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0005) and CaTD

(

< .0001) and reduction of calcium amplitude alternans ratio (

< .0001). Concomitant treatment with Dan prevented the Dox-induced decline in FS and LVEF (

< .002 at both 2 and 4 weeks). Dan also prevented Dox-induced prolongation of CaTD

and CaTD

and improved the CaT alternans ratio (

< .0001). Finally, calcium transient rise time was increased in the doxorubicin-treated group, indicating RyR2 dyssynchrony, and dantrolene prevented this prolongation (

= .02).

Dantrolene prevents cardiac contractile dysfunction following doxorubicin treatment by mitigating dysregulation of calcium dynamics.

Dantrolene prevents cardiac contractile dysfunction following doxorubicin treatment by mitigating dysregulation of calcium dynamics.

Angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF).

We performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit.

We searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate.

We included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.96;

= .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25-0.79;

= .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21-0.74;

= .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58-3.68;

< .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen.

ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Patients with end-stage heart failure are at high risk for sudden cardiac death. However, implantable cardioverter-defibrillator (ICD) is not routinely implanted given the high competing risk of pump failure. A unique population worth separate consideration are patients with end-stage heart failure awaiting heart transplantation, as prolonged survival improves the chances of receiving transplant.

To compare clinical outcomes of heart failure patients with and without an ICD awaiting heart transplant.

We performed an extensive literature search and systematic review of studies that compared end-stage heart failure patients with and without an ICD awaiting heart transplantation. We separately assessed the rates of total mortality, sudden cardiac death, nonsudden cardiac death, and heart transplantation. Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used owing to heterogeneity across study cohorts.

Ten studies with a total of 36,112 patients were included. A total of 62.5% of patients had an ICD implanted. Patients with an ICD had decreased total mortality (RR 0.60, 95% CI 0.51-0.71,

<.00001) and sudden cardiac death (RR 0.27, 95% CI 0.11-0.66,

= .004) and increased rates of heart transplantation (RR 1.09, 95% CI 1.05-1.14,

< .0001). There was no difference in prevalence of nonsudden cardiac death (RR 0.68, 95% CI 0.44-1.04,

= .07).

ICD implantation is associated with improved outcomes in patients awaiting heart transplant, characterized by decreased total mortality and sudden cardiac death as well as higher rates of heart transplantation.

ICD implantation is associated with improved outcomes in patients awaiting heart transplant, characterized by decreased total mortality and sudden cardiac death as well as higher rates of heart transplantation.

Heart failure and reduced ejection fraction (HFrEF) is the predominant indication for cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) implantation. The care gap and opportunity to optimize guideline-directed medical therapy (GDMT) is unclear.

We sought to define uptake, eligibility, dose, and adherence to GDMT in patients with CRT/ICD and HFrEF.

MEDLINE was searched from 2000 to July 2021 for major randomized trials, registries, and cohort studies evaluating GDMT in this population. Thirty-eight studies focused on medical therapy in patients with CRT/ICD devices (CRT = 23, ICD = 11, and both = 4).

In the pivotal device trials, ACEI/ARB and beta-blocker use was high (mean 94%, range 41%-99%; and 83%, range 27%-97%, respectively), but mineralocorticoid receptor antagonists were modest (mean 45%, range 32%-61%), in keeping with guidelines of that era. Similar results were found in observational registries. CRT was associated with beta-blocker uptitration, while the effects on ACEI/ARB were less consistent. For beta blockers, 57%-68% of patients were uptitrated, increasing the mean percent of target dose achieved by 24% from baseline to follow-up. In one study, adherence increased, for ACEI/ARB from 37% to 55% and beta blockers 34% to 58%. Only 1 study assessed potential eligibility at implant for sacubitril-valsartan (72%) or ivabradine (28%), and no study examined sodium-glucose cotransporter-2 inhibitors. Increased uptake, titration, and dose was associated with reduced mortality, hospitalization, and device therapies.

Patients with HFrEF and ICD/CRT are undertreated with respect to GDMT, and there is opportunity to optimize therapy to improve morbidity and mortality.

Patients with HFrEF and ICD/CRT are undertreated with respect to GDMT, and there is opportunity to optimize therapy to improve morbidity and mortality.

Limited data exist regarding complication rates of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy devices (CRT-D) in patients with left ventricular assist devices (LVAD).

We describe the incidence and characteristics of ICD- and CRT-D-related procedures and complications in a multicenter LVAD cohort.

A total of 537 LVAD patients with a pre-existing ICD or CRT-D from 5 centers were included. Details on device type, device therapies, procedural complications, and long-term survival were analyzed.

Of 537 patients, 280 had a CRT-D and 257 had ICD only. During a median follow-up of 538 days, 126 patients underwent generator replacement with significantly higher rate in the CRT group (79 [28.2%] vs 47 [18.3%],

= .0006). Device-related complications occurred in 36 (13%) CRT-D and 20 (8%) ICD patients (

= .06). Incidence of pocket hematoma (3.2% vs 2.7%), infection (4.3% vs 1.6%), and lead malfunction (3.1% vs 2.8%) was similar in both groups, with no effect of device complication on long-term survival (log-rank

= .7). There was a higher incidence of post-LVAD antitachycardia pacing for ventricular arrhythmias in the CRT-D group compared to the ICD group (35% vs 26%,

= .03).

Cardiac implantable electronic device-related procedures are common in LVAD patients. Compared to ICD only, continued CRT-D therapy post-LVAD results in a significantly higher number of generator changes and a trend towards higher device- or lead-related complications. Device-related complications were not associated with reduced survival.

Cardiac implantable electronic device-related procedures are common in LVAD patients. Compared to ICD only, continued CRT-D therapy post-LVAD results in a significantly higher number of generator changes and a trend towards higher device- or lead-related complications. Device-related complications were not associated with reduced survival.

Cardiac resynchronization therapy (CRT) is one of the cornerstones of heart failure (HF) therapy, as it has reduced mortality and morbidity and has shown improvement in functional capacity. Multipoint pacing (MPP) is a way of configuring CRT with the aim to improve the percentage of patients who respond to CRT.

To demonstrate the effectiveness of the MPP compared to traditional biventricular pacing (BiV).

We performed a systematic review and meta-analysis according to PRISMA guidelines of studies in which MPP vs BiV strategy were compared.

MPP use is associated with a higher rate of patients experiencing functional improvement (odds ratio 2.51, 95% confidence interval [CI], 1.56-4.06;

= .0002) and with higher delta LV dP/dt

(mean difference, 1.82; 95% CI, 0.24-3.39;

= .0240) with respect to BiV. MPP and BiV have no significantly different effect on left ventricular end-systolic volume (LVESV) (mean difference, 0.39; 95% CI, -11.12 to 11.89;

= .9475); moreover, there is no significant difference between the 2 treatments regarding hospitalization for HF (odds ratio, 0.70; 95% CI, 0.32 to 1.54;

= .3816) and all-cause death (odds ratio, 0.81; 95% CI, 0.40 to 1.62;

= .5460). MPP is associated with a significantly lower projected battery longevity (mean difference -8.66 months; 95% CI, -13.67 to -3.66;

= .00007) with respect to BiV.

MPP significantly improves functional class and acute hemodynamic parameters with respect to BiV. Prognostic indices and LVESV are not significantly influenced by MPP. MPP is associated with a significant reduction in projected battery longevity.

MPP significantly improves functional class and acute hemodynamic parameters with respect to BiV. Prognostic indices and LVESV are not significantly influenced by MPP. MPP is associated with a significant reduction in projected battery longevity.

Upgrade to cardiac resynchronization therapy (CRT) is common in Europe, despite little and conflicting evidence.

To compare long-term clinical outcomes in a cohort of patients receiving de novo or upgrade to CRT.

Single-center retrospective study of 295 consecutive patients submitted to CRT implantation between 2007 and 2018. Upgraded and de novo patients complying with a dedicated follow-up protocol were compared in terms of clinical (NYHA class improvement without major adverse cardiac events [MACE] in the first year of follow-up) and echocardiographic (left ventricle end-systolic volume reduction of >15% during the first year) response.

No differences in the rate of clinical (59.3% vs 62.6%,

= .765) or echocardiographic response (72.2% vs 71.9%,

= .970) between groups were observed. Device-related complications were also comparable between groups (8.9% vs 8.4%,

= .892). Phleomycin D1 ic50 Occurrence of MACE and all-cause mortality were analyzed over a median follow-up of 3 (interquartile range 1-6) years MACE occurred less frequently in the de novo group (hazard ratio [HR] 0.

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