Objectives This study investigated the prognostic utility of left ventricular (LV) untwisting (UT) in the elderly patients at risk of heart failure (HF). Background LV UT mechanics represent a unique combination of LV filling linking ventricular relaxation and suction. The value of this parameter in the prediction of outcomes in patients at risk of HF is unclear. Methods A group of 465 asymptomatic subjects ≥65 years of age with ≥1 HF risk factor (hypertension, diabetes, obesity), recruited from the community, underwent clinical evaluation and echocardiography including measurement of LV apical and basal peak UT velocities. Cox regression analysis was used to identify predictors of new-onset HF and cardiovascular death after a mean follow-up of 18.2 ± 7.5 months. Results A composite of both of the study endpoints occurred in 54 patients (11.6%). Adverse outcome was significantly associated with apical (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96 to 0.99; p = 0.006) UT but not with basal (p = 0.18) UT. The prognostic value of apical UT was independent of and incremental to clinical data, as expressed by the ARIC (Atherosclerosis Risk In Communities) study risk score, left atrial volume index (LAVI), and LV global longitudinal strain (GLS). The addition of apical UT to the model including ARIC risk score, LAVI, and GLS was associated with a 41% improvement in reclassification (p = 0.006). Conclusions Echocardiographic assessment of apical UT provides incremental value in predicting adverse outcome in asymptomatic patients with HF risk factors. The inclusion of apical UT to the diagnostic algorithm may improve the prognostication process in this population.

More than 26 million people worldwide, predominantly the elderly, currently have heart failure (HF) [(1)][1], and the number is expected to grow as the population ages. Between 2015 and 2050, the proportion of the world's population older than 60 years of age will nearly double from 12% to 22% [(2

Objectives This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction. Background Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined. Methods In a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%. Results Over a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e′ velocities, and increases in E/e′ (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (−2.1%; 95% confidence intervals [CI]: −3.1 to −1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e′ ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022). Conclusions A modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; [NCT01173341][1]) [1]: https://clinicaltrials.gov/ct2/show/NCT01173341

Cancer therapeutics-related cardiac dysfunction (CTRCD) is commonly defined by a threshold change in left ventricular ejection fraction (LVEF) [(1)][1]. Although assessment of diastolic parameters is also recommended in this population, the timing of diastolic dysfunction (DD) in relationship to

Asymptomatic left ventricular diastolic dysfunction (ALVDD) (diastolic abnormalities and normal ejection fraction in the absence of symptoms) is associated with incident heart failure (HF) and decreased survival. Abnormalities of diastolic function might therefore be included in the definition of stage B HF, which denotes individuals at risk for the development of HF. Imaging techniques, especially echocardiography, are necessary for the recognition of preclinical left ventricular (LV) diastolic disturbances, as well as further tracking of pathological changes and responses to treatment. The transition of ALVDD to symptomatic HF is underlain by multiple factors, including both cardiovascular and noncardiovascular determinants. The initiation of management strategies targeting cardiovascular and systemic comorbidities in patients identified as having ALVDD may delay symptomatic progression and improve prognosis.

Left ventricular diastolic function plays an important role in determining left ventricular filling and stroke volume. Abnormal diastolic function has been recognized in many cardiovascular diseases and is associated with worse outcomes, including total mortality and hospitalizations due to heart failure. Using echocardiography, it is possible to diagnose the presence of diastolic dysfunction and the pathophysiologic mechanisms involved as they affect left ventricular and left atrial structure and function. This review addresses the role of echocardiography in understanding the pathophysiology of diastolic dysfunction, its diagnosis, and utility in predicting outcomes.

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

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity that is poorly understood yet present in up to 5.5% of the general population. Proven therapies for this disorder are lacking, even though it has a similar prognosis to that of heart failure with reduced ejection fraction (HFrEF). Innovative imaging techniques have provided in-depth understanding of the unique pattern of left ventricular mechanics in patients with HFpEF who progress through preclinical (Stages A to B) and clinical (Stages C to D) American College of Cardiology/American Heart Association heart failure stages. This review highlights the mechanical basis of this disorder from the cellular and myofiber level to chamber dysfunction. As each chamber of the heart is examined, specific biomarkers and echocardiographic parameters with diagnostic and prognostic values are discussed. Finally, novel phenotyping methods including machine learning are reviewed that integrate these mechanics into clinical groups to advise and treat patients.

Diastolic dysfunction is a key factor in the pathogenesis of heart failure. Around 50% of cases of heart failure, the hemodynamic correlate of which is increased left ventricular filling pressure, are caused by diastolic dysfunction in the setting of apparently normal systolic function. Due to its high prevalence, diastolic dysfunction is often recognized as an incidental finding. Many patients have Doppler echocardiographic evidence of impaired diastolic function but do not have any symptoms of heart failure at rest. In many of these patients, symptoms of diastolic dysfunction occur only during exercise, as left ventricular filling pressure is normal at rest, but increases with exercise. This implies that filling pressures should also be measured during exercise. The diastolic stress test refers to the evaluation of diastolic function, either invasively or noninvasively, during exercise. This review focuses on the clinical need for diastolic stress testing, both invasively and noninvasively.

Heart failure with preserved ejection fraction presents a challenging diagnosis given a heterogeneous patient population and limited therapeutic options. Diastolic function assessment using echocardiography has been a cornerstone in the work-up and is as important as systolic functional assessment. There has been increased awareness to the potential utility of cardiac magnetic resonance (CMR) imaging over the past decade as a promising, radiation-free, robust imaging modality providing an unrestricted field of view and high-resolution images for global and regional functional assessment. CMR provides early markers for detecting myocardial disease using tissue characterization imaging, which might prove useful to improve diagnosis and management. Over the years, several studies have examined CMR-derived diastolic functional indices, including transmitral and pulmonary venous velocities, left ventricular and left atrial strain using myocardial tagging, and, more recently, feature tracking. The relevance of imaging-based diastolic function indices and their clinical application across different modalities is increasingly recognized.

Symptoms of heart failure (HF) are due in large part to elevation of left and/or right ventricular filling pressures. Although abnormal diastolic function is difficult to define, it contributes to the elevation of filling pressures. Tests that characterize aspects of diastolic function or structural changes associated with diastolic dysfunction, may help in establishing a diagnosis of HF, assessing prognosis, and guiding treatments. Individual echocardiographic parameters correlate weakly with LV (LV) filling pressures measured directly. However, a combination of multiple parameters improves accuracy for detection of elevated filling pressures. Serum natriuretic peptide levels are related to ventricular filling pressures and, when elevated, are a key diagnostic criterion for HF. Currently available evidence is not adequate to recommend serial echocardiographic studies or natriuretic peptide level measurements to assess changes in filling pressures or to guide HF therapy. Measurements of inferior vena cava size and dynamics have potential for identifying inadequate decongestion during episodes of acute decompensated HF but have not yet demonstrated utility in improving HF outcomes. Direct measurement of LV filling pressures using implanted pressure sensors is the only “diastolic assessment” thus far that has proven efficacy in reducing HF hospitalization rates.

By assessing nonhospitalized asymptomatic patients, community-based studies inform the prevalence, key clinical characteristics, and outcomes associated with diastolic dysfunction. As the number of parameters to define and grade diastolic function continues to increase, there has been a shift to a focus on readily obtainable measurements with minimal interobserver variability. In this regard, mitral inflow and annular tissue Doppler velocities, as well as measurement of left atrial volume index, are the most feasible and reproducible. Within communities, variations in definitions have limited generalizability regarding the prevalence and risks associated with diastolic dysfunction. Nevertheless, community-based studies have established important associations with hypertension, obesity, and diabetes. Randomized controlled trials of treatment in heart failure with preserved ejection fraction have been disappointing. Importantly, diastolic dysfunction is consistently associated with higher mortality, which emphasizes the importance of early recognition and initiation of appropriate preventative treatments.

Jae K. Oh, MD, William R. Miranda, MD, Jared G. Bird, MD, Garvan C. Kane, MD, PhD Determination of diastolic function is an integral part of an echocardiography examination, especially in patients with symptoms of heart failure. To standardize the evaluation of diastolic function, the American

We read with great interest the study by Lancaster et al. [(1)][1] regarding the use of a machine-learning algorithm for the unsupervised clustering of diastolic function variables. The authors reported improved prediction of clinical outcomes with machine learning over classification with the 2016

We thank Dr. Kampaktsis and colleagues for their interest in our investigation. Although we agree that the 2016 guidelines may have made diastolic dysfunction (DD) more conceptually simple in a clinical approach; there are 2 problems with this apparent simplification. First, the large number of

![Figure][1] “Everything should be made as simple as possible, but no simpler.”—Albert Einstein ![Figure][1] Left ventricular (LV) diastolic function determines LV filling and diastolic pressures. It is a complex process that depends on many factors, including LV end diastolic

This is a new variation of our educational iPix series — where important teaching points are conveyed through visually appealing multimedia. This new feature format is entirely case based — studies were obtained from real patients referred to the imaging laboratory seeking answers to important

A decrease in pump flow in patients with left ventricular assist devices (LVADs) is a life-threatening complication that results in severe heart failure. The main cause, besides right ventricular failure, is outflow graft (OG) obstruction. Through combined use of computed tomography angiography (CTA

Objectives This study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis. Background In patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE. Methods Consecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia. Results Among 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4, 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024). Conclusions In this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.

The prevalence of obesity has dramatically increased. Obesity represents a risk factor for coronary artery disease (CAD) and mortality ([1][1]). The identification of CAD is a major challenge in morbidly obese patients. The capacity for exercise is often limited, leading to inconclusive stress test

Objectives This study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE. Background The PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood. Methods We evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics. Results Mean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups. Conclusions Our findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.

For decades, left ventricular ejection fraction (LVEF) by echocardiography has been the cornerstone of systolic function assessment. It is probably the single most reported imaging parameter in cardiology and is implemented as gatekeeper for clinical decisions in numerous guidelines, including in

Objectives The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. Background Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. Methods A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini’s method. Results Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. Conclusions The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.

Objectives This study sought to evaluate the role of cardiac magnetic resonance (CMR) for the quantification of ischemic mitral regurgitation (IMR) and myocardial infarct size (MIS) in patients with ischemic cardiomyopathy (ICM). This study also sought to explore the interaction between IMR severity and MIS and its association with outcomes in patients with ICM. Background IMR occurs secondary to a disease of the left ventricle and is associated with poor outcomes. The role of CMR for the evaluation and risk stratification of patients with ICM and IMR remains uncertain. Methods Consecutive patients with ICM who underwent baseline CMR were included. MIS was quantified on late gadolinium enhancement imaging as the proportion of left ventricular mass. IMR was quantified with CMR by calculating the mitral regurgitant fraction (MRFraction). Cox proportional hazards models were built to assess the association of IMR and MIS quantification with the combined endpoint of all-cause death or heart transplant. Results We evaluated 578 patients (mean age: 62 ± 11 years, 76% males). The mean left ventricular ejection fraction was 25 ± 11%, with an MIS of 24 ± 16% and MRFraction of 18 ± 17%. Over a median follow-up time of 4.9 years, 198 (34%) patients experienced death or cardiac transplant. On multivariable analysis, after comprehensive medical risk score, subsequent revascularization, implantable cardioverter-defibrillator insertion, and surgical mitral valve intervention were controlled for, the interaction of IMR severity and MIS emerged as a powerful predictor of adverse outcomes (p = 0.008). For patients with significant IMR (MRFraction: ≥35%), the hazard ratio comparing moderate MIS (15% to 29%) versus small MIS (<15%) was 1.51 (0.57 to 3.98), and the hazard ratio comparing large MIS (≥30%) versus small MIS was 5.41 (2.34 to 12.7). Conclusions Risk associated with IMR is more comprehensively described as an interaction between IMR severity and MIS. Further studies in patients IMR using comprehensive CMR evaluation are needed to verify whether this approach can improve patient selection and procedural outcomes to address IMR.

Transthyretin (ATTR) amyloidosis is a deadly disease caused by protein aggregation and is increasingly recognized as an important cause of heart failure ([1–3][1]). In the past year and one-half, 3 novel therapeutic drugs (patisiran, inotersen, and tafamidis) have emerged as the first U.S. Food

Objectives The goal of this study was to evaluate the prognostic value of global longitudinal strain (GLS) derived from cardiac magnetic resonance (CMR) feature-tracking in a large multicenter population of patients with preserved ejection fraction. Background Ejection fraction is the principal parameter used clinically to assess cardiac mechanics and provides prognostic information. However, significant abnormalities of myocardial deformation can be present despite preserved ejection fraction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of strain measured by using CMR feature-tracking have prognostic value in patients with preserved ejection fraction is unknown. Methods Consecutive patients with preserved ejection fraction (≥50%) and a clinical indication for CMR at 4 U.S. medical centers were included in this retrospective study. Feature-tracking GLS was calculated from 3 long-axis cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between GLS and death. The incremental prognostic value of GLS was assessed in nested models. Results Of the 1,274 patients in this study, 115 died during a median follow-up of 6.2 years. By Kaplan-Meier analysis, patients with GLS ≥ median (–20%) had significantly reduced event-free survival compared with those with GLS < median (log-rank test, p < 0.001). By Cox multivariable regression modeling, each 1% worsening in GLS was associated with a 22.8% increased risk of death after adjustment for clinical and imaging risk factors (hazard ratio: 1.228 per percent; p < 0.001). Addition of GLS in this model resulted in significant improvement in the global chi-square test (94 to 183; p < 0.001) and Harrell’s C-statistic (0.75 to 0.83; p < 0.001). Conclusions GLS derived from CMR feature-tracking is a powerful independent predictor of mortality in patients with preserved ejection fraction, incremental to common clinical and imaging risk factors.

Objectives The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction. Background Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. Methods In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. Results Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure. Conclusions LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; [NCT02525185][1]) [1]: https://clinicaltrials.gov/ct2/show/NCT02525185?term=NCT02525185&draw=1&rank=1

Histopathologic studies described subendocardial or transmural intramyocardial fat (IMF) at the site of prior myocardial infarction (MI) ([1][1]). In patients with stable chest pain with no history of MI, myocardial scar phenotypic for MI depicted with late gadolinium enhancement is identified in 11

BASILICA (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction) is an emerging technique to avoid coronary obstruction during transcatheter aortic valve replacement (TAVR) ([1][1]). Although fluoroscopic visualization during BASILICA is

One-third to one-half of patients with acute ST-elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). Their worse prognosis is possibly associated with additional plaque instability, impaired epicardial and microvascular myocardial perfusion, and cardiogenic shock.

Noninfected prosthetic heart valves often display a characteristic pattern of diffuse and homogeneous distribution and mild fluorodeoxyglucose (FDG) uptake when evaluated by 18F-FDG positron emission tomography/computed tomography angiography (PET/CTA) at least during 1 year after implantation.

Objectives This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis. Background The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown. Methods Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80. Results Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%. Conclusions CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.

Ventricular arrhythmias (VA) are associated with increased risk for sudden cardiac death and account for approximately 50% of all cardiovascular deaths with at least 25% presenting as a first symptom ([1][1],[2][2]). Both the 2017 American Heart Association/American College Cardiology and the 2015

With the recent expansion of US Food and Drug Administration approval of the MitraClip to encompass secondary ([1][1]) and primary ([2][2]) mitral regurgitation (MR), the number of procedures is expected to increase considerably. Real-time imaging with transesophageal echocardiography (TEE) is

Calcific aortic stenosis (AS) is one of the most common valvular heart diseases today; its prevalence increases with age and usually manifests after the seventh decade of life ([1][1],[2][2]). Traditionally, it was thought that the calcification of a tricuspid aortic valve resulting in AS was

Transcatheter tricuspid valve repair (TTVr) using the MitraClip system (Abbott Structural Heart, Santa Clara, California) has demonstrated safety and efficacy ([1][1]). Procedural success, which consists of optimal leaflet insertion and reduction in tricuspid regurgitation (TR), is predictive of

Cardiac tumors are rare in children, with an incidence ranging between 0.01% and 0.32% ([1][1]). Although most cardiac tumors are benign, some of them may lead to serious complications. Early diagnosis is crucial because treatment is dependent on the type of tumor. Because of their rarity, centers

Objectives The aim of this study was to assess the diagnostic yield of cardiac magnetic resonance (CMR) including high-resolution (HR) late gadolinium enhancement (LGE) imaging using a 3-dimensional respiratory-navigated method in patients with myocardial infarction with nonobstructed coronary arteries (MINOCA). Background CMR plays a pivotal role for the diagnosis of patients with MINOCA. However, the diagnosis remains inconclusive in a significant number of patients, the results of CMR being either negative or uncertain (i.e., compatible with multiple diagnoses). Methods Consecutive patients categorized as having MINOCA after blood testing, electrocardiography, coronary angiography, and echocardiography underwent conventional CMR, including cine, T2-weighted, first-pass perfusion, and conventional breath-held LGE imaging. HR LGE imaging using a free-breathing method allowing improved spatial resolution (voxel size 1.25 × 1.25 × 2.5mm) was added to the protocol when the results of conventional CMR were inconclusive and was optional otherwise. Diagnoses retained after reviewing conventional CMR were compared with those retained after the addition of HR LGE imaging. Results From 2013 to 2016, 229 patients were included (mean age 56 ± 17 years, 45% women). HR LGE imaging was performed in 172 patients (75%). In this subpopulation, definite diagnoses were retained after conventional CMR in 86 patients (50%): infarction in 39 (23%), myocarditis in 32 (19%), takotsubo cardiomyopathy in 13 (8%), and other diagnoses in 2 (1%). In the remaining 86 patients (50%), results of CMR were inconclusive: negative in 54 (31%) and consistent with multiple diagnoses in 32 (19%). HR LGE imaging led to changes in final diagnosis in 45 patients (26%) and to a lower rate of inconclusive final diagnosis (29%) (p < 0.001). In particular, HR LGE imaging could reveal or ascertain the diagnosis of infarction in 14% and rule out the diagnosis of infarction in 12%. HR LGE imaging was particularly useful when the results of transthoracic echocardiography, ventriculography, and conventional CMR were negative, with a 48% rate of modified diagnosis in this subpopulation. Conclusions HR LGE imaging has high diagnostic value in patients with MINOCA and inconclusive findings on conventional CMR. This has major diagnostic, prognostic, and therapeutic implications.

Objectives This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality. Background ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease. Methods Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement. Results The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m2 vs. 48 ml/m2; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027). Conclusions In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.

Coronary artery calcium (CAC) is a potent marker of subclinical atherosclerotic cardiovascular disease (CVD) and an independent predictor of future cardiovascular events ([1][1]). For these reasons, the 2018 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Guidelines

Objectives The aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF). Background LA mechanics are affected by volume/pressure overload in decompensated HFrEF. Methods A total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality. Results LA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s–1 to 0.38 ± 0.13 s–1), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s–1, respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (–0.25 ± 0.12 s–1 to –0.55 ± 0.29 s–1; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = –0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019). Conclusions LA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome.

Mitral regurgitation (MR) is classified as primary or secondary. Although this classification is an oversimplification, severe primary MR is a disease of the valve causing it to leak, placing a volume overload on the left ventricle that, if left untreated, leads to heart failure and death. In

Objectives This study assessed whether adenosine stress-only perfusion cardiac magnetic resonance (CMR) following a positive coronary artery calcium (CAC) score improved the diagnostic yield of invasive coronary angiography (CAG) in patients with stable chest pain. The study also established the association between positive CAC scores and stress-induced myocardial ischemia. Background The diagnostic yield of catheterization among patients with suspected coronary artery disease (CAD) is low. Improved patient selection and diagnostic testing are necessary. The CAC score can minimize unnecessary diagnostic testing, and in low-risk patients, normal CMR results have a high negative predictive value. Less comprehensive protocols may be sufficient to guide further work-up. Methods A total of 642 consecutive patients (mean age: 63 years; 50% women) with stable chest pain and CAC scores of >0 who were referred for CMR were enrolled. Patients with a perfusion defect were subsequently examined by CAG. Patients were followed up for 1 year. Outcome was obstructive CAD. Results Obstructive CAD was present in 12% of patients. For CAD diagnosis, the sensitivity of adenosine CMR was 90.9% (95% confidence interval [CI]: 88.7 to 93.1), specificity was 98.7% (95% CI: 97.9 to 99.6), positive predictive value was 92.0% (95% CI: 89.8 to 94.1), and negative predictive value was 98.6% (95% CI: 97.6 to 99.5). A CAC score between 0.1 and 100 without typical angina was associated with obstructive CAD in only 3% of patients. Patients with non-anginal chest pain and a CAC score ≥400 had obstructive CAD (16%). Conclusions Stress-only adenosine CMR had high diagnostic accuracy and served as an efficient gatekeeper to CAG in stable patients with a CAC score >0. Patients with CAC scores between 0.1 and 100 could be deferred from further testing in the absence of clinical features that suggested high risk. However, in patients with CAC score ≥400, functional testing should be indicated, regardless of the type of chest pain.

Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomata. Cardiac involvement contributes to life-threatening consequences. The diagnosis of cardiac sarcoidosis (CS) is usually made on the basis of clinical and imaging features including 18F-fluorodeoxyglucose (

The burden of cardiovascular disease in people living with HIV (PLWH) has tripled over the last 20 years, with cardiac manifestations of disease ranging from coronary disease to heart failure ([1][1]). The pathophysiological mechanisms involved in the development of HIV cardiomyopathy remain elusive

Objectives This study sought to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had echocardiography ruled out pathological findings. Background Approximately one-half of sudden cardiac deaths are attributable to malignant VA. Echocardiography is commonly used to identify SHD that is the most frequent substrate of VA. Methods A single-center prospective study was conducted in consecutive patients with significant VA, categorized as >1,000 but <10,000 ventricular ectopic beats [VEBs]/24 h; ≥10,000 VEBs/24 h; nonsustained ventricular tachycardia, sustained ventricular tachycardia, or a history of resuscitated cardiac arrest, and no pathological findings at echocardiography, requiring a clinically indicated CMR. Primary endpoint was CMR detection of SHD. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis. Results A total of 946 patients were enrolled (mean 41 ± 16 years of age; 64% men). CMR studies were used to diagnose SHD in 241 patients (25.5%) and abnormal findings not specific for a definite SHD diagnosis in 187 patients (19.7%). Myocarditis (n = 91) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 55), dilated cardiomyopathy (n = 39), ischemic heart disease (n = 22), hypertrophic cardiomyopathy (n = 13), congenital cardiac disease (n = 10), left ventricle noncompaction (n = 5), and pericarditis (n = 5). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.52 and 2.38, respectively) and sustained ventricular tachycardia (ORs: 2.67 and 2.23, respectively). Conclusions SHD was able to be identified on CMR imaging in a sizable number of patients with significant VA and completely normal echocardiography. Chest pain and sustained ventricular tachycardia were the strongest predictors of positive CMR imaging results.

Corticosteroids are the mainstay of therapy for cardiac saroidosis (CS) ([1][1]); however, long-term exposure may be associated with numerous side effects. Although cardiac 18-fluorodoxyglucose position emission tomography (FDG-PET) is useful in tailoring corticosteroid therapy, the effect of

Intracoronary imaging techniques provide unique insights into the pathobiology and treatment of human coronary artery disease (CAD) ([1–5][1]). The “holy grail” of intracoronary imaging is to identify high-risk, or “vulnerable,” plaques that are associated with an inevitable future

Objectives This study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk. Background Although CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate. Methods The CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD. Results During the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0. Conclusions Across the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.

Despite substantial medical advances over the past decades, sudden cardiac death (SCD) remains a leading cause of cardiovascular deaths in patients with ischemic heart disease. The presence of structural heart disease with left ventricular ejection fraction <35% is the current criteria for implantable cardioverter-defibrillator therapy as a primary prevention to SCD. However, more than 80% of patients who suffer SCD have a left ventricular ejection fraction >35%, whereas few patients who received an implantable cardioverter-defibrillator required appropriate defibrillation. Cardiac magnetic resonance enables the visualization of the arrhythmogenic myocardial substrate including the presence and pattern of scar and fibrosis. The most promising of these features, besides left ventricular function, strain analysis, and morphology, include tissue characterization using late-gadolinium enhancement, T1 mapping, and extracellular volume fraction calculation. We review the current evidence of SCD relating to ischemic heart disease, provide insights into imaging of the arrhythmogenic substrate that produces lethal ventricular arrhythmia, and discuss how imaging may guide therapies toward SCD prevention.

Objectives This study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators. Background The SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function. Methods CMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies. Results The cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response ( r = −0.57; p < 0.0001) than CURE-SVD with feature tracking ( r = −0.28; p = 0.004). Conclusions A combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.

Objectives This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF). Background DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection. Methods A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >−21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization. Results A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006). Conclusions Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death.

Gout is an inflammatory arthropathy with increasing global incidence and association with cardiovascular disease and mortality ([1][1]). Smoking is a well-established risk factor for coronary artery calcium (CAC) and adverse cardiovascular outcomes, yet smoking has been associated with reduced serum

Heterozygous familial hypercholesterolemia (HeFH), an autosomal dominant genetic disorder affecting nearly 1 in 250 individuals, is a major cause of premature atherosclerotic cardiovascular disease (ASCVD) ([1][1]). In the absence of treatment, patients with HeFH manifest a nearly 20-fold higher

Dilated cardiomyopathy (DCM) has a familial basis in 20% to 30% of cases, though up to 60% has been suggested [(1)][1]. However, in familial DCM only up to 40% of cases may have an identifiable genetic basis [(2)][2]. Gene based cascade screening is therefore only suitable for a limited proportion

Objectives The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)–measured native T1, T2, and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD). Background Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability. Methods A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T1 and T2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM. Results Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T1 (29 ms), T2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T1. The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%). Conclusions The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.

Subclinical myocardial dysfunction detected by global longitudinal strain (GLS) is often present in patients with severe aortic stenosis (AS) despite normal left ventricular ejection fraction (LVEF) ([1][1]), but its prognostic value remains unclear in patients with symptomatic severe AS treated

“The value of risk factors (RF) may reside more in determining the targets of intensive therapy in those with increased risk, rather than in factoring them into an equation that performs suboptimally in determining that risk. Once risk is established, either by clinical disease in secondary

Increased left ventricular (LV) myocardial extracellular volume fraction (ECVF) measured by cardiac magnetic resonance (CMR) is now a recognized consequence of anthracycline chemotherapy ([1][1],[2][2]). It remains unknown, however, whether elevated ECVF may be attributable to an expansion of the LV

Cannabis is one of the most widely produced and consumed recreational drugs in the world, with over 192 million global users ([1][1]). The World Health Organization has warned against the potential harmful health effects of nonmedicinal cannabis use and highlighted the need for more research