Should we increase betablocker after cardiac resynchronization therapy: the results of the caribe-hf study (cardiac resynchronization in combination with betablocker treatment in advanced chronic heart failure)

Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials reduces morbidity and mortality. However, patients often cannot tolerate the drug at the targeted dosage. Aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF. Methods: One hundred and 6 patients (aged 65±12 [mean±sd] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction < 35%, NYHA class III-IV and QRS interval ≥ 120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent long-term follow-up till 7 years (1193,98±924 days), while efforts to up-titrate the carvedilol dose were continued during the second phase (471±310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0±17.8 mg, against 32.7±19.1 mg in the remaining 69 patients (p=0.018). At the end of phase 2, CRT patients presented a significantly greater variation of increasing in the carvedilol dose than NO-CRT patients ( 20.0±19.8 mg vs –0.3±20.5 mg; p=0.015), a greater NYHA class reduction (-0.8±0.6 vs -0.2±0.7; p=0.011), and a greater increase in LV ejection fraction ( 10.8±9 vs 3.1±6.1; p=0.018). In conclusion, the data from the CARIBE study suggest that, in ACHF, CRT may be effective in enabling the target dose of carvedilol to be reached. The significant improvement seen in LV function was probably due to a synergistic effect of CRT and carvedilol. During the extended follow-up (mean 1193,98±924 days) the mean dosage of carvedilol in CRT group was significantly higher (

Prevalence and prognostic impact of non-cardiac co-morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community-based study

Aim: To assess adverse outcomes attributable to non-cardiac co-morbidities and to compare their effects by left ventricular ejection fraction (LVEF) group [LVEF <50% (heart failure with reduced ejection fraction, HFrEF), LVEF 6550% (heart failure with preserved ejection fraction, HFpEF)] in a contemporary, unselected chronic heart failure population. Methods and results: This community-based cohort enrolled patients from October 2009 to December 2013. Adjusted hazard ratio (HR) and the population attributable fraction (PAF) were used to compare the contribution of 15 non-cardiac co-morbidities to adverse outcome. Overall, 2314 patients (mean age 77 \ub110 years, 57% men) were recruited [n = 941 (41%) HFrEF, n = 1373 (59%) HFpEF]. Non-cardiac co-morbidity rates were similarly high, except for obesity and hypertension which were more prevalent in HFpEF. At a median follow-up of 31 (interquartile range 16\u201341) months, 472 (20%) patients died. Adjusted mortality rates were not significantly different between the HFrEF and HFpEF groups. After adjustment, an increasing number of non-cardiac co-morbidities was associated with a higher risk for all-cause mortality [HR 1.25; 95% confidence interval (CI) 1.10\u20131.26; P < 0.001], all-cause hospitalization (HR 1.17; 95% CI 1.12\u20131.23; P < 0.001), heart failure hospitalization (HR 1.28; 95% CI 1.19\u20131.38; P < 0.001), non-cardiovascular hospitalization (HR 1.16; 95% CI 1.11\u20131.22; P < 0.001). The co-morbidities contributing to high PAF were: anaemia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and peripheral artery disease. These findings were similar for HFrEF and HFpEF. Interaction analysis yielded similar results. Conclusions: In a contemporary community population with chronic heart failure, non-cardiac co-morbidities confer a similar contribution to outcomes in HFrEF and HFpEF. These observations suggest that quality improvement initiatives aimed at optimizing co-morbidities may be similarly effective in HFrEF and HFpEF

Restrictive Cardiomyopathy, Atrioventricular Block and Mild to Subclinical Myopathy in Patients With Desmin-Immunoreactive Material Deposits

AbstractObjectives. We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin.Background. Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle.Methods. Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy.Results. Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin—one of normal and another of lower molecular weight—in cardiac and skeletal muscle of the familial cases.Conclusions. Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin

Cardiac magnetic resonance in heart failure with preserved ejection fraction:myocyte, interstitium, microvascular, and metabolic abnormalities

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes - with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets

Use of Medications for Management of Alzheimer’s Disease in Ontario’s Home Care Population

Abstract Background: Home care is an important care setting for those with Alzheimer’s disease (AD). It provides support that allows individuals with AD to remain at home and may delay the transition to long-term care homes. Many clients with AD receive medications that are used for managing the symptoms of AD: cholinesterase inhibitors (ChEIs) and memantine. Ontario’s provincial drug benefit plan (ODB) provides subsidies for some of these medications based on specific clinical criteria. These AD medications are costly and can have significant side effects, so it is important to understand how they are being used in practice. Objectives: The objectives of this study were to report the proportion taking AD medications and which types were taken, show the change in receipt of AD medications over time, and show the covariates that were independently associated with receiving AD medications. Methods: Analysis of secondary data was performed on the provincial home care dataset. All home care clients receiving long-term home care services were assessed using the RAI-Home Care (RAI-HC), which is a comprehensive and standardized assessment. One assessment from each individual over the age of 65 who was assessed between January 2004 and September 2008 was used, for a final sample size of 321,013. Results: Overall, 65% of clients with a diagnosis of AD were receiving an AD medication. Logistic regression analysis among those diagnosed with AD showed that increased physical impairment and clinical complexity were associated with decreased odds of receiving AD medication. Contraindicating diagnoses such as congestive heart failure, lack of medical oversight and needing to make economic tradeoffs were also associated with decreased odds of receiving AD medication. Conclusions: The multivariate model showed trends of rational prescribing, such as clients with contraindicating diagnoses or very high clinical complexity having decreased odds of receiving AD medications. At the same time, evidence of structural barriers to receiving the medications was shown. There is debate about the cost-effectiveness of these medications. The provincial government could consider expanding ODB guidelines to include all AD medications for those with all levels of cognitive impairment, but further analyses involving longitudinal outcomes available in this dataset should be performed to ensure it would be in the public interest

Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

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