Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

AIMS: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation. METHODS AND RESULTS: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001). CONCLUSION: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Impact of risk-factor modification on arrhythmia recurrence among morbidly obese patients undergoing atrial fibrillation ablation.

BACKGROUND: Morbid obesity is associated with prohibitively high arrhythmia recurrence rates following atrial fibrillation (AF) ablation. DESIGN: This was a single-center study comprising 239 patients with morbid obesity and symptomatic paroxysmal or persistent AF undergoing AF ablation compared to 239 patients with a body mass index less than 30 kg/m2 matched based on age, sex, ejection fraction, AF type, presence and type of heart failure, and left atrial volume index. METHODS: Our primary outcome of interest was arrhythmia recurrence. RESULTS: During a mean follow-up of 29 months, arrhythmia recurrence was observed in 65% of the morbidly obese cohort compared to 27% of the control group (P < .0001). Among those with morbid obesity, sleep apnea screening, and treatment (91% vs 40%; P < .0001), blood pressure control (62% vs 53%; P = .001), glycemic control (85% vs 56%; P = .004), and weight loss more than equal to 5% (33% vs 57% in those who lost less than 5% and 83% in those who gained weight, P < .0001) were associated with lower arrhythmia recurrence. Recurrent arrhythmia was observed in one (4%) patient who accomplished all four goals, compared to 36% who achieved 3 of 4, 85% who modified 2 of 4%, and 97% of those who modified zero or one risk-factor. Risk-factor modification (RFM) was also associated with substantial reductions in the need for repeat ablation or direct-current cardioversion and arrhythmia-related hospitalization (P < .0001). CONCLUSION: RFM through pragmatic noninvasive means such as blood pressure and glycemic control, sleep apnea screening and treatment, and weight loss is associated with substantially lower rates of recurrent arrhythmia among morbidly obese patients undergoing AF ablation.

Mycotic Pseudoaneurysm Formation at the Cannulation Site in the Ascending Aorta.

The formation of mycotic pseudoaneurysms in the ascending aorta is a rare but sometimes fatal complication after open-heart surgery, requiring cardiopulmonary bypass (CPB). There has been little cited about this rare complication. We present a case of a 51-year-old man who developed a mycotic pseudoaneurysm in the ascending aorta at a previous aortic cannulation site nine years after coronary artery bypass surgery. The patient presented to the emergency department with two weeks of worsening substernal chest pain and was found to have pseudoaneurysm in the anterior wall of the ascending aorta on chest computed tomography angiography (CTA) during his chest pain workup. The patient's blood cultures grew methicillin-susceptible Staphylococcus aureus (MSSA). During the hospital course, the patient's respiratory status worsened, and repeat CTA revealed enlargement of the pseudoaneurysm arising from the anterior proximal arch of the aorta. Chest X-ray obtained because of hypoxia demonstrated widening of the upper mediastinum, which appeared increased compared with the previous exam. Because of concern for rupture of an aneurysm, the patient was taken to the operating room for redo sternotomy and repair of the pseudoaneurysm with femoral artery cannulation for cardiopulmonary bypass. The patient completed eight weeks of IV nafcillin, and rifampin was added to decrease biofilm formation.

Electrophysiological Manifestations of Cardiac Amyloidosis: JACC: CardioOncology State-of-the-Art Review.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by the extracellular deposition of amyloid fibrils in the myocardium. Although cardiac amyloidosis patients primarily present with heart failure symptoms, arrhythmias and conduction system disease are frequently encountered. Atrial fibrillation (AF) is observed in up to 70% of patients at the time of diagnosis, and patients typically have controlled ventricular rates caused by concomitant conduction system disease. Thromboembolic risk is particularly high in patients with CA and AF, and left atrial thrombi have been observed even in the absence of clinically diagnosed AF. Atrioventricular nodal and infra-Hisian disease are common, and permanent pacemakers are frequently required. The use of implantable cardioverter-defibrillators in this population is controversial. This review summarizes the published data and therapeutic strategies surrounding arrhythmias and conduction system disease with the goal of aiding clinicians managing the clinical complexities of CA.

Implementation of a Myocardial Perfusion Imaging Risk Algorithm to Inform Appropriate Downstream Invasive Testing and Treatment.

BACKGROUND: To risk stratify patients undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in accordance with appropriate use criteria for referral to coronary angiography, we developed a risk classification algorithm incorporating appropriate use criteria-defined risk features. We evaluated the association between this algorithm with downstream angiography, revascularization, and all-cause mortality. METHODS: We studied consecutive patients who underwent SPECT-MPI from January 1, 2015, to December 31, 2017, and assigned a scan risk of low, intermediate, high, or indeterminate. With this stratification, we assessed referral for angiography and revascularization within 3 months of SPECT-MPI and intermediate-term mortality. RESULTS: Among 12 799 patients, the mean age was 66 years, and a majority were men (56.8%). Most patients were low risk (83.6%) followed by intermediate (9.9%) and high risk (5.2%). Compared with low-risk patients, intermediate- and high-risk patients were more frequently referred for angiography (14.8% and 13.6% versus 2.0%; P<0.001) and revascularization (7.7% and 6.8% versus 0.7%; P<0.001). In 1008 propensity-matched patients, scan risk was independently associated with angiography after adjustment for ischemia, scar, or stress ejection fraction. At a mean follow-up of 2.3 years, mortality was higher with increased scan risk (high, 10.4%; intermediate, 7.1%; low, 4.1%; P<0.001). Compared with low scan risk, intermediate (hazard ratio, 1.37 [95% CI, 1.09-1.72]; P=0.008) and high scan risk (hazard ratio, 1.98 [95% CI, 1.53-2.56]; P<0.001) were associated with mortality in multivariable analysis. Similar findings were observed for those undergoing pharmacological and exercise SPECT-MPI with comparatively worse prognosis among pharmacological patients. CONCLUSIONS: This appropriate use criteria-derived risk classification algorithm for SPECT-MPI guided referral for coronary angiography and revascularization and was significantly associated with mortality. This algorithm may serve as an important tool to reaffirm appropriate use criteria and direct management of patients with stable ischemic heart disease undergoing stress testing.

Comparative Analysis of Procedural Outcomes and Complications Between De Novo and Upgraded Cardiac Resynchronization Therapy.

OBJECTIVES: This study compared rates of procedural success and complications between de novo cardiac resynchronization therapy (CRT) implantation versus upgrade, including characterization of technical challenges. BACKGROUND: CRT upgrade is common, but data are limited on the incidence of procedural success and complications as compared to de novo implantation. METHODS: All patients who underwent a transvenous CRT procedure at a single institution between 2013 and 2018 were reviewed for procedure outcome, 90-day complications, reasons for unsuccessful left ventricular lead delivery, and the presence of venous occlusive disease (VOD) that required a modified implantation technique. RESULTS: Among 1,496 patients, 947 (63%) underwent de novo implantation and 549 (37%) underwent device upgrade. Patients who received a device upgrade were older (70 ± 12 years vs. 68 ± 13 years; p < 0.01), with a male predominance (75% vs. 66%; p < 0.01) and greater prevalence of comorbidities. There was no difference in the rate of procedural success between de novo and upgrade CRT procedures (97% vs. 96%; p = 0.28) or 90-day complications (5.1% vs. 4.6%; p = 0.70). VOD was present in 23% of patients who received a device upgrade and was more common among patients with a dual-chamber versus a single-chamber device (26% vs. 9%; p < 0.001). Patients with and without VOD had a similar composite outcome of procedural failure or complication (8.0% vs. 7.8%; p = 1.0). CONCLUSIONS: Rates of procedural success and complications were no different between de novo CRT implantations and upgrades. VOD frequently increased procedural complexity in upgrades, but alternative management strategies resulted in similar outcomes. Routine venography before CRT upgrade may aid in procedural planning and execution of these strategies.

Prevalence, Incidence, and Impact on Mortality of Conduction System Disease in Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized infiltrative cardiomyopathy in which conduction system disease is common. The aim of our study was to define the incidence and prevalence of high-grade atrioventricular (AV) block requiring pacemaker implantation in our quaternary referral center. This was a single-center retrospective cohort study of 369 consecutive patients with ATTR-CA who underwent 12-lead electrocardiogram at the time of ATTR-CA diagnosis. During a mean follow-up of 28 months, serial ECGs and the electronic medical record were examined for the development of high-grade AV block and pacemaker implantation. Wild-type ATTR-CA (wtATTR-CA) was diagnosed in 261 patients and 108 had hereditary ATTR-CA (hATTR-CA). A total of 35 (9.5%) had high-grade AV block requiring pacemaker implantation at the time of diagnosis of ATTR-CA. The most common conduction abnormalities evident on the baseline ECG were a wide QRS complex, present in 51% with wtATTR-CA and 48% with hATTR-CA (p = 0.62), followed by first-degree AV block, which was present in 49% with wtATTR-CA and 43% with hATTR-CA (p = 0.31). During follow-up, high-grade AV block developed in 10% of those with hATTR-CA and 12% of patients with wtATTR-CA (p = 0.64). On multivariable models, high-grade AV block was not significantly associated with increased mortality. More advanced ATTR-CA stage and a history of obstructive coronary artery disease were associated with increased mortality on multivariable models. In conclusion, the incidence and prevalence of high-grade AV block is high in patients with ATTR-CA. Patients with ATTR-CA require close monitoring during follow-up for the development of conduction system disease.

Atrial Fibrillation in Transthyretin Cardiac Amyloidosis: Predictors, Prevalence, and Efficacy of Rhythm Control Strategies.

OBJECTIVES: This study sought to determine the incidence and prevalence of atrial fibrillation (AF) in transthyretin cardiac amyloidosis (ATTR-CA); to study the factors associated with the development of AF in this population; to study the prognostic implications of AF and maintenance of normal sinus rhythm (NSR) in patients with ATTR-CA; and to determine the impact of ATTR-CA stage on AF prevalence, outcomes, and efficacy of rhythm control strategies. BACKGROUND: AF is common in patients with ATTR-CA. The aim of this study was to determine the predictors, prevalence, and outcomes of AF in patients with ATTR-CA in addition to the efficacy of rhythm control strategies. METHODS: This was a retrospective cohort study of 382 patients with ATTR-CA diagnosed at our institution between January 2004 and January 2018. Means testing, and univariable and multivariable models were used. RESULTS: AF occurred in 265 (69%) patients. Factors associated with the development of AF included older age, advanced ATTR-CA stage, and higher left atrial volume index. Antiarrhythmic therapy (AAT) was used in 35% of patients with AF; cardioversion was performed in 45%, and 5% underwent AF ablation. Rhythm control strategies were substantially more effective when performed earlier in the disease course. During a mean follow-up of 35 months, no difference in mortality between patients with AF and those without AF was observed (65% vs. 49%; p = 0.76). On Cox proportional hazards analyses, maintenance of normal sinus rhythm and tafamidis use were associated with improved survival, whereas advanced ATTR-CA stage and higher New York Heart Association functional class were associated with increased mortality. CONCLUSIONS: With advancing ATTR-CA stage, AF became more prevalent, occurring in 69% of our entire study cohort. Rhythm control strategies including AAT, direct-current cardioversion, and AF ablation were substantially more effective when performed earlier during the disease course.

Effect of CETP inhibition with evacetrapib in patients with diabetes mellitus enrolled in the ACCELERATE trial.

BACKGROUND: High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial. METHODS AND RESULTS: Time to first occurrence of any component of the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina was compared among patients with DM randomized to treatment with evacetrapib (n=4127) or placebo (n=4109) over a median of 26 months of follow-up. The mean baseline LDL at initiation was 80 mg/dL with a mean baseline HDL of 44 mg/dL. In patients with DM, evacetrapib resulted in a 131% mean increase in HDL levels and a 32% mean decrease in LDL at 3 months that was sustained during the course of the trial. At 6 months, hemoglobin A1c (HbA1c) levels were lower with evacetrapib than placebo (7.08% vs 7.15%, p=0.023). Composite event rates were higher in patients with DM than without DM (Kaplan-Meier estimates: 15.2% vs 10.6%, HR 1.46, 95% CI 1.30 to 1.64, p<0.001). In the DM group, event rates for the composite endpoint (14.5% evacetrapib vs 16% placebo, HR 0.95, 95% CI 0.85 to 1.07, p=0.38) and individual components of the composite were similar for both evacetrapib and placebo groups. No significant treatment interaction between treatment assignment and diabetes status was noted. CONCLUSION: Despite a favorable increase in HDL, and decreases in LDL and HbA1c levels in patients with DM, we observed no benefits of treatment with evacetrapib on prespecified clinical outcomes in this high-risk population.

Impact of Baseline Glycemic Control on Residual Cardiovascular Risk in Patients With Diabetes Mellitus and High-Risk Vascular Disease Treated With Statin Therapy.

Background The contemporary impact of glycemic control on patients with diabetes mellitus at high cardiovascular risk remains unclear. We evaluated the utility of hemoglobin A1c (HbA1c) as a marker of risk on the composite end point of cardiovascular death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization in an optimally treated population with diabetes mellitus and established coronary artery disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. Methods and Results We included all patients with established diabetes mellitus and measured HbA1c (N=8145) and estimated Kaplan-Meier (KM) events rates, stratified by increasing baseline HbA1c levels censored at 30 months. We then performed a multivariable regression for the primary end point. Increasing baseline HbA1c was strongly associated with the occurrence of the primary end point (KM estimate, 12.6-18.2; P<0.001). Increasing baseline HbA1c was also associated with the triple end point of death, nonfatal myocardial infarction, and stroke (KM estimate, 7.8-11.3; P=0.003) as well as the individual end points of nonfatal myocardial infarction (KM estimate, 3.1-7.0; P<0.001), hospitalization for unstable angina (KM estimate, 1.8-5.0; P=0.003), and revascularization (KM estimate, 7.3-11.1; P=0.001), although not stroke (KM estimate, 1.4-2.4; P=0.45). The rates of cardiovascular mortality (KM estimate, 2.6-4.3; P=0.21) and all-cause mortality (KM estimate, 4.8-5.9; P=0.21) were similar regardless of baseline HbA1c levels. When adjusting for relevant baseline characteristics, baseline HbA1c was an independent predictor for the primary end point (hazard ratio, 1.06; 95% CI, 1.02-1.11; P=0.003). Conclusions Glycemic control, as measured by HbA1c, remains strongly and independently associated with cardiovascular outcomes in high-risk patients with diabetes mellitus on statin therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01687998.

Baseline fasting plasma insulin levels predict risk for major adverse cardiovascular events among patients with diabetes and high-risk vascular disease: Insights from the ACCELERATE trial.

BACKGROUND: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. METHODS: We included all patients with type II diabetes mellitus who had a central laboratory measured fasting plasma insulin level drawn at baseline as part of the study protocol. Hazard ratios were generated for the risk of major adverse cardiovascular outcomes (composite of cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization) with increasing quartile of baseline fasting plasma insulin level. We then performed a multivariable regression adjusting for significant baseline characteristics. RESULTS: Among 12,092 patients in ACCELERATE, 2042 patients with type II diabetes mellitus had a baseline fasting plasma insulin level drawn. Median follow-up was 28 months. The study population had a mean age of 66.6 years, 79.2% male and 96.2% had established coronary artery disease. During follow-up, major adverse cardiovascular outcomes occurred in 238 patients (11.6%); of these events, 177 were coronary revascularization (8.7%). We observed a statistically significant relationship between rates of revascularization and rising quartile of baseline fasting plasma insulin level which was not noted for the other individual components of major adverse cardiovascular outcomes. Patients with type II diabetes mellitus who underwent revascularization were noted to have significantly higher baseline fasting plasma insulin levels (27.7 vs 21.4 mU/L, p-value = 0.009) although baseline haemoglobin A1c (6.63% vs 6.55%), body mass index (31.5 vs 31.1 kg/m2) and medical therapy were otherwise similar to the group not undergoing revascularization. Following multivariable regression adjusting for significant characteristics including exposure to evacetrapib, the log of baseline fasting plasma insulin level was found to be an independent predictor for major adverse cardiovascular outcomes (hazard ratio = 1.36, 95% confidence interval = 1.09-1.69, p-value = 0.007); this was driven by need for future revascularization (hazard ratio = 1.56, 95% confidence interval = 1.21-2.00, p-value = 0.001). CONCLUSION: In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.

Plasma Aldosterone Levels Are Not Associated With Cardiovascular Events Among Patients With High-Risk Vascular Disease: Insights From the ACCELERATE Trial.

Background The failure of cholesteryl ester transfer protein inhibitor torcetrapib was associated with an off-target increase in plasma aldosterone. We sought to evaluate the impact of evacetrapib on plasma aldosterone level and determine the association between plasma aldosterone level and major adverse cardiovascular events among patients with stable high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. Methods and Results We included all patients with a plasma aldosterone level (N=1624) and determined the impact of evacetrapib exposure compared with placebo on plasma aldosterone levels after 12 months of treatment. Using baseline and postexposure aldosterone levels, hazard ratios for major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, cerebrovascular accident, hospitalization for unstable angina, and revascularization) with increasing quartile of baseline and percentage change in plasma aldosterone level at follow-up were calculated. The average age was 65.2 years, 75.7% were men, 93.7% were hypertensive, 73.3% were diabetic, and 57.6% had a prior myocardial infarction. Baseline plasma aldosterone level (85.2 [43, 150] versus 86.8 [43, 155] pmol/L; P=0.81) and follow-up percentage change (13.6% [-29, 88] versus 17.9% [-24, 87]; P=0.23) were similar between those who received evacetrapib and placebo. During median follow-up of 28 months, major adverse cardiovascular events occurred in 263 patients (16.2%). The hazard ratios for increasing quartile of baseline or percentage change in plasma aldosterone level at follow-up were not significant for major adverse cardiovascular events. These findings remained consistent when adjusting for significant characteristics. Conclusions Exposure to evacetrapib did not result in significant change in plasma aldosterone levels compared with placebo. Among patients with stable high-risk vascular disease, plasma aldosterone levels were not a predictor for future cardiovascular events. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01687998.