Mazen Hanna

Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis

Background The diagnosis of cardiac amyloidosis (CA) is challenging owing to vague symptomatology and non-specific echocardiographic findings. Objective To describe regional patterns in longitudinal strain (LS) using two-dimensional speckle-tracking echocardiography in CA and to test the hypothesis that regional differences would help differentiate CA from other causes of increased left ventricular (LV) wall thickness. Methods and results 55 consecutive patients with CA were compared with 30 control patients with LV hypertrophy (n=15 with hypertrophic cardiomyopathy, n=15 with aortic stenosis). A relative apical LS of 1.0, defined using the equation (average apical LS/(average basal LS + mid-LS)), was sensitive (93%) and specific (82%) in differentiating CA from controls (area under the curve 0.94). In a logistic regression multivariate analysis, relative apical LS was the only parameter predictive of CA (p=0.004). Conclusions CA is characterised by regional variations in LS from base to apex. A relative ‘apical sparing’ pattern of LS is an easily recognisable, accurate and reproducible method of differentiating CA from other causes of LV hypertrophy.

Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure

OBJECTIVES The purpose of this study was to examine the clinical outcomes of using slow continuous ultrafiltration (SCUF) in patients with acute decompensated heart failure (HF) refractory to intensive medical therapy. BACKGROUND Several studies have demonstrated the clinical usefulness of early SCUF in patients with acute decompensated HF to improve fluid overload and hemodynamics. METHODS We reviewed clinical data from 63 consecutive adult patients with acute decompensated HF admitted to the Heart Failure Intensive Care Unit from 2004 through 2009 who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. RESULTS The mean creatinine level was 1.9 ± 0.8 mg/dl on admission and 2.2 ± 0.9 mg/dl at SCUF initiation. After 48 hours of SCUF, there were significant improvements in hemodynamic variables (mean pulmonary arterial pressure: 40 ± 12 mm Hg vs. 33 ± 8 mm Hg, p = 0.002, central venous pressure: 20 ± 6 mm Hg vs. 16 ± 8 mm Hg, p = 0.007, mean pulmonary wedge pressure: 27 ± 8 mm Hg vs. 20 ± 7 mm Hg, p = 0.02, Fick cardiac index: 2.2 l/min/m(2) [interquartile range: 1.87 to 2.77 l/min/m(2)] vs. 2.6 l/min/m(2) [interquartile range: 2.2 to 2.9 l/min/m(2)], p = 0.0008), and weight loss (102 ± 25 kg vs. 99 ± 23 kg, p < 0.0001). However, there were no significant improvements in serum creatinine levels (2.2 ± 0.9 mg/dl vs. 2.4 ± 1 mg/dl, p = 0.12) and blood urea nitrogen (60 ± 30 mg/dl vs. 60 ± 28 mg/dl, p = 0.97). Fifty-nine percent required conversion to continuous hemodialysis during their hospital course, and 14% were dependent on dialysis at hospital discharge. Thirty percent died during hospitalization, and 6 patients were discharged to hospice care. CONCLUSIONS In our single-center experience, SCUF after admission for acute decompensated HF refractory to standard medical therapy was associated with high incidence of subsequent transition to renal replacement therapy and high in-hospital mortality, despite significant improvement in hemodynamics.

Tricuspid Regurgitation After Cardiac Transplantation: An Old Problem Revisited

Tricuspid regurgitation (TR) is the most common valvular abnormality after orthotopic heart transplantation (OHT), with a reported incidence of up to 84%, depending on the definition of significant regurgitation and surgical methods of OHT employed. While multiple etiologies are implicated in the development of TR after OHT, endomyocardial biopsy (EMB), performed to detect allograft rejection, is the single most important contributor to significant TR by causing anatomic disruption of the tricuspid valvular structure. Although the clinical course of TR is heterogeneous, hemodynamically significant regurgitation generally leads to progressive right-heart dysfunction and symptoms. In cases refractory to diuretic-based medical therapy, surgical correction of TR has been shown to effectively alleviate the condition and provide symptomatic and organ function improvement. Tricuspid valve repair and replacement are viable surgical options, the application of which often depends on the institutions experience and underlying valve pathology. A non-invasive surveillance technique to detect allograft rejection is on the horizon, and may reduce the number of EMBs performed as well as the procedure-related tissue damage that leads to TR.

Prognostic implication of relative regional strain ratio in cardiac amyloidosis

Objective Cardiac amyloidosis (CA) is a rapidly progressive disease that portends poor prognosis. Our objective was to evaluate the prognostic impact of relative regional strain ratio (RRSR, a measure of the relative apical sparing of longitudinal strain (LS)) in CA. Methods This is a retrospective study evaluating 97 patients with CA from 2004 to 2013. Patients were included if they met criteria for CA based on endomyocardial biopsy or advanced imaging criteria coupled with either extracardiac biopsy or genetic analysis. Baseline clinical and imaging data were collected and compared between light-chain amyloidosis (AL) (n=59) and transthyretin amyloidosis (ATTR) (n=38) subtypes. RRSR was defined as the average apical LS divided by the sum of the average mid and basal LS values. A Cox proportional hazards model was used to assess the effects of clinical and echocardiographic characteristics, including RRSR, on the outcome of time to death or heart transplantation. Results Despite younger age, the AL subtype had a statistically significant association with the composite outcome as compared with ATTR (p=0.022). Log-transformed RRSR was independently associated with the composite outcome at 5 years (HR 2.45 (1.36 to 4.40), p=0.003). Patients with low ejection fraction and high RRSR had the worst prognosis. In multivariable analysis, RRSR remained predictive of the primary outcome (p=0.018). Addition of covariates related to systolic function (global LS and ejection fraction) to the model attenuated this effect. Conclusions High RRSR is adversely prognostic in patients with cardiac amyloid. This novel tool is both diagnostic and prognostic and may have implications in management and suitability for treatment.

Combined Heart and Liver Transplantation: The Cleveland Clinic Experience

BACKGROUND Combined heart-liver transplantation (CHLT) has been utilized as a life-saving procedure in those with end-stage cardiac and hepatic pathology. Techniques and outcomes of this procedure are varied. We sought to review the Cleveland Clinic experience with CHLT. METHODS This study is a retrospective chart review of patients who received simultaneous heart and liver transplantation between January 2006 and December 2012. RESULTS Five patients received CHLT. The mean age was 49 (± 20) years. All cardiac pathology was nonischemic cardiomyopathy, with a mean ejection fraction of 0.36 (± 0.13). Three of the 5 were on preoperative inotropic support, 1 of which required placement of a total artificial heart for support pretransplant. Liver pathology was amyloid in 1 patient and hepatitis C in the remaining 4. Mean Model for End-Stage Liver Disease score was 17 (± 5), and mean Childs-Pugh score was 8 (± 1). Survival, now at a mean of 38 (± 20) months remains 100%, with no cardiac or hepatic graft dysfunction or episodes of rejection. One hospital readmission was required for gastroenteritis at 15 months posttransplant. CONCLUSIONS These results suggest that excellent outcomes can be achieved in this extremely sick cohort of patients, and add to the growing literature of perioperative management of CHLT recipients.

Extracorporeal Ultrafiltration vs Conventional Diuretic Therapy in Advanced Decompensated Heart Failure

Compared with conventional diuretic (CD) therapy, ultrafiltration (UF) is associated with greater weight loss and fewer re-hospitalizations in patients admitted with decompensated heart failure (HF). Concerns have been raised regarding its safety and efficacy in patients with more advanced heart failure. The authors conducted a single-center, prospective, randomized controlled trial in patients with advanced HF admitted to an intensive care unit for hemodynamically guided therapy, comparing UF (n=17) with CD (n=19) at admission. The primary end point was the time required for pulmonary capillary wedge pressure (PCWP) to be maintained at a value of ≤18 mm Hg for at least 4 consecutive hours. Secondary end points included levels of cytokines and neurohormones, as well as several clinical outcomes. In our study cohort, the time to achieve the primary end point was lower in the UF group but did not reach statistical significance (P = .08). UF resulted in greater weight reduction, higher total volume removed, and shorter hospital length of stay. There were no differences in kidney function, biomarkers, or adverse events. In patients with advanced HF under hemodynamically tailored therapy, UF can be safely performed to achieve higher average volume removed than CD therapy without leading to adverse outcomes.

Advanced Cardiac Amyloidosis Associated with Normal Interventricular Septal Thickness: An Uncommon Presentation of Infiltrative Cardiomyopathy

BACKGROUND Increased interventricular septal (IVS) thickness on echocardiography is a diagnostic criterion for cardiac amyloidosis and classically precedes decrement in left ventricular ejection fraction (LVEF). The investigators describe patients with histologically confirmed cardiac amyloidosis who had significant myocardial dysfunction (LVEF ≤ 40%) despite having normal IVS thickness. METHODS All patients with systemic amyloidosis and LVEFs ≤ 40% were analyzed to identify the prevalence of normal IVS thickness. Patients with known histories of cardiomyopathy or coronary artery disease were excluded. Histologic evaluation of tissue included assessment of amyloid burden and average myocyte diameter. RESULTS There were 255 patients with amyloidosis with LVEFs ≤ 40%, of whom seven (3%) had normal IVS thickness and histologic confirmation of cardiac involvement. Of these, six had immunoglobulin light chain amyloidosis, and one had senile amyloidosis. A majority of patients (86%) presented with new-onset cardiac dysfunction associated with edema and/or dyspnea. Electrocardiographic findings included low voltage (43%) and a pseudoinfarct pattern (29%). The 1-year survival from initial tissue diagnosis in the cohort with normal IVS thickness was similar to matched patients with amyloidosis with increased IVS thickness and LVEF ≤ 40% (21% vs 18%, respectively, P = .32). Myocardial tissue amyloid burden and average myocyte diameter were significantly reduced in cases compared with controls. CONCLUSIONS Cardiac amyloidosis can uncommonly present with normal IVS thickness despite significant myocardial dysfunction. The prognosis of these patients is as poor as those with increased IVS thickness. Amyloidosis should be considered in the differential diagnosis of patients with cardiomyopathy and reduced LVEFs despite normal IVS thickness.

Management of the sensitized adult heart transplant candidate.

Eckman PM, Hanna M, Taylor DO, Starling RC, Gonzalez‐Stawinski GV. Management of the sensitized adult heart transplant candidate. 
Clin Transplant 2010: 24: 726–734.

Novel Drugs Targeting Transthyretin Amyloidosis

Transthyretin amyloidosis (ATTR) is either a hereditary disease related to a mutation in the transthyretin gene that leads to neuropathy and/or cardiomyopathy or an acquired disease of the elderly that leads to restrictive cardiomyopathy. The prevalence of this disease is higher than once thought and awareness is likely to increase amongst physicians and in particular cardiologists. Until recently there have been no treatment options for this disease except to treat the heart failure with diuretics and the neuropathy symptomatically. However, there are several emerging pharmacologic therapies designed to slow or stop the progression of ATTR. This article reviews novel therapeutic drugs that work at different points in the pathogenesis of this disease attempting to change its natural history and improve outcomes.

Subtype‐Specific Interactions and Prognosis in Cardiac Amyloidosis

Background Light chain (AL) and transthyretin (ATTR) amyloidosis have a similar effect on myocardial function but very different disease trajectories and survival. However, limited data are available evaluating subtype‐specific predictors of outcomes in a large contemporary cohort. Methods and Results We retrospectively investigated 360 patients at the time of initial diagnosis of cardiac amyloidosis (191 AL and 169 ATTR) from 2002 to 2014. Clinical, laboratory, electrical, and morphologic covariates were evaluated based upon amyloid subtype. ATTR etiology was associated with older age, more chronic medical conditions, and the use of standard heart failure medical therapy. Left ventricular mass index and electrocardiographic voltage were higher in ATTR, while there was no difference in ejection fraction or markers of diastology between subtypes. A multivariable Cox model was generated using previously identified predictors of negative outcomes in cardiac amyloidosis and analyzed after stratification for subsequent amyloid‐specific treatment. An AL etiology was the most predictive variable (hazard ratio 3.143, P<0.001) of 3‐year all‐cause mortality. The only covariate that showed a significantly greater magnitude of effect on mortality in 1 amyloid subtype versus the other was amyloid‐specific treatment in AL (P=0.015). The magnitude of effect of other variables on mortality did not significantly differ between subtypes. Conclusions Clinical, morphological, electrical, and biomarker data do not significantly interact with amyloid subtype in its association with mortality, despite the fact that the prognosis in each subtype differs greatly. This suggests an additional factor or factors (such as light chain toxicity) contributing to poorer outcomes in AL amyloid.