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1.
Eur J Heart Fail ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227554

RESUMO

AIMS: Lung congestion in patients with heart failure (HF) has traditionally been treated using interventions that reduce pulmonary capillary hydrostatic pressure. The transient receptor potential vanilloid 4 (TRPV4) channel regulates fluid transit across the pulmonary capillary-interface, and represents a novel target to reduce lung water, independent of pulmonary capillary hypertension. This pilot study examined the safety and potential efficacy of TRPV4 blockade as a novel treatment for HF. METHODS AND RESULTS: In this randomized, double-blind, placebo-controlled crossover pilot trial, 11 subjects with chronic, compensated HF were treated with a novel TRPV4 antagonist (GSK2798745) or placebo. The primary endpoint was lung diffusing capacity for carbon monoxide (DLCO ) after 7 days of treatment with GSK2798745 as compared to placebo. Secondary endpoints included additional diffusion parameters, spirometry and safety assessments. Compared to placebo, treatment with GSK2798745 resulted in a trend to improvement in DLCO (placebo: -0.336 mL/mmHg/min; GSK2798745: +0.458 mL/mmHg/min; treatment difference: +0.793 mL/mmHg/min; 95% confidence interval: -0.925 to 2.512) that was not statistically significant. GSK2798745 was well-tolerated with no serious adverse events. CONCLUSION: In this pilot trial, GSK2798745 was found to be safe and well-tolerated, with a trend toward improved gas transfer. Further investigation is warranted in larger studies to determine whether treatment with TRPV4 antagonists or alternative treatments targeting capillary permeability might be effective to improve lung congestion, pulmonary gas transfer and clinical status in patients with acute or chronic HF.

2.
Int J Cardiol ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32145939

RESUMO

BACKGROUND: Previous studies have described echocardiographic indices of right ventricular (RV) diastolic function in patients with tetralogy of Fallot (TOF) but these indices have not been validated against invasive hemodynamic data. The purpose of this study was to determine echocardiographic predictors of severe RV diastolic dysfunction, and the impact of severe RV diastolic dysfunction on transplant-free survival. METHODS: Cohort study of TOF patients that underwent non-simultaneous cardiac catheterization and echocardiogram at Mayo Clinic. Based on prior studies we selected these indices for assessment: tricuspid E/A, E/e', deceleration time, pulmonary artery forward flow, dilated inferior vena cava (IVC), and hepatic vein diastolic flow reversal (HVDFR). RV diastolic function classes (normal, mild/moderate and severe dysfunction) were created using arbitrary cut-off points of the median values of right ventricular end-diastolic pressure (RVEDP) and right atrial pressure (RAP) for the cohort. RESULTS: Among 173 patients (age 40 ± 13 years), 68 patients were classified as normal (RVEDP≤14 and RAP≤10), 37 as mild/moderate dysfunction (either RVEDP>14 or RAP>10), and 69 as severe dysfunction (RVEDP>14 and RAP>10). Of the indices assessed, dilated IVC had the best sensitivity of 95% (area under the curve [AUC] 0.689) while HVDFR had the best specificity of 69% (AUC 0.648) for detecting severe RV diastolic dysfunction. Severe RV diastolic dysfunction was an independent risk factor for death/transplant (hazard ratio 2.83, p = 0.009). CONCLUSION: Severe RV diastolic dysfunction, as defined by invasive hemodynamic indices, was associated with poor prognosis. Echocardiographic indices can identify these high risk patients, and hence improve risk stratification in clinical practice.

3.
Eur J Heart Fail ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32150314

RESUMO

AIMS: Patient-reported quality of life (QOL) is a highly prognostic and clinically relevant endpoint in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The relationships between QOL and different markers of HF severity remain unclear, particularly as they relate to functional capacity and directly measured activity levels. We hypothesized that QOL would demonstrate a stronger relationship with measures of exercise capacity and adiposity compared to other disease measures. METHODS AND RESULTS: This is a secondary analysis of the National Heart, Lung, and Blood Institute-sponsored RELAX, NEAT-HFpEF and INDIE-HFpEF trials to determine the relationships between QOL (assessed by the Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire) and different domains reflecting HF severity, including maximal aerobic capacity (peak oxygen consumption), submaximal exercise capacity (6-min walk distance), volume of daily activity (accelerometry), physician-estimated functional class, resting echocardiography, and plasma natriuretic peptide levels. A total of 408 unique patients with chronic HFpEF were split into tertiles of QOL scores defined as QOLworst, QOLintermediate , QOLbest . The QOLworst HFpEF group was youngest, with a higher body mass index, greater prevalence of class II obesity and diabetes, and the lowest N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. After adjustment for age, sex and body mass index, poorer QOL was associated with worse physical capacity and activity levels, assessed by peak oxygen consumption, 6-min walk distance and actigraphy, but was not associated with NT-proBNP or indices from resting echocardiography. QOL was similarly reduced in patients with and without prior HF hospitalization. CONCLUSIONS: Quality of life in HFpEF is poorest in patients who are young, obese and have diabetes, and is more robustly tied to measures reflecting functional capacity and daily activity levels rather than elevations in NT-proBNP or prior HF hospitalization. These findings have major implications for the understanding of QOL in HFpEF and for the design of future clinical trials targeting symptom improvement in HFpEF. CLINICAL TRIAL REGISTRATION: RELAX, NCT00763867; NEAT-HFpEF, NCT02053493; INDIE-HFpEF, NCT02742129.

4.
J Am Coll Cardiol ; 75(12): 1471-1487, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32216916

RESUMO

Timely referrals for transplantation and left ventricular assist device implantation play a key role in favorable outcomes in patients with advanced heart failure. Nonetheless, evaluation usually occurs at advanced heart failure centers and is obscured from referring physicians. The purposes of this review are to explain the decision-making process for candidacy for advanced therapies and to describe the potential impact of the new organ allocation algorithm on center decision making. The document first addresses the signs of advanced heart failure, specifically focusing on the importance of the syndrome of low cardiac output as a key feature of advanced heart failure, and then summarizes the evaluation as a 3-step process addressing the following questions: 1) Is transplantation or durable assist device placement indicated? 2) Are there contraindications to either intervention? 3) How can one choose between transplantation and left ventricular assist device implantation if advanced therapies are indicated and not contraindicated?

5.
Circulation ; 141(12): 1001-1026, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32202936

RESUMO

Heart failure with preserved ejection fraction (HFpEF), a major public health problem that is rising in prevalence, is associated with high morbidity and mortality and is considered to be the greatest unmet need in cardiovascular medicine today because of a general lack of effective treatments. To address this challenging syndrome, the National Heart, Lung, and Blood Institute convened a working group made up of experts in HFpEF and novel research methodologies to discuss research gaps and to prioritize research directions over the next decade. Here, we summarize the discussion of the working group, followed by key recommendations for future research priorities. There was uniform recognition that HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach in both humans and animal models to improve understanding of mechanisms and treatment of HFpEF. It was recognized that advances in the understanding of basic mechanisms and the roles of inflammation, macrovascular and microvascular dysfunction, fibrosis, and tissue remodeling are needed and ideally would be obtained from (1) improved animal models, including large animal models, which incorporate the effects of aging and associated comorbid conditions; (2) repositories of deeply phenotyped physiological data and human tissue, made accessible to researchers to enhance collaboration and research advances; and (3) novel research methods that take advantage of computational advances and multiscale modeling for the analysis of complex, high-density data across multiple domains. The working group emphasized the need for interactions among basic, translational, clinical, and epidemiological scientists and across organ systems and cell types, leveraging different areas or research focus, and between research centers. A network of collaborative centers to accelerate basic, translational, and clinical research of pathobiological mechanisms and treatment strategies in HFpEF was discussed as an example of a strategy to advance research progress. This resource would facilitate comprehensive, deep phenotyping of a multicenter HFpEF patient cohort with standardized protocols and a robust biorepository. The research priorities outlined in this document are meant to stimulate scientific advances in HFpEF by providing a road map for future collaborative investigations among a diverse group of scientists across multiple domains.

7.
Circ Cardiovasc Imaging ; 13(2): e009672, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32069118

RESUMO

BACKGROUND: Patients with vascular stiffening may display increased arterial afterload that is out of proportion to systolic blood pressure (SBP). Since vascular and endothelial dysfunction develop in patients with coarctation of aorta (COA), we hypothesized that for any SBP, patients with mild COA (COA peak velocity <2 m/s) will have a higher arterial afterload and increased left ventricular mass index (LVMI) compared with controls, and that Doppler-derived arterial load indices would be a better predictor of LVMI compared with SBP alone. METHODS: We studied 204 COA patients (age 35±12 y) and 204 matched controls. Doppler-derived arterial afterload was assessed using effective arterial elastance index and total arterial compliance index. RESULTS: Despite similar SBP, the mild COA group displayed higher arterial afterload as evidenced by a higher elastance index (3.3±0.9 versus 2.9±0.7 mm Hg/mL·m2; P<0.001) and lower total arterial compliance index (0.8±0.3 versus 1.2±0.5 mL/mm Hg·m2; P<0.001). This was associated with higher LVMI in COA (109±35 versus 93±32, g/m2; P<0.001). Compared with SBP (ß=0.24 [95% CI, 0.02-0.45]), elastance index (ß=20.2 [95% CI, 15.8-44.1]) and total arterial compliance index (ß=-32.5 [95% CI, -43.8 to -123.6]) were better predictors of LVMI. Elastance index (but not SBP) was predictive of longitudinal increases in LVMI (r=0.43, P<0.001). CONCLUSIONS: COA patients had higher arterial afterload compared with controls with similar SBP. In comparison to SBP, Doppler-derived arterial load indices correlate more strongly with LV hypertrophy. These data suggest that SBP may underestimate LV afterload in this population. This has important clinical implications since titration of antihypertensive therapy is currently based on SBP.

8.
Circ Heart Fail ; 13(3): e006363, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32088984

RESUMO

BACKGROUND: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension. METHODS: Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise. CONCLUSIONS: When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02980887.

9.
Eur J Heart Fail ; 22(3): 489-498, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31908127

RESUMO

AIMS: Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. METHODS AND RESULTS: Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P < 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. CONCLUSIONS: Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

11.
J Card Fail ; 26(3): 233-242, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931098

RESUMO

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status. METHODS AND RESULTS: Among 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m2) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO2) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (ß coefficient per 1 SD decrease in eGFR: -0.61, 95% CI: -1.01, -0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (ß coefficient: -0.26, 95% CI: -0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO2. Sildenafil therapy was independently associated with worsening eGFR over the trial (ß coefficient: -2.79, 95% CI: -5.34, -0.24, P = .03). CONCLUSION: Renal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.

12.
Eur Respir J ; 55(2)2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31771997

RESUMO

INTRODUCTION: Identification of elevated pulmonary artery pressures during exercise has important diagnostic, prognostic and therapeutic implications. Stress echocardiography is frequently used to estimate pulmonary artery pressures during exercise testing, but data supporting this practice are limited. This study examined the accuracy of Doppler echocardiography for the estimation of pulmonary artery pressures at rest and during exercise. METHODS: Simultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP. RESULTS: Estimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15-16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p<0.0001; bias -1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p<0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (-14-25 mmHg). CONCLUSIONS: The RV-RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures.

13.
J Card Fail ; 26(2): 112-117, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568830

RESUMO

BACKGROUND: Fluid overload is common in heart failure (HF) and obesity; however, the relationship between the extent of intravascular volume expansion and indices such as body mass index (BMI) in obese and non-obese patients with HF has not been defined to address the issue of a HF obesity phenotype. METHODS: Total blood volume (TBV) was measured clinically using a radiolabeled albumin indicator-dilution technique in patients with predominately class III ambulatory chronic HF (N=66). Obesity was defined by BMI ≥30 kg/m2. RESULTS: Markedly increased intravascular volume expansion (defined by TBV expansion >+25% above normal) was highly prevalent in the obese (53%) compared to non-obese patients with HF (29%, P = .04) driven by plasma volume expansion. TBV was correlated with excess body weight and BMI (both P < .01). Also, cardiac index was higher, systemic vascular resistance lower, and left ventricular filling pressures comparable in obese compared with non-obese patients. CONCLUSIONS: Quantitative assessment of intravascular volume demonstrates for the first time that severe (not mild or moderate) volume expansion is highly common in obese patients with ambulatory chronic HF. This supports an evolving concept of an obesity-specific HF phenotype. Further study is needed to understand the mechanisms controlling volume regulation and the potential compensatory or detrimental impact on outcomes in obesity and HF.

14.
J Card Fail ; 26(2): 101-107, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31618698

RESUMO

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to nonobese patients with HFpEF METHODS AND RESULTS: National Institutes of Health heart failure network studies that enrolled patients with acute decompensated HFpEF (EF ≥ 50%) were included (DOSE, CARRESS, ROSE, and ATHENA). Obese HFpEF was defined as a body mass index ≥ 30 kg/m2. Compared to nonobese HFpEF (n = 118), patients with obese HFpEF (n = 214) were an average of 9 years younger (71 vs 80 years,< 0.001), were more likely to have diabetes (64% vs 31%, P< 0.001) but had less atrial fibrillation (56% vs 75%, P< 0.001). Renal dysfunction (glomerular filtration rate < 60 mL/min/1.73m2) was present in 82% of patients, and there was no difference at baseline between obese and nonobese patients. Despite similar weight loss through decongestive therapies, obese patients with HFpEF demonstrated greater rise in creatinine (Cr) and decline in glomerular filtration rate, with a 2-fold higher incidence of mild worsening renal function (rise in Cr ≥ 0.3 mg/dL) (28 vs 14%, P = 0.008) and a substantially greater increase in severe worsening of renal function (rise in Cr > 0.5 mg/dL) (9 vs 0%, P = 0.002). CONCLUSIONS: Despite being nearly a decade younger, obese patients with HFpEF experience greater deterioration in renal function during decongestion than do nonobese patients with HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF is needed.

15.
Catheter Cardiovasc Interv ; 95(3): 420-428, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31507065

RESUMO

Hemodynamics play a central role in the pathophysiology of heart failure (HF), yet their proper assessment and optimization remains challenging. Heart failure is defined as the inability of the heart to deliver adequate perfusion (cardiac output) to the body at rest or exercise, or to require an elevation in cardiac filling pressures in order to do this. This bedrock definition is important because it relies on measurable quantities (filling pressures and output) that are readily assessed in the cardiac catheterization laboratory. Here we present three cases to illustrate how better understanding of the determinants of cardiac output and stroke volume: preload, afterload, contractility, and lusitropy, as well as the determinants of congestion (high filling pressures) may be used to guide optimization of hemodynamic status. The goal is that the readers will be able to think more critically when evaluating the hemodynamics of their patient in HF and recognize the complex interplay that determines the complex balance between cardiac ejection and filling capabilities, and how this alters symptoms and outcomes for patients with HF. KEY POINTS: Careful assessment of hemodynamics in the catheterization laboratory allows for actionable insight to a patient's volume status, cardiac function and can help prognosticate outcomes. Exercise hemodynamics in heart failure is a powerful tool to better understand the cause of symptoms and predict outcomes. Clinicians should aim to decrease biventricular filling pressures to normal values to improve morbidity and reduce risk for readmission. In patients with heart failure and reduced ejection fraction, clinicians should aim to decrease afterload as much as can be tolerated by the renal function and patient's symptoms. Low cardiac output can often be improved by optimizing preload and afterload rather than initiating inotropes, which should be reserved until needed. In advanced heart failure, the right heart function becomes a key determinant of symptoms and outcomes.

16.
JACC Cardiovasc Imaging ; 13(1 Pt 2): 245-257, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31202759

RESUMO

Research in the last decade has substantially advanced our understanding of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, treatment options remain limited as clinical trials have largely failed to identify effective therapies. Part of this failure may be related to mechanistic heterogeneity. It is speculated that categorizing HFpEF patients based upon underlying pathophysiological phenotypes may represent the key next step in delivering the right therapies to the right patients. Echocardiography may provide valuable insight into both the pathophysiology and underlying phenotypes in HFpEF. Echocardiography also plays a key role in the evaluation of patients with unexplained dyspnea, where HFpEF is suspected but the diagnosis remains unknown. The combination of the E/e' ratio and right ventricular systolic pressure has recently been shown to add independent value to the diagnostic evaluation of patients suspected of having HFpEF. Finally, echocardiography enables identification of the different causes that mimic HFpEF but are treated differently, such as valvular heart disease, pericardial constriction, and high-output heart failure or infiltrative myopathies such as cardiac amyloid. This review summarizes the current understanding of the pathophysiology and phenotyping of HFpEF with particular attention to the role of echocardiography in this context.

17.
Eur J Heart Fail ; 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31840366

RESUMO

BACKGROUND: Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium-dependent and independent coronary microvascular function in HFpEF. METHODS AND RESULTS: Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10-6 -10-4  mol/L) using a Doppler flow wire with quantitative angiography. Endothelium-independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium-dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium-independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co-morbidities or other clinical characteristics. As compared to patients with normal endothelium-independent function, HFpEF patients with endothelium-independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e' 13.1 ± 4.1 vs. 9.6 ± 3.4, P < 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium-dependent coronary vasodilatation. Endothelium-independent microvascular dysfunction was associated with increased mortality. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium-dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co-morbidities alone. Patients with HFpEF and endothelium-independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

18.
JACC Cardiovasc Interv ; 12(21): 2145-2154, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699376

RESUMO

OBJECTIVES: The aim of this study was to test the hypothesis that the acute left ventricular (LV) unloading effect of transcatheter aortic valve replacement (TAVR) would improve right ventricular (RV) function and RV-pulmonary artery (PA) coupling in patients with severe aortic stenosis (AS). BACKGROUND: RV dysfunction is an ominous prognostic marker in patients undergoing TAVR, suggesting that relief of obstruction might be less beneficial in this cohort. However, the left ventricle and right ventricle influence each other through ventricular interaction, which could lead to improved RV function through LV unloading. METHODS: Prospective invasive hemodynamic measurements with simultaneous echocardiography were performed in symptomatic patients with severe AS before and immediately after TAVR. RESULTS: Forty-four patients (mean age 81 ± 8 years, 27% women) with severe AS underwent TAVR. At baseline, right atrial, PA mean (27 ± 7 mm Hg), and pulmonary capillary wedge (16 ± 4 mm Hg) pressures were mildly elevated, with a low normal cardiac index (2.3 l/min/m2). Pulmonary vascular resistance was mildly elevated (222 ± 133 dynes · s/cm5) and PA compliance mildly reduced (3.4 ± 01.4 ml/mm Hg). Following TAVR, aortic valve area increased (from 0.8 ± 0.3 to 2.7 ± 1.1 cm2; p < 0.001) with a reduction in mean aortic gradient (from 37 ± 11 to 7 ± 4 mm Hg; p < 0.001) and an increase in cardiac index (from 2.3 ± 0.5 to 2.5 ± 0.6 l/min/m2; p = 0.03). LV stroke work, end-systolic wall stress, and systolic ejection period decreased by 23% to 27% (p < 0.001 for all), indicating substantial LV unloading. RV stroke work (from 16 ± 7 to 18 ± 7 mm Hg · ml; p = 0.04) and tricuspid annular systolic velocities (from 9.5 ± 2.0 to 10.4 ± 3.5 cm/s; p = 0.01) increased, along with a decrease in PVR (194 ± 113 dynes · s/cm5; p = 0.03), indicating improvement in RV-PA coupling. Increased RV stroke work following TAVR directly correlated with the magnitude of increase in aortic valve area (r = 0.58; p < 0.001). CONCLUSIONS: Acute relief in obstruction to LV ejection with TAVR is associated with improvements in RV function and RV-PA coupling. These findings provide new insights into the potential benefits of LV unloading with TAVR on RV dysfunction in patients with severe AS.

19.
J Am Heart Assoc ; 8(22): e014148, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31701796

RESUMO

Background Right atrial pressure (RAP), a composite metric of right ventricular diastolic function, volume status, and right heart compliance, is a predictor of mortality in patients with heart failure due to acquired heart disease. Because patients with tetralogy of Fallot (TOF) might have abnormal right atrial and ventricular mechanics caused by myocardial injury and remodeling, we hypothesized that RAP would be associated with disease severity and cardiovascular adverse events in this population. Methods and Results We performed a cohort study of adults with TOF who underwent right heart catheterization at the Mayo Clinic Rochester between 1990 and 2017. The objective was to determine the association between RAP and multiple domains of disease severity in TOF (percentage of predicted peak oxygen consumption, atrial or ventricular arrhythmia, and heart failure hospitalization), as well as cardiovascular adverse events, defined as sustained ventricular tachycardia, resuscitated or aborted sudden death, heart transplantation, or death. Among 225 patients (113 male; mean age: 39±14 years), mean RAP was 10.7±5.2 mm Hg and median was 10 mm Hg (interquartile range: 7-13 mm Hg). Increasing RAP was associated with atrial or ventricular arrhythmias (odds ratio: 5.01; 95% CI, 1.22-23.49; P<0.001), heart failure hospitalization (odds ratio: 1.47; 95% CI, 1.10-2.39; P=0.033) per 5 mm Hg, and worsening exercise capacity (peak oxygen consumption; R2=0.74, r=-0.86, P<0.001). RAP was a predictor of cardiovascular adverse events (hazard ratio: 1.28; 95% CI, 1.10-1.47; P=0.028) per 5 mm Hg. Conclusions In symptomatic patients with TOF, increasing RAP correlates with multiple domains of disease severity (risk stratification) and predicts future cardiovascular events (prognostication). These data have potential clinical implications in the target population of symptomatic TOF patients.

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