Unmasking Hydroxychloroquine Cardiotoxicity in a Patient With Heart Failure and Chronotropic Incompetence.
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ABSTRACT:
SUBMITTER: Ezzeddine FM
PROVIDER: S-EPMC8311382 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac β-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects.MethodsThirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac β-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR.ResultsPeak VO2 and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac β-receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had β-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001).ConclusionsContrary to our hypothesis, patients with HFpEF displayed impaired cardiac β-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate β-receptor sensitivity, peak HR remained low, suggesting impaired sinus node β-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.
| S-EPMC7347285 | biostudies-literature
Project description:Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF) and may be a key reason underlying exercise intolerance in these patients. However, the determinants of CI in HFpEF are unknown. We prospectively studied 157 patients with consecutive HFpEF who underwent cardiopulmonary exercise testing and defined CI according to specific thresholds of the percent heart rate reserve (%HRR). CI was diagnosed as present if %HRR <80 if not taking a ? blocker and <62 if taking ? blockers. Participants who achieved inadequate exercise effort (respiratory exchange ratio ?1.05) on cardiopulmonary exercise testing were excluded. Multivariable-adjusted logistic regression was used to determine the factors associated with CI. Of the 157 participants, 108 (69%) achieved a respiratory exchange ratio >1.05 and were included in the final analysis. Of these 108 participants, 70% were women, 62% were taking ? blockers, and 38% had chronic kidney disease. Most patients with HFpEF met criteria for CI (81 of 108; 75%). Lower estimated glomerular filtration rate (GFR), higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure were each associated with CI. A 1-SD decrease in GFR was independently associated with CI after multivariable adjustment (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4, p = 0.02). The association between reduced GFR and CI persisted when considering a variety of measures of chronotropic response. In conclusion, reduced GFR is the major clinical correlate of CI in patients with HFpEF, and further study of the relation between chronic kidney disease and CI may provide insight into the pathophysiology of CI in HFpEF.
| S-EPMC4567946 | biostudies-literature
Project description:Background Patients with a Fontan circulation achieve lower peak heart rates ( HR ) during exercise. Whether this impaired chronotropic response reflects pathology of the sinoatrial node or is a consequence of altered cardiac hemodynamics is uncertain. We evaluated the adequacy of HR acceleration throughout exercise relative to metabolic demand and cardiac output in patients with a Fontan circulation relative to healthy controls. Methods and Results Thirty subjects (20 healthy controls and 10 Fontan patients) underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording via a pulmonary and radial artery catheter during supine bicycle exercise to near maximal exertion. Adequacy of cardiac index, stroke volume, and HR reserve was assessed by determining the exercise-induced increase (∆) in cardiac index, stroke volume, and HR relative to the increase in oxygen consumption ( VO 2). HR reserve was lower in Fontan patients compared with controls (71±21 versus 92±15 bpm; P=0.001). In contrast, increases in HR relative to workload and VO 2 were higher than in controls. The change in cardiac index relative to the change in VO 2 (∆cardiac index/∆ VO 2) was similar between groups, but Fontan patients had increased ∆ HR /∆ VO 2 and reduced ∆ stroke volume/∆ VO 2 compared with controls. There was an early and marked reduction in stroke volume during exercise in Fontan patients corresponding with a plateau in cardiac output at a low peak HR . Conclusions In Fontan patients, the chronotropic response is appropriate relative to exercise intensity, implying normal sinoatrial function. However, premature reductions in ventricular filling and stroke volume cause an early plateau in cardiac output beyond which further increases in HR would be physiologically implausible. Thus, abnormal cardiac filling rather than sinoatrial node dysfunction explains the diminished HR reserve in Fontan patients.
| S-EPMC6512107 | biostudies-literature
Project description:AimsClinical effects of rate-adaptive pacing in heart failure patients with chronotropic incompetence (CI) undergoing cardiac resynchronization therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS in CRT patients with severe CI, focusing primarily on key prognostic variables assessed by cardiopulmonary exercise (CPX) testing.Methods and resultsIn the randomized, crossover, multicentre BIO|CREATE study, 20 CRT patients with severe CI and NYHA Class II/III (60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode, or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode). Patients underwent symptom-limited treadmill-based CPX test in each mode. An improvement (decrease) of the ventilatory efficiency (VE) slope of ≥5% during CLS was regarded as positive response to CLS. Seventeen patients with full data sets had a mean intra-individual VE slope change of -1.8 ± 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS responders, with a -6.1 ± 2.7 (-16.4%) slope change (P = 0.029). Compared to non-responders, CLS responders had a higher left ventricular (LV) ejection fraction (46 ± 3 vs. 36 ± 9%; P = 0.0070), smaller end-diastolic LV volume (121 ± 34 vs. 181 ± 41 mL; P = 0.0085), smaller end-systolic LV volume (65 ± 23 vs. 114 ± 39 mL; P = 0.0076), and were predominantly in NYHA Class II (P = 0.0498).ConclusionThe data of the present pilot study are compatible with the notion that CLS activation may improve VE slope in CRT patients with severe CI and less advanced heart failure. Further research is needed to determine the long-term clinical outcomes of CLS.
| S-EPMC8576282 | biostudies-literature
Project description:BackgroundWhile exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.MethodsForty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 - age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.ResultsOf 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.ConclusionThe study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.Trial registrationClinicalTrials.gov ID NCT02358603 . Registered 16 May 2014.
| S-EPMC5445286 | biostudies-literature
Project description:Chronotropic incompetence (CI), an attenuated heart rate (HR) response to exercise, is common in patients with cardiovascular disease. The aim of this study was to assess changes in the chronotropic response (CR) during cardiopulmonary exercise testing (CPET) in patients undergoing cardiac rehabilitation and investigate the effects of β-blockers.Patients undergoing cardiac rehabilitation performed CPET. Failure to achieve 80% of the age-predicted maximal HR (APMHR) defined CI. Values of the metabolic chronotropic relationship (MCR) were calculated from the ratio of the HR reserve to metabolic reserve at 4 stages, warm-up (MCR-Wu), anaerobic threshold (MCR-AT), respiratory compensation (MCR-Rc), and peak point (MCR-Pk), using the Wilkoff model. In patients who showed an increase in MCR at ≥ 3 of the 4 exercise stages, CR was considered to have improved.Patients with high BNP levels (≥ 80 pg/ml) had a lower MCR at all stages compared with those with low BNP levels (< 80 pg/ml). Of the 80 patients, 47 showed an increase in both peak VO2 and AT, and of these 31 (66.0%) were taking β-blockers. Improvement in CR was observed in 30 of 47 patients with CI, and 70% of these were taking β-blockers. In patients not taking β-blockers, MCR-AT was lower than MCR-Rc, whereas in those taking β-blockers MCR-AT was higher than MCR-Rc.An attenuated HR response may occur during the early stages of exercise. The HR response according to the presence or absence of β-blockers is clearly identifiable by comparing MCR-AT and MCR-Rc using the Wilkoff model.
| S-EPMC5497155 | biostudies-other
Project description:BackgroundExercise echocardiography (EE) is an established method to diagnose coronary artery disease (CAD). Chronotropic incompetence (CI) during the EE may be a marker of myocardial ischemia. The purpose of this investigation was to evaluate the additive value of CI during EE in CAD diagnosis.MethodsBetween 2000 and 2006, 4042 patients (1900 men with a mean age of 56 +/- 11 years) were evaluated by EE. Based on the heart rate (HR) reached during the exercise test, the subjects were divided into two groups: G1 group - 490 patients who failed to achieve 85% of the maximal age-predicted HR, and G2 group - 3552 patients who were able to achieve 85% of the maximal age-predicted HR. Clinical characteristics, left ventricular wall motion abnormalities - wall motion score index (WMSI) - and coronary angiography (CA) were the parameters compared between the two groups.ResultsThe left ventricular wall motion abnormalities were more frequent in G1 group than in G2 group (54% versus 26%; P < 0.00001). WMSI was higher in G1 group than in G2 group, both at rest (1.06 +/- 0.17 versus 1.02 +/- 0.09; P < 0.0001) and after exercise (1.12 +/- 0.23 versus 1.04 +/- 0.21; P < 0.0001). In G1 group, 82% of the patients with positive EE for myocardial ischemia presented obstructive coronary, compared to 71% (P = 0.03) in G2 group.ConclusionCI is associated with a higher frequency of myocardial ischemia during EE, reinforcing the concept that CI is a marker of the severity of myocardial ischemia.
| S-EPMC2186302 | biostudies-literature
Project description:People with schizophrenia die on average 15-20 years earlier than age and gender matched controls in the general population. An essential part of this excess mortality in people with schizophrenia is caused by physical illnesses. Among the physical illnesses, cardiovascular disease (CVD) has been identified as the most common natural cause of death in up to 40-45% of the cases. Chronotropic incompetence (CI) is defined as the inability of the heart to increase its beating frequency in proportion to increased physical activity or higher metabolic demand. It is an established independent cardiovascular risk factor for major cardiac events and overall mortality and might explain adaptation intolerance of the cardiovascular system to even minor exercise courses. CI needs objective exercise testing for definitive diagnosis and therefore represents a biological marker indicating the integrity of the cardiovascular system. It was recently described in patients with schizophrenia and might help explain the reduced physical fitness in these patients and the inability of a subgroup of patients to benefit from exercise interventions. In this study, we tried to replicate the occurrence of CI in an independent sample of patients with schizophrenia and evaluated whether CI can be influenced by a continuous endurance training of 12 weeks. Therefore, we re-analyzed the fitness testing data of 43 patients with schizophrenia and 22 aged and gender matched healthy controls. Parameters of aerobic fitness and chronotropic response to exercise were calculated. Patients with schizophrenia were less physically fit than the healthy controls and displayed a significantly higher heart rate at rest. 10 of 43 patients with schizophrenia and no healthy control subject were classified as chronotropically incompetent. Chronotropic response to exercise did not change significantly after 12 weeks of continuous aerobic exercise training. No differences were observed for baseline heart rate and peak heart rate in both subgroups of schizophrenia patients. Aerobic fitness did not improve significantly in the patients with schizophrenia classified as chronotropically incompetent. Our results confirm the occurrence of CI in patients with multi-episode schizophrenia. This should be taken into account when planning an exercise or lifestyle intervention studies in this population. Schizophrenia patients with CI do not seem to benefit as well as schizophrenia patients without CI from aerobic exercise training interventions. Larger, prospective randomized controlled clinical trials with different training interventions are urgently needed to address the topic of schizophrenia patients not responding to exercise and the relationship to the illness itself.
| S-EPMC6424878 | biostudies-literature
Project description:ObjectivesTo examine the association between chronotropic incompetence and incident atrial fibrillation (AF).BackgroundPatients with inadequate heart rate response during exercise may have abnormalities in sinus node function or autonomic tone that predispose to the development of AF.MethodsWe examined the association between heart rate response and incident AF in 57,402 (mean age=54±13 years, 47% female, 64% white) patients free of baseline AF who underwent exercise-treadmill stress testing from the Henry Ford ExercIse Testing (FIT) Project. Age-predicted maximum heart rate (pMHR) values <85% and chronotropic index values <80% were used to define chronotropic incompetence. Cox regression, adjusting for demographics, cardiovascular risk factors, medications, coronary heart disease, heart failure, and metabolic equivalent of task achieved, was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between chronotropic incompetence and incident AF.ResultsOver a median follow-up of 5.0 years (25th-75th percentiles=2.6, 7.8), a total of 3,395 (5.9%) participants developed AF. pMHR values <85% were associated with an increased risk for AF development (HR=1.33, 95%CI=1.22, 1.44). Chronotropic index values <80% also were associated with an increased risk of AF (HR=1.28, 95%CI=1.19, 1.38). The associations of pMHR and chronotropic index with AF remained significant with varying cut-off points to define chronotropic incompetence.ConclusionsOur analysis suggests that patients with inadequate heart rate response during exercise have an increased risk for developing AF.
| S-EPMC5403158 | biostudies-literature
Project description:BackgroundCardiopulmonary exercise testing (CPET) is a standard part of preoperative evaluation in patients before lung surgical resection. According to current guidelines the risk of such a procedure is estimated according to maximum oxygen consumption (VO2max). Chronotropic incompetence (CI) is a prevalent condition which could possibly influence cardiopulmonary fitness. The aim of this study was to assess the prevalence of CI in patients before surgical lung resections and its influence on CPET results.MethodsThis study enrolled 154 patients (97 men) of average age 66.4±8.3 with newly diagnosed lung cancer indicated for surgical lung resections. All patients underwent CPET (cycle ergometry). Age predicted maximal HR was calculated using the traditional equation (220 – age). Three levels of CI were defined as, 85% HRpred, 80% HRpred and 70% HRpred. The influence of CI on CPET results was evaluated.ResultsCI was present in the following ratios: 85% HRpred—48.7%; 80% HRpred—39.6% and 70% HRpred—16.9%. A significant negative correlation was also found between VO2max, maximal heart rate (HR) and maximal work load among all CI groups (P<0.0001). The presence of CI significantly correlated with beta-blocker treatment (P<0.0001).ConclusionsCI significantly decreases VO2max in patients before lung cancer surgery. It is strongly associated with beta-blocker treatment which could negatively influence risk assessment. It is thus a matter for future discussion, as to whether the evaluation of CI should be part of preoperative care guidelines.
| S-EPMC7330419 | biostudies-literature