Longitudinal Assessment of Left Atrial Remodeling in Patients With Chronic Severe Aortic Regurgitation.

BACKGROUND: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. OBJECTIVES: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. METHODS: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. RESULTS: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. CONCLUSIONS: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters.

Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Impact of Age and Sex on Left Ventricular Remodeling in Patients With Aortic Regurgitation.

BACKGROUND: Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex. OBJECTIVES: The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes. METHODS: We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex. RESULTS: A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m2 vs 32.3 mL/m2, respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m2 vs 32.4 mL/m2). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m2), intermediate for older men (35 mL/m2), and lowest for women (27 mL/m2). CONCLUSIONS: On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes.

Multimodality imaging evaluation of incidentally discovered intracardiac mass.

Incidentally discovered intracardiac masses often represent diagnostic dilemmas. No guideline-directed algorithm exists for evaluation and management in these cases. Understanding the utility and limitations of different imaging modalities expedites evaluation of differential diagnoses and management, particularly when there are discordant imaging findings. This case further demonstrates that benign cardiac tumors may grow rapidly, and that new and rapid emergence of an intracardiac mass does not necessarily correlate with a diagnosis of thrombus or malignancy. It also highlights the importance of a broad differential diagnosis and a systematic management approach in patients with intracardiac masses.

Worsened Tricuspid Regurgitation Following Pericardiectomy for Constrictive Pericarditis.

BACKGROUND: Worsening tricuspid regurgitation (TR) severity may occur after pericardiectomy surgery for constrictive pericarditis patients; however, its mechanisms and predictors are not well established. We evaluated the clinical characteristics, associated factors, and outcomes of worsening TR after pericardiectomy. METHODS: Consecutive patients undergoing pericardiectomy for constrictive pericarditis without tricuspid valve surgery and with pre- and postoperative echocardiography available during 2000 to 2017 were retrospectively studied. Clinical, imaging, hemodynamic, and mortality characteristics were analyzed by those with and without worsening TR by at least one grade. RESULTS: Among 381 patients (age 61 [17] years, 318 [83.5%] male), 193 (50.7%) had worsening TR post-operatively, and 75 died during the 2.5 (5.4) years follow-up. In univariable analysis, worsening TR was associated with a history of congestive heart failure (47.2% versus 31.9%, P=0.003), increased left atrial volume indexed (23 versus 20 mL/m2, P=0.020), reduced right ventricular fractional area change (47% versus 54%, P<0.001), and worsening mitral regurgitation (39.7% versus 16.6%, P<0.001). Worsened TR had a trend toward reduced survival during follow-up (log-rank P=0.080), especially those with worsened TR but no recovery of TR grade on subsequent echocardiography within the first year compared with those without worsened TR (log-rank P=0.02). In multivariable analysis, right ventricular fractional area change, left atrial volume indexed, left ventricular mass indexed, pulmonary artery systolic pressure, and right atrial pressure/pulmonary capillary wedge pressure ratio were most associated with worsened TR, while blood urea nitrogen, hematocrit, lateral and medial e' tissue Doppler and heart rate were most associated with mortality during follow-up. CONCLUSIONS: Worsening TR severity was prevalent after pericardiectomy and had a trend toward reduced survival, especially if TR severity did not recover on subsequent echocardiography. Presence of parameters associated with worsened TR and reduced survival should alert clinicians to carefully manage these patients during follow-up.

Impact of Frailty and Mitral Valve Surgery on Outcomes of Severe Mitral Stenosis Due to Mitral Annular Calcification.

We sought to evaluate the outcomes of patients with severe mitral stenosis (MS) resulting from mitral annular calcification and assessed the prognostic impact of co-morbidities and frailty in guiding management. Among 6,915 patients with calcific MS who underwent echocardiography between January 2011 and March 2020, a total of 283 patients with severe calcific MS were retrospectively enrolled. We calculated the Charlson co-morbidity index (CCI). Frailty was scored from 0 to 3 points, with 1 point each assigned for reduced hemoglobin, reduced albumin, and inactivity. The primary end point was all-cause death. The mean age was 72 ± 11 years. The mean mitral valve (MV) area was 1.1 ± 0.4 cm2, and the mean transmitral gradient was 12 ± 4 mm Hg. Although 33% of the patients underwent MV intervention, 67% were conservatively managed. During a median follow-up of 360 days, 35% died. Patients who underwent MV intervention had an improved prognosis compared with those who were treated conservatively, even after propensity score matching. On multivariate Cox regression analysis, higher CCI (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.04 to 1.38, p = 0.011) and frailty score (HR 1.58, 95% CI 1.12 to 2.23, p = 0.01) were predictors of all-cause mortality, and MV intervention (HR 0.45, 95% CI 0.25 to 0.83, p = 0.011) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use (HR 0.39, 95% CI 0.20 to 0.79, p = 0.009) were associated with an improved prognosis. In conclusion, patients with severe calcific MS were often frail with multiple co-morbidities and were often managed conservatively. Higher CCI and worse frailty were associated with worse prognosis, regardless of the treatment strategy. MV intervention for select patients was associated with improved prognosis.

Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy-a clinical picture printed on lenticular paper.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature. CASE SUMMARY: A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement. DISCUSSION: Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Temporal Trends of Cardiac Outcomes and Impact on Survival in Patients With Cancer.

To evaluate the temporal relations of cardiovascular disease in oncology patients referred to cardio-oncology and describe the impact of cardiovascular disease and cardiovascular risk factors on outcomes. All adult oncology patients referred to the cardio-oncology service at the Cleveland Clinic from January 2011 to June 2018 were included in the study. Comprehensive clinical information were collected. The impact on survival of temporal trends of cardiovascular disease in oncology patients were assessed with a Cox proportional hazards model and time-varying covariate adjustment for confounders. In total, 6,754 patients were included in the study (median age, 57 years; [interquartile range, 47 to 65 years]; 3,898 women [58%]; oncology history [60% - breast cancer, lymphoma, and leukemia]). Mortality and diagnosis of clinical cardiac disease peaked around the time of chemotherapy. 2,293 patients (34%) were diagnosed with a new cardiovascular risk factor after chemotherapy, over half of which were identified in the first year after cancer diagnosis. Patients with preexisting and post-chemotherapy cardiovascular disease had significantly worse outcomes than patients that did not develop any cardiovascular disease (p < 0.0001). The highest 1-year hazard ratios (HR) of post-chemotherapy cardiovascular disease were significantly associated with male (HR 1.81; 95% confidence interval 1.55 to 2.11; p < 0.001] and diabetes [HR 1.51; 95% confidence interval 1.26 to 1.81; p < 0.001]. In conclusion, patients referred to cardio-oncology, first diagnosis of cardiac events peaked around the time of chemotherapy. Those with preexisting or post-chemotherapy cardiovascular disease had worse survival. In addition to a high rate of cardiovascular risk factors at baseline, risk factor profile worsened over course of follow-up.

Performance of diagnostic criteria in patients clinically judged to have cardiac sarcoidosis: Is it time to regroup?

BACKGROUND: The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. AIMS: To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. METHODS: We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. RESULTS: We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). CONCLUSIONS: A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

Multimodality imaging in patients with post-cardiac injury syndrome.

This review article is focused on the role of echocardiography, cardiac CT and cardiac magnetic resonance (CMR) imaging in diagnosing and managing patients with post-cardiac injury syndrome (PCIS). Clinically, the spectrum of pericardial diseases under PCIS varies not only in form and severity of presentation but also in the timing varying from weeks to months, thus making it difficult to diagnose. Pericarditis developing after recent or remote myocardial infarction, cardiac surgery or ablation if left untreated or under-treated could worsen into complicated pericarditis which can lead to decreased quality of life and increased morbidity. Colchicine in combination with other anti-inflammatory agents (non-steroidal anti-inflammatory drugs) is proven to prevent and treat acute pericarditis as well as its relapses under various scenarios. Imaging modalities such as echocardiography, CT and CMR play a pivotal role in diagnosing PCIS especially in difficult cases or when clinical suspicion is low. Echocardiography is the tool of choice for emergent bedside evaluation for cardiac tamponade and to electively study the haemodynamics impact of constrictive pericarditis. CT can provide information on pericardial thickening, calcification, effusions and lead perforations. CMR can provide pericardial tissue characterisation, haemodynamics changes and guide long-term treatment course with anti-inflammatory agents. It is important to be familiar with the indications as well as findings from these multimodality imaging tools for clinical decision-making.

Update in Cardiac Sarcoidosis.

Increasing awareness of cardiac manifestations of sarcoidosis and the widespread availability of advanced imaging tests have led to a tidal wave of interest in a condition that was once considered rare. In this Focused Review, we explore important clinical questions that may confront specialists faced with possible cardiac involvement. In the absence of an ideal reference standard, three main sets of clinical criteria exist: the Japanese Ministry of Health and Welfare, the Heart Rhythm Society, and the World Association for Sarcoidosis and Other Granulomatous Disorders criteria. Once cardiac sarcoidosis is suspected, clinicians should be familiar with the prevalence of the disease in different clinical scenarios. Before obtaining advanced cardiac imaging, electrocardiogram, ambulatory electrocardiogram, echocardiogram, and B-type natriuretic peptide may be useful. The available therapies for cardiac sarcoidosis include immunosuppression, antiarrhythmic medications, heart failure medications, device therapy, ablation therapy, and heart transplantation. Contemporary data suggest that long-term survival in cardiac sarcoidosis is better than previously believed. There is no randomized controlled trial demonstrating benefits of screening, but screening is recommended based on observational data.

Unrecognized Cardiac Amyloidosis at the Time of Mitral Valve Surgery: Incidence and Outcomes.

OBJECTIVE: It is increasingly recognized that cardiac amyloidosis can occur in patients with severe aortic stenosis undergoing both surgical and transcatheter valve replacements. We aimed to investigate whether unrecognized cardiac amyloidosis may also occur in patients with severe mitral valve disease undergoing surgery. METHODS: The pathology department database at our center was retrospectively analyzed over a 10-year period for cases in which the mitral valve or another type of cardiac tissue removed at the time of mitral surgery demonstrated incidental amyloidosis. Clinical and echocardiographic variables were collected from the electronic medical record and the echocardiographic database. RESULTS: Between 2007 and 2016, a total of 7,733 mitral valve surgical specimens were received. Of these, there were 15 cases in which the mitral valve, or another type of cardiac tissue removed at surgery, demonstrated incidentally detected amyloidosis. The most frequent comorbidities were hypertension (87%) and atrial fibrillation (80%); 13 patients (87%) underwent bioprosthetic mitral valve replacement, and 2 patients (13%) underwent mitral valve repair. Sites of amyloid deposition were the mitral valve (80%), left atrial appendage (33%), and subaortic tissue (7%); 14 patients (93%) had wild-type transthyretin amyloid. The mean duration of follow-up was 1,023 days (range: 29-2,811 days). There were no surgical complications in the follow-up period. CONCLUSIONS: Over a 10-year period, incidentally detected cardiac amyloidosis occurred in 0.2% of the mitral valve surgical cases. The outcomes for these patients undergoing mitral valve surgery were excellent, with no complications or deaths attributable to surgery at a mean follow-up of 1,023 days.

Mysterious quad of constrictive pericarditis, recurrent pleural effusions, bone involvement and interstitial lung disease.

Erdheim-Chester disease (ECD) is a rare multisystemic non-Langerhans cell histiocytic neoplasm. The rarity of the disease and heterogenous clinical presentations often leads to delayed diagnosis. Historically, ECD lacked effective treatment and the prognosis was poor. Following the recent discovery of frequent BRAF-V600E mutation in patients with ECD, vemurafenib, a selective BRAF V600 kinase inhibitor has been approved for BRAF-mutated ECD patients. The prognosis of ECD has dramatically improved with early recognition of the disease and available treatment. ECD affects nearly every organ system. Cardiac involvement with pericardial effusion is common but rarely with constrictive physiology or requiring pericardiectomy. We present a case of a 56-year-old woman with recurrent pericarditis with constrictive physiology along with pleural effusion and interstitial lung disease that was diagnosed with ECD 3 years after initial presentation. The patient's symptoms were relieved with pericardiectomy and targeted therapy.

Radiation-Associated Cardiac Disease: From Molecular Mechanisms to Clinical Management.

PURPOSE OF REVIEW: Radiation-associated cardiac disease (RACD) is an increasingly recognized latent manifestation of chest and mediastinal radiation therapy. The delayed presentation reflects increased survival rates from malignancies successfully treated decades previously. However, individuals are now presenting with multiple coexistent manifestations of RACD and pulmonary disease as a consequence of high-dose radiation administered prior to the routine institution of modern dose-modulating regimens. Increased awareness of RACD is critical for implementation of appropriate screening algorithms and for specific management strategies involving the timing and strategies of intervention in these patients. RECENT FINDINGS: Recent advances in multimodality cardiac imaging have demonstrated pathognomonic findings of RACD, which can predict outcomes including mortality. Accurate diagnosis of these typically concurrent manifestations is critical and should prompt referral to a center experienced in managing RACD as surgical risk is significantly increased for this patient cohort, particularly for those undergoing redo operation. The latent effect of RACD and its unique combination of manifestations means that these patients will increasingly present with challenging management issues, resulting in increased rates of morbidity and mortality. Timing of treatment intervention must be carefully considered, although percutaneous options may provide alternative future strategies for this higher risk cohort.