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1.
J Am Acad Dermatol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31678339

RESUMO

BACKGROUND: Psoriasis is associated with elevated risk of heart attack as well as increased accumulation of subclinical non-calcified coronary burden by coronary computed tomography angiography (CCTA). Machine learning algorithms have been shown to effectively analyze well characterized datasets. OBJECTIVE: In this study, we used machine learning algorithms to determine top predictors of non-calcified coronary burden by CCTA in psoriasis. METHODS: The analysis included 263 consecutive patients with 62 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative. The random forest algorithm was utilized to determine top predictors of non-calcified coronary burden by CCTA. We evaluated our results using linear regression models. RESULTS: Using the random forest algorithm, the top 10 predictors of non-calcified coronary burden were: body mass index, visceral adiposity, total adiposity, apolipoprotein A1, high-density lipoprotein, erythrocyte sedimentation rate, subcutaneous adiposity, small low-density lipoprotein particle and cholesterol efflux capacity. Linear regression of non-calcified coronary burden yielded results consistent with our machine learning output. LIMITATION: We were unable to provide external validation and did not study cardiovascular events. CONCLUSION: Machine learning methods identified top predictors of non-calcified coronary burden in psoriasis. These factors were related to obesity, dyslipidemia, and inflammation demonstrating that these are important targets to treat comorbidities in psoriasis.

2.
J Am Soc Echocardiogr ; 32(11): 1379-1395.e2, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31679580

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous syndrome in need of improved classification given its high morbidity and mortality and few effective treatment options. HFpEF represents an ideal setting to examine the utility and feasibility of a precision medicine approach. This article (based on the 20th annual Feigenbaum Lecture, presented at the 2019 American Society of Echocardiography Scientific Sessions) describes the utility of echocardiography as a "digital biopsy" and how deep quantitative echocardiographic phenotyping, coupled with machine learning, can be used to identify novel HFpEF phenotypes. The cellular and ultrastructural basis of abnormal speckle-tracking echocardiography- (STE-) based measurements of cardiac mechanics can provide a window into cardiomyocyte calcium homeostasis. STE-based measurements of longitudinal strain can thus inform the extent of myocardial involvement in patients with HFpEF, which may help to determine responsiveness to cardiac-specific HF medications. However, classifying the complex, systemic, multiorgan nature of HFpEF appropriately likely requires more advanced methods. Using unsupervised machine learning, HFpEF can be classified into three distinct phenogroups with differing clinical and echocardiographic characteristics and outcomes: (1) natriuretic peptide deficiency syndrome; (2) extreme cardiometabolic syndrome; and (3) right ventricle-cardio-abdomino-renal syndrome. Each can be probed to determine their biological basis. The goal of improved classification of HFpEF is to match the right patient with the right treatment, with the hope of improving the track record of HFpEF clinical trials. This article emphasizes the central role of echocardiography in advancing precision medicine and illustrates the integration of basic, translational, clinical, and population research in echocardiography with the goal of better understanding the pathobiology of a complex cardiovascular syndrome.

3.
J Card Fail ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682908

RESUMO

BACKGROUND: Diastolic dysfunction (DD) is common and occurs at an earlier age among human immunodeficiency virus -infected (HIV+) individuals, but the mechanisms and consequences of DD among HIV+ individuals are unclear. METHODS AND RESULTS: The Characterization of Heart Function on Antiretroviral Therapy (CHART) study was a multi-center cross-sectional case-control study of treated and virally suppressed HIV+ individuals with (DD+) and without DD (DD-). All patients had normal ejection fraction (>50%), no significant valvular disease, and no history of coronary revascularization or persistent atrial fibrillation. Overall, 94 DD+ and 101 DD- patients were included. DD+ patients were older with higher body mass index and more likely to have hypertension, renal dysfunction, and dyslipidemia. Groups were similar with respect to sex, race, CD4 count, and HIV RNA copies. NT-pro-B-type natriuretic peptide levels (median 36 [23, 85] vs. 26 [12, 49] pg/mL, p<0.01) and high-sensitivity troponin I (3.6 [2.6, 5.1] vs. 2.5 [1.8, 3.5] pg/mL, p<0.01) were higher among DD+ patients. The latter had similar left atrial size, but increased stiffness (conduit strain, 23.5 [17.5, 36.9] vs. 30.0 [22.9, 37.0], p<0.01) and impaired relaxation (reservoir strain, 39.7 [32.0, 58.0] vs. 45.9 [37.0, 60.6], p=0.04). On CMR, the prevalence of focal fibrosis was higher among DD+ patients (19.0% vs. 5.3%, p<0.01). DD+ patients demonstrated higher levels of carboxyl-terminal telopeptide of collagen type I (p=0.04), and trends towards higher IL-6 and oxidized low-density lipoprotein levels (p≤0.08). KCCQ physical limitation (87.1±21.4 vs. 93.1±18.1, p=0.01) and symptom frequency scores were lower among DD+ patients (86.0±21.5 vs. 92.5±16.8, p=0.01). CONCLUSIONS: In this contemporary HIV+ population receiving antiretroviral therapy, DD was associated with multiple alterations in cardiac structure and function, including myocardial fibrosis and left atrial abnormalities, and worse quality of life. Further studies are needed to assess longitudinal changes in these parameters and their potential as therapeutic targets to prevent progressive cardiac remodeling and dysfunction in HIV. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02860156.

6.
Am J Cardiol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31653352

RESUMO

In patients with heart failure and preserved or mildly reduced ejection fractions (EF ≥40%), implantation of an interatrial shunt device (IASD) resulted in heterogenous changes of the left atrial (LA) volume. Baseline characteristics that correlate with a favorable decrease in LA volume are unknown. We hypothesized that a larger ratio of left to right atrial volume at baseline would correlate strongly with LA volume decongestion following IASD implantation. Reduce Elevated LA Pressure in Patients With Heart Failure was a multicenter study of the safety and feasibility of IASD implantation. Sixty-four patients with EF ≥40% underwent device implantation along with baseline conventional echocardiograms, speckle tracking echocardiography, and resting and exercise hemodynamics. Higher LA compliance (-4.2%, p = 0.048) and right atrial reservoir strain (-0.8%, p = 0.005) were independently associated with a percent decrease in the systolic LA volume index from baseline to 6-months. In conclusion, greater LA volume reduction following IASD implantation is associated with higher baseline compliance of the left atrium and higher reservoir strain of the right atrium.

7.
J Card Fail ; 2019 Oct 13.
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.

8.
JAMA Cardiol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642867

RESUMO

Importance: Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood. Objective: To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV. Design, Setting, and Participants: Prospective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019. Exposures: Two hundred eleven plasma lipid species. Main Outcomes and Measures: Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging. Results: Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque. Conclusions and Relevance: This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.

9.
J Card Fail ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31473267

RESUMO

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

12.
Vasc Med ; : 1358863X19870602, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31480898

RESUMO

This study investigated the relationship between ankle-brachial index (ABI) and risk for heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). ABI has previously been associated with mortality, cardiovascular disease (CVD), and overall HF but the relationship between ABI and risk of HF stratified by EF has not been well characterized. We analyzed data from 6553 participants (53% female; mean age 62 ± 10 years) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of known clinical CVD/HF at baseline (2000-2002) and had baseline ABI measured. Participants were classified as low (≤ 0.90), borderline-low (0.91-1.00), normal (1.01-1.40), and high (> 1.40) ABI. Incident hospitalized HF was determined over a median follow-up of 14 years; we classified HF events (n = 321) as HFrEF with EF < 50% (n = 155, 54%) or HFpEF with EF ⩾ 50% (n = 133, 46%). Low ABI was associated with incident HFrEF (hazard ratio (HR): 2.02, 95% CI 1.19-3.40, p = 0.01) and had no significant association with HFpEF (HR: 0.67, 95% CI 0.30-1.48, p = 0.32). Borderline-low and high ABI were not significantly associated with HFrEF or HFpEF. Cubic spline analyses showed association with both low and high ABI for HFrEF and high ABI for HFpEF. A 1 SD lower ABI (for ABI < 1.1) was associated with incident HFrEF in multivariable analysis (HR: 1.27, 95% CI 1.05-1.54) but was not significant after additionally adjusting for interim myocardial infarction (HR: 1.21, 95% CI 0.99-1.48). Low ABI was associated with higher risk for incident HFrEF but not HFpEF in persons free of known CVD. Future studies of a larger size are needed for high ABI analyses.

13.
Circ Heart Fail ; 12(9): e005730, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31505940

RESUMO

BACKGROUND: Staging criteria for heart failure (HF) range from stage 0 (without risk) to being at risk (stage A) to presence of cardiac structural/functional abnormalities (stage B) to symptomatic/end stage (stages C/D). There are limited data on the prevalence of these stages in early adulthood and predictors of HF stage and symptoms in middle age. METHODS AND RESULTS: The CARDIA study (Coronary Artery Risk Development in Young Adults)-a cohort of generally healthy black and white men and women-collected phenotypic, echocardiographic, and outcomes data at the year 5 and year 30 examinations when participants were 22 to 37 and 47 to 62 years of age. Prevalence of HF stages was calculated and relationship of year 5 stage to year 30 classification and outcomes was assessed. At year 5, 2189 participants had complete data. Prevalence of HF stage A/B increased from 24% to 76% in black men, from 13% to 64% in white men, from 34% to 81% in black women, and from 13% to 56% in white women. Blacks were more likely to be in any stage or with morbidity at both time points because of higher risk factor prevalence. Of 33 participants with HF or HF deaths by year 30, 21 (64%) had been in stage A or B at year 5. Only 6 participants at year 5 in stage A (at risk) improved risk status at year 30. CONCLUSIONS: Risk for HF increased in participants from 1990 (age 22-37 years) to 2015 (age 47-62 years). Symptomatic HF or death from HF is associated with HF stage at 22 to 37 years of age. Blacks are disproportionately affected.

15.
N Engl J Med ; 381(17): 1609-1620, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31475794

RESUMO

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Tetrazóis/administração & dosagem , Valsartana/administração & dosagem , Idoso , Aminobutiratos/efeitos adversos , Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Método Simples-Cego , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
16.
Mol Genet Genomic Med ; 7(10): e00788, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407531

RESUMO

BACKGROUND: Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography. METHODS: We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)-by-drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community-based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta-analyses of main effects of drugs and 2.5 million SNP-by-drug interaction estimates. RESULTS: We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE-Is with consistent effects across cohorts (smallest p = 4.7 × 10-8 , minor allele frequency range 0.09-0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population. CONCLUSIONS: Our study identified one locus having genome-wide significant SNP-by-drug interaction effect on RWT among dCCB users in comparison to ACE-I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.

18.
J Nucl Cardiol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468377

RESUMO

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

19.
J Hypertens ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464800

RESUMO

OBJECTIVES: To evaluate the associations of high awake blood pressure (BP), high asleep BP, and nondipping BP, determined by ambulatory BP monitoring (ABPM), with left ventricular hypertrophy (LVH) and geometry. METHODS: Black and white participants (n = 687) in the Coronary Artery Risk Development in Young Adults study underwent 24-h ABPM and echocardiography at the Year 30 Exam in 2015-2016. The prevalence and prevalence ratios of LVH were calculated for high awake SBP (≥130 mmHg), high asleep SBP (≥110 mmHg), the cross-classification of high awake and asleep SBP, and nondipping SBP (percentage decline in awake-to-asleep SBP < 10%). Odds ratios for abnormal left ventricular geometry associated with these phenotypes were calculated. RESULTS: Overall, 46.0 and 49.1% of study participants had high awake and asleep SBP, respectively, and 31.1% had nondipping SBP. After adjustment for demographics and clinical characteristics, high awake SBP was associated with a prevalence ratio for LVH of 2.79 [95% confidence interval (95% CI) 1.63-4.79]. High asleep SBP was also associated with a prevalence ratio for LVH of 2.19 (95% CI 1.25-3.83). There was no evidence of an association between nondipping SBP and LVH (prevalence ratio 0.70, 95% CI 0.44-1.12). High awake SBP with or without high asleep SBP was associated with a higher odds ratio of concentric remodeling and hypertrophy. CONCLUSION: Awake and asleep SBP, but not the decline in awake-to-asleep SBP, were associated with increased prevalence of cardiac end-organ damage.

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