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Timely and individualized heart failure management: need for implementation into the new guidelines.
Abdin, A, Bauersachs, J, Frey, N, Kindermann, I, Link, A, Marx, N, Lainscak, M, Slawik, J, Werner, C, Wintrich, J, et al
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(8):1150-1158
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Abstract
Due to remarkable improvements in heart failure (HF) management over the last 30 years, a significant reduction in mortality and hospitalization rates in HF patients with reduced ejection fraction (HFrEF) has been observed. Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF to reduce mortality and HF hospitalization. This includes established device therapies, such as implantable defibrillators and cardiac resynchronization therapies, which improved patients' symptoms and prognosis. Over the last 10 years, new HF drugs have merged targeting various pathways, such as those that simultaneously suppress the renin-angiotensin-aldosterone system and the breakdown of endogenous natriuretic peptides (e.g., sacubitril/valsartan), and those that inhibit the If channel and, thus, reduce heart rate (e.g., ivabradine). Furthermore, the treatment of patient comorbidities (e.g., iron deficiency) has shown to improve functional capacity and to reduce hospitalization rates, when added to standard therapy. More recently, other potential treatment mechanisms have been explored, such as the sodium/glucose co-transporter inhibitors, the guanylate cyclase stimulators and the cardiac myosin activators. In this review, we summarize the novel developments in HFrEF pharmacological and device therapy and discuss their implementation strategies into practice to further improve outcomes.
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Contemporary Management of Electrical Storm.
Geraghty, L, Santangeli, P, Tedrow, UB, Shivkumar, K, Kumar, S
Heart, lung & circulation. 2019;(1):123-133
Abstract
Cardiac electrical storm (ES) is characterised by three or more discrete episodes of ventricular arrhythmia within 24hours, or incessant ventricular arrhythmia for more than 12hours. ES is a distinct medical emergency that portends a significant increase in mortality risk and often presages progressive heart failure. ES is also associated with psychological morbidity from multiple implanted cardioverter defibrillator (ICD) shocks and exponential health resource utilisation. Up to 30% of ICD recipients may experience storm in follow-up, with the risk higher in patients with a secondary prevention ICD indication. Storm recurs in a high proportion of patients after an initial episode, and multiple storm clusters may occur in follow-up. The mechanism of storm remains elusive but is likely influenced by a complex interplay of inciting triggers (e.g., ischaemia, electrolyte disturbances), with autonomic perturbations acting on a vulnerable structural and electrophysiologic substrate. Triggers can be identified only in a minority of patients. An emergent treatment approach is warranted, if possible with emergent transfer to a high-volume centre for ventricular arrhythmia management with a multi-modality approach including ICD reprogramming, sympathetic blockade (sedation, intubation, ventilation, beta blockers), and anti-arrhythmic drugs, and adjunctive intervention techniques, such as catheter ablation and neuraxial modulation (e.g., thoracic epidural anaesthesia, stellate ganglion block). Outcomes of catheter ablation of ES are excellent with resolution of storm in over 90% of patients at 1year with a low complication rate (∼2%). ES may occur in the absence of structural heart disease in the context of channelopathies, Brugada syndrome, early repolarisation and premature ventricular contraction-induced ventricular fibrillation. There are unique treatment approaches to these conditions that must be recognised. This state-of-the-art review will summarise the incidence, mechanism, and multi-modality treatment of ES in the contemporary era.
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The necessity of implantable cardioverter defibrillators in patients with Kearns-Sayre syndrome - systematic review of the articles.
Imamura, T, Sumitomo, N, Muraji, S, Mori, H, Osada, Y, Oyanagi, T, Kojima, T, Yoshiba, S, Kobayashi, T, Ono, K
International journal of cardiology. 2019;:105-111
Abstract
The most common cardiac feature of Kearns-Sayre syndrome (KSS) is atrioventricular block (AVB), and pacemaker implantations (PMIs) are recommended for KSS patients with advanced AVB. However, some KSS patients develop fatal arrhythmias such as polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and die suddenly even after PMIs. We report a patient with KSS who developed PMVT, VF, and QT prolongation, and was treated with mexiletine and successfully managed with an implantable cardioverter defibrillator (ICD). We reviewed the literature on arrhythmias in KSS published from 1975 to 2018. There were 112 patients with arrhythmia-associated KSS, 10 died, and 6 died suddenly after the PMI. The first manifestation of an arrhythmia was bundle branch block, then it progressed to AVB, and developed into complete AVB (CAVB) in about half the KSS patients. Ventricular arrhythmias were documented in 12 patients, and 8 were implanted with defibrillators afterwards. One patient after the implantation of a cardiac resynchronization therapy defibrillator (CRT-D) was treated for VF by an appropriate shock. This fact suggested that VF occurred even under proper pacing, and that defibrillators were effective. Pacemakers may suppress early afterdepolarizations (EADs) associated with a QT prolongation due to bradycardia. Similarly, mexiletine may suppress EADs by blocking the late sodium and Ca currents. Ventricular arrhythmias observed under suppression of EADs may be caused by delayed afterdepolarization (DADs) via an increasing intracellular Ca concentration due to mitochondrial dysfunction. Therefore, a PMI alone may not be sufficient to prevent sudden death, and an ICD implantation should be necessary.
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Cardiac resynchronization therapy in the elderly. How much is it safe and beneficial?
Vetta, F, Vetta, G, Bracchitta, S, Mignano, M, Mattatelli, A
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace. 2019;(1)
Abstract
Heart failure is a widespread disease in the western world whose incidence and prevalence are constantly increasing, mainly involving the more advanced age groups. Cardiac resynchronization therapy (CRT) has been shown able to reduce sudden cardiac death and all-cause mortality in patients with heart failure and reduced ejection fraction. Elderly patients are generally under-represented in the clinical trials aimed to evaluate the efficacy of CRT and, chiefly, of implantable cardiac defibrillator (ICD). The simultaneous presence of confounding factors such as co-morbidities, polypharmacy, changes in cognitive status, frailty, are the most important causes for the exclusion of subjects of advanced age from RCTs on the ICD or CRT implant. Current guidelines do not suggest any upper age limit for ICD and CRT but recommend avoiding their use in frail older patients with a life expectancy of less than 1 year. Data from the literature show that CRT has equal dignity in both the elderly and the young, in fostering effective functional and morphological improvements, also suggesting that, in older patients, CRT-D may have little practical value compared to CRT-P given the low incidence of arrhythmic death. Nevertheless, it is necessary to develop RCTs that consider aspects of the elderly patient in relation to CRT such as functional, cognitive and nutritional status.
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Rationale and design of the IRON-CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy.
Martens, P, Dupont, M, Dauw, J, Somers, F, Herbots, L, Timmermans, P, Verwerft, J, Mullens, W
ESC heart failure. 2019;(6):1208-1215
Abstract
AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force-frequency relationship). METHODS AND RESULTS The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON-CRT) trial is a multicentre, prospective, randomized, double-blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 μg/L irrespective of transferrin saturation or a ferritin between 100 and 300 μg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three-dimensional (3D) echo from baseline to 3 month follow-up and the secondary endpoints change in left ventricular end-systolic and end-diastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo, by assessing the force-frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion. CONCLUSIONS The IRON-CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and rate-dependent cardiac contractility in HFrEF patients.
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Innovative Strategies in Heart Failure: Present and Future.
Rodríguez-Mañero, M, Grigorian-Shamagian, L, Rábago, G, Abou-Jokh, C, Álvarez, B, Brion, M, González-Juanatey, JR
Archives of medical research. 2018;(8):558-567
Abstract
Heart failure (HF) is a progressively debilitating disease that considerably decreases the life expectancy and quality of life. It has become an important area of focus since it remains one of the most common reasons for admission in patients over the age of 65. Importantly, the incidence of HF has not declined within the past 20 years, but the survival after onset has increased in younger patients and men. This has been in part due to the growing interest in therapies that may decrease morbidity, mortality, along with the substantial health care expenditures associated with the disease. It can be said that over the past 50 years, there have been three distinct eras relating to HF management; a) the non-pharmacologic era, focused its treatments on fluid restriction; b) the pharmacologic era, marked by the increased use of inotropes and diuretics and the discovery of vasodilators, and the posterior discovery of medications relating to neurohormonal pathways; c) the device era, with the discovery, acceptance, and increased use of implantable cardioverter defibrillators, cardiac resynchronization therapy (CRT), and left ventricular assist devices (LVADs) among others. A new forth era could be about to arrive, with the advent of regenerative therapies. In this review article will discuss new therapeutic discoveries as well as provide insight into future therapies.
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[Electrophysiologic procedure complications in the elderly].
Pfeiffer, D, Neef, M, Jurisch, D, Hagendorff, A
Herzschrittmachertherapie & Elektrophysiologie. 2017;(1):3-8
Abstract
Published registries give limited information on age-dependent complication rates. There are several reasons for this, including limited numbers of patients in subgroups (e.g., contractility management), experience-dependent procedures (e.g., catheter ablation), or in changing indications (e.g., resynchronization). Finally, severely ill and very old patients with limited prognosis are often excluded from electrophysiologic procedures. Therefore, published data are difficult to interpret. Meta-analyses of randomized trials give more precise information on included patient cohorts, but do not necessarily reflect daily practice because elderly patients are often excluded from trials. Therefore, the individual risk of elderly patients has to be estimated on an individual case basis. In summary, the age of patients is not relevant regarding possible complications; thus, there is no age limit for electrophysiologic interventions. Therefore, there is no alternative to the individual estimation of procedural risks of interventions of an informed patient by an experienced cardiologist.
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The prognostic significance of serum sodium in a population undergoing cardiac resynchronisation therapy.
Guha, K, Spießhöfer, J, Hartley, A, Pearse, S, Xiu, PY, Sharma, R
Indian heart journal. 2017;(5):613-618
Abstract
PURPOSE To determine the prognostic implications of changes towards hyponatremia at varying time-points in the treatment of patients undergoing cardiac resynchronisation therapy (CRT). METHODS A retrospective series of 249 patients was studied from 2002 to 2013. The population was categorized on the basis of serum sodium profile at baseline, at 1 month and at 6 month follow up visits following successful CRT implantation. The composite endpoint was all-cause mortality and heart failure hospitalisation (defined by the need for intravenous diuretic therapy) following CRT implantation. RESULTS A total of 249 patients (67.8±12.5 years; NYHA class III/IV 75; LVEF 27.2±8.8%) were followed up for a median of 5.5 years. Hyponatremia at baseline, 1 month or 6 months follow up did not predict the composite endpoint. 26% of patients showed hyponatremia at baseline prior to CRT implantation, while it was present in 19.9% of patients 1 month (p=0.003) and in 16% (p<0.001) 6 months after CRT implantation. There was a significantly worse outcome for those patients who developed hyponatremia 6 months after CRT implantation. In multivariate analysis, the intake of loop diuretics (HR 1.76 [1.04-2.95], p=0.03) and renal impairment (urea>7.0mmol/l) (HR 1.61 [1.05-2.46], p=0.03) at baseline were associated with an increased risk of unplanned heart failure hospitalisation and all-cause mortality after CRT implantation. CONCLUSIONS A change towards hyponatremia when observed 6 months after CRT implantation may predict a worse clinical outcome. Additionally, renal impairment and higher diuretic doses are associated with an increased risk of mortality in the population analysed.
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Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction.
Stone, GW, Chung, ES, Stancak, B, Svendsen, JH, Fischer, TM, Kueffer, F, Ryan, T, Bax, J, Leon, A, ,
European heart journal. 2016;(5):484-93
Abstract
AIMS: We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). METHODS AND RESULTS A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs. non-implanted control. The primary endpoint was the echocardiographic core laboratory-assessed change in LV end-diastolic volume (ΔLVEDV) from baseline to 18 months between the pooled pacing therapy groups and the control group. ΔLVEDV increased by 15.3 ± 28.6 mL in the control group and by 16.7 ± 30.5 mL in the pooled pacing groups during follow-up (adjusted mean difference (95% CI) = 0.6 (-12.3, 13.5) mL, P = 0.92). There were also no significant between-group differences in the change in LV end-systolic volume or ejection fraction over time. Quality of life, as assessed by the Minnesota Living with Heart Failure (HF) and European Quality of Life-5 Dimension questionnaires and New York Heart Association class, was also similar between groups during 18-month follow-up. Six-minute walk distance improved during follow-up to an equal degree between groups, and there were no significant differences in the 18-month rates of death or HF hospitalization between the pooled pacing therapy vs. control groups (17.4 vs. 21.7% respectively, P = 0.59). CONCLUSIONS In the present multicentre, randomized trial, peri-infarct pacing did not prevent LV remodelling or improve functional or clinical outcomes during 18-month follow-up in patients with large first MI. CLINICALTRIALSGOV IDENTIFIER NCT01213251.
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Autoantibodies against β1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.
Michelucci, A, D'Elios, MM, Sticchi, E, Pieragnoli, P, Ricciardi, G, Fatini, C, Benagiano, M, Niccolai, E, Grassi, A, Attanà, P, et al
Pacing and clinical electrophysiology : PACE. 2016;(1):65-72
Abstract
BACKGROUND Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the β1-adrenergic (β1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. MATERIALS AND METHODS We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. β1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. RESULTS A significantly higher percentage of patients positive for β1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. β1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of β1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). CONCLUSIONS Our study suggests that (1) the evaluation of β1-AAb is useful to identify responders to CRT-D; (2) the presence of β1-AAbs is in relationship with elevated renal function parameters.