Hoshang Farhad

Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation

Background Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI). Methods and Results A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow‐up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence. Conclusions Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

The Incidence, Pattern, and Prognostic value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients with Atrial Fibrillation

OBJECTIVES This study sought to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). BACKGROUND There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis. METHODS A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy. RESULTS Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 ± 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.03 to 1.08; chi-square likelihood ratio [LRχ(2)]: 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LRχ(2): 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LRχ(2): 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LRχ(2): 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LRχ(2): 28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LRχ(2): 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death. CONCLUSIONS In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.

Left atrial passive emptying function determined by cardiac magnetic resonance predicts atrial fibrillation recurrence after pulmonary vein isolation.

Background—Although pulmonary vein isolation has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance has a strong association with late recurrent AF after pulmonary vein isolation. Methods and Results—Three hundred forty-six patients with AF referred for cardiac magnetic resonance pulmonary vein mapping before pulmonary vein isolation were included. Maximum LA volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured; LAPEF was calculated as (VOLmax−VOLbac)/VOLmax×100. Kaplan–Meier curves were constructed to determine late recurrent AF stratified by LAPEF quintile. Cox proportional hazards regression was used to adjust for known markers of recurrence. During a median follow-up of 27 months, 124 patients (35.8%) experienced late recurrent AF. Patients with recurrence were more likely to have nonparoxysmal AF (75.8% versus 51.4%; P<0.01), higher mean VOLmax (60.2 versus 52.8 mL/m2; P<0.01), and lower mean LAPEF (19.1% versus 26.0%; P<0.01). Patients in the lowest LAPEF quintile were at highest risk of developing recurrent AF (2-year recurrence for lowest versus highest: 60.5% versus 17.3%; P<0.01). After adjusting for known predictors of recurrence, patients with low LAPEF remained significantly more likely to recur (hazard ratio for lowest versus highest quintile, 3.92; 95% confidence interval, 2.01–7.65). Conclusions—We found a strong association between LAPEF and recurrent AF after pulmonary vein isolation that persisted after multivariable adjustment.

Retinal Vessel Calibers in Predicting Long-term Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study.

Background: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events. Methods: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993–1995). Results: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08–1.18; HR, 1.18; 95% CI, 1.07–1.31; and HR, 1.10; 95% CI, 1.00–1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01–1.11; HR, 1.14; 95% CI, 1.03–1.26; and HR, 1.13; 95% CI, 1.03–1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P=0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations–predicted 10-year atherosclerotic cardiovascular disease event risk <5% (overall risk, 3.9%), women in the narrowest arteriolar quartile had a 10-year event rate of 5.6% compared with 2.8% for women in the widest quartile (5.0% versus 3.4% for wider versus narrower venules). Retinal vessel caliber reclassified 21% of low-risk women (11% of all women) as intermediate risk (>5%). Conclusions: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women.Background: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events. Methods: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993–1995). Results: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08–1.18; HR, 1.18; 95% CI, 1.07–1.31; and HR, 1.10; 95% CI, 1.00–1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01–1.11; HR, 1.14; 95% CI, 1.03–1.26; and HR, 1.13; 95% CI, 1.03–1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P =0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations–predicted 10-year atherosclerotic cardiovascular disease event risk 5%). Conclusions: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women. # Clinical Perspective {#article-title-45}

Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance ImagingCLINICAL PERSPECTIVE

Background—Anthracyclines are cardiotoxic; however, there are limited data characterizing the serial changes in cardiac structure and function after anthracyclines. The aim of this study was to use cardiac magnetic resonance to characterize anthracycline-induced cardiotoxicity in mice. Methods and Results—This was a longitudinal cardiac magnetic resonance and histological study of 45 wild-type male mice randomized to doxorubicin (n=30, 5 mg/kg of doxorubicin/week for 5 weeks) or placebo (n=15). A cardiac magnetic resonance was performed at baseline and at 5, 10, and 20 weeks after randomization. Measures of primary interest included left ventricular ejection fraction, myocardial edema (multiecho short-axis spin-echo acquisition), and myocardial fibrosis (Look-Locker gradient echo). In doxorubicin-treated mice versus placebo, there was an increase in myocardial edema at 5 weeks (T2 values of 32±4 versus 21±3 ms; P<0.05), followed by a reduction in left ventricular ejection fraction (54±6 versus 63±5%; P<0.05) and an increase in myocardial fibrosis (extracellular volume of 0.34±0.03 versus 0.27±0.03; P<0.05) at 10 weeks. There was a strong association between the early (5 weeks) increase in edema and the subacute (10 weeks) increase in fibrosis (r=0.90; P<0.001). Both the increase in edema and fibrosis predicted the late doxorubicin-induced mortality in mice (P<0.001). Conclusions—Our data suggest that, in mice, anthracycline-induced cardiotoxicity is associated with an early increase in cardiac edema and a subsequent increase in myocardial fibrosis. The early increase in edema and subacute increase in fibrosis are strongly linked and are both predictive of late mortality.

Effect of Late Gadolinium Enhancement on the Recovery of Left Ventricular Systolic Function After Pulmonary Vein Isolation

Background The factors that predict recovery of left ventricular (LV) systolic dysfunction among patients with atrial fibrillation (AF) are not completely understood. Late gadolinium enhancement (LGE) of the LV has been reported among patients with AF, and we aimed to test whether the presence LGE was associated with subsequent recovery of LV systolic function among patients with AF and LV dysfunction. Methods and Results From a registry of 720 consecutive patients undergoing a cardiac magnetic resonance study prior to pulmonary vein isolation (PVI), patients with LV systolic dysfunction (ejection fraction [EF] <50%) were identified. The primary outcome was recovery of LVEF defined as an EF >50%; a secondary outcome was a combined outcome of subsequent heart failure (HF), admission, and death. Of 720 patients, 172 (24%) had an LVEF of <50% prior to PVI. The mean LVEF pre‐PVI was 41±6% (median 43%, range 20% to 49%). Forty‐three patients (25%) had LGE (25 [58%] ischemic), and the extent of LGE was 7.5±4% (2% to 19%). During follow‐up (mean 42 months), 91 patients (53%) had recovery of LVEF, 68 (40%) had early recurrence of AF, 65 (38%) had late AF, 18 (5%) were admitted for HF, and 23 died (13%). Factors associated with nonrecovery of LVEF were older age, history of myocardial infarction, early AF recurrence, late AF recurrence, and LGE. In a multivariable model, the presence of LGE and any recurrence of AF had the strongest association with persistence of LV dysfunction. Additionally, all patients without recurrence of AF and LGE had normalization of LVEF, and recovery of LVEF was associated with reduced HF admissions and death. Conclusions In patients with AF and LV dysfunction undergoing PVI, the absence of LGE and AF recurrence are predictors of LVEF recovery and LVEF recovery in AF with associated reduction in subsequent death and heart failure.

Multimodality Imaging in Ischemic Cardiomyopathy

Cardiac multimodality (hybrid) imaging can be obtained from a variety of techniques, such as nuclear medicine with single photon emission computed tomography (SPECT) and positron emission tomography (PET), or radiology with multislice computed tomography (CT), magnetic resonance (MR) and echography. They are typically combined in a side-by-side or fusion mode in order to provide functional and morphological data to better characterise coronary artery disease, with more proven efficacy than when used separately. The gained information is then used to guide revascularisation procedures. We present an up-to-date comprehensive overview of multimodality imaging already in clinical use, as well as a combination of techniques with promising or developing applications.

Pharmacologic manipulation of coronary vascular physiology for the evaluation of coronary artery disease

During the last forty years tremendous progress has been made in our understanding of coronary atherosclerosis and in the development of methods to characterize atherosclerotic disease burden and risk. Stress testing is designed to elucidate abnormalities in myocardial perfusion during stress due to abnormal coronary vasomotor response. We summarize the underlying determinants of normal coronary vasomotor tone as well as its responsiveness to both exercise and pharmacologic stressors. We introduce the various methods of assessing the presence of myocardial ischemia. A detailed discussion of the most commonly used stress agents as well as their clinical advantages and limitations follows.

T1 Measurements for Detection of Expansion of the Myocardial Extracellular Volume in Chronic Obstructive Pulmonary Disease

BACKGROUND We aimed to assess whether chronic obstructive pulmonary disease (COPD) is associated with expansion of the myocardial extracellular volume (ECV) using T1 measurements. METHODS Adult COPD patients Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2 or higher and free of known cardiovascular disease were recruited. All study patients underwent measures of pulmonary function, 6-minute walk test, serum measures of inflammation, overnight polysomnography, and a contrast cardiac magnetic resonance study. RESULTS Eight patients with COPD were compared with 8 healthy control subjects. The mean predicted forced expiratory volume at 1 second of COPD subjects was 68%. Compared with control subjects, patients had normal left ventricular (LV) and right ventricular size, mass, and function. However, compared with control subjects, the LV remodelling index (median, 0.87; interquartile range [IQR], 0.71-1.14; vs median, 0.62; IQR, 0.60-0.77; P ¼ 0.03) and active left atrial emptying fraction was increased (median, 46; IQR, 41-49; vs median, 38; IQR, 33-43; P ¼ 0.005), and passive left atrial emptying fraction was reduced (median, 24; IQR, 20-30; vs median, 44; IQR, 31-51; P ¼ 0.007). The ECV was increased in patients with COPD (median, 0.32; IQR, 0.05; vs median, 0.27; IQR, 0.05; P = 0.001). The ECV showed a strong positive association with LV remodelling (r = 0.72; P = 0.04) and an inverse association with the 6-minute walk duration (r = -0.79; P = 0.02) and passive left atrial emptying fraction (r = -0.68; P = 0.003). CONCLUSIONS Expansion of the ECV, suggestive of diffuse myocardial fibrosis, is present in COPD and is associated with LV remodelling, and reduced left atrial function and exercise capacity.