Prehospital risk stratification in patients with chest pain.

OBJECTIVES: The History, ECG, Age, Risk Factors and Troponin (HEART) Score is a decision support tool applied by physicians in the emergency department developed to risk stratify low-risk patients presenting with chest pain. We assessed the potential value of this tool in prehospital setting, when applied by emergency medical services (EMS), and derived and validated a tool adapted to the prehospital setting in order to determine if it could assist with decisions regarding conveyance to a hospital. METHODS: In 2017, EMS personnel prospectively determined the HEART Score, including point-of-care (POC) troponin measurements, in patients presenting with chest pain, in the north of the Netherlands. The primary endpoint was a major adverse cardiac event (MACE), consisting of acute myocardial infarction or death, within 3 days. The components of the HEART Score were evaluated for their discriminatory value, cut-offs were calibrated for the prehospital setting and sex was substituted for cardiac risk factors to develop a prehospital HEART (preHEART) Score. This score was validated in an independent prospective cohort of 435 patients in 2018. RESULTS: Among 1208 patients prospectively recruited in the first cohort, 123 patients (10.2%) developed a MACE. The HEART Score had a negative predictive value (NPV) of 98.4% (96.4-99.3), a positive predictive value (PPV) of 35.5% (31.8-39.3) and an area under the receiver operating characteristic curve (AUC) of 0.81 (0.78-0.85). The preHEART Score had an NPV of 99.3% (98.1-99.8), a PPV of 49.4% (42.0-56.9) and an AUC of 0.85 (0.82-0.88), outperforming the HEART Score or POC troponin measurements on their own. Similar results were found in a validation cohort. CONCLUSIONS: The HEART Score can be used in the prehospital setting to assist with conveyance decisions and choice of hospitals; however, the preHEART Score outperforms both the HEART Score and single POC troponin measurements when applied by EMS personnel in the prehospital setting.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies.

AIMS: The AFFIRM and RACE studies showed that rate control is an acceptable treatment strategy for atrial fibrillation (AF). We examined whether strict rate control offers benefit over more lenient rate control. METHODS AND RESULTS: We compared the outcome of patients enrolled in the rate-control arms of AFFIRM and RACE, using data from patients who met a composite of overlapping inclusion and exclusion criteria. We evaluated 1091 patients, 874 from AFFIRM and 217 from RACE. In AFFIRM, the rate-control strategy aimed for a resting heart rate < or =80 bpm and heart rate during daily activity of < or =110 bpm. In RACE, a more lenient approach was taken: resting heart rate <100 bpm. Primary endpoint was a composite of mortality, cardiovascular hospitalization, and myocardial infarction. Mean heart rate across all follow-up visits for patients in AF was lower in AFFIRM (76.1 vs. 83.4 bpm). Event-free survival for the occurrence of the primary endpoint did not differ (64% in AFFIRM vs. 66% in RACE). Patients with mean heart rates during AF within the AFFIRM (< or =80) or RACE (<100) criteria had a better outcome than patients with heart rates > or =100 (hazard ratios 0.69 and 0.58, respectively, for < or =80 and <100 compared with > or =100 bpm). CONCLUSION: Stringency of the approach to rate control, based on the comparison of the AFFIRM and RACE studies, was not associated with an important difference in clinical events.

Determinants of sudden cardiac death in patients with persistent atrial fibrillation in the rate control versus electrical cardioversion (RACE) study.

This report evaluated the correlates of sudden cardiac and nonsudden cardiac death in patients with persistent atrial fibrillation randomized to rate or rhythm control in the RAte Control vs Electrical cardioversion (RACE) study. Sudden cardiac death was observed in 16 patients, 8 patients in each group. Previous myocardial infarction resulted in a 4.9-fold increased risk of sudden death (95% confidence interval 1.8 to 13.2). The use of beta blockers showed their protective nature (hazard ratio 0.2, 95% confidence interval 0.05 to 0.9). The randomized treatment strategy, heart rhythm during follow-up, use of antiarrhythmic drugs, and number of stroke risk factors were not associated with sudden cardiac death. In conclusion, the treatment of underlying disease, rather than the heart rhythm, seems essential to prevent mortality.

Implication from randomized trials of rate and rhythm controls on management of patients with persistent atrial fibrillation.

Recently, several randomized trials were published on the issue of rate or rhythm control for patients with atrial fibrillation (AF). Patients were typically minor symptomatic, relatively old, with age above 70, presenting with a recurrence of AF and suffering from only mild to moderate underlying heart disease. The main outcome of these trials is that rate control is not inferior to rhythm control for the management of patients with AF concerning morbidity and mortality. Also patients' quality of life did not differ significantly in follow-up in these trials. However, rhythm control is not redundant in the treatment of AF. Focus is now on subgroups of patients who could still have benefit being in sinus rhythm. For severely symptomatic patients, patients presenting with the first episode of AF and probably those with severe congestive heart failure, to restore and maintain sinus rhythm should still be the goal. With the failure of antiarrhythmic therapy, nonpharmacological approaches such as pulmonary vein isolation can be performed. Another finding of the randomized trials is that being in sinus rhythm does not prevent from the occurrence of thromboembolic complications. This means that for patients with AF, with risk factors for thromboembolic events, adequate anticoagulant therapy is indicated irrespective of the current heart rhythm. As with antiarrhythmic therapy, the search for new and safer anticoagulant therapy is underway. This review will focus on the key aspects we have learned from the randomized trials on rate and rhythm controls for patients with AF.

Mending the rhythm does not improve prognosis in patients with persistent atrial fibrillation: a subanalysis of the RACE study.

AIMS: To compare outcome of AF patients with effective rhythm control with patients treated with rate control. METHODS AND RESULTS: Out of the 266 AF patients randomized to rhythm control in the RACE study, 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation. The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously. Baseline characteristics of both groups were not different. After a mean follow-up of 2.3+/-0.6 years, the primary endpoint (a composite of cardiovascular mortality, heart failure, thrombo-embolic complications (TECs), bleeding, serious adverse effects of antiarrhythmic drugs and pacemaker implants) was 22.4% in the rhythm-control group vs. 15.2% in the rate-control group. Multivariable regression analysis indicated coronary artery disease, heart failure, and digitalis as independent risk indicators of cardiovascular morbidity and mortality. Chronic sinus rhythm did not matter. CONCLUSION: Among patients who remained on warfarin, those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy.

Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) study.

OBJECTIVES: This study sought to compare whether gender affects the outcome of rate versus rhythm control treatment in patients with persistent atrial fibrillation (AF). BACKGROUND: Large trials have shown that rate control is an acceptable alternative to rhythm control. However, the effects of treatment may differ between male and female patients. METHODS: In the Rate Control versus Electrical Cardioversion (RACE) study, 522 patients (192 female) were included and randomized to rate or rhythm control. The occurrence of cardiovascular end points and quality of life (QoL) were compared between female and male patients. RESULTS: At baseline, female patients differed from male patients with regard to age, underlying heart disease, diabetes mellitus, and left ventricular function. Female patients had more AF-related complaints, and QoL was significantly lower. After a mean follow-up of 2.3 +/- 0.6 years, cardiovascular morbidity and mortality was equally distributed between female (21%) and male patients (19%). However, in contrast to male patients, female patients randomized to rhythm control developed more end points (adjusted hazard ratio was 3.1 [95% confidence interval 1.5 to 6.3], p = 0.002), mainly heart failure, thromboembolic complications, and adverse effects of antiarrhythmic drugs, compared with rate control randomized female patients. During follow-up, QoL in female patients remained worse compared with that for male patients. Randomized strategy did not influence QoL in female patients. CONCLUSIONS: In female patients with persistent AF, a rhythm control approach leads to more cardiovascular morbidity and mortality. Because treatment strategy did not influence QoL in female patients, a rate control approach may be considered in these patients.

Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study.

BACKGROUND: This study was conducted to compare rate- and rhythm-control therapy in patients with persistent atrial fibrillation (AF) and mild to moderate chronic heart failure (CHF). Rate control is not inferior to rhythm control in preventing mortality and morbidity in patients with AF. In CHF, this issue is still unsettled. METHODS: In this predefined analysis of the RACE study, a total of 261 patients were in New York Heart Association (NYHA) classes II and III at baseline. These patients were analyzed. The primary end point was a composite of cardiovascular mortality, hospitalization for CHF, thromboembolic complications, bleeding, pacemaker implantation, and life-threatening drug side effects. Furthermore, quality of life was compared. RESULTS: After 2.3 +/- 0.6 years, the primary end point occurred in 29 (22.3%) of the 130 rate-control patients and in 32 (24.4%) of the 131 rhythm-control patients. More cardiovascular deaths, hospitalization for CHF, and bleeding occurred under rate control. Thromboembolic complications, drug side effects, and pacemaker implantation were more frequent under rhythm control. Quality of life did not differ between strategies. In patients successfully treated with rhythm control, the prevalence of end points was not different from those who were in AF at study end. However, the type of end point was different: mortality, bleeding, hospitalization for heart failure, and pacemaker implantation occurred less frequently. CONCLUSIONS: In patients with mild to moderate CHF, rate control is not inferior to rhythm control. However, if sinus rhythm can be maintained, outcome may be improved. A prospective randomized trial is necessary to confirm these results.

Effect of rate and rhythm control on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: results from the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study.

OBJECTIVES: The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control. BACKGROUND: Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function. METHODS: In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters. RESULTS: Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size. CONCLUSIONS: Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.

Clinical characteristics of persistent lone atrial fibrillation in the RACE study.

In the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study, 522 patients were randomized to either rate or rhythm control therapy. Lone atrial fibrillation (AF) was present in 89 patients. Demographics, cardiovascular mortality and morbidity, and quality of life were compared between patients with lone AF and those with underlying structural heart disease. Patients with lone AF were significantly younger (65 +/- 10 vs 69 +/- 8 years) and had fewer complaints of fatigue (p = 0.01) and dyspnea (p = 0.005). With lone AF, quality-of-life scores were higher on almost all 8 Medical Outcomes Study Short-Form health survey questionnaire subscales, and comparable to healthy, age- and gender-matched controls. Mean follow-up was 2.3 +/- 0.6 years. Cardiovascular end points occurred in 9 patients with lone AF (10%), consisting of death (all bleedings) 3%, thromboembolic complications in 3%, nonfatal bleeding in 2%, and pacemaker implantation in 2%, but no heart failure and severe adverse effects due to antiarrhythmic drugs occurred. End points occurred in 95 patients (22%) with underlying diseases. Heart failure and severe adverse effects from drugs did not occur in patients with lone AF in this study. Despite the absence of demonstrable cardiovascular and cerebrovascular disease, lone AF is associated with bleeding and thromboembolism.

Rate control is more cost-effective than rhythm control for patients with persistent atrial fibrillation--results from the RAte Control versus Electrical cardioversion (RACE) study.

Aims To evaluate costs between a rate and rhythm control strategy in persistent atrial fibrillation. Methods and results In a prospective substudy of RACE (Rate control versus electrical cardioversion for persistent atrial fibrillation) in 428 of the total 522 patients (206 rate control and 222 rhythm control), a cost-minimisation and cost-effectiveness analysis was performed to assess cost-effectiveness of the treatment strategies. After a mean follow-up of 2.3+/-0.6 years, the primary endpoint (cardiovascular morbidity and mortality) occurred in 17.5% (36/202) of the rate control patients and in 21.2% (47/222) of the rhythm control patients. Mean costs per patient under rate control were euro 7386 and euro 8284 under rhythm control. Cost-effectiveness analysis showed that per avoided endpoint under rate control, the cost savings were euro 24944. Under rhythm control, more costs were generated due to electrical cardioversions, hospital admissions and anti-arrhythmic medication. Costs were higher in older patients, patients with underlying heart disease, those who reached a primary endpoint and women. Heart rhythm at the end of study, did not influence costs. Conclusions Rate control is more cost-effective than rhythm control for treatment of persistent atrial fibrillation. Underlying heart disease but not heart rhythm largely accounts for costs.

Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study.

OBJECTIVES: We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL). BACKGROUND: Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL. METHOD: Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined. RESULTS: Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement. CONCLUSIONS: Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained.

The RACE study in perspective of randomized studies on management of persistent atrial fibrillation.

Atrial fibrillation is the most common sustained cardiac arrhythmia. Treatment strategies are focused on reducing symptoms and minimizing the risks of atrial fibrillation like stroke and heart failure. First choice therapy is the rhythm control strategy, with restoration of sinus rhythm. Drawback of this approach is the low success rate for maintenance of sinus rhythm. Outcome will improve with the use of antiarrhythmic drugs after electrical cardioversion, unfortunately exposing the patient to the risks of life threatening pro-arrhythmia. The second alternative, a rate control strategy, is easy to achieve but it is unknown whether this treatment strategy results in higher morbidity and mortality rates. RACE (RAte Control versus Electrical cardioversion for persistent atrial fibrillation) was a prospective randomized trial comparing both strategies. The primary end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, pacemaker implants and severe adverse effects of drugs. After a mean follow-up of 2.3 years, the primary end point occurred in 44 of the 256 rate control patients (17.2%) and 60 of the 266 rhythm control patients (22.6%). Other trials as the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), PIAF (Pharmacological Intervention in Atrial Fibrillation) and STAF (Strategies of Treatment of Atrial Fibrillation) also found that rate control was not inferior to rhythm control in terms of morbidity, mortality and quality of life. These four randomized trials demonstrated that a rate control strategy is an acceptable alternative to rhythm control in patients with recurrent atrial fibrillation. For those with severely symptomatic atrial fibrillation, continued rhythm control is unavoidable. For these patients, safer and more effective methods of maintaining sinus rhythm are needed to reduce morbidity related to palpitations and atrial fibrillation-induced heart failure.Furthermore, the randomized studies showed that rhythm control therapy does not prevent stroke. It was observed from RACE that 21 of the 35 thromboembolic complications occurred under rhythm control, the majority while receiving inadequate anticoagulation therapy. Also in AFFIRM, with patients with one or more stroke risk factors, more strokes were present under rhythm control. Therefore, one of the main lesson learned from the randomized studies is that anticoagulation must be continued if stroke risk factors are present even if patients maintain sinus rhythm.

A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.

BACKGROUND: Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation. METHODS: We randomly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs. RESULTS: After a mean (+/-SD) of 2.3+/-0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group. The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups. CONCLUSIONS: Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion.