Ravi V Shah

Massachusetts General Hospital, Boston, Massachusetts, United States

Are you Ravi V Shah?

Claim your profile

Publications (80)450.03 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Reduced coronary flow reserve (CFR), an indicator of coronary microvascular dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac mortality. Since aldosterone plays a key role in vascular injury, the aim of this study was to determine whether mineralocorticoid receptor (MR) blockade improves CFR in individuals with T2DM. Sixty-four men and women with well-controlled diabetes on chronic angiotensin converting enzyme inhibition (enalapril 20 mg/day) were randomized to add-on therapy of spironolactone 25mg, hydrochlorothiazide (HCTZ) 12.5mg, or placebo for 6 months. CFR was assessed by cardiac positron emission tomography (PET) at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with spironolactone and HCTZ but not with placebo. CFR improved with treatment in the spironolactone group as compared with the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR with spironolactone remained significant after controlling for baseline CFR, change in BMI, race and statin use. Treatment with spironolactone improved coronary microvascular function raising the possibility that MR blockade could have beneficial effects in preventing cardiovascular disease in patients with T2DM.
    Diabetes 08/2014; · 7.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR).
    European Journal of Preventive Cardiology 07/2014; · 3.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: -While pulmonary vein isolation (PVI) has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance (CMR) has a strong association with late recurrent AF following PVI.
    Circulation Cardiovascular Imaging 06/2014; · 5.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple guidelines and statements related to hypertension have recently been published. Much discord has arisen from discrepant treatment and target systolic blood pressure thresholds for individuals aged 60 to 79 years of <150 mm Hg in the guideline published by members assigned to the Eighth Joint National Committee and <140 mm Hg in a statement by the American Society of Hypertension and International Society of Hypertension 2013. We sought to evaluate the public health implications of these differences using data from the 2005 to 2010 National Health and Nutrition Examination Survey (NHANES) cycles. NHANES is an ongoing survey designed to allow characterization of the US population and subpopulations. We found that only ≈2.4% (95% confidence interval, 1.5-3.2%) of adults aged 60 to 79 years had indications for antihypertensive treatment under the more stringent American Society of Hypertension and International Society of Hypertension 2013 guideline but not under Eighth Joint National Committee. About 65.7% (95% confidence interval, 62.4-69.0%) of adults aged 60 to 79 years had indications for treatment under both guidelines. Furthermore, those with indications for treatment under American Society of Hypertension and International Society of Hypertension 2013 but not under Eighth Joint National Committee generally had higher systolic blood pressure and less favorable lipid profiles compared with those with indications for treatment under both guidelines. Importantly, a larger group, comprising 21.0% (95% confidence interval, 18.7-23.2%) of adults aged 60 to 79 years, had either untreated or inadequately treated hypertension and represents an important group for continued efforts.
    Hypertension 05/2014; · 6.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study sought to determine feasibility and prognostic performance of stress cardiac magnetic resonance (CMR) in obese patients (body mass index [BMI] ≥30 kg/m(2)). Current stress imaging methods remain limited in obese patients. Given the impact of the obesity epidemic on cardiovascular disease, alternative methods to effectively risk stratify obese patients are needed. Consecutive patients with a BMI ≥30 kg/m(2) referred for vasodilating stress CMR were followed for major adverse cardiovascular events (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indices. Of 285 obese patients, 272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved diagnostic imaging quality. Mean BMI was 35.4 ± 4.8 kg/m(2), with a maximum weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with intravenous sedation). Sixteen patients required scanning by a 70-cm-bore system (6%). Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for those with ischemia and LGE). Median follow-up of the cohort was 2.1 years. In a multivariable stepwise Cox regression including clinical characteristics and CMR indices, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to 28.0; p = 0.002) remained independently associated with MACE. When patients with early coronary revascularization (within 90 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE. Stress CMR is feasible and effective in prognosticating obese patients, with a very low negative event rate in patients without ischemia or infarction.
    JACC. Cardiovascular imaging 04/2014; · 14.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Emerging literature suggests that obesity may be “protective” against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02–1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60–0.96). However, after excluding underweight individuals (body mass index [BMI] <22 kg/m2) and smokers, neither obesity nor IFG was associated with all-cause mortality, but IFG identifies individuals at greater risk in the nonobese population. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22 kg/m2. The obesity paradox may result from confounding by a sicker, underweight referent population and smoking.
    Journal of Clinical Hypertension 04/2014; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is associated with the development of atrial fibrillation (AF), and both obesity and AF are independently associated with the development of heart failure with preserved ejection fraction. We tested the hypothesis that sleep apnea (SA) would have a body mass index (BMI) independent association with adverse left ventricular (LV) remodeling and clinical outcomes in patients with AF and preserved LV function. From 720 consecutive patients with AF, 403 patients without myocardial disease (preserved LV function) were identified and followed up for 3.3 ± 1.5 years. The primary outcome was a combination of all-cause mortality/heart failure hospitalization. Left ventricular mass and LV mass-to-volume ratio were higher in patients with SA and obesity (P < .0001 for all). Body mass index (β per log = .47; P < .0001) and SA (β = .05; P = .045) were independently associated with LV mass index. Patients with treated SA had a lower LV mass index (but not LV mass-to-volume ratio) compared with untreated (P = .002). In a best overall multivariable model, SA therapy (β = -.129; P = .001) and BMI (β per log = .373; P = .0007) had opposing associations with LV mass index. Sleep apnea (hazard ratio [HR] = 2.94; P = .0004) and BMI (HR per 1 kg/m(2) = 1.08; P = .004) were associated with clinical outcome in unadjusted analysis. Only SA was associated with clinical outcome in a best overall multivariable model (HR = 2.14; P = .02). Sleep apnea and obesity are independently associated with adverse LV remodeling and clinical outcomes in patients with preserved LV function, whereas continuous positive airway pressure therapy is associated with a beneficial effect on LV remodeling. Research investigating SA therapies in patients at high risk for LV remodeling and heart failure is warranted.
    American heart journal 04/2014; 167(4):620-6. · 4.65 Impact Factor
  • Ravi V Shah, James L Januzzi
    [Show abstract] [Hide abstract]
    ABSTRACT: Circulating biomarkers that directly reflect disease progression, hemodynamics, and ventricular remodeling at a molecular level are critical to risk stratification in heart failure (HF), affording unique insights into pathophysiology not fully captured by traditional risk markers. Despite the wealth of data confirming the importance of natriuretic peptides in HF diagnosis and prognosis, residual clinical risk in HF suggests that additional biomarkers complementary to natriuretic peptides may be useful. In this article, the current literature addressing the role of these biomarkers in the clinical diagnosis and risk stratification in HF is summarized.
    Clinics in laboratory medicine 03/2014; 34(1):87-97. · 1.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes and insulin resistance have a variety of detrimental effects on cardiovascular health and outcomes. Cardiac magnetic resonance offers a non-invasive means to obtain many layers of information at a tissue level, including fibrosis, edema, intramyocardial motion, triglyceride content, and myocardial energetics. The role of cardiovascular magnetic resonance is particularly important in the evaluation of recognized and unrecognized coronary artery disease. In this review, we address the current state-of-the-art in cardiac magnetic resonance imaging - for both clinical and investigational use - as it applies to diabetic cardiovascular disease.
    Current Cardiology Reports 02/2014; 16(2):449.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Right heart failure is poorly understood and treated. In left heart failure, ventricular restraint can reverse pathologic left ventricular remodeling. The effect of restraint in right heart failure, however, is not known. We hypothesize that ventricular restraint can be applied selectively to the right ventricle (RV) to promote RV reverse remodeling. Right heart failure was induced by right coronary artery ligation in a sheep model. Eight weeks later, a saline-filled epicardial balloon was placed around the RV surface for restraint. Restraint level was defined by measuring balloon luminal pressure at end-diastole. Maximum balloon pressure was determined by the amount of balloon pressure required to decrease systemic mean arterial pressure by 10 mm Hg. We determined end-diastolic transmural myocardial pressure, indices of myocardial oxygen consumption, and RV diastolic compliance at 4 different restraint levels. After coronary ligation, RV ejection fraction (EF) decreased from 0.574 ± 0.04 to 0.362 ± 0.03 (p < 0.05). End-diastolic RV volume increased from 70.8 mL/m(2) ± 9 to 82.2 mL/m(2) ± 7 (p < 0.05) by magnetic resonance imaging. After application of restraint to the RV only, RV transmural pressure decreased significantly by 27%. Greater levels of restraint also improved RV EF (0.347 ± 0.06 to 0.473 ± 0.05) but did not change RV end-diastolic volume. A model of ischemic right heart failure was successfully created. Selective RV restraint results in improved mechanical efficiency, decreased wall stress, and improved EF. The benefits of restraint in right heart failure warrant further investigation.
    The Annals of thoracic surgery 01/2014; · 3.45 Impact Factor
  • Circulation Heart Failure 01/2014; 7(1):203-14. · 6.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. Background Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. Methods We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. Results Normal-weight patients (BMI 18.5 to 25 kg/m2) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m2; p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the “protective” association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004). Conclusions A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The “obesity paradox” is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox.
    Journal of the American College of Cardiology 01/2014; 63(8):778–785. · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR).
    Journal of the American Heart Association. 01/2014; 3(3).
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the association between major adverse cardiovascular events (MACE) and inducible ischemia on regadenoson cardiac magnetic resonance myocardial perfusion imaging (CMRMPI) performed at 3.0-Tesla. Regadenoson stress CMRMPI is increasingly used to assess patients with suspected ischemia; however, its values in patient prognostication and risk reclassification are only emerging. We studied 346 patients with suspected ischemia who were referred for regadenoson CMR. We determined the prognostic association of presence of inducible ischemia by CMR with major adverse cardiac events (MACE). In addition, we assessed the extent of net reclassification improvement (NRI) by CMR beyond a clinical risk model. There were 52 MACE during a median follow-up of 1.9 years. Patients with inducible ischemia were four-fold more likely to experience MACE (HR=4.14, 95% CI 2.37-7.24, P<0.0001). In the best overall model, presence of inducible ischemia conferred a 2.6-fold increased hazard to MACE adjusted to known clinical risk markers (adjusted HR 2.59, 95% CI 1.30-5.18, P=0.0069). Individuals with no inducible ischemia experienced a low rate of cardiac death and MI (0.6% per patient year), while individuals with inducible ischemia had an annual event rate of 3.2%. NRI across risk categories (low <5%, intermediate 5-10%, and high >10%) by CMR was 0.29 [95%CI 0.15-0.44] and continuous NRI was 0.58. In conclusion, patients with a clinical suspicion of myocardial ischemia, regadenoson stress CMRMPI provides robust risk stratification. A CMRMPI negative for ischemia was associated with very low annual rate of hard cardiac events. In addition, CMRMPI provides effective risk reclassification in a substantial proportion of patients.
    The American Journal of Cardiology. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: We tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF. Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 ± 0.03; healthy control patients, 0.29 ± 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'], r = -0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. In patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation.
    JACC. Cardiovascular imaging 11/2013; · 14.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Our purpose was to evaluate coronary artery disease (CAD) prevalence and prognosis according to cardiometabolic (CM) risk.Research Design and Methods Registry of all patients without prior CAD referred for coronary computed tomography angiography (CCTA). Patients were stratified by groups of increasing CM risk factors (hypertension, low HDL, hypertriglyceridemia, obesity, and dysglycemia) as: patients without type 2 diabetes mellitus (T2DM) with <3 or ≥3 CM risk factors, patients with T2DM not requiring insulin or those with T2DM requiring insulin. Patients were followed for a primary endpoint of major adverse cardiovascular events (MACE) composed of unstable angina, late coronary revascularization, myocardial infarction, and cardiovascular mortality.ResultsAmong 1118 patients (mean age 57±13 years) followed for a mean 3.1 years, there were 21 (1.9%) cardiovascular deaths and 13(1.2%) myocardial infarctions. There was a stepwise increase in the prevalence of obstructive CAD with increasing CM risk, from 15% in those without diabetes and <3 CM risk factors to as high as 46% in patients with type 2 diabetes requiring insulin (p<0.001). Insulin exposure was associated with the highest adjusted hazard of MACE (HR = 3.29, 95% CI 1.28-8.45, p=0.01), while both T2DM without insulin (HR=1.35, p=0.3) and ≥3 CM risk factors without T2DM (HR=1.48, p=0.3) were associated with a similar rate of MACE.Conclusion Patients without diabetes who have multiple metabolic risk factors have a similar prognosis and burden of CAD as those with T2DM not requiring insulin. Among patients with diabetes, the need for insulin therapy is associated with greater burden of CAD as well as worse prognosis.
    Diabetes care 10/2013; · 7.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure. We prospectively studied 150 consecutive patients with heart failure and an ejection fraction <=50% referred for CMR. Definitions for "significant clinical impact" of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy). Overall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of "significant clinical impact" (OR 6.72, 95% CI 2.56-17.60, p=0.0001). CMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR.
    Journal of Cardiovascular Magnetic Resonance 10/2013; 15(1):89. · 4.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. Late gadolinium enhancement during cardiac magnetic resonance (CMR) is a marker for myocardial fibrosis. We studied a consecutive group of 664 patients without known prior myocardial infarction being referred for radiofrequency ablation of AF. CMR was requested to assess pulmonary venous anatomy. Overall, 73% were male, with an average age of 56 years, and an ejection fraction of 55±10%. Left ventricular LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort we observed 68 deaths over a median follow-up period of 42 months. On univariable analysis, age (HR 1.05, CI 1.03-1.08, LRχ(2) 15.2, p=0.0001), diabetes (HR 2.39, CI 1.41-4.09, LRχ(2)10.3, p=0.001), a history of heart failure (HR 1.78, CI 1.09-2.91, LRχ(2) 5.37, p=0.02), left atrial dimension (HR 1.04, CI 1.01-1.08, LRχ(2) 6.47, p=0.01), presence of LGE (HR 5.08, CI 3.08-8.36, LRχ(2) 28.8, p<0.0001), and LGE extent (HR 1.15, CI 1.10-1.21, LRχ(2) 35.6, p<0.0001) provided the strongest association with mortality. The mortality rate was 8.1% per patient-years in patients with LGE vs. 2.3% patients without LGE. In the best overall multivariable model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in LGE associated with a 15% increased risk of death. In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.
    Journal of the American College of Cardiology 08/2013; · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study sought to determine whether the extent of late gadolinium enhancement (LGE) can provide additive prognostic information in patients with a nonischemic dilated cardiomyopathy (NIDC) with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death (SCD). Data suggest that the presence of LGE is a strong discriminator of events in patients with NIDC. Limited data exist on the role of LGE quantification. The extent of LGE and clinical follow-up were assessed in 162 patients with NIDC prior to ICD insertion for primary prevention of SCD. LGE extent was quantified using both the standard deviation-based (2-SD) method and the full-width half-maximum (FWHM) method. We studied 162 patients with NIDC (65% male; mean age: 55 years; left ventricular ejection fraction [LVEF]: 26 ± 8%) and followed up for major adverse cardiac events (MACE), including cardiovascular death and appropriate ICD therapy, for a mean of 29 ± 18 months. Annual MACE rates were substantially higher in patients with LGE (24%) than in those without LGE (2%). By univariate association, the presence and the extent of LGE demonstrated the strongest associations with MACE (LGE presence, hazard ratio [HR]: 14.5 [95% confidence interval (CI): 6.1 to 32.6; p < 0.001]; LGE extent, HR: 1.15 per 1% increase in volume of LGE [95% CI: 1.12 to 1.18; p < 0.0001]). Multivariate analyses showed that LGE extent was the strongest predictor in the best overall model for MACE, and a 7-fold hazard was observed per 10% LGE extent after adjustments for patient age, sex, and LVEF (adjusted HR: 7.61; p < 0.0001). LGE quantitation by 2-SD and FWHM both demonstrated robust prognostic association, with the highest MACE rate observed in patients with LGE involving >6.1% of LV myocardium. LGE extent may provide further risk stratification in patients with NIDC with a current indication for ICD implantation for the primary prevention of SCD. Strategic guidance on ICD therapy by cardiac magnetic resonance in patients with NIDC warrants further study.
    JACC. Cardiovascular imaging 08/2013; · 14.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy non-invasively are limited. The goal was to validate a CMR-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy. Two murine models of a) hypertension (N=18, with N=15 controls) induced by L-NG-Nitroarginine Methyl Ester (L-NAME) and b) pressure-overload (N=11) from transaortic constriction (TAC), were imaged by CMR at baseline and 7-weeks after L-NAME treatment, or up to 7 weeks following TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size dependent parameter, and extracellular volume fraction (ECV), a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin stained sections. τic correlated strongly with histologic cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75; P<0.001). Histological cardiomyocyte diameters and cell volume were higher in mice treated with L-NAME compared to controls (P<0.001). In the TAC model, CMR and histology showed an cell hypertrophy at two weeks post TAC, without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic, between 2 and 7 weeks after TAC. The intracellular lifetime (τic) measured by contrast-enhanced CMR provides a non-invasive measure of cardiomyocyte hypertrophy. ECV and τic can track myocardial tissue remodeling from pressure overload.
    Circulation 08/2013; · 15.20 Impact Factor

Publication Stats

533 Citations
450.03 Total Impact Points

Institutions

  • 2007–2014
    • Massachusetts General Hospital
      • • Division of Cardiology
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2006–2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • Brigham and Women's Hospital
      • • Division of Cardiac Surgery
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      Boston, Massachusetts, United States
  • 2013
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • St. James's Hospital
      Dublin, Leinster, Ireland
  • 2012
    • Joslin Diabetes Center
      Boston, Massachusetts, United States