Cardioverter-defibrillator For Primary Prevention Research Articles

Implantable cardioverter defibrillators for primary prevention in cardiomyopathies

BackgroundImplantable cardioverter defibrillators (ICD) are often used as primary prevention strategy for sudden cardiac death (SCD) in young individuals. This study analyzed appropriate therapies, complications and inappropriate shocks in the real-world Indian population. MethodsAll patients in the cardiomyopathy cohort under follow up who had ICD implanted as a primary prevention strategy were studied. The objective was to assess the incidence of appropriate ICD therapies, inappropriate therapies and complications. ICD was interrogated and stored electrograms analyzed. Underlying arrhythmia or conditions resulting in appropriate or inappropriate ICD therapy were studied. Correlation and regression studies was done to assess for the predictors of appropriate therapy. ResultsFifty patients were followed up for a mean follow-up duration of 4.4 ± 3.1 years with total follow up of 220.2 patient years. Appropriate ICD therapy was delivered in 16 out of 50 (32%) patients, with 65 appropriate therapies (median 2 per patient, range: 0–20). Inappropriate therapy delivered in 7 of the 50 (14%) patients, with 44 inappropriate therapies (median 5 per patient, range: 0–20). Complications occurred in 8 of the 50 (16%) patients. Overall, the rate of appropriate therapy was 29.5 per 100 patient years, that of inappropriate therapy was 19.9 per 100 patient years and the rate of complications was 3.6 per 100 patient years. ConclusionsWhen implanted for primary prevention in patients with cardiomyopathies over a mean period of 4.4 ± 3.1 years, appropriate ICD therapy was delivered in 32% patients. However, inappropriate therapy (14% patients) and complications (16% patients) were also common.

Arrhythmias in Patients with Congenital Heart Disease: An Ongoing Morbidity.

With the aging of congenital heart disease (CHD) patients, the burden of arrhythmias is expanding. Atrial arrhythmias, especially intra-atrial reentrant tachycardia and atrial fibrillation, are the most prevalent forms of arrhythmia. Managing comorbidities, such as obesity, using pharmacotherapy, including antiarrhythmics and anticoagulants, and ablation therapy has become the cornerstone of arrhythmia management. Ventricular tachycardias are also not rare; however, except for tetralogy of Fallot patients, recommendations for the use of implantable cardioverter defibrillators for primary prevention in other CHD patients are still not well established. Patients with CHD might also present with atrioventricular blockages because of their anatomy or following a surgical procedure. The scope of this article is to review the current knowledge and discuss the future directions regarding arrhythmia management in CHD patients.

Abstract 12506: Implantable Cardioverter Defibrillators for Primary Prevention in Patients With Ischemic and Non Ischemic Cardiomyopathy: A Meta-Analysis of 15 Randomized Controlled Trial

Background: The evidence to support implantable cardioverter defibrillator (ICD) in patients with ischemic and nonischemic cardiomyopathy for prevention of sudden cardiac death (SCD) is not robust, with conflicting results in randomized controlled trials. Objective: We aim to evaluate the impact of ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic and nonischemic cardiomyopathy. Methods: We performed a systematic literature search on the electronic database for relevant articles from inception until 15th May 2022. Results: A total of 15 randomized controlled trials involving 9,999 patients: 9 (6523 patients) addressed ischemic cardiomyopathy, and 6 studies (3476 patients) reported nonischemic cardiomyopathy. The mean follow-up duration was 3.02 years. Pooled analysis showed that ICD therapy significantly reduced the risk of ACM (HR, 0.75(95%CI: 0.64-0.88), P<0.001) from the control group. The magnitude of reduction was similar with ischemic (HR, 0.75(95%CI: 0.58-0.96), P=0.02), nonischemic (HR, 0.76(95%CI: 0.64-0.90), P<0.01). There was 67% reduction in SCD among ICD therapy group (OR, 0.33(95%CI: 0.25-0.44), P<0.00001) compared to the control, a similar trend was observed in both ischemic (OR, 0.39(95%CI: 0.28-0.56), P<0.00001), and nonischemic cardiomyopathy (OR, 0.24(95%CI: 0.15-0.38), P<0.00001). The ICD therapy group had a significant reduction of 65% reduction in arrhythmia-related death compared to control in ischemic cardiomyopathy (OR, 0.35(95%CI: 0.19-0.64), P<0.001). However, there was a trend of 23% in cardiovascular mortality in the ICD group (OR, 0.77(95%CI: 0.58-1.02), P=0.07) but unable to reach statistical significance. Conclusion: Overall, primary prevention with ICD therapy reduced the incidence of all-cause mortality and sudden cardiac death among ischemic and nonischemic cardiomyopathy patients.

Implantable cardioverter defibrillator for primary prevention in patients with non-ischemic cardiomyopathy in the era of novel therapeutic agents- meta-analysis.

Evidence regarding the mortality benefit of implantable cardioverter defibrillator (ICD) non-ischemic dilated cardiomyopathy (NIDCM) is inconsistent. The most recent randomized study, the DANISH trial, did not find improved outcomes with ICD. However, based on previous studies and meta-analyses, current guidelines still highly recommend ICD implantation in NIDCM patients. The introduction of novel medications for heart failure improved the clinical outcome dramatically. We aimed in this study to evaluate the effect of Angiotensin Receptor-Neprilysin Inhibitors (ARNi) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on the mortality benefit of ICD in NIDCM. We used a previous metanalysis algorithm and added an updated comprehensive literature search in PubMed for randomized control trials that examined the mortality benefit of ICD in NIDCM vs. optimal medical treatment. The primary outcome included death from any cause. We did a meta-regression analysis to search for a single independent factor affecting mortality. Using previous data, we evaluated the theoretical effect of ICD implementation on patients treated with SGLT2 inhibitors and ARNi. No new articles were added to the results of the previous meta-analysis. 2,622 patients with NIDCM from 5 cohort studies published between 2002 and 2016 were included in the analysis. 50% of them underwent ICD implantation for primary prevention of sudden cardiac death, and 50% did not. ICD was associated with a significantly decreased risk for death from any cause compared to control (OR = 0.79, 95%CI: 0.66-0.95, p = 0.01, I2 = 0%). The theoretical addition of ARNi and the SGLT2 inhibitor dapagliflozin did not change the significant mortality effect of ICD (OR = 0.82, 95%CI: 0.7-0.9, p = 0.001, I2 = 0%) and (OR = 0.82, 95%CI: 0.7-0.9, p = 0.001, I2 = 0%). A meta-regression revealed no association between death from any cause and left bundle branch block (LBBB), use of amiodarone, use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers, year initiated enrollment, and the year ended enrollment (R2 = 0.0). In patients with NIDCM, the addition of ARNi and SGLT2i did not affect the mortality advantages of ICD for primary prevention. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023403210.

Sudden death in ischemic heart disease: looking for new predictors: polygenic risk.

The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P < 0.005) and relative (29% vs. 16%; P < 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).

Relationship between Exercise Test Parameters, Device-Delivered Electric Shock and Adverse Clinical Events in Patients with an Implantable Cardioverter Defibrillator for Primary Prevention.

(1) Background: Receiving the first internal electric shock is a turning point for patients with an implantable cardioverter defibrillator (ICD) for primary prevention. However, no study has investigated whether patients who receive a first device-delivered electric shock have a poor prognosis even at the time of ICD implantation. (2) Methods: We retrospectively identified 55 patients with ischemic (n = 31) or dilated (n = 24) cardiomyopathy who underwent ICD implantation for primary prevention with exercise test at the time of implantation. We recorded baseline characteristics, exercise test parameters, and clinical events. (3) Results: After a median follow-up of 5 years, we observed an association between an appropriate device-delivered electric shock, the occurrence of death or heart transplant, and the occurrence of the composite endpoint. There was also a significant relation between a VE/VCO2 slope >35 and the occurrence of the composite endpoint. Conversely, there was no significant association between negative outcomes on the exercise test and the occurrence of a device-delivered electric shock. (4) Conclusions: The exercise test performed at the time of ICD implantation do not predict the occurrence of device-delivered electric shock. The exercise test and the first electric shock are two independent markers of poor prognosis.

661 TWO CARDIOMYOPATHIES IN ONE HEART: LESSONS FROM CLINICAL CASE

Abstract Case description In November 2020, a 55-years-old female with no significant past medical history, was admitted to our Emergency Department for chest pain after acute stressful event. She had a significant family history of ischemic heart disease, and unclear comatose status of her sister. At admission, she was asymptomatic, blood pressure was 115/80 mmHg, and oxygen saturation was 96%. An electrocardiogram (ECG) showed biphasic T wave in anterolateral leads. Elevated levels of troponin I (hs-TnI of 900 ng/L) and B-type natriuretic peptide (BNP) of 864 pg/mL were detected. Transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 30% with apical ballooning of mid and apical segments of the left ventricle (LV) along with a sizable apical thrombus. Aspirin, iv diuretics, iv nitrates and unfractioned heparin were started. After 13 hours, she suffered a sudden transient neurological sign of decreased level of consciousness. Cranial MRI revealed an ischemic lesion in the territory of the apex of basilar artery (thalamic region). After 7 days from stroke, the patients underwent coronary angiography demonstrating unobstructed coronaries. Thus, the diagnosis of takotsubo syndrome was confirmed. During hospitalization, ECG evolution showed T wave inversion in precordial and lateral leads. Hs-TnI declining within normal values. Of note, ventricular arrhythmias burden with polymorphic ventricular contraction (PVC) emerged on continuous ECG-monitoring. Despite resolution of apical balloning and apical thrombosis, there were persistent wall-motion abnormalities in infero-lateral walls and mild LV dysfunction. This was also confirmed by cardiac magnetic resonance (CMR). Further, CMR also showed an intense myocardial edema with elevated LV mass. The patients was discharged on Warfarin, Bisoprolol 2.5 mg/die, Ramipril 5 mg/die, Eplerenone 25 mg/die. A clinical documentation was required to further investigate history of her sister, and neurological sequelae after cardiac arrest at 28s related to ventricular fibrillation emerged. However, no deeply evaluation of underlining heart disease was available. Despite an early favorable follow-up of patient, after six months, she suffered from palpitations and heart failure requiring diuretic therapy. Persistent repolarization abnormalities in infero-lateral leads, and low-voltage in precordial leads were noted. An extensive wall-motion abnormalities and moderate LV dysfunction were detected. Importantly, significant arrhythmic burden with PVC (13%) at 24-hr ECG monitoring was recorded. CMR was requested to further investigate the possibility of underlining coexisting cardiomyopathy. Mild LV dilation, moderate dysfunction (LVEF 39%), wall motion abnormalities and thinning of the inferior wall middle segments were reported. Surprisingly, fibro-fatty replacement in infero-lateral of LV wall was detected, and unexpectedly, right ventricular (RV) fibro-fatty replacement and mild RV dysfunction were also described. Hence, diagnosis of arrhythmogenic cardiomyopathy was made. Since persistent arrhythmic burden despite optimized medical treatment, biventricular involvement, family history of SCD, an implantable cardioverter defibrillator in primary prevention was placed. Furthermore, genetic testing was required and extensive clinical family screening was suggested. Conclusion According to the clinical data collected, takotsubo and arrhytmogenic cardiomyopathy can coexist. A potential link between two myocardial heart disease may be identified in the future, especially among patients presenting takotsubo and long-term unfavorable outcome.

Programming of implantable cardioverter defibrillators for primary prevention: outcomes at centers with high vs. low concordance with guidelines.

While ICD therapy reduction programming strategies are recommended in current multi-society guidelines, concerns remain about a possible trade-off between the benefits of ICD therapy reduction and failure to treat episodes of ventricular arrhythmias. The study is to evaluate the outcomes of primary prevention patients followed in centers with high and low concordance with the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines. Consecutive patients with primary prevention ICD implantation from two centers between 2014 and 2016 were included. One center was classified as high guideline concordance center (HGC) with 47% (146/310) of patients with initial ICD concordant with the guidelines, and the other center was classified as low guideline concordance center (LGC) with only 1% (2/178) of patients with guideline-concordant initial ICD programming. Cox proportional hazard models were used to assess risk of first ICD therapy (ATP or shock), first ICD shock, and mortality. A total of 488 patients were included (mean age, 66 ± 13years). During a mean follow-up of 1.9 ± 0.9years, patients followed at HGC were 63% less likely to receive any ICD therapy (adjusted HR [aHR] 0.37, 95% CI 0.42-0.99). There were no significant differences in the rate of first ICD shock (aHR 0.72, 95% CI 0.34-1.52) or mortality (aHR 1.19, 95% CI, 0.47-3.05). Compared to primary prevention patients followed at LGC, primary prevention ICD patients followed at HGC received a significantly lower rate of ICD therapy, mainly from ATP reduction, without a difference in mortality during follow-up.

Abstract 14643: Benefits and Risks of Single- vs. Dual- Chamber Implantable Cardioverter Defibrillators for Primary Prevention of Sudden Cardiac Death

Introduction: Implantable cardioverter defibrillator (ICD) is the more effective and safer treatment for the primary prevention of sudden cardiac death. It remains unclear whether dual-chamber ICD offers the clinical benefits over single-chamber ICD without increasing complications. Hypothesis: The study aimed to evaluate the benefits and risks of dual-chamber ICD compared with single-chamber ICD for primary prevention of sudden cardiac death in clinical practice. Methods: Using the Korean National Health Insurance Service database from January 2008 to December 2019, we include patients with primary prevention ICD and no documented indication for pacing. The propensity score matching method was used to balance covariates across single- and dual-chamber ICDs. Primary outcomes were all-cause mortality, hospitalization of heart failure, and hospitalization of cardiovascular cause. Results: Among 1,929 patients, 1,098 (56.9%) received a single-chamber ICD and 831 (43.1%) received a dual-chamber ICD. In 752 pairs of patients after propensity matching baseline characteristics were balanced between the 2 groups (median age 62 years; male 72%). Over a mean follow-up of 2.7±2.4 years, 1- and 5-year all-cause mortality (5.5% vs. 5.6%, P=0.910; 19.4% vs. 19.3%, P=0.948), 1- and 5-year hospitalization for cardiovascular cause (14.9% vs. 14.9%, P=1.000; 23.9% vs. 22.6%, P=0.542), and 1- and 5-year hospitalization for heart failure (10.8% vs. 8.6%, P=0.163; 16.8% vs. 14.0%, P=0.133) were similar in both groups. However, cardiac tamponade in the rates of device-related complications was 0.1% in the single-chamber ICD vs. 1.1% in dual-chamber ICD groups (P=0.013). Conclusions: In the real-world population receiving a primary prevention ICD, dual-chamber ICD was associated with higher rates of cardiac tamponade than single-chamber ICD. One and five-year rates of all-cause mortality and hospitalization did not differ significantly between the two groups.

Utilization and in-hospital complications associated with implantation of dual versus single chamber implantable cardioverter defibrillator for primary prevention of sudden cardiac death

Abstract Introduction Multiple studies showed no clinical benefit in implantation of a dual compared to a single chamber implantable cardioverter defibrillator (dICD vs. sICD) for primary prevention of sudden cardiac death (SCD), in patients with no pacing indication. We aimed to investigate the extent of utilization and complications in sICD vs. dICD implantations in the US, using the National In-Patient Sample (NIS) database. Methods Using the NIS database, we identified patients who underwent an elective ICD implantation in the US between 2015 (last quarter)-2019. Patients who had concurrent conduction disorders or indication for atrial pacing were excluded. Baseline demographics, clinical characteristics, cardiomyopathy etiologies as well as outcomes including in-hospital complications, length of stay and mortality were collected. Multivariable logistic regression models were used to identify predictors of complications. Results and discussion An estimated total of 15940 patients, who underwent elective ICD implantation for primary prevention of SCD were identified, 8860 (55.6%) of them received a dICD. Forty percent of patients had ischemic cardiomyopathy. The mean age was 64 years and 66% were males. The complication rates documented in the dICD and sICD groups were 13% and 11%, respectively (p&amp;lt;0.001),driven by increased rate of pneumothorax (4.8% vs 3.2%, p&amp;lt;0.001) and lead dislodgement (3.6% vs 2.3%, p&amp;lt;0.001, Table 1). Multivariate analysis confirmed adding an atrial lead as an independent risk factor for “any complication” during ICD implantation [OR 1.13 (1.02–1.25), p=0.022] as well as for pneumo/hemothorax [OR 1.21 (1.03–1.44), p=0.025] and lead dislodgement [OR 1.41 (1.16–1.72), p&amp;lt;0.001]. Conclusion Despite significant evidence for lack of clinical benefit in adding an atrial lead to a primary prevention ICD implantation, significant proportion of the patients in the US are implanted with a dICD. We show increased risk for complications for dICD compared with sICD implantation in the US in recent years, driven by higher incidence of pneumo/hemothorax and lead dislodgement. Funding Acknowledgement Type of funding sources: None.

Phenotypic variability of FLNC-related cardiomyopathy: insights from a novel Dutch founder variant

Abstract Background Truncating variants in filamin C (encoded by the FLNC gene) are an important cause of dilated cardiomyopathy (DCM). Recently, a new pathogenic FLNC variant c.6864_6867dup, p.(Val2290Argfs*23) was identified in a number of families with DCM in the south of the Netherlands. Objectives The aim of this study was to: (i) investigate whether this FLNC variant is a founder variant; and (ii) to evaluate the clinical phenotype of the affected individuals. Material and methods Genetic and clinical data from these FLNC carriers were retrospectively collected. To determine a possible founder effect, haplotypes were reconstructed. The geographical distribution and age of the variant were determined. Clinical characteristics and outcomes were retrieved from electronic medical records. Cardiac magnetic resonance imaging (CMR) studies were reviewed. Results In total 33 individuals from 9 families carrying this FLNC variant were identified. A shared haplotype spanning 2.1 Mb was present in all subjects that were haplotyped. The variant appears to have originated in the south of the Netherlands between 275 and 650 years ago. Median age was 53 years (range 20–79). Nine (27%) individuals were male. The clinical presentation is heterogeneous, ranging from the presence of DCM with heart failure with reduced ejection fraction in 11 (33%) subjects (median age 57, range 36–79 years), to presentation with sudden cardiac death (SCD) in 1 subject at 28 years of age with LV dilation and fibrosis on pathology, without prior symptoms. Seven subjects (21%) had left ventricular (LV) dilation with normal LV function, and one had midrange LV function without dilation. Nine (27%) subjects had no cardiac abnormalities, with a median age of 56 (range 26–70). CMR was available in 18 subjects and showed late gadolinium enhancement (LGE), indicating fibrosis, in 11 subjects (61%), including 2 with preserved LV function. The LGE was extensively present in epicardial and infrequently in the subepicardial LV segments, with ring-like distributions being observed in 4 (22%) of the assessed patients. During follow-up 1 subject experienced SCD and 3 developed end-stage heart failure and underwent heart transplantation. Six (18%) subjects had asymptomatic non-sustained ventricular arrhythmias detected by Holter monitoring, and 4 (12%) subjects received an implantable cardioverter defibrillator for primary prevention and 1 for secondary prevention. Conclusion The c.6864_6867dup, p.(Val2290Argfs*23) pathogenic FLNC variant is a founder variant originating from the south of the Netherlands. The phenotype is characterized by extensive myocardial fibrosis, even in subjects with preserved LV function, making subjects prone to both arrhythmias and heart failure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation

T-wave alternans poorly prognostic in primary prophylactic ICD patients: a prospective EU-CERT-ICD study

Abstract Background New methods to identify patients who truly benefit from primary prophylactic implantable cardioverter defibrillation (ICD) are urgently needed. T-wave alternans (TWA) represents a beat-to-beat fluctuation in the morphology of the ST-segment and T-wave. It has been shown to associate with arrhythmogenesis of heart and sudden cardiac death [1]. We hypothised that TWA might associate with benefit from ICD implantation in primary prevention. Methods In EU-CERT-ICD study, we prospectively enrolled 2327 primary prophylactic ICD candidates from 15 European countries. A 24-hours Holter-monitoring was taken from all recruited patients at enrolment. TWA was assessed from Holter-monitoring using MMA method with Getemed Cardioday software. To assess the benefit from ICD treatment, we used outcomes all-cause mortality, appropriate shock and survival benefit. We conducted Cox regression model, competing risk regression model and propensity score adjusted Cox regression model. TWA was assessed both as contiguous variable and with cut-off points &amp;lt;47 μV and &amp;lt;60 μV. Results Final cohort included 1,734 valid T-wave alternans samples, 1,211 patients with ICD and 523 control patients with conservative treatment, with mean follow-up time 2.3 years. TWA &amp;lt;60 μV predicted lower all-cause mortality in ICD patients in univariate cox regression model (HR 1.484, 95% CI 1.024–2.151, p=0.0374). In multivariate models, TWA did not predict death or appropriate shocks in ICD patients. In addition, TWA did not predict death in control patients. In propensity score adjusted Cox regression model, TWA did not predict ICD benefit. Conclusion T-wave alternans is poorly prognostic in primary prophylactic ICD patients. Altough it may predict life-threatening arrhythmias and sudden cardiac death in several patient populations, it cannot be used in assessing benefit from implantable cardioverter defibrillator in primary prevention among patients with ejection fraction ≤35%. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Community's 7th Framework Program FP7/2007-2013

A Tachycardia in Disguise.

A Tachycardia in Disguise.

Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction—UK multicentre collaboration

IntroductionThe purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death...

786 A case of end-stage mitochondrial cardiomyopathy undergoing heart and kidney transplantation

Abstract Male, 46 year old. Family history: brother affected by deafness and repeated episodes of stroke at a young age. Pathological history: history of competitive sporting activity in which he underwent periodic outpatient checks and reported sporadic myalgic episodes. The patient was suffering from bilateral keratoconus. For the purpose of discovering Wolf–Parkinson–White syndrome with the presence of a right antero-septal accessory pathway, he underwent an electrophysiological study (2003) negative for inducible arrhythmias. During a routine checkup, a renal biopsy was performed to search for elevated blood creatinine, which concluded with acute interstitial nephritis (2005), treated ineffectively with steroids and resulted in dialysis-dependent stage V renal failure (2020). Following light tiredness, he underwent an echocardiographic examination (2009) which revealed the presence of dilated heart disease with reduced left ventricular systolic function. He underwent a cardiac MRI which showed diffuse spots of subepicardial late enhancement as a possible post-myocarditis outcome. At subsequent clinical-echocardiographic checks, progressive biventricular dysfunction, and signs of congestive heart failure were highlighted, for which medical therapy was progressively increased and insertion of an implantable cardioverter defibrillator in primary prevention for sudden cardiac death. At the subsequent clinical re-evaluations, there was evidence of progressive bilateral hearing loss. In consideration of the clinical picture and family history, considering the syndromic nature of the polypathologies to be likely, genetic investigation was required for mitochondrial diseases. Mutations 3242 and 3271mt-RNA and 13513 mtND5, frequent in the MELAS Syndrome, were searched in peripheral venous samples and resulted as negative. In 2020 he underwent an orthotopic heart transplant sec. Shamway followed by a kidney transplant from a compatible donor. In order to perform further diagnostic investigations, the explanted heart was sent to the Pathological Anatomy laboratory of the Umberto I Hospital: macroscopic analysis showed foci of fat replacement at the level of the anterior and posterior wall of the right ventricle (Figure); under microscopy, marked myocardial hypertrophy was observed, associated with cytoplasmic vacuolization of the cardiomyocytes, fibro-adipose substitution of the right ventricle, and replacement fibrosis in minute foci in the left ventricular level. A widespread and marked reduction in the enzymatic activity of cytochrome oxidase in cardiomyocytes and mitochondrial proliferation was demonstrated using histo-enzymatic staining, by staining for succinate dehydrogenase, concluding with mitochondrial disease. Mitochondrial diseases represent a challenge not only from the prognostic–therapeutic point of view but, remarkably, also from a diagnostic one: the patient received a correct diagnosis of the pathology that afflicted him, with almost two decades of delay. The integrated and multidisciplinary approach is desirable in order to obtain an early diagnosis.

Validation of the 2020 AHA/ACC Risk Stratification for Sudden Cardiac Death in Chinese Patients With Hypertrophic Cardiomyopathy

Background: Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HCM), but identification of patients at a high risk of SCD is challenging. The study aimed to validate the three SCD risk stratifications recommended by the 2011 ACCF/AHA guideline, the 2014 ESC guideline, and the 2020 AHA/ACC guideline in Chinese HCM patients.Methods: The study population consisted of a consecutive cohort of 511 patients with HCM without a history of SCD event. The endpoint was a composite of SCD or an equivalent event (appropriate implantable cardioverter defibrillator therapy or successful resuscitation after cardiac arrest).Results: During a follow-up of 4.7 ± 1.7 years, 15 patients (2.9%) reached the SCD endpoint and 12 (2.3%) were protected by implantable cardioverter defibrillator for primary prevention. A total of 13 (2.8%) patients experiencing SCD events were misclassified as low-risk patients by the 2011 ACCF/AHA guideline, 12 (2.3%) by the 2014 ESC model, and 7 (1.6%) by the 2020 AHA/ACC guideline. The SCD risk stratification in the 2020 AHA/ACC guideline showed greater area under the curve (0.71; 95% CI 0.56–0.87, p < 0.001) than the one in the 2011 ACCF/AHA guideline (0.52; 95% CI 0.37–0.67, p = 0.76) and 2014 ESC guideline (0.68; 95% CI 0.54–0.81, p = 0.02).Conclusion: The SCD risk stratification recommended by the 2020 AHA/ACC guideline showed a better discrimination than previous stratifications in Chinese patients with HCM. A larger multicenter, independent, and prospective study with long-term follow-up would be warranted to validate our result.

Effect of SAcubitril/Valsartan on left vEntricular ejection fraction and on the potential indication for Implantable Cardioverter Defibrillator in primary prevention: the SAVE-ICD study.

Sacubitril/valsartan has been associated with a positive reverse left ventricular remodelling in patients with heart failure with reduced ejection fraction (HFrEF). These patients may also benefit from an ICD implant. We aimed to assess EF improvement after 6months of treatment with sacubitril/valsartan, evaluating when ICD as primary prevention was no longer indicated. Multicentre, observational, prospective study enrolling all consecutive patients with HFrEF and EF ≤ 35% with an ICD as primary prevention and starting treatment with sacubitril/valsartan (NCT03935087). Resynchronization therapy and patients experiencing appropriate ICD therapies before sacubitril/valsartan were excluded. Two-hundred-and-thirty patients were enrolled (73.9% males, mean age 64.3 ± 12.1years) After 6months of treatment, a reduction in left ventricular end-diastolic and end-systolic volumes was noted and LVEF increased from 28.3 ± 5.6% to 32.2 ± 6.5% (p < 0.001). At 6months, a non-ischemic aetiology of cardiomyopathy and a final dose of sacubitril/valsartan > 24/26mg twice daily were associated with a higher probability of an absolute increase of > 5% in LVEF. A total of 5.3% of primary prevention patients still had an arrhythmic event in the first 6months after treatment with sacubitril/valsartan started. Sacubitril/valsartan improves systolic function in HFrEF, mainly due to reverse left ventricular remodelling. Improvement in EF after 6months of treatment could help prevent ICD implantation in nearly one out of four patients, with important clinical and economic implications. However, the risk of sudden cardiac death in this recovered HFrEF population has not been thoroughly studied, and the present data should be interpreted only as hypothesis-generating.

The prognostic role of late gadolinium enhancement on cardiac magnetic resonance in patients with nonischemic cardiomyopathy and reduced ejection fraction, implanted with cardioverter defibrillators for primary prevention. A systematic review and meta-analysis.

Previous studies suggest that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with arrhythmic events in patients with nonischemic cardiomyopathy (NICM), while others have questioned the role of left ventricular ejection fraction (LVEF) as a sole predictor of future events. To evaluate the role of LGE on CMR in identifying patients with NICM and reduced LVEF for whom a benefit from defibrillator implantation for primary prevention is not anticipated, thus they are mainly exposed to potential risks. Major electronic databases were searched for studies reporting the incidence of appropriate device therapy (ADT), sudden cardiac death (SCD), and cardiac death based on the presence of LGE on CMR, among patients with NICM and reduced LVEF, implanted with a cardioverter defibrillator for primary prevention. Eleven studies (1652 patients, 947 with LGE) were included in the final analysis. LGE presence was strongly associated with ADT (logOR: 1.95, 95%CI: 1.21-2.69) and cardiac death (logOR: 0.91, 95%CI: 0.14-1.68), but not with SCD (logOR: 0.26, 95%CI: -1.09-1.6). Diagnostic accuracy analysis demonstrated that contrast enhancement is a sensitive marker of future ADT and cardiac death (93%, 95%CI: 85.8-96.7%; 82.9%, 95%CI: 70.6-90.7%; respectively), with moderate specificity ( 44%, 95%CI: 27.2-62.6%; 37.7%, 95%CI: 23.4-54.6%; respectively). LGE is a highly sensitive predictor of ADT and cardiac death in NICM patients implanted with a defibrillator for primary prevention. However, due to moderate specificity, derivation of a cutoff with adequate predictive values and probably a multifactorial approach are needed to improve discrimination of patients who will not benefit from ICDs.

Ethical issues in two parallel trials of personalised criteria for implantation of implantable cardioverter defibrillators for primary prevention: the PROFID project—a position paper

AimTo discuss ethical issues related to a complex study (PROFID) involving the development of a new, partly artificial intelligence-based, prediction model to enable personalised decision-making about the implantation of an...

Enhanced adaptive matched filter for automated identification and measurement of electrocardiographic alternans

Electrocardiographic alternans, consisting of P-wave alternans (PWA), QRS-complex alternans (QRSA) and T-wave alternans (TWA), is an index of cardiac risk. However, only automated TWA measurement methods have been proposed so far. Here, we presented the enhanced adaptive matched filter (EAMF) method and tested its reliability in both simulated and experimental conditions. Our methodological novelty consists in the introduction of a signal enhancement procedure according to which all sections of the electrocardiogram (ECG) but the wave of interest are set to baseline, and in the extraction of the alternans area (AAr) in addition to the standard alternans amplitude (AAm). Simulated data consisted of 27 simulated ECGs representing all combinations of PWA, QRSA and TWA of low (10 μV) and high (100 μV) amplitude. Experimental data consisted of exercise 12-lead ECGs from 266 heart failure patients with an implanted cardioverter defibrillator for primary prevention. EAMF was able to accurately identify and measure all kinds of simulated alternans (absolute maximum error equal to 2%). Moreover, different alternans kinds were simultaneously present in the experimental data and EAMF was able to identify and measure all of them (AAr: 545 μV × ms, 762 μV × ms and 1382 μV × ms; AAm: 5 μV, 9 μV and 7 μV; for PWA, QRSA and TWA, respectively) and to discriminate TWA as the prevalent one (with the highest AAr). EAMF accurately identifies and measures all kinds of electrocardiographic alternans. EAMF may support determination of incremental clinical utility of PWA and QRSA with respect to TWA only.