Topic: Journal Club Selection

Abstract

A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis.

China L, Freemantle N, Forrest E, Kallis Y, ... O\'Brien A, ATTIRE Trial Investigators
Background
Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown.
Methods
We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment.
Results
A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.
Conclusions
In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 03 Mar 2021; 384:808-817
China L, Freemantle N, Forrest E, Kallis Y, ... O'Brien A, ATTIRE Trial Investigators
N Engl J Med: 03 Mar 2021; 384:808-817 | PMID: 33657293
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk.

Leon MB, Mack MJ, Hahn RT, Thourani VH, ... Pibarot P, PARTNER 3 Investigators
Background
In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year.
Objectives
This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial.
Methods
This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis.
Results
Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years.
Conclusions
At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Mar 2021; 77:1149-1161
Leon MB, Mack MJ, Hahn RT, Thourani VH, ... Pibarot P, PARTNER 3 Investigators
J Am Coll Cardiol: 08 Mar 2021; 77:1149-1161 | PMID: 33663731
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Spironolactone in Patients With Heart Failure, Preserved Ejection Fraction, and Worsening Renal Function.

Beldhuis IE, Myhre PL, Bristow M, Claggett B, ... Solomon SD, Desai AS
Background
Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood.
Objectives
The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF.
Methods
In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term.
Results
WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p < 0.001). Regardless of treatment, incident WRF was associated with increased risk for the primary endpoint (hazard ratio: 2.04; 95% confidence interval: 1.52 to 2.72; p < 0.001) after multivariable adjustment. Although there was no statistical interaction between treatment assignment and WRF regarding the primary endpoint (interaction p = 0.11), spironolactone-associated WRF was associated with lower risk of CV death (interaction p = 0.003) and all-cause mortality (interaction p = 0.001) compared with placebo-associated WRF.
Conclusions
Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 08 Mar 2021; 77:1211-1221
Beldhuis IE, Myhre PL, Bristow M, Claggett B, ... Solomon SD, Desai AS
J Am Coll Cardiol: 08 Mar 2021; 77:1211-1221 | PMID: 33663739
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

10-Year Follow-Up of Patients With Everolimus-Eluting Versus Bare-Metal Stents After ST-Segment Elevation Myocardial Infarction.

Brugaletta S, Gomez-Lara J, Ortega-Paz L, Jimenez-Diaz V, ... Serruys PW, Sabaté M
Background
Outcomes data for a durable-polymer everolimus-eluting stent (EES) at extended long-term follow-up in patients with ST-segment elevation myocardial infarction (STEMI) are unknown.
Objectives
The aim of this study was to assess the 10-year outcomes of patients enrolled in the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction) trial.
Methods
The EXAMINATION-EXTEND (10-Years Follow-Up of the EXAMINATION Trial) study is an investigator-driven 10-year follow-up of the EXAMINATION trial, which randomly assigned 1,498 patients with STEMI in a 1:1 ratio to receive either EES (n = 751) or bare-metal stents (n = 747). The primary endpoint was a patient-oriented composite endpoint of all-cause death, any myocardial infarction, or any revascularization. Secondary endpoints included a device-oriented composite endpoint of cardiac death, target vessel myocardial infarction, or target lesion revascularization; the individual components of the combined endpoints; and stent thrombosis.
Results
Complete 10-year clinical follow-up was obtained in 94.5% of the EES group and 95.9% of the bare-metal stent group. Rates of the patient-oriented composite endpoint and device-oriented composite endpoint were significantly reduced in the EES group (32.4% vs. 38.0% [hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.96; p = 0.013] and 13.6% vs. 18.4% [hazard ratio: 0.72; 95% confidence interval: 0.55 to 0.93; p = 0.012], respectively), driven mainly by target lesion revascularization (5.7% vs. 8.8%; p = 0.018). The rate of definite stent thrombosis was similar in both groups (2.2% vs. 2.5%; p = 0.590). No differences were found between the groups in terms of target lesion revascularization (1.4% vs. 1.3%; p = 0.963) and definite or probable stent thrombosis (0.6% vs. 0.4%; p = 0.703) between 5 and 10 years.
Conclusions
At 10-year follow-up, EES demonstrated confirmed superiority in combined patient- and device-oriented composite endpoints compared with bare-metal stents in patients with STEMI requiring primary percutaneous coronary intervention. Between 5- and 10-year follow-up, a low incidence of adverse cardiovascular events related to device failure was found in both groups. (10-Years Follow-Up of the EXAMINATION Trial; NCT04462315).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Mar 2021; 77:1165-1178
Brugaletta S, Gomez-Lara J, Ortega-Paz L, Jimenez-Diaz V, ... Serruys PW, Sabaté M
J Am Coll Cardiol: 08 Mar 2021; 77:1165-1178 | PMID: 33663733
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Randomized, Double-Blind Comparison of Half-Dose Versus Full-Dose Edoxaban in 14,014 Patients With Atrial Fibrillation.

Steffel J, Ruff CT, Yin O, Braunwald E, ... Antman EM, Giugliano RP
Background
In the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, the lower dose edoxaban regimen (LDER) and the higher dose edoxaban regimen (HDER) were noninferior to well-managed warfarin for stroke prevention in atrial fibrillation.
Objectives
The objective of the present analysis of the ENGAGE AF TIMI-48 trial was to comprehensively compare the net clinical outcome (NCO) of LDER (30 mg once daily, dose reduced to 15 mg in selective patients) versus HDER (60 mg once daily, dose reduced to 30 mg in selective patients).
Methods
This study performed a pre-specified analysis of the ENGAGE AF-TIMI 48 trial, comparing patients on LDER versus HDER.
Results
The pre-defined primary NCO (stroke/systemic embolism [SEE], major bleeding, death) was less frequent with LDER (7.26% vs. 8.01%; hazard ratio: 0.90; 95% confidence interval: 0.84 to 0.98; p = 0.014). The secondary (disabling stroke, life-threatening bleeding, or all-cause mortality) and tertiary pre-defined NCOs (stroke, SEE, life-threatening bleeding, or all-cause mortality) were similar between the 2 dosing regimens. Patients randomized to LDER versus HDER had a significantly higher risk of stroke/SEE (2.04% vs. 1.56%; hazard ratio: 1.31; 95% confidence interval: 1.12 to 1.52; p < 0.001). Conversely, major bleeding, intracranial hemorrhage, major gastrointestinal bleeding, and life-threatening bleeding occurred significantly less frequently with LDER compared with those of HDER. These findings were supported by multiple pharmacokinetic findings.
Conclusions
In the ENGAGE AF-TIMI 48 trial, the primary NCO was reduced with LDER versus HDER, whereas the secondary and tertiary NCOs were similar between the 2 dosing regimens. These results may aid physicians in evidence-based individualization of edoxaban dosing. However, the approved HDER remains the standard therapy among the available edoxaban dosing regimens for stroke prevention in atrial fibrillation. (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48 [ENGAGE AF-TIMI 48]; NCT00781391).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Mar 2021; 77:1197-1207
Steffel J, Ruff CT, Yin O, Braunwald E, ... Antman EM, Giugliano RP
J Am Coll Cardiol: 08 Mar 2021; 77:1197-1207 | PMID: 33663737
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Yu H, Zhang F, Yan P, Zhang S, ... Sun K, Zhang B
Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. La ribonucleoprotein domain family member 7 (LARP7) is a master regulator that governs the DNA damage response and RNAPII pausing pathway, but the role of it in heart failure pathogenesis is incompletely understood.
Methods:
We assessed LARP7 expression in human HF, and in non-human primate and mouse HF models. To study the function of LARP7 in heart, we generated global and cardiac-specific LARP7 knockout mice. We acutely abolished LARP7 in mature cardiomyocytes by Cas9-mediated LARP7 somatic knockout. We overexpressed LARP7 in cardiomyocytes using adeno-associated virus serotype 9 (AAV9) and ataxia telangiectasia mutated protein (ATM) inhibitor. The therapeutic potential of LARP7-regulated pathways in heart failure was tested in a mouse myocardial infarction model.
Results:
LARP7 was profoundly downregulated in failing human hearts and in non-human primate and murine hearts after myocardial infarction (MI). Low LARP7 levels in failing hearts was linked to elevated reactive oxygen species (ROS), which activated the ATM-mediated DNA damage response pathway and promoted LARP7 ubiquitination and degradation. Constitutive LARP7 knockout in mouse resulted in impaired mitochondrial biogenesis, myocardial hypoplasia, and midgestational lethality. Cardiac-specific inactivation resulted in defective mitochondrial biogenesis, impaired oxidative phosphorylation, elevated oxidative stress and HF by 4 months of age. These abnormalities were accompanied by reduced SIRT1 stability and deacetylase activity which impaired SIRT1-mediated transcription of genes for oxidative phosphorylation and energy metabolism and dampened cardiac function. Restoring LARP7 expression after MI by either AAV-mediated LARP7 expression or small molecule ATM inhibitor substantially improved the function of injured heart. Conclusions: LARP7 is essential for mitochondrial biogenesis, energy production and cardiac function by modulating SIRT1 homeostasis and activity. Reduction of LARP7 in diseased hearts due to activation of the ATM pathway contributes to heart failure pathogenesis, and restoring LARP7 in the injured heart confers myocardial protection. These results identify the ATM-LARP7-SIRT1 pathway as a target for therapeutic intervention in heart failure.




Circulation: 04 Mar 2021; epub ahead of print
Yu H, Zhang F, Yan P, Zhang S, ... Sun K, Zhang B
Circulation: 04 Mar 2021; epub ahead of print | PMID: 33663221
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension.

Zhu L, Liu F, Hao Q, Feng T, ... Dupuis J, Hu Q
Background: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown.
Methods:
We developed a sensitive HPLC technique to quantify dietary GGPP and conducted proteomics, qRT-PCR screening and western blot to determine signaling cascades, gene expression, protein-protein interaction and protein membrane trafficking in wild type and transgenic rats.
Results:
GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate-rich garlic extracts. In human pulmonary artery smooth muscle cells (HPASMCs) treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2/Rab10 signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and HPASMCs upregulated the expression of Ca2+-sensing receptor (CaSR) and hypoxia-induced mitogenic factor/FIZZ1 (HIMF), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10-knockdown almost abrogated hypoxia-promoted CaSR membrane-trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed with a high GGPP diet, blood GGPP levels were increased, and this abolished statin-lowering effects on plasma GGPP and hypoxia-enhanced RhoA activity of blood monocytes that were both also rescued by garlic extracts. Conclusions: There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of i) RhoA-ROCK2 cascade activation and ii) Rab10-faciliated CaSR membrane trafficking with iii) subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin together with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.




Circulation: 03 Mar 2021; epub ahead of print
Zhu L, Liu F, Hao Q, Feng T, ... Dupuis J, Hu Q
Circulation: 03 Mar 2021; epub ahead of print | PMID: 33660517
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Malonate Promotes Adult Cardiomyocyte Proliferation and Heart Regeneration.

Bae J, Salamon RJ, Brandt EB, Paltzer WG, ... Fan J, Mahmoud AI
Background: Neonatal mouse cardiomyocytes undergo a metabolic switch from glycolysis to oxidative phosphorylation, which results in a significant increase in reactive oxygen species (ROS) production that induces DNA damage. These cellular changes contribute to cardiomyocyte cell cycle exit and loss of the capacity for cardiac regeneration. The mechanisms that regulate this metabolic switch and the increase in ROS production have been relatively unexplored. Current evidence suggests that elevated ROS production in ischemic tissues occurs due to accumulation of the mitochondrial metabolite succinate during ischemia via succinate dehydrogenase (SDH), and this succinate is rapidly oxidized at reperfusion. Interestingly, mutations in SDH in familial cancer syndromes have been demonstrated to promote a metabolic shift into glycolytic metabolism, suggesting a potential role for SDH in regulating cellular metabolism. Whether succinate and SDH regulate cardiomyocyte cell cycle activity and the cardiac metabolic state remains unclear.
Methods:
Here, we investigated the role of succinate and succinate dehydrogenase (SDH) inhibition in regulation of postnatal cardiomyocyte cell cycle activity and heart regeneration.
Results:
Our results demonstrate that injection of succinate in neonatal mice results in inhibition of cardiomyocyte proliferation and regeneration. Our evidence also shows that inhibition of SDH by malonate treatment after birth extends the window of cardiomyocyte proliferation and regeneration in juvenile mice. Remarkably, extending malonate treatment to the adult mouse heart following myocardial infarction injury results in a robust regenerative response within 4 weeks following injury via promoting adult cardiomyocyte proliferation and revascularization. Our metabolite analysis following SDH inhibition by malonate induces dynamic changes in adult cardiac metabolism. Conclusions: Inhibition of SDH by malonate promotes adult cardiomyocyte proliferation, revascularization, and heart regeneration via metabolic reprogramming. These findings support a potentially important new therapeutic approach for human heart failure.




Circulation: 04 Mar 2021; epub ahead of print
Bae J, Salamon RJ, Brandt EB, Paltzer WG, ... Fan J, Mahmoud AI
Circulation: 04 Mar 2021; epub ahead of print | PMID: 33666092
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hypertension Burden and the Risk of New-Onset Atrial Fibrillation: A Nationwide Population-Based Study.

Lee SR, Park CS, Choi EK, Ahn HJ, ... Oh S, Lip GYH
The association between the cumulative hypertension burden and the development of atrial fibrillation (AF) is unclear. We aimed to investigate the relationship between hypertension burden and the development of incident AF. Using the Korean National Health Insurance Service database, we identified 3 726 172 subjects who underwent 4 consecutive annual health checkups between 2009 and 2013, with no history of AF. During the median follow-up of 5.2 years, AF was newly diagnosed in 22 012 patients (0.59% of the total study population; 1.168 per 1000 person-years). Using the blood pressure (BP) values at each health checkup, we determined the burden of hypertension (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), stratified as 0 to 4 per the hypertension criteria. The subjects were grouped according to hypertension burden scale 1 to 4: 20% (n=742 806), 19% (n=704 623), 19% (n=713 258), 21% (n=766 204), and 21% (n=799 281). Compared with normal people, subjects with hypertension burdens of 1, 2, 3, and 4 were associated with an 8%, 18%, 26%, and 27% increased risk of incident AF, respectively. On semiquantitative analyses with further stratification of stage 1 (systolic BP of 130-139 mm Hg or diastolic BP of 80-89 mm Hg) and stage 2 (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) hypertension, the risk of AF increased with the hypertension burden by up to 71%. In this study, both a sustained exposure and the degree of increased BP were associated with an increased risk of incident AF. Tailored BP management should be emphasized to reduce the risk of AF.



Hypertension: 02 Mar 2021; 77:919-928
Lee SR, Park CS, Choi EK, Ahn HJ, ... Oh S, Lip GYH
Hypertension: 02 Mar 2021; 77:919-928 | PMID: 33486985
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Influence of Chronic Obstructive Pulmonary Disease on Atrial Mechanics by Speckle Tracking Echocardiography in Patients With Atrial Fibrillation.

Goedemans L, Leung M, van der Bijl P, Abou R, ... Delgado V, Bax JJ
The present study aimed to examine differences in left- and right atrial characteristics between atrial fibrillation (AF) patients with and without chronic obstructive pulmonary disease (COPD). For this, 420 patients (mean age 68 ± 10 years, 73% female) with first diagnosis of AF and baseline echocardiography were included. Of these, 143 COPD patients were compared with 277 patients without COPD matched by age, gender and body surface area. Additionally 38 healthy controls without cardiovascular risk factors, matched for age, were included. For all 3 groups, left atrial (LA) volumes and diameter, LA reservoir strain (LASr), left ventricular ejection fraction (LVEF), right atrial (RA) area and diameter, RA reservoir strain (RASr) and tricuspid annular plane systolic excursion were evaluated on transthoracic echocardiography. Baseline characteristics were similar in patients with and without COPD except for smoking and a history of heart failure (42% vs 11%, p < 0.001 and 48% vs 37%, p = 0.036 for COPD and non-COPD patients, respectively). Also, COPD patients less often used β-blockers (63% vs 75%, p = 0.017). There were no significant differences in LVEF, LA volume and RA area between COPD and non-COPD patients. Compared to the controls, AF patients had impaired LVEF, LASr and RASr. Only RASr was significantly worse in COPD patients as compared to non-COPD patients (15.3% [9.0 to 25.1] vs 19.6% [11.8 to 28.5], p = 0.013). Additionally, a trend towards worse RASr was observed with increasing COPD severity. In conclusion, AF patients with concomitant COPD have more impaired RA function compared to patients without COPD but with similar atrial size and LA function.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Mar 2021; 143:60-66
Goedemans L, Leung M, van der Bijl P, Abou R, ... Delgado V, Bax JJ
Am J Cardiol: 14 Mar 2021; 143:60-66 | PMID: 33359195
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic Role of Left Ventricular Intramyocardial Fatty Metaplasia in Patients With Previous Myocarditis (MYOFAT Study).

Di Bella G, Gentile G, Irsuti F, Giuseppe R, ... Bogaert J, Aquaro GD
Left ventricular intramyocardial fat (LV-IMF) is often found in patients with previous irreversible myocardial damage and may be detected by cardiac magnetic resonance (CMR). No data are currently available about the prevalence of LV-IMF in patients with previous myocarditis. Our aim was to assess the prevalence of LV-IMF in patients with previous myocarditis by repeating after >3 years a follow-up CMR examination and to evaluate its clinical and prognostic role. Patients with clinical suspected myocarditis who underwent CMR within the first week from the onset of their symptoms and underwent repeated CMR were enrolled. LV-IMF was detected as areas of left ventricular intramyocardial \"India ink\" black boundary with or without a hyperintense core. Overall, in 235 patients with a definitive diagnosis of acute myocarditis, CMR was repeated after a median of 4 (3 to 6) years from symptom onset. LV-IMF positive patients (n = 35, 15%) presented greater ventricular volumes and more frequently a mid-wall late gadolinium enhancement than those without LV-IMF (both p < 0.05). Patients presenting major cardiac events (sudden cardiac deaths, resuscitated cardiac arrest, and appropriate implantable cardioverter-defibrillator-firing) at follow-up had a greater prevalence of LV-IMF than those without (55% vs 11%, p < 0.001). Patients with LV-IMF had a higher incidence myocarditis relapse (27% vs 9%, p = 0.003) and a greater risk of major cardiac events (p < 0.0001) than those without. At logistic regression analysis, LV-IMF was an independent predictor of major cardiac events. In conclusion, LV-IMF is not an uncommon finding in patients with previous myocarditis and is associated with worse ventricular remodeling and prognosis.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Mar 2021; 143:135-144
Di Bella G, Gentile G, Irsuti F, Giuseppe R, ... Bogaert J, Aquaro GD
Am J Cardiol: 14 Mar 2021; 143:135-144 | PMID: 33352209
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac Resynchronization Therapy response assessment with electromechanical activation mapping within 24 hours of device implantation - a pilot study.

Melki L, Wang DY, Grubb CS, Weber R, ... Garan H, Konofagou EE
Background
Cardiac Resynchronization Therapy (CRT) response assessment relies on the QRS complex narrowing criterion. Yet, a third of patients do not improve despite narrowed QRS post-implantation. Electromechanical Wave Imaging (EWI) is a quantitative echocardiography-based technique capable of non-invasively mapping cardiac electromechanical activation in 3D. This exploratory study investigates the EWI technique, sensitive to ventricular dyssynchrony, for informing CRT response on the day of implantation.
Methods
Forty-four (N=44) heart failure patients with left bundle branch block or right-ventricular paced rhythm and decreased left ventricular ejection fraction (LVEF = 25.3 ± 9.6%), underwent EWI without and with CRT within 24 hours of device implantation. Of those, sixteen were also scanned while in LV pacing. Improvement in LVEF at 3-, 6-, or 9-month follow-up defined: (i) super-responders(LVEF≥20%); (ii) responders(10%≤LVEF<20%); and (iii) non-responders(LVEF≤5%). 3D-rendered electromechanical maps were obtained under RV, LV and biventricular (BiV) CRT pacing conditions. Mean RV free wall and LV lateral wall activation times (LWAT) were computed. The percentage of resynchronized myocardium (%RMLV) was measured by quantifying the percentage of LV activated within 120 ms of QRS onset. Correlations between %RMLV and the type of CRT response were assessed.
Results
LWAT was significantly different (p≤0.05) between all three pacing conditions in the sixteen patients: LWAT with CRT in BiV pacing (73.1±17.6ms) was lower compared to LV pacing (89.5±21.5ms) and RV pacing (120.3±17.8ms), respectively. Retrospective analysis showed that the %RMLVmetric with CRT was a reliable response predictor within 24 hours of implantation for significantly (p≤0.05) identifying super-responders (n=7, 97.7±1.9%) from non-responders (n=17, 89.9±9.9%).
Conclusion
Electromechanical activation mapping constitutes a valuable 3D visualization tool within 24 hours of implantation and could potentially aid in the timely assessment of CRT response rates, including during implantation for adjustment of lead placement and pacing outcomes.

Copyright © 2021. Published by Elsevier Inc.

J Am Soc Echocardiogr: 02 Mar 2021; epub ahead of print
Melki L, Wang DY, Grubb CS, Weber R, ... Garan H, Konofagou EE
J Am Soc Echocardiogr: 02 Mar 2021; epub ahead of print | PMID: 33675941
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.