Wild-Type Transthyretin Amyloid Cardiomyopathy: The Gordian-Knot of Novel Therapeutic Regimens.

Wild-type TTR amyloidosis (wtATTR) represents a disease difficult to diagnose with poor prognosis. Increased clinical suspicion is key, allowing for timely diagnosis. Until recently, only off-label therapies were available but recent introduction of disease specific therapy has shown potential to alter the natural history of the disease. Tafamidis, the only currently approved drug for the therapy of wtATTR, provided significantly better survival and quality of life. However, not all subgroups of patients derived equal benefit. This, along with the increased cost of treatment raised question on whether treatment should be invariably administered through the wtATTR population. This review aims to summarize current evidence on the natural history and staging systems for wtATTR, as well as available treatment options. Special consideration is given to the selection process of patients who would be expected to gain maximum benefit from tafamidis treatment, based on an ethical and cost-effective point of view.

Real world data on light chain cardiac amyloidosis: Still a delayed diagnosis.

Cardiac amyloidosis (CA) represents a myocardial disorder developed by fibril deposition of a heterogeneous group of misfolding proteins. Despite being rare, a high clinical index of suspicion and novel advanced diagnostic methods seem to facilitate its early recognition. Currently nine types of cardiac amyloidosis have been described with AL and ATTR being the most common. Light chain amyloidosis (AL) is a life-threatening disease, resulting from clonal plasma cells that produce amyloidogenic light chain fragments causing organ damage including the heart. Morbidity and mortality of these patients is strongly associated with the severity of cardiac involvement. Thus, early and precise diagnosis is crucial for prompt treatment initiation. In this study, we retrospectively analyzed data of 36 consecutive patients who were diagnosed with AL amyloidosis and treated in our center over the past 15 years. Heart involvement was present in 33 (92%) of them while 76% had severe cardiac disease as of stage IIIa and IIIb, according to the Mayo2004/European staging system. Almost one third of these patients experienced an early death occurring the first five months of diagnosis. To capture everyday clinical practice, we provide details on clinical presentation, diagnostic challenges, and outcome of these patients.

A novel quantitative method for assessing the therapeutic response to Tafamidis therapy in patients with cardiac TTR amyloidosis. A preliminary report.

OBJECTIVE: Cardiomyopathy is a common manifestation of transthyretin amyloidosis (ATTR), leading to heart failure, associated with high morbidity and mortality. The aim of this study was to investigate the effect of Tafamidis treatment by means of cardiac radiotracer uptake on myocardial scintigraphy. SUBJECTS AND METHODS: Five male patients, mean age 76.2 years, with wild-type ATTR were included in the protocol. Total body scanning using technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (in four patients) and technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) (in one) was performed pre- and one year post-Tafamidis therapy. A novel quantitation method for assessing radiotracer cardiac uptake was employed. The geometric mean was computed for both cardiac and thigh region of interest (ROI) and the heart-to-thigh (HtT) ratio was assessed by dividing the corresponding geometric mean counts. RESULTS: Heart-to-thigh ratio was improved (decreased) in four of the patients receiving Tafamidis, in keeping with lower uptake to the cardiac region. These patients also demonstrated a relatively favorable clinical response to Tafamidis. The patient evaluated by 99mTc-HMDP exhibited minimal HtT ratio reduction and stable clinical and echocardiographic characteristics. CONCLUSION: Sequential HtT ratio measurements could potentially identify patients with a favorable response to Tafamidis treatment at earlier stages, compared to other imaging modalities or serological biomarkers.

Mitral regurgitation impact on left atrial myopathy in hypertrophic cardiomyopathy.

BACKGROUND: Recent studies have shown that mitral regurgitation (MR) represents a major determinant of left atrial (LA) function in patients with heart failure with preserved ejection fraction. The role of MR in determining LA myopathy in hypertrophic cardiomyopathy (HCM) is unknown. The aim of this study was to examine the association of MR with LA myopathy, assessed by LA strain values in HCM patients. METHODS: In total 250 consecutive patients (mean age 51 ± 16 years, 67.2% male) with an established diagnosis of HCM and with sinus rhythm at index echocardiography evaluation were included. LA reservoir, conduit and booster strain were analyzed, besides LA size, left ventricular (LV) systolic and diastolic function. The predictors of LA strain values were identified with linear regression analysis. RESULTS: Significant (more than mild) MR was a significant univariate predictor of all the three LA strain values. In multivariate linear regression analysis, independent predictors of LA reservoir strain were more than mild MR (r = -.23), LV global longitudinal strain (r = -.49), LA volume index (r = -.27) and patient age (r = -.23). Significant MR was also an independent determinant of LA conduit (r = -.17) and booster strain (r = -.12). In patients with LA volume index < 34 ml/m2 more than mild MR was an independent predictor of LA reservoir (r = -.32) and conduit strain (r = -.27), but not LA booster strain. CONCLUSION: Significant MR is associated with LA myopathy independently of the LV diastolic and systolic function and LA size.

A simple algorithm for a clinical step-by-step approach in the management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease with an autosomal dominant pattern and a reported prevalence of about 0.2%. In this review, we present a simple algorithm for the management of first diagnosed HCM patients. Initially, the clinical examination, medical and detailed family history and the ECG are essential. The etiological diagnosis of left ventricular hypertrophy is important in order to differentiate HCM due to sarcomeric genes mutation from other phenocopies, such as cardiac amyloidosis. The next step consists of the cardiovascular imaging and ambulatory electrocardiography. Cardiopulmonary exercise testing may also be considered if available. All of the above provide evidence for the critical step of the risk stratification of patients for sudden cardiac death. The therapeutic strategy, with respect to obstructive and nonobstructive disease, arrhythmias and end-stage HCM is also described.