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1.
Eur Heart J ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221588

RESUMO

AIMS: Hypertension is a well-established heart failure (HF) risk factor, especially in the context of adverse left ventricular (LV) remodelling. We aimed to use myocardial flow reserve (MFR) and global longitudinal strain (GLS), markers of subclinical microvascular and myocardial dysfunction, to refine hypertensive HF risk assessment. METHODS AND RESULTS: Consecutive patients undergoing symptom-prompted stress cardiac positron emission tomography (PET)-computed tomography and transthoracic echocardiogram within 90 days without reduced left ventricular ejection fraction (<40%) or flow-limiting coronary artery disease (summed stress score ≥ 3) were included. Global MFR was quantified by PET, and echocardiograms were retrospectively analysed for cardiac structure and function. Patients were followed over a median 8.75 (Q1-3 4.56-10.04) years for HF hospitalization and a composite of death, HF hospitalization, MI, or stroke. Of 194 patients, 155 had adaptive LV remodelling while 39 had maladaptive remodelling, which was associated with lower MFR and impaired GLS. Across the remodelling spectrum, diastolic parameters, GLS, and N-terminal pro-B-type natriuretic peptide were independently associated with MFR. Maladaptive LV remodelling was associated with increased adjusted incidence of HF hospitalization and death. Importantly, the combination of abnormal MFR and GLS was associated with a higher rate of HF hospitalization compared to normal MFR and GLS [adjusted hazard ratio (HR) 3.21, 95% confidence interval (CI) 1.09-9.45, P = 0.034), including in the adaptive remodelling subset (adjusted HR 3.93, 95% CI 1.14-13.56, P = 0.030). CONCLUSION: We have demonstrated important associations between coronary microvascular dysfunction and myocardial mechanics that refine disease characterization and HF risk assessment of patients with hypertension based on subclinical target organ injury.

2.
J Am Coll Cardiol ; 75(9): 1003-1013, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32138959

RESUMO

BACKGROUND: Type 2 myocardial infarction (MI) and myocardial injury are associated with increased short-term mortality. However, data regarding long-term mortality are lacking. OBJECTIVES: This study compared long-term mortality among young adults with type 1 MI, type 2 MI, or myocardial injury. METHODS: Adults age 50 years or younger who presented with troponin >99th percentile or the International Classification of Diseases code for MI over a 17-year period were identified. All cases were adjudicated as type 1 MI, type 2 MI, or myocardial injury based on the Fourth Universal Definition of MI. Cox proportional hazards models were constructed for survival free from all-cause and cardiovascular death. RESULTS: The cohort consisted of 3,829 patients (median age 44 years; 30% women); 55% had type 1 MI, 32% had type 2 MI, and 13% had myocardial injury. Over a median follow-up of 10.2 years, mortality was highest for myocardial injury (45.6%), followed by type 2 MI (34.2%) and type 1 MI (12%) (p < 0.001). In an adjusted model, type 2 MI was associated with higher all-cause (hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.7; p = 0.004) and cardiovascular mortality (hazard ratio: 2.7; 95% confidence interval: 1.4 to 5.1; p = 0.003) compared with type 1 MI. Those with type 2 MI or myocardial injury were younger and had fewer cardiovascular risk factors but had more noncardiovascular comorbidities. They were significantly less likely to be prescribed cardiovascular medications at discharge. CONCLUSIONS: Young patients who experience a type 2 MI have higher long-term all-cause and cardiovascular mortality than those who experience type 1 MI, with nearly one-half of patients with myocardial injury and more than one-third of patients with type 2 MI dying within 10 years. These findings emphasize the need to provide more aggressive secondary prevention for patients who experience type 2 MI and myocardial injury.

3.
Circulation ; 141(1): 21-33, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31779467

RESUMO

BACKGROUND: Cardiac dysfunction and cardiovascular events are prevalent among patients with chronic kidney disease without overt obstructive coronary artery disease, but the mechanisms remain poorly understood. Coronary microvascular dysfunction has been proposed as a link between abnormal renal function and impairment of cardiac function and cardiovascular events. We aimed to investigate the relations between chronic kidney disease, coronary microvascular dysfunction, cardiac dysfunction, and adverse cardiovascular outcomes. METHODS: Patients undergoing cardiac stress positron emission tomography, echocardiogram, and renal function ascertainment at Brigham and Women's Hospital were studied longitudinally. Patients free of overt coronary (summed stress score <3 and without a history of ischemic heart disease), valvular, and end-organ disease were followed up for the adverse composite outcome of death or hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was determined from positron emission tomography. Echocardiograms were used to measure cardiac mechanics: diastolic (lateral and septal E/e') and systolic (global longitudinal, radial, and circumferential strain). Image analyses and event adjudication were blinded. The associations between estimated glomerular filtration rate (eGFR), CFR, diastolic and systolic indices, and adverse cardiovascular outcomes were assessed in adjusted models and mediation analyses. RESULTS: Of the 352 patients (median age, 65 years; 63% female; 22% black) studied, 35% had an eGFR <60 mL·min-1·1.73 m-2, a median left ventricular ejection fraction of 62%, and a median CFR of 1.8. eGFR and CFR were associated with diastolic and systolic indices, as well as future cardiovascular events (all P<0.05). In multivariable models, CFR, but not eGFR, was independently associated with cardiac mechanics and cardiovascular events. The associations between eGFR, cardiac mechanics, and cardiovascular events were partly mediated via CFR. CONCLUSIONS: Coronary microvascular dysfunction, but not eGFR, was independently associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. Coronary microvascular dysfunction may mediate the effect of chronic kidney disease on abnormal cardiac function and cardiovascular events in those without overt coronary artery disease.

4.
J Nucl Cardiol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741326

RESUMO

BACKGROUND: An upcoming national mandate will require consultation of appropriate use criteria (AUC) through a clinical decision support mechanism (CDSM) for advanced imaging. We aimed to evaluate our current ability to ascertain test appropriateness. METHODS: We prospectively collected data on 288 consecutive stress tests and coronary computed tomography angiography studies for medical inpatients. Study appropriateness was determined independently by two physicians using the 2013 Multimodality AUC. RESULTS: The median age of the study population was 66 years [interquartile range (IQR) 56, 75], 40.8% were female, and 52.8% had a history of coronary artery disease. Review of the electronic health record (EHR) alone was sufficient to deem appropriateness for 87.2% of cases. The most common reason it was insufficient was inability to determine if the patient could exercise (59.5%). After reviewing the EHR and pilot CDSM data together, appropriateness could be determined for 95.8% of the cases. The most common reason appropriateness could not be determined was that the exam indication was not addressed by an AUC criterion (83.3%). CONCLUSION: In preparing for the mandate, it will be important for future CDSM to obtain information on the patient's ability to exercise and for future AUC to include additional indications that are not currently addressed.

5.
Am J Med ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715169

RESUMO

BACKGROUND: Despite significant progress in primary prevention, the rate of myocardial infarction has not decreased in young adults. We sought to compare the risk factor profiles and outcomes between individuals who experienced a first myocardial infarction at a very young (≤40 years) and a young (age 41-50 years) age. METHODS: We evaluated all patients ≤50 years of age admitted with a Type 1 myocardial infarction to 2 large academic hospitals from 2000 to 2016. Risk factors were determined by review of electronic medical records. The primary outcomes of interest were all-cause and cardiovascular mortality. RESULTS: Among 2097 consecutive young patients with myocardial infarction, 431 (20.5%) were ≤40 years of age. When compared with their older counterparts, very young patients had similar risk profiles, with the exception of greater substance abuse (17.9% vs 9.3%, P < .001) and less hypertension (37.9% vs 50.9%, P < .001). Spontaneous coronary artery dissection was more prevalent in very young patients (3.1% vs 1.1%, P = .003). Over a median follow-up of 11.2 years, very young myocardial infarction patients had a similar risk of all-cause and cardiovascular mortality. CONCLUSIONS: Despite being, on average, 10 years younger and having a lower prevalence of hypertension, very young myocardial infarction patients had similar 1-year and long-term outcomes when compared with those aged 41 to 50 years at the time of their index infarction. Our findings suggest the need for aggressive secondary prevention measures in very young patients who experience a myocardial infarction.

7.
Diabetes Care ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548242

RESUMO

OBJECTIVE: We sought to determine the prevalence of diabetes and associated cardiovascular outcomes in a contemporary cohort of young individuals presenting with their first myocardial infarction (MI) at age ≤50 years. RESEARCH DESIGN AND METHODS: We retrospectively analyzed records of patients presenting with a first type 1 MI at age ≤50 years from 2000 to 2016. Diabetes was defined as a hemoglobin A1c ≥6.5% (48 mmol/mol) or a documented diagnosis of or treatment for diabetes. Vital status was ascertained for all patients, and cause of death was adjudicated. RESULTS: Among 2,097 young patients who had a type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), diabetes was present in 416 (20%), of whom 172 (41%) were receiving insulin. Over a median follow-up of 11.2 years (interquartile range 7.3-14.2 years), diabetes was associated with a higher all-cause mortality (hazard ratio 2.30; P < 0.001) and cardiovascular mortality (2.68; P < 0.001). These associations persisted after adjusting for baseline covariates (all-cause mortality: 1.65; P = 0.008; cardiovascular mortality: 2.10; P = 0.004). CONCLUSIONS: Diabetes was present in 20% of patients who presented with their first MI at age ≤50 years and was associated with worse long-term all-cause and cardiovascular mortality. These findings highlight the need for implementing more-aggressive therapies aimed at preventing future adverse cardiovascular events in this population.

12.
Am J Physiol Heart Circ Physiol ; 317(3): H617-H626, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31298558

RESUMO

We previously described a novel "chemogenetic" animal model of heart failure that recapitulates a characteristic feature commonly found in human heart failure: chronic oxidative stress. This heart failure model uses a chemogenetic approach to activate a recombinant yeast d-amino acid oxidase in rat hearts in vivo to generate oxidative stress, which then rapidly leads to the development of a dilated cardiomyopathy. Here we apply this new model to drug testing by studying its response to treatment with the angiotensin II (ANG II) receptor blocker valsartan, administered either alone or with the neprilysin inhibitor sacubitril. Echocardiographic and [18F]fluorodeoxyglucose positron emission tomographic imaging revealed that valsartan in the presence or absence of sacubitril reverses the anatomical and metabolic remodeling induced by chronic oxidative stress. Markers of oxidative stress, mitochondrial function, and apoptosis, as well as classical heart failure biomarkers, also normalized following drug treatments despite the persistence of cardiac fibrosis. These findings provide evidence that chemogenetic heart failure is rapidly reversible by drug treatment, setting the stage for the study of novel heart failure therapeutics in this model. The ability of ANG II blockade and neprilysin inhibition to reverse heart failure induced by chronic oxidative stress identifies a central role for cardiac myocyte angiotensin receptors in the pathobiology of cardiac dysfunction caused by oxidative stress.NEW & NOTEWORTHY The chemogenetic approach allows us to distinguish cardiac myocyte-specific pathology from the pleiotropic changes that are characteristic of other "interventional" animal models of heart failure. These features of the chemogenetic heart failure model facilitate the analysis of drug effects on the progression and regression of ventricular remodeling, fibrosis, and dysfunctional signal transduction. Chemogenetic approaches will be highly informative in the study of the roles of redox stress in heart failure providing an opportunity for the identification of novel therapeutic targets.

13.
Acad Med ; 94(11): 1675-1678, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31299672

RESUMO

Burnout has become commonplace in residency training, affecting more than half of residents and having negative implications for both their well-being and their ability to care for patients. During the authors' year as chief medical residents at Brigham and Women's Hospital in 2017-2018, they became intimately familiar with the burnout epidemic in residency training. The authors argue that addressing resident burnout requires residency programs and teaching hospitals to focus not on the individual contributors to burnout but instead on fostering meaning within residency to help residents find purpose and professional satisfaction in their work. In this Perspective, they highlight 4 important elements of residency that provide meaning: patient care, intellectual engagement, respect, and community. Patient care, intellectual engagement, and community provide residents with a focus that is larger than themselves, while respect is necessary for a resident's sense of belonging. The authors provide examples from their own experiences and from the literature to suggest ways in which residency programs and teaching hospitals can strengthen each of these elements within residency and curb the epidemic of burnout.

14.
Circ Cardiovasc Imaging ; 12(6): e008975, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177817

RESUMO

Background The diagnostic yield of cardiac sarcoidosis (CS) by endomyocardial biopsy is limited. Fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) may facilitate noninvasive diagnosis, but the accuracy of this approach is not well defined. We aimed to correlate findings from FDG PET and cardiac MRI with histological findings from explanted hearts of patients who underwent cardiac transplantation. Methods We analyzed the explanted heart histology for all patients who underwent cardiac transplant at our center from April 2008 to July 2018 and had pretransplant FDG PET (n=18) or cardiac MRI (n=31). The likelihood of CS based on FDG PET or cardiac MRI was categorized in a blinded fashion using a previously published method. RESULTS: Using a CS probable cutoff for FDG PET resulted in a sensitivity of 100.0% (95% CI, 54.1%-100.0%) and a specificity of 33.3% (95% CI, 9.9%-65.1%). Three of the 9 CS probable by FDG PET cases were found to be arrhythmogenic cardiomyopathy. The test characteristics of cardiac MRI are more challenging to comment on using our data as there was only one confirmed case of CS on post-transplant histological assessment. Of the 8 CS highly probable or probable cases by cardiac MRI, 3 were found to be dilated cardiomyopathy, and 2 were found to be end-stage hypertrophic cardiomyopathy. Conclusions FDG PET and cardiac MRI can help facilitate the diagnosis of CS in patients with advanced heart failure with a high degree of sensitivity but lower specificity.

16.
J Nucl Cardiol ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31044406

RESUMO

BACKGROUND: We investigated role of coronary microvascular disease (CMD) in maladaptive LV remodeling and prognosis in patients with aortic sclerosis or stenosis and no overt CAD. METHODS: This was a retrospective cohort study of patients with aortic sclerosis or stenosis, normal myocardial perfusion and LV ejection fraction (EF) > 50% (n = 43) and matched controls without AS (n = 43). PET and echocardiograms were performed within 1 year of each other. Myocardial perfusion and myocardial flow reserve (MFR) were quantified using PET imaging. LV structure and function, including global longitudinal strain (GLS), were quantified by transthoracic echocardiography. RESULTS: Global MFR declined with increasing AS severity (P = 0.04). Probability of impaired MFR increased with severity of adverse LV remodeling (OR 1.88, CI 1.03 to 3.41, P =0.04). Reduced MFR associated with impaired GLS (r = - 0.29, P = 0.002) and associated with reduced MACE-free survival at 7.27 years median follow-up. Adjusted annualized rate of MACE was highest in those with impaired GLS and MFR and lowest in those with normal GLS and MFR (30.99% vs 1.86%, P =0.002). CONCLUSION AND RELEVANCE: In patients with AS and no overt CAD, impaired MFR associates with adverse LV remodeling and subclinical LV mechanical dysfunction, and is a marker increased clinical risk.

19.
J Am Coll Cardiol ; 71(22): 2540-2551, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29535062

RESUMO

BACKGROUND: Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited. OBJECTIVES: The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes. METHODS: The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death. RESULTS: A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates. CONCLUSIONS: Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/mortalidade , Abuso de Maconha/diagnóstico , Abuso de Maconha/mortalidade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Adulto , Transtornos Relacionados ao Uso de Cocaína/terapia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Abuso de Maconha/terapia , Pessoa de Meia-Idade , Mortalidade/tendências , Infarto do Miocárdio/terapia , Sistema de Registros , Estudos Retrospectivos
20.
J Am Coll Cardiol ; 70(19): 2393-2410, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29096811

RESUMO

The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide-dependent and -independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Óxidos de Nitrogênio/administração & dosagem , Nitroglicerina/administração & dosagem , Animais , Fármacos Cardiovasculares/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Vias de Administração de Medicamentos , Humanos , Óxidos de Nitrogênio/metabolismo , Nitroglicerina/metabolismo
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