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Highlights • Chronic severe AR progresses slowly with a long asymptomatic compensated phase. • Stress echocardiography (SE) has the ability to uncover subclinical LV dysfunction. • SE can identify patients with severe AR who may benefit from earlier intervention., Graphical abstract

Objective: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp +/− mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident HFpEF. Aortic PWV was increased in older, but not young, female Mgp +/− mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. Conclusions: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future HFpEF in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in HFpEF.

This study reports a case of partial atrioventricular canal defect with an anomalous left circumflex coronary artery in an elderly veteran presenting with unexplained dyspnea on exertion. This is a rare finding in this population and emphasizes the importance of a broad differential diagnosis and meticulous evaluation when more common conditions have been excluded. (Level of Difficulty: Intermediate.), Graphical abstract, This study reports a case of partial atrioventricular canal defect with an anomalous left circumflex coronary artery in an elderly veteran presenting…

Graphical abstract, Highlights • Adults with SM have slower hemodynamic progression and more rapid AS progression. • Changes in LVOT velocities are minimal over time. • Presence of SM with AS poses challenges in determining hemodynamic significance. • In general, surgery should be recommended when AS is severe and symptoms develop.

Introduction: Valvular aortic stenosis (AS) is common with high morbidity and mortality in the absence of surgical intervention, but no current medical therapies are known to prevent or slow disease progression. Previous genetic studies have identified several genetic loci associated with prevalent AS, including LPA and PALMD , although most evidence is limited to populations of European ancestry. Methods: We performed a trans-ethnic genome-wide association study (GWAS) of prevalent AS in the Veterans Administration Million Veteran Program (MVP). Cases were identified by a combination of diagnostic billing and surgical codes and validated by association to the known LPA variant (rs10455872). GWAS was run separately for White, Black, and Hispanic individuals, controlling for age, sex, and six principal components, and combined using fixed effects meta-analysis. Results were limited to variants with a minor allele frequency greater than 1% in the trans-ancestry analysis. Lead independent genome wide significant loci were annotated by nearest gene. Results: 300,182 White, 80,744 Black, and 32,069 Hispanic participants were available for analysis. Of these, there were 12,385 (4.1%) White, 1,444 (1.8%) Black, and 611 (1.9%) Hispanic AS cases. Trans-ethnic analyses identified 10 independent genome wide significant (GWS, p≤5x10 -8 ) loci, replicating 6 known AS genetic loci ( ALPL, PALMD, TEX41, LPA, IL6, FADS1 ), and identifying 4 novel genetic loci ( CEP85L, CELSR2, NCK1, SLMAP ), of which 2 were present at nominal significance in Hispanic ( CELS2R ) or Black ( SLMAP ) individuals. Ethnicity-specific analyses additionally identified 9 novel GWS loci in White individuals, and 3 novel GWS loci in Hispanic individuals. Newly identified loci supported known biological pathways in AS including lipid/metabolic, inflammatory, and calcification, but also implicated new pathways such as those pertaining to QT interval ( SLC35F1 ) and the Brugada Syndrome ( SLMAP ). Conclusions: In this large trans-ethnic GWAS for AS we replicate previously identified genetic loci for AS, and identified several novel loci both in trans-ethnic and in ethnic-specific analyses. These loci implicate known and novel biological mechanisms for future prevention and treatment of AS.

Transthoracic echocardiography is the primary cardiac imaging modality for the detection of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) through evaluation of serial changes in left ventricular ejection fraction (LVEF). However, LVEF assessment by standard methods including 3D Echo has important limitations including the fact that reduction in LVEF occurs late in the process of CTRCD. In contrast, by detecting early myocardial change, myocardial strain or deformation imaging has evolved to be a preferred parameter for detecting CTRCD. Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) has become an important prechemotherapy parameter that can independently predict subsequent adverse cardiac events as these abnormalities typically precede reduction in LVEF. While an absolute GLS measurement may be informative, a 10%-15% early reduction in GLS by STE appears to be the most useful prognosticator for cardiotoxicity while on therapy. In this paper, we present a current systematic literature review of application of myocardial strain imaging in cancer patients performed following PRISMA guidelines using electronic databases from MEDLINE, Embase, and SCOPUS Library from their inception until June 11th 2020. This review demonstrates the incremental value of myocardial deformation imaging over traditional LVEF in detection and its clinical implication in management of CTRCD.

Bioprosthetic valve thrombosis (BPVT) is more common than previously thought and likely underreported. BPVT can be accurately diagnosed with cardiac imaging and treated successfully with anticoagulation, thus preventing reoperation. We hereby report a case of recurrent BPVT in the mitral position successfully treated with anticoagulation along with review of literature.

Objectives This study sought to evaluate the course, correlates, and prognosis of longitudinal changes in left ventricular (LV) diastolic dysfunction (DD) in the community-based Framingham Heart Study. Background Relationships of clinical risk factors to longitudinal progression of DD are incompletely understood. Methods Diastolic function was assessed by echocardiography performed at consecutive examinations (visits 1 and 2, mean interval 5.6 years) in 1,740 participants (64 ± 8 years of age at visit 1, 59% women) with normal LV systolic function and no atrial fibrillation. Results Of 1,615 individuals with normal-to-mild DD at visit 1, 198 (12%) progressed to ≥ moderate DD at visit 2. Progression was more likely in women and with advancing age (p Conclusions In a community-based cohort of middle-aged to older adults, cardiometabolic risk factors and noncardiac comorbidities were associated with DD progression. Moderate or worse DD was associated with higher risk of CVD or death.

Objectives The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation. Background Temporal trends in the prevalence and management of major risk factors may affect the epidemiology of HF. Methods We compared the frequency, correlates, and prognosis of LVSD (left ventricular ejection fraction [LVEF] Results Among participants without HF (12,857 person-observations, mean age 53 years, 56% women), the prevalence of LVSD on echocardiography decreased (3.38% in 1985 to 1994 vs. 2.2% in 2005 to 2014; p Conclusions The profile of HF in the community has changed in recent decades, with a lower prevalence of LVSD and an increased frequency of HFpEF, presumably due to concomitant risk factor trends.

Sinus of Valsalva aneurysm (SVA) is a rare but potentially serious condition. Proper and timely diagnosis is crucial to the outcome of patients, particularly when rupture has occurred. Echocardiography is often the initial diagnostic imaging modality of choice as it is ubiquitous, relatively inexpensive, and without need for radiation or iodinated contrast administration. There are several congenital abnormalities that can appear similar to SVA on echocardiography, making the diagnosis challenging especially if providers are unfamiliar with these conditions. Here, we present a case series of three patients with SVA, representing a wide spectrum ranging from a young man presenting with acute rupture and decompensated heart failure to an elderly asymptomatic male with an incidental unruptured aneurysm. We will also present a brief literature overview and our approach to differentiating SVA from other congenital abnormalities on echocardiography.

Background In recent decades, novel echocardiographic measures have constantly emerged. It is still unclear which echocardiographic measures have the most significant prognostic value in the general population. Accordingly, the aim of this study was to compare the prognostic value of a large panel of echocardiographic measures to identify the most promising measures. Methods A total of 1,497 Framingham study participants (mean age, 65 years; 55.4% women) who underwent echocardiographic measurements of left ventricular ejection fraction, left ventricular mass index, global longitudinal strain, global circumferential strain, mitral annular plane systolic excursion, mitral E/e′ ratio, maximum and minimum left atrial (LA) volume index, LA emptying fraction, and left ventricular longitudinal synchrony were evaluated. These measures were related to the incidence of two composite outcomes: cardiovascular disease (CVD) or death and atrial fibrillation (AF) or congestive heart failure (CHF). Results On follow-up (mean, 8.3 years), there were 241 CVD events or deaths and 139 AF or CHF events. In multivariate-adjusted Cox models, higher LA emptying fraction was associated with a lower risk (hazard ratios per SD, 0.80 and 0.70 for CVD or death and AF or CHF, respectively; P ≤ .001 for both) while higher minimum LA volume index (hazard ratios per SD, 1.32 and 1.70 for CVD or death and AF or CHF, respectively; P ≤ .001 for both) and maximum LA volume index (hazard ratios per SD, 1.26 and 1.54 for CVD or death and AF or CHF, respectively; P ≤ .002 for both) were associated with a higher risk for both composite outcomes. Conclusions In this community-based sample, LA volumes and function were the best echocardiographic predictors of clinical outcomes. Therefore, these values should be considered for inclusion in standard echocardiographic assessments for the purpose of risk stratification.

Carfilzomib, a selective proteasome inhibitor, is approved for use in relapsed and refractory multiple myeloma. Its link to left ventricular dysfunction is well established but little is known about its effects on the right ventricle. One of its rare complications is pulmonary hypertension, which at its extreme may result in right ventricular dysfunction. Here, we present a case of an elderly male veteran with multiple myeloma status post various failed therapies who developed acute dyspnea after four cycles of carfilzomib and subsequently found to have severe pulmonary hypertension with resultant acute right ventricular failure, which recovered after cessation of carfilzomib. This case highlights the need for careful cardiovascular surveillance while on carfilzomib and the importance of knowing even its rarest complications as these cardiotoxicities are reversible with discontinuation of the drug.

The purpose of this study was to describe the prevalence and prognosis of HF stages in the community; to evaluate if preclinical HF stages are characterized by elevation of pro-inflammatory (C-reactive protein), neurohormonal activation (B-type natriuretic peptide, renin and aldosterone), and cardiac stress biomarkers (high-sensitivity troponin I, ST-2, and growth differentiation factor-15).The American Heart Association/American College of Cardiology heart failure (HF) classification has 3 stages. Knowledge regarding the community burden of HF stages is limited, and data on the biomarker profile associated with HF stages are scarce, although higher concentrations of certain biomarkers are associated with preclinical HF.We evaluated 6,770 participants (mean age 51 years; 54% women) from the Framingham Study, defining 4 stages: 1) healthy: no risk factors; 2) stage A: presence of HF risk factors (hypertension, diabetes, obesity, coronary artery disease), no cardiac structural/functional abnormality; 3) stage B: presence of prior myocardial infarction, valvular disease, left ventricular (LV) systolic dysfunction, LV hypertrophy, regional wall motion abnormality, or LV enlargement; 4) stage C/D: prevalent HF.The prevalence of HF stages A and B were 36.5% and 24.2%, respectively, rising with age (odds ratio: 1.70 [95% confidence interval: 1.64 to 1.77] per decade increment). In age- and sex-adjusted models, we observed a gradient of increasing biomarker levels across HF stages (p 0.05; n = 3,416). Adjusting for age and sex, mortality rose across HF stages (232 deaths, mean follow-up 7 years), with 2- and 8-fold mortality risks for stages B and C/D, respectively, compared with healthy.Approximately 60% of our sample has preclinical HF, and those in stage B had higher concentrations of HF biomarkers and experienced a substantial mortality risk.

Objectives This study sought to examine the association of a borderline left ventricular ejection fraction (LVEF) of 50% to 55% with cardiovascular morbidity and mortality in a community-based cohort. Background Guidelines stipulate a LVEF >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a “borderline” LVEF, 50% to 55%, is unknown. Methods This study evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n = 10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF and continuous LVEF with the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome). Results During follow-up (median 7.9 years), HF developed in 355 participants, and 1,070 died. Among participants with an LVEF of 50% to 55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years of follow-up, respectively, versus 0.16 and 0.05 in participants having a normal LVEF. In multivariable-adjusted analyses, LVEF of 50% to 55% was associated with increased risk of the composite outcome (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.05 to 1.80) and HF (HR: 2.15; 95% CI: 1.41 to 3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12; 95% CI: 1.07 to 1.16) and HF (HR per 5 LVEF% decrement: 1.23; 95% CI: 1.15 to 1.32). Conclusions Persons with an LVEF of 50% to 55% in the community have greater risk for morbidity and mortality relative to persons with an LVEF >55%. Additional studies are warranted to elucidate the optimal management of these individuals.

Background Left ventricular diastolic dysfunction ( DD ) is common, particularly in women and older individuals, and it is associated with adverse cardiovascular outcomes. We evaluated the impact of age‐ and sex‐specific diagnostic criteria on the assessment of DD in the community‐based Framingham Heart Study. Methods and Results We estimated age‐ and sex‐specific reference limits for echocardiographic measures of DD in a healthy reference subsample (N=2355, mean age 44 years, 66% women). The prevalence, correlates, and association with future cardiovascular disease were compared for DD using age‐ and sex‐specific versus single cut point reference limits in a broad sample (N=6102, mean age 50 years, 56% women). Using age‐ and sex‐specific criteria, DD was present in ≈25% to 30% of individuals across age groups, and it was directly associated with a number of modifiable risk factors. In contrast, with single cut point criteria, age was the primary determinant of DD . During follow‐up (mean 7.9±2.2 years), incident cardiovascular disease occurred in 213 of 5770 individuals. Using age‐ and sex‐specific criteria, mild and moderate‐severe DD were associated with 50% (95% confidence interval, 1.09–2.05) and 65% (95% confidence interval, 1.14–2.38) higher incidences of cardiovascular disease, respectively, in age‐ and sex‐adjusted analyses. With single cut point criteria, moderate‐severe DD (hazard ratio, 1.66; 95% confidence interval, 1.05–2.61), but not mild DD (hazard ratio, 0.94; 95% confidence interval, 0.63–1.40), was associated with incident cardiovascular disease. Conclusions Age‐ and sex‐specific reference limits may result in DD assessments that are less dependent on age, more robustly related to modifiable risk factors, and are more closely associated with incident cardiovascular disease.

Background Left atrial ( LA ) size, a marker of atrial structural remodeling, is associated with increased risk for atrial fibrillation ( AF ) and cardiovascular disease ( CVD ). LA function may also relate to AF and CVD , irrespective of LA structure. We tested the hypothesis that LA function index ( LAFI ), an echocardiographic index of LA structure and function, may better characterize adverse LA remodeling and predict incident AF and CVD than existing measures. Methods and Results In 1786 Framingham Offspring Study eighth examination participants (mean age, 66±9 years; 53% women), we related LA diameter and LAFI (derived from the LA emptying fraction, left ventricular outflow tract velocity time integral, and indexed maximal LA volume) to incidence of AF and CVD on follow‐up. Over a median follow‐up of 8.3 years (range, 7.5–9.1 years), 145 participants developed AF and 139 developed CVD . Mean LAFI was 34.5±12.7. In adjusted Cox regression models, lower LAFI was associated with higher risk of incident AF (hazard ratio=3.83, 95% confidence interval=2.23–6.59, lowest [Q1] compared with highest [Q4] LAFI quartile) and over 2‐fold higher risk of incident CVD (hazard ratio=2.20, 95% confidence interval=1.32–3.68, Q1 versus Q4). Addition of LAFI , indexed maximum LA volume, or LA diameter to prediction models for AF or CVD did not significantly improve model discrimination for either outcome. Conclusions In our prospective investigation of a moderate‐sized community‐based sample, LAFI , a composite measure of LA size and function, was associated with incident AF and CVD . Addition of LAFI to the risk prediction models for AF or CVD , however, did not significantly improve their performance.

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs. Bhatt, Aragam, and Maron), who respond to the information, sharing reasoning with the reader (regular type). A discussion by the authors follows. A 63-year-old man was evaluated in consultation for unexplained dyspnea. At the time of the initial clinical encounter at our institution, the patient endorsed a 10-year history of progressive exertional dyspnea, which had become debilitating over the preceding 3 months and was characterized by shortness of breath accompanying subtle physical activities such as tying shoelaces. The patient underwent multiple hospital admissions reportedly for the treatment of congestive heart failure ascribed to impaired left ventricular (LV) diastolic function. Review of systems identified postural dizziness and history of near syncope, possible nocturnal dyspnea, and peripheral neuropathy, but not cardiac angina, orthopnea, nocturia, edema, cough, palpitations, syncope, claudication, or other cardiopulmonary symptoms. He related that he was first noted to have a cardiac murmur detected 4 decades previously during a military service physical examination but that the murmur was not characterized further and that he served in the Vietnam conflict without functional limitation. The patient’s relevant medical history included rate-controlled atrial fibrillation, 90 pack-year tobacco use (3 packs daily between 21 and 51 years of age), dyslipidemia, systemic hypertension, type 2 diabetes mellitus, moderate chronic obstructive pulmonary disease, obstructive sleep apnea not currently treated, and gastrointestinal bleed caused by colon cancer treated with hemicolectomy 11 years earlier. There was no illicit drug use, but a remote history of heavy alcohol consumption was reported. Family history was unremarkable except that his father died at 55 years of age of myocardial infarction. Medications included aspirin 81 mg daily, warfarin 2 mg daily, losartan 50 mg daily, metoprolol tartrate 25 mg twice daily, simvastatin 10 mg daily, fenofibrate 48 …

Aims Non-invasive measures of cardiac mechanical function may have the potential to serve as markers of risk for heart failure; however, limited data exist regarding clinical correlates and heritability of these measures in the community. Methods and results We used speckle-tracking echocardiography to assess LV strain and synchrony in the Framingham Offspring Study (n = 2816; mean age 67 years, 54% women). In multivariable regression analyses, male gender (vs. female, P < 0.001), higher heart rate (P < 0.0001), and presence of cardiovascular disease (P < 0.001) were associated with worse global peak strains across all planes analysed (longitudinal, transverse, circumferential, and radial). Higher diastolic blood pressure and diabetes were associated with worse longitudinal strain (P < 0.01), and greater body mass index was associated with worse radial strain (P = 0.0004). Overall, however, clinical correlates accounted for only 4–19% of the variation in measures of LV mechanical function. Select measures of LV strain were heritable: longitudinal strain (h2 = 16%, P = 0.002), transverse strain (h2 = 15%, P = 0.006), and circumferential strain (h2 = 30%, P < 0.0001). Furthermore, in a subset of 1437 participants with parental data available, parental heart failure was associated with worse circumferential strain in the offspring free of heart failure (P = 0.01). Conclusions Our investigation in a large community-based sample identified heritablity and clinical correlates of LV mechanical function, and highlighted an association of parental heart failure with worse global circumferential strain in offspring.

The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation.Temporal trends in the prevalence and management of major risk factors may affect the epidemiology of HF.We compared the frequency, correlates, and prognosis of LVSD (left ventricular ejection fraction [LVEF] 50%) among Framingham Study participants without and with clinical HF in 3 decades (1985 to 1994, 1995 to 2004, and 2005 to 2014).Among participants without HF (12,857 person-observations, mean age 53 years, 56% women), the prevalence of LVSD on echocardiography decreased (3.38% in 1985 to 1994 vs. 2.2% in 2005 to 2014; p 0.0001), whereas mean LVEF increased (65% vs. 68%; p 0.001). The elevated risk associated with LVSD (∼2- to 4-fold risk of HF or death) remained unchanged over time. Among participants with new-onset HF (n = 894, mean age 75 years, 52% women), the frequency of heart failure with preserved ejection fraction (HFpEF) increased (preserved LVEF ≥50%: 41.0% in 1985 to 1994 vs. 56.17% in 2005 to 2014; p 0.001) and heart failure with reduced ejection fraction (HFrEF) decreased (reduced LVEF 40%: 44.10% vs. 31.06%; p = 0.002), whereas heart failure with midrange LVEF remained unchanged (LVEF 40% to 50%: 14.90% vs. 12.77%; p = 0.66). Cardiovascular mortality associated with HFrEF declined across decades (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.97), but remained unchanged for heart failure with midrange LVEF and HFpEF. Approximately 47% of the observed increase in LVEF among those without HF and 75% of the rising proportion of HFpEF across decades was attributable to trends in risk factors, especially a decline in the prevalence of coronary heart disease among those with HF.The profile of HF in the community has changed in recent decades, with a lower prevalence of LVSD and an increased frequency of HFpEF, presumably due to concomitant risk factor trends.

BackgroundLeft atrial (LA) remodeling is a predictor of cardiovascular disease (CVD). We performed measurement of the LA function index (LAFI), a composite measure of LA structure and function, in a community-based cohort and here report the distribution and cross-sectional correlates of LAFI.MethodsIn 1,719 Framingham Offspring Study participants (54% women, mean age 66±9years), we derived LAFI from the LA emptying fraction, left ventricular (LV) outflow tract velocity time integral, and indexed maximal LA volume. We used multivariable linear regression to assess the clinical and echocardiographic correlates of LAFI adjusting for age, sex, anthropometric measurements, and CVD risk factors.ResultsThe average LAFI was 35.2±12.1. Overall, LAFI declined with advancing age (β=-0.27, P&nbsp

Background— Obesity and cardiometabolic dysfunction are associated with increased risk of heart failure and other cardiovascular diseases. We sought to examine the association of cardiometabolic traits with left ventricular (LV) cardiac mechanics. We hypothesized that specific obesity-related phenotypes are associated with distinct aspects of LV strain. Methods and Results— We evaluated the associations of obesity-related phenotypes, including central adiposity, diabetes mellitus, insulin resistance, and circulating adipokine concentrations with echocardiographic measures of LV mechanical function among participants of the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231 participants, the mean age was 51±16 years, and 54% were women. Greater body mass index was associated with worse LV longitudinal strain, radial strain (apical view), and longitudinal synchrony (multivariable-adjusted P P ≤0.006). Measures of insulin resistance, dyslipidemia, and diabetes mellitus also were associated with distinct aspects of LV mechanical function. Circulating leptin concentrations were associated with global longitudinal and radial strain (apical view, P Conclusions— Our findings highlight the association of central obesity and related cardiometabolic phenotypes above and beyond body mass index with subclinical measures of LV mechanical function. Interestingly, obesity-related traits were associated with distinct aspects of LV mechanics, underscoring potential differential effects along specific LV planes of deformation. These findings may shed light onto obesity-related cardiac remodeling and heart failure.

Background Aortic stiffness impairs optimal ventricular–vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain ( GLS ) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community‐based sample. Methods and Results In 2495 participants (age 39–90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid–femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking–based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid–femoral pulse wave velocity (B± SE : 0.122±0.030% strain per SD , P P =0.002) were both associated with worse GLS . We observed effect modification by sex on the relation between characteristic impedance and GLS ( P =0.004); in sex‐stratified multivariable analyses, the relation between greater characteristic impedance and worse GLS persisted in women (0.145±0.039, P =0.0003) but not in men ( P =0.73). Conclusions Multiple measures of increased aortic stiffness were cross‐sectionally associated with worse GLS after adjusting for hemodynamic variables. Parallel reductions in left ventricular long axis shortening and proximal aortic longitudinal strain in individuals with a stiffened proximal aorta, from direct mechanical ventricular‐vascular coupling, offers an alternative explanation for the observed relations.

Objectives This study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow-up period. Background It is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance. Methods This study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years. Four groups were defined on the basis of the sex-specific distributions of left ventricular mass (LVM) and relative wall thickness (RWT) (normal: LVM and RWT Results At baseline, 2,874 of 4,492 observations (64%) had normal LVM and RWT. Participants with normal geometry or concentric remodeling progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change from eccentric to concentric hypertrophy was uncommon (8%). Among participants with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4-year period. Among participants with abnormal LV geometry at baseline, a significant proportion (29% to 53%) reverted to normal geometry within 4 years. Higher blood pressure, greater body mass index (BMI), advancing age, and male sex were key correlates of developing an abnormal geometry. Development of an abnormal LV geometric pattern over 4 years was associated with increased CVD risk (140 events) during a subsequent median follow-up of 12 years (adjusted-hazards ratio: 1.59; 95% confidence interval: 1.04 to 2.43). Conclusions The longitudinal observations in the community suggest that dynamic changes in LV geometric pattern over time are common. Higher blood pressure and greater BMI are modifiable factors associated with the development of abnormal LV geometry, and such progression portends an adverse prognosis.

Background— There is rapidly growing interest in applying measures of myocardial strain and synchrony in clinical investigations and in practice; data are limited regarding their reference ranges in healthy individuals. Methods and Results— We performed speckle-tracking–based echocardiographic measures of left ventricular myocardial strain and synchrony in healthy adults (n=739, mean age 63 years, 64% women) without cardiovascular disease. Reference values were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were: −14.4% to −17.1% (women) and −14.4 to −15.2% (men) for longitudinal strain; −22.3% to −24.7% (women) and −17.9% to −23.7% (men) for circumferential strain; 121 to 165 ms (women) and 143 to 230 ms (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and 200 to 222 ms (women) and 216 to 303 ms (men) for transverse segmental synchrony. In multivariable analyses, women had ≈1.7% greater longitudinal strain, ≈2.2% greater transverse strain, and ≈3.2% greater circumferential strain ( P P Conclusions— We estimated age- and sex-specific reference limits for measures of left ventricular strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed to only a modest proportion of the variation. These data may facilitate the interpretation of left ventricular strain-based measures obtained in future clinical research and practice.

Objectives The aim of this study was to investigate the association between aortic root remodeling and incident heart failure (HF). Background Age-associated increases in aortic root diameter (AoD) might be associated with arterial stiffening, afterload changes, cardiac remodeling, and the development of HF. Methods The study sample consisted of participants of the Framingham Heart Study Original and Offspring cohorts who underwent serial echocardiographic measurements of AoD and continuous surveillance for new-onset HF. The AoD was measured at baseline, and the change in AoD between 8-year examination cycles was calculated. Pooled repeated observations (total 13,605 person-observations) in multivariable Cox regression analyses were used to relate baseline AoD and change in AoD to the incidence of HF on follow-up. Models were adjusted for known HF risk factors (age, sex, body mass index, blood pressure, hypertension treatment, diabetes, smoking, prior myocardial infarction, and valve disease). Results With adjustment for clinical risk factors, the risk of incident HF increased with greater AoD at baseline (hazard ratio: 1.19/1 SD; 95% confidence interval: 1.07 to 1.33) as well as increases in AoD over 8 years (hazard ratio: 1.20/1 SD; 95% confidence interval: 1.04 to 1.38). The AoD correlated with left ventricular mass (r = 0.50; p l 0.001). After adjustment for left ventricular mass in addition to clinical risk factors, the association of AoD with incident HF was rendered nonsignificant. Conclusions Aortic root remodeling is associated with future risk of HF among middle-aged and older adults in the community, potentially because it reflects parallel ventricular-vascular remodeling in those with an enlarged aortic root. Additional studies are warranted to confirm our findings.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. J.T. and P.H. are consultants for Servier. J.C. received research grants and honoraria from Servier. K.S. obtained research support from Boehringer Ingelheim. The remaining authors declared no competing financial interests.

Obesity is associated with pathological cardiac remodeling and risk of heart failure (HF). Adipocytokines (ADKs) may mediate the increased risk of cardiovascular disease associated with excess adiposity. Yet data relating ADKs to cardiac remodeling phenotypes are sparse. We related two circulating ADKs, resistin and adiponectin, to three important echocardiographic markers of cardiac remodeling, left ventricular mass (LVM), left atrial diameter (LAD), and LV fractional shortening (LVFS) in 2,615 participants (mean age 61 years, 55% women) in the Framingham Offspring Study. Adiponectin concentrations were inversely related to LVM in multivariable linear regression models adjusting for key clinical correlates including BMI (regression coefficient per s.d.-increment in ln-adiponectin = −3.37, P = 0.02; P for trend across quartiles = 0.02). Adiponectin was not associated with LAD or LVFS (P > 0.56). Resistin concentrations were inversely related to LVFS (regression coefficient per s.d.-increment in ln-resistin = −0.01, P = 0.03; P for trend across quartiles = 0.04). Resistin was not associated with LVM or LAD (P > 0.05). In our moderate-sized, community-based sample, higher circulating concentrations of adiponectin and resistin were associated with lower LVM and lower LVFS, respectively. In conclusion, these associations identify potential mechanisms by which excess adiposity may mediate adverse cardiac remodeling and HF risk.

Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis.

Background— Aortic root remodeling in adulthood is known to be associated with cardiovascular outcomes. However, there is a lack of longitudinal data defining the clinical correlates of aortic root remodeling over the adult life course. Methods and Results— We used serial routine echocardiograms in participants of the Framingham Heart Study to track aortic root diameter over 16 years in mid to late adulthood and to determine its short-term (4 years; n=6099 observations in 3506 individuals) and long-term (16 years; n=14 628 observations in 4542 individuals) clinical correlates by multilevel modeling. Age, sex, body size, and blood pressure were principal correlates of aortic remodeling in both short- and long-term analyses (all P ≤0.01). Aortic root diameter increased with age in both men and women but was larger in men at any given age. Each 10-year increase in age was associated with a larger aortic root (by 0.89 mm in men and 0.68 mm in women) after adjustment for body size and blood pressure. A 5-kg/m 2 increase in body mass index was associated with a larger aortic root (by 0.78 mm in men and 0.51 mm in women) after adjustment for age and blood pressure. Each 10-mm Hg increase in pulse pressure was related to a smaller aortic root (by 0.19 mm in men and 0.08 mm in women) after adjustment for age and body size. Conclusions— These longitudinal community-based data show that aortic root remodeling occurs over mid to late adulthood and is principally associated with age, sex, body size, and blood pressure. The underlying basis for these differences and implications for the development of cardiovascular events deserve further study.

To evaluate the association of serum phosphorus with cardiac structure/function and incident heart failure. Methods We related serum phosphorus to echocardiographic left ventricular (LV) measurements cross-sectionally, and to inci- dent heart failure prospectively in 3300 participants (mean age 44 years, 51% women) free of heart failure, myocardial infarction, and chronic kidney disease (estimated glomerular filtration rate (eGFR),60 mL/min/1.73 m 2 ). Cross- sectionally, serum phosphorus was related positively to LV mass, internal dimensions, and systolic dysfunction. On follow-up (mean 17.4 years), 157 individuals developed heart failure. In models adjusting for established risk factors as time-varying covariates, each mg/dL increment in serum phosphorus was associated with a 1.74-fold risk of heart failure (95% confidence intervals (CI) 1.17-2.59). Individuals in the highest serum phosphorus quartile experienced a two-fold (95% CI 1.28-3.40) risk of heart failure compared with participants in the lowest quartile. These relations were maintained upon additional adjustment for LV mass/dimensions and systolic dysfunction. In ana- lyses restricted to individuals with eGFR .90 mL/min/1.73 m 2 , no proteinuria and serum phosphorus ,4.5 mg/dL, the association of serum phosphorus with heart failure remained robust. Conclusion In our community-based sample, higher serum phosphorus was associated with greater LV mass cross-sectionally, and with an increased risk of heart failure prospectively.

Background— Increased left atrial diameter (LAD) is associated with elevated risk of atrial fibrillation (AF) and cardiovascular disease. Information is limited regarding the short- or long-term correlates of LAD. Methods and Results— We evaluated clinical correlates of LAD for a 16-year period in 4403 Framingham Study participants (mean age, 45 years; 52% women; median observations/participant=3) using multilevel modeling. We related age, sex, body mass index (BMI), systolic and diastolic blood pressure (BP), diabetes, and antihypertensive treatment to LAD. Sex-specific growth curves for LAD were estimated for individuals with low, intermediate, and high risk factor burden. We also related risk factors to changes in LAD during a 4-year period in 3365 participants. Age, male sex (3.83 mm compared to women), greater BMI, higher systolic BP (0.24 mm per 10 mm Hg increment), and antihypertensive treatment (0.54 mm) were associated positively with LAD ( P P Conclusions— Our longitudinal study of a large community-based sample identified higher BP and greater BMI as key modifiable correlates of LAD, suggesting that maintaining optimal levels of these risk factors through the life course may prevent atrial remodeling and AF.

ObjectiveThe impact of the severity of secondary mitral regurgitation (MR) on the risk of death and heart failure (HF) hospitalisations in patients with reduced left ventricular (LV) systolic function is poorly defined. The study sought to identify the incremental risk of secondary MR in patients with reduced LV systolic function.MethodsWe studied 615 consecutive patients with LV ejection fraction ≤35% by transthoracic echocardiography at a single medical centre. Patients were divided into three groups of no MR, mild, or moderate to severe MR. The median follow-up was 2.9 years. The primary endpoint was a composite of death or HF hospitalisations.ResultsCompared with patients with no MR, the risk of death or HF hospitalisations was higher for mild MR (HR 1.7, P=0.003) and moderate to severe MR (HR 2.7, P

Background— Information is limited on the longitudinal tracking of left ventricular (LV) mass over the adult life course and the determinants of such change. Methods and Results— We used multilevel modeling to evaluate the correlates of LV mass prospectively over a 16-year period in 4217 Framingham study participants (mean age 45 years, 53% women) using up to 4 serial routine echocardiographic observations on each individual (11 762 observations). Age, sex, body mass index, systolic blood pressure, antihypertensive treatment, smoking, and diabetes mellitus were related to longitudinal measures of LV mass. Women and participants with diabetes mellitus experienced a steeper increase in LV mass with advancing age (compared with men and those without diabetes mellitus; P for interactions P =0.04 for interaction). Participants with optimal values of these risk factors experienced lesser increases in LV mass over time. Analyses evaluating short-term (4-year) changes in LV mass (2605 unique individuals providing 4494 observations) identified the same key determinants that influenced its long-term trajectory (ie, body mass index, sex, systolic blood pressure, antihypertensive treatment, and smoking). Conclusions— Our longitudinal observations on a large community-based sample identified higher blood pressure, excess adiposity, smoking, and diabetes mellitus as fundamental determinants of LV mass tracking over the adult life course. These observations are consistent with the notion that maintenance of optimal levels of these risk factors in midlife will reduce the burden of LV hypertrophy, and possibly heart failure, in older age.

Objective Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and l-arginine levels are related to cardiac structure and function in the general population. Methods We related plasma ADMA and l-arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1919 Framingham Offspring Study participants (mean age 57 years, 58% women). Results Overall, neither ADMA or l-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models ( p >0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size ( p for interaction p =0.04): ADMA was positively related to LA size in obese individuals (adjusted- p =0.0004 for trend across ADMA quartiles) but not in non-obese people. Conclusion In our large community-based sample, plasma ADMA and l-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation.

The upper interventricular septum may be prominent in elderly individuals, a finding referred to as discrete upper septal thickening (DUST). We examined the prevalence, clinical and echocardiographic correlates, and prognostic significance of DUST in a community-based sample. We evaluated Framingham Study participants who underwent routine echocardiography. In 3562 Framingham Study participants (mean age 58 years, 57% women), DUST was observed in 52 participants. The clinical correlates of DUST were increasing age (odds ratio [OR] per 10 year increment 2.59, 95% confidence intervals [CI] 1.64-4.08) and systolic blood pressure (OR per SD increment 1.55, 95% CI 1.15-2.09). DUST was positively associated with left ventricular (LV) fractional shortening and mitral annular calcification but inversely with LV diastolic dimensions (P0.02 for all). On follow-up (mean 15 years), 732 individuals died (33 with DUST) and 560 experienced a cardiovascular disease (CVD) event (18 with DUST). Adjusting for cardiovascular risk factors, DUST was not associated with CVD or mortality risk (P0.30 for both). The follow-up component of our study suggests that DUST is not independently associated with adverse prognosis.

Background— Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear. Methods and Results— We evaluated 2119 Framingham Offspring Study participants (mean age, 57 years; 57% women) who underwent measurements of biomarkers of inflammation (C-reactive protein), hemostasis (fibrinogen and plasminogen activator inhibitor-1), neurohormonal activation (B-type natriuretic peptide), and renin-angiotensin-aldosterone system (aldosterone and renin modeled as a ratio [ARR]) and echocardiography at a routine examination. LV geometry was defined on the basis of sex-specific distributions of LV mass (LVM) and relative wall thickness (RWT): normal (LVM and RWT P P Conclusions— Our cross-sectional observations on a large community-based sample identified ARR as a key correlate of concentric and eccentric LV hypertrophy, consistent with a major role for the renin-angiotensin-aldosterone system in LV remodeling.

Background There are few data relating novel measures of left ventricular ( LV ) mechanical function to cardiovascular disease ( CVD ) outcomes in the community. Whether distinct components of LV mechanical function provide information regarding risk for different CVD outcomes is unclear. Methods and Results We used speckle tracking echocardiography to quantify distinct components of LV mechanical function (measured as LV strain in multiple planes) in 2831 Framingham Offspring Study participants (mean age, 66 years; 57% women, 97% with LV fractional shortening >0.29). Participants were followed for 6.0±1.2 years for onset of 69 coronary heart disease ( CHD ), 71 heart failure ( HF ), and 199 mortality events. Adjusting for CVD risk factors, longitudinal LV strain appeared associated with incident CHD (hazards ratio [ HR ] per SD increment, 1.29; 95% confidence interval [ CI ], 1.00–1.67; P =0.05), whereas circumferential and radial strain were not ( P >0.37 for both); however, the association of longitudinal strain with CHD was nonsignificant after Bonferroni correction. By contrast, circumferential strain was a significant predictor of incident HF ( HR per SD increment, 1.79; 95% CI , 1.35–2.37; P P LV mass and fractional shortening. Conclusions In our large, community‐based sample, distinct components of LV mechanical function were associated with specific CVD outcomes. Additional studies are needed to replicate these findings and investigate the prognostic and therapeutic utility of these novel measures of LV mechanical function.

We report a case of recurrent shock induced by pheochromocytoma in a previously healthy, normotensive patient. We review pathophysiology and clinical features of shock and cardiomyopathy in patients with pheochromocytoma. We discuss diagnostic evaluation and therapy for pheochromocytoma-induced shock.

A 67-year-old US military veteran was referred to our clinic for evaluation of progressive dyspnea on exertion over the previous 2 years. His medical history was significant for systemic hypertension, obstructive sleep apnea, and the absence of primary lung disease, significant tobacco use, or coronary artery disease. At the time of consultation, his peripheral blood oxygenation saturation was 85%, hepatojugular reflux and lower-extremity edema were noted, and 6-minute walk distance was 34 m. Transthoracic echocardiography demonstrated normal left ventricular systolic structure and function, a severely dilated right ventricle, and a tricuspid regurgitant jet velocity of 4.85 m/s, indicating an estimated pulmonary artery systolic pressure of 94 mm Hg. However, an elevated flow velocity of 65 cm/s was detected by Doppler interrogation of the posterior aspect of the right atrium adjacent to the interatrial septum. To investigate this further, transesophageal echocardiography was performed, which demonstrated a 1.2-cm communication between the right upper pulmonary vein and the superior vena cava (Figure 1A) and a respirophasic bidirectional shunt through this lesion (Figure 1B and Video I in the online-only Data Supplement). Three-dimensional echocardiography (Figure 2A and Video II in the online-only Data Supplement) and multislice 3-dimensional reconstructive computed tomographic angiography (Figure 2B) characterized the defect further and confirmed a normal anatomic origin and insertion of the right upper pulmonary vein …

A 29 year-old male with a history of recurrent embolic stroke and patent foramen ovale (PFO) presented for elective percutaneous closure. The PFO size was 10 mm diameter when measured with a sizing balloon inflated within the defect. A 25-mm HELEX® septal occluder device (WL Gore Assoc. Inc., Flagstaff, AZ) was deployed successfully using intracardiac echo and fluoroscopy to guide the procedure. The patient was observed in the hospital overnight and was stable. However, a routine transthoracic echocardiography (TTE) performed prior to discharge showed that the closure device had migrated into the right atrium and was attached to the tricuspid valve leaflet (Fig. 1A and B). Transesophageal echocardiogram (TEE) confirmed these findings (Fig. 1C, Video 1). There was no significant tricuspid valvular dysfunction demonstrated by TTE or TEE. The patient remained hemodynamically stable without symptoms. He was taken again to the catheterization laboratory, and the device location was confirmed on fluoroscopy (Fig. 2A). A 14 Fr long sheath was introduced through the right common femoral vein and advanced to the junction of the inferior vena cava and right atrium. An 8F intracardiac ultrasound catheter was advanced to the right atrium from the contralateral

Non-invasive measures of cardiac mechanical function may have the potential to serve as markers of risk for heart failure; however, limited data exist regarding clinical correlates and heritability of these measures in the community.We used speckle-tracking echocardiography to assess LV strain and synchrony in the Framingham Offspring Study (n = 2816; mean age 67 years, 54% women). In multivariable regression analyses, male gender (vs. female, P0.001), higher heart rate (P0.0001), and presence of cardiovascular disease (P0.001) were associated with worse global peak strains across all planes analysed (longitudinal, transverse, circumferential, and radial). Higher diastolic blood pressure and diabetes were associated with worse longitudinal strain (P0.01), and greater body mass index was associated with worse radial strain (P = 0.0004). Overall, however, clinical correlates accounted for only 4-19% of the variation in measures of LV mechanical function. Select measures of LV strain were heritable: longitudinal strain (h(2) = 16%, P = 0.002), transverse strain (h(2) = 15%, P = 0.006), and circumferential strain (h(2) = 30%, P0.0001). Furthermore, in a subset of 1437 participants with parental data available, parental heart failure was associated with worse circumferential strain in the offspring free of heart failure (P = 0.01).Our investigation in a large community-based sample identified heritablity and clinical correlates of LV mechanical function, and highlighted an association of parental heart failure with worse global circumferential strain in offspring.

Diet soda consumption increases cardiometabolic risk. The aim of this investigation was to assess the relations between self-reported soda consumption and subclinical cardiac remodeling.We assessed the relations between self-reported soda consumption and left ventricular mass (LVM) and left atrial dimension (LAD) (both standardized within sex) in a sample of middle-aged attendees from the Framingham Heart Offspring cohort examination 5 and 6.The overall mean age was 55 years and 59% of the participants were women. Compared to non-consumers (n=1010), soda consumers (n=3192) had greater body weight (mean 86 vs. 82 kg among men, and 70 vs. 67 kg among women). Compared with non-consumers, age- and height-adjusted LAD was increased (standard deviation units) among soda consumers by 0.15 standard error 0.042, (p0.001) for those drinking0-7 diet soda (n=1023), -0.010 (0.043, p=0.82) for people drinking0-7 regular soda (n=907), 0.22 (0.057, p0.0001) for individuals consuming7 diet soda (n=372), and 0.20 (0.092, p=0.034) for participants drinking7 regular soda (n=116) per week. LVM was increased among participants consuming diet soda (p0.05), but not in regular soda consumers (p0.05). Upon adjustment for weight, however, all aforementioned associations were attenuated.The observed associations between soda consumption and LAD or LVM were likely related to the greater body weight of soda drinkers relative to non-drinkers.

This study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow-up period.It is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance.This study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years. Four groups were defined on the basis of the sex-specific distributions of left ventricular mass (LVM) and relative wall thickness (RWT) (normal: LVM and RWT 80th percentile; concentric remodeling: LVM 80th percentile but RWT ≥80th percentile; eccentric hypertrophy: LVM ≥80th percentile but RWT 80th percentile; and concentric hypertrophy: LVM and RWT ≥80th percentile).At baseline, 2,874 of 4,492 observations (64%) had normal LVM and RWT. Participants with normal geometry or concentric remodeling progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change from eccentric to concentric hypertrophy was uncommon (8%). Among participants with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4-year period. Among participants with abnormal LV geometry at baseline, a significant proportion (29% to 53%) reverted to normal geometry within 4 years. Higher blood pressure, greater body mass index (BMI), advancing age, and male sex were key correlates of developing an abnormal geometry. Development of an abnormal LV geometric pattern over 4 years was associated with increased CVD risk (140 events) during a subsequent median follow-up of 12 years (adjusted-hazards ratio: 1.59; 95% confidence interval: 1.04 to 2.43).The longitudinal observations in the community suggest that dynamic changes in LV geometric pattern over time are common. Higher blood pressure and greater BMI are modifiable factors associated with the development of abnormal LV geometry, and such progression portends an adverse prognosis.

A previously asymptomatic 37-yr-old man presented to the hospital with acute hypertension of 220/120 mm Hg and unstable ventricular tachycardia requiring cardioversion. A transthoracic echocardiogram (TTE) 1 yr earlier had shown mitral valve prolapse with moderate mitral regurgitation (MR), normal left ventricular (LV) size and function and mild right ventricular (RV) dilation. His TTE after admission revealed dilated, hypokinetic RV with mild tricuspid regurgitation and flattening of the interventricular septum (IVS) (Video Clip 1; please see video clip available at www.anesthesia-analgesia.org). The estimated LV ejection fraction (EF) was 55% with moderate MR. The rest of the TTE was unremarkable. Further workup revealed elevated urine catecholamine levels and a 5 6 cm right adrenal mass. The patient was started on phenoxybenzamine and labetalol and was scheduled for adrenalectomy. A repeat, preoperative TTE 1 wk after admission demonstrated a deteriorated LVEF of 30% and an otherwise unchanged examination. Consequently, the diagnosis of pheochromocytoma and catecholamine-induced cardiomyopathy was made. A biventricular assist device was on standby in anticipation of intraoperative cardiac deterioration. Intraoperative transesophageal echocardiography (TEE) demonstrated a massively dilated and severely hypokinetic RV distorting the normal cardiac anatomy. Systolic and diastolic IVS flattening was present (Fig. 1, Video Clip 2; please see video clip available at www.anesthesia-analgesia.org). The right atrium was enlarged and tricuspid regurgitation remained mild. The LV was also significantly dilated with an estimated EF of 25%–30% (Video 1). The mitral valve annulus was widened at 5.1 cm. Mitral valve prolapse with severe, eccentric MR (vena contracta width 1 cm) was visualized (Video Clip 3; please see video clip available at www.anesthesiaanalgesia.org). The intraoperative anesthetic management was based on the stage of surgery, hemodynamic changes and TEE findings. His measured pulmonary artery pressures were mildly elevated with episodic increases to 80/40 mm Hg. The cardiac index was 2.6 L/m and the systemic vascular resistance was 1500 dynes s cm . Sodium nitroprusside, esmolol, and phentolamine were titrated to effect for intermittent hypertension of up to 240/130 mm Hg. Severe hypotension to 60/30mm Hg (cardiac index 3.2 L/m, systemic vascular resistance 500 dynes s cm ) followed adrenalectomy requiring treatment with epinephrine, norepinephrine, arginine vasopressin, and volume expansion. His arterial blood pressure slowly improved to 90/60 mm Hg. The estimated LVEF improved to 35% and ventricular assist device placement was deemed unnecessary. The patient had an uncomplicated postoperative course. TTE 1 mo later showed normalization of LV size and function. The mitral valve annulus was less dilated (4.2 cm) and the MR was moderate (vena contracta width of 0.55 cm). RV function improved slightly with less dilation and minimal IVS flattening (Video 1). This article has supplementary material on the Web site: www.anesthesia-analgesia.org.