concept study and further research, preferably in the form of multicenter study trials, is needed for confirmation of the results.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

Do Patients with Asymptomatic Congenital Complete Heart Block Require a Pacemaker for Non-Cardiac Surgery?

The appropriate preparation of the patient with asymptomatic congenital complete heart block (CCHB) and a narrow QRS complex for elective non-cardiac surgery is controversial. Prophylactic temporary pacemaker insertion is associated with well-defined risks, and less invasive techniques exist to treat transient, hemodynamically significant intraoperative brady-arrhythmias. The present case report details the performance of general anesthesia for arthroscopic knee surgery in an adult patient with this condition without a pacemaker. Documentation of preoperative chronotropic competence with isoproterenol may be of value in deciding whether to proceed without temporary pacing capability in this setting.

Chronotropic Competence Indices Extracted from Wearable Sensors for Cardiovascular Diseases Management.

Chronotropic incompetence (CI) has been proven to be an important factor in the diagnosis and management of cardiovascular diseases. In this paper, we extend the existing CI parameters and propose chronotropic competence indices (CCI) to describe the exercise response of the cardiopulmonary system. A cardiac chronotropic competence Test (3CT), dedicated to CCI measurement using a wearable device, is also presented. Preliminary clinical trials are presented for the validation of 3CT measurement accuracy, and to show the potential of CCI in the prevention and rehabilitation of cardiovascular diseases.

A novel ‘splice site’ HCN4 Gene mutation, c.1737 + 1 G > T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability

BackgroundThe most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. Methods and resultsA novel c.1737+1 G>T ‘splice-site’ HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate<60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings. ConclusionsThe identified novel ‘splice site’ HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers.

Cardiac chronotropic competence to beta‐adrenergic stimulation in insulin resistance

Insulin resistance (IR) precedes clinical manifestation of diseases such as diabetes mellitus and hypertension and is associated with increased sympathetic modulation. However, in the dexamethasone‐induced IR no changes have been noted in heart rate (HR). Therefore, we evaluated the heart chronotropic competence through beta‐adrenergic agonist stimulation in dexamethasone‐induced IR. Young male rats were divided into two groups: Control (CT)(n=6) and IR (n=6). CT and IR groups received vehicle or dexamethasone (DEX) (2mg/kg/day) i.p during seven days, respectively. To confirm Insulin resistance, insulin tolerance test (ITT) was performed after 6h fasted. Left femoral artery and vein were cannulated to measure blood pressure (2 kHz sampling rate) and isoproterenol (4μg/kg) administration respectively, 24h before evaluation. IR group presented attenuated decrease in glycaemia during ITT (CT: 42.5 ± 5 vs IR: 110.7 ± 14), hypertension (CT: 100 ± 2 vs IR: 135 ± 9 mmHg) without heart rate changes. In addition, increased cardiac sympathetic modulation by spectral analysis (LF/HF ratio CT: 0.52 ± 0.03 vs IR: 0.69 ± 0.04 un). After beta‐adrenergic stimulation IR group showed lower variation from basal level (ΔHR CT: 179 ± 4 vs IR: 78 ± 5 bpm). The reduction in heart chronotropic competence observed in this IR model could be a defense mechanism due cardiac sympathetic over activity.Support or Funding InformationFapitec‐SE; CAPES; CNPq.

Chronotropic Incompetence in Patients with Cardiac Rhythm Devices Undergoing Evaluation for Cardiac Transplantation

Background: We sought to report the prevalence of chronotropic incompetence (CI) and associated invasive haemodynamic indices in patients with heart failure with reduced ejection fraction with implanted cardiac devices. Methods: Retrospective review of cardiopulmonary exercise and right heart catheterisation data in 60 consecutive patients (mean age 54 ± 12 years) admitted for cardiac transplant assessment. CI was defined as inability to achieve 80% of the heart rate reserve (HRR): (Peak heart rate–rest heart rate)/(220 –age–rest heart rate). Results: All patients exercised to fatigue and achieved a respiratory exchange ratio >1.0. 59 patients had a HRR of < 80%. 19 patients had a single chamber device, 16 had a dual chamber device and 25 had a biventricular pacing device. Rate enhancement was programmed ON in 17 (28.3%) patients but this did not restore chronotropic competence. Increased severity of CI was associated with worse peak oxygen uptake (11.7 ± 2.5 vs. 15.1 ± 3.5 vs. 16.6 ± 14.5 ml/min/Kg, lowest to highest tertile of HRR, ANOVA p < 0.001) and higher right atrial pressure (8.7 ± 5.2 vs. 8.1 ± 5.7 vs. 4.8 ± 3.8 mmHg, ANOVA p = 0.036). Greater CI was associated with reduced survival; there were 19 deaths in our cohort (10 in the lowest tertile of HRR, 7 in the middle and 2 in the highest, Fisher's Exact p = 0.032). Conclusions: Chronotropic incompetence is highly prevalent in our population of end-stage heart failure. Rate response was ON in only 28%, but it did not restore chronotropic function. Increasing severity of CI is associated with increased right atrial pressure, reduced exercise capacity and reduced survival.

Home Exercise Training in Children and Adolescents with Pulmonary Arterial Hypertension: A Pilot Study.

Pulmonary arterial hypertension (PAH) is often associated with impaired exercise capacity. It has been shown that supervised training can improve exercise capacity in adult patients with PAH. The objective of this prospective study was to assess the feasibility of a home exercise training program in children with PAH. Nine children and adolescents (mean age 15.2±3.8years) with low-risk PAH (defined as mean pulmonary to systemic arterial pressure ratio <0.75; WHO functional class I and II) performed home-based exercise training for 16weeks. Cardiopulmonary exercise testing and health-related quality of life was evaluated before and after 16weeks of training. The amount of training at home and patients' well-being was supervised by periodical phone calls and online-questionnaires. Home exercise training was well tolerated in all patients, and no adverse events occurred. After 16weeks of training, patients significantly improved their exercise capacity [treadmill running distance increased from 589.5±153.9 to 747.9±209.2m (p=0.036)]. Oxygen consumption at the anaerobic threshold increased from 1307.8 (±417) to 1406.4 (±418)ml (p=0.028). Chronotropic index improved from 0.77±0.12 to 0.82±0.11 (p=0.004) and was slightly related to the increase in running distance (r=0.62; p=0.07). Home exercise training is feasible in children and adolescents with low-risk PAH, and the preliminary results of this pilot study indicate beneficial effects. The observed increase in exercise capacity was accompanied by an improved chronotropic competence and increased oxygen consumption at the anaerobic threshold. Future research is needed to investigate the safety and efficacy of home exercise training in a larger population of children with PAH including also patients in WHO functional class III or IV.

Hemodynamics and Exercise Tolerance after Senning Operation for Transposition of Great Arteries and Its Limiting Factors: A Longitudinal Study

Objectives: The purpose of this longitudinal study was to assess hemodynamics and exercise capacity in patients after Senning operation and to determine its limiting factors. Methods: 87 long-term survivors of the Senning operation for transposition of great arteries were recruited for a longitudinal follow-up study consisting of two cross-sectional evaluations at a mean of 12.6 and 22.6 years after surgery, respectively. The protocol included a questionnaire, echocardiography, radionuclide angiocardiography, magnetic resonance imaging and cardiopulmonary exercise test. Decreased exercise capacity was defined as maximum oxygen uptake <-2 Z-scores. Results: Hemodynamic variables (right ventricular function and degree of tricuspid regurgitation) and chronotropic competence did not change significantly with time. Decreased exercise tolerance was present in 55.6 and 49.3% of patients at the first and second evaluation, respectively (NS) and had multi-variable correlation with lower right ventricular end-diastolic volume (P=0.039, OR 0.963) and increased ventilation/carbon dioxide production slope (P=0.040, OR 1.293). None of other hemodynamic variables correlated with decreased functional capacity. Conclusions: Long-term survivors of the Senning operation have stable hemodynamics and exercise capacity on longitudinal follow-up. Decreased exercise tolerance is found in approximately half of the patients and is significantly associated with lower ventilation efficiency. This data may point to the usefulness of targeted respiratory rehabilitation in this patient group.

Catheter ablation of inappropriate sinus tachycardia.

Catheter ablation for inappropriate sinus tachycardia (IST) is recommended for patients symptomatic for palpitations and refractory to other treatments. The current approach consists in sinus node modification (SNM), achieved by ablation of the cranial part of the sinus node to eliminate faster sinus rates while trying to preserve chronotropic competence. This approach has a limited efficacy, with a very modest long-term clinical success. To overcome this, proper patient selection is crucial and an epicardial approach should always be considered. This brief review will discuss the current role and limitations of catheter ablation in the management of patients with IST.

Supervised Exercise Training in Children and Adolescents with Moderate Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is often associated with an impaired exercise and functional capacity. It has been shown previously that supervised training can improve exercise capacity in adult patients with PAH. Experience of supervised exercise training in the pediatric age group is limited. The objective of this prospective study was to assess the feasibility and efficacy of an exercise training program in children and adolescents with moderate PAH. Patients and Methods: Nine children with moderate PAH (6 female, mean age 15.2 ± 3.8 years; mean pulmonary to systemic arterial pressure ratio 0.51 ± 0.19) performed supervised exercise training (ergometer and theraband) for 16 weeks. Efficacy parameters (cardiopulmonary exercise testing (CPET), pulmonary function testing (PFT), systemic arterial endothelial function testing (EFT), tricuspid annular plane systolic excursion (TAPSE), and b-type natriuretic peptide (BNP)) were evaluated before and after 16 weeks of training. Medication remained unchanged during the study period. Results: Exercise training was well tolerated in all patients. After 16 weeks of supervised training, patients significantly improved their exercise capacity and chronotropic competence during CPET, i.e., treadmill running distance increased from 589.5 ± 153.9 m to 747.9 ± 209.2 m (p = 0.036), oxygen consumption at the anaerobic threshold improved from 1307.8 ± 416.9 ml/min to 1406.4 ± 417.9 ml/min (p = 0.028), and peak heart rate increased from 177.6 ± 13.6 to 184.4 ± 11.2 (p = 0.009). Measures of PFT, EFT, TAPSE, and BNP were similar before and after the training period. Conclusion: According to our experience, supervised exercise training is safe and effective and may serve as an innovative supportive therapy (as add-on to PAH-specific therapy) in children and adolescents with moderate PAH.

Effects of Renal Sympathetic Denervation on Exercise Blood Pressure, Heart Rate, and Capacity in Patients With Resistant Hypertension

Renal denervation reduces office blood pressure in patients with resistant hypertension. This study investigated the effects of renal denervation on blood pressure, heart rate, and chronotropic index at rest, during exercise, and at recovery in 60 patients (renal denervation group=50, control group=10) with resistant hypertension using a standardized bicycle exercise test protocol performed 6 and 12 months after renal denervation. After renal denervation, exercise blood pressure at rest was reduced from 158±3/90±2 to 141±3/84±4 mm Hg (P<0.001 for systolic blood pressure/P=0.007 for diastolic blood pressure) after 6 months and 139±3/83±4 mm Hg (P<0.001/P=0.022) after 12 months. Exercise blood pressure tended to be lower at all stages of exercise at 6- and 12-month follow-up in patients undergoing renal denervation, although reaching statistical significance only at mild-to-moderate exercise levels (75-100 W). At recovery after 1 minute, blood pressure decreased from 201±4/95±2 to 177±4/88±2 (P<0.001/P=0.066) and 188±6/86±2 mm Hg (P=0.059/P=0.01) after 6 and 12 months, respectively. Heart rate was reduced after renal denervation from 71±3 bpm at rest, 128±5 bpm at maximum workload, and 96±5 bpm at recovery after 1 minute to 66±2 (P<0.001), 115±5 (P=0.107), and 89±3 bpm (P=0.008) after 6 months and to 69±3 (P=0.092), 122±7 (P=0.01), and 93±4 bpm (P=0.032) after 12 months. Mean exercise time increased from 6.59±0.33 to 8.4±0.32 (P<0.001) and 9.0±0.41 minutes (P=0.008), and mean workload increased from 93±2 to 100±2 (P<0.001) and 101±3 W (P=0.007) at 6- and 12-month follow-up, respectively. No changes were observed in the control group. In conclusion, renal denervation reduced blood pressure and heart rate during exercise, improved mean workload, and increased exercise time without impairing chronotropic competence.

Cardiac rehabilitation: improving the prognosis of ischemic heart disease

Introduction: Cardiac Rehabilitation (CR) aims to help patients overcome the limitations experienced after a significant cardiac event. Even though its benefits are well established, CR is still underused. Moreover, the evidence that CR can bring benefits on hard endpoints in real-world patients is extremely important in an era of strict control of costs. Our goal was to determine the success of CR in the global performance of our patients, to explore the effect of CR on validated surrogate markers of prognosis and attempt to evaluate the long-term benefits of CR. Methods: We studied all the patients referred to a hospital-based multidisciplinary Cardiac Rehabilitation Program after acute coronary syndrome or elective percutaneous coronary intervention. All patients completed 2 to 3 months of biweekly supervised aerobic exercise of moderate intensity. They underwent exercise stress testing at the beginning of the Program (EST1) and after 3 months (EST2). We tested the maximal exercise capacity, proBNP, maximal heart rate and Duke treadmill score as potential prognostic markers. The endpoint was the occurrence of major adverse cardiac composite events (MACCE): cardiac death, urgent revascularization and hospitalization from cardiac causes. Level of statistical significance p<0,05. Results: A total of 723 consecutive patients that attended the Program were included, the mean age was 60 years old and 75% were male. The median follow-up time was 25 months. After completion of the CR, there was a significant improvement in functional capacity (8.8±3.8 METs at EST1 vs 10.1±2.3 METs at EST2; p<0.001). The Duke score decreased significantly (6,8±4,9 at EST1 vs 7,9±5,2 at EST2; p<0,001) and the maximal heart rate during exercise increased (from 130 bpm ±20 to 134 bpm ±20; p<0.001), a manifestation of chronotropic competence. The proBNP decreased from 751±930 pg/mL to 366±442 pg/mL; p<0.001. We verified that each one of these 4 markers, when evaluated after completion of the CR program, was a predictor of MACCE, even after adjustment for multiple characteristics such as age, gender, comorbidities and left ventricular systolic function. Conclusions: We observed a tremendous beneficial effect of CR on prognostic markers in our large sample of real-life patients with coronary disease, highlighting its role in secondary prevention. This benefit translated into MACCE even after 2 years and was seen in all groups of patients. We also verified that the maximal exercise capacity, Duke treadmill score, proBNP and maximal heart rate could be used as markers of success of a CR program.

Berberine behind the thriller of marked symptomatic bradycardia

Patients with chronic aortic dissections are at high risk of catheter-induced complications. We report a Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for the onset of fatigue and dyspnoea upon exertion after he started berberine to treat hypercholesterolaemia. An electrocardiogram showed sinus bradycardia (45 bpm), first-degree atrioventricular block, and competitive junctional rhythm. An ergometric stress test showed slightly reduced chronotropic competence and the presence of runs of competitive junctional rhythm, atrial tachycardia, and sinus pauses in the recovery. After 10 d of wash-out from berberine, the patient experienced a complete resolution of symptoms, and an ergometric stress test showed good chronotropic competence. An electrocardiogram Holter showed a latent hypervagotonic state. This is the first case report that shows that berberine could present certain side effects in hypervagotonic people, even in the absence of a situation that could cause drug accumulation. Therefore, berberine's use should be carefully weighed in hypervagotonic people due to the drug's bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks.

Chronotropic incompetence predicts impaired response to exercise training in heart failure patients with sinus rhythm

In most patients with chronic heart failure (CHF), endurance training improves exercise capacity. However, some patients do not respond favourably. The purpose of this study was to explore the reasons of non-response and to determine their predictive value. We studied a cohort of 120 consecutive CHF patients with sinus rhythm (mean age 57 ± 12 years, ejection fraction 29.3 ± 9.9%, peak VO₂ 17.3 ± 5.1 ml/min/kg), participating in a 3-month outpatient cardiac rehabilitation programme. Responders were defined as subjects who improved peak VO₂ by more than 5%, work load by more than 10%, or VE/VCO₂ slope by more than 5%. Subjects who did not fulfil at least one of the above criteria were characterized as non-responders. Multivariate regression analyses were performed to identify parameters that were predictive for a response. Receiver operating characteristic (ROC) analyses were performed for predictive parameters to identify thresholds for response or non-response. Multivariate regression analyses revealed heart rate (HR) reserve, HR recovery at 1 min, and peak HR as significant predictors for a positive training response. ROC curves revealed the optimal thresholds separating responders from non-responders at less than 30 bpm for HR reserve, less than 6 bpm for HR recovery and less than 101 bpm for peak HR. The presence of impaired chronotropic competence is a major predictor of poor training response in CHF patients with sinus rhythm.

Cardiorespiratory Response to Exercise After Renal Sympathetic Denervation in Patients With Resistant Hypertension

This study sought to investigate the effects of interventional renal sympathetic denervation (RD) on cardiorespiratory response to exercise. RD reduces blood pressure at rest in patients with resistant hypertension. We enrolled 46 patients with therapy-resistant hypertension as extended investigation of the Symplicity HTN-2 (Renal Denervation With Uncontrolled Hypertension) trial. Thirty-seven patients underwent bilateral RD and 9 patients were assigned to the control group. Cardiopulmonary exercise tests were performed at baseline and 3-month follow-up. In the RD group, compared with baseline examination, blood pressure at rest and at maximum exercise after 3 months was significantly reduced by 31 ± 13/9 ± 13 mm Hg (p < 0.0001) and by 21 ± 20/5 ± 14 mm Hg (p < 0.0001), respectively. Achieved work rate increased by 5 ± 13 W (p = 0.029) whereas peak oxygen uptake remained unchanged. Blood pressure 2 min after exercise was significantly reduced by 29 ± 17/8 ± 15 mm Hg (p < 0.001 for systolic blood pressure; p = 0.002 for diastolic blood pressure). Heart rate at rest decreased after RD (4 ± 11 beats/min; p = 0.028), whereas maximum heart rate and heart rate increase during exercise were not different. Heart rate recovery improved significantly by 4 ± 7 beats/min after renal denervation (p = 0.009). In the control group, there were no significant changes in blood pressure, heart rate, maximum work rate, or ventilatory parameters after 3 months. RD reduces blood pressure during exercise without compromising chronotropic competence in patients with resistant hypertension. Heart rate at rest decreased and heart rate recovery improved after the procedure. (Renal Denervation With Uncontrolled Hypertension; [Symplicity HTN-2]; NCT00888433).

The Cardiac Conduction System

The human heart beats 2.5 billion times during a normal lifespan, a feat accomplished by cells of the cardiac conduction system (CCS). The functional components of the CCS can be broadly divided into the impulse-generating nodes and the impulse-propagating His-Purkinje system. Human diseases of the conduction system have been identified that alter impulse generation, impulse propagation, or both. CCS dysfunction is primarily due to acquired conditions such as myocardial ischemia/infarct, age-related degeneration, procedural complications, and drug toxicity. Inherited forms of CCS disease are rare, but each new mutation provides invaluable insight into the molecular mechanisms governing CCS development and function. Applying a multidisciplinary approach, which includes human genetic screening, biophysical analysis, and transgenic mouse technology, has yielded a broad array of gene families involved in maintaining normal CCS physiology (Figure 1). In this review, we discuss gene families that have been implicated in human CCS diseases of rhythm, conduction block, accessory conduction, and development (Table). We also investigate evolving therapeutic strategies that may serve as adjuvant or replacement therapy to current implantable pacemakers. Figure 1. Cardiac conduction system cell. Genes identified in human cardiac conduction system disease are highlighted. View this table: Table. Genetic Basis of Conduction System Disease The human sinoatrial node (SAN) is a crescent-shaped, intramural structure with its head located subepicardially at the junction of the right atrium and the superior vena cava and its tail extending 10 to 20 mm along the crista terminalis.26 The SAN has complex 3-dimensional tissue architecture with central and peripheral components made up of distinct ion channel and gap junction expression profiles.27 Central and peripheral cells have different action potential characteristics and conduction properties (Figure 2).27 Experimental and computational models have demonstrated that SAN heterogeneity is necessary to maintain normal automaticity and impulse conduction.28,–,30 Figure 2. Electrophysiological heterogeneity of the …

Successful treatment of catecholaminergic polymorphic ventricular tachycardia with flecainide: a case report and review of the current literature

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF). While pharmacological therapy with beta-blockers and/or Ca(2)(+) antagonists is often unreliable, a recent study has demonstrated that flecainide can effectively suppress arrhythmia in a murine model of CPVT as well as clinically in two human subjects suffering from CPVT. We here present the case of an 11-year-old boy suffering from CPVT-1 as well as a review of the current relevant literature. After resuscitation due to VF at age 9, an automated implantable cardioverter-defibrillator (ICD) was implanted in 2007. Under beta-blocker therapy, repeated shocks were delivered due to either fast ventricular tachycardia (VT) or VF. This persisted under additional therapy with verapamil. Implantable cardioverter-defibrillator routine interrogations showed frequent non-sustained VT with an average of 8.8 per day. Additionally, the patient suffered from impaired physical performance due to decreased chronotropic competence. In July 2009, flecainide was added to the beta-blocker/verapamil regimen, resulting in a plasma level of 0.20 mg/L. No ICD shock or sustained VT occurred until December 2010. Genetic testing revealed an RyR2 receptor mutation. The case demonstrates the challenge of diagnosis and management of CPVT. It furthermore supports recent experimental evidence that the class 1 antiarrhythmic drug flecainide can suppress CPVT. The presented case supports a novel strategy in treating CPVT with the class I antiarrhythmic agent flecainide.