[New Treatment Strategies in Patients with Heart Failure with Reduced Ejection Fraction: Beyond Neurohormonal Inhibition].

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure. The following review will debate about emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the new therapeutic strategies in cardiorenal patients.

High-density mapping of Koch's triangle during sinus rhythm and typical atrioventricular nodal re-entrant tachycardia, integrated with direct recording of atrio-ventricular node structure potential.

BACKGROUND: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known. OBJECTIVE: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit. METHODS: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures. RESULTS: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT. CONCLUSION: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias.

Minimal fluoroscopy approach for right-sided supraventricular tachycardia ablation with a novel ablation technology: Insights from the multicenter CHARISMA clinical registry.

BACKGROUND: No data exist on the ability of the novel Rhythmia 3-D mapping system to minimize fluoroscopy exposure during transcatheter ablation of arrhythmias. We report data on the feasibility and safety of a minimal fluoroscopic approach using this system in supraventricular tachycardia (SVT) procedures. METHODS: Consecutive patients were enrolled in the CHARISMA registry at 12 centers. All right-sided procedures performed with the Rhythmia mapping system were analyzed. The acquired electroanatomic information was used to reconstruct 3-D cardiac geometry; fluoroscopic confirmation was used whenever deemed necessary. RESULTS: Three hundred twenty-five patients (mean age = 56 ± 17 years, 57% male) were included: 152 atrioventricular nodal reentrant tachycardia, 116 atrial flutter, 41 and 16 right-sided accessory pathway and atrial tachycardia, respectively. Overall, 27 481 s of fluoroscopy were used (84.6 ± 224 s per procedure, equivalent effective dose = 1.1 ± 3.7 mSv per patient). One hundred ninety-two procedures (59.1%) were completed without the use of fluoroscopy (zero fluoroscopy, ZF). In multivariate analysis, the presence of a fellow in training (OR = 0.15, 95% CI: 0.05-0.46; p = .0008), radiofrequency application (0.99, 0.99-1.00; p = .0002), and mapping times (0.99, 0.99-1.00; p = .042) were all inversely associated with ZF approach. Acute procedural success was achieved in 97.8% of the cases (98.4 vs. 97% in the ZF vs. non-ZF group; p = .4503). During a mean of 290.7 ± 169.6 days follow-up, no major adverse events were reported, and recurrence of the primary arrhythmia was 2.5% (2.1 vs. 3% in the ZF vs. non-ZF group; p = .7206). CONCLUSIONS: The Rhythmia mapping system permits transcatheter ablation of right-sided SVT with minimal fluoroscopy exposure. Even more, in most cases, the system enables a ZF approach, without affecting safety and efficacy.

Noninvasive cardiovascular imaging for myocardial necrosis, viability, stunning and hibernation: evidence from an umbrella review encompassing 12 systematic reviews, 286 studies, and 201,680 patients.

INTRODUCTION: The concomitant presence of myocardial necrosis with myocardial ischemia, stunning or hibernation may complicates appraisal of left ventricular (LV) function and patient management. Several imaging modalities have been proposed for the accurate assessment of myocardial necrosis, viability, stunning and hibernation, with mixed results. We aimed to review the evidence base on myocardial necrosis, stunning and hibernation by conducting an umbrella review (i.e. overview of systematic reviews). EVIDENCE ACQUISITION: We searched PubMed and The Cochrane Library for meta-analyses focusing on the diagnostic, prognostic, or management appraisal of myocardial necrosis, viability, stunning and hibernation. Diagnostic test accuracy, prognostic yield, and clinical outcomes were systematically abstracted from shortlisted reviews. EVIDENCE SYNTHESIS: From an initial set of 6069 citations, 12 systematic reviews were finally included, encompassing 286 studies and 201,680 patients. Cardiac magnetic resonance imaging (CMR) had favorable results in 4 reviews that focused on the diagnosis of myocardial stunning or hibernation in patients followed for 6±4 months after coronary revascularization (sensitivity 96% and specificity 91%). Positron emission tomography (PET), single photon emission tomography (SPECT) and CMR in 6 meta-analyses had each a significant and independent prognostic role for the prediction of fatal and non-fatal cardiovascular events in patients with follow-up of 2.8±1.7 years. Finally, 2 reviews with 2.3±1.1 years of follow-up showed moderate quality evidence in favor of coronary revascularization in patients with objective signs of myocardial viability. CONCLUSIONS: The appraisal of myocardial necrosis and residual viability remains a cornerstone of the modern management of patients with CAD. Current imaging modalities (echocardiography, PET, SPECT and CMR) are widely used. Further trials using contemporary methods are warranted to further clarify the impact of viability assessment on patient management, and the cumulative risk of morbidity and mortality.

Clinical impact of defibrillation testing in a real-world S-ICD population: Data from the ELISIR registry.

BACKGROUND: Current guidelines recommend defibrillation testing (DT) performance in patients with a subcutaneous implantable cardioverter defibrillator (S-ICD), theoretically to reduce the amount of ineffective shocks. DT, however, has been proven unnecessary in transvenous ICD and real-world data show a growing trend in avoidance of DT after S-ICD implantation. METHODS: All patients undergoing S-ICD implant at nine associated Italian centers joining in the ELISIR registry (ClinicalTrials.gov Identifier: NCT04373876) were enrolled and classified upon DT performance. Long-term follow-up events were recorded and compared to report the long-term efficacy and safety of S-ICD implantations without DT in a real-world setting. RESULTS: A total of 420 patients (54.0 ± 15.5 years, 80.0% male) were enrolled in the study. A DT was performed in 254 (60.5%) patients (DT+ group), while in 166 (39.5%) was avoided (DT- group). Over a median follow-up of 19 (11-31) months, a very low rate (0.7%) of ineffective shocks was observed, and no significant differences in the primary combined arrhythmic outcome were observed between the two groups (p = .656). At regression analysis, the only clinical predictor associated with the primary combined outcome was S-ICD placement for primary prevention (odds ratio: 0.42; p = .013); DT performance instead was not associated with a reduction in primary outcome (p = .375). CONCLUSION: Implanting an S-ICD without DT does not appear to impact the safety of defibrillation therapy and overall patients' survival.

Current diagnostic ECG criteria for left ventricular hypertrophy: is it time to change paradigm in the analysis of data?

BACKGROUND: Twelve-lead ECG represents the most common diagnostic tool in clinical cardiology and allows an immediate screening of left ventricular hypertrophy (LVH), but current criteria might have poor clinical usefulness in everyday clinical practice due to lack of sensitivity. METHODS: The current study aims to review and compare the clinical performance of known ECG criteria of LVH in a real-life setting; 2134 patients had ECG and echocardiographic exams performed during the same hospitalization. All traces were retrospectively analysed, and the amplitudes of the waves were manually measured. Transthoracic echocardiography was considered as the gold standard to assess LVH. RESULTS: LVH had a prevalence of 58%. Considering the diagnostic performance of ECG criteria for LVH, the Cornell voltage carried the best area under the receiver operating characteristic curve (0.678), while RaVF (R wave in aVF lead) had the poorer result (0.440). The R5/R6 criterion had the best sensitivity (60%), but with the worst specificity (37.4%). The 'Q or S aVR' had the best specificity (99.9%) but lacks sensitivity (0.80%). The Peguero Lo Presti criterion had a sensitivity of 42.3% and a specificity of 75.8%. The Cornell voltage and the Cornell product had similar area under the receiver operating characteristic curve values which were found to be significantly greater compared with other criteria. CONCLUSION: Current ECG criteria of LVH have low sensitivity despite an acceptable specificity. Among these, Cornell voltage and Cornell product criteria were equally found to have a more accurate diagnostic performance compared with other criteria. To overcome the intrinsic limitations of the current ECG LVH criteria, a new paradigm in the analysis of electrocardiographic data might be necessary.

Assessment of the fate of myocardial necrosis by serial myocardial perfusion imaging.

BACKGROUND: Myocardial necrosis after myocardial infarction (MI) is common; extent and severity are however variable. The pattern is recognized by myocardial perfusion imaging (MPI) as fixed perfusion defects (FPD). The fate of such FPD is not well appraised. This study addressed this important issue in a large number of patients undergoing serial MPI in relation to type of intervening therapy. METHODS: Patients with prior MI or MPI-evidence of myocardial necrosis undergoing serial MPI without intervening acute coronary syndromes were included. The fate of necrosis by MPI on per-patient and per-region analysis was analyzed, factoring also the impact of intervening coronary revascularization (CR). RESULTS: A total of 3691 patients with 25,837 regions were identified, including 1413 (38.3%) subjects with 3358 (13.0%) regions exhibiting necrosis. Serial MPI after 29±21 months confirmed the persistent presence of myocardial necrosis FPD in the vast majority of patients and regions (86%); the consistency was even higher in the presence of moderate or severe necrosis (99%). Neither type nor site of CR significantly impacted on the presence and extent of myocardial necrosis at multivariable analysis. CONCLUSIONS: The finding of myocardial necrosis by MPI remains highly consistent over time, and is not significantly altered by CR.

Prognostic accuracy of myocardial perfusion imaging in octogenarians.

BACKGROUND: Myocardial perfusion imaging (MPI) has an established role in the work-up of coronary artery disease (CAD), but its comparative accuracy is debated in elderly patients. We examined a large administrative database to appraise the performance of MPI in octogenarians. METHODS: Our institutional database was queried for patients undergoing MPI without recent coronary revascularization or myocardial infarction (MI). We compared baseline, procedural, diagnostic, and prognostic features in patients aged < 80 vs ≥ 80 years with bivariate and propensity-adjusted analyses. RESULTS: From 13,254 patients, 12,737 (96.1%) were < 80 years old and 517 (3.9%) ≥ 80 years. Octogenarians were less likely to undergo exercise testing, had more severe and extensive myocardial ischemia (all P < 0.001), whereas CAD was more prevalent and diffuse in them (P = 0.012), and major adverse cardiac events more common during follow-up (P = 0.009). Diagnostic accuracy of MPI was similar or higher in octogenarians than in younger patients (e.g., sensitivity for three-vessel disease 92% in octogenarians vs 91% in younger patients), as was prognostic accuracy. Using propensity-matched analyses, MPI again yielded satisfactory prognostic accuracy in octogenarians. CONCLUSIONS: Use of MPI in octogenarians is associated with similar or better prognostic accuracy than in younger subjects.

Temporal Trends in the Prevalence, Severity, and Localization of Myocardial Ischemia and Necrosis at Myocardial Perfusion Imaging After Myocardial Infarction.

The definition, presentation, and management of myocardial infarction (MI) have changed substantially in the last decade. Whether these changes have impacted on the presence, severity, and localization of necrosis at myocardial perfusion imaging (MPI) has not been appraised to date. Subjects undergoing MPI and reporting a history of clinical MI were shortlisted. We focused on the presence, severity, and localization of necrosis at MPI with a retrospective single-center analysis. A total of 10,476 patients were included, distinguishing 5 groups according to the period in which myocardial perfusion scintigraphy had been performed (2004 to 2005, 2006 to 2007, 2008 to 2009, 2010 to 2011, 2012 to 2013). Trend analysis showed over time a significant worsening in baseline features (e.g., age, diabetes mellitus, and Q waves at electrocardiogram), whereas medical therapy and revascularization were offered with increasing frequency. Over the years, there was also a lower prevalence of normal MPI (from 16.8% to 13.6%) and ischemic MPI (from 35.6% to 32.8%), and a higher prevalence of ischemic and necrotic MPI (from 12.0% to 12.7%) or solely necrotic MPI (from 35.7% to 40.9%, p <0.001). Yet the prevalence of severe ischemia decreased over time from 11.4% to 2.0%, with a similar trend for moderate ischemia (from 15.9% to 11.8%, p <0.001). Similarly sobering results were wound for the prevalence of severe necrosis (from 19.8% to 8.2%) and moderate necrosis (from 8.5% to 7.8%, p = 0.028). These trends were largely confirmed at regional level and after propensity score matching. In conclusion, the outlook of stable patients with previous MI has substantially improved in the last decade, with a decrease in the severity of residual myocardial ischemia and necrosis, despite an apparent worsening in baseline features.

Impact of coronary revascularization vs medical therapy on ischemia among stable patients with or suspected coronary artery disease undergoing serial myocardial perfusion scintigraphy.

BACKGROUND: Randomized trials have challenged the role of revascularization in stable coronary artery disease. We aimed to appraise the impact of revascularization on ischemia in patients undergoing serial myocardial perfusion scintigraphy (MPS). METHODS: We queried our institutional database for stable subjects undergoing serial MPS and appraised the impact of revascularization on changes in ischemia. RESULTS: A total of 3631 patients were included: 967 (27%) undergoing revascularization and 2664 (73%) receiving medical therapy only. Patients treated with revascularization had a significantly lower burden of myocardial ischemia at follow-up (odds ratio = 0.577 [95% confidence interval 0.483-0.689] vs medical therapy, P < .001). Among all those having moderate or severe ischemia at baseline, revascularization was associated with a follow-up prevalence of 80% for no, minimal, or mild ischemia and 20% for moderate or severe ischemia, vs 43% and 57% for medical therapy (P < .001). Even at multivariable analysis and propensity-adjusted, and propensity-matched analyses, revascularization was associated with a significantly lower prevalence of moderate or severe ischemia at follow-up (respectively P < .001, P = .001, and P = .042). CONCLUSIONS: Revascularization appears superior to medical therapy in reducing ischemic burden and normalizing myocardial perfusion among subjects with moderate or severe ischemia at baseline.

Impact of the high-frequency cutoff of bandpass filtering on ECG quality and clinical interpretation: A comparison between 40Hz and 150Hz cutoff in a surgical preoperative adult outpatient population.

BACKGROUND: In 1990 the American Heart Association (AHA) established a standard 0.05 to 150Hz bandwidth for the routine recording of 12-lead electrocardiograms (ECGs). However, subsequent studies have indicated a very high prevalence of deviations from the recommended cutoffs. OBJECTIVE: This prospective observational study investigates the impact of 40Hz compared to 150Hz high-frequency cutoffs on ECG quality and clinical interpretation in a single-center surgical outpatient population. METHODS: 1582 consecutive adult patients underwent two standard 12-lead ECG tracings using different high-frequency cutoffs (40Hz and 150Hz). Two blinded cardiologists randomly reviewed and interpreted the recordings according to pre-defined parameters (PR and ST segment, Q and T wave abnormalities). An arbitrary score, ranging from 1 to 3, was established to evaluate the perceived quality of the recordings and the non-interpretable ECGs were noted. The tracings were then matched to compare interpretations between 40 and 150Hz filters. RESULTS: A 40Hz high-frequency cutoff resulted in an increased rate of optimal quality ECGs compared to the 150Hz cutoff (93.4% vs 54.6%; p<0.001) and a lower rate of non-interpretable traces (0.25% vs 4.80%; p<0.001). Analyzing the morphologic parameters, no significant differences between the filter settings were found, except for a higher incidence of the J-point elevation in the 40Hz high-frequency cutoff (p=0.007) and a higher incidence of left ventricular hypertrophy in the 150Hz high-frequency cutoff (7.4% vs 5.4%, p<0.001). The latter was noted only in ECGs with borderline QRS amplitudes (between 3.3 and 3.7mV; p<0.001). CONCLUSION: Despite current recommendations, the large deviation from standard high-frequency cutoff in clinical practice does not seem to significantly affect ECG clinical interpretation and a 40Hz high-frequency cutoff of the band-pass filtering may be acceptable in a low risk population, allowing for a better quality of tracings.

Primary prevention implantation of cardioverter defibrillator without defibrillation threshold testing: 2-year follow-up.

BACKGROUND: Even though the intraoperative threshold testing of the implantable cardioverter defibrillator (ICD) may cause hemodynamic impairment or be unfeasible, it is still considered required standard practice at the time of implantation. We compared the outcome of ICD recipients who underwent defibrillation threshold testing (DFT) with that of patients in whom no testing was performed. METHODS: A total of 291 subjects with ischemic dilated cardiomyopathy received transvenous ICDs between January 2000 and December 2004 in five Italian cardiology centers. In two centers, DFT was routinely performed in 137 patients (81% men; mean age 69+/-9 years; mean ejection fraction 26+/-4%) (DFT group), while three centers never performed DFT in 154 patients (90% men; mean age 69+/-9 years; mean ejection fraction 27+/-5%) (no-DFT group). RESULTS: We compared total mortality, total cardiovascular mortality, sudden cardiac death (SCD), and spontaneous episodes of ventricular arrhythmia (sustained ventricular tachycardia, VT, and ventricular fibrillation, VF) between these groups 2 years after implantation (median 23 months, 25th-75th percentile, 12-44 months). On comparing the DFT and no-DFT groups, we found an overall mortality rate of 20% versus 16%, cardiovascular mortality of 13% versus 10%, SCD of 3% versus 0.6%, VT incidence of 8% versus 10%, and VF incidence of 6% versus 4% (no significant difference in any comparison). CONCLUSIONS: No significant differences in the incidence of clinical outcomes considered emerged between no-DFT and DFT groups. These results should be confirmed in larger prospective studies.

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Dual site right atrial pacing in the prevention of symptomatic atrial fibrillation refractory to drug therapy and unrelated to sinus bradycardia.

UNLABELLED: Dual-site right atrial pacing has been shown recently to prevent atrial fibrillation relapses in patients affected by drug-refractory, highly-recurring tachyarrhythmia, associated to sinus bradycardia. The aim of our study was to verify whether this stimulation modality could be useful in patients affected by refractory atrial fibrillation unassociated to sinus bradycardia. METHODS AND RESULTS: Fifteen patients (6 males) affected by refractory, symptomatic atrial fibrillation, and potential candidates to AV node ablation, were prospectively enrolled. Mean age was 65 +/- 5 years (range 62-78). Associated pathology was arterial hypertension in 12, and dilated cardiomyopathy in 3. Eight patients were affected by persistent atrial fibrillation, and seven by paroxysmal atrial fibrillation. The duration of the arrhythmia was 61 +/- 63 months (range 3-216). Left atrial diameter was 39.4 +/- 4.2 mm (range 33-46), left ventricular end-diastolic diameter was 52.4 +/- 12.2 mm (range 41-90), and left ventricular ejection fraction was 55 +/- 16 (range 18-81). Single chamber atrial pacing was used in 10 patients, dual chamber in 5 patients. The mean duration of follow up was 24 +/- 12 months (range 3-41). During this period the number of episodes of atrial fibrillation decreased from a mean of 13 +/- 38 (range 1-150) to 0.4 +/- 0.7 (range 0-2.3) per month (p < 0.001). In the subgroup of patients with persistent atrial fibrillation the number of episodes decreased from a mean of 20.4 +/- 52.4 (range 1-150) to 0.6 +/- 0.9 (range 0-2.3) (p < 0.001). In patients with paroxysmal atrial fibrillation the number of episodes decreased from 4.6 +/- 3.5 (range 2-12) to 0.2 +/- 0.5 (range 0-1.4) (p < 0.001). One patient (6.7%) developed chronic atrial fibrillation 16 months after the implant, 2 remaining patients (13%) had their arrhythmia unaltered. After the implant the number of Class 1 antiarrhythmic drugs fell from 18 to 6 (p < 0.001) and that of Class 2 changed from 0 to 7 p < 0.001). The use of Class 3 and 4 did not change significantly. No complications related to implant were observed. CONCLUSIONS: Permanent dual-site right atrial pacing can prevent atrial fibrillation recurrences in patients affected by highly symptomatic episodes unassociated to sinus bradycardia.