Abstract Background A treatment based on an interatrial shunt device has been proposed for counteracting elevated pulmonary capillary wedge pressure (PCWP) in patients with heart failure and mildly ...reduced or preserved ejection fraction (HFpEF). We tested the theoretical hemodynamic effects of this approach with the use of a previously validated cardiovascular simulation. Methods and Results Rest and exercise hemodynamics data from 2 previous independent studies of patients with HFpEF were simulated. The theoretical effects of a shunt between the right and left atria (diameter up to 12 mm) were determined. The interatrial shunt lowered PCWP by ∼3 mm Hg under simulated resting conditions (from 10 to 7 mm Hg) and by ∼11 mm Hg under simulated peak exercise conditions (from 28 to 17 mm Hg). Left ventricular cardiac output decreased ∼0.5 L/min at rest and ∼1.3 L/min at peak exercise, with corresponding increases in right ventricular cardiac output. However, because of the reductions in PCWP, right atrial and pulmonary artery pressures did not increase. A majority of these effects were achieved with a shunt diameter of 8–9 mm. The direction of flow though the shunt was left to right in all of the conditions tested. Conclusions The interatrial shunt reduced left-sided cardiac output with a marked reduction in PCWP. This approach may reduce the propensity for heart failure exacerbations and allow patients to exercise longer, thus attaining higher heart rates and cardiac outputs with the shunt compared with no shunt. These results support clinical investigation of this approach and point out key factors necessary to evaluate its safety and hemodynamic effectiveness.
Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver ...disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.
The aim of this study was to determine the feasibility and accuracy of a new real-time 3-dimensional (RT3D) matrix-array transesophageal echocardiographic probe for the determination of left atrial ...appendage (LAA) geometry.
Sixty-six consecutive patients (mean age, 53 +/- 17 years) referred for 2-dimensional (2D) transesophageal echocardiography (TEE) underwent additional RT3D TEE. The feasibility of RT3D TEE for LAA geometry was studied in the first 37 patients, and 2D and RT3D transesophageal echocardiographic quantification of the LAA were compared in the subsequent 29 patients. The LAA orifice diameter and depth were measured using biplane 2D TEE, and LAA orifice area was calculated as an ellipse. LAA orifice area and depth were measured in 3D and correlated to 2D measurement and were also correlated to 64-slice cardiac computed tomography (CT) in 8 patients.
All 66 patients underwent RT3D matrix-array TEE without complication. In the feasibility study, the LAA was well visualized in 95%. In the quantitation study, 2D TEE underestimated LAA orifice area compared with 3D imaging (3.1 +/- 1.3 vs 4.2 +/- 2.2 cm(2); r = 0.55). LAA depth by 2D and 3D imaging were well correlated (3.7 +/- 0.7 vs 3.4 +/- 0.7 cm; r = 0.77). LAA orifice area on CT was well correlated with area on 3D TEE (r = 0.98) but not with area 2D TEE (r = 0.13). Bland-Altman analysis demonstrated that 2D TEE systematically underestimated LAA orifice area compared with 3D TEE (mean bias, -1.0 cm(2), with wide limits of agreement -4.6 to 2.6 cm(2)). In the 8 patients who underwent both 3D TEE and CT, the mean bias was 0.15 cm(2), with narrow limits of agreement (-0.50 to 0.20 cm(2)).
RT3D TEE for the visualization and quantitative analysis of LAA orifice area is feasible and correlates well with 64-slice cardiac CT.
Summary Background Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure ...to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. Methods We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m2 ) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5–6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. Findings Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). Interpretation Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. Funding None.
Left atrial appendage (LAA) is implicated in maintenance of atrial fibrillation (AF) and atrial tachycardia (AT) associated with persistent AF (PsAF) ablation, although little is known about the ...incidence and mechanism of LAA AT.
The purpose of this study was to characterize LAA ATs associated with PsAF ablation.
In 74 consecutive patients undergoing stepwise PsAF ablation, 142 ATs were encountered during index and repeat procedures. Out of 78 focal-source ATs diagnosed by activation and entrainment mapping, 15 (19%) arose from the base of LAA. Using a 20-pole catheter, high-density maps were constructed (n = 10; age 57 ± 6 years) to characterize the mechanism of LAA-AT. The LAA orifice was divided into the posterior ridge and anterior-superior and inferior segments to characterize the location of AT.
Fifteen patients with LAA AT had symptomatic PsAF for 17 ± 15 months before ablation. LAA AT (cycle length CL 283 ± 30 ms) occurred during the index procedure in four and after 9 ± 7 months in 11 patients. We could map 89% ± 8% AT CLs locally with favorable entrainment from within the LAA, which is suggestive of localized reentry with centrifugal atrial activation. ATs were localized to inferior segment (n = 4), anterior-superior segment (n = 5), and posterior ridge (n = 6) with 1:1 conduction to the atria. Ablation targeting long fractionated or mid-diastolic electrogram within the LAA resulted in tachycardia termination. Postablation, selective contrast radiography demonstrated atrial synchronous LAA contraction in all but one patient. At 18 ± 7 months, 13/15 (87%) patients remained in sinus rhythm without antiarrhythmic drugs.
LAA is an important source of localized reentrant AT in patients with PsAF at index and repeat ablation procedures. Ablation targeting the site with long fractionated or mid-diastolic LAA electrogram is highly effective in acute and medium-term elimination of the arrhythmia.
Red blood cell distribution width (RDW), a widely available biomarker, independently predicts adverse outcomes in left-sided heart failure. The relation between RDW and death in pulmonary ...hypertension (PH) is unknown. In a prospective study of 162 consecutive patients with PH, RDW was recorded during initial diagnostic right-sided cardiac catheterization, and patients were followed for 2.1 ± 0.8 years to determine vital status. Demographic, clinical, laboratory, and hemodynamic variables were compared by tertile of RDW. Cox proportional-hazards models were used to determine whether RDW was independently associated with death, and the prognostic utility of RDW was compared to that of other laboratory predictors, including N-terminal–pro–B-type natriuretic peptide (NT–pro-BNP). Of the 162 study patients, 78% were women, and 62% had pulmonary arterial hypertension. The mean age was 53 ± 15 years, and most patients had severe PH (mean pulmonary artery pressure 48 ± 13 mm Hg). The highest tertile of RDW predicted death (univariate hazard ratio 4.86, 95% confidence interval 1.37 to 17.29, p = 0.015; multivariate hazard ratio 2.4, 95% confidence interval 1.02 to 5.84, p = 0.045, after adjusting for age, gender, diabetes mellitus, connective tissue disease, diuretic use, phosphodiesterase inhibitor use, hemoglobin, mean corpuscular volume, and blood urea nitrogen BUN). Of the laboratory data, only RDW, BUN, and NT–pro-BNP were associated with death on univariate analysis. When RDW, BUN, and NT–pro-BNP were entered into a multivariate model, only RDW was still associated with death (p = 0.037 for RDW, p = 0.18 for BUN, and p = 0.39 for NT–pro-BNP). Adding NT–pro-BNP to RDW did not improve the prediction of mortality. In conclusion, RDW is independently associated with death in patients with PH and performs better as a prognostic indicator than NT–pro-BNP.
Higher urine albumin-to-creatinine ratio (UACR) has been associated with cardiac dysfunction in the general population. We assessed the association of UACR with cardiac structure and function in the ...Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos across 4 US sites. Echo-SOL participants underwent standard 2-dimensional echocardiography, including speckle-tracking strain analysis. UACR was categorized as normal and high-normal (based on the midpoint of values below microalbuminuria), microalbuminuria (≥17 mg/g for men; ≥25 mg/g for women), and macroalbuminuria (≥250 mg/g; ≥355 mg/g). Simultaneous assessments were made of left ventricular (LV) mass index and hypertrophy and measures of LV systolic and diastolic dysfunction. We assessed the association of UACR with subclinical cardiac measures, adjusting for sociodemographic and cardiometabolic factors. Among 1,815 participants (median age 54, women 65%), 42% had normal UACR, 43% high-normal UACR, 13% microalbuminuria, and 2% macroalbuminuria. Prevalence of LV hypertrophy was 13%, LV systolic dysfunction (ejection fraction <50%) 3%, and diastolic dysfunction 53%. After covariate adjustment, both micro- and macroalbuminuria were significantly associated with a twofold increase in LV hypertrophy. Microalbuminuria but not macroalbuminuria was associated with worse global longitudinal strain. Elevated UACR, even at high-normal levels, was significantly associated with greater diastolic dysfunction. In conclusion, elevated UACR was associated with LV hypertrophy and diastolic dysfunction in the largest known population sample of US Hispanic/Latinos. Screening and detection of even high-normal UACR could be of value to guide cardiovascular disease prevention efforts among Hispanic/Latino Americans.
Abstract Objectives The aims of this study were to explore the relationship of baseline levels of natriuretic peptides (NPs) with outcomes and to test for an interaction between baseline levels of ...NPs and the effects spironolactone. Background Plasma NPs are considered to be helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF), and elevated levels are associated with adverse outcomes. Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. Methods The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) trial randomized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels (B-type NP BNP ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml) to spironolactone or placebo. Baseline BNP (n = 430) or N-terminal proBNP (n = 257) levels were available in 687 patients enrolled from the Americas in the elevated-NP stratum of TOPCAT. Results Higher levels of NPs were independently associated with an increased risk for TOPCAT’s primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for HF when analyzed either continuously or grouped by terciles, adjusting for region of enrollment, age, sex, atrial fibrillation, diabetes, renal function, body mass index, and heart rate. There was a significant interaction between the effect of spironolactone and baseline NP terciles for the primary outcome (p = 0.017), with greater benefit of the drug in the lower compared with higher NP terciles. Conclusions Similar to the effects of irbesartan in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, a greater benefit of spironolactone was observed in the group with lower levels of NPs and overall risk in TOPCAT. Elevated NPs in HFpEF identify patients at higher risk for events but who may be less responsive to treatment. The mechanism of this apparent interaction between disease severity and response to therapy requires further exploration. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function TOPCAT; NCT00094302 )
Whether autonomic dysfunction predates the development of symptomatic heart failure (HF) or is simply a consequence of severe HF is unknown. We hypothesized that reduced heart rate variability (a ...marker of abnormal autonomic function) at baseline is associated with incident HF in subjects free of clinically recognized cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical cardiovascular disease in adults aged 45 to 84 years, we measured the heart rate variability using a standard 30-second, 12-lead electrocardiogram to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). During a median follow-up of 7.6 years, 95 participants developed HF (incidence rate 2.7/1,000 person-years). After adjusting for age, gender, and ethnicity, the hazard ratio for incident HF stratified by the RMSSD tertile was 2.4 (95% confidence interval 1.4 to 4.2) for the lowest tertile and 1.7 (95% confidence interval 1.0 to 3.2) for the middle tertile (highest tertile was the referent group; p for trend <0.001). The inverse association between the RMSSD and incident HF persisted after adjustment for additional covariates, including diabetes, systolic blood pressure, heart rate, subclinical atherosclerosis, left ventricular end-systolic volume, interim myocardial infarction, and high-sensitivity C-reactive protein (p for trend = 0.009). A similarly significant inverse association was also observed for SDNN. In conclusion, baseline autonomic dysfunction was a risk factor for the development of HF in a multiethnic cohort. These population-based findings implicate autonomic dysfunction in the pathogenesis of HF, and decreased short-term heart rate variability might be a novel form of stage B (asymptomatic) HF.
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The heterogeneity of the HFpEF syndrome may explain ...why (1) diagnosing and treating HFpEF is so challenging and (2) clinical trials in HFpEF have failed thus far. Here we describe 4 ways of categorizing HFpEF based on pathophysiology, clinical/etiologic subtype, type of clinical presentation, and quantitative phenomics (phenomapping analysis). Regardless of the classification method used, improved phenotypic characterization of HFpEF, and matching targeted therapies with specific HFpEF subtypes, will be a critical step towards improving outcomes in this increasingly prevalent syndrome.
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